gebhart/patrepeval huggingface dataset:
Convergent Mechanisms of Somatic Mutations In Polycythemia Vera (2010)

Abstract Abstract 1979 Polycythemia vera (PV) is an acquired clonal blood disorder characterized by variable increased number of clonal myeloid cells (erythrocytes, granulocytes and platelets) and mostly normal polyclonal T lymphocytes. Most patients carry a gain-of function JAK2 V617F mutation in 2 copies acquired by a uniparenteral disomy; i.e. a copy-neutral loss of heterozygosity (LOH) in chromosome 9p in PV pathogenesis. Yet, JAK2 V617F mutation is not a PV-initiating event and the family clustering of PV suggests a contribution of inherited genetic events to its pathogenesis. Interestingly, majority of PV subjects acquire the JAK2 V617F mutation on a distinct a germline SNP 9p24.1 haplotype. Using whole-genome SNP arrays, we assayed 34 T-cells and 66 granulocytes from PV patients (including 32 pairs from the same patient). Comparison to a control population identified multiple germline SNPs around JAK2 as being associated with PV susceptibility (rs11999802, P=1.8×10-8, OR=4.4). Analysis of somatic genomic changes in granulocytes revealed strong genetic heterogeneity: we detected 9p LOH in 36% of the patients, 9p chromosomal gain in 1 patient, as well as “fractional LOH” in 14% of the patients where a small fraction of granulocytes have LOH. Interestingly, the magnitude of somatic LOH in 9p was strongly associated with somatic V617F allelic dosage (r=0.74, P=4.8×10-12), suggesting that LOH preferentially increase V617 PV subclone without altering genomic copy number. Adjusting for the fractional LOH, we did not have sufficient power to detect association between rs11999802 germline genotypes and increased dosage of somatic V617F mutations. Analysis of granulocytes with heterozygous rs11999802 genotypes demonstrated that LOH increases the relative fraction of germline risk alleles versus non-risk alleles. In summary, germline risk variants surrounding JAK2 predispose to somatic SNVs within JAK2, whose allelic dosage can be further increased by a serial subclonal expansion of allele-specific copy-neutral LOH or chromosomal duplications. Our study illustrates how convergent mechanisms of somatic mutations increase the genetic load of gain-of-function mutations contributing to the clonal expansion and disease pathogenesis. Figure 1 Box plot of the percentage of somatic V617F mutation in JAK2 over each of the fractional LOH measures in granulocytes. Strong correlation between these two measures was detected (r=0.74, P=4.8×10-12). Figure 1. Box plot of the percentage of somatic V617F mutation in JAK2 over each of the fractional LOH measures in granulocytes. Strong correlation between these two measures was detected (r=0.74, P=4.8×10-12). Disclosures: No relevant conflicts of interest to declare.
3-, 6-, and 12-month results of autologous transplantation ofmononuclear bone marrow cells in patients with acute myocardialinfarction (2007)

3-, 6-, and 12-month results of autologous transplantation of
mononuclear bone marrow cells in patients with acute myocardial
infarction
Section Review Pulmonary-Allergy, Dermatological, Gastrointestinal &amp; Arthritis: Experimental cytokine modulation therapy of inflammatory bowel disease (Crohn's disease and ulcerative colitis) (1996)

Crohn's disease and ulcerative colitis are chronic, idiopathic inflammatory bowel diseases (IBD). Although current drugs are reasonably efficient in the treatment of IBD, there are still a significant number of patients with either insufficient response to, or inhibitory side-effects following standard treatment. New approaches to the treament of these patients are therefore warranted. Immunoinflammatory reactions are initiated and controlled by cytokines. Cytokines relay distinct information between cells involved in all aspects of inflammation. This makes them interesting targets for therapy. This article outlines the basis for specific cytokine-directed therapy in IBD as well as the current use of experimental, cytokine-modulating drugs.
The Peptide-Substrate-binding Domain of Human Collagen Prolyl 4-Hydroxylases (2003)

