bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis
Authors: Kazantseva Marina G , Highton John , Stamp Lisa K , Hessian Paul A 
Published: October 2012

Abstract
Introduction
Smoking increases the risk of developing rheumatoid arthritis (RA) and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor (AHR), a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin (IL)-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A.

Methods
Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells (mo-DCs) to the AHR agonist, benzo(a)pyrene (BaP) was compared in vitro.

Results
AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase (IDO)1 expression.

Conclusion
Our findings show that one effect of smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation.
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes
Authors: Peck Amy R , Witkiewicz Agnieszka K , Liu Chengbao , Klimowicz Alexander C , Stringer Ginger A , Pequignot Edward , Freydin Boris , Yang Ning , Ertel Adam , Tran Thai H , Girondo Melanie A , Rosenberg Anne L , Hooke Jeffrey A , Kovatich Albert J , Shriver Craig D , Rimm David L , Magliocco Anthony M , Hyslop Terry , Rui Hallgeir 
Published: October 2012

Abstract
Introduction
Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome.

Methods
Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models.

Results
Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome.

Conclusions
Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.
Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression
Authors: C Cao , X Yu , Z Liao , N Zhu , H Huo , M Wang , G Ji , H She , Z Luo , S Yue 
Published: October 2012

Abstract
Introduction
Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action.

Methods
Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance.

Results
Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro.

Conclusions
Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes.
Blood levels of copeptin on admission predict outcomes in out-of-hospital cardiac arrest survivors treated with therapeutic hypothermia
Authors: Ostadal Petr , Kruger Andreas , Zdrahalova Vladimira , Janotka Marek , Vondrakova Dagmar , Neuzil Petr , Prucha Miroslav 
Published: October 2012

Abstract
Introduction
Prognostic stratification of cardiac arrest survivors is essential for the selection of the most appropriate therapeutic strategy. However, accurate early outcome predictions for this patient population remain challenging. At present, there is a lack of data examining the prognostic value of C-terminal provasopressin (copeptin) in cardiac arrest survivors.

Methods
A group of 40 out-of-hospital cardiac arrest survivors who were treated with endovascular hypothermia was analyzed. Copeptin levels were measured in blood samples taken at admission using a commercially available immunoassay. Neurological outcome was assessed at 30 days post admission according to the Cerebral Performance Category (CPC): CPC 1, no neurological deficit; CPC 2, mild to moderate dysfunction; CPC 3, severe dysfunction; CPC 4, coma; and CPC 5, death.

Results
Copeptin levels were significantly lower in patients with CPC 1 compared with CPC 2 or CPC 3 to CPC 5 (74.3 ± 14.4 pmol/l, 219.8 ± 33.9 pmol/l and 302.7 ± 52.1 pmol/l, respectively; P < 0.0001). Using an optimal cutoff value ≤ 217.9 pmol/l calculated from the receiver operating characteristic curve (area under curve = 0.801, 95% confidence interval = 0.644 to 0.910; P = 0.0001), the sensitivity of predicting survival with good neurological outcome was 78.6% and the specificity was 75.0%. Multiple logistic regression analysis revealed that a copeptin level > 217.9 pmol/l was an independent predictor of severe neurological dysfunction or death, with an adjusted odds ratio of 27.00 (95% confidence interval = 2.27 to 321.68; P = 0.009).

Conclusion
The present study found that copeptin levels have a significant prognostic value at the time of hospital admission, and are a promising diagnostic tool for predicting outcomes in out-of-hospital cardiac arrest survivors.
Suppression of Food Intake by Glucagon-Like Peptide-1 Receptor Agonists: Relative Potencies and Role of Dipeptidyl Peptidase-4
Authors: Jessen Lene , Aulinger Benedikt A. , Hassel Jonathan L. , Roy Kyle J. , Smith Eric P. , Greer Todd M. , Woods Stephen C. , Seeley Randy J. , D'Alessio David A. 
Published: October 2012

