Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of unique loci that underlie nematode responses to benzimidazoles

Parasitic nematodes impose a debilitating health and economic burden across much of the world. Nematode resistance to anthelmintic drugs threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to these critical drugs remains largely unexplored. Here, we exploit natural variation in the model nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely used in human and animal medicine. High-throughput phenotyping of albendazole, fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant lines led to the discovery of over 15 QTL in C. elegans and four QTL in C. briggsae associated with divergent responses to these anthelmintics. Many of these QTL are conserved across benzimidazole derivatives, but others show drug and dose specificity. We used near-isogenic lines to recapitulate and narrow the C. elegans albendazole QTL of largest effect and identified candidate variants correlated with the resistance phenotype. These QTL do not overlap with known benzimidazole resistance genes from parasitic nematodes and present specific new leads for the discovery of novel mechanisms of nematode benzimidazole resistance. Analyses of orthologous genes reveal significant conservation of candidate benzimidazole resistance genes in medically important parasitic nematodes. These data provide a basis for extending these approaches to other anthelmintic drug classes and a pathway towards validating new markers for anthelmintic resistance that can be deployed to improve parasite disease control. Author Summary The treatment of roundworm (nematode) infections in both humans and animals relies on a small number of anti-parasitic drugs. Resistance to these drugs has appeared in veterinary parasite populations and is a growing concern in human medicine. A better understanding of the genetic basis for parasite drug resistance can be used to help maintain the effectiveness of anti-parasitic drugs and to slow or to prevent the spread of drug resistance in parasite populations. This goal is hampered by the experimental intractability of nematode parasites. Here, we use non-parasitic model nematodes to systematically explore responses to the critical benzimidazole class of anti-parasitic compounds. Using a quantitative genetics approach, we discovered unique genomic intervals that control drug effects, and we identified differences in the genetic architectures of drug responses across compounds and doses. We were able to narrow a major-effect genomic region associated with albendazole resistance and to establish that candidate genes discovered in our genetic mappings are largely conserved in important human and animal parasites. This work provides new leads for understanding parasite drug resistance and contributes a powerful template that can be extended to other anti-parasitic drug classes.
The role of DOK7 and its variants in colorectal cancer

The downstream of tyrosine kinase (Dok) protein family has seven members, Dok 1-7. The precise role of these proteins is not entirely clear although some authors have suggested a potential tumour suppressor role. The aims of this clinically oriented PhD were to determine the expression profile and role of DOK7 in human colorectal cancer, to determine whether DOK7 expression is associated with tumour pathology and clinical outcome data, to determine the functional role of DOK7 in colorectal cancer cells and to evaluate DOK7 coordinated cell signalling in colorectal cancer. Initial work revealed that DOK7 mRNA expression is significantly reduced in colorectal cancer tissue compared with normal colorectal tissue and is associated with overall survival in patients with colorectal cancer. DOK7 is variably expressed in colorectal cancer cell lines with high expression in HRT-18 cells and low expression in HT-115 and RKO cells. Difficulties in obtaining DOK7 knockdown and expression subsequently revealed that DOK7 has several splice variants coding for different isoforms. Further work investigating DOK7 variants 1-3 (DOK7V1-3) revealed that DOK7V1 mRNA expression is significantly reduced in colorectal cancer tissue compared with normal colorectal tissue and is associated with disease-free status and length of diseasefree survival. In contrast, DOK7V2 and DOK7V3 mRNA expression is significantly increased in colorectal cancer tissue compared with normal colorectal tissue. Functional assays using a DOK7V2 overexpression model did not show a significant difference in colorectal cancer cell growth, adhesion or invasion in RKO DOK7V2 overexpression cells compared to the control cell line. However, antibody based protein microarray revealed that DOK7V2 overexpression is associated with significant changes in the expression and phosphorylation (activation) of numerous proteins in RKO cells. Cell signalling pathways potentially implicated include PI-3K-Akt, mTOR, MAPK, Jak/STAT and angiogenesis signalling pathways. Our findings suggest that DOK7 plays an important role in colorectal carcinogenesis and that DOK7 isoforms may ply different and possibly opposing roles. Protein microarray data provides a number of potential avenues for further work to elucidate the interaction of Dok7 with other cell signalling proteins and may help identify future potential therapeutic targets.
Collective creativity: strategies for catalyzing interdisciplinary research

