gebhart/patrepeval huggingface dataset:
MEMBRANE LYSIS IN CHINESE HAMSTER OVARY CELLS TREATED WITH HEMATOPORPHYRIN DERIVATIVE PLUS LIGHT (1982)

Abstract Chinese hamster ovary cells in exponential growth were incubated with various concentrations of hematoporphyrin derivative (HpD). Cellular porphyrin content was determined after 2 h incubation at 37°C using [ 3 H]‐hematoporphyrin derivative. Photoactivation of cell‐bound HpD by red light resulted in a family of survival curves with terminal slopes proportional to cellular HpD concentration. The degree of cellular lysis, assayed 1 h after illumination using a chromium‐51 labeling technique, was also found to be related to cellular HpD concentration. The amount of 51Cr released increased with post‐irradiation incubation to a level parallel to cell lethality as measured by colony formation. These data suggest that lysis of the cell membrane may be largely responsible for cellular inactivation following HpD photoirradiation.
Chemokines, lymphocytes, and HIV (1998)

Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-gamma and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3 alpha, and STRL22 has been renamed CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit.
mclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models (2016)

Finite mixture models are being used increasingly to model a wide variety of random phenomena for clustering, classification and density estimation. mclust is a powerful and popular package which allows modelling of data as a Gaussian finite mixture with different covariance structures and different numbers of mixture components, for a variety of purposes of analysis. Recently, version 5 of the package has been made available on CRAN. This updated version adds new covariance structures, dimension reduction capabilities for visualisation, model selection criteria, initialisation strategies for the EM algorithm, and bootstrap-based inference, making it a full-featured R package for data analysis via finite mixture modelling.
The immediate future for the medical treatment of atrial fibrillation (2002)

Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a common reason for mortality and morbidity. Atrial fibrillation causes disease for three reasons: i) the ventricular rate is often high, which leads to symptoms ranging from discomfort to life threatening heart failure; ii) the rhythm causes loss of atrioventricular synchrony, which reduces diastolic filling and may lead to heart failure; and iii) atrial contraction is lost leading to stagnant blood that again may lead to atrial thrombi and peripheral embolism. Thus, the treatment of atrial fibrillation is focused on the maintenance of sinus rhythm, rate control and prevention of embolism. For the maintenance of sinus rhythm, all drugs under current development are potassium channel blockers; the so-called class III anti-arrhythmic drugs. Those which have been further investigated appear to be valuable for maintenance of sinus rhythm but all carry a significant risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia. Rate control has been a focus of treatment for many years and several very old drugs, including digoxin, are used for this. There is, to the author's knowledge, no current effort for evaluating new drugs for this indication. Prevention of embolism has for many years been obtained with vitamin K antagonists for which the clinical evidence is overwhelming. Previous attempts to replace vitamin K antagonists with aspirin have not been fruitful. A large number of newer anticoagulation regimes are in development, but to the author's knowledge only a single thrombin inhibitor is actively being developed for atrial fibrillation.
Editorial: Proteomics 9/2005 (2005)

Abstract No abstracts.
Cloning of the Enomycin Structural Gene from Streptomyces mauvecolor and Production of Recombinant Enomycin in Escherichia coli. (1997)

A genomic DNA library from the enomycin (ENM) producer, Streptomyces mauvecolor, was screened for the ENM structural gene (enm) by use of a segment of the phenomycin gene (phm) as the probe, and a plasmid, pENI, was constructed. By primer-walking along the insert, a 573 bp DNA sequence that contain an ORF corresponding to preENM was determined. The deduced amino acid composition of ENM was close to that previously reported (MIZUNO, S.; K. NITTA & H. UMEZAWA: Mode of action of enomycin, an antitumor antibiotic of high molecular weight. I. Inhibition of protein synthesis. J. Biochem. 61: 373 approximately 381, 1967). The producer cells expressed enm during an ENM-productive fermentation. An enm-expression plasmid, pENE 1, was constructed, with which E. coli AD202 was transformed. The transformant produced a fusion protein consisting of glutathione-S-transferase (GST) and ENM. The genetically engineered ENM (rENM) inhibited the growth of Hela cells in vitro. Comparison of the base sequence spanning enm with that spanning phm showed that the structural genes were conserved more extensively than were the flanking regions, though the genes were unlikely to be essential to the lives of the producers.
Quantum Signal Splitting that Avoids Initialization of the Targets (1997)

