gebhart/patrepeval huggingface dataset:
Subcellular compartmentalization of maize storage proteins in Xenopus oocytes injected with zein messenger RNAs. (1981)

Maize storage proteins synthesized in oocytes were compartmentalized in membrane vesicles because they were resistant to hydrolysis by protease, unless detergent was present. The site of storage protein deposition within the oocyte was determined by subcellular fractionation. Optimal separation of oocyte membranes and organelles was obtained when EDTA and high concentrations of NaCl were included in the homogenization and gradient buffers. Under these conditions, fractions in sucrose gradients containing a heterogeneous mixture of smooth membranes (presumably endoplasmic reticulum, Golgi apparatus, and plasma membrane, density = 1.10-1.12 g/cm3), mitochondria (densities = 1.14 and 1.16 g/cm3), yolk platelets (density = 1.21 g/cm3), and a dense matrix material (density = 1.22 g/cm3) could be separated. Some zein proteins were recovered in the mixed membrane fraction, but the majority occurred in vesicles sedimenting with yolk platelets and granular material at a density of approximately 1.22 g/cm3. When metrizamide was included in the gradient to increase the density, little of the dense matrix material was isolated, and vesicles containing zein proteins were separated from other oocyte components. These vesicles were similar to protein bodies in maize endosperm because they were of identical density and contained the same group of polypeptides.
Interaction of c-Src with Gap Junction Protein Connexin-43 (2001)

Cell-cell communication via connexin-43 (Cx43)-based gap junctions is transiently inhibited by certain mitogens, but the underlying regulatory mechanisms are incompletely understood. Our previous studies have implicated the c-Src tyrosine kinase in mediating transient closure of Cx43-based gap junctions in normal fibroblasts. Here we show that activated c-Src (c-SrcK(+)) phosphorylates the COOH-terminal tail of Cx43, both in vitro and in intact cells. Coimmunoprecipitation experiments reveal that Cx43 associates with c-SrcK(+) and, to a lesser extent, with wild-type c-Src, but not with kinase-dead c-Src. Mutation of residue Cx43 Tyr(265) (Cx43-Y265F mutant) abolishes both tyrosine phosphorylation of Cx43 and its coprecipitation with c-Src. Expression of c-SrcK(+) in Rat-1 cells disrupts gap junctional communication. Strikingly, the communication-defective phenotype is bypassed after coexpression of the Cx43-Y265F mutant or a COOH-terminally truncated version of Cx43 (Cx43Delta263) that lacks residue Tyr(265). Our results support a model in which activated c-Src phosphorylates the COOH-terminal tail of Cx43 on residue Tyr(265), resulting in a stable interaction between both proteins leading to inhibition of gap junctional communication.
Effective use of marine algal products in the management of plant-parasitic nematodes. (1987)

Algal extracts were ineffective against Meloidogyne spp., Panagrellus redivivus, and Neoaplectana carpocapsae at 1.0% aqueous concentrations, with the exception of Spatoglossum schroederi. S. schroederi killed Meloidogyne incognita, M. javanica, M. acrita, and Hoplolaimus galeatus at concentrations of 1.0, 0.75, and 0.50%. Extracts from S. schroederi at a concentration of 1.0% were ineffective against Hirschmanniella caudacrena and Belonolaimus longicaudatus. Spatoglossum schroederi, Botryocladia occidentalis, and Bryothamnion triquestrum when used as soil amendments at 0.5-1.0% concentrations (by weight) produced significant reduction of root gall development in tomato plants infected with M. incognita. Tomato plant growth was significantly improved by these algae, as well as by Caulerpa prolifera. Soil amendments of S. schroederi at concentrations of 0.5 and 1.0% significantly reduced root galling of tomato infected with M. incognita, M. arenaria, and M. javanica. Tomatoes grown in algal-soil mixture produced significantly heavier shoots and roots than plants raised in autoclaved soil. No significant differences in root-knot indices, nor in fresh and dry weights of tomato, were noted between the two concentrations of algal-soil mixture.
Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes (1998)

This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the MBGV genome and the chloramphenicol acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these minigenomes were replicated and encapsidated and could be passaged. Unlike most other members of the order Mononegavirales, filoviruses possess four proteins presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To determine the protein requirements for replication and transcription, a reverse genetic system was established for MBGV based on the vaccinia virus T7 expression system. Northern blot analysis of viral RNA revealed that three nucleocapsid proteins (NP, VP35, and L) were essential and sufficient for transcription as well as replication and encapsidation. These data indicate that VP35, rather than VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The reconstituted replication system was profoundly affected by the NP-to-VP35 expression ratio. To investigate whether CAT gene expression was achieved entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back minireplicon containing the CAT gene but lacking MBGV-specific transcriptional start sites was employed in the artificial replication system. This construct was replicated without accompanying CAT activity. It was concluded that the CAT activity reflected MBGV-specific transcription and not replication.
RNase P Ribozymes Selected in Vitro to Cleave a Viral mRNA Effectively Inhibit Its Expression in Cell Culture (2000)

