gebhart/patrepeval huggingface dataset:
Neurovirulent strains of Alphavirus induce apoptosis in bcl-2-expressing cells: role of a single amino acid change in the E2 glycoprotein. (1994)

The isolation and sequence comparison of avirulent and neurovirulent strains of polio virus, alpha virus, herpes virus, immunodeficiency virus, and other viruses have identified genetic changes that are required to cause disease in the nervous system. The molecular mechanisms by which these genetic changes result in neurovirulence are unknown. An avirulent laboratory strain of the Alphavirus Sindbis kills most cultured cell lines not by lethal parasitism, but by inducing apoptosis or programmed cell death. Transfection of cultured cells with the human bcl-2 oncogene can block Sindbis virus-induced apoptosis, resulting in a persistent viral infection resembling that observed in brains of immunodeficient mice. We investigated the possibility that neurovirulent strains of Sindbis virus could overcome the protective effects of bcl-2--a potential mechanism to explain the ability of these strains to cause fatal disease. Strains of Sindbis virus that were lethal for 2- to 4-week-old mice induced apoptotic death in cultured cells despite the presence of bcl-2. Using recombinant viruses, we show that a single amino acid change in the E2 glycoprotein of Sindbis virus confers both neurovirulence and the ability to kill cells expressing bcl-2.
The cloning and characterization of a second brain enzyme with NAAG peptidase activity (2004)

Abstract The peptide neurotransmitter N ‐acetylaspartylglutamate is inactivated by extracellular peptidase activity following synaptic release. It is speculated that the enzyme, glutamate carboxypeptidase II (GCPII, EC 3.14.17.21), participates in this inactivation. However, CGCPII knockout mice appear normal in standard neurological tests. We report here the cloning and characterization of a mouse enzyme (tentatively identified as glutamate carboxypeptidase III or GCPIII) that is homologous to an enzyme identified in a human lung carcinoma. The mouse peptidase was cloned from two non‐overlapping EST clones and mouse brain cDNA using PCR. The sequence (GenBank, AY243507 ) is 85% identical to the human carcinoma enzyme and 70% homologous to mouse GCPII. GCPIII sequence analysis suggests that it too is a zinc metallopeptidase. Northern blots revealed message in mouse ovary, testes and lung, but not brain. Mouse cortical and cerebellar neurons in culture expressed GCPIII message in contrast to the glial specific expression of GCPII. Message levels of GCPIII were similar in brains obtained from wild‐type mice and mice that are null mutants for GCPII. Chinese hamster ovary (CHO) cells transfected with rat GCPII or mouse GCPIII expressed membrane bound peptidase activity with similar V max and K m values (1.4 µ m and 54 pmol/min/mg; 3.5 µ m and 71 pmol/min/mg, respectively). Both enzymes are activated by a similar profile of metal ions and their activities are blocked by EDTA. GCPIII message was detected in brain and spinal cord by RT‐PCR with highest levels in the cerebellum and hippocampus. These data are consistent with the hypothesis that nervous system cells express at least two differentially distributed homologous enzymes with similar pharmacological properties and affinity for NAAG.
Adatom Capture and Growth Rates of Nuclei (1971)

A comprehensive treatment for the growth of cap- and disk-shaped nuclei on surfaces is developed. The results are important for a description of high-vacuum thin-film deposition, chemical-vapor deposition, electrodeposition, oxidation, and dropwise-condensation heat-transfer processes. The curvature effects of small nuclei on the adatom concentration field are included and shown to be negligible for nuclei appreciably larger than the critical size. The extent of the nucleation-exclusion zone surrounding a growing nucleus is shown to be strongly size dependent and initially much smaller than the adatom-capture zone. This obtains until the nucleus radius approaches the mean adatom-diffusion distance. Growth is considered to begin at the instant a nucleus exceeds the critical size. Analytical solutions and numerical integration have yielded results which are suitable for the evaluation of nuclei growth rates and growth times under most experimental conditions. This treatment also enables an evaluation of the adatom mean surface-diffusion distance and desorption energy to be made independent of the nucleation-rate model (classical or atomistic) chosen. Growth rates and times are shown to be essentially independent of the critical nucleus size for supersaturations greater than 100 and sizes greater than several times the critical. Growth on a substrate saturated with nuclei is also treated.
Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine. (1981)

