bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Body Mass Index on Fluoroscopic Time and Radiation Dose During Intra‐articular Hip Injections
Authors: Cushman Daniel M. , Mattie Ryan , Clements Nathan D. , McCormick Zachary L.
Published: January 2016

Background

Intra‐articular hip injections are commonly performed for both diagnostic and therapeutic interventions. Because of the risk of damage to neurovascular structures, fluoroscopic guidance with injection of contrast material has been established as the gold standard to ensure proper needle placement into the intra‐articular space. However, fluoroscopically guided intra‐articular hip injections put patients at risk due to radiation exposure.

Objective

To examine the relationship between body mass index (BMI) and fluoroscopy time and radiation dose during intra‐articular hip injections.

Design

Retrospective study.

Setting

The study was conducted at an academic orthopedic center. All procedures were performed by physicians board‐certified in PM&R and/or with subspecialty certification in sports medicine, or by a trainee under close supervision from an attending physician.

Participants

All patients who underwent fluoroscopically guided intra‐articular hip injections between the years 2003‐2014 with a documented height/weight, fluoroscopy time, and radiation dose.

Interventions

All patients received unilateral or bilateral intra‐articular hip injections with fluoroscopic guidance. Fluoroscopy time and dose were recorded.

Main Outcome Measures

The main outcome measures were fluoroscopy time and radiation dose. A Bonferroni correction was implemented for multiple comparisons, defining statistical significance at P < .01.

Results

A total of 438 subjects (446 injections) were included. Mean fluoroscopy times were 17.4 ± 9.9, 17.5 ± 11.4, and 19.1 ± 13.4 seconds for normal, overweight, and obese body mass (BMI) index groups, respectively, with no significant difference between groups (P = .148). The mean radiation doses were 601 ± 690, 678 ± 558, and 1049 ± 812 mGy‐cm2, respectively (P < .001, r = 0.29). There was no association of age (P = .03), needle length (P = .34) or trainee involvement (P = .159) with fluoroscopy time.

Conclusion

This study demonstrates that increasing BMI leads to elevated radiation dose during fluoroscopically guided intra‐articular hip injections. The increased radiation experienced by patients with a larger BMI, however, is likely negligible.
Measuring Foreign Policy Positions of Members of the US Congress
Authors: Jeong Gyung-Ho
Published: January 2016

Studies have shown that a foreign policy position of a member of Congress is often distinct from a domestic one. Despite this, measures commonly used to determine the foreign policy positions of members of Congress are based on congressional votes on domestic as well as foreign policy matters. As foreign policy votes take up only a small portion of all congressional votes, these measures conflate a member’s foreign policy position with his or her domestic policy position. While there are other measures based exclusively on foreign policy votes, these are also problematic because they tend to use a small number of controversial votes and thus inflate extremism. To address these shortcomings, I present a new measure by applying a Bayesian item response theory model to all foreign policy votes. This paper demonstrates the similarities, differences, and advantages of this measure by comparing it with the existing measures in a series of analyses of foreign policy positions of political parties and individual legislators.
Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs
Authors: Madeira Marta S. , Rolo Eva A. , Alfaia Cristina M. , Pires Virgínia R. , Luxton Richard , Doran Olena , Bessa Rui J. B. , Prates José A. M.
Published: January 2016

The isolated or combined effects of betaine and arginine supplementation of reduced protein diets (RPD) on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pigm. longissimus lumborumand subcutaneous adipose tissue (SAT) were assessed. The experiment was performed on forty intact male pigs (Duroc×Large White×Landrace cross-breed) with initial and final live weights of 60 and 93 kg, respectively. Pigs were randomly assigned to one of the following five diets (n8): 16·0 % of crude protein (control), 13·0 % of crude protein (RPD), RPD supplemented with 0·33 % of betaine, RPD supplemented with 1·5 % of arginine and RPD supplemented with 0·33 % of betaine and 1·5 % of arginine. Data confirmed that RPD increase intramuscular fat (IMF) content and total fat content in SAT. The increased total fat content in SAT was accompanied by higher GLUT type 4, lipoprotein lipase and stearoyl-CoA desaturase mRNA expression levels. In addition, the supplementation of RPD with betaine and/or arginine did not affect either IMF or total fat in SAT. However, dietary betaine supplementation slightly affected fatty acid composition in both muscle and SAT. This effect was associated with an increase of carnitineO-acetyltransferase mRNA levels in SAT but not in muscle, which suggests that betaine might be involved in the differential regulation of some key genes of lipid metabolism in pig muscle and SAT. Although the arginine-supplemented diet decreased the mRNA expression level ofPPARGin muscle and SAT, it did not influence fat content or fatty acid composition in any of these pig tissues.
Comparison of short-term energy intake and appetite responses to active and seated video gaming, in 8–11-year-old boys
Authors: Allsop Susan , Green Benjamin P. , Dodd-Reynolds Caroline J. , Barry Gillian , Rumbold Penny L. S.
Published: January 2016

