bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll‐like Receptor 2 Controls Acute Immune Complex–Driven Arthritis in Mice by Regulating the Inhibitory Fcγ Receptor IIB
Authors: Abdollahi‐Roodsaz Shahla , Koenders Marije I. , Walgreen Birgitte , Bolscher Judith , Helsen Monique M. , van den Bersselaar Liduine A. , van Lent Peter L. , van de Loo Fons A. J. , van den Berg Wim B. 
Published: July 2013

ObjectivePrevious studies have demonstrated a protective role of Toll‐like receptor 2 (TLR‐2) and a proinflammatory function of TLR‐4 during chronic T cell–driven arthritis. The involvement of TLRs in T cell–independent arthritic processes, however, remains unclear. This study was undertaken to determine the functional significance of TLR‐2 and TLR‐4 in T cell–independent immune complex–driven arthritis.MethodsSerum‐transfer arthritis was induced in wild‐type and TLR‐deficient mice by intraperitoneal injections of arthritogenic K/BxN mouse serum. Arthritis was assessed macroscopically and by histologic analysis. The influence of TLR‐2 on macrophage cytokine profile, Fcγ receptor (FcγR) expression, and response to immune complexes was determined.ResultsWhile TLR‐4, unexpectedly, did not play any significant role, TLR‐2 deficiency accelerated the onset and markedly increased the severity of acute immune complex–driven arthritis in mice. TLR‐2 deficiency resulted in a substantial increase in joint inflammation, bone erosion, and cartilage pathology, indicating a protective function of TLR‐2 in passive FcγR‐driven disease. Ex vivo study of the macrophage inflammatory phenotype revealed increased production of tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) despite similar levels of IL‐10, along with a significant increase in FcγR‐specific response, in TLR‐2−/− mouse macrophages early in the disease. Although distinct FcγR messenger RNA expression was not affected, cell surface protein expression of the inhibitory FcγRIIB in TLR‐2−/− naive primary macrophages was specifically diminished, resulting in a higher proinflammatory response. Accordingly, TLR‐2 stimulation specifically up‐regulated FcγRIIB, but not the activating FcγR, on macrophages.ConclusionTLR‐2 regulates acute immune complex–driven arthritis by controlling macrophage FcγR response. Our findings indicate that the protective role of TLR‐2 is extended beyond its previously described role in promoting Treg cells during T cell–mediated arthritis.
Prediction of inclusion body solubilization from shaken to stirred reactors
Authors: Walther Cornelia , Mayer Sabrina , Trefilov Alexandru , Sekot Gerhard , Hahn Rainer , Jungbauer Alois , Dürauer Astrid 
Published: July 2013

ABSTRACTInclusion bodies (IBs) were solubilized in a µ‐scale system using shaking microtiter plates or a stirred tank reactor in a laboratory setting. Characteristic dimensionless numbers for mixing, the Phase number Ph and Reynolds number Re did not correlate with the kinetics and equilibrium of protein solubilization. The solubilization kinetics was independent of the mixing system, stirring or shaking rate, shaking diameter, and energy input. Good agreement was observed between the solubilization kinetics and yield on the µ‐scale and laboratory setting. We show that the IB solubilization process is controlled predominantly by pore diffusion. Thus, for the process it is sufficient to keep the IBs homogeneously suspended, and additional power input will not improve the process. The high‐throughput system developed on the µ‐scale can predict solubilization in stirred reactors up to a factor of 500 and can therefore be used to determine optimal solubilization conditions on laboratory and industrial scale. Biotechnol. Bioeng. 2014;111: 84–94. © 2013 Wiley Periodicals, Inc.
Development and characterization of AND‐gate dynamic controllers with a modular synthetic GAL1 core promoter in Saccharomyces cerevisiae
Authors: Teo Wei Suong , Chang Matthew Wook 
Published: July 2013

