bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutionalization of Islam in Secular Europe: The Influence of State–Religion Relations on Anti‐Muslim Attitudes
Authors: Kaya Serdar
Published: March 2019

This study examines church–state relations in Europe, and analyzes their influence on anti‐immigrant attitudes. The literature explains this relationship primarily with religious demographics, or state privileges for the majority faith. Alternately, this study focuses on the status of the majority religion. It argues that, in countries with a national church, citizens are more likely to consider the institutionalization of a new religion to be occurring at the expense of the national heritage, and react negatively. To test that hypothesis, the study focuses on Muslim immigrants in Europe, and builds an index that gauges the extent to which European states institutionalize Islam. Then, employing multilevel regression analysis, it investigates how the institutionalization of Islam influences anti‐Muslim prejudice in different contexts of church–state regimes. Individual‐level data come from the latest wave of the European Values Study, and cover 31 countries. Findings indicate that, in European countries with a national church, institutionalization of Islam increases anti‐Muslim prejudice. In countries without a national church, however, institutionalization leads to tolerance. These results confirm the continuing relevance of religion on the national level in Europe, despite the decline in individual religiosity.
Immune response of pearl oysters to stress and diseases
Authors: Adzigbli Linda , Hao Ruijuan , Jiao Yu , Deng Yuewen , Du Xiaodong , Wang Qingheng , Huang Ronglian
Published: March 2019

Pearl oysters are found in the marine ecosystem. Due to their frequent exposure to microbial pathogens and environmental perturbations, they have developed a multifaceted innate immune system with differentially expressed immune‐related genes in response to a range of stress via vast coordinated immune reactions, such as immune recognition, signal transduction, synthesis of antimicrobial peptides, encapsulation and phagocytosis of the circulating haemocytes. The species are farmed to produce pearls. With the increasing adoption of aquaculture techniques in pearl production, there is the need to understand their culture environment and their immune response mechanisms. Multi‐omic studies have documented responses to nuclei insertion operation, diseases and various environmental conditions in Pinctada fucata martensii (Dunker, 1880), Pinctada maxima (Jameson, 1901), Pinctada margaritifera and Pteria penguin (Roding, 1798). Among the various stressors, nuclei insertion operation has been identified as a prevailing factor modifying gene expression. Other factors include life stage, air exposure, temperature, salinity, metals and organic contaminants. This manuscript details the response mechanism of these pearl oysters to the various stressors.
Arabidopsis seedlings display a remarkable resilience under severe mineral starvation using their metabolic plasticity to remain self‐sufficient for weeks
Authors: Réthoré Elise , d'Andrea Sabine , Benamar Abdelilah , Cukier Caroline , Tolleter Dimitri , Limami Anis M. , Avelange‐Macherel Marie‐Hélène , Macherel David
Published: March 2019

During the life cycle of plants, seedlings are considered vulnerable because they are at the interface between the highly stress tolerant seed embryos and the established plant, and must develop rapidly, often in a challenging environment, with limited access to nutrients and light. Using a simple experimental system, whereby the seedling stage of Arabidopsis is considerably prolonged by nutrient starvation, we analysed the physiology and metabolism of seedlings maintained in such conditions up to 4 weeks. Although development was arrested at the cotyledon stage, there was no sign of senescence and seedlings remained viable for weeks, yielding normal plants after transplantation. Photosynthetic activity compensated for respiratory carbon losses, and energy dissipation by photorespiration and alternative oxidase appeared important. Photosynthates were essentially stored as organic acids, while the pool of free amino acids remained stable. Seedlings lost the capacity to store lipids in cytosolic lipid droplets, but developed large plastoglobuli. Arabidopsis seedlings arrested in their development because of mineral starvation displayed therefore a remarkable resilience, using their metabolic and physiological plasticity to maintain a steady state for weeks, allowing resumption of development when favourable conditions ensue.
Structural diversification during glucosinolate breakdown: mechanisms of thiocyanate, epithionitrile and simple nitrile formation
Authors: Eisenschmidt‐Bönn Daniela , Schneegans Nicola , Backenköhler Anita , Wittstock Ute , Brandt Wolfgang
Published: March 2019