The acute effects of active and seated video gaming on energy intake (EI), blood glucose, plasma glucagon-like peptide-1 (GLP-17–36) and subjective appetite (hunger, prospective food consumption and fullness) were examined in 8–11-year-old boys. In a randomised, crossover manner, twenty-two boys completed one 90-min active and one 90-min seated video gaming trial during which food and drinks were provided ad libitum. EI, plasma GLP-17–36, blood glucose and subjective appetite were measured during and following both trials. Time-averaged AUC blood glucose was increased (P=0·037); however, EI was lower during active video gaming (1·63 (sem 0·26) MJ) compared with seated video gaming (2·65 (sem 0·32) MJ) (P=0·000). In a post-gaming test meal 1 h later, there were no significant differences in EI between the active and seated gaming trials. Although estimated energy expenditure was significantly higher during active video gaming, there was still no compensation for the lower EI. At cessation of the trials, relative EI (REI) was significantly lower following active video gaming (2·06 (sem 0·30) MJ) v. seated video gaming (3·34 (sem 0·35) MJ) (P=0·000). No significant differences were detected in time-averaged AUC GLP-17–36 or subjective appetite. At cessation of the active video gaming trial, EI and REI were significantly less than for seated video gaming. In spite of this, the REI established for active video gaming was a considerable amount when considering the total daily estimated average requirement for 8–11-year-old boys in the UK (7·70 MJ).
Hungry for Change: Urban Bias and Autocratic Sovereign Default
Authors: Ballard-Rosa Cameron
Published: January 2016

What drives autocrats to default on their sovereign debt? This article develops the first theory of sovereign debt default in autocracies that explicitly investigates survival incentives of political actors in nondemocracies. Self-interested elites, fearful of threats to their tenure because of urban unrest, may be willing to endure the long-term borrowing costs that defaulting creates rather than risk the short-term survival costs of removing cheap food policies for urban consumers. I test my main claims that both urbanization and food imports should be associated with greater likelihood of autocratic default using panel data covering forty-three countries over fifty years, finding that autocracies that are more reliant on imported food and that are more urbanized are significantly more likely to be in default on their external sovereign debt. I emphasize the regime-contingent nature of these effects by demonstrating that they are reversed when considering democratic sovereign default. I also substantiate the mechanisms put forward in my theory through illustrative historical cases of sovereign debt default in Zambia and Peru, in which I demonstrate that fear of urban unrest in the face of rapidly increasing food prices did indeed drive autocratic elites to default on international debt obligations. In addition to providing the first political theory of debt default in autocracies, the article introduces two robust predictors of autocratic default that have been overlooked in previous work, and highlights the importance of urban-rural dynamics in nondemocratic regimes.
Molecular and comparative morphological analysis of central European parasitic flatworms of the superfamily Brachylaimoidea Allison, 1943 (Trematoda: Plagiorchiida)
Authors: HENEBERG PETR , SITKO JILJÍ , BIZOS JIŘÍ
Published: January 2016

