bluuebunny/crossref_metadata_2025 huggingface dataset:
STAKEHOLDERS’ PERCEPTIONS OF HEALTH TECHNOLOGY ASSESSMENT IN TURKEY
Authors: Ozturk Kirstin , Karadayı Bilgehan , Şener Olgun
Published: November 2017

Background: In April of 2014, the Turkish Ministry of Health held the First Annual Health Technology Assessment (HTA) Meeting in Antalya.

Objectives: The objectives were to understand the perceptions of stakeholders regarding the current status of HTA and document their recommendations and strategies for promoting systematic use of HTA in Turkey.

Methods: The study was conducted using a qualitative written survey assessing current compliance with the fifteen HTA principles suggested by Drummond et al. (Key principles for the improved conduct of health technology assessments for resource allocation decision. Int J Technol Assess Health Care. 2008;24:244–258) and a qualitative method referred to as the Collective Intelligence Platform®.

Results: A total of 216 stakeholders representing academic, public, and the private health sector attended the annual meeting; 178 completed the survey and 183 participated in the Platform. Quantitative Results: Survey participants reported that, although Turkey does not currently fully comply with any of the fifteen HTA principles, there is some compliance with all of them. The overall average score for all fifteen principles was 3.04. Quantitivate Results: Participants recommended a more transparent, independent, and evidence-based policy decision-making system through better coordination of HTA activities, data aggregation, capacity development, and a national HTA core model and framework.

Conclusions: Platform participants described the current HTA environment as disjointed and lacking in resources and support from policy-making leaders. Despite the persisting challenges, awareness of the strengths and weaknesses of the current system combined with increasing interaction among Turkish stakeholders and the international HTA community can meaningfully contribute to the continued development and promotion of HTA in Turkey.
IMPROVING THE PERFORMANCE OF POLLING MODELS USING FORCED IDLE TIMES
Authors: Aurzada Frank , Schwinn Sebastian
Published: November 2017

We consider polling models in the sense of Takagi [19]. In our case, the feature of the server is that it may be forced to wait idly for new messages at an empty queue instead of switching to the next station. We propose four different wait-and-see strategies that govern these waiting periods. We assume Poisson arrivals for new messages and allow general service and switchover time distributions. The results are formulas for the mean average queueing delay and characterizations of the cases where the wait-and-see strategies yield a lower delay compared with the exhaustive strategy.
A reinterpretation of set differential equations as differential equations in a Banach space
Authors: Rasmussen Martin , Rieger Janosch , Webster Kevin
Published: November 2017

Set differential equations are usually formulated in terms of the Hukuhara differential. As a consequence, the theory of set differential equations is perceived as an independent subject, in which all results are proved within the framework of the Hukuhara calculus. We propose to reformulate set differential equations as ordinary differential equations in a Banach space by identifying the convex and compact subsets of ℝd with their support functions. Using this representation, standard existence and uniqueness theorems for ordinary differential equations can be applied to set differential equations. We provide a geometric interpretation of the main result, and demonstrate that our approach overcomes the heavy restrictions that the use of the Hukuhara differential implies for the nature of a solution.
Mouse oocytes nucleoli rescue embryonic development of porcine enucleolated oocytes
Authors: Morovic Martin , Strejcek Frantisek , Nakagawa Shoma , Deshmukh Rahul S. , Murin Matej , Benc Michal , Fulka Helena , Kyogoku Hirohisa , Pendovski Lazo , Fulka Josef , Laurincik Jozef
Published: November 2017

It is well known that nucleoli of fully grown mammalian oocytes are indispensable for embryonic development. Therefore, the embryos originated from previously enucleolated (ENL) oocytes undergo only one or two cleavages and then their development ceases. In our study the interspecies (mouse/pig) nucleolus transferred embryos (NuTE) were produced and their embryonic development was analyzed by autoradiography, transmission electron microscopy (TEM) and immunofluorescence (C23 and upstream binding factor (UBF)). Our results show that the re-injection of isolated oocyte nucleoli, either from the pig (P + P) or mouse (P + M), into previously enucleolated and subsequently matured porcine oocytes rescues their development after parthenogenetic activation and some of these develop up to the blastocyst stage (P + P, 11.8%; P + M, 13.5%). In nucleolus re-injected 8-cell and blastocyst stage embryos the number of nucleoli labeled with C23 in P + P and P + M groups was lower than in control (non-manipulated) group. UBF was localized in small foci within the nucleoli of blastocysts in control and P + P embryos, however, in P + M embryos the labeling was evenly distributed in the nucleoplasm. The TEM and autoradiographic evaluations showed the formation of functional nucleoli and de novo rRNA synthesis at the 8-cell stage in both, control and P + P group. In the P + M group the formation of comparable nucleoli was delayed. In conclusion, our results indicate that the mouse nucleolus can rescue embryonic development of enucleolated porcine oocytes, but the localization of selected nucleolar proteins, the timing of transcription activation and the formation of the functional nucleoli in NuTE compared with control group show evident aberrations.
Spontaneous ventricular thrombosis in patients with inflammatory bowel disease
Authors: Pak Stella , Linares Juan , Yatsynovich Yan , Cha David , Nye Dexter , Kaminski Diana , Costello Jillian
Published: November 2017

Inflammatory bowel disease is closely associated with an increased risk for thrombotic events. Thrombosis mostly occurs in the extremities, lungs, and liver; but it can also occur in the ventricles of the heart. The primary goal of this article is to increase awareness of the risk for ventricular thrombosis in this patient population among healthcare professionals and, thus, appropriate prompt use of thromboprophylaxis therapy for these patients during acute flare-ups. Early diagnosis and intervention are critical for ventricular thrombosis to prevent systemic embolisation of the thrombus. Concisely, inflammatory bowel disease predisposes to the development of thrombi. A low threshold for the use of imaging studies to detect such thrombi is warranted.
Why Earthquakes Threaten Two Major European Cities: Istanbul and Bucharest
Authors: Houseman Gregory A.
Published: November 2017

Istanbul and Bucharest are major European cities that face a continuing threat of large earthquakes. The geological contexts for these two case studies enable us to understand the nature of the threat and to predict more precisely the consequences of future earthquakes, although we remain unable to predict the time of those events with any precision better than multi-decadal. These two cities face contrasting threats: Istanbul is located on a major geological boundary, the North Anatolian Fault, which separates a westward moving Anatolia from the stable European landmass. Bucharest is located within the stable European continent, but large-scale mass movements in the upper mantle beneath the lithosphere cause relatively frequent large earthquakes that represent a serious threat to the city and surrounding regions.
Exposure and perceptions of marketing for caffeinated energy drinks among young Canadians
Authors: Hammond David , Reid Jessica L
Published: November 2017

Objective

To examine exposure to energy drink marketing among youth and young adults, and test perceptions of energy drink advertisements (ads) regarding target audience age and promoting energy drink use during sports.

Design

A between-group experiment randomly assigned respondents to view one of four energy drink ads (sport-themed or control) and assessed perceptions of the ad. Regression models examined marketing exposure and perceptions.

Setting

Online survey (2014).

Subjects

Canadians aged 12–24 years (n 2040) from a commercial panel.

Results

Overall, 83 % reported ever seeing energy drink ads through at least one channel, including on television (60 %), posters/signs in stores (49 %) and online (44 %). Across experimental conditions, most respondents (70·1 %) thought the ad they viewed targeted people their age or younger, including 42·2 % of those aged 12–14 years. Two sport-themed ads were more likely to be perceived as targeting a younger audience (adjusted OR (95 % CI): ‘X Games’ 36·5 %, 4·16 (3·00, 5·77); ‘snowboard’ 19·2 %, 1·50 (1·06, 2·13)) v. control (13·3 %). Participants were more likely to believe an ad promoted energy drink use during sports if they viewed any sport-themed ad (‘X Games’ 69·9 %, 8·29 (6·24, 11·02); ‘snowboard’ 76·7 %, 11·85 (8·82, 15·92); ‘gym’ 66·8 %, 7·29 (5·52, 9·64)) v. control (22·0 %). Greater reported exposure to energy drink marketing was associated with perceiving study ads as promoting energy drink use during sports.

Conclusions

Energy drink marketing has a high reach among young people. Ads for energy drinks were perceived as targeting youth and promoting use during sports. Such ads may be perceived as making physical performance claims, counter to Canadian regulations.
Differences in the sodium content of bread products in the USA and UK: implications for policy
Authors: Coyne Kasey J , Baldridge Abigail S , Huffman Mark D , Jenner Katharine , Xavier Dagan , Dunford Elizabeth K
Published: November 2017

Objective

Americans consume Na in excess of daily recommendations. Most dietary Na comes from packaged foods, and bread is a major contributor. In the UK, national Na reduction strategies contributed to lower Na levels in packaged foods and lower population Na intake. Similar initiatives are emerging in the USA and require surveillance to assess effectiveness. We aimed to examine Na levels in bread products in the USA and compare levels with similar UK products.

Design

Na data for bread products were obtained from the US Label Insight Open Data Initiative (n 4466) and the FoodSwitch UK database (n 1651). Mean, median and range of Na content, and proportion of products meeting Na targets established by the National Salt Reduction Initiative (NSRI) and the UK Department of Health (DH) were calculated overall, by bread type and by country.

Results

Mean (sd) Na content in bread was 455 (170) mg/100 g in the USA and 406 (179) mg/100 g in the UK. In both countries, savoury bread had the highest mean Na (USA=584 mg/100 g, UK=543 mg/100 g) and fruit bread the lowest mean Na (USA=345 mg/100 g, UK=277 mg/100 g). Na content of US bread products was 12 % higher than in the UK, with 21 % of US bread products and 31 % of UK bread products meeting the NSRI and DH targets, respectively.

Conclusions

US bread products have, on average, 12 % more Na than similar products in the UK. Variation in Na content within product categories, and between countries, suggests the feasibility of manufacturing products with lower Na to lower dietary Na intake.
Spectacles of Sovereignty in Digital Time: ISIS Executions, Visual Rhetoric and Sovereign Power
Authors: Euben Roxanne L.
Published: November 2017

The ISIS videos staging the executions of James Foley and Steven Sotloff are usually understood as devices to deter, recruit, and “sow terror.” Left unanswered are questions about how these videos work; to whom they are addressed; and what about them can so continuously bring new audiences into existence. The evident durability of ISIS despite the imminent defeat of its state, coupled with the political impact of these particular videos, make these questions unusually urgent. Complete answers require analysis of the most understudied aspect of the videos that also happens to be vastly understudied in US political science: the visual mode of the violence. Approaching these videos as visual texts in need of close reading shows that they are, among other things, enactments of “retaliatory humiliation” (defined by Islamists) that perform and produce an inversion of power in two registers. It symbolically converts the public abjection of Foley and Sotloff by the Islamist executioner into an enactment of ISIS’ invincibility and a demonstration of American impotence. It also aims to transpose the roles between the US, symbolically refigured as mass terrorist, failed sovereign, and rogue state, and ISIS, now repositioned as legitimate, invincible sovereign. Such rhetorical practices seek to actually constitute their audiences through the very visual and visceral power of their address. The affective power of this address is then extended and intensified by the temporality that conditions it—what I call digital time. Digital time has rendered increasingly rare ordinary moments of pause between rapid and repetitive cycles of reception and reaction—moments necessary for even a small measure of distance. The result is a sensibility, long in gestation but especially ofthistime, habituated to thinking less and feeling more, to quick response over deliberative action.
Dual-wideband bandpass filter with independently controllable center frequencies and wide stopband
Authors: Xiong Yang , Wang Litian , Pang Doudou , Zhang Wei , Zhang Fan , He Ming , Zhao Xinjie , Zhang Xu
Published: November 2017

In this paper, a dual-wideband bandpass filter (BPF) with independently controllable center frequencies (CFs) and wide stopband suppression is presented using a new quintuple-mode resonator (QMR). By applying the classical odd-/even-mode analysis method, the resonant characteristics of the new QMR have been analyzed. It shows that five modes can be excited, and two of them can be employed to form the lower passband, while the other three modes contribute to the higher passband. For verification, a dual-wideband BPF using the new QMR is designed, fabricated, and tested. Experimental results show that the CFs of the dual-wideband BPF centered at 2.96 GHz and 5.695 GHz with 3 dB fractional bandwidths of 27.7 and 23.4%, respectively. In addition, 20-dB suppression in upper-stopband ranges from 2.23 to 4.04f0, where f0 is the center frequency of the first passband. The measurement results are in good agreement with the prediction results.
Global constitutionalism and constitutional imagination
Authors: ANGELI OLIVIERO
Published: November 2017

There is a difference between the normative reasons for endorsing global constitutionalism and the conditions determining its emergence. This article addresses the latter issue. Specifically, the article claims that global constitutionalism rests on an underexploredshift in constitutional imagination. To account for this claim, the article is structured in several parts. It begins by clarifying the meaning of ‘constitutional imagination’. In so doing it builds on Kant’s concept of imagination (‘Einbildungskraft’) and in its reception by Hannah Arendt. The article then illustrates the significance of constitutional imagination by focusing on two major developments in constitutional thinking. The first development involves the shift away from a narrative reconstruction of constitutional authority; the second points to acosmopolitanisationof constitutional imagination.
Constructivism in cosmopolitan law: Kant’s right to visit
Authors: CORRADETTI CLAUDIO
Published: November 2017

Kant is regarded as one of the most influential cosmopolitan thinkers. Indeed his legacy still influences the contemporary legal and philosophical debate on this issue. But what is the Kantian conception of cosmopolitan law? In which terms does it arise out of his notion of a ‘right to visit’? How does it contribute to the construction of a ‘cosmopolitan constitution’? In this article the view is advanced that Kant was a legal constructivist. The argument assumes also that within Kant’s view of an ‘original community of interaction’, the justification of a cosmopolitan notion of authority allows exercises of freedom under a general scheme of right. Kant’s ‘cosmopolitan constitution’ depends therefore upon such rationale, as well as on the jurisdictional link that the right to visit determines in allowing individuals with the possibility to have a ‘place on earth’.
Civil disobedience as transnational disruption
Authors: SMITH WILLIAM
Published: November 2017

