gebhart/patrepeval huggingface dataset:
Preparation and Characterization of Latent α1-Antitrypsin (1995)

Members of the serine proteinase inhibitor or serpin superfamily have a common molecular architecture based on a dominant five-membered A beta-pleated sheet and a mobile reactive center loop. The reactive center loop has been shown to adopt a range of conformations from the three turn alpha-helix of ovalbumin to the cleaved or latent inhibitor in which the reactive center loop is fully inserted into the A sheet of the molecule. While the cleaved state can be achieved in all inhibitory serpins only plasminogen activator inhibitor-1 and, more recently, antithrombin have been shown to adopt the latent conformation. We show here that the archetypal serpin, alpha 1-antitrypsin, can also be induced to adopt the latent conformation by heating at high temperatures in 0.7 M citrate for 12 h. The resulting species elutes at a lower sodium chloride concentration on an anion-exchange column and has a more cathodal electrophoretic mobility on non-denaturing polyacrylamide gel electrophoresis and isoelectric focusing than native M antitrypsin. Latent antitrypsin is inactive as an inhibitor of bovine alpha-chymotrypsin, is stable to unfolding with 8 M urea, and is more resistant to heat-induced loop-sheet polymerization than native but less resistant than cleaved antitrypsin. The reactive center loop of latent antitrypsin is inaccessible to proteolytic cleavage, and its occupancy of the A sheet prevents the molecule accepting an exogenous reactive center loop peptide. The activity of latent antitrypsin may be increased from < 1% to approximately 35% by refolding from 6 M guanidinium chloride.
Backpropagation (2001)

The popular backpropagation algorithm for training neural nets is a special case of an earlier principle of significance feedback, which in turn has much in common with Selfridge’s “Pandemonium” and a connection with McCulloch’s “redundancy of potential command”. Ways in which the effects might operate in real neural nets are reviewed, and the ideas are related to the current interest in heterogeneous agents. The tendency to restrict attention to numerical optimisation is regretted.
Authentication for distributed systems (1997)

A fundamental concern in building a secure distributed system is authentication of local and remote entities in the system. We survey authentication issues in distributed system design. Two basic paradigms underlying the design of authentication protocols are presented. We then propose an authentication framework that can be used for designing secure distributed systems, including specific protocols for secure bootstrapping, user-host authentication, and peer-peer authentication. We conclude with an overview of two existing authentication systems, namely, Kerberos and SPX. This work was sponsored by grants from the Texas Advanced Research Program, National Science Foundation, and the NSA INFOSEC University Research Program. This is a revised version of a paper with the same title published in Computer, Volume 25, Number 1, pages 39--52, January 1992. To appear in Internet Besieged: Countering Cyberspace Scofflaws, Dorothy Denning and Peter Denning (editors), ACM Press and Addison-Wes...
Alphavirus replicon particles containing the gene for HER2/neuinhibit breast cancer growth and tumorigenesis (2004)

On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted.
Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo‐controlled, double‐blind study (2000)

A clinical study was conducted to evaluate the effectiveness of lactoferrin, which is a protein component of cow's milk, in the treatment of tinea pedis. Doses of either 600 mg or 2000 mg of lactoferrin, or a placebo was orally administered daily for 8 weeks to 37 adults who were judged to have mild or moderate tinea pedis. Dermatological improvement and antifungal efficacy were assessed. In the analysis of all subjects, dermatological symptoms scores in all groups decreased but the differences were not statistically significant comparing the three groups. However, in the analysis limited to subjects with moderate vesicular or interdigital tinea pedis, dermatological symptoms scores in the lactoferrin-treated groups decreased significantly in comparison with the placebo group (P < 0.05). The organisms isolated were Trichophyton rubrum and Trichophyton mentagrophytes. A mycological cure was not seen in any of the subjects. In the 37 subjects there were no adverse events and no subject withdrew from the study because of an adverse event. These results suggest that orally administered lactoferrin can improve the dermatological symptoms in some subjects. The potential usefulness of lactoferrin as a functional food material for treating tinea pedis was seen for the first time in this study.
Inaccuracies of Nitric Oxide Delivery Systems during Adult Mechanical Ventilation (1997)

NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow-response analyzers.
The farnesoid X receptor induces very low density lipoprotein receptor gene expression (2004)

The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). In response to ligand-binding, FXR regulates many genes involved in BA, lipid, and lipoprotein metabolism. To identify new FXR target genes, microarray technology was used to profile total RNA extracted from HepG2 cells treated with the natural FXR agonist chenodeoxycholic acid (CDCA). Interestingly, a significant increase of transcript level of the very low density lipoprotein receptor (VLDLR) was observed. Our data, resulting from selective FXR activation, FXR RNA silencing and FXR-deficient mice, clearly demonstrate that BAs up-regulate VLDLR transcript levels via a FXR-dependent mechanism in vitro in human and in vivo in mouse liver cells.
A COMPARATIVE STUDY OF THE MICROBIAL ANTI-ADHERENCE CAPACITIES OF THREE ANTIMICROBIAL AGENTS (1987)

The antimicrobioal agents, taurolidine, chlorhexidine and povidone-iodine were examined for microbial anti-adherence activity. Two adherence systems were investigated using light microscopic and radio-isotopic assay methods: that of an oral isolate of Candida albicans to human buccal epithelial cells and of a urine isolate of Escherichia coli to human uroepithelial cells. Each of the three agents exhibited significant anti-adherence activity which was concentration dependent. The activity was expressed at subminimum inhibitory concentrations of the agents. Treatment of either the microbial or epithelial cells resulted in significant reductions in adhering micro-organisms. Consideration of the data in respect of the skewness coefficient and percentage clear epithelial cells indicated that the agents exhibited a broadly based anti-adherence capacity.
Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice (2013)

The principal reason for failure of targeted cancer therapies is the emergence of resistant clones that regenerate the tumor. Therapeutic efficacy therefore depends on not only how effectively a drug inhibits its target, but also the innate or adaptive functional redundancy of that target and its attendant pathway. In this regard, the Myc transcription factors are intriguing therapeutic targets because they serve the unique and irreplaceable role of coordinating expression of the many diverse genes that, together, are required for somatic cell proliferation. Furthermore, Myc expression is deregulated in most-perhaps all-cancers, underscoring its irreplaceable role in proliferation. We previously showed in a preclinical mouse model of non-small-cell lung cancer that systemic Myc inhibition using the dominant-negative Myc mutant Omomyc exerts a dramatic therapeutic impact, triggering rapid regression of tumors with only mild and fully reversible side effects. Using protracted episodic expression of Omomyc, we now demonstrate that metronomic Myc inhibition not only contains Ras-driven lung tumors indefinitely, but also leads to their progressive eradication. Hence, Myc does indeed serve a unique and nondegenerate role in lung tumor maintenance that cannot be complemented by any adaptive mechanism, even in the most aggressive p53-deficient tumors. These data endorse Myc as a compelling cancer drug target.
Troglitazone Improves Psoriasis and Normalizes Models of Proliferative Skin Disease (2000)

Peroxisome proliferator-activated receptor-gamma might be a useful intracellular target for the treatment of psoriasis; further study is needed to assess the clinical value of ligands for PPARgamma, including troglitazone.
NAD(P)H dehydrogenase and its role in the vitamin K (2-methyl-3-phytyl-1,4-naphthaquinone)-dependent carboxylation reaction (1978)

A simple three-step method was established for the purification of NAD(P)H dehydrogenase (quinone) ('DT-diaphorase', EC 1.6.99.2) from rat liver by affinity chromatography with a recovery of above 50%. The final enzyme preparation was purified about 750-fold and was electrophoretically homogeneous. Gel filtration showed that the enzyme had a mol.wt. of about 55 000, and one molecule of FAD was found per 55 000 mol.wt. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis gave a mol.wt. of about 27 000. Two N-terminal amino acids, asparagine/aspartic acid and glutamine/glutamic acid, were found in about equal yield, suggesting the presence of two non-identical polypeptide chains in the enzyme. NAD(P)H dehydrogenase was selectively removed by this affinity-chromatographic method from a microsomal carboxylation system. The system, which was solubilized by detergent and is dependent on vitamin K (2-methyl-3-phytyl-1,4-naphthaquinone or analogues with other side chains), lost its activity on the removal of the enzyme. The activity can be completely restored to the system by adding purified cytoplasmic NAD(P)H dehydrogenase or by using the quinol form of vitamin K1 (2-methyl-3-phytyl-1,4-naphthaquinol).
The role of neuropilins in cancer (2006)

