gebhart/patrepeval huggingface dataset:
A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy (1995)

The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous. The mean survival times of animals in the control and placebo groups were statistically equivalent (21 +/- 4 days vs 18 +/- 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 +/- 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.
Preassembly of Membrane-Active Peptides Is an Important Factor in Their Selectivity toward Target Cells (2002)

Membrane-active peptides comprise a large group of toxins used in the defense and offense systems of all organisms including plants and humans. They act on diverse targets including microorganisms and mammalian cells, but the factors that determine their target cell selectivity are not yet clear. Here, we tested the role of peptide length and preassembly on the ability of diastereomeric cationic antimicrobial peptides to discriminate among bacteria, erythrocytes, and fungal cells, by using peptides with variable lengths (13, 16, and 19 amino acids long) and their covalently linked pentameric bundles. All the bundles expressed similar potent antifungal activity (minimal inhibitory concentration of 0.2-0.3 microM) and high antimicrobial activity. Hemolytic activity was also observed at concentrations higher than those required for antifungal activity. In contrast, all the monomers showed length-dependent antimicrobial activity, were less active toward bacteria and fungi, and were devoid of hemolytic activity. BIAcore biosensor experiments revealed a approximately 300-fold increase in peptide-membrane binding affinity between the 13- and 19-residue monomers toward zwitterionic (egg phosphatidylcholine (PC)/egg spingomyelin (SM)/cholesterol) vesicles. All the monomeric peptides display a similar high affinity to negatively charged (E. coli phosphatidylethanolamine (PE)/egg phosphatidylglycerol (PG)) vesicles regardless of their length. In contrast, irrespective of the size of the monomeric subunit, all the bundles bind irreversibly and strongly disrupt both PC/SM/cholesterol and PE/PG membranes. Attenuated total reflectance Fourier-transform infrared spectroscopy revealed that peptide assembly also affects structure as observed by an increased alpha-helical and beta-sheet content in membranes and enhances acyl chain disruption of PC/cholesterol. The correlation between the antibacterial activity and ability to depolarize the transmembrane potential of E. coli spheroplasts, as well as the ability to induce calcein release from vesicles, suggests that the bacterial membrane is their target. The data demonstrate that preassembly of cationic diastereomeric antimicrobial peptides is an essential factor in their membrane targeting.
Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor ? monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis (1998)

Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.
Mechanism of Virulence Attenuation of Glycosaminoglycan-Binding Variants of Japanese Encephalitis Virus and Murray Valley Encephalitis Virus (2002)

The in vivo mechanism for virulence attenuation of laboratory-derived variants of two flaviviruses in the Japanese encephalitis virus (JEV) serocomplex is described. Host cell adaptation of JEV and Murray Valley encephalitis virus (MVE) by serial passage in adenocarcinoma cells selected for variants characterized by (i) a small plaque phenotype, (ii) increased affinity to heparin-Sepharose, (iii) enhanced susceptibility to inhibition of infectivity by heparin, and (iv) loss of neuroinvasiveness in a mouse model for flaviviral encephalitis. We previously suggested that virulence attenuation of the host cell-adapted variants of MVE is a consequence of their increased dependence on cell surface glycosaminoglycans (GAGs) for attachment and entry (E. Lee and M. Lobigs, J. Virol. 74:8867-8875, 2000). In support of this proposition, we find that GAG-binding variants of JEV and MVE were rapidly removed from the bloodstream and failed to spread from extraneural sites of replication into the brain. Thus, the enhanced affinity of the attenuated variants for GAGs ubiquitously present on cells and extracellular matrices most likely prevented viremia of sufficient magnitude and/or duration required for virus entry into the brain parenchyma. This mechanism may also account, in part, for the attenuation of the JEV SA14-14-2 vaccine, given the sensitivity of the virus to heparin inhibition. A pronounced loss of the capacity of the GAG-binding variants to produce disease was also noted in mice defective in the alpha/beta interferon response, a mouse strain shown here to be highly susceptible to infection with JEV serocomplex flaviviruses. Despite the close genetic relatedness of JEV and MVE, the variants selected for the two viruses were altered at different residues in the envelope (E) protein, viz., Glu(306) and Asp(390) for JEV and MVE, respectively. In both cases the substitutions gave the protein an increased net positive charge. The close spatial proximity of amino acids 306 and 390 in the predicted E protein structure strongly suggests that the two residues define a receptor-binding domain involved in virus attachment to sulfated proteoglycans.
Rhodium-Catalyzed Enantioselective Diboration of Simple Alkenes (2003)