Secondary metabolism is characterized by an impressive structural diversity. Here, we have addressed the mechanisms underlying structural diversification upon damage‐induced activation of glucosinolates, a group of thioglucosides found in the Brassicales. The classical pathway of glucosinolate activation involves myrosinase‐catalyzed hydrolysis and rearrangement of the aglucone to an isothiocyanate. Plants of the Brassicaceae possess specifier proteins, i.e. non‐heme iron proteins that promote the formation of alternative products by interfering with this reaction through unknown mechanisms. We have used structural information available for the thiocyanate‐forming protein from Thlaspi arvense (TaTFP), to test the impact of loops protruding at one side of its β‐propeller structure on product formation using the allylglucosinolate aglucone as substrate. In silico loop structure sampling and semiempirical quantum mechanical calculations identified a 3L2 loop conformation that enabled the Fe2+ cofactor to interact with the double bond of the allyl side chain. Only this arrangement enabled the formation of allylthiocyanate, a specific product of TaTFP. Simulation of 3,4‐epithiobutane nitrile formation, the second known product of TaTFP, required an alternative substrate docking arrangement in which Fe2+ interacts with the aglucone thiolate. In agreement with these results, substitution of 3L2 amino acid residues involved in the conformational change as well as exchange of critical amino acid residues of neighboring loops affected the allylthiocyanate versus epithionitrile proportion obtained upon myrosinase‐catalyzed allylglucosinolate hydrolysis in the presence of TaTFP in vitro. Based on these insights, we propose that specifier proteins are catalysts that might be classified as Fe2+‐dependent lyases.
An Experimental Investigation of Adiabatic Film Cooling Effectiveness and Heat Transfer Coefficient on a Transonic Squealer Tip
Authors: Saul Andrew J. , Ireland Peter T. , Coull John D. , Wong Tsun Holt , Li Haidong , Romero Eduardo
Published: March 2019

The effect of film cooling on a transonic squealer tip has been examined in a high speed linear cascade, which operates at engine-realistic Mach and Reynolds numbers. Tests have been performed on two uncooled tip geometries with differing pressure side rim edge radii, and a cooled tip matching one of the uncooled cases. The pressure sensitive paint technique has been used to measure adiabatic film cooling effectiveness on the blade tip at a range of tip gaps and coolant mass flow rates. Complementary tip heat transfer coefficients have been measured using transient infrared thermography, and the effects of the coolant film on the tip heat transfer and engine heat flux were examined. The uncooled data show that the tip heat transfer coefficient distribution is governed by the nature of flow reattachments and impingements. The squealer tip can be broken down into three regions, each exhibiting a distinct response to a change in the tip gap, depending on the local behavior of the overtip leakage flow. Complementary computational fluid dynamics (CFD) shows that the addition of casing motion causes no change in the flow over the pressure side rim. Injected coolant interacts with the overtip leakage flow, which can locally enhance the tip heat transfer coefficient. The film effectiveness is dependent on both the coolant mass flow rate and tip clearance. At increased coolant mass flow, areas of high film effectiveness on the pressure side rim coincide strongly with a net heat flux reduction and in the subsonic tip region with low heat transfer coefficient.
Modeling and Prediction of Residual Stresses in Additive Layer Manufacturing by Microplasma Transferred Arc Process Using Finite Element Simulation
Authors: Nikam Sagar H. , Jain N. K.
Published: March 2019

Prediction of residual stresses induced by any additive layer manufacturing process greatly helps in preventing thermal cracking and distortion formed in the substrate and deposition material. This paper presents the development of a model for the prediction of residual stresses using three-dimensional finite element simulation (3D-FES) and their experimental validation in a single-track and double-track deposition of Ti-6Al-4V powder on AISI 4130 substrate by the microplasma transferred arc (µ-PTA) powder deposition process. It involved 3D-FES of the temperature distribution and thermal cycles that were validated experimentally using three K-type thermocouples mounted along the deposition direction. Temperature distribution, thermal cycles, and residual stresses are predicted in terms of the µ-PTA process parameters and temperature-dependent properties of substrate and deposition materials. Influence of a number of deposition tracks on the residual stresses is also studied. Results reveal that (i) tensile residual stress is higher at the bonding between the deposition and substrate and attains a minimum value at the midpoint of a deposition track; (ii) maximum tensile residual stress occurs in the substrate material at its interface with deposition track. This primarily causes distortion and thermal cracks; (iii) maximum compressive residual stress occurs approximately at mid-height of the substrate material; and (iv) deposition of a subsequent track relieves tensile residual stress induced by the previously deposited track.
A Gouge-Free Tool Axis Reorientation Method for Kinematics Compliant Avoidance of Singularity in 5-Axis Machining
Authors: Sun Shuoxue , Sun Yuwen , Lee Yuan-Shin
Published: March 2019

When a cutter traverses a region local to the singularity in 5-axis machining, the stability of machine tool motion may be violated and inevitably lead to a reduction in machining quality and accuracy. In this paper, the underlying cause of the singular machine behaviors is first investigated by differentiating tool path motions, on the basis of the tool path motion expressions in part and machine coordinate systems. A further investigation indicates abrupt kinematic changes to be inevitable when the rotary axes approach a singularity. To eliminate such possible singular risks in 5-axis machining, a local tool path modification method is proposed by adjusting the two rotary axes out of a singular configuration. The critical kinematics smoothing and the consequent gouging concerns resulting from reorientation are comprehensively incorporated in the process of singularity avoidance, by means of a novel tool orientation optimization model. Specifically, the algorithm starts with the determination of an appropriate adjustment range in a simple yet effective manner, and then the primary rotary axis is adjusted in a constrained region away from zero, so as to avoid singularity. After that, the second rotary axis is accordingly adjusted, with no gouging requirements being violated. In this way, singularity problems in 5-axis machining are solved, and both the machine axes kinematics and surface gouging errors are under control. Machining simulation and laboratory experiments were conducted to validate the effectiveness of the proposed method.
What’s in a Name: Why Do We Call a Bouncy Ball Bouncy?
Authors: Sullivan Kelley D.
Published: March 2019

