gebhart/patrepeval huggingface dataset:
Comparison of Lactobacillus crispatus isolates from Lactobacillus-dominated vaginal microbiomes with isolates from microbiomes containing bacterial vaginosis-associated bacteria (2016)

Vaginal lactobacilli can inhibit colonization by and growth of other bacteria, thereby preventing development of bacterial vaginosis (BV). Amongst the lactobacilli, Lactobacillus crispatus appears to be particularly effective at inhibiting growth of BV-associated bacteria. Nonetheless, some women who are colonized with this species can still develop clinical BV. Therefore, we sought to determine whether strains of L. crispatus that colonize women with lactobacilli-dominated vaginal microbiomes are distinct from strains that colonize women who develop BV. The genomes of L. crispatus isolates from four women with lactobacilli-dominated vaginal microbiomes ( <1% 16S rRNA reads above threshold from genera other than Lactobacillus) and four women with microbiomes containing BV-associated bacteria (>12% 16S rRNA reads from bacterial taxa associated with BV) were sequenced and compared. Lactic acid production by the different strains was quantified. Phage induction in the strains was also analysed. There was considerable genetic diversity between strains, and several genes were exclusive to either the strains from Lactobacillus-dominated microbiomes or those containing BV-associated bacteria. Overall, strains from microbiomes dominated by lactobacilli did not differ from strains from microbiomes containing BV-associated bacteria with respect to lactic acid production. All of the strains contained multiple phage, but there was no clear distinction between the presence or absence of BV-associated bacteria with respect to phage-induced lysis. Genes found to be exclusive to the Lactobacillus-dominated versus BV-associated bacteria-containing microbiomes could play a role in the maintenance of vaginal health and the development of BV, respectively.
Association of interleukin‐18 expression with enhanced levels of both interleukin‐1β and tumor necrosis factor α in knee synovial tissue of patients with rheumatoid arthritis (2003)

Our results show that expression of IL-18 is associated with that of IL-1beta and TNFalpha and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1beta and TNFalpha.
Development of a Femtomolar-Acting Humanin Derivative Named Colivelin by Attaching Activity-Dependent Neurotrophic Factor to Its N Terminus: Characterization of Colivelin-Mediated Neuroprotection against Alzheimer's Disease-Relevant InsultsIn VitroandIn Vivo (2005)

Alzheimer's disease (AD) is the most common cause of dementia. Humanin (HN) is a short bioactive peptide abolishing neuronal cell death induced by various familial AD (FAD)-causative genes and amyloid-beta (Abeta) in vitro. It has been shown that HN suppresses memory impairment of mice induced by intracerebroventricular administration of Abeta. To potentiate the neuroprotective effect of HN, we synthesized a hybrid peptide named Colivelin composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)HNG17, a potent HN derivative. Colivelin completely suppresses death induced by overexpressed FAD-causative genes and Abeta1-43 at a concentration of 100 fM, whereas AGA-(C8R)HNG17 does so at a concentration of 10 pM. Colivelin-induced neuroprotection has been confirmed to occur via two neuroprotective pathways: one mediated by Ca2+/calmodulin-dependent protein kinase IV, triggered by ADNF, and one mediated by signal transducer and activator of transcription 3, triggered by HN. In vivo animal studies have further indicated that intracerebroventricular administration of Colivelin not only completely suppresses impairment in spatial working memory induced by repetitive intracerebroventricular injection of Abeta25-35 or Abeta1-42, but also it antagonizes neuronal loss in the CA1 region of hippocampus induced by hippocampal injection of Abeta1-42. In addition, intraperitoneally administered Colivelin suppresses memory impairment caused by a muscarinic acetylcholine receptor antagonist, 3-quinuclidinyl benzilate, indicating that a substantial portion of intraperitoneally administered Colivelin passes through the blood-brain barrier and suppresses functional memory deficit. Thus, Colivelin might serve as a novel drug candidate for treatment of AD.
Imaging brain tumor proliferative activity with [124I]iododeoxyuridine. (2000)

Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [124I]IUdR in 20 patients with brain tumors, including meningiomas and gliomas. The PET images were directly compared with gadolinium contrast-enhanced or T2-weighted magnetic resonance images. Estimates for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct the 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standard uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also calculated from the 24-h image data. The Ki, SUV, and Tm/Br values were related to tumor type and grade, tumor labeling index, and survival after the PET scan. The plasma half-life of [124I]IUdR was short (2-3 min), and the arterial plasma input function was similar between patients (48 +/- 12 SUV*min). Plasma clearance of the major radiolabeled metabolite ([124I]iodide) varied somewhat between patients and was markedly prolonged in one patient with renal insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [124I]iodide) remained in the tumors after the 24-h washout period, and this fraction varied between the different tumor groups. Because the SUV and Tm:Br ratio values reflect both IUdR-DNA incorporated and exchangeable nonincorporated radioactivity, any residual nonincorporated radioactivity will amplify their values and distort their significance and interpretation. This was particularly apparent in the meningioma and glioblastoma multiforme groups of tumors. Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2.3 microl/min/g (peak value for glioblastoma multiforme, GBM). Comparable SUV and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and from 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. Thus, the range of values was much greater for Ki (approximately 8-fold) compared with that for SUV (approximately 2.2-fold) and Tm:Br (approximately 3-fold). The expected relationships between Ki, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient survival) were observed. However, greater image specificity and significance of the SUV and Tm:Br values would be obtained by achieving greater washout and clearance of the exchangeable fraction of residual (background) radioactivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [124I]IUdR administration.
Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. (1984)

The C3d receptor (CR2) of human B lymphocytes mediates the binding to these cells of immune complexes that have activated the complement system and bear the fragments of C3, iC3b, C3d,g, and C3d. A 145,000 Mr membrane protein previously described as being recognized by the monoclonal antibody HB-5 and shown to be expressed only by B lymphocytes and B lymphoblastoid cell lines, such as Raji, was assessed for its possible identity as CR2. Treatment of Raji cells with HB-5 and goat F(ab')2 anti-mouse IgG (GaM) diminished the capacity of these cells to form rosettes with sheep erythrocyte (E) intermediates bearing 130,000 molecules of iC3b or C3d, whereas treatment with the monoclonal antibody alone had no effect. The capacity of peripheral blood B lymphocytes to bind EC3d was similarly inhibited by the combination of HB-5 and GaM. The possibility that HB-5 may interact with a site on CR2 that is distinct from the ligand binding site permitted the direct analysis of the capacity of the HB-5 antigen to bind to the C3 fragments. Protein A-containing Staphylococcus aureus particles to which HB-5 had been bound were incubated with detergent lysates of Raji cells and B lymphocytes under conditions that had been shown to be associated only with the binding of the 145,000 Mr antigen. These particles bearing HB-5 and antigen derived from either cell type were shown to adhere specifically to EiC3b and EC3d, demonstrating that transfer of the HB-5 antigen from CR2-bearing cells to S. aureus particles led to the acquisition of CR2 function by the particles. The additional findings that the relatively weak capacity of Raji cells to form rosettes with EC3b was inhibited by HB-5 and that the S. aureus particles bearing immunoadsorbed HB-5 antigen bound to EC3b indicated that the C3b-binding function of the CR1-negative Raji cell resides in CR2, rather than in other membrane proteins.
Lower financial results - due to market slowdown or poor management? : finance (2009)

Sales are down. Profits are below budget. Margins are being squeezed. But why? you ask and in return you hear, It's the downturn, Its ... these markets or even It's the recession. Are you hearing this from your divisional heads or business unit leaders? How do you know weak business performance is really due to the market downturn? How do you know, the market downturn is not being used as an excuse for poor management?
Zymogen-activation kinetics. Modulatory effects of trans-4-(aminomethyl)cyclohexane-1-carboxylic acid and poly-d-lysine on plasminogen activation (1985)

The kinetics of plasminogen activation catalysed by urokinase and tissue-type plasminogen activator were investigated. Kinetic measurements are performed by means of a specific chromogenic peptide substrate for plasmin, D-valyl-L-leucyl-L-lysine 4-nitroanilide. Two methods are proposed for the analysis of the resulting progress curve of nitroaniline formation in terms of zymogen-activation kinetics: a graphical transformation of the parabolic curve and transformation of the curve for nitroaniline production into a linear progress curve by the addition of a specific inhibitor of plasmin, bovine pancreatic trypsin inhibitor. The two methods give similar results, suggesting that the reaction between activator and plasminogen is a simple second-order reaction at least at plasminogen concentrations up to about 10 microM. The kinetics of both Glu1-plasminogen (residues 1-790) and Lys77-plasminogen (residues 77-790) activation were investigated. The results confirm previous observations showing that trans-4-(aminomethyl)cyclohexane-1-carboxylic acid at relatively low concentrations enhances the activation rate of Glu1-plasminogen but not that of Lys77-plasminogen. At higher concentrations both Glu1- and Lys77-plasminogen activation are inhibited. The concentration interval for the inhibition of urokinase-catalysed reactions is shown to be very different from that of the tissue-plasminogen activator system. Evidence is presented indicating that binding to the active site of urokinase (KD = 2.0 mM) is responsible for the inhibition of the urokinase system, binding to the active site of tissue-plasminogen activator is approx. 100-fold weaker, and inhibition of the tissue-plasminogen activator system, when monitored by plasmin activity, is mainly due to plasmin inhibition. Poly-D-lysine (Mr 160 000) causes a marked enhancement of plasminogen activation catalysed by tissue-plasminogen activator but not by urokinase. Bell-shaped curves of enhancement as a function of the logarithm of poly-D-lysine concentration are obtained for both Glu1- and Lys77-plasminogen activation, with a maximal effect at about 10 mg/litre. The enhancement of Glu1-plasminogen activation exerted by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid is additive to that of poly-D-lysine, whereas poly-D-lysine-induced enhancement of Lys77-plasminogen activation is abolished by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Analogies are drawn up between the effector functions of poly-D-lysine and fibrin on the catalytic activity of tissue-plasminogen activator.
An isoleucine/leucine residue in the carboxyltransferase domain of acetyl-CoA carboxylase is critical for interaction with aryloxyphenoxypropionate and cyclohexanedione inhibitors (2001)

