gebhart/patrepeval huggingface dataset:
Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue (2001)

Oral administration of beraprost may result in long lasting clinical and haemodynamic improvements in patients with severe pulmonary hypertension.
The secreted oligomeric form of α‐synuclein affects multiple steps of membrane trafficking (2013)

α-Synuclein (α-syn) can be secreted from neurons into the extracellular space, affecting the homeostasis of neighboring cells, but the pathophysiology of secreted α-syn remains largely unknown. We found that when exogenously applied to COS-7 cells, α-syn secreted from differentiated SH-SY5Y cells was taken up by dynamin-dependent endocytosis. Upon internalization, α-syn significantly increased the rate of transferrin receptor (TfR) internalization and recycling, and subsequently the surface levels of TfR. The effects are attributable to the oligomeric form, but not monomeric or fibrillar form, of extracellular α-syn. Together, multiple alterations in membrane trafficking by secreted oligomeric α-syn may contribute to the early stages of pathogenesis in Parkinson's disease.
Using Geographical Information Systems to Evaluate Decentralized Management of Municipal Food Waste (1997)

The implementation of decentralized waste management plans is stymied by an inability to communicate the costs and benefits of these plans in the decision making arena. The use of Geographical Information Systems (GIS) is vital toward carrying out feasibility tests, life-cycle assessments, and in presenting the results thereof. A preliminary GIS-based analysis was done for a decentralized in-vessel composting scheme for Bangkapi Ward in Bangkok, Thailand. The use of GIS in the introduction of decentralized waste management is discussed in general.
Selective area growth of InP through narrow openings by MOCVD and its application to InP HBT (2003)

Selective growth behavior of InP through narrow openings (<2 /spl mu/m) by metal-organic chemical vapor deposition (MOCVD) was investigated. The lateral overgrowth was observed to be significantly affected by both the opening width and orientation. The lateral overgrowth showed a 'diffraction-like' behavior, with the lateral overgrowth length increasing with decreasing opening width. The application of InP lateral overgrowth to InP/InGaAs heterojunction bipolar transistor (HBT) is proposed and the device behaviors of the HBT prototypes with the extrinsic base laterally overgrown on buried SiO/sub 2/ are demonstrated.
Residue Met156 Contributes to the Labile Enzyme Conformation of Coagulation Factor VIIa (2001)

Serine protease activation is typically controlled by proteolytic cleavage of the scissile bond, resulting in spontaneous formation of the activating Ile(16)-Asp(194) salt bridge. The initiating coagulation protease factor VIIa (VIIa) differs by remaining in a zymogen-like conformation that confers the control of catalytic activity to the obligatory cofactor and receptor tissue factor (TF). This study demonstrates that the unusual hydrophobic Met(156) residue contributes to the propensity of the VIIa protease domain to remain in a zymogen-like conformation. Mutation of Met(156) to Gln, which is found in the same position of the highly homologous factor IX, had no influence on the amidolytic and proteolytic activity of TF-bound VIIa. Furthermore, the mutation did not appreciably stabilize the labile Ile(16)-Asp(194) salt bridge in the absence of cofactor. VIIa(Gln156) had increased affinity for TF, consistent with a long range conformational effect that stabilized the cofactor binding site in the VIIa protease domain. Notably, in the absence of cofactor, amidolytic and proteolytic function of VIIa(Gln156) were enhanced 3- and 9-fold, respectively, compared with wild-type VIIa. The mutation thus selectively influenced the catalytic activity of free VIIa, identifying the Met(156) residue position as a determinant for the zymogen-like properties of free VIIa.
Amino‐acid‐sequence determination and biological activity of tessulin, a naturally occurring trypsin‐chymotrypsin inhibitor isolated from the leech Theromyzon tessulatum (1998)

We purified a new trypsin-chymotrypsin inhibitor, designated tessulin, from the rhynchobdellid leech Theromyzon tessulatum. This 9-kDa peptide was purified to apparent homogeneity by gel-permeation and anion-exchange chromatographies followed by reverse-phase HPLC. The structure of tessulin was determined by reduction, S-beta-pyridylethylation, trypsin digestion, automated Edman degradation and matrix-assisted laser desorption mass spectrometry (m/z 8985 Da). The 81-amino-acid peptide possesses 16 cysteines and exhibits a 16% sequence similarity with antistasin-type inhibitors. Tessulin inhibits trypsin (Ki 1 pM) and chymotrypsin (Ki 150 pM) and exhibits no activity with thrombin, factor Xa, cathepsin G and elastase. This is the first trypsin-chymotrypsin inhibitor isolated from leeches that does not inhibit elastase or cathepsin G, except for cytin and therin. Furthermore, tessulin, in conjunction with other serine-protease inhibitors isolated from Theromyzon (therin, theromin), significantly diminishes the level of human granulocyte and monocyte activation induced by lipopolysaccharides (10 microg). The combined level of inhibition is higher than that of aprotinin, another serine-protease inhibitor used biomedically. Thus, tessulin may be clinically significant in reducing inflammatory events.
Voltage- and cold-dependent gating of single TRPM8 ion channels (2011)

