bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy
Authors: Chaitanya Sundeep , Das Madhusmita , Bhat Pritesh , Ebenezer Mannam
Published: April 2015

The molecular basis for determination of resistance to anti‐leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6‐hydroxymethyl‐7, 8‐dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014‐3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å3 in native vs. 233.6 Å3 in Thr53Ala, 659.9 Å3 in Thr53Ile, 400 Å3 for Thr53Val, 385 Å3 for Pro55Arg, and 210 Å3 for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (−51.92 Kcal/mol for native vs. −35.64, −35.24, −46.47, −47.69, and −41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy. J. Cell. Biochem. 116: 2293–2303, 2015. © 2015 Wiley Periodicals, Inc.
Race/Ethnicity and Treatment Outcome in a Randomized Controlled Trial for Trichotillomania (Hair‐Pulling Disorder)
Authors: Falkenstein Martha J. , Rogers Kate , Malloy Elizabeth J. , Haaga David A. F.
Published: April 2015

Objective

Treatment outcome was compared among non‐Hispanic White and racial/ethnic minority participants with trichotillomania (TTM), or hair‐pulling disorder.

Method

Symptom severity, quality of life, and TTM‐related disability were compared in a behavior therapy trial with a stepped care approach: web‐based self‐help and then individual behavior therapy. The sample comprised 72% (n = 38) non‐Hispanic White participants and 28% (n = 15) minority participants.

Results

The ethnic groups responded differently to treatment, with fewer minority participants showing improvement during web‐based self‐help. Response rates were equivalent between ethnic groups during the in‐person behavior therapy. These results should be interpreted with caution because of the small sample size of minorities in the study and consequent inability to analyze results for each racial/ethnic group individually.

Conclusions

Future studies should focus on the investigation of factors that may enable or hinder racial and ethnic minority participants to benefit from online and/or self‐help behavior therapy for TTM.
Rapid in vivo multicomponent T2 mapping of human knee menisci
Authors: Liu Fang , Samsonov Alexey , Wilson John J. , Blankenbaker Donna G. , Block Walter F. , Kijowski Richard
Published: April 2015

Purpose

To compare multicomponent T2 parameters of menisci measured using Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and osteoarthritis (OA) patients with intact and torn menisci.

Materials and Methods

The prospective study was performed with Institutional Review Board approval and with all subjects signing written informed consent. mcDESPOT was performed on the knee joint of 12 asymptomatic volunteers and 14 patients with knee OA. Single‐component T2 relaxation time (T2Single), T2 relaxation time of the fast relaxing water component (T2F), and the slow relaxing water component (T2S), and fraction of the fast relaxing water component (FF) of the medial and lateral menisci were measured. Multivariate linear regression models were used to compare mcDESPOT parameters between normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients with adjustment for differences in age between subjects.

Results

The mean mcDESPOT parameters for normal menisci in asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA patients were respectively 16.1 msec, 18.8 msec, and 22.7 msec for T2Single; 9.0 msec, 10.0 msec, and 11.1 msec for T2F; 24.4 msec, 27.7 msec, and 31.4 msec for T2S; and 34%, 32%, 27% for FF. There were significant differences (P < 0.05) in T2Single, T2F, T2S, and FF between the three groups of menisci.

Conclusion

The menisci of OA patients had significantly higher T2Single, T2F, and T2S and significantly lower FF than normal menisci in asymptomatic volunteers with greater changes in multicomponent T2 parameters noted in torn than intact menisci in OA patients. J. Magn. Reson. Imaging 2015;42:1321–1328.
Expression of the toxin‐antitoxin genes yefMLrh, yoeBLrh in human Lactobacillus rhamnosus isolates
Authors: Krügel Hans , Klimina Ksenia M. , Mrotzek Grit , Tretyakov Alexander , Schöfl Gerhard , Saluz Hans‐Peter , Brantl Sabine , Poluektova Elena U. , Danilenko Valery N.
Published: April 2015

Lactobacilli are important microorganisms in various activities, for example, diary products, meat ripening, bread and pickles, but, moreover, are associated directly with human skin and cavities (e.g., mouth, gut, or vagina). Some of them are used as probiotics. Therefore, the molecular biological investigation of these bacteria is important. Earlier we described several toxin antitoxin systems (type II) in lactobacilli. Here, we describe the structure and transcriptional regulation of genes, encoding TA system YefM‐YoeBLrh in three strains of Lactobacillus rhamnosus comparing stationary and exponential growth phases, the influence of stress factors and mRNA stability. The same TA system is responding to physiological and stress conditions differently in related strains. Using primer extension and RLM‐RACE methods we determined three transcription start sites of RNAs in the operon. The promoter region of the operon is preceded by a conserved BOX element occurring at multiple positions in the genomes of L. rhamnosus strains. Downstream of and partially overlapping with the 3′ end of the yoeBLrh toxin gene, a divergently transcribed unexpected RNA was detected.
NDVI‐indicated long‐term vegetation dynamics in Mongolia and their response to climate change at biome scale
Authors: Bao Gang , Bao Yuhai , Sanjjava Amarjargal , Qin Zhihao , Zhou Yi , Xu Guang
Published: April 2015