The classical signal splitting and copying are not possible in quantum mechanics. Specifically, one cannot copy the basis up and down states of the input (I) two-state system (qubit, spin) into the copy (C) and duplicate-copy (D) two-state systems if the latter systems are initially in an arbitrary state. We consider instead a quantum evolution in which the basis states of I at time t are duplicated in at least two of the systems I, C, D, at time t+Δt. In essence, the restriction on the initial target states is exchanged for uncertainty as to which two of the three qubits retain copies of the initial source state.
TAT fusion proteins against ischemic stroke: Current status and future perspectives (2006)

The delivery of proteins across the blood-brain barrier is severely limited by the proteins' size and biochemical properties. Thus, a large number of peptides have been characterized in recent years that efficaciously prevent neuronal death in vitro, but which may not be applied in vivo, since they are unable to cross cell membrane barriers. In the 1990ies, it had been shown that the HIV TAT protein is able to cross cell membranes even when coupled with larger peptides. Subsequent studies with fusion proteins of the 11-amino acid protein transduction domain of HIV-TAT revealed that TAT fusion proteins may successfully be used for therapeutic purposes in vivo, even when systemically applied. Indeed, intravenous delivery of TAT proteins linked with anti-apoptotic (Bcl-XL) and neurotrophic (GDNF) factors resulted in a rapid and highly efficacious transduction of the brain tissue. When administered after focal cerebral ischemia, intravenous TAT-Bcl-XL and TAT-GDNF significantly reduced brain injury, both when applied after severe and mild ischemic insults. These data provided the first in vivo evidence of the efficacy of fusion proteins in the ischemic brain, thus raising new hopes that neuroprotection is feasible after stroke. Yet, molecular biological studies have pointed out more recently that there are also limitations of the TAT protein strategy, which still need to be addressed. The development of clinically-applicable treatments for ischemic stroke based on fusion protein technologies deserves concerted efforts in the future.
Sex Differences in Clinical Characteristics and Prognosis in a Broad Spectrum of Patients With Heart Failure (2007)

Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.
Characterization of a Processive Form of the Vaccinia Virus DNA Polymerase (1997)

We have previously shown that the purified, 116-kDa DNA polymerase encoded by vaccinia virus is inherently distributive, synthesizing only a few nucleotides per template binding event under moderate reaction conditions (W. F. McDonald and P. Traktman, J. Biol. Chem. 269, 31190-31197). These properties would be incompatible with efficient DNA replication in vivo and suggest that the polymerase most probably interacts with accessory proteins that stabilize the template/polymerase interaction. Here we show that a highly processive form of the enzyme is indeed present with cytoplasmic lysates prepared from infected cells, and demonstrate that this form of the enzyme is likely to comprise the DNA polymerase in association with an early viral protein with a native molecular weight of approximately 48K.
Rabi Oscillations in a Large Josephson-Junction Qubit (2002)

We have designed and operated a circuit based on a large-area current-biased Josephson junction whose two lowest energy quantum levels are used to implement a solid-state qubit. The circuit allows measurement of the qubit states with a fidelity of 85% while providing sufficient decoupling from external sources of relaxation and decoherence to allow coherent manipulation of the qubit state, as demonstrated by the observation of Rabi oscillations. This qubit circuit is the basis of a scalable quantum computer.
Antibody response to the M2 protein of influenza A virus expressed in insect cells (1993)

A recombinant baculovirus expressing the M2 protein from influenza A/Ann Arbor/6/60 (H2N2) virus (AA60 virus) was constructed. The expressed M2 protein was recognized by a monoclonal antibody specific for the M2 protein and comigrated with the M2 protein from cells infected with AA60 virus on SDS-polyacrylamide gels. Immunofluorescence studies indicated that the expressed M2 protein was present on the surface of Spodoptera frugiperda (Sf9) cells infected with the recombinant baculovirus. Immunoassays using the expressed M2 protein were able to detect antibodies to the M2 protein in serum samples from humans and ferrets infected with influenza A viruses.
Antisense technology : a practical approach (1997)

