gebhart/patrepeval huggingface dataset:
Preclinical Development of New Therapy for Glycogen Storage Diseases (2015)

Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available.
Protein-Lipid Interplay in Fusion and Fission of Biological Membranes (2003)

Disparate biological processes involve fusion of two membranes into one and fission of one membrane into two. To formulate the possible job description for the proteins that mediate remodeling of biological membranes, we analyze the energy price of disruption and bending of membrane lipid bilayers at the different stages of bilayer fusion. The phenomenology and the pathways of the well-characterized reactions of biological remodeling, such as fusion mediated by influenza hemagglutinin, are compared with those studied for protein-free bilayers. We briefly consider some proteins involved in fusion and fission, and the dependence of remodeling on the lipid composition of the membranes. The specific hypothetical mechanisms by which the proteins can lower the energy price of the bilayer rearrangement are discussed in light of the experimental data and the requirements imposed by the elastic properties of the bilayer.
Are class II phosphoinositide 3-kinases potential targets for anticancer therapies? (2006)

Of the three classes of true phosphoinositide (PI) 3-kinases, the class II subdivision, which consists of three isoforms, PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma, is the least well understood. There are a number of reasons for this. This class of PI 3-kinase was identified exclusively by PCR and homology cloning approaches and not on the basis of cellular function. Like class I PI 3-kinases, class II PI 3-kinases are activated by diverse receptor types. To complicate the elucidation of class II PI 3-kinase function further, their in vitro substrate specificity is intermediate between the receptor activated class I PI 3-kinases and the housekeeping class III PI 3-kinase. The class II PI 3-kinases are inhibited by the two commonly used PI 3-kinase family selective inhibitors, wortmannin and LY294002, and there are no widely available, specific inhibitors for the individual classes or isoforms. Here the current state of understanding of class II PI 3-kinase function is reviewed, followed by an appraisal as to whether there is enough evidence to suggest that pharmaceutical companies, who are currently targeting the class I PI 3-kinases in an attempt to generate anticancer agents, should also consider targeting the class II PI 3-kinases.
Microbiological effects of mouthrinses containing antimicrobials (1988)

A number of mouthrinse formulations containing antimicrobials have been evaluated to determine their effectiveness as antiplaque and/or antigingivitis agents. These have included the bis-biguanides, phenols, quaternary ammonium compounds, oxygenating compounds, plant extracts, fluorides, antibiotics and antimicrobial combinations. These mouthrinses have often been tested as adjuncts to normal oral hygiene procedures as well as in the experimental gingivitis model. 2 agents in particularly, chlorhexidine gluconate and listerine, have been shown to both inhibit or reduce plaque accumulation and the severity of gingivitis. Chlorhexidine has been reported to reduce the accumulation of plaque by approximately 60% and the severity of gingivitis by 50-80% as determined by improvements in clinical indices. A 0.12% chlorhexidine gluconate rinse resulted in significant reductions after both 3 and 6 months use in the numbers of total anaerobes, total aerobes, streptococci, and actinomyces recovered from supragingival plaque. Listerine has been reported to retard the development of plaque by 45 to 56% and to reduce existing plaque by 39 to 48%. Gingivitis scores were reduced as much as 59%. Microbial studies have shown that the effect of listerine is exerted against the total microbial mass and results in an overall decrease in both the biomass and the activity. Long-term use of neither mouthrinse, chlorhexidine or listerine, resulted in the emergence of opportunistic or oral pathogens. Preliminary data obtained following the use of a novel mouthrinse consisting of a combination of povidone-iodine and hydrogen peroxide appears promising. This combination was more effective than was more effective than either single component alone in reducing gingivitis scores.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of the Osem gene by abscisic acid and the transcriptional activator VP1: analysis of cis‐acting promoter elements required for regulation by abscisic acid and VP1 (1995)

Osem, a rice gene homologous to the wheat Em gene, which encodes one of the late-embryogenesis abundant proteins was isolated. The gene was characterized with respect to control of transcription by abscisic acid (ABA) and the transcriptional activator VP1, which is involved in the ABA-regulated gene expression during late embryo-genesis. A fusion gene (Osem-GUS) consisting of the Osem promoter and the bacterial beta-glucuronidase (GUS) gene was constructed and tested in a transient expression system, using protoplasts derived from a suspension-cultured line of rice cells, for activation by ABA and by co-transfection with an expression vector (35S-Osvp1) for the rice VP1 (OSVP1) cDNA. The expression of Osem-GUS was strongly (40- to 150-fold) activated by externally applied ABA and by over-expression of (OS)VP1. The Osem promoter has three ACGTG-containing sequences, motif A, motif B and motif A', which resemble the abscisic acid-responsive element (ABRE) that was previously identified in the wheat Em and the rice Rab16. There is also a CATGCATG sequence, which is known as the Sph box and is shown to be essential for the regulation by VP1 of the maize anthocyanin regulatory gene C1. Focusing on these sequence elements, various mutant derivatives of the Osem promoter in the transient expression system were assayed. The analysis revealed that motif A functions not only as an ABRE but also as a sequence element required for the regulation by (OS)VP1.
Self-repairing mechanism of plastics (2003)

