gebhart/patrepeval huggingface dataset:
Structure-Function Relationship of Glucose 6-Phosphate Dehydrogenase from Leuconostoc Mesenteroides (1982)

The previous procedure for the isolation of glucose 6-phosphate dehydrogenase (G6PD) from Leuconostoc mesenteroides was modified to allow the preparation of large quantities of homogeneous enzyme suitable for structural studies. The enzyme was shown to consist of two identical subunits containing N-terminal valine and C-terminal glycine. Three aspects were examined that probe the relationship between structure and function of L. mesenteroides G6PD. First, the enzyme was covalently labelled with a phosphopyridoxyl group at a unique lysine residue. Previous work had suggested that this lysine is located at the active site and that it participates in binding G6P {Milhausen and Levy, Eur., J. Biochem. 50 (1975), 453-461}. Two pyridoxyl peptides, DIIA and DIIB, were isolated from the tryptic digest of the modified enzyme. The amino acid sequence of each peptide revealed that the sequence of the pyridoxyl binding site was Phe-Leu-Leu-Lys(Pxy)-Ser-Pro-Ser-Tyr-(Asp, Val)-Lys. This is the first report of sequence information from the active site of any G6PD. Support for the role of the modified lysine is provided in the second part of this dissertation, in which three fluorescent probes were exploited to provide information on ligand binding and conformational transitions that the enzyme undergoes. First, the intrinsic protein fluorescence was quenched by binding various ligands to the enzyme. These measurements permitted the monitoring of overall conformational changes of the enzyme upon ligand binding and calculation of binding constants. Second, the covalently bound phosphopyridoxyl group in the modified enzyme served as a fluorescence reporter group to monitor the conformational changes produced by NAD('+) or NADP('+) and to calculate their binding constants. The results of these experiments showed that pyridoxylation promotes a conformational change similar to that produced by NAD('+) or G6P (see below). Binding of NAD('+) to pyridoxyl enzyme is accompanied by a smaller conformational change than that seen when it binds to the native enzyme. Conversely, NADP('+) binding leads to a larger conformational change in the pyridoxylated than in the native enzyme. This was supported by the fact that the dissociation constant for NAD('+) is lower, and for NADP('+) is higher, for pyridoxyl enzyme than for native enzyme. Third, the fluorescence of S-NADPH was used as an extrinsic probe of the coenzyme binding region of the enzyme. The fluorescence properties of S-NADPH are reported for the first time. ...
Prevalence of Bacterial Febrile Illnesses in Children in Kilosa District, Tanzania (2015)

The study has underscored the importance of febrile bacterial diseases including zoonoses such as leptospirosis and brucellosis in febrile children, and thus such illnesses should be considered by clinicians in the differential diagnoses of febrile diseases. However, access to diagnostic tests for discrimination of febrile illnesses is needed. This would allow febrile patients to receive the correct diagnoses and facilitation of accurate and prompt treatment.
Anti-CD137 Suppresses Tumor Growth by Blocking Reverse Signaling by CD137 Ligand (2017)

CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy. Recently, it was found that CD137<sup>-/-</sup> mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here, we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL12-producing CD103<sup>+</sup> DC and type 1 tumor-associated macrophages (TAM). Differentiation of these cell types is important because they are required to generate IFNγ-producing CD8<sup>+</sup> cytotoxic T lymphocytes (Tc1). Notably, CD137L blockade increased levels of IL12 and IFNγ, which promoted intratumoral differentiation of IFNγ-producing Tc1, IL12-producing CD103<sup>+</sup> DC, and type 1 TAM within tumors. Our results offer an explanation for the paradoxical effects of CD137 blockade, based on differential immunomodulatory effects of CD137 signaling and reverse signaling in T cells and DC, respectively. Further, they show how CD137L blockade can seed a forward-feedback loop for activation of CD103<sup>+</sup> DC/type 1 TAM and Tc1 that can create a self-perpetuating cycle of highly effective immunosurveillance. <i>Cancer Res; 77(21); 5989-6000. ©2017 AACR</i>.
Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. (2000)