Transient receptor potential (TRP) channels play critical roles in cell signaling by coupling various environmental factors to changes in membrane potential that modulate calcium influx. TRP channels are typically activated in a polymodal manner, thus integrating multiple stimuli. Although much progress has been made, the underlying mechanisms of TRP channel activation are largely unknown. The TRPM8 cation channel has been extensively investigated as a major neuronal cold sensor but is also activated by voltage, calcium store depletion, and some lipids as well as by compounds that produce cooling sensations, such as menthol or icilin. Several models of TRPM8 activation have been proposed to explain the interaction between these diverse stimuli. However, a kinetic scheme is not yet available that can describe the detailed single-channel kinetics to gain further insight into the underlying gating mechanism. To work toward this goal, we investigated voltage-dependent single-channel gating in cell-attached patches at two different temperatures (20 and 30 °C) using HEK293 cells stably expressing TRPM8. Both membrane depolarization and cooling increased channel open probability (P(o)) mainly by decreasing the duration of closed intervals, with a smaller increase in the duration of open intervals. Maximum likelihood analysis of dwell times at both temperatures indicated gating in a minimum of five closed and two open states, and global fitting over a wide range of voltages identified a seven-state model that described the voltage dependence of P(o), the single-channel kinetics, and the response of whole-cell currents to voltage ramps and steps. The major action of depolarization and cooling was to accelerate forward transitions between the same two sets of adjacent closed states. The seven-state model provides a general mechanism to account for TRPM8 activation by membrane depolarization at two temperatures and can serve as a starting point for further investigations of multimodal TRP activation.
Phospholipid-Stabilized Au−Nanoparticles (2005)

This communication outlines a simple two-step approach of modification of 1 nm diameter Au nanoparticles using an aqueous solution of (1,2-dipalmitoyl-sn-glycero-3-phosphothio-ethanol) phospholipid (PL). Transmission electron microscopy as well as particle size analysis show that, as a result of PL reactions with Au particles, the initial Au nanoparticle size increases to 5 nm. Considering the size of the PL and their ability to form liposomes, 5 nm diameter spheres indicate that the PL bilayer was attached to the surface of Au particles and the PL-Au interactions are facilitated by the presence of thiol functionality. The change of surface electronic properties of PL-stabilized Au particles is manifested by the disappearance of the 217 and 290 nm absorbances due to 5d-6sp transitions in Au, which is likely attributed to the presence of S-H functionalities which increase the free electron density of the particle. As a consequence, two surface plasmons resulting from a collective oscillation of electrons in response to UV excitation disappear.
Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides (2008)

In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.
Simplified-antiresonant reflecting optical waveguide-type vertical-cavity surface-emitting lasers (2000)

A two-step metalorganic chemical vapor deposition growth process is used to fabricate antiguided vertical-cavity surface-emitting lasers (VCSELs) incorporating a simplified-antiresonant reflecting optical waveguide (S-ARROW) design. Preliminary results show single-mode cw operation up to 1 mW output power from a 12 μm-diam (λ=930 nm) S-ARROW VCSEL with a large lateral index step (Δn=0.1). Modal discrimination in the S-ARROW-VCSEL is calculated using a fiber-mode approximation and device optimization for high-single-mode powers is discussed.
The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia, infarction, and reperfusion (1988)

The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.
It's not what you know, but who you know (2009)

Backup authentication mechanisms help users who have forgotten their passwords regain access to their accounts-or at least try. Today's systems fall short in meeting both security and reliability requirements. We designed, built, and tested a new backup authentication system that employs a social-authentication mechanism. The system employs trustees previously appointed by the account holder to verify the account holder's identity. We ran three experiments to determine whether the system could (1) reliably authenticate account holders, (2) resist email attacks that target trustees by impersonating account holders, and (3) resist phone-based attacks from individuals close to account holders. Results were encouraging: seventeen of the nineteen participants who made the effort to call trustees authenticated successfully. However, we also found that users must be reminded of who their trustees are. While email-based attacks were largely unsuccessful, stronger countermeasures will be required to counter highly-personalized phone-based attacks.
Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro (2000)

