gebhart/patrepeval huggingface dataset:
Multiepitopic B- and T-Cell Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine (2000)

We have attempted to develop an anti-human immunodeficiency virus (HIV) lipopeptide vaccine with several HIV-specific long peptides modified by C-terminal addition of a single palmitoyl chain. A mixture of six lipopeptides derived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) was prepared. A phase I study was conducted to evaluate immunogenicity and tolerance in lipopeptide vaccination of HIV-1-seronegative volunteers given three injections of either 100, 250, or 500 microg of each lipopeptide, with or without immunoadjuvant (QS21). This report analyzes in detail B- and T-cell responses induced by vaccination. The lipopeptide vaccine elicited strong and multiepitopic B- and T-cell responses. Vaccinated subjects produced specific immunoglobulin G antibodies that recognized the Nef and Gag proteins. After the third injection, helper CD4(+)-T-cell responses as well as specific cytotoxic CD8(+) T cells were also obtained. These CD8(+) T cells were able to recognize naturally processed viral proteins. Finally, specific gamma interferon-secreting CD8(+) T cells were also detected ex vivo.
Role of FAP48 in HIV‐associated lipodystrophy (2012)

The highly active antiretroviral therapy (HAART) can cause a metabolic syndrome consisting of lipodystropy/lipoatrophy, dyslipidemia, and type 2 diabetes mellitus with an increased cardiovascular risk. The pathogenetic bases of HAART-associated lipodystrophy are poorly known. A genetic screen was used to evaluate proteins that are modulated in HIV-1-infected patients with or without lipodystrophy syndrome, that are routinely treated with HAART regimens. The most significant modulation was represented by FAP48 expression. Stable over-expression of FAP48 was able to alter, in vitro, adipogenesis, acting both on calcineurin and glucocorticoid pathways. Finally, we demonstrated that FAP48 over-expression was able to influence the capacity of some HIV drugs, Saquinavir and Efavirenz, but not Stavudine, Amprenavir, and Indinavir to inhibit adipocyte formation. In conclusion, this molecule could be a potential target for novel therapeutic approaches to the HAART related lipodystrophy in HIV patients.
Chromosomes of Human Cancer Cells (1962)

Case 21: Tumour cells were identified in the circula- ting blood. Three-day blood culture revealed one coll with 76 chromosomes, the rest being normal.
The Acid-Mediated Denaturation Pathway of Transthyretin Yields a Conformational Intermediate That Can Self-Assemble into Amyloid (1996)

Transthyretin (TTR) amyloid fibril formation is observed during partial acid denaturation and while refolding acid-denatured TTR, implying that amyloid fibril formation results from the self-assembly of a conformational intermediate. The acid denaturation pathway of TTR has been studied in detail herein employing a variety of biophysical methods to characterize the intermediate(s) capable of amyloid fibril formation. At physiological concentrations, tetrameric TTR remains associated from pH 7 to pH 5 and is incapable of amyloid fibril formation. Tetrameric TTR dissociates to a monomer in a process that is dependent on both pH and protein concentration below pH 5. The extent of amyloid fibril formation correlates with the concentration of the TTR monomer having an altered, but defined, tertiary structure over the pH range of 5.0-3.9. The inherent Trp fluorescence-monitored denaturation curve of TTR exhibits a plateau over the pH range where amyloid fibril formation is observed (albeit at a higher concentration), implying that a steady-state concentration of the amyloidogenic intermediate with an altered tertiary structure is being detected. Interestingly, 1-anilino-8-naphthalenesulfonate fluorescence is at a minimum at the pH associated with maximal amyloid fibril formation (pH 4.4), implying that the amyloidogenic intermediate does not have a high extent of hydrophobic surface area exposed, consistent with a defined tertiary structure. Transthyretin has two Trp residues in its primary structure, Trp-41 and Trp-79, which are conveniently located far apart in the tertiary structure of TTR. Replacement of each Trp with Phe affords two single Trp containing variants which were used to probe local pH-dependent tertiary structural changes proximal to these chromophores. The pH-dependent fluorescence behavior of the Trp-79-Phe mutant strongly suggests that Trp-41 is located near the site of the tertiary structural rearrangement that occurs in the formation of the monomeric amyloidogenic intermediate, likely involving the C-strand-loop-D-strand region. Upon further acidification of TTR (below pH 4.4), the structurally defined monomeric amyloidogenic intermediate begins to adopt alternative conformations that are not amyloidogenic, ultimately forming an A-state conformation below pH 3 which is also not amyloidogenic. In summary, analytical equilibrium ultracentrifugation, SDS-PAGE, far- and near-UV CD, fluorescence, and light scattering studies suggest that the amyloidogenic intermediate is a monomeric predominantly beta-sheet structure having a well-defined tertiary structure.
Direct Interaction of the Spinal Muscular Atrophy Disease Protein SMN with the Small Nucleolar RNA-associated Protein Fibrillarin (2001)

