Miracle-dz/UniFAR-FTUs huggingface dataset:
Unraveling the Morphological Variation of Triatoma infestans in the Peridomestic Habitats of Chuquisaca Bolivia: A Geometric Morphometric Approach

Simple Summary Triatoma infestans is the main vector of the Chagas disease transmission and has been for years one of the main sanitary problems in Bolivia, particularly for the movement between isolated population to the urban areas. In the following research, we analyze the pattern of biological adaptation of this vector species from two different areas in Bolivia (areas of the Bolivian Chaco with the inter-Andean valleys). Using advanced geometric morphometric tools, it was possible to unravel T. infestans morphological variation and understand the biological adaptation of this important insect species. Abstract Morphometrics has been used on Triatomines, a well-known phenotypically variable insect, to understand the process of morphological plasticity and infer the changes of this phenomenon. The following research was carried out in two regions of the inter-Andean valleys and two Chaco regions of Chuquisaca-Bolivia. Triatoma infestans adults were collected from the peridomestic (pens and chicken coops) along a geographic gradient in order to evaluate the morphological differentiation between groups and their pattern of sexual shape dimorphism. Geometric morphometric methods were applied on the wings and heads of T. infestans. The main findings include that we proved sexual dimorphism in heads and wings, determined the impact of environmental factors on size and shape and validated the impact of nutrition on head shape variation. These results show that geometric morphometric procedures can be used to provide key insight into the biological adaptation of T. infestans on different biotic (nutrition) and abiotic (environment) conditions, which could serve in understanding and evaluating infestation processes and further vector control programs.
EPHA2 Segregates with Microphthalmia and Congenital Cataracts in Two Unrelated Families

EPHA2 is a transmembrane tyrosine kinase receptor that, when disrupted, causes congenital and age-related cataracts. Cat-Map reports 22 pathogenic EPHA2 variants associated with congenital cataracts, variable microcornea, and lenticonus, but no previous association with microphthalmia (small, underdeveloped eye, ≥2 standard deviations below normal axial length). Microphthalmia arises from ocular maldevelopment with >90 monogenic causes, and can include a complex ocular phenotype. In this paper, we report two pathogenic EPHA2 variants in unrelated families presenting with bilateral microphthalmia and congenital cataracts. Whole genome sequencing through the 100,000 Genomes Project and cataract-related targeted gene panel testing identified autosomal dominant heterozygous mutations segregating with the disease: (i) missense c.1751C>T, p.(Pro584Leu) and (ii) splice site c.2826-9G>A. To functionally validate pathogenicity, morpholino knockdown of epha2a/epha2b in zebrafish resulted in significantly reduced eye size ± cataract formation. Misexpression of N-cadherin and retained fibre cell nuclei were observed in the developing lens of the epha2b knockdown morphant fish by 3 days post-fertilisation, which indicated a putative mechanism for microphthalmia pathogenesis through disruption of cadherin-mediated adherens junctions, preventing lens maturation and the critical signals stimulating eye growth. This study demonstrates a novel association of EPHA2 with microphthalmia, suggesting further analysis of pathogenic variants in unsolved microphthalmia cohorts may increase molecular diagnostic rates.
FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-β/Smad Pathway

Purpose Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC. Patients and Methods Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1. Results Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-β/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo. Conclusion This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-β/Smad signaling.
An Ensemble Learning Solution for Predictive Maintenance of Wind Turbines Main Bearing

A novel and innovative solution addressing wind turbines’ main bearing failure predictions using SCADA data is presented. This methodology enables to cut setup times and has more flexible requirements when compared to the current predictive algorithms. The proposed solution is entirely unsupervised as it does not require the labeling of data through work orders logs. Results of interpretable algorithms, which are tailored to capture specific aspects of main bearing failures, are merged into a combined health status indicator making use of Ensemble Learning principles. Based on multiple specialized indicators, the interpretability of the results is greater compared to black-box solutions that try to address the problem with a single complex algorithm. The proposed methodology has been tested on a dataset covering more than two year of operations from two onshore wind farms, counting a total of 84 turbines. All four main bearing failures are anticipated at least one month of time in advance. Combining individual indicators into a composed one proved effective with regard to all the tracked metrics. Accuracy of 95.1%, precision of 24.5% and F1 score of 38.5% are obtained averaging the values across the two windfarms. The encouraging results, the unsupervised nature and the flexibility and scalability of the proposed solution are appealing, making it particularly attractive for any online monitoring system used on single wind farms as well as entire wind turbine fleets.
DNA polymerase chain reaction: A model of error frequencies and extension rates