We examined the role of constitutional genetic variation at the UDP-glucuronosyltransferase (UGT) 1A1 locus in breast cancer susceptibility. The UGT1A1 enzyme is a major UGT involved in estradiol glucuronidation. To date, four UGT1A1 variant alleles characterized by a variation in the number of TA from five through eight repeats in the atypical TATA box region have been described in the African-American population. Functional analyses of the transcriptional activity in breast and liver cells revealed that the transcription activation of a reporter gene is inversely correlated with the number of repeats. Reverse transcription-PCR analysis confirmed the expression of UGT1A1 in human liver in the hepatocarcinoma cell line HepG2 and provided evidence of the expression of UGT1A1 in breast cancer tissue, where a positive signal was observed in 11 of 12 breast cancer cell lines tested. The population-based case-control study involved 200 women with breast cancer and 200 female controls of African ancestry. We postulated that breast cancer cases might have a higher prevalence of low activity allele-containing genotypes than controls (alleles presenting seven and eight repeats in the A(TA)nTAA motif of the TATA box). The age-adjusted odds ratio (OR) for breast cancer comparing women with seven and eight allele-containing genotypes versus 5/5, 5/6, and 6/6 genotypes was 1.8 [95% confidence interval (CI), 1.0-3.1; P = 0.06] in premenopausal women and 1.0 (95% CI, 0.5-1.7; P = 0.9) in postmenopausal women. The observed 1.8-fold elevated risk in premenopausal women with invasive breast cancer is highly suggestive of a possible interaction between UGT genotype and hormones. Additional analyses suggested a stronger association of UGT1A1 genotype with estrogen receptor (ER)-negative breast cancer. Among premenopausal women, the association was stronger for ER- breast cancer (OR, 2.1; 95% CI, 1.0-4.2; P = 0.04) than ER+ breast cancer (OR, 1.3; 95% CI, 0.6-3.0; P = 0.5). The OR was slightly stronger among women who used oral contraceptives, and the association remained null in postmenopausal women, regardless of whether they took hormone replacement therapy. Our current findings suggest that further investigations are warranted to elucidate the role of UGT1A1 in breast cancer risk.
Vector-valued active contours (1996)

A framework for object segmentation in vector-valued images is presented in this paper. The first scheme proposed is based on geometric active contours moving towards the objects to be detected in the vector-valued image. Objects boundaries are obtained as geodesics or minimal weighted distance curves in a Riemannian space. The metric in this space is given by a definition of edges in vector-valued images. The curve flow corresponding to the proposed active contours holds formal existence, uniqueness, stability, and correctness results. The technique is applicable for example to color and texture images. The scheme automatically handles changes in the deforming curve topology. We conclude the paper presenting an extension of the color active contours which leads to a possible image flow for vector-valued image segmentation. The algorithm is based on moving each one of the image level-sets according to the proposed color active contours. This extension also shows the relation of the color geodesic active contours with a number of partial-differential-equations based image processing algorithms as anisotropic diffusion and shock filters.
The Kolbe-Schmitt Reaction (1957)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTThe Kolbe-Schmitt ReactionAlan S. Lindsey and Harold JeskeyCite this: Chem. Rev. 1957, 57, 4, 583–620Publication Date (Print):August 1, 1957Publication History Published online1 May 2002Published inissue 1 August 1957https://pubs.acs.org/doi/10.1021/cr50016a001https://doi.org/10.1021/cr50016a001research-articleACS PublicationsRequest reuse permissionsArticle Views6443Altmetric-Citations336LEARN 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
Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy (2019)