Enantioselective catalytic reactions that operate directly on inexpensive unactivated alkenes are extraordinarily useful for the preparation of chiral organic building blocks and new materials. While a number of such processes have been developed, our ability to meet the intensifying demand for inexpensive stereochemically complex materials will require a significant expansion of practical catalytic asymmetric reaction methodology. In this regard, the rhodium-catalyzed enantioselective diboration reaction has been developed in order to address a number of extant problems in catalytic alkene transformation simultaneously. This process provides an enantiomerically enriched reactive dimetalated intermediate which can be converted to a variety of difunctional reaction products.
Regulatory T Cell Suppression Is Potentiated by Target T Cells in a Cell Contact, IL-35- and IL-10-Dependent Manner (2009)

Regulatory T cells (T(reg)) are believed to suppress conventional T cell (T(conv)) proliferation in vitro in a contact-dependent, cytokine-independent manner, based in part on experiments in which T(reg) and T(conv) are separated by a permeable membrane. We show that the production of IL-35, a novel inhibitory cytokine expressed by natural T(reg), increases substantially following contact with T(conv). Surprisingly, T(reg) were able to mediate potent suppression of T(conv) across a permeable membrane when placed in direct contact with T(conv) in the upper chamber of a Transwell plate. Suppression was IL-35 and IL-10 dependent, and T(conv) activation was required for maximal potentiation of T(reg) suppression. These data suggest that it is the induction of suppression, rather than the function of T(reg) that is obligatorily contact dependent.
The action of trypsin on polylysine (1953)

1. Glycerol is oxidized and assimilated by washed suspensions of Mycobacterium 8megmati8 and Mycobacterium butyricum.
Improved Glucose Tolerance in Zucker Fatty Rats by Oral Administration of the Dipeptidyl Peptidase IV Inhibitor Isoleucine Thiazolidide (1998)

The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1 act on the pancreas to potentiate glucose-induced insulin secretion (enteroinsular axis). These hormones (incretins) are rapidly hydrolyzed by the circulating enzyme dipeptidyl peptidase IV (DP IV) into biologically inactive NH2-terminally truncated fragments. This study describes the effect of inhibiting endogenous DP IV with a specific DP IV inhibitor, isoleucine thiazolidide (Ile-thiazolidide), on glucose tolerance and insulin secretion in the obese Zucker rat. In initial studies, the specificity of Ile-thiazolidide as an inhibitor of incretin degradation was determined using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. These results showed that inhibiting DP IV activity with Ile-thiazolidide blocked the formation of NH2-terminally truncated GIP and GLP-1. Oral administration of Ile-thiazolidide resulted in rapid inhibition of circulating DP IV levels by 65% in obese and lean Zucker rats. Suppression of DP IV levels enhanced insulin secretion in both phenotypes with the most dramatic effect occurring in obese animals (150% increase in integrated insulin response vs. 27% increase in lean animals). Ile-thiazolidide treatment improved glucose tolerance in both phenotypes and restored glucose tolerance to near-normal levels in obese animals. This was attributed to the glucose-lowering actions of increasing the circulating half-lives of the endogenously released incretins GIP and, particularly, GLP-1. This study suggests that drug manipulation of plasma incretin activity by inhibiting the enzyme DP IV is a valid therapeutic approach for lowering glucose levels in NIDDM and other disorders involving glucose intolerance.
Absorption and translocation of glyphosate with conventional and organosilicone adjuvants (2008)

This study was conducted to determine the effects of three organosilicone‐based and six conventional organic adjuvants on the absorption and translocation of 14 C‐glyphosate in guineagrass and redroot pigweed. The organosilicone adjuvants produced rapid absorption of the 14 C‐glyphosate into the redroot pigweed leaves, reaching maximum absorption within 0.5–1.0 h after application. The conventional adjuvants produced slower absorption of the 14 C‐glyphosate, as the maximum absorption was not achieved until at least 24 h after application in redroot pigweed, remaining similar until 72 h. In guineagrass, the maximum absorption of the glyphosate was earlier than 24 h with the organosilicone‐based adjuvants, compared with longer times for the conventional adjuvants. The organosilicone‐based adjuvants also increased the glyphosate translocation in redroot pigweed, but not in guineagrass. Organosilicone adjuvants have the potential to provide greater rainfastness to glyphosate on redroot pigweed and, to a lesser extent, on guineagrass.
Detection and correction of abnormal pixels in Hyperion images (2003)

Hyperion images are currently processed to level 1a (from level 0 or raw data). These level 1a images are files of radiometrically corrected data in units of either watts/(sr /spl times/ micron /spl times/ m/sup 2/) /spl times/ 40 for VNIR bands or watts/(sr /spl times/ micron /spl times/ m/sup 2/) /spl times/ 80 for SWIR bands. Each distributed Hyperion level 1a image tape contains a log file, called "(EO-1 identifier).fix.log", that reports the bad or corrupted pixels (called known bad pixels) found during the pre-flight checking, and details how they were fixed. All bad pixels should be corrected in a level 1a image. However, bad pixels are still evident. In addition, there are dark vertical stripes in the image that are not reported in the log file. In this paper, we introduce a method to detect and correct the bad pixels and vertical stripes (we will refer to these occurrences as abnormal pixels). Images from the Greater Victoria Watershed and other EVEOSD test sites are used to determine how stationary the locations of the abnormal pixels are. After abnormal pixel correction a Hyperion image is ready for geometric correction, atmospheric correction, and further analysis.
Ion and Temperature Effects on the Binding of γ‐Aminobutyrate to Its Receptors and the High‐Affinity Transport System (1990)

A set of procedures was developed to study the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to GABAA and GABAB receptors, and to the Na(+)-dependent transport carrier, at 25 and 37 degrees C in the presence of physiological concentrations of Na+. The membrane preparation used in these procedures was not subjected to freeze-thawing or treatment with Triton X-100. Isoguvacine, (-)-baclofen, and (-)-nipecotate were used to block selectively the binding to GABAA receptors, GABAB receptors, and the transport site, respectively. Analysis of the binding characteristics of [3H]GABA to the GABAA receptor suggested the existence of high-(KD less than 30 nM), middle- (KD = 100-500 nM), and low-affinity (KD greater than 5 microM) binding sites. However, the binding data in the middle-affinity region (100-1,000 nM) were often indicative of cooperativity. The affinity between GABA and the GABAA receptor was reduced modestly by increases in temperature and by the presence of Cl- at physiological concentrations. Binding to the GABAB receptor required Ca2+ and Cl-. Apparent binding to the transport carrier required both Na+ and Cl-. A comparison of Bmax values in three brain regions revealed an inverse relationship between the high-affinity site of the GABAA receptor and the transport binding site.
Preparation and Lithium Insertion Properties of Mesoporous Vanadium Oxide (2002)

The first successful deposition of mesoporous vanadium oxide films and their application as high-rate cathode materials for lithium batteries are described in this communication. The novel electrochemical deposition process developed for the preparation of these films makes use of non-ionic surfactant templates. The Figure illustrates the mesoporosity of the material.
DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research (2004)

The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory anti-parasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks (1997)

Staphylococcus aureus has long been recognized as an important pathogen in human disease. Due to an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) strains, therapy has become problematic. Therefore, prevention of staphylococcal infections has become more important. Carriage of S. aureus appears to play a key role in the epidemiology and pathogenesis of infection. The ecological niches of S. aureus are the anterior nares. In healthy subjects, over time, three patterns of carriage can be distinguished: about 20% of people are persistent carriers, 60% are intermittent carriers, and approximately 20% almost never carry S. aureus. The molecular basis of the carrier state remains to be elucidated. In patients who repeatedly puncture the skin (e.g., hemodialysis or continuous ambulatory peritoneal dialysis [CAPD] patients and intravenous drug addicts) and patients with human immunodeficiency virus (HIV) infection, increased carriage rates are found. Carriage has been identified as an important risk factor for infection in patients undergoing surgery, those on hemodialysis or CAPD, those with HIV infection and AIDS, those with intravascular devices, and those colonized with MRSA. Elimination of carriage has been found to reduce the infection rates in surgical patients and those on hemodialysis and CAPD. Elimination of carriage appears to be an attractive preventive strategy in patients at risk. Further studies are needed to optimize this strategy and to define the groups at risk.
G.W.F. Hegel (1995)

Writing in 1946, Merleau-Ponty declared that “all the great philosophical ideas of the past century — the philosophies of Marx and Nietzsche, phenomenology, German existentialism, and psychoanalysis — had their beginnings in Hegel.” (Merleau-Ponty, “Hegel’s Existentialism”, p. 63) Although this is in some respects an exaggeration, Merleau-Ponty’s assessment is nonetheless broadly speaking correct, and indeed some other schools of thought, such as critical theory, could perhaps be added to the list. Hegel’s work provides the background against which the major developments in European ideas since 1831 have emerged, and for many of the philosophers to be discussed in this book, only once they had come to terms with Hegel could their own thinking begin. Furthermore, as Merleau-Ponty observes, “interpreting Hegel means taking a stand on all the philosophical, political, and religious problems of our century”, for often the central debates within post-Hegelian continental philosophy have been couched in terms of competing readings of his work. Hegel is therefore a good place to start for two reasons: firstly, because he decisively influenced the thinking of those who came after him, if only negatively, and secondly because so much European philosophy has been written by developing different aspects of his thought, and by providing competing approaches to problems in his terms.
Automated, compositional and iterative deadlock detection (2005)

We present an algorithm to detect deadlocks in concurrent message-passing programs. Even though deadlock is inherently noncompositional and its absence is not preserved by standard abstractions, our framework employs both abstraction and compositional reasoning to alleviate the state space explosion problem. We iteratively construct increasingly more precise abstractions on the basis of spurious counterexamples to either detect a deadlock or prove that no deadlock exists. Our approach is inspired by the counterexample-guided abstraction refinement paradigm. However, our notion of abstraction as well as our schemes for verification and abstraction refinement differs in key respects from existing abstraction refinement frameworks. Our algorithm is also compositional in that abstraction, counterexample validation, and refinement are all carried out component-wise and do not require the construction of the complete state space of the concrete system under consideration. Finally, our approach is completely automated and provides diagnostic feedback in case a deadlock is detected. We have implemented our technique in the MAGIC verification tool and present encouraging results (up to 20 times speed-up in time and 4 times less memory consumption) with concurrent message-passing C programs. We also report a bug in the real-time operating system MicroC/OS version 2.70.
Blog Fingerprinting: Identifying Anonymous Posts Written by an Author of Interest Using Word and Character Frequency Analysis (2009)

Internet blogs are an easily accessible means of global communications. Monitoring blogs for criminal and terrorist activity is a serious challenge, due to blogs' anonymous nature and the sheer volume of data. The intelligence community is often faced with more information than it can process. The need exists to develop methods for processing the massive amounts of data this media presents, without a significant increase in manpower. An automated tool capable of indentifying posts written by an individual, given a sample of his writing, would allow law enforcement and intelligence agencies to gather evidence that would otherwise be overlooked due to manpower and time constraints. This research focuses on identifying blog posts written by a particular author, when we do not have a model of every potential author. Previous research either builds a distinct model for every possible author, or limits itself to large documents. Neither approach is appropriate for processing blog posts. Blog posts tend to be short documents, and building a distinct model of each author is unreasonable if you are looking for one author among millions. We address this problem by combining sample posts by other authors to create a model of an "average author."
Spinocerebellar ataxia type 5 (2004)

The authors report a German family with autosomal dominant cerebellar ataxia tightly linked to the spinocerebellar ataxia type 5 (SCA5) locus (multipoint lod score 5.76). The phenotype is characterized by a purely cerebellar syndrome with a downbeat nystagmus occurring prior to the development of other features. Imaging studies demonstrated cortical cerebellar atrophy. Progression is slow even in patients with a disease onset during the second decade. The age at onset varies from 15 to 50 years.
Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors (2012)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTDiscovery and Development of Spleen Tyrosine Kinase (SYK) InhibitorsRajinder Singh*, Esteban S. Masuda, and Donald G. PayanView Author Information Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, California 94080, United States*Telephone: (650) 624-1167. E-mail: [email protected]Cite this: J. Med. Chem. 2012, 55, 8, 3614–3643Publication Date (Web):January 18, 2012Publication History Received23 September 2011Published online14 February 2012Published inissue 26 April 2012https://pubs.acs.org/doi/10.1021/jm201271bhttps://doi.org/10.1021/jm201271breview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views5419Altmetric-Citations77LEARN 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 SUBJECTS:Assays,Inhibition,Inhibitors,Peptides and proteins,Receptors Get e-Alerts