Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract 2599: COSMIC Cancer Gene Census: expert descriptions across genes in oncogenesis

The Cancer Gene Census is an ongoing effort to catalogue genes for which somatic mutations have been causally implicated in cancer. The Census comprises manually curated summaries of the most relevant information for cancer-driving genes and their somatic mutations and brings together the expertise of a dedicated curation team, cancer scientists and the comprehensive resources of the COSMIC database. Current research focuses on characterising the participation of 609 census genes in hallmarks of cancer and identification of additional genes involved in these biological traits primarily via altered expression, CNA or epigenetic changes. New overviews of cancer gene function focused on hallmarks of cancer pull together manually curated information on the function of proteins coded by cancer genes and summarises the data in simple graphical form. It presents a condensed overview of most relevant facts with quick access to the literature source, aiming to provide summary characteristics of a cancer gene, rather than a full monography, to avoid information overload. This functional characterisation enables the creation of lists of genes of interest focused on the particular role they play in the development of cancer, as well as aiming to identify the cellular functions affected by mutations in particular tumours, and help to choose right targets for targeted therapy or synthetic lethality experiments. The Census is available from the COSMIC website for online use or download at: http://cancer.sanger. ac.uk/census. Citation Format: Zbyslaw Sondka, Sally Bamford, Charlotte G. Cole, Elisabeth Dawson, Laura Ponting, Raymund Stefancsik, Sari A. Ward, John Tate, Peter J. Campbell, Simon A. Forbes. COSMIC Cancer Gene Census: expert descriptions across genes in oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2017-2599
Mathematical and Software for Designing Rational Schemes of Cutting Rectangular Materials on Flat Geometric Objects With Complex Configuration of External Contours

The paper considers mathematical and software for automated design of rational schemes of cutting rectangular materials into flat geometric objects with a complex configuration of external contours. To solve this problem successfully, it is divided into the following four tasks: construction of a set of dense tabs for each of the flat geometric objects; generating a rational cutting scheme (sections) for each of the flat geometric objects; dense placement of sections in the cutting scheme; interactive adjustment of the received cutting scheme. For each of these four problems, mathematical models and methods for solving them are proposed. The tasks were implemented in software for the design of rational schemes for cutting rectangular materials on flat geometric objects with a complex configuration of external contours.
Molecular Mimicry and Uveitis

Molecular or antigenic mimicry is a term for the similarity of different antigens, which can be confused by the immune system. Antigen recognition by antibodies and T cell receptors is specific, but not restricted to a single antigen. Both types of receptors specifically recognize antigens and are expressed with a very high but still restricted variability compared to the number of different antigens they potentially could bind. T cell receptors only can bind to antigen peptides presented on certain self-MHC-molecules by screening only some amino acid side chains on both the presented peptides and the MHC molecule. The other amino acids of the peptide are not directly perceived by the T cell, offering the opportunity for a single T cell to recognize a variety of different antigens with the same receptor, which significantly increases the immune repertoire. The immune system is usually tolerant to autoantigens, especially to those of immune privileged sites, like the eye. Therefore, autoimmune diseases targeting these organs were hard to explain, unless a T cell is activated by an environmental peptide (e.g. pathogen) that is similar, but not necessarily identical with an autoantigen. Here we describe antigenic mimicry of retinal autoantigens with a variety of non-ocular antigens resulting in the induction of intraocular inflammation. T cells that are activated by mimotopes outside of the eye can pass the blood-retina barrier and enter ocular tissues. When reactivated in the eye by crossreaction with autoantigens they induce uveitis by recruiting inflammatory cells.
Revealing intricate acto-myosin dynamics at a membrane surface using interferometric scattering microscopy

The surface of mammalian cells, i.e. the plasma membrane and the underlying cytoskeletal cortex, constitutes an active platform for many cellular processes including cargo uptake, signaling and formation of cell adhesions. Experimental and theoretical work has recently shown that acto-myosin dynamics can modify the local membrane organization, but the molecular details are not well understood. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer. We demonstrate that we are able to detect and distinguish actin and myosin filaments label-free based on their interferometric scattering contrast. The scattering-based approach allows us to follow diffusion of single actin filaments attached to the bilayer at high frame rates revealing different types of diffusion depending on filament length. We investigate the directed motion of myosin II filaments on the actin network quantifying binding kinetics and processivity at varying ATP concentrations. Finally, we follow long-term network flow and organization enabling us to compare our observations with theoretical models of network dynamics. Our results demonstrate that iSCAT microscopy is an ideal tool to investigate multi-component systems on a broad range of length scales, resolving molecular scale mechanisms such as single myosin filament dynamics as well as acto-myosin network contraction on the mesoscopic scale.
Semantic enriched deep learning for document classification

