bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiofrequency thermotherapy in the treatment of tongue base lymphoid hyperplasia: case report
Authors: Nicoli T K , Gupta S , Kotecha B
Published: March 2015

Objective:

This paper describes a case where a patient diagnosed with tongue base lymphoid hyperplasia was successfully treated with radiofrequency excision and interstitial radiofrequency-induced thermotherapy.

Case report:

A 53-year-old female presented with globus sensation, mild dysphagia, nocturnal breathing problems and ‘hot potato voice’ dysphonia. On flexible nasendoscopy, a visible tongue mass was seen to obstruct the posterior oropharynx. On magnetic resonance imaging scans, this mass looked suspicious of lymphoma, but on histology was confirmed to be benign reactive lymphoid hyperplasia. Sleep study findings indicated moderate obstructive sleep apnoea, with an apnoea–hypopnoea index of 18.1 events per hour. She was treated with radiofrequency-induced thermotherapy on three separate occasions.

Results:

A post-operative sleep study showed a dramatic improvement in the patient's apnoea–hypopnoea index (3.8 events per hour). This correlated well with the improvement in her sleep quality and reduction of snoring. Over the follow-up period, there has been sustained resolution of dyspnoea, with almost total restoration of voice quality.
Complementary control for robots with actuator redundancy: an underwater vehicle application
Authors: Indiveri Giovanni , Malerba Alessandro
Published: March 2015

Complementary filtering is a frequency based method used to design data processing algorithms exploiting signals with complementary spectra. The technique is mostly used in sensor fusion architectures, but it may also be effective in the design of state estimators. In spite of its potential in several areas of robotics, the complementary filtering paradigm is poorly used as compared to alternative time domain methods. The first part of the paper aims at reviewing the basics of complementary filtering in sensor data processing and linear systems state estimation. The second part of the paper describes how to exploit the main ideas of complementary filtering to design a depth controller for an actuator redundant autonomous underwater vehicle (AUV). Unlike with alternative state space methods commonly used to address the design of control solutions for actuator redundant systems, the proposed approach allows to fully exploit the knowledge of frequency characteristics of actuators. Simulation results are reported to demonstrate the effectiveness of the proposed solution.
EUnetHTA INFORMATION MANAGEMENT SYSTEM: DEVELOPMENT AND LESSONS LEARNED
Authors: Chalon Patrice X. , Kraemer Peter
Published: March 2015

Objectives: The aim of this study was to describe the techniques used in achieving consensus on common standards to be implemented in the EUnetHTA Information Management System (IMS); and to describe how interoperability between tools was explored.

Methods: Three face to face meetings were organized to identify and agree on common standards to the development of online tools. Two tools were created to demonstrate the added value of implementing interoperability standards at local levels. Developers of tools outside EUnetHTA were identified and contacted.

Results: Four common standards have been agreed on by consensus; and consequently all EUnetHTA tools have been modified or designed accordingly. RDF Site Summary (RSS) has demonstrated a good potential to support rapid dissemination of HTA information. Contacts outside EUnetHTA resulted in direct collaboration (HTA glossary, HTAi Vortal), evaluation of options for interoperability between tools (CRD HTA database) or a formal framework to prepare cooperation on concrete projects (INAHTA projects database).

Conclusions: While being entitled a project on IT infrastructure, the work program was also about people. When having to agree on complex topics, fostering a cohesive group dynamic and hosting face to face meetings brings added value and enhances understanding between partners. The adoption of widespread standards enhanced the homogeneity of the EUnetHTA tools and should thus contribute to their wider use, therefore, to the general objective of EUnetHTA. The initiatives on interoperability of systems need to be developed further to support a general interoperable information system that could benefit the whole HTA community.
SUCCESS FACTORS FOR INTERNATIONAL HTA PROJECTS: EVALUATING EUnetHTA JOINT ACTION AS AN EXEMPLAR
Authors: Guegan Eleanor Woodford , Cook Andrew
Published: March 2015

Objectives: Evaluation is essential for the management of international projects or networks in health technology assessment (HTA). It extends beyond the normal process of project management by incorporating qualitative dimensions and provides information about a project's effectiveness and achievements. This article aimed to identify the factors that are important for the success of international HTA projects. The European network for Health Technology Assessment Joint Action (EUnetHTA JA) is presented as an exemplar.

Methods: Methods for the evaluation of international HTA projects include interviews, focus groups, questionnaires, observations and documentary review, and the key points of these approaches have been summarized. The impact and effectiveness of the EUnetHTA JA was evaluated by questionnaires of project participants and external stakeholders, and by documentary review.

