Influence of Tilting Angle on Temperature Measurements of Different Object Sizes Using Fiber-Optic Pyrometers.

This article presents a new model of optical power gathered by a fiber-optic pyrometer when there is a tilting angle between the fiber longitudinal axis and the vector perpendicular to the tangent plane of the emitted surface. This optical power depends on the fiber specifications, such as the diameter and the numerical aperture (NA), as well as the object parameters, including its diameter, emissivity, and tilting angle. Some simulations are carried out using other pyrometers from the literature without tilting to validate the model. Additional simulations with different optical fibers, object sizes, and distances at different tilting angles allow us to describe the behavior of the pyrometer when the object is smaller than the optical fiber field of view (the light cone defined by its NA). The results show that for a finite surface object, the power collected by the optical fiber is affected by changes in the tilting angle, greater tilting lesser gathered power, and reaching the maximum power when the field of view of the fiber covers up the entire object, as expected. On the other hand, additional equations are presented to describe the maximum tilting angle, and distance that allow the maximum power gathered for a determined object diameter and fiber, avoiding temperature measurement errors.

Exploring the druggability of the binding site of aurovertin, an exogenous allosteric inhibitor of FOF1-ATP synthase.

In addition to playing a central role in the mitochondria as the main producer of ATP, FOF1-ATP synthase performs diverse key regulatory functions in the cell membrane. Its malfunction has been linked to a growing number of human diseases, including hypertension, atherosclerosis, cancer, and some neurodegenerative, autoimmune, and aging diseases. Furthermore, inhibition of this enzyme jeopardizes the survival of several bacterial pathogens of public health concern. Therefore, FOF1-ATP synthase has emerged as a novel drug target both to treat human diseases and to combat antibiotic resistance. In this work, we carried out a computational characterization of the binding sites of the fungal antibiotic aurovertin in the bovine F1 subcomplex, which shares a large identity with the human enzyme. Molecular dynamics simulations showed that although the binding sites can be described as preformed, the inhibitor hinders inter-subunit communications and exerts long-range effects on the dynamics of the catalytic site residues. End-point binding free energy calculations revealed hot spot residues for aurovertin recognition. These residues were also relevant to stabilize solvent sites determined from mixed-solvent molecular dynamics, which mimic the interaction between aurovertin and the enzyme, and could be used as pharmacophore constraints in virtual screening campaigns. To explore the possibility of finding species-specific inhibitors targeting the aurovertin binding site, we performed free energy calculations for two bacterial enzymes with experimentally solved 3D structures. Finally, an analysis of bacterial sequences was carried out to determine conservation of the aurovertin binding site. Taken together, our results constitute a first step in paving the way for structure-based development of new allosteric drugs targeting FOF1-ATP synthase sites of exogenous inhibitors.

Community Response to Noise from Hot-Spots at a Major Road in Quito (Ecuador) and Its Application for Identification and Ranking These Areas.

Environmental legislation in Ecuador is advancing with the legitimate aspiration of providing citizens with new standards of quality and environmental health. In the context of environmental noise, these legislative advances are based on the experience accumulated in other countries, which is an advantage that must be managed with caution by incorporating local factors into noise management procedures. This study advances two lines of work. The first is to survey the population about their attitude towards noise from a major road to try to detect local factors in the annoyance and sleep disturbances. The second uses this information to compare noise indicators for the detection and ranking of hot-spots from major roads. The interviewees exhibited a high level of annoyance and sleep disturbance due to noise compared with the results of other studies. Results show that there are small differences in the definition of hot-spots when using WHO's dose-response curves for Lden ≥ 68 dB for and for Lnight ≥ 58 dB, in comparison with the curves generated in this study (CS). Regarding the application of both dose-response curves (WHO vs. CS) to the estimation of the population at risk of the harmful effect of nighttime traffic noise (HSD), small oscillations are also observed even when Lnight ≥ 58 dB and Lnoche ≥ 60 dB are used.

