Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Recently, there has been renewed interest in the performance, functionality, and sustainability of traditional small-scale storage interventions (check dams, farm bunds and tanks) used across India for the improvement of local water security. The Central Groundwater Board of India is en-couraging the construction of such interventions for the alleviation of water scarcity. It is of critical importance to understand the hydrological effect of these interventions at basin scales to maximise their effectiveness. The quantification of small-scale interventions in hydrological modelling is often neglected, especially in large-scale modelling exercises. A bespoke version of the GWAVA model was developed to assess the impact of interventions on the water balance of the Cauvery Basin and two smaller sub-catchments. Model results demonstrate that farm bunds appear to have a negligible effect on the estimated average annual simulated streamflow at the outlets of the two sub-catchments and the basin whereas tanks and check dams have a more significant effect. In-terventions generally were found to increase evaporation losses across the catchment. The model adaption used in this study provides a step-change in the conceptualisation and quantification of the consequences of small-scale storage interventions in large- or basin-scale hydrological models.

In the last years, more and more studies highlight the advantages of complementing traditional master classes with additional activities that improve students´ learning experience. This combination of teaching techniques is specially advised in the field of structural engineering, where intuition of the structural response it is of vital importance to understand the studied concepts. This paper deals with the introduction of a new (and more encouraging) educational tool to introduce intuitively students in the dynamic response of structures excited with an educational shaking table. Most of the educational structural health monitoring systems use sensors to determine the dynamic response of the structure. The proposed tool is based on a radically different approach, as it is based on low-cost image-recognition techniques. In fact, it only requires the use an amateur camera, a black background and a computer. In this study, the effects of both the camera location and the image quality are also evaluated. Finally, to validate the applicability of the proposed methodology, the dynamic response of small-scale buildings with different typologies is analyzed. In addition, a series of surveys were conducted in order to evaluate the activity based on student´s satisfaction and the actual acquisition and strengthening of knowledge.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

[NiFe]-hydrogenases are gas-processing metalloenzymes that catalyze the conversion of dihydrogen (H2) to protons and electrons in a broad range of microorganisms. Within the framework of green chemistry, the molecular proceedings of biological hydrogen turnover inspired the design of novel catalytic compounds for H2 generation. The bidirectional “O2-sensitive” [NiFe]-hydrogenase from Escherichia coli HYD-2 has recently been crystallized; however, a systematic infrared characterization in the presence of natural reactants is not available yet. In this study, we analyze HYD-2 from E. coli by in situ ATR FTIR spectroscopy under quantitative gas control. We provide an experimental assignment of all catalytically relevant redox intermediates alongside the O2- and CO-inhibited cofactor species. Furthermore, the reactivity and mutual competition between H2, O2, and CO was probed in real time, which lays the foundation for a comparison with other enzymes, e.g., “O2-tolerant” [NiFe]-hydrogenases. Surprisingly, only Ni-B was observed in the presence of O2 with no indications for the “unready” Ni-A state. The presented work proves the capabilities of in situ ATR FTIR spectroscopy as an efficient and powerful technique for the analysis of biological macromolecules and enzymatic small molecule catalysis.

In this paper, we calculate the deflection angle of photon by Casimir wormhole in the weak field limit approximation. First we calculate Gaussian optical curvature with the help of optical spacetime geometry and so we use the Gauss-Bonnet theorem on the Gaussian optical metric. Then we find the deflection angle of photon by Casimir wormhole. Moreover, we calculate the photon's deflection angle in the presence of plasma medium and we also see the graphical nature of deflection angle in both cases. Second, we move towards the shadow of Casimir wormhole. After the observations of Event Horizon Telescope, the study of shadow become very important so that we plot the shapes of shadow of Casimir wormhole, and we calculate the photon geodesic around the Casimir wormhole.

Background A body composition monitor (BCM) has a role not only in determining over-hydration (OH) but also as an aid to nutritional assessment. For dialysis patient-specific clinical applications of BCM, it is necessary to clarify the relationship between body composition parameters and OH in healthy Chinese individuals. Methods This cross-sectional study involved 314 healthy individuals with a mean age of 45.7±13.1 years. BCM measurements were performed while the subjects were fasting. Results The mean OH level was 0.379±0.81 L. Lean tissue index (LTI) and Lean tissue mass (LTM) were significantly higher in males (p<0.001), while fat tissue index (FTI) was significantly higher in females (p<0.001). In univariate correlation analysis, FTI, Fat, and ATM had a negative correlation with OH in females and all subjects (p<0.05), while LTM and BCM had a positive correlation in all subjects (p<0.05). There was a significant negative correlation between phase angle (PhA) and OH in males, females, and all subjects (r=-0.634, p<0.001; r=-0.666, p<0.001; r=-0.484, p<0.001, respectively). In multivariate linear regression analysis, PhA (b=-1.266, p<0.001), LTM (b=0.987, p<0.001), age (b=-0.307, p<0.001) were independent predictors of OH. Conclusions This study demonstrated that age, LTM and especially PhA, had important roles in predicting OH in healthy Chinese individuals. In the future, PhA may aid in clinical assessment by helping to titrate dry weight among hemodialysis patients with malnutrition.

An accurate understanding of jointed rock mass behavior is important in many applications ranging from deep geological disposal of nuclear waste to deep mining to urban geoengineering projects. The roughness of rock fractures and the matching of the fracture surfaces are the key contributors to the shear strength of rock fractures. In this research, push shear tests with three normal stress levels of 3.6, 6.0, and 8.5 kPa were conducted with two granite samples with artificially induced well-matching tensile fractures with sizes of 500 mm × 250 mm and 1000 mm × 500 mm. The large sample reached on average a -60 % weaker peak shear stress than the medium-sized sample, and a strong negative scale effect was observed in the peak shear strength. The roughness of the surfaces was measured using a profilometer and photogrammetry. The scale-corrected profilometer-based method (JRC) underestimates the peak friction angle for the medium-sized slabs by -27 % for the medium sample and -9 % for the large sample. The photogrammetry-based (Z’2) method produces an estimate with -7% (medium) and +12 % (large) errors. The photogrammetry-based Z’2 is an objective method that consistently produces usable estimates for the JRC and peak friction angle.

In this paper, we study the weak gravitational deflection angle of relativistic massive particles by the Kerr-like black hole in the bumblebee gravity model. In particular, we focus on weak field limits and calculate the deflection angle for a receiver and source at a finite distance from the lens. To this end, we use the Gauss-Bonnet theorem of a two-dimensional surface defined by a generalized Jacobi metric. The spacetime is asymptotically non-flat due to the existence of a bumblebee vector field. Thus the deflection angle is modified and can be divided into three parts: the surface integral of the Gaussian curvature, the path integral of a geodesic curvature of the particle ray and the change in the coordinate angle. In addition, we also obtain the same results by defining the deflection angle. The effects of the Lorentz breaking constant on the gravitational lensing are analyzed. We then consider the finite-distance correction for the deflection angle of massive particles.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

The paper is aimed to develop an improved acoustic-based Structural Health Monitoring (SHM) and Non-Destructive Evaluation (NDE) techniques, which provide the waves directivity emitting by the angle-beam wedge actuators in the thin-walled structures made of plastic materials and polymeric composites. Our investigation includes the dispersive analysis of the waves that can be excited in the studied plastic panel. Its results allowed to find two kinds of the generated acoustic waves - anti-symmetric Lamb waves A0 and shear horizontally polarized SH waves SS0. The bounds of the chosen frequency range for the experimental and numerical studies were accepted as a compromise between the desire to obtain high defects resolution by generating short waves, their adjustable directivity and maximum propagation length. The finite element model for the transducer was built by using the results of actuator structure experimental study. The frequency response functions for the actuator current and oscillation amplitude of the footprint surface demonstrated good agreement. The found eigenfrequencies of actuator's structure were used for the numerical and experimental study of the Lamb and SH wave generation and propagation in a thin-walled plastic panel. Our results convincingly demonstrated the satisfactory directivity of the actuated waves at their excitation on the frequencies that corresponded to the natural modes of the actuator oscillation. The authors assume that an efficient use of the proposed technique for other analyzed quasi-isotropic materials and applied actuators can be provided by a preliminary research using the similar approach and methods presented in this article.

The purpose of this study is to compare and analyze the kinematic characteristics of the upper limb segments during the archery shooting of Paralympic Wheelchair Class archers (ARW2 - second wheelchair class – paraplegia or comparable disability) and Paralympic Standing Class archers (ARST - standing archery class – loss of 25 points in the upper limbs or lower limbs), where archers are classified according to their disability grade among elite disabled archers. The participants of this study were selected as seven elite athletes with disabilities, 4 ARW2, and 3 ARST. The analysis variables were 1) the time required for each phase, 2) the angle of inclination of the body center, 3) the change of trajectory of body center, and 4) the change of movement locus of bow center by phase when performing six shots in total. The ARW2 group showed a longer time than the ARST group, and the angle of the body did not show a significant difference between the two groups. Although there was no significant difference in the mean score between the two groups, it was judged that kinematic performance according to each group was, in that there was a measurable variation in kinematic variables.

We report fabrication of crystalline microresonators of high quality (Q) factors with a controllable wedge angle on lithium niobate on insulator (LNOI). Our technique relies on femtosecond laser assisted chemo-mechanical polish which allows us to achieve ultrahigh surface smoothness as critically demanded by high Q microresonator applications. We show that by refining the polish parameters, Q factors as high as 4.7 × 10⁷ can be obtained and the wedge angle of the LNOI can be continuously tuned from 9° to 51°.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Purpose: To investigate the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). Methods: Twenty anterior segments of porcine eyes were assigned to 5 groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4) and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 hours after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. Results: Baseline outflow facilities of the five groups were similar (F = 0.922, P = 0.477). Complete, circumferential occlusion over 360° induced a significant decrease in facility from baseline at all time-points (P ≤ 0.023 at 3, 12, 24 and 36 hours). However, no difference from baseline was found in any of the partially-occluded (0–270°) groups (F ≥ 0.067, P ≥ 0.296 at 3, 12, 24 and 36 hours). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. Conclusion: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. 90° of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.

Recent studies on seafloor mapping have presented different modelling methods for the automatic classification of seafloor sediments. However, most of these studies have applied these models to seafloor data with appropriate number of ground-truth samples, which raises the question whether these methods are applicable to studies with smaller numbers of ground-truth data. In this study, we aim to address this issue by conducting sediment class-specific predictions using ensemble modelling to map areas with limited or without ground-truth data and combined with hydro-acoustic datasets. The resulting class-specific maps were then assembled into one map, where the most probable class was assigned to the appropriate location. Our approach was able to predict sediment classes without bias to the class with more ground-truth data and produced reliable seafloor sediment distributions maps that can be used for seafloor monitoring. Sediment shifts of a heterogenous seafloor in the Sylt Outer Reef, German North Sea were also assessed to understand the sediment dynamics in the area. The analyses of sediment shifts showed that the western area of the Sylt Outer Reef is highly active, and the results of the analyses assisted in providing recommendations on future seafloor monitoring activities.

High-performance motor drives that operate in harsh conditions require an accurate and robust angular position measurement to correctly estimate the speed and reduce the torque ripple produced by angular estimation error. For that reason, a resolver is used in motor drives as a position sensor due to its robustness. A resolver-to-digital converter (RDC) is an observer used to get the angular position from the resolver signals. Most RDCs are based on angle tracking observers (ATOs). On the other hand, generalized predictive control (GPC) has become a powerful tool in developing controllers and observers for industrial applications. However, no GPC-based RDC with zero steady-state error during constant speed operation was proposed. This paper proposes an RDC based on a second-order difference GPC (SOD-GPC). In SOD-GPC, the second-order difference operator is applied to design a GPC model with two embedded integrators. Thus, the SOD-GPC is used to design a type-II ATO whose steady-state angle estimation error tends to zero during constant speed operation. Simulation and experimental results prove that the proposed RDC system has better performance than other literature approaches.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

The aim of this study is to provide the scientists with a straightforward correlation that can be applied for predicting the Fanning friction factor and consequently the pressure drop during blood flow in small caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. The study has been conducted using CFD simulations validated with relevant experimental data acquired using an appropriate experimental set-up. The experiments concern pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e. an aqueous glycerol solution that contains a small amount of xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L=5.6cm and D=400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the flow rate, the hematocrit value (35-55%) and the vessel diameter (300-1800 μm) and predicts with better than ±10% the Fanning friction factor and consequently the pressure drop during laminar blood flow in small caliber vessels.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO’s performance does not deteriorate as PVS volume increases. Second, the performance of all “vesselness” filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

To investigate the effect of acidic nanoparticles on proton conductivity, permeability and fuel cell performance, a commercial Nafion® 117 membrane was impregnated with zirconium phosphates (ZrP) and sulfated zirconium (S-ZrO2) nanoparticles. The tensile test, water uptake, methanol crossover, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermal gravimetric analysis (TGA) and Scanning Electron Microscopy (SEM) were used to assess the ca-pacity of nanocomposite membrane to function in a fuel cell. The modified Nafion® membrane obtained the higher water uptake and a lower water content angle than the commercial Nafion® 117 membrane, indicating that it has a greater impact on conductivity. Under strain rates of 40, 30 and 20 mm/min, the nanocomposite membranes demonstrate more stable thermal deterioration and higher mechanical strength, which offers tremendous promise for fuel cell applications. When compared to 0.113 S/cm and 0.013 S/cm, respectively, of commercial Nafion® 117 and Nafion® ZrP membranes, the modified Nafion® membrane with ammonia sulphate acid had the highest proton conductivity of 7.891 S/cm. When tested using a direct single cell methanol fuel cell, it had the highest power density of 183 m. cm-2 which is better than commercial Nafion® 117 and Nafion® ZrP membranes.

In this paper, we study light rays in a Kazakov-Solodukhin black hole. To this end, we use the optical geometry of the Kazakov-Solodukhin black hole within the Gauss-bonnet theorem. We first show the effect of the deformation parameter $a$ on the Gaussian optical curvature, and then we use the modern method popularized by Gibbons and Werner to calculate the weak deflection angle of light. Our calculations of deflection angle show how gravitational lensing is affected by the deformation parameter $a$. Moreover, we demonstrate the effect of a plasma medium on weak gravitational lensing by the Kazakov-Solodukhin black hole. We discuss that the increasing the deformation parameter $a$, will increase the weak deflection angle of the black hole. Our analysis also uncloak how one may find a observational evidence for a deformation parameter on the deflection angle.