1: Nucleic acid structures. 2: Evaluation of antisense effects. 3: Selecting, preparing, and handling antisense oligodeoxyribonucleotides. 4: In vitro RNAs. 5: Catalytic antisense RNA based on hammerhead ribozymes. 6: 2-5 A-Antisense chimaeras for targeted degradation of RNA. 7: In vitro applications of antisense RNA and DNA. 8: Antisense applications in Dictyostelium: a lower eukaryotic model system. 9: Applications of antisense technology in plants. 10: Antisense molecules and ribozymes: medical applications. 11: Non-antisense effects of oligodeoxynucleotides. 12: Antisense rescue. 13: Shotgun antisense mutants. 14: Detection of sense-antisense duplexes by structure-specific anti-RNA antibodies
Discrete protein interactions with the Grb2/c-Cbl complex in SCF- and TPO-mediated myeloid cell proliferation. (1996)

Hemopoietic cell proliferation is mediated by non-tyrosine and tyrosine kinases that signal via uncommon and common sets of downstream effector molecules including the Grb2/c-Cbl. In the present study we evaluated tyrosine phosphorylation of c-Cbl and the interaction of the Grb2/c-Cbl complex with signaling proteins upon activation of non-tyrosine (c-Mpl) and tyrosine kinase (c-Kit) receptors leading to myeloid cell proliferation. By using the growth factor dependent M-07e cell line, we found that both c-Mpl and c-Kit ligands, namely: SCF and TPO, induce c-Cbl tyrosine phosphorylation. In these cells the adaptor protein Grb2 constitutively binds a substantial fraction of c-Cbl through the N-terminal SH3 domain. In vitro experiments showed that the stable Grb2/c-Cbl complex interacts, through the Grb2 SH2 domain, with the SCF-activated c-Kit. By contrast stimulation with TPO leads to the formation of a Grb2 complex containing JAK2. In vitro and in vivo experiments support the hypothesis that Grb2 mediates the association of c-Kit with c-Cbl. Moreover we found that, upon SCF stimulation, the Grb2/c-Cbl complex recruits Shc, probably via Grb2. By contrast the Ras exchanger factor (Sos1) was not detected in anti-c-Cbl immunoprecipitates suggesting that Grb2/Sos1 and Grb2/c-Cbl are present in different complexes. Taken together our results demonstrate that c-Cbl plays an important role in coupling both tyrosine and non-tyrosine kinase receptors to downstream effector molecules and that different signaling molecules interact with Grb2/c-Cbl complex when non-tyrosine or tyrosine kinase receptors are activated.
DARE: A Framework for Dynamic Authentication of Remote Executions (2008)

With the widespread use of the distributed systems comes the need to secure such systems against a wide variety of threats. Recent security mechanisms are grossly inadequate in authenticating the program executions at the clients or servers, as the clients, servers and the executing programs themselves can be compromised after the clients and servers pass the authentication phase. This paper presents a generic framework for authenticating remote executions on a potentially untrusted remote server - essentially validating that what is executed at the server on behalf of the client is actually the intended program. Details of a prototype Linux implementation are also described, along with some optimization techniques for reducing the run-time overhead of the proposed scheme. The performance overhead of our technique varies generally from 7% to 24% for most benchmarks, as seen from the actual remote execution of SPEC benchmarks.
The Kinetocardiogram (1953)

A simple method of recording low-frequency precordial movements is presented and termed kinetocardiogram to indicate movements as the result of the motions of the heart. The normal precordial patterns are described as well as the time relationships to the cardiac cycle and ballistocardiogram.
Robust dynamic motion estimation over time (2002)

A novel approach to incrementally estimating visual motion over a sequence of images is presented. The authors start by formulating constraints on image motion to account for the possibility of multiple motions. This is achieved by exploiting the notions of weak continuity and robust statistics in the formulation of a minimization problem. The resulting objective function is non-convex. Traditional stochastic relaxation techniques for minimizing such functions prove inappropriate for the task. A highly parallel incremental stochastic minimization algorithm is presented which has a number of advantages over previous approaches. The incremental nature of the scheme makes it dynamic and permits the detection of occlusion and disocclusion boundaries.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes (2013)

To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.
Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene (2010)

Nonsense mutations are usually predicted to function as null alleles due to premature termination of protein translation. However, nonsense mutations in the DMD gene, encoding the dystrophin protein, have been associated with both the severe Duchenne Muscular Dystrophy (DMD) and milder Becker Muscular Dystrophy (BMD) phenotypes. In a large survey, we identified 243 unique nonsense mutations in the DMD gene, and for 210 of these we could establish definitive phenotypes. We analyzed the reading frame predicted by exons flanking those in which nonsense mutations were found, and present evidence that nonsense mutations resulting in BMD likely do so by inducing exon skipping, confirming that exonic point mutations affecting exon definition have played a significant role in determining phenotype. We present a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of BMD nonsense mutations with a subset of DMD exons prone to mutation-induced exon skipping.
Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice. (1999)