Based on the vegetation map of Mongolia, Global Inventory Monitoring and Modelling Studies (GIMMS) normalized difference vegetation index (NDVI) (1982–2006), the Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI (2000–2010), and temperature and precipitation data derived from 60 meteorological stations, this study has thoroughly examined vegetation dynamics in Mongolia and their responses to regional climate change at biome scale. To ensure continuity and consistency between the two NDVI datasets, the MODIS NDVI was first calibrated to the GIMMS NDVI based on the overlapping period of 2000–2006. Good calibration results with R2 values of 0.86–0.98 between the two NDVI datasets were obtained and can detect subtle trends in the long‐term vegetation dynamics of Mongolia. The results indicated that for various biomes, although NDVI changes during 1982–2010 showed great variation, vegetation greening for all biomes in Mongolia seem to have stalled or even decreased since 1991–1994, particularly for meadow steppe (0.0015 year−1), typical steppe (−0.0010 year−1), and desert steppe (−0.0008 year−1), which is an apparent turning point (TP) of the vegetation growth trend in Mongolia. A pronounced drying trend (from −4.399 mm year−1 in meadow steppe since 1990 to −2.445 mm year−1 in alpine steppe since 1993) occurred between 1990 and 1994, and persistently warming temperatures (0.015 °C year−1 in alpine steppe to 0.070 °C year−1 in forest and meadow steppe) until recently have likely played a major role in this NDVI trend reversal. However, the NDVI TP varied by biome, month, and climate and was not coupled exactly with climatic variables. The impact on climate of both same‐time and lagged‐time temperature and precipitation effects also varied strongly across biomes and months. On the whole, climate‐related vegetation decline and associated potential desertification trends will likely be among the major sources of ecological pressure for each biome in Mongolia, which could intensify environmental problems like sandstorms in other East Asian regions.
Melatonin alleviates cold‐induced oxidative damage in maize seedlings by up‐regulating mineral elements and enhancing antioxidant activity
Authors: Turk Hulya , Erdal Serkan
Published: April 2015

Melatonin, known as an animal hormone and an antioxidant with a low molecular weight, is one of the most commonly used substances to improve plant resistance against various environmental stresses. However, there are no studies explaining the effects of melatonin on the relationship between defense system and mineral composition of plants under stressed and unstressed‐conditions. The present study was conducted to investigate whether the mitigating effect of melatonin is associated with its modulating influence on the mineral elements of cold‐stressed maize seedlings. The seedlings were treated with melatonin (1 mM) and cold stress (10/7°C) for 3 d separately and in combination. After 3 d, the seedlings were harvested to determine several physiological, biochemical, and molecular parameters. Melatonin application effectively mitigated the damages from cold stress, as demonstrated by higher relative water concentration, chlorophyll concentration and antioxidant enzyme activities (superoxide dismutase, guaiacol peroxidase, catalase, ascorbate peroxidase, and glutathione reductase), as well as lower superoxide, hydrogen peroxide, and malondialdehyde concentrations. Similarly, melatonin significantly ameliorated cold‐induced reductions in the concentrations of potassium, phosphorus, sulfur, magnesium, iron, copper, manganese, and zinc. Besides, it further increased calcium and boron concentrations compared to cold stress alone. Our results reveal that melatonin has an important modulating influence on the mineral element composition of plants and mitigates cold stress through up‐regulation of these elements and simultaneously enhanced antioxidant activity.
Projected future distribution of date palm and its potential use in alleviating micronutrient deficiency
Authors: Shabani Farzin , Kumar Lalit , Nojoumian Amir Hadi , Esmaeili Atefeh , Toghyani Mehdi
Published: April 2015

BACKGROUND

Micronutrient deficiency develops when nutrient intake does not match nutritional requirements for maintaining healthy tissue and organ functions which may have long‐ranging effects on health, learning ability and productivity. Inadequacy of iron, zinc and vitamin A are the most important micronutrient deficiencies. Consumption of a 100 g portion of date flesh from date palm (Phoenix dactylifera L.) has been reported to meet approximately half the daily dietary recommended intake of these micronutrients. This study investigated the potential distribution of P. dactylifera under future climates to address its potential long‐term use as a food commodity to tackle micronutrient deficiencies in some developing countries.

RESULTS

Modelling outputs indicated large shifts in areas conducive to date palm cultivation, based on global‐scale alteration over the next 60 years. Most of the regions suffering from micronutrient deficiencies were projected to become highly conducive for date palm cultivation.