The Brachylaimoidea are digenean parasites of vertebrates, including humans, domestic animals, poultry and wild game. Numerous Brachylaimoidea, particularly adults ofBrachylaimaandLeucochloridium, are difficult to identify to species. We provide and analyse sequences of two nuclear (18S rDNA, ITS2) and two mitochondrial (CO1, ND1) DNA loci of central European species of the Brachylaimoidea, namelyLeucochloridium holostomum, Leucochloridium paradoxum, Leucochloridium perturbatum, Leucochloridium subtilis, Leucochloridium vogtianum, Urotocus rossitensis, Urogonimus macrostomus, Michajlovia migrata, Leucochloridiomorpha lutea, Brachylaima arcuatus, Brachylaima fuscataandBrachylaima mesostoma. We identified three clades in the genusLeucochloridium, which do not correspond to the previously suggested subgeneraNeoleucochloridium, PapilloleucochloridiumandLeucochloridium. We reject classification ofUrotocusandUrogonimusin Leucochloridiinae, and, instead, re-establish the subfamilies Urotocinae and Urogoniminae. We synonymize the genusRenylaimawith the genusBrachylaima. We rejectM. migrataas a member of Leucochloridiinae sensu stricto or Brachylaimidae suggested by some previous authors. We found that the previously sequencedGlaphyrostomumsp. does not cluster with any hitherto sequenced Brachylaimidae. We also provide comparative measurements of the examined central European Brachylaimoidea, address the the specificity of their localization in the host and discuss their host-specific prevalence and intensity of infections based on the extensive dataset of birds examined in 1962–2015.
One Health: competing perspectives in an emerging field
Authors: KINGSLEY P. , TAYLOR E. M.
Published: January 2016

Over the last decade, One Health has attracted considerable attention from researchers and policymakers. The concept argues that the fields of human, animal and environmental health ought to be more closely integrated. Amid a flurry of conferences, projects and publications, there has been substantial debate over what exactly One Health is and should be. This review summarizes the main trends in this emerging discussion, highlighting the fault lines between different perspectives on One Health. Some have shown that One Health's call to synthesize knowledge from different disciplines can lead to better interventions. Others, however, argue that One Health's challenge to existing practice must go further, and set out a vision that foregrounds the social and economic drivers of disease. Meanwhile, recent examples of One Health in practice highlight the potential but also the challenges of institutionalizing cooperation. We also discuss the promise and pitfalls of using complexity theory to tackle multifaceted problems, and consider how the One Health concept has been brought to bear on other issues, such as emerging new technologies. Ultimately, One Health is an important and worthwhile goal, and requires a debate that clarifies both the competing uses and the political nature of the project.
Silencing nonstandard speakers: A content analysis of accent portrayals on American primetime television
Authors: Dragojevic Marko , Mastro Dana , Giles Howard , Sink Alexander
Published: January 2016

Accent is a potent cue to social categorization and stereotyping. An important agent of accent-based stereotype socialization is the media. The present study is the first quantitative content analysis to comprehensively examine accent portrayals on American primetime television. We focused our analysis on portrayals of Standard American (SA), Nonstandard American (NSA), Foreign-Anglo (FA), and Foreign-Other (FO) accents. Results provide clear evidence that American media's portrayals of different accents are biased, reflecting pervasive societal stereotypes. Whereas SA and FA speakers are over-represented on television, NSA and FO speakers are effectivelysilenced, by virtue of their sheer absence and gross under-representation. Moreover, when NSA and FO speakers do rarely appear on television, they tend to be portrayed less favorably on status-related traits and physical appearance than SA and FA speakers. These findings provide insight into the potential influence of media consumption on consumers’ social perceptions of different linguistic groups. (Accents, media, language attitudes, stereotypes, content analysis)*
‘Planning for uncertainty’: narratives on retirement transition experiences
Authors: MOFFATT SUZANNE , HEAVEN BEN
Published: January 2016

Retirement is a major life transition which is associated in public discourses with reduced economic productivity and a raft of personal vulnerabilities. Consequently, governmental, health and employment sectors have promoted ‘active’ planning of affordable and ‘healthy’ retirements. This study presents a qualitative exploration of retirement transition and preparation experiences among 52 men and women from rural and urban areas of North East England, United Kingdom. The sample was diverse in terms of social class, income level, health status and type of work exit. Health, finance, social relationships and third-age opportunities were required resources for a good transition into retirement, and a degree of planning was required to mobilise these resources. However, the degree of choice and control around the transition to retirement was highly variable and socially structured. Thenotionof planning was embedded as a normative practice, particularly in relation to finances, but the practice of planning was highly contingent primarily due to personal circumstances (ill-health, bereavement, relationships) and work exit (redundancy, work stress, changes to shift patterns or hours). The findings offer insights into the reasons why many people do not plan and indicate that many of the assumptions associated with retirement planning warrant further consideration both theoretically and practically.
Noninvasive imaging of the thirteen-lined ground squirrel photoreceptor mosaic
Authors: SAJDAK BENJAMIN , SULAI YUSUFU N. , LANGLO CHRISTOPHER S. , LUNA GABRIEL , FISHER STEVEN K. , MERRIMAN DANA K. , DUBRA ALFREDO
Published: January 2016