Neuropilins are multifunctional non-tyrosine kinase receptors that bind to class 3 semaphorins and vascular endothelial growth factor. NRP-1 and NRP-2 were first identified for their key role in mediating axonal guidance in the developing nervous system through their interactions with class 3 semaphorins. Growing evidence supports a critical role for these receptors in tumor progression. Neuropilin expression is up-regulated in multiple tumor types, and correlates with tumor progression and prognosis in specific tumors. Neuropilins may indirectly mediate effects on tumor progression by affecting angiogenesis or directly through effects on tumor cells. This article reviews emerging evidence for the role of neuropilins in tumor biology. The therapeutic implications of these data are far-reaching and suggest that neuropilin-targeted interventions may be useful as a component of antineoplastic therapy.
The Extracellular Domain of Herpes Simplex Virus gE Is Indispensable for Efficient Cell-to-Cell Spread: Evidence for gE/gI Receptors (2005)

Herpes simplex virus (HSV) spreads rapidly and efficiently within epithelial and neuronal tissues. The HSV glycoprotein heterodimer gE/gI plays a critical role in promoting cell-to-cell spread but does not obviously function during entry of extracellular virus into cells. Thus, gE/gI is an important molecular handle on the poorly understood process of cell-to-cell spread. There was previous evidence that the large extracellular (ET) domains of gE/gI might be important in cell-to-cell spread. First, gE/gI extensively accumulates at cell junctions, consistent with being tethered there. Second, expression of gE/gI in trans interfered with HSV spread between epithelial cells. To directly test whether the gE ET domain was necessary for gE/gI to promote virus spread, a panel of gE mutants with small insertions in the ET domain was constructed. Cell-to-cell spread was reduced when insertions were made within either of two regions, residues 256 to 291 or 348 to 380. There was a strong correlation between loss of cell-to-cell spread function and binding of immunoglobulin. gE ET domain mutants 277, 291, and 348 bound gI, produced mature forms of gE that reached the cell surface, and were incorporated into virions yet produced plaques similar to gE null mutants. Moreover, all three mutants were highly restricted in spread within the corneal epithelium, in the case of mutant 277 to only 4 to 6% of the number of cells compared with wild-type HSV. Therefore, the ET domain of gE is indispensable for efficient cell-to-cell spread. These observations are consistent with our working hypothesis that gE/gI can bind extracellular ligands, so-called gE/gI receptors that are concentrated at epithelial cell junctions. This fits with similarities in structure and function of gE/gI and gD, which is a receptor binding protein.
Large swing CMOS power amplifier (1983)

A CMOS class AB power amplifier is presented in which supply-to-supply voltage swings across low-impedance loads are efficiently and readily handled. The amplifier consists of a high-gain input stage and a push-pull unity-gain amplifier output stage. The amplifier dissipates only 7 mW of DC power and delivers 36 mW of AC power to a 300-/spl Omega/ load, using standard power supplies of /spl plusmn/5.0 V. Lower impedance loads can be driven to higher power levels, providing the internal current limiting level is not exceeded.
Determinants of osteoporotic thoracic vertebral fracture (1992)

A population sample of 27,000 Finnish women and 30,000 men was studied for the presence of a thoracic vertebral fracture. In both sexes, the prevalence of such fractures increased with age: after 40 years of age in the men and after 55 years of age in the women. The interaction of sex and age was significant, and even when the other determinants were adjusted for. In the women aged 35-44, 55-64, and 75 years or more, the prevalence per 1,000 was respectively 2.4, 5.1, and 29, and in the men in the corresponding age groups 5.2, 15, and 28. A previous history of trauma was a fracture determinant in both sexes. In the men, but not in the women, there was an increased risk of fracture when there was a history of tuberculosis and/or peptic ulcer, and in current smokers. Thus, contrary to observations on extremity fractures, the men had an increased risk of sustaining a thoracic vertebral fracture compared with the women. This may reflect differences in the development of osteoporosis in the axial skeleton versus the appendicular skeleton.
The Ras-related Protein Rheb Is Farnesylated and Antagonizes Ras Signaling and Transformation (1997)