The enzyme 20 alpha-hydroxysteroid dehydrogenase (20 alpha SDH) has previously been shown to be a specific enzyme marker of mature T cells. In vivo, the expression of 20 alpha SDH is thymus dependent, in that splenic lymphocytes from athymic mice have only low levels of activity, although the levels of enzyme activity increase gradually with age. In vitro, 20 alpha SDH can be induced in splenic lymphocytes from nu/nu mice by conditioned media from mitogen- or alloantigen-stimulated normal lymphocytes. Induction is rapid in vitro. Beginning after a lag period of approximately 6 hr, enzyme activity increases linearly for approximately 20 to 30 hr resulting in a 5- to 10-fold increase in activity. Induction is blocked by mitomycin C, suggesting a requirement for cell proliferation. The phenotype of both the precursor and the induced lymphocyte populations is Thy 1.2-, Lyt 1-, 2-, suggesting that induction of 20 alpha SDH expression is an early step in T cell differentiation. The factor responsible for 20 alpha SDH induction has been partially purified and is distinct from other known lymphokines in both its biochemical and functional properties. The term interleukin 3 is proposed for this factor.
Sub-pixel super-resolution by decoding frames from a reconfigurable coded-aperture camera: theory and experimental verification (2009)

In a previous paper we presented initial results for sub-detector-pixel imaging in the mid-wave infra-red (MWIR) using an imager equipped with a coded-aperture based on a re-configurable MOEMS micro-shutter. It was shown in laboratory experiments that sub-pixel resolution is achievable via this route. The purpose of the current paper is to provide detail on the reconstruction method and to discuss some challenges which arise when imaging real-world scenes. The number of different mask patterns required to achieve a certain degree of super-resolution is also discussed. New results are presented to support the theory.
Pyloric motor response to sympathetic nerve stimulation in dogs. (1981)

Through this study we evaluated the effect of electrical stimulation of the greater splanchnic nerve on gastroduodenal motility in anesthetized dogs. The majority of stimulations (at a frequency of 10 Hz for 5 msec at a strength of 10V for a train of 10 sec) produced contractions in the gastric antrum and pylorus and relaxation in the duodenum. The antral, pyloric, and duodenal motor responses were unaffected by cervical vagosympathectomy, thoracic vagotomy, and adrenalectomy. Administration of phentolamine, propranolol, or hexamethonium and pretreatment with reserpine failed to affect the contractile gastroduodenal motor response. The inhibitory motor response in the duodenum was also unaffected by these surgical procedures and administration of drugs. After atropine administration, contractions induced by splanchnic nerve stimulation were abolished in the pylorus, as well as in the antrum and duodenum. Tetrodotoxin also abolished the gastroduodenal motor response. The greater splanchnic nerve contains an excitatory cholinergic pathway to the musculature of the pylorus.
Experimental Demonstration and Tolerancing of a Large-Scale Neural Network (165 000 Synapses) Using Phase-Change Memory as the Synaptic Weight Element (2015)

Using two phase-change memory devices per synapse, a three-layer perceptron network with 164 885 synapses is trained on a subset (5000 examples) of the MNIST database of handwritten digits using a backpropagation variant suitable for nonvolatile memory (NVM) + selector crossbar arrays, obtaining a training (generalization) accuracy of 82.2% (82.9%). Using a neural network simulator matched to the experimental demonstrator, extensive tolerancing is performed with respect to NVM variability, yield, and the stochasticity, linearity, and asymmetry of the NVM-conductance response. We show that a bidirectional NVM with a symmetric, linear conductance response of high dynamic range is capable of delivering the same high classification accuracies on this problem as a conventional, software-based implementation of this same network.
Dual Flying Capacitor Active-Neutral-Point-Clamped Multilevel Converter (2015)

Hybrid multilevel converters combine features of conventional multilevel topologies to provide an acceptable tradeoff between the advantages and disadvantages of these converters. For many industrial applications, common dc link is a requirement that limits the choice of topologies to neutral point clamped (NPC) and flying capacitor multicell (FCM) hybrid types. This paper investigates the operation of a hybrid five-level topology and proposes a modulation method that takes the advantage of the combined features of NPC and FCM. The dual flying capacitor (FC) active-neutral-point-clamped (DFC-ANPC) converter provides certain advantages such as natural soft switching of line frequency switches, elimination of the transient voltage balancing snubbers, and a more even loss distribution. Simulation results and experimental verification of the five-level DFC-ANPC converter are presented to validate the performance of the converter as well as the applied modulation technique.
Cumulative stabilizing effects of hydrophobic interactions on the surface of the neutral protease from Bacillus subtilis (1996)

Using genetically engineered mutants of the neutral protease from Bacillus stearothermophilus (BsteNP), it had been shown that the surface-exposed structural motif constituted by Phe63 embedded in a four amino acid hydrophobic pocket is critical for the thermal stability of the thermophilic neutral proteases from Bacilli. To measure the stabilizing contribution of each hydrophobic interaction taking place between Phe63 and the hydrophobic pocket, we grafted this structural motif in the neutral protease from the mesophile Bacillus subtilis (BsubNP). This was accomplished by first creating the Thr63-->Phe mutant of BsubNP and then generating a series of mutants in which the four amino acids which in thermolysin surround Phe63 and form the hydrophobic pocket were added one after the other. By analysing the thermal stability of each mutant it was found that the 2 degrees C destabilizing effect of the Thr63-->Phe substitution was completely suppressed by the addition of the four amino acid hydrophobic pocket, each replacement providing a stabilizing contribution of approximately 0.8-1 degrees C. These results are discussed in the light of the peculiar mechanism of thermal inactivation of proteolytic enzymes.
Blended Dual-source Acquisition and Processing of Broadband Data (2014)