CONCLUSIONS

These results could inform strategic planning by government and agricultural organizations by identifying areas to cultivate this nutritionally important crop in the future to support the alleviation of micronutrient deficiencies. © 2015 Society of Chemical Industry
Military Sexual Assault, Gender, and PTSD Treatment Outcomes of U.S. Veterans
Authors: Tiet Quyen Q. , Leyva Yani E. , Blau Kathy , Turchik Jessica A. , Rosen Craig S.
Published: April 2015

This study examined whether gender and military sexual assault (MSA) were associated with psychiatric severity differences at initiation of treatment for posttraumatic stress disorder (PTSD) and whether MSA and gender predicted psychiatric treatment outcomes. Male (n= 726) and female (n= 111) patients were recruited from 7 U.S. Department of Veterans Affairs (VA) PTSD specialty intensive treatment programs and completed an intake survey; 69% (n= 574) of the participants completed a 4‐month postdischarge follow‐up survey. Measures included current PTSD and depressive symptoms, aggressive/violent behaviors, alcohol and drug use severity, and quality of life. Multilevel multivariate regression analyses were conducted to examine the main and interaction effects of gender and MSA on psychiatric treatment outcomes at 4‐month follow‐up, including demographics, baseline severity, hostile fire, and treatment length of stay. Baseline PTSD severity did not differ by gender or MSA status, but women had more severe depressive symptoms (d= 0.40) and less aggressive/violent symptoms (d= −0.46) than men. Gender, MSA status, and the interaction between gender and MSA did not predict treatment outcomes as hypothesized. Male and female veterans with and without MSA responded equally well to treatment in VA PTSD intensive treatment programs.
Should invertebrates receive greater inclusion in wildlife research journals?
Authors: Grodsky Steven M. , Iglay Raymond B. , Sorenson Clyde E. , Moorman Christopher E.
Published: April 2015

Invertebrates are among the most diverse organisms on Earth, significantly contribute to ecosystem function and integrity, and possess high potential as bioindicators. By definition, invertebrates also are wildlife. Yet, inclusion of invertebrates in peer‐reviewed wildlife journals has not been investigated. As such, our objective was to assess inclusion of invertebrates in prominent wildlife journals published in the last decade. Based on our review and first‐hand experience, we also aimed to provide recommendations for integration of invertebrates into wildlife science, education, and peer‐reviewed literature. We performed a systematic literature review by manually searching all issues and articles from 2003–2013 of the following journals: European Journal of Wildlife Research, Journal of Wildlife Management, South African Journal of Wildlife Research, Wildlife Biology, Wildlife Research, and Wildlife Society Bulletin. We analyzed data derived from our review to elucidate trends in the inclusion of invertebrates in these journals. We identified 4,916 articles that involved animal taxa, of which 122 (2.5%) included invertebrates and <1% included invertebrates as focal taxa. Our results indicated invertebrates are included in a minute portion of articles in top wildlife journals. We recommend a paradigm shift to a less taxonomically homogenized and vertebrate‐centric approach to wildlife science and education, integrating invertebrates into wildlife studies, and publishing results of those studies in wildlife journals to facilitate effective management of all wildlife species. © 2015 The Wildlife Society.
Seam Guided Laser Remote Welding with Automated Gap Bridging
Authors: Fixemer Peter , Albert Florian , Sievi Pravin , Graham Tom
Published: April 2015

Due to high productivity and potential for cycle time reduction, Laser Remote Welding is gaining more and more attention particularly in automotive manufacturing and its tiered supply base. In a typical industrial setup, component tolerances are a major challenge to the usage of laser remote technology. The difference between programmed beam position and the actual component location can only be compensated by complex and thus costly design measures. In addition, a changing gap situation makes it difficult to choose suitable process parameters to reach a bridged weld seam. The presented approach for a laser remote welding system not only detects the correct component location, but furthermore measures the actual gap real time during the process and adapts process parameters according to a process model. The focus will be for fillet type welds of aluminum and steel alloys and their model based parameters.
BOOK REVIEW
Authors: Mitchum Gary T.
Published: April 2015

PUGH, DAVID. 2004. Changing Sea Levels: Effects of Tides, Weather and Climate. Cambridge University Press. ISBN 0‐521‐53218‐3 (paperback). xiii + 265 p. US $50.
BOOK REVIEW
Authors: Arnosti Carol
Published: April 2015

BURDIGE, DAVID J. 2006. Geochemistry of Marine Sediments. Princeton University Press. ISBN 978–0–691–09506–6 (cloth). xviii + 609 p. US $85.
Telbivudine in liver transplant recipients: Renal protection does not overcome the risk of polyneuropathy and myopathy
Authors: Turan Ilker , Yapali Suna , Bademkiran Fikret , Kose Timur , Duman Soner , Sozbilen Murat , Gunsar Fulya , Ersoz Galip , Akarca Ulus Salih , Ozutemiz Omer , Karasu Zeki
Published: April 2015