Fostering interdisciplinary collaboration is critical for addressing complex research problems. At the earliest stages of research ideation and mobilization, we need to create environments that cultivate collective creativity, curiosity and decision making among those with diverse expertise. The fields of design and design thinking offer excellent tools and approaches for promoting rich conversations while simultaneously navigating ambiguity. Here we describe how design strategies can support team science, specifically as loosely formed groups collaboratively brainstorm around intractable problems. Abstract
Chewing behaviour and particle size distribution in faeces in sheep fed silages of whole-crop barley and grass

Sheep in Sweden are generally kept on pasture when suitable and fed with a diet consisting mainly of forage, composed mainly by grass, when kept indoors. Lamb production in Sweden is steadily growing and with that the interest of different feedstuff to get a profitable production. Whole-crop barley silage has a high content of nutrients and a higher digestibility in comparison to whole-crop spring-sown wheat and oat. The aim of this experiment was to study the effect of whole crop barley silage and grass silage harvested at different maturity stages on consumption, chewing behaviour and faecal particle size in sheep. The silages used were two grass silages harvested May 31 and June 30 and two whole-crop barley silages harvested at heading stage June 30 and at milk stage July 18. Eight wethers were divided into two 4 x 4 Latin Squares (four wethers and four periods) with one group fed forage only and the other group fed forage an rapeseed meal as protein supplementation. Each period was four weeks where the wethers were fed ad libitum during the first three weeks and during the fourth week they were fed restricted with 80% of ad libitum. At the end of the trial, all wethers had been fed all diets. During the restricted period they were kept in metabolic cages where all faeces were collected and their chewing patterns were registered. The live weight of the wethers, the body condition score and the feed intake was continuously measured throughout the trial. Samples of feed and faeces were collected daily during the restricted period. The dry matter intake as percentage of live weight was lower for grass silages compared to the barley silages (P < 0.01). No difference between the maturity stages was found regarding dry matter intake. The intake of neutral detergent fibre increased with advancing maturity of the grass silages, but this could not be seen for the whole-crop barley silages (P < 0.001). Time spent chewing ranged from 629 to709 minutes per day, time spent ruminating ranged from 475 to 542 minutes per day and time spent eating ranged from 141 to 175 minutes per day. This is in line with other studies. The particle size in faeces was effected by forage type (P < 0.05). The proportion of large particles was higher in wethers fed whole-crop barley silage harvested at milk stage compared to the other silages (P < 0.05). In conclusion, no large differences between the four treatments were found suggesting that whole-crop barley silages could be a suitable equivalent to grass silage in lamb production given that it is not harvested too late.
Production and characterisation of glycoside hydrolases from GH3, GH5, GH10, GH11 and GH61 for chemo-enzymatic synthesis of xylo- and mannooligosaccharides

