gebhart/patrepeval huggingface dataset:
Mechanisms of Muscle Injury, Repair, and Regeneration (2011)

Skeletal muscle continuously adapts to changes in its mechanical environment through modifications in gene expression and protein stability that affect its physiological function and mass. However, mechanical stresses commonly exceed the parameters that induce adaptations, producing instead acute injury. Furthermore, the relatively superficial location of many muscles in the body leaves them further vulnerable to acute injuries by exposure to extreme temperatures, contusions, lacerations or toxins. In this article, the molecular, cellular, and mechanical factors that underlie muscle injury and the capacity of muscle to repair and regenerate are presented. Evidence shows that muscle injuries that are caused by eccentric contractions result from direct mechanical damage to myofibrils. However, muscle pathology following other acute injuries is largely attributable to damage to the muscle cell membrane. Many feaures in the injury-repair-regeneration cascade relate to the unregulated influx of calcium through membrane lesions, including: (i) activation of proteases and hydrolases that contribute muscle damage, (ii) activation of enzymes that drive the production of mitogens and motogens for muscle and immune cells involved in injury and repair, and (iii) enabling protein-protein interactions that promote membrane repair. Evidence is also presented to show that the myogenic program that is activated by acute muscle injury and the inflammatory process that follows are highly coordinated, with myeloid cells playing a central role in modulating repair and regeneration. The early-invading, proinflammatory M1 macrophages remove debris caused by injury and express Th1 cytokines that play key roles in regulating the proliferation, migration, and differentiation of satellite cells. The subsequent invasion by anti-inflammatory, M2 macrophages promotes tissue repair and attenuates inflammation. Although this system provides an effective mechanism for muscle repair and regeneration following acute injury, it is dysregulated in chronic injuries. In this article, the process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury, to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle.
How do viral infections predispose patients to bacterial infections? (2004)

Respiratory viral infections may facilitate secondary bacterial infections and increase host immunopathology through the overproduction of inflammatory cytokines. Preventive measures, including vaccination and aggressive antimicrobial therapy early in the course of infection, may significantly reduce the morbidity and mortality of sepsis.
Interactions between hematopoietic progenitor kinase 1 and its adaptor proteins (2017)

Hematopoietic progenitor kinase 1 (HPK1), also known as mitogen‑activated protein kinase kinase kinase kinase 1 is a serine/threonine protein kinase. It is involved in various cellular events, including mitogen‑activated protein kinase signaling, nuclear factor‑κB signaling, cytokine signaling, cellular proliferation and apoptosis, T cell receptor/B cell receptor signaling and T/B/dendritic cell‑mediated immune responses. Therefore, HPK1 has variety of roles in immunity, and is associated with the pathogenesis of autoimmune diseases, cancer, and the inflammatory response. In these cellular and immune events, HPK1 interacts with several adaptor proteins, including caspase recruitment domain family, member 11, hematopoietic cell‑specific protein 1, HPK1‑interacting protein of 55 kDa, the growth factor receptor‑bound protein 2 family, linker for activated T‑cells, the SH2 domain‑containing leukocyte protein of 76 kDa family, the v‑crk avian sarcoma virus CT10 oncogene homolog family, B‑cell adaptor molecule of 32 kDa and non‑catalytic region of tyrosine kinase adaptor protein. These adaptor proteins can couple HPK1 with various effector molecules, leading to the transmission of upstream signals to downstream targets. They are crucial in regulating the relocation, phosphorylation, activation and functions of HPK1. HPK1 can also phosphorylate certain proteins, consequently modulating their functions. This review aims to describe the adaptor proteins, which interact with HPK1, particularly focusing on their modes of interaction with HPK1, and the effects that these interactions cause.
Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. (1993)