Abstract
Administration of the glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1 and exendin-4 (Ex-4) directly into the central nervous system decreases food intake. But although Ex-4 potently suppresses food intake after peripheral administration, the effects of parenteral GLP-1 are variable and not as strong. A plausible explanation for these effects is the rapid inactivation of circulating GLP-1 by dipeptidyl peptidase-4 (DPP-4), an enzyme that does not alter Ex-4 activity. To test this hypothesis, we assessed the relative potency of Ex-4 and GLP-1 under conditions in which DPP-4 activity was reduced. Outbred rats, wild-type mice, and mice with a targeted deletion of DPP-4 (Dpp4−/−) were treated with GLP-1 alone or in combination with the DPP-4 inhibitor vildagliptin, Ex-4, or saline, and food intake was measured. GLP-1 alone, even at high doses, did not affect feeding in wild-type mice or rats but did reduce food intake when combined with vildagliptin or given to Dpp4−/− mice. Despite plasma clearance similar to DPP-4-protected GLP-1, equimolar Ex-4 caused greater anorexia than vildagliptin plus GLP-1. To determine whether supraphysiological levels of endogenous GLP-1 would suppress food intake if protected from DPP-4, rats with Roux-en-Y gastric bypass and significantly elevated postprandial plasma GLP-1 received vildagliptin or saline. Despite 5-fold greater postprandial GLP-1 in these animals, vildagliptin did not affect food intake in Roux-en-Y gastric bypass rats. Thus, in both mice and rats, peripheral GLP-1 reduces food intake significantly less than Ex-4, even when protected from DPP-4. These findings suggest distinct potencies of GLP-1 receptor agonists on food intake that cannot be explained by plasma pharmacokinetics.
Epigenetic Changes Through DNA Methylation Contribute to Uterine Stromal Cell Decidualization
Authors: Gao Fei , Ma Xinghong , Rusie Allison , Hemingway Jennifer , Ostmann Alicia B. , Chung Daesuk , Das Sanjoy K. 
Published: October 2012

AbstractEmbryo-uterine interaction during early pregnancy critically depends on the coordinated expression of numerous genes at the site of implantation. The epigenetic mechanism through DNA methylation (DNM) plays a major role in the control of gene expression, although this regulatory event remains unknown in uterine implantation sites. Our analysis revealed the presence of DNA methyltransferase 1 (Dnmt1) in mouse endometrial cells on the receptive d 4 of pregnancy and early postattachment (d 5) phase, whereas Dnmt3a had lower abundant expression. Both Dnmt1 and Dnmt3a were coordinately expressed in decidual cells on d 6–8. 5-Methycytosine showed a similar expression pattern to that of Dnmt1. The preimplantation inhibition of DNM by 5-aza-2′-deoxycytodine was not antagonistic for embryonic attachment, although endometrial stromal cell proliferation at the site of implantation was down-regulated, indicating a disturbance with the postattachment decidualization event. Indeed, the peri- or postimplantation inhibition of DNM caused significant abrogation of decidualization, with concomitant loss of embryos. We next identified decidual genes undergoing alteration of DNM using methylation-sensitive restriction fingerprinting. One such gene, Chromobox homolog 4, an epigenetic regulator in the polycomb group protein family, exhibited hypomethylation in promoter DNA and increased expression with the onset of decidualization. Furthermore, inhibition of DNM resulted in enhanced expression of hypermethylated genes (Bcl3 and Slc16a3) in the decidual bed as compared with control, indicating aberration of gene expression may be associated with DNM-inhibition-induced decidual perturbation. Overall, these results suggest that uterine DNM plays a major role for successful decidualization and embryo development during early pregnancy.
Sunitinib- and Sorafenib-lnduced Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor
Authors: Turan Nedim , Benekli Mustafa , Ozturk Selcuk Cemil , Inal Salih , Memis Leyla , Guz Galip , Cetin Bulent , Buyukberber Suleyman 
Published: October 2012

