bluuebunny/crossref_metadata_2025 huggingface dataset:
Youth innovation showcase: achieving high-impact success with novel technologies
Authors: Kanevsky Jonathan , Crepy Mathieu , Fitzgerald Edward , Pogharian Anya , Sadagopan Swathi , Aggarwal Rajesh
Published: March 2017

Universities provide a dynamic environment that enables innovation in healthcare. Challenges to the delivery of healthcare are best overcome by fostering relationships that lead to solutions developed by young innovators. The Youth Innovation Showcase highlights the creative solutions of 5 young entrepreneurs as part of the Simnovate International Summit. Challenges in the process of innovation, finding balance as a young innovator, government support for student entrepreneurs, innovation and global health and how to adapt to the process of innovation are all topics covered in this summary.
BET 1: IN PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME, DOES WELLENS' SIGN ON THE ELECTROCARDIOGRAPH IDENTIFY CRITICAL LEFT ANTERIOR DESCENDING ARTERY STENOSIS?
Authors: Morris Niall , Howard Laura
Published: March 2017

Wellens’ syndrome consists of a history suggestive of an acute coronary syndrome and biphasic or deeply inverted T waves in ECG leads V2–V3. A shortcut review was carried out to establish whether this ECG pattern identifies patients with a critical left anterior descending artery stenosis. Six relevant papers were found. The clinical bottom line is that biphasic T-wave inversion in lead V2–V3 should alert the clinician to a probable critical stenosis of the left anterior descending artery.
Does the type of activity “break” from prolonged sitting differentially impact on postprandial blood glucose reductions? An exploratory analysis
Authors: Larsen Robyn N. , Dempsey Paddy C. , Dillon Francis , Grace Megan , Kingwell Bronwyn A. , Owen Neville , Dunstan David W.
Published: March 2017

Frequent breaks in prolonged sitting are associated beneficially with glycaemic control. However, the contribution of energy expenditure to this relationship has not been well characterised. In this exploratory analysis, data from 3 laboratory trials that standardised test meals, cohort characteristics (overweight/obese, sedentary), and break frequency and duration were pooled. Higher energy expenditures of different types of breaks (standing, light- or moderate-intensity walking) were associated with lower postprandial glucose and insulin responses in a dose-dependent manner.
High energy physics, past, present and future
Authors: Sugawara Hirotaka
Published: March 2017

At the beginning of last century we witnessed the emergence of new physics, quantum theory and gravitational theory, which gave us correct understanding of the world of atoms and deep insight into the structure of universe we live in. Towards the end of the century, string theory emerged as the most promising candidate to unify these two theories.

In this talk, I would like to assert that the understanding of the origin of physical constants, [Formula: see text] (Planck constant) for quantum theory, and G (Newton’s gravitational constant) for gravitational theory within the framework of string theory is the key to understanding string theory.

Then, I will shift to experimental high energy physics and discuss the necessity of world-wide collaboration in the area of superconducting technology which is essential in constructing the 100 TeV hadron collider.
The world of long-range interactions: A bird’s eye view
Authors: Gupta Shamik , Ruffo Stefano
Published: March 2017

In recent years, studies of long-range interacting (LRI) systems have taken center stage in the arena of statistical mechanics and dynamical system studies, due to new theoretical developments involving tools from as diverse a field as kinetic theory, non-equilibrium statistical mechanics, and large deviation theory, but also due to new and exciting experimental realizations of LRI systems. In the first, introductory, Section 1, we discuss the general features of long-range interactions, emphasizing in particular the main physical phenomenon of non-additivity, which leads to a plethora of distinct effects, both thermodynamic and dynamic, that are not observed with short-range interactions: Ensemble inequivalence, slow relaxation, broken ergodicity. In Section 2, we discuss several physical systems with long-range interactions: mean-field spin systems, self-gravitating systems, Euler equations in two dimensions, Coulomb systems, one-component electron plasma, dipolar systems, free-electron lasers. In Section 3, we discuss the general scenario of dynamical evolution of generic LRI systems. In Section 4, we discuss an illustrative example of LRI systems, the Kardar–Nagel spin system, which involves discrete degrees of freedom, while in Section 5, we discuss a paradigmatic example involving continuous degrees of freedom, the so-called Hamiltonian mean-field (HMF) model. For the former, we demonstrate the effects of ensemble inequivalence and slow relaxation, while for the HMF model, we emphasize in particular the occurrence of the so-called quasistationary states (QSSs) during relaxation towards the Boltzmann–Gibbs equilibrium state. The QSSs are non-equilibrium states with lifetimes that diverge with the system size, so that in the thermodynamic limit, the systems remain trapped in the QSSs, thereby making the latter the effective stationary states. In Section 5, we also discuss an experimental system involving atoms trapped in optical cavities, which may be modelled by the HMF system. In Section 6, we address the issue of ubiquity of the quasistationary behavior by considering a variety of models and dynamics, discussing in each case the conditions to observe QSSs. In Section 7, we investigate the issue of what happens when a long-range system is driven out of thermal equilibrium. Conclusions are drawn in Section 8.
Implications of Lorentz symmetry violation on a 5D supersymmetric model
Authors: García-Aguilar J. D. , Pérez-Lorenzana A.
Published: March 2017