Civil disobedience has been theorised as an informal guardian of the constitution in democratic societies, but such accounts struggle to accommodate protest that has an international or global dimension. This article addresses this issue through offering a theory of civil disobedience as transnational disruption. Civil disobedience is ‘transnational’ insofar as it is an appeal to a national, international or global public that highlights failures to observe moral, political or legal values that are an appropriate source of normative authority in global contexts. Civil disobedience is ‘disruptive’ insofar as it obstructs the routine activities of relevant parties in order to draw attention to the demands of protesters. The core argument is that civil disobedience can uphold normative standards that have been incorporated into a dense network of treaties, conventions and global regulatory frameworks. It can thus make a modest but valuable contribution to the processes through which publics deliberate about the meaning and interpretation of these contested norms.
The Impact of Brexit on the Environment: Exploring the Dynamics of a Complex Relationship
Authors: Hilson Chris
Published: November 2017

The departure of the United Kingdom (UK) from the European Union (EU) (often referred to as ‘Brexit’) is likely to have a significant impact on the environment. In this article I argue against seeing the traffic as all one way. While there was a temptation for the advocates of staying in the EU, in the context of referendum campaigning, to portray the UK as a laggard pressured into positive environmental performance by the EU as leader, the reality is that the UK has also strengthened the EU’s environmental policy in some areas and seen its own weakened in others. Influence in both directions has also varied over time. The article goes on to consider core ‘Leave’ arguments around sovereignty and ‘taking back control’, exploring the implications of these in the specific context of environmental governance. In discussing subsidiarity, it concludes that leaving the EU will not remove the need for pooling some sovereignty over environmental matters at the international level and, in the context of devolution, at the UK level.
The Causes of School Failure in Secondary School Students: Validation of a Psychosocial Model with Structural Equations
Authors: Chacón Fuertes Fernando , Huertas Hurtado Carlos A.
Published: November 2017

The objective of the study was to determine the causal effects of school failure (SF) among secondary school students, belonging to five public schools within the region of Girardota, Colombia, through the validation of a psychosocial model with structural equations. A total of 319 students, 25% more males, enrolled in classes between 6th and 11th year, with an average age of 14 years. Furthermore, 265 parents and 200 teachers were also included in the sample. Participants answered the questions raised in 9 instruments. Of the total number of students, 63.8% were surveyed. The instruments were subjected to a pilot test and to the judgment of experts. In order to reduce the amount of data, exploratory and confirmatory factorial analyses were used. Other techniques of multivariate analysis such as decision trees and linear regressions were also used in order to previously evaluate the relationships between the independent variables (IV) and the dependent variable (DV). Afterwards, theFull SEMwas calculated, yielding a model consisting of 34 variables (10 latent and 24 observable), with the following indexes of goodness of fit: CMIN/DF = 1.146,p= .058, IFI = 0.974, TLI = .970, CFI = .974, RMSEA = .027 and PCLOSE = 0.998. Theoretically, the model confirms the predictive value of the selected variables, with respect to school failure. The results are applicable to both the design of educational policies and the direct intervention in the classroom. In both contexts, strategies can be developed that reduce factors that negatively affect school performance, actively linking students, teachers and parents.
Using airbrushes to pattern reagents for microarrays and paper-fluidic devices
Authors: Cassano Christopher L. , Georgiev Teodor Z. , Fan Z Hugh
Published: November 2017

We report using an airbrush to pattern a number of reagents, including small molecules, proteins, DNA, and conductive microparticles, onto a variety of mechanical substrates such as paper and glass. Airbrushing is more economical and easier to perform than many other patterning methods available (for example, inkjet printing). In this work, we investigated the controllable parameters that affect patterned line width and studied their mechanisms of action, and we provide examples of possible patterns. This airbrushing approach allowed us to pattern lines and dot arrays from hundreds of μm to tens of mm with length scales comparable to those of other patterning methods. Two applications, enzymatic assays and DNA hybridization, were chosen to demonstrate the compatibility of the method with biomolecules. This airbrushing method holds promise in making paper-based platforms less expensive and more accessible.
Erratum: ESRP1 is overexpressed in ovarian cancer and promotes switching from mesenchymal to epithelial phenotype in ovarian cancer cells
Authors: Jeong H M , Han J , Lee S H , Park H-J , Lee H J , Choi J-S , Lee Y M , Choi Y-L , Shin Y K , Kwon M J
Published: November 2017

Correction to: Oncogenesis (2017) 6, e389; doi:10.1038/oncsis.2017.87; Published online 9 October 2017 The legend of Figure 5 was published incorrectly. The correct legend should read as follows: Figure 5. Association between ESRP1 gene expression and OS or PFS in patients with ovarian serous adenocarcinoma.
The North American bullfrog draft genome provides insight into hormonal regulation of long noncoding RNA
Authors: Hammond S. Austin , Warren René L. , Vandervalk Benjamin P. , Kucuk Erdi , Khan Hamza , Gibb Ewan A. , Pandoh Pawan , Kirk Heather , Zhao Yongjun , Jones Martin , Mungall Andrew J. , Coope Robin , Pleasance Stephen , Moore Richard A. , Holt Robert A. , Round Jessica M. , Ohora Sara , Walle Branden V. , Veldhoen Nik , Helbing Caren C. , Birol Inanc
Published: November 2017

Frogs play important ecological roles, and several species are important model organisms for scientific research. The globally distributed Ranidae (true frogs) are the largest frog family, and have substantial evolutionary distance from the model laboratory Xenopus frog species. Unfortunately, there are currently no genomic resources for the former, important group of amphibians. More widely applicable amphibian genomic data is urgently needed as more than two-thirds of known species are currently threatened or are undergoing population declines. We report a 5.8 Gbp (NG50 = 69 kbp) genome assembly of a representative North American bullfrog (Rana [Lithobates] catesbeiana). The genome contains over 22,000 predicted protein-coding genes and 6,223 candidate long noncoding RNAs (lncRNAs). RNA-Seq experiments show thyroid hormone causes widespread transcriptional change among protein-coding and putative lncRNA genes. This initial bullfrog draft genome will serve as a key resource with broad utility including amphibian research, developmental biology, and environmental research.
Anaerobic microsites have an unaccounted role in soil carbon stabilization
Authors: Keiluweit Marco , Wanzek Tom , Kleber Markus , Nico Peter , Fendorf Scott
Published: November 2017

Soils represent the largest carbon reservoir within terrestrial ecosystems. The mechanisms controlling the amount of carbon stored and its feedback to the climate system, however, remain poorly resolved. Global carbon models assume that carbon cycling in upland soils is entirely driven by aerobic respiration; the impact of anaerobic microsites prevalent even within well-drained soils is missed within this conception. Here, we show that anaerobic microsites are important regulators of soil carbon persistence, shifting microbial metabolism to less efficient anaerobic respiration, and selectively protecting otherwise bioavailable, reduced organic compounds such as lipids and waxes from decomposition. Further, shifting from anaerobic to aerobic conditions leads to a 10-fold increase in volume-specific mineralization rate, illustrating the sensitivity of anaerobically protected carbon to disturbance. The vulnerability of anaerobically protected carbon to future climate or land use change thus constitutes a yet unrecognized soil carbon–climate feedback that should be incorporated into terrestrial ecosystem models.
Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma
Authors: Natsuizaka Mitsuteru , Whelan Kelly A. , Kagawa Shingo , Tanaka Koji , Giroux Veronique , Chandramouleeswaran Prasanna M. , Long Apple , Sahu Varun , Darling Douglas S. , Que Jianwen , Yang Yizeng , Katz Jonathan P. , Wileyto E. Paul , Basu Devraj , Kita Yoshiaki , Natsugoe Shoji , Naganuma Seiji , Klein-Szanto Andres J. , Diehl J. Alan , Bass Adam J. , Wong Kwok-Kin , Rustgi Anil K. , Nakagawa Hiroshi
Published: November 2017

Notch1 transactivates Notch3 to drive terminal differentiation in stratified squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be stochastically activated to promote carcinogenesis in murine models of SCC. Activated form of Notch1 promotes xenograft tumor growth when expressed ectopically. Here, we demonstrate that Notch1 activation and epithelial–mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in concert with transforming growth factor (TGF)-β present in the tumor microenvironment. We find that TGFβ activates the transcription factor ZEB1 to repress Notch3, thereby limiting terminal differentiation. Concurrently, TGFβ drives Notch1-mediated EMT to generate tumor initiating cells characterized by high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC cells at the invasive tumor front and predicts for poor prognosis of esophageal SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC.
Antagonistic bacteria disrupt calcium homeostasis and immobilize algal cells
Authors: Aiyar Prasad , Schaeme Daniel , García-Altares María , Carrasco Flores David , Dathe Hannes , Hertweck Christian , Sasso Severin , Mittag Maria
Published: November 2017

Photosynthetic unicellular organisms, known as microalgae, are key contributors to carbon fixation on Earth. Their biotic interactions with other microbes shape aquatic microbial communities and influence the global photosynthetic capacity. So far, limited information is available on molecular factors that govern these interactions. We show that the bacterium Pseudomonas protegens strongly inhibits the growth and alters the morphology of the biflagellated green alga Chlamydomonas reinhardtii. This antagonistic effect is decreased in a bacterial mutant lacking orfamides, demonstrating that these secreted cyclic lipopeptides play an important role in the algal–bacterial interaction. Using an aequorin Ca2+-reporter assay, we show that orfamide A triggers an increase in cytosolic Ca2+ in C. reinhardtii and causes deflagellation of algal cells. These effects of orfamide A, which are specific to the algal class of Chlorophyceae and appear to target a Ca2+ channel in the plasma membrane, represent a novel biological activity for cyclic lipopeptides.
GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl−-sensitive WNK1 kinase
Authors: Heubl Martin , Zhang Jinwei , Pressey Jessica C. , Al Awabdh Sana , Renner Marianne , Gomez-Castro Ferran , Moutkine Imane , Eugène Emmanuel , Russeau Marion , Kahle Kristopher T. , Poncer Jean Christophe , Lévi Sabine
Published: November 2017

