gebhart/patrepeval huggingface dataset:
Replication and Packaging of Transmissible Gastroenteritis Coronavirus-Derived Synthetic Minigenomes (1999)

The sequences involved in the replication and packaging of transmissible gastroenteritis virus (TGEV) RNA have been studied. The structure of a TGEV defective interfering RNA of 9.7 kb (DI-C) was described previously (A. Mendez, C. Smerdou, A. Izeta, F. Gebauer, and L. Enjuanes, Virology 217: 495-507, 1996), and a cDNA with the information to encode DI-C RNA was cloned under the control of the T7 promoter. The molecularly cloned DI-C RNA was replicated in trans upon transfection of helper virus-infected cells and inhibited 20-fold the replication of the parental genome. A collection of 14 DI-C RNA deletion mutants (TGEV minigenomes) was synthetically generated and tested for their ability to be replicated and packaged. The smallest minigenome (M33) that was replicated by the helper virus and efficiently packaged was 3.3 kb. A minigenome of 2.1 kb (M21) was also replicated, but it was packaged with much lower efficiency than the M33 minigenome, suggesting that it had lost either the sequences containing the main packaging signal or the required secondary structure in the packaging signal due to alteration of the flanking sequences. The low packaging efficiency of the M21 minigenome was not due to minimum size restrictions. The sequences essential for minigenome replication by the helper virus were reduced to 1,348 nt and 492 nt at the 5' and 3' ends, respectively. The TGEV-derived RNA minigenomes were successfully expressed following a two-step amplification system that couples pol II-driven transcription in the nucleus to replication supported by helper virus in the cytoplasm, without any obvious splicing. This system and the use of the reporter gene beta-glucuronidase (GUS) allowed minigenome detection at passage zero, making it possible to distinguish replication efficiency from packaging capability. The synthetic minigenomes have been used to design a helper-dependent expression system that produces around 1.0 microgram/10(6) cells of GUS.
Removal and Utilization of Capping Agents in Nanocatalysis (2013)

Capping agents are frequently used in colloidal synthesis to inhibit nanoparticle overgrowth and aggregation as well as to control the structural characteristics of the resulted nanoparticles in a precise manner. Study of the effect of the residual capping agents on particle surface has unveiled various adverse and favorable behaviors in catalytic applications. In essence, while the capping agents usually act as a physical barrier to restrict the free access of reactants to catalytic nanoparticles, they can also be utilized to promote catalytic performance of nanocrystals. Due to the complexity of these effects, a general survey of capping agents in nanocatalysis is therefore necessary. This short review starts from a brief introduction of common capping agents in nanoparticle synthesis and their adverse impact on heterogeneous catalysis. Next, representative progresses in capping agent removal and surfactant-free synthesis for obtaining surface-clean nanocatalysts are summarized. Lastly, we discuss the recent advance in utilizing the capping agent effect including chiral modification, molecular recognition, adsorption regulation, surface crowding, and charge transfer at the metal–organic interface and so on to improve the catalytic performance of nanocatalysts.
Expression of matrix metalloproteinase 9 (96‐kd gelatinase B) in human rheumatoid arthritis (1996)

