Intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominant basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%) and basal-like immune-activated (IHC-BLIA, 10.9%). The pathological complete response (pCR) rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes. Although, IHC-BLIA demonstrated a trend toward better survival and IHC-mesenchymal worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

Background: Extracellular Vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties, clinical and therapeutical applications, even towards cancer. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates the cancer’s growth and spread. Methods: The most valuable and significant PubMed Literature about extracellular vesicles and adipose–derived stem cells exosomes was selected and analyzed in order to report their biological properties and potential applications, in particular on the Triple–Negative Breast Cancer. Results: Adipose–derived stem cells exosomes represent a potential tool to target the tumor core of the Triple–Negative Breast Cancer, its microenvironment and surrounding tissues including metastasis. The authors are developing a supportive Triple–Adipose–derived stem cells Exosomes [T.A.E.] Technology against breast cancer in order to perform a selective preconditioning of the cancer before or while the traditional oncological treatments are running. Conclusion: The possibility to exploit the impact of Adipose–derived stem cells exosomes within the T.A.E. Technology against the Triple–Negative breast cancer is real, highlighting a new era for supportive measures against breast cancer.Keywords: Extracellular vesicles; Exosomes; Adipose–derived stem cells, Tumor microenvironment, Triple–Negative Breast Cancer, T.A.E. Technology.

The design is described of a readily useable technology for routine paddock-scale soil porosity estimation. The method is non-contact (proximal) and typically from sensors mounted on a small farm vehicle around 1 m above the soil surface. Challenges arise from the need to have a compact low-power rigid structure and to allow for pasture cover and surface roughness. The high-frequency regime for acoustic reflections from a porous material is a function of the porosity , the tortuosity , and the angle of incidence . There is no dependence on frequency, so measurements must be conducted at two or more angles of incidence in order to obtain two or more equations in the unknown soil properties and . A system requiring a single transmitter/receiver pair to be moved from one angle to another is not viable for rapid sampling. Therefore, the design includes at least two transmitter/reflector pairs placed at identical distances from the ground so that they would respond identically to power reflected from a perfectly reflecting surface. A single 25 kHz frequency is a compromise which allows for the frequency-dependent signal loss from a natural rough agricultural soil surface. Multiple-transmitter and multiple-microphone arrays are described which give a good signal to noise ratio while maintaining a compact system design. The resulting arrays have a diameter of 100 mm. Pulsed ultrasound is used so that the reflected sound can be separated from sound travelling directly through the air horizontally from transmitter to receiver. The average porosity estimated for soil samples in the laboratory and in the field is found to be within around 0.04 of the porosity measured independently. This level of variation is consistent with uncertainties in setting the angle of incidence, although assumptions made in modelling the interaction of ultrasound with the rough surface no doubt also contribute.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

The development of saltiness enhancement peptides is important in reducing salt intake and promoting dietary health. Our study aimed to analyze and identify straw mushroom enzymatic peptides with salty taste enhancing effects. The taste-related peptides within the straw mush-room extract were isolated via ultrafiltration and identified using UPLC-Q-TOF-MS/MS. Sub-sequent, E-tongue and sensory analyses unveiled that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides exhibited a saltiness enhancement effect. The UPLC-Q-TOF-MS/MS analysis identified 220 peptides within the ultrafiltration fractions (500-2000 Da), which were then assessed for their interaction with the T1R1/T1R3 receptor. The investigation underscored the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in the binding of peptides from triple enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Notably, 3.2 mmol of VPGGQEIKDR enhanced a 0.05% NaCl solution to the saltiness level of a 0.15% NaCl solution. Also, 0.8 mmol of YNEDNGIVK elevated a 0.05% NaCl solution to the saltiness of a 0.1% NaCl solution.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

The effect of defects and microstructure on mechanical properties of Ti-6Al-4V welds produced by tungsten inert gas welding, plasma arc welding, electron beam welding and laser beam welding was studied in the present work. The mechanical properties of the different weld types have been evaluated with respect to micro hardness, yield strength, ultimate tensile strength, ductility and fatigue at room temperature and at elevated temperature. Metallographic investigation was carried out to characterize the microstructures of different weld types and fractographic investigation to relate the effect of defects on fatigue performance. Electron and laser beam welding produced welds with finer microstructure, higher tensile ductility and better fatigue performance than tungsten inert gas welding and plasma arc welding. Large pores and pores located close to the specimen surface were found to be most detrimental to fatigue life.

Uchino first initiated the study of generalized Reynolds operators on associative algebras. Recently, related research has become a hot topic. In this paper, we first introduce the notion of generalized Reynolds operators on Hom-Lie triple systems associated to a representation and a 3-cocycle. Then, we develop cohomology of generalized Reynolds operators on Hom-Lie triple systems with coefficients in a suitable representation. As applications, we use the first cohomology group to classify linear deformations and we study the obstruction class of an extendable order $n$ deformation. Finally, we introduce and investigate Hom-NS-Lie triple system as the underlying structure of generalized Reynolds operators on Hom-Lie triple systems.

The current investigation presents porous ceramic materials prepared of cenospheres prepared by spark plasma sintering. The impact of sintering temperature, mould diameter (20 and 30 mm diameter) and cenosphere size on the properties of the sintered material was investigated. Shrinkage of the samples during sintering started at 900 °C. Sample shrinkage during sintering increases with increasing temperature and decreases with increasing mould size; increasing sample sintering temperature increases the apparent density of all sample series CS 63-150 µm in 20 mm mould from 0.97 to 2.3 g·cm-3 at 1050 - 1300 °C, in 30 mm mould 0.81 - 1.87 g·cm-3 at 1050 - 1200 °C, in 50 mm mould 0.54 - 0.75 g·cm-3 at 1050 - 1150 °C, while CS 150-250 µm in 20 mm mould 0.93 - 1.96 g·cm-3 at 1050 - 1200 °C. Total porosity decreases from 61.5% to 3.9% with increasing sintering temperature from 1050 to 1250 °C, while open porosity reduces at lower temperatures, with closed porosity being highest in samples sintered at 1150 °C. When the sintering temperature increases from 1050 to 1300 °C, the compressive strength of the CS 63-150 samples produced in a 20 mm mould increases from 11 MPa to 312 MPa. These results correlate with the Rice model, which describes an exponential dependence of compressive strength on material porosity and fully dense material compressive strength.

The feasibility of replacing the toxic chlorobenzene antisolvent with the environmentally friendly anisole in the fabrication of planar triple cation perovskite solar cells was explored. The successful integration of anisole not only ensures comparable device performance but also contributes to the development of more sustainable and green fabrication processes for next-generation photovoltaic technologies. Nevertheless, to ensure the possibility to achieve well-functioning unencapsulated devices, at any time of the year, with changed temperature and relative humidity, several batches with different cesium concentration were realized. We found that 10% of CsI in the precursor solution makes devices with low hysteresis index and sustained performance stability over a 90-day period both with cholorobenzene and anisole antisolvent. However the use of anisole as a green antisolvent ensures enhanced performance.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including virulence factors and host interactions, are discussed in detail. Diagnostic methods, ranging from traditional techniques to advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.

