gebhart/patrepeval huggingface dataset:
Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma (2015)

This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.
Functional and Phylogenetic Characterization of Vaginolysin, the Human-Specific Cytolysin fromGardnerella vaginalis (2008)

Pore-forming toxins are essential to the virulence of a wide variety of pathogenic bacteria. Gardnerella vaginalis is a bacterial species associated with bacterial vaginosis (BV) and its significant adverse sequelae, including preterm birth and acquisition of human immunodeficiency virus. G. vaginalis makes a protein toxin that generates host immune responses and has been hypothesized to be involved in the pathogenesis of BV. We demonstrate that G. vaginalis produces a toxin (vaginolysin [VLY]) that is a member of the cholesterol-dependent cytolysin (CDC) family, most closely related to intermedilysin from Streptococcus intermedius. Consistent with this predicted relationship, VLY lyses target cells in a species-specific manner, dependent upon the complement regulatory molecule CD59. In addition to causing erythrocyte lysis, VLY activates the conserved epithelial p38 mitogen-activated protein kinase pathway and induces interleukin-8 production by human epithelial cells. Transfection of human CD59 into nonsusceptible cells renders them sensitive to VLY-mediated lysis. In addition, a single amino acid substitution in the VLY undecapeptide [VLY(P480W)] generates a toxoid that does not form pores, and introduction of the analogous proline residue into another CDC, pneumolysin, significantly decreases its cytolytic activity. Further investigation of the mechanism of action of VLY may improve understanding of the functions of the CDC family as well as diagnosis and therapy for BV.
Thalidomide analogues: derivatives of an orphan drug with diverse biological activity (2004)

Introduced as a sedative during the late 1950s, the realisation of the potent human embryotoxicity of thalidomide led to its withdrawal from the market in early 1961. Although the drug was discontinued, its teratogenic properties attracted unceasing interest as evidenced by numerous reports over the years. As investigations into its teratogenicity continued, thalidomide was serendipitously found, in separate investigations, to be effective therapy for the symptoms of leprosy (erythema nodosum leprosum). Later, the compound was found to be active against the aphthous ulcers of Behcet’s syndrome and effective as a substitute for immunosuppressive therapy for graft-versus-host disease. The relevance of thalidomide in immunosuppressive therapy has also included ailments such as cachexia, HIV wasting and Crohn’s disease. Although reports dating from the mid 1990s have disclosed the antiangiogenic activity of thalidomide, its inhibition of TNF-α, together with its immunomodulatory properties and therapeutic effectiveness in multiple myeloma, have been fast gaining attention. Consequently, a number of synthetic and biological investigations have targeted analogues with higher potencies in several of the above-mentioned therapeutic areas, as well as having lower undesirable side effects. As a result, a number of interesting compounds of varied structure have been synthesised and tested for their ability to inhibit angiogenesis or act as immunosuppressant, immunomodulatory, anti-inflammatory or anticancer agents.
Sensor-based coverage with extended range detectors (2006)

Coverage path planning determines a path that passes a robot, a detector, or some type of effector over all points in the environment. Prior work in coverage tends to fall into one of two extremes: coverage with an effector the same size of the robot, and coverage with an effector that has infinite range. In this paper, we consider coverage in the middle of this spectrum: coverage with a detector range that goes beyond the robot, and yet is still finite in range. We achieve coverage in two steps: The first step considers vast, open spaces, where the robot can use the full range of its detector; the robot covers these spaces as if it were as big as its detector range. Here we employ previous work in using Morse cell decompositions to cover unknown spaces. A cell in this decomposition can be covered via simple back-and-forth motions, and coverage of the vast space is then reduced to ensuring that the robot visits each cell in the vast space. The second step considers the narrow or cluttered spaces where obstacles lie within detector range, and thus the detector "fills" the surrounding area. In this case, the robot can cover the cluttered space by simply following the generalized Voronoi diagram (GVD) of that space. In this paper, we introduce a hierarchical decomposition that combines the Morse decompositions and the GVDs to ensure that the robot indeed visits all vast, open, as well as narrow, cluttered, spaces. We show how to construct this decomposition online with sensor data that is accumulated while the robot enters the environment for the first time.
Online community search using thread structure (2009)

