gebhart/patrepeval huggingface dataset:
Antigen Presentation Assays to Investigate Uncharacterized Immunoregulatory Genes (2012)

Antigen presentation to T lymphocytes is the seminal triggering event of the specific immune response, and poxviruses encode immunomodulatory genes that disrupt this process. Discovery of viral proteins that interfere with steps in the antigen presentation process requires a robust, easily manipulated antigen-presenting and T lymphocyte response system. Use of fresh primary antigen-presenting cells (APC) is preferable because cell lines that can present antigen in vitro are often not representative of APC in vivo and are typically weak stimulators. To study immunomodulatory poxvirus genes, we have used infected primary rat macrophages to present a model antigen, the myelin basic protein peptide, to a cognate CD4+ RsL11 T cell clone. Using this system, viruses can be assessed for difference in immunomodulation, and viral gene functions may also be assayed by comparing effects of wild type virus and mutant viruses (e.g., a deletion in the putative immunomodulatory gene). While antigen presentation can be thought of as a single event, it can also be considered as a larger process comprising multiple steps including: antigen acquisition, antigen processing, peptide loading onto MHC molecules, transport to the surface, MHC binding to T cell receptor, interaction of costimulatory molecules, cell signaling, cytokine synthesis by both cells, and proliferation of antigen specific T lymphocytes. This system allows for the initial determination of whether there is a phenotype and then also allows the stepwise deconstruction of the system to analyze this process at several points to focus in on the mechanism of immunomodulation. We have used this model system to elucidate the function of a highly conserved but previously uncharacterized poxvirus gene that we showed was important for virulence in rodents. The experimental system developed should be broadly applicable to analyzing viral effects on immunity.
Parathyroid hormone stimulates ecto-5'-nucleotidase activity in renal epithelial cells: role of protein kinase-C (1995)

PTH-induced phosphaturia is exerted in part by cAMP added to the renal tubular lumen under the influence of the hormone. Modulation of renal phosphate transport by luminal cAMP requires degradation of the nucleotide into adenosine by brush-border membrane ectoenzymes, among them ecto-5'-nucleotidase (5'-NU). Hormonal modulation of 5'-NU activity was evaluated in cultured opossum kidney cells. PTH (1-100 nM) stimulated 5'-NU in a time-, concentration-, and protein synthesis-dependent manner. The effect of PTH-(1-34) was mimicked by PTH-(3-34), which does not activates adenylate cyclase, and by phorbol 12-myristate 13-acetate (PMA), but not by forskolin or (Bu)2cAMP. Down-regulation or pharmacological inhibition of protein kinase-C (PKC) abolished the effect of PTH fragments and PMA. PTH fragments increased intracellular Ca2+ and translocated PKC activity to the membrane. PTH or PMA did not affect 5'-NU messenger RNA content. Inhibition of sodium-phosphate cotransport by extracellular cAMP was decreased by 5'-NU inhibition and was magnified by PTH. These results indicate that 1) PTH stimulates 5'-NU activity in renal proximal tubular cells in a manner involving PKC activation and de novo protein synthesis; and 2) this effect participates in PTH modulation of renal phosphate transport.
Nitrosourea Derivatives of 3',4'-Didemethoxy-3',4'-dioxo-4-deoxypodophyllotoxin and Urea Derivatives of 4'-O-Demethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase (1994)

Nitrosourea derivatives of Y.4'-didemethoxy-3',4'-dioxo-4deoxypodophyllotoxin and urea derivatives of 4'-Q-demethylpodophyllotoxin were synthesized and evaluated for their inhibitory activity against DNA topoisomerase II and KB cells.Although the 4P-X-nitrosoureido compounds demonstrated good inhibitory activity against topoisomerase ll.they were found to possess low activity for protein linked-DNA complex formation ability.On the other hand, the 4p-ureido compounds exhibited better or similar activity compared to 1, etoposide.Etoposide (1: VP-16) and teniposide (2) are known to be potent chemotherapeutic agents for the treament of small-cell lung carcinoma, testicular cancer, and malignant lymphoma.Since they inhibit the catalytic activity of DNA topoisomerase II by stabilizing a cleavable enzyme-DNA complex, in which DNA is cleaved and covalently linked to the enzyme, DNA topoisomerase 1 1 has been considered as a target enzyme of 1.2 We t Dedicated to Dr. Arnold Brossi on the occasion of hi 70th birthday.
VEGF TrapR1R2 Suppresses Experimental Corneal Angiogenesis (2010)