Ground squirrels are an increasingly important model for studying visual processing, retinal circuitry, and cone photoreceptor function. Here, we demonstrate that the photoreceptor mosaic can be longitudinally imaged noninvasively in the 13-lined ground squirrel (Ictidomys tridecemlineatus) using confocal and nonconfocal split-detection adaptive optics scanning ophthalmoscopy using 790 nm light. Photoreceptor density, spacing, and Voronoi analysis are consistent with that of the human cone mosaic. The high imaging success rate and consistent image quality in this study reinforce the ground squirrel as a practical model to aid drug discovery and testing through longitudinal imaging on the cellular scale.
Cross-cultural study of caregiver burden for Alzheimer's disease in Japan and Taiwan: result from Dementia Research in Kumamoto and Tainan (DeReKaT)
Authors: Matsushita Masateru , Pai Ming-Chyi , Jhou Cai-Ying , Koyama Asuka , Ikeda Manabu
Published: January 2016

Background:

Caregiver burden (CB) of Alzheimer's disease (AD) in Taiwan is becoming an urgent social issue as well as that in Japan. The comparison of CB may explain how caregiver feels burden in each country.

Methods:

The participants were 343 outpatients with AD and their caregivers of Japan (n= 230) and Taiwan (n= 113). We assessed the CB using the Japanese and Chinese version of Zarit Caregiver Burden Interview (ZBI). The initial analysis was an exploratory factor analysis for each group to confirm the factor structure of ZBI. Then, the multiple-group structural equation modeling (MG-SEM) was used to assess the measurement invariance of ZBI such as configural, metric, and scalar invariances. Lastly, we compared the latent factor means of the ZBI between Japan and Taiwan.

Results:

In both groups, the confirmatory factor analysis extracted 3 factors which were labeled “Impact on caregiver's life”, “Embarrassed/anger”, and “Dependency”. The MG-SEM indicated an acceptable model fit, and established the partial scalar measurement invariance (comparative fit index (CFI) = 0.901, root mean square error of approximation (RMSEA) = 0.066). When we compared the latent factor means, the score of “Impact on caregiver's life” in Taiwanese caregivers was significantly higher than that in Japanese (p= 0.001). However, “Dependency” in Taiwanese caregivers was lower than that in Japanese (p< 0.001).

Conclusions:

Partial measurement invariance allowed comparing the latent factor mean across two countries. The results of comparisons suggested that there may be differences in the way of feeling CB between Japan and Taiwan.
Examination of level of knowledge in Italian general practitioners attending an education session on diagnosis and management of the early stage of Alzheimer's disease: pass or fail?
Authors: Veneziani Federica , Panza Francesco , Solfrizzi Vincenzo , Capozzo Rosa , Barulli Maria Rosaria , Leo Antonio , Lozupone Madia , Fontana Andrea , Arcuti Simona , Copetti Massimiliano , Cardinali Valentina , Grasso Alessandra , Tursi Marianna , Iurillo Annalisa , Imbimbo Bruno Pietro , Seripa Davide , Logroscino Giancarlo
Published: January 2016

Background:

We detected the general level of knowledge about the early diagnosis of Alzheimer's disease (AD) and subsequent care in general practitioners (GPs) from Southern Italy. We explored also the GP perception about their knowledge and training on diagnosis and management of AD.

Methods:

On a sample of 131 GPs, we administered two questionnaires: the GP-Knowledge, evaluating GPs’ expertise about AD epidemiology, differential diagnosis, and available treatments, and the GP-QUestionnaire on Awareness of Dementia (GP-QUAD), assessing the GPs’ attitudes, awareness, and practice regarding early diagnosis of dementia.