Online communities are valuable information sources where knowledge is accumulated by interactions between people. Search services provided by online community sites such as forums are often, however, quite poor. To address this, we investigate retrieval techniques that exploit the hierarchical thread structures in community sites. Since these structures are sometimes not explicit or accurately annotated, we use structure discovery techniques. We then make use of thread structures in retrieval experiments. Our results show that using thread structures that have been accurately annotated can lead to significant improvements in retrieval performance compared to strong baselines.
K Banhatti Polynomials of Remdesivir, Chloroquine, Hydroxychloroquine: Research Advances for the Prevention and Treatment of COVID-19 (2020)

In this study, we obtain some topological properties of remdesivir, chloroquine, hydroxychloroquine used to inhibit the outbreak of COVID-19. We determine some K Banhatti polynomials for these three chemical structures. In Chemical Science, chemical, biological, pharmaceutical properties of molecular structure are useful for drug design. These properties can be studied by topological index calculation. Considering this, our findings may be useful in obtaining new drug and vaccine for the treatment of COVID-19.
Anterior Ischemic Optic Neuropathy (1980)

• Findings are described from 13 eyes in which post-cataract-extraction anterior ischemic optic neuropathy (PCE-AION) developed immediately after an uncomplicated cataract extraction. During the early stages of the disease, the disc is edematous, with optic disc-related visual-field defects, but after about two months, the disc is pale. The almost invariable high rise of intraocular pressure during the immediate postoperative period plays a critical role in production of PCE-AION in eyes with vulnerable optic nerve head circulation. There is a high risk of development of PCE-AION in the second eye in patients with PCE-AION in the first eye, but this can be prevented by prophylactic measures. Post-cataract-extraction AION needs to be differentiated from ordinary AION seen in aphakic eyes months or years after the cataract extraction.
GROUP B STREPTOCOCCAL VACCINES (1986)

* Hugh Dillon, M.D., Stuart Foshee, M.D., Ralph Feigin, M.D., and H. David Wilson, M.D. From the Department of Pediatrics, University of Texas Health Science Center at Dallas, Dallas, TX. Reprints not available.
Calcium and Signal Transduction in Plants (1993)

Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.
Optically-amplified WDM ring network incorporating channel-dropping filters (1994)

We analyze the critical parameters in an optically-amplified WDM ring network. We find that a ring can accommodate 27 nodes when incorporating an EDFA and a channel-dropping filter in each node, a significant advance over nonamplified rings. We compare several node configurations, and find that the sequence of an EDFA followed by an optical tap and a channel dropping filter provides the highest performance for a wide range in system variables including input signal power, inter-node link loss and its variability, power-tapping ratio, and small-signal gain. Limited network modularity can he achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Purification and Characterization of Amino Acid Racemase with Very Broad Substrate Specificity fromAeromonas caviae (1987)

A bacterium which grows in a medium containing d-serine as a sole nitrogen source has been isolated from soil and identified as Aeromonas caviae. The bacterium had a high enzyme activity catalyzing racemization of various amino acids. The enzyme, purified to homogeneity by polyacrylamide gel electrophoresis and ultracentrifugation, has a molecular weight of about 76,000, and is composed of two subunits identical in molecular weight (40,000). The results of enantiomeric analysis of the reaction product and kinetic examination of the reaction indicate that the enzyme catalyzes the complete racemization of substrates. The enzyme has absorption maxima at 280 and 420 nm, and contains 2 mol of pyridoxal 5'-phosphate per mol of enzyme. The holoenzyme is resolved to the apoenzyme by treatment with hydroxylamine, and reconstituted by the addition of pyridoxal 5′-phosphate. The very broad substrate specificity of the A. caviae amino acid racemase is comparable to that of the Pseudomonas striata enzyme. However, they share no common antigenic determinants.
Key Roles of AXL and MER Receptor Tyrosine Kinases in Resistance to Multiple Anticancer Therapies (2017)