Field models with [Formula: see text] extra spatial dimensions have a larger [Formula: see text] Lorentz symmetry which is broken down to the standard [Formula: see text] four-dimensional one by the compactification process. By considering Lorentz violating operators in a 5D supersymmetric Wess–Zumino model, which otherwise conserve the standard four-dimensional Poincaré invariance, we show that supersymmetry (SUSY) can be restored upon a simple deformation of the supersymmetric transformations. However, SUSY is not preserved in the effective 4D theory that arises after compactification when the 5D Lorentz violating operators do not preserve [Formula: see text] bulk parity. Our mechanism unveils a possible connection among Lorentz violation and the Scherk–Schwarz mechanism. We also show that parity preserving models, on the other hand, do provide well defined supersymmetric KK models.
Effects of Ga content on the stability of Fe-X (X = 6.25, 12.5, 18.75, 25 at.% Ga) alloys from first-principles calculations
Authors: Yan Xiang-Hong , Lin Ya-Ning
Published: March 2017

First-principles calculations based on density functional theory (DFT) were employed to investigate the influence of Ga concentration on the stability of binary Fe–Ga alloy. The contents of Ga element are 6.25, 12.5, 18.75 and 25 at.% for Fe[Formula: see text]Ga, Fe[Formula: see text]Ga, Fe[Formula: see text]Ga[Formula: see text] and Fe[Formula: see text]Ga alloys, respectively. Cohesive energy, elastic properties, electronic structures and phonon properties of optimized Fe–Ga models were calculated. Our results of calculated elastic constants and elastic moduli are in good accordance with the determined available literature. Our study shows that with increasing Ga content, the absolute value of cohesive energy of Fe–Ga alloy is decreasing. From the calculations of elastic constants, we found that the value of [Formula: see text] decreases with the increasing Ga content, which indicates that the stability of Fe–Ga along the [001] direction is decreasing with the increasing Ga content. The calculated bulk moduli of Fe–Ga alloys increase with increasing Ga content because of the increase of the average bonding number evaluated by our calculations of densities of states. Conversely, the shear moduli decrease with increasing Ga content, which indicates that the stability of Fe–Ga is decreasing with the increasing Ga content. Tetragonal shear elastic constant [Formula: see text] almost decreases linearly with increasing Ga content, which follows the same decreasing trend as the cohesive energy and the shear modulus. It is worth noting that with the increasing Ga content, the pseudogap between two major peaks in the minority-spin state became softer. The softness brings the Fermi level into a high state, which lowers the stability of the Fe–Ga alloy. According to the phonon calculations, the acoustic mode of Fe-25 at.% Ga appeared to be softening along the [001] direction, which is in good accordance with the direction predicted by the calculations of elastic constant. But this softening trend cannot be observed in the phonon dispersion spectrum of Fe-6.25 at.% Ga, which proved that Fe-6.25 at.% Ga is more stable than the Fe-25 at.% Ga alloy.
Modified relativistic dynamics
Authors: Qadir Asghar , Lee Hyung Won , Kim Kyoung Yee
Published: March 2017

One of the major problems in Cosmology is the fact that there is no good candidate of dark matter in the Standard Model of Particle Physics or any experimentally supported modifications of it. At the same time, one of the major problems of General Relativity is that it cannot be unified with Quantum Theory. Here, we present a program to see if there is not a common source of both problems. The idea is that an interaction term between matter fields and the gravitational field in the total Lagrangian, analogous to that for Electromagnetism, could possibly provide the dynamical effect for which the dark matter is postulated, on the one hand and a Quantum-Field Theory (QFT) incorporating Gravity, that does not have unmanageable divergences, on the other. One could first check that the modified relativistic dynamics, if fitted for the dark matter in individual galaxies fits also for systems and clusters of galaxies, at all scales. If there is no problem with the explanation of the dynamics usually explained by dark matter at all scales, we could check if it leads to a workable QFT of Relativity.
Evolution of spherical overdensities in new agegraphic dark energy model
Authors: Setare M. R. , Felegary F. , Darabi F.
Published: March 2017

We study the structure formation by investigating the spherical collapse model in the context of new agegraphic dark energy (NADE) model in flat FRW cosmology. We compute the perturbational quantities [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] for the NADE model and compare the results with those of EdS and [Formula: see text] models. We find that there is a dark energy-dominated universe at low redshifts and a matter-dominated universe at high redshifts in agreement with the observations. Also, the size of structures, the overdense spherical region, and the halo size in the NADE model are found to be smaller, denser, and larger than those of EdS and [Formula: see text] models. We compare our results with the results of tachyon scalar field and holographic dark energy models.
Stability and Dynamic Analyses of Transmission Tower-Line Systems Subjected to Conductor Breaking
Authors: Li Jia-Xiang , Li Hong-Nan , Fu Xing
Published: March 2017