The recently reported benefit of telbivudine for renal function has not been systematically studied in long‐term liver transplantation (LT) recipients who are at high risk for renal impairment. We aimed to examine whether switching lamivudine therapy to telbivudine could improve renal function in LT recipients who have impaired renal function. This single‐center, prospective cohort study enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV) prophylaxis and who had renal impairment for at least 1 year. Lamivudine was switched to telbivudine. The primary outcome was to evaluate the change in renal function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine in the posttransplant setting. After 45 patients were enrolled, the study was terminated early because of increased rates of polyneuropathy/myopathy. During telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate (eGFR) increased in 34 patients (76%). The improvement in renal function was prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as prophylaxis against HBV recurrence. Twenty‐six patients (58%) developed polyneuropathy and/or myopathy. The 1‐year estimated incidence of polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49‐11.50; P = 0.007). In conclusion, although it seems to have a favorable effect in the improvement of renal function and seems to be effective in the prevention of HBV recurrence, the high risk of polyneuropathy and myopathy hampers the use of telbivudine in LT recipients. Liver Transpl 21:1066‐1075, 2015. © 2015 AASLD.
Right lobe split liver transplantation versus whole liver transplantation in adult recipients: A systematic review and meta‐analysis
Authors: Wan Ping , Li Qigen , Zhang Jianjun , Xia Qiang
Published: April 2015

Split liver transplantation (SLT) has proven to be an effective technique to reduce the mortality of children on the waiting list, but whether creating 2 split grafts from 1 standard‐criteria whole liver would compromise outcomes of adult recipients remains uncertain. We conducted this meta‐analysis to compare outcomes of right lobe SLT and whole liver transplantation (WLT) in adult patients. PubMed, Embase, and the Cochrane Library were searched for relevant articles published before December 2014. Outcomes assessed were patient survival (PS), graft survival (GS), and major surgical complications after transplantation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to synthesize the results. Seventeen studies with a total of 48,457 patients met the full inclusion criteria. PS and GS rates were all found to be equivalent between SLT and WLT recipients. However, SLT was associated with higher rates of overall biliary complications (OR = 1.66; 95% CI = 1.29‐2.15; P < 0.001), bile leaks (OR = 4.30; 95% CI = 2.97‐6.23; P < 0.001), overall vascular complications (OR = 1.81; 95% CI = 1.29‐2.53; P < 0.001), hepatic artery thromboses (OR = 1.71; 95% CI = 1.17‐2.50; P = 0.005), and outflow tract obstructions (OR = 4.17; 95% CI = 1.75‐9.94; P = 0.001). No significant difference was observed in incidences of biliary stricture, portal vein complications, postoperative bleeding requiring surgical treatments, primary nonfunction, and retransplantations. In subgroup analyses, biliary and vascular complications only increased after ex vivo SLT rather than in situ SLT, and SLT recipients had more retransplantations if they matched with WLT recipients in terms of urgent status. In conclusion, adult right lobe SLT was associated with increased biliary and vascular complications compared with WLT, but it did not show significant inferiority in PSs and GSs. Liver Transpl 21:928‐943, 2015. © 2015 AASLD.
Chemo‐Enzymatic Synthesis of Linear and Branched Cationic Peptides: Evaluation as Gene Carriers
Authors: Ageitos Jose Manuel , Chuah Jo‐Ann , Numata Keiji
Published: April 2015

Cationic peptides such as poly(l‐lysine) and poly(l‐arginine) are important tools for gene delivery since they can efficiently condense DNA. It is difficult to produce cationic peptides by recombinant bacterial expression, and its chemical synthesis requires several steps of protection/deprotection and toxic agents. Chemo‐enzymatic synthesis of peptides is a clean chemistry technique that allows fast production under mild conditions. With the aim to simplify the production of cationic peptides, the present work develops an enzymatic reaction which enables the synthesis of linear cationic peptides and, through terminal functionalization with tris(2‐aminoethyl)amine, of branched cationic peptide conjugates, which show improved DNA complex formation. Cytotoxicity and transfection efficiency of all the chemo‐enzymatically synthesized cationic peptides are evaluated for their novel use as gene delivery agents. Synthesized peptides exhibit transfection efficiencies comparable to previously reported monodisperse peptides. Chemo‐enzymatic synthesis opens the door for efficient production of cationic peptides for their use as gene delivery carriers.
Ethylene Carbonate used as Reagent and Green Solvent in the Chemical Modification of Corncob
Authors: Chamú‐Muñoz Adriana , Hernández‐Meléndez Oscar , Hernández‐Luna Martín , Alcaraz‐Cienfuegos Jorge , Vivaldo‐Lima Eduardo , Bárzana Eduardo
Published: April 2015

Ethylene carbonate (EC) is selected as reagent and green solvent for the modification of corncob (CC), a lignocellulosic residue obtained from wet or dry milling processes during industrial and food applications of corn grains, as well as from ethanol production plants, using the following three reaction systems: (i) liquid phase (LP) and LP‐pressurized at moderate temperatures (85–175°C); (ii) solid phase at low temperatures (65–85 °C); and (iii) vapor phase at moderate temperatures (120–160 °C). Both the LP and LP‐pressurized systems allow the incorporation of large amounts of EC units. LP‐pressurized systems promote faster CC modification (25–35 min) at 165 °C and reduced consumption of EC monomer. CC modification in solid phase promotes moderate incorporation of EC units at low temperatures (60–80 °C) using K2CO3 as catalyst. CC modification in the vapor phase system is acceptable, efficient, and shows low monomer consumption.
Psychological and behavioral effects in epidemiological model with imperfect vaccination compartment
Authors: Cheng Yan , Pan Qiuhui , He Mingfeng
Published: April 2015

