gebhart/patrepeval huggingface dataset:
Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by negative charge in the R domain. (1993)

Phosphorylation by cAMP-dependent protein kinase (PKA) regulates the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. We previously showed that in vivo PKA phosphorylated 4 serines (Ser-660, Ser-737, Ser-795, and Ser-813) within the R domain. Here we show that a mutant CFTR lacking all 4 serines can still be phosphorylated by PKA to yield an activated Cl- channel, but channel open-state probability was substantially reduced. We also observed phosphorylation and Cl- channel activity in another mutant lacking all 8 consensus PKA serines in the R domain. We were unable to identify the residual phosphorylation sites by tryptic phosphopeptide mapping. These data suggest two possible interpretations: (a) additional, as yet unidentified, phosphorylation sites within CFTR may also open the channel, or (b) the 4 serines, previously identified as in vivo PKA phosphorylation sites, are the primary regulatory sites within CFTR, but in their absence, other sites can be phosphorylated to open the channel. The additional sites are likely located within the R domain: CFTR delta R-S660A, which lacks much of the R domain (residues 708-835) and replaces Ser-660 with an alanine, was no longer regulated by PKA. Substitution of aspartate for consensus PKA phosphorylation sites in the R domain mimicked the effect of phosphorylation. Mutants containing six or more serine-to-aspartate substitutions generated Cl- channels that opened without PKA phosphorylation. These results suggest that the R domain keeps the channel closed and that phosphorylation of the R domain or insertion of the negatively charged aspartate opens the channel, perhaps by electrostatic interactions.
Seeing Is Believing: Illuminating the Source ofIn VivoInterleukin-7 (2011)

Interleukin-7 (IL-7) is an essential cytokine for T cells. However, IL-7 is not produced by T cells themselves such that T cells are dependent on extrinsic IL-7. In fact, in the absence of IL-7, T cell development in the thymus as well as survival of naive T cells in the periphery is severely impaired. Furthermore, modulating IL-7 availability in vivo either by genetic means or other experimental approaches determines the size, composition and function of the T cell pool. Consequently, understanding IL-7 expression is critical for understanding T cell immunity. Until most recently, however, the spatiotemporal expression of in vivo IL-7 has remained obscured. Shortage of such information was partly due to scarce expression of IL-7 itself but mainly due to the lack of adequate reagents to monitor IL-7 expression in vivo. This situation dramatically changed with a recent rush of four independent studies that describe the generation and characterization of IL-7 reporter mice, all utilizing bacterial artificial chromosome transgene technology. The emerging consensus of these studies confirmed thymic stromal cells as the major producers of IL-7 but also identified IL-7 reporter activities in various peripheral tissues including skin, intestine and lymph nodes. Strikingly, developmental and environmental cues actively modulated IL-7 reporter activities in vivo suggesting that IL-7 regulation might be a new mechanism of shaping T cell development and homeostasis. Collectively, the availability of these new tools opens up new venues to assess unanswered questions in IL-7 biology in T cells and beyond.
Innovation in organ transplantation: A meeting report (2018)

This workshop targeted opportunities to stimulate transformative innovation in organ transplantation. Participants reached consensus regarding the following: (1) Mechanisms are needed to improve the coordination of policy and oversight activities, given overlapping responsibilities for transplantation and clinical investigation among federal agencies. Innovative clinical trials span traditional administrative boundaries and include stakeholders with diverse interests. Participants identified the need for a governmental interagency working group to coordinate nationwide transplant-related activities. (2) Improvements are required in clinical metrics for transplantation, with alignment of performance goals across transplantation organizations and any development of data requirements being consistent with those goals. Database coordination among clinical centers, organ procurement organizations, regulatory agencies, and payers would facilitate research and better inform policy. New data requirements should provide actionable insights into clinical performance. (3) Innovative research seen as potentially adversely affecting Program-Specific Reports may reduce centers' participation. Cutting-edge research requires mitigation of risk-aversive behaviors created by reporting of clinical outcomes data. Participants proposed a new review process in advance of implementation of clinical trials to guide "carve-outs" of transplant center outcomes data from Program-Specific Reports. Clinical transplantation will be advanced by the development of a shared and comprehensive research agenda to facilitate coordination of research and policy.
Contextual Visualization (2018)

Unseen information can lead to various "threats to validity" when analyzing complex datasets using visual tools, resulting in potentially biased findings. We enumerate sources of unseen information and argue that a new focus on contextual visualization methods is needed to inform users of these threats and to mitigate their effects.
Adaptive Fuzzy Systems (1991)

Fuzziness is multivaluedness. Truth, set membership, and subset containment take on degrees in [0, 1] instead of taking on only the limiting bivalent extremes in {0, 1}. The degrees in [0, 1] define fuzzy units, or fits. Statements are true to some degree. An element belongs to, or fits in, a fuzzy set to some degree. One fuzzy set contains another fuzzy set to some degree.
Single dose vaccine based on biodegradable polyanhydride microspheres can modulate immune response mechanism (2005)