Nucleobase-containing molecules are compounds essential in biology due to the fundamental role of nucleic acids, and in particular G-quadruplex DNA and RNA in life. Moreover, some molecules different from nucleic acids isolated from different vegetal sources or microorganisms show nucleobase moieties in their structure. Nucleoamino acids and peptidyl nucleosides belong to this molecular class. Closely related to the above, nucleopeptides also known as nucleobase-bearing peptides are chimeric derivatives of synthetic origin and more rarely isolated from plants. Herein the self-assembly properties of a vast number of structures, belonging to the nucleic acid and nucleo amino acid/nucleopeptide family, is explored in the light of the recent scientific literature. Moreover, several technologically relevant properties such as the hydrogelation ability of some of the nucleobase-containing derivatives are reviewed in order to open the door to future experimental investigations of newly-inspired nucleobase-driven hydrogels. Nucleobase-containing molecules, such as mononucleosides, DNA, RNA, quadruplex (G4)-forming oligonucleotides and nucleopeptides, are paramount in gel and hydrogel formation owing to their distinctive molecular attributes and ability to self-assemble in biomolecular nanosystems with the most diverse applications in different fields of biomedicine and nanotechnology. In fact, these molecules and their gels present numerous advantages, underscoring their significance and applicability in both material science and biomedicine. Their versatility, capability for molecular recognition, responsiveness to stimuli, biocompatibility, and biodegradability collectively contribute to their prominence in modern nanotechnology and biomedicine. In this review, we emphasize the critical role of nucleobase-containing molecules of different nature in pioneering novel materials with multifaceted applications highlighting their potential in therapy, diagnostics, and new nanomaterials fabrication as required in order to address the numerous current biomedical and nanotechnological challenges.

The aim of this research was to undertake laboratory testing to investigate the beneficial effects of epoxy resin grouts on the physical and mechanical properties of sands with a wide range of granulometric characteristics. Six sands, of different particle size and uniformity coefficients, were grouted using epoxy resin solutions with three ratios of epoxy resin to water (3.0, 2.0 and 1.5). A set of unconfined compressive strength tests were conducted on grouted samples at different curing periods and a set of long-term unconfined compressive creep tests in dry and wet conditions after 180 days of curing were also carried out, in order to evaluate the development of the mechanical properties of the sands, as well as, the impact of water on them. The findings of the investigation showed that epoxy resin resulted in appreciable strength values in the specimens, especially those of fine sands, grouted with the different epoxy resin grouts. In general, the compressive strength varied between 0.68 - 5.60 MPa and the modulus of elasticity between 75 - 480 MPa, after a curing period of 180 days. In terms of physical properties, the permeability and porosity (before and after the grouting process) were estimated. Grouts with an epoxy resin to water ratio of 3 decreased permeability by up to four orders of magnitude. Using laboratory results and regression analysis, three mathematical equations were developed that relate each of the dependent variables; compressive strength, elastic modulus, and coefficient of permeability, with particular explanatory variables.

Slags and ashes generated in thermal waste treatment facilities require proper management. In line with the principles of the circular economy, new, more economical and ecological possibilities for utilizing these substances are sought. These waste materials exhibit characteristics similar to rocks in many aspects. This study focuses on analyzing the similarities and differences between nine selected rocks and three samples of slags and ashes obtained from municipal waste incineration. The main research device used was a polarizing microscope, using reflected, transmitted and fluorescent light. Additionally, low-pressure gas adsorption equipment, as well as helium and quasi-liquid pycnometers, were used for complementary analysis. The parameters analyzed mainly covered broadly defined petrographic properties of rocks and slags, with a particular emphasis on porosity, porous structure and the spatial distribution of pores and fractures. The conducted analyses confirmed a significant similarity between slags and ashes and clastic sedimentary rocks such as sandstones and mudstones. The research results underscore the importance of petrographic microscopic studies for analyzing materials other than rocks. They also allow for exploring applications for slags and ashes in areas traditionally reserved for natural rock resources. The findings also indicate the necessity of using methods other than microscopic ones to describe the pore space of rocks. The lower measurement range of the optical microscope is limited to approximately 1 μm, covering only macropores. Other methods extend this characteristic to micro- and mesopores. Therefore, a combination of different methods is often employed to obtain a more comprehensive characterization of rock porosity.

Permeability is an important transport property of porous materials, and its accurate evaluation is relevant in studying applied tasks such as CO2 injection into reservoirs and investigating groundwater quality issues. This study examines the dependence of permeability on total and connected porosity, hydraulic tortuosity, specific surface area, and mean pore radius based on the data of 408 cubic sub-volumes extracted from heterogeneous and naturally fractured cylindrical carbonate samples before and after injection of HCl solutions into them. These parameters were computed using pore-scale modeling of fluid flow. It has been shown that permeability correlates well with porosity and mean pore radius with correlation coefficients of R2≈0.65-0.79 for heterogeneous samples. It was found that the presence of natural fractures significantly influenced the relationship between permeability and other parameters. The relationship between permeability k, tortuosity τ, and specific surface area S is described by power laws k~τ-α and k~S-β, with coefficients α and β substantially exceeding those in the Kozeny-Carman equation. It was also found that there is a parabolic relationship between connected and total porosities both before and after rock dissolution with R2≈0.96-0.99. This allowed for estimation of percolation threshold porosity that are in good agreement with the literature data.

Permeable asphalt pavement refers to an asphalt mixture layer with an air void content of more than 18% and internal water permeability and drainage capabilities, which can quickly drain away water on the road surface, improve rainy day travel safety and ride comfort. This paper aims to explore the optimal asphalt mixture mix design for long longitudinal slope roads. By using CT scanning technology to analyze the air void content of different rotated and compacted asphalt mixture specimens, and extensively testing and evaluating the performance of permeable pavement mixtures, the following conclusions are drawn: Based on the research philosophy of functional integration, a new asphalt mixture gradation suitable for long longitudinal slope roads is proposed, with the optimal key factor composition being: 0.075mm passing rate of 7%, 2.36mm passing rate of 20%, 9.5mm passing rate of 55%, and oil-stone ratio of 4.8%. The FAM mixture was divided into three parts for air void analysis, with the upper part having a slightly higher air void content than the lower part. The air void distribution diagram of the FAM mixture is concave, with higher air void rate curves on both sides and a lower middle curve. Compared with laboratory dry measurement method, CT scanning test showed slightly higher air void content in specimens. Through dynamic modulus testing, the strength requirement for road asphalt mixture in pavement structure design was evaluated. It was found that at high temperature conditions (50℃), the minimum dynamic modulus value of the FAM mixture was 323 MPa, with a peak value of 22746MPa at a temperature of -10℃ and a frequency of 25HZ. The dynamic modulus value at high temperature conditions is lower than at low temperature conditions, while the dynamic modulus value at high frequency conditions is higher than at low frequency conditions. This study provides useful information and experimental data for the design of new asphalt mixtures for long longitudinal slope roads, and has conducted in-depth research on the air void distribution and performance of the mixture, providing strong support for related research fields and practical applications.

Descriptive geometry has indispensable applications in many engineering activities, some of which are presented in the first chapter of this paper in order to place the development presented here among them. As a result of the continuous variability of the technological environment according to various optimization aspects, the engineering activities must also be continuously adapted to the changes, which an appropriate approach and formulation are required from the practitioners of descriptive geometry, and can even lead to improvement in the field of descriptive geometry. The imaging procedures are always based on the methods and theorems of descriptive geometry. Resolving contradictions in spatial geometry reconstruction research is a constant challenge, to which a possible answer in many cases is the search for the right projection direction. A special method of enumerating the possible infinite viewpoints for the representation of the surface edge curves is presented in another part of the paper. The procedure for determining the correct directions in a mathematically exact way is also presented through examples. The analysis and some of the results of the Monge mapping, which is suitable for the solution of a mechanical engineering task to be solved in a specific technical environment, are also presented.

The efficiencies of conventional triple organic Rankine cycle (TORC) configurations are restricted by the low critical temperatures of common working fluids (＜320 °C). This paper proposes a high-temperature TORC system. A near-azeotropic mixture biphenyl/diphenyl oxide (BDO), which has stellar track record in the high-temperature ORC applications, is innovatively adopted as the top and middle ORC fluid simultaneously. The top cycle evaporation temperature is up to 400 °C in view of BDO’s high stability. Five conventional organic fluids are chosen for the bottom ORC. Fundamentals of the TORC system are illustrated, and mathematical models are built. Thermo-economic performance is investigated. The results hint that the optimal thermodynamic property is achieved on the use of benzene as the bottom fluid. The maximum thermal and exergy efficiencies are respectively 40.86% and 74.14%. The largest irreversible loss occurs inside the heat exchanger coupling the middle and bottom ORCs, accounting for above 30% of the total entropy generation. The levelized energy cost (LEC) is 0.0284 $/kWh. Given the same heat source condition, the TORC system can boost efficiency by 1.02% and drive down LEC by 0.0024 $/kWh compared with a BDO mixture-based cascade ORC.

