gebhart/patrepeval huggingface dataset:
Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine (2012)

T(H)17 cells are a lineage of CD4(+) T cells that are critical for host defense and autoimmunity by expressing the cytokines IL-17A, IL-17F, and IL-22. A feature of T(H)17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-state intestinal T(H)17 (sT(H)17) cells is dependent on the presence of the microbiota. However, the signaling pathway linking the microbiota to the development of intestinal sT(H)17 cells remains unclear. In this study, we show that IL-1β, but not IL-6, is induced by the presence of the microbiota in intestinal macrophages and is required for the induction of sT(H)17 cells. In the absence of IL-1β-IL-1R or MyD88 signaling, there is a selective reduction in the frequency of intestinal sT(H)17 cells and impaired production of IL-17 and IL-22. Myeloid differentiation factor 88-deficient (MyD88(-/-)) and germ-free (GF) mice, but not IL-1R(-/-) mice, exhibit impairment in IL-1β induction. Microbiota-induced IL-1β acts directly on IL-1R-expressing T cells to drive the generation of sT(H)17 cells. Furthermore, administration of IL-1β into GF mice induces the development of retinoic acid receptor-related orphan receptor γt-expressing sT(H)17 cells in the small intestine, but not in the spleen. Thus, commensal-induced IL-1β production is a critical step for sT(H)17 differentiation in the intestine, which may have therapeutic implications for T(H)17-mediated pathologies.
Acid Sphingomyelinase-deficient Macrophages Have Defective Cholesterol Trafficking and Efflux (2001)

Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol transport, requires trafficking of cholesterol from intracellular sites to the plasma membrane. Sphingomyelin is a cholesterol-binding molecule that transiently exists with cholesterol in endosomes and lysosomes but is rapidly hydrolyzed by lysosomal sphingomyelinase (L-SMase), a product of the acid sphingomyelinase (ASM) gene. We therefore hypothesized that sphingomyelin hydrolysis by L-SMase enables cholesterol efflux by preventing cholesterol sequestration by sphingomyelin. Macrophages from wild-type and ASM knockout mice were incubated with [(3)H]cholesteryl ester-labeled acetyl-LDL and then exposed to apolipoprotein A-I or high density lipoprotein. In both cases, [(3)H]cholesterol efflux was decreased substantially in the ASM knockout macrophages. Similar results were shown for ASM knockout macrophages labeled long-term with [(3)H]cholesterol added directly to medium, but not for those labeled for a short period, suggesting defective efflux from intracellular stores but not from the plasma membrane. Cholesterol trafficking to acyl-coenzyme A:cholesterol acyltransferase (ACAT) was also defective in ASM knockout macrophages. Using filipin to probe cholesterol in macrophages incubated with acetyl-LDL, we found there was modest staining in the plasma membrane of wild-type macrophages but bright, perinuclear fluorescence in ASM knockout macrophages. Last, when wild-type macrophages were incubated with excess sphingomyelin to "saturate" L-SMase, [(3)H]cholesterol efflux was decreased. Thus, sphingomyelin accumulation due to L-SMase deficiency leads to defective cholesterol trafficking and efflux, which we propose is due to sequestration of cholesterol by sphingomyelin and possibly other mechanisms. This model may explain the low plasma high density lipoprotein found in ASM-deficient humans and may implicate L-SMase deficiency and/or sphingomyelin enrichment of lipoproteins as novel atherosclerosis risk factors.
OPERATIONAL EXPERIENCE WITH SUPERCONDUCTING SYNCHROTRON MAGNETS (2015)

Abstract Operation The operational experience with the Fermilab Tevatron is presented, with emphasis on reliabilty and failure ‘nodes. Comparisons are made between the operating efficiencies for the superconducting machine and for the conventional Main Ring.
TANDEM GENETIC DUPLICATIONS IN PHAGE AND BACTERIA (1977)

SELECTION OF TANDEM DUPLICATIONS 478 Gene Dosage 478 Coinheritance of Allelic Markers 485 Operon Fusion ..... ....... ...... .... ... ......... 496
CDC27 protein is involved in radiation response in squamous cell cervix carcinoma. (2005)