Factores de riesgo asociados a la transmisión de malaria en zona endemica de Córdoba, Colombia / Risk factors associated with the transmission of malaria in the endemic zone of Córdoba, Colombia

El objetivo del trabajo fue determinar factores de riesgo asociados a la transmisión de la malaria en el municipio de Puerto Libertador, Córdoba. Se realizó un estudio observacional analítico transversal, retrospectivo, con enfoque cuantitativo de casos de malaria de zonas rurales del municipio. La información se organizó en Excel, se describieron variables sociodemográficas, aspectos clínicos de los pacientes, de vivienda y ambientales y se realizó un análisis de riesgo para establecer asociación entre las variables y la malaria, además se clasificaron especies de anofelinos vectores y se utilizaron los softwares SatScan y QGis para identificar puntos calientes de malaria en la zona de estudio. Se incluyeron 170 casos de malaria, se identificó que 92% de los individuos carecen de servicio de recolección de basuras, 86,5% sin acueducto, más del 90% no utilizan angeos, repelentes, insecticidas o fumigaciones, se encontró asociación estadística significativa (OR>1) con las aguas estancadas, la falta de acueducto y agua continua como factores de riesgo de malaria; además se clasificaron cinco especies de mosquitos que estarían involucradas en la transmisión y se identificó un punto caliente compuesto por seis veredas del municipio. La malaria en el municipio de Puerto Libertador está asociada principalmente a problemáticas sociales, que se constituyen en factores de riesgo que favorecen la incidencia de esta enfermedad. En la zona de estudio la identificación de los mosquitos Anopheles y del punto caliente, permitirán orientar las medidas de control del vector y dirigir las intervenciones a las localidades focalizadas con mayor riesgo de malaria(AU)

The objective of the work was to determine risk factors associated with the transmission of malaria in the municipality of Puerto Libertador, Córdoba. A retrospective, cross-sectional analytical observational study was carried out, with a quantitative approach to malaria cases in rural areas of the municipality. The information was organized in Excel, sociodemographic variables, clinical aspects of the patients, housing and environmental variables were described, and a risk analysis was carried out to establish an association between the variables and malaria.In addition, vector anopheline species were classified and the SatScan and QGis software to identify malaria hot spots in the study area. 170 cases of malaria were included, it was identified that 92% of the individuals lack garbage collection service, 86.5% without aqueduct, more than 90% do not use angeos, repellents, insecticides or fumigations, a significant statistical association was found ( OR> 1) with stagnant water, lack of aqueduct and continuous water as risk factors for malaria; In addition, five species of mosquitoes that would be involved in the transmission were classified and a hotspot made up of six villages in the municipality was identified. Malaria in the municipality of Puerto Libertador is mainly associated with social problems, which constitute risk factors that favor the incidence of this disease. In the study area, the identification of Anopheles mosquitoes and the hotspot will make it possible to orient vector control measures and direct interventions to targeted localities with the highest risk of malaria(AU)

Silicon Microchannel-Driven Raman Scattering Enhancement to Improve Gold Nanorod Functions as a SERS Substrate toward Single-Molecule Detection.

The investigation of enhanced Raman signal effects and the preparation of high-quality, reliable surface-enhanced Raman scattering (SERS) substrates is still a hot topic in the SERS field. Herein, we report an effect based on the shape-induced enhanced Raman scattering (SIERS) to improve the action of gold nanorods (AuNRs) as a SERS substrate. Scattered electric field simulations reveal that bare V-shaped Si substrates exhibit spatially distributed interference patterns from the incident radiation used in the Raman experiment, resulting in constructive interference for an enhanced Raman signal. Experimental data show a 4.29 increase in Raman signal intensity for bare V-shaped Si microchannels when compared with flat Si substrates. The combination of V-shaped microchannels and uniform aggregates of AuNRs is the key feature to achieve detections in ultra-low concentrations, enabling reproducible SERS substrates having high performance and sensitivity. Besides SIERS effects, the geometric design of V-shaped microchannels also enables a "trap" to the molecule confinement and builds up an excellent electromagnetic field distribution by AuNR aggregates. The statistical projection of SERS spectra combined with the SIERS effect displayed a silhouette coefficient of 0.83, indicating attomolar (10-18 mol L-1) detection with the V-shaped Si microchannel.