The LK26 antigen is a cell surface glycoprotein (M(r)35,000 to 40,000) of normal placenta and gestational choriocarcinomas that shows highly restricted distribution in normal tissues, being expressed primarily in a subset of simple epithelia. In this study, immunohistochemical methods were used to examine LK26 expression in 78 ovarian tumors and > 400 tumors of other histological types. Ovarian carcinomas derived from coelomic epithelium showed the most consistent and strongest immunostaining for LK26, with 52 of 56 cases being LK26+. Ovarian tumors of sex cord, germ cell, and stromal origin were generally LK26-. LK26 was not found in normal fetal or adult ovary; however, it was present in the lining epithelia of some benign ovarian cysts. Mesotheliomas, which share a common mesothelial origin with LK26+ ovarian tumors, expressed no or only low levels of LK26. Other epithelial cancers expressed LK26 in subsets of cases and generally showed heterogeneous or weak immunostaining; this group of LK26+ tumors includes endometrial (10 of 11 cases tested), colorectal (six of 27), breast (11 of 53), lung (six of 18), and renal cell (nine of 18) carcinomas. Four of five brain metastases derived from epithelial cancers and three of 21 neuroendocrine carcinomas showed prominent LK26 immunoreactivity. Only rare neuroectodermal tumors (two of 70) and none of the sarcomas (none of 58) or lymphomas tested (none of 21) were LK26+. Tests with cultured cells showed that the LK26 proteins expressed in choriocarcinoma and ovarian cancer cells are biochemically similar, and transfection experiments identified LK26 as an adult-type, high-affinity folate-binding protein. The present study provides the first detailed specificity and sensitivity analysis for folate-binding protein/LK26 in human tumors and defines a role for folate-binding protein/LK26 in immunobiological studies of ovarian cancers and other LK26+ neoplasms.
Vascular endothelial growth factor : a blood biomarker in canine pulmonary fibrosis. (2014)

peer reviewed
Catalytic C−H Bond Functionalization with Palladium(II):  Aerobic Oxidative Annulations of Indoles (2003)

A palladium-catalyzed aerobic oxidative annulation of indoles is described. We have demonstrated that a variety of factors influence these cyclizations, and in particular the electronic nature of the pyridine ligand is crucial. It is also remarkable that these oxidative cyclizations can proceed in good yield despite background oxidative decomposition pathways, testament to the facile nature with which molecular oxygen can serve as the direct oxidant for Pd(0). We have also shown that the mechanism most likely involves initial indole palladation (formal C-H bond activation) followed by migratory insertion and beta-hydrogen elimination.
Data mining methods for detection of new malicious executables (2002)

A serious security threat today is malicious executables, especially new, unseen malicious executables often arriving as email attachments. These new malicious executables are created at the rate of thousands every year and pose a serious security threat. Current anti-virus systems attempt to detect these new malicious programs with heuristics generated by hand. This approach is costly and oftentimes ineffective. We present a data mining framework that detects new, previously unseen malicious executables accurately and automatically. The data mining framework automatically found patterns in our data set and used these patterns to detect a set of new malicious binaries. Comparing our detection methods with a traditional signature-based method, our method more than doubles the current detection rates for new malicious executables.
Ultrasensitive Detection of Low‐Abundance Surface‐Marker Protein Using Isothermal Rolling Circle Amplification in a Microfluidic Nanoliter Platform (2010)

With advances in immunology and cancer biology, there is an unmet need for increasingly sensitive systems to monitor the expression of specific cell markers for the development of new diagnostic and therapeutic tools. To address this challenge, a highly sensitive labeling method that translates antigen-antibody recognition processes into DNA detection events that can be greatly amplified via isothermal rolling circle amplification (RCA) is applied. By merging the single-molecule detection power of RCA reactions with microfluidic technology, it is demonstrated that the identification of specific protein markers can be achieved on tumor-cell surfaces in miniaturized nanoliter reaction droplets. Furthermore, this combined approach of signal amplification in a microfluidic format could extend the utility of existing methods by reducing sample and reagent consumption and enhancing the sensitivities and specificities for various applications, including early diagnosis of cancer.
Benzopyrones. Part I. 6-Amino- and 6-hydroxy-2-substituted chromones (1970)