This study focuses on the development of single dose vaccines based on biodegradable polyanhydride microspheres that have the unique capability to modulate the immune response mechanism. The polymer system employed consists of copolymers of 1,6-bis(p-carboxyphenoxy)hexane and sebacic acid. Two copolymer formulations that have been shown to provide extended release kinetics and protein stability were investigated. Using tetanus toxoid (TT) as a model antigen, in vivo studies in C3H/HeOuJ mice demonstrated that the encapsulation procedure preserves the immunogenicity of the TT. The polymer itself exhibited an adjuvant effect, enhancing the immune response to a small dose of TT. The microspheres provided a prolonged exposure to TT sufficient to induce both a primary and a secondary immune response (i.e., high antibody titers) with high-avidity antibody production, without requiring an additional administration. Antigen-specific proliferation 28 weeks after a single immunization indicated that immunization with the polyanhydride microspheres generated long-lived memory cells and plasma cells (antibody-secreting B cells) that generally do not occur without maturation signals from T helper cells. Furthermore, by altering the vaccine formulation, the overall strength of the T helper type 2 immune response was selectively diminished, resulting in a balanced immune response, without reducing the overall titer. This result is striking, considering free TT induces a T helper type 2 immune response, and has important implications for developing vaccines to intracellular pathogens. The ability to selectively tune the immune response without the administration of additional cytokines or noxious adjuvants is a unique feature of this delivery vehicle that may make it an excellent candidate for vaccine development.
Analysis ofCFH,TLR4, andAPOEPolymorphism in India Suggests the Tyr402His Variant ofCFHto be a Global Marker for Age-Related Macular Degeneration (2006)

The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance (2015)

Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8(+) T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors. Although Cish is commonly thought to block STAT5 activation, we found that the primary molecular basis of Cish suppression is through inhibition of TCR signaling. Cish physically interacts with the TCR intermediate PLC-γ1, targeting it for proteasomal degradation after TCR stimulation. These findings establish a novel targetable interaction that regulates the functional avidity of tumor-specific CD8(+) T cells and can be manipulated to improve adoptive cancer immunotherapy.
Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice infected with highly pathogenic influenza A H7N7 virus (2008)

Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded nucleic acid-analogue antisense agents that enter cells readily and can reduce gene expression by steric blocking of complementary RNA (cRNA) sequences. Here, we tested a panel of PPMO designed to target conserved sequences in the RNA genome segments encoding polymerase subunits of a highly pathogenic mouse-adapted influenza A virus (SC35M; H7N7). Three PPMO, targeting the translation start site region of PB1 or NP mRNA or the 3'-terminal region of NP viral RNA (vRNA), potently inhibited virus replication in MDCK cells. Primer extension assays showed that treatment with any of the effective PPMO led to markedly reduced levels of mRNA, cRNA and vRNA. Initially, the potential toxicity of a range of intranasally administered PPMO doses was evaluated, by measuring their effect on body weight of uninfected mice. Subsequently, a non-toxic dosing regimen was used to investigate the effect of various PPMO on SC35M infection in a mouse model. Mice administered intranasal treatment of PPMO targeting the PB1-AUG region or NP vRNA, at 3 mug per dose, given once 3 h before and once 2 days after intranasal infection with 10xLD(50) of SC35M, showed a 2 log(10) reduction of viral titre in the lungs and 50 % survival for the 16 day duration of the experiment, whereas the NP-AUG-targeted PPMO treatment resulted in 30 % survival of an otherwise lethal infection. These data suggest that PPMO provide a useful reagent to investigate influenza virus molecular biology and may constitute a therapeutic strategy against highly pathogenic influenza viruses.
Indirect 17O‐magnetic resonance imaging of cerebral blood flow in the rat (2003)

Proton T(1rho)-dispersion MRI is demonstrated for indirect, in vivo detection of (17)O in the brain. This technique, which may be readily implemented on any clinical MRI scanner, is applied towards high-resolution, quantitative mapping of cerebral blood flow (CBF) in the rat by monitoring the clearance of (17)O-enriched water. Strategies are derived and employed for 1) quantitation of absolute H(2) (17)O tracer concentration from a ratio of high- and low-frequency spin-locked T(1rho) images, and 2) mapping CBF without having to transform the T(1rho) signal to H(2) (17)O tracer concentration. Absolute regional blood flow was mapped in a single 3-mm brain slice at an in-plane resolution of 0.4 x 0.8 mm within a 5-min tracer washout time; these data are consistent with the less localized CBF measurements reported in the literature. T(1rho)-weighted imaging yields excellent signal-to-noise ratios, spatiotemporal resolution, and anatomical contrast for mapping CBF.
Enhancement of Wound Healing by Growth Factors (1989)