Disruption of the survival motor neuron (SMN) gene leads to selective loss of spinal motor neurons, resulting in the fatal human neurodegenerative disorder spinal muscular atrophy (SMA). SMN has been shown to function in spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis and pre-mRNA splicing. We have demonstrated that SMN also interacts with fibrillarin, a highly conserved nucleolar protein that is associated with all Box C/D small nucleolar RNAs and functions in processing and modification of rRNA. Fibrillarin and SMN co-immunoprecipitate from HeLa cell extracts indicating that the proteins exist as a complex in vivo. Furthermore, in vitro binding studies indicate that the interaction between SMN and fibrillarin is direct and salt-stable. We show that the glycine/arginine-rich domain of fibrillarin is necessary and sufficient for SMN binding and that the region of SMN encoded by exon 3, including the Tudor domain, mediates the binding of fibrillarin. Tudor domain missense mutations, including one found in an SMA patient, impair the interaction between SMN and fibrillarin (as well as the common snRNP protein SmB). Our results suggest a function for SMN in small nucleolar RNP biogenesis (akin to its known role as an snRNP assembly factor) and reveal a potential link between small nucleolar RNP biogenesis and SMA.
Increased Levels of Nuclear SREBP-1c Associated with Fatty Livers in Two Mouse Models of Diabetes Mellitus (1999)

Hepatic steatosis is common in non-insulin-dependent diabetes and can be associated with fibrosis and cirrhosis in a subset of individuals. Increased rates of fatty acid synthesis have been reported in livers from rodent models of diabetes and may contribute to the development of steatosis. Sterol regulatory element-binding proteins (SREBPs) are a family of regulated transcription factors that stimulate lipid synthesis in liver. In the current studies, we measured the content of SREBPs in livers from two mouse models of diabetes, obese ob/ob mice and transgenic aP2-SREBP-1c436 (aP2-SREBP-1c) mice that overexpress nuclear SREBP-1c only in adipose tissue. The aP2-SREBP-1c mice exhibit a syndrome that resembles congenital generalized lipodystrophy in humans. Both lines of mice develop hyperinsulinemia, hyperglycemia, and hepatic steatosis. Nuclear SREBP-1c protein levels were significantly elevated in livers from ob/ob and aP2-SREBP-1c mice compared with wild-type mice. Increased nuclear SREBP-1c protein was associated with elevated mRNA levels for known SREBP target genes involved in fatty acid biosynthesis, which led to significantly higher rates of hepatic fatty acid synthesis in vivo. These studies suggest that increased levels of nuclear SREBP-1c contribute to the elevated rates of hepatic fatty acid synthesis that leads to steatosis in diabetic mice.
Mre11-Dependent Degradation of Stalled DNA Replication Forks Is Prevented by BRCA2 and PARP1 (2012)

PARP inhibitors are currently being used in clinical trials to treat BRCA1- or BRCA2-defective tumors, based on the synthetic lethal interaction between PARP1 and BRCA1/2-mediated homologous recombination (HR). However, the molecular mechanisms that drive this synthetic lethality remain unclear. Here, we show increased levels of Mre11, a key component of MRN (Mre11-Rad50-Nbs1) complex that plays a role in the restart of stalled replication forks and enhanced resection at stalled replication forks in BRCA2-deficient cells. BRCA2-deficient cells also showed hypersensitivity to the Mre11 inhibitor mirin. Interestingly, PARP1 activity was required to protect stalled forks from Mre11-dependent degradation. Resistance to PARP inhibition in BRCA2-mutant cells led to reduced levels of Mre11 foci and also rescued their sensitivity to mirin. Taken together, our findings not only show that Mre11 activity is required for the survival of BRCA2 mutant cells but also elucidate roles for both the BRCA2 and PARP1 proteins in protecting stalled replication forks, which offers insight into the molecular mechanisms of the synthetic lethality between BRCA2 and PARP1.
The biochemistry of erythropoietin: an approach to its mode of action. (1980)