ABSTRACTExpression of heterologous proteins in metabolic engineering endeavors can be detrimental to host cells due to increased usage of cellular resources. Dynamic controls, where protein expression can be triggered on‐demand, are effective for the engineering and optimization of bio‐catalysts towards robust cell growth and enhanced biochemical productivity. Here, we describe the development and characterization of AND‐gate dynamic controllers in Saccharomyces cerevisiae which combine two dynamic control strategies, inducible promoters and sensing‐regulation. These dynamic controllers were constructed based on synthetic hybrid promoters. Promoter enhancer sequences were fused to a synthetic GAL1 core promoter containing DNA binding sites for the binding of a repressor that reduced DNA affinity upon interaction with key intermediates in a biochemical pathway. As fatty acids are key intermediates for production of fatty alcohols, fatty acid esters, alkenes, and alkanes, which are advanced biofuels, we used the fatty acid responsive FadR repressor and its operator sequence to demonstrate the functionality of the dynamic controllers. We established that the synthetic GAL1 core promoter can be used as a modular promoter part for constructing synthetic hybrid promoters and conferring fatty acid inducibility. We further showed the performance of the AND‐gate dynamic controllers, where two inputs (fatty acid and copper presence/phosphate starvation) were required to switch the AND‐gate ON. This work provides a convenient platform for constructing AND‐gate dynamic controllers, that is, promoters that combine inducible functionality with regulation of protein expression levels upon detection of key intermediates towards the engineering and optimization of bio‐catalytic yeast cells. Biotechnol. Bioeng. 2014;111: 144–151. © 2013 Wiley Periodicals, Inc.
Design of short membrane selective antimicrobial peptides containing tryptophan and arginine residues for improved activity, salt‐resistance, and biocompatibility
Authors: Saravanan Rathi , Li Xiang , Lim Kaiyang , Mohanram Harini , Peng Li , Mishra Biswajit , Basu Anindya , Lee Jong‐Min , Bhattacharjya Surajit , Leong Susanna Su Jan 
Published: July 2013

ABSTRACTAntimicrobial peptides (AMPs) kill microbes by non‐specific membrane permeabilization, making them ideal templates for designing novel peptide‐based antibiotics that can combat multi‐drug resistant pathogens. For maximum efficacy in vivo and in vitro, AMPs must be biocompatible, salt‐tolerant and possess broad‐spectrum antimicrobial activity. These attributes can be obtained by rational design of peptides guided by good understanding of peptide structure‐function. Toward this end, this study investigates the influence of charge and hydrophobicity on the activity of tryptophan and arginine rich decamer peptides engineered from a salt resistant human β‐defensin‐28 variant. Mechanistic investigations of the decamers with detergents mimicking the composition of bacterial and mammalian membrane, reveal a correlation between improved antibacterial activity and the increase in tryptophan and positive residue content, while keeping hemolysis low. The potent antimicrobial activity and high cell membrane selective behavior of the two most active decamers, D5 and D6, are attributed to an optimum peptide charge to hydrophobic ratio bestowed by systematic arginine and tryptophan substitution. D5 and D6 show surface localization behavior with binding constants of 1.86 × 108 and 2.6 × 108 M−1, respectively, as determined by isothermal calorimetry measurements. NMR derived structures of D5 and D6 in SDS detergent micelles revealed proximity of Trp and Arg residues in an extended structural scaffold. Such potential cation–π interactions may be critical in cell permeabilization of the AMPs. The fundamental characterization of the engineered decamers provided in this study improves the understanding of structure–activity relationship of short arginine tryptophan rich AMPs, which will pave the way for future de novo design of potent AMPs for therapeutic and biomedical applications. Biotechnol. Bioeng. 2014;111: 37–49. © 2013 Wiley Periodicals, Inc.
Management and outcome of 239 adolescent and adult rhabdomyosarcoma patients
Authors: Dumont Sarah N. , Araujo Dejka M. , Munsell Mark F. , Salganick Jason A. , Dumont Amaury G. , Raymond Kevin A. , Linassier Claude , Patel Shreyaskumar , Benjamin Robert S. , Trent Jonathan C. 
Published: July 2013