An in vitro selection procedure was used to select RNase P ribozyme variants that efficiently cleaved the sequence of the mRNA encoding thymidine kinase of herpes simplex virus 1. Of the 45 selected variants sequenced, 25 ribozymes carried a common mutation at nucleotides 224 and 225 of RNase P catalytic RNA from Escherichia coli (G(224)G(225) --> AA). These selected ribozymes exhibited at least 10 times higher cleavage efficiency (k(cat)/K(m)) than that derived from the wild type ribozyme. Our results suggest that the mutated A(224)A(225) are in close proximity to the substrate and enhance substrate binding of the ribozyme. When these ribozyme variants were expressed in herpes simplex virus 1-infected cells, the levels of thymidine kinase mRNA and protein were reduced by 95-99%. Our study provides the first direct evidence that RNase P ribozyme variants isolated by the selection procedure can be used for the construction of gene-targeting ribozymes that are highly effective in tissue culture. These results demonstrate the potential for using RNase P ribozymes as gene-targeting agents against any mRNA sequences, and using the selection procedure as a general approach for the engineering of RNase P ribozymes.
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Clinical investigation of the immunogenicity of interferon-alpha 2a. (1997)

The following confounding array of variables can affect the reporting of antibodies to interferon (IFN)-alpha or any other protein injected into humans for prophylactic or therapeutic purposes: route, dose, frequency, and duration of administration; timing and frequency of blood sampling; methods used to determine antibody presence (sensitivity); calculation of the units used to report the results; intrinsic immunogenicity of the protein product; major histocompatibility complex genotype of the challenged individual; associated diseases and medication. Without specification of all these factors, it is difficult to put forward a valid statement from the published literature regarding the comparative incidence of antibodies to various forms of IFN. Furthermore, because units are not standardized and rarely reported, it becomes impossible to make any comparisons of antibody titers. This evaluation confirms, by clinical trial results, the decrease in immunogenicity observed in vitro and in vivo of different IFN-alpha 2a products manufactured between 1989 and 1993 following incremental improvements in process specifications and expanded quality control. Serial serum samples were taken, prepared, stored, and shipped according to identical protocols in five different clinical trials performed with IFN-alpha 2a between 1989 and 1995 in comparable patient populations with chronic hepatitis C. The coded samples were screened using sensitive enzyme immunoassay (EIA). Positive samples were further analyzed and quantified by bioassay [antiviral inhibition assay (AVIA)]. The data from these clinical trials confirm the results from extensive preclinical testing. Refrigerated lyophilisate and a new human serum albumin (HSA)-free formulation of IFN-alpha 2a, produced according to the latest process specification, are less immunogenic than earlier products.
Candidate Taste Receptors in Drosophila (2000)

Little is known about the molecular mechanisms of taste perception in animals, particularly the initial events of taste signaling. A large and diverse family of seven transmembrane domain proteins was identified from the Drosophila genome database with a computer algorithm that identifies proteins on the basis of structure. Eighteen of 19 genes examined were expressed in the Drosophila labellum, a gustatory organ of the proboscis. Expression was not detected in a variety of other tissues. The genes were not expressed in the labellum of a Drosophila mutant, pox-neuro70, in which taste neurons are eliminated. Tissue specificity of expression of these genes, along with their structural similarity, supports the possibility that the family encodes a large and divergent family of taste receptors.
Cross‐linking CD28 leads to activation of 70‐kDa S6 kinase (1994)

Proliferation of T lymphocytes in response to antigen/MHC complexes is dependent upon the presence of a co-stimulatory signal; in its absence, T cells are rendered unresponsive to specific antigen CD28 is a T cell surface glycoprotein that acts as a co-stimulatory molecule when combined with signals initiated by the T cell receptor CD3 complex. While the biochemical signaling events following CD28 stimulation are still poorly defined, monoclonal antibodies (mAb) directed against CD28 have been shown to transduce a variety of early signals that are different in the presence of cross-linking antibody or the presence of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Stimulation of human T cells with cross-linked anti-CD28 mAb alone resulted in the activation of 70-kDa (p70) S6 kinase, a rapamycin-sensitive serine/threonine kinase that is believed to be important for cell cycle progression. Activation of p70 S6 kinase through CD28 was inhibited by rapamycin. Activation of p70 S6 kinase also increased in response to cross-linked CD3, but followed a more rapid time course than activation via CD2. Cyclosporin A and FK506 had no effect on p70 S6 kinase activity initiated via either pathway. The combination of cross-linked CD28 and cross-linked CD3 had no more than an additive effect on the induction of p70 S6 kinase activity. Thus, recruitment of p70 S6 kinase activity appears to represent a common signal transduction event shared by both the CD28 and CD3 pathways of T cell activation.
The Virtual Cell (1998)