Gene therapy transfer of angiostatin and endostatin represents an alternative method of delivering angiogenic polypeptide inhibitors. We examined whether liposomes complexed to plasmids encoding angiostatin or endostatin inhibited angiogenesis and the growth of MDA-MB-435 tumors implanted in the mammary fat pads of nude mice. We determined that plasmids expressing angiostatin (PCI-Angio) or endostatin (PCI-Endo) effectively reduced angiogenesis using an in vivo Matrigel assay. We then investigated the efficacy of these plasmids in reducing the size of tumors implanted in the mammary fat pad of nude mice. Both PCI-Angio and PCI-Endo significantly reduced tumor size when injected intratumorally (P < 0.05). Compared to the untreated control group, the mice treated with PCI-Angio and PCI-Endo exhibited a reduction in tumor size of 36% and 49%, respectively. In addition, we found that i.v. injections of liposomes complexed to PCI-Endo reduced tumor growth in the nude mice by nearly 40% when compared to either empty vector (PCI) or untreated controls (P < 0.05). These findings provide a basis for the further development of nonviral delivery of antiangiogenic genes.
Man-Portable Networked Sensor System (1998)

The Man-Portable Networked Sensor System (MPNSS), with its baseline sensor suite of a pan/tilt unit with video and FLIR cameras and laser rangefinder, functions in a distributed network of remote sensing packages and control stations designed to provide a rapidly deployable, extended-range surveillance capability for a wide variety of security operations and other tactical missions.While first developed as a man-portable prototype, these sensor packages can also be deployed on UGVs and UAVs, and a copy of this package been demonstrated flying on the Sikorsky Cypher VTOL UAV in counterdrug and MOUT scenarios.The system makes maximum use of COTS components for sensing, processing, and communications, and of both established and emerging standard communications networking protocols and system integration techniques.This paper will discuss the technical issues involved in: (1) system integration using COTS components and emerging bus standards, (2) flexible networking for a scalable system, and (3) the human interface designed to maximize information presentation to the warfighter in battle situations.
DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response. (2005)

Arylamine N-acetyltransferase (NAT) genes were targeted for inhibition using short hairpin RNA (shRNA) using two different RNA polymerase III promoters. Constructs were developed for NAT1 and NAT2, the endogenous mouse genes, and for human NAT1. There were fetal and neonatal deaths with these constructs, perhaps due in part to an interferon response as reflected in increases in oligoadenylate synthetase I mRNA levels. Seven out of 8 founders with the U6 promoter generated offspring but only 2 gave positive offspring. Out of 15 founders for H1 promoted constructs, only 4 had positive offspring. When transgenic lines were successfully established, the expression of the targeted genes was variable between animals and was not generally inhibitory.
Immunoregulatory properties of IL-13 in patients with inflammatory bowel disease; comparison with IL-4 and IL-10 (1996)

Activated monocytes with increased expression of proinflammatory cytokines play a major role in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4 and IL-10 can effectively suppress the proinflammatory response of activated monocytes. IL-13 is a recently described antiinflammatory agent in vitro. The aim of our study was to determine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL-10 in patients with IBD. Peripheral blood monocytes were isolated from 27 patients with ulcerative colitis (UC), 27 patients with Crohn's disease (CD) and 16 healthy controls. Cells were stimulated with pokeweed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secretion of IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 was assessed using sandwich ELISA systems. Peripheral blood monocytes secreted significantly increased amounts of TNF-alpha and IL-6 under stimulation with PWM in patients with CD, while UC patients showed significantly elevated levels of IL-1beta. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretion of IL-1beta in a dose-dependent manner. With regard to IL-13 and IL-4, there was no significant suppression of TNF-alpha and IL-6 in patients with active IBD. By contrast, IL-10 was able to down-regulate all proinflammatory cytokines in active IBD as well as in controls. Proinflammatory cytokines from patients with inactive IBD could be significantly down-regulated by all three immunoregulatory cytokines. The inhibitory effect of IL-13 on TNF-alpha and IL-6 production in differentiated macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-alpha and IL-6 after treatment with IL-13. In conclusion, the antiinflammatory activity of IL-13 is partially reduced in patients with active IBD. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.