Ice loads exerted on the transmission line can increase the probability of conductor breaking, which will lead to the stability failure of transmission towers. In this paper, a transmission tower-line system is established for two towers and three span lines. Then the nonlinear static stability analysis and nonlinear dynamic stability analysis induced by the conductor breaking are carried out to obtain the load versus displacement curves, while studying the failure modes of the transmission tower-line system. Moreover, the ice load and initial eccentricity are considered in the numerical simulation. In addition, a parametric analysis is performed to investigate the influence of span, insulator length and initial tension force on the stability failure of the system. The results show that the dynamic instability will occur earlier than the static instability due to the dynamic impact effect and conductor breaking with ice loads can lead to the progressive collapse of the transmission tower-line system. Finally, the span length has the greatest effect on the response of transmission tower caused by conductor breaking.
China’s Partnership Network Versus the U.S. Alliance System: Coexistence or Conflict?
Authors: Zhou Yiqi
Published: March 2017

One interesting fact to note about China’s expanding partnership network is the inclusion of many security allies of the United States. China’s partnership network (CPN) and the U.S. alliance system (UAS) are quite different in nature, with the former emphasizing economic cooperation and the latter focused on security deterrence. Due to such factors as the geographical locations of U.S. allies, strategic positions, and perceptions of external threats, China’s partnerships with U.S. allies are generally more successful in Europe than in the Asia-Pacific. Based on an analysis of the dynamics of interaction between CPN and UAS, this article categorizes their past interaction into two basic models: coexistence (both easy and hard) and confrontation. With regard to the growing uncertainties in the global economy and global politics, the interaction between CPN and UAS may either create a platform for enhanced cooperation or an arena for escalating contention among related countries. To avoid the latter scenario, China must remain prudent in expanding its partnership network, and try to strengthen mutual security reassurance with the United States and its allies through more win-win cooperation in all areas.
Bridging the Conceptual Gaps: New Imperatives for Managing China-U.S. Relations
Authors: Yang Jiemian
Published: March 2017

The election of Donald Trump as the 45th U.S. President earmarks a new beginning of American domestic and foreign policies, to which his populist thinking and unconventional approach have caused great uncertainty. While recognizing the challenges that President Trump may bring to the world in general and China-U.S. relations in particular, the Chinese government under the core leadership of President Xi Jinping firmly believes in the world’s general trend for sustained progress, remains committed to the track of win-win cooperation with other countries, and is adopting both reactive and proactive attitudes toward the great changes in global arenas while taking every precaution against the worst possible scenario. To better manage China-U.S. relations at this critical juncture of world development, it is imperative for both countries to adapt to various new changes, deepen their mutual understanding of each other’s diplomatic philosophy, and continue sharing the dividends of peace and development. If the two countries can manage to pass the first few rounds of tests through more active conceptual matching-up and pragmatic cooperation, they will be in a better position to realize their respective national agendas of “rejuvenation of the Chinese nation” and “making America great again.” Otherwise, both countries and even the whole world may fall into devastating confrontation and escalating conflicts.
The impact of skew on the pricing of CoCo bonds
Authors: De Spiegeleer Jan , Forys Monika B. , Marquet Ine , Schoutens Wim
Published: March 2017

This paper presents a Heston-based pricing model for contingent convertible bonds (CoCos). The main finding is that skew in the implied volatility surface has a significant impact on the CoCo price. Hence stochastic volatility models, like the Heston model, which incorporate smile and skew are appropriate in the context of pricing CoCos. The financial crisis of 2007–2008 triggered an avalanche of financial worries for financial institutions around the globe. After the collapse of Lehman Brothers, governments intervened and bailed out banks using tax-payer’s money. Preventing such bail-outs in the future and designing a more stable banking sector in general, requires both higher capital levels and regulatory capital of a higher quality. Bank debt needed therefore to be made absorbing. This is where CoCos come in. The Lloyds Banking Group introduced the first CoCo bonds as early as December 2009. Since the first issuance of a CoCo bond more than five years ago, the market has continued to grow and has now reached a size over €120[Formula: see text]bn. CoCos are hybrid financial instruments that convert into equity or suffer a write-down of the face value upon the appearance of a trigger event, often in terms of the bank’s CET1 level in combination with a regulatory trigger. The valuation of CoCos boils down to the quantification of the trigger probability and the expected loss suffered by the investors if such a trigger event eventually takes place. There are at least two schools of thought regarding valuation of CoCos. Structural models can be put at work or investors can rely on market implied models. The latter category uses market data (share prices, CDS levels and implied volatility, etc.) in order to calculate the theoretical price of a CoCo bond. In De Spiegeleer and Schoutens The Journal of Derivatives, the pricing of CoCo notes has been worked out in a market implied Black–Scholes context. In this paper we move away from the assumption of a constant volatility which is the back-bone of Black–Scholes based valuation and put the Heston model at work and study CoCos in a stochastic volatility context. The existence of a semi closed-form formula for European options pricing under the Heston model allows for a fast calibration of the model. In our approach we combined market quotes of listed option prices with CDS data. As a case study, the procedure was applied on the Tier 2 10NC [Formula: see text] CoCo issued by Barclays in 2012.
The effects of negative interest rates on the estimation of option sensitivities: The impact of switching from a log-normal to a normal model
Authors: Giribone Pier Giuseppe , Ligato Simone , Mulas Martina
Published: March 2017

The estimation of partial derivatives of the price in respect to the main financial variables, called Greeks, is an essential task for a trader in order to understand the sensitivity of a derivative to the input of pricing model. The study of the level of reactivity of the mark to market is an essential task to manage properly the market risk of a portfolio. Due to the negative interest rates in Euro Area, the pricing model of interest-rates options (cap, floor and swaption) has been changed from a log-normal to a normal framework. The aim of this paper is to investigate the effects of this model change on the calculation of option sensitivities.
Community detection in social networks
Authors: Fani Hossein , Bagheri Ebrahim
Published: March 2017

Online social networks have become a fundamental part of the global online experience. They facilitate different modes of communication and social interactions, enabling individuals to play social roles that they regularly undertake in real social settings. In spite of the heterogeneity of the users and interactions, these networks exhibit common properties. For instance, individuals tend to associate with others who share similar interests, a tendency often known as homophily, leading to the formation of communities. This entry aims to provide an overview of the definitions for an online community and review different community detection methods in social networks. Finding communities are beneficial since they provide summarization of network structure, highlighting the main properties of the network. Moreover, it has applications in sociology, biology, marketing and computer science which help scientists identify and extract actionable insight.
Semantic summarization of web news
Authors: Amato Flora , Moscato Vincenzo , Picariello Antonio , Sperlí Giancarlo , D’Acierno Antonio , Penta Antonio
Published: March 2017

In this paper, we present a general framework for retrieving relevant information from news papers that exploits a novel summarization algorithm based on a deep semantic analysis of texts. In particular, we extract from each Web document a set of triples (subject, predicate, object) that are then used to build a summary through an unsupervised clustering algorithm exploiting the notion of semantic similarity. Finally, we leverage the centroids of clusters to determine the most significant summary sentences using some heuristics. Several experiments are carried out using the standard DUC methodology and ROUGE software and show how the proposed method outperforms several summarizer systems in terms of recall and readability.
High-level surveillance event detection
Authors: Persia Fabio , D’Auria Daniela
Published: March 2017

Security has been raised at major public buildings in the most famous and crowded cities all over the world following the terrorist attacks of the last years, the latest one at the Promenade des Anglais in Nice. For that reason, video surveillance systems have become more and more essential for detecting and hopefully even prevent dangerous events in public areas. In this work, we present an overview of the evolution of high-level surveillance event detection systems along with a prototype for anomaly detection in video surveillance context. The whole process is described, starting from the video frames captured by sensors/cameras till at the end some well-known reasoning algorithms for finding potentially dangerous activities are applied.
Entity linking for tweets
Authors: Basile Pierpaolo , Caputo Annalina
Published: March 2017

Named Entity Linking (NEL) is the task of semantically annotating entity mentions in a portion of text with links to a knowledge base. The automatic annotation, which requires the recognition and disambiguation of the entity mention, usually exploits contextual clues like the context of usage and the coherence with respect to other entities. In Twitter, the limits of 140 characters originates very short and noisy text messages that pose new challenges to the entity linking task. We propose an overview of NEL methods focusing on approaches specifically developed to deal with short messages, like tweets. NEL is a fundamental task for the extraction and annotation of concepts in tweets, which is necessary for making the Twitter’s huge amount of interconnected user-generated contents machine readable and enable the intelligent information access.
Survival analysis via cox proportional hazards additive models
Authors: Bai Lu , Gillen Daniel
Published: March 2017

The Cox proportional hazards model is commonly used to examine the covariate-adjusted association between a predictor of interest and the risk of mortality for censored survival data. However, it assumes a parametric relationship between covariates and mortality risk though a linear predictor. Generalized additive models (GAMs) provide a flexible extension of the usual linear model and are capable of capturing nonlinear effects of predictors while retaining additivity between the predictor effects. In this paper, we provide a review of GAMs and incorporate bivariate additive modeling into the Cox model for censored survival data with applications to estimating geolocation effects on survival in spatial epidemiologic studies.
Two-stage and sequential sampling for estimation and testing with prescribed precision
Authors: Zacks Shelemyahu
Published: March 2017