Corneal keratocytes express VEGF after bFGF stimulation and bFGF-induced corneal NV is blocked by intraperitoneal VEGF TrapR1R2 administration. Systemic administration of VEGF TrapR1R2 may have potential therapeutic applications in the management of corneal NV.
Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells (2008)

IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55(-/-) but not p75(-/-) mice. The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55(-/-) mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. Treatment of macrophages with rTNF also inhibited p40 production in vitro. These findings indicate that at least one of the ways in which TNF regulates Th1/Th17 responses in arthritis is by down-regulating the expression of p40. Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells.
Role of ultrasound in the diagnosis of testicular lesions (2011)

Ultrasound is the main imaging technique in the assessment of the scrotal contents, providing unparalleled imaging of exquisite resolution. Ultrasound is effectively the sole scrotal imaging technique that a patient will undergo prior to definitive surgery. The accurate assessment of focal intratesticular lesions in the adult patient is of paramount importance, although most focal lesions will be malignant and require an orchidectomy, the recognition of the benign entity is essential to the individual patient. This article covers the salient features of benign and malignant focal intratesticular lesions to allow a confident diagnosis and to prevent unnecessary orchidectomy. We detail the range of intratesticular malignancies from germ cell tumors to lymphoma and metastases. Operator confidence is necessary to establish a benign diagnosis and we highlight important benign lesions that may benefit from a ‘watch and wait’ policy, such as infarction, abscess formation, focal orchitis, rete testis; as well as ...
Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate (2015)

Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation.
Low moisture polymer adhesive for hermetic packages (1992)

The chemical and physical characteristics of a novel thermoset die-attach paste developed to meet the low moisture requirement of attaching Si chips to ceramic substrates in hermetic packages and its functional performance as a die-attach medium are discussed. The combination of a glass transition temperature around 240 degrees C and high thermal stability up to 360 degrees C provides significant performance enhancement over conventional epoxies. In addition, the material exhibits high adhesive strength and very low stress on the die. Experimental results show that the moisture content in the cavity of a Au-Sn solder sealed ceramic package is less than 1000 ppm. The low moisture characteristic is found to be an inherent property of the material. Reliability tests such as thermal cycling, high-temperature storage showed that the low moisture level is still maintained after 1000 cycles or 1000 h at 150 degrees C. Results of the thermal performance of the material on thermal test chips are discussed and compared to results for silver-filled glass.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Receptor Component of the Chloroplast Protein Translocation Machinery (1994)

The chloroplast outer envelope protein OEP86 functions as a receptor in precursor protein translocation into chloroplasts. Sequence analysis suggests that the precursor of OEP86 is directed to the chloroplast outer envelope by a cleavable, negatively charged, and unusually long amino-terminal peptide. This presequence is unlike other potential targeting signals and suggests the existence of another membrane insertion pathway. Insertion of precursor OEP86 required the hydrolysis of adenosine triphosphate and the existence of surface exposed chloroplast membrane components, and it was not competed by another precursor protein destined for the internal plastid compartments.
Assessing the antioxidative status in critically ill patients (2004)

The occurrence of oxidative stress in critically ill patients is associated with a poor prognosis. The measurement of a cluster of assays representative of the quantification of reactive species or of antioxidants may improve the usefulness of therapeutic intervention and increase knowledge of pathophysiological alterations.
Practical applications of 2-D optical proximity corrections for enhanced performance of 0.25 μm random logic devices (2002)

Simplified 2-D Optical Proximity Correction (OPC) algorithms have been devised, calibrated and implemented on a state-of-the-art 0.25 /spl mu/m random logic process in order to reduce metal line pullback on critical layers. The techniques used are rules-based, but are characterized by fast and robust data conversion algorithms, calibrations based on actual process data, and inspectability of the resultant OPC corrected reticles. Application to local interconnect and metal patterning has corrected fundamental yield-limiting mechanisms in these levels.
Single-Antibody, Targeted Nanoparticle Delivery of Camptothecin (2013)