DOI 10.1002/aic.10604Published online September 13, 2005 in Wiley InterScience (www.interscience.wiley.com). The polymerase chain reaction (PCR) is one of the most important reactions inmolecular biology. The detailed mechanistic studies of the polymerase chain reactionhave revealed a complex sequence of reversible reactions that involve intermediaries andactivated complexes. The DNA polymerase does not merely facilitate the insertion ofdNMP (deoxynucleotide monophosphates), but it also performs rapid screening of sub-strates to ensure a high degree of ﬁdelity. The main result of this study is an expressionfor the average extension rate of the enzyme. The model is versatile and additionalcomplexities, such as the type of nucleotide to be inserted, the GC content of the sequencein the vicinity of the insertion site, and the topology of the template, such as kinks andhairpins, are easy to incorporate. The insertion of incorrect nucleotides into the sequenceis also addressed. Expressions to predict error frequencies are presented. It is shown thata relation exists between error frequency and extension rate: the error frequency is aminimumwhentheextensionrateisoptimal.
The Eco-Bio-Social Factors That Modulate Aedes aegypti Abundance in South Texas Border Communities

Simple Summary The Aedes aegypti mosquito is distributed worldwide and has become a major public health concern due to its proclivity for the urban environment, human feeding behavior, and ability to transmit agents of diseases such as Zika, chikungunya, and dengue. In the continental United States, the region known as the Lower Rio Grande Valley is one of the few areas with local mosquito transmission of these pathogens transmitted by Ae. aegypti. With limited resources for mosquito control in this region, understanding the ecological, biological, and social factors that affect Ae. aegypti population can help guide and improve current control efforts. We were able to observe widespread knowledge regarding Zika, but with very low importance given to mosquitoes as a problem. We found that the presence of window-mounted air conditioning units, number of windows and doors, characteristics of the property, and presence of children in the household all influenced the abundance of Ae. aegypti. The current results not only show a need for improved community engagement for increasing disease and mosquito risk awareness, but also provide risk factors that can guide current vector control activities. Abstract Aedes aegypti control requires dedicated resources that are usually scarce, limiting the reach and sustainability of vector control programs. This generates a need to focus on areas at risk of disease transmission and also understand the factors that might modulate local mosquito abundance. We evaluated the eco-bio-social factors that modulate indoor and outdoor relative abundance of female Ae. aegypti in communities of South Texas. We conducted housing quality and Knowledge Attitudes and Practices surveys in households that were part of a weekly mosquito surveillance program in November of 2017 and 2018. Our results showed widespread knowledge of mosquitoes and Zika virus by our participants. However, less than 35% considered them as serious problems in this region. The presence of window-mounted air conditioning units increased the risk of female mosquito relative abundance indoors. An increase in outdoor relative abundance was associated with larger properties and a higher number of children between 6 to 17 years of age. Interestingly, we observed that an increasing number of children <5 years of age modulated both indoor and outdoor relative abundance, with a 52% increase indoors and 30% decrease outdoors. The low perception of mosquito and disease risk highlights engagement needs for vector-borne disease prevention in this region. The identified risk factors can help guide public health officials in their efforts to reduce human and vector contact.
A Comprehensive miRNome Analysis of Macrophages Isolated from db/db Mice and Selected miRNAs Involved in Metabolic Syndrome-Associated Cardiac Remodeling

Cardiac macrophages are known from various activities, therefore we presume that microRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myocardial remodeling in individuals with metabolic syndrome (MetS). We aim to assess the cardiac macrophage miRNA profile by selecting those miRNA molecules that potentially exhibit regulatory functions in MetS-related cardiac remodeling. Cardiac tissue macrophages from control and db/db mice (an animal model of MetS) were counted and sorted with flow cytometry, which yielded two populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Total RNA was then isolated, and miRNA expression profiles were evaluated with Next Generation Sequencing. We successfully sequenced 1400 miRNAs in both macrophage populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow. Among the 1400 miRNAs, about 150 showed different expression levels in control and db/db mice and between these two subpopulations. At least 15 miRNAs are possibly associated with MetS pathology in cardiac tissue due to direct or indirect regulation of the expression of miRNAs for proteins involved in angiogenesis, fibrosis, or inflammation. In this paper, for the first time we describe the miRNA transcription profile in two distinct macrophage populations in MetS-affected cardiac tissue. Although the results are preliminary, the presented data provide a foundation for further studies on intercellular cross-talk/molecular mechanism(s) involved in the regulation of MetS-related cardiac remodeling.
Efficacy and safety of anti-PD-1/PD-L1 combinations versus standard of care in cancer: a systematic review and meta-analysis.

ABSTRACT Immune checkpoint inhibitors (ICIs) as monotherapy in different solid tumors showed an early detrimental effect in a subset of patients reflected by the early crossover of the progression-free survival (PFS) curves. Currently, combination therapies with ICIs added to chemotherapy or targeted therapy are expanding the landscape of metastatic solid tumors. We have examined the benefits and risks of adding ICIs to the standard of care (SOC) versus SOC alone. A search of randomized clinical trials (RCTs) comparing ICIs combinations versus the corresponding SOC in different metastatic tumors according to the PRISMA guidelines was performed. Selected endpoints included PFS, time-to-response (TTR), overall survival (OS), overall response rate (ORR), and ≥ grade 3 adverse events (AEs). Subgroup analyses based on backbone treatment and tumor type were included. A total of 10536 patients (19 studies) were included (ICIs-arm: 5596 patients; SOC-arm: 4940 patients). Globally, PFS, OS, and ORR results favored ICIs-arm. No differences in terms of TTR were found between arms. ICI-arm was associated with a slight increase of ≥ G3 AEs (relative risk: 1.07). The results in multiple myeloma patients are controversial in favor of ICIs combinations. Adding ICIs to SOC benefits a greater number of patients, prolonging survival with no early detrimental effect. The toxicity profile is safe, with a mild increase of high-grade manageable AEs.
DIRECT CONVERSION OF METHANE AND CARBON DIOXIDE TO HIGHER HYDROCARBONS USING CATALYTIC DIELECTRIC-BARRIER DISCHARGES WITH ZEOLITES

Direct higher hydrocarbon formation from the greenhouse gases methane and carbon dioxide using a dielectric-barrier discharge (DBD) with zeolite catalysts is presented. This catalytic DBD can be operated at ambient conditions and leads to direct hydrocarbon formation. The products include alkanes, alkenes, oxygenates, and syngas (CO + H2). The product distribution depends on the pressure, the input power, the flow rate, the CH4/CO2 feed ratio, and the catalyst used. It is not sensitive to gas temperature in the range from room temperature to 150 °C. From the experiments it can be concluded that a cogeneration of syngas and higher hydrocarbons can be achieved using the catalytic DBD. The optimum CH4/CO2 ratio in the feed for such cogeneration is in the range 2/1 to 3/1. The energy efficiency of CO2 and CH4 conversion increases substantially at higher discharge powers.
The Prevalence and Determinants of Being Offered and Accepting Operational Management Services—A Cohort Study

In Germany, employers are obliged to offer “operational integration management” (OIM) services to employees returning from long-term sick leave. OIM aims to improve employees’ workability and to prevent future sick leave or early retirement. This study examined (i) to what extent OIM services are offered to eligible employees, (ii) to what extent offers are accepted and (iii) the determinants of both outcomes. We used data from a cohort of employees eligible for OIM. Thirty-four potential determinants were assessed in 2013 (i.e., the baseline) using participant reports. In 2015 (i.e., the follow-up), participants were asked (a) whether they had ever been offered OIM services by their employer, and (b) whether they had accepted that offer (i.e., the outcomes). We estimated relative risks by multivariable binomial regression to identify predictors based on backward elimination. In total, 36.0% of the participants were offered OIM services and 77.2% of them accepted that offer. The likelihood of an OIM offer at follow-up was elevated in participants with mental impairment, cancer or long-term absenteeism and increased with organizational justice, neuroticism, and company size. The likelihood of accepting that OIM offer was positively associated with mental impairment and decreased with increasing company size.
1,2-Diarylethanols—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

An initial study of 1,2-diarylethanols derivatives as new potential antibacterial drugs candidates was conducted. Particular emphasis was placed on the selection of the structure of 1,2-diarylethanols with the highest biological activity of lipopolysaccharides (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2–R4 (with different lengths of LPS in its structure). In the presented studies, based on the conducted minimum inhibitory concentration (MIC) and MBC tests, it was demonstrated that the antibacterial (toxic) effect of 1,2-diarylethanols depends on their structure and the length of LPS bacteria in the membrane of specific strains. Moreover, the oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylases was analysed. The analysed damage values were compared with modification with appropriate antibiotics; bacterial DNA after the use of kanamycin, streptomycin, ciprofloxacin, bleomycin and cloxicillin. The presented research clearly shows that 1,2-diarylethanol derivatives can be used as potential candidates for substitutes for new drugs, e.g., the analysed antibiotics. Their chemical and biological activity is related to two aromatic groups and the corresponding chemical groups in the structure of the substituent. The observed results are particularly important in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of pandemics caused by microorganisms.
Microstructures and Mechanical Properties of Hybrid, Additively Manufactured Ti6Al4V after Thermomechanical Processing