Druggable hot spots in trypanothione reductase: novel insights and opportunities for drug discovery revealed by DRUGpy.

Assessment of target druggability guided by search and characterization of hot spots is a pivotal step in early stages of drug-discovery. The raw output of FTMap provides the data to perform this task, but it relies on manual intervention to properly combine different sets of consensus sites, therefore allowing identification of hot spots and evaluation of strength, shape and distance among them. Thus, the user's previous experience on the target and the software has a direct impact on how data generated by FTMap server can be explored. DRUGpy plugin was developed to overcome this limitation. By automatically assembling and scoring all possible combinations of consensus sites, DRUGpy plugin provides FTMap users a straight-forward method to identify and characterize hot spots in protein targets. DRUGpy is available in all operating systems that support PyMOL software. DRUGpy promptly identifies and characterizes pockets that are predicted by FTMap to bind druglike molecules with high-affinity (druggable sites) or low-affinity (borderline sites) and reveals how protein conformational flexibility impacts on the target's druggability. The use of DRUGpy on the analysis of trypanothione reductases (TR), a validated drug target against trypanosomatids, showcases the usefulness of the plugin, and led to the identification of a druggable pocket in the conserved dimer interface present in this class of proteins, opening new perspectives to the design of selective inhibitors.

Genomic Organization and Generation of Genetic Variability in the RHS (Retrotransposon Hot Spot) Protein Multigene Family in Trypanosoma cruzi.

Retrotransposon Hot Spot (RHS) is the most abundant gene family in Trypanosoma cruzi, with unknown function in this parasite. The aim of this work was to shed light on the organization and expression of RHS in T. cruzi. The diversity of the RHS protein family in T. cruzi was demonstrated by phylogenetic and recombination analyses. Transcribed sequences carrying the RHS domain were classified into ten distinct groups of monophyletic origin. We identified numerous recombination events among the RHS and traced the origins of the donors and target sequences. The transcribed RHS genes have a mosaic structure that may contain fragments of different RHS inserted in the target sequence. About 30% of RHS sequences are located in the subtelomere, a region very susceptible to recombination. The evolution of the RHS family has been marked by many events, including gene duplication by unequal mitotic crossing-over, homologous, as well as ectopic recombination, and gene conversion. The expression of RHS was analyzed by immunofluorescence and immunoblotting using anti-RHS antibodies. RHS proteins are evenly distributed in the nuclear region of T. cruzi replicative forms (amastigote and epimastigote), suggesting that they could be involved in the control of the chromatin structure and gene expression, as has been proposed for T. brucei.

Chemometric Models of Differential Amino Acids at the Navα and Navß Interface of Mammalian Sodium Channel Isoforms.

(1) Background: voltage-gated sodium channels (Navs) are integral membrane proteins that allow the sodium ion flux into the excitable cells and initiate the action potential. They comprise an α (Navα) subunit that forms the channel pore and are coupled to one or more auxiliary ß (Navß) subunits that modulate the gating to a variable extent. (2) Methods: after performing homology in silico modeling for all nine isoforms (Nav1.1α to Nav1.9α), the Navα and Navß protein-protein interaction (PPI) was analyzed chemometrically based on the primary and secondary structures as well as topological or spatial mapping. (3) Results: our findings reveal a unique isoform-specific correspondence between certain segments of the extracellular loops of the Navα subunits. Precisely, loop S5 in domain I forms part of the PPI and assists Navß1 or Navß3 on all nine mammalian isoforms. The implied molecular movements resemble macroscopic springs, all of which explains published voltage sensor effects on sodium channel fast inactivation in gating. (4) Conclusions: currently, the specific functions exerted by the Navß1 or Navß3 subunits on the modulation of Navα gating remain unknown. Our work determined functional interaction in the extracellular domains on theoretical grounds and we propose a schematic model of the gating mechanism of fast channel sodium current inactivation by educated guessing.

Using Electronic Medical Record Data to Better Understand Obesity in Hispanic Neighborhoods in El Paso, Texas.

