The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of dopaminergic system modulation in the in-vivo and in-vitro rat models of migraine. Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol, and 5-HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin-induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal CGRP release in-vitro hemiskull preparations. Mechanical allodynia was tested by von-Frey filaments. CGRP concentrations in trigeminovascular structures and in-vitro superfusates, and c-Fos levels in brainstem were determined by ELISA. Meningeal-mast cells were evaluated with toluidine-blue staining. Apomorphine further enhanced nitroglycerin-induced mechanical allodynia, brainstem c-fos expression, trigeminal ganglion and brainstem CGRP concentrations, and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine-induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine- or nitroglycerin-induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in-vitro, while the other administrations were ineffective. Apomorphine-mediated dopaminergic activation exacerbated nitroglycerin-stimulated migraine pain by further enchancing c-fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5-HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine-related parameters in dopaminergic activation- and/or NTG-induced migrane like conditions.

Software testing is an essential process in software development that aims to identify defects and ensure that software is functioning as intended. Various testing techniques are employed to achieve this goal, but the effectiveness of these techniques varies. In this research paper, analyzes the effectiveness of different testing techniques in ensuring software quality. The paper explores different testing techniques, including manual and automated testing, and evaluate their effectiveness in terms of identifying defects, reducing the number of defects in software, and ensuring that software meets its functional and non-functional requirements. Moreover, the paper will also investigate the impact of factors such as testing time, test coverage, and testing environment on the effectiveness of these techniques. This research aims to provide valuable insights into the effectiveness of different testing techniques, enabling software development teams to make informed decisions about the testing approach that is best suited to their needs. By improving testing techniques, the number of defects in software can be reduced, enhancing the quality of software and ultimately providing better software for users.

Diatoms are microalgae, known to present several characteristics that make them excellent bioindicators. In this study, we analyzed the epiphytic diatom communities of shallow lakes, with the aim of exploring the genetic variability explained by physical, chemical or geographical variables. We selected 77 lakes within the Spanish part of the Duero River Basin characterized by wide chemical variability. In each lake, physical parameters were measured in situ and water samples were taken to determine nutrient levels in the laboratory. Diatom communities were collected and identified by both microscopy and DNA-metabarcoding, amplifying a genetic barcode of rbcL gene. We analyzed the phylogenetic signal for several environmental parameters at the genus level for the three most representative genera of these lakes. Our results indicate significant phylogenetic signals that differ from a genus to another. Processes related to spatial scales appear to be the main predictors controlling the genetic diversity of diatom communities in these ponds, with genetic variants deffering among geographical areas for a given species. These molecular studies confirm the enormous diversity present in the diatom communities that inhabit these ecosystems, but further research is needed to apply diatom-based techniques in shallow lakes monitoring or conservation programs. Our results reinforce the view that considering not only morphological but also molecular and ecological characters is necessary to describe new diatom species, especially given the high number of species described each year.

One of the leading problems in today's world is poverty. It is very difficult for a person to overcome from a poverty stage and move to life filled with luxury and all the riches in the world. Poverty is something which tends to slow down the speed of swiftly developing mankind, as the people in poverty have a very big disadvantage in life which holds them back. Most of the time, people in poverty have no other option but to be born, live and die in poverty, it is also the duty of the walks of life to show some sympathetic behavior towards the in need. Poverty is something which can be overcome with difficulty and with help from other people as well. In this paper, a system which can be used to move away from a poverty life and move towards a wealthy life. Studies carried out and with references to personnels that are experts in this field, the system that is being system implemented will consist of a job portal which is targeting the uneducated people, such a system which targets that part of the society has not yet been developed, as states that a stable bread winner for a family can have monthly income. In addition, inspiring a donation gateway which is programmed to assist the poor people. According to, advertising and publishing about events organized for fundraising and betterment of the poor people is being embedded in the system.

Outbreak of Marburg Virus in northwest Tanzania: Unleashing health emergency

Zika virus (ZIKV) and Dengue Virus (DENV) share a lot of similarities, being both flaviviruses and neglected tropical diseases that cause a worldwide burden that is increasing with climate change. Studying the interactions of cell recptors and viruses is essential to further the knowledge and development of ways to prevent and control flaviviral diseases. An important interaction occurs between the envelopeof the two viruses and a protein on the surface of immune cells, called DC-SIGN. We describe this interaction in a structural comparison involving homology modeling of these proteins, guided docking based on deposited crystallography, molecular dynamics of the docked complexes and for the decomposition of interacting residues we employed an analysis of the surface area accessible by the Generalized Bourne method. The region of interest for the discussion is predominantly electropositive in the DENV envelope, but when comparing the same region in the ZIKV envelope, we can observe that there is a decrease in charges, not to the point of making the region electronegative as a whole, but enough for the surroundings of the interaction region to become neutral with electronegative trends. These results suggest better interaction of ZIKV with the DC-SIGN receptor, particularly in the CRD portion