The early work on growth factors raised hopes of new insights into cancer. In addition, even before Cohen and Levi-Montalcini shared a Nobel prize in 1986 for their work on epidermal and nerve growth factors, it was clear that the effect of growth factors on wound healing would be studied. Rarely is cell replication as rapid as it is in wounds. Many poorly healing wounds appear to be failures of this process, and enhancement of the growth signal seems to be a logical therapy. It even seems possible that the pace of "normal" repair might be accelerated.Unfortunately, the conditions . . .
Type-Specific Antibodies to Herpes Simplex Virus Type 2 (HSV-2) Glycoprotein G in Pregnant Women, Infants Exposed to Maternal HSV-2 Infection at Delivery, and Infants with Neonatal Herpes (1988)

We used a murine monoclonal antibody to herpes simplex virus (HSV) type 2 (HSV-2) glycoprotein G (gG) to develop an enzyme immunoassay that detected HSV-2 type-specific antibodies in human sera. Antibodies to HSV-2 gG were detected in 98 (96%) of 102 sera from pregnant women with culture-proved HSV-2 infection. Sixty-five percent of the women had serological evidence of past HSV-2 infection by the Rawls index, based on titers of neutralizing antibody to HSV type 1 and HSV-2. Thirty (88%) of 34 infants exposed to maternal HSV infection at delivery had antibodies to HSV-2 gG and remained well. One infant exposed to primary maternal HSV-2 infection lacked antibodies to HSV-2 gG and developed neonatal HSV-2 infection. The mean +/- SD optical density by HSV-2 gG enzyme-linked immunosorbent assay for sera obtained from 17 infants within one week after onset of neonatal HSV-2 infection was 0.25 +/- 0.12, compared with 1.15 +/- 0.34 in cord blood sera from exposed infants who did not develop symptoms (P less than .0001 by t test).
Thrombogenicity of Factor IX Concentrates:in vitro and in vivo (Rabbit) Studies (1978)

The reproducibility and correlation between the NAPTT, TGt(50) in (vitro) tests and the Wessler (rabbit) stasis thrombus (in vivo) model have been studied using 10 different factor IX concentrates. The TGt(50) test was more reproducible than the NAPTT and the overall reproducibility of the rabbit model was poor. The low reproducibility of the rabbit model appeared to be largely confined to those factor IX concentrates which showed a poor correlation between the NAPTT and TGt(50) results. The TGt(50) test emerged as the in vitro test which correlated most closely with the in vivo (rabbit) test. It is concluded that the NAPTT and TGt(50) test are measuring different thrombogenic moieties in factor IX concentrates and that further studies are required to elucidate this phenomenon.
SOLUBILITY. (1916)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSOLUBILITY.Joel H. HildebrandCite this: J. Am. Chem. Soc. 1916, 38, 8, 1452–1473Publication Date (Print):August 1, 1916Publication History Published online1 May 2002Published inissue 1 August 1916https://pubs.acs.org/doi/10.1021/ja02265a002https://doi.org/10.1021/ja02265a002research-articleACS PublicationsRequest reuse permissionsArticle Views2883Altmetric-Citations128LEARN 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
An overview of cooperative communications (2012)

Cooperative communications have recently been migrated to one of state-of-the-art features of 3GPP LTE-Advanced (LTE-A). Cooperative communications fundamentally change the abstraction of a wireless link and offer significant potential advantages for wireless communication networks. This article visits cooperative techniques, such as relay, distributed antennas systems (DAS), multicell coordination, Group Cell, Coordinated Multiple Point transmission and reception (CoMP), those turn the traditional cellular system into a cooperative system. In particular, we propose several joint processing policies to demonstrate the Group Cell (CoMP) concept. Results of a trial network implementation and a performance evaluation of the concept are also reported.
Genetic Factors Influencing Drug-Induced Liver Injury: Do They Have a Role in Prevention and Diagnosis? (2017)

With the exception of abacavir for HIV therapy, no other prospective genetic screening tests have met the threshold for clinical application. This is largely because DILI incidence is too low to warrant the cost and effort associated with testing. Perhaps, with the development of personalised medicine, a panel of genes for disease susceptibility, drug efficacy and adverse reactions could be tested once off. This would change the cost-effectiveness paradigm, personalise healthcare and reduce DILI risk by avoiding medications in patients with specific HLA alleles.
Human Multipotent Adipose-Derived Stem Cells Differentiate into Functional Brown Adipocytes (2009)

