gebhart/patrepeval huggingface dataset:
CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation (1999)

Abstract CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation.
The DCU-ICTCAS MT system at WMT 2014 on German-English Translation Task (2014)

This paper describes the DCU submission to WMT 2014 on German-English translation task. Our system uses phrasebased translation model with several popular techniques, including Lexicalized Reordering Model, Operation Sequence Model and Language Model interpolation. Our final submission is the result of system combination on several systems which have different pre-processing and alignments.
FOUR-WEEK INTRAVENOUS REPEATED DOSE TOXICITY STUDY OF L-CYSTEINE IN MALE RATS. (2003)

A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this compound and to determine the dose level at which these toxic effects are observed following repeated intravenous administration. Male rats were randomly allocated to 4 groups to receive L-Cys by intravenous administration at dosages of 0, 100, 300, and 1,000 mg/kg body weight/day. Body weight gain was significantly suppressed throughout the study period in the 1,000-mg/kg group, although food consumption was reduced only on study day 3. A decrease in spontaneous activity, salivation, stereotypy, ptosis, and tremor were observed in the 1,000-mg/kg group. Mild anemia characterized by decreases in hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and an increase in the reticulocyte count was also noted in the 1,000-mg/kg group. Histopathological examination showed sperm granulomas in the epididymis and necrosis of the Purkinje cells and granular layer in the cerebellum in the 1,000-mg/kg group. Slight tubular basophilia with blood or hyaline casts was observed in the kidney in the 300-mg/kg and 1,000-mg/kg groups, associated with proteinuria or occult blood in urinalysis. Additional studies are needed to clarify the causes for these toxicological findings by excess of L-Cys.
Opsonic Activities of Surfactant Proteins A and D in Phagocytosis of Gram-Negative Bacteria by Alveolar Macrophages (1995)

Surfactant proteins A and D (SP-A, SP-D) can interact with lipopolysaccharide (LPS) and stimulate alveolar macrophages. The opsonic activities of SP-A and SP-D for bacteria with different types of LPS and alveolar macrophages were investigated. In flow cytometric studies with fluorescein-labeled rough (J5) and smooth (O111) Escherichia coli and rat alveolar macrophages, SP-A enhanced binding of J5 but not O111 bacteria to macrophages. Most importantly, SP-A enhanced ingestion of J5 bacteria by alveolar macrophages and subsequent bacterial killing. Immunoelectron microscopy demonstrated that J5 bacteria, the interface between the bacterium and the outer membrane of the alveolar macrophage, and ingested bacteria were heavily labeled with SP-A. In contrast, SP-D did not mediate phagocytosis. SP-A acted as an opsonin in the phagocytosis of rough LPS-containing bacteria by alveolar macrophages, emphasizing the possible role for SP-A in the alveolar defense system.
Development of an Oral Dosage Form of Azacitidine: Overcoming Challenges in Chemistry, Formulation, and Bioavailability. (2006)

Abstract Azacitidine (Vidaza®), an epigenetic modifier which exerts its therapeutic effect through gene demethylation, is currently approved in a subcutaneous (sc) dosage form for the treatment of myelodysplastic syndromes (MDS). Low-dose, chronic demethylation may lead to improved antiproliferative activity while minimizing side effects. Such chronic demethylation would require a convenient, more frequent dosing schedule. It has, therefore, been an objective of Pharmion Corporation to develop an oral dosage form of azacitidine that could improve the safety and efficacy attributes of the parenterally administered formulation plus have desirable pharmacokinetic characteristics. Azacitidine presents several significant challenges with respect to oral administration including sub-optimal physiochemical characteristics, hydrolytic instability, and active enzymatic degradation - all non-conducive to high passive intestinal tract absorption. Moreover, the drug requires formulated tablet strengths accommodating widely flexible treatment regimens yet must be formulated to avoid the chemical and enzymatic degradation occurring presystemically. Additionally, nonclinical testing of azacitidine bioavailability is hampered by inappropriate animal models representing human gastrointestinal tracts conditions, low tolerability of the drug in several animal species, widely variable pharmacokinetic behavior, and lack of highly sensitive bioanalytical methods for measuring the drug. Data on orally administered azacitidine are sparse but hint at some degree of bioavailability in mice where multiple oral dosing with the drug resulted in lower LD50 values than multiple dosing by the intravenous route (data on file at Pharmion). A published report following long term oral dosing (0.2 mg/kg/day of azacitidine plus 200 mg tetrahydrouridine 3 days per week) in a patient with sickle cell disease resulted in significant increases in total and fetal hemoglobin suggesting absorption of the drug followed by systemic effects (Dover, 1985). A study recently conducted in dogs given azacitidine orally (6 mg/kg) compared to sc and iv (2 mg/kg) showed the drug was absorbed rapidly by the oral route (Tmax, 15 min) with absolute bioavailability of 67% (compared to 71% following sc dosing). Additional in vitro and ex vivo characterization of azacitidine stability and permeability have been performed. Data from these studies have been utilized to develop a solid oral dosage form of azacitidine that will move forward into additional animal testing and clinical evaluation. Highly sensitive bioanalytical methods have also been developed for the quantitation of azacitidine in dog and human plasma. A single oral dose escalation study will be conducted in patients to assess the safety, tolerability, and pharmacokinetics of orally administered azacitidine. Data will be evaluated continuously during the dose escalation study. Information generated from these studies will be used to appropriately design a full oral azacitidine clinical development program.
Stereospecific Polymerization of Chiral Oxazolidinone-Functionalized Alkenes (2010)

Acryloyl and vinyl monomers functionalized with a chiral oxazolidinone auxiliary have been successfully polymerized in a stereospecific fashion to highly isotactic, optically active polymers, through either the previously established isospecific coordination polymerization (for acryloyl monomers) or a novel isospecific cationic polymerization (for vinyl monomers). Specifically, conjugated chiral acryloyloxazolidinones, N-acryloyl-(R or S)-4-phenyl-2-oxazolidinone [(R or S)-AOZ], are readily polymerized by chiral ansa-zirconocenium coordination catalysts, (R,R-, S,S-, or R,R/S,S)-[C2H4(η5-Ind)2]Zr+(THF)[OC(OiPr)═CMe2][MeB(C6F5)3]− (1), in an isospecific manner through a catalyst-site-controlled mechanism, producing the corresponding optically active chiral polymers, (R or S)-PAOZ. Owing to the nature of stereocontrol dictated by the chiral catalyst site, even the coordination polymerization of the parent AOZ, without the chiral side group, also affords PAOZ with nearly quantitative isotacticity. A series of experiments have shown that the chiral polymers (R or S)-PAOZ exhibit no chiral amplifications, despite having stereoregularly placed stereogenic centers in the main chain, and the optical activity of the polymers arises solely from their chiral auxiliary, a consequence of adopting a random-coil secondary structure and thus having a cryptochiral chain. In sharp contrast, the chiral isotactic polymers derived from nonconjugated chiral vinyl oxazolidinones, N-vinyl-(R)-4-phenyl-2-oxazolidinone [(R)-VOZ] and its p-hexyloxyphenyl derivative (R)-HVOZ (designed to solve the solubility issue of the resulting polymer), exhibit substantial chiral amplifications by virtue of adopting a solution-stable, one-handed helical conformation. The synthesis of such helical vinyl polymers has been accomplished by the development of a novel isospecific cationic polymerization using Lewis and Brønsted acids, such as [Ph3C][B(C6F5)4], BF3·Et2O, and [H(Et2O)2][B(C6F5)4], through a chiral auxiliary-controlled mechanism. Noteworthy is the combination of the near-quantitative isotactic placement of the stereogenic centers of the polymer main chain with the chiral side groups located near those stereocenters that renders one-handed helicity of (R)-PVOZ and (R)-PHVOZ. Significantly, this novel cationic polymerization process, operating at ambient temperature, effectively assembles two elements of polymer local chirality—side-chain chirality and main-chain chirality—into global chirality in the form of excess one-handed helicity. Furthermore, the resulting chiral helical vinyl polymers exhibit considerably higher thermal decomposition temperatures and polymer crystallinity, in comparison to the random-coil chiral acryloyl polymers, having a similarly high degree of main-chain stereoregularity.
Brain Oligomeric β-Amyloid but Not Total Amyloid Plaque Burden Correlates With Neuronal Loss and Astrocyte Inflammatory Response in Amyloid Precursor Protein/Tau Transgenic Mice (2011)

It has long been assumed that β-amyloid (Aβ) had to assemble into fibrillar amyloid plaques to exert its neurotoxic effects in Alzheimer disease. An alternative hypothesis is that soluble oligomers ofAβ play a much larger role in neuronal damage than the insoluble component. We have tested these competing hypotheses in vivo by studying the clinicopathologic correlates of oligomeric Aβ species and classic fibrillar amyloid plaques in the brains of double-transgenic APP-tau mice up to 17 months of age. Biochemical and immunohistochemical measures of brain oligomeric Aβ exponentially increased with age. Oligomeric Aβ load correlated with morphological markers of fibrillar Aβ deposition. In contrast to total amyloid plaque burden, the amount of oligomeric Aβ deposits labeled by the conformational epitope-specific antibody Nab61 closely correlated with neuronal loss and numbers of astrocytes in the entorhinal cortex and the CA1 hippocampal subfield. However, like other morphological Aβ measurements, brain oligomeric Aβ burden did not correlate well with memory deficits in these mice. The number of glial fibrillary acidic protein-positive astrocytes in entorhinal cortex and CA1 most tightly correlated with memory impairment and neuronal cell loss. Based on these findings, we hypothesize that the astrocyte response, which is likely triggered by brain oligomeric Aβ accumulation, adversely affects cognition and might also contribute to neuronal cell death in this model.
Identification of a Novel Citrobacter rodentium Type III Secreted Protein, EspI, and Roles of This and Other Secreted Proteins in Infection (2004)

Citrobacter rodentium is a member of a group of pathogens that colonize the lumen of the host gastrointestinal tract via attaching and effacing (A/E) lesion formation. C. rodentium, which causes transmissible colonic hyperplasia in mice, is used as an in vivo model system for the clinically significant A/E pathogens enterohemorrhagic and enteropathogenic Escherichia coli. These bacteria all contain a pathogenicity island called the locus of enterocyte effacement (LEE), which encodes a type III secretion system that is designed to deliver effector proteins into eukaryotic host cells. These effectors are involved in the subversion of host eukaryotic cell functions to the benefit of the bacterium. In this study we used mutant strains to determine the effects of the C. rodentium LEE-encoded effectors EspF, EspG, EspH, and Map on virulence in the mouse model. In addition, we identified a novel secreted protein, EspI encoded outside the LEE, whose secretion is also dependent on a functional type III secretion system. Mutant strains with each of the effectors investigated were found to be outcompeted by wild-type bacteria in mixed-infection experiments in vivo, although the effects of EspF and EspH were only subtle. In single-infection experiments, we found that EspF, EspG, and EspH are not required for efficient colonization of the mouse colon or for the production of hyperplasia. In contrast, strains producing EspI and Map had significant colonization defects and resulted in dramatically reduced levels of hyperplasia, and they exhibited very different growth dynamics in mice than the wild-type strain exhibited.
pH Neutralization Process as a Benchmark for Testing Nonlinear Controllers (2001)

This work outlines the pH neutralization process as a benchmark for nonlinear control design. The typical industrial conditions for this class of process are analyzed in order to elaborate a proposal for laboratory equipment that closely resembles a real system and also furnishes an excellent test bench for verifying new control strategies. This equipment has been installed at National University of San Juan, Argentina. The control problem, namely, the benchmark, with all of its operating restrictions is presented for real applications. The benchmark representation capability is discussed. The final goal is to define a pH region where the model has a good representation capability for industrial acid mixtures. Several experiments conducted at the laboratory assembly demonstrate the effectiveness of the proposed benchmark. Finally, a PID controller is presented as a reference for comparing the performance of tested nonlinear controllers.
Parasporal Body of Bacillus thuringiensis israelensis STRUCTURE, PROTEIN COMPOSITION, AND TOXICITY (1990)

Since its discovery inJapan and Germany during the early part of this century, more than 25 subspecies of the spore-forming insecticidal bac­ terium Bacillus thuringiensis Berliner have been described (de Barjac 1985). The most distinctive characteristic of this bacterium is a parasporal body produced during sporulation that consists primarily of insecticidal pro­ teins (Angus 1965; Heimpe11967; Aronson, Beckman, and Dunn 1986; H6fte and Whiteley 1989). In most subspecies, the parasporal body is a bipyramidal crystal containing one or more similar proteins of about 135 kDa that are tox­ ic to lepidopterous larvae. When ingested by a larva, this toxin-containing inclusion dissolves in the alkaline gut juices, and midgut proteases cleave the protoxin, yielding an active peptide toxin of 60-70 kDa, the ?)-endotoxin. Although the toxin's precise mode of action is not fully understood, intoxica­ tion results in an osmotic imbalance across the midgut epithelial cell mem­ brane, which leads quickly to hypertrophy and lysis of midgut cells. Lysis is followed by disruption of the basement membrane, leakage of digestive juices into the hemocoel, and larval death (Luthy and Ebersold 1981). The ?)­ endotoxins of different subspecies of B. thuringiensis can vary considerably in toxicity to larvae. These variations are thOUght to be due to differences in the amino acid sequence of the toxins, and are currently the subject of much interest because of the potential for increasing toxicity and host spectrum through site-directed mutagenesis. The first isolate of B. thuringiensis shown to possess characteristics markedly different from those described above was ONR-60A. This isolate was collected by Goldberg and Margalit (1977) from a mosquito larval hab­ itat in the Negev Desert of Israel and demonstrated to be highly toxic to the
Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene. (1985)

Transformation of fibroblasts by protooncogene fos (c-fos) requires the linkage of viral long terminal repeat (LTR) sequences and interruption of 3'-noncoding sequences. We have identified an A + T-rich stretch of 67 nucleotides, located 627-693 base pairs downstream from the coding domain and 123-189 base pairs upstream from the putative poly(A) addition site, removal of which confers transforming activity to the c-fos gene. A novel regulation of the expression of the c-fos gene is proposed, which may be functional in vivo to prevent the gene from becoming an oncogene.
Disconnected Operation in the Thor Object-Oriented Database System (1994)

This paper discusses issaes raised by providing disconnected operation in the Thor object-ortented database system. Disconnected operation in such a system poses new challenges because of the small size of obiects, the richness and complexity of their interconnections, the huge number of them, and the fact that they are accessed within atomic transactions. We propose three techniques to address these challenges: (l) using the database query language for hoarding; (2) using dependent commits to tentatively com' mit transactions at the disconnected client; (3) using the high-level semantic of objects to avoidtransaction aborts.
Androgen-independent expression ofhoxb-13 in the mouse prostate (1999)

These data demonstrate that hoxb-13 expression is androgen-independent in mouse prostate glands. The identification of hoxb-13 as an androgen-independent gene expressed in adult mouse prostate epithelial cells provides a new potential target for developing therapeutics to treat advanced prostate cancer.
Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failure (2003)

The past few years have witnessed a major breakthrough in the understanding of the molecular mechanisms and ultrastructural changes behind the development of proteinuria. The discovery of several proteins in the glomerular podocyte and slit diaphragm, where mutations lead to disease, has revealed the importance of this cell with its diaphragm as the major filtration barrier as opposed to the glomerular basement membrane (GBM) previously ascribed this function. Furthermore, accumulating clinical as well as experimental evidence points to the harmful effects of proteinuria, irrespective of the original damage. The purpose of this review is to shed light on what we know today about the two sides of this 'coin', the causes and the consequences of proteinuria.
SHAPE FROM SHADING: A METHOD FOR OBTAINING THE SHAPE OF A SMOOTH OPAQUE OBJECT FROM ONE VIEW (1970)

A method will be described for finding the shape of a smooth opaque object from a monocular image, given a knowledge of the surface photometry, the position of the light-source and certain auxiliary information to resolve ambiguities. This method is complementary to the use of stereoscopy which relies on matching up sharp detail and will fail on smooth objects. Until now the image processing of a single views has been restricted to objects which can meaningfully be considered two-dimensional or bounded by plane surfaces.
The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels (1996)

Vpu is a small phosphorylated integral membrane protein encoded by the human immunodeficiency virus type 1 genome and found in the endoplasmic reticulum and Golgi membranes of infected cells. It has been linked to roles in virus particle budding and degradation of CD4 in the endoplasmic reticulum. However, the molecular mechanisms employed by Vpu in performance of these functions are unknown. Structural similarities between Vpu and the M2 protein of influenza A virus have raised the question of whether the two proteins are functionally analogous: M2 has been demonstrated to form cation-selective ion channels in phospholipid membranes. In this paper we provide evidence that Vpu, purified after expression in Escherichia coli, also forms ion channels in planar lipid bilayers. The channels are approximately five- to sixfold more permeable to sodium and potassium cations than to chloride or phosphate anions. A bacterial cross-feeding assay was used to demonstrate that Vpu can also form sodium-permeable channels in vivo in the E. coli plasma membrane.
Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas (2005)

Over the past two decades, several known genes have been shown to govern important functions in the development of primary and metastatic melanomas. However, from this limited number of genes, it is not possible to establish detailed molecular profiles for the early and advanced stages of melanoma development. To gain insights into the genetic profile of every stage of the melanoma progression pathway, and to determine to what extent these profiles are similar or distinct, we performed whole-genome expression profiling of tissue specimens representing normal skin, benign and atypical nevi, and early and advanced-stage melanomas. The results of this study provide first-time evidence that significant molecular changes occur distinctly at the border of/transition from melanoma in situ to primary melanoma, and that genes involved in mitotic cell cycle regulation and cell proliferation constitute the two leading categories of genes associated with these changes.