The prevalence of obesity has been persistent amongst Hispanics over the last 20 years. Socioeconomic inequities have led to delayed diagnosis and treatment of chronic medical conditions related to obesity. Factors contributing include lack of insurance and insufficient health education. It is well-documented that obesity amongst Hispanics is higher in comparison to non-Hispanics, but it is not well-understood how the socioeconomic context along with Hispanic ethnic concentration impact the prevalence of obesity within a community. Specifically studying obesity within Hispanic dominant regions of the United States, along the Texas-Mexico border will aid in understanding this relationship. El Paso, Texas is predominantly Mexican-origin Hispanic, making up 83% of the county's total population. Through the use of electronic medical records, BMI averages along with obesity prevalence were analyzed for 161 census tracts in the El Paso County. Geographic weighted regression and Hot Spot technology were used to analyze the data. This study did identify a positive association between Hispanic ethnic concentration and obesity prevalence within the El Paso County. Median income did have a direct effect on obesity prevalence while evidence demonstrates that higher education is protective for health.

ECO-FRIENDLY hybrid hydrogels for detection of phenolic RESIDUES in water using SERS.

Herein is presented a simple and sensible method to determine organic pollutants in water, based on the utilization of silver nanoparticles (AgNPs) loaded in Polyacrylamide (PAAm)/starch hybrid hydrogels combined with surface-enhanced Raman scattering (SERS) spectroscopy. The materials were characterized by swelling degree studies, UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD) and scanning electron microscopy (SEM). PAAm/starch hydrogels showed variable swelling capacity, according to the synthetic molar composition. The most promising results were attributed to lower concentrations of starch and crosslink agent (N,N'-methylenebisacrylamide - MBA). Spectroscopic analysis confirmed the formation of AgNPs, by noticing the peak at around 420 nm, due to its surface plasmon resonance (SPR) effect. The results showed that AgNPs were stabilized by hydrogels networks. The average size of the AgNPs was smaller than 100 nm and the size and quantity of nanoparticles were influenced by the molar composition of the hydrogel matrix. The SERS substrate based on the AgNPs-PAAm/starch exhibited reproducibility, stability, and limit of detection (LOD) of phenol in water of 1 × 10-8 M. The average mass of AgNPs-PAAm/starch hydrogels used for each detection analysis was around 10 mg. The spectra with enhanced intensities were possible due to a large number of hot spots generated on the AgNPs-PAAm/starch hydrogel substrate, which leads to potential use for organic pollutant detection. In addition, there is also the possibility of reusing the hydrogel matrix substrate in other analyzes.

In silico Strategies to Support Fragment-to-Lead Optimization in Drug Discovery.

Fragment-based drug (or lead) discovery (FBDD or FBLD) has developed in the last two decades to become a successful key technology in the pharmaceutical industry for early stage drug discovery and development. The FBDD strategy consists of screening low molecular weight compounds against macromolecular targets (usually proteins) of clinical relevance. These small molecular fragments can bind at one or more sites on the target and act as starting points for the development of lead compounds. In developing the fragments attractive features that can translate into compounds with favorable physical, pharmacokinetics and toxicity (ADMET-absorption, distribution, metabolism, excretion, and toxicity) properties can be integrated. Structure-enabled fragment screening campaigns use a combination of screening by a range of biophysical techniques, such as differential scanning fluorimetry, surface plasmon resonance, and thermophoresis, followed by structural characterization of fragment binding using NMR or X-ray crystallography. Structural characterization is also used in subsequent analysis for growing fragments of selected screening hits. The latest iteration of the FBDD workflow employs a high-throughput methodology of massively parallel screening by X-ray crystallography of individually soaked fragments. In this review we will outline the FBDD strategies and explore a variety of in silico approaches to support the follow-up fragment-to-lead optimization of either: growing, linking, and merging. These fragment expansion strategies include hot spot analysis, druggability prediction, SAR (structure-activity relationships) by catalog methods, application of machine learning/deep learning models for virtual screening and several de novo design methods for proposing synthesizable new compounds. Finally, we will highlight recent case studies in fragment-based drug discovery where in silico methods have successfully contributed to the development of lead compounds.

Dataset for recognition of snail trails and hot spot failures in monocrystalline Si solar panels.