This paper describes a computational framework for cell biological modeling and simulation that is based on the mapping of experimental biochemical and electrophysiological data onto experimental images. The framework is designed to enable the construction of complex general models that encompass the general class of problems coupling reaction and diffusion.
Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study (2016)

ClinicalTrials.gov NCT02516085.
Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus (1997)

Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk.
Characterization and expression of a Pinus radiata putative ortholog to the Arabidopsis SHORT-ROOT gene (2008)

We characterized a Pinus radiata D. Don putative ortholog to the Arabidopsis thaliana (L.) Heynh. SHORT--ROOT gene (AtSHR) and analyzed its expression in different organs during vegetative development and in response to exogenous auxin during adventitious rooting. The predicted protein sequence contained domains characteristic of the GRAS protein family and showed a strong similarity to the SHORT--ROOT (SHR) proteins. Quantitative reverse transcriptase--polymerase chain reaction (qRT-PCR) and in situ hybridization showed that the gene is predominantly expressed in roots, root primordia and in the cambial region of hypocotyl cuttings. Increased mRNA levels were observed, independently of the presence or absence of exogenous auxin, in the cambial region and rooting competent cells of hypocotyl cuttings within the first 24 h of adventitious rooting, before the activation of cell divisions and the organization of the adventitious root meristem. The expression pattern in organs and during adventitious rooting was similar to that of a Pinus radiata SCARECROW-LIKE (PrSCL1) gene, except that PrSCL1 is induced in response to exogenous auxin. Results suggest that the Pinus radiata SHORT-ROOT (PrSHR) gene has a role in root meristem formation and maintenance and in the cambial region of hypocotyl cuttings.
IMPROVED ESTIMATION OF TRAFFIC FLOW FOR REAL-TIME CONTROL (DISCUSSION AND CLOSURE) (1981)

A critical review of the most widely accepted demand prediction algorithms is presented. Based on data collected at four intersections, sensitivity analysis of the best existing algorithms indicates that very little improvement in their performance could be achieved. A new, simpler algorithm, which requires considerably less information and fewer computations, is subsequently proposed and compared with the best of the existing algorithms. The results suggest that for 5-min prediction the second-generation Urban Traffic Control System predictor (UTCS-2) is usually better. However, in cycle-by-cycle prediction the proposed algorithm is considerably (as much as 41 percent) better than the best of the existing algorithms. (Authors)
Bioavailability of low-dose oral etoposide. (1993)

Bioavailability of a 100-mg oral etoposide dose is greater than suggested in the package insert from Bristol Laboratories (Evansville, IN). Comparable oral etoposide doses are not uniformly twice that of an IV dose, as suggested by the package insert, but will depend on the final oral dose administered. Bioavailability is better at lower oral etoposide doses. This study confirms the wide interpatient and intrapatient variability in oral etoposide bioavailability.
A NOVEL INERT COLLAGEN MATRIX FOR HYPOSPADIAS REPAIR (1999)

The use of a collagen inert matrix appears to be beneficial in patients who have undergone previous hypospadias repair and who may lack sufficient genital skin for reconstruction.
11 Inhibitors of HIV Reverse Transcriptase as Antiviral Agents and Drug Resistance (1993)

The fundamental role played by reverse transcriptase (RT) in the replication of retroviruses has made this enzyme a key target in the chemotherapy of human immunodeficiency virus (HIV) infection. The initial part of this chapter briefly reviews the most promising antiviral agents known to inhibit the function of HIV RT. These agents fall broadly into two classes: nucleoside analogs that are active in the triphosphorylated form and nonnucleosides that interact directly with RT. The nucleoside analog most prominent to date in the therapy of HIV disease and AIDS is zidovudine (3′-azido-3′-deoxythymidine, AZT) (Mitsuya et al. 1985; Furman et al. 1986), although a number of other nucleoside analogs are now being used clinically. Less advanced is the development of nonnucleosides for the potential treatment of HIV infection. However, a number of promising RT inhibitors of this nature have been described recently and are currently undergoing clinical investigation. Much of this chapter is devoted to the issue of drug resistance mediated by mutation of HIV RT. Not surprisingly, the bulk of our current knowledge relates to AZT resistance due to the extensive analysis of HIV isolates from treated individuals and from in vitro studies of RT and the virus. We initially describe RT mutagenesis studies where enzyme specificity toward various inhibitors was altered by making a number of amino acid substitutions. These experiments provided an early indication that resistance to RT inhibitors could potentially occur. We next review our knowledge of AZT resistance, derived mainly from the examination of HIV clinical isolates,...
Skew-resistant parallel processing of feature-extracting scientific user-defined functions (2010)