Statistical data analysis includes several phases. First, there is the phase of data collection. Second, there is the phase of analysis and inference. The two phases are interconnected. There are two types of data analysis. One type is called parametric and the other type is nonparametric. In the present paper, we discuss parametric inference. In parametric inference, we model the results of a given experiment as realization of random variables having a particular distribution, which is specified by its parameters. A random sample is a sequence of independent and identically distributed (i.i.d.) random variables. Statistics are functions of the data in the sample, which do not involve unknown parameters. A statistical inference is based on statistics of a given sample. We discuss two kinds of parametric inference. Estimating the values of parameters, or testing hypotheses concerning the parameters in either kind of inference, we are concerned with the accuracy and precision of the results. In estimation of parameters, the results are precise if, with high probability, they belong to a specified neighborhoods of the parameters. In testing hypotheses, one has to decide which one of two or several hypotheses should be accepted. Hypotheses which are not accepted are rejected. We distinguish between two types of errors. Type I error is the one committed by rejecting a correct hypothesis. Type II is that of accepting a wrong hypothesis. It is desired that both types of errors will occur simultaneously with small probabilities. Both precision in estimation or small error probabilities in testing depend on the statistics used (estimators or test functions) and on the sample size. In this paper, we present sampling procedures that attain the desired objectives. In Sec. 2, we discuss estimation of the parameters of a binomial distribution. In Sec. 3, more general results about estimation of expected values are presented. In Sec. 4, we discuss the Wald Sequential Probability Ratio Test (SPRT), which has optimal properties for testing two simple hypotheses.
Computational thinking for teacher education
Authors: Yadav Aman , Stephenson Chris , Hong Hai
Published: March 2017

This framework for developing pre-service teachers' knowledge does not necessarily depend on computers or other educational technology.
Progressive Random Indexing
Authors: Ciesielczyk Michał , Szwabe Andrzej , Morzy Mikołaj , Misiorek Paweł
Published: March 2017

The vector space model is undoubtedly among the most popular data representation models used in the processing of large networks. Unfortunately, the vector space model suffers from the so-called curse of dimensionality, a phenomenon where data become extremely sparse due to an exponential growth of the data space volume caused by a large number of dimensions. Thus, dimensionality reduction techniques are necessary to make large networks represented in the vector space model available for analysis and processing. Most dimensionality reduction techniques tend to focus on principal components present in the data, effectively disregarding local relationships that may exist between objects. This behavior is a significant drawback of current dimensionality reduction techniques, because these local relationships are crucial for maintaining high accuracy in many network analysis tasks, such as link prediction or community detection. To rectify the aforementioned drawback, we propose Progressive Random Indexing, a new dimensionality reduction technique. Built upon Reflective Random Indexing, our method significantly reduces the dimensionality of the vector space model while retaining all important local relationships between objects. The key element of the Progressive Random Indexing technique is the use of the gain value at each reflection step, which determines how much information about local relationships should be included in the space of reduced dimensionality. Our experiments indicate that when applied to large real-world networks (Facebook social network, MovieLens movie recommendations), Progressive Random Indexing outperforms state-of-the-art methods in link prediction tasks.
A Temporal Logic Approach to Binding-Time Analysis
Authors: Davies Rowan
Published: March 2017

This article demonstrates that there is a fundamental relationship between temporal logic and languages that involve multiple stages, such as those used to analyze binding times in the context of partial evaluation. This relationship is based on an extension of the Curry-Howard isomorphism, which identifies proofs with programs, and propositions with types. Our extension involves the “next time” (○) operator from linear-time temporal logic and yields a λ-calculus λ° with types of the form ○
A
for expressions in the subsequent stage, with appropriate introduction and elimination forms. We demonstrate that λ° is equivalent to the core of a previously studied multilevel binding-time analysis. This is similar to work by Davies and Pfenning on staged computation based on the necessity (□) operator of modal logic, but □ only allows closed code, and naturally supports a code evaluation construct, whereas ○ captures open code, thus is more flexible, but is incompatible with such a construct. Instead, code evaluation is an external global operation that is validated by the proof theory regarding closed proofs of ○ formulas. We demonstrate the relevance of λ° to staged computation directly by showing that that normalization can be done in an order strictly following the times of the logic. We also extend λ° to small functional language and show that it would serve as a suitable basis for directly programming with multiple stages by presenting some example programs.
Upward Max-Min Fairness
Authors: Danna Emilie , Hassidim Avinatan , Kaplan Haim , Kumar Alok , Mansour Yishay , Raz Danny , Segalov Michal
Published: March 2017

Often one would like to allocate shared resources in a fair way. A common and well-studied notion of fairness is
Max-Min Fairness
, where we first maximize the smallest allocation, and subject to that the second smallest, and so on. We consider a networking application where multiple commodities compete over the capacity of a network. In our setting, each commodity has multiple possible paths to route its demand (for example, a network using Multiprotocol Label Switching (MPLS) tunneling). In this setting, the only known way of finding a max-min fair allocation requires an iterative solution of multiple linear programs. Such an approach, although polynomial time, scales badly with the size of the network, the number of demands, and the number of paths, and is hard to implement in a distributed environment. More importantly, a network operator has limited control and understanding of the inner working of the algorithm.

In this article we introduce Upward Max-Min Fairness, a novel relaxation of Max-Min Fairness, and present a family of simple dynamics that converge to it. These dynamics can be implemented in a distributed manner. Moreover, we present an efficient combinatorial algorithm for finding an upward max-min fair allocation. This algorithm is a natural extension of the well-known Water Filling Algorithm for a multiple path setting.