cDNA fragments encoding the carboxyltransferase domain of the multidomain plastid acetyl-CoA carboxylase (ACCase) from herbicide-resistant maize and from herbicide-sensitive and herbicide-resistant Lolium rigidum were cloned and sequenced. A Leu residue was found in ACCases from herbicide-resistant plants at a position occupied by Ile in all ACCases from sensitive grasses studied so far. Leu is present at the equivalent position in herbicide-resistant ACCases from other eukaryotes. Chimeric ACCases containing a 1000-aa fragment of two ACCase isozymes found in a herbicide-resistant maize were expressed in a yeast ACC1 null mutant to test herbicide sensitivity of the enzyme in vivo and in vitro. One of the enzymes was resistant/tolerant, and one was sensitive to haloxyfop and sethoxydim, rendering the gene-replacement yeast strains resistant and sensitive to these compounds, respectively. The sensitive enzyme has an Ile residue, and the resistant one has a Leu residue at the putative herbicide-binding site. Additionally, a single Ile to Leu replacement at an equivalent position changes the wheat plastid ACCase from sensitive to resistant. The effect of the opposite substitution, Leu to Ile, makes Toxoplasma gondii apicoplast ACCase resistant to haloxyfop and clodinafop. In this case, inhibition of the carboxyltransferase activity of ACCase (second half-reaction) of a large fragment of the Toxoplasma enzyme expressed in Escherichia coli was tested. The critical amino acid residue is located close to a highly conserved motif of the carboxyltransferase domain, which is probably a part of the enzyme active site, providing the basis for the activity of fop and dim herbicides.
Reversible photoswitching conjugated polymer nanoparticles for cell and ex vivo tumor imaging (2014)

Fluorescent photoswitchable conjugated polymer nanoparticles (PCPNPs) bearing poly(9,9-dihexylfluorene-alt-2,1,3-benzoxadiazole) (PFBD) as the fluorescent host polymer and the photochromic diarylethene as toggle are synthesized via a modified nano-precipitation method using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG-NH₂) as the encapsulation matrix. The PCPNPs are spherical in shape with diameters around 34 nm. The fluorescence switching processes upon UV and white light illumination are successfully demonstrated with high contrast up to 90-fold, recovery efficiency of 95%, and excellent repeatability in solution. The cationic PCPNPs can be easily internalized into cancer cells, and accumulate in tumor tissues, where the fluorescence photoswitching processes can be used to self-validate the imaging results.
miR-221 overexpression contributes to liver tumorigenesis (2009)

MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment.
Genomic Footprinting Using Nucleases (2003)

Gene expression is regulated by complex mechanisms involving dynamic interactions between cis-acting elements and trans-acting factors in a highly structured chromatin environment. Investigations of protein/DNA interactions in vitro may not have relevance to a living cell system. To analyze events occurring at the DNA level in a living cell, Church et al. introduced the genomic footprinting procedure (). The procedure was developed further () but ligation-mediated PCR (LM-PCR) was the breakthrough that rendered the technique accessible to many laboratories ().
Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: revised recommendations (2007)