Objective TO report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. Case Summary A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. Discussion Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. Conclusions The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.
Proton Pump Inhibitor Use and Association with Spontaneous Bacterial Peritonitis in Patients with Cirrhosis and Ascites
Authors: Siple Jolene F , Morey Jessica M , Gutman Tracy E , Weinberg Kathy L , Collins Peggie D 
Published: October 2012

Objective: To evaluate the literature regarding the efficacy and safety of proton pump inhibitors (PPIs) when they are used in patients with cirrhosis and ascites. Data Sources: A literature search was conducted using MEDLINE (1966-May 2012) and Web of Science (1990-May 2012) with the terms proton pump inhibitor, antisecretory therapy, cirrhosis, ascites, spontaneous bacterial peritonitis, and Clostridium difficile. The search was restricted to articles published in English on the use of PPIs in humans. Reference citations from identified published articles were reviewed for relevant information. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated for inclusion. One case series, 8 retrospective case-control trials, and 1 meta-analysis were identified. Data Synthesis: Cirrhosis may cause complications such as portal hypertension, esophageal varices, and ascites. Patients may be prescribed PPIs without clear indications or because of their propensity to develop upper gastrointestinal symptoms and bleeding. However, gastric acidity is a major nonspecific defense mechanism and there is insufficient evidence on the need for chronic acid suppression in patients with cirrhosis. It is postulated that the portal hypertensive environment in cirrhosis and the acid suppression from PPIs can increase the risk of spontaneous bacterial peritonitis and C. difficile infection in patients with cirrhosis with ascites. Several retrospective studies and 1 meta-analysis have confirmed this association. Conclusions: Patients with cirrhosis and ascites should be monitored carefully while on PPIs for a possible increased risk of infection from spontaneous bacterial peritonitis and C. difficile. Prospective randomized trials are needed to confirm this association. Clinicians should be aware of this lesser known adverse effect of PPIs.
Local Electronic Structure and UV Electroluminescence of n-ZnO:N/p-GaN Heterojunction LEDs Grown by Remote Plasma Atomic Layer Deposition
Authors: Chien Jui F. , Chen Ching H. , Shyue Jing J. , Chen Miin J. 
Published: October 2012

ABSTRACTNitrogen-doped ZnO (ZnO:N) films have been prepared by remote plasma atomic layer deposition (RP-ALD) and treated by rapid thermal annealing (RTA) in oxygen atmosphere. The local electronic structures of the (ZnO:N) films were investigated by X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge spectroscopy (XANES) at the O K-edge. The XPS reveals the presence of the Zn-N bond in the ZnO:N films, indicating that partial amounts of oxygen sites are occupied by nitrogen species. This is correspondent with the decrease of electron concentration in ZnO:N films with the nitrogen doping concentration, as indicated by the Hall effect measurement. The RP-ALD technique was applied to fabricate the n-type ZnO:N/p-type GaN heterojunction LEDs. Dominant ultraviolet electroluminescence at 371 nm from the ZnO:N layer was observed at room temperature.
Influence of Post Growth Annealing on the Optical Properties of Gallium Nitride Films Grown by Pulsed Laser Deposition
Authors: Haider M. Baseer , Al-Kuhaili M. F. , Durrani S. M. A. , Bakhtiari Imran 
Published: October 2012

Abstract:Gallium nitride thin films were grown by pulsed laser deposition. Subsequently, post-growth annealing of the samples was performed at 400, and 600 oC in the nitrogen atmosphere. Surface morphology of the as-grown and annealed samples was performed by atomic force microscopy, surface roughness of the films improved after annealing. Chemical analysis of the samples was performed using x-ray photon spectroscopy, stoichiometric Gallium nitride thin films were obtained for the samples annealed at 600 oC. Optical measurements of the samples were performed to investigate the effect of annealing on the band gap and optical constants the films.
GaN HEMT Reliability: From Time Dependent Gate Degradation to On-state Failure Mechanisms
Authors: Zanoni Enrico , Meneghesso Gaudenzio , Meneghini Matteo , Stocco Antonio 
Published: October 2012