The ubiquitous bouncy ball, or “superball,” is an engaging child’s toy that has endured for more than 50 years. But what makes a bouncy ball so uniquely suited to its name? Steel balls, for example, are more highly elastic than are butadiene bouncy balls. Yet it is butadiene balls, and not steel balls, that appear in toy stores and vending machines across the globe. I present an experiment that uses the physics of inelastic collisions to provide compelling evidence for awarding butadiene balls the moniker “bouncy.” In this experiment, students mimic the everyday use of bouncy balls by dropping steel and butadiene balls onto different surfaces from a modest range of heights. By analyzing videos of the bouncing balls, the students determine the coefficient of restitution and the energy loss—a key concept related to inelastic collisions—for each bounce of a ball. Having students capture videos using their own smartphone ensures that the students are comfortable with data taking and engaged in the activity. The data analysis uses simple yet powerful open-source video tracking software that further ensures that the experiment is accessible and low cost. The surprising results of this inquiry highlight the need to consider the material properties of both objects (ball and surface) when analyzing inelastic collisions. This important detail has been acknowledged yet not explicitly explored in other published experiments on the coefficient of restitution of bouncing balls.
A Proposal for Discussing the Electrical Efficiency Concept
Authors: de Oliveira Cruz Frederico Alan , dos Santos Léo Rodrigues M. , Carvalho Paulo Simeão
Published: March 2019

Within the new world perspective, it is expected that the school, as a formal education space, will be able to provide students with the basic information regarding human knowledge accumulated over the years, and also help them be capable of understanding various scientific and technological issues present today. In the specific case of knowledge in physics, one of the topics of great relevance is the generation and consequent use of electric energy. For developing scientific literacy and also to give an overall view of this content to the students, teachers must be able to present to them information related to generation, transformation, transfer, and the effective performance of the apparatus that makes use of this energy. This topic, however, is sometimes reduced to the representation of electric circuits, a lecture about Ohm’s law, and talking about the Joule effect in conductors. Real discussions concerning daily contexts or phenomena, such as motors in this case, transformations of electric-to-internal and electric-to-mechanical energies and mechanical (fan)-to-mechanical (wind) transfer of energy, are full of potential for a conceptual learning of physics.
Thomas Young and the Rosetta Stone
Authors: Manos Harry
Published: March 2019

Thomas Young (1773–1829) is best known in the physics community for his double-slit experiment demonstrating the wave property of light and for his work on the tensile properties of solids (Young’s modulus). His reputation as a physicist was built almost entirely upon a short, three-year period (1801–1803) of intense work as an instructor in physics and philosophy at the Royal Institution. The culmination of his work at the Royal Institution is described in A Course in Lectures on Natural Philosophy and Mechanical Arts (1807), a two-volume set containing a wide diversity of topics, including his double-slit experiments. Physics teachers and their students should be aware that Thomas Young’s contributions went far beyond these two accomplishments. Little known is that, despite having a reputation as a physicist, Young never took degrees in natural philosophy (physics). He studied to become a physician by attending prestigious medical schools in London, Edinburgh, and Göttingen. To become certified as a physician, he completed a bachelor’s and doctorate degrees at Cambridge University in physic (medicine).
Augmenting the fine beam tube: From hybrid measurements to magnetic field visualization
Authors: Bodensiek Oliver , Sonntag Dörte , Wendorff Nils , Albuquerque Georgia , Magnor Marcus
Published: March 2019

Since the emergence of augmented reality (AR), it has been a constant subject of educational research, as it can improve conceptual understanding and generally promote learning. In addition, a motivational effect and improved interaction and collaboration through AR were observed. Recently, AR technologies have taken a major leap forward in development, such that head-mounted devices or smartglasses in particular are now finding their first applications in STEM education, especially in experiments. In line with these developments, we here present an AR experiment in electrodynamics for undergraduate laboratory courses in physics using real-time physical data from and virtual tools on mobile devices to both analyze and visualize physical phenomena.
A primer on some celestial geometry
Authors: Heafner Joe
Published: March 2019

In anticipation of AstroNotes articles planned for the near future, a short primer on certain fundamental aspects of the celestial sphere and its associated geometry is in order. While astronomers proper and longtime astronomy faculty will already be familiar with this topic, newer faculty and perhaps those from other disciplines, but teaching astronomy for the first time, may find it helpful. The geometry of planes, spheres, and great circles figures heavily in celestial geometry.
Current models of speech motor control: A control-theoretic overview of architectures and properties
Authors: Parrell Benjamin , Lammert Adam C. , Ciccarelli Gregory , Quatieri Thomas F.
Published: March 2019