The collagen prolyl 4-hydroxylases (C-P4Hs) catalyze the formation of 4-hydroxyproline by the hydroxylation of proline residues in -Xaa-Pro-Gly-sequences. The vertebrate enzymes are alpha 2 beta 2 tetramers in which protein-disulfide isomerase serves as the beta subunit. Two isoforms of the catalytic alpha subunit have been identified and shown to form [alpha(I)]2 beta 2 and [alpha(II)]2 beta 2 tetramers, the type I and type II C-P4Hs, respectively. The peptide-substrate-binding domain of type I C-P4H has been shown to be located between residues 138 and 244 in the 517-residue alpha(I) subunit and to be distinct from the catalytic domain that is located in the C-terminal region. We report here that a recombinant human C-P4H alpha(I) polypeptide Phe144-Ser244 forms a folded domain consisting of five alpha helices and one short beta strand. This structure is quite different from those of other proline-rich peptide-binding modules, which consist mainly of beta strands. Binding of the peptide (Pro-Pro-Gly)2 to this domain caused major chemical shifts in many backbone amide resonances, the residues showing the largest shifts being mainly hydrophobic, including three tyrosines. The Kd values determined by surface plasmon resonance and isothermal titration calorimetry for the binding of several synthetic peptides to the alpha(I) and the corresponding alpha(II) domain were very similar to the Km and Ki values for these peptides as substrates and inhibitors of the type I and type II C-P4H tetramers. The Kd values of the alpha(I) and alpha(II) domains for (Gly-Pro-4Hyp)5 were much higher than those for (Pro-Pro-Gly)5, indicating a marked decrease in the affinity of hydroxylated peptides for the domain. Many characteristic features of the binding of peptides to the type I and type II C-P4H tetramers can thus be explained by the properties of binding to this domain rather than the catalytic domain.
Bell Correlations at Ising Quantum Critical Points (2019)

When a collection of distant observers share an entangled quantum state, the statistical correlations among their measurements may violate a many-body Bell inequality, demonstrating a nonlocal behavior. Focusing on the Ising model in a transverse field with power-law (1/r^{α}) ferromagnetic interactions, we show that a permutationally invariant Bell inequality based on two-body correlations is violated in the vicinity of the quantum-critical point. This observation, obtained via analytical spin-wave calculations and numerical density-matrix renormalization group computations, is traced back to the squeezing of collective-spin fluctuations generated by quantum-critical correlations. We observe a maximal violation for infinite-range interactions (α=0), namely, when interactions and correlations are themselves permutationally invariant.
Thromboembolic prophylaxis protocol with warfarin after radiofrequency catheter ablation of infarct‐related ventricular tachycardia (2018)

A slowly escalating bridging regimen of UFH, followed by 3 months of oral anticoagulation, is associated with low thromboembolic and bleeding risks after infarct-related VT ablation. In the absence of extensive ablation, antiplatelet therapy alone is reasonable.
Multidimensional degradomics identifies systemic autoantigens and intracellular matrix proteins as novel gelatinase B/MMP-9 substrates (2009)

The action radius of matrix metalloproteinases or MMPs is not restricted to massive extracellular matrix (ECM) degradation, it extends to the proteolysis of numerous secreted and membrane-bound proteins. Although many instances exist in which cells disintegrate, often in conjunction with induction of MMPs, the intracellular MMP substrate repertoire or degradome remains relatively unexplored. We started an unbiased exploration of the proteolytic modification of intracellular proteins by MMPs, using gelatinase B/MMP-9 as a model enzyme. To this end, multidimensional degradomics technology was developed by the integration of broadly available biotechniques. In this way, 100-200 MMP-9 candidate substrates were isolated, of which 69 were identified. Integration of these results with the known biological functions of the substrates revealed many novel MMP-9 substrates from the intracellular matrix (ICM), such as actin, tubulin, gelsolin, moesin, ezrin, Arp2/3 complex subunits, filamin B and stathmin. About 2/3 of the identified candidates were autoantigens described in multiple autoimmune conditions and in cancer (e.g. annexin I, nucleolin, citrate synthase, HMGB1, alpha-enolase, histidyl-tRNA synthetase, HSP27, HSC70, HSP90, snRNP D3). These findings led to the insight that MMPs and other proteases may have novel (immuno)regulatory properties by the clearance of toxic and immunogenic burdens of abundant ICM proteins released after extensive necrosis. In line with the extracellular processing of organ-specific autoantigens, proteolysis might also assist in the generation of immunodominant 'neo-epitopes' from systemic autoantigens. The study of proteolysis of ICM molecules, autoantigens, alarmins and other crucial intracellular molecules may result in the discovery of novel roles for proteolytic modification.
An Outstanding Scientific Knee Paper from the Specialty Societies (2009)

Learning Objective Understand the predictions relative to demand for total joint replacement and supply of arthroplasty-trained surgeons in the United States
ChemInform Abstract: Metal‐Free C—H Arylation of Aminoheterocycles with Arylhydrazines. (2016)