In the present study, an attempt was made to identify genes involved in radiation response in cervix carcinoma. Differential display technique was used to study the expression profiles of tumour biopsy samples obtained from patients, responding and not responding to treatment. The samples were obtained prior to radiotherapy and subsequent to treatment with Tele-radiation at 10 Gray (Gy). One of the differentially expressed cDNAs, when sequenced was identified to be CDC27. Immuno-histochemical analysis of pre- and post-treated tumour samples from fifteen patients showed the downregulation of expression of CDC27 protein in seven patients. Down-regulation was associated with poorer response to radiotherapy. Cervical cancer cell lines SiHa and C33A were irradiated and their nuclei were stained for expression of CDC27 and analyzed using fluorescent-activated cell sorting (FACS). Down-regulation of CDC27 protein in the irradiated SiHa cell line was associated with greater survival fraction, compared to the irradiated C33A cell line, which had only slight fall in the level of CDC27 protein. This is the first study to suggest a role for CDC27 in radiation response. However, a larger cohort is needed to further confirm the value of CDC27 protein as a predictive marker, for radiation response in cervix cancer.
Succinylated Collagen Crosslinked by Thermal Treatment for Coating Vascular Prostheses (1998)

Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.
The Direct and Enantioselective Organocatalytic α-Oxidation of Aldehydes (2003)

The first direct enantioselective catalytic alpha-oxidation of carbonyls has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective oxyamination of aldehydes, to generate alpha-oxyaldehydes, important chiral synthons for natural product and medicinal agent synthesis. The use of l-proline as the asymmetric catalyst has been found to mediate the oxidation of a large variety of aldehyde substrates with nitrosobenzene serving as the electrophilic oxidant. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 2 mol % were generally employed in this study, successful oxidations conducted using catalyst loadings as low as 0.5 mol % are described.
Bradykinin, a new potential mediator of inflammation‐induced bone resorption (1987)

The effect of bradykinin and desArg9-bradykinin on bone was studied in cultures of calvarial bones taken from 6-7-day-old mice. Bradykinin, at and above a 3-nM concentration, caused a dose-dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin-stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5, 8, 11, 14-eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast-mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E2, was potentiated by the angiotensin-converting enzyme inhibitor, BPP5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulate 45Ca release. DesArg9-bradykinin (1 mumole/liter) stimulated 45Ca release to the same degree as did bradykinin. Bradykinin (3 microM) did not affect the degradation of cartilage proteoglycans, as assessed by the release of 35S-sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.
Overview: Generation of Gene Knockout Mice (2009)

The technique of gene targeting allows for the introduction of engineered genetic mutations into a mouse at a determined genomic locus. The process of generating mouse models with targeted mutations was developed through both the discovery of homologous recombination and the isolation of murine embryonic stem cells (ES cells). Homologous recombination is a DNA repair mechanism that is employed in gene targeting to insert a designed mutation into the homologous genetic locus. Targeted homologous recombination can be performed in murine ES cells through electroporation of a targeting construct. These ES cells are totipotent and, when injected into a mouse blastocyst, they can differentiate into all cell types of a chimeric mouse. A chimeric mouse harboring cells derived from the targeted ES cell clone can then generate a whole mouse containing the desired targeted mutation. The initial step for the generation of a mouse with a targeted mutation is the construction of an efficient targeting vector that will be introduced into the ES cells.
Mode of Action of Peroxisome Proliferators as Hypolipidemic Drugs. (1995)

The hypolipidemic effect exerted by beta,beta'-tetramethyl-hexadecanedioic acid (Medica 16) is accounted for by enhanced catabolism of plasma triglyceride-rich lipoproteins due to a decrease in plasma apolipoprotein C-III (Frenkel, B., Mayorek, N., Hertz, R., and Bar-Tana, J. (1988) J. Biol. Chem. 263, 8491-8497; Frenkel, B., Bishara-Shieban, J., and Bar-Tana, J. (1994) Biochem. J. 298, 409-414). Decrease in apolipoprotein C-III exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates (e.g. Medica 16, fibrate drugs) is shown here to result from suppression of apolipoprotein C-III gene expression. Transcriptional suppression of apolipoprotein C-III is due to transcriptional suppression of hepatic nuclear factor (HNF)-4 as well as displacement of HNF-4 from the apolipoprotein C-III promoter. HNF-4 displacement exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates is mediated by the peroxisome proliferators activated receptor (PPAR). Transcriptional suppression of HNF-4-enhanced genes (e.g. apolipoprotein C-III) along with transcriptional activation of peroxisomal and other genes by hypolipidemic drugs may account for their broad spectrum pharmacological effect.
Demand Shifts, Population Adjustments, and Labor Market Outcomes during the 1980s (2000)

