bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural analysis of enzymes used for bioindustry and bioremediation
Authors: Tanokura Masaru , Miyakawa Takuya , Guan Lijun , Hou Feng 
Published: June 2015

Abstract
Microbial enzymes have been widely applied in the large-scale, bioindustrial manufacture of food products and pharmaceuticals due to their high substrate specificity and stereoselectivity, and their effectiveness under mild conditions with low environmental burden. At the same time, bioremedial techniques using microbial enzymes have been developed to solve the problem of industrial waste, particularly with respect to persistent chemicals and toxic substances. And finally, structural studies of these enzymes have revealed the mechanistic basis of enzymatic reactions, including the stereoselectivity and binding specificity of substrates and cofactors. The obtained structural insights are useful not only to deepen our understanding of enzymes with potential bioindustrial and/or bioremedial application, but also for the functional improvement of enzymes through rational protein engineering. This review shows the structural bases for various types of enzymatic reactions, including the substrate specificity accompanying cofactor-controlled and kinetic mechanisms.
John H. Laragh MD: The Man
Authors: Sealey-Laragh Jean 
Published: June 2015

Abstract
John has been variously described as an inspiration, mentor, teacher, friend (fiend—a typo?), charming, warm, enthusiastic, visionary scientist, pioneer, innovator, egalitarian, and golfer. At other times he was called street fighter, competitor, and some unprintables. I believe he was all of these, and more.
Join us in celebrating the life of Dr. John Laragh
FDF-PAGE: a powerful technique revealing previously undetected small RNAs sequestered by complementary transcripts
Authors: Harris C. Jake , Molnar Attila , Müller Sebastian Y. , Baulcombe David C. 
Published: June 2015

Abstract
Small RNAs, between 18nt and 30nt in length, are a diverse class of non-coding RNAs that mediate a range of cellular processes, from gene regulation to pathogen defense. They guide ribonucleoprotein complexes to their target nucleic acids by Watson–Crick base pairing. We report here that current techniques for small RNA detection and library generation are biased by formation of RNA duplexes. To address this problem, we established FDF-PAGE (fully-denaturing formaldehyde polyacrylamide gel electrophoresis) to prevent annealing of sRNAs to their complement. By applying FDF-PAGE, we provide evidence that both strands of viral small RNA are present in near equimolar ratios, indicating that the predominant precursor is a long double-stranded RNA. Comparing non-denaturing conditions to FDF-PAGE uncovered extensive sequestration of miRNAs in model organisms and allowed us to identify candidate small RNAs under the control of competing endogenous RNAs (ceRNAs). By revealing the full repertoire of small RNAs, we can begin to create a better understanding of small RNA mediated interactions.
Do clusters matter to firm and regional development and growth?
Authors: Rocha Hector 
Published: June 2015

Purpose– This paper aims to analyse the impact of clusters on development and growth at the firm and regional level in Latin America (LA). The past 20 years have witnessed an acceleration of cluster initiatives, assuming their positive impact on firm performance and regional development. However, theoretical development and empirical meta-studies in emerging countries to validate this assumed relationship are scarce.Design/methodology/approach– This paper reviews empirical evidence from a population of 123 studies and a sample of 45 empirical studies including 216 clusters in LA.Findings– It concludes that clusters contribute to both development and growth at the firm- and regional-level contingent to factors such as cluster stage of development, collective efficiency, the pattern of governance of the value chain and the sector in which the firm operates; however, clusters are also a potential source of socio-economic divides.Originality/value– Therefore, these results qualify the conclusions of studies of clusters in developed countries (Porter, 2003; Delgadoet al., 2010).
Risk‐Adjusted In‐Hospital Mortality Models for Congestive Heart Failure and Acute Myocardial Infarction: Value of Clinical Laboratory Data and Race/Ethnicity
Authors: Lim Eunjung , Cheng Yongjun , Reuschel Christine , Mbowe Omar , Ahn Hyeong Jun , Juarez Deborah T. , Miyamura Jill , Seto Todd B. , Chen John J. 
Published: June 2015

