gebhart/patrepeval huggingface dataset:
Efficient reconstruction of block-sparse signals (2011)

In many sparse reconstruction problems, M observations are used to estimate K components in an N dimensional basis, where N >; M ≫ K. The exact basis vectors, however, are not known a priori and must be chosen from an M × N matrix. Such under-determined problems can be solved using an ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> optimization with an ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> penalty on the sparsity of the solution. There are practical applications in which multiple measurements can be grouped together, so that K × P data must be estimated from M × P observations, where the ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> sparsity penalty is taken with respect to the vector formed using the ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> norms of the rows of the data matrix. In this paper we develop a computationally efficient block partitioned homotopy method for reconstructing K × P data from M × P observations using a grouped sparsity constraint, and compare its performance to other block reconstruction algorithms.
Genetic and Immunologic Analyses of PlpE, a Lipoprotein Important in Complement-Mediated Killing ofPasteurella haemolyticaSerotype 1 (1998)

Pasteurella haemolytica serotype 1 is the bacterium most commonly associated with bovine shipping fever. The presence of antibodies against P. haemolytica outer membrane proteins (OMPs) correlates statistically with resistance to experimental P. haemolytica challenge in cattle. Until now, specific P. haemolytica OMPs which elicit antibodies that function in host defense mechanisms have not been identified. In this study, we have cloned and sequenced the gene encoding one such protein, PlpE. Analysis of the deduced amino acid sequence revealed that PlpE is a lipoprotein and that it is similar to an Actinobacillus pleuropneumoniae lipoprotein, OmlA. Affinity-purified, anti-PlpE antibodies recognize a protein in all serotypes of P. haemolytica except serotype 11. We found that intact P. haemolytica and recombinant E. coli expressing PlpE are capable of absorbing anti-PlpE antibodies from bovine immune serum, indicating that PlpE is surface exposed in P. haemolytica and assumes a similar surface-exposed conformation in E. coli. In complement-mediated killing assays, we observed a significant reduction in killing of P. haemolytica when bovine immune serum that was depleted of anti-PlpE antibodies was used as the source of antibody. Our data suggest that PlpE is surface exposed and immunogenic in cattle and that antibodies against PlpE contribute to host defense against P. haemolytica.
Genetic variability of hepatitis A virus (2003)

Knowledge of the molecular biology of hepatitis A virus (HAV) has increased exponentially since its identification. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. HAV has been characterized by the emergence of different genotypes, three human antigenic variants and only one major serotype. This paper reviews the genetic variability and molecular epidemiology of HAV. Its evolutionary mechanisms are described with particular emphasis on genetic recombination and HAV mutation rate. Genotypic classification methods are also discussed.
Mutations to nonsense codons in human genetic disease: implications for gene therapy by nonsense suppressor tRNAs (1994)

Nonsense suppressor tRNAs have been suggested as potential agents for human somatic gene therapy. Recent work from this laboratory has described significant effects of 3' codon context on the efficiency of human nonsense suppressors. A rapid increase in the number of reports of human diseases caused by nonsense codons, prompted us to determine how the spectrum of mutation to either UAG, UAA or UGA codons and their respective 3' contexts, might effect the efficiency of human suppressor tRNAs employed for purposes of gene therapy. This paper presents a survey of 179 events of mutations to nonsense codons which cause human germline or somatic disease. The analysis revealed a ratio of approximately 1:2:3 for mutation to UAA, UAG and UGA respectively. This pattern is similar, but not identical, to that of naturally occurring stop codons. The 3' contexts of new mutations to stop were also analysed. Once again, the pattern was similar to the contexts surrounding natural termination signals. These results imply there will be little difference in the sensitivity of nonsense mutations and natural stop codons to suppression by nonsense suppressor tRNAs. Analysis of the codons altered by nonsense mutations suggests that efforts to design human UAG suppressor tRNAs charged with Trp, Gln, and Glu; UAA suppressors charged with Gln and Glu, and UGA suppressors which insert Arg, would be an essential step in the development of suppressor tRNAs as agents of human somatic gene therapy.
DNA POLYMERASE III HOLOENZYME: Structure and Function of a Chromosomal Replicating Machine (1995)