Results: The response rate for the three annual questionnaires sent to project participants ranged from 86 percent to 88 percent and for external stakeholders ranged from 65 percent to 88 percent. Key factors for project success included production of deliverables according to the workplan, achievement of objectives, added value generated, effective communication, involvement of external stakeholders, workstream management and progress from the preceding EUnetHTA 2006–2008 project.

Conclusions: The experience of this project can inform the evaluation of future international HTA collaborations, such as the EUnetHTA 2nd Joint Action and HTAsiaLink. A high response rate was achieved to the self-completion questionnaires and the strategy followed is recommended for evaluation of international HTA projects. Future assessments of international HTA projects should strive to measure outcomes and impact, not just outputs and process.
IS THE PLANNED AND ONGOING PROJECT (POP) DATABASE A SUITABLE TOOL TO REDUCE DUPLICATION IN THE PROCESS OF ASSESSING NEW HEALTH TECHNOLOGIES IN THE EUROPEAN UNION? PRELIMINARY EXPERIENCE IN THE CONTEXT OF THE EUNETHTA JOINT ACTION PROJECT FRAMEWORK (2010–2012)
Authors: Vondeling Hindrik , Sandvei Marianne
Published: March 2015

Objectives: The European Network for Health Technology Assessment (EUnetHTA) Joint Action Project Framework, 2010–12, Work Package 7B (WP 7B), was aimed at facilitating collaboration between HTA agencies to avoid duplication of assessment efforts. A major task of WP 7B was to collect information on planned and ongoing (POP) projects by EUnetHTA agencies and to incorporate this information in a POP Database. We analyzed whether the Database served its intended purpose.

Methods: A survey was sent to all fifty-seven EUnetHTA partners, complemented by telephone interviews with the Ludwig Boltzmann Institute of HTA in Austria (lead institution). Furthermore, detailed documentation on the activities of the POP Database was provided to the research team at CAST (University of Southern Denmark) by the lead institution.

Results: Forty-two of fifty-seven agencies (74 percent) responded to the survey. Eleven collaborations initiated by agencies themselves were reported. The scope of these collaborative activities was usually limited to information exchange on for example literature search protocols. A slight reduction of duplication of effort was documented. In addition, twelve collaborations at the full report level were initiated by the lead institution.

Conclusion: While the POP Database has the potential to reduce duplication of effort, this has not been realized during the 3-year period of the EUnetHTA Joint Action Project Framework, 2010–12. Further evidence needs to be gathered to determine whether the POP Database is effective and whether the benefits outweigh the resources required to maintain it.
Expectations and the Limits of Legal Validity
Authors: FORCEHIMES ANDREW T.
Published: March 2015

Drawing on the work of Jeremy Bentham, we can forward a parity thesis concerning formal and substantive legal invalidity. Formal and substantive invalidity are, according to this thesis, traceable to the same source, namely, the sovereign's inability to adjust expectations to motivate obedience. The parity thesis, if defensible, has great appeal for positivists. Explaining why contradictory or contrary mandates yield invalidity is unproblematic. But providing an account of content-based invalidity invites the collapse of the separation between what the law is and what the law ought to be. Grounding formal and substantive invalidity in a unified source – the sovereign's inability to adjust expectations to motivate obedience – allows us to avoid bringing in any additional apparatus that might compromise this separation. This essay fleshes out and defends the parity thesis.
A New Counterexample to Prioritarianism
Authors: ORD TOBY
Published: March 2015

Prioritarianism is the moral view that a fixed improvement in someone's well-being matters more the worse off they are. Its supporters argue that it best captures our intuitions about unequal distributions of well-being. I show that prioritarianism sometimes recommends acts that will make things more unequal while simultaneously lowering the total well-being and making things worse for everyone ex ante. Intuitively, there is little to recommend such acts and I take this to be a serious counterexample for prioritarianism.
Interface closure in the root region of steady deep-cellular growth in directional solidification
Authors: XU J.-J. , CHEN Y.-Q.
Published: March 2015

The present paper investigates the mechanism of interface closure in the root region of the solutions for steady deep-cellular growth. This phenomenon is determined by a transcendentally small factor beyond all orders. It is found that the root region comprises three inner-inner regions; the inner system in the root region has a simple turning point, whose presence generates the so-called trapped-waves mechanism, which is responsible for the interface closure at the bottom of root. The quantization condition derived from the trapped-waves mechanism yields the eigenvalue that determines the location of interface closure and its dependence on the interfacial energy and other physical parameters.
Homogenization of a compressible cavitation model
Authors: FABRICIUS JOHN , TSANDZANA AFONSO , WALL PETER
Published: March 2015

We develop a mathematical model in hydrodynamic lubrication that takes into account three phenomena: cavitation, surface roughness and compressibility of the fluid. Like the classical Reynolds equation, the model is mass preserving. We compute the homogenized coefficients in the case of unidirectional roughness. A one-dimensional problem is also solved explicitly.
The effect of water stress on the temperature range for germination ofOrobanche aegyptiacaseeds
Authors: Kebreab Ermias , Murdoch Alistair J.
Published: March 2015

Non-dormant seeds ofOrobanche aegyptiacawere incubated at water potentials of 0 to –1.33 MPa and at constant temperatures from 5 to 29°C. Effects of water potential and temperature on final germination were modelled. In general, germination increased with increased temperature from 5 to 20°C and decreased above 26°C. Maximum germination occurred at 20–26°C and 0 MPa. Germination was reduced as the water potential decreased. Water potential also affected the temperature range over which high germination was observed; at 0 MPa high germination occurred over 9° (17–26°C) compared with 3° at -1.25 MPa (17–20°C). The optimum germination temperature also tended to decrease with a decrease in water potential. Final germination could be accounted for by seed-to-seed variation in the population assuming that each seed had a minimum temperature for germination and a maximum temperature above which it would not germinate. Seed-to-seed variation in these characteristics was assumed to be normally distributed, and it was further assumed that the two characteristics were independent. Effects of water potential on these temperature requirements were quantified, and the resulting empirical model accounted for final germination with reasonable accuracy (R2= 0.96).
Mass Gathering Medicine: A Review
Authors: De Lorenzo Robert A.
Published: March 2015

The provision for emergency medical care for spectators and participants at large events is a growing area of interest. This article describes the definition and characteristics of medical care at mass gatherings. The literature is reviewed with regard to the planning, organization, personnel, and staffing required at these events. The equipment and transportation assets needed are also discussed. Disaster and mass casualty planning implications also are described.
Did Hamilton, Jefferson, and Madison “Cause” the U.S. Government Shutdown? The Institutional Path from an Eighteenth Century Republic to a Twenty-first Century Democracy
Authors: Aldrich John H.
Published: March 2015

This address asks how we got to today’s politics in America; a politics of polarized political parties engaged in close political competition in a system of checks and balances. The result has often been divided control of government and an apparent inability to address major political problems. This address develops the historical foundation for these characteristics. Historically, the Founding period set the stage of separated powers and the first party system. America developed a market economy, a middle class, and a mass-based set of parties in the Antebellum period. Through the Progressive era, nation-wide reforms led to a more democratic but increasingly candidate-centered politics in the North, and the establishment of Jim Crow politics in the South. The post-War period saw the full development of candidate-centered elections. While the breakup of Jim Crow due to the Civil Rights and Voting Rights Acts in the mid-1960s ended Jim Crow and made possible a competitive party system in the South, the later was delayed until the full implementation of the Republican’s “southern strategy” in 1980 and beyond. This set in motion the partisan polarization of today, to combine with separated powers to create what many refer to as the “current” political “dysfunction.”
Seeing Like an Autocrat: Liberal Social Engineering in an Illiberal State
Authors: Jones Calvert W.
Published: March 2015

Recent studies of autocratic liberalization adopt a rationalist approach in which autocrats’ motives and styles of reasoning are imputed or deduced. By contrast, I investigate these empirically. I focus on liberal social engineering in the Persian Gulf, where authoritarian state efforts to shape citizen hearts and minds conform incongruously to liberal ideals of character. To explain this important but under-studied variant on autocratic liberalization, I present evidence from rare palace ethnography in the United Arab Emirates, including analysis of the jokes and stories ruling elites tell behind closed doors and regular interviews with a ruling monarch. I find that autocrats’ deeply personal experiences in the West as young men and women supplied them with stylized ideas about how modern, productive peoples ought to act and how their own cultures underperform. The evidence also reveals that such experiences can influence autocrats, even years later, leading them to trust in Western-style liberal social engineering as the way forward, despite the risks. Ethnographic findings challenge the contemporary scholarly stereotype of the autocrat as a super-rational being narrowly focused on political survival, illustrating how memory and emotion can also serve as important influences over reasoning and can drive liberal change.
Corrupting the Cyber-Commons: Social Media as a Tool of Autocratic Stability
Authors: Gunitsky Seva
Published: March 2015

Non-democratic regimes have increasingly moved beyond merely suppressing online discourse, and are shifting toward proactively subverting and co-opting social media for their own purposes. Namely, social media is increasingly being used to undermine the opposition, to shape the contours of public discussion, and to cheaply gather information about falsified public preferences. Social media is thus becoming not merely an obstacle to autocratic rule but another potential tool of regime durability. I lay out four mechanisms that link social media co-optation to autocratic resilience: 1) counter-mobilization, 2) discourse framing, 3) preference divulgence, and 4) elite coordination. I then detail the recent use of these tactics in mixed and autocratic regimes, with a particular focus on Russia, China, and the Middle East. This rapid evolution of government social media strategies has critical consequences for the future of electoral democracy and state-society relations.
On the Genetic and Environmental Correlations between Trait Emotional Intelligence and Vocational Interest Factors
Authors: Schermer Julie Aitken , Petrides Konstantinos V. , Vernon Philip A.
Published: March 2015