This article presents a dataset for thermal characterization of photovoltaic systems to identify snail trails and hot spot failures. This dataset has 277 thermographic aerial images that were acquired by a Zenmuse XT IR camera (7-13 µ m wavelength) from a DJI Matrice 100 1drone (quadcopter). Additionally, our dataset includes the next environmental measurements: temperature, wind speed, and irradiance. The experimental set up consisted in a photovoltaic array of 4 serial monocrystalline Si panels (string) and an electronic equipment emulating a real load. The conditions for images acquisition were stablished in a flight protocol in which we defined altitude, attitude, and weather conditions.

Phenotypic and Molecular Evaluation of Echinocandin Susceptibility of Candida glabrata, Candida bracarensis, and Candida nivariensis Strains Isolated during 30 Years in Argentina.

The echinocandin susceptibilities of 122 Candida glabrata complex strains (including 5 Candida nivariensis and 3 Candida bracarensis strains) were evaluated by microdilution and compared with the results from a molecular tool able to detect FKS mutations. No echinocandin resistance was detected. The PCR results coincide with the MIC data in 99.25% of the cases (1 C. glabrata strain was misidentified as resistant) but were 20 h faster. C. nivariensis FKS genes were sequenced and showed differences with C. glabrataFKS genes.

Niche shifts and range expansions along cordilleras drove diversification in a high-elevation endemic plant genus in the tropical Andes.

The tropical Andes represent one of the world's biodiversity hot spots, but the evolutionary drivers generating their striking species diversity still remain poorly understood. In the treeless high-elevation Andean environments, Pleistocene glacial oscillations and niche differentiation are frequently hypothesized diversification mechanisms; however, sufficiently densely sampled population genetic data supporting this are still lacking. Here, we reconstruct the evolutionary history of Loricaria (Asteraceae), a plant genus endemic to the Andean treeless alpine zone, based on comprehensive population-level sampling of 289 individuals from 67 populations across the entire distribution ranges of its northern Andean species. Partly incongruent AFLP and plastid DNA markers reveal that the distinct genetic structure was shaped by a complex interplay of biogeography (spread along and across the cordilleras), history (Pleistocene glacial oscillations) and local ecological conditions. While plastid variation documents an early split or colonization of the northern Andes by at least two lineages, one of which further diversified, a major split in the AFLP data correlate with altitudinal ecological differentiation. This suggests that niche shifts may be important drivers of Andean diversification not only in forest-alpine transitions, but also within the treeless alpine zone itself. The patterns of genetic differentiation at the intraspecific level reject the hypothesized separation in spatially isolated cordilleras and instead suggest extensive gene flow among populations from distinct mountain chains. Our study highlights that leveraging highly variable markers against extensive population-level sampling is a promising approach to address mechanisms of rapid species diversifications.

Evolución espacial y temporal de la malaria en el municipio Sifontes del estado Bolívar, Venezuela. 1980-2013 / Spatial and temporal evolution of malaria in the municipality of Sifontes, Bolívar State, Venezuela. 1980-2013

La malaria es endemo-epidémica en el estado Bolívar, con brotes epidémicos frecuentes debido a causas naturales y antrópicas. En el municipio Sifontes, ubicado en el noreste del estado, durante el último decenio se ha registrado un aumento considerable de los casos, cerrando 2013 con 46.610 casos, 71% % de la malaria del estado y 61% del país. Este es un foco meso-endémico de malaria inestable donde la transmisión ocurre durante todo el año, con brotes epidémicos estrechamente relacionados con la minería aurífera. A partir de 1983, gran parte de la malaria en Venezuela depende de la generada en el estado Bolívar, y esta a su vez de la generada en el municipio Sifontes. La revisión de la data de malaria del estado en el periodo 1980-2013 reveló la existencia de dos niveles epidemiológicos, uno basal y otro adicional, este último ligado a la minería aurífera; sin embargo, no se encontró correlación con la lluvia, para el nivel basal (R = 0,41, P= 0,78) ni para el nivel epidémico (R = 0,41; P = 0,32). Asimismo, la proyección geográfica de los datos reveló la naturaleza focal de la enfermedad en el municipio, el cual reúne todas las condiciones epidemiológicas, ambientales, climáticas y sociales para ser considerado un foco caliente. Las características espaciales y temporales de la malaria en el municipio Sifontes lo configuran como el foco de malaria más importante en Venezuela, el cual debe ser priorizado en los planes de control de la enfermedad.