ObjectiveTo examine the impact of key laboratory and race/ethnicity data on the prediction of in‐hospital mortality for congestive heart failure (CHF) and acute myocardial infarction (AMI).Data SourcesHawaii adult hospitalizations database between 2009 and 2011, linked to laboratory database.Study DesignCross‐sectional design was employed to develop risk‐adjusted in‐hospital mortality models among patients with CHF (n = 5,718) and AMI (n = 5,703).Data Collection/Extraction MethodsResults of 25 selected laboratory tests were requested from hospitals and laboratories across the state and mapped according to Logical Observation Identifiers Names and Codes standards. The laboratory data were linked to administrative data for each discharge of interest from an all‐payer database, and a Master Patient Identifier was used to link patient‐level encounter data across hospitals statewide.Principal FindingsAdding a simple three‐level summary measure based on the number of abnormal laboratory data observed to hospital administrative claims data significantly improved the model prediction for inpatient mortality compared with a baseline risk model using administrative data that adjusted only for age, gender, and risk of mortality (determined using 3M's All Patient Refined Diagnosis Related Groups classification). The addition of race/ethnicity also improved the model.ConclusionsThe results of this study support the incorporation of a simple summary measure of laboratory data and race/ethnicity information to improve predictions of in‐hospital mortality from CHF and AMI. Laboratory data provide objective evidence of a patient's condition and therefore are accurate determinants of a patient's risk of mortality. Adding race/ethnicity information helps further explain the differences in in‐hospital mortality.
Percutaneous insertion of peritoneal dialysis catheters using ultrasound and fluoroscopic guidance: A single centre experience and review of literature
Authors: De Boo Diederick W , Mott Nigel , Tregaskis Peter , Quach Trung , Menahem Solomon , Walker Rowan G , Koukounaras Jim 
Published: June 2015

SummaryVarious methods of peritoneal dialysis (PD) catheter insertion are available. The purpose of this study was to evaluate a percutaneous insertion technique using ultrasound (US) and fluoroscopy performed under conscious sedation and as day case procedure. Data of 87 percutaneous inserted dialysis catheters were prospectively collected, including patients' age, gender, body mass index, history of previous abdominal surgery and cause of end stage renal failure. Length of hospital stay, early complications and time to first use were also recorded. Institutional review board approval was obtained. A 100% technical success rate was observed. Early complications included bleeding (n = 3), catheter dysfunction (n = 6), exit site infection (n = 1) and exit site leakage (n = 1). All cases of catheter dysfunction and one case of bleeding required surgical revision. Median time of follow‐up was 18 months (range 3–35), and median time from insertion to first use was days 14 (1–47). Of the 82 patients who started dialysis, 20 (23%) ceased PD at some stage during follow‐up. Most frequently encountered reasons include deteriorating patient cognitive or functional status (n = 5), successful transplant kidney (n = 4) and pleuro‐peritoneal fistula (n = 4). Sixty‐two (71%) PD catheter insertions were performed as day case. The remaining insertions were performed on patients already admitted to the hospital. Percutaneous insertion of dialysis catheter using US and fluoroscopy is not only safe but can be performed as day case procedure in most patients, even with a medical history of abdominal surgery and/or obesity.
Ropivacaine and dexamethasone: a potentially dangerous combination for therapeutic pain injections
Authors: Watkins Trevor William , Dupre Simon , Coucher John Richard 
Published: June 2015

AbstractIntroductionTargeted spinal steroid injections are effective in reducing back pain in selected patient populations and carry a small risk of significant adverse neurological outcomes. Recent recommendations are for the use of non‐particulate steroid agents for all spinal injections to reduce the risk of neurovascular embolic adverse events. Many injections have used a combination of local anaesthetic agent with the steroid. At our institutions, we have recently observed interactions between ropivacaine and dexamethasone combinations ascribed to the incompatibility of the former with alkaline solutions, resulting in rapid crystallisation. This study has further investigated the combinations of commonly used local anaesthetic and steroid combinations to determine if such precipitation effects are more widespread.MethodsThe commonly used local anaesthetics (lignocaine, bupivacaine, ropivacaine) and the non‐particulate steroid dexamethasone sodium phosphate combinations were evaluated macroscopically, microscopically, and pH values measured. Where crystallisation was observed the rate of precipitation and crystal size was measured. Contamination of ropivacaine with sodium bicarbonate solution was also evaluated. Particulate size of the particulate steroid agent betamethasone acetate was evaluated as a comparison.ResultsAll mixtures of ropivacaine and the non‐particulate dexamethasone sodium phosphate assessed demonstrated a pH‐dependent crystallisation of the solution. No precipitation was demonstrated with the combinations of dexamethasone and lignocaine or bupivacaine. Contamination of ropivacaine with residual sodium bicarbonate in a drawing up needle following air clearing had a precipitation effect.ConclusionWe describe the effect of crystallisation with the combination of ropivacaine and the non‐particulate steroid, dexamethasone sodium phosphate, a mixture that has been used in the literature for targeted pain injections. As this may be considered a non‐particulate steroid/anaesthetic injectate, this would potentially carry increased risk if inadvertent intravascular injection occurred during a targeted spinal injection, as has been described with particulate steroid agents. This is due to the elevated pH of dexamethasone and the incompatibility of ropivacaine with alkaline solutions.
The Role of Credit Spreads and Structural Breaks in Forecasting the Term Structure of Korean Government Bond Yields
Authors: Lee Chang Hoon , Kang Kyu Ho 
Published: June 2015

AbstractWe examine whether Korean credit spreads are informative enough to help improve the predictive accuracy of Korean government bond yields. To do this, we analyze a joint dynamic Nelson‐Siegel (DNS) model of Korean government bond yields and credit spreads. In the model multiple change‐points at unknown time points in the factor process are allowed in order to capture the possibility of structural breaks in the yield and credit spread curve dynamics. We find that the joint DNS model of the yield and credit spread curves outperforms the standard DNS model of the yield curve in terms of out‐of‐sample yield curve prediction. Further, the predictive gains are maximized at the two change‐points. The two change‐points seem to be closely associated with the beginning of the recent financial crisis and the subsequent stabilization of Korean bond markets.
A Study of the Causality Between Convertible Bond Prices and Stock Prices in Conversion‐price Reset Periods—Time‐series and Cross‐section Analyses
Authors: Wang Ma‐Ju , Lin Yun‐Wei , Lee Tsun‐Siou 
Published: June 2015

AbstractThis study examines the causality between the returns of convertible bonds and stocks during periods of conversion‐price resets and general pre‐reset in Taiwan. Profits, stock turnover, and firm size affect the significance of causality. The empirical results indicate that the returns of convertible bonds always lag behind the stock returns for general pre‐reset periods. However, for reset periods, the numbers of companies for which convertible bonds lead ahead of the stock market increases. The causality reversal is based on uprising liquidity and information transparency. These results provide evidence that various reset price mechanisms affect financing market efficiency.
Systematic review: colitis associated with anti‐CTLA‐4 therapy
Authors: Gupta A. , De Felice K. M. , Loftus E. V. , Khanna S. 
Published: June 2015

SummaryBackgroundCytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) has an important role in T‐cell regulation, proliferation and tolerance. Anti‐CTLA‐4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune‐related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common.AimsTo discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti‐CTLA‐4‐associated colitis, and to present a management algorithm for it.MethodsWe searched PubMed for studies published through October 2014 using the terms ‘anti‐CTLA,’ ‘ipilimumab,’ ‘tremelimumab,’ ‘colitis,’ ‘gastrointestinal,’ ‘immune‐related adverse effect,’ ‘immunotherapy,’ ‘melanoma,’ and ‘diarrhoea.’ResultsWatery diarrhoea is commonly associated with anti‐CTLA‐4 therapy (27–54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8–22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti‐CTLA‐4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid‐resistant cases may respond to anti‐tumour necrosis factor‐alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy.ConclusionGiven the increasing use of anti‐CTLA‐4 therapy, clinicians must be aware of related adverse events and their management.
Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF‐1 suppression to octreotide LAR in healthy volunteers
Authors: Tiberg Fredrik , Roberts John , Cervin Camilla , Johnsson Markus , Sarp Severine , Tripathi Anadya Prakash , Linden Margareta 
Published: June 2015

AimsThe aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.MethodsThis was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg.ResultsOne hundred and twenty‐two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four‐ to five‐fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml–1 h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin‐like growth factor 1 (IGF‐1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF‐1. Maximum inhibition of IGF‐1 at steady‐state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related.ConclusionsOctreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF‐1 than octreotide LAR in healthy volunteers.
MD‐2 as the target of a novel small molecule, L6H21, in the attenuation of LPS‐induced inflammatory response and sepsis
Authors: Wang Yi , Shan Xiaoou , Chen Gaozhi , Jiang Lili , Wang Zhe , Fang Qilu , Liu Xing , Wang Jingying , Zhang Yali , Wu Wencan , Liang Guang 
Published: June 2015

