gebhart/patrepeval huggingface dataset:
Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes (1999)

Human telomerase consists of two essential components, telomerase RNA template (hTER) and telomerase reverse transcriptase (hTERT), and functions to synthesize telomere repeats that serve to protect the integrity of chromosomes and to prolong the replicative life span of cells. Telomerase activity is expressed selectively in germ-line and malignant tumor cells but not in most normal human somatic cells. As a notable exception, telomerase is expressed in human lymphocytes during development, differentiation, and activation. Recent studies have suggested that regulation of telomerase is determined by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contribution of transcriptional regulation of hTERT and hTER. We report here an analysis of hTERT expression by Northern and in situ hybridization. It was found that hTERT mRNA is expressed at detectable levels in all subsets of human lymphocytes isolated from thymus, tonsil, and peripheral blood, regardless of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikingly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to account for telomerase activity in human lymphocytes, indicating a likely role of posttranscriptional factors in the control of enzyme function.
Multiparty key distribution and secret sharing based on entanglement swapping (2000)

A general proof of the security against eavesdropping of a previously introduced protocol for two-party quantum key distribution based on entanglement swapping [Phys. Rev. A {\bf 61}, 052312 (2000)] is provided. In addition, the protocol is extended to permit multiparty quantum key distribution and secret sharing of classical information.
Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus (1998)

Melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiological roles remain largely unknown. In this study, we examined the interactions between MCH and alpha-MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving ACTH. In contrast, alpha-MSH decreased food intake and increased glucocorticoid levels. MCH, at a twofold molar excess, antagonized both actions of alpha-MSH. alpha-MSH, at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did not block alpha-MSH binding or the ability of alpha-MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain alpha-MSH receptor subtypes. These data suggest that MCH and alpha-MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor.
Nuclear localization signal binding proteins in higher plant nuclei. (1995)

The import of proteins into the nucleus is a vital process that is mediated by proteins which specifically recognize nuclear localization signals (NLSs). These factors have not been identified in plants. Previously, we demonstrated that higher plants possess a low-affinity binding site at the nuclear pore that specifically binds to several classes of functional NLSs. By the use of crosslinking reagents and a radiolabeled peptide to the bipartite NLS from the endogenous plant transcription factor Opaque2, two NLS binding proteins (NBPs) of 50-60 kDa and at least two NBPs of 30-40 kDa were identified. Competition studies indicated that labeling was specific for the functional NLS but not a mutant NLS impaired in vivo or a peptide unrelated to NLSs. Also, the apparent dissociation constant (100-300 microM) for labeling was similar to that of the binding site. Proteins of similar mass were labeled with two different crosslinking reagents, and concentration and time studies indicated that these NBPs were distinct proteins and not aggregates. Treatment with salt, detergent, or urea before or during NLS binding demonstrated that the properties of the binding site and the NBPs were identical. This tight correlation strongly indicates that some or all of the NBPs constitute the nuclear pore binding site. Overall, our results indicate that some components of NLS recognition are located at the nuclear pores in higher plants.
Plasmid-based gene transfer for treatment of erectile dysfunction and overactive bladder: results of a phase I trial. (2007)

Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that hMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access.
A Planner for Composing Services Described in DAML-S (2003)

A web service is a web-accessible piece of software or hardware. In recent years, industry has been showing increasing interest in web services as a technology for building distributed web applications. However, web services as a technology lacks in several departments. Representations for describing web services have been widely investigated by industry and academia. Service composition-that is, automated methods for constructing a sequence of web services to achieve a desired result- has been relatively neglected. We present in this paper, a planner that composes atomic/basic services described in DAML-S (Ankolenkar et al. 2002) into a composite service. We discuss issues involved with the design of planners for composition. We also propose a set of guidelines for describing services that facilitates composition.
Efficient transparent application recovery in client-server information systems (1998)

Database systems recover persistent data, providing high database availability. However, database applications, typically residing on client or “middle-tier” application-server machines, may lose work because of a server failure. This prevents the masking of server failures from the human user and substantially degrades application availability. This paper aims to enable high application availability with an integrated method for database server recovery and transparent application recovery in a client-server system. The approach, based on application message logging, is similar to earlier work on distributed system fault tolerance. However, we exploit advanced database logging and recovery techniques and request/reply messaging properties to significantly improve efficiency. Forced log I/Os, frequently required by other methods, are usually avoided. Restart time, for both failed server and failed client, is reduced by checkpointing and log truncation. Our method ensures that a server can recover independently of clients. A client may reduce logging overhead in return for dependency on server availability during client restart.
Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation (2005)