This study explores the implementation of an interdisciplinary curriculum in product and media design education and its impact on knowledge innovation and competency development. The curriculum is based on scaffolding theory, incorporating design proposals, workshops, digital design, marketing tests, and marketing activities guided by teachers and mentors from a branded ceramic workshop. The research findings demonstrate that the interdisciplinary curriculum facilitates knowledge innovation and fosters the development of students' professional skills, creativity, and problem-solving skills. The study also highlights the importance of stable scaffolding, including artefact, peer, and teacher support, which significantly contributes to cultivating transformational competencies, as outlined in the 2030 OECD Learning Compass. Additionally, the collaboration with Shanshing Four Seasons Celadon Studio on a patented ceramic product, "Funny Monkey," is a tangible example of the journey towards a triple-helix knowledge economy. This research underscores the importance of interdisciplinary curricula in promoting knowledge innovation and integrating transformational competencies in education. Scaffolding theory provides practical guidance for student learning and teaching strategies, presenting a sustainable roadmap for developing interdisciplinary curricula and offering a concrete and transferable pedagogical prototype for educational innovation.

This study reports the synthesis and characterization of novel per-fluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers reveal variations in the fluorine content via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers, which enhanced their hydrophobic nature. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights between 4886 to 11948 g/mol. All polymers exhibit thermal stability in the range of 350-500°C, with varying thermal stability depending on the fluorine and nitrogen content. Conjugation of the polymers was confirmed through changes in the UV-Vis spectra, with a hypsochromic shift observed in all cases, more pronounced in azo-based fluorinated chains due to H-bonding on the nitrogen sites, chain conformations, and planarity. The optical band gap (Eg) of the polymers was determined from the UV-Vis data, with the Eg values of the azo-based fluorinated polymers being 1 eV higher than those of their corresponding linkers. The cross-linking formation was characterized by porosity measurements, with the azo-based polymer exhibiting the highest surface area of 770 m²/g with a pore volume of 0.35 cm³/g, while the open-chain azomethine-based polymer exhibited the lowest surface area of 285 m²/g with a pore volume of 0.0872 cm³/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. DAB-Z-1h, with the highest surface area and rich in nitrogen sites, exhibited the highest CO₂ uptake at 298 K (17.25).

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

This study aims to formulate binary cementitious systems containing silica fume (SF) and micro quartz (MQ) to improve cementitious concrete's durability and mechanical properties. In this investigation, we examined the effects of different essential variables, such as the level of SF and MQ replacement and the ratio of the water-binder (w/b). In this study, the w/b ratios were 0.25, 0.3, 0.35, and 0.4. Replacement levels for SF were 8, 10, and 12%, while replacement levels for MQ were 5, 8, 10, 15, 25, and 35%. The porosity and permeability decreased with an increase in replacement levels, regardless of the type of fine material used or the amount of replacement. Meanwhile, the strength increased markedly with SF replacement, reaching its maximum MQ of 25% at the SF level. The strength of the SF mixing was the highest in all mixes, and it remained the highest until 15% of MQ was replaced. The ultrafine size of MQ particles contributes to the improvement of compressive strength, porosity, and permeability in a similar way to SF particles, despite their high crystalline structure. Furthermore, in this study, analysis of variance (ANOVA) was employed to verify the influence of each variable on the studied response.

This work investigates a new nanostructured gas-diffusion-layer (nano-GDL) to improve performance of air-cathode Single-Chamber-Microbial-Fuel-Cells (a-SCMFCs). The new nano-GDLs improves the direct oxygen-reduction-reaction by exploiting the best of nanofibers from electrospinning in terms of high surface ratio to volume and high porosity, and laser-based processing to promote adhesion. Nano-GDLs by electrospinning were fabricated directly collecting two nanofibers mats on the same carbon-based electrode, acting as the substrate. Each layer was designed with a specific function: water resistant, oxygen permeable polyvinylidene-difluoride (PVDF) nanofibers served as a barrier to prevent water-based electrolyte leakage, while an inner layer of cellulose nanofibers was added to promote oxygen diffusion towards the catalytic sites. The maximum current density obtained for a-SCMFCs with the new nano-GDLs is (132.2 ± 10.8) mA m^-2, and it doubles the current density obtained with standard PTFE-based GDL (58.5 ± 2.4 mA m^-2), used as reference material. The energy recovery (EF) factor, i.e. the ratio of the power output to the inner volume of the device, was then used to evaluate the overall performance of a-SCMFCs. a-SCMFCs with nano-GDL provided an EF value of 60.83 mJ m^-3: one order of magnitude higher than the value of 3.92 mJ m^-3 obtained with standard GDL

Sustainable Forest Management (SFM) can fully use forest resources and improve the economic, environmental and social sustainability of forest areas. Forestry enterprises play a crucial role in the implementation of SFM. To better play the role of forestry enterprises in implementing SFM, it is necessary to establish a comprehensive and reasonable performance evaluation model for SFM in forestry enterprises. However, the previous literature pays little attention to this research question. Taking the Triple Bottom Line (TBL) as a theoretical framework and the Montreal Process Criteria and Indicators (MP C&I) as a basis, this paper constructs an indicator system to evaluate the performance of SFM of forest enterprises from economic, social and environmental aspects. This paper applies the integrated MCDM method, i.e. the BWM method and the VIKOR method, to construct the methodological system for SFM performance evaluation of forestry enterprises. The effectiveness of this SFM performance evaluation model is then demonstrated through its application to a case study of forestry enterprises in China. Through the application of the model, this paper evaluates the enterprise's SFM performance over the five-year period 2017-2021 and proposes appropriate policy recommendations and improvements.

Recently, the triple-network convergence system (TNCS) has emerged from the deep integration of the power grid, transportation network, and information network. Fault recovery research in the TNCS is important since this system's complexity and interactivity can expand the faults scale and increase faults impact. Currently, fault recovery focuses primarily on single power grids and cyber-physical systems, but there are certain shortcomings, such as ignoring uncertainties including generator start-up failures and the occurrence of new faults during recovery, energy supply-demand imbalances leading to system security issues and communication delay caused by network attacks. In this study, we propose a recovery method based on the improved TD3 algorithm, factoring in shortcomings of the existing research. Specifically, we establish a TNCS model to analyze interaction mechanisms and design a state matrix to represent the uncertainty changes in the TNCS, a negative reward to reflect the impact of unit start-up failures, a special reward to reflect the impact of communication delay and an improved Actor network update mechanism. Experimental results show that our method obtains the optimal recovery decisions, maximizes restoration benefit in power grid failure scenarios and demonstrates a strong resilience against communication delay caused by DoS attacks.

: This study aims at examining how B Corporations advance Sustainable Development Goals (SDGs) in their practices by analyzing the socioenvironmental problems they address and the solutions they provide to those problems. All Argentinian B corporations, certified by early 2023 (135 companies), were investigated using a mixed approach, combining social network analysis with textual data analysis. The results showed that the environmental practices are primarily linked to waste, water, energy and chemical management, as well as product innovation. In turn, the social practices address the training, education, and well-being of employees and other stakeholders, diversity, equity and inclusion management, and the creation of an inclusive and fair environment, integrating local communities. Thus, in the flow of their sustainability practices, Argentinian B Corporations contribute to SDGs 8, 12, 13, 9, 6, 7, 5, 10, 11, 4, and 17, in line with the SDGs declared by these companies. Our findings contribute to the theoretical knowledge of the B Corp movement and have practical implications by providing inputs to improve the management of B Corporations and to guide public policies encouraging these companies to advance sustainable development dimensions lacking attention.