Contrary to a report in the literature, mono- and di-nitration of 6-hydroxy-2-methylchromone (I) gives the 5-nitro- and the 5,7-dinitro-derivative according to the conditions. 2,5-Dihydroxy-3-nitroacetophenone, whose m.p. is given erroneously in the literature, has been synthesized. The earlier literature on mono- and di-bromination of (I) is corrected and the structure of each product is elucidated.4-Oxochromen-2-carboxylic acid and its ethyl ester have been nitrated; the catalytic hydrogenation of the resulting 6-nitro-compound has been studied; according to the conditions, the products are the 6-hydroxyamino-and the 6-amino-chromone (VIII), and the 6-aminochromanone. Diazotization of (VIII) followed by hydrolysis gave 6-hydroxy-4-oxochromen-2-carboxylic acid.
Simulation and modeling of intermodulation distortion in communication circuits (2003)

Distortion in circuits along the signal path of a transceiver plays a key role in determining the overall performance of digital communication systems. This paper describes how recent improvements in the mixed frequency/time algorithm (MFT) expand our ability to predict the distortion of these circuits. The MFT algorithm extends traditional shooting methods to directly compute the quasiperiodic steady-state response of circuits driven by two or more periodic signals, each at independent frequencies. With these improvements, MFT can be directly applied to accurately and efficiently compute the intermodulation distortion of large circuits driven by a small number of discrete tones. This is representative of the signals found in receivers. However in transmitters, concern focuses on the affect of intermodulation distortion from complex digitally modulated signals. Such signals cannot be handled directly by MFT, but we demonstrate how a macromodel can be constructed that is used to rapidly predict the spectral regrowth caused by the power amplifier and associated circuitry. This approach allows much more of the transmitter to be simulated than with envelope-transient methods.
Sea surface visualization in world of warships (2016)

We describe algorithms used for the visualization of the sea in World of Warships. Being an MMO project, it requires excellent scalability for a wide range of hardware, while still satisfying artistic requirements. We achieve good image quality both near and far from the viewpoint. Moreover, our approach gives us reliable geometric stability and preserves wave structure at a distance. We also describe how to create foam, deformations, reflections, shadows and other features related to the visualization of water.
In vitro reassembly of vesicular stomatitis virus skeletons (1982)

Vesicular stomatitis virus (VSV) has been disrupted with nonionic detergent plus 0.5 M NaCl under conditions which result in solubilization of the viral glycoprotein (G), matrix protein (M), and lipids, leaving the nucleocapsid in a highly extended state. Dialysis of these suspensions to remove NaCl was found to result in reassociation of nucleocapsids with M protein. Reassociated structures were highly condensed and similar in appearance to "native" VSV skeletons produced by extraction of virions with detergent at low ionic strength. For instance, electron microscopic analysis revealed that, like "native" skeletons, "reassembled" skeletons were cylindrical in shape, with diameters in the range of 51.0 to 55.0 nm and cross-striations spaced approximately 6.0 nm apart along the length of the structure. Like native skeletons, reassembled skeletons were found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to contain the viral N and M proteins, but they lacked the glycoprotein entirely. Both native and reassembled skeletons were found to be capable of in vitro RNA-dependent RNA synthesis (transcription). In vivo skeleton assembly required the presence of M protein and nucleocapsids. No skeleton-like structures were formed by dialysis of nucleocapsids in the absence of M protein or of M protein in the absence of nucleocapsids. These results provide strong support for the view that the VSV M protein plays a functional role in condensing the viral nucleocapsid in vitro and raise the possibility that it may play a similar role in vivo.
Diazo‐Transfer Reaction with Diphenyl Phosphorazidate (1995)