The K+–Cl−co-transporter KCC2 (SLC12A5) tunes the efficacy of GABAAreceptor-mediated transmission by regulating the intraneuronal chloride concentration [Cl−]i. KCC2 undergoes activity-dependent regulation in both physiological and pathological conditions. The regulation of KCC2 by synaptic excitation is well documented; however, whether the transporter is regulated by synaptic inhibition is unknown. Here we report a mechanism of KCC2 regulation by GABAAreceptor (GABAAR)-mediated transmission in mature hippocampal neurons. Enhancing GABAAR-mediated inhibition confines KCC2 to the plasma membrane, while antagonizing inhibition reduces KCC2 surface expression by increasing the lateral diffusion and endocytosis of the transporter. This mechanism utilizes Cl−as an intracellular secondary messenger and is dependent on phosphorylation of KCC2 at threonines 906 and 1007 by the Cl−-sensing kinase WNK1. We propose this mechanism contributes to the homeostasis of synaptic inhibition by rapidly adjusting neuronal [Cl−]ito GABAAR activity.
Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy
Authors: Chen Wei , Tian Rui , Xu Can , Yung Bryant C. , Wang Guohao , Liu Yijing , Ni Qianqian , Zhang Fuwu , Zhou Zijian , Wang Jingjing , Niu Gang , Ma Ying , Fu Liwu , Chen Xiaoyuan
Published: November 2017

The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli. In this manner, the system enables glucose-responsive and closed-loop release to significantly improve Ex4 therapeutic performance. Moreover, integration of mineralized particles can enhance the mechanical strength of alginate-based MN by crosslinking to facilitate skin penetration, thus supporting painless and non-invasive transdermal administration. We believe this smart glucose-responsive Ex4 delivery holds great promise for type 2 diabetes therapy by providing safe, long-term, and on-demand Ex4 therapy.
Benchmarking organic mixed conductors for transistors
Authors: Inal Sahika , Malliaras George G. , Rivnay Jonathan
Published: November 2017

Organic mixed conductors have garnered significant attention in applications from bioelectronics to energy storage/generation. Their implementation in organic transistors has led to enhanced biosensing, neuromorphic function, and specialized circuits. While a narrow class of conducting polymers continues to excel in these new applications, materials design efforts have accelerated as researchers target new functionality, processability, and improved performance/stability. Materials for organic electrochemical transistors (OECTs) require both efficient electronic transport and facile ion injection in order to sustain high capacity. In this work, we show that the product of the electronic mobility and volumetric charge storage capacity (µC*) is the materials/system figure of merit; we use this framework to benchmark and compare the steady-state OECT performance of ten previously reported materials. This product can be independently verified and decoupled to guide materials design and processing. OECTs can therefore be used as a tool for understanding and designing new organic mixed conductors.
Feature-based learning improves adaptability without compromising precision
Authors: Farashahi Shiva , Rowe Katherine , Aslami Zohra , Lee Daeyeol , Soltani Alireza
Published: November 2017

Learning from reward feedback is essential for survival but can become extremely challenging with myriad choice options. Here, we propose that learning reward values of individual features can provide a heuristic for estimating reward values of choice options in dynamic, multi-dimensional environments. We hypothesize that this feature-based learning occurs not just because it can reduce dimensionality, but more importantly because it can increase adaptability without compromising precision of learning. We experimentally test this hypothesis and find that in dynamic environments, human subjects adopt feature-based learning even when this approach does not reduce dimensionality. Even in static, low-dimensional environments, subjects initially adopt feature-based learning and gradually switch to learning reward values of individual options, depending on how accurately objects’ values can be predicted by combining feature values. Our computational models reproduce these results and highlight the importance of neurons coding feature values for parallel learning of values for features and objects.
Reconciling grain growth and shear-coupled grain boundary migration
Authors: Thomas Spencer L. , Chen Kongtao , Han Jian , Purohit Prashant K. , Srolovitz David J.
Published: November 2017

Conventional models for grain growth are based on the assumption that grain boundary (GB) velocity is proportional to GB mean curvature. We demonstrate via a series of molecular dynamics (MD) simulations that such a model is inadequate and that many physical phenomena occur during grain boundary migration for which this simple model is silent. We present a series of MD simulations designed to unravel GB migration phenomena and set it in a GB migration context that accounts for competing migration mechanisms, elasticity, temperature, and grain boundary crystallography. The resultant formulation is quantitative and validated through a series of atomistic simulations. The implications of this model for microstructural evolution is described. We show that consideration of GB migration mechanisms invites considerable complexity even under ideal conditions. However, that complexity also grants these systems enormous flexibility, and that flexibility is key to the decades-long success of conventional grain growth theories.
Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions
Authors: Cattoni Diego I. , Cardozo Gizzi Andrés M. , Georgieva Mariya , Di Stefano Marco , Valeri Alessandro , Chamousset Delphine , Houbron Christophe , Déjardin Stephanie , Fiche Jean-Bernard , González Inma , Chang Jia-Ming , Sexton Thomas , Marti-Renom Marc A. , Bantignies Frédéric , Cavalli Giacomo , Nollmann Marcelo
Published: November 2017