Τwo β-xylosidases of glycoside hydrolase family 3 (GH 3) from Aspergillus nidulans FGSC A4, BxlA and BxlB were produced recombinantly in Pichia pastoris and secreted to the culture supernatants in yields of 16 and 118 mg/L, respectively. BxlA showed about 6 fold higher catalytic efficiency (kcat/Km) than BxlB towards para-nitrophenyl β-D-xylopyranoside (pNPX) and β-1,4xylo-oligosaccharides (degree of polymerisation 2−6). For both enzymes kcat/Km decreased with increasing β-1,4-xylo-oligosaccharide chain length. Using pNPX as donor with 9 monosaccharides, 7 disaccharides, and two sugar alcohols as acceptors 18 different β-xylosyl-oligosaccharides were synthesised in 2−36% (BxlA) and 6−66% (BxlB) yields by transxylosylation. BxlA utilised the monosaccharides D-mannose, D-lyxose, D-talose, D-xylose, D-arabinose, L-fucose, D-glucose, Dgalactose, and D-fructose as acceptors, whereas BxlB used the same except for D-lyxose, Darabinose, and L-fucose. BxlB transxylosylated the disaccharides xylobiose, lactulose, sucrose, lactose, and turanose in up to 35% yield, while BxlA gave inferior yields. The regioselectivity was acceptor dependent and primarily involved β-1,4 or 1,6 product linkage formation although minor products with different linkages were also obtained. Five of the 18 transxylosylation products obtained from D-lyxose, D-galactose, turanose and sucrose (two products) as acceptors were novel xylosyl-oligosaccharides, β-D-Xylp-(1→4)-D-Lyxp, β-D-Xylp-(1→6)-D-Galp, β-D-Xylp-(1→4)-αD-Glcp-(1→3)-β-D-Fruf, β-D-Xylp-(1→4)-α-D-Glcp-(1→2)-β-D-Fruf, and β-D-Xylp-(1→6)-β-DFruf-(2→1)-α-D-Glcp, as structure-determined by 2D NMR, indicating that GH3 β-xylosidases are able to transxylosylate a larger variety of carbohydrate acceptors than earlier reported. Furthermore, transxylosylation of certain acceptors resulted in mixtures of products of which the individual structures have not been determined. Some of these products are also novel.
Regression with Gaussian Mixture ModelsApplied to Track Fitting

This note describes the application of Gaussian mixture regression to track fitting with a Gaussian mixture model of the position errors. The mixture model is assumed to have two components with identical component means. Under the premise that the association of each measurement to a specific mixture component is known, the Gaussian mixture regression is shown to have consistently better resolution than weighted linear regression with equivalent homoskedastic errors. The improvement that can be achieved is systematically investigated over a wide range of mixture distributions. The results confirm that with constant homoskedastic variance the gain is larger for larger mixture weight of the narrow component and for smaller ratio of the width of the narrow component and the width of the wide component.
Investigation of brain computer interface for rich multimedia environment

The brain computer interface (BCI) can provide a direct channel of communication between an external device and the brain without including any type of muscular activity. Various applications of BCI have been stated in literature, and one of the most exciting areas which have not been extensively investigated is the field of multimedia. BCI can find huge potential in the area of command and control of video games. Video games have found huge potential for improving the gait and balance of people struggling with Parkinson's disease. Such systems make use of the brain signals which are captured through electrodes on scalp as electroencephalogram (EEG) or through implanted electrodes as electrocorticography (ECoG). The signals are then used as input commands to get desired output in an external device. To address the memory management issue arising due to the huge volume of ECoG data and to achieve distributed computation for improving the efficiency of BCI, the computations are implemented in Cloud. In this work, ECoG signals are pre‐processed, and all features are extracted by using the wavelet packet transform (WPT), common spatial patterns (CSPs), Laplacian filter, and the Kalman filter. The Adaboost classifier was employed for ECoG signal classification.
STABILITY CHARACTERISTICS OF COMPRESSIBLE BINARY PLANAR JETS