The sublimation enthalpies of four highly energetic materials (HEMs): triacetone triperoxide (TATP), 2,4-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitrohexahydro-s-triazine (RDX) deposited on stainless steel (SS) substrates were determined by optical fibre coupled-grazing angle probe (GAP) FTIR spectroscopy and thermogravimetric analysis (TGA) for bulk crystaline HEMs samples. The desorption energy of RDX on SS was also studied using grazing angle FTIR microscopy. Metastable phases of 2,4-DNT and TNT were observed when deposited on SS, and their sublimation enthalpies values were obtained by GAP measurements and compared with those for the crystalline phases. The sublimation enthalpies for the alpha phase RDX was also determined by TGA measurements. A layer of crystalline beta phase RDX was observed on SS, and it's sublimation enthalpies was determinate by GAP. PLS calibration curves for the surface concentrations of RDX on SS were generated using GAP to determinate the surface concentration with time at different temperatures.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

In general, remote sensing has proven to be a powerful tool in the overall understanding of natural and anthropogenic phenomena. Satellites have become useful tools for tasks such as characterization, monitoring, and the continuous prospecting of natural resources. This research aims to analyze spatial dynamic and destructive on coral reefs area and correlation between live coral reduction and population on small islands. Landsat MSS, TM, ETM, and OLI-TIRS are used to spatial analyze of coral reef dynamics from 1972 to 2016. The image processing includes gap-filling, atmospheric correction, geometric correction, image composite (true color), water column correction, unsupervised classification, reclassification, accuracy assessment. The statistical analysis identifies the relationship between dynamic population data with a reduction of live coral, namely Principal Component Analysis (PCA) and Multiple Regression Analysis. The effect of the population shows a positive correlation with the reduction in the area of live coral, although it is significant. The fact is the practice of coral destruction on an island; it is usually not only caused or carried out by residents who live on the island but also carried out by other residents of different islands.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Water quality retrieval for small urban waterbodies by remote sensing get used to be difficult due to coarse spatial resolution of the remote sensing imagery. The recently launched Sentinel-2 produces imagery with a spatial resolution of 10 m. It provides an opportunity to solve the problem of retrieving water quality for small waterbodies. Additionally, many water management issues also require fine resolution of imagery, e.g. illegal discharge to an urban waterbody. Since illegal discharges are an important issue for urban water management, chemical oxygen demand (COD), total phosphorous (TP), and total nitrogen (TN) were chosen as the target parameters for water quality retrieval in this study. COD, TP and TN, however, are non-optically active parameters. There were limited studies in the past to retrieve these parameters in comparison with optically active parameters, e.g. Chlorophyll-A etc. This study compared three machine learning models, namely Random Forest (RF), Support Vector Regression (SVR), and Neural Networks (NN), to investigate the opportunity to retrieve the above non-optically active parameters. Results showed that R² of TP, TN, and COD by NN, RF and SVR were 0.94, 0.88, and 0.86, respectively. The performances of water quality retrieval for these non-optically active parameters were significantly improved by the optimized machine learning models. These models hence solved the problem to use remote sensing data to retrieve these non-optically active water quality parameters and provided a new monitoring strategy for small waterbodies. Water quality mapping obtained by Sentinel-2 imagery provided a full spatial coverage of the water quality characterization for the entire water surface. Compared with water samples collecting and testing, it greatly reduced labor cost, reagents cost, and waste treatment cost. It also may help identify illegal discharges to urban waterbodies. The method developed in this research provides a new practical and efficient water quality monitoring strategy in managing water with consideration of environmental sustainability.

The apparent shape of the black hole shadow provides a full description of the spin, the inclination angle and the charge of a Kerr black hole, without any astrophysical process or underlying theory in the astrophysical process.

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood-brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS=5.75 ± 0.932 L·Kg-1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.

In this paper, we discuss the weak gravitational lensing in the context of stringy black holes. Initially, we examine the deflection angle of photon by charged stringy black hole. For this desire, we compute the Gaussian optical curvature and implement the Gauss-Bonnet theorem to investigate the deflection angle for spherically balanced spacetime of stringy black hole. We also analyze the influence of plasma medium in the weak gravitational lensing for stringy black hole. Moreover, the graphical impact of coupling constant $\alpha$, impact parameter $b$ , black hole charge $Q$ on deflection angle by charged stringy black hole has been studied in plasma as well as non-plasma medium.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

We propose a new estimator for creating expansion factors for survey plots in the USDA Forest Inventory and Analysis program. This is a regularized version of the raking estimator widely used in sample surveys. The regularized raking method differs from other predictive modeling methods for integrating survey and ancillary data in that it produces a single set of expansion factors that can have general purpose use to produce small area estimates and wall-to-wall maps of any plot characteristic. This method also differs from other more widely used survey techniques, such of GREG estimation, in that it is guaranteed to produce positive expansion factors. We extend the previous method here to include cross-validation, and provide a comparison to expansion factors between the regularized raking and ridge GREG survey calibration.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

The main goal of this paper is to study the weak gravitational lensing by Horndeski black hole in weak field approximation. In order to do so, we exploit the Gibbons-Werner method to the optical geometry of Horndeski black hole and implement the Gauss-Bonnet theorem to accomplish the deflection angle of light in weak field region. Furthermore, we have endeavored to extend the scale of our work by comprising the impact of plasma medium on the deflection angle as properly. Later, the graphical influence of the deflection angle of photon on Horndeski black hole in plasma and non-plasma medium is examined.

The adoption of Pump as Turbines (PATs) both in small scale hydroelectric plants and water supply systems has brought different advantages, the most recognized being cost-effectiveness as compared to other hydroturbines. However, due to their lack of flow control ability, their intolerance to off-design operations constitutes one tough shortfall. Moreover, this technology’s newness leads to PAT flow dynamics still being ununderstood even to date. Therefore, this study intends to numerically investigate the mixed flow PAT’s pump mode flow dynamics for five operating conditions expanding from optimum (1QBEP) to deep part-load (0.41 QBEP) conditions. Moreover the effect of runner blade angle on the same has been investigated where three angles namely -2°, 0°, and 2° have been considered. PAT flow stability was found to deteriorate as the flow decreased, where associated pressure pulsation level worsened at different flow zones. In addition, the blade angle increase led correspondingly increasing flow unsteadiness and pressure pulsation levels, where the pulsation frequencies from rotor-stator interactions were dominant for most of flow zones. This study’s findings are of a crucial importance to both scientific and engineering communities as they contribute to thorough understanding of PAT flow dynamics.

During recent years UAVs have been increasingly used in agriculture and forestry research and application. Nevertheless, most of this work has been devoted to improving accuracy and explanatory power, often at the cost of usability and affordability. We tested a low-cost UAV and a simple workflow to apply four different greenness indices to the monitoring of pine (Pinus sylvestris and P. nigra) after-fire regeneration in a Mediterranean forest. We selected two sites and masured all pines within a pre-selected plot. Winter flights were carried out at each of the sites, at two flight altitudes (50 and 100 m). Automatically normalizing images entered an SfM based photogrammetric software for restitution and the obtained point cloud and orthomosaic processed to get a canopy height model and four different greenness indices. Sum of pine DBH was regressed on summary statistics of greenness indices and canopy height model. ExGI and GCC indices outperformed VARI and GRVI in estimating pine DBH, while canopy height model slightly improved the models. Flight altitude did not severely affect model performance. Our results show that low cost UAVs may improve forest monitoring after disturbance, even in those habitats and situations were resource limitation is an issue.

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites (e.g., exosites, ectosites) through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches such as proteomics and N-terminomics to identify new MMP substrates and achieve a better understanding of the roles of these proteases in diseases.

Cogging torque is a pulsating, parasitic and undesired torque ripple intrinsic of the design of a permanent magnet synchronous generator (PMSG), which should be minimized due to its adverse effects: vibration and noise. In addition, as aerodynamic power is low during start-up at low wind speeds in small wind energy systems, the cogging torque must be as low as possible to achieve a low cut-in speed. A novel mitigation technique using compound pre-slotting, based on a combination of magnetic and non-magnetic materials, is investigated. The finite element technique is used to calculate the cogging torque of a real PMSG design for a small wind turbine, with and without using compound pre-slotting. The results show that cogging torque can be reduced by a factor of 48% with this technique, while avoiding the main drawback of the conventional pre-slotting technique: the reduction of induced voltage due to leakage flux between stator teeth. Furthermore, through a combination of pre-slotting and other cogging torque optimization techniques, 84%, cogging torque can be eliminated for a given design.