In all, 143 human embryos obtained 3 days (day 3) after insemination or intracytoplasmic sperm injection (ICSI) were biopsied and a single nucleated cell removed for identification of aneuploidy by fluorescent in-situ hybridization (FISH) for chromosomes X, Y, 13, 16, 18 and 21. Fifty-one per cent of embryos were aneuploid and significantly more aneuploid embryos blocked in further development to morulae and blastocysts than euploid embryos (59 versus 34%; P < 0.001). Chromosomal analysis of the generated blastocysts revealed 40% were aneuploid (16 of 40 generated blastocysts). Re-examination of cells by FISH for the same chromosome probes of the inner cell mass (ICM) of expanded and hatching blastocysts derived from the aneuploid embryos revealed a high incidence of mosaicism of ICM cell lineages that were usually predictable from observations of day 3 single-cell biopsies. These data would not support the hypothesis of a preferential allocation of euploid cells to the ICM and aneuploid cells to the trophectoderm. A high concordance between day 3 aneuploidy diagnosis and ICM cell lineages was observed with trisomies (97%), and multiple complex chromosome numerical abnormalities (100%). A reduced concordance was observed with monosomies (65%) and haploidy (18%). Concomitantly, the proportion of ICM cell lineages was increased in blastocysts whose chromosomal condition was diagnosed as haploid (21%) or with complex numerical abnormalities (50%).
Finals Full House (1990)

Margaret Lane deseribes the game she designed that can help in nurse education
Expression of S100A6 in Cardiac Myocytes Limits Apoptosis Induced by Tumor Necrosis Factor-α (2008)

S100A6 is induced in myocardium post-infarction in vivo and in response to growth factors and inflammatory cytokines in vitro. Forced expression of S100A6 in cardiomyocytes inhibits regulation of cardiac specific gene expression in response to trophic stimulation. To define regulation and function of S100A6, we characterized the human S100A6 promoter and mapped upstream regulatory elements in rat neonatal cardiac myocytes, fibroblasts, and vascular smooth muscle cells and defined a functional role for S100A6 in tumor necrosis factor-alpha-induced myocyte apoptosis. The functional S100A6 promoter was localized to region -167/+134 containing 167 upstream base pairs. The S100A6 promoter is regulated by positive (-361/-167 and -588/-361) and negative (-1371/-1194) elements. Tumor necrosis factor-alpha induced the maximal S100A6 promoter and transcription factor NF-kappaB (p65 subunit). Electrophoretic mobility shift showed that tumor necrosis factor-alpha induced p65 binding to a potential NF-kappaB-binding site at -460/-451. Chromatin immunoprecipitation analysis revealed p65 is recruited to the S100A6 promoter upon tumor necrosis factor-alpha stimulation. The NF-kappaB inhibitor caffeic acid phenethyl ester and mutation of the NF-kappaB-binding site inhibited S100A6 promoter activation by tumor necrosis factor-alpha. Tumor necrosis factor-alpha induced cardiac myocyte apoptosis. Specific inhibition of S100A6 using a small interfering RNA directed against S100A6 potentiated tumor necrosis factor-alpha-induced myocyte apoptosis, whereas overexpression of S100A6 by gene transfer prevented tumor necrosis factor-alpha-induced myocyte apoptosis by interfering with p53 phosphorylation. These results demonstrate that S100A6 is induced by tumor necrosis factor-alpha via an NF-kappaB-dependent mechanism, serving a role in homeostasis to limit tumor necrosis factor-alpha-induced apoptosis by regulating p53 phosphorylation.
HER-2/neu oncogene amplification and chromosome 17 aneusomy in endometrial carcinoma: correlation with oncoprotein expression and conventional pathological parameters. (2003)

The objective of the present study was to evaluate the correlation between HER-2 gene amplification and HER-2 protein overexpression in endometrial carcinoma using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We also analyzed chromosome 17 aneusomy and the association between these biological parameters and conventional clinicopathological variables. FISH analysis was performed on 73 selected paraffin-embedded sections from endometrial carcinomas which previously had HER-2 status determined immunohistochemically using monoclonal antibodies (MoAb) 300G9 and CB11. Using a ratio of more than two oncogene signals/centromere to indicate amplification, a total of 42 out of the 73 endometrial tumors included in this study resulted positive by FISH where as protein overexpression was identified in 29 out of 73 with a concordance rate of 74.3%. However, when the mean signals/centromere per nucleus increased (ratio > 4 < or = 5) a higher concordance between the two assays was seen (p = 0.007). In addition, HER-2 amplification was significantly correlated with tumor stage (p = 0.021) and myometrial invasion (p = 0.010), whereas chromosome 17 polisomy showed a positive correlation only with myometrial invasion (p = 0.004) No significant correlation was found between HER-2 gene amplification, chromosome 17 aneusomy and patient outcome. Nevertheless, the probability of a 5 year overall survival decreased from 70% to 43%, respectively, for ratio > 2 < or = 4 and ratio > 4 < or = 5 when we grouped the amplified cases on the basis of HER-2:CEP17 ratio. In conclusion, molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer.
Induction of myogenic differentiation by an expression vector encoding the DNA methyltransferase cDNA sequence in the antisense orientation. (1992)