We test the expected behavior of this new algorithm and show that on realistic networks upward max-min fair allocations are comparable to the max-min fair allocations both in fairness and in network utilization.
Guilt-free data reuse
Authors: Dwork Cynthia , Feldman Vitaly , Hardt Moritz , Pitassi Toniann , Reingold Omer , Roth Aaron
Published: March 2017

Existing approaches to ensuring the validity of inferences drawn from data assume a fixed procedure to be performed, selected before the data are examined. Yet the practice of data analysis is an intrinsically interactive and adaptive process: new analyses and hypotheses are proposed after seeing the results of previous ones, parameters are tuned on the basis of obtained results, and datasets are shared and reused.

In this work, we initiate a principled study of how to guarantee the validity of statistical inference in adaptive data analysis. We demonstrate new approaches for addressing the challenges of adaptivity that are based on techniques developed in privacy-preserving data analysis.

As an application of our techniques we give a simple and practical method for reusing a holdout (or testing) set to validate the accuracy of hypotheses produced adaptively by a learning algorithm operating on a training set.
Does anybody listen to you?
Authors: Matsudaira Kate
Published: March 2017

How do you step up from mere contributor to real change-maker?
Barrett’s metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux
Authors: Minacapelli Carlos D. , Bajpai Manisha , Geng Xin , Cheng Christina L. , Chouthai Abhishek A. , Souza Rhonda , Spechler Stuart J. , Das Kiron M.
Published: March 2017

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett’s metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk. Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk. Markers of columnar lineage and inflammation increased progressively, while squamous lineage-determining transcriptional factors were significantly decreased both at the mRNA and/or protein level in the NES-B10T cells at/after A + B treatment for 30 wk. Distinct modifications in morphological features were only observed at/after 30 wk of A + B exposure. These changes acquired by the NES-B10T 30-wk cells were retained even after cessation of A + B exposure for at least 3 wk. This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells.

NEW & NOTEWORTHY This study provides evidence of the origins of Barrett’s metaplasia from lineage transcommitment of resident esophageal cells after chronic exposure to gastroesophageal refluxate. The preterminal progenitor-like squamous cells alter their differentiation and develop biphenotypic characteristics, expressing markers of incomplete-type columnar metaplasia. Development of these biphenotypic precursors in vitro is a unique model to study pathogenesis of Barrett’s metaplasia and esophageal adenocarcinoma.
Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size
Authors: Lee David E. , Brown Jacob L. , Rosa-Caldwell Megan E. , Blackwell Thomas A. , Perry Richard A. , Brown Lemuel A. , Khatri Bhuwan , Seo Dongwon , Bottje Walter G. , Washington Tyrone A. , Wiggs Michael P. , Kong Byung-Whi , Greene Nicholas P.
Published: March 2017

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20–40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia.
Therapie indolenter Lymphome bei Patienten mit transformiertem NHL: weiterhin eine Herausforderung
Authors: Crysandt Martina
Published: March 2017

Hintergrund: Bei einigen Patienten mit niedriggradig malignen Lymphomen kommt es zu einer Transformation der Erkrankung, die eine Stammzelltransplantation (SZT) erforderlich macht. Die SZT-Ergebnisse bei transformierten niedriggradig malignen Lymphomen können sich von denen bei nicht-transformierter Krankheit oder anderen aggressiven Non-Hodgkin-Lymphomen unterscheiden. Wir führten eine gepoolte Analyse der klinischen Ergebnisse von allogener SZT im Vergleich zur Hochdosistherapie (HDT) mit autologer SZT bei erwachsenen Patienten mit transformierten niedriggradig malignen Lymphomen durch. Methoden: Eine Suche in PubMed, EMBASE und Cochrane ergab 4 Vergleichsstudien, die über die Ergebnisse von allogener SZT im Vergleich zu HDT mit autologer SZT bei Erwachsenen (≥18 Jahre alt) mit transformierten niedriggradig malignen Lymphomen, darunter follikuläre, chronische/kleinzellige Lymphome und Marginalzonen-Lymphome, berichteten. Risikoverhältnis (RR) und 95%-KI wurden mit Hilfe von Random-Effects-Modellen berechnet. Ergebnisse: Die Raten für das Gesamtüberleben (OS) betrugen 51,0% gegenüber 69,5% (RR = 1,55; 95%-KI 1,19-2,02%, p = 0,001), Rückfallraten betrugen 37,3% gegenüber 35,3% (RR = 1,04; 95%-KI 0,70-1,55%, p = 0,84), und die Raten der transplantationsassoziierten Mortalität (TRM) betrugen 33,3% gegenüber 7,2% (RR = 4,52; 95%-KI 2,75-7,43%, p < 0,00001) für die allogene SZT im Vergleich zur autologen SZT. Keine Auswirkungen auf die Prognose hatten eine vorherige Rituximab-Behandlung, eine weniger intensive Konditionierung vor der SZT oder die ursprüngliche Pathologie. Schlussfolgerung: Eine HDT mit anschließender autologer SZT war mit niedrigerer TRM und einem besseren OS verbunden, es gab jedoch keinen Unterschied bei Rückfällen im Vergleich zur allogenen Stammzelltransplantation. Die autologe SZT ist möglicherweise die bessere therapeutische Option, wenn man berücksichtigt, dass bei einem Rückfall eine zweite Chance mit der allogenen SZT besteht.
Sildenafil Enhances Quantity of Immature Neurons and Promotes Functional Recovery in the Developing Ischemic Mouse Brain
Authors: Engels Jonas , Elting Natalie , Braun Lisa , Bendix Ivo , Herz Josephine , Felderhoff-Müser Ursula , Dzietko Mark
Published: March 2017

