gebhart/patrepeval huggingface dataset:
Suppression of Anti-Tumor Immunity in Chronic Lymphocytic Leukemia Via Interleukin-10 Production (2016)

Abstract The most common human leukemia is B-cell chronic lymphocytic leukemia (B-CLL), which is characterized by a progressive accumulation of abnormal B-lymphocytes in blood, bone marrow and secondary lymphoid organs. Typically disease progression is slow, but as the number of leukemic cells increases, they interfere with the production of other important blood cells, causing the patients to be in an immunosuppressive state. To study the basis of this immunoregulation, we used cells from the transgenic Eμ-Tcl1 mouse, which spontaneously develop B-CLL due to a B-cell specific expression of the oncogene, Tcl1. Previously we showed that Eμ-Tcl1 CLL cells constitutively produce an anti-inflammatory cytokine, IL-10. Here we studied the role of IL-10 in CLL cell survival in vitro and the development of CLL in vivo. We found that neutralization of IL-I0 using anti-IL-10 antibodies or blocking the IL-10 receptor (IL-10R) using anti-IL-10R antibodies did not affect the survival of CLL cells in vitro. On the other hand, adoptively transferred Eμ-Tcl1 cells grew at a slower rate in IL-10R KO mice vs. wild type (WT) mice. There was a significant reduction in CLL cell engraftment in the spleen, bone marrow, peritoneal cavity and liver of the IL-10R KO compared to WT mice. Further studies revealed that IL-10 could be playing a role in the tumor microenvironment possibly by affecting anti-tumor immunity. This was seen by a reduction in the activation of CD8+ T cells as well as a significantly lower production of IFN-γ by CD4+ T cells purified from CLL-injected WT mice compared to those purified from CLL-injected IL-10R KO mice. These studies demonstrate that CLL cells suppress host anti-tumor immunity via IL-10 production. This led us to investigate possible mechanisms by which IL-10 is produced. We found a novel role of B-cell receptor (BCR) signaling pathway in constitutive IL-10 secretion. Inhibition of Src or Syk family kinases reduces the constitutive IL-10 production by Eμ-Tcl1 cells in a dose dependent manner. In addition, we found that Eμ-Tcl1 CLL cells exhibit clonal variation in their IL-10 production in response to BCR cross-linking. Further studies are being performed to understand the mechanisms by which BCR signaling affects IL-10 production. Disclosures No relevant conflicts of interest to declare.
Structure of a ribulose 5‐phosphate 3‐epimerase from <i>Plasmodium falciparum</i> (2005)

The crystal structure of Pfal009167AAA, a putative ribulose 5-phosphate 3-epimerase (PfalRPE) from Plasmodium falciparum, has been determined to 2 A resolution. RPE represents an exciting potential drug target for developing antimalarials because it is involved in the shikimate and the pentose phosphate pathways. The structure is a classic TIM-barrel fold. A coordinated Zn ion and a bound sulfate ion in the active site of the enzyme allow for a greater understanding of the mechanism of action of this enzyme. This structure is solved in the framework of the Structural Genomics of Pathogenic Protozoa (SGPP) consortium.
Steroidal nonspecific esterase metabolism of <i>N</i>-hydroxy-2-acetylaminofluorene: evidence for selective activation by the cellular reductant NADPH (1992)

The significance of the nonspecific esterases of human mononuclear leukocytes (HMLs) in arylamine carcinogenesis is suggested by data showing that the metabolically formed hydroxamic acid derivative of 2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, is a substrate for this class of enzymes. A viable cell assay for the nonspecific esterases using alpha-naphthyl acetate as substrate is described, and data showing this activity to be sensitive to already known substrates for HML esterases as measured by three previously described assays are presented. All four assays of the same esterase activity are shown to be highly sensitive to up- and down-regulation by addition of NADPH or NADP to viable HML cultures. Selective activation of a purified rabbit nonspecific esterase by NADPH, but not by the other cellular reductants, NADH and glutathione, was demonstrated. Cytosols prepared from normal human tissue samples of liver, breast, colon, and brain were also activated by the presence of NADPH. These data do not indicate that steroidal nonspecific esterases are redox-modulated by the presence of mixed disulfides in their structure. Instead, they support the direct and specific influence of NADPH as a widespread activator of esterase activity by a mechanism not yet understood.
A 13 kDa carboxy‐terminal fragment of ApoE stabilizes Abeta hexamers (2005)

