gebhart/patrepeval huggingface dataset:
Bioengineering of AAV2 Capsid at Specific Serine, Threonine, or Lysine Residues Improves Its Transduction Efficiency in Vitro and in Vivo (2013)

We hypothesized that the AAV2 vector is targeted for destruction in the cytoplasm by the host cellular kinase/ubiquitination/proteasomal machinery and that modification of their targets on AAV2 capsid may improve its transduction efficiency. In vitro analysis with pharmacological inhibitors of cellular serine/threonine kinases (protein kinase A, protein kinase C, casein kinase II) showed an increase (20-90%) on AAV2-mediated gene expression. The three-dimensional structure of AAV2 capsid was then analyzed to predict the sites of ubiquitination and phosphorylation. Three phosphodegrons, which are the phosphorylation sites recognized as degradation signals by ubiquitin ligases, were identified. Mutation targets comprising eight serine (S) or seven threonine (T) or nine lysine (K) residues were selected in and around phosphodegrons on the basis of their solvent accessibility, overlap with the receptor binding regions, overlap with interaction interfaces of capsid proteins, and their evolutionary conservation across AAV serotypes. AAV2-EGFP vectors with the wild-type (WT) capsid or mutant capsids (15 S/T→alanine [A] or 9 K→arginine [R] single mutant or 2 double K→R mutants) were then evaluated in vitro. The transduction efficiencies of 11 S/T→A and 7 K→R vectors were significantly higher (~63-90%) than the AAV2-WT vectors (~30-40%). Further, hepatic gene transfer of these mutant vectors in vivo resulted in higher vector copy numbers (up to 4.9-fold) and transgene expression (up to 14-fold) than observed from the AAV2-WT vector. One of the mutant vectors, S489A, generated ~8-fold fewer antibodies that could be cross-neutralized by AAV2-WT. This study thus demonstrates the feasibility of the use of these novel AAV2 capsid mutant vectors in hepatic gene therapy.
WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. III. Structures of WS-7338 A, B, C and D and total synthesis of WS-7338 B. (1992)

1 ~4), in the culture broth of a Streptomyces sp. No. 7338.
Performance assessment of multivariate control loops on a paper‐machine headbox (1997)

Abstract A large number of control loops in the pulp and paper industry are multivariate in nature. The main control objective of these loops is to reduce process variation. The satisfactory performance of these loops is therefore important for maintaining product quality. This paper introduces a multivariate performance measure of such control loops. The multivariate minimum variance control performance which provides an absolute lower bound on process variance can be estimated from routine operating data, and serves as a good benchmark to assess control loop performance. The proposed measure of performance is evaluated by application to the multiloop control of a headbox machine.
HMf, a DNA-binding protein isolated from the hyperthermophilic archaeon Methanothermus fervidus, is most closely related to histones. (1990)

Methanothermus fervidus grows optimally at 83 degrees C. A protein designated HMf (histone M. fervidus) has been isolated from this archaeal hyperthermophile that binds to double-stranded DNA molecules and increases their resistance to thermal denaturation. HMf binding to linear double-stranded DNA molecules of greater than 2 kilobase pairs also increases their electrophoretic mobilities through agarose gels. Visualization of this compaction process by electron microscopy has demonstrated the formation of quasispherical, macromolecular HMf-DNA complexes. HMf is a mixture of approximately equal amounts of two very similar polypeptides designated HMf-1 and HMf-2. Determination of the DNA sequence of the gene encoding HMf-2 (hmfB) has revealed that over 30% of the amino acid residues in HMf-2 are conserved in the consensus sequences derived for eucaryal histones H2A, H2B, H3, and H4. These archaeal polypeptides and eucaryal histones appear therefore to have evolved from a common ancestor and are likely to have related structures and functions.
Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein. (1989)

The SNF1 gene of Saccharomyces cerevisiae encodes a protein-serine/threonine kinase that is required for derepression of gene expression in response to glucose limitation. We present evidence that the protein kinase activity is essential for SNF1 function: substitution of Arg for Lys in the putative ATP-binding site results in a mutant phenotype. A polyhistidine tract near the N terminus was found to be dispensable. Deletion of the large region C terminal to the kinase domain only partially impaired SNF1 function, causing expression of invertase to be somewhat reduced but still glucose repressible. The function of the SNF4 gene, another component of the regulatory system, was required for maximal in vitro activity of the SNF1 protein kinase. Increased SNF1 gene dosage partially alleviated the requirement for SNF4. C-terminal deletions of SNF1 also reduced dependence on SNF4. Our findings suggest that SNF4 acts as a positive effector of the kinase but does not serve a regulatory function in signaling glucose availability.
Nicotine potentiation of haloperidol in reducing tic frequency in Tourette's disorder [published erratum appears in Am J Psychiatry 1991 Sep;148(9):1282] (1991)