In contrast to the earlier contention, adult humans have been shown recently to possess active brown adipose tissue with a potential of being of metabolic significance. Up to now, brown fat precursor cells have not been available for human studies. We have shown previously that human multipotent adipose-derived stem (hMADS) cells exhibit a normal karyotype and high self-renewal ability; they are known to differentiate into cells that exhibit the key properties of human white adipocytes, that is, uncoupling protein two expression, insulin-stimulated glucose uptake, lipolysis in response to beta-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one (UCP1) and CIDEA mRNA. This switch is accompanied by an increase in oxygen consumption and uncoupling. The expression of UCP1 protein is associated to stimulation of respiration by beta-AR agonists, including beta3-AR agonist. Thus, hMADS cells represent an invaluable cell model to screen for drugs stimulating the formation and/or the uncoupling capacity of human brown adipocytes that could help to dissipate excess caloric intake of individuals.
Growth inhibition by transforming growth factor beta (TGF-beta) type I is restored in TGF-beta-resistant hepatoma cells after expression of TGF-beta receptor type II cDNA. (1993)

The growth of human hepatoma Hep 3B cells is potently inhibited by TGF-beta 1 (ID50 = 0.2 ng/ml, 8 pM). A mutant cell line was derived that was not inhibited in growth by TGF-beta 1 at 5 ng/ml (200 pM) and that lacked TGF-beta receptor type II (TGF-beta RII) gene. Transfection of the cloned cDNA for human TGF-beta RII to this mutant cell line restored receptor expression as well as the inhibition in growth by TGF-beta 1. In both wild-type and mutant cells stably transfected with TGF-beta RII cDNA, TGF-beta RII coimmunoprecipitated with TGF-beta receptor type I in the presence of ligand. These experiments provide direct evidence for the role of TGF-beta RII in the inhibitory effect of TGF-beta on growth and suggest that TGF-beta RII acts by means of a heteromeric surface complex with TGF-beta receptor type I.
Disintegrants in Tableting (2008)

Since man first began to treat illnesses using oral administration of herbs and otheravailable materials, there have been a problems of how to take the medicines becausemany drugs, whether natural or synthetic, are bitter. Many of the early developments informulations were designed with taste masking and convenience in mind. We formulateto convert bulk drugs into medicines that the patient can use. In the case of oraladministration, both tablets and capsules are convenient for patients as they allow self-medication and can be easily designed to mask any unpleasant taste. Besides tablets andcapsules, there are also powders, usually taken dispersed in water. But tablets and cap-sules are comparatively recent developments. In the past drugs were formulated aspowders, cachets (made of rice starch), and pillules (pills). Tablets and capsules are usedtoday because, in many respects, they are easier and quicker to manufacture, and lendthemselves to more automated methods. Tablets in particular can be manufactured at veryhigh speed on today’s modern equipment.
Production and Implantation of Renal Extracellular Matrix Scaffolds From Porcine Kidneys as a Platform for Renal Bioengineering Investigations (2012)

Our investigations show that pig kidneys can be successfully decellularized to produce renal ECM scaffolds. These scaffolds maintain their basic components, are biocompatible, and show intact, though thrombosed, vasculature.
Analysis of viral infections by in situ hybridization. (1986)

In situ hybridization provides a versatile means of analysis of the life cycles of viruses in single cells. This kind of analysis in "real life" situations has provided considerable insight into the spread of viruses, mechanisms of tissue damage by viruses, and virus-host cell interactions in chronic diseases. In this article I describe refinements in technology underlining these advances, especially developments that have made the technique such a sensitive and quantitative one. I also describe a method for combined macroscopic and microscopic in situ hybridization, new assays for the simultaneous detection of genes and gene products in a single cell, and a double-label in situ hybridization technique. These methods have already proved useful in analyzing the molecular ecology of viral infections, and should find wide application to problems of genetic regulation in many other systems.
Rapid endo‐lysosomal escape of poly(DL‐lactide‐ co glycolide) nanoparticles: implications for drug and gene delivery (2002)

The endo-lysosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially the payloads that are susceptible to lysosomal degradation. Current vectors that enable the endo-lysosomal escape of macromolecules such as DNA are limited by their toxicity and by their ability to carry only limited classes of therapeutic agents. In this paper, we report the rapid (<10 min) endo-lysosomal escape of biodegradable nanoparticles (NPs) formulated from the copolymers of poly(DL-lactide-co-glycolide) (PLGA). The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endo-lysosomal compartment, which causes the NPs to interact with the endo-lysosomal membrane and escape into the cytosol. PLGA NPs are able to deliver a variety of therapeutic agents, including macromolecules such as DNA and low molecular weight drugs such as dexamethasone, intracellularly at a slow rate, which results in a sustained therapeutic effect. PLGA has a number of advantages over other polymers used in drug and gene delivery including biodegradability, biocompatibility, and approval for human use granted by the U.S. Food and Drug Administration. Hence PLGA is well suited for sustained intracellular delivery of macromolecules.