The main objective of the paper is to provide a thorough analysis of currently used modulation control schemes for single phase bidirectional dual active bridge DC/DC converter. In this article, it will be shown that single phase shift, extended phase shift and Dual phase shift modulation schemes are special cases of triple phase shift (TPS) modulation scheme. The article aims to highlight six TPS switching modes and their complements with the operational constraints. Unlike previous studies that regarded TPS as a complex scheme, this paper simplifies the analysis of each mode and aims to standardize the understanding of TPS modulation in DAB converters. Power equations, range of power transferred and zero voltage switching (ZVS) are derived for all the modes under TPS without assuming fundamental component analysis. Additionally, a generic optimization algorithm is developed to show the advantages of TPS modulation and thus, detailed analysis presented in this paper provides valuable insights for single phase DAB converter designers in identifying a wide range of optimization algorithms to achieve higher efficiency under TPS modulation. This analysis contributes to the advancement of bidirectional DAB converter technology and facilitates its application in various power electronic systems.

Enhanced oil recovery (EOR) refers to the various techniques used to increase the amount of crude oil that can be extracted from an oil field. These techniques are used after the primary and secondary recovery methods have been depleted. There are three main types of EOR: thermal, gas injection, and chemical. EOR techniques can be expensive and complex, but they can help to recover additional oil that would otherwise be left in the reservoir. EOR can also extend the life of an oil field and increase the overall production from a given field. The parameters affecting oil recovery are a major concern in EOR systems, and these parameters need more consideration with the factors affecting them. In this study, the influence of permeability variations on fluid flow in a sandstone reservoir was explored, as well as an up-to-date description of three states of EOR with thorough explanations of the methods utilized and the mechanisms driving their oil recovery application. The difficulties encountered in the use of the different standard EOR Mechanisms were noted, and solutions to these difficulties were proposed. Furthermore, the contemporary trend of adding nanotechnology and its synergistic effects on the stability and efficiency of traditional chemicals for EOR were examined and analysed. Finally, laboratory findings and field initiatives were discussed. The review went into detail about the transport of nanoparticles across reservoirs, as well as the evaluation of EOR, mobility ratio, and fluid displacement efficiency. This review provides thorough information on the uses of improved oil recovery mechanisms for sustainable energy production.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

Background and Objectives: The prevalence of osteoporosis is high, reportedly affecting 200 million people worldwide. A major problem associated with osteoporosis is that femoral fractures cause a decline in general function and loss of independence, greatly reducing patients’ quality of life. Notably, osteoporosis is an asymptomatic chronic metabolic disease, and its detection is thus often delayed. Interestingly, mandibular cortical index (MCI) classification using dental panoramic radiography is reportedly useful for early detection of osteoporosis. However, this visual classification method can lead to differences in diagnosis among surgeons. Therefore, this preliminary study was performed to analyze cone-beam computed tomography (CBCT) data and examine an objective MCI classification using the findings obtained. Materials and Methods: MCI classification (classified as C1, C2, or C3) was performed by three examiners on 70 women (91 sites) aged ≥20 years. The mandibular cortical width of all sites was measured using CBCT images. Results: The results showed that the mandibular cortical width was not particularly correlated with age or number of present teeth, and no significant quantitative differences were found between C1 and C2. However, coronal CBCT images of C2 revealed multiple characteristic bone trabecular structures. Conclusions: These structures may be an important finding affecting the classification of two-dimensional dental panoramic radiography images.

Knowledge of permafrost’s ice and unfrozen water content is critical for predicting the permafrost behavior during ice–water–ice transition. This is especially relevant when ice and permafrost are melting in many regions under the influence of global warming. It is well-known that only a part of the formation's pore water turns into ice at 0 ^oC. After the further lowering the temperature, the water phase transition continues, but at gradually decreasing rates. Thus, the porous space is filled with ice and unfrozen water. The laboratory data show that frozen formations' mechanical, thermal, and rheological properties strongly depend on the moisture content. Hence, porosity and temperature are essential parameters of permafrost. In this paper, it is shown how, and by combining research in three fields: (1) geophysical exploration, (2) numerical modeling, and (3) temperature logging, it is possible to estimate in-situ the porosity of permafrost. To demonstrate the procedure, five examples of numerical modeling (where all input parameters are specified) are given. This investigation is the first attempt to analyze the permafrost’s porosity in situ quantitively.

Fatigue-related subchondral bone injury of the third metacarpal/ metatarsal (McIII/ MtIII) bone is a common cause of wastage and welfare concern in racehorses. Better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. Porosity index (PI) of bone is an indirect measure of osseous pore size and number and is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods even with short echo times fails to generate enough signal to assess bone architecture as the water protons are tightly bound. Ultrashort echo time (UTE) sequences aim to increase the amount of signal detected in the equine McIII/MtIII condyle. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD). BMD and PI are inversely correlated in the equine distal Mc/ MtIII with a mean r value of -0.29. The r value is significantly different between fore- and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of the bone and to evaluate PI in horses with and without clinically relevant stress injury.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

Information is given on the application of the acoustic emission method for studying the kinetics of destruction of protective and decorative coatings of cement concrete. A different nature of the destruction of coatings has been established. When evaluating the nature of the destruction, it was found that for coatings based on polymer-lime and PF-115 paints, after curing, an adhesive type of destruction is characteristic, while for PVAC coatings it is cohesive. Thermal aging mainly changes the nature of destruction of PVAC coatings from cohesive to adhesive. With a decrease in the porosity of the substrate, higher values of the energy released when the coatings are detached from the substrates are observed. It was revealed that during aging as a result of alternating freezing-thawing, the greatest destructive effect is observed in the contact zone of the coating with the substrate. With an increase in the cycles of alternating freezing-thawing, the amount of energy released at the last stage of loading decreases

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Porous ferroelectric lead zirconate-titanate (PZT) films are a promising material for various electronics applications. This study focuses on understanding how structure-directing agent (polyvinylpyrrolidone) can change structure and electrical properties of porous PZT films prepared by chemical solution deposition. The films with various porosity up to ~ 40 vol.% and pore connectivity changing from 3-0 to 3-3 were prepared and studied by capacitance-voltage, dielectric hysteresis, transient current, photocurrent, and local current techniques. We have found that the linear decrease in the material volume in a porous film is not the only factor governing film properties. The key role in changing electrical properties plays the creation of new internal grain boundaries. This research expands the understanding of physical phenomena in porous ferroelectric films and may enable the development of new materials and devices.

The purpose of this work is to compare two fracture prediction models with real-world data. The pure Artificial Neural Network (ANN) model emphasizes regression analysis, while the hybrid model (SVM-ANN) focuses on the combination of regression and classification analysis or Support Vector Machine. The results were subsequently tested against logging data by combining the Machine Learning approach with advanced logging tools. In this context, we used electrical image logs and the dipole acoustic tool which together allowed the distinction of 404 open fractures and 231 closed fractures and, consequently the estimation of fracture porosity. The results are then fed into two machine-learning algorithms. Pure Artificial Neural Networks and hybrid models are used to establish comprehensive results, which are subsequently tested to check the accuracy of the models. The outputs obtained from the two methods demonstrate that the hybridized model has a lower Root Mean Square Error (RMSE) than pure ANN. The results of our approach strongly suggest that incorporating hybridized machine learning algorithms in fracture porosity estimations can contribute to the development of more trustworthy static reservoir models in simulation programs. Finally, the combination of Machine Learning (ML) and well-log analysis do permit reliable estimation of fracture porosity in the Ahnet field in Algeria, where, in many places, advanced logging data is absent and costly.

Fractures are present in hydrocarbon reservoirs of different porosity ranges. Seismic anisotropy has been widely used in fracture characterization and shown to be sensitive to background matrix porosities in theoretical studies. An understanding of the effects of background porosity on seismic anisotropy could improve seismic characterization in different fractured reservoirs. Based on synthetic rocks with controlled fractures, we conducted laboratory experiments to investigate the influence background porosity has on P wave anisotropy and shear wave splitting. A set of rocks containing the same fracture density (0.06) with varying porosities of 15.3%, 22.1%, and 30.8% were constructed. P and S wave velocities were measured at 0.5 MHz as rocks were water saturated. Results show that when porosity increased from 15.3% to 22.1%, P wave anisotropy and shear wave splitting exhibit slight fluctuations. However, when porosity continued to increase to 30.8%, P wave anisotropy declined sharply while shear wave splitting stayed nearly constant. The measured results were compared with predictions from equivalent medium theories. Qualitative agreements were found between theoretical predictions and measured results. In Eshelby-Cheng model, the increase of porosity reduces the fracture-induced perturbation in the fracture normal direction, resulting in a lower P wave anisotropy. In Gurevich(2003) model, the increase of porosity can reduce the compressional stiffness in parallel direction to a larger extent than that in perpendicular direction, thus leading to lower P wave anisotropy.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

This study investigates the efficiency of a biogas-powered cooling system through the utilization of energy and exergy calculations. Biogas, which can be generated and stored in small-scale plants as needed, serves as a viable fuel source for absorption cooling systems. The present research focuses on the biogas consumption of a triple-effect absorption cooling system, specifically designed to supply a fixed cooling load of 100 kW under varying operational conditions. The study highlights the COP (Coefficient of Performance) and ECOP (Exergetic Coefficient of Performance) values of the system, along with the exergy destruction rates of its individual components, at the optimal temperatures of operation. Furthermore, to determine the necessary biogas consumption, the study explores the establishment of dedicated farms for various animal species, ensuring an adequate number of animals for biogas production. The findings reveal a COP of 1.78 and an ECOP of 35.4% at the optimized operating temperatures. The minimum mass flow rate of biogas is determined to be 0.0034 kg/s, facilitating the operation of the boiler with a methane content of 65%. The study concludes that a total of 290 head of cattle is required to generate the annual biogas consumption necessary for the cooling system. Also, number of the cattle is enough to establish 284 biogas plants in Bursa province in Türkiye.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). This technology has been shown to produce SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite plenty of research on SCC of SS316L, little is known about SCC in sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on susceptibility to SCC initiation and crack-branching. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. To better understand the SCC behavior of SS316L, solution-annealed (SA) and cold-drawn (CD) wrought SS316L were tested for comparison. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L. Moreover, sinter-based AM SS316L showed noticeably better resistance to crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy (LOM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and micro-computed tomography (micro-CT)

A new three-dimensional numerical model of a polymer electrolyte fuel cell (PEFC) with a single straight channel has been developed to primarily investigate the important impact of the double-sided microporous layer (MPL) coating on the overall performance of the fuel cell and the distribution of the current and the oxygen concentration within the cathode gas diffusion layers (GDLs). Realistic experimentally estimated interfacial contact resistance values between the gas diffusion layer and each of the bipolar plates and the catalyst layer values were incorporated into the model, and parametric studies were performed. The results showed that the double-sided MPL coating could significantly improve the fuel cell performance by up to 30%. Also, it was shown that the neglect of the contact resistance between the MPL and the catalyst layer could overestimate the fuel cell performance by up to 6%. In addition, the results showed that the fuel cell performance and the distribution of the current and oxygen are more sensitive to the porosity of the MPL facing the bipolar plate than the porosity of the MPL facing the catalyst layer. All the above results are presented and critically discussed in detail.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Porous structured metallic implants are preferable as bone graft substitutes due to their faster tissue integration mediated by bone in-growth and vascularization. The porous scaffolds/ implants should also mimic the graded structure of natural bone to ensure a match of mechanical properties. This article presents a method to design graded porous structured acetabular implant and identifies the suitable parameters for manufacturing the model through additive manufacturing. The design method is based on slice-wise modification to ensure continuity of gradation. Modification of the slices was achieved through the binary image processing route. A geodesic dome type design was adopted for developing the acetabular cup model from the graded porous structure. The model had a solid shell with the target porosity and pore size gradually changing from 65% and 950 µm, respectively, in the inner side to 75% and 650 µm, respectively, towards the periphery. The required dimensions of the unit structures, and the combinations of pore structure and strut diameter to obtain the target porosity and pore size were determined analytically. Suitable process parameters were identified to manufacture the model by Direct Metal Laser Sintering (DMLS) using Ti6Al4V powder after carrying out a detailed experimental study to minimize the variation of surface roughness and warping over different build angles of the strut structures. A dual contour scanning was implemented to simplify the scan strategy. The minimum diameter of struts that could be manufactured using the selected scanning strategy and scanning parameters was found to be 375 µm. Finally, the model was built and from the micro-CT data, the porosities and pore sizes were found to be closely conforming to the designed values. The stiffness of the structures, as found from compression testing, was also found to be well matching with that of human trabecular bone. Further, the structure exhibited compliant bending-dominated behavior under compressive loading.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

In the extended scalar sector of the SMASH (Standard Model - Axion - Seesaw - Higgs portal inflation) framework, we conduct a phenomenological investigation of the observable effects. In a suitable region of the SMASH scalar parameter spaces, we solve the vacuum metastability problem and discuss the one-loop correction to the triple Higgs coupling, $\lambda_{HHH}$. The $\lambda_{HHH}$ and SM Higgs quartic coupling $\lambda_H$ corrections are found to be proportional to the threshold correction. A large $\lambda_{HHH}$ correction ($\gtrsim 5 \%$) implies vacuum instability in the model and thus limits the general class of theories that use threshold correction. We performed a full two-loop renormalization group analysis of the SMASH model. The SMASH framework has also been used to estimate the evolution of lepton asymmetry in the universe.

The use of additive manufacturing in fabricating composite components has been gaining traction in the past decade. However, some issues with mechanical perfor-mance still need to be resolved. The issue of material porosity remains a pertinent one that needs more understanding to be able to determine viable solutions. Different re-searchers have examined the subject of porosity issues in AM-fabricated CFRP compo-sites. However, more research to quantitatively determine the effects of fabrication temperatures at the micro-scale is still needed. This study employed micro CT scan analysis to quantitatively compare the effects of fabrication temperatures at 230°C, 250°C, 270°C, and 290°C for CF-PA and CF-ABS composites. This followed an SEM evaluation which was used to determine the effects of the temperatures on interlayer and intralayer porosity generation. The porosity volume was related to the mechanical properties results in which it was determined how deposition temperatures affect the porosity volumes. It was also determined that semicrystalline composites are generally more affected by fabrication temperatures than amorphous composites, with the rela-tionship between porosity and mechanical properties also established. The overall po-rosity volume from the interlayer and intralayer voids was also determined, with the interlayer voids found to play a more determinant role in influencing the mechanical properties.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

The research aims to improve some of the physical and hydro-physical properties of some Vertisols in the southern region (part of the eastern Houran Plateau) in Sweda Governorate at the south of Syria. Using different quantities of volcanic ash, soil samples were collected from the Al-Thahallah village from a depth of (0-30) cm, The experiment was designed according to the complete random design with one factor that represents the ash quantity (1.25, 2.5, 5) %, with three replicates for each treatment in addition to the control treatment a0. The experiment was carried out within the plastic pots during agricultural season 2018/2019, in which the wheat of the Sham variety 3 were cultivated as a cover plant. The results showed that the addition of volcanic ash at the quantity of 5% led to a significant increase in the infiltration rate by (328.60) %,%, where the filtration rate increased from 0.42 cm/hr -1 to 1.80 cm.h-1, as well as for each of the air porosity by (89) % and the volume of infiltrate water by (40) %, compared with the control. The above-mentioned addition also resulted in a decrease in both dry bulk density, total soil porosity and volumetric swelling coefficient by (18.60, 5.80, 314) % Respectively, compared to the control. The addition also contributed to the reduce in the weighted moisture content when saturation and the field capacity, at the level of significance of 5%. The research recommends adding volcanic ash to the soil at a quantity of 5%, and adding enhancements with volcanic ash at various levels such as organic waste.

The reported study was devoted to the investigation of viscoelastic behavior for solid and porous ultra-high-molecular-weight polyethylene (UHMWPE) under compression. The obtained experimental stress curves were interpreted using a two-term Prony series to represent the superposition of two coexisting activation processes corresponding to long molecular (~160 s) and short structural (~20 s) time scales, respectively, leading to good statistical correlation with the observations. In the case of porous polymer, the internal strain redistribution during relaxation was quantified using Digital Image Correlation (DIC) analysis. The strongly inhomogeneous deformation of the porous polymer was found not to affect the relaxation times. In order to generalize the results to three dimensions, X-ray tomography was used to examine the porous structure at the macro- and micro-scale levels. DIC analysis revealed positive correlation between the applied force and relative density. The apparent stiffness variation for UHMWPE foams with mixed open and closed cells was described using a newly proposed three-term expression. Furthermore, the in situ tensile loading and X-ray scattering study was applied for isotropic solid UHMWPE specimens to investigate their parameters of internal structure during orientation and stress relaxation process at another mode.

The present study explores the effect of using two porous deflectors on the performance of the Savonius wind turbine compared to only one porous deflector. The numerical simulation is performed to solve the unsteady Navier-Stokes equations using the SST k-

Technological advancements and innovations have profoundly changed the lives of people giving rise to smart environments, cities, and societies. As homes are the building block of cities and societies, smart homes are critical to establishing smart living and are expected to play a key role in enabling smart cities and societies. The current academic literature and commercial advancements on smart homes have mainly focused on developing and providing smart functions for homes to provide security management and facilitate the residents in their various activities such as ambiance management. Homes are much more than physical structures, buildings, appliances, operational machines, and systems. Homes are composed of families and are inherently complex phenomena underlined by humans and their relationships with each other, subject to individual, intragroup, intergroup, and intercommunity goals. There is a clear need to understand, define, consolidate existing research, and actualize the overarching roles of smart homes, the roles of smart homes that would serve the needs of future smart cities and societies. This paper introduces our data-driven parameter discovery methodology and uses it to provide, for the first time, an extensive, rather fairly comprehensive, analysis of the families and homes landscape seen through the eyes of academics and the public using over a hundred thousand research papers and nearly a million tweets. We develop a methodology using deep learning, natural language processing (NLP), and big data analytics methods and apply it to automatically discover parameters that capture a comprehensive knowledge and design space of smart families and homes comprising social, political, economic, environmental, and other dimensions. The 66 discovered parameters and the knowledge space comprising 100s of dimensions are explained by reviewing and referencing over 300 articles from the academic literature and tweets. The knowledge and parameters discovered in this paper can be used to develop a holistic understanding of matters related to families and homes facilitating the development of better, community-specific, policies, technologies, solutions, and industries for families and homes, leading to strengthening families and homes, and in turn, empowering sustainable societies across the globe.

The main functions of the automated systems rely on the advanced sensors for detection and perception of the environment around the vehicle. Radars and cameras are commonly utilized to detect the potential obstacles and vehicles ahead on the road. Nevertheless, cameras can generate spurious detections in the extreme weather conditions such as fog, rain, dust, snow, dark, and heavy sunlight in the sky. Due to limitations in vertical field view of the radars, single radars are not reliable to detect the height of the targets precisely. In this paper, a triple radar arrangement (long-range, medium-range, and short-range radars) based on sensor fusion technique is proposed to detect objects with different size in level 2 Advanced Driver-Assistance (ADAS) system. The typical objects including truck, pedestrians, and animals are detected in different scenarios. The developed model considered ISO 26262 and ISO/PAS 21448 to reasonably address insufficient robustness and inability of the sensors. The models of sensor and level 2 ADAS systems are developed using MATLAB toolbox and Simulink. Sensor detection performance is determined by running simulations with triple radar setup. Obtained results demonstrate that the proposed approach generates accurate detections of targets in all tested scenarios.

Up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse despite the improvement achieved by the introduction of HER2-targeted therapy. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown an improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6) as they are downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies play a key role in cell cycle and proliferation. Different trials have explored these strategies with encouraging results, but definitive results are needed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents have been investigated in this setting, with promising but controversial results obtained to date.

Triple X syndrome (TXS, also known as trisomy X or 47,XXX) has been associated with impaired overall neurocognitive functioning in children and relatively young adults. However, neurocognitive functioning in adults with TXS is poorly understood. The aim of this study was, therefore, to examine cognitive functioning in adults with TXS. Methods: In this cross-sectional study, data were collected from 34 adult women with TXS (mean age = 32.9; SD = 13.1) and 31 controls (mean age = 34.9; SD = 13.7). General intellectual functioning, semantic/verbal memory, visual/episodic memory, psychomotor speed, and attention and executive functioning were then compared between these two groups. Results: We found that general intellectual functioning was significantly lower in the TXS group compared to the control group. In addition, women with TXS had more attention problems and lower psychomotor speed, particularly motor processing speed. When the analyses were adjusted for IQ, the strength of these associations decreased. The women in the TXS group also scored significantly lower at free recall in the verbal memory test, but not in immediate or delayed recognition. Finally, visual/episodic memory and executive functioning did not differ significantly between groups. Conclusions: Our analysis revealed that women with TXS score lower in general intellectual functioning and have impairments in motor processing speed and attention compared to controls, but do not differ with respect to executive functioning. These results offer new insights for improving the support of adults with TXS both at school and in the workplace.

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evalu-ated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cy-tokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Treatment response and prognosis imformation of patients and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was sig-nificantly expressed by TNBC cell lines than luminal cell lines (log2 fold change: 5.31, p <0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohisto-chemistry demonstrated IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p<0.05) and a favorable survival compared to IL-33 low group (OR 6.48, p<0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in IL-33 high group com-pared to the low IL-33 low group (hazard ratio (HR) 2.1, p=0.02), and IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p=0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

Calcium dihydrogen phosphate monohydrate [Ca(H2PO4)2·H2O] (a fertilizer) was successfully synthesized by the recrystallization process by using a prepared triple superphosphate (TSP) that derived from oyster shell waste as starting material. This bio-green, eco-friendly process to produce an important fertilizer can promote a sustainable society. The shell-waste-derived TSP was dissolved in distilled water and kept at 30, 50, and 80 °C. Non-soluble powder and TSP solution were obtained. The TSP solution fraction were then dried and the recrystallized products (RCP30, RCP50, and RCP80) were obtained and confirmed as Ca(H2PO4)2·H2O. Whereas the non-soluble products (NSP30, NSP50, and NSP80) were observed as calcium hydrogen phosphate dihydrate (CaHPO4·2H2O). The recrystallized yields of RCP30, RCP50, and RCP80 were found to be 51.0%, 49.6%, and 46.3%, whereas the soluble percentages were 98.72%, 99.16%, and 96.63%, respectively. RCP30 shows different morphological plate sizes, while RCP50 and RCP80 present the coagulate crystal plates. X-ray diffractograms confirm the formation of both the NSP and RCP. The infrared adsorption spectra confirmed the vibrational characteristics of HPO42‒, H2PO4‒ and H2O existed in CaHPO4·2H2O and Ca(H2PO4)2·H2O. Three thermal dehydration steps of Ca(H2PO4)2·H2O (physisorbed water, polycondensation, and re-polycondensation) were observed. Ca(H2PO4)2 and CaH2P2O7 are the thermodecomposed products from the first and second steps, whereas the final product is CaP2O6.

Improved oil recovery from tight carbonate formations may provide the world with a major source of lower-rate power over several decades. Here we provide an overview of the Arab D formation in the largest oil field on earth, the Ghawar. We investigate the occurrence of microporosity of different origins and sizes using scanning electron microscopy (SEM) and pore casting techniques. Then, we present a robust calculation of the probability of invasion and oil saturation distribution in the nested micropores using mercury injection capillary pressure data available in the literature. We show that large portions of the micropores in Arab D formation would have been bypassed during primary drainage unless the invading crude oil ganglia were sufficiently long. Considering the asphaltenic nature of oil in the Ghawar, we expect the invaded portions of the pores to turn mixed-wet, thus becoming inaccessible to waterflooding until further measures are taken to modify the system’s chemistry.

An explanation of aerodynamic lift still is under controversial discussion as can be seen, for example, in a recent published article in Scientific American [1]. In contrast to an approach via integral conservation laws we here review an approach via the classical Kutta-Condition and its relation to boundary layer theory. Thereby we summarize known results for viscous correction to the lift coefficient for thin aerodynamic profiles and try to remember the work on triple-deck or higher order Boundary Layer theory, its connection to interactive boundary layer theory, viscous/inviscid coupling as implemented to well-known engineering code Xfoil. Finally we compare its findings to simple 2D numerical solution of full Navier Stokes equations (CFD)models. As a conclusion, a clearer definition of terms like understanding and explanation applied to the phenomenon of aerodynamic lift will be given.

Universities have increasingly incorporated a third mission into their strategic planning. In addition to teaching and research, they have emphasised the training of entrepreneurs. However, there is still a lot of work to be done, as this process is facing resistance. The Entrepreneurial University covers all disciplines, including faculties of education. However, it has been shown that entrepreneurship tends to be more related to the faculties of economics and engineering, with a lesser presence in the faculties of education for various reasons: they consider entrepreneurship to be alien to their teaching role, there is a lack of entrepreneurial culture, and the objective of the Entrepreneurial University is unknown. The aim of this study is to analyse the level of entrepreneurship in Spanish faculties and schools of education. Forty deans and heads of education faculties in Spain took part in the survey. The results indicated a sufficient level of entrepreneurship; the dimensions related to active methodologies, and mission and strategy were the most developed, whereas entrepreneurship funding and entrepreneurship training for faculty employees were the least developed areas. Some deans noted that entrepreneurship was alien to their professional performance, although courses and good practices for the development of entrepreneurial initiative are gradually being implemented.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Chemical flooding is one of the effective methods to recover large volumes of oil from sandstone formations after primary depletion. However, silica dissolution often occurs during Alkaline-Surfactant-Polymer (ASP) flooding, affecting the petro-physical properties of the formation. To address this issue, samples from Berea sandstone formations were treated with various brine solutions, through static tube tests and core flooding experiments. Analytical tests such as DR/2800 spectrophotometer and scanning electron microscope were used to evaluate the silica solubility and the alteration in mineral content. The results indicated that the silicate contents decreased after the saturation due to silica solubility in the solution. Increasing brine salinity to 40,000ppm and introducing Magnesium and Calcium ions to the solution, reduces the silicate contents by 5.03 % and 7.32 %. Moreover, saturating the samples with ASP solution, further reduced the silicate contents by 14.86 %. This reduction is associated with a relative increase in silica solubility and pH of the solution. Silica dissolution affects the pore microstructure, which resulted in increasing the porosity and pore volume after the core flooding. The injection of the ASP solution increased the porosity by 5.83%, thus the pore volume increased from 17.72 to 18.76cc. This is associated with the high silica solubility and the increase of solution pH in the ASP solution. The permeability of the samples generally reduced after the core flooding, due to the silica solubility. However, injecting the ASP solution, resulted in a major reduction of the permeability by more than 75%. These changes in the petro-physical properties can lead to severe formation damage, and affect hydrocarbon production. This study assists in understanding the impact of silica dissolution during ASP treatment and addresses the factors involved. Efficient utilization of chemical flooding can help mitigating silicate scaling within the formation, and extend field productivity.

Mereotopology is a concept rooted in analytical philosophy. The phase-field concept is based on mathematical physics and finds applications in materials engineering. The two concepts seem to be disjoint at a first glance. While mereotopology qualitatively describes static relations between things like x isConnected y (topology) or x isPartOf y (mereology) by first order logic and Boolean algebra, the phase-field concept describes the geometric shape of things and its dynamic evolution by drawing on a scalar field. The geometric shape of any thing is defined by its boundaries to one or more neighboring things. The notion and description of boundaries thus provides a bridge between mereotopology and the phase-field concept. The present article aims to relate phase-field expressions describing boundaries and especially triple junctions to their Boolean counterparts in mereotopology and contact algebra. An introductory overview on mereotopology is followed by an introduction to the phase-field concept already indicating first relations to mereo- topology. Mereotopological axioms and definitions are then discussed in detail from a phase-field perspective. A dedicated section introduces and discusses further notions of the isConnected relation emerging from the phase-field perspective like isSpatiallyConnected, isTemporallyConnected, isPhysicallyConnected, isPathConnected and wasConnected. Such relations introduce dynamics and thus physics into mereotopology as transitions from isDisconnected to isPartOf can be described.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

This research was specifically aimed at assessing the influence of sulfur in triple-super phosphate (TSP) on wheat yield. From the results, wheat showed response to sulfur (S) from gypsum (in 67%); and nitrogen (N) from urea in about 100% (of 24 sites). Based on this N was found to be the most limiting element to wheat production followed by sulfur, and then by phosphorus. TSP is tested to contain agronomically up to 2-6% by weight of S. However, wheat didn’t show response to S impurity supplied in the form of TSP. Though, not statistically significant, it is observed that there have always been yield increments by certain percent due to S from TSP in 8 out of 10 target sites, which is depicted in the increasing trends of yield response curves. From this it is learnt that, the benefits of the accidental/incidental application of such high analysis fertilizers can be many-folds in the quality attributes of wheat, if the soils of such investigation at the same time would contain significant amount of organic matter (OM). Indeed, such analysis would be vital in varietal specific nutrient requirement studies in precision-farming and/or in categorizing soils into fertility gradients and fertilizer recommendation domains.

Our investigations show that electrochemical corrosion of copper is faster than electrochemical corrosion of aluminium at temperatures below 100oC. Literature data analysis shows that the Al atoms diffuse faster than the Cu atoms at temperatures higher than 475oC, Al rich intermetallic compounds (IMCs) are formed faster in the Cu-Al system, and the Kirkendall plane shifts toward Al side. Electrochemical corrosion occurs due to electric current and due to diffusion. An electronic devise working time, for example, depends on initial copper cover thickness on aluminium wire, connected to the electronic devise, temperature, and volume and dislocation pipe diffusion coefficients, so copper, iron, and aluminium electrochemical corrosion rates are investigated experimentally at room temperature and at temperature 100oC. Intrinsic diffusivities ratios of copper and aluminium at different temperatures and diffusion activation energies in the Cu-Al system are calculated by proposed here methods using literature experimental data. Dislocation pipe and volume diffusion activation energies of pure iron are calculated separately by earlier proposed method using literature experimental data. Aluminium dissolved into NaCl solution as the Al3+ ions at room temperature and at temperature 100oC, iron dissolved into NaCl solution as the Fe2+ (not Fe3+) ions at room temperature and at temperature 100oC, copper dissolved into NaCl solution as the Cu+ ions at room temperature and as the Cu+ and the Cu2+ ions at temperature 100oC. It is founded experimentally that copper corrosion is higher than aluminium corrosion, and ratio of electrochemical corrosion rates, kCu/kAl>1, decreases with temperature increasing, although iron electrochemical corrosion rate doesn’t depend on temperature below 100oC. It is obvious, because melting point of iron is more higher then melting point of copper or aluminium. It is calculated that copper electrochemical corrosion rate is approximately equal to aluminium electrochemical corrosion at temperature about 300oC, so copper can dissolve into NaCl solution mostly as the Cu2+ ions at temperature about 300oC. Ratio of intrinsic diffusivities, DCu/DAl <1, increases with temperature increasing, and intrinsic diffusivity of aluminium could be approximately equal to intrinsic diffusivity of copper at temperature about 460oC.

