gebhart/patrepeval huggingface dataset:
Advanced Hepatocellular Carcinoma: Treatment with High-Intensity Focused Ultrasound Ablation Combined with Transcatheter Arterial Embolization (2005)

The combination of high-intensity focused ultrasound ablation and TACE is a promising approach in patients with advanced-stage HCC, but large-scale randomized clinical trials are necessary for confirmation.
Epitope-Specific Regulatory T cells Differentially Modulate the CD8 T Cell Response to Respiratory Syncytial Virus in Mice (45.29) (2009)

Abstract RSV infection is the leading cause of lower respiratory disease in infants and young children, accounting for &amp;gt;120,000 hospitalizations each year in the US alone. Although CD8 T cell effector function is key to virus clearance, CD4 T cells coordinate the immune response and can lead to immunopathology. Therefore, they play a central role in the immunity and immunopathogenesis of RSV infection. To facilitate in depth evaluation of RSV-induced CD4 T cell responses we identified two new I-Ab- restricted dominant CD4 T cell epitopes, M213-223 and M227-37, in RSV M and M2 that also contain well characterized CD8 T cell epitopes. CD4 T cells from lung and spleen of RSV-infected CB6F1 mice produce different patterns of IL-2, IFN-γ and other cytokines after peptide stimulation. Novel tetrameric peptide-I-Ab complexes identified 0.5% and 1.6% RSV M- and M2-specific CD4 T cells in lungs of the infected mice. Peptide-stimulated CD4 T cells produced different patterns of regulation on CD8 T cell responses to RSV M and M2 epitopes in vitro. The regulatory function of the CD4 T cell correlated with the level of FoxP3 expression in epitope-specific CD4 T cells Our study demonstrates that the biophysical properties of the epitope may dictate the functional properties of the CD4 T cell response. Understanding how epitope structure influences T cell function will provide new insight into viral pathogenesis and may improve vaccine design.
RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis (2012)

Prostate cancer is the third leading cause of male cancer deaths in the developed world. The current lack of highly specific detection methods and efficient therapeutic agents for advanced disease have been identified as problems requiring further research. The integrins play a vital role in the cross-talk between the cell and extracellular matrix, enhancing the growth, migration, invasion and metastasis of cancer cells. Progression and metastasis of prostate adenocarcinoma is strongly associated with changes in integrin expression, notably abnormal expression and activation of the β3 integrins in tumour cells, which promotes haematogenous spread and tumour growth in bone. As such, influencing integrin cell expression and function using targeted therapeutics represents a potential treatment for bone metastasis, the most common and debilitating complication of advanced prostate cancer. In this review, we highlight the multiple ways in which RGD-binding integrins contribute to prostate cancer progression and metastasis, and identify the rationale for development of multi-integrin antagonists targeting the RGD-binding subfamily as molecularly targeted agents for its treatment.
Using discrete event simulation to evaluate housestaff work schedules (1990)

A discrete-event simulation model of work performed by hospital interns and residents was developed. The model incorporates such complex features as interruptions of one activity by another, involved decision processes by mobile resources, and highly variable work arrival processes. Where historical data were lacking and too expensive to collect, surveys of experts produced sufficient information to use the VISIFIT distribution fitting package to specify input processes. Validation efforts showed that the model accurately predicted the results of changes to the schedule. With its validity established, the model has since been used to investigate the ramifications of alternative systems, including the addition of a night-float team and more help from subspecialty fellows. The consequences of changes in patient load or decreased availability of senior students were also examined. The prospect for regulatory or legislative restrictions on housestaff hours make the model a valuable tool for evaluating scheduling rules and plans. >
Proteome Maps of the Main Human Peripheral Blood Constituents (2009)

Clinical proteome analysis will almost inevitably be confronted with blood constituents. Purified plasma, serum, cell or tissue samples may easily be contaminated with some other constituents, affecting the final proteome analysis result. To recognize proteins which are potentially indicative for the presence of major blood constituents, we purified T cells, monocytes, neutrophils, erythrocytes, platelets and plasma and performed comparative proteome profiling employing 2D-PAGE in addition to shotgun proteomics. By mass analysis, 594 different proteins were identified in the 2D gels. Six of the 594 proteins displayed a highly specific expression pattern. A total of 1774 proteins were identified by shotgun proteomics, including 50 proteins with highly specific expression patterns. Indeed, proteins specific for each of the constituents were successfully identified. All protein lists including mass spectrometry details and expression specificity are freely available via the PRIDE database and the CPL/MUW database. The present protein maps of each of the constituents may serve as references for comparative analyses and will aid the interpretation of proteome profiles of clinical samples.
Glioma cell interactions with fetal rat brain aggregates in vitro and with brain tissue in vivo. (1986)