Abstract Heterocyclic amines and diamine (Ib) are successfully arylated under atmospheric conditions in the presence of an inexpensive base.
FUNCTIONAL CONNECTIVITY CHANGES IN MILD TRAUMATIC BRAIN INJURY ASSESSED USING MAGNETOENCEPHALOGRAPHY (2012)

In this study, we analyzed brain connectivity profiles from 10 mild traumatic brain injury (mTBI) patients and 10 age- and gender-matched normal controls. We computed Granger causality measures from magnetoencephalographic (MEG) activity obtained at the resting state, in an attempt to understand how the default network is affected by mTBI. A connectivity matrix was computed for each subject individually and then group templates were estimated by averaging all matrices in each group. Furthermore, we performed classification of the subjects using support vector machines and Fisher's criterion to rank the features and identify the best subset for maximum separation of the groups. Our results show that a combined model based on connectivity matrices and graph theory measures can provide a minimum of 85% classification accuracy in separating the two groups, with a sensitivity and specificity of 90% and 80%, respectively. These findings suggest that analysis of functional connectivity patterns may provide a valuable tool for early detection of mTBI.
Use of IMMS for the investigation of the effects of shapes, densities and dipole moments on the CCS of small metal complexes (2019)

Ion mobility mass spectrometry provides the collision cross section (CCS) of ions in the gas phase. The CCS growth of ions sharing similar physicochemical properties such as charge state, geometry, shape, apparent density and dipole moments correlates well with their masses evolution. In this presentation, we study the effect on the CCS/mass correlations after variation of these physicochemical properties using a set of negatively charged iron center complexes with halogens (chloride, bromide and iodide) and carboxylates (linear or branched mono carboxylate) as ligands. Due to the halogen ligands are more compact and denser than the carboxylate ligands, all combinations of these ligands lead to a set of iron center complexes (theoretically superior to 250 complexes) having different CCS growth. Indeed, the number of ligands imposes the geometry (linear, trigonal plan, tetrahedral) while the halogen/carboxylate ligands ratio influences the apparent densities and the shape (spherical or near spherical) of the complex ions. Moreover, theses complex ions also share different dipole moment. These properties have been estimated by computational chemistry (Molecular Mechanism or Density Functional Theory levels) for each complex whereas the CCS and mass values have been measured by traveling wave ion mobility (Water’s Synapt G2). Comparing all the experimental CCS/mass trends in function of the physicochemical properties shows that the apparent density is the main factor influencing these correlations following by the shape and geometry factors. The variations on the dipole moment of theses complexes seems to be insufficient to significantly affect the CCS/mass correlation. This work also highlights the capability of CCS prediction of a given ion based on its mass, apparent density, shape, geometry, and the dipole moment.
Modelling, design and optimisation of a battery charger for plug-in hybrid electric vehicles (2011)

A PowerPC-centred 110 VAC/2.5 kW full-bridge isolated battery charger was developed for the plug-in hybrid electric vehicle (PHEV). Genetic algorithm was adopted to optimise the system key parameters. Phase-shift-based operation modes were analysed in detail. The system-level safe operational area and other practical design considerations were discussed in detail. Experiments validated the design strategies. Finally, the optimisation of a fast PHEV charger was provided.
The Guanidinium Group as a Key Part of Water‐Soluble Polymer Carriers for siRNA Complexation and Protection against Degradation (2014)

Here, the preparation of a novel block copolymer consisting of a statistical copolymer N-(2-hydroxypropyl) methacrylamide-s-N-(3-aminopropyl) methacrylamide and a short terminal 3-guanidinopropyl methacrylamide block is reported. This polymer structure forms neutral but water-soluble nanosized complexes with siRNA. The siRNA block copolymer complexes are first analyzed using agarose gel electrophoresis and their size is determined with fluorescence correlation spectroscopy. The protective properties of the polymer against RNA degradation are investigated by treating the siRNA block copolymer complexes with RNase V1. Heparin competition assays confirm the efficient release of the cargo in vitro. In addition, the utilization of microscale thermophoresis is demonstrated for the determination of the binding strength between a fluorescently labeled polyanion and a polymer molecule.
Electron waves through quantum point contacts (1992)

