bluuebunny/crossref_metadata_2025 huggingface dataset:
Training dual tasks together or apart in Parkinson's disease: Results from the DUALITY trial
Authors: Strouwen Carolien , Molenaar Esther A. L. M. , Münks Liesbeth , Keus Samyra H. J. , Zijlmans Jan C. M. , Vandenberghe Wim , Bloem Bastiaan R. , Nieuwboer Alice
Published: April 2017

Background and Objectives: Many controversies surround the usefulness of dual‐task training in Parkinson's disease (PD). This study (1) compared the efficacy of two different dual‐task training programs for improving dual‐task gait and (2) assessed the possible fall risk of such training.

Methods: Patients (N = 121) with a diagnosis of PD (aged 65.93 [±9.22] years, Hoehn and Yahr stage II‐III on‐medication) were randomized to (1) a consecutive group in which gait and cognitive tasks were trained separately or (2) an integrated group in which gait and cognitive tasks were trained simultaneously. Both interventions involved 6 weeks of at‐home physiotherapist‐led training. Two baseline tests were performed as a 6‐week control period before training. Posttests were performed immediately after training and at 12‐week follow‐up. Dual‐task gait was assessed during trained and untrained secondary tasks to assess consolidation of learning. Fall risk was determined by a weekly telephone call for 24 weeks.

Results: No significant time by group interactions were found, suggesting that both training modes had a similar effect on dual‐task gait. Immediately after training, and not after the control period, significant improvements (P < .001) in dual‐task gait velocity were found in all trained and untrained dual tasks. Improvements ranged between 7.75% and 13.44% when compared with baseline values and were retained at 12‐week follow‐up. No significant change in fall risk occurred in both study arms (P = .84).

Conclusions: Consecutive and integrated dual‐task training led to similar and sustained improvements in dual‐task gait velocity without increasing fall risk. These novel findings support adoption of dual‐task training in clinical practice. © 2017 International Parkinson and Movement Disorder Society
Severe wind shear at Hong Kong International Airport: climatology and case studies
Authors: Chan P. W.
Published: April 2017

Severe wind shear (headwind change of 30 kn or more) at Hong Kong International Airport is documented in this study. Its climatology, including the number of reports from pilots each year, captured by the wind shear alerting service, its cause and its magnitude are presented. The purpose of the study is to document the characteristics of severe wind shear at an operating airport. Some typical cases of severe wind shear are also examined, such as observation by remote‐sensing instruments and flight data analysis. It is found that the shear magnitudes in pilot reports of severe wind shear, as with pilot reports of wind shear in general, are subjective in nature. They may not be consistent with headwind changes as determined from the flight data. Sometimes, the pilot reports of wind shear may be based on wind trend information available onboard for certain fleets of aircraft. The wind shear can be transient in nature, for which an alert beforehand is difficult.
Effectiveness of cause‐related marketing for differential positioning of market entrant in developing market: An exploratory study in Indian context
Authors: Shree Deep , Gupta Ankush , Sagar Mahim
Published: April 2017

Cause‐related marketing is being increasingly used for forging strong relation between the brand and the customer. It is primarily being used by the well‐established brands to further strengthen their position in the market as it leads to a positive image of the brand, and customers are more receptive towards such brands because they tend to provide them with tangible as well as intangible benefits. This study tends to identify the effectiveness of cause‐related marketing as a marketing tool for newly launched products in developing market of India, which has so far remained a less explored area. A sample of 150 consumers was taken, and case studies were undertaken for validating these findings. The findings suggest that cause‐related marketing campaigns, even at early stages of brand development, can lead to customer trial and differential positioning thus providing these new entrants with an opportunity to interact with the customers. The proposed framework can provide useful insights to brand managers to design cause‐related marketing campaigns for newly launched brands. The results and findings have been deduced from real‐time market research, and it can help in furthering research in the field of cause‐related marketing in India and other developing economies with similar market conditions.
Ability to adjust nocturnal fat oxidation in response to overfeeding predicts 5‐year weight gain in adults
Authors: Rynders Corey A. , Bergouignan Audrey , Kealey Elizabeth , Bessesen Daniel H.
Published: April 2017

Objective

To determine whether metabolic responses to short‐term overfeeding predict longitudinal changes in body weight.

Methods

Twenty‐four‐hour energy expenditure (EE) and substrate utilization were measured at baseline in a room calorimeter following 3 days of eucaloric and hypercaloric feeding (40% excess) in a sample of lean adults (n: 34; age: 28 ± 2 y; BMI: 22 ± 3 kg/m2). Body mass and fat mass (dual‐energy x‐ray absorptiometry) were measured annually for 5 years. Regression analyses examined whether changes in EE and fuel use with overfeeding predicted body weight and composition changes over 5 years.

Results

Overfeeding increased EE and reduced fat oxidation when examined over the 24‐hour, waking, and nocturnal periods. Absolute change in body mass over 5 years was 3.0 ± 0.6 kg (average rate of change = 0.7 ± 0.1 kg/y,P < 0.001). Lower nocturnal (but not 24‐hour or waking) fat oxidation (r = −0.42,P = 0.01) and EE (r = −0.33,P = 0.05) with overfeeding were the strongest predictors of 5‐year weight gain. When adjusted for covariates, changes in nocturnal fat oxidation and EE with overfeeding predicted 41% of the variance in weight change (P = 0.02).