In an open, nonblind study, 10 patients with Tourette's disorder who were being treated with haloperidol were videotaped before, while, and after chewing nicotine gum. The frequency of tics was reduced significantly during the 30-minute gum-chewing period and during the 1 hour after gum chewing. Nicotine appears to potentiate haloperidol effects in patients with Tourette's disorder.
Broadly reacting precipitating and agglutinating antigen of leptospirae (1978)

A saprophytic Leptospira biflexa strain of equine origin was found which cross-reacts with immune rabbit antisera to 14 pathogenic Leptospira interrogans serotypes. Sera from goats experimentally inoculated with the saprophyte showed multiple low-level cross-agglutination reactions against a battery of live L. interrogans serotypes. Sonically treated and saline-extracted suspensions of the L. biflexa strain and serotypes canicola, icterohaemorrhagiae, and pomona yielded a common precipitating protein antigen that was detected by immunodiffusion and immunoelectrophoresis with all of the antileptospiral sera examined. In cross-absorption and gel diffusion tests, the precipitinogen from each of the strains was shown to be identical. Formaldehyde treatments and heating at 100 degree C suggest that the cellular location of the common antigen is either somatic or subsurface, and Sephadex G-200 gel filtration enabled the isolation of the active fraction of the L. biflexa antigen. Monoprecipitin sera against the common antigen of L. biflexa were produced by immunizing rabbits with specific precipitates in agar. In gel diffusion and immunoelectrophoresis tests the antisera with each of the soluble antigens developed a single precipitin formation, and the antisera agglutinated formolized and heated whole-cell suspensions of serotypes canicola, icterohaemorrhagiae, and pomona at low dilutions. The soluble L. biflexa antigen was evaluated as an immunogen and in passive immunity tests for protection against death and kidney infection in hamsters. No cross-protection occurred when the hamsters were challenged with virulent leptospires. In contrast, the animals vaccinated or administered hamster immune serum before challenge died earlier than the control animals.
Amplitude optimization and pitch prediction in multipulse coders (1989)

Although the multipulse model is conceptually simple, the problem of locating the pulses is computationally complex. The authors discuss the basic multipulse model and describe a procedure to compute the excitation with optimally adjusted amplitudes. The algorithm provides a framework for computing multipulse excitation with varying degrees of optimization and computational complexity. The authors find that speech quality depends on the pulse rate. They also find that for the same quality, female speech requires a higher pulse rate than male speech. The pitch dependence can be reduced and speech quality improved for high-pitched speakers by incorporating long delay prediction in the multipulse model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Carbon nanotube film interlayer for strain and damage sensing in composites during dynamic compressive loading (2012)

A major challenge in the damage assessment of materials under dynamic, high strain rate loading lies in the inability to apply most health monitoring methodologies to the analysis and evaluation of damage incurred on short timescales. Here, we present a resistance-based sensing method utilizing an electrically conductive carbon nanotube film in a fiberglass/vinyl ester composite. This method reveals that applied strain and damage in the form of matrix cracking and delamination give rise to electrical resistance increases across the composite specimen; these can be measured in real-time during high strain rate loading. Damage within the composite specimens is confirmed through pre- and post-mortem x-ray micro computed tomography imaging.
Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant (1990)

Abstract Developing axons are guided to their targets by molecular cues in their local environment. Some cues are shortrange, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.
Cocaine-Induced Channelopathies: Emerging Evidence on the Multiple Mechanisms of Sudden Death (2002)

Sudden death due to cocaine in the absence of myocardial infarction has been attributed to the precipitation of life-threatening arrhythmias not unlike that due to antiarrhythmic drugs. Cocaine is a slow on-off sodium blocker and a fast on-off potassium blocker. Effects on repolarization are biphasic: At low concentrations, cocaine delays ventricular recovery, whereas at higher levels, cocaine hastens it. Two distinct clinical profiles emerge from case reports of electrocardiographically documented life-threatening arrhythmias attributed to cocaine. The first is monomorphic slow ventricular tachycardia or idioventricular rhythm that occurs in overdose situations and appears to reflect excessive sodium channel block; it may respond to sodium bicarbonate. The second is torsade de pointes that occurs in recreational users who have underlying risks for this tachycardia (such as fully or partially expressed congenital long QT syndrome) and reflects potassium channel blockade. These clinical observations can be explained by recent findings regarding the electrophysiologic effects of cocaine. Other patterns of severe arrhythmias due to cocaine may yet emerge.
Type III secretion genes identify a putative virulence locus of Chlamydia (1997)

Four genes of Chlamydia psittaci strain guinea pig inclusion conjunctivitis (GPIC), whose predicted products are highly homologous to structural and regulatory components of a contact-dependent or type III secretion apparatus, were isolated. Related to genes present in several animal and plant bacterial pathogens, these genes may represent a section of a previously undetected chromosomal virulence locus analogous to several recently described virulence-associated type III secretion loci. The existence of contact-dependent secretion in Chlamydia strongly suggests that these bacteria use pathogenic mechanisms that are similar to those of other intracellular bacterial pathogens. Unlike other intracellular bacteria, however, chlamydiae are metabolically inactive extracellularly and only become capable of global protein synthesis several hours after infection. This implies that chlamydial contact-dependent secretion is only active from within, uniquely after the bacteria have been internalized by eukaryotic cells. The possible role(s) of this pathway in chlamydial pathogenesis are discussed.
Heterogeneous surface distribution of the fibrinogen-binding protein on Candida albicans (1994)

As detected by indirect immunofluorescence and confocal microscopy, fibrinogen binding was heterogeneously distributed on the surface of Candida albicans. A low level of binding was generally observed homogeneously distributed on some yeast and most hyphal extensions of germ tubes. However, on most hyphal extensions, there were randomly distributed areas of increased expression, as revealed by patches of greater fluorescence intensity.
Tonsillar biopsy and PrP Sc detection in the preclinical diagnosis of scrapie (1998)

Preliminary findings have indicated that in naturally infected sheep, fully susceptible to scrapie (VRQ-homozygous), PrPSc can be detected in the tonsils approximately one year before the expected onset of clinical disease, whereas no immunostaining can be detected in animals with a semi-resistant genotype. This paper describes the technique for taking tonsillar biopsies from sheep and gives the results of the completed experiment. In another experiment PrPSc was detected even earlier in comparable VRQ-homozygous sheep born and raised in different surroundings. At three-and-a-half months of age no PrPSc could be detected in three homozygous susceptible sheep (VRQ/VRQ), but PrPSc was detected at four months in one similar sheep. At eight months of age all seven sampled VRQ/VRQ sheep showed positive immunostaining in the biopsies, but none of the biopsies from three VRQ/ARQ heterozygotes showed any immunostaining; they were positive when sampled at 14 to 15 months of age. Biopsies from VRQ/ARR sheep were negative throughout this period. On the basis of the established or expected incubation period, PrPSc could thus be detected in the tonsils of live susceptible animals at between one-third and a half of the incubation period, more than one-and-a-half years before clinical signs normally appear in both these genotypes.
QuDot Nets: Quantum Computers and Bayesian Networks (2016)

We present a new implementation of quantum computation that treats quantum computers as a special type of Bayesian Network called a QuDot Net. QuDot Nets allow for the efficient representation of some qubit systems. Single qubit quantum gates can be implemented as edge transformations on QuDot Nets. The X, H, R(k), M and SWAP gates are discussed in detail and results show linear scaling as the number of qubits are increased. We show that measurement and semi-quantum control gates can be efficiently implemented using QuDot Nets and present results from a QuDot Net implementation of the terminal Quantum Fourier Transform. We show how QuDot Nets can implement coherent control gates using multi-digraphs by labelling parallel edges. Lastly, we discuss implications to quantum foundations if a classical implementation of quantum computation is realized.
N-acetylcysteine inhibits muscle fatigue in humans. (1994)

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively inhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experiments test the hypothesis that NAC pretreatment can inhibit acute muscular fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in water by intravenous infusion. The subject then sat in a chair with surface electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimulated to contract electrically (40-55 mA, 0.2-ms pulses) and force production was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions (MVC) of ankle dorsiflexor muscle groups and during electrical stimulation of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1). Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subsequently were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did not alter the function of unfatigued muscle; MVC performance and the force-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force output by approximately 15% (P < 0.0001), an effect that was evident after 3 min of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz stimuli or on recovery from fatigue. N-acetylcysteine pretreatment can improve performance of human limb muscle during fatiguing exercise, suggesting that oxidative stress plays a causal role in the fatigue process and identifying antioxidant therapy as a novel intervention that may be useful clinically.
Virtual environment display system (1987)

A head-mounted, wide-angle, stereoscopic display system controlled by operator position, voice and gesture has been developed for use as a multipurpose interface environment. The system provides a multisensory, interactive display environment in which a user can virtually explore a 360-degree synthesized or remotely sensed environment and can viscerally interact with its components. Primary applications of the system are in telerobotics, management of large-scale integrated information systems, and human factors research. System configuration, application scenarios, and research directions are described.
Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine. (1991)

We have previously reported that fatty acid synthase mRNA levels increase 10-15-fold during the differentiation of 3T3-L1 cells to adipocytes, correlating well with the increase in the relative rate of synthesis for this enzyme. Here we show by transcription run-on assays that fatty acid synthase is highly transcribed in both preadipocytes and adipocytes. Furthermore, the transcription rate of the fatty acid synthase gene increased only 1.5-fold during the adipose conversion, whereas the apparent mRNA half-life increased from 2.5 h in preadipocytes to approximately 20 h in adipocytes. These results indicate that the increase in mRNA level during adipose conversion is not only due to the transcriptional activation of this gene but reflects the post-transcriptional stabilization of the message in adipocytes compared to preadipocytes. As thyroid hormone has been reported to increase lipogenic enzyme activities including fatty acid synthase in adipose tissue and in differentiating adipocytes in vitro, we used fully differentiated 3T3-L1 adipocytes to study T3 regulation of mammalian fatty acid synthase expression. We measured the effect of T3 on the relative rate of protein synthesis, mRNA content, and transcription rate of this gene. When mature adipocytes were treated with 10 nM T3, the relative rate of synthesis of fatty acid synthase increased 1.9-fold at 6 h, and it reached a maximum of 2.9-fold at 12 h. In addition, Northern blot analysis showed that T3 increased the steady-state mRNA level for fatty acid synthase by 2.4-fold at 12 h and 4.5-fold at 24 h. Furthermore, run-on transcription analysis with isolated nuclei from cells treated with T3 showed that the transcription rate of the fatty acid synthase gene increased 4.1-fold after 6 h of T3 treatment and remained at the stimulated level for 24 h. These results demonstrate that the increase in transcription of the fatty acid synthase gene preceded that of the steady-state mRNA level, indicating that T3 regulates expression of fatty acid synthase primarily by modulating the transcription rate of the gene. In conclusion, while the differentiation-dependent increase in fatty acid synthase is mediated by both transcriptional and posttranscriptional processes, T3 regulation is primarily at the transcriptional level.
Generation and analysis of defective genomes of Autographa californica nuclear polyhedrosis virus (1992)

We have generated defective genomes of Autographa californica nuclear polyhedrosis virus (AcNPV) by serial, undiluted passage in IPLB-SF-21 cell culture in an attempt to identify potential cis-acting sequences important for AcNPV DNA replication. Viral DNA isolated from some of the 81 serial passages was analyzed by pulsed-field gel electrophoresis, restriction endonuclease analysis, and Southern blot hybridization. AcNPV-defective genomes appeared to be generated through a series of successively smaller and transiently stable intermediates. Although the defective genomes at passages later than passage 65 (P65) were somewhat heterogeneous in size, those of the majority of the population had a mean size estimated to be 50 kb, or 40% of that of standard virus. Defective genomic DNA at P81 hybridized strongly only to a 2.8-kb region mapping within 85.0 to 87.2 map units of AcNPV DNA (most of HindIII-K and a small part of HindIII-B), suggesting that the majority of P81-defective genomes were missing most of the 128-kb wild-type DNA sequence, except for this small 2.8-kb fragment. Furthermore, our results indicated that the defective genomes of P81 were composed largely of reiterations of this sequence. We suggest that the 2.8-kb DNA segment retained by the defective AcNPV genomes of P81 contains an important cis-acting element(s) sufficient for viral DNA replication in AcNPV-infected cells.