The area of Central and Eastern Europe, and thus Poland, is not exposed to effects of seismic actions. Any possible tremors can be caused by coal or copper mining. Wind, rheological effects, the impact of other objects or a non-uniform substrate are the predominant types of loading included in calculations for stiffening walls. The majority of buildings in Poland, as in most other European countries, are low, medium-high brick buildings. Some traditional materials, like solid brick (>10% of construction materials market) are still used. But autoclaved aerated concrete (AAC) and cement-sand calcium-silicate (Ca-Si) elements with thin joints are prevailing (>70% of the market) on the Polish market. Adding reinforcement only to bed joints in a wall is a satisfactory solution (in addition to confining) for seismic actions occurring in Poland that improves ULS and SLS. This paper presents results from our own tests on testing horizontal shear walls without reinforcement and with different types of reinforcement. This discussion includes 51 walls made of solid brick (CB) reinforced with steel bars and steel trusses, results from tests on 15 walls made of calcium-silicate (Ca-Si) and AAC masonry units reinforced with steel trusses and plastic meshes. Taking into account our own tests and those conducted by other authors, empirical relationships were determined on the basis of more than 90 walls. They are applicable to design and construction phase to determine the likely effect of reinforcement on cracking stress that damage shear deformation and wall stiffness.

“White matter disease” identifies series of different conditions and pathological mechanisms: autoimmune, infectious, toxic-metabolic and vascular. Each of these leads to a global impairment of the neural myelination process through the secondary destruction of previously myelinated structures. To date, the imaging spectrum represents an irreplaceable tool to detect these lesions, describe their distribution patterns and stage them over time. This study aims presents a pictorial review of white matter disease, from pathology to imaging spectrum, reporting current main staging systems with greater emphasis to relationship between cerebrovascular disease and white matter hyper-intensity appearance, and the newest advances in this field.

Market turbulence with fiscal investment influences has altered IT infrastructure performance as business pursue extravagant new technology adoption. Yet, few studies have examined how shareware solution goes beyond Medium Size Enterprise that pushes efficiency and sustainability. This PLS-SEM integrated with dual primary compilation approach lessens shallow perceptions coupled with outlooks that streamline each phenomenal activity that is worthy of the necessity for competitive innovation. This unified model was applied to sampling respondents and analyzed using an ordinal regression relationship that generates a robust association that triggers the hypothesis acceptance. The adopting of BOINC shareware mesh network towards unified processing designs that were employed to build the yield by promising financial possibility using coordinated interworks hence improved group accomplishment and establishing greater esteem. This paper showcases a flexible inner IT infrastructure alongside the economic uncertainty with the framework advancement for Exostructure as a Service. Associated theoretical and practical implications were discussed.

Advanced manufacturing techniques, aimed at implants with high dependability, flexibility, and low manufacturing costs, are crucial in meeting the growing demand for high-quality products like biomedical implants. Incremental sheet forming is a promising flexible manufacturing approach for rapidly prototyping sheet metal components using low-cost tools. Titanium and its alloys are used to shape most biomedical implants because of its superior mechanical qualities, biocompatibility, low weight, and great structural strength. The poor formability of titanium sheets at room temperature, however, limits their widespread use. The goal of this research is to show that gradual sheet formation of a titanium biomedical implant is possible. The possibility of creative and cost-effective concepts for the manufacturing of such complicated shapes with significant wall angles is explored in this study. A numerical simulation based on finite element modeling as well as a design process tailored to metal forming is used to complete the development. The mean of uniaxial tensile tests with a constant strain rate was used to study the flow behavior of the studied material. To forecast the crack, the obtained flow behavior was modeled using the behavior model and failure model.

Higher-risk myelodysplastic syndrome (HR-MDS) has a poor prognosis in the absence of efficient therapy. The evaluation of new therapies in animal models of HR-MDS is hampered by the absence of accurate in vivo biomarkers of the disease. In this study we compared [18F]Fluoro-desoxyglucose Positron Emission Tomography (FDG-PET) and [18F]Fluoro-thymidine (FLT)-PET imaging for disease follow-up in a triple transgenic MMTVtTA/TetoBCL-2/MRP8NRASD12 mouse model of HR-MDS. Normal control FVB/N mice (G1,n=9) and HR-MDS mice (G2,n=12) underwent both FDG- and FLT-PET procedures at 2-day intervals, on a dedicated small animal device. Blood cell counting, BCL-2 and Mac-1hi/Gr-1lo expression measurements in blood were performed before each PET procedure. Visually, PET images of G2 mice demonstrated homogeneous FDG uptake in the whole skeleton similar to that observed in G1 mice, and abnormal FLT hot spots in bone marrow not observed in G1 mice. The intensity of FLT hot spots in bone marrow was higher in 3-months old G2 mice than in 2-months old G2 mice, concordant with a higher percentage of cells expressing Mac-1hi/Gr-1lo and lower platelets counts. We conclude that FLT-PET/CT imaging is a more valuable surrogate non-invasive quantitative marker of HR-MDS bone marrow involvement than FDG-PET/CT in our mouse model of HR-MDS.

Mediterranean catchments are characterized by significant spatial and temporal hydrological variability caused by the interaction of natural as well human-induced abiotic and biotic factors. This study investigates the (non-)linearity rainfall-runoff relationship at multiple temporal scales in representative small Mediterranean catchments (i.e., < 10 km2) to achieve a better understanding of the hydrological response. Rainfall-runoff relationship was evaluated in 44 catchments at annual and event –203 events in 12 of these 44 catchments– scales. A linear rainfall-runoff relation was observed at annual scale with higher scatter in pervious than impervious catchments. Larger scattering was observed at event scale, although pervious lithology and agricultural land use promoted significant rainfall-runoff linear relations in winter and spring. These relationships were particularly analysed during five hydrological years in Es Fangar catchment (3.35 km2; Mallorca, Spain) as a temporal downscaling to assess intra-annual variability in which antecedent wetness conditions played a significant role in runoff generation.

Sustainable Development Goal (SDG) 6.2 sets an ambitious target of leaving no one without adequate sanitation by 2030. The key concern is the lack of local human and financial capital to fund the collection of reliable information to monitor progress towards the goal. As a result, national and local records may be telling a different story of the proportion of safely managed sanitation that counts towards achieving the SDGs. This paper unveils such inconsistency in sanitation data generated by urban authorities and proposes a simple approach for collecting reliable and verifiable information on access to safely managed sanitation. The paper is based on a study conducted in Babati Town Council in Tanzania. Using a smartphone-based survey tool, city health officers were trained to map 17,383 housing units in the town. A housing unit may comprise of two or more households. The findings show that 5% practice open defecation, while 82% of the housing units have some forms of sanitation. Despite the extensive coverage, only 31% of the faecal sludge generated is safely contained, while 64% is not. This study demonstrates the possibility of using simple survey tools to collect reliable data for monitoring progress towards safely managed sanitation in the towns of global south.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

The evaluation of HAADF-STEM images of a sample with the composition Nb18W16O93 provided new insights in its real structure. The basic structure comprises an intact octahedral framework of the tetragonal tungsten bronze (TTB) type. The partial occupation of the pentagonal tunnels (PT) by metal-oxygen strings determines the oxygen to metal ratio (O/SM with M = Nb,W). For a large area, the O/SM was determined to be 2.755 which is smaller than the value of Nb18W16O93 which is O/SM = 2. 735. To a large extent, the threefold TTB superstructure structure of Nb8W9O47 with a high oxygen content is present (O/SM = 2.765). In addition, a new fourfold TTB superstructure was found in small domains: Nb12W11O63 with an O/SM = 2.739 obviously accommodates a part of the sample’s metal excess compared to the stable phase Nb8W9O47.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

In this article, we analyze the weak gravitational lensing in the context of Einstein-non-linear Maxwell-Yukawa black hole. To this desire, we derive the deflection angle of light by Einstein-non-linear Maxwell-Yukawa black hole using the Gibbons and Werner method. For this purpose, we obtain the Gaussian optical curvature and implement the Gauss-Bonnet theorem to investigate the deflection angle of Einstein-non-linear Maxwell-Yukawa black hole. Moreover, we derive the deflection angle of light in the presence of plasma medium. We also analyze the graphical behavior of deflection angle by Einstein-non-linear Maxwell-Yukawa black hole in the presence of plasma as well as non-plasma medium.

