gebhart/patrepeval huggingface dataset:
The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation (2010)

An account is given of the discovery of the classical Cys(2)His(2) zinc finger, arising from the interpretation of biochemical studies on the interaction of the Xenopus protein transcription factor IIIA with 5S RNA, and of structural studies on its structure and its interaction with DNA. The finger is a self-contained domain stabilized by a zinc ion ligated to a pair of cysteines and a pair of histidines, and by an inner hydrophobic core. This discovery showed not only a new protein fold but also a novel principle of DNA recognition. Whereas other DNA binding proteins generally make use of the two-fold symmetry of the double helix, zinc fingers can be linked linearly in tandem to recognize nucleic acid sequences of varying lengths. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA (or RNA). It is therefore not surprising that the zinc finger is found widespread in nature, including 3% of the genes of the human genome. The zinc finger design is ideally suited for engineering proteins to target specific genes. In the first example of their application in 1994, a three-finger protein was constructed to block the expression of an oncogene transformed into a mouse cell line. In addition, a reporter gene was activated by targeting an inserted zinc finger promoter. Thus, by fusing zinc finger peptides to repression or activation domains, genes can be selectively switched off or on. It was also suggested that by combining zinc fingers with other effector domains, e.g., from nucleases or integrases, to form chimeric proteins, genomes could be manipulated or modified. Several applications of such engineered zinc finger proteins are described here, including some of therapeutic importance.
Efficacy and Safely of a Topical Gel Formulation of Recombinant Human Platelet-Derived Growth Factor-BB (Becaplermin) in Patients With Chronic Neuropathic Diabetic Ulcers: A phase III randomized placebo-controlled double-blind study (1998)

Becaplermin gel 100 micrograms/g, in conjunction with good wound care, significantly increased the incidence of complete wound closure and significantly reduced the time to complete closure of chronic diabetic neuropathic ulcers. The safety profile of becaplermin gel was similar to that of placebo gel.
Structure Solution of Misfolded Conformations Adopted by Intrinsically Disordered Alzheimers Tau Protein (2009)

Until now it was impossible to obtain atomic structure of intrinsically disordered protein (IDP) tau and/or its assembly in Alzheimer's paired helical filaments as neither of them could have been prepared in the form amenable to X-ray or NMR techniques. Using IDP tau property to attain regular tertiary structure after binding events during self-assembly or when complexed with its target we propose monoclonal antibodies as surrogate tau protein binding partners to form complexes and crystals for structure solution by X-ray technique.
Cluster-based retrieval using language models (2004)

Previous research on cluster-based retrieval has been inconclusive as to whether it does bring improved retrieval effectiveness over document-based retrieval. Recent developments in the language modeling approach to IR have motivated us to re-examine this problem within this new retrieval framework. We propose two new models for cluster-based retrieval and evaluate them on several TREC collections. We show that cluster-based retrieval can perform consistently across collections of realistic size, and significant improvements over document-based retrieval can be obtained in a fully automatic manner and without relevance information provided by human.
Reduction by Cobra Venom Factor of Myocardial Necrosis after Coronary Artery Occlusion (1978)

Components of the complement system are known to play an important role in the cytolytic process and in chemotaxis of leukocytes. Cobra venom factor specifically cleaves C3 activity via activation of the alternative (properdin) complement pathway. It does not act directly on C3. If C3 is involved in tissue necrosis after ischemic injury, cobra venom factor might reduce tissue damage after acute coronary occlusion. Accordingly, in 14 control dogs occlusion of the left anterior descending artery was carried out for 24 h. Epicardial electrograms were recorded 15 min after occlusion, and 24 h later transmural specimens for creatine phosphokinase activity (CPK) and for histological analysis were obtained from the same sites. In another 14 experimental dogs, 20 U/kg cobra venom factor was given intravenously 30 min after occlusion. Serum complement levels fell within 2-4 h to <20% of normal. In the control dogs, the relationship between ST-segment elevation and CPK activity 24 h later was: log CPK = -0.06 ST + 1.48 (n = 111 specimens, 14 dogs, r = 0.77). In the experimental dogs, log CPK = -0.024 ST + 1.46 (n = 111 specimens, 14 dogs, r = 0.60), showing significantly different slopes (P < 0.001), i.e., less CPK depression for any level of ST-segment elevation. Histologically, 69 of 71 sites (97%) with ST-segment elevation exceeding 2 mV in the control dogs showed signs of necrosis 24 h later, whereas in the experimental group only 43 of 79 sites (54%) with abnormal ST-segment elevations showed signs of necrosis (P < 0.0005). At the same time, it was shown that the administration of cobra venom factor did not alter cardiac performance, collateral blood flow to the ischemic myocardium or the clotting system, but infiltration of polymorphonuclear leukocytes into the myocardium was decreased. It is concluded that cobra venom factor, by reducing the amount of C3 and C5 substrate available for chemotactic factor generation, or other as yet undefined mechanisms, protects the ischemic myocardium from undergoing necrosis, as judged by histology and local CPK activity. Hence, a new approach to limiting the extent of myocardial infarcts after experimental coronary occlusion, based upon inhibition of complement-dependent inflammatory processes, is demonstrated.
Deubiquitinating Enzyme Purification, Assay Inhibitors, and Characterization (2005)