ABSTRACTIn this paper, we compare degradation modes and failure mechanisms of different AlGaN/GaN HEMT technologies. We present data concerning reverse-bias degradation of GaN-based HEMTs, which results in a dramatic increase of gate leakage current, and present a timedependent model for gate degradation. Some of the tested technologies demonstrated to be immune from this failure mechanism up to drain-gate voltages in excess of 100 V. When this was the case, the main failure mode consisted of drain current degradation during on-state tests, resulting from charge trapping in the gate-drain access region attributed to hot-electron effects. Finally, the use of diagnostic techniques such as electroluminescence microscopy and Deep Level Transient Spectroscopy for the identification of failure modes and mechanisms of GaNbased HEMTs is reviewed. Concerning reverse-bias degradation of GaN-based HEMTs, we demonstrate that, (i) when submitted to reverse-gate stress, HEMTs can show both recoverable and permanent degradation. (ii) recoverable degradation consists of a decrease in gate current and threshold voltage, which are ascribed to the simultaneous trapping of negative charge in the AlGaN layer, and of positive charge close to the AlGaN/GaN interface. (iii) permanent degradation is manifested by the generation of parasitic leakage paths. Time-dependent analysis suggests that permanent degradation can be ascribed to a defect generation and percolation process. Results supports the existence of a time to breakdown for HEMT degradation, which significantly depends on the stress voltage level. On the contrary, AlGaN/GaN technologies which were found to be resistant to gate degradation (off-state critical voltage larger than 100 V for a 0.25 um gate device) were subjected to on-state tests at different gate and drain voltage levels. All tests showed a non-recoverable degradation of electrical parameters (drain saturation current, threshold voltage and on-state resistance) and electroluminescence signal EL, with a strong dependence on the EL value of the bias point, and a negligible dependence of temperature. Once verified that EL intensity represents a reliable estimate of channel hot electron effects, we attributed the degradation to hot electron trapping in the gate-drain access region. Using EL intensity as a measure of the stress acceleration factor, we derived an acceleration law for GaN HEMT hot electron degradation similar to the one already demonstrated for GaAs devices.
MEMS-CMOS Integrated Tactile Sensor with Digital Signal Processing for Robot Application
Authors: Makihata M. , Muroyama M. , Tanaka S. , Yamada H. , Nakayama T. , Yamaguchi U. , Mima K. , Nonomura Y. , Fujiyoshi M. , Esashi M. 
Published: October 2012

ABSTRACTAn ultra-small tactile sensor with functions of signal processing and digital communication has been prototyped based on MEMS-CMOS integration technology. The designed analog-digital mixed signal ASIC allows many tactile sensors to connect each other on a common bus line, which drastically reduces the number of wire. The ASIC capacitively detects the deformation of a force sensor and sends digital data to the common bus line when the force exceeds a threshold. The digital data contain a physical ID of each sensor, 32-bit sensing data and 16-bit cyclic redundancy check (CRC) code. In this study, a novel wafer-level integration and packaging technology were developed, and a chip-size-packaged tactile sensor with a small footprint (2.5mm×2.5mm) and a low profile (0.27mm) was prototyped and tested. The sensor autonomously sends digital data like a tactile receptor of human.
Modeling of Exciplex Recombination in Organic Bilayer Structures
Authors: Liu Feilong , Ruden P. Paul , Campbell Ian H. , Smith Darryl L. 
Published: October 2012

ABSTRACTThe effect of exciplex dynamics on the device characteristics of organic semiconductor bilayer structures is explored. Exciplex formation, dissociation, and relaxation to the ground state are incorporated into a physics-based device model. The model is applied to both organic light emitting diodes and photovoltaic cells. In the examples, C60and tetracene parameters are used for the electron and hole transport layers, respectively.