DNA polymerase III holoenzyme contains two DNA polymerases embedded in a particle with 9 other subunits. This multisubunit DNA polymerase is the Eschericia coli chromosomal replicase, and it has several special features that distinguish it as a replicating machine. For example, one of its subunits is a circular protein that slides along DNA while clamping the rest of the machinery to the template. Other subunits act together as a matchmaker to assemble the ring onto DNA. Overall, E. coli DNA polymerase III holoenzyme is very similar in both structure and function to the chromosomal replicases of eukaryotes, from yeast all the way up to humans. This review summarizes our present knowledge about the function of the 10 subunits of this replicating machine and how they coordinate their actions for smooth duplication of chromosomes.
MECHANISMS OF BACILLUS CALMETTE-GUERIN MEDIATED NATURAL KILLER CELL ACTIVATION (2004)

Following BCG stimulation the monocyte derived TH1 cytokines IL-12 and IFN-alpha activate tumor cytotoxic CD3/CD56/NKG2A NK cells. Our results elucidate NK activating mechanisms that are operative during BCG immunotherapy for bladder cancer and are relevant for an early, innate antimycobacterial immune response.
Earlier Expression of the Transcription Factor Hfh–11B Diminishes Induction of P21Cip1/Waf1 Levels and Accelerates Mouse Hepatocyte Entry Into S–Phase Following Carbon Tetrachloride Liver Injury (2001)

Partial hepatectomy (PH) or toxic liver injury induces the proliferation of terminally differentiated hepatic cells to regenerate the original size of the adult liver. Previous PH liver regeneration studies showed that premature transgenic expression of the Forkhead Box M1b (FoxM1b, HFH-11B) transcription factor accelerated hepatocyte entry into DNA replication (S-phase). In this study, we used carbon tetrachloride (CCl(4)) liver injury to induce a different type of mouse liver regeneration and show that premature hepatic HFH-11B levels also accelerate the onset of hepatocyte S-phase in this injury model. Unlike PH liver regeneration, earlier hepatocyte proliferation after CCl(4) liver injury is correlated with diminished transgenic hepatic levels of p21(CIP1/WAF1) at the G1/S transition of the cell cycle. Differential hybridization of cDNA arrays and RNase protection studies determined that CCl(4) regenerating liver of transgenic mice displayed early stimulated expression of the S-phase promoting cyclin D1 and cyclin E and sustained levels of Cdc25a phosphatase genes. Compared with previous PH liver regeneration studies, our data suggest that premature expression of HFH-11B activates distinct S-phase promotion pathways in the CCl(4) liver injury model. Although proliferating transgenic hepatocytes induced by either PH or CCl(4) liver injury displayed early expression of identical M-phase cyclin genes (cyclin B1, B2, A2, and F), only CCl(4) regenerating transgenic liver exhibited earlier expression of the M-phase promoting Cdc25b. These studies suggest that CCl(4) injury of transgenic liver not only uses the same mechanisms as PH to mediate accelerated hepatocyte entry into mitosis, but also promotes M-phase entry by stimulating Cdc25b expression.
Analysis of a novel stress-sensing technique based on light scattering by an array of birefringent optical waveguides (2003)

We propose a new stress-sensing technique based upon measurement of light scattering produced by an array of birefringent waveguides. When external stress is applied to the array of waveguides, their optical properties are modified via the photoelastic effect. Specifically, the intensity of light scattered by the optical waveguides is significantly affected by stress. In this work we analyse theoretically this stress-induced change. Our numerical simulations show that this effect provides a means to assess the strength and direction of the external force.
L-DOPA in the Treatment of Negative Schizophrenic Symptoms: A Single-Subject Experimental Study (1986)

Adjunctive Sinemet (L-DOPA plus carbidopa) therapy was assessed for a neuroleptic nonresponsive schizophrenic with a longstanding negative syndrome. A twenty-seven week double-blind placebo-controlled reversal design found significant improvement specifically for negative symptoms while treated with combined haloperidol-Sinemet as compared against haloperidol-placebo. The eight-week adjunctive treatment reversed a worsening trend in attention, abstract thinking, passive withdrawal, psychomotor retardation, and a cluster of seven negative parameters, while positive symptoms were unaffected. This seemed to represent more than simple reversal of drug-induced akinesia and underscores the importance of distinguishing between positive and negative syndromes in psychopharmacological research.
Apoptosis in the intestinal epithelium: Its relevance in normal and pathophysiological conditions (2000)

Apoptosis is now recognized as an important process responsible for maintenance of the cellular balance between proliferation and death. Apoptosis is distinct from necrosis in that it is a programmed form of cell death and occurs without any accompanying inflammation. This form of cell death can be induced by a wide range of cellular signals, which leads to activation of cell death machinery within the cell and is characterized by distinct morphological changes. Apoptosis is especially relevant in the gastrointestinal tract, as the mammalian intestinal mucosa undergoes a process of continual cell turnover that is essential for maintenance of normal function. Cell proliferation is confined to the crypts, while differentiation occurs during a rapid, orderly migration up to the villus. The differentiated enterocytes, which make up the majority of the cells, then undergo a process of programmed cell death (apoptosis). Although apoptosis is essential for the maintenance of normal gut epithelial function, dysregulated apoptosis is seen in a number of pathological conditions in the gastrointestinal tract. The cellular mechanisms regulating this tightly regimented process have not been clearly defined and this topic represents an area of active investigation as delineation of this process will lead to a better understanding of normal gut mucosal growth.
Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituted derivatives (1991)

A series of novel N-1-(mono-,-(di- and -(trifluoro-tert-butyl)quinolones and -naphthyridines has been prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity than the nonfluorinated-tert-butyl equivalents. In vivo PD50 values of the 1-fluoro-tert-butyl-substituted derivatives reflect pharmacokinetic behavior and incomplete oral absorption.
<title>Full color laser projection display using Kr-Ar laser (white laser) beam-scanning technology</title> (1997)

Full color laser projection display is realized on the large screen using a krypton-argon laser (white laser) as a light source, and acousto-optic devices as light modulators. The main wavelengths of red, green and blue color are 647, 515, and 488 nm separated by dichroic mirrors which are designed to obtain the best performance for the s-polarized beam with the 45 degree incident angle. The separated beams are modulated by three acousto-optic modulators driven by rf drivers which has energy level of 1 watt at 144 MHz and recombined by dichroic mirrors again. Acousto-optic modulators (AOM) are fabricated to satisfy high diffraction efficiency over 80% and fast rising time less than 50 ns at the video bandwidth of 5 MHz. The recombined three beams (RGB) are scanned by polygonal mirrors for horizontal lines and a galvanometer for vertical lines. The photodiode detection for monitoring of rotary polygonal mirrors is adopted in this system for the compensation of the tolerance in the mechanical scanning to prevent the image joggling in the horizontal direction. The laser projection display system described in this paper is expected to apply HDTV from the exploitation of the acousto- optic modulator with the video bandwidth of 30 MHz.
Microstructural Study of an Iron Silicate Catalyst by Electron Microscopy (1989)

The effects of various synthesis conditions on the structure of iron silicate analogs of zeolite ZSM-5 were considered. Scanning electron microscopy (SEM) was used to determine the particle size distributions and morphologies. Particle sizes vary from tenths of a micron to several microns, depending on degree of agitation during crystal growth, while morphology is additionally dependent on the concentration of iron in the gel during crystallization. Transmission electron microscopy (TEM) was used to determine the size and spatial distributions of iron-rich (as compared to the FeZSM-5 matrix) second phase particles within the ZSM-5 framework as a function of SiO2/Fe2O3-ratio, thermal and hydrothermal treatments.
BCL-2 Selectively Interacts with the BID-induced Open Conformer of BAK, Inhibiting BAK Auto-oligomerization (2003)

Caspase-8 cleaves BID to tBID, which targets mitochondria and induces oligomerization of BAX and BAK within the outer membrane, resulting in release of cytochrome c from the organelle. Here, we have initiated these steps in isolated mitochondria derived from control and BCL-2-overexpressing cells using synthetic BH3 peptides and subsequently analyzed the BCL members by chemical cross-linking. The results show that the BH3 domain of BID interacts with and induces an "open" conformation of BAK, exposing the BAK N terminus. This open (activated) conformer of BAK potently induces oligomerization of non-activated ("closed") conformers, causing a cascade of BAK auto-oligomerization. Induction of the open conformation of BAK occurs even in the presence of excess BCL-2, but BCL-2 selectively interacts with this open conformer and blocks BAK oligomerization and cytochrome c release, dependent on the ratio of BID BH3 and BCL-2. This mechanism of inhibition by BCL-2 also occurs in intact cells stimulated with Fas or expressing tBID. Although BID BH3 interacts with both BCL-2 and BAK, the results indicate that when BCL-2 is in excess it can sequester the BID BH3-induced activated conformer of BAK, effectively blocking downstream events. This model suggests that the primary mechanism for BCL-2 blockade targets activated BAK rather than sequestering tBID.
The Role of the Orbitofrontal Cortex in Anxiety Disorders (2007)

Advances in neuroimaging techniques over the past two decades have allowed scientists to investigate the neurocircuitry of anxiety disorders. Such research has implicated the orbitofrontal cortex (OFC). Characterizing the role of OFC in anxiety disorders, however, is principally complicated by two factors-differences in underlying pathophysiology across the anxiety disorders and heterogeneity in function across different OFC sub-territories. Contemporary neurocircuitry models of anxiety disorders have primarily focused on amygdalo-cortical interactions. The amygdala is implicated in generating fear responses, whereas cortical regions, specifically the medial OFC (mOFC) and the ventromedial prefrontal cortex (vmPFC), are implicated in fear extinction. In contrast to mOFC, anterolateral OFC (lOFC) has been associated with negative affects and obsessions and thus dysfunctional lOFC may underlie different aspects of certain anxiety disorders. Herein, we aim to review the above-mentioned theories and provide a heuristic model for conceptualizing the respective roles of mOFC and lOFC in the pathophysiology and treatment of anxiety disorders. We will also review the role of the OFC in fear extinction and the implications of this role to the pathophysiology of anxiety disorders.
Copolymer 1 (Glatiramer Acetate) in Relapsing Forms of Multiple Sclerosis: Open Multicenter Study of Alternate-Day Administration (2002)

Daily 20-mg doses of Copolymer 1 have been shown to significantly decrease the relapse rate in patients with multiple sclerosis (MS). In the present open-label study, patients with relapsing MS were treated with the same dose of Copolymer 1 administered on alternate days. Sixty-eight patients were recruited: fifty-one and forty-one patients completed 1 and 2 years of treatment respectively. The relapse rate during the 2 years of treatment decreased by 80.8% compared with the 2 years before treatment (means, 0.56 +/- 1.02 versus 2.91 +/- 1.10, respectively; p < 0.0001). This lower rate is comparable with that obtained with daily open-label administration previously reported by the authors. The score on the Expanded Disability Status Scale did not differ from that at baseline after the first year of treatment, although it increased somewhat at the end of the second year (baseline = 2.72 +/- 1.55, 1 year = 2.71 +/- 1.59, 2 years = 2.97 +/- 1.80; p < 0.008). The drug was very well tolerated. This preliminary open-label study suggests that alternate-day therapy has beneficial effects and is well tolerated, comparing favorably with the effects of daily injections of Copolymer 1 in patients with relapsing MS. These results should be confirmed by randomized double-blind examinations.
Structural and functional heterogeneity of integrated recombinant AAV genomes (1997)

Adeno-associated Virus (AAV) has emerged as a promising vector for gene therapy because of its ability to generate high titer recombinant stocks and the potential for site specific integration. However, much of the current knowledge regarding the transduction and integration biology of this virus is based on studies evaluating wild type AAV or recombinant AAV which was unknowingly contaminated with wild type virus. Given the fact that recombinant AAV is replication incompetent, by virtue of deleted viral rep proteins responsible for site specific integration of the wild type virus, the integration process for recombinant AAV may likely be different from its wild type counterpart. To this end, the present study has attempted to elucidate the proviral structure of stably integrated recombinant AAV genomes harboring the alkaline phosphatase reporter gene in 293 and IB3 cell lines. Initial studies attempted to functionally characterize differences in proviral genomes using mobilization assays with assessed both liberated episomal recombinant AAV and infectious virus following transfection with Rep/Cap containing plasmids and/or infection with recombinant adenovirus (Ad). Using Southern and polymerase chain reaction (PCR) analysis, evaluation of genomic DNA from AAV clonal cell lines indicated that head to tail orientations of ITRs were absolutely required for excision of episomal genomes and rescue of infectious recombinant virus. Furthermore, mobilization of proviral DNA could be achieved in the presence of exogenous Rep/Cap without adenovirus, while mobilization of infectious recombinant virus required the addition of both Rep/Cap and Ad. Genomic Southerns suggest that two predominant proviral structures exist for recombinant AAV including head to head and tail to head duplex genomes. A third class of monomer proviral genomes with head to tail oriented ITRs was also observed. No evidence for tail to tail ITR oriented proviral genomes was detected in any of the clonal cell lines. Such findings have begun to lay the foundation for a clearer understanding of the mechanism of recombinant AAV integration and how this process differs from wild type AAV.
The Effects of Green Tea Consumption on Incidence of Breast Cancer and Recurrence of Breast Cancer: A Systematic Review and Meta-analysis (2005)

To date, the epidemiological data indicates that consumption of 5 or more cups of green tea a day shows a non-statistically significant trend towards the prevention of breast cancer development. Evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers. However, conclusions as to the potential therapeutic application of green tea are currently impossible to make due to the small number of studies conducted, the lack of any clinical trial evidence, the lack of a consistent dose-response relationship, and the potential for interaction with standard care.
Ion-Sensitive Field-Effect Transistor for Biological Sensing (2009)

In recent years there has been great progress in applying FET-type biosensors for highly sensitive biological detection. Among them, the ISFET (ion-sensitive field-effect transistor) is one of the most intriguing approaches in electrical biosensing technology. Here, we review some of the main advances in this field over the past few years, explore its application prospects, and discuss the main issues, approaches, and challenges, with the aim of stimulating a broader interest in developing ISFET-based biosensors and extending their applications for reliable and sensitive analysis of various biomolecules such as DNA, proteins, enzymes, and cells.
Constructing Proteins by Dovetailing Unprotected Synthetic Peptides: Backbone-Engineered HIV Protease (1992)

Backbone-engineered HIV-1 protease was prepared by a total chemical synthesis approach that combines the act of joining two peptides with the generation of an analog structure. Unprotected synthetic peptide segments corresponding to the two halves of the HIV-1 protease monomer polypeptide chain were joined cleanly and in high yield through unique mutually reactive functional groups, one on each segment. Ligation was performed in 6 molar guanidine hydrochloride, thus circumventing limited solubility of protected peptide segments, the principal problem of the classical approach to the chemical synthesis of proteins. The resulting fully active HIV-1 protease analog contained a thioester replacement for the natural peptide bond between Gly51-Gly52 in each of the two active site flaps, a region known to be highly sensitive to mutational changes of amino acid side chains.
Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary‐induced obesity and insulin resistance (2010)

Liraglutide administered peripherally not only improves metabolic parameters but exerts additional beneficial effects on cognitive function and hippocampal synaptic plasticity. Whether therapy with GLP-1 mimetics has similar effects in humans with type 2 diabetes needs to be established.