Results:

Specific screening tests or protocols to diagnose and manage dementia were not used by 53% of our GPs. The training on the recognition of early AD signs and symptoms was considered inadequate by 55% of the participants. Females were more likely to consider their training insufficient (58%) compared to males (53%). Female GPs were less likely to prescribe antipsychotic drugs to control neuropsychiatric symptoms (NPS) and suggest specialist advice in late stage of cognitive impairment. Multiple Correspondence Analysis (MCA) performed only on GP-QUAD suggested two dimensions explaining 26.1% (“GP attitude”) and 20.1% (“GP knowledge”) of the inertia for a total of 46.2%,

Conclusion:

In our survey on GP clinical practice, several problems in properly recognizing early AD symptoms and subsequently screening patients to be referred to secondary/tertiary care centers for diagnosis confirmation have emerged. In the future, specific training programs and educational projects for GPs should be implemented also in Italy to improve detection rates and management of dementia in primary care.
PICKWICK'S OTHER PAPERS: CONTINUALLY READING DICKENS
Authors: Han Carrie Sickmann
Published: January 2016

While carefully crafting a valentine to his would-be-lover Mary, Sam Weller finishes rather abruptly, and his father, looking over his shoulder, asks, “That's rayther a sudden pull up, ain't it, Sammy?” Sam's response emblematizes the driving force of the serial novel: “Not a bit on it. . . she'll vish there wos more, and that's the great art o' letter writin'” (344; no. XII, ch. XXXIII). Charles Dickens's great art of serial writing aimed to leave his readers repeatedly wishing there was more: more pages, more plot, more world, and above all, more time with their favorite characters. This desire encouraged readers to imagine beyond the novel – to pursue characters outside the pages of The Pickwick Papers itself. Their desires were rewarded with a wide range of continuations that included theatrical adaptations, plagiarisms, or unauthorized sequels – anything that, like the valentine, could reunite readers with their beloved Sam.
Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus
Authors: Rossetti Maria A. , Piryatinsky Irene , Ahmed Fayeza S. , Klinge Petra M. , Relkin Norman R. , Salloway Stephen , Ravdin Lisa D. , Brenner Einat , Malloy Paul F. , Levin Bonnie E. , Broggi Michael , Gavett Rebecca , Maniscalco James S. , Katzen Heather
Published: January 2016

Objective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. Methods: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). Results: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p≤.001) and SDT (p<.001). Conclusions: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. (JINS, 2016, 22, 341–349)
High maternal sodium intake alters sex-specific renal renin–angiotensin system components in newborn Wistar offspring
Authors: Maia D. R. R. , Lopes K. L. , Heimann J. C. , Furukawa L. N. S.
Published: January 2016

This study aimed to evaluate the systemic and renal renin–angiotensin–aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.
Discontinuing benzodiazepines: best practices
Authors: Guaiana G. , Barbui C.
Published: January 2016

In July 2015, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a Rapid Response report summary, with a critical appraisal, on discontinuation strategies for patients with long-term benzodiazepines (BDZ) use. The CADTH document is a review of the literature. It includes studies whose intervention is BDZ discontinuation. Also, clinical guidelines, systematic reviews and meta-analyses are included. What emerges from the CADTH guidelines is that the best strategy remains gradual tapering of BDZ with little evidence for the use of adjunctive medications. The results show that simple interventions such as discontinuation letters from clinicians, self-help information and support in general, added to gradual tapering may be associated with a two- to three-fold higher chance of successful withdrawal, compared with treatment as usual. We suggest possible implications for day-to-day clinical practice.
A Behavioral Parent-Training Intervention for a Child With Avoidant/Restrictive Food Intake Disorder
Authors: Murphy Jillian , Zlomke Kimberly R.
Published: January 2016

Avoidant/restrictive food intake disorder (ARFID) is a feeding disorder classification in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. ( DSM–5; American Psychiatric Association, 2013 ) that describes a pervasive and disruptive pattern of food refusal and/or severe food selectivity. Currently, there is need for the development of evidence-based behavioral treatments for food selectivity that can be implemented in outpatient clinics, involve parents in treatment, and generalize to the child’s real-world environment. We have described in this study a behavioral feeding intervention that integrates components from intensive feeding programs with parent-training strategies in the treatment of a 6-year-old girl with ARFID. Treatment was primarily parent-mediated and included psychoeducation, in vivo parent coaching, parent modeling, differential reinforcement, gradual exposure to novel foods, and contingency management. The course of the intervention was divided into an initial differential reinforcement phase and subsequent directive strategies phase. Results indicate increased dietary repertoire, clinically significant decreases in problematic parent and child feeding behaviors, and acceptance of bites of 30 novel foods from pre to postintervention. Positive treatment outcomes were maintained at 6-week posttreatment follow-up.
Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1
Authors: Qiu L , Wu J , Pan C , Tan X , Lin J , Liu R , Chen S , Geng R , Huang W
Published: January 2016