The phenotypic (observed), genetic, and environmental correlations were examined in a sample of adult twins between the four factors and global score of the trait emotional intelligence questionnaire (TEIQue) and the seven vocational interest factors of the Jackson Career Explorer (JCE). Multiple significant correlations were found involving the work style vocational interest factor (consisting of job security, stamina, accountability, planfulness, and interpersonal confidence) and the social vocational interest factor (which included interests in the social sciences, personal services, teaching, social services, and elementary education), both of which correlated significantly with all of the TEIQue variables (well-being, self-control, emotionality, sociability, and global trait EI). Following bivariate genetic analyses, most of the significant phenotypic correlations were found to also have significant genetic correlations as well as significant non-shared (unique) environmental correlations.
Was hilft bei Zwängen? Wirkfaktoren der multimodalen stationären Behandlung von Zwangsstörungen aus Betroffenensicht
Authors: Külz Anne Katrin , Czernek Anne , Hahn Fabian , Landmann Sarah , Hertenstein Elisabeth , Voderholzer Ulrich
Published: March 2015

Während die Effektivität störungsspezifischer, multimodaler stationärer Verhaltenstherapie mit Exposition gut belegt ist, wurde bislang noch nicht systematisch untersucht, wie dieses Verfahren von Patienten mit Zwangserkrankung selbst erlebt und bezüglich seiner Wirksamkeit eingeschätzt wird. Die vorliegende Untersuchung widmete sich der Frage, welche Behandlungselemente von Patientenseite als wichtigste Bausteine betrachtet werden. Insbesondere interessierte das Ausmaß der erlebten Belastung durch Exposition im Verhältnis zu ihrem Nutzen sowie die Einschätzung der therapeutischen Beziehung. 124 stationär behandelte Patienten mit Zwangsstörung gaben mit Hilfe eines anonymisierten Fragebogens Auskunft über die Effektivität der stationären Behandlungsbausteine sowie der Elemente im Rahmen des einzelpsychotherapeutischen Prozesses. Die Ergebnisse zeigen, dass Einzelpsychotherapie und Medikamente aus Patientensicht ca. ein Drittel des Behandlungserfolges ausmachen. Innerhalb der Einzelpsychotherapie wird Expositionsbehandlung als wichtigstes Element erlebt, wobei der subjektive Nutzen gegenüber der wahrgenommenen Belastung überwiegt. Die Resultate verdeutlichen den Wert eines multimodalen Behandlungskonzeptes und ermutigen zur Durchführung von Exposition in Begleitung und Eigenmanagement.
MicroRNA-146a regulates ICOS–ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres
Authors: Pratama Alvin , Srivastava Monika , Williams Naomi J. , Papa Ilenia , Lee Sau K. , Dinh Xuyen T. , Hutloff Andreas , Jordan Margaret A. , Zhao Jimmy L. , Casellas Rafael , Athanasopoulos Vicki , Vinuesa Carola G.
Published: March 2015

Tight control of T follicular helper (Tfh) cells is required for optimal maturation of the germinal centre (GC) response. The molecular mechanisms controlling Tfh-cell differentiation remain incompletely understood. Here we show that microRNA-146a (miR-146a) is highly expressed in Tfh cells and peak miR-146a expression marks the decline of the Tfh response after immunization. Loss of miR-146a causes cell-intrinsic accumulation of Tfh and GC B cells. MiR-146a represses several Tfh-cell-expressed messenger RNAs, and of these, ICOS is the most strongly cell autonomously upregulated target in miR-146a-deficient T cells. In addition, miR-146a deficiency leads to increased ICOSL expression on GC B cells and antigen-presenting cells. Partial blockade of ICOS signalling, either by injections of low dose of ICOSL blocking antibody or by halving the gene dose of Icos in miR-146a-deficient T cells, prevents the Tfh and GC B-cell accumulation. Collectively, miR-146a emerges as a post-transcriptional brake to limit Tfh cells and GC responses.
Chromatin organization at the nuclear pore favours HIV replication
Authors: Lelek Mickaël , Casartelli Nicoletta , Pellin Danilo , Rizzi Ermanno , Souque Philippe , Severgnini Marco , Di Serio Clelia , Fricke Thomas , Diaz-Griffero Felipe , Zimmer Christophe , Charneau Pierre , Di Nunzio Francesca
Published: March 2015