The aim of this paper is to investigate the dynamic of two SEIVS models, which incorporate an imperfect vaccination compartment. In this paper, we focus on the psychological inhibition effect of vaccinated individuals and the efficacy of vaccine on the spread of disease. For the susceptible individuals, we consider the psychological inhibition effect through the nonmonotone incidence rate. We find the disease‐free and the disease persistent conditions. We also give some numerical simulations to demonstrate the effect of behavioral change of the vaccinated individuals and the efficiency of vaccine. Copyright © 2015 John Wiley & Sons, Ltd.
Fast hybrid multi‐dimensional NMR methods based on ultrafast 2D NMR
Authors: Akoka Serge , Giraudeau Patrick
Published: April 2015

Conventional multi‐dimensional (nD) NMR experiments are characterized by inherent long acquisition durations, while ultrafast (UF) NMR makes it possible to reduce to a few hundreds of milliseconds the overall acquisition duration of a complete nD NMR dataset. Although extremely promising for a number of specific applications, the UF strategy suffers from significant limitations compared with its conventional counterpart. The main limitations concern the sensitivity, the resolution, and the accessible spectral width. However, when the targeted applications are compatible with an acquisition duration between a few seconds and a few minutes, hybrid UF techniques can be used to improve the performance of UF nD NMR while remaining faster than conventional acquisitions. Much better results in terms of signal‐to‐noise ratio can be achieved with the multi‐scan single‐shot approach or with interleaved acquisitions. Even more, for the same experimental duration, and in the case of homonuclear 2D NMR, the multi‐scan single‐shot approach has a much higher precision than conventional 2D NMR. Interleaved 2D NMR overcomes the drawbacks of single‐scan UF NMR in terms of spectral width and provides spectra for which the quality is not significantly different from that obtained with conventional 2D NMR. Finally, high spectral qualities have been demonstrated from hybrid conventional/UF 3D approaches capable of recording a whole 3D spectrum in the time needed to record a conventional 2D spectrum. This mini‐review aims at describing the principles, the recent advances and the latest applications of these hybrid techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Inhibition of MDM2 by RG7388 confers hypersensitivity to X‐radiation in xenograft models of childhood sarcoma
Authors: Phelps Doris , Bondra Kathryn , Seum Star , Chronowski Christopher , Leasure Justin , Kurmasheva Raushan T. , Middleton Steven , Wang Dian , Mo Xiaokui , Houghton Peter J.
Published: April 2015

Background

Curative therapy for childhood sarcoma presents challenges when complete resection is not possible. Ionizing radiation (XRT) is used as a standard modality at diagnosis or recurrence for childhood sarcoma; however, local recurrence is still problematic. Most childhood sarcomas are TP53 wild type at diagnosis, although approximately 5–10% have MDM2 amplification or overexpression.

Procedures

The MDM2 inhibitor, RG7388, was examined alone or in combination with XRT (20Gy given in 2 Gy daily fractions) to immune‐deficient mice bearing Rh18 (embryonal) or a total of 30 Gy in 2 Gy fractions to mice bearing Rh30 (alveolar) rhabdomyosarcoma xenografts. RG7388 was administered by oral gavage using two schedules (daily ×5; schedule 1 or once weekly; schedule 2). TP53‐responsive gene products (p21, PUMA, DDB2, and MIC1) as well as markers of apoptosis were analyzed.

Results

RG7388 showed no significant single agent antitumor activity. Twenty Grays XRT induced complete regressions (CR) of Rh18 with 100 percent tumor regrowth by week 7, but no tumor regrowth at 20 weeks when combined with RG7388. RG7388 enhanced time to recurrence combined with XRT in Rh30 xenografts compared to 30 Gy XRT alone. RG7388 did not enhance XRT‐induced local skin toxicity. Combination treatments induced TP53 responsive genes more rapidly and to a greater magnitude than single agent treatments.

Conclusions

RG7388 enhanced the activity of XRT in both rhabdomyosarcoma models without increasing local XRT‐induced skin toxicity. Changes in TP53‐responsive genes were consistent with the synergistic activity of RG7388 and XRT in the Rh18 model. Pediatr Blood Cancer 2015;62:1345–1352. © 2015 Wiley Periodicals, Inc.
Impaired exercise capacity and left ventricular function in long‐term adult survivors of childhood acute lymphoblastic leukemia
Authors: Christiansen Jon R. , Kanellopoulos Adriani , Lund May B. , Massey Richard , Dalen Håvard , Kiserud Cecilie E. , Ruud Ellen , Aakhus Svend
Published: April 2015

Background

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late cardiotoxic effects of cancer treatment, but conflicting evidence exists on the effects of anthracyclines on left ventricular (LV) diastolic function and exercise capacity.