This paper reviews the authors work on the experimental and theoretical analyses of the angular distribution of electrons injected through a single quantum point contact. They observed double peaks in the distribution with the point contact quantized in two modes. The authors calculation of the distribution using a Fraunhofer diffraction approximation through a quantized single slit agreed well with results. In this calculation they use a Green's function in weak magnetic fields and constructed mirror images there. They also investigated the possibility of observing interference in the angular distribution between the first and second modes, and found that the interference terms of the angular distribution were cancelled due to system symmetry. Another possible way to observe interference is due to electron waves through double point contacts. To measure this interference, the authors developed submicron air bridges to make double point contacts with independently controlled widths. The authors measured the controlled additivity of the conductance for four point contacts.
Blind adaptive analog nonlinear filters for noise mitigation in powerline communication systems (2015)

It has been shown that the performance of power line communication (PLC) systems can be severely limited by non-Gaussian and, in particular, impulsive interference from a variety of sources. The non-Gaussian nature of this interference provides an opportunity for its effective mitigation by nonlinear filtering. In this paper, we introduce blind adaptive analog nonlinear filters, referred to as Adaptive Nonlinear Differential Limiters (ANDLs), that are characterized by several methodological distinctions from the existing digital solutions. When ANDLs are incorporated into a communications receiver, these methodological differences can translate into significant practical advantages, improving the receiver performance in the presence of non-Gaussian interference. A Nonlinear Differential Limiter (NDL) is obtained from a linear analog filter by introducing an appropriately chosen feedback-based nonlinearity into the response of the filter, and the degree of nonlinearity is controlled by a single parameter. ANDLs are similarly controlled by a single parameter, and are suitable for improving quality of non-stationary signals under time-varying noise conditions. ANDLs are designed to be fully compatible with existing linear devices and systems (i.e., ANDLs' behavior is linear in the absence of impulsive interference), and to be used as an enhancement, or as a simple low-cost alternative, to the state-of-art interference mitigation methods. We provide an introduction to the NDLs and illustrate their potential use for noise mitigation in PLC systems.
Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment (2016)

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression.
A Conversation with Don Bartel (2014)

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Nutritional Impact and Its Potential Consequences on COVID-19 Severity (2021)

<b>Background:</b> During late 2019 a viral disease due to a novel coronavirus was reported in Wuhan, China, which rapidly developed into an exploding pandemic and poses a severe threat to human health all over the world. Until now (May 2021), there are insufficient treatment options for the management of this global disease and shortage of vaccines. Important aspects that help to defeat coronavirus infection seems to be having a healthy, strong, and resilient immune system. Nutrition and metabolic disorders, such as obesity and diabetes play a crucial role on the community health situation in general and especially during this new pandemic. There seems to be an enormous impact of lifestyle, metabolic disorders, and immune status on coronavirus disease 2019 (COVID-19) severity and recovery. For this reason, it is important to consider the impact of lifestyle and the consumption of well-defined healthy diets during the pandemic. <b>Aims:</b> In this review, we summarise recent findings on the effect of nutrition on COVID-19 susceptibility and disease severity and treatment. Understanding how specific dietary features might help to improve the public health strategies to reduce the rate and severity of COVID-19.
Polymer membranes with selective gas and vapor permeation properties (1990)

Abstract Since many years synthetic membranes have been used in reverse osmosis or ultrafiltration for the separation of aqueous mixtures. More recently the separation of gases and vapors by selective membrane permeation has gained significant technical and commercial interest. The recovery of hydrogen from petrochemical purge gases and ammonia production processes or the removal of CO 2 from natural gas by selective membrane permeation are today state of the art procedures. The recovery of organic solvents from waste air streams is another very promising application of synthetic membranes. In this paper the main parameters determining the performance of a membrane in gas and vapor separation are described. The requested intrinsic properties of the polymer to be useful as a barrier for a selective gas and vapor transport are discussed. The preparation of appropriate membranes is described. Their performance in practicle applications is illustrated in selected examples.
3D Surface Reconstruction of Plant Seeds by Volume Carving: Performance and Accuracies (2016)

We describe a method for 3D reconstruction of plant seed surfaces, focusing on small seeds with diameters as small as 200 μm. The method considers robotized systems allowing single seed handling in order to rotate a single seed in front of a camera. Even though such systems feature high position repeatability, at sub-millimeter object scales, camera pose variations have to be compensated. We do this by robustly estimating the tool center point from each acquired image. 3D reconstruction can then be performed by a simple shape-from-silhouette approach. In experiments we investigate runtimes, theoretically achievable accuracy, experimentally achieved accuracy, and show as a proof of principle that the proposed method is well sufficient for 3D seed phenotyping purposes.