Presently, nothing is known about the function of the Ras-related protein Rheb. Since Rheb shares significant sequence identity with the core effector domains of Ras and KRev-1/Rap1A, it may share functional similarities with these two structurally related, yet functionally distinct, small GTPases. Furthermore, since like Ras, Rheb terminates with a COOH terminus that is likely to signal for farnesylation, it may be a target for the farnesyltransferase inhibitors that block Ras processing and function. To compare Rheb function with those of Ras and KRev-1, we introduced mutations into Rheb that generate constitutively active or dominant negative forms of Ras and Ras-related proteins and were designated Rheb(64L) and Rheb(20N), respectively. Expression of wild type or mutant Rheb did not alter the morphology or growth properties of NIH 3T3 cells. Thus, aberrant Rheb function is distinct from that of Ras and fails to cause cellular transformation. Instead, similar to KRev-1, co-expression of Rheb antagonized oncogenic Ras transformation and signaling. In vitro and in vivo analyses showed that like Ras, Rheb proteins are farnesylated and are sensitive to farnesyltransferase inhibition. Thus, it is possible that Rheb function may be inhibited by farnesyltransferase inhibitors treatment and, consequently, may contribute to the ability of these inhibitors to impair Ras transformation.
Direct Delivery of the Bordetella pertussis Adenylate Cyclase Toxin to the MHC Class I Antigen Presentation Pathway (1999)

Among bacterial toxins, the adenylate cyclase toxin of Bordetella pertussis (CyaA) has a unique mechanism of entry that consists in the direct translocation of its catalytic domain across the plasma membrane of target cell, a mechanism supposed to be independent of any endocytic pathway. Here, we report that the CyaA toxin is delivered to the cytosolic pathway for MHC class I-restricted Ag presentation. Using peritoneal macrophages as APC, we show that the OVA 257-264 CD8+ epitope genetically inserted into a detoxified CyaA (CyaA-OVA E5) is presented to CD8+ T cells by a mechanism requiring 1) proteasome processing, 2) TAP, and 3) neosynthesis of MHC class I. We demonstrate that the presentation of CyaA-OVA E5, like the translocation of CyaA into eukaryotic cells, is dependent on extracellular Ca2+ and independent of vacuolar acidification. Moreover, inhibitors of the phagocytic and macropinocytic endocytic pathways do not affect the CyaA-OVA E5 presentation. The absence of specific cellular receptors for CyaA correlates with the ability of various APC to present the recombinant CyaA toxin, including dendritic cells, macrophages, splenocytes, and lymphoid tumoral lines. Taken together, our results show that the CyaA presentation pathway is not cell type specific and is unrelated to a defined type of endocytic mechanism. Thus, it represents a new and unconventional delivery of an exogenous Ag into the conventional cytosolic pathway.
Improved tolerance to salinity and low temperature in transgenic tobacco producing glycine betaine (2000)

Glycine betaine is an osmoprotectant found in many organisms, including bacteria and higher plants. The bacterium Escherichia coli produces glycine betaine by a two-step pathway where choline dehydrogenase (CDH), encoded by betA, oxidizes choline to betaine aldehyde which is further oxidized to glycine betaine by the same enzyme. The second step, conversion of betaine aldehyde into glycine betaine, can also be performed by the second enzyme in the pathway, betaine aldehyde dehydrogenase (BADH), encoded by betB. Transformation of tobacco (Nicotiana tabacum), a species not accumulating glycine betaine, with the E. coli genes for glycine betaine biosynthesis, resulted in transgenic plants accumulating glycine betaine. Plants producing CDH were found to accumulate glycine betaine as did F1 progeny from crosses between CDH- and BADH-producing lines. Plants producing both CDH and BADH generally accumulated higher amounts of glycine betaine than plants producing CDH alone, as determined by 1H NMR analysis. Transgenic tobacco lines accumulating glycine betaine exhibited increased tolerance to salt stress as measured by biomass production of greenhouse-grown intact plants. Furthermore, experiments conducted with leaf discs from glycine betaine-accumulating plants indicated enhanced recovery from photoinhibition caused by high light and salt stress as well as improved tolerance to photoinhibition under low temperature conditions. In conclusion, introduction of glycine betaine production into tobacco is associated with increased stress tolerance probably partly due to improved protection of the photosynthetic apparatus.
Molecular Evolution of N-Methylputrescine Oxidase in Tobacco (2013)

Biosynthesis of nicotine in tobacco requires N-methylputrescine oxidase (MPO), which belongs to the copper-containing amine oxidase superfamily. Previous studies identified tobacco MPO1 and its close homolog NtDAO1 (formerly called MPO2), of which MPO1 has been shown preferentially to oxidize N-methylated amines. We show here that NtDAO1, as well as a homologous Arabidopsis diamine oxidase (DAO), accept non-N-methylated amines more efficiently than their corresponding N-methylated amines. MPO1 is coordinately regulated with other nicotine biosynthesis genes with regard to COI1-MYC2-dependent jasmonate induction and its dependence on nicotine-specific ERF transcription factors, whereas NtDAO1 is constitutively expressed at low basal levels in tobacco plants. Both MPO1 and NtDAO1 are targeted to peroxisomes by their C-terminal motifs, and the peroxisomal localization of MPO1 is required for it to function in nicotine biosynthesis in jasmonate-elicited cultured tobacco cells. Restricted occurrence of the MPO subfamily in Nicotiana and Solanum indicates that, during the formation of the Solanaceae, MPO has evolved from a DAO, which functions in polyamine catabolism within peroxisomes, by optimizing substrate preference and gene expression patterns to be suitable for alkaloid formation.
MPI: A Message-Passing Interface (1994)

This paper presents an overview of MPI, a proposed standard message passing interface for MIMD distributed memory concurrent computers. The design of MPI has been a collective effort involving researchers in the Untied states and Europe from many organizations and institutions. MPI includes point-to-point and collective communication routines, as well as support for process groups, communication contexts, and application topologies. While making use of new ideas where appropriate, the MPI standard is based largely on current practice.
Embryogenesis in vitro: Study of Differentiation of Embryonic Stem Cells (1995)

Embryogenesis is the fundamental process of differentiation of all tissues from a fertilized egg. This process involves establishment of distinct stem cells that will later differentiate to all cell types. Recently, lines of embryonic stem cells have been established in culture from blastocysts. The cells are pluripotent and can differentiate in vivo to all lineages. Interestingly, differentiation of these cells can also be induced in vitro. Morphological and molecular events that are characteristic of the development of the embryo can be mimicked in vitro by growing the cells under controlled conditions. Furthermore, the process of early development can now be studied and manipulated in vitro and specific lineages of stem cells can be obtained and grown in culture.
Boron-Nitrogen Polymers. (1985)

The objective was to develop processible preceramic polymers amenable to transformation into pure boron nitride for potential applications as fibers and coatings. A series of alkyl, aryl, and trimethylsilyl-substituted borazines was synthesized and subjected to pyrolysis to determine the type of substituent leading to an optimum preceramic polymer. The feasibility of the process was established. From trimethylsilyl-substituted precursors, following stepwise pyrolysis, fibers were drawn and cured in an ammonia atmosphere giving pure boron nitride. Mechanisms responsible for borazine condensations were elucidated; processes involved in precursor synthesis were investigated.
A client‐generated psychometric instrument: The development of ‘PSYCHLOPS’ (2004)

PSYCHLOPS (Psychological Outcome Profiles) is a recently developed, client‐generated, psychometric instrument that can be used as an outcome measure. Based on a similar instrument developed primarily for use in physical illnesses (MYMOP — ‘Measure Your Medical Outcome Profile’), it seeks the client's perspective on their psychological distress. It asks them to describe and then score the problem that troubles them the most at the start of counselling. We describe the development of PSYCHLOPS, including the involvement of the Plain English Campaign and two national mental health organisations: the mental health charity and support group, Depression Alliance (DA) and Primary Care Mental Health Education (PRIMHE). We review the literature and suggest that PSYCHLOPS, by focusing on the problems of greatest priority to the client, might prove a sensitive measure of improvement after counselling.