The elucidation of the mechanism of action of erythropoietin depends upon a detailed assessment of its effects at the molecular level. We have now begun to examine the effects of human erythropoietin and other inducers on clonal lines of Rauscher murine erythroleukemia cells. Over 100 clonal lines have been examined by assessing the hemglobinization of colonies grown in plasma clot culture in response to erythropoietin and dimethylsulfoxide. Many of the clones respond to both inducers. However, some clones respond only to erythropoietin. The cells also differentiate in suspension culture, exhibiting striking morphological changes characteristic of erythroid development. This system should serve as an excellent model for the study of control mechanisms in erythropoiesis.
Optoelectronic Integrated Circuits For High Speed Signal Processing (1986)

Advances in computational speed and system complexity are pro-ceeding at a rapid pace. As systems become more complex and demands for computation speed increase, parallel processing becomes the solution to meet-ing the requirements for future systems. A significant bottleneck in these and other systems is interconnect and communication problems between chips and subsystems. In addition, communication systems designers need rugged and reliable high speed transmitters and receivers. This paper discusses the design, development, and performance of GaAs optoelectronic integrated circuits for application in optical interconnection control and signal processing. We review the requirements and approaches for realization of practical optical intercon-nects and report on work in progress at Rockwell. Performance and design criteria of optical transmitters and receivers as well as data obtained on 1:8 demultiplexed receivers are given.
Long-term culture of capillary endothelial cells. (1979)

Capillary endothelial cells from rats, calves, and humans, have been carried in long-term culture. Bovine capillary endothelial cells have been cloned and maintained by serial passage for longer than 8 months. This prolonged culture was accomplished by using tumor-conditioned medium, gelatin-coated plates, and a method of enriching cells in primary culture. Cultured bovine capillary endothelial cells produce Factor VIII antigen and angiotensin-converting enzyme, but do not have Weibel-Palade bodies. Human cells do contain Weibel-Palade bodies. Capillary endothelial cells are distinguished from aortic endothelial cells by their requirement for conditioned medium. Bovine capillary endothelial cells in regular medium grow slowly with a mean doubling time of 67 hr and eventually die. In tumor-conditioned medium, these cells grow rapidly with a doubling time of 28 hr and continue to proliferate for as long as the tumor-conditioned medium is present. In contrast, bovine aortic endothelial cells grow as rapidly in regular medium as in tumor-conditioned medium. This method allows the production of pure capillary endothelial cells that may prove useful for studies of tumor angiogenesis, metastatic mechanisms, and the role of capillary endothelium in other pathologic states.
Dry Powder versus Intravenous and Nebulized Gentamicin in Cystic Fibrosis and Bronchiectasis: A Pilot Study (1999)

Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonas aeruginosa (Psa). Traditionally, aerosolized antibiotics are delivered by liquid nebulization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially safe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intravenously. The study was done according to a randomized, single-dose, and triple crossover protocol. Ten patients with CF or non-CF bronchiectasis and chronically infected with Psa were recruited. Patients received a single dose of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by intravenous infusion. In seven of the 10 patients, the minimum inhibitory concentration (MIC) was achieved in sputum after DPI and SVN, with mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 microgram/g sputum (range: 2.2 to 23.9 microgram/g) and 97.2 microgram/g sputum (range: 0.3 to 194.2 microgram/g), respectively, whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIC. Gentamicin given by DPI and SVN significantly decreased the sputum Psa density (p < 0.05), by almost one order of magnitude. No significant decline in bacterial counts was observed after intravenous gentamicin. When gentamicin was inhaled, blood concentrations were minimal, and were below concentrations known to cause systemic toxicity. For treatment of Psa infections susceptible to gentamicin, gentamicin administration by DPI appeared to be as efficient as by SVN, despite the delivery of a 7-fold lower dose to the airways.
Sequence-Specific Molecular Lithography on Single DNA Molecules (2002)