Summary The potential to cut acquisition time and cost continues to create interest for simultaneous shooting. Many synthetically blended datasets have been generated to validate the viability of such an approach. This paper presents results from a broadband variable-depth streamer acquisition conducted offshore Indonesia. The acquisition consisted of simultaneous firing of dual sources with a randomised timing pattern specifically designed to enable separation of low frequency cross-talk noise. After source separation, the data were processed through a 3D broadband processing flow. The results validate the effectiveness of the source separation strategy and compatibility with the broadband processing sequence.
Iterative Saturation Mutagenesis Accelerates Laboratory Evolution of Enzyme Stereoselectivity: Rigorous Comparison with Traditional Methods (2010)

Efficacy in laboratory evolution of enzymes is currently a pressing issue, making comparative studies of different methods and strategies mandatory. Recent reports indicate that iterative saturation mutagenesis (ISM) provides a means to accelerate directed evolution of stereoselectivity and thermostability, but statistically meaningful comparisons with other methods have not been documented to date. In the present study, the efficacy of ISM has been rigorously tested by applying it to the previously most systematically studied enzyme in directed evolution, the lipase from Pseudomonas aeruginosa as a catalyst in the stereoselective hydrolytic kinetic resolution of a chiral ester. Upon screening only 10,000 transformants, unprecedented enantioselectivity was achieved (E = 594). ISM proves to be considerably more efficient than all previous systematic efforts utilizing error-prone polymerase chain reaction at different mutation rates, saturation mutagenesis at hot spots, and/or DNA shuffling, pronounced positive epistatic effects being the underlying reason.
Bayesian Estimation of Disease Prevalence and the Parameters of Diagnostic Tests in the Absence of a Gold Standard (1995)

It is common in population screening surveys or in the investigation of new diagnostic tests to have results from one or more tests investigating the same condition or disease, none of which can be considered a gold standard. For example, two methods often used in population-based surveys for estimating the prevalence of a parasitic or other infection are stool examinations and serologic testing. However, it is known that results from stool examinations generally underestimate the prevalence, while serology generally results in overestimation. Using a Bayesian approach, simultaneous inferences about the population prevalence and the sensitivity, specificity, and positive and negative predictive values of each diagnostic test are possible. The methods presented here can be applied to each test separately or to two or more tests combined. Marginal posterior densities of all parameters are estimated using the Gibbs sampler. The techniques are applied to the estimation of the prevalence of Strongyloides infection and to the investigation of the diagnostic test properties of stool examinations and serologic testing, using data from a survey of all Cambodian refugees who arrived in Montreal, Canada, during an 8-month period.
Complex Loci in Human and Mouse Genomes (2006)

Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs), along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis-antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.
MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles (2009)

Recent transcriptome analyses have shown that thousands of noncoding RNAs (ncRNAs) are transcribed from mammalian genomes. Although the number of functionally annotated ncRNAs is still limited, they are known to be frequently retained in the nucleus, where they coordinate regulatory networks of gene expression. Some subnuclear organelles or nuclear bodies include RNA species whose identity and structural roles are largely unknown. We identified 2 abundant overlapping ncRNAs, MENepsilon and MENbeta (MENepsilon/beta), which are transcribed from the corresponding site in the multiple endocrine neoplasia (MEN) I locus and which localize to nuclear paraspeckles. This finding raises the intriguing possibility that MENepsilon/beta are involved in paraspeckle organization, because paraspeckles are, reportedly, RNase-sensitive structures. Successful removal of MENepsilon/beta by a refined knockdown method resulted in paraspeckle disintegration. Furthermore, the reassembly of paraspeckles disassembled by transcriptional arrest appeared to be unsuccessful in the absence of MENepsilon/beta. RNA interference and immunoprecipitation further revealed that the paraspeckle proteins p54/nrb and PSF selectively associate with and stabilize the longer MENbeta, thereby contributing to the organization of the paraspeckle structure. The paraspeckle protein PSP1 is not directly involved in either MENepsilon/beta stabilization or paraspeckle organization. We postulate a model for nuclear paraspeckle body organization where specific ncRNAs and RNA-binding proteins cooperate to maintain and, presumably, establish the structure.
Gene expression of tumor angiogenesis dissected: specific targeting of colon cancer angiogenic vasculature (2006)