Conclusions

Failure to maintain fat oxidation at night following a period of overfeeding appears to be associated with a metabolic phenotype favoring weight gain.
Attenuated Low‐Grade Inflammation Following Long‐Term Dietary Intervention in Postmenopausal Women with Obesity
Authors: Blomquist Caroline , Alvehus Malin , Burén Jonas , Ryberg Mats , Larsson Christel , Lindahl Bernt , Mellberg Caroline , Söderström Ingegerd , Chorell Elin , Olsson Tommy
Published: April 2017

Objective

Abdominal fat accumulation after menopause is associated with low‐grade inflammation and increased risk of metabolic disorders. Effective long‐term lifestyle treatment is therefore needed.

Methods

Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic‐type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation‐related parameters.

Results

Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long‐term significant effects (P < 0.001) on adipose gene expression were found for toll‐like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL‐6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet‐by‐time interaction for serum IL‐6 (P = 0.022). High‐sensitivity C‐reactive protein was decreased in the PD group at 24 months (P = 0.001).

Conclusions

A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation‐related adipose gene expression.
Weight gain and supplemental O2: Risk factors during the hematopoietic cell transplant admission in pediatric patients
Authors: Rowan Courtney M. , Nitu Mara E. , Moser Elizabeth A. S. , Swigonski Nancy L. , Renbarger Jamie L.
Published: April 2017

Background

Respiratory failure in the pediatric hematopoietic cell transplant (HCT) recipient is the leading cause for admission to the intensive care unit and carries a high mortality rate. The objective of this study is to investigate the association of clinical risk factors with the development of respiratory failure in the pediatric allogeneic HCT recipient.

Procedures

This is a single‐center, retrospective review of allogeneic pediatric HCT from 2008 to 2014. Multiple variables were examined. The primary outcome was respiratory failure. Percent weight gain was investigated at multiple time points. Bivariate and multivariate regression was used.

Results

Of the 87 allogeneic HCT recipients, 22 (25%) developed respiratory failure. Mortality for entire cohort was 13.8%. All who died were intubated prior to death. The group with respiratory failure had significantly higher percent weight gain increase at multiple time points: peak weight prior to discharge or intubation (P = 0.008), weight at discharge or intubation (P = .001), and weight at day 43 (median day for intubation) (P = 0.02). Odds ratio (OR) for respiratory failure increased with increasing percentage peak weight gain: 10% increase (3.1 [1.1, 9.0]), 15% increase (4.1 [1.5, 11.2]), and 20% (8.3 [2.4. 28.9]). Fifty percent of all patients required supplemental O2. OR for respiratory failure in patients requiring more than 1 l supplemental O2 is 25.3 (6.5, 98.7).

Conclusion

Percent weight gain and need for supplemental oxygen is highly associated with the development of respiratory failure in pediatric HCT recipients, representing predictors of acute respiratory failure in pediatric HCT. These data could be incorporated into an algorithm that should be developed, implemented, and validated in a prospective, multicenter fashion.
The research on educational leadership and management in the Arab world since the 1990s: A systematic review
Authors: Oplatka Izhar , Arar Khalid
Published: April 2017

As most of the scholarship about educational leadership and management refers to developed countries, our aim in this review is to systematically collect, document, scrutinise and critically analyse at time of writing date research on educational leadership in Arab countries and to identify the key strengths and weaknesses in the research literature. Based on a systematic review of 48 articles, it was found that the vast majority of research on Arab educational leadership focused on either identifying patterns of leadership styles and orientations and the barriers faced by educational leaders in applying some of the leadership models originated in Western scholarship, or on exploring and examining leaders’ managerial perceptions and practices both in times of routine and reforms. Our analysis identified several theoretical, conceptual and methodological limitations contributing to and, in many cases, impeding researchers’ ability to predict or explain the nature of Arab educational leadership.
A new interpretation and palaeoecological significance of the fossil bee cell cluster Rosellichnus patagonicus (Celliformidae)
Authors: Sarzetti Laura C. , Genise Jorge F. , Bellosi Eduardo S. , Cantil Liliana F.
Published: April 2017

The trace fossil Rosellichnus patagonicus preserved in palaeosols is a cluster of vertical bee cells with smooth inner surface and discrete walls. R. patagonicus was originally described from two fragmentary specimens which limited a morphological analysis, the correct interpretation of the producer and palaeoecological inferences. Abundant specimens of R. patagonicus recently collected from several Cenozoic localities of Patagonia, principally from the La Pava Formation at Paso del Sapo, have allowed the recognition of a complete set of morphological characters, among which the curved neck of some cells is particularly significant. Isolated cells in the same outcrops show similar curved necks. Such cells are constructed only by diphaglossinae bees, to which clusters and isolated cells may be attributed. These trace fossils are particularly comparable with extant cells and clusters of Cadeguala albopilosa (Diphaglossinae) which at present nests in forest clearings with grass cover. Accordingly, the andic mollisols from the Miocene La Pava Formation, where R. patagonicus is abundant, formed in warm‐temperate, sub‐humid and seasonal conditions, under grass‐dominated vegetation with subordinate tree coverage.
Cost‐Effectiveness of Craniotomy for Epidural Hematomas at a Major Government Hospital in Cambodia
Authors: Moran Dane , Shrime Mark G. , Nang Sam , Vycheth Iv , Vuthy Din , Hong Raksmey , Padula William V. , Park Kee B.
Published: April 2017

Background

Epidural hematoma (EDH) is a common and potentially deadly occurrence following a severe traumatic brain injury. Our aim was to determine whether craniotomy is cost‐effective when indicated for the treatment of EDH when a trained neurosurgeon is available.