Procedure

We performed a cross‐sectional study with comprehensive echocardiography in 138 adult survivors of childhood ALL, median 23.4 years after diagnosis. Pulsed tissue Doppler measurements of early diastolic mitral annular velocities (e’) were used for the assessment of diastolic function, and compared to 138 matched controls. Of the survivors, 133 also performed ergospirometry measuring peak oxygen uptake (VO2max). Associations between cancer treatment, LV function, and VO2max were analyzed.

Results

The survivor group had lower e’ values than controls (e’ septal 11.0 vs. 12.6 cm/s, P < 0.001), but the difference was confined to the subgroup of anthracycline treated survivors (median cumulative dose 120 mg/m2). Anthracycline exposure was inversely correlated with e’ (regression coefficient −1.581, P = 0.009). Reduced VO2max/kg occurred in 47% of the survivors, but more often in anthracycline treated survivors (56%) than anthracycline naïve survivors (17%, P < 0.001). Anthracycline exposure was inversely correlated with VO2max/kg (regression coefficient −3.084, P = 0.05 in multivariate analysis). Furthermore, associations were observed between measures of LV function and VO2max/kg, and e’ was the best predictor of VO2max/kg (standardized coefficient 0.355, P < 0.001 in multivariate analysis).

Conclusions

Adult survivors of childhood ALL have increased risk for impaired LV diastolic function and impaired exercise capacity, both associated with previous anthracycline exposure. Furthermore, there is an association between LV diastolic function and exercise capacity. Pediatr Blood Cancer 2015;62:1437–1443. © 2015 Wiley Periodicals, Inc.
Antibodies to BK virus in children prior to allogeneic hematopoietic cell transplant
Authors: Laskin Benjamin L. , Sullivan Kathleen E. , Hester Jeff , Goebel Jens , Davies Stella M. , Jodele Sonata
Published: April 2015

BK virus (BKV) is associated with kidney and bladder disease after hematopoietic cell transplantation (HCT) but less is known about the seroprevalence of pre‐transplant antibodies to BKV in children. We measured BKV IgG antibody titers in 36 children before HCT. BKV IgG antibodies were detected in all 36 patients, with 28/36 (77.8%) developing BK viremia in the first 100 days. Pre‐HCT BKV IgG antibody titers >1:40,960 were protective against later BK viremia ≥10,000 copies/ml. The seroprevalence of antibodies to BKV is high in children undergoing HCT and post‐transplant BK viremia, which is associated with bladder and kidney injury, is common. Pediatr Blood Cancer 2015;62:1670–1673. © 2015 Wiley Periodicals, Inc.
Synthesis, characterization and evaluation of a quadripolymer with low molecular weight as a water based drilling fluid viscosity reducer at high temperature (245 °C)
Authors: Huang Weian , Zhao Cong , Qiu Zhengsong , Leong Yee‐Kwong , Zhong Hanyi , Cao Jie
Published: April 2015

To construct an ultra‐high temperature stable drilling mud with a relatively low viscosity, a new viscosity‐reducing additive was synthesized and evaluated. This additive is a quadripolymer of acrylic acid (AA), 2‐acryl‐amido‐2‐methyl‐1‐propane sulfonic acid (AMPS), methyl acrylate (MA) and dimethyl diallyl ammonium chloride (DDAC) with low molecular weight synthesized by free radical polymerization, and its general molecular composition was confirmed by Fourier transform infrared spectroscopy. Thermal gravimetric analysis showed that the polymer has a very high temperature tolerance, i.e. it is stable up to 340 °C. Turbidity measurements with a UV−visible spectrophotometer showed that the polymer has a high salt tolerance in solution. It remained in solution at NaCl concentrations of up to 266 958 mg L−1 and at CaCl2 concentrations of up to 5000 mg L−1. The quadripolymer was found to inhibit hydration of the exchangeable ions in the clay particles and this was affirmed by a reduction in interlayer spacing. It also displayed high adsorption on calcium montmorillonite at different pH and even in the presence of NaCl, and caused the breakup of the particle network structure. This additive, when added to drilling mud prepared in both fresh and salt water, was found to reduce the mud viscosity and yield stress before and after aging for 16 h at 245 °C compared to base mud especially below 220 °C and 4.5 MPa. Importantly, this additive in mud was found to perform effectively at a relatively high pH and in a broad pH range of 7–11. © 2015 Society of Chemical Industry
New Insights into Project Management Research: A Natural Sciences Comparative
Authors: Joslin Robert , Müller Ralf
Published: April 2015

In this article, a new research perspective toward project management phenomena is developed; it builds on the existing natural science theory of genotyping and phenotyping by developing a contemporary comparative model for project management research, which compares natural science molecular biology (genomics) as a way to investigate social science (specifically, project management) phenomena. The comparative maps concepts and terminology and, in doing so, explains why phenomena in genomics (study of genetics) can be compared with practices, behaviors, and established thinking in project management. To support the theory building process, the attributes of complex adaptive systems (CAS) are used to validate the constructs of the research. The comparative is then used to answer the research question by identifying two social science phenomena: “lessons intentionally not learned” and “bricolage of competing methodology subelements,” followed by a detailed explanation of the reasons for the phenomena using the attributes of the comparative. This article provides further examples of phenomena that were derived from the comparative model as well as the types of research questions where the model would provide insight.