Background: It is unknown whether Torque Teno virus (TTV) DNA load monitoring could anticipate the development of infectious events in hematological patients undergoing treatment with small molecular targeting agents. We characterized the kinetics of plasma TTV DNA in patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring could predict the occurrence of Cytomegalovirus (CMV) DNAemia or the magnitude of CMV-specific T-cell responses. Methods: Multicenter, retrospective, observational study, recruiting 20 patients treated with ibrutinib and 21 with ruxolitinib. Plasma TTV and CMV DNA loads were quantified by real-time PCR at baseline and days +15, +30, +45, +60, +75, +90, +120, +150, and +180 after treatment inception. Enumeration of CMV-specific IFN-γ-producing CD8 + and CD4 + T cells in whole blood was performed by flow cytometry. Results: Median TTV DNA load in ibrutinib-treated patients increased significantly ( P=0.025) from baseline (median, 5.76 log 10 copies/ml) to day +120 (median, 7.83 log 10 copies/ml). A moderate inverse correlation (Rho=-0.46; P<0.001) was found between TTV DNA load and absolute lymphocyte count (ALC). In ruxolitinib-treated patients, TTV DNA load quantified at baseline was not significantly different from that measured after treatment inception ( P ≥0.12). TTV DNA loads were not predictive of the subsequent occurrence of CMV DNAemia in either patient group. No correlation was observed between TTV DNA loads and CMV-specific IFN-γ-producing CD8 + and CD4 + T cell counts in either patient group. Conclusion: The data did not support the hypothesis that TTV DNA load monitoring in hematological patients treated with ibrutinib or ruxolitinib could be useful to predict either the occurrence of CMV DNAemia or the level of CMV-specific reconstitution.

Global climate change is threatening aquatic organisms with rapid changes in habitat salinity and temperature. In response to such changing conditions, adaptation could rescue populations from extinction. Gene flow is a key factor that could either promote or hinder local adaptation, with either beneficial or maladapted alleles immigrating from elsewhere. This interplay between local adaptation and gene flow has not been fully explored in passive dispersers, such as plankton. Thus, we investigated patterns of gene flow and genomic signatures of local adaptation in populations of the copepod Eurytemora affinis spanning natural salinity and temperature gradients in the Baltic and North Seas. Based on whole-genome sequencing of 11 populations, we found population genomic signatures of selection associated with salinity and temperature gradients in both seas, indicating local adaptation, with ‘ion transmembrane transport’ as the most enriched gene ontology category under selection. Interestingly, the single nucleotide polymorphisms (SNPs) associated with responses to salinity and temperature were uncorrelated. We found clear population structure between the Baltic and North Seas, along with signals of admixture between populations, consistent with the presence of gene flow both within and between the seas. Our results suggest that gene flow of beneficial alleles from across the environmental gradients could provide the genetic substrate for populations to adapt to future climate change.

A document by Carlos F de Paule. Click on the document to view its contents.

Glucose-Methanol-Choline (GMC) family enzymes are very important in catalyzing the oxidation of a wide range of structurally diverse substrates. Enzymes that constitute the GMC family, share a common tertiary fold but < 25% sequence identity. Cofactor FAD, FAD binding signature motif, and similar structural scaffold of the active site are common features of oxidoreductase enzymes of the GMC family. Protein functionality mainly depends on protein three-dimensional structures and dynamics. In this study, we used the normal mode analysis method to search the intrinsic dynamics of GMC family enzymes. We have explored the dynamical behavior of enzymes with unique substrate catabolism and active site characteristics from different classes of the GMC family. Analysis of individual enzymes and comparative ensemble analysis of enzymes from different classes has shown conserved dynamic motion at FAD binding sites. The present study revealed that GMC enzymes share a strong dynamic similarity (Bhattacharyya coefficient >90% and root mean squared inner product >52%) despite low sequence identity across the GMC family enzymes. The study predicts that local deformation energy between atoms of the enzyme may be responsible for the catalysis of different substrates. This study may help that intrinsic dynamics can be used to make meaningful classifications of proteins or enzymes from different organisms.

A document by Yasmin Sheikhhassani. Click on the document to view its contents.