Background: Hypoxic-ischemic (HI) injury to the developing brain occurs in 1 out of 1,000 live births and remains a major cause of significant morbidity and mortality. A large number of survivors suffer from long-term sequelae including seizures and neurological deficits. However, the pathophysiological mechanisms of recovery after HI insult are not clearly understood, and preventive measures or clinical treatments are nonexistent or not sufficiently effective in the clinical setting. Sildenafil as a specific phosphodiesterase 5 inhibitor leads to increased levels of the second messenger cyclic guanosine monophosphate (cGMP) and promotes functional recovery and neurogenesis after ischemic injury to the adult brain. Objective: Here, we investigated the effect of sildenafil treatment on activation of intracellular signaling pathways, histological and neurogenic response including functional recovery after an ischemic insult to the developing brain. Design/Methods: Nine-day-old C57BL/6 mice were subjected either to sham operation or underwent ligation of the right common carotid artery followed by hypoxia (8%) for 60 min. Animals were either administered sildenafil (10 mg/kg, i.p.) or vehicle 2 h after hypoxia. A subgroup of animals received multiple injections of 10 mg/kg daily on 5 consecutive days. Pups were either perfusion fixed at postnatal days 14 or 47 for immunohistochemical analysis, or brains were dissected 2, 6, 12, and 24 h after the end of hypoxia and analyzed for cGMP, pAkt, pGSK-3β, and β-catenin by means of ELISA or immunoblotting. In addition, behavioral studies using the wire hang test and elevated plus maze were conducted 21 and 38 days after HI injury. Results: Based on cresyl violet staining, single or multiple sildenafil injections did not reveal any differences in injury scoring compared to sham animals. However, cerebral levels of cGMP were altered after sildenafil therapy. Treatment significantly increased numbers of immature neurons, as indicated by doublecortin immunoreactivity in the ipsilateral subventricular zone and striatum. In addition, animals treated with sildenafil after HI insult demonstrated improved functional recovery. pAkt, pGSK-3β, and β-catenin levels vary after HI injury but additional sildenafil treatment had no impact on protein expression compared to the level of sham controls. Conclusions: Here, we report that treatment with sildenafil after HI insult did not improve histological brain injury scores. Nevertheless, our results suggest involvement of the cGMP and PI3K/Akt/GSK-3β signaling pathway with promotion of a neurogenic response and reduction of neurological deficits. In summary, sildenafil may have a role in promoting recovery from HI injury in the developing brain.
КОРИГУВАЛЬНИЙ ВПЛИВ ТІОТРИАЗОЛІНУ НА ТОКСИЧНІСТЬ І СТАН ПРО- ТА АНТИОКСИДАНТНОГО ГОМЕОСТАЗУ В ЩУРІВ ЗА УМОВ ТОКСИЧНОЇ ДІЇ НАНОХРОМУ ЦИТРАТУ
Authors: Sadogurska К. V. , Kosuba R. B. , Yaremiy І. М.
Published: March 2017

Мета роботи. Вивчити коригувальний вплив тіотриазоліну на загальну токсичність та параметри біохімічної детоксикації за дії токсичних доз нанохрому цитрату.Матеріали і методи. У гострому досліді на щурах досліджено вплив тіотриазоліну (100 мг/кг) на токсичність нанохрому цитрату (НХЦ) і стан про- та антиоксидантного гомеостазу на тлі одноразового введення сублетальних (DL0) та летальних (DL50, DL100) доз сполуки (3 мг/кг, 4,5 мг/кг, 5 мг/кг). В еритроцитах крові визначали вміст малонового альдегіду (МА), відновленого глутатіону (Г-SH) та активність каталази (КТ). У плазмі крові – загальну антиоксидантну активність (АОА), вміст окисно-модифікованих білків (ОМБ) та вільних SН-груп. У постядерних супернатантах гомогенатів печінки визначали вміст МА, Г-SH, ОМБ та активність КТ. Результати й обговорення. Введення тіотриазоліну з лікувальною метою на тлі сублетальних і летальних доз НХЦ значно зменшило загальні прояви отруєння, подовжило життя тварин. Якщо неліковані тварини гинули на 2–3 добу, то при дії тіотриазоліну – на 6–8 добу. При введенні токсичних доз НХЦ посилюються процеси вільнорадикального окиснення ліпідів і променів, знижується активність КТ, АОА плазми крові, вміст вільних SН-груп та відновленого Г-SH. Ефективнішою виявилася дія тіотріазоліну на тлі мінімально токсичної дози НХЦ (3 мг/кг) – порівняно з нелікованими тваринами вірогідно зросла АОА в плазмі крові без помітних змін вмісту SН-груп.Висновки. У гострому досліді на щурах на тлі токсичних доз нанохрому цитрату тривале введення тіотриазоліну зменшує прояви інтоксикації та летальність тварин. Тіотріазолін запобігає розвитку порушень оксидантно-антиоксидантного гомеостазу в організмі інтоксикованих тварин, однак на тлі летальних доз нанохрому цитрату одноразове введення тіотриазоліну малоефективне.
ДОСЛІДЖЕННЯ СТАБІЛЬНОСТІ СУПОЗИТОРІЇВ «ФІТОПРОСТ» У ПРОЦЕСІ ЗБЕРІГАННЯ
Authors: Grytsenko V. I. , Ruban O. A. , Gubar S. M.
Published: March 2017