This paper reviews the current state of several formal models of speech motor control, with particular focus on the low-level control of the speech articulators. Further development of speech motor control models may be aided by a comparison of model attributes. The review builds an understanding of existing models from first principles, before moving into a discussion of several models, showing how each is constructed out of the same basic domain-general ideas and components—e.g., generalized feedforward, feedback, and model predictive components. This approach allows for direct comparisons to be made in terms of where the models differ, and their points of agreement. Substantial differences among models can be observed in their use of feedforward control, process of estimating system state, and method of incorporating feedback signals into control. However, many commonalities exist among the models in terms of their reliance on higher-level motor planning, use of feedback signals, lack of time-variant adaptation, and focus on kinematic aspects of control and biomechanics. Ongoing research bridging hybrid feedforward/feedback pathways with forward dynamic control, as well as feedback/internal model-based state estimation, is discussed.
Comment on “Giant electromechanical coupling of relaxor ferroelectrics controlled by polar nanoregion vibrations”
Authors: Gehring P. M. , Xu Zhijun , Stock C. , Xu Guangyong , Parshall D. , Harriger L. , Gehring C. A. , Li Xiaobing , Luo Haosu
Published: March 2019

Phantom indications of phonon anticrossing in relaxor ferroelectrics can arise via an inelastic double-scattering process.
Characterization of β-Lactamase Content of Ceftazidime-Resistant Pathogens Recovered during the Pathogen-Directed Phase 3 REPRISE Trial for Ceftazidime-Avibactam: Correlation of Efficacy against β-Lactamase Producers
Authors: Mendes Rodrigo E. , Castanheira Mariana , Woosley Leah N. , Stone Gregory G. , Bradford Patricia A. , Flamm Robert K.
Published: March 2019

REPRISE was a pathogen-directed (ceftazidime-resistant) phase 3 prospective, open-label, randomized, multicenter trial that evaluated the efficacy, safety, and tolerability of ceftazidime-avibactam (CAZ-AVI) and best available therapy (BAT) in the treatment of hospitalized adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). This study characterized the β-lactamase content of ceftazidime-resistant
Enterobacteriaceae
and
Pseudomonas aeruginosa
recovered during the baseline visits of patients enrolled in REPRISE.
Microcin PDI Inhibits Antibiotic-Resistant Strains of Escherichia coli and
Shigella
through a Mechanism of Membrane Disruption and Protection by Homotrimer Self-Immunity
Authors: Lu Shao-Yeh , Graça Telmo , Avillan Johannetsy J. , Zhao Zhe , Call Douglas R.
Published: March 2019

Microcins represent potential alternatives to conventional antibiotics for human and veterinary medicine. For them to be applied in this manner, however, we need to better understand their spectrum of activity, how these proteins interact with susceptible cells, and how producer cells are protected against the antimicrobial properties of the microcins. For microcin PDI (MccPDI), we report that the spectrum of activity likely includes most
E. coli
strains due to a conserved binding motif found on an outer membrane protein.
Shigella
has this motif as well and is susceptible to MccPDI killing via damage to the bacterial membrane. Receptor specificity suggests that these proteins could be used without causing large-scale disruptions to a microbiota, but this also increases the likelihood that resistance can evolve via random mutations. As with conventional antibiotics, good stewardship will be needed to preserve the efficacy of microcins should they be deployed for clinical use.
Lipoproteins and Their Trafficking to the Outer Membrane
Authors: Grabowicz Marcin
Published: March 2019

Lipoproteins are produced by both Gram-positive and Gram-negative bacteria. Once secreted, lipoproteins are quickly acylated, anchoring them into the plasma membrane. Recent work has shown that Gram-positive bacteria are able to generate considerable diversity in the acylation of their lipoproteins, though the mechanisms involved are only just beginning to emerge. In Gram-negative organisms, most lipoproteins are subsequently trafficked to the outer membrane (OM). Lipoprotein trafficking is an essential pathway in these bacteria. At least one OM lipoprotein component is required by each of the essential machines that assemble the OM (such as the Bam and Lpt machines) and build the peptidoglycan cell wall (Lpo-penicillin-binding protein complexes). The Lol pathway has been the paradigm for OM lipoprotein trafficking: a complex of LolCDE extracts lipoproteins from the plasma membrane, LolA shuttles them through the periplasmic space, and LolB anchors them into the OM. The peptide signals responsible for OM-targeting via LolCDE have long been known for
Escherichia coli
. Remarkably, production of novel lipoprotein acyl forms in
E. coli
has reinforced the idea that lipid signals also contribute to OM targeting via LolCDE. Moreover, recent work has shown that lipoprotein trafficking can occur in
E. coli
without either LolA or LolB. Therefore, current evidence suggests that at least one additional, LolAB-independent route for OM lipoprotein trafficking exists. This chapter reviews the posttranslocation modifications of all lipoproteins, with a focus on the trafficking of lipoproteins to the OM of Gram-negative bacteria.
An Immunodominant and Conserved B-Cell Epitope in the Envelope of Simian Foamy Virus Recognized by Humans Infected with Zoonotic Strains from Apes
Authors: Lambert Caroline , Batalie Damien , Montange Thomas , Betsem Edouard , Mouinga-Ondeme Augustin , Njouom Richard , Gessain Antoine , Buseyne Florence
Published: March 2019

Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18
LP
, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.
Mantle cell lymphoma presenting with exaggerated skin reaction to insect bites
Authors: Darji Kavita , Bahram-ahi Emily , Dhandha Maulik , Guo Mary
Published: March 2019

We present the case of a 62-year-old African-American woman with medical history of hypertension and hyperlipidaemia who presented to dermatology clinic for ‘bug bites’. Skin examination showed resolving bullae on the shins and postinflammatory pigment changes. Histopathology showed eosinophilic spongiosis and direct immunofluorescence (DIF) was negative for IgG, IgM, IgA and C3. After returning to clinic with recurrent severe bullous eruptions, the patient presented with anaemia, lymphocytosis, posterior cervical lymphadenopathy and weight loss. An exuberant bite reaction in the setting of lymphoma was suspected. Further workup with haematology revealed elevated IgG level and total protein levels. Flow cytometry showed a B cell lymphoma subtype. Extensive imaging was positive for diffuse lymphadenopathy, with accompanying evidence of Ebstein-Barr virus infection. Our case highlights the importance of considering exuberant arthropod bite reaction in the setting of undiagnosed lymphoma in a patient with bullous eruption and negative DIF.
Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world
Authors: Dailey George , Bajaj Harpreet S , Dex Terry , Groleau Melanie , Stager William , Vinik Aaron
Published: March 2019

Objective

To assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW).

Research design and methods

Post hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O (NCT02058147; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L (NCT02058160; inadequately controlled patients on basal insulin; NA, n=196; RoW, n=535). Efficacy outcomes were: change from baseline to Week 30 in glycated hemoglobin (HbA1c), postprandial glucose (PPG), PPG excursions, fasting plasma glucose (FPG) and body weight; proportion of patients achieving HbA1c <42 mmol/mol (<7.0%); proportion of patients achieving composite endpoint: HbA1c <42 mmol/mol (<7.0%), no weight gain or symptomatic hypoglycemia (blood glucose ≤3.9 mmol/L (≤70 mg/dL)). Safety endpoints included incidence of documented symptomatic hypoglycemia and gastrointestinal (GI) adverse events.

Results

Significantly larger reductions (p≤0.003) in HbA1c from baseline to Week 30 were achieved with iGlarLixi, compared with iGlar or lixisenatide, in NA and RoW patients in LixiLan-O (iGlarLixi vs iGlar: −0.31 and −0.29, respectively; iGlarLixi vs lixisenatide: −0.84 and −0.69, respectively) and in LixiLan-L (iGlarLixi vs iGlar: −0.5 and −0.51, respectively). Documented symptomatic hypoglycemia was similar between NA and RoW patients. iGlarLixi resulted in significant weight benefits versus iGlar (change from baseline –1.58 and –1.29 kg for NA and RoW patients, respectively; p<0.001). GI adverse events were similar for iGlarLixi and iGlar, but significantly higher for lixisenatide.

Conclusions

iGlarLixi improved glycemic parameters versus iGlar or lixisenatide alone in both NA and RoW patients, with beneficial weight effects versus iGlar. iGlarLixi treatment responses, hypoglycemia risk and GI adverse events in NA patients were comparable with patients in the RoW.

Trial registry

Clinicaltrials.govNCT02058147andNCT02058160.-
Eligibility of patients with type 2 diabetes for sodium–glucose cotransporter 2 inhibitor cardiovascular outcomes trials: a global perspective from the DISCOVER study
Authors: Pintat Stéphane , Fenici Peter , Hammar Niklas , Ji Linong , Khunti Kamlesh , Medina Jesús , Tang Fengming , Wittbrodt Eric , Surmont Filip
Published: March 2019

Objective

To assess the eligibility of patients participating in DISCOVER (a 3-year, prospective, observational study program of 15 992 patients with type 2 diabetes [T2D] initiating a second-line glucose-lowering therapy across 38 countries) for four cardiovascular outcomes trials (CVOTs) of sodium–glucose cotransporter 2 inhibitors (CANagliflozin cardioVascular Assessment Study [CANVAS], Dapagliflozin effect on CardiovascuLAR Events trial [DECLARE-TIMI 58], EMPAgliflozin cardiovascular OUTCOME event trial [EMPA-REG OUTCOME], and eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial [VERTIS-CV]).

Research design and methods

In this cross-sectional analysis, baseline characteristics of DISCOVER patients were compared with the inclusion and exclusion criteria of the CVOTs to assess patient eligibility, overall and in four regions (Asia-Pacific, Europe, Latin America, and Middle East and Africa).