Dysregulated cell cycle progression has a critical role in tumorigenesis. Cell division cycle 27 (CDC27) is a core subunit of the anaphase-promoting complex/cyclosome, although the specific role of CDC27 in cancer remains unknown. In our study, we explored the biological and clinical significance of CDC27 in colorectal cancer (CRC) growth and progression and investigated the underlying molecular mechanisms. Results showed that CDC27 expression is significantly correlated with tumor progression and poor patient survival. Functional assays demonstrated that overexpression of CDC27 promoted proliferation in DLD1 cells, whereas knockdown of CDC27 in HCT116 cells inhibited proliferation both in vitro and in vivo. Further mechanistic investigation showed that CDC27 downregulation resulted in G1/S phase transition arrest via the significant accumulation of p21 in HCT116 cells, and the upregulation of CDC27 promoted G1/S phase transition via the attenuation of p21 in DLD1 cells. Furthermore, we also demonstrated that CDC27 regulated inhibitor of DNA binding 1 (ID1) protein expression in DLD1 and HCT116 cells, and rescue assays revealed that CDC27 regulated p21 expression through modulating ID1 expression. Taken together, our results indicate that CDC27 contributes to CRC cell proliferation via the modulation of ID1-mediated p21 regulation, which offers a novel approach to the inhibition of tumor growth. Indeed, these findings provide new perspectives for the future study of CDC27 as a target for CRC treatment.
X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity
Authors: Evans M K , Sauer S J , Nath S , Robinson T J , Morse M A , Devi G R
Published: January 2016

Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.
Amplification and generation of ultra-intense twisted laser pulses via stimulated Raman scattering
Authors: Vieira J. , Trines R. M. G. M. , Alves E. P. , Fonseca R. A. , Mendonça J. T. , Bingham R. , Norreys P. , Silva L. O.
Published: January 2016

Twisted Laguerre–Gaussian lasers, with orbital angular momentum and characterized by doughnut-shaped intensity profiles, provide a transformative set of tools and research directions in a growing range of fields and applications, from super-resolution microcopy and ultra-fast optical communications to quantum computing and astrophysics. The impact of twisted light is widening as recent numerical calculations provided solutions to long-standing challenges in plasma-based acceleration by allowing for high-gradient positron acceleration. The production of ultra-high-intensity twisted laser pulses could then also have a broad influence on relativistic laser–matter interactions. Here we show theoretically and with ab initio three-dimensional particle-in-cell simulations that stimulated Raman backscattering can generate and amplify twisted lasers to petawatt intensities in plasmas. This work may open new research directions in nonlinear optics and high–energy-density science, compact plasma-based accelerators and light sources.
Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
Authors: Imamura Minako , Takahashi Atsushi , Yamauchi Toshimasa , Hara Kazuo , Yasuda Kazuki , Grarup Niels , Zhao Wei , Wang Xu , Huerta-Chagoya Alicia , Hu Cheng , Moon Sanghoon , Long Jirong , Kwak Soo Heon , Rasheed Asif , Saxena Richa , Ma Ronald C. W. , Okada Yukinori , Iwata Minoru , Hosoe Jun , Shojima Nobuhiro , Iwasaki Minaka , Fujita Hayato , Suzuki Ken , Danesh John , Jørgensen Torben , Jørgensen Marit E. , Witte Daniel R. , Brandslund Ivan , Christensen Cramer , Hansen Torben , Mercader Josep M. , Flannick Jason , Moreno-Macías Hortensia , Burtt Noël P. , Zhang Rong , Kim Young Jin , Zheng Wei , Singh Jai Rup , Tam Claudia H. T. , Hirose Hiroshi , Maegawa Hiroshi , Ito Chikako , Kaku Kohei , Watada Hirotaka , Tanaka Yasushi , Tobe Kazuyuki , Kawamori Ryuzo , Kubo Michiaki , Cho Yoon Shin , Chan Juliana C. N. , Sanghera Dharambir , Frossard Philippe , Park Kyong Soo , Shu Xiao-Ou , Kim Bong-Jo , Florez Jose C. , Tusié-Luna Teresa , Jia Weiping , Tai E Shyong , Pedersen Oluf , Saleheen Danish , Maeda Shiro , Kadowaki Takashi
Published: January 2016

Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10−8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency
Authors: Song Jun , Yang Dongshan , Xu Jie , Zhu Tianqing , Chen Y. Eugene , Zhang Jifeng
Published: January 2016

Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.
Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
Authors: Aloulou Meryem , Carr Edward J. , Gador Mylène , Bignon Alexandre , Liblau Roland S. , Fazilleau Nicolas , Linterman Michelle A.
Published: January 2016

T follicular regulatory (Tfr) cells are a subset of Foxp3+ regulatory T (Treg) cells that form in response to immunization or infection, which localize to the germinal centre where they control the magnitude of the response. Despite an increased interest in the role of Tfr cells in humoral immunity, many fundamental aspects of their biology remain unknown, including whether they recognize self- or foreign antigen. Here we show that Tfr cells can be specific for the immunizing antigen, irrespective of whether it is a self- or foreign antigen. We show that, in addition to developing from thymic derived Treg cells, Tfr cells can also arise from Foxp3− precursors in a PD-L1-dependent manner, if the adjuvant used is one that supports T-cell plasticity. These findings have important implications for Tfr cell biology and for improving vaccine efficacy by formulating vaccines that modify the Tfr:Tfh cell ratio.
Facile Access to Graphene Oxide from Ferro-Induced Oxidation
Authors: Yu Chao , Wang Cai-Feng , Chen Su
Published: January 2016

Methods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers’ method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time-saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials.
All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations
Authors: Kuroda Yutaka , Suenaga Atsushi , Sato Yuji , Kosuda Satoshi , Taiji Makoto
Published: January 2016

In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 106 Å3 cubic boxes containing ~3 × 104 water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any “artificial” hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y and H formed large amorphous clusters and those containing A, P, S and T formed smaller ones. Tetra-peptides made of D, E, K and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations.
Nucleosome architecture throughout the cell cycle
Authors: Deniz Özgen , Flores Oscar , Aldea Martí , Soler-López Montserrat , Orozco Modesto
Published: January 2016

Nucleosomes provide additional regulatory mechanisms to transcription and DNA replication by mediating the access of proteins to DNA. During the cell cycle chromatin undergoes several conformational changes, however the functional significance of these changes to cellular processes are largely unexplored. Here, we present the first comprehensive genome-wide study of nucleosome plasticity at single base-pair resolution along the cell cycle in Saccharomyces cerevisiae. We determined nucleosome organization with a specific focus on two regulatory regions: transcription start sites (TSSs) and replication origins (ORIs). During the cell cycle, nucleosomes around TSSs display rearrangements in a cyclic manner. In contrast to gap (G1 and G2) phases, nucleosomes have a fuzzier organization during S and M phases, Moreover, the choreography of nucleosome rearrangements correlate with changes in gene expression during the cell cycle, indicating a strong association between nucleosomes and cell cycle-dependent gene functionality. On the other hand, nucleosomes are more dynamic around ORIs along the cell cycle, albeit with tighter regulation in early firing origins, implying the functional role of nucleosomes on replication origins. Our study provides a dynamic picture of nucleosome organization throughout the cell cycle and highlights the subsequent impact on transcription and replication activity.
Nonlinear dynamics induced anomalous Hall effect in topological insulators
Authors: Wang Guanglei , Xu Hongya , Lai Ying-Cheng
Published: January 2016

We uncover an alternative mechanism for anomalous Hall effect. In particular, we investigate the magnetisation dynamics of an insulating ferromagnet (FM) deposited on the surface of a three-dimensional topological insulator (TI), subject to an external voltage. The spin-polarised current on the TI surface induces a spin-transfer torque on the magnetisation of the top FM while its dynamics can change the transmission probability of the surface electrons through the exchange coupling and hence the current. We find a host of nonlinear dynamical behaviors including multistability, chaos and phase synchronisation. Strikingly, a dynamics mediated Hall-like current can arise, which exhibits a nontrivial dependence on the channel conductance. We develop a physical understanding of the mechanism that leads to the anomalous Hall effect. The nonlinear dynamical origin of the effect stipulates that a rich variety of final states exist, implying that the associated Hall current can be controlled to yield desirable behaviors. The phenomenon can find applications in Dirac-material based spintronics.
Estimating the minimum control count of random network models
Authors: Ruths Derek , Ruths Justin
Published: January 2016