Land degradation is a critical issue globally putting our future generations at risk. The decrease in farm productivity over the years is evidence of land degradation severity in Nepal. Among the many strategies in place, agroforestry, which is an integrated tree-based farming, is widely recommended to address this productivity issue. This paper thoroughly examines what influences the choice of agroforestry adoption by farmers and what discourages the adoption. For this, a total of 288 households were surveyed using a structured questionnaire. Two agroforestry practices were compared with conventional agriculture with the help of the Multinomial Logistic Regression (MNL) model. The likelihood of adoption was found to be influenced by gender; the male-headed households were more likely to adopt the tree-based farming practice. Having a source of off-farm income was positively associated with the adoption decision of farmers. Area of farmland was found being the major constraint to agroforestry adoption for smallholder farmers. Some other variables that affected positively included livestock herd size, provision of extension service, home-to- forest distance, farmers’ group membership and awareness of farmers about environmental benefits of agroforestry. Irrigation was another adoption constraint that the study area farmers were faced with. The households with means of transport and with larger family (household) size were found to be reluctant towards agroforestry adoption. A collective farming practice could be a strategy to engage the smallholder farmers in agroforestry.

Abstract. This article proposes new fuzzy controller to regulation the voltage, damp the oscillations and limit the overshoot behavior in single-machine infinite-bus power system. Two different independent MISO fuzzy controllers are designed. First controller, is voltage stabilizer and it composes of two adaptive fuzzy modules and proportional gain AVR. The voltage stabilizer is designed to regulate the terminal voltage, damp the voltage oscillation and limit the voltage overshoot to the industrial maximum allowable limit. The input signals of this stabilizer is are taken from the terminal voltage and the imposed voltage disturbance that can be read from any smart relay. The fuzzy output is used as feedback signal to control the AVR in order to achieve stabilized voltage equal to the reference voltage. The second fuzzy controller is designed with two input signals; “mechanical angle” and its derivative, and one output which is used as feedback signal to adapt the damping torque in order to damp the mechanical oscillation fast and with maximum overshoot not exceeding 10%, and hence damp the power angle oscillation that is important in the PSS improvement. MATLAB-SIMULINK was used for modelling and the test cases simulation. The results show very good performance for the proposed fuzzy controllers.

After globalization, South Korea’s retail landscape has been saturated with large-scale, corporate type retails. However, recently new commercial districts composed of small retail units are returning and bringing about a change. This study sought to take note of this phenomenon and identify its features and meanings from the perspective of urban ecology. A density-distribution analysis was conducted to investigate how they were forms, and an analysis of traces on the Internet and an analysis on the types of businesses were done to identify sociocultural characteristics. Results showed that they had similar type of locations and growth patterns, that they harmoniously congregated in a form of smaller-individual stores, and that their use of similar names for their stores had an impact of branding their entire districts. It was also noted that a shared culture through social networking services served as a growth boost for their unfavorable location. The spontaneous formation of such commercial districts can be an outcome of an urban ecological process geared toward blank niches burgeoning in the current retail structure of Korea. The causes and conditions found in the cases reveal meaningful policy implications for cities facing the same urban crisis diversity.

Cytochrome P450 monooxygenases (P450s) are promising versatile oxidative biocatalysts. However, the practical use of P450s in vitro is limited by their dependence on the co-enzyme NAD(P)H and the complex electron transport system. Using H2O2 simplifies the catalytic cycle of P450s; however, most P450s are inactive in the presence of H2O2. By mimicking the molecular structure and catalytic mechanism of natural peroxygenases and peroxidases, an artificial P450 peroxygenase system has been designed with the assistance of a dual-functional small molecule (DFSM). DFSMs, such as N-(ω-imidazolyl fatty acyl)-l-amino acids, use an acyl amino acid as an anchoring group to bind the enzyme, and the imidazolyl group at the other end functions as a general acid-base catalyst in the activation of H2O2. In combination with protein engineering, the DFSM-facilitated P450 peroxygenase system has been used in various oxidation reactions of non-native substrates, such as alkene epoxidation, thioanisole sulfoxidation, and alkanes and aromatic hydroxylation, which showed unique activities, and regio- and enantioselectivities when compared with native P450s. Moreover, the DFSM-facilitated P450 peroxygenase system can switch to the peroxidase mode by mechanism-guided protein engineering. In this short review, the design, mechanism, evolution, application, and perspective of these novel non-natural P450 peroxygenases for the oxidation of non-native substrates are discussed.

This paper presents an optimal design for the inner current control loop of the continuous current conduction mode (CCM) power factor correction (PFC) stage, which it can be used as the front stage of the two stages alternating current-direct current (AC-DC) telecom power supply. Conventional single-phase CCM-PFC boost converter usually implemented with using of the proportional-integral (PI) controllers in both of the voltage and current control loops, to regulate the output DC voltage to the specified value, moreover to maintains the input current follows the input voltage which offers converter with high power factor (P.F) and low current total harmonic distortion (THD). However, due to the slow dynamic response of the PI controller at the zero-crossing point of the input supply current, input current can’t fully follow the input voltage which leads to high THD. Digitally controlled PFC converter with an optimal design of the inner current control loop using doubly control loops IP controller to reduce the THD and to offer input current with unity P.F was performed in this paper. Furthermore, for the economic design of the digitally control PFC converter, two isolated AC and DC voltage sensors are proposed and designed for the interfacing with the microcontroller unit (MCU). PSIM software was used to test the converter performance with using the proposed designed current controllers and isolated voltage sensors. High power density digitally controlled telecom PFC stage with P.F of about 99.93%, full load efficiency of about 98.70% and THD less 5.50% is achieved in this work.

The rural population percentage decreased from 82.7% to 68.9% in 2011, even though there is an increase in the total rural population, which stands at 833.7 million, and the rural population were now more than three times compared to the population seven decades ago. Another observation is the decrease in cultivators percentage from 71.9% to 45.1 %, while agriculture labour increase from 28.1% to 54.9% during the same period. Despite the increase in irrigated land and net area sown, the average holdings' size under the farmers is continuously decreasing, and it requires a study to look into the reasons. The research probes the role of Minimum Support Price (MSP) in supporting farmers and measuring market price above MSP needed to help marginal and small farmers remain above the poverty level. It explains how different market rates above MSP have a different impact on different categories of agriculture landholding. The study works on developing a common model that relates the impact of MSP on different farmers categories. The model can be generalized to all crops and regions and useful in designing policies that focus on uplifting the income of agricultural farmers.

Taking four of the United Nations Development Goals as reference, this overview describes the need to see from a systemic perspective, the food certifications programs along the food chain in Mexico as today food certifications are voluntary. Using secondary data, the main objectives were: a) there is a fall short in food safety policies and those federal agencies responsible for food safety, to guarantee safe food along the whole domestic food chain, especially in that for low income players; b) the amount of the Mexican Federal Budget Expenses devoted to safety food issues is really low, considering the health, well- being, and food security consequences; and c) due the structural heterogeneity of the Mexican food market, there is a lack of coordination in food regulations along all agents of the food supply chain, bringing to alternate informal markets that put at risk peoples´ health, increasing poverty and inequalities. According to this exercise, only 0.7- 8.7% of producers, 12.5% of supermarkets as well as 42.8% of restaurants would have some type of certifications. Public policies must attend this issue in order to improve food safety and security for the whole population, reducing inequalities, poverty and ensuring them a healthy live.

Potato is among one of the most important food crops, yet maintaining plant productivity in this drought-sensitive crop has become a challenge. Competition for scarce water resources and the continued effects of global warming exacerbate current constraints on crop production. While plants’ response to drought in above-ground tissues has been well documented, the regulatory cascades in developing tubers have been largely unexplored. Using the commercial Canadian cultivar ‘Vigor’, plants were subjected to a drought treatment under high-tunnels causing a 4 ℃ increase in canopy temperature when compared to the well-watered control. Tubers were sampled for RNAseq and metabolite analysis. Approximately 2600 genes and 3898 transcripts were differentially expressed by at least four-fold in drought-stressed potato tubers, with 75 % and 69 % being down-regulated respectively. A further 229 small RNAs were implicated in gene regulation during drought. The comparison of protein homologues between Solanum tuberosum L. and Arabidopsis thaliana L. indicates that downregulated genes are associated with phenylpropanoid, carotenoid, and patatin biosynthesis. This suggests that there may be nutritive implications to drought stress occurring during the potato tuber bulking phase in sensitive cultivars.