Methods

A decision tree was used to model the cost‐effectiveness of craniotomy available versus craniotomy unavailable for the management of traumatic EDH from a Cambodian societal and provider perspective. Costs and effectiveness parameters were obtained from patient data at a large government hospital in Cambodia. Outcomes were measured in quality‐adjusted life years (QALYs). Incremental cost per QALY and budget impact were calculated for each intervention at a willingness‐to‐pay (WTP) threshold of $9787.80/QALY (3× GDP per capita PPP). The time horizon reflected full life span, and costs and QALYs were discounted at 3%. Sensitivity analysis was also conducted.

Results

Compared to craniotomy unavailable for EDH ($945.80; 11.78 QALYs), craniotomy available came at a higher cost and greater effectiveness ($1520.73; 12.78 QALYs), resulting in an incremental cost‐effectiveness ratio (ICER) of $574.93. One‐way analysis demonstrated that craniotomy unavailable became more cost‐effective than craniotomy available when the percent chance of having a GOS of 4 or 5 was 60% for patients with an EDH where craniotomy was indicated but not performed. Probabilistic sensitivity analysis revealed that craniotomy available was more cost‐effective than conservative management in 84.4% of simulations at the WTP threshold.

Conclusions

Craniotomy is a cost‐effective treatment for patients with a traumatic EDH who meet criteria for operation when trained neurosurgeons are available onsite.
Model-based biotechnological potential analysis of Kluyveromyces marxianus central metabolism
Authors: Pentjuss A , Stalidzans E , Liepins J , Kokina A , Martynova J , Zikmanis P , Mozga I , Scherbaka R , Hartman H , Poolman M G , Fell D A , Vigants A
Published: April 2017

The non-conventional yeast Kluyveromyces marxianus is an emerging industrial producer for many biotechnological processes. Here, we show the application of a biomass-linked stoichiometric model of central metabolism that is experimentally validated, and mass and charge balanced for assessing the carbon conversion efficiency of wild type and modified K. marxianus. Pairs of substrates (lactose, glucose, inulin, xylose) and products (ethanol, acetate, lactate, glycerol, ethyl acetate, succinate, glutamate, phenylethanol and phenylalanine) are examined by various modelling and optimisation methods. Our model reveals the organism’s potential for industrial application and metabolic engineering. Modelling results imply that the aeration regime can be used as a tool to optimise product yield and flux distribution in K. marxianus. Also rebalancing NADH and NADPH utilisation can be used to improve the efficiency of substrate conversion. Xylose is identified as a biotechnologically promising substrate for K. marxianus.
Measuring hemophilia caregiver burden: validation of the Hemophilia Caregiver Impact measure
Authors: Schwartz Carolyn E. , Powell Victoria E. , Eldar-Lissai Adi
Published: April 2017

Aims

The purpose of this article is to describe the psychometric development of the Hemophilia Caregiver Impact measure.

Methods

Qualitative interviews (n = 22) and a cross-sectional web-based study (n = 458) were implemented with caregivers of people with hemophilia. Classical test theory and item response theory analyses were implemented to evaluate the psychometric characteristics of the measure.

Results

The study sample had a mean age of 39 and a median level of college education. It was predominantly female (88%), and had an average of two children. 85% of this study sample had at least one child with hemophilia. The final 36-item Hemophilia Caregiver Impact measure is composed of seven subscales assessing relevant negative aspects of caregiver impact (Burden Summary) as well as one subscale reflecting a positive aspect of caregiver impact (Positive Emotions). These two summary scores are orthogonal and can be used together in analyses examining negative and positive aspects of caregiver impact. The items included within each subscale reflect a unidimensional construct, demonstrate good item information and trace lines, and lack of local dependence. The resulting subscales demonstrate high reliability, and good construct validity. They show moderate incremental and discriminant validity.