The authors believe that using a comparative model will challenge established thinking so that many aspects of project management will be seen in a new light in both the research and practitioner communities of project management.
Professionalism in Project Management: Redefining the Role of the Project Practitioner
Authors: Konstantinou Efrosyni
Published: April 2015

This article suggests that the project practitioner can have a significant role in defining and legitimizing the knowledge that is important for practice and the profession due to the situated nature of project knowledge. In-depth interviews with highly successful project practitioners revealed an unmediated relationship with practice centering on client/market priorities and emerging notions of professionalism. Here, project practitioners identified the need for a more meaningful relationship with the academic community in order to handle the challenges of situated practice.
Epi‐fluorescence Microscopy as a Tool for Relative Quantification of the Anti‐Biofouling Character of Atmospheric Pressure Plasma‐Polymerized Biomaterials
Authors: Nisol Bernard , Meunier Anne , Buess‐Herman Claudine , Reniers François
Published: April 2015

This study deals with the development of an original epi‐fluorescence‐based protocol to evaluate the anti‐biofouling character of atmospheric pressure plasma‐polymerized poly(ethylene glycol) samples. In this work, fluorescence microscopy is considered as an alternative to XPS for the evaluation of protein adsorption. The full set of samples is tested before and after bovine serum albumin‐fluorescein isothiocyanate treatment. It appears that their anti‐biofouling property, expressed by the variation of fluorescence intensity, is reduced when the power of the discharge is increased. The reproducibility of the experiments and the relatively high sensitivity of the proposed method are underlined.
Toxocariasis: An unusual cause of pleural effusion
Authors: Vallentin Blandine , Carsin Ania , Dubus Jean‐Christophe
Published: April 2015

Toxocara canis, one of the most frequent parasites worldwide, rarely triggers respiratory symptoms. We report the case of a 5‐year‐old girl hospitalized for a unilateral eosinophilic pleural effusion due to Toxocara canis. Besides the fact that she was living in a squat, no other medical condition was reported. There was no other site of infection caused by the parasite and she was successfully treated with albendazole. This case report is obviously unique as very few cases of pleural effusion due to Toxocara canis are reported in literature, all in adult patients. Pediatr Pulmonol. 2015; 50:E35–E36. © 2015 Wiley Periodicals, Inc.
TLR4 activation by lipopolysaccharide confers survival advantage to growth factor deprived prostate cancer cells
Authors: Jain Sumeet , Suklabaidya Sujit , Das Biswajit , Raghav Sunil K. , Batra Surinder K. , Senapati Shantibhusan
Published: April 2015

BACKGROUND

Prostate cancer (PCa) cells express Toll‐like receptor‐4 (TLR4), a known pro‐tumorigenic molecule for different cancer cells. The cancer cells residing in the avascular region of the tumor confront various metabolic stresses and continuously adapt mechanisms to overcome them. We hypothesized that TLR4 activation might provide direct survival advantage to metabolically stressed PCa cells.

METHODS

We first investigated the effect of LPS on survival of serum deprived PCa cells. To understand the molecular mechanisms involved in TLR4 mediated PCa survival, we next investigated change in expression of markers for apoptosis, senescence and autophagy. Ultimately, the effect of LPS on established prostate tumors was confirmed in vivo using a syngeneic rat model for PCa.

RESULTS

Lipopolysaccharide (LPS)‐mediated TLR4 activation significantly enhanced survival of serum deprived (SD) PC3, DU145 and MAT‐LyLu PCa cells. TLR4 inhibition by a specific inhibitor resulted in rapid death of SD‐PC3 cells, which was significantly suppressed by LPS. Interestingly, LPS treatment suppressed macroautophagy in SD‐PC3 cells and increased expression of CCL2 (C–C motif ligand‐2), a known autophagy inhibitor and pro‐survival factor. Intra‐tumor LPS injection resulted in increased tumor mass, induced TLR4 activation, suppressed autophagy, and increased the macrophage population in MAT‐LyLu‐tumors.

CONCLUSIONS

Our study reveals that bacterial LPS enhance survival of PCa cells under conditions of nutrient stress through TLR4 activation. Moreover, LPS induces overexpression of CCL2 involved in the suppression of starvation‐induced macroautophagy in PCa cells, and enhanced macrophage population in prostate tumors in vivo. Taken together, the current study suggests the importance of bacterial infection or TLR4‐activation in prostate cancer pathogenesis. Prostate 75:1020–1033, 2015. © 2015 Wiley Periodicals, Inc.
Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation
Authors: Yu Yue , Yang Ou , Fazli Ladan , Rennie Paul S. , Gleave Martin E. , Dong Xuesen
Published: April 2015

BACKGROUND

The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer‐associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated.