Abstract Objective . To determine the expression of matrix metalloproteinase 9/gelatinase B (MMP‐9) in synovial fluid (SF), plasma, and synovial tissue from individuals with rheumatoid arthritis (RA), inflammatory arthritis (IA), and osteoarthritis (OA), using specific monoclonal antibody reagents. Methods . Gelatinolytic activity in the SF and plasma of patients with RA, IA, and OA was assessed by gelatin zymography. A mouse monoclonal antiserum, 277.13, which selectively recognizes soluble latent forms of human MMP‐9, was used to quantitate MMP‐9 levels in patient synovial effusions, plasma, and synovial tissue with a capture sandwich enzyme‐linked immunosorbent assay (ELISA). Fifty‐one SF samples (31 RA, 9 OA, 11 IA) were analyzed. Immunolocalization of MMP‐9 in RA, OA, and normal synovium was investigated using MMP‐9–specific antisera. Results . MMP‐9 antigen levels in synovial effusions were elevated 67‐fold in RA samples compared with OA samples. In addition, although MMP‐9 antigen levels in IA synovial effusions were 2.7‐fold less than the values in RA samples, they were elevated 34‐fold over the values in OA samples. These data indicate an association between increased MMP‐9 levels and inflammatory arthritis. A predominant 92‐kd gelatinolytic activity (specifically inhibited by EDTA) was evident in RA and IA samples, but no activity was observed in OA samples. Among 86 plasma samples (17 RA, 9 IA, 60 normal controls) analyzed for MMP‐9 antigen levels by immunocapture ELISA, MMP‐9 antigen levels were elevated 7‐fold in RA plasma compared with normal plasma. RA synovial tissue extracts demonstrated elevated levels of MMP‐9 antigen compared with OA synovial tissue. MMP‐9 immunolocalization studies demonstrated expression in infiltrating leukocytes (neutrophils and macrophages), endothelial cells, and synovial fibroblasts in RA synovium. Conclusion . Latent MMP‐9 and/or MMP‐9–tissue inhibitor of metalloproteinases 1 (TIMP‐1) complexes are elevated in RA and IA SF compared with OA SF. In addition, MMP‐9 is increased in RA plasma versus normal control plasma. Synovial tissue levels of MMP‐9 antigen are also elevated in RA versus OA. The tissue distribution of MMP‐9 within RA synovium is localized to sites of inflammation comprising surface synovial lining cells, endothelium, and leukocytes. Taken together, these observations suggest that connective tissue turnover occurs as a result of excessive MMP activity over TIMP action in the invading pannus, periarticular tissue, or SF. Further studies such as those used in the present investigation will help elucidate the role of a number of different enzymes and inhibitors in the destructive arthropathies.
Chemoenzymic Production of Lactams from Aliphatic α,ω-Dinitriles (1998)

Five- and six-membered ring lactams have been prepared by first converting an aliphatic α,ω-dinitrile to an ω-cyanocarboxylic acid ammonium salt, using a microbial cell catalyst having an aliphatic nitrilase activity (Acidovorax facilis 72W, ATCC 55746) or a combination of nitrile hydratase and amidase activities (Comamonas testosteroni 5-MGAM-4D, ATCC 55744). The ω-cyanocarboxylic acid ammonium salt was then directly converted to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate ω-cyanocarboxylic acid or ω-aminocarboxylic acid. Only one of two possible lactam products was produced from α-alkyl-substituted α,ω-dinitriles, where the nitrilase of A. facilis 72W regioselectively hydrolyzed only the ω-cyano group to produce a single cyanocarboxylic acid ammonium salt in greater than 98% yield.
Recent developments in lipid-based pharmaceutical nanocarriers (2010)

Within the broad spectrum of nanoparticulate carriers, polymeric and lipid-core micelles, liposomes, solid nanoparticles and many others have demonstrated great biological properties which make them excellent pharmaceutical delivery systems. In particular, micelles and liposomes have been shown to have good longevity in the blood that allows their accumulation in pathological areas with a compromised vasculature; can possess specific targeting to disease sites when various targeting ligands are attached to the surface of the nanocarriers or to surface-attached cell-penetrating molecules (like TAT peptide) to enhance intracellular penetration; possess stimulus-sensitivity allowing for drug release from the carriers under certain pathological conditions; and show contrast properties with carrier loading of various contrast materials that allow for direct carrier visualization in vivo. The engineering of "multifunctional pharmaceutical nanocarriers" based on the combination of several useful properties in the same system can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This review considers the current status and next future directions in the emerging area of nanomedicine with particular attention to two lipid-based nanoparticulate systems: liposomes and micelles.
Overview Phenotype Assessment: Are You Missing Something? (2000)

Background and Purpose: Phenotype assessment of genetically modified rodents is an essential component of animal model development and their eventual use. Described here is a paradigm to consider as we collectively pursue phenotype assessment of the constantly increasing number of genetically modified rodent models, as well as those with spontaneously occurring mutations. Methods: Review of past experiences and the literature provides useful examples to illustrate the principles described. Conclusion: A practical approach to phenotype assessment can be divided into a primary level of assessment to find abnormalities, and a secondary level of more specialized assessment to quantify and evaluate the abnormalities detected. There are many subtle, but important phenotypic characteristics that can be markedly affected by the background genetics and environment of the animal being assessed. The phenotype of an animal is determined by a complex interaction of genetics and environment. It is the evaluation of phenotype that allows us to determine the usefulness of a mutant strain as a model for biomedical research. In the present era of designing genetically altered animals, particularly mice, we are faced with the daunting task of determining the phenotype. This requirement for phenotype assessment also applies to the wealth of spontaneous mutant animals. This assessment requires sorting out genetic effects from environmental ones. A
Now You See Them (2008)

