gebhart/patrepeval huggingface dataset:
Changeable interfaces and promised messages for concurrent components (1999)

Statically checked process types ensure that a server understands all messages sent by (concurrent) clients. although the acceptability of messages may change dynamically. But. as proposed so far, process types do not ensure that ser\'ers return appropriate answers. In this paper an extension is proposed: Servers must send promised messages (to return results), possibly after receiving further messages. -4 type checker statically ensures that promised messages cannot be involved in deadlocks and lifelocks. The proposed type concept supports subtyping as well as separate compilation.
Assessing the conservation potential and degree of threat among ecoregions of Latin America and the Caribbean : a proposed landscape ecology approach (1994)

This note complements previous attempts at setting regional, and national priorities for bio-diversity conservation in the Latin America and Caribbean region. Based on a tiered analysis, the note focuses on the identification of original habitat areas within discrete ecoregions, whose landscape features, contribute to the persistence of bio-diversity. Detailed analyses on patterns of bio-diversity, and critical habitats for important ecological phenomena, requires finer geographical scales, thus such information was extracted from national conservation strategies, regional analyses, and species-based studies. The approach is that macroeconomic policies, land tenure, migration patterns, among others, impinge upon the ability to conserve bio-diversity over the long-term, and defines conservation potential as the degree of intactness of original ecosystems within an ecoregion.
Interactions between Human Glutamate Carboxypeptidase II and Urea-Based Inhibitors: Structural Characterization (2008)

Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.
Fibrin Sealant in Orthopedic Surgery (1988)

The use of clotting substances from blood for hemostasis dates back to 1909. In 1972, modern fibrin sealing (FS) was developed in Vienna. For application, the two components, i.e., a sealer protein solution (mainly fibrinogen) and a thrombin solution, are mixed to produce the fibrin clot. The sealant may be applied with a needle, as a spray, or by premixing (e.g., with antibiotics, bone chips) for subsequent sealant application in cavities. While the positive effect of FS in normal wound healing has been conclusively demonstrated, its influence on bone healing remains controversial. The positive experimental results mostly refer to the early phase of bone healing in rabbits (cortical drill hole, autologous and heterologous (Kiel) cancellous transplants, osteotomies, osteochondral fractures) and dogs (cortical bone and spongiosa defects). Some authors observed no effects (in dogs, osteotomy) or delayed healing in artificial bone growth chambers with the use of heterologous sealant. FS was also applied in combination with implantation material (tricalcium phosphate and bone gelatin) to facilitate application. Clinical results are especially convincing as to osteochondral fractures, repair of the Achilles tendon, and in hemophiliacs. Fibrin sealant facilitates hemostasis, permits tissue fixation, enhances plasticity of granular implant material, and stimulates fibroblast growth. Although its direct osteogenic effect remains questionable, fibrin sealant is known to be an excellent tool in orthopedic and trauma surgery.
A Decade of Protein Engineering on Ribonuclease T1— Atomic Dissection of the Enzyme‐Substrate Interactions (1997)

During the last decade, protein engineering has been used to identify the residues that contribute to the ribonuclease-T1-catalyzed transesterification. His40, Glu58 and His92 accelerate the associative nucleophilic displacement at the phosphate atom by the entering 2'-oxygen downstream guanosines in a highly cooperative manner. Glu58, assisted by the protonated His40 imidazole, abstracts a proton from the 2'-oxygen, while His92 protonates the leaving group. Tyr38, Arg77 and Phe100 further stabilize the transition state of the reaction. A functionally independent subsite, including Asn36 and Asn98, contributes to chemical turnover by aligning the substrate relative to the catalytic side chains upon binding of the leaving group. An invariant structural motive, involving residues 42-46, renders ribonuclease T1 guanine specific through a series of intermolar hydrogen bonds. Tyr42 contributes significantly to guanine binding through a parallel face-to-face stacking interaction. Tyr45, often referred to as the lid of the guanine-binding site, does not contribute to the binding of the base.
An AC electrokinetic method for enhanced detection of DNA nanoparticles (2009)