Two malignant rat neurogenic cell lines have been confronted with reaggregation cultures of fetal rat brain in a stationary culture system. In this organ culture system several morphological aspects of the developing brain are imitated. The malignant cell lines showed invasive and progressive growth into the brain tissue, ending with a completely destroyed aggregate within 10 days of coculture. One cell line (BT5C) showed solid invasion with groups of cells replacing different layers of the brain tissue. A considerable degree of normal cell lysis was seen, both at the edge of invasion and at distant parts of the aggregate. This cell line seemed to activate macrophages in the aggregates. In addition, conditioned medium from these cultures caused degeneration of the brain aggregates. The other cell line (BT4Cn) showed invasion by single cells where the replacement and destruction of the tissue was not accompanied by distant lysis. Both cell lines showed the same pattern of invasion in vitro as was seen in the brains of isogeneic animals in vivo, showing that the individual tumor characteristics were also reflected during invasive growth in organ culture.
Expression of Recombinant Mouse/Human Chimeric Antibody Specific to Human GMP-140/P-selectin (1994)

To construct a mouse/human chimeric antibody, we cloned the genomic DNAs for Ig from a murine hybridoma that produces PL7-6 monoclonal antibody specific to human P-selectin and expressed them in SP2/0 myelomas using a series of pSV2 vectors. Transfected cells that produce the mouse/human chimeric anti-human P-selectin antibody were geneticin-selected and screened by an immunoassay using immobilized antigen. The chimeric antibody, cPL-2R1, expressed by the resultant clone has the murine Ig variable region and the human Ig constant region. The native antibody PL7-6 and the chimeric antibody cPL-2R1 react equally with purified P-selectin and thrombin-stimulated platelets. Competitive inhibition tests demonstrated that the native antibody PL7-6 and the chimeric antibody cPL-2R1 had identical affinity for purified human P-selectin. Thus, although human IgG1 constant region was substituted for the murine counterpart in this chimeric antibody, its specificity and binding affinity for P-selectin was not altered. This chimeric antibody may prove useful when employed in combination with imaging reagents or therapeutic drugs for targeting activated platelets or endothelium in patients with thrombosis or intravascular inflammation.
Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate (2009)

SFN was found to inhibit synovial hyperplasia, activated T cell proliferation, and the production of IL-17 and TNFalpha by rheumatoid T cells in vitro. The antiarthritic and immune regulatory effects of SFN, which were confirmed in vivo, suggest that SFN may offer a possible treatment option for RA.
Regulation of Human Chemokine Receptors CXCR4 (1997)

Members of the chemokine receptor family CCR5 and CXCR4 have recently been shown to be involved in the entry of human immunodeficiency virus (HIV) into target cells. Here, we investigated the regulation of CXCR4 in rat basophilic leukemia cells (RBL-2H3) stably transfected with wild type (Wt CXCR4) or a cytoplasmic tail deletion mutant (DeltaCyto CXCR4) of CXCR4. The ligand, stromal cell derived factor-1 (SDF-1) stimulated higher G-protein activation, inositol phosphate generation, and a more sustained calcium elevation in cells expressing DeltaCyto CXCR4 relative to Wt CXCR4. SDF-1 and phorbol 12-myristate 13-acetate (PMA), but not a membrane permeable cAMP analog induced rapid phosphorylation as well as desensitization of Wt CXCR4. Phosphorylation of DeltaCyto CXCR4 was not detected under any of these conditions. Despite lack of receptor phosphorylation, calcium mobilization by SDF-1 in DeltaCyto CXCR4 cells was partially desensitized by prior treatment with SDF-1. Of interest, the rapid release of calcium was inhibited without affecting the sustained calcium elevation, indicating independent regulatory pathways for these processes. PMA completely inhibited phosphoinositide hydrolysis and calcium mobilization in Wt CXCR4 but only partially inhibited these responses in DeltaCyto CXCR4. cAMP also partially inhibited these responses in both Wt CXCR4 and DeltaCyto CXCR4. SDF-1, PMA, and cAMP caused phosphorylation of phospholipase Cbeta3 in Wt and DeltaCyto CXCR4 cells. Both SDF-1 as well as PMA induced rapid internalization of Wt CXCR4. SDF-1 but not PMA induced internalization of DeltaCyto CXCR4 albeit at reduced levels relative to Wt CXCR4. These results indicate that signaling and internalization of CXCR4 are regulated by receptor phosphorylation dependent and independent mechanisms. Desensitization of CXCR4 signaling, independent of receptor phosphorylation, appears to be a consequence of the phosphorylation of phospholipase Cbeta3.
Unusual cutaneous features associated with a heterozygous gain-of-function mutation inIFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes (2015)

Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi-Goutières syndrome. To date, seven genes related to Aicardi-Goutières syndrome have been described. The most recently described encodes the cytosolic double-stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon-mediated innate immune response. Enhanced type I interferon signalling secondary to gain-of-function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi-Goutières syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon-stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi-Goutières syndrome and Singleton-Merten syndrome.
Role of the Heme Active Site and Protein Environment in Structure, Spectra, and Function of the Cytochrome P450s (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRole of the Heme Active Site and Protein Environment in Structure, Spectra, and Function of the Cytochrome P450sGilda H. Loew and Danni L. HarrisView Author Information Molecular Research Institute, 2495 Old Middlefield Way, Mountain View, California 94043 Cite this: Chem. Rev. 2000, 100, 2, 407–420Publication Date (Web):February 9, 2000Publication History Received14 October 1999Published online9 February 2000Published inissue 1 February 2000https://pubs.acs.org/doi/10.1021/cr980389xhttps://doi.org/10.1021/cr980389xresearch-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1974Altmetric-Citations256LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Bioinorganic chemistry,Ligands,Peptides and proteins,Pyrroles,Quantum mechanics Get e-Alerts
VPV-videotext programs videorecorder (1988)

The VPV (video programs video recorder) systems standard allows unequivocal recognition and interpretation of video cassette recorded (VCR) timer preprogramming data in a teletext program schedule. Together with a machine-readable page memory this makes it possible to implement fully-automatic timer-programming procedures in the VCR. The VPV specification defines data formats and rules for their correlation; it gives a number of example program tables to show the broadcaster how to apply the standards. For the VCR manufacturer, it recommends how to process the VPV program pages.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1 (1989)

(1) Many cell types secrete insulin-like growth factor (IGF)-binding proteins that can be expected to sequester free IGF and modify the biological activities of the growth factors. (2) A binding protein purified from bovine kidney (MDBK) cells potently inhibited the ability of IGF-2 to stimulate DNA synthesis or protein accumulation as well as to reduce rates of protein breakdown in chick embryo fibroblasts. The binding protein did not influence the biological activities of des-(1-3)-IGF-1, while effects on IGF-1 were intermediate. Since the chick embryo fibroblasts contain only the type 1 IGF receptor, the MDBK-cell binding protein must have reduced the accessibility of IGF-2 and IGF-1 to that receptor. Binding to the type 2 receptor on L6 myoblasts was also inhibited. (3) Inhibiting effects on both protein breakdown responsiveness to IGF and IGF binding to cell receptors were also observed with human amniotic fluid binding protein, although here IGF-1 and IGF-2 were equipotent. These results contrast with stimulatory responses on different IGF-1 actions of the same binding protein reported previously [Elgin, Busby & Clemmons (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 3254-3258]. (4) The biological potencies of IGF-1, IGF-2 and des-(1-3)-IGF-1 correlate inversely with their binding to proteins released into the medium by cells, so that the enhanced potency of des-(1-3)-IGF-1 is a consequence of it not binding to purified binding proteins or those released by cultured cells.
Two Pathways of Glutamate Fermentation by Anaerobic Bacteria (1974)

Two pathways are involved in the fermentation of glutamate to acetate, butyrate, carbon dioxide, and ammonia-the methylaspartate and the hydroxyglutarate pathways which are used by Clostridium tetanomorphum and Peptococcus aerogenes, respectively. Although these pathways give rise to the same products, they are easily distinguished by different labeling patterns of the butyrate when [4-(14)C]glutamate is used as substrate. Schmidt degradation of the radioactive butyrate from C. tetanomorphum yielded equally labeled propionate and carbon dioxide, whereas nearly all the radioactivity of the butyrate from P. aerogenes was recovered in the corresponding propionate. This procedure was used as a test for the pathway of glutamate fermentation by 15 strains (9 species) of anaerobic bacteria. The labeling patterns of the butyrate indicate that glutamate is fermented via the methylaspartate pathway by C. tetani, C. cochlearium, and C. saccarobutyricum, and via the hydroxyglutarate pathway by Acidaminococcus fermentans, C. microsporum, Fusobacterium nucleatum, and F. fusiformis. Enzymes specific for each pathway were assayed in crude extracts of the above organisms. 3-Methylaspartase was found only in clostridia which use the methylaspartate pathway, including Clostridium SB4 and C. sticklandii, which probably degrade glutamate to acetate and carbon dioxide by using a second amino acid as hydrogen acceptor. High levels of 2-hydroxyglutarate dehydrogenase were found exclusively in organisms that use the hydroxyglutarate pathway. The data indicate that only two pathways are involved in the fermentation of glutamate by the bacteria analyzed. The methylaspartate pathway appears to be used only by species of Clostridium, whereas the hydroxyglutarate pathway is used by representatives of several genera.
Sensitization to the Lysosomal Cell Death Pathway by Oncogene-Induced Down-regulation of Lysosome-Associated Membrane Proteins 1 and 2 (2008)