Despite the identification of numerous deubiquitinating enzymes (DUBs) in recent years, the large majority of this class of enzymes has not been well characterized. This chapter describes biochemical methods that can be used to characterize the function and substrate specificity of DUBs. Methods described will include: fluorescence assay using ubiquitin-amidomethylcoumarin (AMC); a high-performance liquid chromatography assay using ubiquitin ethyl ester or ubiquitin fusion peptides as model substrates to monitor DUB activity; and the purification of a recombinant human DUB, isopeptidase T, in E. coli using low-temperature expression as well as ion-exchange and affinity chromatography.
Dynamic Interaction of PTPμ with Multiple Cadherins In Vivo (1998)

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPmu associates with the cadherin-catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S. M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977- 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPmu interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPmu and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPmu and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPmu from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPmu in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513-1517) have asserted that the association we observed between PTPmu and the cadherin-catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPmu, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPmu obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPmu antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPmu and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.
Effective Small RNA Destruction by the Expression of a Short Tandem Target Mimic in Arabidopsis (2012)

MicroRNAs (miRNAs) and other endogenous small RNAs act as sequence-specific regulators of the genome, transcriptome, and proteome in eukaryotes. The interrogation of small RNA functions requires an effective, widely applicable method to specifically block small RNA function. Here, we report the development of a highly effective technology that targets specific endogenous miRNAs or small interfering RNAs for destruction in Arabidopsis thaliana. We show that the expression of a short tandem target mimic (STTM), which is composed of two short sequences mimicking small RNA target sites, separated by a linker of an empirically determined optimal size, leads to the degradation of targeted small RNAs by small RNA degrading nucleases. The efficacy of the technology was demonstrated by the strong and specific developmental defects triggered by STTMs targeting three miRNAs and an endogenous siRNA. In summary, we developed an effective approach for the destruction of endogenous small RNAs, thereby providing a powerful tool for functional genomics of small RNA molecules in plants and potentially animals.
Phospholipase A2 inhibition and modification by manoalogue (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhospholipase A2 inhibition and modification by manoalogueLaure J. Reynolds, Bradley P. Morgan, Gary A. Hite, Edward D. Mihelich, and Edward A. DennisCite this: J. Am. Chem. Soc. 1988, 110, 15, 5172–5177Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July 1988https://pubs.acs.org/doi/10.1021/ja00223a044https://doi.org/10.1021/ja00223a044research-articleACS PublicationsRequest reuse permissionsArticle Views236Altmetric-Citations56LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Total Synthesis of Caloporoside (1998)

The first total synthesis of the fungal metabolite caloporoside 1, a strong and selective inhibitor of phospholipase C, is described. Both sugar units of its complex disaccharidic segment were obtained from 3,4,6-tri-O-benzyl-d-glucopyranose 14 as a common building block, with d-gluco → d-manno inversions as the key strategic elements. This particular substitution reaction occurred readily on the acyclic segment (27 → 28), whereas ultrasonication was required to override adverse stereoelectronic effects upon formation of β-d-mannopyranoside unit 34. The (16R)-hydroxyheptadecylsalicylic acid part of 1 was efficiently prepared by a palladium-catalyzed Suzuki cross coupling reaction of aryltriflate 7 with the 9-alkyl-9-BBN derivative formed from alkene 6 and 9-H-9-BBN.
Effectiveness of computer-generated (virtual reality) graded exposure in the treatment of acrophobia (1995)

The authors conclude that treatment with virtual reality graded exposure was successful in reducing fear of heights.
Vanadium Pentoxide Nanobelts: Highly Selective and Stable Ethanol Sensor Materials (2005)

Ethanol sensing has important applications, including breath alcohol checkers. A highly selective and stable ethanol sensor—see Figure—based on single-crystalline divanadium pentoxide nanobelts is described, representing a new strategy for the design of novel practicable gas sensors. Potential problems caused by changes of relative humidity or the presence of other gases are ruled out.
Enteric glia (1991)