At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine high-content super-resolution microscopies with state-of-the-art DNA-labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We find that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type. Critically, despite this large heterogeneity, we are able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs are to a large extent defined by genomic distance, higher-order chromosome architecture, and epigenetic identity. We propose that TADs and compartments are organized by multiple, small-frequency, yet specific interactions that are regulated by epigenetics and transcriptional state.
A galactic microquasar mimicking winged radio galaxies
Authors: Martí Josep , Luque-Escamilla Pedro L. , Bosch-Ramon Valentí , Paredes Josep M.
Published: November 2017

A subclass of extragalactic radio sources known as winged radio galaxies has puzzled astronomers for many years. The wing features are detected at radio wavelengths as low-surface-brightness radio lobes that are clearly misaligned with respect to the main lobe axis. Different models compete to account for these peculiar structures. Here, we report observational evidence that the parsec-scale radio jets in the Galactic microquasar GRS 1758-258 give rise to a Z-shaped radio emission strongly reminiscent of the X and Z-shaped morphologies found in winged radio galaxies. This is the first time that such extended emission features are observed in a microquasar, providing a new analogy for its extragalactic relatives. From our observations, we can clearly favour the hydrodynamic backflow interpretation against other possible wing formation scenarios. Assuming that physical processes are similar, we can extrapolate this conclusion and suggest that this mechanism could also be at work in many extragalactic cases.
Simultaneous fabrication of line and dot dual nanopatterns using miktoarm block copolymer with photocleavable linker
Authors: Choi Chungryong , Park Jichoel , Vincent Joseph Kanniyambatti L. , Lee Jaeyong , Ahn Seonghyeon , Kwak Jongheon , Lee Kyu Seong , Kim Jin Kon
Published: November 2017

Block copolymers with various nanodomains, such as spheres, cylinders, and lamellae, have received attention for their applicability to nanolithography. However, those microdomains are determined by the volume fraction of one block. Meanwhile, nanopatterns with multiple shapes are required for the next-generation nanolithography. Although various methods have been reported to achieve dual nanopatterns, all the methods need sophisticated processes using E-beam. Here, we synthesized a miktoarm block copolymer capable of cleavage of one block by ultraviolet. Original cylindrical nanodomains of synthesized block copolymer were successfully transformed to lamellar nanodomains due to the change of molecular architecture by ultraviolet. We fabricated dual nanopatterns consisting of dots and lines at desired regions on a single substrate. We also prepared dual nanopatterns utilizing another phase transformation from spheres to cylinders in a block copolymer with higher interaction parameter. Since our concept has versatility to any block copolymer, it could be employed as next-generation nanolithography.
The rumen microbiome: an underexplored resource for novel antimicrobial discovery
Authors: Oyama Linda B. , Girdwood Susan E. , Cookson Alan R. , Fernandez-Fuentes Narcis , Privé Florence , Vallin Hannah E. , Wilkinson Toby J. , Golyshin Peter N. , Golyshina Olga V. , Mikut Ralf , Hilpert Kai , Richards Jennifer , Wootton Mandy , Edwards Joan E. , Maresca Marc , Perrier Josette , Lundy Fionnuala T. , Luo Yu , Zhou Mei , Hess Matthias , Mantovani Hilario C. , Creevey Christopher J. , Huws Sharon A.
Published: November 2017

Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.
Sorption Hysteresis of Light Hydrocarbons and Carbon Dioxide in Shale and Kerogen
Authors: Zhao Huangjing , Lai Zhiping , Firoozabadi Abbas
Published: November 2017

We present adsorption and desorption isotherms of methane, ethane, propane, n-butane and iso-butane as well as carbon dioxide for two shales and isolated kerogens determined by a gravimetric method. The sorption measurements of two shales were performed at three different temperatures, 308.15, 323.15, and 338.15 K. For the isolated kerogens, the measurements were conducted at 338.15 K. Methane and ethane sorption isotherms were measured to 35 bar. Carbon dioxide sorption isotherms were studied to 30 bar. Due to the low vapor pressure at room temperature, the sorption isotherms of propane, n-butane and iso-butane were measured to 8, 2, and 2 bar, respectively. The adsorptions of propane, n-butane, and iso-butane were much higher than methane at the highest pressures where the measurements were conducted. The adsorption of n-butane was 10 times higher than methane by mole at 2 bar, followed by iso-butane and propane. Our data show significant adsorption hysteresis in ethane, propane, n-butane and iso-butane. The most pronounced hysteresis was found in n-butane and iso-butane. Significant hysteresis is attributed to the reversible structural changes of kerogens. Dissolution of adsorbates into organic matter may also affect the hysteresis. This is the first report of propane and butane sorption isotherms in shales.
Acupuncture analgesia involves modulation of pain-induced gamma oscillations and cortical network connectivity
Authors: Hauck Michael , Schröder Sven , Meyer-Hamme Gesa , Lorenz Jürgen , Friedrichs Sunja , Nolte Guido , Gerloff Christian , Engel Andreas K.
Published: November 2017

Recent studies support the view that cortical sensory, limbic and executive networks and the autonomic nervous system might interact in distinct manners under the influence of acupuncture to modulate pain. We performed a double-blind crossover design study to investigate subjective ratings, EEG and ECG following experimental laser pain under the influence of sham and verum acupuncture in 26 healthy volunteers. We analyzed neuronal oscillations and inter-regional coherence in the gamma band of 128-channel-EEG recordings as well as heart rate variability (HRV) on two experimental days. Pain ratings and pain-induced gamma oscillations together with vagally-mediated power in the high-frequency bandwidth (vmHF) of HRV decreased significantly stronger during verum than sham acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC), mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions of pain ratings and vmHF-power were significantly correlated with increase of connectivity between the insula and MCC. In contrast, connectivity between left and right PFC and between PFC and insula correlated positively with vmHF-power without a relationship to acupuncture analgesia. Overall, these findings highlight the influence of the insula in integrating activity in limbic-saliency networks with vagally mediated homeostatic control to mediate antinociception under the influence of acupuncture.
Similarities between acylcarnitine profiles in large for gestational age newborns and obesity
Authors: Sánchez-Pintos Paula , de Castro Maria-Jose , Roca Iria , Rite Segundo , López Miguel , Couce Maria-Luz
Published: November 2017

Large for gestational age (LGA) newborns have an increased risk of obesity, insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese children and adults are characterized by increased levels of C3, C5, and certain medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also increased in insulin-resistant states. In this 1-year observational study of 2514 newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018 appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine profiles in LGA newborns with profiles described for obese individuals. Acylcarnitine analysis was performed by tandem mass spectrometry on dried-blood spots collected on day 3 of life. LGA newborns had higher levels of total short-chain acylcarnitines (p < 0.001), C2 (p < 0.01) and C3 (p < 0.001) acylcarnitines, and all C12, C14, and C16 acylcarnitines except C12:1. They also had a higher tendency towards carnitine insufficiency (p < 0.05) and carnitine deficiency (p < 0.001). No significant differences were observed between LGA newborns born to mothers with or without a history of gestational diabetes. This novel study describes a postnatal acylcarnitine profile in LGA with higher levels of C2, C3, total acylcarnitines, and total short-chain acylcarnitines that is characteristic of childhood and adult obesity and linked to an unhealthy metabolic phenotype.
Computational derivation of a molecular framework for hair follicle biology from disease genes
Authors: Severin Rachel K. , Li Xinwei , Qian Kun , Mueller Andreas C. , Petukhova Lynn
Published: November 2017

Knowledge about genetic drivers of disease increases the efficiency of interpreting patient DNA sequence and helps to identify and prioritize biological points of intervention. Discoveries of genes with single mutations exerting substantial phenotypic impact reliably provide new biological insight, although such approaches tend to generate knowledge that is disjointed from the complexity of biological systems governed by elaborate networks. Here we sought to facilitate diagnostic sequencing for hair disorders and assess the underlying biology by compiling an archive of 684 genes discovered in studies of monogenic disorders and identifying molecular annotations enriched by them. To demonstrate utility for this dataset, we performed two data driven analyses. First, we extracted and analyzed data implicating enriched signaling pathways and identified previously unrecognized contributions from Hippo signaling. Second, we performed hierarchical clustering on the entire dataset to investigate the underlying causal structure of hair disorders. We identified 35 gene clusters representing genetically derived biological modules that provide a foundation for the development of a new disease taxonomy grounded in biology, rather than clinical presentations alone. This Resource will be useful for diagnostic sequencing in patients with diseases affecting the hair follicle, improved characterization of hair follicle biology, and methods development in precision medicine.
Wind-generated Electricity in China: Decreasing Potential, Inter-annual Variability and Association with Changing Climate
Authors: Sherman Peter , Chen Xinyu , McElroy Michael B.
Published: November 2017

China hosts the world’s largest market for wind-generated electricity. The financial return and carbon reduction benefits from wind power are sensitive to changing wind resources. Wind data derived from an assimilated meteorological database are used here to estimate what the wind generated electricity in China would have been on an hourly basis over the period 1979 to 2015 at a geographical resolution of approximately 50 km × 50 km. The analysis indicates a secular decrease in generating potential over this interval, with the largest declines observed for western Inner Mongolia (15 ± 7%) and the northern part of Gansu (17 ± 8%), two leading wind investment areas. The decrease is associated with long-term warming in the vicinity of the Siberian High (SH), correlated also with the observed secular increase in global average surface temperatures. The long-term trend is modulated by variability relating to the Pacific Decadal Oscillation (PDO) and the Arctic Oscillation (AO). A linear regression model incorporating indices for the PDO and AO, as well as the declining trend, can account for the interannual variability of wind power, suggesting that advances in long-term forecasting could be exploited to markedly improve management of future energy systems.