In this article we explore the effects of labor demand shifts and population adjustments across metropolitan areas on the employment and earnings of various demographic groups during the 1980s. We find that population shifts across areas at least partially offset the effects of these demand shifts, but less‐educated workers showed substantially lower population adjustments in response to these demand shifts. These limited supply responses apparently contributed importantly to relatively greater deterioration of employment and earnings of these groups in declining areas during the 1980s.
Wave propagation through an assembly of spheres: IV. Relations between different multiple scattering theories (1967)

The exact determinantal equation satisfied by the coherent wave vector in a statistically defined medium of spherical scatterers, which was obtained by Lloyd in III of this series of papers, is used to show two things.
Effects of Uncinula necator on the yield and quality of grapes ( Vitis vinifera ) and wine (2004)

The effects of powdery mildew ( Uncinula necator ) on grape yield, juice and wine quality were quantified for cultivar Cabernet Sauvignon (CSa) in 1997 and 1999, and for Sauvignon blanc (Sa) in 1999. Analyses were carried out on batches of healthy berries to which known percentages (0–50%) of diseased berries were added, and on natural clusters that were classified into four visual classes from low (C 1 ) to high (C 4 ) disease severity. CSa diseased berries showed an average weight reduction of 12% (1997) and 20% (1999). The direct consequence of a higher percentage of smaller, diseased berries was a reduction in yield. The accompanying loss of weight in must from C 1 to C 4 clusters increased from 10 to 45%. Sugar content in diseased berries was not significantly different from disease‐free berries in 1997, but was 20–21% (CSa) and 14% (Sa) higher in 1999. Severely infected batches also showed a higher total acidity than healthy ones. The total anthocyanin content of CSa was decreased by 0·91% (1997) and 0·66% (1999) per percentage mildewed berries added by weight. In Sa wines the concentration of 3‐mercaptohexanol, a component of varietal aroma, was decreased by powdery mildew. Multidimensional analyses, based on all the variables studied, successfully grouped batches of CSa according to disease severity. Using directional triangular tests wine experts were able to recognize CSa wines produced from berries with ≈25% of powdery mildew; the threshold for nonexperts was 50%. CSa wines obtained from samples with more than 30% of diseased berries by weight were significantly classified as the worst according to preference order criteria, but below this value the preference was not significant. Sa wines with &lt;50% mildewed berries could not be differentiated significantly by organoleptic tests performed by nonprofessionals.
Dose-Response Study of N,N-Dimethyltryptamine in Humans (1994)

These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.
Identification of a Gene Encoding a Yeast Histone H4 Acetyltransferase (1995)

A collection of yeast temperature-sensitive mutants was screened by an enzymatic assay to find a mutant defective in the acetylation of histone H4. The assay used a fractionated cell extract and measured acetylation of a peptide corresponding to amino acids 1-28 of H4. There are at least two activities in this fraction that acetylate the peptide. A mutation, hat1-1, that eliminates one of the activities was identified and mapped to a locus near the centromere of chromosome XVI. The HAT1 gene was cloned and found to encode a protein of 374 amino acids. Analysis of the peptide used in the assay demonstrated that the HAT1 enzyme acetylates lysine 12 of histone H4. hat1 mutants have no obvious growth defects or phenotypes other than the enzyme defect itself. The HAT1 protein expressed in Escherichia coli gave histone acetyltransferase activity in vitro, demonstrating that HAT1 is the structural gene for the enzyme.
The Clinical Course of Epilepsy and Its Psychosocial Correlates: Findings from a U.K. Community Study (1996)

As part of a large community-based study, we retrospectively examined the clinical course of epilepsy in an unselected population of people who had a recent history of seizures or were receiving antiepileptic drugs (AEDs). Clinical information was collected from medial records, and information about psychosocial functioning was obtained by means of postal questionnaires sent to identified subjects. The response rate to the postal questionnaire was 71%. There were some deficiencies in the recording of clinical data, which is not unusual since data were taken from records held by primary physicians rather than from hospital clinics. Nevertheless, findings regarding the clinical course of epilepsy corresponded to those of earlier studies. Fifty-seven percent of the sample had had at least a 2-year seizure-free period and 46% of subjects were currently in a remission of at least 2-year duration. There was a clear relationship between current seizure frequency and levels of anxiety and depression, perceived impact of epilepsy, perceived stigma, and marital and employment status. The relationship of seizure frequency and other clinical variables to psychosocial function was explored by multivariate analysis techniques. The amount of variation in scores on the various measures of function accounted for by the clinical variables was small. The most important predictor was current seizure activity, which was the first variable to enter the regression analyses for six of the eight measures of psychosocial function considered. Age at epilepsy onset also emerged as a significant predictor for depression, stigma, and marital status. In individuals with epilepsy in remission, there was little evidence that psychosocial functioning was associated with length of remission, a finding which may in part reflect the nature of this study population. The results indicate that there are several more important predictors of psychopathology and social dysfunction in epilepsy and suggest several implications for treatment interventions.
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2017)

WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Magnetic resonance image-guided focused ultrasound surgery. (2003)

The powerful union of focused ultrasound and magnetic resonance imaging (MRI) has created a new approach to noninvasive surgery. By using this integrated therapy delivery system, the physician can correctly localize tumors, optimally target acoustic energy, monitor energy deposition in real time, and accurately control the deposited thermal dose within the entire tumor volume. This satisfies the requirements for "ideal surgery." In a real sense, MRI provides the "road map" by which focused ultrasound surgery (FUS) is followed. The advantages of MRI over ultrasound guidance in controlling FUS lie in the more sensitive detection of tumor target, the real-time detection of tissue temperature, and the confirmation of thermally induced tissue changes-powerful features that eventually can replace the traditional surgical approach. Applying software that connects the therapy and imaging system (the "Dosimetry Workstation"), the physician can generate an entire treatment plan from quantifying temperature changes to positioning the therapy transducer. The noninvasive debulking of tumors without disturbing adjacent, functionally intact structures is thereby accomplished.
Targeting the Binding Interface on a Shared Receptor Subunit of a Cytokine Family Enables the Inhibition of Multiple Member Cytokines with Selectable Target Spectrum (2015)

The common γ molecule (γc) is a shared signaling receptor subunit used by six γc-cytokines. These cytokines play crucial roles in the differentiation of the mature immune system and are involved in many human diseases. Moreover, recent studies suggest that multiple γc-cytokines are pathogenically involved in a single disease, thus making the shared γc-molecule a logical target for therapeutic intervention. However, the current therapeutic strategies seem to lack options to treat such cases, partly because of the lack of appropriate neutralizing antibodies recognizing the γc and, more importantly, because of the inherent and practical limitations in the use of monoclonal antibodies. By targeting the binding interface of the γc and cytokines, we successfully designed peptides that not only inhibit multiple γc-cytokines but with a selectable target spectrum. Notably, the lead peptide inhibited three γc-cytokines without affecting the other three or non-γc-cytokines. Biological and mutational analyses of our peptide provide new insights to our current understanding on the structural aspect of the binding of γc-cytokines the γc-molecule. Furthermore, we provide evidence that our peptide, when conjugated to polyethylene glycol to gain stability in vivo, efficiently blocks the action of one of the target cytokines in animal models. Collectively, our technology can be expanded to target various combinations of γc-cytokines and thereby will provide a novel strategy to the current anti-cytokine therapies against immune, inflammatory, and malignant diseases.
Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome (2003)

Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab's. Currently, therapy for pregnant women with APS is focused on preventing thrombosis, but anticoagulation is only partially successful in averting miscarriage. We hypothesized that complement activation is a central mechanism of pregnancy loss in APS and tested this in a model in which pregnant mice receive human IgG containing aPL Ab's. Here we identify complement component C5 (and particularly its cleavage product C5a) and neutrophils as key mediators of fetal injury, and we show that Ab's or peptides that block C5a-C5a receptor interactions prevent pregnancy complications. The fact that F(ab)'2 fragments of aPL Ab's do not mediate fetal injury and that C4-deficient mice are protected from fetal injury suggests that activation of the complement cascade is initiated via the classical pathway. Studies in factor B-deficient mice, however, indicate that alternative pathway activation is required and amplifies complement activation. In contrast, activating Fc gamma Rs do not play an important role in mediating aPL Ab-induced fetal injury. Our findings identify the key innate immune effectors engaged by pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide novel and important targets for prevention of pregnancy loss in APS.
Perspectives on Treatment of Metastatic Castration-Resistant Prostate Cancer (2013)

The arrival of several new agents--cabazitaxel, abiraterone acetate, enzalutamide, and radium-223--is changing the treatment options and management of patients with metastatic castration-resistant prostate cancer (mCRPC). Many other novel agents are also being investigated. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. This review article is a summary of a European Treatment Practices Meeting, which was convened to discuss these latest data on novel agents and current treatment strategies in the mCRPC setting.