METHODS

Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration‐resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α‐SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells.

RESULTS

PR protein levels decreased in cancer‐associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre‐castration levels when tumors progressed to the castration‐resistant stage. Enhanced PR expression in human prostate stromal cells increased α‐SMA, but decreased vimentin and FSP protein levels ligand‐independently.

CONCLUSION

These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. Prostate 75:1043–1050, 2015. © 2015 Wiley Periodicals, Inc.
The changing role of CCGs in general practice
Authors: Chaplin Steve
Published: April 2015

Two years since CCGs were introduction in to primary care the King's Fund and the Nuffield Trust look at how they have performed and outline what is needed to enable them to succeed.
Putting patients in charge of the purse strings
Authors: Chaplin Steve
Published: April 2015

Personal health budgets allow a patient to choose what care they need and access it in a convenient manner. But does it work?
Benefits of SMART therapy for asthma management
Authors: Storrar William M , Chauhan Anoop J
Published: April 2015

A combination ICS and LABA in a single inhaler can improve adherence, and data suggest it can also reduce frequency of severe exacerbations.
Reversible quenching of luminescence in ZnO films by electric field action
Authors: Yalishev Vadim Sh. , Yuldashev Shavkat U. , Park Bae Ho , Kang Tae Won
Published: April 2015

We report the effect of the external electric field on the photoluminescence (PL) properties of ZnO films grown by a pulsed laser deposition method. The PL quenching of bound excitons under the electric field was attributed to a decrease in the capture cross section of the radiative centers. In addition, the change in the surface/grain boundaries charge induced a degradation of the 3.33 eV emission line over the whole sample, which remained even after voltage removal. Besides the PL degradation, this emission at 3.33 eV demonstrates the change in the thermal quenching process, where the activation energy of exciton detachment corresponds to its binding energy. All behaviors were restored to the initial state by application of the voltage with opposite polarity. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Likelihood‐based inferences about the mean area under a longitudinal curve in the presence of observations subject to limits of detection
Authors: Chandrasekhar Rameela , Shi Yi , Hutson Alan D. , Wilding Gregory E.
Published: April 2015

Comparison of groups in longitudinal studies is often conducted using the area under the outcome versus time curve. However, outcomes may be subject to censoring due to a limit of detection and specific methods that take informative missingness into account need to be applied. In this article, we present a unified model‐based method that accounts for both the within‐subject variability in the estimation of the area under the curve as well as the missingness mechanism in the event of censoring. Simulation results demonstrate that our proposed method has a significant advantage over traditionally implemented methods with regards to its inferential properties. A working example from an AIDS study is presented to demonstrate the applicability of our approach. Copyright © 2015 John Wiley & Sons, Ltd.
Flaviviral NS4b, chameleon and jack‐in‐the‐box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention
Authors: Zmurko Joanna , Neyts Johan , Dallmeier Kai
Published: April 2015

Dengue virus and other flaviviruses such as the yellow fever, West Nile, and Japanese encephalitis viruses are emerging vector‐borne human pathogens that affect annually more than 100 million individuals and that may cause debilitating and potentially fatal hemorrhagic and encephalitic diseases. Currently, there are no specific antiviral drugs for the treatment of flavivirus‐associated disease. A better understanding of the flavivirus–host interactions during the different events of the flaviviral life cycle may be essential when developing novel antiviral strategies. The flaviviral non‐structural protein 4b (NS4b) appears to play an important role in flaviviral replication by facilitating the formation of the viral replication complexes and in counteracting innate immune responses such as the following: (i) type I IFN signaling; (ii) RNA interference; (iii) formation of stress granules; and (iv) the unfolded protein response. Intriguingly, NS4b has recently been shown to constitute an excellent target for the selective inhibition of flavivirus replication. We here review the current knowledge on NS4b. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.
End Temperature Prediction of Molten Steel in LF based on CBR–BBN
Authors: Feng Kai , He Dongfeng , Xu Anjun , Wang Hongbing
Published: April 2015

To improve the control level about the end temperature of molten steel in ladle furnace (LF) refining, a combined method of case‐based reasoning (CBR) and Bayesian belief network (BBN) has been proposed to predict the end temperature of molten steel in LF. The evaluation of the reliability of cases is conducted by applying BBN for the assessment which the CBR method lacks in. A BBN is established based on the actual production process of LF refining. Statistical interval is then determined for each node, and finally the probability of each case in the case base is computed to evaluate the reliability. On such basis, the case retrieval algorithm in CBR is revised using the reliability of cases and the prediction accuracy of the revised algorithm is compared with ordinary CBR and back propagation neural network (BPNN). The results show that CBR–BBN has higher prediction accuracy than ordinary CBR and BPNN in the prediction about the end temperature of molten steel in LF refining.