Textual data are available in large unstructured volumes. Processing this data is becoming crucial and document classiﬁcation is a way of structuring and processing this information based on its content. This paper introduces an effective semantic text mining approach for document classiﬁcation. The proposed approach Semantic Enriched Deep Learning Architecture (SE-DLA) allows the model to learn simultaneously from the generated semantic vector representations and the original document vectors. We evaluated the proposed method on topic categorizations and multi-label classiﬁcation. The experiments demonstrate that the proposed hybrid architecture with the additional semantic knowledge improves the results. This approach was compared to some state-of-the-art text classiﬁcation approaches not including semantic knowledge. The proposed SE-DLA achieved higher accuracy and maintained great results during the experimental process.
Heart Development and Regeneration in Non-mammalian Model Organisms

Cardiovascular disease is a serious threat to human health and a leading cause of mortality worldwide. Recent years have witnessed exciting progress in the understanding of heart formation and development, enabling cardiac biologists to make significant advance in the field of therapeutic heart regeneration. Most of our understanding of heart development and regeneration, including the genes and signaling pathways, are driven by pioneering works in non-mammalian model organisms, such as fruit fly, fish, frog, and chicken. Compared to mammalian animal models, non-mammalian model organisms have special advantages in high-throughput applications such as disease modeling, drug discovery, and cardiotoxicity screening. Genetically engineered animals of cardiovascular diseases provide valuable tools to investigate the molecular and cellular mechanisms of pathogenesis and to evaluate therapeutic strategies. A large number of congenital heart diseases (CHDs) non-mammalian models have been established and tested for the genes and signaling pathways involved in the diseases. Here, we reviewed the mechanisms of heart development and regeneration revealed by these models, highlighting the advantages of non-mammalian models as tools for cardiac research. The knowledge from these animal models will facilitate therapeutic discoveries and ultimately serve to accelerate translational medicine.
Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility

Background: Changes in calcium metabolism are quite common in sarcoidosis: hypercalciuria is linked to a persistent clinical phenotype and more active disease. No data is yet available on the specificity of parameters of calcium metabolism as biomarkers for distinguishing different chronic interstitial lung diseases (ILD). Here we assessed calcium metabolism in an Italian population of sarcoidosis patients, which included a group with stage IV fibrotic disease, and compared the results with those of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP) patients. Population and Methods: We recruited sarcoidosis, IPF and cHP patients retrospectively. All patients were diagnosed through multidisciplinary discussion and were monitored at the Regional ILD Referral Centre in Siena. Clinical, radiological, functional, immunological and laboratory parameters were collected and entered in an electronic database for data analysis. Results: A total of 305 patients (237 sarcoidosis, 40 IPF and 28 cHP) were enrolled. Sarcoidosis patients included a predominance of females and were significantly younger than IPF and cHP patients (p < 0.0001 for both). In the sarcoidosis population, 17 patients (7.2%) showed radiological evidence of lung fibrosis, according the Scadding classification; fibrotic disease was also confirmed by CT scan. Concerning calcium metabolism, sarcoidosis patients showed significantly higher serum and urinary concentrations of calcium than IPF and cHP patients (p = 0.0004 and p < 0.0001, respectively). These findings were also confirmed when comparing groups with fibrotic sarcoidosis, IPF and cHP (p = 0.0237 and p = 0.0138). According to receiver operating characteristics (ROC) curve analysis, urinary calcium showed better diagnostic accuracy than serum calcium in discriminating sarcoid and non-sarcoid lung fibrosis (AUC 0.7658 vs. 0.6205; p = 0.0026 vs. p = 0.1820). Discussion: Our results confirmed that changes in calcium metabolism, particularly hypercalciuria, occur in a substantial percentage of patients with sarcoidosis. Higher serum and urinary concentrations of calcium were found than in IPF and cHP; the same results were observed when the comparison was limited to patients with fibrotic sarcoidosis, supporting the hypothesis that dysregulation of calcium metabolism may be a special feature of sarcoid granulomas. Hypercalciuria distinguished fibrotic sarcoidosis from IPF and cHP, suggesting that assessment of calcium metabolism may be useful in the diagnostic pathway of ILDs.
Natural Killer Lytic-Associated Molecule (NKLAM): An E3 Ubiquitin Ligase With an Integral Role in Innate Immunity

