bluuebunny/crossref_metadata_2025 huggingface dataset:
Stateless model checking of event-driven applications
Authors: Jensen Casper S. , Møller Anders , Raychev Veselin , Dimitrov Dimitar , Vechev Martin
Published: December 2015

Modern event-driven applications, such as, web pages and mobile apps, rely on asynchrony to ensure smooth end-user experience. Unfortunately, even though these applications are executed by a single event-loop thread, they can still exhibit nondeterministic behaviors depending on the execution order of interfering asynchronous events. As in classic shared-memory concurrency, this nondeterminism makes it challenging to discover errors that manifest only in specific schedules of events. In this work we propose the first stateless model checker for event-driven applications, called R4. Our algorithm systematically explores the nondeterminism in the application and concisely exposes its overall effect, which is useful for bug discovery. The algorithm builds on a combination of three key insights: (i) a dynamic partial order reduction (DPOR) technique for reducing the search space, tailored to the domain of event-driven applications, (ii) conflict-reversal bounding based on a hypothesis that most errors occur with a small number of event reorderings, and (iii) approximate replay of event sequences, which is critical for separating harmless from harmful nondeterminism. We instantiate R4 for the domain of client-side web applications and use it to analyze event interference in a number of real-world programs. The experimental results indicate that the precision and overall exploration capabilities of our system significantly exceed that of existing techniques.
Runtime pointer disambiguation
Authors: Alves Péricles , Gruber Fabian , Doerfert Johannes , Lamprineas Alexandros , Grosser Tobias , Rastello Fabrice , Pereira Fernando Magno Quintão
Published: December 2015

To optimize code effectively, compilers must deal with memory dependencies. However, the state-of-the-art heuristics available in the literature to track memory dependencies are inherently imprecise and computationally expensive. Consequently, the most advanced code transformations that compilers have today are ineffective when applied on real-world programs. The goal of this paper is to solve this conundrum through dynamic disambiguation of pointers. We provide different ways to determine at runtime when two memory locations can overlap. We then produce two versions of a code region: one that is aliasing-free - hence, easy to optimize - and another that is not. Our checks let us safely branch to the optimizable region. We have applied these ideas on Polly-LLVM, a loop optimizer built on top of the LLVM compilation infrastructure. Our experiments indicate that our method is precise, effective and useful: we can disambiguate every pair of pointer in the loop intensive Polybench benchmark suite. The result of this precision is code quality: the binaries we generate are 10% faster than those that Polly-LLVM produces without our optimization, at the -O3 optimization level of LLVM.
The chemical approach to typestate-oriented programming
Authors: Crafa Silvia , Padovani Luca
Published: December 2015

We study a novel approach to typestate-oriented programming based on the chemical metaphor: state and operations on objects are molecules of messages and state transformations are chemical reactions. This approach allows us to investigate typestate in an inherently concurrent setting, whereby objects can be accessed and modified concurrently by several processes, each potentially changing only part of their state. We introduce a simple behavioral type theory to express in a uniform way both the private and the public interfaces of objects, to describe and enforce structured object protocols consisting of possibilities, prohibitions, and obligations, and to control object sharing.
A Mathematical Model of a Direct Propane Fuel Cell
Authors: Khakdaman Hamidreza , Bourgault Yves , Ternan Marten
Published: December 2015

A rigorous mathematical model for direct propane fuel cells (DPFCs) was developed. Compared to previous models, it provides better values for the current density and the propane concentration at the exit from the anode. This is the first DPFC model to correctly account for proton transport based on the combination of the chemical potential gradient and the electrical potential gradient. The force per unit charge from the chemical potential gradient (concentration gradient) that pushes protons from the anode to the cathode is greater than that from the electrical potential gradient that pushes them in the opposite direction. By including the chemical potential gradient, we learn that the proton concentration gradient is really much different than that predicted using the previous models that neglected the chemical potential gradient. Also inclusion of the chemical potential gradient made this model the first one having an overpotential gradient (calculated from the electrical potential gradient) with the correct slope. That is important because the overpotential is exponentially related to the reaction rate (current density). The model described here provides a relationship between the conditions inside the fuel cell (proton concentration, overpotential) and its performance as measured externally by current density and propane concentration.
A Novel Statistical Approach for Brain MR Images Segmentation Based on Relaxation Times
Authors: Baselice Fabio , Ferraioli Giampaolo , Pascazio Vito
Published: December 2015

Brain tissue segmentation in Magnetic Resonance Imaging is useful for a wide range of applications. Classical approaches exploit the gray levels image and implement criteria for differentiating regions. Within this paper a novel approach for brain tissue joint segmentation and classification is presented. Starting from the estimation of proton density and relaxation times, we propose a novel method for identifying the optimal decision regions. The approach exploits the statistical distribution of the involved signals in the complex domain. The technique, compared to classical threshold based ones, is able to globally improve the classification rate. The effectiveness of the approach is evaluated on both simulated and real datasets.
Somatosensory and Brainstem Auditory Evoked Potentials Assessed between 4 and 7 Days after Severe Stroke Onset Predict Unfavorable Outcome
Authors: Zhang Yan , Su Ying Ying , Xiao Shu Ying , Liu Yi Fei
Published: December 2015

Our objective was to explore the best predictive timing of short-latency somatosensory evoked potentials (SLSEP) and brainstem auditory evoked potentials (BAEP) for unfavorable outcomes in patients with early stage severe stroke. One hundred fifty-six patients with acute severe supratentorial stroke were monitored according to SLSEP, BAEP, and the Glasgow Coma Scale (GCS) at 1–3 days and 4–7 days after the onset of stroke. All patients were followed up for outcomes at 6 months after onset using the modified Rankin Scale (mRS), with a score of 5-6 considered unfavorable. The predictive values of SLSEP, BAEP, and the GCS at 1–3 days were compared with 4–7 days after onset. Our results show that, according to the analysis of prognostic authenticity, the predictive values of SLSEP and BAEP at 4–7 days after stroke onset improved when compared with the values at 1–3 days for unfavorable outcomes. Most of the patients with change of worsening evoked potentials from 1–3 days to 4–7 days after onset had unfavorable outcomes. In conclusion, SLSEP and BAEP assessed at 4–7 days after onset predicted unfavorable outcomes for acute severe stroke patients. The worsening values of SLSEP and BAEP between 1–3 days and 4–7 days also present a prognostic value.
Relative Movements of Domains in Large Molecules of the Immune System
Authors: Schreiner Wolfgang , Karch Rudolf , Ribarics Reiner , Cibena Michael , Ilieva Nevena
Published: December 2015

Molecular dynamics was used to simulate large molecules of the immune system (major histocompatibility complex class I, presented epitope, T-cell receptor, and a CD8 coreceptor.) To characterize the relative orientation and movements of domains local coordinate systems (based on principal component analysis) were generated and directional cosines and Euler angles were computed. As a most interesting result, we found that the presence of the coreceptor seems to influence the dynamics within the protein complex, in particular the relative movements of the twoα-helices, Gα1and Gα2.
Zearalenone Inhibits Rat and Human 11β-Hydroxysteroid Dehydrogenase Type 2
Authors: Li Linxi , Wu Xiaolong , Guan Hongguo , Mao Baiping , Wang Huang , Yuan Xiaohuan , Chu Yanhui , Sun Jianliang , Ge Ren-Shan
Published: December 2015

Zearalenone is a mycotoxin produced byFusariumspp. 11β-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local level of active glucocorticoid, which has a broad range of physiological actions. In the present study, the potency of zearalenone was tested for the inhibition of HSD11B1 and HSD11B2 in rat and human tissues. Zearalenone showed potent inhibition of HSD11B2 with the half-maximal inhibitory concentration (IC50) calculated at 49.63 and 32.22 μM for the rat and human, respectively. Results showed that zearalenone competitively inhibited HSD11B2 when a steroid substrate was used. However, it served as an uncompetitive inhibitory factor when the cofactor NAD+was used. In contrast, the potency of zearalenone to inhibit both rat and human HSD11B1 was diminished, with the concentration of 100 μM causing almost no inhibitory effect on the isoform. In conclusion, we observed that zearalenone is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as kidney and placentas.
Random 2D Composites and the Generalized Method of Schwarz
Authors: Mityushev Vladimir
Published: December 2015