In the present study, we propose a hybrid manufacturing route to produce high-quality Ti6Al4V parts, combining additive powder laser directed energy deposition (L-DED) for manufacturing of preforms, with subsequent hot forging as a thermomechanical processing (TMP) step. After L-DED, the material was hot formed at two different temperatures (930 °C and 1070 °C) and subsequently heat-treated for stress relief annealing. Tensile tests were performed on small sub-samples, taking into account different sample orientations with respect to the L-DED build direction and resulting in very good tensile strengths and ductility properties, similar or superior to the forged material. The resulting microstructure consists of very fine grained, partially globularized alpha grains, with a mean diameter ~0.8–2.3 µm, within a beta phase matrix, constituting between 2 and 9% of the sample. After forging in the sub-beta transus temperature range, the typical L-DED microstructure was no longer discernible and the anisotropy in tensile properties, common in additive manufacturing (AM), was significantly reduced. However, forging in the super-beta transus temperature range resulted in remaining anisotropies in the mechanical properties as well as an inferior tensile strength and ductility of the material. It was shown, that by combining L-DED with thermomechanical processing in the sub-beta transus temperature range of Ti6Al4V, a suitable microstructure and desirable mechanical properties for many applications can be obtained, with the advantage of reducing the material waste.
Shear and Extensional Rheology of Linear and Branched Polybutylene Succinate Blends

The molecular architecture and rheological behavior of linear and branched polybutylene succinate blends have been investigated using size-exclusion chromatography, small-amplitude oscillatory shear and extensional rheometry, in view of their processing using cast and blown extrusion. Dynamic viscoelastic properties indicate that a higher branched polybutylene succinate amount in the blend increases the relaxation time due to an increased long-chain branching degree. Branched polybutylene succinate exhibits pronounced strain hardening under uniaxial elongation, which is known to improve processability. Under extensional flow, the 50/50 wt % blend exhibits the same behavior as linear polybutylene succinate.
Integrin-Linked Kinase Links Integrin Activation to Invadopodia Function and Invasion via the p(T567)-Ezrin/NHERF1/NHE1 Pathway

Tumor cell invasion depends largely on degradation of the extracellular matrix (ECM) by protease-rich structures called invadopodia, whose formation and activity requires the convergence of signaling pathways engaged in cell adhesion, actin assembly, membrane regulation and ECM proteolysis. It is known that β1-integrin stimulates invadopodia function through an invadopodial p(T567)-ezrin/NHERF1/NHE1 signal complex that regulates NHE1-driven invadopodia proteolytic activity and invasion. However, the link between β1-integrin and this signaling complex is unknown. In this study, in metastatic breast (MDA-MB-231) and prostate (PC-3) cancer cells, we report that integrin-linked kinase (ILK) integrates β1-integrin with this signaling complex to regulate invadopodia activity and invasion. Proximity ligation assay experiments demonstrate that, in invadopodia, ILK associates with β1-integrin, NHE1 and the scaffold proteins p(T567)-ezrin and NHERF1. Activation of β1-integrin increased both invasion and invadopodia activity, which were specifically blocked by inhibition of either NHE1 or ILK. We conclude that ILK integrates β1-integrin with the ECM proteolytic/invasion signal module to induce NHE1-driven invadopodial ECM proteolysis and cell invasion.
Buckling Resistance of Two-Segment Stepped Steel Columns

Columns of stepwise variable bending stiffness are encountered in the engineering practice quite often. Two different load cases can be distinguished: firstly, the axial force acting only at the end of the column; secondly, besides the force acting at the end, the additional force acting at the place where the section changes suddenly. Expressions for critical forces for these two cases of loading are required to correctly design such columns. Analytical formulae defining critical forces for pin-ended columns are derived and presented in the paper. Derivations were based on the Euler-Bernoulli theory of beams. The energetic criterion of Timoshenko was adopted as the buckling criterion. Both formulae were derived in the form of Rayleigh quotients using the Mathematica® system. The correctness of formulae was verified based on one the of transcendental equations derived from differential equations of stability and presented by Volmir. Comparisons to results obtained by other authors were presented, as well. The derived formulae on the critical forces can be directly used by designers in procedures leading to the column’s buckling resistance assessment. The relatively simple procedure leading to buckling resistance assessment of steel stepped columns and based on general Ayrton-Perry approach was proposed in this work. The series of experimental tests made on steel, stepped columns and numerical simulations have confirmed the correctness of the presented approach.