A major challenge in anticancer treatment is the pre-existence or emergence of resistance to therapy. AXL and MER are two members of the TAM (TYRO3-AXL-MER) family of receptor tyrosine kinases, which, when activated, can regulate tumor cell survival, proliferation, migration and invasion, angiogenesis, and tumor-host interactions. An increasing body of evidence strongly suggests that these receptors play major roles in resistance to targeted therapies and conventional cytotoxic agents. Multiple resistance mechanisms exist, including the direct and indirect crosstalk of AXL and MER with other receptors and the activation of feedback loops regulating AXL and MER expression and activity. These mechanisms may be innate, adaptive, or acquired. A principal role of AXL appears to be in sustaining a mesenchymal phenotype, itself a major mechanism of resistance to diverse anticancer therapies. Both AXL and MER play a role in the repression of the innate immune response which may also limit response to treatment. Small molecule and antibody inhibitors of AXL and MER have recently been described, and some of these have already entered clinical trials. The optimal design of treatment strategies to maximize the clinical benefit of these AXL and MER targeting agents are discussed in relation to the different cancer types and the types of resistance encountered. One of the major challenges to successful development of these therapies will be the application of robust predictive biomarkers for clear-cut patient stratification.
Silencing of PINK1 Expression Affects Mitochondrial DNA and Oxidative Phosphorylation in DOPAMINERGIC Cells (2009)

This report highlights a novel function of PINK1 in mitochondrial biogenesis and a role in maintaining mitochondrial ETC activity. Dysfunction of both has been implicated in sporadic forms of PD suggesting that these may be key pathways in the development of the disease.
Deep Learning-Based Advances in Protein Structure Prediction (2021)

Obtaining an accurate description of protein structure is a fundamental step toward understanding the underpinning of biology. Although recent advances in experimental approaches have greatly enhanced our capabilities to experimentally determine protein structures, the gap between the number of protein sequences and known protein structures is ever increasing. Computational protein structure prediction is one of the ways to fill this gap. Recently, the protein structure prediction field has witnessed a lot of advances due to Deep Learning (DL)-based approaches as evidenced by the success of AlphaFold2 in the most recent Critical Assessment of protein Structure Prediction (CASP14). In this article, we highlight important milestones and progresses in the field of protein structure prediction due to DL-based methods as observed in CASP experiments. We describe advances in various steps of protein structure prediction pipeline viz. protein contact map prediction, protein distogram prediction, protein real-valued distance prediction, and Quality Assessment/refinement. We also highlight some end-to-end DL-based approaches for protein structure prediction approaches. Additionally, as there have been some recent DL-based advances in protein structure determination using Cryo-Electron (Cryo-EM) microscopy based, we also highlight some of the important progress in the field. Finally, we provide an outlook and possible future research directions for DL-based approaches in the protein structure prediction arena.
Similarity Measures for Rational Set Selection and Analysis of Combinatorial Libraries:  The Diverse Property-Derived (DPD) Approach (1997)

The generation of new chemical leads for biological targets is a very challenging task for researchers in the pharmaceutical industry. The design of representative screening sets and combinatorial libraries is central to achieving this objective. In this paper, we describe a novel molecular descriptor, the Diverse Property-Derived (DPD) code, that contains information about key molecular and physicochemical properties of a molecule. The utility of this descriptor is explored through its application for the selection of a maximally diverse representative screening set, through the selection of secondary screening sets to obtain more information concerning the structure-activity relationships (SAR) of a particular target receptor, and through the profiling of combinatorial libraries. The usefulness of physicochemical/molecular property descriptors, such as the DPD code, is discussed critically.
Comparison Study for Identifying Promoter Allelic Polymorphism in Interleukin 10 and Tumor Necrosis Factor α Genes (2000)

Cytokines such as tumor necrosis factor (TNF)-alpha and Interleukin (IL)-10 play significant roles in autoimmunity and transplantation tolerance. Allelic polymorphisms that occur in the regulatory regions of these cytokine genes are closely associated with acute and chronic transplant rejection. The presence of a G-to-A polymorphism at position -308 in the promoter region of the TNF-alpha gene can increase transcription six- to sevenfold. Likewise, the G-A polymorphism at position -1082 of the IL-10 promoter results in lower levels of IL-10 protein. Accordingly, a genotype that dictates the production of high levels of TNF-alpha with low IL-10 capabilities is most likely to generate an inflammatory environment that is less receptive to the transplant. The potential for determining a patient's haplotype before transplantation may be an effective way of monitoring the post-transplant status of such patients. A variety of methodologies that address the detection of mutations have been used both in research and clinical diagnostic tests. This study analyzes the genetic variations in cytokines using two methodologies: the traditional allele-specific oligonucleotide (ASO) polymerase chain reaction (PCR) and the newer and more flexible Invader technology. The sensitivity and specificity of the Invader assay for simultaneous investigation of multiple targets makes it a useful tool in such analyses.
Activation of the ACE2/Angiotensin-(1–7)/Mas Receptor Axis Enhances the Reparative Function of Dysfunctional Diabetic Endothelial Progenitors (2012)