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Water Deficit Triggers Phospholipase D Activity in the Resurrection Plant Craterostigma plantagineum (2000)

Phospholipids play an important role in many signaling pathways in animal cells. Signaling cascades are triggered by the activation of phospholipid cleaving enzymes such as phospholipases C, D (PLD), and A(2). Their activities result in the formation of second messengers and amplification of the initial signal. In this study, we provide experimental evidence that PLD is involved in the early events of dehydration in the resurrection plant Craterostigma plantagineum. The enzymatic activity of the PLD protein was activated within minutes after the onset of dehydration, and although it was not inducible by abscisic acid, PLD activity did increase in response to mastoparan, which suggests a role for heterotrimeric G proteins in PLD regulation. Two cDNA clones encoding PLDs, CpPLD-1 and CpPLD-2, were isolated. The CpPLD-1 transcript was constitutively expressed, whereas CpPLD-2 was induced by dehydration and abscisic acid. Immunological studies revealed changes in the subcellular localization of the PLD protein in response to dehydration. Taken together, the data on enzymatic activity as well as transcript and protein distributions allowed us to propose a role for PLD in the events leading to desiccation tolerance in C. plantagineum.
Machine Learning in Computer-Aided Synthesis Planning (2018)

Computer-aided synthesis planning (CASP) is focused on the goal of accelerating the process by which chemists decide how to synthesize small molecule compounds. The ideal CASP program would take a molecular structure as input and output a sorted list of detailed reaction schemes that each connect that target to purchasable starting materials via a series of chemically feasible reaction steps. Early work in this field relied on expert-crafted reaction rules and heuristics to describe possible retrosynthetic disconnections and selectivity rules but suffered from incompleteness, infeasible suggestions, and human bias. With the relatively recent availability of large reaction corpora (such as the United States Patent and Trademark Office (USPTO), Reaxys, and SciFinder databases), consisting of millions of tabulated reaction examples, it is now possible to construct and validate purely data-driven approaches to synthesis planning. As a result, synthesis planning has been opened to machine learning techniques, and the field is advancing rapidly. In this Account, we focus on two critical aspects of CASP and recent machine learning approaches to both challenges. First, we discuss the problem of retrosynthetic planning, which requires a recommender system to propose synthetic disconnections starting from a target molecule. We describe how the search strategy, necessary to overcome the exponential growth of the search space with increasing number of reaction steps, can be assisted through a learned synthetic complexity metric. We also describe how the recursive expansion can be performed by a straightforward nearest neighbor model that makes clever use of reaction data to generate high quality retrosynthetic disconnections. Second, we discuss the problem of anticipating the products of chemical reactions, which can be used to validate proposed reactions in a computer-generated synthesis plan (i.e., reduce false positives) to increase the likelihood of experimental success. While we introduce this task in the context of reaction validation, its utility extends to the prediction of side products and impurities, among other applications. We describe neural network-based approaches that we and others have developed for this forward prediction task that can be trained on previously published experimental data. Machine learning and artificial intelligence have revolutionized a number of disciplines, not limited to image recognition, dictation, translation, content recommendation, advertising, and autonomous driving. While there is a rich history of using machine learning for structure-activity models in chemistry, it is only now that it is being successfully applied more broadly to organic synthesis and synthesis design. As reported in this Account, machine learning is rapidly transforming CASP, but there are several remaining challenges and opportunities, many pertaining to the availability and standardization of both data and evaluation metrics, which must be addressed by the community at large.
High-Rate Uncorrelated Bit Extraction for Shared Secret Key Generation from Channel Measurements (2009)

Secret keys can be generated and shared between two wireless nodes by measuring and encoding radio channel characteristics without ever revealing the secret key to an eavesdropper at a third location. This paper addresses bit extraction, i.e., the extraction of secret key bits from noisy radio channel measurements at two nodes such that the two secret keys reliably agree. Problems include 1) nonsimultaneous directional measurements, 2) correlated bit streams, and 3) low bit rate of secret key generation. This paper introduces high-rate uncorrelated bit extraction (HRUBE), a framework for interpolating, transforming for decorrelation, and encoding channel measurements using a multibit adaptive quantization scheme which allows multiple bits per component. We present an analysis of the probability of bit disagreement in generated secret keys, and we use experimental data to demonstrate the HRUBE scheme and to quantify its experimental performance. As two examples, the implemented HRUBE system can achieve 22 bits per second at a bit disagreement rate of 2.2 percent, or 10 bits per second at a bit disagreement rate of 0.54 percent.
Role of the tissue factor pathway in synovial inflammation (2003)

Abstract Objective Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis. Methods Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen‐induced arthritis (AIA) was assessed by administering systemically active site–blocked activated factor VIIa (FVIIai). Results Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TFPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin ( P = 0.024) and with histologic inflammation ( P = 0.03) scores. In AIA, inhibition of TF‐induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance ( P &lt; 0.04). Finally, in FVIIai‐treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition. Conclusion Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.
<title>Developing power tools for video indexing and retrieval</title> (1994)

Computer-assisted content-based indexing is a critical enabling technology and currently a bottleneck in productive use of video resources. This paper presents the Video Classification Project, an effort toward automating content-based video indexing and retrieval, at the Institute of Systems Science of the National University of Singapore. We discuss in detail three goals of the project: image processing tools for video parsing, feature extraction and retrieval; a knowledge-based approach to representing video content; and stratified tools which allow greater flexibility in browsing a video resource, either before or after performing specific retrieval operations.
Replication‐associated gene dosage effects shape the genomes of fast‐growing bacteria but only for transcription and translation genes (2006)

The bidirectional replication of bacterial genomes leads to transient gene dosage effects. Here, we show that such effects shape the chromosome organisation of fast-growing bacteria and that they correlate strongly with maximal growth rate. Surprisingly the predicted maximal number of replication rounds shows little if any phylogenetic inertia, suggesting that it is a very labile trait. Yet, a combination of theoretical and statistical analyses predicts that dozens of replication forks may be simultaneously present in the cells of certain species. This suggests a strikingly efficient management of the replication apparatus, of replication fork arrests and of chromosome segregation in such cells. Gene dosage effects strongly constrain the position of genes involved in translation and transcription, but not other highly expressed genes. The relative proximity of the former genes to the origin of replication follows the regulatory dependencies observed under exponential growth, as the bias is stronger for RNA polymerase, then rDNA, then ribosomal proteins and tDNA. Within tDNAs we find that only the positions of the previously proposed 'ubiquitous' tRNA, which translate the most frequent codons in highly expressed genes, show strong signs of selection for gene dosage effects. Finally, we provide evidence for selection acting upon genome organisation to take advantage of gene dosage effects by identifying a positive correlation between genome stability and the number of simultaneous replication rounds. We also show that gene dosage effects can explain the over-representation of highly expressed genes in the largest replichore of genomes containing more than one chromosome. Together, these results demonstrate that replication-associated gene dosage is an important determinant of chromosome organisation and dynamics, especially among fast-growing bacteria.
Cross-reactive antibodies binding to H4 hemagglutinin protect against a lethal H4N6 influenza virus challenge in the mouse model (2019)

Influenza viruses of the H4 subtype are widespread in wild birds, circulate in domestic poultry, readily infect mammals, and tolerate the insertion of a polybasic cleavage site. In addition, serological evidence suggests that humans working with poultry are exposed to these viruses. While H4 viruses are not of immediate pandemic concern, there is a lack of knowledge regarding their antigenicity. In order to study viruses of the H4 subtype, we generated and characterized a panel of antibodies that bind a wide variety of H4 hemagglutinins from avian and swine isolates of both the Eurasian and North American lineage. We further characterized these antibodies using novel recombinant H4N6 viruses that were found to be lethal in DBA/2J mice. Non-neutralizing antibodies, which had activity in an antibody dependent cell-mediated cytotoxicity reporter assay in vitro, protected mice against challenge in vivo, highlighting the importance of effector functions. Our data suggest a high degree of antigenic conservation of the H4 hemagglutinin.
Controlled drug delivery: therapeutic and pharmacological aspects (2000)

Concerted work to develop human pharmaceuticals based on rate-controlled drug delivery systems began in 1970. Today there are over three dozen such products, plus a few for veterinary use. In addition, osmotic minipumps have been extensively used since 1978, resulting in over 6000 publications in the pharmacological, endocrinological and physiological literature. Rate-controlled delivery provides for drug entry into the bloodstream continuously at either a constant or a modulated rate. By this means, one avoids the usual peak and trough pattern of drug concentrations in plasma, with its echoing peak and trough pattern of drug actions, during the interval between successive doses. In contrast to the happenstance release kinetics of rapid-release dosage forms, rate-controlled delivery systems can be designed to provide specific temporal patterns of drug concentration in plasma, for the purpose of optimizing the selectivity of drug action, the interval between successive administerings of drug and the likelihood that the next administering will occur at the proper time.