In chronic lymphocytic leukemia (CLL), acquired T-cell dysfunction impedes development of effective immunotherapeutic strategies, through as-yet unresolved mechanisms. We have previously shown that CD8<sup>+</sup> T cells in CLL exhibit impaired activation and reduced glucose uptake after stimulation. CD8<sup>+</sup> T cells in CLL patients are chronically exposed to leukemic B cells, which potentially impacts metabolic homeostasis resulting in aberrant metabolic reprogramming upon stimulation. Here, we report that resting CD8<sup>+</sup> T cells in CLL have reduced intracellular glucose transporter 1 (GLUT1) reserves, and have an altered mitochondrial metabolic profile as displayed by increased mitochondrial respiration, membrane potential, and levels of reactive oxygen species. This coincided with decreased levels of peroxisome proliferator-activated receptor γ coactivator 1-α, and in line with that, CLL-derived CD8<sup>+</sup> T cells showed impaired mitochondrial biogenesis upon stimulation. In search of a therapeutic correlate of these findings, we analyzed mitochondrial biogenesis in CD19-directed chimeric antigen receptor (CAR) CD8<sup>+</sup> T cells prior to infusion in CLL patients (who were enrolled in NCT01747486 and NCT01029366 [https://clinicaltrials.gov]). Interestingly, in cases with a subsequent complete response, the infused CD8<sup>+</sup> CAR T cells had increased mitochondrial mass compared with nonresponders, which positively correlated with the expansion and persistence of CAR T cells. Our findings demonstrate that GLUT1 reserves and mitochondrial fitness of CD8<sup>+</sup> T cells are impaired in CLL. Therefore, boosting mitochondrial biogenesis in CAR T cells might improve the efficacy of CAR T-cell therapy and other emerging cellular immunotherapies.
A Novel Stacked Design of a LC VCO-Prescaler Combination in Sub-Micron PDSOI CMOS (2006)

The work described in this paper extends the novel idea of stacking circuit blocks in a PDSOI CMOS technology. Two of the most crucial (and yet power hungry) components of a frequency synthesiser, namely a prescaler and VCO, are cascaded in a current-mode fashion with an extended power supply beyond that quoted for the technology. Results show the combination to function at 2GHz with VDD = 6.5V and the circuit stack to sit on a 5mA current source.
Load-dependent effects of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men (2007)

Both load and duration of small intestinal lipid infusion affect antropyloroduodenal motility and CCK and peptide YY (PYY) release at loads comparable to and higher than the normal gastric emptying rate. We determined 1) the effects of intraduodenal lipid loads well below the mean rate of gastric emptying on, and 2) the relationships between antropyloroduodenal motility, CCK, PYY, appetite, and energy intake. Sixteen healthy males were studied on four occasions in double-blind, randomized fashion. Antropyloroduodenal motility, plasma CCK and PYY, and appetite perceptions were measured during 50-min IL (Intralipid) infusions at: 0.25 (IL0.25), 1.5 (IL1.5), and 4 (IL4) kcal/min or saline (control), after which energy intake at a buffet meal was quantified. IL0.25 stimulated isolated pyloric pressure waves (PWs) and CCK release, albeit transiently, and suppressed antral PWs, PW sequences, and hunger (P < 0.05) but had no effect on basal pyloric pressure or PYY when compared with control. Loads >/= 1.5 kcal/min were required for the stimulation of basal pyloric pressures and PYY and suppression of duodenal PWs (P < 0.05). All of these effects were related to the lipid load (R > 0.5 or < -0.5, P < 0.05). Only IL4 reduced energy intake (in kcal: control, 1,289 +/- 62; IL0.25, 1,282 +/- 44; IL1.5, 1,235 +/- 71; and IL4, 1,139 +/- 65 compared with control and IL0.25, P < 0.05). In conclusion, in healthy males the effects of intraduodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, appetite, and energy intake are load dependent, and the threshold loads required to elicit responses vary for these parameters.
Attenuation of blood pressure in spontaneously hypertensive rats by acupuncture was associated with reduction oxidative stress and improvement from endothelial dysfunction (2016)

The effects of acupuncture in treating hypertension were associated with reduced oxidative stress, increased nitric oxide bioavailability and endothelial function in SHRs.
Expression and regulation of chemokines in bacterial pneumonia (1996)

Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells which is dependent on the coordinated expression of both pro and anti-inflammatory cytokines. In this review, we present evidence indicating that both C-X-C and C-C chemokines are integral components of antibacterial host defense. Specifically, in vitro studies indicate that C-X-C chemokines [interleukin-8 (IL-8) and macrophage inflammatory protein 2 (MIP-2) and the C-C chemokine macrophage inflammatory protein 1 alpha (MIP-1 alpha) augment the ability of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, respectively, to phagocytose and kill Escherichia coli. In addition, the intratracheal instillation of Klebsiella pneumoniae in CD-1 mice results in time-dependent production of MIP-2 and MIP-1 alpha and the inhibition of MIP-2 bioactivity in vivo results in decreases in lung PMN influx, impaired bacterial clearance, and early mortality. Finally, the anti-inflammatory cytokine interleukin-10 (IL-10) is also expressed within the lung during the evolution of Klebsiella pneumonia, and neutralization of IL-10 in vivo results in enhanced proinflammatory cytokine production, bacterial clearance, and increases in both short- and long-term survival. In conclusion, our studies indicate that specific chemokines are important mediators of leukocyte recruitment and/or activation in bacterial pneumonia and that the expression of these chemokines is regulated by endogenously produced IL-10.
Linear unbalanced dc bridge (1977)

A modification of the classic Wheatstone bridge is presented in which the output voltage is exactly proportional to the increase in measured resistance. This modification is based on a special system of connection with the power supply. In its original version the circuit was successfully applied to high-pressure measurement by the manganin sensor method.
Full C-L band tunable wavelength conversion by zero dispersion and zero dispersion slope HNLF (2009)

We demonstrated full C-L band tunable wavelength conversion by zero dispersion and zero dispersion slope HNLF. A signal from whole C-L band was converted to an arbitrary wavelength in almost whole C-L band.
Caldecrin Is a Novel-Type Serine Protease Expressed in Pancreas, but Its Homologue, Elastase IV, Is an Artifact during Cloning Derived from Caldecrin Gene (1998)

As reported previously, caldecrin, a serum calcium-decreasing factor, from pancreas was found to be a serine protease, but the proteolytic activity was not necessary for its serum calcium decreasing activity. The caldecrin cDNA encoded a protease zymogen of the chymotrypsin/elastase superfamily consisting of a signal peptide, an activation peptide and a mature enzyme. On a homology search, we found that the sequence of rat caldecrin is almost identical to that of rat elastase IV (nucleotides: 99.3%175B amino acids: 90.3%) with the exception of the central region. However, it is not known whether or not elastase IV is transcribed and translated in vivo, and has proteolytic activity. In the present study, we constructed a rat elastase IV cDNA by means of combinatorial PCR, and compared the recombinant elastase IV with the recombinant caldecrin synthesized in a baculovirus expression system. The recombinant caldecrin protein was expressed in the cells and secreted mainly into the medium. In contrast, in the case of elastase IV, no recombinant protein was immunologically or enzymatically detected in the medium, while an immunoreactive protein with much lower protease activity was found in the cells in an amount comparable to that of the caldecrin protein. Using the RT-PCR method to discriminate caldecrin mRNA from elastase IV mRNA, we detected caldecrin mRNA expression in rat pancreas, but no elastase IV mRNA expression in any tissues examined. PCR analysis of rat genomic DNA revealed the presence of caldecrin and the absence of elastase IV sequences. These results indicate that caldecrin is expressed in the pancreas, but that elastase IV is an artifact produced during cloning. Furthermore, we investigated the protein-chemical and enzymological properties of the rat and human caldecrins using their recombinant proteins. Both recombinant proteins were secreted into the medium as proforms and showed protease activity after trypsin treatment. Some differences were found in the activation process and stability between human and rat caldecrins; human caldecrin was more easily activated by trypsin, but was much more labile than rat caldecrin. Although both caldecrins were found to be chymotrypsin-type proteases, on the basis of their substrate and inhibitor specificities, they were not inhibited by TPCK, suggesting that caldecrin is a novel type of serine protease.
25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production (2009)