The present work investigates the stability of compressible binary planar jets. Different from a homogeneous jet, where a single chemical species is present, the binary jet may have strong density gradients due to the choice of the chemical species considered in each stream. The goal is to identify the possible instability modes for simple and co-flowing jets and investigate the effect of density gradients on the flow structure, growth rates, unstable frequency range and disturbance phase speed for each mode. The effect of species concentration on free shear layer stability has been reported previously in the literature, but detailed comparisons between stability modes and characteristics for a range of density ratios typical of oxygen and hydrogen mixtures as well as the identification of inner and outer sinuous and varicose modes are new. Linear stability theory is used to determine the stability characteristics of the different configurations. For the co-flowing jet four different modes are found, the inner and outer shear layers both have sinuous and varicose modes. Both for the sinuous and varicose modes the simple jet is more unstable when the fluid with the highest density is at the inner jet, with amplification rates twice as high as the lowest density ratio considered, but the range of unstable frequencies can be four times lower. The sinuous mode is less dispersive than the varicose and the disturbance speeds may vary by one order of magnitude with density ratio. For co-flowing jets the external mode is up to seven times more unstable, but this is due to the choice of the velocity ratio considered. For the inner mode the density gradient has a stabilizing effect regardless of which species is at the center. The co-flowing jet is more dispersive, except for the varicose inner mode. The variation of phase speed with density gradient is not as strong as in the simple jet. The ratio of larges to lower phase speeds are of the order of 2 for the co-flowing jet and 4 for the simple jet.
A complex Fourier series solution for free vibration of arbitrary straight-sided quadrilateral laminates with variable angle tows

Abstract Based on classical laminated plate theory, the free vibration of arbitrary straight-sided quadrilateral laminates with variable angle tows (VAT) is studied. It is assumed that the fiber orientation angle in each ply of VAT laminate varies linearly along x direction. The laminates have elastic restraints on the boundaries to simulate arbitrary boundary conditions. A four-node coordinate transformation is used to transform the arbitrary quadrilateral plate in physical domain into a square one. The complex Fourier series is employed to denote the transverse vibration mode of VAT laminates. The natural frequency and mode shape are obtained. Convergence and accuracy of the present method are verified through the comparison with those existing results. The influence of fiber path, boundary stiffness and boundary conditions on the natural frequency of VAT laminate is investigated in detail. The results presented here may be helpful for the design of VAT composite laminates.
New insights on potential therapeutic options and vaccines for corona virus disease-2019

In December 2019, world health organization was acquainted of the outbreak of pneumonia of unknown cause The causative agent was identified as a novel coronavirus and named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the disease coronavirus disease-19 (COVID-19) This disease is a pandemic, which has so far, caused more than 376 320 deaths globally Owing to the high transmission and mortality of COVID-19, identifying ways to circumvent the imbroglio has become the top priority of researchers across different parts of the world To date, no treatment or preventive approach has been developed Two approaches can be employed to solve the conundrum, a curative/therapeutic and a preventive approach The therapeutic approach can be divided into two aspects, blocking various aspects of viral entry into target cells and completion of its life cycle using antiviral drugs whereas the second aspect involves modification of host immune responses and inhibition of cell surface receptors and enzymes required for SARS-CoV-2 infection The preventive approach involves the development of vaccines Recent advances in the development of drugs targeting host cell receptors and enzymes, SARS-CoV-2-specific antibodies, immunomodulatory drugs, and vaccines have been discussed in this review
Flow cytometric analysis of leukocyte surface molecule expression in critical illness : comparison between septic and non-septic patients

Sepsis is a common problem in the intensive care unit (ICU) still having a high mortality and causing high costs to health care system. Currently, there is no marker to distinguish sepsis from other causes of systemic inflammation. Leukocyte surface molecules have been proposed as markers of sepsis. The most promising markers have been neutrophil CD64 and CD11b on monocytes and neutrophils and HLA-DR on monocytes. In this thesis, leukocyte surface molecules were investigated using quantitative flow cytometry in critically ill patients with sepsis, non-septic ICU controls, and healthy volunteers. The surface molecules of interest were neutrophil CD11b and CD64, monocyte CD11b, CD14, CD40, CD64, CD80, HLA-DR, and lymphocyte CD69. First, a special emphasize was indicated in methodological aspects of the quantitative flow cytometry. Then, the surface molecule kinetics was investigated in different types of critically ill patients. Finally, the diagnostic performance of the molecules was determined and compared to that of traditionally used sepsis markers. Furthermore, an example of multiple marker analysis was introduced as a diagnostic tool. The optimal circumstances for leukocyte surface molecule analysis were +4°C temperature throughout the collection and preparation of the samples using tubes containing acid citrate dextrose (ACD) as an anticoagulant, followed by flow cytometry within 6 hours from sampling. Monocyte CD11b and CD40, neutrophil CD11b and CD64, and CD69 on CD4+ T cells and natural killer (NK) cells separated sepsis from non-septic ICU controls and healthy volunteers, neutrophil CD64, having the best area under curve. Procalcitonin (PCT) was second best marker. Monocyte CD40 and NK CD69 may predict positive blood culture detection, whereas CD11b may predict early mortality. In multiple marker analysis, combination of positive neutrophil CD64, Creactive protein (CRP) and PCT increased post-test probability for sepsis. In conclusion, pre-analytical and analytical factors have effects on results of leukocyte surface molecule analysis. Leukocyte surface molecules may improve sepsis diagnostics in ICU setting. Neutrophil CD64 was the most promising marker. Combination of CD64, CRP and PCT increased the detection of sepsis in ICU.
Hybrid thematic analysis reveals themes for assessing student understanding of biotechnology

Abstract Despite efforts to increase teaching of biotechnology worldwide, there are concerns that public literacy of genetic technologies remains insufficient. Improved education strategies are expected to empower individuals to make informed decisions about biotechnology. To evaluate the teaching and learning of this complex topic, qualitative assessment tools are needed. In this case study, we performed a hybrid thematic analysis to identify a set of overarching themes that can be used to evaluate individuals’ understanding of genetic technologies. We analysed the written justifications students gave for their attitudes on a range of genetic technologies, before and after peer-led discussion of each topic. We identified seven themes commonly detected in student responses, five of which have been previously described in studies of mass media communication of biotechnology. Our preliminary analysis suggests that peer-led discourse can promote changes in student understanding of biotechnology. We conclude that hybrid thematic analysis is a useful approach for evaluating the teaching and learning of genetic technologies. We discuss the utility of the hybrid approach and the themes described here for future studies of biotechnology education.
Tillage and weed management on yield and nutrient uptake of wheat under maize-wheat cropping system in Western Himalayas

A field experiment was conducted during Rabi season of 2013–14 and 2014–15 at SKUAST-Jammu to study the effect of tillage and weed management on yield and nutrient uptake of wheat under maizewheat cropping system in sub-tropical irrigated conditions. The results revealed that different tillage systems recorded non-significant grain yield of wheat. However, ZT in wheat either preceded by conventional tillage (CT) or zero tillage (ZT) in maize was more beneficial as it recorded higher net returns and benefit: cost ratio than CT in wheat. Among the weed management, post-emergence application of metribuzin at 200 g/ha resulted in lowest total weed density and biomass of weeds, which was statistically at par with two hand weedings and significantly lower than weedy check. The postemergence application of metribuzin at 200 g/ha also recorded highest weed control efficiency (WCE), net returns and B: C ratio during both the years of experimentation followed by two hand weedings.
Isolation and activity of a Bacillus thuringiensis toxins which is toxic to the Aedes eagypti.

A Bacillus thuringiensis isolates has been discovered which is toxic to the dengue fever vector, Aedes eagypti as well as other Diptera and Lepidoptera . Crystal &endotoxins purified from this isolates killed 50% of Aedes aegypti larvae at the concentration of 10.2 ug/ml , and β-exotoxin was not detected . Sodium dodecyl polyacrylamide get electrophoresis of the purified crystals revealed three protein species which were related to Cry IA(b),CryIB and CryIIA toxins on the basis of immunoreactivity and amino-terminal sequence determination. southern bolt and DNA restriction analysis suggested that the strain has sequences related to one cryIA(b),one cryIIA, and two cryIIB genes . [Al-Zahrani, H. A. A, and Abuldahab, F. F. Isolation and activity of a Bacillus thuringiensis Toxins which is Toxic to the Aedes eagypti]. Journal of American Science 2011; 7(11):269-273]. (ISSN: 1545-1003). http://www.americanscience. org.