In biomedical research and diagnostics it is a challenge to isolate and detect low levels of nanoparticles and nanoscale biomarkers in blood and other biological samples. While highly sensitive epifluorescent microscope systems are available for ultra low level detection, the isolation of the specific entities from large sample volumes is often the bigger limitation. AC electrokinetic techniques like dielectrophoresis (DEP) offer an attractive mechanism for specifically concentrating nanoparticles into microscopic locations. Unfortunately, DEP requires significant sample dilution thus making the technology unsuitable for biological applications. Using a microelectrode array device, special conditions have been found for the separation of hmw-DNA and nanoparticles under high conductance (ionic strength) conditions. At AC frequencies in the 3000-10 000 Hz range, 10 mum microspheres and human T lymphocytes can be isolated into the DEP low field regions, while hmw-DNA and nanoparticles can be concentrated into microscopic high field regions for subsequent detection using an epifluorescent system.
Nontoxic Amyloid β Peptide1-42 Suppresses Acetylcholine Synthesis (1997)

We show here that amyloid beta peptide1-42 (Abeta1-42) may play a key role in the pathogenesis of the cholinergic dysfunction seen in Alzheimer's disease (AD), in addition to its putative role in amyloid plaque formation. Abeta1-42 freshly solubilized in water (non-aged Abeta1-42), which was not neurotoxic without preaggregation, suppressed acetylcholine (ACh) synthesis in cholinergic neurons at very low concentrations (10-100 nM), although non-aged Abeta1-40 was ineffective. Non-aged Abeta1-42 impaired pyruvate dehydrogenase (PDH) activity by activating mitochondrial tau protein kinase I/glycogen synthase kinase-3beta, as we have already shown in hippocampal neurons (Hoshi, M., Takashima, A., Noguchi, K., Murayama, M., Sato, M., Kondo, S., Saitoh, Y., Ishiguro, K., Hoshino, T., and Imahori, K. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 2719-2723). Neither choline acetyltransferase activity nor choline metabolism was affected. Therefore, the major cause of reduced ACh synthesis was considered to be an inadequate supply of acetyl-CoA owing to PDH impairment. Soluble Abeta1-42 increases specifically in AD brain (Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., and Roher, A. E. (1996) J. Biol. Chem. 271, 4077-4081). This increase in soluble Abeta1-42 may disturb cholinergic function, leading to the deterioration of memory and cognitive function that is characteristic of AD.
Human Toll-Like Receptor 2 Mediates Monocyte Activation by Listeria monocytogenes , But Not by Group B Streptococci or Lipopolysaccharide (2000)

Human Toll like receptor (TLR) 2 has been implicated as a signaling receptor for LPS from Gram-negative bacteria and cell wall components from Gram-positive organisms. In this study, we investigated whether TLR2 can signal cell activation by the heat-killed group B streptococci type III (GBS) and Listeria monocytogenes (HKLM). HKLM, but not GBS, showed a time- and dose-dependent activation of Chinese hamster ovary cells transfected with human TLR2, as measured by translocation of NF-kappaB and induction of IL-6 production. A mAb recognizing a TLR2-associated epitope (TL2.1) was generated that inhibited IL-6 production from Chinese hamster ovary-TLR2 cells stimulated with HKLM or LPS. The TL2.1 mAb reduced HKLM-induced TNF production from human monocytes by 60%, whereas a CD14 mAb (3C10) reduced the TNF production by 30%. However, coadministrating TL2.1 and 3C10 inhibited the TNF response by 80%. In contrast to this, anti-CD14 blocked LPS-induced TNF production from monocytes, whereas anti-TLR2 showed no inhibition. Neither TL2.1 nor 3C10 affected GBS-induced TNF production. These results show that TLR2 can function as a signaling receptor for HKLM, possibly together with CD14, but that TLR2 is unlikely to be involved in cell activation by GBS. Furthermore, although LPS can activate transfected cell lines through TLR2, this receptor does not seem to be the main transducer of LPS activation of human monocytes. Thus, our data demonstrate the ability of TLR2 to distinguish between different pathogens.
Cloning, expression, and site-directed mutagenesis of chicken skeletal muscle troponin C. (1988)