The molecular mechanisms that allow HIV to integrate into particular sites of the host genome are poorly understood. Here we tested if the nuclear pore complex (NPC) facilitates the targeting of HIV integration by acting on chromatin topology. We show that the integrity of the nuclear side of the NPC, which is mainly composed of Tpr, is not required for HIV nuclear import, but that Nup153 is essential. Depletion of Tpr markedly reduces HIV infectivity, but not the level of integration. HIV integration sites in Tpr-depleted cells are less associated with marks of active genes, consistent with the state of chromatin proximal to the NPC, as analysed by super-resolution microscopy. LEDGF/p75, which promotes viral integration into active genes, stabilizes Tpr at the nuclear periphery and vice versa. Our data support a model in which HIV nuclear import and integration are concerted steps, and where Tpr maintains a chromatin environment favourable for HIV replication.
Paper and Flexible Substrates as Materials for Biosensing Platforms to Detect Multiple Biotargets
Authors: Shafiee Hadi , Asghar Waseem , Inci Fatih , Yuksekkaya Mehmet , Jahangir Muntasir , Zhang Michael H. , Durmus Naside Gozde , Gurkan Umut Atakan , Kuritzkes Daniel R. , Demirci Utkan
Published: March 2015

The need for sensitive, robust, portable and inexpensive biosensing platforms is of significant interest in clinical applications for disease diagnosis and treatment monitoring at the point-of-care (POC) settings. Rapid, accurate POC diagnostic assays play a crucial role in developing countries, where there are limited laboratory infrastructure, trained personnel and financial support. However, current diagnostic assays commonly require long assay time, sophisticated infrastructure and expensive reagents that are not compatible with resource-constrained settings. Although paper and flexible material-based platform technologies provide alternative approaches to develop POC diagnostic assays for broad applications in medicine, they have technical challenges integrating to different detection modalities. Here, we address the limited capability of current paper and flexible material-based platforms by integrating cellulose paper and flexible polyester films as diagnostic biosensing materials with various detection modalities through the development and validation of new widely applicable electrical and optical sensing mechanisms using antibodies and peptides. By incorporating these different detection modalities, we present selective and accurate capture and detection of multiple biotargets including viruses (Human Immunodeficieny Virus-1), bacteria (Escherichia coli and Staphylococcus aureus) and cells (CD4+ T lymphocytes) from fingerprick volume equivalent of multiple biological specimens such as whole blood, plasma and peritoneal dialysis effluent with clinically relevant detection and sensitivity.
Mice lacking the cerebral cortex develop normal song: Insights into the foundations of vocal learning
Authors: Hammerschmidt Kurt , Whelan Gabriela , Eichele Gregor , Fischer Julia
Published: March 2015

Mouse models play an increasingly important role in the identification and functional assessment of speech-associated genes, with a focus on genes involved in vocal production and possibly vocal learning. Moreover, mice reportedly show direct projections from the cortex to brainstem vocal motor neurons, implying a degree of volitional control over vocal output. Yet, deaf mice did not reveal differences in call structures compared to their littermates, suggesting that auditory input is not a prerequisite for the development of species-specific sounds. To elucidate the importance of cortical structures for the development of mouse ultrasonic vocalizations (USVs) in more detail, we studied Emx1-CRE;Esco2fl/fl mice, which lack the hippocampus and large parts of the cortex. We conducted acoustic analyses of the USVs of 28 pups during short-term isolation and 23 adult males during courtship encounters. We found no significant differences in the vocalizations of Emx1-CRE;Esco2fl/fl mice and only minor differences in call type usage in adult mice, compared to control littermates. Our findings question the notion that cortical structures are necessary for the production of mouse USVs. Thus, mice might be less suitable to study the mechanisms supporting vocal learning than previously assumed, despite their value for studying the genetic foundations of neurodevelopment more generally.
3D Pharmacophoric Similarity improves Multi Adverse Drug Event Identification in Pharmacovigilance
Authors: Vilar Santiago , Tatonetti Nicholas P. , Hripcsak George
Published: March 2015

Adverse drugs events (ADEs) detection constitutes a considerable concern in patient safety and public health care. For this reason, it is important to develop methods that improve ADE signal detection in pharmacovigilance databases. Our objective is to apply 3D pharmacophoric similarity models to enhance ADE recognition in Offsides, a pharmacovigilance resource with drug-ADE associations extracted from the FDA Adverse Event Reporting System (FAERS). We developed a multi-ADE predictor implementing 3D drug similarity based on a pharmacophoric approach, with an ADE reference standard extracted from the SIDER database. The results showed that the application of our 3D multi-type ADE predictor to the pharmacovigilance data in Offsides improved ADE identification and generated enriched sets of drug-ADE signals. The global ROC curve for the Offsides ADE candidates ranked with the 3D similarity score showed an area of 0.7. The 3D predictor also allows the identification of the most similar drug that causes the ADE under study, which could provide hypotheses about mechanisms of action and ADE etiology. Our method is useful in drug development, screening potential adverse effects in experimental drugs and in drug safety, applicable to the evaluation of ADE signals selected through pharmacovigilance data mining.
A Novel Mechanism for Small Heat Shock Proteins to Function as Molecular Chaperones
Authors: Zhang Kaiming , Ezemaduka Anastasia N. , Wang Zhao , Hu Hongli , Shi Xiaodong , Liu Chuang , Lu Xinping , Fu Xinmiao , Chang Zengyi , Yin Chang-Cheng
Published: March 2015

Small heat shock proteins (sHSPs) are molecular chaperones ubiquitously present in all forms of life, but their function mechanisms remain controversial. Here we show by cryo-electron microscopy and single particle 3D reconstruction that, at the low temperatures (4–25°C), CeHSP17 (a sHSP from Caenorhabditis elegans) exists as a 24-subunit spherical oligomer with tetrahedral symmetry. Our studies demonstrate that CeHSP17 forms large sheet-like super-molecular assemblies (SMAs) at the high temperatures (45–60°C) and such SMAs are apparently the form that exhibits chaperone-like activity. Our findings suggest a novel molecular mechanism for sHSPs to function as molecular chaperones.
Submarine fresh groundwater discharge into Laizhou Bay comparable to the Yellow River flux
Authors: Wang Xuejing , Li Hailong , Jiao Jiu Jimmy , Barry D. A. , Li Ling , Luo Xin , Wang Chaoyue , Wan Li , Wang Xusheng , Jiang Xiaowei , Ma Qian , Qu Wenjing
Published: March 2015

Near- and off-shore fresh groundwater resources become increasingly important with the social and economic development in coastal areas. Although large scale (hundreds of km) submarine groundwater discharge (SGD) to the ocean has been shown to be of the same magnitude order as river discharge, submarine fresh groundwater discharge (SFGD) with magnitude comparable to large river discharge is never reported. Here, we proposed a method coupling mass-balance models of water, salt and radium isotopes based on field data of 223Ra, 226Ra and salinity to estimate the SFGD, SGD. By applying the method in Laizhou Bay (a water area of ~6000 km2), we showed that the SFGD and SGD are 0.57 ~ 0.88 times and 7.35 ~ 8.57 times the annual Yellow River flux in August 2012, respectively. The estimate of SFGD ranges from 4.12 × 107 m3/d to 6.36 × 107 m3/d, while SGD ranges from 5.32 × 108 m3/d to 6.20 × 108 m3/d. The proportion of the Yellow River input into Laizhou Bay was less than 14% of the total in August 2012. Our method can be used to estimate SFGD in various coastal waters.
Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes
Authors: Sanjabi Bahram , Dashty Monireh , Özcan Behiye , Akbarkhanzadeh Vishtaseb , Rahimi Mehran , Vinciguerra Manlio , van Rooij Felix , Al-Lahham Saad , Sheedfar Fareeba , van Kooten Theo G. , Spek C. Arnold , Rowshani Ajda T. , van der Want Johannes , Klaassen Rene , Sijbrands Eric , Peppelenbosch Maikel P. , Rezaee Farhad
Published: March 2015

Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional. Insulin concentrations and release are fat mass- and LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D. The expression of genes, like PCSK1 (proinsulin conversion enzyme), GCG (Glucagon), GPLD1, CD38 and NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue (AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived from prediabetes BB rats with destructed pancreatic β-cells and controls than pancreas derived from the same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.
Defining the light emitting area for displays in the unipolar regime of highly efficient light emitting transistors
Authors: Ullah Mujeeb , Armin Ardalan , Tandy Kristen , Yambem Soniya D. , Burn Paul L. , Meredith Paul , Namdas Ebinazar B.
Published: March 2015

Light-emitting field effect transistors (LEFETs) are an emerging class of multifunctional optoelectronic devices. It combines the light emitting function of an OLED with the switching function of a transistor in a single device architecture. The dual functionality of LEFETs has the potential applications in active matrix displays. However, the key problem of existing LEFETs thus far has been their low EQEs at high brightness, poor ON/OFF and poorly defined light emitting area - a thin emissive zone at the edge of the electrodes. Here we report heterostructure LEFETs based on solution processed unipolar charge transport and an emissive polymer that have an EQE of up to 1% at a brightness of 1350 cd/m2, ON/OFF ratio > 104 and a well-defined light emitting zone suitable for display pixel design. We show that a non-planar hole-injecting electrode combined with a semi-transparent electron-injecting electrode enables to achieve high EQE at high brightness and high ON/OFF ratio. Furthermore, we demonstrate that heterostructure LEFETs have a better frequency response (fcut-off = 2.6 kHz) compared to single layer LEFETs. The results presented here therefore are a major step along the pathway towards the realization of LEFETs for display applications.
Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia
Authors: Nasrollahzadeh Dariush , Malekzadeh Reza , Ploner Alexander , Shakeri Ramin , Sotoudeh Masoud , Fahimi Saman , Nasseri-Moghaddam Siavosh , Kamangar Farin , Abnet Christian C. , Winckler Björn , Islami Farhad , Boffetta Paolo , Brennan Paul , Dawsey Sanford M. , Ye Weimin
Published: March 2015

Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage I–II) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control) and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus.
Perturbation theory of a superconducting 0 − π impurity quantum phase transition
Authors: Žonda M. , Pokorný V. , Janiš V. , Novotný T.
Published: March 2015

A single-level quantum dot with Coulomb repulsion attached to two superconducting leads is studied via the perturbation expansion in the interaction strength. We use the Nambu formalism and the standard many-body diagrammatic representation of the impurity Green functions to formulate the Matsubara self-consistent perturbation expansion. We show that at zero temperature second order of the expansion in its spin-symmetric version yields a nearly perfect agreement with the numerically exact calculations for the position of the 0 − π phase boundary at which the Andreev bound states reach the Fermi energy as well as for the values of single-particle quantities in the 0-phase. We present results for phase diagrams, level occupation, induced local superconducting gap, Josephson current and energy of the Andreev bound states with the precision surpassing any (semi)analytical approaches employed thus far.
Surface properties of atomically flat poly-crystalline SrTiO3
Authors: Woo Sungmin , Jeong Hoidong , Lee Sang A. , Seo Hosung , Lacotte Morgane , David Adrian , Kim Hyun You , Prellier Wilfrid , Kim Yunseok , Choi Woo Seok
Published: March 2015

Comparison between single- and the poly-crystalline structures provides essential information on the role of long-range translational symmetry and grain boundaries. In particular, by comparing single- and poly-crystalline transition metal oxides (TMOs), one can study intriguing physical phenomena such as electronic and ionic conduction at the grain boundaries, phonon propagation and various domain properties. In order to make an accurate comparison, however, both single- and poly-crystalline samples should have the same quality, e.g., stoichiometry, crystallinity, thickness, etc. Here, by studying the surface properties of atomically flat poly-crystalline SrTiO3 (STO), we propose an approach to simultaneously fabricate both single- and poly-crystalline epitaxial TMO thin films on STO substrates. In order to grow TMOs epitaxially with atomic precision, an atomically flat, single-terminated surface of the substrate is a prerequisite. We first examined (100), (110) and (111) oriented single-crystalline STO surfaces, which required different annealing conditions to achieve atomically flat surfaces, depending on the surface energy. A poly-crystalline STO surface was then prepared at the optimum condition for which all the domains with different crystallographic orientations could be successfully flattened. Based on our atomically flat poly-crystalline STO substrates, we envision expansion of the studies regarding the TMO domains and grain boundaries.
Prolonged-acting, Multi-targeting Gallium Nanoparticles Potently Inhibit Growth of Both HIV and Mycobacteria in Co-Infected Human Macrophages
Authors: Narayanasamy Prabagaran , Switzer Barbara L. , Britigan Bradley E.
Published: March 2015

Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, macrophage and dendritic cell). Therefore, we hypothesized that one way this can be achieved is through drug-targeting by a nanoformulated drug that ideally would be active against both HIV and TB. Accordingly, we validated macrophage targeted long acting (sustained drug release) gallium (Ga) nanoformulation against HIV-mycobacterium co-infection. The multi-targeted Ga nanoparticle agent inhibited growth of both HIV and TB in the macrophage. The Ga nanoparticles reduced the growth of mycobacterium and HIV for up to 15 days following single drug loading. These results provide a potential new approach to treat HIV-TB co-infection that could eventually lead to improved clinical outcomes.
Renal progenitors derived from human iPSCs engraft and restore function in a mouse model of acute kidney injury
Authors: Imberti Barbara , Tomasoni Susanna , Ciampi Osele , Pezzotta Anna , Derosas Manuela , Xinaris Christodoulos , Rizzo Paola , Papadimou Evangelia , Novelli Rubina , Benigni Ariela , Remuzzi Giuseppe , Morigi Marina
Published: March 2015

Acute kidney injury (AKI) is one of the most relevant health issues, leading to millions of deaths. The magnitude of the phenomenon remarks the urgent need for innovative and effective therapeutic approaches. Cell-based therapy with renal progenitor cells (RPCs) has been proposed as a possible strategy. Studies have shown the feasibility of directing embryonic stem cells or induced Pluripotent Stem Cells (iPSCs) towards nephrogenic intermediate mesoderm and metanephric mesenchyme (MM). However, the functional activity of iPSC-derived RPCs has not been tested in animal models of kidney disease. Here, through an efficient inductive protocol, we directed human iPSCs towards RPCs that robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin-mice with AKI. These results demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy.
Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas
Authors: Furukawa Toru , Sakamoto Hitomi , Takeuchi Shoko , Ameri Mitra , Kuboki Yuko , Yamamoto Toshiyuki , Hatori Takashi , Yamamoto Masakazu , Sugiyama Masanori , Ohike Nobuyuki , Yamaguchi Hiroshi , Shimizu Michio , Shibata Noriyuki , Shimizu Kyoko , Shiratori Keiko
Published: March 2015

Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3 and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.
Parameterization of temperature sensitivity of spring phenology and its application in explaining diverse phenological responses to temperature change
Authors: Wang Huanjiong , Ge Quansheng , Rutishauser This , Dai Yuxiao , Dai Junhu
Published: March 2015

Existing evidence of plant phenological change to temperature increase demonstrates that the phenological responsiveness is greater at warmer locations and in early-season plant species. Explanations of these findings are scarce and not settled. Some studies suggest considering phenology as one functional trait within a plant's life history strategy. In this study, we adapt an existing phenological model to derive a generalized sensitivity in space (SpaceSens) model for calculating temperature sensitivity of spring plant phenophases across species and locations. The SpaceSens model have three parameters, including the temperature at the onset date of phenophases (Tp), base temperature threshold (Tb) and the length of period (L) used to calculate the mean temperature when performing regression analysis between phenology and temperature. A case study on first leaf date of 20 plant species from eastern China shows that the change of Tp and Tb among different species accounts for interspecific difference in temperature sensitivity. Moreover, lower Tp at lower latitude is the main reason why spring phenological responsiveness is greater there. These results suggest that spring phenophases of more responsive, early-season plants (especially in low latitude) will probably continue to diverge from the other late-season plants with temperatures warming in the future.
Real-time Measurement of Biomagnetic Vector Fields in Functional Syncytium Using Amorphous Metal
Authors: Nakayama Shinsuke , Uchiyama Tusyoshi
Published: March 2015

Magnetic field detection of biological electric activities would provide a non-invasive and aseptic estimate of the functional state of cellular organization, namely a syncytium constructed with cell-to-cell electric coupling. In this study, we investigated the properties of biomagnetic waves which occur spontaneously in gut musculature as a typical functional syncytium, by applying an amorphous metal-based gradio-magneto sensor operated at ambient temperature without a magnetic shield. The performance of differentiation was improved by using a single amorphous wire with a pair of transducer coils. Biomagnetic waves of up to several nT were recorded ~1 mm below the sample in a real-time manner. Tetraethyl ammonium (TEA) facilitated magnetic waves reflected electric activity in smooth muscle. The direction of magnetic waves altered depending on the relative angle of the muscle layer and magneto sensor, indicating the existence of propagating intercellular currents. The magnitude of magnetic waves rapidly decreased to ~30% by the initial and subsequent 1 mm separations between sample and sensor. The large distance effect was attributed to the feature of bioelectric circuits constructed by two reverse currents separated by a small distance. This study provides a method for detecting characteristic features of biomagnetic fields arising from a syncytial current.
Three-dimensional Aerographite-GaN hybrid networks: Single step fabrication of porous and mechanically flexible materials for multifunctional applications
Authors: Schuchardt Arnim , Braniste Tudor , Mishra Yogendra K. , Deng Mao , Mecklenburg Matthias , Stevens-Kalceff Marion A. , Raevschi Simion , Schulte Karl , Kienle Lorenz , Adelung Rainer , Tiginyanu Ion
Published: March 2015

Three dimensional (3D) elastic hybrid networks built from interconnected nano- and microstructure building units, in the form of semiconducting-carbonaceous materials, are potential candidates for advanced technological applications. However, fabrication of these 3D hybrid networks by simple and versatile methods is a challenging task due to the involvement of complex and multiple synthesis processes. In this paper, we demonstrate the growth of Aerographite-GaN 3D hybrid networks using ultralight and extremely porous carbon based Aerographite material as templates by a single step hydride vapor phase epitaxy process. The GaN nano- and microstructures grow on the surface of Aerographite tubes and follow the network architecture of the Aerographite template without agglomeration. The synthesized 3D networks are integrated with the properties from both, i.e., nanoscale GaN structures and Aerographite in the form of flexible and semiconducting composites which could be exploited as next generation materials for electronic, photonic and sensors applications.
Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles
Authors: Park Hanwook , Yeom Eunseop , Seo Seung-Jun , Lim Jae-Hong , Lee Sang-Joon
Published: March 2015

Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases.