The Covid-19 pandemic is a tragedy for those who have been hard hit worldwide. At the same time, it is also a test of concepts and practices of what good care is and requires, and how quality of care can be accounted for. In this paper, we present our Care-Ethical Model of Quality (CEMQ) and apply it to the case of residential care for older people in the Netherlands during the Covid-19 pandemic. Instead of thinking about care in healthcare and social welfare as a set of separate care acts, we think about care as a complex practice of relational caring, crossed by other practices. Instead of thinking about professional caregivers as functionaries obeying external rules, we think about them as practically wise professionals. Instead of thinking about developing external quality criteria and systems, we think about cultivating (self-)reflective quality awareness. Instead of abstracting from societal forces that make care possible but also limit it, we acknowledge them and find ways to deal with them. Based on these critical insights, the CEMQ model can be helpful to describe, interrogate, evaluate, and improve existing care practices. It has four entries: (i) the care receiver considered from their humanness, (ii) the caregiver considered from their solicitude, (iii) the care facility considered from its habitability and (iv) the societal, institutional and scholarly context considered from the perspective of the good life, justice and decency. The crux is enabling all these different entries with all their different aspects to be taken into account. In Corona times this turns out to be more crucial than ever.

The aim of this paper is to analyze the real impact of ICT skill mismatch on SME’s sustainable competitiveness in presence of minimum wage guaranteed. As part of public policies – the minimum wage need to maintain a balance between increasing employment and not being a burden for the companies, leading them to bankruptcies, especially in times of disruptive change in which economy have to be more resilient. The rapid progress in information and communication technologies has dramatically redefined the rising unemployment as a result of skills mismatch. This paper aims to understand, on one side if, there is a match between the supply demand of ICT skills and how increasingly powerful digital technologies affect skills, jobs, and the demand for human labour. On the other, if increasing productivity and a fair minimum wage could be an integrated approach in stimulating SME’s in increasing sustainable competitiveness.

The strategy of any organization is based on the growth of its customer base, and one of 5 its principles is that selling a product to an existing customer is much more profitable than acquiring 6 a new customer. However, this approach has several opportunities for improvement, since it usu- 7 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 8 customer experience and recovery, to give an effective response for that moment, since the customer 9 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 10 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 11 riods or months, is performed. This thesis work challenges the way to face this problem, and pro- 12 poses the development of a complete solution, which does not focus exclusively on the prediction 13 of churn, as is usually done in the state of the art research, but to intervene in different interactions 14 that can be carried out with customers. The above focused not only to prevent customer churn, but 15 to generate an added value of continuous improvement in sales processes, increase customer pene- 16 tration, leading to an improvement in customer experience and consequently, an increase in cus- 17 tomer loyalty.

The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.

This contribution is an attempt to reconstruct the favorable atmosphere that prevailed in Lau-sanne in 1986-87 and provided the backdrop of our invention of two-dimensional ion cyclotron resonance mass spectroscopy (2D ICR-MS). To avoid a self-centered histoire d’ancien combattant, we shall try to emphasize the context, the contributions of key players within our nascent research group at UNIL and the established group of Tino Gäumann at EPFL, the role of external speakers, and the open atmosphere that was not yet polluted by bibliometrics, obsessive concern with im-pact factors, and top-down management of research. We shall also explain why the idea of 2D ICR-MS has been ignored for many years and still has a limited impact: different scientific cul-tures in the ICR and NMR communities, different concerns with fundamental vs. applied research, different status of theory and numerical simulations, different levels of commitment of instrument manufacturers, not to mention many theoretical problems that appear to be at least as challenging in ICR as in NMR.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Validation of satellite sea surface salinity (SSS) products is typically based on comparisons with in-situ measurements at a few meters depth, that are mostly done at a single location and time. The difference in term of spatio-temporal resolution between the in-situ near-surface salinity and the two-dimensional satellite SSS results in a sampling mismatch uncertainty. The Climate Change Initiative (CCI) project has merged SSS from three satellite missions. Using an optimal interpolation, weekly and monthly SSS and their uncertainties are estimated at a 50 km spatial resolution over the global ocean. Over the 2016-2018 period the mean uncertainty on weekly CCI SSS is 0.13, whereas the standard deviation of weekly CCI minus in-situ Argo salinities is 0.24. Using high resolution SSS simulations, we estimate the expected uncertainty due to the CCI versus Argo sampling mismatch. Most of the largest spatial variability of the satellite minus Argo salinity are observed in regions with large mismatch. A quantitative validation is performed by considering the statistical distribution of the CCI minus Argo salinity normalized by the sampling and retrieval uncertainties. This quantity should follow a Gaussian distribution with a standard deviation of 1, if all uncertainty contributions are properly considered. We find that 1) the sampling mismatch can explain most of the observed differences between Argo and CCI data, especially for monthly products and in dynamical regions (river plumes, fronts), 2) overall, the uncertainties are well estimated in CCI version 3, much better compared to CCI version 2. There are a few dynamical regions where discrepancies remain, and where the satellite SSS, their associated uncertainties and the sampling mismatch estimates should be further validated.

The strategy of any organization is based on the growth of its customer base, and one of 5 its principles is that selling a product to an existing customer is much more profitable than acquiring 6 a new customer. However, this approach has several opportunities for improvement, since it usu- 7 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 8 customer experience and recovery, to give an effective response for that moment, since the customer 9 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 10 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 11 riods or months, is performed. This paper challenges the way to face this problem, and proposes 12 the development of a complete solution, which does not focus exclusively on the prediction of 13 churn, as is usually done in the state of the art research, but to intervene in different interactions 14 that can be carried out with customers. The above focused not only to prevent customer churn, but 15 to generate an added value of continuous improvement in sales processes, increase customer pene- 16 tration, leading to an improvement in customer experience and consequently, an increase in cus- 17 tomer loyalty.

Partial shading on solar photovoltaic (PV) arrays is a prevalent problem in photovoltaic systems that impair the performance of PV modules and is responsible for reduced power output as compared to that in standard irradiance conditions thereby resulting in the appearance of multiple maximas on panel output power characteristics. These maxims contribute to mismatch power losses among PV modules. The mismatch losses depend on shading characteristics together with different interconnected configuration schemes of PV modules. The research presents a comparative analysis of partial shading effects on a 4 x4 PV array system connected in series(S), parallel (P), serries-parallel (SP),total-cross-tied (TCT),central-cross-tied(CCT),bridge-linked(BL),bridge-linked total cross-tied (BLTCT) ,honey-comb(HC), honey-comb total-cross-tied (HCTCT) and ladder (LD) configurations using MATLAB/Simulink. The PV module SPR-X20-250-BLK was used for modeling and simulation analysis. Each module is comprised of 72 number of PV cells and a combination of 16 PV modules was employed for the contextual analysis. Accurate mathematical modeling for the HCTCT configuration under partial shading conditions (PSCs) is provided for the first time and is verified from the simulation. The different configuration schemes were investigated under short-narrow,short-wide,long-narrow,long-wide, diagonal, entire row distribution, and entire column distribution partial shading condition patterns with mathematical implementation and simulation of passing clouds. The performance of array configurations is compared in terms of maximum power generated ), mismatch power loss (∆), relative power loss ) and the fill factor (FF). It was inferred that on average, TCT configuration yielded maximum power generation under all shading patterns among all PV modules interconnection configurations with minimum mismatch power losses followed by hybrid and conventional PV array configurations respectively.

Hyper spectral imaging (HSI) is a technique that is used to obtain the spectrum for each pixel in the image. It helps in finding objects and identifying materials etc. Such an identification is very difficult using other imaging techniques. It allows the researchers to investigate the documents without any physical contact. Nowadays detection of unequal Ink mismatch based on HSI has shown vast improvement in distinguishing the inks. Detection of unequal Ink mismatch is an unbalanced clustering problem. This paper used K-means Clustering for ink mismatch detection. K-means Clustering find same subgroups in the data based on Euclidean distance. This paper demonstrates performance in unequal Ink mismatch based on HSI.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

The endoplasmic reticulum (ER) is the major site of membrane biogenesis in most eukaryotic cells. As the entry point to the secretory pathway, it handles more than 10.000 different secretory and membrane proteins. The membrane insertion of proteins, their folding, and ER exit are affected by the lipid composition of the ER membrane and its collective membrane stiffness. The ER is also a hotspot of lipid metabolism for membrane lipids including sterols, glycerophospholipids, ceramides and neural storage lipids. The unfolded protein response (UPR) bears an evolutionary conserved, dual sensitivity to both protein folding-imbalances in the ER lumen and aberrant compositions of the ER membrane, referred to as lipid bilayer stress (LBS). Through transcriptional and non-transcriptional mechanisms, the UPR upregulates the protein folding capacity of the ER and balances the production of proteins and lipids to maintain a functional secretory pathway. In this review, we discuss how UPR transducers sense unfolded proteins and LBS with a particular focus on their role as guardians of the secretory pathway.

In document forensic, Ink mismatch relays very important information about forgeries in this way we can find out the authenticity of documents. Finding out and distinguishing these unique inks from the multispectral document is very challenging task. In this paper we proposed the method to identify the inks using clustering. We used K-Mean clustering instead of widely known Fuzzy C-Means Clustering (FCM) and successfully identity the number of inks. For the purpose of optimizing and improving our results we used two optimization techniques such as Elbow and silhouette optimization techniques.

This paper presents work done as part of a transformation effort towards a greener and more sustainable Aluminium manufacturing plant. The effort includes reducing the carbon footprint by minimising waste and increasing operational efficiency. The contribution of this work includes the reduction of waste through the implementation of autonomous, real-time quality measurement and classification at an Aluminium casthouse. Data is collected from the MV20/20 which uses ultrasound pulses to detect molten Aluminium inclusions, which degrade the quality of the metal and cause subsequent metal waste. The sensor measures cleanliness, inclusion counts and distributions from 20 - 160 microns. The contribution of this work is in the development of business analytics to implement condition-based monitoring through anomaly detection, and to classify inclusion types for samples that failed. For anomaly detection, multivariate K-Means and DBSCAN algorithms are compared as they have been proven to work in a wide range of datasets. For classification, a two-stage classifier is implemented. The first stage classifies the success or failure of the sample, while the second stage classifies the inclusion responsible for the failed sample. The algorithms considered include logistic regression, support vector machine, multi-layer perceptron and radial basis function network. The multi-layer perceptron offers the best performance using k-fold cross-validation, and is further tuned using grid search to explore the possibility of an even better performance. The results reveal that the model has achieved a global maximum in performance. Recommendations include the integration of additional sensor systems and the improvements in quality assurance practices.

Metallic substrates and polymer adhesive in composite-metal joints have a relatively large coefficient of thermal expansion (CTE) mismatch, which is a barrier in the growing market of electric vehicles and their battery structures. It is reported that adding carbon nanotubes (CNTs) to the adhesive reduces the CTE of the CNT enhanced polymer adhesive multi-material system, therefore when used in adhesively bonded joints it would, theoretically, result in low CTE mismatch in the joint system. The current article presents the influence of two specific mass ratios of CNTs on the CTE of the enhanced polymer. It was observed that the addition of 1.0 wt% and 2.68 wt% of multi-walled CNTs (MWCNTs) decreased the CTE of the polymer adhesive from 7.5e-5 1/C (pristine level) to 5.87e-5 1/C and 4.43e-5 1/C, respectively by 22% and 41% reduction. The reduction in the CTE was predicted, theoretically, which showed that CTE should have been reduced to 3.6e-5 1/C (52% reduction) and 1.4e-5 1/C (81% reduction). This may be due to the fact that, Raman spectroscopy of the MWCNTs identified defects in the raw material, and scanning electron microscopy (SEM) identified agglomeration of MWCNTs on the surface and cross-section of the modified polymers.

The difficulty in the clinical diagnosis of labor is due to an evolutionary mismatch. The ability to hide the signs and symptoms of labor is an evolutionary trait that was once advantageous, but became maladaptive due to environmental changes. Prospective diagnosis of labor is not possible with certainty using only clinical criteria; however, by analyzing the urinary metabolome of women in labor, this diagnosis is likely possible in all cases. In this review, we explain why the two methods (clinical and metabolomic) differ in efficacy and sensitivity, and we try to fit this difference into an evolutionary framework that explains these discrepancies considering evolutionary mismatch. The study of metabolomics allows the truth to emerge from the past, and the diffusion of metabolomic techniques and their application to clinical reality in the form of POC (Point of Care) could change the management of labor and childbirth in the future.

Purpose: Emotional voice conveys important social cues that demand listeners’ attention and timely processing. This event-related potential study investigated the feasibility of a multi-feature oddball paradigm to examine adult listeners’ neural responses to detecting emotional prosody changes in non-repeating naturally spoken words. Method: Thirty-three adult listeners completed the experiment by passively listening to the words in neutral and three alternating emotions while watching a silent movie. Previous research documented pre-attentive change-detection electrophysiological responses (e.g., MMN, P3a) to emotions carried by fixed syllables or words. Given that the MMN and P3a have also been shown to reflect extraction of abstract regularities over repetitive acoustic patterns, the current study employed a multi-feature oddball paradigm to compare listeners’ MMN and P3a to emotional prosody change from neutral to angry, happy, and sad emotions delivered with hundreds of non-repeating words in a single recording session. Results: Both MMN and P3a were successfully elicited by the emotional prosodic change over the varying linguistic context. Angry prosody elicited the strongest MMN compared to happy and sad prosodies. Happy prosody elicited the strongest P3a in the centro-frontal electrodes, and angry prosody elicited the smallest P3a. Conclusions: The results demonstrated that listeners were able to extract the acoustic patterns for each emotional prosody category over constantly changing spoken words. The findings confirm the feasibility of the multi-feature oddball paradigm in investigating emotional speech processing beyond simple acoustic change detection, which may potentially be applied to pediatric and clinical populations.

This study investigates the spatio-temporal variability of the onset, offset, and Length of the rainy season in Senegal over the 1981-2018 period. The onset, offset dates, and length of the rainy season are crucial parameters for agricultural planning in West Africa, which exhibits high interannual and spatial variability in rainfall. The objective is to detect and spatially classify these phenological parameters across Senegal using different approaches. Daily precipitation data from the Climate Hazards group InfraRed Precipitation with Stations (CHIRPS) dataset over the study period and ERA5 reanalysis were used. The method of was applied to detect the onset, offset dates, and length of the rainy season. The Kohonen algorithm was then used to spatially classify these parameters on topological maps. A hierarchical ascendant classification was also performed to reduce the number of classes obtained. Finally, a composite analysis of moisture transport before the onset and end of the 1984 and 2007 seasons was conducted with ERA5 data. The results show a meridional gradient of the start of the season, progressively later from southeast to northwest, while the end follows a north-south gradient. The duration of the rainy season ranges from 45 days in northern Senegal to 150 days in the south. The maximum number of dry days also decreases from north to south. The Kohonen self-organizing maps allow spatial prediction of the onset, end date, and duration of the rainy season across Senegal. The dynamics analysis reveals that early onset years are associated with stronger and earlier northward moisture transport over West Africa, underscoring the role of this parameter in triggering the rainy season. These promising results can provide an early warning to policymakers and farmers on the start and end dates of the season in each area of Senegal.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly in gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5,397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS > 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (< 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS > 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Forensic document examiners can determine the authenticity of questioned documents by analyzing the ink used to create them. If an ink mismatch is found, it could be a sign of scam, backdating, or forgery. In this research a Hyperspectral Images of iVision HHID dataset is used to detect number of possible inks used in document. By using Hyperspectral Images, it’s possible to detect ink mismatch in a given document. In this research unsupervised learning method K-means is used to detect number of inks. Approximate number of clusters are determined by Elbow and Silhouette method before implementation of K-means.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Background: There is poor evidence about sensitivity to chemotherapy according to microsatellite instability (MSI)/mismatch repair (MMR) status in endometrial cancer (EC). Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h) /deficient (d) MMR and MSI- low (l)/proficient (p)MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. Results: 312 patients treated between 2010-2022 in 4 high volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31–91) years. Among patients with localized disease, median RFS was 100.0 months (95%CI 59.4–140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p=0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p=0.039). In patients receiving platinum-based chemotherapy, no statistically significant difference in PFS (p=0.21) and OS (p=0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Conclusion: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

This study compared cortical responses to speech in preschoolers with typical language development (TLD) and Developmental Language Disorder (DLD), and in adults. We investigated whether top-down language effects modulate speech perception in an adult-like manner. We compared cortical mismatch responses (MMR) during passive perception of speech differing in linguistic complexity in three groups of participants: preschoolers with TLD (n=11), preschoolers with DLD (n=16) and adults (n=20). We also measured children’s phonological skills and investigated if they are associated with the cortical responses. MMR results indicated top-down language effects in adults, with enhanced cortical discrimination of lexical stimuli but not of non-words. In preschoolers, the TLD and DLD groups did not differ on the MMR measures and no top-down effects were detected. Moreover, we found no association between MMRs and phonological awareness skills, even though the DLD group’s phonological skills were significantly lower. Our findings suggest that top-down language modulations on speech discrimination may not be present during early childhood, and that children with DLD may not exhibit cortical speech perception deficits. The lack of association between phonological and MMR measures indicates that further research is needed to understand the link between language skills and cortical activity in preschoolers.

To date, radiation adaptation response has been reported as a low-dose related phenomenon and has been associated with radiation hormesis. Well-known cancers are caused by non-radiation active reactants, in addition to radiation. A model of suppression for radiation-specific cancers was previously reported, but the model did not target radiation-nonspecific cancers. In this paper, we describe kinetic models of radiation-induced suppressors for general radiation non-specific cancers, estimating the dose that induces the maximum hormesis effect while satisfying the condition that the risk is approximately proportional to dose above 100 mSv. It was found that the radiation hormesis effect is maximal at about 20 mSv when the rate constant for generation is the same as the rate constant for decomposition. When the two rate constants are different, the dose at which the radiation hormesis effect is maximized depends on both rate constants, but the dose increases as the two rate constants approach each other, reaching a maximum of about 20 mSv. This conclusion may lead to the discovery of unknown cancer suppressors at low doses and the development of cancer suppression methods in the future.

The timely diagnosis of defects at their incipient stage of formation is crucial to extend the life-cycle of technical appliances. This is the case of mechanical-related stress, either due to long aging degradation processes (e.g., corrosion) or in-operation forces (e.g., impact events), which might provoke detrimental damages, such as cracks, disbonding or delaminations, most commonly followed by the release of acoustic energy. The localization of these sources can be successfully fulfilled via adoption of Acoustic Emission (AE)-based inspection techniques through the computation of the Time of Arrival (ToA), namely the time at which the induced mechanical wave released at the occurrence of the acoustic event arrives to the acquisition unit. However, the accurate estimation of the ToA may be hampered by poor Signal-to-Noise ratios (SNRs). In these conditions, standard statistical methods typically fail. In this work, two alternative Deep Learning methods are proposed for ToA retrieval, namely a Dilated Convolutional Neural Network (DilCNN) and a Capsule Neural Network for ToA (CapsToA). These methods have the additional benefit of being portable on resource-constrained microprocessors. Their performance has been extensively studied on both synthetic and experimental data, focusing on the problem of ToA identification for the case of a metallic plate. Results show that the two novel methods can achieve localization errors which are up to 70% more precise than those yielded by conventional strategies, even when the SNR is severely compromised (i.e., down to 2 dB). Moreover, DilCNN and CapsNet have been implemented in a tiny machine learning environment and then deployed on microcontroller units, showing a negligible loss of performance with respect to offline realizations.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

Запропонована методика спрямована на визначення та прогнозування технічного стану елементів мосту, що може слугувати прогресивним інженерним інструментом для оцінки надійності та довговічності. Розроблено на основі фундаментальних досліджень, які узагальнюють досвід вивчення фізико-механічних і фізико-хімічних властивостей матеріалів мостових конструкцій, що експлуатуються в реальних умовах. Теоретичною основою методики є модель надійності та прогнозування залишкового ресурсу елементів мосту на основі теорії Маркова. Розроблена методика призначена для оцінки технічного стану окремих елементів мосту з подальшою комплексною оцінкою всієї конструкції. За показник технічного стану прийнята надійність при експлуатації. Цей кількісний показник надійності в моделі є критерієм для: оцінки рівня безпеки елементів мосту; ранжування елементів мосту за необхідністю для конкретних видів ремонту, реконструкції або заміни; стратегічне планування витрат на ремонт або реконструкцію в умовах обмеженого фінансування; прогнозування залишкового ресурсу елементів. Для застосування розробленої методики запропоновано алгоритм оцінки та прогнозування технічного стану мостів. Було проведено математичний експеримент розробленої методики, який підтвердив адекватність висунутої гіпотези, тобто використання моделі надійності та прогнозування залишкового ресурсу елементів мосту. По-перше, запропоновано триступеневий механізм уточнення технічного стану мосту, суттєво підвищення точності розрахунків. Тому розроблена методика має практичне значення і може слугувати основою для інформаційно-аналітичних систем управління станом мостів.

This study investigates the long-term stability of the Suomi National Polar-orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) moderate-resolution Thermal Emissive Bands (M TEBs; M12 – M16) covering a period from February 2012 to August 2020. It also assesses inter-sensor consistency of the VIIRS M TEBs among three satellites-S-NPP, NOAA-20, and NOAA-21 over eight months spanning from March 18 to November 30, 2023. The field of interesting is limited to the ocean surface between 60°S and 60°N, specifically under clear-sky conditions. Taking radiative transfer modeling (RTM) as the transfer reference, we employed the Community Radiative Transfer Model (CRTM) to simulate VIIRS TEB brightness temperature (BTs), incorporating European Centre for Medium-range Weather Forecasts (ECMWF) reanalysis data as inputs. Our results reveal two key findings. Firstly, the reprocessed S-NPP VIIRS TEBs exhibit a robust long-term stability, as demonstrated through analyses of the observation minus background BT differences (O-B ∆BTs) between VIIRS measurements (O) and CRTM simulations (B). The drifts of the O-B BT differences are consistently less than 0.105 K/Decade across all S-NPP VIIRS M TEB bands. Notably, observations from VIIRS M14 and M16 stand out with drifts well within 0.04 K/Decade, reinforcing their exceptional reliability for climate change studies. Secondly, excellent inter-sensor consistency among these three VIIRS instruments is confirmed through the double-difference analysis method (O-O). This method relies on the O-B BT differences obtained from daily data. The mean inter-VIIRS O-O BT differences remain within 0.08 K for all M TEBs, except for M13. Even in the case of M13, the O-O BT differences between NOAA-21 and NOAA-20/S-NPP have values of 0.312 K and 0.234 K, respectively, which are comparable to the 0.2 K difference between some TEBs among VIIRS and MODIS. These disparities are primarily attributed to the significant differences in the Spectral Response Function (SRF) of NOAA-21 compared to NOAA-20 and S-NPP. Our study confirms the RTM-based TEB quality evaluation method’s versatility and effectiveness in assessing long-term sensor stability and inter-sensor consistency. The double-difference approach effectively mitigates uncertainties and biases inherent to CRTM simulations, establishing itself a robust mechanism for assessing inter-sensor consistency. In addition, we’ve observed that, except for M13, M12 always exhibits larger spatial variations of O-O BT differences with greater uncertainties compared to the other M TEBs. The influence of solar contribution through sea surface reflection on the Top of Atmosphere (TOA) radiance measurements during daytime in M12 should not be underestimated.

This study examined infants' neural responses to emotional prosody in natural speech. A multi-feature oddball paradigm was used with 34 3~11 month-old infants. Results showed distinct early (100-200 ms) and late (300-500 ms) mismatch responses to different emotional prosodies. Older infants had more negative early responses with happy and angry prosodies evoking stronger responses compared to sad prosody while younger infants showed a clearer distinction between angry and sad prosodies. In the late time window, angry prosody elicited more negative responses than sad prosody with younger infants showing more distinct responses between these two prosodies. Males exhibited stronger early mismatch responses than females. These findings call for further research on the implications for socio-emotional and language development.

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.

The role of DNA mismatch repair (MMR) tumor testing in colon and endometrial carcinomas is well-established, yet the universal application of this testing faces challenges due to limited data on its efficacy in diverse populations. This retrospective study at a community hospital in Northern Indiana examined MMR immunohistochemistry (IHC) results across 549 cases. Our analysis found intact MMR expression in 469 cases, while 80 demonstrated MMR deficiency, translating to MMR deficiency rates of 10% in colon cancers and 22% in uterine carcinomas. Notably, only 16 patients (2.9%) were categorized as high microsatellite instability (MSI-H), a rate significantly lower than the 3-5-fold higher incidences reported in other Midwestern populations, including Ohio. These findings suggest that the benefits of universal cascade methylation testing, particularly in MLH1/PMS2 IHC-negative tumors, may vary significantly based on regional demographics. Given the notably lower MSI-H incidence in this study, re-evaluating reflex testing protocols in low-resource settings could lead to more targeted, cost-effective approaches without compromising diagnostic accuracy. This study challenges the one-size-fits-all approach to MMR testing, highlighting the need for tailored strategies that consider regional variations in cancer genetics.

Thirteen benzylethylenearyl ureas and one carbamate have been designed, synthesized and biologically evaluated as regards their antiproliferative activity on tumor cell lines HEK-293 and A-549 and on the immune and endothelial Jurkat T cells and HMEC-1, respectively. A relationship between the structure of the synthetic compounds and their antiproliferative activity has been established. Compounds C.1, C.3, C.12 and C.14 were chosen for further biological studies in order to determine their potential as oncoimmunomodulating agents. Some compounds exhibited significant inhibitory effects on both total PD-L1 and VEGFR-2 in HT-29 cell line, showing urea C.12 active against both targets. Some compounds could reduce more than 50% of cancer living cells, compared to non-treated ones, when assessed in co-cultures using HT-29 and THP-1 cells. In addition, these compounds showed no effect on the immune cell viability and significantly reduce CD11b expression, which is a promising target for immune modulation in anti-cancer therapies.

Outcome of redo-mitral valve replacement in the small mitral annulus with the use of the chimney technology is not well documented. From 2019 to 2020, 77 consecutive patients underwent redo-mitral valve replacement with the use of the chimney technology because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. Mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. Preoperative Mitral valve mean gradient was 18.07 ± 9.40 mmHg. Postoperative mitral prosthesis size 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. Mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg and at follow-up echocardiogram performed at 3 years after the procedure was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while 4-year survival was 89.3% with no reoperation. Use of the chimney technology in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable intraoperatively and over time.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

This study proposes self-calibration of capacitor mismatch errors for high-resolution pipeline analog-to-digital converters (ADCs). The proposed calibration circuit recursively amplifies the capacitor mismatch error by re-utilizing a multiplying digital-to-analog converter in a pipeline stage without increasing the circuit complexity, and the amplified error voltage is converted into digital code by utilizing the remaining pipeline stages. Error correction is performed by subtracting the digital code from the ADC output during normal operation. A prototype of a 12-bit pipeline ADC is fabricated in a 0.18 µm standard CMOS process. The ADC comprises eight 1.5-bit stages, followed by a 4-bit flash ADC as the final stage; the capacitor mismatch errors in the first two pipeline stages are corrected by utilizing the proposed self-calibration technique. At a sampling rate of 30 MS/s, the measured differential and integral nonlinearities improve from +0.82/-0.75 and +1.12/-1.79 to +0.45/-0.41 and +0.47/-0.91 after calibration, respectively. Further, the measured dynamic performances improve significantly with calibration. For an input frequency of 2.09 MHz, the ADC achieves a spurious-free dynamic range (SFDR) and signal-to-noise and distortion ratios (SNDR) of 69.3dB and 63.9dB before calibration, respectively. After calibration, the SFDR and SNDR increase to 84.1dB and 68.9dB, respectively, and the effective number of bits is approximately 11.1bit. The power consumption of the ADC is 35mW under 1.8V supply, and the resulting figure of merit is 514fJ/conversion step.

Delay in data transmission is one of key performance indicators (KPIs) of a network. The planning and project value of delay in network management is of crucial importance for the optimal allocation of network resources and their performance focuses. To create optimal solutions, predictive models, which are currently most often based on machine learning (ML), are used. This paper aims to investigate the training, testing and selection of the best predictive delay model for a VoIP service in an Long Term Evolution (LTE) network using three ML techniques - Neural Networks (NN), Support Vector Machines (SVM) and k-Nearest Neighbors (k-NN). The space of model input variables is optimized by dimensionality reduction techniques: RReliefF algorithm, Backward selection via the recursive feature elimination algorithm and the Pareto 80/20 rule. A three-segment road in the geo-space between the cities of Banja Luka (BL) and Doboj (Db) in the Republic of Srpska (RS), Bosnia and Herzegovina (BiH), covered by the cellular network (LTE) of the M:tel BL operator was chosen for the case study. The results show that, in all three optimization approaches, the k-NN model is selected as the best solution. For the RReliefF optimization algorithm, the best model has 6 inputs and minimum relative error (RE), RE=0.109; for the Backward selection via the recursive feature elimination algorithm, the best model has 4 inputs and RE=0.041; and for the Pareto 80/20 rule, the best model has 11 inputs and RE= 0.049. The comparative analysis of the results concludes that according to observed criteria for the selection of the final model, the best solution is an approach to optimizing the number of predictors based on the Backward selection via the recursive feature elimination algorithm.

Statistical denoising techniques have been well studied, however many challenges still remain. This 9 article focuses on determining the least necessary number of significant samples in a statistical pop-10 ulation sampling, while minimizing the impact on the statistical detection of the fiber Bragg grating 11 (FBG) power spectra. This is achieved by using Bayesian decision making, small population statis-12 tics while excluding false detection. First, we investigate the impact of two-sided sliding window 13 technique applied near the cell under the test. The window size varies from 8 to 60 samples. The 14 considered maximum size of population sampling is connected with the number of wavelength 15 samples within the bandwidth of the symmetrical FBG power spectra peaks. Regarding the sym-16 metry of FBG power spectra peaks and the possible reduction of computational demands, we inves-17 tigate the impact of a one-sided sliding window. This enables to achieve less processing latency for 18 real time applications thus brings benefits to FBG-based fiber optical sensing. Both, two- and one-19 sided small population sampling techniques are then experimentally verified. Detection results are 20 analyzed in depth via calculating detection thresholds by using the small size window sliding along-21 side the waveband. From results achieved, it was found that the normality three-sigma rule does 22 not need to be followed while using the small population sampling. Experimental demonstrations 23 and analyses showed that the proposed concept of denoising and statistical threshold detection 24 based on the sliding window does not depend on the prior knowledge of probability distribution 25 functions of the FBG power spectra peaks level and background noise. We have also found that the 26 thresholds’ adaptability mainly depends on the statistical numerical characteristics of the above ad-27 ditive mixture of the FBG power spectra peaks signals and background noise.