High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells,activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation end-products), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 +/- 8.18 ng/ml, mean +/- SD), malignancies (2.15 +/- 5.34 ng/ml),and traumas (6.47 +/- 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 +/- 12.56 ng/ml) in these patients. The highest HMGB1 levels were in patients with organ failure (8.29 +/- 10.99 ng/ml) and non-survivors (16.58 +/- 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.
Effects of inductance on the propagation delay and repeater insertion in VLSI circuits (2000)

A closed-form expression for the propagation delay of a CMOS gate driving a distributed RLC line is introduced that is within 5% of dynamic circuit simulations for a wide range of RLC loads. It is shown that the error in the propagation delay if inductance is neglected and the interconnect is treated as a distributed RC line can be over 35% for current on-chip interconnect. It is also shown that the traditional quadratic dependence of the propagation delay on the length of the interconnect for RC lines approaches a linear dependence as inductance effects increase. On-chip inductance is therefore expected to have a profound effect on traditional high-performance integrated circuit (IC) design methodologies. The closed-form delay model is applied to the problem of repeater insertion in RLC interconnect. Closed-form solutions are presented for inserting repeaters into RLC lines that are highly accurate with respect to numerical solutions. RC models can create errors of up to 30% in the total propagation delay of a repeater system as compared to the optimal delay if inductance is considered. The error between the RC and RLC models increases as the gate parasitic impedances decrease with technology scaling. Thus, the importance of inductance in high-performance very large scale integration (VLSI) design methodologies will increase as technologies scale.
Calcitonin gene-related peptide: an update on the biology (2009)

The advent of CGRP receptor antagonists as a novel therapy for migraine attacks may represent a new era in the acute management of migraine. More than a simple addition to the currently available treatments, this group of drugs may become an outstanding option for patients with cardiovascular disease, given the lack of associated vasoconstriction. Furthermore, nonpeptide CGRP receptor antagonists, CGRP antibodies and CGRP-binding RNA-Spiegelmer are valuable research tools that will further advance our understanding of migraine pathophysiology.
Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display (2010)

To demonstrate the utility of phage display in generating highly specific antibodies, affinity selections were conducted on 20 related Src Homology 2 (SH2) domains (ABL1, ABL2, BTK, BCAR3, CRK, FYN, GRB2, GRAP2, LYN, LCK, NCK1, PTPN11 C, PIK3R1 C, PLCgamma1 C, RASA1 C, SHC1, SH2D1A, SYK N, VAV1 and the tandem domains of ZAP70). The domains were expressed in Escherichia coli, purified and used in affinity selection experiments. In total, 1292/3800 of the resultant antibodies were shown to bind the target antigen. Of the 695 further evaluated in specificity ELISAs against all 20 SH2 domains, 379 antibodies were identified with unique specificity (i.e. monospecific). Sequence analysis revealed that there were at least 150 different clones with 1-19 different antibodies/antigen. This includes antibodies that distinguish between ABL1 and ABL2, despite their 89% sequence identity. Specificity was confirmed for many on protein arrays fabricated with 432 different proteins. Thus, even though the SH2 domains share a common three-dimensional structure and 20-89% identity at the primary structure level, we were able to isolate antibodies with exquisite specificity within this family of structurally related domains.
Establishment and characterization of a new human leukemia cell line derived from M4E0 (1991)

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2- methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL- 4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.
A Novel Serum-Free Monolayer Culture for Orderly Hematopoietic Differentiation of Human Pluripotent Cells via Mesodermal Progenitors (2011)

Elucidating the in vitro differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells is important for understanding both normal and pathological hematopoietic development in vivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfully trace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayer culture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitive blood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced the hematopoietic mesodermal progenitors via primitive streak cells. These progenitors were then differentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors were induced in our culture. Our system provides a new, robust, and simple method for investigating the mechanisms of mesodermal and hematopoietic differentiation.
Microbiological hydroxylation. Part XIV. Hydroxylation in the terminal rings of dioxygenated 5α-androstanes with the fungi Wojnowicia graminis and Ophiobolus herpotrichus (1975)