Recent advances in the realization of individual molecular-scale electronic devices emphasize the need for novel tools and concepts capable of assembling such devices into large-scale functional circuits. We demonstrated sequence-specific molecular lithography on substrate DNA molecules by harnessing homologous recombination by RecA protein. In a sequence-specific manner, we patterned the coating of DNA with metal, localized labeled molecular objects and grew metal islands on specific sites along the DNA substrate, and generated molecularly accurate stable DNA junctions for patterning the DNA substrate connectivity. In our molecular lithography, the information encoded in the DNA molecules replaces the masks used in conventional microelectronics, and the RecA protein serves as the resist. The molecular lithography works with high resolution over a broad range of length scales from nanometers to many micrometers.
Superconductivity at 155 K (1987)

Transition to a superconducting zero-resistance state at 155 K is observed for the first time in bulk material. A new five-element compound has been synthesized with nominal composition ${\mathrm{Y}}_{1}$${\mathrm{Ba}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{F}}_{2}$${\mathrm{O}}_{\mathrm{y}}$@B. Fluorine plays a critical role in achieving this effect. X-ray diffraction and electron microprobe analysis indicate that the samples are multiphasic. Evidence is presented that the samples contain superconducting phases with onset temperatures considerably above 155 K. Magnetic measurements suggest a flux-trapping effect below 260 K, and diamagnetic deviations from Curie-Weiss behavior in the range 250 K\ensuremath{\le}T\ensuremath{\le}100 K indicate a Meissner effect in a small superconducting volume fraction.
Acute and Chronic Alcohol Exposure Impair the Phagocytosis of Apoptotic Cells and Enhance the Pulmonary Inflammatory Response (2010)

Acute alcohol exposure impairs pulmonary efferocytosis, whereas exposure to chronic alcohol is only associated with impaired efferocytosis following LPS-induced lung injury. Both forms of alcohol exposure are associated with increased alveolar neutrophil numbers in response to LPS. The acute effects of alcohol on efferocytosis appear to be mediated, at least in part, by RhoA-independent activation of ROCK. Further studies are needed to dissect the differences between the effects of acute and chronic alcohol exposure on efferocytosis and to determine the effects of alcohol on alternative activators of ROCK.
Micromachined array tip for multifocus fiber-based optical coherence tomography (2004)

High-resolution optical coherence tomography demands a large detector bandwidth and a high numerical aperture for real-time imaging, which is difficult to achieve over a large imaging depth. To resolve these conflicting requirements we propose a novel multifocus fiber-based optical coherence tomography system with a micromachined array tip. We demonstrate the fabrication of a prototype four-channel tip that maintains a 9-14-microm spot diameter with more than 500 microm of imaging depth. Images of a resolution target and a human tooth were obtained with this tip by use of a four-channel cascaded Michelson fiber-optic interferometer, scanned simultaneously at 8 kHz with geometric power distribution across the four channels.
Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing. (1985)

Rabbits of the Basilea strain do not produce normal K1b9 light chains but continue to produce immunoglobulins with light chains of the rare K2 isotype and of lambda type. To understand the molecular basis for this unusual expression of kappa light chains in Basilea rabbits, we undertook an analysis of their kappa genes. We isolated and sequenced the mutant kappa 1b9 gene and found a substitution of A for G in the highly conserved AG dinucleotide of the 3' acceptor splice site. Although we cannot rule out additional alterations of portions of the gene we did not sequence, this spontaneous change of the G found in the normal gene provides a likely molecular explanation for the loss of K1 light chain expression in Basilea rabbits.
Protective effect of SK&F 86002, a novel dual inhibitor of arachidonic acid metabolism, in murine models of endotoxin shock: inhibition of tumor necrosis factor as a possible mechanism of action. (1989)