Fire retardancy for textiles is important to prevent the rapid spread of fire and minimize damage to property and harm to human life. To infer fire-resistance on textile materials such as cotton or nylon, chemical coatings are often used. These chemicals are usually toxic and economically and environmentally unsustainable, however, some naturally produced protein-based fire retardants could be an alternative. A biofilm protein from Bacillus subtilis (BslA) was identified and recombinantly expressed in Escherichia coli with a double cellulose binding domain. It was then applied to a range of natural and synthetic fabric materials. A flame retardancy test found that use of BslA reduced fire damage by up to 51% and would pass fire retardancy testing according to British standards. It is therefore a viable and sustainable alternative to current industrial fire-retardant coatings.

Millimeter wave (mm-Wave) communication is a promising technology for high-speed wireless communication like 5G. However, it is highly susceptible to numerous perturbations that cause significant signal loss especially rain attenuation. In this paper, we investigate the use of adaptive transmit power control as a mitigating technique for rain attenuation in mm-Wave communication. We compare the performance of this technique to that of adaptive coding and modulation using simulations of a point-to-point communication link over distances of 10m to 1000m, with transmit power varying from 100mW to 1W. Virtual experimental results show that adaptive transmit power control provides better performance than adap-tive coding and modulation in mitigating rain attenuation in mm Wave communication, This is promising for 5G technology implementation and commissioning in the tropics where rainfall is prevalent all year round.

A trade-off between allocated resources for photosynthesis and stress tolerance is generally observed in nature. Thus, the search for outlier species breaking this trend is an interesting approach to identity new mechanisms for plant breeding purposes. Hypothetically, outlier extremophyte species present a distinctive arrangement of physiological functions that favor stress tolerance mechanisms without jeopardizing investment allocation into photosynthesis. We explored this trade-off, analyzing twenty-one plant species for desiccation tolerance, and photosynthetic capacity, under the extreme arid environments of the Atacama Desert and the Surire Salar in the Chilean Altiplano. Most of the studied species followed the trade-off tendency, however, we did find one outlier species, Prosopis tamarugo. To study the mechanisms involved in this atypical response, the Prosopis genus was analyzed more deeply. Our results suggest that the outlier response of P. tamarugo is multifactorial. This species presented a high photochemistry activity, associated with a higher synthesis of chlorophylls, photoprotective pigments, and complex antioxidant molecules. Moreover, the synthesis of no-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in P. tamarugo, would allow the allocation of nitrogen to support its high photosynthetic capacity, without compromising its leaf desiccation stress tolerance.

Small heat shock proteins (sHSPs), a family of proteins with high level of diversity, significantly influence plant stress tolerance and plant development. We have cloned a creeping bentgrass chloroplast-localized sHSP gene, AsHSP26.2 responsive to IAA, GA and 6-BA stimulation. Transgenic creeping bentgrass overexpressing AsHSP26.2 exhibited significantly enhanced plant growth with increased stolon number and length as well as enlarged leaf blade width and leaf sheath diameters, but inhibited leaf trichomes initiation and development in the under-epidermis. Furthermore, AsHSP26.2 overexpression altered phytohormone biosynthesis and signaling transduction, resulting in elevated auxin and gibberellins (GA) accumulation. The results obtained provide novel insights implicating the sHSPs in plant growth and development regulation, and strongly suggest AsHSP26.2 to be a novel candidate for use in crop genetic engineering for enhanced plant biomass production and grain yield.

Liposomal drug products are playing an increasing role in the field of drug delivery. With this increased demand comes the need to increase the capabilities and capacity of manufacturing options. Continuous manufacturing techniques present a significant opportunity to address these needs for liposomal manufacturing processes. Liposomal formulations have unique considerations that impact translation from batch to continuous process designs. This article examines aspects of converting to a continuous design that were previously viewed as inconsequential in a batch process. The batch process involves the removal of ethanol through tangential flow filtration (TFF). Ethanol was found to reduce the permeability of the hollow fibers used for TFF. This effect was determined to have minimal impact on the overall batch process design but considerable influence on the design of continuous TFF such as inline diafiltration (ILDF). Using a pilot scale setup, ethanol was found to decrease permeability in an inverse manner to ethanol concentration. Further assessment found that dilution of the ethanol levels prior to diafiltration can significantly reduce the amount of ILDF stages needed and that a continuous design requires less buffer to the commensurate batch design.

A document by Bea Andersson. Click on the document to view its contents.