Dioxo-5α-androstanes having one keto-group in a terminal ring (at position 3 or 2, or at position 17) and the second at a middle ring position (7 or 11) are hydroxylated in the other terminal ring (at 17 or 16, or at 3 or 2) by the fungi Wojnowicia graminis and Ophiobolus herpotrichus. Efficient transformations include the 2α-hydroxylation of 5α-androstane-7,17-dione (with W. graminis), the 16-substitution of the 3,11-dione (with O. herpotrichus), and the 17β-hydroxylation of 3,7-dioxygenated substrates (with both fungi).
Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease. (1984)

Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis.
Analysis of a DtxR-Regulated Iron Transport and Siderophore Biosynthesis Gene Cluster in Corynebacterium diphtheriae (2005)

This report describes a genetic locus associated with siderophore biosynthesis and transport in Corynebacterium diphtheriae. A BLAST search of the C. diphtheriae genome identified a seven-gene cluster that included four genes, designated ciuA, ciuB, ciuC, and ciuD, whose predicted products are related to ABC-type iron transporters. Downstream from ciuD is the ciuE gene, whose predicted product is similar to the aerobactin biosynthetic enzymes IucA and IucC. The CiuE protein, which has a predicted mass of 121,582 Da and is approximately twice the size of either IucC or IucA, is homologous to each of these proteins in both its N- and C-terminal regions. C. diphtheriae ciuE deletion mutants exhibited a defect in siderophore production, iron uptake, and growth in low-iron medium. Mutations in the ciuA gene, whose predicted product is a lipoprotein component of an iron transport system, resulted in a severe defect in iron uptake and reduced ability to use the C. diphtheriae siderophore as an iron source. Site-directed mutations in irp6A, a gene previously reported to be associated with siderophore transport, had no effect on iron uptake or the utilization of the C. diphtheriae siderophore as an iron source. Transcriptional analysis demonstrated that expression of ciuA and ciuE is DtxR and iron regulated, and DNase I protection experiments confirmed the presence of DtxR binding sites upstream from each of these genes. Thus, this iron- and DtxR-regulated gene cluster is involved in the synthesis and transport of the C. diphtheriae siderophore.
One-step hydrothermal synthesis of ordered mesostructured carbonaceous monoliths with hierarchical porosities (2008)

Hierarchical carbonaceous monoliths with ordered 2-D hexagonal mesostructures have been successfully synthesized by using phenolic resols as precursors and mixed triblock copolymers as templates via a one-step hydrothermal approach.
Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed in vitro. (1988)

A recombinant plasmid was constructed with six synthetic DNA oligomers such that the DNA sequence corresponding to yeast tRNA(Phe) is flanked by a T7 promoter and a BstNI restriction site. Runoff transcription of the BstNI-digested plasmid with T7 RNA polymerase gives an unmodified tRNA of the expected sequence having correct 5' and 3' termini. This tRNA(Phe) transcript can be specifically aminoacylated by yeast phenylalanyl-tRNA synthetase and has a Km only 4-fold higher than that of the native yeast tRNA(Phe). The Km is independent of Mg2+ concentration, whereas the Vmax is very dependent on Mg2+ concentration. Comparison of the melting profiles of the native and the unmodified tRNA(Phe) at different Mg2+ concentrations suggests that the unmodified tRNA(Phe) has a less stable tertiary structure. Using one additional DNA oligomer, a mutant plasmid was constructed having a guanosine to thymidine change at position 20 in the tRNA gene. A decrease in Vmax/Km by a factor of 14 for aminoacylation of the mutant tRNA(Phe) transcript is observed.
Survival after the onset of congestive heart failure in Framingham Heart Study subjects. (1993)

CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.
Small‐Molecule PROTACS: New Approaches to Protein Degradation (2016)

The current inhibitor-based approach to therapeutics has inherent limitations owing to its occupancy-based model: 1) there is a need to maintain high systemic exposure to ensure sufficient in vivo inhibition, 2) high in vivo concentrations bring potential for off-target side effects, and 3) there is a need to bind to an active site, thus limiting the drug target space. As an alternative, induced protein degradation lacks these limitations. Based on an event-driven model, this approach offers a novel catalytic mechanism to irreversibly inhibit protein function by targeting protein destruction through recruitment to the cellular quality control machinery. Prior protein degrading strategies have lacked therapeutic potential. However, recent reports of small-molecule-based proteolysis-targeting chimeras (PROTACs) have demonstrated that this technology can effectively decrease the cellular levels of several protein classes.
A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules. (1990)

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states.