Skeletal muscle troponin C (TNC) is structured into two separate domains linked by a nine-turn alpha-helix (D/E helix). It has been demonstrated that calcium binding to the regulatory sites within the N-terminal domain induces conformational changes in the C-terminal domain of isolated TNC. Since the only contact between the two domains is the long D/E helix, the transfer of information must involve conformational changes within this helix. The center of the helix is occupied by a glycine (Gly-92). A postulated mechanism for allowing interdomain interaction involves a conformational change of the D/E helix around Gly-92 (Herzberg, O., and James, M. N. G. (1985) Nature 312, 653-659). We tested this hypothesis using site-directed mutants of troponin C. Two separate mutants containing an alanine and a proline replacing Gly-92 were constructed and compared with wild type TNC. Calcium binding studies showed no significant differences among the TNC species. The different TNC were assembled into thin filaments and used to assay the calcium regulation of actin-activated ATPase of myosin. All TNC species were able to mediate the calcium regulation of ATPase. Under the conditions used for the assays, no differences were detected among the TNC species. These results show that Gly-92 is not essential for the proper interaction of the calcium regulatory sites with the other components of the thin filament, and therefore exclude a large rotation around Gly-92 as the mechanism of information transfer between the two domains of troponin C.
Type 1 T-Helper Cell Predominance in Granulomas of Crohn's Disease (1999)

The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.
Regulation of Autoimmune Disease Physiological and Therapeutic (1986)

An important question is how the immune system can control the behavior of autoimmune effector lymphocytes. My colleagues and I have investigated this question in four models. Three models of organ specific autoimmune diseases were studied using the specific autoimmune lines or clones of T lymphocytes functionally involved in the disease process. The fourth model was an anti-idiotypic network triggered spontaneously by autoantibodies. This article reviews the evidence indicating that healthy individuals can carry potentially virulent autoimmune T lymphocytes without symptoms. This carrier state of autoimmunity implies the existence of natural mechanisms of counter-autoimmunity. One natural element appears to be clones of suppressor-inducer T lymphocytes that arise in the course of the autoimmune response. We have discovered that autoimmune effector T lymphocytes can serve as inducers of their own suppression either artificially, by manipulating the T cell membrane, or naturally, by exposing the individual to very low concentrations of some effector T cell clones. Regarding the regulation of autoreactive B lymphocytes, we have observed that spontaneous generation of anti-idiotypic antibodies may have a particular bias for autoantibody idiotypes. Counter-autoimmunity appears to involve recognition of the self-reactive lymphocyte receptors resulting in the activation of suppressor cells. These suppressor cells can prevent disease or cause remission of established disease.
Regioselective N1-Alkylation of Guanosine Derivatives Protected atN2by anN,N-Dialkyl Amidine Group (1999)

International audience
A Controlled Trial of Colchicine to Reduce the Elastase Load in the Lungs of Ex-cigarette Smokers with Chronic Obstructive Pulmonary Disease (1991)

A great deal of experimental evidence suggests that emphysema in smokers is caused by the action of neutrophil elastase on lung elastin. In order to test this hypothesis, it is necessary to find a drug that reduces the load of neutrophil elastase in the lungs of patients with emphysema. In a previous study we treated smokers with emphysema with colchicine, a drug that prevents neutrophil elastase secretion, to determine if it would reduce the elastase burden in the lungs. Colchicine was unable to reduce the elastase load while the stimulus of smoking continued. In this study we treated ex-smokers with emphysema to determine if colchicine could reduce the elastase burden in the lungs. The objective of the study was to determine if colchicine can reduce the elastase load and putative indicators of elastase load in the lungs of patients with chronic obstructive pulmonary disease. The study was a prospective, double-blind, randomized, and placebo-controlled clinical trial. The subjects were outpatients seeking treatment at the University of Texas Health Center at Tyler. We studied 16 ex-cigarette smokers between 45 and 75 yr of age with lung disease defined by FEV1 less than 70% of predicted but greater than 1.2 L whose airflow obstruction was less than 20% reversible with bronchodilators. Colchicine or placebo was taken by mouth in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of theodur by mouth and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)
Expanding the relevancy of the environmental movement (1995)