The pathological role of ApoE4 in Alzheimer's disease (AD) is not fully elucidated yet but there is strong evidence that ApoE is involved in Abeta deposition, which is an early hallmark of AD neuropathology. Overexpression of ApoE in neuroblastoma cells (Neuro2a) leads to the generation of an intracellular 13 kDa carboxy-terminal fragment of ApoE comparable to fragments seen in brains of AD patients. ApoE4 generates more of this fragment than ApoE2 and E3 suggesting a potential pathological role of these fragments in Alzheimer's disease. Analysis of this intracellular ApoE4 fragment by protease digest followed by MALDI-TOF mass spectrometry showed the proteolytic cleavage site close to residue 187 of ApoE. We have engineered and expressed the corresponding ApoE fragments in vitro. The recombinant 13 kDa carboxy-terminal fragment inhibited fibril formation of Abeta; this contrasts with the full-length ApoE and the corresponding amino-terminal ApoE fragment. Moreover, we show that the 13 kDa carboxy-terminal fragment of ApoE stabilizes the formation of Abeta hexamers. Complexes of Abeta with the 13 kDa carboxy-terminal ApoE fragment show toxicity in PC12 cells comparable to Abeta fibrils. These data suggest that cleavage of ApoE, leading to the generation of this fragment, contributes to the pathogenic effect of ApoE4 in AD.
Food Safety (2014)

Abstract Most consumers expect the food they eat to be safe. This concern is not lost on governments around the world, which explains why there are numerous laws and regulations intended to ensure food safety. There are many misconceptions about food safety, such as the belief that organic foods are safer than conventional food products. This article examines food safety, first by considering the factors that explain why genetically modified (GM) crops as well as the foods and feeds produced from them, are assumed to be as safe as any other food. It provides an overview of the history of the use of recombinant DNA in food crops and the production of transgenic crops. It then looks at the scientific food-safety risk assessment of crops produced using biotechnology. It also discusses food safety in relation to proteins in food, as well as food allergy and allergens. Finally, it reviews the results of animal studies designed to demonstrate the safety of GM crops and the politics underlying such studies.
ChemInform Abstract: CHEMIE DES CIS‐TRIAZA‐TRIS‐SIGMA‐HOMOBENZOLS, CIS‐DIAZA‐BIS‐SIGMA‐HOMOBENZOLE, SYNTHESE UND 2SIGMA‐2PI‐ISOMERISIERUNG ZU 1,4‐DIAZA‐2,5,7‐CYCLOOCTATRIEN‐DERIVATEN (1975)

Abstract Die aus dem Trisaza‐trishomobenzol (Ia) erhältlichen Derivate (Ib)‐(Id) liefern mit Nitrosyltetrafluoroborat bei tiefen Temperaturen die Nitrosoaziridine (IIa)‐(IIc); (IIa) geht bei ‐10°C in das Benzoldiimin (IIIa) und dieses bei 75°C in das Diazocin (IVa) über.
Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen (1999)

The present parenteral regimen is an efficient and time-saving estrogen regimen with a favorable side-effect profile. PEP seems to offer a potential for revival of the most cost-effective endocrine treatment of cancer of the prostate, i.e., estrogen.
Metabolic influences on the absorption of serous subretinal fluid. (1988)

Experimental detachments were made in Dutch rabbit eyes by injecting autologous serum or Hanks' solution into the subretinal space through a glass micropipette. The serum was resorbed at a rate of 0.064 +/- 0.023 microliter/mm2/hr, which is approximately half as fast as Hanks' solution. Both cyclic GMP and dibutyryl cyclic GMP accelerated serum resorption by 23%, whereas cyclic AMP and dibutyryl cyclic AMP (both used with IBMX) decreased the absorption rate by 46%. The absorption rate for Hanks' solution did not differ significantly between light and dark. Intravenous administration of acetazolamide (50 mg/Kg) and mannitol (2.5 g/kg) failed to alter the serum resorption rate significantly. Thus, cyclic nucleotides (and presumably metabolic transport) are important to absorption of serous fluid, but acetazolamide and hyperosmotic agents have less effect than on nonproteinaceous subretinal fluid.
Estimation of Radioactivity of Graphite Blocks in Tokai Power Station Using Statistical Method (2010)

Tokai Power Station (graphite moderated, gas-cooled reactor, GCR) stopped its commercial operation in March 1998 and is decommissioning now. Since graphite blocks in Tokai reactor core are major low level wastes (LLWs), the realistic and reasonable method to estimate radioactivity of graphite blocks is required for final disposal and its licensing procedure. In general, LLWs, which were installed in or around a reactor core, have large radioactivity, theoretical calculations can be applied to the estimation of the radioactivity. This paper describes the concept of the method using statistical approach to determine the radioactivity of the graphite blocks in the reactor core. This method directly considers the variations of input calculation conditions, for example, compositions of impurity elements, irradiation neutron flux and irradiation period. In this paper, the variations of the compositions of impurity elements were statistically considered with the mean value and the standard deviation that were determined with elemental analyses. Many activation calculations were performed with the compositions that were determined with pseudorandom numbers, the mean value and the standard deviation. The calculated radioactivities distribute also statistically and a mean value and a standard deviation of radioactivity can be determined. The distribution of calculated radioactivities shows consistency to radiochemical analyses of graphite blocks from the reactor core and this shows that the method is applicable to the estimation of the graphite block radioactivity. Furthermore, this method can be considered to reduce over-excess estimation margin and can obtain reasonable radioactivity rather than using maximum or conservative values of all input conditions. This method is now being developed and approved as one of basic procedure for determining the radioactivity of wastes by Standards Committee of the Atomic Energy Society of Japan.
MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1 (2016)

Colorectal cancer (CRC) is the third most common cancer causing high mortality rates world-wide. Delineating the molecular mechanisms leading to CRC development and progression, including the role of microRNAs (miRNAs), are currently being unravelled at a rapid rate. Here, we report frequent downregulation of the microRNA miR-320 family in primary CRC tissues and cell lines. Lentiviral-mediated re-expression of miR-320c (representative member of the miR-320 family) inhibited HCT116 CRC growth and migration in vitro, sensitized CRC cells to 5-Fluorouracil (5-FU), and inhibited tumor formation in SCID mice. Global gene expression analysis in CRC cells over-expressing miR-320c, combined with in silico prediction identified 84 clinically-relevant potential gene targets for miR-320 in CRC. Using a series of biochemical assays and functional validation, SOX4, FOXM1, and FOXQ1 were validated as novel gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression levels of this gene panel (SOX4, FOXM1, and FOXQ1) in The Cancer Genome Atlas (TCGA) colorectal cancer data set (319 patients) revealed significantly poor disease-free survival in patients with elevated expression of this gene panel (P-Value: 0.0058). Collectively, our data revealed a novel role for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC.
Cerebral infarction in a young female following snake bite. (1985)

We present a normal 13-year old female who developed left cerebral infarction following envenomation by the carpet viper (Echis carinatus). We have read of only one other case of cerebral infarction following viper envenomation (Viperi russelli). Possible mechanisms for cerebral infarction in these circumstances are discussed. It is believed that this complication may be more common than is reported in the literature.
Conformation of non‐aromatic ring compounds. Part 61 Conformational equilibrium in <i>trans</i>‐2‐halogenocyclohexanols (1970)

Abstract The conformational equilibrium in trans ‐2‐bromo‐ and trans ‐2‐chloro‐cyclohexanol has been studied with the aid of dipole moments, NMR, IR and Raman spectroscopy. The physical properties of the individual conformers are obtained from the suitably biased 4‐ or 5‐ t ‐butyl derivatives. The diequatorial form appears to predominate strongly in solution. A comparison is made with the conformational features of the trans ‐1,2‐dihalogenocyclohexanes.
Bureaucracy, Informality and Taxation : Essays in Development Economics and Public Finance (2009)

This thesis consists of three self-contained essays. Essay 1, "Dispatchers", is a study of a specialized service sector that has arisen in many developing countries. It is a well-established fact that the government bureaucracy in many developing countries is large, difficult to understand, non-transparent and time-consuming. However, "de jure" procedures sometimes have little to do with how firms or individuals actually go about when dealing with the government bureaucracy. One institution that has emerged is a specialized intermediary, henceforth called dispatcher, that assists individuals and firms in their contacts with the public sector. A model is developed to study the effects of dispatchers on time and resources spent in obtaining licenses, on informality and on the incentives of bureaucrats and dispatchers to make regulation more/less complicated. Essay 2, "Informal firms, investment incentives and formalization", studies informal firms in developing countries. In a typical developing country, the majority of small firms are informal and entry costs into formality are high. What can we expect in terms of firm investment, growth and formalization in such a setting? I show that investment and growth trajectories differ substantially between firms that choose to formalize and those that do not. The formalization decision depends non-trivially on the informal firm's productivity. This, in turn, has an effect on how policies should be designed. The long-run firm size distribution exhibits a "missing middle" and depends on the initial firm-level stock of capital, a result that can be interpreted as a poverty trap. Essay 3, "Compositional and dynamic Laffer effects in a model with constant returns to scale", studies dynamic effects of tax cuts. The possibility of tax cuts paying for themselves over time seems like an attractive option for policy makers. In a constant returns to scale model, I study conditions under which reductions in capital taxes are self-financing
Magnetic Resonance Imaging in Stress Fractures and Shin Splints (2004)

The purpose of the current study was to determine whether stress fractures and shin splints could be discriminated with MRI in the early phase. Twenty-two athletes, who had pain in the middle or distal part of their leg during or after sports activity, were evaluated with radiographs and MRI scans. Stress fractures were diagnosed when consecutive radiographs showed local periosteal reaction or a fracture line, and shin splints were diagnosed in all the other cases. In all eight patients with stress fractures, an abnormally wide high signal in the localized bone marrow was the most detectable in the coronal fat-suppressed MRI scan. In 11 patients with shin splints, the coronal fat-suppressed MRI scans showed a linear abnormally high signal along the medial posterior surface of the tibia, and in seven patients with shin splints, the MRI scans showed a linear abnormally high signal along the medial bone marrow. No MRI scans of shin splints showed an abnormally wide high signal in the bone marrow as observed on MRI scans of stress fractures. This study showed that fat-suppressed MRI is useful for discrimination between stress fracture and shin splints before radiographs show a detectable periosteal reaction in the tibia.
Association of Plasminogen with Dipeptidyl Peptidase IV and Na+/H+ Exchanger Isoform NHE3 Regulates Invasion of Human 1-LN Prostate Tumor Cells (2005)

Binding of plasminogen type II (Pg 2) to dipeptidyl peptidase IV (DPP IV) on the surface of the highly invasive 1-LN human prostate tumor cell line induces an intracellular Ca2+ ([Ca2+]i) signaling cascade accompanied by a rise in intracellular pH (pHi). In endothelial cells, Pg 2 regulates intracellular pH via Na+/H+ exchange (NHE) antiporters; however, this mechanism has not been demonstrated in any other cell type including prostate cancer cells. Because the Pg 2 receptor DPP IV is associated with NHE3 in kidney cell plasma membranes, we investigated a similar association in 1-LN human prostate cancer cells and a mechanistic explanation for changes in [Ca2+]i or pHi induced by Pg 2 in these cells. Our results suggest that the signaling cascade initiated by Pg 2 and its receptor proceeds via activation of phospholipase C, which promotes formation of inositol 3,4,5-trisphosphate, an inducer of Ca2+ release from endoplasmic reticulum stores. Furthermore, our results suggest that Pg 2 may regulate pHi via an association with NHE3 linked to DPP IV in these cells. These associations suggest that Pg has the potential to simultaneously regulate calcium signaling pathways and Na+/H+ exchanges necessary for tumor cell proliferation and invasiveness.
Double-Contrast Arthrography of the Elbow (1979)