AbstractAdult rhabdomyosarcoma (RMS) is a rare tumor that has inferior outcome compared to younger patient population. The present work aims to study the age‐related differences in management of adolescents and adults with RMS. Under an institutional review board‐approved protocol, we retrospectively analyzed 239 patients, 10 years of age and greater, diagnosed with RMS at MD Anderson Cancer Center from 1957 through 2003. Of the 239 patients, 163 patients were nonmetastatic with a median overall survival (OS) of 3.8 years (95% CI 2.8–7.6). In the multivariate analysis, age >50 was significantly associated with shorter OS and recurrence‐free survival (RFS) for primary patients. Metastases were present in 76 patients, the median OS was 1.4 years. Approximately 13% of metastatic patients <50 years old had a long‐term survival exceeding 15 years. Multimodality therapy, including surgery, radiotherapy, and chemotherapy was significantly associated with longer OS in primary and metastatic patients. Use of bi‐ and triple modality treatment decreased in metastatic patients over 50 years of age compared to younger patients. RMS in adolescents and adults has a poor outcome compared with younger individuals. Increased use of multidisciplinary therapy may improve older patient clinical outcome.
A Catalyst for One‐step Isoparaffin Production via Fischer–Tropsch Synthesis: Growth of a H‐Mordenite Shell Encapsulating a Fused Iron Core
Authors: Lin Qihang , Yang Guohui , Li Xiaonian , Yoneyama Yoshiharu , Wan Huilin , Tsubaki Noritatsu 
Published: July 2013

AbstractFused iron (FI), is a general Fischer–Tropsch synthesis (FTS) catalyst and can be used to convert syngas (CO+H2) into normal hydrocarbons. The syntheses of HZSM‐5 or H‐β zeolite‐shell encapsulated catalysts for FTS have been reported previously, however, conventional zeolite‐shell synthesis generally employs an organic template, which is neither economic nor environmentally benign. Here we report the synthesis, without using an organic template, of a millimeter‐sized defect‐free capsule catalyst covered by a MOR zeolite shell (thickness of 23 μm) on FI pellets. The capsule catalyst (HMOR/FI) exhibited excellent performance for FTS, greatly increasing the selectivity of middle isoparaffins. Compared with the pure FI catalyst, the CO conversion of the HMOR/FI capsule catalyst increased remarkably and the iso/n ratio was almost 8 times that of the pure FI catalyst. This report provides an effective route to synthesize a capsule catalyst, which can reduce costs effectively and is also more environmentally benign than the current conventional zeolite‐shell synthesis.
Catalysis with Gold Complexes Immobilised on Carbon Nanotubes by π–π Stacking Interactions: Heterogeneous Catalysis versus the Boomerang Effect
Authors: Vriamont Charles , Devillers Michel , Riant Olivier , Hermans Sophie 
Published: July 2013

AbstractA new pyrene‐tagged gold(I) complex has been synthesised and tested as a homogeneous catalyst. First, a simple 1,6‐enyne was chosen as a model substrate for cyclisation by using different solvents to optimise the reaction conditions. The non‐covalent immobilisation of our pyrene‐tagged gold complex onto multi‐walled carbon nanotubes through π–π stacking interactions was then explored to obtain a supported homogeneous catalyst. The heterogenised catalyst and its homogeneous counterpart exhibited similar activity in a range of enyne cyclisation reactions. Bearing in mind that π–π interactions are affected by temperature and solvent polarity, the reuse and robustness of the supported homogeneous catalyst was tested to explore the scope and limitations of the recyclability of this catalyst. Under the optimised conditions, recyclability was observed by using the concept of the boomerang effect.
Construction of Quaternary Stereocenters: Asymmetric α‐Amination of Branched Aldehydes Catalyzed by Monoimide Substituted Cyclohexane‐1,2‐Diamines
Authors: Fu Ji‐Ya , Wang Qi‐Lin , Peng Lin , Gui Yong‐Yuan , Xu Xiao‐Ying , Wang Li‐Xin 
Published: July 2013