Sulfur dioxide (SO2) reduction remains an area of global necessity further enhanced by the current international focus on pandemic diseases mitigation, elimination of air pollution, and promotion of renewable green energy. The dynamics of chemical bond-strength breaking and reformation in the transition state (TS) is a fundamental process in the reduction of SO2 by CO. Density Functional Theory (DFT) has been used to determine optimal TS reaction pathway via a novel triple-hybrid catalyst utilizing doubly-charged negative atomic V, Mn, and Au. The triple-hybrid catalyst is furthermore tailored to the subsequent minimization of each individual step of the 3-Step SO2 reduction by CO chemical reaction. Each optimized step 1, 2, and 3 is minimized with doubly-charged V, Mn, and Au, respectively, with TS barrier reductions ranging from 1.18 eV to 0.002 eV. Super-benzene, armchair (6, 6) single wall carbon nanotube, and fullerene TS reaction pathways have also been calculated to compare the nanoscale catalytic effectiveness with that of the atomic scale transition metals.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

This work describes a method to carry out 2-D inversion of gravity data in terms of porosity and matrix density distribution using previous DC resistivity inversion results to constraint the fractional pore-water content in the rocks. The inversion is carried out using a controlled random search (CRS) algorithm for global optimization. The method was tested on synthetic data generated from a model representing a graben, and the results show that it can estimate accurate values of contrast-density and porosity. The method was also applied to gravity and dc experimental data collected in NE Portugal, showing results that agree quite well with the known geological information.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

Time-domain spectroscopy (TDS) in the Terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data itself without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

The organic solar cells (OSCs) have drawn attention in the past decade due to its cynosure in industrial manufacturing because of its promising properties such as low weight, highly flexible and low cost production. However, low η restricts the utilization of OSCs for potential application such as low cost energy harvesting devices. In this paper, OSCs structure based on triple junction tandem scheme is reported with three different absorber materials with the objective to enhance the absorption of photons which in turn improves the η, as well as its correlating performance parameters. The investigated structure gives the higher value of η = 14.33% with Jsc=16.87 (mA/m2), Voc=1.0 (V), and FF=84.97% by utilizing a stack of three different absorber layers with different band energies. The proposed structure is tested under 1.5 (AM) with 1 sun (W/m2). The impact of top, middle and bottom sub cells thickness on η is analyzed with a terse to find the optimum thickness for three sub cells to extract high η. The optimized structure is then tested with different electrode combination and the highest η is recorded with FTO/Ag. Moreover, the influence of upsurge temperature is also demonstrated on the proposed structure and observed that the upsurge temperature has greatly affected the electrical parameters of the device and η decreases from 14.33% to 11.40% when the temperature of the device rises from 300-400 K.

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

For the Altai mountainous region, especially the arid south-eastern part, the history of glacier fluctuations in Pleistocene and Holocene is still poorly known. The key plots were located in the Kargy valley (2288-2387 m a. s. l.) that is not currently affected by glaciations. The relative dating method was applied to define Pleistocene moraine chronology and configuration in the Kargy valley. Taking into account that relative dating methods are primarily based on weathering pat-terns, the mineralogy, porosity, and specificity of biological colonization as an agent of weath-ering were obtained for the moraine samples. Three moraine groups of different age (presumably MIS 6, MIS 4, and MIS 2) were identifies based on detailed investigation of morphological features. The moraine age was indirectly confirmed by the mesostructure of the moraine samples repre-sented by fine-grained shale: the older sample is characterized by a more developed fractal sur-face than the younger one. The growth of biota (crustose lichen and micromycetes) leads to initial biomass accumulation and subsequent rock disintegration. The accumulation of autochthonous fine earth on the rock surface was considered the initial stage of fine earth formation affected by biota.

Shipbreaking research has not been in the forefront until the last decade in which environmental and occupational hazards have been highlighted while economic sustainability and contextual conditions were not equally considered. The adoption of a triple bottom line approach across core business issues (environmental impacts, workplace safety ) as well as peripheral stakeholders expectation (environmental sustainability focus) has been retarded due to the less attention on the latter. Based on the findings of the 128 review papers, the study suggests that organizational learning and economic sustainability needs to prioritize through the formation of strange alliance among the stakeholders. The study argues that the dialogue and discussion on the peripheral stakeholders (NGOs, yard managers, national and international policy organizations) would lead to a more sustainable shipbreaking industry in the south Asian regions.

In deep geological analysis of data, these are input data that are few and include a small set of data. In a small set of case data, it is necessary to obtain reliable data of individual geological variables from this type of data. The paper analyzes the possibility of applying the bootstrap method on variables that are important in the exploration and production of hydrocarbons. The variables analyzed were the following: porosity and total costs of disposal formation water. The case study was made on the data of reservoir "K", field "B" located in the western part of the Sava Depression. The analysis of the results showed the possibility of applying the bootstrap method in the analysis of deep geological data with the application of three different sizes of resampling dataset.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

The study presents a mathematical modeling for supporting the premise that our body is composed of blockchain systems. A cell population is considered a space with peer-to-peer communication networks for applying blockchain protocol. Transaction is defined as gene expression that constantly occurs for protein synthesis in each cell. The transaction process proceeds according to the blockchain protocol with sharing and recording the data on the blockchain ledger. The premise comes from the clues of the previous research such that the cell population is a complex structured network system having cell-to-cell connections. Although individual cells exhibit stochastic nonlinear dynamic behavior, cell population shows consensus behavior that reaches to ensemble through interaction among cells. It is inferred that gene expression is not regulated by the corresponding cell only nor determined by external intelligence such as the brain. This is achieved through a consensus through stochastic interactions between cells over the whole cell population. These findings imply that mathematical blockchain modeling is a suitable for gene expression process. The original contribution of the study is a methodology for applying mathematically the blockchain protocol to the real biological gene expression process. In other words, the DNA sequence is converted into a numeral bit sequence that makes it possible to implement the blockchain protocol. A new DNA sequence scheme is proposed with adding methylated cytosine and adenine as the 5th and 6th bases for including epigenetic information which has profound effect on gene expression and regulation. The methodology was applied to the real biological synthesis process of protein samples. The protein is composed of amino acids that are encoded by triplet codons of 216 kinds with 6 base RNA sequence. The gene expression information is traced backward from a synthesized protein sample, amino acids of codons, RNA transcript up to DNA sequence. One of the results is a numeric value in the form of a bit sequence with which mathematical blockchain modeling is applicable. The cryptographic authentication and the consensus process are mathematically proven to work properly by the blockchain protocol. It implies that the same protein is synthesized, but with different epigenetic data, then protein's latent material properties will certainly be different. Although the result has not been justified by the biologic experiment yet, it is sure that the biological hidden algorithm inside DNA sequence will be revealed by the binary bit-logic with physical on/off states which is mathematically proven. The research will greatly contribute to disease treatment and medicine development as well as epigenetics in the future.

The deep Cretaceous tight sandstone in Kuqa Depression of Tarim foreland basin is an ultra-low porosity and ultra-deep gas-bearing reservoir, which is characterized by small pores, fine throats, and poor connectivity. The wireline logging responses are so complex, and especially, it is difficult to identify fluid types from resistivity logs. Based on acoustic, density, and neutron logs response differences in gas and water layers, effective fluid sensitivity factors are constructed for gas layer identification. From conventional logs, acoustic-neutron porosity difference, density-neutron porosity difference, and triple-porosity ratio are all sensitive parameters to the gas layer. From the NMR logging response mechanism, the density and NMR porosity difference, and T2 geometric mean of the movable fluid are also two sensitive parameters to the gas layer. Based on these parameters, a series of fluid typing charts are constructed and their adaptabilities are analyzed and compared. By contrast, NMR log interpretation is better, and triple-porosity comprehensive method from conventional logs is also effective when NMR logging is not available. Finally, the comprehensive fluid typing strategy by combining some methods for ultra-low porosity tight sandstone is summarized and optimized. This study is another alternative for fluid identification using non-electrical logs.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients, compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and this is associated with cancer metastasis to the bone and poor prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression that may be linked to the pathogenic behavior of fibroblast-like synoviocytes, cartilage destruction, and bone erosion.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.