Abstract Diphenyl phosphorazidate (DPPA) was used as the azide source in a one‐pot synthesis of 2,2‐disubstituted 3‐amino‐2 H ‐azirines 1 ( Scheme 1 ). The reaction with lithium enolates of amides of type 2 , bearing two substituents at C(2), proceeded smoothly in THF at 0°; keteniminium azides C and azidoenamines D are likely intermediates. Under analogous reaction conditions, DPPA and amides of type 3 with only one substituent at C(2) gave 2‐diazoamides 5 in fair‐to‐good yield ( Scheme 2 ). The corresponding 2‐diazo derivatives 6–8 were formed in low yield by treatment of the lithium enolates of N , N ‐dimethyl‐2‐phenylacetamide, methyl 2‐phenylacetate, and benzyl phenyl ketone, respectively, with DPPA. Thermolysis of 2‐diazo‐ N ‐methyl‐ N ‐phenylcarboxamides 5a and 5b yielded 3‐substituted 1,3‐dihydro‐ N ‐methyl‐2 H ‐indol‐2‐ones 9a and 9b , respectively ( Scheme 3 ). The diazo compounds 5–8 reacted with 1,3‐thiazole‐5 (4 H )‐thiones 10 and thiobenzophenone ( 13 ) to give 6‐oxa‐1,9‐dithia‐3‐azaspiro[4.4]nona‐2,7‐dienes 11 ( Scheme 4 ) and thiirane‐2‐carboxylic acid derivatives 14 ( Scheme 5 ), respectively. In analogy to previously described reactions, a mechanism via 1,3‐dipolar cycloaddition, leading to 2,5‐dihydro‐1,3,4‐thiadiazoles, and elimination of N 2 to give the ‘thiocarbonyl ylides’ of type H or K is proposed. These dipolar intermediates with a conjugated CO group then undergo either a 1,5‐dipolar electrocyclization to give spirohetrocycles 11 or a 1,3‐dipolar electrocyclization to thiiranes 14 .
Reconstruction of regulatory and metabolic pathways in metal-reducing delta-proteobacteria. (2004)

Phylogenetically diverse delta-proteobacteria appear to have homologous regulatory components. This study for the first time demonstrates the adaptability of the comparative genomic approach to de novo reconstruction of a regulatory network in a poorly studied taxonomic group of bacteria. Recent efforts in large-scale functional genomic characterization of Desulfovibrio species will provide a unique opportunity to test and expand our predictions.
Coupled modelling of hydro‐mechanical behaviour of unsaturated compacted expansive soils (2011)

SUMMARY The Barcelona basic model cannot predict the mechanical behaviour of unsaturated expansive soils, whereas the Barcelona expansive model (BExM) can only predict the stress–strain behaviour of unsaturated expansive soils without the water‐retention behaviour being incorporated. Moreover, the micro‐parameters and the coupling function between micro‐structural and macro‐structural strains in the BExM are difficult to determine. Experimental data show that the compression curves for non‐expansive soils under constant suctions are shifted towards higher void ratios with increasing suction, whereas the opposite is true for expansive soils. According to the observed water‐retention behaviour of unsaturated expansive soils, the air‐entry value increases with density, and the relationship between the degree of saturation and void ratio is linear at constant suction. According to the above observation, an elastoplastic constitutive model is developed for predicting the hydraulic and mechanical behaviour of unsaturated expansive soils, based on the existing hydro‐mechanical model for non‐expansive unsaturated soil. The model takes into consideration the effect of degree of saturation on the mechanical behaviour and that of void ratio on the water‐retention behaviour. The concept of equivalent void ratio curve is introduced to distinguish the plastic potential curve from the yield curve. The model predictions are compared with the test results of an unsaturated expansive soil, including swelling tests under constant net stress, isotropic compression tests and triaxial shear tests under constant suction. The comparison indicates that the model offers great potential for quantitatively predicting the hydraulic and mechanical behaviour of unsaturated expansive soils. Copyright © 2011 John Wiley &amp; Sons, Ltd.
DUALCAST: a scheme for reliable multicasting (2002)

With the rapid deployment of high speed networks and the increased use of applications that blend voice, data, and video traffic, protocols have to be looked at anew. The problem of trying to conserve bandwidth is being replaced by the problems of overcoming latency and processing bottlenecks. In this paper, we introduce the conflicting demands in implementing reliable multicast and then present a new heuristic that balances the tradeoffs by using redundancy while not loading the network excessively.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis and Structural Characterization of a Novel Covalently-Bound Corrole Dimer (2001)