The protection mechanism of a living body and man-made materials can be classified into two categories. One is a passive protection by which the body and materials are guarded by simple chemicals such as light absorbents, and the other is anactive protection that repairs with metabolic reactions the internal injury suffered by many kinds of deterioration factors from the outside. Polyphenylene–ether was selected as a man-made material in which the metabolic reaction can be achieved in the atmosphere (21% of oxygen) and at room temperature (20–40 8C). The polymer introduces oxygen as an energy source,transports it with copper-complex and repairs the scission point of the chain. Such active protections were attempted for several polymers and some advantages and problems were elucidated. In this paper, the mechanisms of active protections in some plastics are reviewed and are also compared with protection systems of a living body, which provide us with very useful information on the development of advanced materials.
Characterization of CRISPR RNA processing in Clostridium thermocellum and Methanococcus maripaludis (2012)

The CRISPR arrays found in many bacteria and most archaea are transcribed into a long precursor RNA that is processed into small clustered regularly interspaced short palindromic repeats (CRISPR) RNAs (crRNAs). These RNA molecules can contain fragments of viral genomes and mediate, together with a set of CRISPR-associated (Cas) proteins, the prokaryotic immunity against viral attacks. CRISPR/Cas systems are diverse and the Cas6 enzymes that process crRNAs vary between different subtypes. We analysed CRISPR/Cas subtype I-B and present the identification of novel Cas6 enzymes from the bacterial and archaeal model organisms Clostridium thermocellum and Methanococcus maripaludis C5. Methanococcus maripaludis Cas6b in vitro activity and specificity was determined. Two complementary catalytic histidine residues were identified. RNA-Seq analyses revealed in vivo crRNA processing sites, crRNA abundance and orientation of CRISPR transcription within these two organisms. Individual spacer sequences were identified with strong effects on transcription and processing patterns of a CRISPR cluster. These effects will need to be considered for the application of CRISPR clusters that are designed to produce synthetic crRNAs.
The Distinct Roles of T Cell-Derived Cytokines and a Novel Follicular Dendritic Cell-Signaling Molecule 8D6 in Germinal Center-B Cell Differentiation (2001)

Germinal center-B (GC-B) cells differentiate into memory B cells and plasma cells (PC) through interaction with T cells and follicular dendritic cells (FDC). Activated T cell and FDC play distinct roles in this process. The detailed kinetic experiments revealed that cytokines secreted by activated T cells determined the pathway of GC-B cell differentiation. IL-4 directs GC-B cells to differentiate into memory B cells, whereas IL-10 steers them into PC. FDC/HK cells do not direct either pathway, but provide signals for proliferation of GC-B cells. A novel FDC-signaling molecule 8D6 (FDC-SM-8D6) produced by FDC augments PC generation in the GC. FDC-SM-8D6-specific mAb blocked PC generation and IgG secretion but not memory B cell proliferation. COS cells expressing FDC-SM-8D6 enhanced GC-B cell proliferation and Ab secretion, which was blocked by mAb 8D6. In the cultures with B cell subsets, PC generation was inhibited by mAb 8D6 in the cultures with CD27(+) B cells but not in the culture with CD27(-) B cells, suggesting that CD27(+) PC precursor is the specific target of FDC-SM-8D6 stimulation.
The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42 (2010)