Our approach to managing natural resources should be guided by a moral and ethical approach to life as well as by practical and scientific considerations. Examples abound of instances in which Americans have created and willfully ignored environmental externalities. These externalities have had racist consequences through their disproportional impacts on people of color, and they pose serious consequences for future generations.
DNA methyltransferases affecting the sequence 5′LCCGG (1981)

B. subtilis phage SPbeta and Moraxella sp. code for DNA methyltransferases which methylate both cytosines of the sequence 5'CCGG. Experiments using a B. subtilis strain whose DNA is sensitive to HpaII and resistant to MspI degradation, indicated that methylation of the outer C of this sequence provides protection against the restriction enzyme MspI.
Trench isolation for 0.45 μm active pitch and below (2002)

A trench isolation technology which realizes a 0.45 /spl mu/m active pitch while maintaining latch-up holding voltage above 3.0 V for n+/p+ spaces /spl ges/0.6 /spl mu/m for 0.35 /spl mu/m deep trenches is described. Process optimization yields superior gate oxide (t/sub ox/=55 /spl Aring/) and diode performance comparable to LOCOS type isolations. Inverse narrow width effects are minimal at 30 mV (PMOS) and 100 mV (NMOS) for channel widths down to 0.17 /spl mu/m. Anomalous MOSFET sub-threshold conduction due to field crowding at the active edge has been avoided. The variation of field oxide thickness is 40 nm within a wafer and 10 nm within a 15 mm square die.
Radiomic Features Are Superior to Conventional Quantitative Computed Tomographic Metrics to Identify Coronary Plaques With Napkin-Ring Sign (2017)

A large number of radiomic features are different between NRS and non-NRS plaques and exhibit excellent discriminatory value.
Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. (1998)

Benzylacyclouridine (BAU, IND 039655) is a potent and specific inhibitor of uridine phosphorylase (UrdPase; EC 2.4.2.3). This enzyme plays a major role in regulating uridine homeostasis and also catalyzes the conversion of fluoropyrimidine nucleosides to their respective bases. Inhibition of UrdPase enzyme activity 18-24 h after 5-fluorouracil (5-FU) administration increased plasma levels of uridine and enhanced the therapeutic index of 5-FU by rescuing normal tissues. Moreover, in vitro preclinical studies have also shown that inhibiting UrdPase enzyme activity by BAU prior to administration of 5-FU increased cytotoxicity in a number of human cancer cell lines. A series of preclinical studies was performed in dogs and pigs to evaluate the pharmacological and pharmacodynamic properties of BAU. These data showed a sustained elevation in plasma uridine concentration in both animal models. The rapid degradation of a tracer dose of uridine into uracil was virtually arrested by BAU administered both p.o. or i.v. The t1/2 of BAU was 1.8-3.6 h in dogs, with bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg). In pigs, the half-life varied from 1.6 to 2.3 h, with a bioavailability of 40% at 120 mg/kg. The drug was distributed into most tissues with a tissue: plasma ratio of approximately 0.7. On the basis of these preclinical studies, we performed a Phase I clinical trial of BAU in patients with advanced cancer. Patients received 200, 400, 800, and 1600 mg/m2 BAU as a single oral dose. Toxicities included grade 2 anemia, grade 1 fever, grade 1 fatigue, grade 1 constipation, and grade 1 elevation in alkaline phosphatase; none of these toxicities were observed to be dose dependent. The maximum tolerated dose and dose-limiting toxicity were not reached at the doses given. BAU plasma concentrations and area under the curve correlated linearly with the oral dose level. The pharmacokinetics of BAU were consistent with a first-order clearance, with average peak concentrations ranging from 19 microM (200 mg/m2) to 99 microM (1600 mg/m2) and tbeta1/2 ranging from 3.0 to 3.9 h at the four dose levels. Compared with baseline plasma uridine, treatment of patients with 200, 400, 800, and 1600 mg/m2 BAU increased peak uridine concentrations by 120, 150, 250, and 175%, respectively. On the basis of this clinical study, the suggested Phase II starting dose of BAU in combination with 5-FU is 800 mg/m2. Studies combining BAU with 5-FU and incorporating appropriate molecular and biochemical end points to assess the effects of this drug combination on tumor and/or surrogate tumor tissue are under way.
Abstract B62: Beta-2 adrenergic receptor polymorphisms and risk of breast cancer among Hispanic and non-Hispanic white women: The 4-Corners Breast Cancer Study (2011)