Conclusions

The Hemophilia Caregiver Impact measure is a useful new tool for clinical research on hemophilia. In addition to having eight relevant subscales, the measure can also be summarized with two scores. This versatility can be useful in analyzing studies with very small samples, which is to be expected when dealing with a rare condition like hemophilia.
Engineering model for the quantitative consideration of residual stresses in fatigue design of welded components
Authors: Hensel Jonas , Nitschke-Pagel Thomas , Dilger Klaus
Published: April 2017

Residual stresses are one of the major factors influencing the fatigue strength of welded components. However, the current IIW bonus factor concept for the mean stress correction is limited to a qualitative evaluation of residual stress effects. By combining residual stress measurements and fatigue testing, the authors derive an improved bonus factor concept that considers residual stresses quantitatively. The proposed concept considers the combined effect of load mean stresses and cyclically stabilized residual stresses. It is pointed out that the yield strength is not a capable measure to determine whether residual stresses have “low” or “extreme” impact on the fatigue strength of welded steels. It is rather recommended to evaluate residual stress effects based on the effective stress ratio reflecting local loading conditions.
Free Expression and Democracy
Authors: Saunders Kevin W.
Published: April 2017

Free Expression and Democracy takes on the assumption that limits on free expression will lead to authoritarianism or at least a weakening of democracy. That hypothesis is tested by an examination of issues involving expression and their treatment in countries included on The Economist's list of fully functioning democracies. Generally speaking, other countries allow prohibitions on hate speech, limits on third-party spending on elections, and the protection of children from media influences seen as harmful. Many ban Holocaust denial and the desecration of national symbols. Yet, these other countries all remain democratic, and most of those considered rank more highly than the United States on the democracy index. This book argues that while there may be other cultural values that call for more expansive protection of expression, that protection need not reach the level present in the United States in order to protect the democratic nature of a country.
HEALTH TECHNOLOGY ASSESSMENT IN EVALUATION OF PHARMACEUTICALS IN THE CZECH REPUBLIC
Authors: Vostalová Lenka , Mazelová Jana , Samek Jiří , Vocelka Milan
Published: April 2017

Objectives: In the Czech Republic, the health technology assessment (HTA) approaches have been implemented in evaluation of medicinal products since 2008.

The aim of this study was to provide an overview of the implementation of HTA and different levels thereof in the evaluation process conducted by the State Institute for Drug Control (SUKL) and to describe the impact of HTA on the entrance of new medicinal entities into out-patient healthcare system including highly innovative and orphan drugs.

Methods: Materials supporting this overview were collected using the records in the database of administrative proceedings of SUKL, in-house standard operating procedures, and the legislation in force. Based on these sources as well as the hands-on knowledge of the current practice, a brief description of the general rules of administrative proceedings involving HTA of varying complexity was elaborated. Characteristic features of the individual types of proceedings, basic differences in the complexity of HTA employed, and its most important challenges were summarized.

Results: In Czech Republic, HTA in the formal administrative proceedings ensures a transparent process of introduction of new medicinal products into clinical practice and leaves space for restriction of reimbursement conditions to minimize budget impact.

Conclusions: As a robust as well as pragmatic HTA methodology has been implemented by SUKL, relevant stakeholders (marketing authorization holders, Health Care Funds, clinical expert groups) are now able to influence reimbursement of new technologies.
Eternity clauses in post-conflict and post-authoritarian constitution-making: Promise and limits
Authors: SUTEU SILVIA
Published: April 2017

The literature on entrenchment as a means to achieve constitutional endurance has grown in recent years, as has the scholarship on unamendable provisions as a mechanism intended to safeguard the constitutional project. However, little attention has been paid to the promise and limits of eternity clauses in transitional settings. Their appeal in this context is great. In an effort to safeguard hard-fought agreements, drafters often declare unamendable what they consider the fundamentals to the political deal: the number of presidential term limits, the commitment to human rights and to democracy, the form of the state (whether republican or monarchical), the territorial integrity of the state, the territorial division of power, secularism or the official religion. This article explores the distinctive role and problems posed by eternity clauses in transitional constitution-building, as guarantees of the pre-constitutional political settlement in such fragile periods. The article also compares unamendability to other techniques of constitution-making in uncertain times, such as sunset clauses, deferring hard choices and other forms of constitutional incrementalism.
What Causes Rock Avalanches?
Authors: Cook Terri
Published: April 2017

Experimental studies of frictional weakening beneath a deadly rock avalanche in China help to clarify the mechanisms that cause these devastating natural disasters.
What Happens When Ocean Eddies Hit a Wall?
Authors: Underwood Emily
Published: April 2017

A new study tracks two ocean eddies passing over the Pacific Ocean's Izu-Ogasawara Ridge.
Dispersal timing and drought history influence the response of bacterioplankton to drying–rewetting stress
Authors: Székely Anna J , Langenheder Silke
Published: April 2017

The extent and frequency of drought episodes is expected to increase in the following decades making it a crucial stress factor for smaller water bodies. However, very little is known about how bacterioplankton is affected by increased evaporation and how these communities reassemble after rewetting. Here, we present results from a microcosm experiment that assessed the effect of drying–rewetting stress on bacterioplankton in the light of the stress history and the rate and timing of dispersal after the rewetting. We found that the drying phase resulted mainly in a change of function, whereas the complete desiccation and rewetting processes strongly affected both composition and function, which were, however, influenced by the initial conditions and stress history of the communities. Effects of dispersal were generally stronger when it occurred at an early stage after the rewetting. At this stage, selective establishment of dispersed bacteria coupled with enhanced compositional and functional recovery was found, whereas effects of dispersal were neutral, that is, predictable by dispersal rates, at later stages. Our studies therefore show that both the stress history and the timing of dispersal are important factors that influence the response of bacterial communities to environmental change and stress events.
Ruthenium-cobalt nanoalloys encapsulated in nitrogen-doped graphene as active electrocatalysts for producing hydrogen in alkaline media
Authors: Su Jianwei , Yang Yang , Xia Guoliang , Chen Jitang , Jiang Peng , Chen Qianwang
Published: April 2017

The scalable production of hydrogen could conveniently be realized by alkaline water electrolysis. Currently, the major challenge confronting hydrogen evolution reaction (HER) is lacking inexpensive alternatives to platinum-based electrocatalysts. Here we report a high-efficient and stable electrocatalyst composed of ruthenium and cobalt bimetallic nanoalloy encapsulated in nitrogen-doped graphene layers. The catalysts display remarkable performance with low overpotentials of only 28 and 218 mV at 10 and 100 mA cm−2, respectively, and excellent stability of 10,000 cycles. Ruthenium is the cheapest platinum-group metal and its amount in the catalyst is only 3.58 wt.%, showing the catalyst high activity at a very competitive price. Density functional theory calculations reveal that the introduction of ruthenium atoms into cobalt core can improve the efficiency of electron transfer from alloy core to graphene shell, beneficial for enhancing carbon–hydrogen bond, thereby lowing ΔGH* of HER.
Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales
Authors: Bhérer Claude , Campbell Christopher L. , Auton Adam
Published: April 2017

In humans, males have lower recombination rates than females over the majority of the genome, but the opposite is usually true near the telomeres. These broad-scale differences have been known for decades, yet little is known about differences at the fine scale. By combining data sets, we have collected recombination events from over 100,000 meioses and have constructed sex-specific genetic maps at a previously unachievable resolution. Here we show that, although a substantial fraction of the genome shows some degree of sexually dimorphic recombination, the vast majority of hotspots are shared between the sexes, with only a small number of putative sex-specific hotspots. Wavelet analysis indicates that most of the differences can be attributed to the fine scale, and that variation in rate between the sexes can mostly be explained by differences in hotspot magnitude, rather than location. Nonetheless, known recombination-associated genomic features, such as THE1B repeat elements, show systematic differences between the sexes.
A reversible dendrite-free high-areal-capacity lithium metal electrode
Authors: Wang Hui , Matsui Masaki , Kuwata Hiroko , Sonoki Hidetoshi , Matsuda Yasuaki , Shang Xuefu , Takeda Yasuo , Yamamoto Osamu , Imanishi Nobuyuki
Published: April 2017

Reversible dendrite-free low-areal-capacity lithium metal electrodes have recently been revived, because of their pivotal role in developing beyond lithium ion batteries. However, there have been no reports of reversible dendrite-free high-areal-capacity lithium metal electrodes. Here we report on a strategy to realize unprecedented stable cycling of lithium electrodeposition/stripping with a highly desirable areal-capacity (12 mAh cm−2) and exceptional Coulombic efficiency (>99.98%) at high current densities (>5 mA cm−2) and ambient temperature using a diluted solvate ionic liquid. The essence of this strategy, that can drastically improve lithium electrodeposition kinetics by cyclic voltammetry premodulation, lies in the tailoring of the top solid-electrolyte interphase layer in a diluted solvate ionic liquid to facilitate a two-dimensional growth mode. We anticipate that this discovery could pave the way for developing reversible dendrite-free metal anodes for sustainable battery chemistries.
Correction: Corrigendum: Proteogenomic integration reveals therapeutic targets in breast cancer xenografts
Authors: Huang Kuan-lin , Li Shunqiang , Mertins Philipp , Cao Song , Gunawardena Harsha P. , Ruggles Kelly V. , Mani D. R. , Clauser Karl R. , Tanioka Maki , Usary Jerry , Kavuri Shyam M. , Xie Ling , Yoon Christopher , Qiao Jana W. , Wrobel John , Wyczalkowski Matthew A. , Erdmann-Gilmore Petra , Snider Jacqueline E. , Hoog Jeremy , Singh Purba , Niu Beifang , Guo Zhanfang , Sun Sam Qiancheng , Sanati Souzan , Kawaler Emily , Wang Xuya , Scott Adam , Ye Kai , McLellan Michael D. , Wendl Michael C. , Malovannaya Anna , Held Jason M. , Gillette Michael A. , Fenyö David , Kinsinger Christopher R. , Mesri Mehdi , Rodriguez Henry , Davies Sherri R. , Perou Charles M. , Ma Cynthia , Townsend R. Reid , Chen Xian , Carr Steven A. , Ellis Matthew J. , Ding Li
Published: April 2017

Nature Communications 8: Article number: 14864 (2017)); Published: 28 March 2017; Updated: 25 April 2017 The original version of this Article contained a typographical error in the spelling of the author Beifang Niu, which was incorrectly given as Beifung Niu. This has now been corrected in both thePDF and HTML versions of the Article.
Correction: Corrigendum: Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice
Authors: Schweiger Martina , Romauch Matthias , Schreiber Renate , Grabner Gernot F , Hütter Sabrina , Kotzbeck Petra , Benedikt Pia , Eichmann Thomas O , Yamada Sohsuke , Knittelfelder Oskar , Diwoky Clemens , Doler Carina , Mayer Nicole , De Cecco Werner , Breinbauer Rolf , Zimmermann Robert , Zechner Rudolf
Published: April 2017

Nature Communications 8: Article number: 14859 2017); Published: 22 March 2017; Updated: 25 April 2017 The affiliation details for R. Zimmermann, R. Zechner and R. Breinbauer are incorrect in this Article. The correct affiliation details for these authors are given below: Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, 8010 Graz, Austria.
Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
Authors: Zoeller Jason J. , Bronson Roderick T. , Selfors Laura M. , Mills Gordon B. , Brugge Joan S.
Published: April 2017

Several lines of evidence suggest that components of the tumor microenvironment, specifically basement membrane and extracellular matrix proteins, influence drug sensitivities. We previously reported differential drug sensitivity of tumor cells localized adjacent to laminin-rich extracellular matrix in three-dimensional tumor spheroid cultures. To evaluate whether differential intra-tumor responses to targeted therapy occur in vivo, we examined the sensitivity of human epidermal growth factor receptor 2-positive tumors to lapatinib using a previously described ductal carcinoma in situ-like model characterized by tumor cell confinement within ductal structures surrounded by an organized basement membrane. Here we show that tumor cells localized to a ‘niche’ in the outer layer of the intraductal tumors adjacent to myoepithelial cells and basement membrane are resistant to lapatinib. We found that the pro-survival protein BCL2 is selectively induced in the niche-protected tumor cells following lapatinib treatment, and combined inhibition of HER2 and BCL-2/XL enhanced targeting of these residual tumor cells. Elimination of the niche-protected tumor cells was achieved with the HER2 antibody–drug conjugate T-DM1, which delivers a chemotherapeutic payload. Thus, these studies provide evidence that subpopulations of tumor cells within specific microenvironmental niches can adapt to inhibition of critical oncogenic pathways, and furthermore reveal effective strategies to eliminate these resistant subpopulations.
Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes
Authors: Kriszt Rókus , Arai Satoshi , Itoh Hideki , Lee Michelle H. , Goralczyk Anna G. , Ang Xiu Min , Cypess Aaron M. , White Andrew P. , Shamsi Farnaz , Xue Ruidan , Lee Jung Yeol , Lee Sung-Chan , Hou Yanyan , Kitaguchi Tetsuya , Sudhaharan Thankiah , Ishiwata Shin’ichi , Lane E. Birgitte , Chang Young-Tae , Tseng Yu-Hua , Suzuki Madoka , Raghunath Michael
Published: April 2017

The identification of brown adipose deposits in adults has led to significant interest in targeting this metabolically active tissue for treatment of obesity and diabetes. Improved methods for the direct measurement of heat production as the signature function of brown adipocytes (BAs), particularly at the single cell level, would be of substantial benefit to these ongoing efforts. Here, we report the first application of a small molecule-type thermosensitive fluorescent dye, ERthermAC, to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes. ERthermAC accumulated in the endoplasmic reticulum of BAs and displayed a marked change in fluorescence intensity in response to adrenergic stimulation of cells, which corresponded to temperature change. ERthermAC fluorescence intensity profiles were congruent with mitochondrial depolarisation events visualised by the JC-1 probe. Moreover, the averaged fluorescence intensity changes across a population of cells correlated well with dynamic changes such as thermal power, oxygen consumption, and extracellular acidification rates. These findings suggest ERthermAC as a promising new tool for studying thermogenic function in brown adipocytes of both murine and human origins.
Paper-based RNA detection and multiplexed analysis for Ebola virus diagnostics
Authors: Magro Laura , Jacquelin Béatrice , Escadafal Camille , Garneret Pierre , Kwasiborski Aurélia , Manuguerra Jean-Claude , Monti Fabrice , Sakuntabhai Anavaj , Vanhomwegen Jessica , Lafaye Pierre , Tabeling Patrick
Published: April 2017

The most performing techniques enabling early diagnosis of infectious diseases rely on nucleic acid detection. Today, because of their high technicality and cost, nucleic acid amplification tests (NAAT) are of benefit only to a small fraction of developing countries population. By reducing costs, simplifying procedures and enabling multiplexing, paper microfluidics has the potential to considerably facilitate their accessibility. However, most of the studies performed in this area have not quit the lab. This letter brings NAAT on paper closer to the field, by using clinical samples and operating in a resource-limited setting. We first performed isothermal reverse transcription and Recombinase Polymerase Amplification (RT-RPA) of synthetic Ribonucleic Acid (RNA) of Ebola virus using paper microfluidics devices. We further applied this method in Guinea to detect the presence of Ebola virus in human sample RNA extracts, with minimal facilities (carry-on detection device and freeze-dried reagents on paper). RT-RPA results were available in few minutes and demonstrate a sensitivity of 90.0% compared to the gold-standard RT-PCR on a set of 43 patient samples. Furthermore, the realization of a nine-spot multilayered device achieving the parallel detection of three distinct RNA sequences opens a route toward the detection of multiple viral strains or pathogens.
Exploring genetic variation for salinity tolerance in chickpea using image-based phenotyping
Authors: Atieno Judith , Li Yongle , Langridge Peter , Dowling Kate , Brien Chris , Berger Bettina , Varshney Rajeev K. , Sutton Tim
Published: April 2017

Soil salinity results in reduced productivity in chickpea. However, breeding for salinity tolerance is challenging because of limited knowledge of the key traits affecting performance under elevated salt and the difficulty of high-throughput phenotyping for large, diverse germplasm collections. This study utilised image-based phenotyping to study genetic variation in chickpea for salinity tolerance in 245 diverse accessions. On average salinity reduced plant growth rate (obtained from tracking leaf expansion through time) by 20%, plant height by 15% and shoot biomass by 28%. Additionally, salinity induced pod abortion and inhibited pod filling, which consequently reduced seed number and seed yield by 16% and 32%, respectively. Importantly, moderate to strong correlation was observed for different traits measured between glasshouse and two field sites indicating that the glasshouse assays are relevant to field performance. Using image-based phenotyping, we measured plant growth rate under salinity and subsequently elucidated the role of shoot ion independent stress (resulting from hydraulic resistance and osmotic stress) in chickpea. Broad genetic variation for salinity tolerance was observed in the diversity panel with seed number being the major determinant for salinity tolerance measured as yield. This study proposes seed number as a selection trait in breeding salt tolerant chickpea cultivars.
Comparative transcriptome analysis of venom glands from Cotesia vestalis and Diadromus collaris, two endoparasitoids of the host Plutella xylostella
Authors: Zhao Wei , Shi Min , Ye Xi-qian , Li Fei , Wang Xiao-wei , Chen Xue-xin
Published: April 2017

Venoms secreted by the venom gland (VG) of parasitoid wasp help ensure successful parasitism by host immune suppression and developmental regulation.Cotesia vestalis, a larval endoparasitoid, andDiadromus collaris, a pupal endoparasitoid, parasitize the diamondback moth (DBM),Plutella xylostella. To explore and compare the venom components of two endoparasitoids, we sequenced transcriptomes of the VGs and wasp bodies without VGs (BWVGs) of the two endoparasitoids. Statistically enriched GO terms and KEGG pathways of the two VGs compared to respective whole-body background were similar and reflected active protein biosynthesis activities in the two VGs. 1,595 VG specific genes of theD.collarisVG and 1,461 VG specific genes of theC.vestalisVG were identified by comparative transcript profiling. A total of 444 and 513 genes encoding potential secretory proteins were identified and defined as putative venom genes inD.collarisVG andC.vestalisVG, respectively. The putative venom genes of the two wasps showed no significant similarity or convergence. More venom genes were predicted inD.collarisVG thanC.vestalisVG, especially hydrolase-coding genes. Differences in the types and quantities of putative venom genes shed light on different venom functions.
Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes
Authors: Eitan Erez , Green Jamal , Bodogai Monica , Mode Nicolle A. , Bæk Rikke , Jørgensen Malene M. , Freeman David W. , Witwer Kenneth W. , Zonderman Alan B. , Biragyn Arya , Mattson Mark P. , Noren Hooten Nicole , Evans Michele K.
Published: April 2017

Cells release lipid-bound extracellular vesicles (EVs; exosomes, microvesicles and apoptotic bodies) containing proteins, lipids and RNAs into the circulation. Vesicles mediate intercellular communication between both neighboring and distant cells. There is substantial interest in using EVs as biomarkers for age-related diseases including cancer, and neurodegenerative, metabolic and cardiovascular diseases. The majority of research focuses on identifying differences in EVs when comparing disease states and matched controls. Here, we analyzed circulating plasma EVs in a cross-sectional and longitudinal study in order to address age-related changes in community-dwelling individuals. We found that EV concentration decreases with advancing age. Furthermore, EVs from older individuals were more readily internalized by B cells and increased MHC-II expression on monocytes compared with EVs from younger individuals, indicating that the decreased concentration of EVs with age may be due in part to increased internalization. EVs activated both monocytes and B cells, and activation of B cells by LPS enhanced EV internalization. We also report a relative stability of EV concentration and protein amount in individual subjects over time. Our data provide important information towards establishing a profile of EVs with human age, which will further aid in the development of EV-based diagnostics for aging and age-related diseases.
IVIG regulates the survival of human but not mouse neutrophils
Authors: Schneider Christoph , Wicki Simone , Graeter Stefanie , Timcheva Tankica M. , Keller Christian W. , Quast Isaak , Leontyev Danila , Djoumerska-Alexieva Iglika K. , Käsermann Fabian , Jakob Stephan M. , Dimitrova Petya A. , Branch Donald R. , Cummings Richard D. , Lünemann Jan D. , Kaufmann Thomas , Simon Hans-Uwe , von Gunten Stephan
Published: April 2017

Intravenous immunoglobulin (IVIG) are purified IgG preparations made from the pooled plasma from thousands of healthy donors and are being tested in preclinical mouse models. Inherent challenges, however, are the pluripotency of IVIG and its xenogeneicity in animals. IVIG can alter the viability of human neutrophils via agonistic antibodies to Fas and Siglec-9. In this study, we compared the effects of IVIG on human and mouse neutrophils using different death assays. Different commercial IVIG preparations similarly induced cytokine-dependent death in human neutrophils, whereas they had no effects on the survival of either peripheral blood or bone marrow neutrophils from C57BL/6 or BALB/c mice. F(ab’)2 but not Fc fragments of IVIG induced death of human neutrophils, whereas neither of these IVIG fragments, nor agonistic monoclonal antibodies to human Fas or Siglec-9 affected the viability of mouse neutrophils. Pooled mouse IgG, which exhibited a different immunoprofile compared to IVIG, also had no effect on mouse cells. Together, these observations demonstrate that effects of IVIG on neutrophil survival are not adequately reflected in current mouse models, despite the key role of these cells in human inflammatory and autoimmune diseases.
Two-port connecting-layer-based sandwiched grating by a polarization-independent design
Authors: Li Hongtao , Wang Bo
Published: April 2017

In this paper, a two-port connecting-layer-based sandwiched beam splitter grating with polarization-independent property is reported and designed. Such the grating can separate the transmission polarized light into two diffraction orders with equal energies, which can realize the nearly 50/50 output with good uniformity. For the given wavelength of 800 nm and period of 780 nm, a simplified modal method can design a optimal duty cycle and the estimation value of the grating depth can be calculated based on it. In order to obtain the precise grating parameters, a rigorous coupled-wave analysis can be employed to optimize grating parameters by seeking for the precise grating depth and the thickness of connecting layer. Based on the optimized design, a high-efficiency two-port output grating with the wideband performances can be gained. Even more important, diffraction efficiencies are calculated by using two analytical methods, which are proved to be coincided well with each other. Therefore, the grating is significant for practical optical photonic element in engineering.
Insights into the structures and electronic properties of Cun+1

μ
and CunS
μ
(n = 1–12; μ = 0, ±1) clusters
Authors: Li Cheng-Gang , Shen Zi-Gang , Hu Yan-Fei , Tang Ya-Nan , Chen Wei-Guang , Ren Bao-Zeng
Published: April 2017

Abstarct

The stability and reactivity of clusters are closely related to their valence electronic configuration. Doping is a most efficient method to modify the electronic configuration and properties of a cluster. Considering that Cu and S posses one and six valence electrons, respectively, the S doped Cu clusters with even number of valence electrons are expected to be more stable than those with odd number of electrons. By using the swarm intelligence based CALYPSO method on crystal structural prediction, we have explored the structures of neutral and charged Cun+1 and CunS (n = 1–12) clusters. The electronic properties of the lowest energy structures have been investigated systemically by first-principles calculations with density functional theory. The results showed that the clusters with a valence count of 2, 8 and 12 appear to be magic numbers with enhanced stability. In addition, several geometry-related-properties have been discussed and compared with those results available in the literature.
Thermodynamic Scaling of the Dynamics of a Strongly Hydrogen-Bonded Glass-Former
Authors: Romanini Michela , Barrio María , Macovez Roberto , Ruiz-Martin María D. , Capaccioli Simone , Tamarit Josep Ll.
Published: April 2017

We probe the temperature- and pressure-dependent specific volume (v) and dipolar dynamics of the amorphous phase (in both the supercooled liquid and glass states) of the ternidazole drug (TDZ). Three molecular dynamic processes are identified by means of dielectric spectroscopy, namely the α relaxation, which vitrifies at the glass transition, a Johari-Goldstein βJG relaxation, and an intramolecular process associated with the relaxation motion of the propanol chain of the TDZ molecule. The lineshapes of dielectric spectra characterized by the same relaxation time (isochronal spectra) are virtually identical, within the studied temperature and pressure ranges, so that the time-temperature-pressure superposition principle holds for TDZ. The α and βJG relaxation times fulfil the density-dependent thermodynamic scaling: master curves result when they are plotted against the thermodynamic quantity Tv
γ
, with thermodynamic exponent γ approximately equal to 2. These results show that the dynamics of TDZ, a system characterized by strong hydrogen bonding, is characterized by an isomorphism similar to that of van-der-Waals systems. The low value of γ can be rationalized in terms of the relatively weak density-dependence of the dynamics of hydrogen-bonded systems.
Multivariate assessment and attribution of droughts in Central Asia
Authors: Li Zhi , Chen Yaning , Fang Gonghuan , Li Yupeng
Published: April 2017

While the method for estimating the Palmer Drought Severity Index (PDSI) is now more closely aligned to key water balance components, a comprehensive assessment for measuring long-term droughts that recognizes meteorological, agro-ecological and hydrological perspectives and their attributions is still lacking. Based on physical approaches linked to potential evapotranspiration (PET), the PDSI in 1965–2014 showed a mixture of drying (42% of the land area) and wetting (58% of the land area) that combined to give a slightly wetting trend (0.0036 per year). Despite the smaller overall trend, there is a switch to a drying trend over the past decade (−0.023 per year). We designed numerical experiments and found that PDSI trend responding to the dramatic increase in air temperature and slight change in precipitation. The variabilities of meteorological and agro-ecological droughts were broadly comparable to various PDSI drought index. Interestingly, the hydrological drought was not completely comparable to the PDSI, which indicates that runoff in arid and semi-arid regions was not generated primarily from precipitation. Instead, fraction of glacierized areas in catchments caused large variations in the observed runoff changes.