To test the hypothesis that DNA methylation controls the state of differentiation of a mammalian cell, we transfected the stable mesenchymal line 10T1/2 with an expression vector encoding sequences from the DNA methyltransferase (DNA MeTase) cDNA in the antisense orientation. 10T1/2 cells transfected with the antisense construct (pZ alpha M), but not with the vector alone, exhibit morphological changes, convert into multinucleated tubular cells, and express the skeletal myosin heavy chain protein. The conversion to myogenic phenotype is a late event and is dependent on the number of replication events that the cell has undergone, suggesting that induction of myogenesis is a multistep process. Demethylation of sequences that are not involved in the myogenic process is detected at early passages, while demethylation and expression of the MyoD gene is a late event. This report establishes for the first time that demethylation is a very early event in commitment to myogenic differentiation, while demethylation and expression of MyoD is a late event. We suggest that other genes serve as the initial targets for demethylation and commitment of mesenchymal cells to myogenesis. The cell lines described in this report can serve as an important system for identifying these genes.
N-Pantoyl-(substituted)amines, Pantothenic Acid Analogues (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-Pantoyl-(substituted)amines, Pantothenic Acid AnaloguesJohn D. Fissekis, Charles G. Skinner, and William ShiveCite this: J. Med. Chem. 1959, 2, 1, 47–56Publication Date (Print):February 1, 1960Publication History Published online1 May 2002Published inissue 1 February 1960https://pubs.acs.org/doi/10.1021/jm50008a004https://doi.org/10.1021/jm50008a004research-articleACS PublicationsRequest reuse permissionsArticle Views71Altmetric-Citations6LEARN 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 options Get e-Alerts
Synthesis and Characterization of Dextran−Peptide−Methotrexate Conjugates for Tumor Targeting via Mediation by Matrix Metalloproteinase II and Matrix Metalloproteinase IX (2004)

We designed and synthesized new dextran-peptide-methotrexate conjugates for tumor-targeted delivery of chemotherapeutics via the mediation of matrix metalloproteinase II (MMP-2) and matrix metalloproteinase IX (MMP-9), both being widely known tumor-associated enzymes. A robust and flexible synthesis procedure and process monitoring chromatography assays were developed. The linker chemistry and the backbone charge were optimized to allow high sensitivity of the conjugates toward the targeted enzymes. The optimal conjugate carries Pro-Val-Gly-Leu-Ile-Gly as the peptide linker, and the charge on the dextran backbone is fully neutralized. In the presence of the targeted enzymes, the peptide was cleaved and peptidyl methotrexate was released, with a kcat/Km value of 1.21 x 10(5) M(-1) s(-1) for MMP-2 and 3.60 x 10(3) M(-1) s(-1) for MMP-9, respectively. Satisfactory stability of the new conjugates was demonstrated in serum containing conditions, suggesting the conjugates can remain intact in systemic circulation. These findings supported the tumor targeting capability of the new conjugates and warranted further investigation with in vivo study.
Clinical Application of Sonographic Elasticity Imaging for Aging of Deep Venous Thrombosis (2003)

In this preliminary work, the 2 thrombi appeared very different, and these results suggest that elasticity imaging may be able to age deep venous thrombosis.
Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8+ T Cell Exhaustion (2009)

The failure of CD8(+) T cells to respond to chronic infection has been termed "exhaustion" and describes the condition in which CD8(+) T cells exhibit reduced differentiation, proliferation, and effector function. CD8(+) T cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (LCMV). Although LCMV-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and Ag-driven exhaustion. We have created a system of chronic Ag stimulation using murine influenza A virus that leads to exhaustion and functional disability of virus-specific CD8(+) T cells, in the absence of high viral titers, sustained proinflammatory cytokine production and lymphocyte infection. Our findings show that Ag alone is sufficient to drive CD8(+) T cell impairment, that Ag-driven loss of virus-specific CD8(+) T cells is TRAIL mediated, and that removal of Ag reverses exhaustion. Although programmed death 1 was up-regulated on chronic Ag-stimulated CD8(+) T cells, it played no role in the exhaustion. These findings provide a novel insight into the mechanisms that control functional exhaustion of CD8(+) T cells in chronic infection.