The (triphenylphosphine)cobalt(III) complex (2) of 5,10,15-tris(pentafluorophenyl)corrole (1) is shown to be an valuable precursor to complexes that have not been fully characterized previously. In contrast to other cobalt corroles, aromatic amines can be substituted for the triphenylphosphine in 2 to form six-coordinate bis(amine)cobalt(III) complexes. This is demonstrated by spectroscopic methods and by X-ray crystallography of the bis-pyridine complex 4, the first of its kind. While 2 and 4 and even their one-electron oxidized complexes are stable, a spontaneous dimerization of the corrole takes place in the absence of strongly bound ligands. The bis-cobalt complex of the novel corrole dimer 6 was fully characterized by spectroscopic methods and X-ray crystallography.
Sustained multilineage gene persistence and expression in dogs transplanted with CD34+ marrow cells transduced by RD114-pseudotype oncoretrovirus vectors (2001)

Previous studies have shown that the choice of envelope protein (pseudotype) can have a significant effect on the efficiency of retroviral gene transfer into hematopoietic stem cells. This study used a competitive repopulation assay in the dog model to evaluate oncoretroviral vectors carrying the envelope protein of the endogenous feline virus, RD114. CD34-enriched marrow cells were divided into equal aliquots and transduced with vectors produced by the RD114-pseudotype packaging cells FLYRD (LgGLSN and LNX) or by the gibbon ape leukemia virus (GALV)-pseudotype packaging cells PG13 (LNY). A total of 5 dogs were studied. One dog died because of infection before sustained engraftment could be achieved, and monitoring was discontinued after 9 months in another animal that had very low overall gene-marking levels. The 3 remaining animals are alive with follow-ups at 11, 22, and 23 months. Analyses of gene marking frequencies in peripheral blood and marrow by polymerase chain reaction revealed no significant differences between the RD114 and GALV-pseudotype vectors. The LgGLSN vector also contained the enhanced green fluorescent protein (GFP), enabling us to monitor proviral expression by flow cytometry. Up to 10% of peripheral blood cells expressed GFP shortly after transplantation and approximately 6% after the longest follow-up of 23 months. Flow cytometric analysis of hematopoietic subpopulations showed that most of the GFP-expressing cells were granulocytes, although GFP-positive lymphocytes and monocytes were also detected. In summary, these results show that RD114-pseudotype oncoretroviral vectors are able to transduce hematopoietic long-term repopulating cells and, thus, may be useful for human stem cell gene therapy.
Structure of the Escherichia coli Fumarate Reductase Respiratory Complex (1999)

The integral membrane protein fumarate reductase catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The homologous enzyme succinate dehydrogenase also plays a prominent role in cellular energetics as a member of the Krebs cycle and as complex II of the aerobic respiratory chain. Fumarate reductase consists of four subunits that contain a covalently linked flavin adenine dinucleotide, three different iron-sulfur clusters, and at least two quinones. The crystal structure of intact fumarate reductase has been solved at 3.3 angstrom resolution and demonstrates that the cofactors are arranged in a nearly linear manner from the membrane-bound quinone to the active site flavin. Although fumarate reductase is not associated with any proton-pumping function, the two quinones are positioned on opposite sides of the membrane in an arrangement similar to that of the Q-cycle organization observed for cytochrome bc1.
Deep Reinforcement Learning with Double Q-Learning (2016)

The popular Q-learning algorithm is known to overestimate action values under certain conditions. It was not previously known whether, in practice, such overestimations are common, whether they harm performance, and whether they can generally be prevented. In this paper, we answer all these questions affirmatively. In particular, we first show that the recent DQN algorithm, which combines Q-learning with a deep neural network, suffers from substantial overestimations in some games in the Atari 2600 domain. We then show that the idea behind the Double Q-learning algorithm, which was introduced in a tabular setting, can be generalized to work with large-scale function approximation. We propose a specific adaptation to the DQN algorithm and show that the resulting algorithm not only reduces the observed overestimations, as hypothesized, but that this also leads to much better performance on several games.