gebhart/patrepeval huggingface dataset:
High critical current densities in YBa2Cu3O7−x films on polycrystalline zirconia (1990)

We report the growth on polycrystalline yttria-stabilized zirconia substrates of YBa2Cu3O7−x films with Jc (77 K)=11 000 A/cm2 and Jc (4.2 K)=122 000 A/cm2 by pulsed laser ablation. These Jc values are among the highest reported for YBa2Cu3O7−x on any polycrystalline substrate and approach the intrinsic upper limit for films with large-angle grain boundaries, as indicated by recent bicrystal experiments. We find that the substrate temperature during film growth is most important in obtaining high Jc polycrystalline films. Although the magnetic field dependence of Jc indicates the presence of weak links, the behavior of Jc (4.2 K, H) suggests that a percolative path consisting of low-angle grain boundaries exists in the films, resulting in Jc (4.2 K, 60 kOe)=4100 A/cm2.
ChemInform Abstract: Synthesis of 2‐Phenylimidazo[2,1‐b]benzothiazole Derivatives as Modulators of Multidrug Resistance for Tumor Cells. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pseudomonas - Candida Interactions: An Ecological Role for Virulence Factors (2002)

Bacterial-fungal interactions have great environmental, medical, and economic importance, yet few have been well characterized at the molecular level. Here, we describe a pathogenic interaction between Pseudomonas aeruginosa and Candida albicans , two opportunistic pathogens. P. aeruginosa forms a dense biofilm on C. albicans filaments and kills the fungus. In contrast, P. aeruginosa neither binds to nor kills yeast-form C. albicans . Several P. aeruginosa virulence factors that are important in disease are involved in the killing of C. albicans filaments. We propose that many virulence factors studied in the context of human infection may also have a role in bacterial-fungal interactions.
Serologic, Virologic, and Histopathologic Observations of Encephalomyocarditis Virus Infection in Mummified and Stillborn Pigs (1989)

Stillborn and mummified swine fetuses from swine farms experiencing reproductive problems were investigated for evidence of infection with encephalomyocarditis (EMC) virus by fetal serology, virus isolation, and histopathologic examination. Fetal sera or thoracic fluids of 478 abnormal fetuses collected during January through December 1987 were tested for the presence of antibody specific to EMC virus. Of 478 samples tested, 175 (36.6%) had EMC virus serum neutralizing antibody titers of 1:64 or greater. The samples positive for EMC virus antibody were obtained from 38 swine farms located in 9 states in the United States. In addition to serologic observations, tissue samples of some abnormal fetuses were examined for the presence of virus and histopathologic lesions. The EMC virus was isolated in 1 case from the fetuses of an aborted litter. The isolate was serologically identical to a reference EMC virus. Nonsuppurative encephalitis and myocarditis were observed in the fetal samples collected from 2 different herds. Thoracic fluid of 1 stillborn pig with lesions was positive for EMC virus antibody at a titer of 1:512. We suggest that a widespread reproductive problem recently experienced in several major swine-producing areas of the United States may have been caused by EMC virus infection.
Conversion of the Pyrolytic Vapor of Radiata Pine over Zeolites (2007)

Direct conversion of the pyrolytic vapor of radiata pine was conducted in a fixed catalyst bed reactor installed at the upper part of a bubbling fluidized bed reactor. The influence of different catalysts, the catalyst bed temperature, and the residence time of the vapor on the product distribution was investigated. The for- mation of char or tar in the fixed catalyst bed reactor could be inhibited through direct catalytic pyrolysis of the vapor of radiata pine over different catalysts. After catalysis, the bio-oil yield decreased while the gas yield increased. HZSM-5, in which strong acidic sites are properly distributed, was more efficient in bio-oil upgrad- ing than HY; the oxygen in the bio-oil was largely converted into H2O, CO, and CO2. For Ga/HZSM-5, the bio-oil yield and the selectivity of aromatic hydrocarbons in the bio-oil increased.
Induction of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Cytolytic T Lymphocyte Responses in Seronegative Adults by a Nonreplicating, Host-Range-Restricted Canarypox Vector (ALVAC) Carrying the HIV-1MN env Gene (1995)