Saponite is a trioctahedral 2:1 smectite with the ideal composition MxMg3AlxSi4-xO10(OH,F)2.nH2O (M = interlayer cation). Both the success of the saponite synthesis and the determination of its applications depends on robust knowledge of the structure and composition of saponite. Among the routine characterization techniques spectroscopic methods are the most common. This review, thus, provides an overview of various spectroscopic methods to characterize natural and synthetic saponite with focus on the extensive work by one of the authors (JTK). The IR and Raman spectra of natural and synthetic saponites are discussed in detail including the assignment of the observed bands. The crystallization of saponite is discussed based on the changes in the IR and Raman spectra and a possible crystallization model is provided. Infrared emission spectroscopy has been used to study the thermal changes of saponite in-situ including the dehydration and (partial) dehydroxylation up to 750˚C. 27Al and 29Si Magic-Angle-Spinning Nuclear Magnetic Resonance Spectroscopy is discussed (as well as 11B and 71Ga for B- and Ga-Si substitution) with respect to, in particular, Al(IV)/Al(VI) and Si/Al(IV) ratios. X-ray Photoelectron Spectroscopy provides besides chemical information also some information related to the local environments of the different elements in the saponite structure as reflected by their binding energies.

The principal objective of this project is to investigate the gravitational lensing by asymptotically flat black holes in the framework of Horndeski theory in weak field limits. To achieve this objective, we utilize the Gauss-Bonnet theorem to the optical geometry of asymptotically flat black holes and applying the Gibbons-Werner technique to achieve the deflection angle of photons in weak field limits. Subsequently, we manifest the influence of plasma medium on deflection of photons by asymptotically flat black holes in the context of Horndeski theory. We also examine the graphical impact of deflection angle on asymptotically flat black holes in the background of Horndeski theory in plasma as well as non-plasma medium.

Glaucoma is one of the most common causes of irreversible vision loss worldwide. It is an insidious disease with a multifactorial pathogenesis. Despite progress in treatment methods, prevention and lifestyle modifications may be useful in slowing the progression of this disease. This systematic review aimed to evaluate the influence of diet, oxidative stress, and disturbances in blood serum levels of nutrients on the incidence and severity of glaucoma based on scientific reports on the role of nutrition in the pathogenesis and course of glaucoma. This paper presents an analysis of the above issues; however, further research is required to develop this topic. Future clinical trials are needed to assess the influence of nutrition and to develop nutritional management strategies for patients with glaucoma.

To contribute to small and medium enterprises (SMEs) sustainable transition into the circular economy, the study proposes the activation of organizational learning (OL) processes – denoted here as multi-level knowledge creation, transfer, and retention processes – as a key phase in introducing circular business models (CBMs) at SME and supply chain (SC) level. The research employs a mixed-method approach, using the focus group methodology to identify contextual elements impacting on CBM-related OL processes, and a survey-based evaluation to single out the most frequently used OL processes inside Italian construction SMEs. As main result, a CBM-oriented OL multi-level model offers a fine-grained understanding of contextual elements acting mutually as barriers and drivers for OL processes, as possible OL dynamics among them. The multi-level culture construct – composed of external stakeholders’, SC stakeholders’, and organizational culture – identify the key element to activate CBM-oriented OL processes. Main implications are related to the identification of cultural, structural, regulatory, and process contextual elements across the external, SC, and organizational levels, and their interrelation with applicable intraorganizational and interorganizational learning processes. The proposed model would contribute to an improved implementation of transitioning into the circular economy utilizing sustainable business models in the construction SMEs.

Impact of the Corona, dielectric barrier discharge and low pressure radiofrequency air plasmas on the chemical composition and wettability of the medical grade polyvinylchloride was investigated. Corona plasma treatment exerted the most pronounced increase in the hydrophilization of polyvinylchloride. The specific energy of adhesion of the pristine and plasma treated PVC tubing is reported. The kinetics of hydrophobic recovery following the plasma treatment was explored. The time evolution of the apparent contact angle under the hydrophobic recovery is satisfactorily described by the exponential fitting. Energy-dispersive X-ray spectroscopy of the chemical composition of the near-surface layers of the plasma treated catheters revealed their oxidation. The effect of the hydrophobic recovery is hardly correlated with oxidation of the polymer surface, which is irreversible.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

The paper presents a new procedure for assessing the polarity and hydrophobicity of deep eutectic solvents (DESs) based on the measurement of the DES contact angle on glass. DESs consisting of benzoic acid derivatives and quaternary ammonium chlorides – tetrabutylammonium chloride (TBAC) and benzyldimethylhexadecylammonium chloride (16-BAC) in selected mole ratios were chosen for the study. To investigate the DESs polarity, an optical goniometer and an ET(30) solvatochromic scale based on the Reichardt’s dye were used. The research demonstrated the high accuracy and precision of the developed procedure. The simplicity of the examination and the availability of basic equipment allow the implementation of the developed procedure in routine investigations of DESs.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

The logarithmic correction to Bekenshtein$-$Hawking entropy in the framework of 4D Einstein - Gauss - Bonnet gravity coupled with nonlinear electrodynamics is obtained. We explore the black hole solution with the spherically symmetric metric. The logarithmic term in the entropy has a structure similar to the entropy correction in the semi-classical Einstein equations which mimics the quantum correction to the area low. The energy emission rate of black holes and energy conditions are studied. The quasinormal modes of a test scalar field are investigated. The gravitational lensing of light around BHs was studied. We calculated the deflection angle for some model parameters.

Particle deposition on the surface of the drying chamber poses the main drawback in the spray drying process, which reduces the product recovery and affects the quality of the product. In view of this, the potential application of chemical surface modification to produce a hydrophobic surface that reduces the powder adhesion (biofouling) on the wall of the drying chamber was investigated in this study. The hydrophobic Polydimethylsiloxane (PDMS) solution was used in the vertical dipping method at room temperature to determine the optimum coating parameters on borosilicate glass and stainless-steel substrates, which were used to mimick the wall surface of the drying chamber, to achieve highly hydrophobic surfaces. A single-factor experiment was used to define the range of the PDMS concentration and treatment duration using the Response Surface Methodology (RSM). The Central Composite Rotatable Design (CCRD) was used to study the effects of the concentration of the PDMS solution (X1, %) and the treatment duration (X2, hr) on the contact angle of the substrate (°), which reflected the hydrophobicity of the surface. A three-dimensional (3D) response surface was constructed to examine the influence of the PDMS concentration and treatment duration on the contact angle readings, which serve as an indicator of the surface's hydrophobic characteristic. Based on the optimisation study, the PDMS coating for the borosilicate glass achieved an optimum contact angle of 99.33° through the combination PDMS concentration: X1 = 1% (w/v) and treatment time X2 = 4.94 hr, while the PDMS coating for the stainless-steel substrate achieved an optimum contact angle of 98.31° with PDMS concentration: X1 = 1% (w/v) and treatment time X2 = 1 hr. Additionally, the infrared spectra identified several new peaks that appeared on the PDMS-treated surfaces, which represented the presence of Si-O-Si, Si-CH3, CH2, and CH3 functional groups for the substrates coated with PDMS. Furthermore, the surface morphology analysis using the Field Emission Scanning Electron Microscopy (FESEM) showed the presence of significant roughness and uniform nanostructure on the surface of PDMS-treated substrates, which indicated the reduction of wettability and the potential effect on unwanted biofouling on the spray drying chamber.