Results

Overall, 11 385 patients (71.2%) had sufficient data for the analysis; 56.1% were men. The mean age and time since T2D diagnosis were 57.4 and 5.6 years, respectively. The mean glycated hemoglobin level was 8.3%. DISCOVER patients were younger, and fewer had a history of cardiovascular disease, than those enrolled in the CVOTs. Eligibility varied across the CVOTs; the proportion of eligible DISCOVER patients was highest for DECLARE-TIMI 58 (40.5%), followed by CANVAS (19.9%), VERTIS-CV (7.2%), and EMPA-REG OUTCOME (7.1%); 54.6% of patients were not eligible for any CVOT. Eligibility for each CVOT varied across regions, which was explained by the differing proportions of patients with established cardiovascular disease.

Conclusions

In a large, international population of patients with T2D initiating a second-line glucose-lowering therapy, DECLARE-TIMI 58 was the most inclusive CVOT, suggesting that its study population will be more representative of patients encountered in routine clinical practice than those of CANVAS, EMPA-REG OUTCOME, and VERTIS-CV.
Islwyn Thomas
Authors: Crispin Sheila , Grove‐White Dai ,   with contributions from colleagues and friends
Published: March 2019

His endeavour in life was to find contentment and happiness. Being defined as a pillar of the community brought him a sense of meaning and purpose. He was kind to others and was a true gentleman.
Scattering of high-energy cosmic ray electrons off the Dark Matter
Authors: Beylin V. , Bezuglov M. , Kuksa V. , Tretyakov E. , Yagozinskaya A.
Published: March 2019

High-energy cosmic ray electrons interaction with Dark Matter particles is considered. In particular, a weakening of energy spectrum of cosmic electrons is predicted resulting from inelastic electron scattering on hyperpions in the hypercolor extension of the Standard Model. Corresponding cross-section and angular distributions of secondary neutrino are calculated and studied. The number of events with these neutrinos at IceTop is also estimated.
From the Potential of the Mean Force to a Quasiparticle’s Effective Potential in Narrow Ion Channels
Authors: Barabash M. L. , Gibby W. A. T. , Guardiani C. , Luchinsky D. G. , McClintock P. V. E.
Published: March 2019

We consider the selective permeation of ions through narrow water-filled channels in the presence of strong interaction between the ions. These interactions lead to highly correlated ionic motion, which can conveniently be described via the concept of a quasiparticle. Here, we connect the quasiparticle’s effective potential and the multi-ion potential of the mean force, found through molecular dynamics simulations, and we validate the method on an analytical toy model of the KcsA channel. Possible future applications of the method to the connection between molecular dynamical calculations and the experimentally measured current-voltage and current-concentration characteristics of the channel are discussed.
A Data Analytic Approach of Job Satisfaction: A Case Study on Airline Industry
Authors: Kalawilapathirage Hansani , Omisakin Olufemi , Zeidan Susan
Published: March 2019

Intense competition has made it critical for airlines to retain its highly capable staff by ensuring the highest job satisfaction of its employees. This competition has resulted from the emergence of budget airlines focussed on a niche market. To provide a differentiated passenger experience whilst flying with airlines, the management should ensure that all the staff, including ground level and cabin crew, who are the initial contact point with customers are highly satisfied in terms of their job roles. The study evaluates human resource (HR) factors affecting job satisfaction with a given (anonymous) airline. A detailed study and analysis of major factors contributing to job satisfaction in the said airline was carried out. In analysing the relationship and current level of job satisfaction, the study uses a quantitative approach, with primary data obtained from questionnaires completed by employees in one of the airlines. Further, the study has identified independent variables as being financial rewards and recognition, training and development, and work environment. Statistical tools, such as correlation and regression analysis, are used to evaluate the responses from questionnaires and to provide significance of the independent variables contributing to job satisfaction.
The quantum geometric tensor from generating functions
Authors: Alvarez-Jimenez Javier , Vergara J. David
Published: March 2019

We introduce a new method to compute the Quantum Geometric Tensor, this procedure allows us to compute the Quantum Information Metric and the Berry curvature perturbatively for a theory with an arbitrary interaction Hamiltonian. The calculation uses the generating function method, and it is illustrated with the harmonic oscillator with a linear and a quartic perturbation.
A Novel Resistive Memory-based Process-in-memory Architecture for Efficient Logic and Add Operations
Authors: Li Taozhong , Wang Qin , Zhu Yongxin , Jiang Jianfei , He Guanghui , Jin Jing , Mao Zhigang , Jing Naifeng
Published: March 2019