We have developed a new method for assembling targeted nanoparticles that utilizes the complexation between targeting agents that contain boronic acids and polymer-drug conjugates that possess diols. Here, we report the first in vivo, antitumor results of a nanoparticle formed via this new assembly methodology. A nanoparticle consisting of a mucic acid polymer conjugate of camptothecin (CPT), MAP-CPT, and containing on average one Herceptin antibody is investigated in nude mice bearing HER2 overexpressing BT-474 human breast cancer tumors. Nontargeted MAP-CPT and antibody-containing MAP-CPT nanoparticles of ca. 30-40 nm diameter and slightly negative zeta potential show prolonged in vivo circulation and similar biodistributions after intravenous tail vein injections in mice. The maximum tolerated dose (MTD) of the nontargeted and Herceptin-containing MAP-CPT nanoparticles is found to be 10 and 8 mg of CPT/kg, respectively, in mice. Mice bearing BT-474 human breast tumors treated with nontargeted MAP-CPT nanoparticles at 8 mg of CPT/kg show significant tumor growth inhibition (mean tumor volume of 63 mm(3)) when compared to irinotecan at 80 mg/kg (mean tumor volume of 575 mm(3)) and CPT at 8 mg/kg (mean tumor volume of 808 mm(3)) at the end of the study. Herceptin antibody treatment at 5.9 mg/kg results in complete tumor regressions in 5 out of 8 mice, with a mean tumor volume of 60 mm(3) at the end of the study. Mice treated with MAP-CPT nanoparticles at 1 mg of CPT/kg do not show tumor inhibition. However, all mice receiving administrations of MAP-CPT nanoparticles (1 mg of CPT/kg) that contain on average a single Herceptin molecule per nanoparticle (5.9 mg of Herceptin equivalent/kg) show complete tumor regression by the end of the study. These results demonstrate that the antitumor efficacy of nanoparticles carrying anticancer drugs can be enhanced by incorporating on average a single antibody.
A Frequency Shift Dielectric Soil Moisture Sensor (1978)

Field implantable and laboratory sensors for the measurement of moisture in soil based on the increase of soil dielectric permittivity with volume fraction of water were developed. A typical sensor consists of a case containing a high-frequency (31-MHz) oscillator whose frequency determining resonance LC network is coupled to the built-in electrode via a capacitor T network. Increases in moisture cause a shift in the resonance frequency, which is detected by an external differential frequency counter or readout. The T network and electrode electronic switches reduce the undesirable influence of soil conductivity on the frequency shift. Although the sensor contains active elements, it acts as a passive transducer since power is supplied to the sensor from the readout unit through the two-conductor cable which transmits the RF.
The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene (2007)

Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.
dewA encodes a fungal hydrophobin component of the Aspergillus spore wall (1995)

An anonymous cDNA clone, pCAN4, was shown previously to correspond to an mRNA that accumulates preferentially during asexual sporulation of the filamentous fungus Aspergillus nidulans. The peptide encoded by pCAN4 is a fungal hydrophobin, a group of small, hydrophobic cell wall proteins. When the CAN4 gene was disrupted, conidia and conidiophores appeared to be normal, but sporulating colonies wetted more rapidly with detergent solutions than did the wild type. We renamed CAN4 dewA for the detergent wettable phenotype and mapped it to chromosome V, 24 map units from cysC. The A. nidulans rodA gene also encodes a sporulation-specific fungal hydrophobin. Spores of a dewA- rodA- double mutant were less hydrophobic than those of either mutant alone, showing that dewA and rodA contribute independently to spore-wall hydrophobicity. Immunolocalization of DewA by epitope tagging demonstrated that DewA is present in the spore wall, but not in the walls of germ tubes, hyphae or cells of the spore-producing conidiophore. We conclude that dewA encodes a new fungal hydrophobin component of the conidial wall.
Query-adaptive shape topic mining for hand-drawn sketch recognition (2012)

In this work, we study the problem of hand-drawn sketch recognition. Due to large intra-class variations presented in hand-drawn sketches, most of existing work was limited to a particular domain or limited pre-defined classes. Different from existing work, we target at developing a general sketch recognition system, to recognize any semantically meaningful object that a child can recognize. To increase the recognition coverage, a web-scale clipart image collection is leveraged as the knowledge base of the recognition system. To alleviate the problems of intra-class shape variation and inter-class shape ambiguity in this unconstrained situation, a query-adaptive shape topic model is proposed to mine object topics and shape topics related to the sketch, in which, multiple layers of information such as sketch, object, shape, image, and semantic labels are modeled in a generative process. Besides sketch recognition, the proposed topic model can also be used for related applications such as sketch tagging, image tagging, and sketch-based image search. Extensive experiments on different applications show the effectiveness of the proposed topic model and the recognition system.
Evidence for involvement of the proteasome complex (26S) and NFkappaB in IL-1beta-induced nitric oxide and prostaglandin production by rat islets and RINm5F cells. (1998)