Cell-derived extracellular vesicles (EVs) are evolutionary-conserved secretory organelles that, based on their molecular composition, are important intercellular signaling regulators. At least three classes of circulating EVs are known based on mechanism of biogenesis: exosomes (sEVs/Exos), microparticles (lEVs/MPs) and shed midbody remnants (sMB-Rs). sEVs/Exos are of endosomal pathway origin, microparticles (lEVs/MPs) from plasma membrane blebbing, and shed midbody remnants (sMB-Rs) arise from symmetric cytokinetic abscission. Here, we isolate sEVs/Exos, lEVs/MPs and sMB-Rs secreted from human isogenic primary (SW480) and metastatic (SW620) colorectal cancer (CRC) cell lines in milligram quantities for label-free MS/MS-based proteomic profiling. Purified EVs revealed selective composition packaging of exosomal protein markers in SW480/SW620-sEVs/Exos, metabolic enzymes in SW480/SW620-lEVs/MPs, while centralspindlin complex proteins, nucleoproteins, splicing factors, RNA granule proteins, translation-initiation factors, and mitochondrial proteins selectively traffic to SW480/SW620-sMB-Rs. Collectively, we identify 39 human cancer-associated genes in EVs; 17 associated with SW480-EVs, 22 with SW620-EVs. We highlight oncogenic receptors/transporters selectively enriched in sEVs/Exos (EGFR/ FAS in SW480-Exos and MET, TGFBR2, ABCB1 in SW620-sEVs/Exos). Interestingly, MDK, STAT1, and TGM2 are selectively enriched in SW480-sMB-Rs, and ADAM15 to SW620-sMB-Rs. Our study reveals sEVs/Exos, lEVs/MPs and sMB-Rs have distinct protein signatures that open potential diagnostic avenues of distinct types of EVs for clinical utility.

Artificial intelligence (AI) has been a new, advanced, and fast-growing concept in recent decades. Stem cells are also widely used in regenerative medicine, high-scale cell production, drug screening, stem cell therapies, etc.. Stem cell sorting based on AI methods, machine learning, and deep learning approaches is one of the applications of AI in biology and medicine, which leads to fast, accurate, human-error-free, high-throughput, time-efficient, and cost-efficient approaches. Acquiring big data for the production of reliable, accurate, repeatable, and sensitive sorting algorithms is a bottleneck in AI applications in stem cell sorting, and will become easier with more research in this area. In this review, a new category for AI-based stem cell sorting algorithms is introduced, and the studies are summarized based on different factors such as input data, AI approaches, stem cell types, the goal of the study, and accuracy values.

Background: There has been a trend toward birth at earlier gestational age and increased use of both induction of labour (IOL) and caesarean section (CS) for women with term pregnancies in many countries, particularly high-income countries. Unnecessary use of obstetric interventions during pregnancy and birth is associated with an increased risk of adverse health outcomes for women and babies, as well as adding financial costs to the health care systems. Existing evidence regarding the association between IOL at term and CS is mixed and conflicting, and little evidence has been known about the differential effect at each gestation between 37 +0 – 41 +6 weeks, separately among nulliparous and parous women. Objective: The aim of this study was to explore the association between IOL and primary CS for women with singleton term pregnancies, compared with expectant management (EM) of pregnancy. Methods: We performed an analysis of population-based retrospective cohort data on women who gave birth in one Australian state (Queensland), between 01/07/2012 and 30/06/2018. All no-labour births (i.e., prelabour CS), multiple births (e.g., twins or triplets), and women with a prior CS were excluded. Five sub-datasets were created based on the time of birth following IOL (37 +0 - 37 +6; 38 +0 - 38 +6; 39 +0 - 39 +6; 40 +0 - 40 +6; and 41 +0 - 41 +6). Unadjusted relative risk (RR) and adjusted relative risk (aRR) were calculated in each sub-dataset to explore the risk of primary CS following IOL, compared to EM. Analysis was stratified by parity (nulliparas versus paras). Sensitivity analyses were conducted by limiting to women with low-risk pregnancies. Results: The risk of primary CS following IOL was significantly higher for women with singleton pregnancies, compared with EM, before or after adjustment, at 38 +0 - 38 +6 (nulliparas: aRR = 1.14, 95% CI: 1.10 - 1.18; paras: aRR = 1.35, 95% CI: 1.25 - 1.46), at 39 +0 - 39 +6 (nulliparas: aRR = 1.18, 95% CI: 1.14 - 1.22; paras: aRR = 1.36, 95% CI: 1.24 - 1.49), at 40 +0 - 40 +6 (nulliparas: aRR = 1.25, 95% CI: 1.21 - 1.29; paras: aRR = 1.40, 95% CI: 1.26 - 1.56) and at 41 +0 - 41 +6 (nulliparas: aRR=1.42, 95% CI: 1.36 - 1.48; paras: aRR=1.61, 95% CI: 1.40 - 1.84). After adjusting for potential confounders, there was no significant difference in the risk of primary CS at 37 +0 - 37 +6 for nulliparas who had IOL and EM (aRR = 1.03, 95% CI: 0.95 - 1.12). Results remain stable in the sensitivity analyses. Conclusion: Our results demonstrated that the risk of primary CS following IOL was higher at each weeks’ gestation between 38 +0 - 38 +6 – 41 +0 - 41 +6 for both nulliparas and paras with singleton pregnancies, compared with EM, and the risk increased with gestational age. This has important implications to support shared decision making between women and health professionals regarding best clinical management and optimal timing of birth.

Objective. To assess the potential of using machine learning and administrative birth data for predicting premature births. Design. The performance of ordinary least square (OLS) and deep neural network (DNN) classifiers for predicting low birth weight (LBW) and preterm birth (PTB) was compared using randomly selected two million birth records from the US CDC between 2016 and 2018. One million records from 2016 and 2017 were used to train the classifiers, while another million records from 2018 were utilized to test them. For hyperparameter tuning, a grid search with varying numbers of hidden layers, class weights on positive cases, and thresholds, was undertaken. Setting and Population: All births in the US Methods: ordinary least squares regression, deep neural networks Main Outcome Measures. LBW (<2,500g) and PTB(<37 weeks) Results. The classifiers generally showed high accuracy and specificity, however, the DNN classifiers showed much improvement in increasing sensitivity. Based on the results, the highest sensitivity with comparable specificity was 0.71 for LBW and 0.65 for PTB. Conclusion. These findings highlight that a ML approach could benefit PCHV programs by helping identify mothers with a high risk of premature birth. In particular, the DNN classifiers with administrative data can provide accessible solutions for public agencies and nonprofit organizations providing PCHV services that are not likely to possess massive clinical data or highly accurate genetic testing equipment.

Aluminum matrix composites reinforced with irregularly arranged fibers was fabricated using liquid metal infiltration technology. The cooling-induced residual stress and the subsequent tensile behavior were investigated by numerical and experimental method. The results show that the macroscopic thermal shrinkage curves obtained from the numerical simulation are consistent with the experimental ones. After the cooling process, the matrix and fiber are in the tensile and compressive stress states, respectively. The irregular fiber arrangement leads to an inhomogeneous residual stress distribution, which causes the plastic deformation and damage initiation of the matrix alloy within the smallest inter-fiber gaps. The numerical simulations involving the residual stress yield the tensile stress-strain curves that are in good agreement with the experimental ones. The cooling-induced residual stress and local damage promote the failure evolution behavior of the matrix and interface during the tensile process. As a result, the presence of residual stress resulted in reductions in axial strength and elastic modulus of 17.1% and 18.2%, and in transverse strength and fracture strain of 11.4% and 10.6%. The failure modes obtained from the numerical simulations are further validated by the fracture morphology of the tensile specimens.

In this paper, a microwave near-field power focusing approach is proposed using a cylindrical circumferential array of electric line sources for any arbitrary homogenous medium with zero magnetic losses. In order to focus the dissipated power at the arbitrary desired point, an efficient way to obtain the excitation phases of the array elements is provided using the theoretical analysis of the complex conjugate of the electric field. Also, a closed form for the concentrated power is obtained. Using full-wave simulations, it has been shown that the theoretical analysis results are well applicable for power focusing using an array of half-wave dipole antennas.

Pemigatinib treatment for intrahepatic cholangiocarcinoma with FGFR2 fusion detected by a liquid comprehensive genomic profiling testShun Ishido¹*, Nobuharu Tamaki¹*, Kento Inada¹, Jun Itakura¹, Yuka Takahashi¹, Naoki Uchihara¹, Keito Suzuki¹, Yuki Tanaka¹, Haruka Miyamoto¹, Michiko Yamada¹, Hiroaki Matsumoto¹, Tsubasa Nobusawa¹, Taisei Keitoku¹, Kenta Takaura¹, Shohei Tanaka¹, Chiaki Maeyashiki¹, Yutaka Yasui¹, Kaoru Tsuchiya¹, Hiroyuki Nakanishi¹, Masayuki Kurosaki¹#, Namiki Izumi¹*These authors equally contributed to this case report.#This author (Masayuki Kurosaki) is corresponding author.Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, JapanGuarantor of this article: Masayuki Kurosaki