Crucial to designing angiostatic and vascular targeting agents is the identification of target molecules. Because angiogenesis is not limited to pathologic conditions, careful evaluation of putative therapeutic targets is warranted to prevent adverse effects associated with impaired physiologic angiogenesis. To identify tumor-specific angiogenesis markers, we compared transcriptional profiles of angiogenic endothelial cells isolated from malignant and nonmalignant tissues with those of resting endothelial cells. We identified 17 genes that showed specific overexpression in tumor endothelium but not in angiogenic endothelium of normal tissues, creating a therapeutic window for tumor vasculature-specific targeting. Antibody targeting of 4 cell-surface-expressed or secreted products (vimentin, CD59, HMGB1, IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. Our results demonstrate the usefulness of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.
Ellipsometric monitoring and control of the rapid thermal oxidation of silicon (1993)

Single wavelength ellipsometry is demonstrated for in situ process monitoring and control in a rapid thermal processing system. Simultaneous in situ ellipsometric measurements of the temperature and oxide film thickness allow closed-loop feedback control during film growth. Data are presented for the rapid thermal oxidation of silicon under computer control for oxide thickness ranging from 60 to 175 Å and temperatures from 850 to 1000 °C.
Mutations in two cysteine-histidine-rich clusters in adenovirus type 2 DNA polymerase affect DNA binding (1992)

Several point and linker insertion mutations in two Cys-His-rich regions of adenovirus (Ad) DNA polymerase (Pol) gene have been expressed in recombinant vaccinia virus. The resulting mutant enzymes were analyzed in vitro for their effects on DNA synthesis activity, on Ad-specific initiation assays, on gel shifts of Ad origin sequences, and on interactions with adenovirus preterminal protein (pTP) and nuclear factor I (NFI). In general, mutants in downstream Cys-His sequences had a pronounced effect in these assays. Mutants in the upstream Cys-His region had a moderate effect on DNA synthesis and elongation but failed to make dCMP-pTP initiation complexes and failed to make specific shifted complexes in a gel retardation assay. These mutants could still bind to pTP and NFI in a coimmunoprecipitation experiment, suggesting that this upstream Cys-His region of Ad Pol is involved either in specific Ad DNA origin binding or in nonspecific DNA binding. Changing residues within Cys doublets in the downstream Cys-His region had pronounced effects on many Ad Pol functions such as DNA synthesis, DNA binding, and in vitro initiation; however, these mutants showed little reduction in binding to pTP and NFI; mutants at other cysteines or histidines within this region of Ad Pol did not appear to have an effect on enzyme function. This observation suggests that the downstream Cys-His region of Ad Pol is important for DNA binding and might fold into a Zn finger motif.
Dual Deep-Structure to Associate a Shape with its Linguistic Description: A Hypothetical Framework and an Experimental Implementation (2003)

This paper discusses how formal language representation brings about some burdens in design support system after giving the outline of formal representation in design. Then, this paper proposes, without formal representation, a framework to represent the relation between shapes and natural language expression about the shapes, though the framework is not completed since it is a part of an on going project. Finally, an experimental implementation, which uses a connectionism model, of the proposed framework and the behavior of the implemented system are described.
Bone Morphogenetic Protein 1 Is an Extracellular Processing Enzyme of the Laminin 5 γ2 Chain (2000)

Epithelial cells maintained in culture medium containing low calcium proteolytically process laminin 5 (alpha3beta3gamma2) within the alpha3 and gamma2 chains (). Experiments were designed to identify the enzyme(s) responsible for the laminin 5 processing and the sites of proteolytic cleavage. To characterize the nature of laminin 5 processing, we determined the N-terminal amino acid sequences of the proteolytic fragments produced by the processing events. The results indicate that the first alpha3 chain cleavage (200-l65 kDa alpha3) occurs within subdomain G4 of the G domain. The second cleavage (l65-l45 kDa alpha3) occurs within the lIla domain, 11 residues N-terminal to the start of domain II. The gamma chain is cleaved within the second epidermal growth factor-like repeat of domain Ill. The sequence cleaved within the gamma2 chain matches the consensus sequence for the cleavage of type I, II, and III procollagens by bone morphogenetic protein-1 (BMP-1), also known as type I procollagen C-proteinase (). Recombinant BMP-1 cleaves gamma2 in vitro, both within intact laminin 5 and at the predicted site of a recombinant gamma2 short arm. alpha3 is also cleaved by BMP-1 in vitro, but the cleavage site is yet to be determined. These results show the laminin alpha3 and gamma2 chains to be substrates for BMP-1 in vitro. We speculate that gamma2 cleavage is required for formation of the laminin 5-6 complex and that this complex is directly involved in assembly of the interhemidesmosomal basement membrane. This further suggests that BMP-1 activity facilitates basement membrane assembly, but not hemidesmosome assembly, in the laminin 5-rich dermal-epidermal junction basement membrane in vivo.