The structure of the enteric nervous system (ENS) is different from that of extraenteric peripheral nerve. Collagen is excluded from the enteric plexuses and support for neuronal elements is provided by astrocyte-like enteric glial cells. Enteric glia differ from Schwann cells in that they do not form basal laminae and they ensheath axons, not individually, but in groups. Although enteric glia are rich in the S-100 and glial fibrillary acidic proteins, it has been difficult to find a single chemical marker that distinguishes enteric glia from non-myelinating Schwann cells. Nevertheless, two monoclonal antibodies have been obtained that recognize antigens that are expressed on Schwann cells (Ran-1 in rats and SMP in avians) but not enteric glia. Functional differences between enteric glia and non-myelinating Schwann cells, including responses to gliotoxins and in vitro proliferative rates, have also been observed. Developmentally, enteric glia, like Schwann cells, are derived from the neural crest. In both mammals and birds the precursors of the ENS appear to migrate to the bowel from sacral as well as vagal levels of the crest. These crest-derived emigrés give rise to both enteric glia and neurons; however, analyses of the ontogeny of the enteric innervation in a mutant mouse (the ls/ls), in which the original colonizing waves of crest-derived precursor cells are unable to invade the terminal colon, suggest that enteric glia can also arise from Schwann cells that enter the gut with the extrinsic innervation. When induced to leave back-transplanted segments of avian bowel, enteric crest-derived cells migrate into peripheral nerves and form Schwann cells. Enteric glia and Schwann cells thus appear to be different cell types, but ones that derive from lineages that diverge relatively late in ontogeny.
Gene Gun-Mediated DNA Immunization Primes Development of Mucosal Immunity against Bovine Herpesvirus 1 in Cattle (2000)

Vaccination by a mucosal route is an excellent approach to the control of mucosally acquired infections. Several reports on rodents suggest that DNA vaccines can be used to achieve mucosal immunity when applied to mucosal tissues. However, with the exception of one study with pigs and another with horses, there is no information on mucosal DNA immunization of the natural host. In this study, the potential of inducing mucosal immunity in cattle by immunization with a DNA vaccine was demonstrated. Cattle were immunized with a plasmid encoding bovine herpesvirus 1 (BHV-1) glycoprotein B, which was delivered with a gene gun either intradermally or intravulvomucosally. Intravulvomucosal DNA immunization induced strong cellular immune responses and primed humoral immune responses. This was evident after BHV-1 challenge when high levels of both immunoglobulin G (IgG) and IgA were detected. Intradermal delivery resulted in lower levels of immunity than mucosal immunization. To determine whether the differences between the immune responses induced by intravulvomucosal and intradermal immunizations might be due to the efficacy of antigen presentation, the distributions of antigen and Langerhans cells in the skin and mucosa were compared. After intravulvomucosal delivery, antigen was expressed early and throughout the mucosa, but after intradermal administration, antigen expression occurred later and superficially in the skin. Furthermore, Langerhans cells were widely distributed in the mucosal epithelium but found primarily in the basal layers of the epidermis of the skin. Collectively, these observations may account for the stronger immune response induced by mucosal administration.
Recommendations for IPv6 in Third Generation Partnership Project (3GPP) Standards (2002)

This document contains recommendations from the Internet Engineering Task Force (IETF) IPv6 Working Group to the Third Generation Partnership Project (3GPP) community regarding the use of IPv6 in the 3GPP standards. Specifically, this document recommends that the 3GPP specify that multiple prefixes may be assigned to each primary PDP context, require that a given prefix must not be assigned to more than one primary PDP context, and allow 3GPP nodes to use multiple identifiers within those prefixes, including randomly generated identifiers.
Cross-recognition of HLA DR4 alloantigen by virus-specific CD8+ T cells: a new paradigm for self-/nonself-recognition (2009)

The ability of CD8(+) T cells to engage a diverse range of peptide-major histocompatibility complex (MHC) complexes can also lead to cross-recognition of self and nonself peptide-MHC complexes and thus directly contribute toward allograft rejection or autoimmunity. Here we present a novel form of cross-recognition by herpes virus-specific CD8(+) cytotoxic T cells that challenges the current paradigm of self/non-self recognition. Functional characterization of a human leukocyte antigen (HLA) Cw*0602-restricted cytomegalovirus-specific CD8(+) T-cell response revealed an unusual dual specificity toward a pp65 epitope and the alloantigen HLA DR4. This cross-recognition of HLA DR4 alloantigen was critically dependent on the coexpression of HLA DM and was preferentially directed toward the B-cell lineage. Furthermore, allostimulation of peripheral blood lymphocytes with HLA DRB*0401-expressing cells rapidly expanded CD8(+) T cells, which recognized the pp65 epitope in the context of HLA Cw*0602. T-cell repertoire analysis revealed 2 dominant populations expressing T-cell receptor beta variable (TRBV)4-3 or TRBV13, with cross-reactivity exclusively mediated by the TRBV13(+) clonotypes. More importantly, cross-reactive TRBV13(+) clonotypes displayed markedly lower T-cell receptor binding affinity and a distinct pattern of peptide recognition, presumably mimicking a structure presented on the HLA DR4 allotype. These results illustrate a novel mechanism whereby virus-specific CD8(+) T cells can cross-recognize HLA class II molecules and may contribute toward allograft rejection and/or autoimmunity.
hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis (1983)

Except for a small fraction of persisters, 10(-6) to 10(-5), Escherichia coli K-12 is killed by prolonged inhibition of murein synthesis. The progeny of persisters are neither more resistant to inhibition of murein synthesis nor more likely to persist than normal cells. Mutants have been isolated in which a larger fraction, 10(-2), persists. The persistent response of the mutants, Hip (high persistence), is to inhibition of murein synthesis at early or late steps by antibiotics (phosphomycin, cycloserine, and ampicillin) or by metabolic block (starvation for diaminopimelic acid). Killing of the parent strain by each of the four inhibitors has two phases: The first is rapid and lasts about 30 min; the second is slower, but still substantial, and lasts 3 to 4 h. The first phase also occurs in the Hip mutants, but then viability of the mutants remains constant after about 30 min. Neither tolerance, resistance, impaired growth, nor reversion of spheroplasts accounts for high-frequency persistence. Two of the mutations map at 33.8 min in a region containing few other recognized functions. This position and the phenotypes define hipA as a newly recognized gene. Transposons Tn5 and Tn10 have been inserted close to hipA making it possible to explore the molecular genetics of persistence, a long recognized but poorly understood phenomenon.
Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors (2001)

The concept for cellular immunotherapy of solid tumors relies heavily on the capacity of class I MHC-restricted cytotoxic T lymphocytes (CTLs) to eliminate tumor cells. However, tumors often have managed to escape from the cytolytic machinery of these effector cells. Therefore, it is very important to chart the mechanisms through which this escape can occur. Target-cell killing by CTLs involves the induction of apoptosis by two major mechanisms: through death receptors and the perforin/granzyme B (GrB) pathway. Whereas tumors previously were shown to exhibit mechanisms for blocking the death receptor pathway, we now demonstrate that they also can resist CTL-mediated killing through interference with the perforin/GrB pathway. This escape mechanism involves expression of the serine protease inhibitor PI-9/SPI-6, which inactivates the apoptotic effector molecule GrB. Expression of PI-9 was observed in a variety of human and murine tumors. Moreover, we show that, indeed, expression results in the resistance of tumor cells to CTL-mediated killing both in vitro and in vivo. Our data reveal that PI-9/SPI-6 is an important parameter determining the success of T cell-based immunotherapeutic modalities against cancer.
The biotin requirement of HeLa cells (1981)

We have examined the effect of alterations in the biotin content of the medium on the growth, viability, biotin content, and the activities of biotin-independent and biotin-independent enzymes of the HeLa cells. The inclusion in the growth medium of avidin, which almost irreversibly binds with biotin (Kd, 10(-15) M), results in an increase in cellular biotin content and biotin enzyme activity over that seen when the cells are grown in a biotin-depleted medium. The addition of avidin-bound biotin to the growth medium led to a forty-fold increase in cellular biotin when compared to the inclusion of an equivalent amount of free biotin in the medium. HeLa cells are able to internalize avidin-bound biotin. Biotin is released from this complex to function as the prosthetic group of biotin enzymes. HeLa cells do have a nutritional requirement for biotin.
Primary fibromyalgia syndrome: a critical evaluation of recent criteria developments. (1990)

Although nonspecific musculoskeletal aching of nonarticular origin has been described in European literature since the 17th century under such names as muscular rheumatism, the fibrositis syndrome with generalized musculoskeletal aches or stiffness, fatigue, poor sleep, and multiple tender points as a characteristic rheumatologic entity was not described until the 1960s. Smythe first suggested criteria for this condition based on clinical experience in the 1970s. However, the first data-based criteria of "fibrositis" (appropriately called fibromyalgia) was not published until 1981. Since then other criteria have been published, and in 1989 criteria studies on fibromyalgia with appropriate design and controls were reported. This article critically evaluates current criteria developments in fibromyalgia.