Guanidine exchange factor (GEF)-catalysed activation of Rho proteins such as Cdc42 has been shown to have a crucial role in cellular transformation, malignant progression and invasion. We have previously shown that the HPV16 E6 oncoprotein binds to the PDZ domain protein Tax-interacting-protein 1 (Tip-1) and we now report identification and functional analysis of a novel Tip-1 binding GEF. Yeast two-hybrid, in vitro pull-down, site-directed mutagenesis, semiquantitative PCR, co-immunoprecipitation and western blotting were used to identify/confirm novel Tip-1 binding partners and analyse cellular expression levels. In vitro kinetic analyses of recombinant proteins, siRNA gene silencing and in cell assays were used to measure Rho protein activation. Tax-interacting-protein 1 was shown to interact with ARHGEF16 by its carboxyl PDZ binding motif. Levels of ARHGEF16 were increased in transformed and immortalised cells expressing ectopic HPV16 E6 and Cdc42 was co-immunoprecipitated by ARHGEF16 in the presence of high-risk HPV E6. In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42 and this was increased by the addition of recombinant Tip-1 and E6. Cells expressing HPV16 E6 had higher levels of Cdc42 activation, which was decreased by siRNA silencing of either Tip-1 or ARHGEF16. These data suggest that HPV16 E6, Tip-1 and ARHGEF16 may cooperate to activate Cdc42 and support a potential link between the expression of HPV16 E6 and Cdc42 activation.
Use of cell proliferation data in modeling urinary bladder carcinogenesis. (1993)

A multistage, probabilistic, biologically based model of carcinogenesis has been developed involving qualitative and quantitative aspects of the process. A chemical can affect the risk of cancer by directly damaging DNA and/or increasing the number of cell divisions during which errors in DNA replication can occur. Based on this model, carcinogens are classified as genotoxic versus nongenotoxic; nongenotoxic chemicals are further divided on the basis of whether or not they act through a specific cell receptor. Nongenotoxic compounds, particularly those acting through a nonreceptor mechanism, are likely to have dose and/or species-specific thresholds. This classification also implies the existence of chemicals that will be carcinogenic at high doses in animal models, but because of dose and/or mechanistic considerations, will not be carcinogenic to humans at levels of exposure. N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) and 2-acetylaminofluorene (AAF) are classical genotoxic bladder carcinogens that also cause proliferative effects at higher doses. Although there is an apparent no-effect level for the urinary bladder carcinogenicity of these two compounds at low doses, in reality, DNA adducts form at these low levels, and it is likely that there is a cancer effect (no threshold), but it is below the level of detection of the bioassay. These conclusions are based on studies involving multiple doses and time points in rodents, including results from the ED01. Pellets implanted directly into the rodent bladder lumen or calculi formed in the urine as a result of an administered chemical cause abrasion of the urothelium, and a marked increase in cell proliferation and cell number, and ultimately tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Free Fetal DNA in Maternal Circulation (2004)

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Interferon γ Receptor Extracellular Domain Expressed as IgG Fusion Protein in Chinese Hamster Ovary Cells (1995)

Agents that antagonize the functions of interferon gamma (IFN gamma) are potential pharmaceuticals against several immunological and inflammatory disorders. IFN gamma receptor-immunoglobulin G fusion proteins (IFN gamma R-IgG) function as antagonists of endogenous IFN gamma and have longer half-lives in vivo in comparison with soluble IFN gamma receptors (sIFN gamma R), consisting of the extracellular region of the native sequence. A fusion protein comprising the extracellular domain of the human IFN gamma receptor and the hinge, CH2 and CH3 domains of the human IgG3 constant region, was expressed in Chinese hamster ovary cells. The IFN gamma R-IgG3 fusion protein was secreted into the culture medium as a 175-kDa glycoprotein and was purified over Protein G-Sepharose, DEAE-Sepharose, and size exclusion chromatography. IFN gamma R-IgG3 bound IFN gamma in solid phase assays and ligand blots, competed for the binding of radiolabeled IFN gamma to the cell surface receptor of Raji cells, and inhibited the IFN gamma-mediated antiviral activity with an efficiency at least one order of magnitude higher than that of the soluble receptor produced in the same expression system. Two IFN gamma R-IgG3 fusion proteins bound two IFN gamma dimers forming a complex of approximately 380 kDa. In immunodiffusion assays, the IFN gamma R-IgG3 fusion protein did not precipitate IFN gamma. Dissociation of bound IFN gamma from IFN gamma R-IgG3 was 2-fold slower than from the sIFN gamma R produced in insect cells.
Improved performance of a random OFDMA mobile communication system (2002)

In this paper we consider the uplink performance of an OFDMA (orthogonal frequency division multiple access) system for mobile communications. First, we describe the random OFDMA system which is based on MC-FDMA (multicarrier FDMA), and where each user has a set of randomly selected subchannels. We also describe the performance criteria considered for the evaluation of this system and present different system implementations depending on the level of block synchronization assumed. In the last section we describe different methods for improving the system performance, one based on different receiver configurations and another based on different sets of subchannels per user depending on the traffic load. We also show some simulation results for the performance of the system under the different assumptions.
Integrated dynamic channel assignment and power control in TDMA mobile wireless communication systems (1999)