Interleukin-1beta (IL-1beta) has been implicated as an effector molecule of beta-cell destruction in autoimmune diabetes. IL-1beta inhibits insulin secretion from pancreatic beta-cells by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide. IL-1beta also induces the coexpression of the inducible isoform of cyclooxygenase (COX-2) that results in the overproduction of proinflammatory prostaglandins. The current studies were designed to characterize the involvement of protease(s) in the signaling pathway of IL-1beta-induced iNOS and COX-2 expression by rat islets and transformed rat pancreatic beta-cells. Because of the limitations of cell numbers of purified primary beta-cells obtained from rat islets, biochemical and molecular studies were performed using the rat insulinoma beta-cell line RINm5F. A serine protease inhibitor, Nalpha-P-tosyl-L-lysine chloromethyl ketone (TLCK), and a proteasome complex (26S) inhibitor, MG 132, inhibited IL-1beta-induced nitrite formation, an oxidation product of nitric oxide produced by iNOS, in a concentration-dependent manner, with complete inhibition observed at 100 micromol/l and 10 micromol/l, respectively. Both TLCK and MG 132 also inhibited iNOS gene expression at the level of mRNA and protein. In an analogous manner, TLCK (100 micromol/l) and MG 132 (10 micromol/l) inhibited IL-1beta-induced COX-2 enzyme activity (PGE2 formation) and COX-2 gene expression at the level of mRNA and protein. In human islets, the proteasome inhibitor MG 132 also inhibited the formation of the products of iNOS and COX-2 enzyme activity, nitrite, and PGE2, respectively. These findings suggest that the inhibitory action of TLCK and MG 132 on iNOS and COX-2 expression precedes transcription. The transcription factor NFkappaB is essential for activation of a number of cytokine-inducible enzymes and was evaluated as a possible site of protease action necessary for IL-1beta-induced coexpression of iNOS and COX-2. TLCK and MG 132 inhibited both IL-1beta-induced activation of NFkappaB and degradation of IkappaBalpha by islets and RINm5F cells. These results implicate protease activation as an early signaling event in IL-1beta-induced inhibition of beta-cell function. This study also suggests that IL-1beta-induced iNOS and COX-2 coexpression by pancreatic beta-cells share a common signaling pathway in utilizing the proteasome complex (26S) and the transcription factor NFkappaB, and it identifies sites of intervention to prevent the overproduction of their inflammatory products.
Analysis of microRNA-size, small RNAs in Streptococcus mutans by deep sequencing (2011)

MicroRNAs (miRNAs) are important modulators of gene expression in eukaryotic cells. However RNAs of the same size in bacteria have not been specifically discussed previously. Here, we provide a library of miRNA-size RNAs (msRNAs), which were registered by deep sequencing in Streptococcus mutans. Bioinformatic analysis of the whole set revealed more than 900 individual msRNA species. The cellular content of selected msRNAs was verified by quantitative RT-PCR and Northern blotting. The high abundance and discrete size of the subset of registered msRNAs suggest their functional significance, although the precise biological role of the RNA species revealed in S. mutans, which is one of the principle causative agents of dental caries, has to be elucidated.
Recombinant inbred strain and interspecific backcross analysis of molecular markers flanking the murine agouti coat color locus. (1989)

Recombinant inbred strain and interspecific backcross mice were used to create a molecular genetic linkage map of the distal portion of mouse chromosome 2. The orientation and distance of the Ada, Emv-13, Emv-15, Hck-1, Il-1a, Pck-1, Psp, Src-1 and Svp-1 loci from the beta 2-microglobulin locus and the agouti locus were established. Our mapping results have provided the identification of molecular markers both proximal and distal to the agouti locus. The recombinants obtained provide valuable resources for determining the direction of chromosome walking experiments designed to clone sequences at the agouti locus. Comparisons between the mouse and human genome maps suggest that the human homolog of the agouti locus resides on human chromosome 20q. Three loci not present on mouse chromosome 2 were also identified and were provisionally named Psp-2, Hck-2 and Hck-3. The Psp-2 locus maps to mouse chromosome 14. The Hck-2 locus maps near the centromere of mouse chromosome 4 and may identify the Lyn locus. The Hck-3 locus maps near the distal end of mouse chromosome 4 and may identify the Lck locus.