Double-contrast arthrography using gravity provides more detail than single-contrast techniques. With gravity, air rises to the uppermost portion of the joint and the positive contrast material settles. The cartilagenous articular surfaces and the synovial lining of the elbow are coated with contrast material and highlighted by the intra-articular air. Cartilagenous intra-articular bodies can be identified and located and the size of cartilagenous encapsulated osseous bodies can be confirmed. This method is faster to perform and easier to interpret than single-contrast studies, exposes the patient less than a tomographic examination, and is helpful before surgical exploration.
Active-Site-Directed Inactivation of Aspergillus oryzae β-Galactosidase with β-D-Galactopyranosylmethyl-pnitrophenyltriazene (1990)

beta-D-Galactopyranosylmethyl-p-nitrophenyltriazene (beta-GalMNT), a specific inhibitor of beta-galactosidase, was isolated as crystals by HPLC and its chemical and physicochemical characteristics were examined. Aspergillus oryzae beta-galactosidase was inactivated by the compound. We studied the inhibition mechanism in detail. The inhibitor was hydrolyzed by the enzyme to p-nitroaniline and an active intermediate (beta-galactopyranosylmethyl carbonium or beta-galactopyranosylmethyldiazonium), which inactivated the enzyme. The efficiency of inactivation of the enzyme (the ratio of moles of inactivated enzyme to moles of beta-GalMNT hydrolyzed by the enzyme) was 3%; the efficiency of Escherichia coli beta-galactosidase was 49%. In spite of the low efficiency, the rate of inactivation of A. oryzae enzyme was not very different from that of the E. coli enzyme, because the former hydrolyzed beta-GalMNT faster than the latter did. A. oryzae beta-galactosidase was also inactivated by p-chlorophenyl, p-tolyl, and m-nitrophenyl derivatives of beta-galactopyranosylmethyltriazene. However, E. coli beta-galactosidase was not inactivated by these triazene derivatives. The results showed that the inactivation of A. oryzae and E. coli beta-galactosidases by beta-GalMNT was an enzyme-activated and active-site-directed irreversible inactivation. The possibility of inactivation by intermediates produced nonenzymatically was ruled out for E. coli, but not for the A. oryzae enzyme.
Synthesis of .omega.-bromo ketones (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of .omega.-bromo ketonesHerbert O. House, Chia-Yeh Chu, William V. Phillips, Trevor S. B. Sayer, and Cheuk-Chung YauCite this: J. Org. Chem. 1977, 42, 10, 1709–1717Publication Date (Print):May 1, 1977Publication History Published online1 May 2002Published inissue 1 May 1977https://pubs.acs.org/doi/10.1021/jo00430a009https://doi.org/10.1021/jo00430a009research-articleACS PublicationsRequest reuse permissionsArticle Views922Altmetric-Citations33LEARN 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 Get e-Alerts
Paralleling non-isolated multi-phase PWM converters (2002)

In paralleling converters, it is desirable to have a directly connected structure because of compact size, low cost, simplicity and easy expandability. However, the parallel converters may have interactions due to their nonisolation. This paper develops an average model of the parallel converters in rotating coordinates. Based on the model, interactions between the parallel converters are analyzed. Because of its symmetrical structure, the parallel system can reduce both the common-mode dv/dt noise and the differential-mode current ripple with a proposed modulation scheme.
ON THE THEORY OF SPECTRAL LINE BROADENING IN PLASMA (1958)

The theory of spectral line broadening in the Stark emitting atoms of a large group of moving charged particles by the electric field. The relation between the statistical and impact theories which up to the present time were considered (for the Stark effect) only in the approximation of consequent atomic collisions with separate disturbace particles is examined. In the theory proposed it is assumed that the electrons as well as the ions can be classically described, that the spatial distribution is accidental in a given mean density, and that the disturbance field is homogeneous and has an adiabatic action on the atom. (R.V.J.)
The Pharmacological Profile of Aceclofenac, a New Nonsteroidal Antiinflammatory and Analgesic Drug (1991)

Aceclofenac is a new phenylacetic acid derivative provided with marked antiinflammatory, antiarthritic, analgesic and antipyretic activities in animal experimental models. While maintaining its potency Aceclofenac demonstrates better gastric tolerance and consequently offers greater potential security than other highly active agents such as Indomethacin and Diclofenac.