25-Hydroxycholesterol is produced in mammalian tissues. The function of this oxysterol is unknown. Here we describe a central role for 25-hydroxycholesterol in regulating the immune system. In initial experiments, we found that stimulation of macrophage Toll-like receptors (TLR) induced expression of cholesterol 25-hydroxylase and the synthesis of 25-hydroxycholesterol. Treatment of naïve B cells with nanomolar concentrations of 25-hydroxycholesterol suppressed IL-2-mediated stimulation of B cell proliferation, repressed activation-induced cytidine deaminase (AID) expression, and blocked class switch recombination, leading to markedly decreased IgA production. Consistent with these findings, deletion of the mouse cholesterol 25-hydroxylase gene caused an increase in serum IgA. Conversely, inactivation of the CYP7B1 oxysterol 7alpha-hydroxylase, which degrades 25-hydroxycholesterol, decreased serum IgA. The suppression of IgA class switching in B cells by a macrophage-derived sterol in response to TLR activation provides a mechanism for local and systemic negative regulation of the adaptive immune response by the innate immune system.
Poly(<i>N</i>‐hydroxyethylacrylamide) Prepared by Atom Transfer Radical Polymerization as a Nonionic, Water‐Soluble, and Hydrolysis‐Resistant Polymer and/or Segment of Block Copolymer with a Well‐Defined Molecular Weight (2009)

Abstract N ‐Hydroxyethylacrylamide (HEAA) was polymerized using the atom transfer radical polymerization (ATRP) with ethyl 2‐chloropropionate (ECP), copper(I) chloride (CuCl), and tris[2‐(dimethylamino)ethyl]amine (Me 6 TREN) in ethanol/water, producing poly( N ‐hydroxyethylacrylamide) (PHEAA) with well‐defined molecular weights. The thermogravimetric analysis (TGA) indicated that the obtained PHEAA broadly decomposed with a two‐stage weight loss. The first loss was due to the decomposition of the hydroxyethyl groups, which started at temperatures ranging from 249.2 to 277.1 °C. The remaining polyacrylamide backbones started to decompose at temperatures ranging from 352.5 to 383.4 °C. The differential scanning calorimetry (DSC) indicated that PHEAA had a glass transition temperature ( T g ) ranging from 70.6 to 117.8 °C. The ability of the obtained PHEAA as a prepolymer to initiate other acrylamide derivatives is described. N , N ‐Dimethylacrylamide (DMAA), N ‐acyloylmorpholine (NAM), and N ‐[3‐(dimethylamino)propyl]acrylamide (DMAPAA) were subsequently added to the solutions after the polymerization of HEAA with ECP/CuCl/Me 6 TREN, producing the corresponding block copolymers. magnified image
A putative role for microRNA-205 in mammary epithelial cell progenitors (2010)

In an effort to understand the potential role of microRNAs (miRNAs) in mammary-gland stem or progenitor cells, miRNA microarrays were performed on subpopulations of the mouse mammary epithelial cell (MEC) line COMMA-DbetaGeo. This cell line contains a heterogeneous subpopulation of progenitors characterized by the expression of stem cell antigen 1 (Sca-1; encoded by Ly6a). Microarray analysis indicated that the Sca-1 subpopulations have distinct miRNA expression profiles. Functional studies were performed on miR-205, which was highly expressed in the Sca-1-positive (Sca-1(+)) cells. When miR-205 was overexpressed in vitro, the COMMA-DbetaGeo cells underwent several significant morphological and molecular changes. miR-205 overexpression led to an expansion of the progenitor-cell population, decreased cell size and increased cellular proliferation. In addition, the colony-forming potential of the two Sca-1 subpopulations was increased. Target prediction for miR-205 indicated that it might regulate the expression of the tumor-suppressor protein PTEN. Overexpression studies using reporter constructs confirmed that PTEN expression is regulated by miR-205. In addition to PTEN, several other putative and previously validated miR-205 targets were identified by microarray analysis, including the previously reported miR-205 targets ZEB1 and ZEB2. Additionally, in normal mouse MECs, high expression of miR-205 was observed in stem-cell-enriched cell populations isolated by FACS using established cell-surface markers.