There is an accelerating requirement for ocean sensing where autonomous vehicles can play an essential role in assisting engineers, researchers, and scientists with environmental monitoring and collecting oceanographic data. This paper is performed to develop a rigid sail for the autonomous sailing drone. Our study aims to numerically analyze the aerodynamic characteristics of curvy twin sail and compare it with wing sail. Because racing regulations limit the sail shape, only the two-dimensional geometry was open for an optimization. Therefore, this study’s first objective was to identify the aerodynamic performance of such curvy twin sails. Simultaneously, a secondary objective was to estimate the effect of the sail’s spacing and shapes. A viscous Navier-Stokes flow solver is used for the numerical aerodynamic analysis. The 2D aerodynamic investigation is a preliminary evaluation. The results have shown that the curvy twin sail designs have improved lift, drag, and driving force coefficient compared to the wing sails. The spacing between the port and starboard sails of curvy twin sail is an important parameter. The spacing is 0.035L, 0.07L, and 0.14L shows the lift coefficient reduction because of dramatically stall effect, while flow separation is improved with spacing is 0.21L, 0.28L, and 0.35L. Significantly, the spacing 0.28L shows the maximum high pressure at the lower area and the small low pressure area at leading edges, so the highest lift is generated.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

Social customer relationship management (SCRM) is a new philosophy influencing the relationship between customer and organization, where the customer gets opportunity to control relationship through social media. The paper aims on (a) identification of current level of SCRM and also on (b) influence of basic organizational characteristics on SCRM level. The data were gathered through the questionnaire distributed in 362 organization headquartered in the Czech Republic. The questionnaire comprised 54 questions focusing on the significance of marketing and CRM practices, establishing a relationship with the customer, online communities, the use of social media in marketing, and acquiring and managing information. The majority of questions were scalable and used typical five-level Likert scale. Results showed that larger firms more often set up their own online communities and manage them strategically, moreover they are able to manage information better. Contrariwise, small sized organizations use social networks as a way to establish communication with the customer more than large sized entities. Use of social media for marketing purposes is significantly higher in organizations oriented on consumer markets than on business markets.

Small modular reactors (SMR) (&lt;300 MW) offer a potentially attractive nuclear energy option for the middle-east region (MER). Currently, the MER uses a significant amount of fossil fuel to process heat applications such as water desalination and in petroleum refineries and chemical plants, besides generating electricity. SMR technologies represent an opportunity to meet future energy demand in the MER. This paper discusses issues related to the future development and use of SMR technology in nuclear-renewable hybrid energy systems for application in the middle east. SMRs have also been examined as part of a resilient hybrid energy system that combines nuclear energy with renewable energy and traditional fossil energy to produce chemicals, fuels, and electricity. This paper presents the results of a techno-economic analysis of a Nuclear-Renewable-Conventional Hybrid Energy System. The paper concludes that SMR technology will be an essential feature of future hybrid energy systems for the MER.

This paper presents a robust and efficient fault detection and diagnosis framework for handling small faults and oscillations in synchronous generator (SG) systems. The proposed framework utilizes the Brunovsky form representation of nonlinear systems to mathematically formulate the fault detection problem. A differential-flatness model of SG systems is provided to meet the conditions of the Brunovsky form representation. A combination of high-gain observer and group method of data handling neural network is employed to estimate the trajectory of the system and to learn/ approximate the fault and uncertainties associated functions. The fault detection mechanism is developed based on output residual generation and monitoring so that any unfavourable oscillation and/or fault occurrence can be detected rapidly. Accordingly, an average L1-norm criterion is proposed for rapid decision making of faulty situations. The performance of the proposed framework is investigated for two benchmark scenarios which are actuation fault and fault impact on system dynamics. The simulation results demonstrate the capacity and effectiveness of the proposed solution for rapid fault detection and diagnosis in SG systems in practice, and thus enhancing service maintenance, protection, and life cycle of SGs.

For better export performance in cross border e-commerce, a contingency model integrates e-commerce into traditional export marketing strategy (EMS) with internal and external determinants of EMS. However, EMS of Micro, small, and medium-sized enterprises (MSMEs) is understudied. This study validates and modifies existing model for MSMEs. As a qualitative study, multiple sources of data including interviews, internal documents, and group discussions were used regarding business cases of entrepreneurs and supporting organizations in Mongolia and Korea. This research suggets contingency model for MSMEs with modified factors and different strategies in each factor. Specifically, intermal determinants are managerial capability, product competitiveness, and strategic marketing orientation. External determinants are export market competitivceness, export market infrastructure and entry barriers. EMS for MSMEs consists of the same factors with the original model but come up with different strategies. Theoretical and managerial implications were discussed.

In this work, we investigate the weak deflection angle of light from exact black hole within the non-linear electrodynamics. First we calculate the Gaussian optical curvature using the optical spacetime geometry. With the help of modern geometrical way popularized by Gibbons and Werner, we examine the deflection angle of light from exact black hole. For this desire, we determine the optical Gaussian curvature and execute the Gauss-Bonnet theorem on optical metric and calculate the leading terms of deflection angle in the weak limit approximation. Furthermore, we likewise study the plasma medium's effect on weak gravitational lensing by exact black hole. Hence we expose the effect of the non-linear electrodynamics on the deflection angle in the weak gravitational field.

The purpose of this paper is twofold. First, we introduce a geometric approach to study the circular orbit of a particle in static and spherically symmetric spacetime based on Jacobi metric. Second, we apply the circular orbit to study the weak gravitational deflection of null and time-like particles based on Gauss-Bonnet theorem. By this way, we obtain an expression of deflection angle and extend the study of deflection angle to asymptotically non-flat black hole spacetimes. Some black holes as lens are considered such as a static and spherically symmetric black hole in the conformal Weyl gravity and a Schwarzschild-like black hole in bumblebee gravity. Our results are consistent with the previous literature. In particular, we find that the connection between Gaussian curvature and the radius of a circular orbit greatly simplifies the calculation.

Traceability is the ability to determine the path of a product from purchase to consumption to determine when and where it originated. This paper aimed to determine the factors that influence fishers’ decision-making to participate in tuna traceability program, it also explores the determinants of fish catch for small-scale fishers and the feasibility of implementing tuna traceability in the Davao Gulf, Philippines. The result of the interview showed that the significant factors that highly affected the decision-making of fishers in implementating tuna traceability program: boat capacity, fishing hours and communication of fishers (P≤0.05). Household size, years in community, fishing hours, volume of fish sold, and the fishers' communication in the fishing ground (P≤0.05) were other factors that determined the daily catch of the fishers. The results of this study showed that fishers from the Davao Gulf were willing to be part of traceability program that would sustain and increase the value of their fish catch. Moreover, communication was shown to be critically needed in such programs adjusting it for the fish catch to remain fresh or of good quality. Our study will help in deterring and mitigating illegal, unregulated and unreported fishing (IUU) through fish catch traceability.

Despite UAV multi-target detection exhibits considerable developmental potential worldwide, it suffers distinct challenges compared with traditional tasks in this field. These challenges include insufficient feature extraction capabilities for small targets, limited capabilities for multi-dimensional feature fusion, as well as constraints on hardware computation parameters. Especially in mission scenarios such as disaster detection, these challenges will be further amplified. Consequently, this paper introduces SSE-YOLO, an innovative YOLO framework algorithm specially designed to address these challenges. To enhance the model's feature extraction capability, we employ the SPDConv module to replace the original Conv in the backbone section, utilizing depth-separable convolution instead of traditional convolution pooling. Concurrently, we eliminate the SPPF module at the bottom and address a new Separate Kernel Attention Pyramid Pooling (SKAPP) module, substantially enhancing the feature fusion capability at the model's core. Moreover, to address the challenge of multi-dimensional feature fusion, we replace the Concat module of the neck and head with E-BiFPN, transmitting feature information from the backbone to the lower network through four CBS blocks, which effectively resolves the issue of lost contextual information in the model. Meanwhile, SSE-YOLO undergoes ablation experiments on the VisDrone2019 dataset to evaluate its effectiveness against alternative methods, and experimental results illustrate the model's exceptional precision in detecting UAV targets. In comparison to models with comparable experimental accuracy, SSE-YOLO requires remarkably fewer parameters. On the VisDrone2019-DET-test-dev dataset, SSE-YOLO enhances mAP by 17.3%, with a 42.5% reduction in the parameter amounts. Therefore, the proposed method effectively tackles the challenge of reconciling low parameters and high accuracy, presenting a novel pathway for deep learning-based UAV multi-target detection.