Since publication of the Australasian Creatinine Consensus Working Group's position statement in 2005, most Australasian laboratories now automatically report an estimated glomerular filtration rate (eGFR) (based on the Modification of Diet in Renal Disease [MDRD] formula) with results of serum creatinine tests in adults. Anecdotal evidence suggests that automatic reporting of eGFR helps to identify asymptomatic kidney dysfunction at an earlier stage and to develop rational and appropriate management plans. Changes to the measurement and calibration of serum creatinine assays and issues regarding implementation of eGFR in clinical practice led the Australasian Creatinine Consensus Working Group to reconvene in 2007. The recommendations contained here build on the original 2005 position statement and consolidate the role of eGFR in clinical practice. The Working Group recommends that the eGFR upper reporting limit be extended to 90 mL/min/1.73 m2, with eGFR values above this amount being reported as "> 90 mL/min/1.73 m2", rather than as a precise figure. The Working Group has concluded that it is currently premature to recommend age-related decision points for eGFR. However, it is appropriate to advise medical practitioners that, in people aged >/= 70 years, an eGFR in the range 45-59 mL/min/1.73 m2, if stable over time and unaccompanied by other evidence of kidney damage, may be interpreted as consistent with a typical eGFR for this age group and is unlikely to be associated with chronic kidney disease-related complications. Pending publication of validation studies, the Working Group recommends that Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples and other ethnic groups. The Working Group supports the use of eGFR to assist drug dosing decision making in general practice.
Identification of RPE65 in transformed kidney cells1 (1999)

The protein RPE65 has an important role in retinoid processing and/or retinoid transport in the eye. Retinoids are involved in cell differentiation, embryogenesis and carcinogenesis. Since the kidney is known as an important site for retinoid metabolism, the expression of RPE65 in normal kidney and transformed kidney cells has been examined. The RPE65 mRNA was detected in transformed kidney cell lines including the human embryonic kidney cell line HEK293 and the African green monkey kidney cell lines COS-1 and COS-7 by reverse transcription PCR. In contrast, it was not detected in human primary kidney cells or monkey kidney tissues under the same PCR conditions. The RPE65 protein was also identified in COS-7 and HEK293 cells by Western blot analysis using a monoclonal antibody to RPE65, but not in the primary kidney cells or kidney tissues. The RPE65 cDNA containing the full-length encoding region was amplified from HEK293 and COS-7 cells. DNA sequencing showed that the RPE65 cDNA from HEK293 cells is identical to the RPE65 cDNA from the human retinal pigment epithelium. The RPE65 from COS-7 cells shares 98 and 99% sequence identity with human RPE65 at the nucleotide and amino acid levels, respectively. Moreover, the RPE65 mRNA was detected in three out of four renal tumor cultures analyzed including congenital mesoblastic nephroma and clear cell sarcoma of the kidney. These results demonstrated that transformed kidney cells express this retinoid processing protein, suggesting that these transformed cells may have an alternative retinoid metabolism not present in normal kidney cells.
Stresses in silicon substrates near isolation trenches (1991)

We describe a methodology for obtaining stresses near isolation trenches in silicon considering the entire trench forming process. A two-dimensional plane strain finite element stress analysis is performed for a trench with a thermal SiO2 sidewall and polysilicon ‘‘fill’’ which includes the cumulative stresses from the superposition of (i) residual stresses from the thermal oxidation step, (ii) the intrinsic stress from the polysilicon deposition, and (iii) stresses due to the coefficient of thermal expansion mismatch between SiO2 and silicon during the temperature cycles involved in the process. The thermal oxidation step is simulated using a two-dimensional nonlinear viscoelastic program novel [in Proceedings of the Second International Symposium on Process Physics and Modeling in Semiconductor Technology, edited by G. R. Srinivasan, J. D. Plummer, and S. T. Pantelides (Electrochemical Society, Pennington, NJ, 1991), p. 772], that produces the oxide shape and stress at the oxide-silicon interface which is converted into equivalent nodal forces on the finite element grid. We have also made a three-dimensional finite element analysis of the thermal mismatch stresses between a parallelopipedic oxide inclusion in silicon with anisotropic properties and have compared these results with the analytical results [J. Appl. Phys. 66, 2741 (1989); 67, 1092 (1990)] in which the oxide and silicon are assumed to have identical isotropic elastic properties.
Infection and intravenous catheters (1985)

Journal Article Infection and intravenous catheters Get access R. FREEMAN, R. FREEMAN Department of Microbiology. Freeman HospitalNewcastle upon Tyne, England Search for other works by this author on: Oxford Academic PubMed Google Scholar F. K. GOULD F. K. GOULD Department of Microbiology. Freeman HospitalNewcastle upon Tyne, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 15, Issue 2, February 1985, Page 258, https://doi.org/10.1093/jac/15.2.258 Published: 01 February 1985
Proactive case management of high-risk patients with type 2 diabetes mellitus by a clinical pharmacist: a randomized controlled trial. (2005)

Proactive diabetes case management by a pharmacist substantially improved glycemic control and diabetes process-of-care measures. This approach, integrated with and based in the primary care setting, was an effective and efficient approach to improving care, especially for those with poor glycemic control at baseline.