CD8+ cytolytic T lymphocytes (CTL) are likely to be an important component of effective vaccines against human immunodeficiency virus type 1 (HIV-1). CTL can be induced most effectively with live virus vectors. However, because of concerns about the safety of such vectors, a nonreplicating canarypox vector (ALVAC) capable of expressing foreign genes in mammalian cells has been developed. This study evaluated the capacity of an ALVAC vector expressing the HIV-1MN envelope (env) glycoprotein to induce HIV-1-specific CTL in seronegative volunteers. Protocols were designed to determine whether immunization with ALVAC alone or in combination with subunit boosting could induce CTL in vaccinia-immune and -naive volunteers. A simple method for antigen-specific in vitro stimulation was used to detect CTL responses in HIV-1-seronegative vaccine recipients. The results indicate that low doses of a nonreplicating virus vector alone can elicit both CD4+ and CD8+ HIV-1-specific CTL in a subset of seronegative volunteers.
Efficient mapping and characterization of a T cell epitope by the simultaneous synthesis of multiple peptides (1989)

Prediction, identification and analysis of T cell epitopes in protein antigens has become a central theme in fundamental and applied immunology. However, while for the characterization of linear B cell epitopes the so-called Pepscan procedure was found to be extremely effective, no such technique has so far been available for T cell studies. Recently, we described the identification and localization of a T cell epitope in a mycobacterial 65-kDa shock protein in the model of adjuvant arthritis. This was done by molecular cloning and conventional solid-phase synthesis techniques. We now show that the delineation of such a T cell epitope and its further characterization can be accomplished in a much more rapid and efficient manner by a modification of the existing Pepscan technique. We show for the first time that several hundreds of peptides, simultaneously synthesized in an automated way on activated polyethylene rods, can be easily recovered from these rods in adequate quantities, enabling a systematic analysis of T cell epitopes. Synthesis of sequentially overlapping peptides along the 65-kDa protein revealed that the adjuvant arthritis T cell clones are fully stimulated by peptides that comprise a minimal sequence of seven residues, corresponding to positions 180-186 in the sequence of the 65-kDa protein of M. bovis Bacillus Calmette Guerin (BCG). Detailed examination of the epitope by peptides containing a single amino acid substitution showed that, apart from one conservative replacement (Glu----Asp), the requirement for the native residue at all positions in peptide 180-186 was absolute for full T cell stimulation. Their indispensability was confirmed with deletion and insertion peptides. It is concluded that the occurrence of indifferent or spacer residues in a minimal stimulatory sequence, as observed by others, is not a general feature of T cell epitopes.
Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia (1988)

Abstract Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3′ bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.
Delayed Treatment with Systemic (S)-Roscovitine Provides Neuroprotection and Inhibits In Vivo CDK5 Activity Increase in Animal Stroke Models (2010)

Altogether, our data bring new evidences for the further development of pharmacological CDK inhibitors in stroke therapy.
A synthetic peptide inhibitor for alpha-chemokines inhibits the growth of melanoma cell lines. (1997)

Melanoma growth stimulatory activity (MGSA/GROalpha) is a 73 amino acid peptide sharing sequence characteristics with the alpha-chemokine superfamily. MGSA/GROalpha is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROalpha to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could bind to MGSA/GROalpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of alpha-chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/ GROalpha. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 microM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROalpha. The viability of Hs 294T cells in the presence of 100 microM peptide was > 92%. These findings suggest that MGSA/GROalpha is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROalpha from binding to its receptors.
A Gene-Targeting Approach Identifies a Function for the First Intron in Expression of the α1(I) Collagen Gene (1998)

The role of the first intron of the Col1A1 gene in the regulation of type I collagen synthesis remains uncertain and controversial despite numerous studies that have made use of transgenic and transfection experiments. To examine the importance of the first intron in regulation of the gene, we have used the double-replacement method of gene targeting to introduce, by homologous recombination in embryonic stem (ES) cells, a mutated Col1A1 allele (Col-IntDelta). The Col-IntDelta allele contains a 1. 3-kb deletion within intron I and is also marked by the introduction of a silent mutation that created an XhoI restriction site in exon 7. Targeted mice were generated from two independently derived ES cell clones. Mice carrying two copies of the mutated gene were born in the expected Mendelian ratio, developed normally, and showed no apparent abnormalities. We used heterozygous mice to determine whether expression of the mutated allele differs from that of the normal allele. For this purpose, we developed a reverse transcription-PCR assay which takes advantage of the XhoI polymorphism in exon 7. Our results indicate that in the skin, and in cultured cells derived from the skin, the intron plays little or no role in constitutive expression of collagen I. However, in the lungs of young mice, the mutated allele was expressed at about 75% of the level of the normal allele, and in the adult lung expression was decreased to less than 50%. These results were confirmed by RNase protection assays which demonstrated a two- to threefold decrease in Col1A1 mRNA in lungs of homozygous mutant mice. Surprisingly, in cultured cells derived from the lung, the mutated allele was expressed at a level similar to that of the wild-type allele. Our results also indicated an age-dependent requirement for the intact intron in expression of the Col1A1 gene in muscle. Since the intron is spliced normally, and since the mutant allele is expressed as well as the wild-type allele in the skin, reduced mRNA stability is unlikely to contribute to the reduction in transcript levels. We conclude that the first intron of the Col1A1 gene plays a tissue-specific and developmentally regulated role in transcriptional regulation of the gene. Our experiments demonstrate the utility of gene-targeting techniques that produce subtle mutations for studies of cis-acting elements in gene regulation.
TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling (2012)

Rab4A is a master regulator of receptor recycling from endocytic compartments to the plasma membrane. The protein TBC1D16 is up-regulated in melanoma, and TBC1D16-overexpressing melanoma cells are dependent on TBC1D16. We show here that TBC1D16 enhances the intrinsic rate of GTP hydrolysis by Rab4A. TBC1D16 is both cytosolic and membrane associated; the membrane-associated pool colocalizes with transferrin and EGF receptors (EGFRs) and early endosome antigen 1, but not with LAMP1 protein. Expression of two TBC1D16 isoforms, but not the inactive R494A mutant, reduces transferrin receptor recycling but has no effect on transferrin receptor internalization. Expression of TBC1D16 alters GFP-Rab4A membrane localization. In HeLa cells, overexpression of TBC1D16 enhances EGF-stimulated EGFR degradation, concomitant with decreased EGFR levels and signaling. Thus, TBC1D16 is a GTPase activating protein for Rab4A that regulates transferrin receptor recycling and EGFR trafficking and signaling.
K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: a combined analysis of 881 cases (1999)

The treatment of non-small cell lung cancer (NSCLC) remains unsatisfactory, with most patients succumbing to metastatic disease within 5 years of diagnosis. Improved selection of patients for aggressive adjuvant therapy may contribute to improved survival. Mutation of the k-ras oncogene is considered a potentially clinically useful prognostic biomarker for this purpose. This report presents the results of a meta-analysis performed to determine whether the existing data support such a role for k-ras mutations in NSCLC. Two year survival data derived from 881 NSCLC patients in eight published studies were analyzed using a general variance-based meta-analytical method employing confidence intervals. The outcome of interest was a summary relative risk (RR(s)) reflecting the risk of death at 2 years associated with k-ras mutation-positive versus k-ras mutation-negative disease. Prior to calculation of RR(s), analysis for heterogeneity showed Q to equal 15.52 (7 df, P = 0.03). This indicated heterogeneity across the analyzed studies in terms of their estimate of effect. Possible sources of heterogeneity were identified and included selection bias and various other sources of uncontrolled confounding. Although a RR(s) of 2.35 (95% CI = 1.61-3. 22) was found when all eight studies were combined (favoring a negative prognostic role for k-ras mutation), it is unclear whether the magnitude of the RR(s) would persist after adjusting for other well-established prognostic indicators (e.g. stage). The existing data suggest that k-ras mutation may be associated with shortened survival in NSCLC, although this finding awaits confirmation in well-designed multivariate analyses which adjust for the effect of known prognostic indicators.
Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance in mice inoculated with killed mycobacterial vaccines (1988)

A number of nonliving mycobacterial preparations were tested in vivo for their capacity to generate various relevant parameters of cellular immunity. All preparations tested had some detectable activity in raising resistance to challenge with Mycobacterium tuberculosis or with Listeria monocytogenes and in conferring the ability to mount a delayed-type hypersensitivity response to tuberculin. This report presents the first evidence, however, that none of these preparations were able to generate protective T cells capable of adoptive immunization against virulent tuberculosis. These data are discussed in terms of the use of these preparations in generating M. tuberculosis-reactive T-cell lines and the application of these lines in the continuing search for an improved vaccine against tuberculosis.
Dapper 1 Antagonizes Wnt Signaling by Promoting Dishevelled Degradation (2006)

Wnt signaling plays pivotal roles in the regulation of embryogenesis and cancer development. Xenopus Dapper (Dpr) was identified as an interacting protein for Dishevelled (Dvl), a Wnt signaling mediator, and modulates Wnt signaling. However, it is largely unclear how Dpr regulates Wnt signaling. Here, we present evidence that human Dpr1, the ortholog of Xenopus Dpr, inhibits Wnt signaling. We have identified the regions responsible for the Dpr-Dvl interaction in both proteins and found that the interaction interface is formed between the DEP (Dishevelled, Egl-10, and pleckstrin) domain of Dvl and the central and the C-terminal regions of Dpr1. The inhibitory function of human Dpr1 requires both its N and C terminus. Overexpression of the C-terminal region corresponding to the last 225 amino acids of Dpr1, in contrast to wild-type Dpr1, enhances Wnt signaling, suggesting a dominant negative function of this region. Furthermore, we have shown that Dpr1 induces Dvl degradation via a lysosome inhibitor-sensitive and proteasome inhibitor-insensitive mechanism. Knockdown of Dpr1 by RNA interference up-regulates endogenous Dvl2 protein. Taken together, our data indicate that the inhibitory activity of Dpr on Wnt signaling is conserved from Xenopus to human and that Dpr1 antagonizes Wnt signaling by inducing Dvl degradation.
Development of Acute Lymphoblastic Leukemia and Myeloproliferative Disorder in Transgenic Mice Expressing p210bcr/abl: A Novel Transgenic Model for Human Ph1-Positive Leukemias (1998)

The Philadelphia (Ph) chromosome can be detected in chronic myelogenous leukemia (CML) and a significant number of acute lymphoblastic leukemia (ALL) cases. Generation of p210bcr/abl, a chimeric protein with enhanced kinase activity, is thought to be involved in the pathogenesis of these diseases. To elucidate the biological properties of p210bcr/abl and to create an animal model for human Ph1-positive leukemias, we generated transgenic mice expressing p210bcr/abl driven by the promoter of the tec gene, a cytoplasmic tyrosine-kinase preferentially expressed in the hematopoietic lineage. The founder mice showed excessive proliferation of lymphoblasts shortly after birth and were diagnosed as suffering from ALL based on surface marker and Southern blot analyses. Expression and enhanced kinase activity of the p210bcr/abl transgene product were detected in the leukemic tissues. In contrast, transgenic progeny exhibited marked granulocyte hyperplasia with thrombocytosis after a long latent period and developed myeloproliferative disorders (MPDs) closely resembling human CML. Expression of p210(bcr/abl) mRNA in the proliferating granulocytes was detected by RT-PCR. In particular, one MPD mouse showed remarkable proliferation of blast cells in the lung, which might represent an extramedullar blast crisis. The results demonstrate that the expression of p210bcr/abl in hematopoietic progenitor cells in transgenic mice can contribute to two clinically distinct hematopoietic malignancies, CML and ALL, indicating that this transgenic system provides a novel transgenic model for human Ph1-positive leukemias.
Rapid Generation of a High Quality Lead for Transforming Growth Factor-β (TGF-β) Type I Receptor (ALK5) (2009)

A novel class of 4-pyridinoxy-2-anilinopyridine-based TGF-beta type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors is reported. The binding mode of this scaffold was successfully predicted by analyzing possible docked binding modes of literature inhibitors and novel synthetic ideas. Compounds such as 19 are potent ALK5 inhibitors with good physicochemical and pharmacokinetic properties and thus represent high quality leads for further optimization.
Characterization of a region of steric interference at the cannabinoid receptor using the active analog approach (1993)

In this paper, it is hypothesized that the distinction between certain active and inactive cannabinoids is that the inactive analogs possess extra volume associated with their carbocyclic rings that may be responsible for an unfavorable interaction at the cannabinoid receptor. Using the active analog approach, a model is developed of a region of steric interference at this receptor using the active cannabinoids (-)-trans-delta 9-tetrahydrocannabinol, (-)-trans-delta 8-tetrahydrocannabinol, (-)-11-hydroxy-beta-hexahydrocannabinol, and a (-)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative and the inactive cannabinoids (9S,6aR)-trans-delta 10,10a-tetrahydrocannabinol and a (+)-trans-11-hydroxy-delta 8-tetrahydrocannabinol dimethylheptyl derivative. Each of these molecules satisfy the cannabinoid pharmacophoric requirements, i.e., a phenolic oxygen at C1 and a side chain of acceptable length at C3. Accessible conformers of each molecule were identified by using the method of molecular mechanics as encoded in the MMP2(85) program. The MAP facility within the Chem-X molecular modeling program was then used to calculate the region of steric interference (termed the receptor essential volume, REV) from these accessible conformers. The calculations revealed an REV region located near the top of the carbocyclic ring in the bottom face of the molecule. In order to explore the use of this REV to account for the activities of other cannabinoids, the minimally active classical cannabinoid (-)-11-hydroxy-alpha-hexahydrocannabinol, an active benzofuran cannabinoid, and the active nonclassical cannabinoid CP-47,497 were then studied. In each case, the activity or minimal activity of each compound can be explained on the basis of the ability of one or more accessible conformer of each molecule to clear the REV calculated here. The results of this study provide an explanation at the molecular level for observed activity differences between cannabinoids that exhibit shape differences associated with their carbocyclic rings.