Scientists today have the ability to generate data at an unprecedented scale and rate and, as a result, they must increasingly turn to parallel data processing engines to perform their analyses. However, the simple execution model of these engines can make it difficult to implement efficient algorithms for scientific analytics. In particular, many scientific analytics require the extraction of features from data represented as either a multidimensional array or points in a multidimensional space. These applications exhibit significant computational skew, where the runtime of different partitions depends on more than just input size and can therefore vary dramatically and unpredictably. In this paper, we present SkewReduce, a new system implemented on top of Hadoop that enables users to easily express feature extraction analyses and execute them efficiently. At the heart of the SkewReduce system is an optimizer, parameterized by user-defined cost functions, that determines how best to partition the input data to minimize computational skew. Experiments on real data from two different science domains demonstrate that our approach can improve execution times by a factor of up to 8 compared to a naive implementation.
Precise Cas9 targeting enables genomic mutation prevention (2016)

ABSTRACT Here we present a generalized method of guide RNA “tuning” that enables Cas9 to discriminate between two target sites that differ by a single nucleotide polymorphism. We employ our methodology to generate a novel in vivo mutation prevention system in which Cas9 actively restricts the occurrence of undesired gain-of-function mutations within a population of engineered organisms. We further demonstrate that the system is scalable to a multitude of targets and that the general tuning and prevention concepts are portable across engineered Cas9 variants and Cas9 orthologs. Finally, we show that the designed mutation prevention system maintains robust activity even when placed within the complex environment of the mouse gastrointestinal tract.
Saliency detection by multi-context deep learning (2015)

Low-level saliency cues or priors do not produce good enough saliency detection results especially when the salient object presents in a low-contrast background with confusing visual appearance. This issue raises a serious problem for conventional approaches. In this paper, we tackle this problem by proposing a multi-context deep learning framework for salient object detection. We employ deep Convolutional Neural Networks to model saliency of objects in images. Global context and local context are both taken into account, and are jointly modeled in a unified multi-context deep learning framework. To provide a better initialization for training the deep neural networks, we investigate different pre-training strategies, and a task-specific pre-training scheme is designed to make the multi-context modeling suited for saliency detection. Furthermore, recently proposed contemporary deep models in the ImageNet Image Classification Challenge are tested, and their effectiveness in saliency detection are investigated. Our approach is extensively evaluated on five public datasets, and experimental results show significant and consistent improvements over the state-of-the-art methods.
Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection (1996)

Herpes simplex virus type 1 (HSV-1) infection on the murine cornea induces an intense inflammatory response which can lead to blindness. This disease, known as herpes stromal keratitis, can be prevented by the timely passive transfer of monoclonal antibody specific for viral glycoprotein D (gD). Precisely how antibody treatment prevents excessive corneal inflammation is not known. In this study we investigated whether chemokine mRNA expression is inhibited by antibody treatment. Total cellular RNAs isolated from normal corneas and at various times after virus infection were analyzed via reverse transcription-PCR for mRNA coding for seven different chemokines. Constitutive levels of IP-10, KC, MIP-2, MCP-1, MIP-1 beta, and RANTES mRNA were detected in uninfected corneas of BALB/c mice. When the cornea was mechanically traumatized, message for all six chemokines was transiently elevated above constitutive levels. In contrast, HSV-1 infection resulted in prolonged enhanced chemokine message expression. The kinetics of mRNA accumulation was distinctive for each chemokine analyzed. MIP-1 alpha message, not detected constitutively, was not evident until day 7 postinfection. Administration of anti-HSV gD monoclonal antibody 1 day after infection was associated with reduced message for MIP-2, MCP-1, MIP-1 alpha, and MIP-1 beta. IP-10, KC, and RANTES messages were not altered. Collectively, our results suggest that anti-gD treatment may protect, at least in part, by inhibiting production of chemokines believed to promote inflammation.
Room temperature preparation of conductive silver features using spin-coating and inkjet printing (2009)

Inkjet printing and spin-coating have been used to prepare patterns using a silver-containing metallo-organic decomposition ink. The patterned ink was reduced to silver by exposure to UV light and subsequent treatment with hydroquinone solution. This process, which took less than a minute, was performed at room temperature, which allowed low glass transition temperature polymeric substrates, such as PET, to be used. The conductivity of the silver patterns was found to be 10% that of bulk silver. The mechanical stability was also measured, with a linear increase in resistance seen for increasing strain, and no significant change in resistance seen after 12 000 cyclic deformations.