In this paper, we use a new asymptotically flat and spherically symmetric solution in the generalized Einstein-Cartan-Kibble-Sciama (ECKS) theory of gravity to study the weak gravitational lensing and its shadow cast. To this end, we first compute the weak deflection angle of generalized ECKS black hole using the Gauss–Bonnet theorem in plasma medium and in vacuum. Next by using the Newman-Janis algorithm without complexification, we derive the rotating generalized ECKS black hole and in the sequel study its shadow. Then, we discuss the effect of the ECKS parameter on the shadow of the black hole and weak deflection angle. In short, the goal of this paper is to give contribution to the ECKS theory and look for evidences to understand how the ECKS parameter effects the gravitational lensing.

(1) Background: This study aimed to evaluate the role of cervical pessary for preventing preterm birth in singleton pregnant women with a cervical length (CL) ≤25 mm and a uterocervical angle (UCA) ≥95o and ≥105o. (2) Methods: A quasi-experimental study was conducted on 225 singleton pregnant women with a gestational age of 16+o-23+6 weeks and transvaginal ultrasound CL measurements ≤25 mm, whose pregnancy was man-aged at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, from September 2020 to September 2022. Participants were allocated into two groups: prophylactic treatment with progesterone (123 pregnant women) and combined with a cervical pessary (102 pregnant women). The UCAs measured via transvaginal ultrasound by a single sonographer were divided into groups with UCA measurements ≥95o and ≥105o. The gestational age at birth was classified into full-term and preterm <37 weeks and <34 weeks. A binary regression model assessed the association between CL, UCA, and pre-term birth outcomes. The difference was statistically significant, with p<0.05. (3) Results: There was no statistically significant difference in the rate of preterm birth <37 weeks and <34 weeks between the two groups (16.3% vs. 11.8% and 6.5% vs. 4.9%, p>0.05). The probability of preterm birth <37 weeks in the group of pregnant women with a UCA ≥95o treated via cervical pessary plus progesterone decreased by 60.6%, OR (95% CI) of 0.394 (0.165-0.941), p<0.05. In the group of pregnant women with a UCA ≥105o, there was a significant association in the group of progesterone treatment combined with a cervical pessary, with the lower rate of PTB <37 weeks and <34 weeks, with OR (95% CI) of 0.028 (0.005-0.146), p<0.001, and 0.141 (0.030-0.664), p<0.05, respectively. (4) Conclusion: The results of this study suggest that cervical pessary is beneficial to the prevention of preterm birth in singleton pregnant women with an obtuse uterocervical angle. Further randomized studies among pregnant women with obtuse uterocervical angles will be needed to clarify the role of a cervical pessary in preventing preterm birth.

The increasing use of energy resources recovered from the subsurface environments and the resulting carbon imbalance in the environment has motivated the need to develop thermodynamically downhill pathways to convert and store CO₂ as water insoluble calcium or magnesium carbonates. While previous studies extensively explored aqueous routes to produce calcium and magnesium carbonates from CO₂, there has been a limited scientific understanding of the phase evolution and textural changes during the direct gas-solid conversion routes to produce calcium carbonate from calcium hydroxide, which is one of the abundant constituents of alkaline industrial residues. With increasing interest in developing integrated pathways for capturing, converting and storing CO₂ from dilute flue gases, understanding the compositions of the product phases as they evolve is essential for evaluating the efficacy of a given processing route. Therefore, in this study, we investigate the phase evolution and the corresponding textural changes as calcium hydroxide is converted to calcium carbonate under the continuous flow of CO₂ at an ambient pressure of 1 atm and on heating continuously from 30 °C to 500 °C using in-operando wide angle X-ray scattering (WAXS), small angle X-ray scattering (SAXS), and ultra-small angle X-ray scattering (USAXS) measurements.

Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high resolution Computed Tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis Lung Carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate stabilized or passivated with Bovine Serum Albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n=8 mice/group). Significant difference is highlighted between citrate-GNP and BSA-GNP groups (**p < 0.005, Tukey’s multiple comparisons test), confirming the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo highlighting the spatial heterogeneity of the solid tumor.

Nicotine exposure may affect NSCLC is associated with lung cancer in humans. Whether nicotine exhibits carcinogenesis promoted activities in tumor growth still unknown. Nicotine is known to have dichotomous effects on cancer biology, acting like a pro- or anti-carcinogenesis agent. There are different functions between adenocarcinoma and squamous NSCLC cancer cells. Excess generation of nicotine may inhibit mitochondrial metabolism, protein modification, and DNA cleavage. Materials and Methods: We used the H520 NSCLC line obtained from human lung epithelial cells to detected nicotine growth and toxicity using MTT assay and western blotting. The concentration of nicotine stimulated cell growth to correspond to low concentration, while high concentration was cytotoxic. Results: According to MTT assay results, at 1.0 μM nicotine has significantly enhanced the H520 cell viability (%). Nicotine induced lung cancer carcinogenesis through mechanisms of α7nAchR, EGFR, HDAC2/4/5, Cyclin D/Cyclin E, Bcl-2, p-Akt, and inflammatory proteins of NF-KappaB and COX2 increases at 1.0 μM. Apoptosis proteins were decreases at 1.0 μM nicotine by p21, p27, c-jun, and p38α using western blotting. Nicotine stimulates tumor growth is mediated through α7nicotinic-acetylcholine receptors (α7nAChR), possibly involving inflammation. On the other hand, at high nicotine concentrations (> 1.0 μM) with consistent cytotoxic effects and appeared to be due to direct cell kill. Nicotine can prevent apoptosis induced by NSCLC. Conclusion: Therefore, the effects on chemotherapeutics by NSCLC malignant cell lines, nicotine in concentrations as low as 1.0 μM decreased. These mechanisms are responsible for the genotoxic effects caused by nicotine. This leads to downstream effects on decreased apoptosis, increased cell proliferation and transformation. The malignant NSCLC cells respond to the treatment with nicotine in lung cancer, the nicotine-mediated induction of growth may provide one of its links to α7nAchR or EGFR.

We study wave patterns of gravity-capillary waves from moving localized sources within the classic setup of the problem of ship wakes. The focus is made on the co-existence of two wave systems with opposite signatures of group velocity relative to the localized source. It leads to the problem of choice of signs for phase functions of the gravity (“slow”) and capillary (“fast”) branches of the dispersion relation: the question generally ignored when constructing phase patterns of the solutions. We detail characteristic angles of the wake patterns: (i) angle of demarcation of gravity and capillary waves – “the phase Mach” cone, (ii) angle of the minimal group velocity of gravity-capillary waves – “the group Mach” cone, (iii, iv) angles of cusps of isophases that appear after a threshold current speed. The outer cusp cone is naturally associated with the classic cone of Kelvin for pure gravity waves. The inner one results from the effect of capillarity and tends to the “group Mach” pattern at high speeds of current. Amplitudes of the wave patterns are estimated within the recently proposed approach of reference functions for the problem of propagation of packets of linear dispersive waves. The effect of shape is discussed for elliptic reference sources.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

The ever-growing repertoire of genomic techniques continues to expand our understanding of true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbour robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in annotation and characterization of such proteins, yet many challenges remain to fully understand the pervasive nature of small proteins and their impact on bacterial biology. In this work we review recent developments in the dynamic field of bacterial genome reannotation, catalogue important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.