Malaria is endemo-epidemic in Bolívar state with frequent epidemic outbreaks occurring due to both natural and anthropic factors. The Sifontes municipality, located in the northeastern corner of the state, has reported a considerable increase in the number of cases over the last decade; with 46.610 cases registered during 2013. This represents 71% of the number of malaria cases reported for the state and 61% for the country in this same year. Sifontes municipality is a meso-endemic focus of unstable malaria, and transmission occurs throughout the year with epidemic outbreaks tightly linked to gold mining activities. Since 1988 the increase in the number of cases reported in Venezuela has been determined by the number of cases reported in Bolívar state which, in turn, is correlated with the number of cases reported in Sifontes. A review of malaria data between 1980 and 2013 reveals the existence of two epidemiological categories: a base level and an additional level, the latter associated with gold mining; nevertheless, there was not correlation whit the rainfall for basal (R = 0,41, P= 0,78) or additional level (R = 0,41; P = 0,32). In addition, a geographic plotting of the data revealed the focal nature of malaria in the municipality, which to gather all environmental, climatic, social and epidemiological factors that have produced conditions typical of a hot spot. The spatial and temporal characteristics of malaria in the Sifontes municipality demonstrates that this is the most important malaria focus in Venezuela, and must be prioritized when designing strategies for the control of this disease.

Diseño de microsondas mediante hibridación virtual para el estudio de variantes en los sitios REP-CMT1A / Microarray design using virtual hybridization to study variations in REP-CMT1A sites

Antecedentes: El gen PMP22 se encuentra duplicado en pacientes con Charcot-Marie-Tooth 1A (CMT1A); se ha descrito que el origen de la duplicación es el intercambio desigual de las cromátidas durante la meiosis entre dos regiones de 24 kb denominadas sitios REPCMT1A, encontrándose un REP proximal y un REP distal, los cuales tienen una homología de 98%. Dentro de cada uno de estos sitios existen zonas denominadas puntos calientes de mutación (hot spot), donde se presenta el mayor número de variantes y mutaciones que pudieran dar origen al intercambio desigual. El objetivo de este trabajo fue diseñar un conjunto de microsondas para elaborar un microarreglo con el cual pueda detectarse la presencia de variantes y puntos de mutación en los sitios REP-proximal y REP-distal CMT1A. Material y métodos A partir de las secuencias informadas de los REP distal y proximal, se delimitaron los sitios hot spot dentro de las regiones proximal y distal. Estas secuencias se alinearon, se empalmaron y se detectaron 12 zonas de diferencia secuencial. Resultados y conclusiones. Se diseñaron y analizaron 24 microsondas mediante el programa Genosensor Probe Designer. Las sondas podrán ser sintetizadas y utilizadas en un microarreglo que permita encontrar variaciones, puntos de mutación, y facilitar el diagnóstico de pacientes con CMT1A.

BACKGROUND: Gene PMP22 is duplicated in patients with CMT1A. Duplication is due to an unequal chromatid interchange during meiosis that takes place between two 24 Kb regions named REP-CMT1A proximal and distal sites. Homology is approximately 98%. Within each one of the sites we find zones termed hot spots where a greater number of variants and mutations could give origin to an unequal interchange. The aim of this study was to design a set of probes to create a microarray that could detect the presence of variants and mutation points in distal and proximal REP sites among patients with CMT1A. MATERIAL AND METHODS: With reported sequences of distal and proximal REPs, we determined hot spot sites within proximal and distal regions. These sequences were aligned and matched, hence 12 zones were detected. RESULTS AND CONCLUSIONS: Twenty four probes were designed and analyzed using the Genosensor Probe Designer program. Probes could be synthesized and used in a microarray that is able to find variations and mutation points and facilitates diagnosis of patients with CMT1A.