The coming era of
big data
revives the Processing-in-memory (PIM) architecture to relieve the
memory wall
problem that embarrasses the modern computing system. However, most existing PIM designs just put computing units closer to memory, rather than a complete integration of them due to their incompatibility in CMOS manufacturing. Fortunately, the emerging Resistive-RAM (ReRAM) offers new hope to this dilemma owing to its inherent memory and computing capability using the same device. In this article, we propose a ReRAM memory structure with efficient PIM capability of both logic and add operations. It first leverages non-linearity to suppress
sneak current
and thus sustains high memory density. Using a differential bit cell, it also enables efficient processing of arbitrary logic functions using the same memory cells with non-destructive operations. Then, a novel PIM adder is proposed, which customizes a sneak current path as the carry-chain for fast carry propagation and improves adder performance significantly. In the experiment, the proposed PIM demonstrates higher efficiency in both computing area and performance for logic and addition, which greatly increases the ReRAM PIM applicability for future computable architectures.
Cancer Treatment in the Genomic Era
Authors: Doherty Gary J. , Petruzzelli Michele , Beddowes Emma , Ahmad Saif S. , Caldas Carlos , Gilbertson Richard J.
Published: March 2019

The complexity of human cancer underlies its devastating clinical consequences. Drugs designed to target the genetic alterations that drive cancer have improved the outcome for many patients, but not the majority of them. Here, we review the genomic landscape of cancer, how genomic data can provide much more than a sum of its parts, and the approaches developed to identify and validate genomic alterations with potential therapeutic value. We highlight notable successes and pitfalls in predicting the value of potential therapeutic targets and discuss the use of multi-omic data to better understand cancer dependencies and drug sensitivity. We discuss how integrated approaches to collecting, curating, and sharing these large data sets might improve the identification and prioritization of cancer vulnerabilities as well as patient stratification within clinical trials. Finally, we outline how future approaches might improve the efficiency and speed of translating genomic data into clinically effective therapies and how the use of unbiased genome-wide information can identify novel predictive biomarkers that can be either simple or complex.
An NMR View of Protein Dynamics in Health and Disease
Authors: Sekhar Ashok , Kay Lewis E.
Published: March 2019

Biological molecules are often highly dynamic, and this flexibility can be critical for function. The large range of sampled timescales and the fact that many of the conformers that are continually explored are only transiently formed and sparsely populated challenge current biophysical approaches. Solution nuclear magnetic resonance (NMR) spectroscopy has emerged as a powerful method for characterizing biomolecular dynamics in detail, even in cases where excursions involve short-lived states. Here, we briefly review a number of NMR experiments for studies of biomolecular dynamics on the microsecond-to-second timescale and focus on applications to protein and nucleic acid systems that clearly illustrate the functional relevance of motion in both health and disease.
Thermodynamic Principles for the Design of Polymers for Drug Formulations
Authors: Fischlschweiger Michael , Enders Sabine
Published: March 2019

Polymers play an essential role in drug formulation and production of medical devices, implants, and diagnostics. Following drug discovery, an appropriate formulation is selected to enable drug delivery. This task can be exceedingly challenging owing to the large number of potential delivery methods and formulation and process variables that can interact in complex ways. This evolving solubility challenge has inspired an increasing emphasis on the developability of drug candidates in early discovery as well as various advanced drug solubilization strategies. Among the latter, formulation approaches that lead to prolonged drug supersaturation to maximize the driving force for sustained intestinal absorption of an oral product, or to allow sufficient time for injection after reconstitution of a parenteral lyophile formulation, have attracted increasing interest. Although several kinetic and thermodynamic components are involved in stabilizing amorphous dispersions, it is generally assumed that maximum physical stability, defined in terms of inhibition of drug crystallization, requires that the drug and excipient remain intimately mixed. Phase separation of the drug from its excipient may be the first step that ultimately leads to crystallization. We discuss the role of advanced thermodynamics using two examples: ASD and vitamin E–stabilized ultrahigh–molecular weight polyethylene implants.
Management of Persistent Air Leaks Using Endobronchial Autologous Blood Patch and Spigot Occlusion: A Multicentre Randomized Controlled Trial in China
Authors: Zhang Hai-tao , Xie Yong-hong , Gu Xing , Li Wang-ping , Zeng Yi-ming , Li Shi-yue , Liu Zhi-guang , Wang Hong-wu , Bai Chong , Jin Fa-guang
Published: March 2019

Background: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. Objective: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. Methods: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. Results: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. Conclusion: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.
Mentalization as Mediator between Adult Attachment and Interpersonal Distress
Authors: Hayden Markus C. , Müllauer Pia K. , Gaugeler Richard , Senft Birgit , Andreas Sylke
Published: March 2019

Background: The aim of this study was to investigate the mediating role of mentalization in the association between adult attachment and interpersonal problems. Methods: The sample consisted of 89 patients with different types of mental disorders who were at the beginning of treatment in one of two medical centers. Both mediational analysis and path analysis were used to test the model. Results: The proposed model revealed a good model fit. The data indicate that mentalization fully mediates the effect of attachment on interpersonal distress. Symptom severity proved to be a strong confounding variable that influenced all other variables and reduced existing effects. Conclusion: We conclude that both mentalization and symptom distress are key components in the association of adult attachment and interpersonal problems. Therefore, we recommend research on integrative psychotherapy concepts rather than unilateral approaches.
The Bone Markers Sclerostin, Osteoprotegerin, and Bone-Specific Alkaline Phosphatase Are Related to Insulin Resistance in Children and Adolescents, Independent of Their Association with Growth and Obesity
Authors: Stanik Juraj , Kratzsch Jürgen , Landgraf Kathrin , Vogel Mandy , Thiery Joachim , Kiess Wieland , Körner Antje
Published: March 2019