Natural Killer Lytic-Associated Molecule (NKLAM), also designated RNF19B, is a unique member of a small family of E3 ubiquitin ligases. This 14-member group of ligases has a characteristic cysteine-rich RING-IBR-RING (RBR) domain that mediates the ubiquitination of multiple substrates. The consequence of substrate ubiquitination varies, depending on the type of ubiquitin linkages formed. The most widely studied effect of ubiquitination of proteins is proteasome-mediated substrate degradation; however, ubiquitination can also alter protein localization and function. Since its discovery in 1999, much has been deciphered about the role of NKLAM in innate immune responses. We have discerned that NKLAM has an integral function in both natural killer (NK) cells and macrophages in vitro and in vivo. NKLAM expression is required for each of these cell types to mediate maximal killing activity and cytokine production. However, much remains to be determined. In this review, we summarize what has been learned about NKLAM expression, structure and function, and discuss new directions for investigation. We hope that this will stimulate interest in further exploration of NKLAM.
Characterization of the Secondary Neutron Field Produced in a Thick Aluminum Shield by 1 GeV/u 56Fe Ions Using TLD-Based Ambient Dosimeters

The neutron ambient dose equivalent induced by galactic cosmic-ray-like (1 GeV/u 56Fe) radiation stopped in a thick aluminum shield was measured at different angles with a GSI neutron ball, the standard TLD (thermoluminescent dosimeters)-based neutron dosimeter for area monitoring at the GSI facility. In order to measure reliably at large angles, a modified version of the GSI ball, including a set of three more sensitive TLD600H/700H cards, instead of one standard TLD600/700 card was used. The modified GSI balls were calibrated in neutron reference fields of 241Am-Be(α,n) available at the Physikalisch-Technische Bundesanstalt (PTB). The neutron ambient dose equivalent was measured at five different angles (15, 40, 90, 115, and 130 degrees) with respect to the beam direction and compared to the calculated detector response and neutron ambient dose equivalent results from FLUKA simulations. The dosimeter readings were corrected for signal contributions coming from secondary charged particles. An agreement within 15% was found between the measured and calculated GSI ball response and an agreement within 30% was found between experiments and calculated neutron dose equivalents.
The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling

VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The Vangl2Lp mutation causes lung branching defects due to dysfunctional actomyosin-driven morphogenesis. Since the actomyosin network regulates cell mechanics, we speculated that mechanosignaling could be impaired when VANGL2 is disrupted. Here, we used live-imaging of precision-cut lung slices (PCLS) from Vangl2Lp/+ mice to determine that alveologenesis is attenuated as a result of impaired epithelial cell migration. Vangl2Lp/+ tracheal epithelial cells (TECs) and alveolar epithelial cells (AECs) exhibited highly disrupted actomyosin networks and focal adhesions (FAs). Functional assessment of cellular forces confirmed impaired traction force generation in Vangl2Lp/+ TECs. YAP signaling in Vangl2Lp airway epithelium was reduced, consistent with a role for VANGL2 in mechanotransduction. Furthermore, activation of RhoA signaling restored actomyosin organization in Vangl2Lp/+, confirming RhoA as an effector of VANGL2. This study identifies a pivotal role for VANGL2 in mechanosignaling, which underlies the key role of the PCP pathway in tissue morphogenesis.
Transportation of broilers: An issue of welfare

Broiler industry is the one of the fastest growing sectors in India. Approximately 4.2 million metric tonnes of broiler chicken meat is currently produced in India. Poultry chicken meat production increased from 0.79 million tons to 4.2 million tons during the year 1980 and 2017 (Livestock Census). The proportion of broiler chickens dead on arrival (DOA) has been reported to vary from around 0.15% to 0.67% (Mitchell, 2006) . Transportation is considered a major stressor for broilers and might have deleterious effects on health, well-being, performance, and product quality. Transportation stress not only affects the chicken welfare but also decrease the quality of chicken and meat.
Microbial β-Glucosidase: Sources, Production and Applications

Cellulose is the most abundant biopolymer in biosphere and the major constituent of plant biomass. Cellulose polymer is made up of β-glucose units linked by β-glucosidic bonds. Cellulase is an enzymatic system that catalyzes the hydrolysis of cellulose polymer to glucose monomers. This enzymatic system consists of three individual enzymes namely endoglucanase, exoglucanase and β-glucosidase which act synergistically to degrade cellulose molecules into glucose. Cellulases are produced by bacteria, fungi, plants, and animals and used in many industrial applications such as textile industries, laundry and detergent industries, paper and pulp industry, animal feeds, and biofuels production. β-Glucosidase is a diverse group of enzymes with wide distribution in bacteria, fungi, plants and animals and has the potential to be utilized in various biotechnological processes such as biofuel production, isoflavone hydrolysis, flavor enhancement and alkyl/aryl β-D-glucoside and oligosaccharides synthesis. Thus, there is increased demand of β-glucosidase production from microbial sources under profitable industrial conditions. In this review, β-glucosidase classification, localization, and mechanism of action will be described. Subsequently, the various sources of β-glucosidase for industrial sector will be discussed. Moreover, Fermentation methods and various parameters affecting β-glucosidase production will be highlighted on the light of recent findings of different researchers. Finally, β-glucosidase applications in biofuel production, flavors enhancement, isoflavones hydrolysis, cassava detoxification and oligosaccharide synthesis will be described.
Origin of the Galilean satellites: Slow-pebble-accretion scenario