ABSTRACTA highly efficient enantioselective α‐amination of branched aldehydes catalyzed by chiral imide monosubstituted 1,2‐diamine derivatives was reported to afford the quaternary stereogenic centers in excellent yields (up to 99%) and enantioselectivities (up to 97% ee). Chirality 25:668–672, 2013. © 2013 Wiley Periodicals, Inc
Nonparametric estimation of the conditional survival function for bivariate failure times
Authors: Lakhal‐Chaieb Lajmi , Abdous Belkacem , Duchesne Thierry 
Published: July 2013

AbstractThis paper discusses the nonparametric estimation of the conditional survival function for bivariate failure time data in the presence of dependent censoring. We use local polynomial smoothing techniques to obtain a simple estimator of the conditional survival function and investigate its asymptotic properties. Several censoring structures are considered. The proposal is compared to an existing alternative by simulation and illustrated with two real data sets. The Canadian Journal of Statistics 41: 439–452; 2013 © 2013 Statistical Society of Canada
Matching tumor risk with aggressiveness of treatment in men with multiple comorbidities and early‐stage prostate cancer
Authors: Daskivich Timothy J. , Chamie Karim , Kwan Lorna , Dash Atreya , Greenfield Sheldon , Litwin Mark S. 
Published: July 2013

BACKGROUNDMen with multiple comorbidities are often overtreated for low‐risk prostate cancer, but it is unclear whether they are undertreated for high‐risk cancer, which has appreciable short‐term prostate cancer‐specific mortality. This study characterized the impact of comorbidity on treatment and survival in men with differing tumor risks.METHODSThe researchers sampled 1482 men with nonmetastatic prostate cancer at 2 Veterans Affairs hospitals between 1998 and 2004, using multivariate probit regression to determine probabilities of aggressive treatment among men with differing Charlson comorbidity scores within D'Amico tumor risk strata. Using competing‐risks regression, a comparison was made of 8‐year cancer‐specific mortality for men treated aggressively and nonaggressively among Charlson score‐tumor risk pairs.RESULTSThe study sample comprised 516 men (36%) with low‐risk, 475 men (33%) with intermediate‐risk, and 432 men (30%) with high‐risk prostate cancer. Men with high‐risk disease tended to have lower probability of aggressive treatment than other risk strata, regardless of comorbidity. Among men with Charlson scores 3+, probabilities of aggressive treatment did not increase with higher tumor risk (0.48, 0.61, 0.49 for low‐, intermediate‐, and high‐risk disease, respectively). In competing‐risks analysis, aggressive treatment was not associated with cancer‐specific survival benefit in men with multiple comorbidities (Charlson scores of 2 or 3+) and low‐ and intermediate‐risk disease, but there was a strong trend toward survival advantage in such men with high‐risk disease.CONCLUSIONSAggressiveness of treatment is poorly matched with tumor risk in men with significant comorbidity. Men with major comorbidities should consider conservative management for low‐ and intermediate‐risk disease and aggressive treatment for high‐risk disease. Cancer 2013;119:3446–3453.. © 2013 American Cancer Society.
Trends in the occurrence of high‐grade anal intraepithelial neoplasia in San Francisco: 2000‐2009
Authors: Simard Edgar P. , Watson Meg , Saraiya Mona , Clarke Christina A. , Palefsky Joel M. , Jemal Ahmedin 
Published: July 2013

BACKGROUNDAlthough screening of human immunodeficiency virus (HIV)‐positive individuals for anal intraepithelial neoplasia (AIN; a precursor of anal cancer) has been practiced in San Francisco among HIV health care providers since the early 1990s, to the authors' knowledge no study to date has focused on evaluating recent AIN trends.METHODSCases of high‐grade AIN 3 and invasive anal cancer from 2000 to 2009 were obtained from the San Francisco/Oakland Surveillance, Epidemiology, and End Results (SEER) population‐based cancer registry. Age‐standardized rates of AIN 3 and anal cancer were calculated overall and by demographic characteristics (sex, race, and age group). Log‐linear regression calculated annual percent change in rates during 2000 to 2009, and rate ratios (RRs) and 95% confidence intervals (95% CIs), evaluated differences in rates during 2000 through 2004 and 2005 through 2009.RESULTSDuring 2000 through 2009, the majority of AIN 3 cases occurred among men (1152 of 1320 men; 87.3%). Rates of AIN 3 during the corresponding period increased by 11.48% per year (P < .05) among men and were stable among women. Comparing rates among men during 2000 to 2004 with those during 2005 to 2009, the largest increases were noted among those aged 50 years to 64 years (RR, 2.47; 95% CI, 1.93‐3.17) and among black individuals (RR, 3.49; 95% CI, 2.14‐5.85). During the same period, anal cancer rates were stable among men and women.CONCLUSIONSRates of AIN 3 increased in San Francisco during 2000 through 2009, in conjunction with an anal cytology screening program for high‐risk groups, whereas rates of invasive anal cancer were unchanged. Continued surveillance is necessary to evaluate the impact of screening and human papillomavirus vaccination on the prevention of human papillomavirus‐related AIN and anal cancer. Cancer 2013;119:3539–3545.. © 2013 American Cancer Society.
Are physician recommendations for BRCA1/2 testing in patients with breast cancer appropriate? A population‐based study
Authors: McCarthy Anne Marie , Bristol Mirar , Fredricks Tracey , Wilkins Lache , Roelfsema Irene , Liao Kaijun , Shea Judy A. , Groeneveld Peter , Domchek Susan M. , Armstrong Katrina 
Published: July 2013

BACKGROUNDTo the best of the authors' knowledge, few population‐based studies to date have examined the use of BRCA1/2 testing or patterns of physician recommendations for genetic testing among women diagnosed with breast cancer. The objective of the current study was to evaluate the rates and predictors of physician recommendation for BRCA1/2 testing among patients with breast cancer.METHODSWomen aged 18 years to 64 years who were diagnosed with invasive breast cancer in 2007 were identified from the Pennsylvania Cancer Registry and mailed a survey regarding their family history of cancer, physician treatment recommendations, and BRCA1/2 testing. Of the 4009 women who were sent surveys, 2258 responded (56%). Based on age at diagnosis and family history, women were categorized as being at high, moderate, or low risk of BRCA1/2 mutations.RESULTSNearly 25% of the participants were classified as being at high risk of carrying a BRCA1/2 mutation based on their age at the time of breast cancer diagnosis and family history of breast and/or ovarian cancer. Physician recommendations for BRCA1/2 testing were found to be strongly associated with risk of carrying a mutation, with 53% of high‐risk women reporting a testing recommendation compared with 9% of low‐risk women. In addition, physician recommendations were strongly correlated with the use of testing in all risk groups. Among high‐risk women, the lack of a recommendation for BRCA1/2 testing was more common among older, low‐income, and employed women.CONCLUSIONSAlthough BRCA1/2 testing recommendations appear to be appropriately correlated with mutation risk, a significant percentage of patients with breast cancer who meet criteria for BRCA1/2 testing may not receive a recommendation for such testing from their health care providers. Cancer 2013;119:3596–3603. © 2013 American Cancer Society.
Glucose transporter 1 protein detected by enzyme‐linked immunosorbent assay and immunocytochemistry
Authors: Liao Nai‐Ding , Chiang Tai‐An , Lee Wen‐Ying 
Published: July 2013

BACKGROUNDGlucose transporter 1 (GLUT1) is a hallmark of metabolic change in cancer cells. The objective of this study was to determine the role of GLUT1 protein in diagnosing malignant pleural effusions by enzyme‐linked immunosorbent assay (ELISA) and immunocytochemistry.METHODSIn total, 82 pleural effusions were collected and classified as benign (n = 42), atypical (n = 8), or malignant (n = 32) based on cytologic diagnosis and etiology. GLUT1 protein levels in effusions were measured by ELISA. GLUT1 expression also was determined by immunocytochemistry using cell blocks.RESULTSGLUT1 levels were significantly higher in the malignant group compared with the benign group. Receiver operating characteristic curve analysis of benign and malignant pleural effusions for GLUT1 yielded an area under the curve of 0.77, with a value of 1355.87 pg/dL as the optimal threshold for distinguishing benign from malignant effusions. With the ELISA method, the sensitivity, specificity, and accuracy were 78.1%, 69%, and 73%, respectively. Malignant effusion cell blocks were positive for GLUT1 expression in 84.4% of cases with 100% specificity and 93.2% accuracy. With the combination of high GLUT1 protein levels (>10,000 pg/dL) and immunocytochemistry to detect malignant pleural effusions, the sensitivity and accuracy increased to 93.8% and 94.6%, respectively. The GLUT1 level measured by ELISA and the GLUT1 expression detected by immunocytochemistry were positively correlated. In atypical effusions, 3 cases (37.5%) had GLUT1 levels higher than the cutoff value.CONCLUSIONSThe detection of GLUT1 protein by ELISA and immunocytochemistry may have utility in the diagnosis of malignant pleural effusions. Cancer (Cancer Cytopathol) 2013;121:695–702. © 2013 American Cancer Society.
Using the ASC:SIL ratio, human papillomavirus, and interobserver variability to assess and monitor cytopathology fellow training performance
Authors: Chebib Ivan , Rao Rema A. , Wilbur David C. , Tambouret Rosemary H. 
Published: July 2013

BACKGROUNDThe goal of this study was to assess objective measurements of cytopathology fellow performance during their training.METHODSThe authors examined cytopathology performance characteristics (the ratio of atypical squamous cells to squamous intraepithelial lesions [ASC:SIL], interobserver variability [IOV], high‐risk human papillomavirus [hr‐HPV]–positive atypical squamous cells of undetermined significance [ASC‐US]) of cytopathology fellows and assessed whether they could be used as tools to further their education.RESULTSThe ASC:SIL ratio, the proportion of hr‐HPV–positive ASC‐US, and IOV were calculated for 5 consecutive cytopathology fellows. The average ASC:SIL ratio for the fellows was 1.15. The overall average Cohen κ‐coefficient (κ‐value) between fellow and cytopathologist interpretation was 0.75 (substantial agreement). The conditional κ‐value for ASC‐US only was higher for cases the fellows called ASC‐US (0.70) than for cases the cytopathologist called ASC‐US (0.60). Of the cases that were diagnosed as “negative for intraepithelial lesion or malignancy” (NILM) by the fellow and ASC‐US by the pathologist, 33.2% were positive for hr‐HPV. This was higher than the expected frequency of hr‐HPV–positive results in the NILM population, suggesting that the fellows were over‐interpreting NILM in hr‐HPV–positive cases that had cytologic features sufficient for an ASC‐US interpretation.CONCLUSIONSIn this study, agreement was compared between trainee and cytopathologist to determine where a fellow's interpretation differed. With the use of IOV, the ASC:SIL ratio, and the percentage of hr‐HPV–positive results in the NILM, ASC‐US, and low‐grade SIL categories, the authors attempted to outline objective assessments and areas of improvement for fellows before they enter independent practice. Cancer (Cancer Cytopathol) 2013;121:638–43. © 2013 American Cancer Society.