Мета роботи. Дослідження стабільності супозиторіїв «Фітопрост» у процесі зберігання.Матеріали і методи. Об’єктами досліджень стали супозиторії «Фітопрост», що містять у своєму складі сухі рослинні екстракти плодів пальми Сабаль, кореня кропиви та насіння гарбуза, виготовлені на основі твердого жиру методом виливання. У процесі зберігання супозиторіїв за допомогою фізичних, фізико-хімічних, фармако-технологічних, мікробіологічних і аналітичних методів визначали такі показники відповідно до вимог Державної Фармакопеї України (ДФУ): зовнішній вигляд, середню масу, час розпадання, температуру плавлення, рН, кількісний вміст суми стеринів, мікробіологічну чистоту.Результати й обговорення. Результати проведених досліджень показали, що супозиторії є стабільними при зберіганні у сухому, захищеному від світла місці при кімнатній температурі – протягом одного року, в сухому, захищеному від світла, прохолодному місці – протягом 2 років.Висновки. Проведено дослідження стабільності ректальних супозиторіїв «Фітопрост» для лікування захворювань передміхурової залози в процесі зберігання. Експериментально доведено, що всі показники якості препарату відповідають вимогам, розробленим проектом методик контролю якості. Встановлено режим зберігання супозиторіїв «Фітопрост» – у сухому темному прохолодному місці протягом 2 років.
ІНСТИТУЦІЙНИЙ ВИМІР МІЖНАРОДНОГО ФАРМАЦЕВТИЧНОГО САМОРЕГУЛЮВАННЯ
Authors: Hromovyk B. P. , Pankevych O. B.
Published: March 2017

Мета роботи. Дослідження інституційних засад саморегулювання фармацевтичної практики (СР ФП) у міжнародному аспекті.Матеріали і методи. Наукові публікації, що стосуються саморегулювання, офіційні сайти міжнародних фармацевтичних асоціацій та методологія інституційного виміру. Результати й обговорення. За даними літературних джерел виявлено історичні передумови становлення СР ФП. Шляхом вивчення інституційних засад СР ФП у міжнародному аспекті встановлено, що майже третина країн, професійні організації яких є членами Міжнародної фармацевтичної федерації (МФФ), представляла Європу. Показано, що трохи більше половини членів ООН через професійні спілки є країнами-членами МФФ, при тому дві третіх європейських країн-членів ООН є членами МФФ. На підставі порівняльного дослідження структури членів МФФ, Фармацевтичної групи Європейського Союзу (ФГЄС) і Європейської асоціації лікарняних фармацевтів (ЄАЛФ) виявлено, що загалом у трьох досліджуваних асоціаціях присутні 94 фармацевтичні організації із 39 держав Європи. Поряд з цим у кожній фармацевтичній асоціації членами є фармацевтичні товариства двох третіх країн і лише чотири професійні організації є членами водночас трьох фармацевтичних асоціацій, а саме: Фармацевтична палата Македонії, Хорватське фармацевтичне товариство, Фармацевтичне товариство Федерації Боснії і Герцеговини та Турецька асоціація фармацевтів. Дані інституційного виміру показують суттєво низьку участь у діяльності міжнародних асоціацій українських фармацевтичних товариств. При цьому, за умови приведення статутних документів до вимог конкретної асоціації, відкрито їх доступ не лише до МФФ (Україна – член ООН і ВООЗ), а й до ФГЄС (наша держава – член Європейської асоціації вільної торгівлі) та ЄАЛФ (Україна – член Ради Європи).Висновки. Отримані результати показують різний рівень членства в трьох міжнародних фармацевтичних асоціаціях (МФФ, ФГЄС і ЄАЛФ) як держав, так й окремих фармацевтичних товариств, а також надзвичайно низьку участь українських фармацевтичних товариств у СР ФП у міжнародному аспекті.