Abstract Polymorphisms in the adrenergic receptor beta-2 (ADRB2) gene have been studied in relation to risk of type 2 diabetes and obesity, but few studies have investigated associations with breast cancer. The purpose of this research was to evaluate the hypothesis that ADRB2 variants (rs1042713-Arg16Gly and rs1042714-Glu27Gln) are associated with breast cancer risk in non-Hispanic white (NHW) and Hispanic (H) women using data from a population-based case-control study conducted in the southwestern United States: ‘The 4-Corners Breast Cancer Study’. A total of 1,244 NHW and 606 H cases with incident primary breast were ascertained and 1,330 NHW and 728 H population-based controls were selected. Information on lifestyle and physical activity, diet, demographics, and reproductive background was collected through an in-person questionnaire, and blood samples were taken for genetic analyses from consenting participants. ADRB2 genotypes for rs1042713 and rs1042714 were determined using PCR. Each genotype as well as their combined haplotype was evaluated in multivariable logistic regression models to estimate the associations with breast cancer risk while adjusting for potential confounders, including study center, history of diabetes, body mass index, family history of breast cancer, genetic admixture, and menopausal status. ADRB2 genotype frequencies were significantly different between NHW and H women. Individually, the ADRB2 polymorphisms were not associated with breast cancer in either ethnic group. However, having 2 copies compared to one or zero copies of the ADRB2 G-G haplotype was associated significantly with increased risk of breast cancer among NHW women [odds ratio (OR), 1.95; 95% confidence interval (95% CI), 1.26–3.01] but reduced risk among Hispanic women [OR, 0.74; 95% CI, 0.50–1.09], (p-for interaction=0.004). Risk was significantly decreased in Hispanic women with a history of type 2 diabetes and 2 copies of the G-G haplotype [OR, 0.33; 95% CI, 0.12–0.92] while the association was increased, but not statistically significant among NHW women, [OR, 4.91; 95% CI, 0.52–46.60], (p-for interaction = 0.025). While the interaction between obesity (body mass index (BMI) ≥ 30 kg/m2) and the G-G haplotype was not significant (p=0.200), the association in NHW obese women with 2 copies of the G-G haplotype was similarly increased [OR, 3.01; 95% CI, 1.22–7.44], but decreased in Hispanics [OR, 0.42; 95% CI, 0.20–0.56]. These data suggest that ethnicity modifies the association between the ADRB2 G-G haplotype and breast cancer risk and history of type 2 diabetes and obesity enhances the divergence of risk between Hispanic and NHW women. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B62.
Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. (1993)

We provide the first link between a known molecular motor and morphogenesis, the fundamental process of cell shape changes and movements that characterizes development throughout phylogeny. By reverse genetics, we generate mutations in the Drosophila conventional nonmuscle myosin (myosin II) heavy chain gene and show that this gene is essential. We demonstrate that these mutations are allelic to previously identified, recessive, embryonic-lethal zipper mutations and thereby identify nonmuscle myosin heavy chain as the zipper gene product. Embryos that lack functional myosin display defects in dorsal closure, head involution, and axon patterning. Analysis of cell morphology and myosin localization during dorsal closure in wild-type and homozygous mutant embryos demonstrates a key role for myosin in the maintenance of cell shape and suggests a model for the involvement of myosin in cell sheet movement during development. Our experiments, in conjunction with the observation that cytokinesis also requires myosin, suggest that the processes of cell shape change in morphogenesis and cell division are intimately and mechanistically related.