Background and PurposeMyeloid differentiation 2 (MD‐2) recognizes LPS, which is required for TLR4 activation, and represents an attractive therapeutic target for severe inflammatory disorders. We previously found that a chalcone derivative, L6H21, could inhibit LPS‐induced overexpression of TNF‐α and IL‐6 in macrophages. Here, we performed a series of biochemical experiments to investigate whether L6H21 specifically targets MD‐2 and inhibits the interaction and signalling transduction of LPS‐TLR4/MD‐2.Experimental ApproachThe binding affinity of L6H21 to MD‐2 protein was analysed using computer docking, surface plasmon resonance analysis, elisa, fluorescence measurements and flow cytometric analysis. The effects of L6H21 on MAPK and NF‐κB signalling were determined using EMSA, fluorescence staining, Western blotting and immunoprecipitation. The anti‐inflammatory effects of L6H21 were confirmed using elisa and RT‐qPCR in vitro. The anti‐inflammatory effects of L6H21 were also evaluated in septic C57BL/6 mice.Key ResultsCompound L6H21 inserted into the hydrophobic region of the MD‐2 pocket, forming hydrogen bonds with Arg90 and Tyr102 in the MD‐2 pocket. In vitro, L6H21 subsequently suppressed MAPK phosphorylation, NF‐κB activation and cytokine expression in macrophages stimulated by LPS. In vivo, L6H21 pretreatment improved survival, prevented lung injury, decreased serum and hepatic cytokine levels in mice subjected to LPS. In addition, mice with MD‐2 gene knockout were universally protected from the effects of LPS‐induced septic shock.Conclusions and ImplicationsOverall, this work demonstrated that the new chalcone derivative, L6H21, is a potential candidate for the treatment of sepsis. More importantly, the data confirmed that MD‐2 is an important therapeutic target for inflammatory disorders.
The impact of public ownership in the lending sector
Authors: Bose Arup , Pal Debashis , Sappington David E. M. 
Published: June 2015

AbstractWe examine the effects of increased government ownership of suppliers in the lending sector, which induces increased concern with total welfare and reduced concern with profit. Such increased ownership of a lender can have unanticipated effects. For instance, it can increase lender profit. Furthermore, borrower welfare often declines as government ownership increases in a lender with a relatively limited ability to discern the true quality of borrowers’ projects. In addition, there are settings in which increased government ownership of a lender has no impact on either lender profit or borrower welfare.
Conservation authority board composition and watershed management in Ontario
Authors: Lyons Joseph 
Published: June 2015

AbstractThis article contributes to the general debate about specialized governments, which may represent one or many municipalities. The research compares the Upper Thames River Conservation Authority (UTRCA) and its fragmented board and the consolidated board of the Hamilton Conservation Authority (HCA) to assess whether board composition affects policy implementation. It finds that the UTRCA is more responsive to the provincial mandate for watershed management than the HCA. This suggests that specialized governments serving several municipalities are likely to be more faithful to their mandate than those serving a single municipality.
Phylogenetic position of the house dust mite subfamily Guatemalichinae (Acariformes: Pyroglyphidae) based on integrated molecular and morphological analyses and different measures of support
Authors: Klimov Pavel B. , Bochkov Andre V. , OConnor Barry M. 
Published: June 2015

AbstractBased on multilocus phylogenetic analyses (18S, 28S, EF1‐α, SRP54, HSP70, CO1, 10 860 nt aligned), we show that the house dust mite subfamily Guatemalichinae is nested within non‐onychalgine pyroglyphid mites and forms the sister group to the genus Sturnophagoides (bootstrap support 100, posterior probability 1.0). Because high bootstrap support values may be misleading in the presence of incongruence, we evaluate robustness of the Guatemalichinae+Sturnophagoides clade using: (1) internode certainty indices to estimate the frequency of conflicting bipartitions in maximum‐likelihood bootstrap trees, (ii) consensus networks to investigate conflict among different loci; and (iii) statistical hypothesis testing based on information theory, both multi‐scale and regular bootstrap. Results suggest that this grouping is very well supported given the data. The molecular analyses were integrated with detailed morphological study using scanning electron and light microscopy. We suggest that the subfamilial status of Guatemalichinae should be reconsidered, and this lineage should be placed within the subfamily Dermatophagoidinae. The latter subfamily is currently accepted in the literature as a monophyletic group but was here inferred as paraphyletic and was not supported by any morphological synapomorphy. The paraphyly involved the most species‐rich and medically important genus, Dermatophagoides. Our findings suggest the need for a comprehensive revision of the higher‐level relationships of pyroglyphid house dust mites using both DNA sequences and morphology coupled with a broad taxonomic sampling.
Health‐related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross‐sectional study
Authors: Delgado J.F. , Almenar L. , González‐Vilchez F. , Arizón J.M. , Gómez M. , Fuente L. , Brossa V. , Fernández J. , Díaz B. , Pascual D. , Lage E. , Sanz M. , Manito N. , Crespo‐Leiro M.G. 
Published: June 2015

AbstractA multicenter cross‐sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health‐related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (±1), 12 (±2), 36 (±6), 60 (±10), or 120 (±20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ‐5D, the Duke‐UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ‐5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions.