bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract

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

AbstractResidual 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.
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

Abstract: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.
Dispersal timing and drought history influence the response of bacterioplankton to drying–rewetting stress
Authors: Székely Anna J , Langenheder Silke 
Published: April 2017

Abstract
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

AbstractThe 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

AbstractIn 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

AbstractReversible 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.
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

AbstractSeveral 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

AbstractThe 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

AbstractThe 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

AbstractSoil 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

AbstractVenoms 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

AbstractCells 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.