It is generally accepted that the Galilean satellites formed out of the gas disk that accompanied Jupiter's formation. We construct a new scenario for the origin of the Galilean system, based on the capture of several planetesimal seeds and subsequent slow accretion of pebbles. Our “slow-pebble-accretion” scenario then simultaneously and consistently reproduces the following characteristics: (1) the mass of all the Galilean satellites; (2) the orbits of Io, Europa, and Ganymede captured in mutual 2:1 mean motion resonances; (3) the ice mass fractions of all the Galilean satellites; (4) the unique ice-rock partially differentiated Callisto and the complete differentiation of the other satellites.
Effect of extrusion cooking and simulated in vitro gastrointestinal digestion on condensed tannins and radical scavenging activity of type II and type III whole grain sorghum

Summary The effect of extrusion cooking and simulated in vitro gastrointestinal digestion on proanthocyanidins in type II and III tannin sorghums was studied. Extrusion cooking was performed at different feed moisture levels (2 L h−1, 3 L h−1, 5 L h−1 and 8 L h−1), with a barrel temperature of 150 °C followed by in vitro gastrointestinal digestion. Extrusion cooked samples had lower total phenols, tannin content and radical scavenging properties than unprocessed tannin sorghum flour. For extrudates, there was progressive increase in total phenols and tannin content with increase in feed moisture. Extrusion cooked samples had increased proportion of dimers and decreased oligomers in the two tannin sorghums. Gastric and duodenal digests of the extrudates contained high proportions of monomers and dimers and some oligomeric proanthocyanidin species. Undigested porridges, gastric and duodenal digests inhibited radical-induced oxidative DNA damage. Extruded tannin sorghum may have health-promoting potential in relation to combating chronic diseases associated with oxidative stress.
Large unstained cells are correlated with inflammatory biomarkers in patients with invasive aspergillosis

Abstract Objective The percentage of large unstained cells (%LUCs) reflects peroxidase-negative cells and activated lymphocytes. Unlike other infections, the value of %LUCs in the diagnosis of fungal infections is not clear. We aimed to evaluate %LUCs and its correlations with other inflammatory parameters of invasive aspergillosis (IA) patients. Methods Twenty patients and 20 healthy participants were included. Full blood count parameters including %LUCs values were recorded. Platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), eosinophil to lymphocyte ratio (ELR) were calculated. Results There was a significant difference between the study groups for %LUCs [2.40 (2.22–3.25); 1.43 (1.25–2.10), respectively; p<0.001]. Furthermore, %LUCs were statistically significantly correlated with PLR, NLR and MLR (p=0.020, 0.040, 0.040; respectively) but not correlated with ELR (p>0.05). Conclusion The %LUCs values were significantly increased and correlated with markers of inflammation in patients. We suggest that the %LUCs is a useful predictor and may be an aid in the diagnosis and/or the management of IA and may help clinicians for follow up these patients in therapy process. Our study provides target pathways for further studies in the diagnosis of Aspergillus-infected patients using inflammatory parameters.
Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population

Background Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. Methods This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. Results During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators. Conclusion Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.
Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology

Glutamate delta (GluD) receptors belong to the ionotropic glutamate receptor family, yet they don’t bind glutamate and are considered orphan. Progress in defining the ion channel function of GluDs in neurons has been hindered by a lack of pharmacological tools. Here, we used a chemo-genetic approach to engineer specific and photo-reversible pharmacology in GluD2 receptor. We incorporated a cysteine mutation in the cavity located above the putative ion channel pore, for site-specific conjugation with a photoswitchable pore blocker. In the constitutively open GluD2 Lurcher mutant, current could be rapidly and reversibly decreased with light. We then transposed the cysteine mutation to the native receptor, to demonstrate with high pharmacological specificity that metabotropic glutamate receptor signaling triggers opening of GluD2. Our results assess the functional relevance of GluD2 ion channel and introduce an optogenetic tool that will provide a novel and powerful means for probing GluD2 ionotropic contribution to neuronal physiology.