We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD34(+) cells from patients with diabetes were compared with those of nondiabetic controls. Ang-(1-7) restored impaired migration and nitric oxide bioavailability/cGMP in response to stromal cell-derived factor and resulted in a decrease in NADPH oxidase activity. The survival and proliferation of CD34(+) cells from diabetic individuals were enhanced by Ang-(1-7) in a Mas/phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. ACE2 expression was lower, and ACE2 activators xanthenone and diminazine aceturate were less effective in inducing the migration in cells from patients with diabetes compared with controls. Ang-(1-7) overexpression by lentiviral gene modification restored both the in vitro vasoreparative functions of diabetic cells and the in vivo homing efficiency to areas of ischemia. A cohort of patients who remained free of microvascular complications despite having a history of longstanding inadequate glycemic control had higher expression of ACE2/Mas mRNA than patients with diabetes with microvascular complications matched for age, sex, and glycemic control. Thus, ACE2/Ang-(1-7)\Mas pathway activation corrects existing diabetes-induced CD34(+) cell dysfunction and also confers protection from development of this dysfunction.
One-Shot Imitation Learning (2017)

Imitation learning has been commonly applied to solve different tasks in isolation. This usually requires either careful feature engineering, or a significant number of samples. This is far from what we desire: ideally, robots should be able to learn from very few demonstrations of any given task, and instantly generalize to new situations of the same task, without requiring task-specific engineering. In this paper, we propose a meta-learning framework for achieving such capability, which we call one-shot imitation learning. Specifically, we consider the setting where there is a very large set of tasks, and each task has many instantiations. For example, a task could be to stack all blocks on a table into a single tower, another task could be to place all blocks on a table into two-block towers, etc. In each case, different instances of the task would consist of different sets of blocks with different initial states. At training time, our algorithm is presented with pairs of demonstrations for a subset of all tasks. A neural net is trained that takes as input one demonstration and the current state (which initially is the initial state of the other demonstration of the pair), and outputs an action with the goal that the resulting sequence of states and actions matches as closely as possible with the second demonstration. At test time, a demonstration of a single instance of a new task is presented, and the neural net is expected to perform well on new instances of this new task. The use of soft attention allows the model to generalize to conditions and tasks unseen in the training data. We anticipate that by training this model on a much greater variety of tasks and settings, we will obtain a general system that can turn any demonstrations into robust policies that can accomplish an overwhelming variety of tasks. Videos available at https://bit.ly/nips2017-oneshot .
Liposomal Spherical Nucleic Acids (2014)

A novel class of metal-free spherical nucleic acid nanostructures was synthesized from readily available starting components. These particles consist of 30 nm liposomal cores, composed of an FDA-approved 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid monomer. The surface of the liposomes was functionalized with DNA strands modified with a tocopherol tail that intercalates into the phospholipid layer of the liposomal core via hydrophobic interactions. The spherical nucleic acid architecture not only stabilizes these constructs but also facilitates cellular internalization and gene regulation in SKOV-3 cells.
Reactive oxygen species and peroxisomes: Struggling for balance (2009)

Reactive oxygen species (ROS) can surely be considered as multifunctional biofactors within the cell. They are known to participate in regular cell functions, for example, as signal mediators, but overproduction under oxidative stress conditions leads to deleterious cellular effects, cell death and diverse pathological conditions. Peroxisomal function has long been linked to oxygen metabolism due to the high concentration of H(2)O(2)-generating oxidases in peroxisomes and their set of antioxidant enzymes, especially catalase. Still, mitochondria have been very much placed in the centre of ROS metabolism and oxidative stress. This review discusses novel findings concerning the relationship between ROS and peroxisomes, as they revealed to be a key player in the dynamic spin of ROS metabolism and oxidative injury. An overview of ROS generating enzymes as well as their antioxidant counterparts will be given, exemplifying the precise fine-tuning between the opposing systems. Various conditions in which the balance between generation and scavenging of ROS in peroxisomes is perturbed, for example, exogenous manipulation, ageing and peroxisomal disorders, are addressed. Furthermore, peroxisome-derived oxidative stress and its effect on mitochondria (and vice versa) are discussed, highlighting the close interrelationship of both organelles.