Expression and activity of lysosomal cysteine cathepsins correlate with the metastatic capacity and aggressiveness of tumors. Here, we show that transformation of murine embryonic fibroblasts with v-H-ras or c-src(Y527F) changes the distribution, density, and ultrastructure of the lysosomes, decreases the levels of lysosome-associated membrane proteins (LAMP-1 and LAMP-2) in an extracellular signal-regulated kinase (ERK)- and cathepsin-dependent manner, and sensitizes the cells to lysosomal cell death pathways induced by various anticancer drugs (i.e., cisplatin, etoposide, doxorubicin, and siramesine). Importantly, K-ras and erbb2 elicit a similar ERK-mediated activation of cysteine cathepsins, cathepsin-dependent down-regulation of LAMPs, and increased drug sensitivity in human colon and breast carcinoma cells, respectively. Notably, reconstitution of LAMP levels by ectopic expression or by cathepsin inhibitors protects transformed cells against the lysosomal cell death pathway. Furthermore, knockdown of either lamp1 or lamp2 is sufficient to sensitize the cells to siramesine-induced cell death and photo-oxidation-induced lysosomal destabilization. Thus, the transformation-associated ERK-mediated up-regulation of cysteine cathepsin expression and activity leads to a decrease in the levels of LAMPs, which in turn contributes to the enhanced sensitivity of transformed cells to drugs that trigger lysosomal membrane permeabilization. These data indicate that aggressive cancers with high cysteine cathepsin levels are especially sensitive to lysosomal cell death pathways and encourage the further development of lysosome-targeting compounds for cancer therapy.
Nanoparticle Luminescence Thermometry (2002)

A new concept of using luminescent nanoparticles for thermometry is described in this paper. To demonstrate this idea, the temperature-dependent emission characteristics of several luminescent nanoparticles have been investigated. The results show that some of them have a linear response above room temperature, which could be applied to temperature sensing. Semiconductor nanoparticles of CdTe and doped nanoparticles of ZnS:Mn2+ show a reversible linear temperature response over the physiological temperature range and have potential for biomedical thermometry. Double-doped nanoparticles of ZnS:Mn2+,Eu3+ show a different temperature response for each dopant; the ratio of their intensities provides a robust temperature measurement approach. Thermal instability of the nanoparticle stabilizer and nanoparticle surface defects is a possible reason for the irreversible thermal response of some nanoparticles.
The Synchronization of Ventilation and Locomotion in Horses (Equus Caballus) (1992)

Ciné film and synchronized records of respiratory flow were obtained from Thoroughbred racehorses cantering on a treadmill at speeds of 9 and 11 m s-1. Horses and some other galloping and hopping mammals link their breathing and locomotion, taking exactly one breath per stride. Three theoretical mechanisms by which the movements of locomotion might drive ventilation are considered. (i) Flexion of the lumbosacral joint and the resulting forward sweep of the pelvis pushes the viscera against the diaphragm. However, back flexion lags behind ventilation at 11 m s-1 and could not exclusively drive ventilation at this speed. (ii) Loading of the thorax by the impact of the forelimbs with the ground might force air out of the lungs. If the respiratory system were damped sufficiently to perform as this mechanism requires, the work of driving ventilation would make up approximately 15% of the total work of running. In comparison with other estimates of the work of ventilation this seems improbably high. (iii) The observed phase relationship between displacements of the viscera, caused by the accelerations of the body during running, and respiratory airflow is not consistent with a tuned visceral piston mechanism driving breathing. Thus, it would seem likely that back flexion is likely to contribute towards driving ventilation but loading of the thorax and the visceral piston mechanism do not.
Identification and genomic characterization of a novel human torque teno virus of 3.2 kb (2007)

In the process of searching for the recently described small anelloviruses 1 and 2 (SAVs) with the genomic DNA length of 2.2 or 2.6 kb in human sera, we isolated a novel virus with its genomic organization resembling those of torque teno virus (TTV) of 3.8-3.9 kb and torque teno mini virus (TTMV) of 2.8-2.9 kb. The entire genomic sequence of three isolates (MD1-032, MD1-073 and MD2-013), which comprised 3242-3253 bases and exhibited 76-99 % identities with the SAVs within the overlapping sequence, was determined. Although the MD1-032, MD1-073 and MD2-013 isolates differed by 10-28 % from each other over the entire genome, they segregated into the same cluster and were phylogenetically distinguishable from all reported TTVs and TTMVs. These results suggest that SAVs are deletion mutants of the novel virus with intermediate genomic length between those of TTV and TTMV and that the novel virus can be classified into a third group of the genus Anellovirus.