The study of controllability of complex networks has introduced the minimum number of controls required for full controllability as a new network measure of interest. This network measure, like many others, is non-trivial to compute. As a result, establishing the significance of minimum control counts (MCCs) in real networks using random network null models is expensive. Here we derive analytic estimates for the expected MCCs of networks drawn from three commonly-used random network models. Our estimates show good agreement with exact control counts. Furthermore, the analytic expressions we derive offer insights into the structures within each random network model that induce the need for controls.
Ultradispersed Nanoarchitecture of LiV3O8 Nanoparticle/Reduced Graphene Oxide with High-Capacity and Long-Life Lithium-Ion Battery Cathodes
Authors: Mo Runwei , Du Ying , Rooney David , Ding Guqiao , Sun Kening
Published: January 2016

Lack of high-performance cathode materials has become the major barriers to lithium-ion battery applications in advanced communication equipment and electric vehicles. In this paper, we report a versatile interfacial reaction strategy, which is based on the idea of space confinement, for the synthesis of ultradispersed LiV3O8 nanoparticles (~10 nm) on graphene (denoted as LVO NPs-GNs) with an unprecedented degree of control on the separation and manipulation of the nucleation, growth, anchoring and crystallization of nanoparticles in a water-in-oil emulsion system over free growth in solution. The prepared LVO NPs-GNs composites displayed high performance as an cathode material for lithium-ion battery, including high reversible lithium storage capacity (237 mA h g−1 after 200 cycles), high Coulombic efficiency (about 98%), excellent cycling stability and high rate capability (as high as 176 mA h g−1 at 0.9 A g−1, 128 mA h g−1 at 1.5 A g−1, 91 mA h g−1 at 3 A g−1 and 59 mA h g−1 at 6 A g−1, respectively). Very significantly, the preparation method employed can be easily adapted and may opens the door to complex hybrid materials design and engineering with graphene for advanced energy storage.
Robustly photogenerating H2 in water using FeP/CdS catalyst under solar irradiation
Authors: Cheng Huanqing , Lv Xiao-Jun , Cao Shuang , Zhao Zong-Yan , Chen Yong , Fu Wen-Fu
Published: January 2016

Photosplitting water for H2production is a promising, sustainable approach for solar-to-chemical energy conversion. However, developing low-cost, high efficient and stable photocatalysts remains the major challenge. Here we report a composite photocatalyst consisting of FeP nanoparticles and CdS nanocrystals (FeP/CdS) for photogenerating H2in aqueous lactic acid solution under visible light irradiation. Experimental results demonstrate that the photocatalyst is highly active with a H2-evolution rate of 202000 μmol h−1g−1for the first 5 h (106000 μmol h−1g−1under natural solar irradiation), which is the best H2evolution activity, even 3-fold higher than the controlin situphoto-deposited Pt/CdS system and the corresponding to an apparent quantum efficiency of over 35% at 520 nm. More important, we found that the system exhibited excellent stability and remained effective after more than 100 h in optimal conditions under visible light irradiation. A wide-ranging analysis verified that FeP effectively separates the photoexcited charge from CdS and showed that the dual active sites in FeP enhance the activity of FeP/CdS photocatalysts.
Metasurface-based broadband hologram with high tolerance to fabrication errors
Authors: Zhang Xiaohu , Jin Jinjin , Wang Yanqin , Pu Mingbo , Li Xiong , Zhao Zeyu , Gao Ping , Wang Changtao , Luo Xiangang
Published: January 2016

With new degrees of freedom to achieve full control of the optical wavefront, metasurfaces could overcome the fabrication embarrassment faced by the metamaterials. In this paper, a broadband hologram using metasurface consisting of elongated nanoapertures array with different orientations has been experimentally demonstrated. Owing to broadband characteristic of the polarization-dependent scattering, the performance is verified at working wavelength ranging from 405 nm to 914 nm. Furthermore, the tolerance to the fabrication errors, which include the length and width of the elongated aperture, the shape deformation and the phase noise, has been theoretically investigated to be as large as 10% relative to the original hologram. We believe the method proposed here is promising in emerging applications such as holographic display, optical information processing and lithography technology etc.