Background/Aims: Sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase (B-ALP), which are primarily related to bone metabolism, have been linked with insulin resistance in adults. We aimed to evaluate the association of these markers with growth, obesity, and parameters of insulin resistance in lean and obese children and adolescents. Methods: We measured sclerostin, osteoprotegerin, and B-ALP in fasting and oral glucose tolerance test (oGTT) serum samples from 1,325 children and adolescents, and during 24-h profiles and after exercise and glucose exposure in young adults. Results: In addition to the positive relationship with height standard deviation scores (SDS), sclerostin (r = 0.035, p < 0.001) and B-ALP (r = 0.06, p = 0.028) increased, whereas osteoprotegerin (r = –0.098, p < 0.001) decreased with BMI SDS. Furthermore, B-ALP correlated with fasting- and oGTT-derived markers of glucose and insulin metabolism suggestive of insulin resistance. To evaluate potential confounding diurnal variation of bone markers, we performed 24-h profiles. B-ALP and osteoprotegerin had lower night-time levels. Exercise acutely and transiently increased B-ALP and osteoprotegerin levels, but glucose ingestion had no effect. Conclusions: Besides their association with growth, sclerostin and osteoprotegerin levels are altered in childhood obesity. Particularly B-ALP was related to insulin resistance indices. Our findings accent the link between bone, growth, and insulin resistance.
Age-Dependent Electrocorticogram Dynamics and Epileptogenic Responsiveness in Rats Subjected to Prenatal Hypoxia
Authors: Kalinina Daria S. , Vasilev Dmitrii S. , Volnova Anna B. , Nalivaeva Natalia N. , Zhuravin Igor A.
Published: March 2019

Using electrocorticogram (ECoG) analysis, we compared age-related dynamics of general neuronal activity and convulsive epileptiform responsiveness induced by intracortical microinjections of 4-aminopyridine (4-AP) in control Wistar rats and those subjected to prenatal hypoxia (Hx; E14; 7% O2, 3 h). The studies were carried out in three age periods roughly corresponding to childhood (P20–27), adolescence (P30–45), and adulthood (P90–120). It was found that in the process of postnatal development of the control rats, the peak of the ECoG power spectrum density (PSD) of the theta rhythm during wakefulness shifted from the low to the higher frequency, while in the Hx rats this shift had the opposite direction. Moreover, the Hx rats had different frequency characteristics of the ECoG PSD and longer episodes of spike-and-wave discharges caused by 4-AP injections compared to the controls. The total ECoG PSD of slow-wave sleep (1–5 Hz) was also dramatically decreased in the process of development of the Hx rats. Such alterations in PSD could be explained by the changes in balance of the excitation and inhibition processes in the cortical networks. Analyzing protein levels of neurotransmitter transporters in the brain structures of the Hx rats, we found that the content of the glutamate transporter EAAT1 was higher in the parietal cortex in all age groups of Hx rats while in the hippocampus it decreased during postnatal development compared to controls. Furthermore, the content of the vesicular acetylcholine transporter in the parietal cortex, and of the inhibitory GABA transporter 1 in the hippocampus, was also affected by prenatal Hx. These data suggest that prenatal Hx results in a shift in the excitatory and inhibitory balance in the rat cortex towards excitation, making the rat’s brain more vulnerable to the effects of proconvulsant drugs and predisposing animals to epileptogenesis during postnatal life.
Are Preferred Scalp Locations for Alopecia Areata Patches a Clue to Neuronal Etiology?
Authors: Juhasz Margit , Mesinkovska Natasha Atanaskova
Published: March 2019

Background: Alopecia areata (AA) is an autoimmune disease causing hair loss in 2% of the population. Anecdotally, hair specialists report that patches localize to the scalp periphery. Changes in sensory innervation and/or scalp vasculature may play a role in the development and localization of alopecic patches. Objective: To evaluate the most common locations of initial alopecic scalp patches. Materials and Methods: A retrospective chart review, with comprehensive evaluation of clinical photographs, was conducted from July 2016 to June 2018 to include AA patients (n = 112). Clinical data was collected on gender, age, race, time until presentation at the clinic, and areas of hair loss on initial presentation. Results: The most common areas of initial AA patches in both females and males were the occiput (49 vs. 48.5%), parietal (46.9 vs. 21.2%), vertex (26.5 vs. 18.2%), and frontal (24.5 vs. 18.2%) regions; 26.8% of patients present with either alopecia totalis or universalis. Limitations: This is a single-center study with underrepresentation of minority races. Conclusion: AA patches most commonly present on the occiput of the scalp in both female and male patients. Cervical spine nerves C3 and C2 supply sensory innervation and the occipital artery supplies blood to this area.