The effect of a new, structurally novel, dual inhibitor of arachidonic acid (AA) metabolism, SK&F 86002, was studied in two murine models of endotoxin shock. The first model was the injection of C57BL/6 mice with lipopolysaccharide (LPS) in combination with D-galactosamine (D-gal), which resulted in death within 6-48 hr. Treatment of these mice with SK&F 86002 (100 mg/kg, p.o.) 30 min to 2 hr prior to the administration of D-gal and LPS protected the animals from mortality. Protection was also provided by treatment with the corticosteroid dexamethasone, whereas only partial protection was afforded by the dual inhibitor of AA metabolism phenidone and the cyclooxygenase inhibitors naproxen and indomethacin. In a similar dosing protocol, SK&F 86002 also protected mice in a second endotoxin shock model in which mice sensitized with Proprionibacterium acnes received LPS 10 days later. Moreover, partial protection was obtained when SK&F 86002 was administered therapeutically after LPS injection. The administration of SK&F 86002 to P. acnes/LPS-treated mice decreased serum levels of tumor necrosis factor (TNF), which was not observed following naproxen or indomethacin treatment. Consistent with the role of TNF in this model of endotoxin shock was the observation that treatment with antibodies against TNF also prevented or reduced mortality.
Selective Preparation of Unsymmetric Isoxazole from Enones (1981)

We recently succeeded in preparation of unsymmetric isoxazoles from a-bromoenones with hydroxylamine.When the mixture of hydroxylamine hydrochloride and
Characterization of the Human Tryptophan Hydroxylase Gene Promoter (1995)

We isolated and sequenced 2,117 nucleotides of the promoter region of the human tryptophan hydroxylase (TPH) gene. Transient transfection in pinealocyte cultures and PC12 cells was used to investigate the human TPH (hTPH) gene promoter activity and its regulation by the cAMP signaling pathway. A region of 2,117 base pairs upstream of the transcription initiation site of the hTPH gene efficiently directed the transcription of a luciferase reporter gene but not in a cell-specific manner. The hTPH promoter activity was significantly enhanced by a cyclic AMP analog in the two cell types. Deletion analysis showed that the promoter region from -73 to +2 is sufficient to direct cAMP-dependent transcription, although it does not contain a motif exhibiting a significant identity to the cAMP-responsive element (CRE) or AP-2 binding site. Following site-directed mutagenesis of the region between -73 and -51, an inverted CCAAT box motif was identified as essential for cAMP inducibility of the hTPH promoter. This sequence between -73 and -51 alone allowed cAMP enhancement of transcription when fused to a heterologous promoter. Additionally, electrophoretic mobility shift assays showed that a specific protein-DNA complex is formed between an oligonucleotide corresponding to the inverted CCAAT box motif and nuclear proteins from pinealocytes treated or not treated with cAMP. Thus cAMP responsiveness of hTPH gene expression is mediated by a cis-acting element, which shares strong identity with an inverted CCAAT box and which binds to a constitutively produced nuclear factor.
Purification and Characterization of a Keratinase from a Feather-Degrading Bacillus licheniformis Strain (1992)

A keratinase was isolated from the culture medium of feather-degrading Bacillus licheniformis PWD-1 by use of an assay of the hydrolysis of azokeratin. Membrane ultrafiltration and carboxymethyl cellulose ion-exchange and Sephadex G-75 gel chromatographies were used to purify the enzyme. The specific activity of the purified keratinase relative to that in the original medium was approximately 70-fold. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and Sephadex G-75 chromatography indicated that the purified keratinase is monomeric and has a molecular mass of 33 kDa. The optimum pH and the pI were determined to be 7.5 and 7.25, respectively. Under standard assay conditions, the apparent temperature optimum was 50 degrees C. The enzyme is stable when stored at -20 degrees C. The purified keratinase hydrolyzes a broad range of substrates and displays higher proteolytic activity than most proteases. In practical applications, keratinase is a useful enzyme for promoting the hydrolysis of feather keratin and improving the digestibility of feather meal.
Effects of carbon on the electrical and optical properties of InN, GaN, and AlN (2014)

Carbon is a common impurity in the group-III nitrides, often unintentionally incorporated during growth. Nevertheless, the properties of carbon impurities in the nitrides are still not fully understood. We investigate the impact of carbon impurities on the electrical and optical properties of GaN, AlN, and InN using density functional calculations based on a hybrid functional. We examine the stability of substitutional and interstitial configurations as a function of the Fermi-level position and chemical potentials. In all nitrides studied here, C${}_{\mathrm{N}}$ acts as a deep acceptor and gives rise to deep, broad photoluminescence bands. Carbon on the cation site acts as a shallow donor in InN and GaN, but behaves as a $DX$ center in AlN. A split interstitial is the most stable configuration for the C impurity in InN, where it acts as a double donor and likely contributes to $n$-type conductivity.