With the evolution of analog mobile wireless communications systems into digital second- and third-generation systems, there is growing interest in finding more efficient ways of managing the available resources, in particular radio spectrum and power. In the context of time division multiple access (TDMA) systems, this interest has led to the development of a variety of dynamic channel assignment (DCA) and power control (PC) algorithms. Despite the intense activity in both the DCA and the PC arenas and some proposals for combined DCA with PC, not enough work has been devoted to effectively integrating them. In this paper, the integration of DCA and PC is investigated and a family of integrated algorithms is presented. These algorithms, fully distributed and cost adaptive, achieve capacity levels significantly higher than those of a system with only DCA or PC. With respect to a system without any DCA or PC, several-fold capacity increases are obtained. Furthermore, these capacity levels are attained with user mobility included in the analysis.
A Short Review on Basalt Fiber (2012)

A hard, dense, inert rock found world wide, basalt is an igneous rock, wh ich is solid ified volcanic lava. Cast basalt liners for steel tubing shows very high abrasion resistance in various industrial applications. In recent years, continuous basalt fibers ext ruded fro m naturally fire-resistant basalt are attracted attention as a rep lacement fo r asbestos fibers. In the last decade, basalt has emerged as a contender in the fiber reinforcement of co mposites. Some manufacturer of basalts claims it offers performance similar to S-2 glass fibers at a price point between S-2 glass and E-g lass, and may offer manufacturers a less -expensive alternative to carbon fiber. Basalt fibre (BF) is capable to withstand very high temperature and can act as fire blocking element.
A Simple Syntax for Complex Semantics (2002)

As part of a long-ranged project that aims at establishing database-theoretic semantics as a model of computational semantics, this presentation focuses on the development of a syntactic component for processeing strings of words or sentences to construct semantic data structures. For design and modeling purposes, the present treatment will be restricted to the analysis of some problematic constructions of Korean involving semi-free word order, conjunction and temporal anchoring, and adnominal modification and antecedent binding. The present work heavily relies on Hausser``s (1999, 2000) SLIM theory for language that is based on surface compositionality, time-linearity and two other conditions on natural language processing. Time-linear syntax for natural language has been shown to be concep-tually simple and computationally efficient. The associated semantics is complex, however, because it must deal with situated language involving interactive multi-agents. Nevertheless, by processing input word strings in a time-linear mode, the syntax can incrementally construct the necessary semantic structures for relevant queries and valid inferences. The fragment of Korean syntax will be implemented in Malaga, a C-type implementation language that was enriched for both programming and debugging purposes and that was particluarly made suitable for implementing in Left-Associative Grammar. This presentation will show how the system of syntactic rules with constraining subrules processes Korean sentences in a step-by-step time-linear manner to incrementally construct semantic data structures that mainly specify relations with their argument, temporal, and binding structures.
Animal Models of Rheumatoid Arthritis (1991)

Animal models of rheumatoid arthritis (RA) provide useful systems for the characterization of the immunopathogenic mechanisms of chronic inflammatory synovitis. Although at least eight models have been described, the adjuvant arthritis, streptococcal cell wall-induced arthritis, and collagen-induced arthritis models have provided the most useful insights. Each of these three models has contributed clues to our understanding of RA and have yielded promising new approaches to treatment. These include combination pharmacotherapy, antigen-specific therapy, cell-specific therapy, and monoclonal antibody therapy. All of these immunotherapeutic interventions have been shown to be beneficial in one or more animal systems. This suggests that future therapies for RA and other human autoimmune diseases may be more immunoselective and, potentially, less toxic.
Suppression of the neoplastic state with the acquisition of specialized functions in cells, tissues, and organs of crown gall teratomas of tobacco. (1976)

The neoplastic state in cells of tissues and organs that develop from cloned lines of crown gall teratomas of tobacco may be completely but reversibly suppressed. Stems and leaves found on teratoma shoots may appear morphologically normal and such organs contain all of the specialized cell types and are histologically and functionally indistinguishable from those found in normal tobacco shoots of comparable age. When however, specialized cells of several different kinds that are present in stems and leaves of the teratomas are excised from the plant and grown on a basic culture medium they again assume their neoplastic properties. The results of this study indicate that the morphogenetic factors and mechanisms that govern so precisely growth, cellular differentiation, and organogenesis during the normal course of development can completely suppress the tumorous state, leading to the formation of cells, tissues, and organs that appear normal in every respect but are, in fact, inherently neoplastic. Whether the normal or tumor phenotype is expressed appears to depend on the activation or repression of select biosynthetic systems, one of which, the auxin sytems, has been identified here.