Two-phase composites with nonoverlapping inclusions randomly embedded in matrix are investigated. A straightforward approach is applied to estimate the effective properties of random 2D composites. First, deterministic boundary value problems are solved for all locations of inclusions, that is, for all events of the considered probabilistic spaceCby the generalized method of Schwarz. Second, the effective properties are calculated in analytical form and averaged overC. This method is related to the traditional method based on the average probabilistic values involving then-point correlation functions. However, we avoid computation of the correlation functions and compute their weighted moments of high orders by an indirect method which does not address the correlation functions. The effective properties are exactly expressed through these moments. It is proved that the generalized method of Schwarz converges for an arbitrary multiply connected doubly periodic domain and for an arbitrary contrast parameter. The proposed method yields an algorithm which can be applied with symbolic computations. The Torquato-Milton parameterζ1is exactly written for circular inclusions.
The Effect of Perioperative Ischemia and Reperfusion on Multiorgan Dysfunction following Abdominal Aortic Aneurysm Repair
Authors: Katseni Konstantina , Chalkias Athanasios , Kotsis Thomas , Dafnios Nikolaos , Arapoglou Vassilis , Kaparos Georgios , Logothetis Emmanuel , Iacovidou Nicoletta , Karvouni Eleni , Katsenis Konstantinos
Published: December 2015

Abdominal aortic aneurysms (AAAs) are relatively common and are potentially life-threatening medical problems. The aim of this review is to provide an overview of the effect of I/R injury on multiorgan failure following AAA repair. The PubMed, CINAHL, EMBASE, Medline, Cochrane Review, and Scopus databases were comprehensively searched for articles concerning the pathophysiology of I/R and its systemic effects. Cross-referencing was performed using the bibliographies from the articles obtained. Articles retrieved were restricted to those published in English. One of the most prominent characteristics of AAA open repair is the double physiological phenomenon of ischemia-reperfusion (I/R) that happens either at the time of clamping or following the aortic clamp removal. Ischemia-reperfusion injury causes significant pathophysiological disturbances to distant organs, increasing the possibility for postoperative multiorgan failure. Although tissue injury is mediated by diverse mechanisms, microvascular dysfunction seems to be the final outcome of I/R.
Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis
Authors: Leth Thomas , Wilkens Rune , Bonderup Ole K.
Published: December 2015

Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis.
Relationship between Clinical and Immunological Features of Thyroid Autoimmunity and Ophthalmopathy during Pregnancy
Authors: Wall Jack R. , Lahooti Hooshang , Hibbert Emily J. , Champion Bernard
Published: December 2015

Problem. Clinical features of Graves’ hyperthyroidism (GH) generally improve during pregnancy and rebound in the postpartum period. It is unclear whether the ophthalmopathy that is associated with GH and, less often, Hashimoto’s thyroiditis (HT) changes in parallel with the thyroid associated antibody reactions and clinical features or runs a different course.Method of Study. We retrospectively studied 19 patients with autoimmune thyroid disease over 22 pregnancies: 9 pregnancies with GH and 13 with HT. Ophthalmopathy was defined by NOSPECS class.Results. Thyroid peroxidase (TPO) and thyroglobulin (Tg) antibody titres decreased during pregnancy and rose in the postpartum period. During pregnancy, 5 patients with GH and 4 patients with HT developed mild ophthalmopathy and two patients with GH and HT developed new upper eyelid retraction (UER). In the postpartum period, eye scores improved in 3 patients with GH and 3 with HT, remained stable in two and 5 patients, respectively, and worsened in 2 patients with GH and one with HT.Conclusions. In patients with mild to moderate eye signs associated with GH and HT, the orbital and thyroid reactions ran different courses during pregnancy. Since no patient had severe ophthalmopathy, we cannot draw definitive conclusions from this preliminary study.
Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab
Authors: Broehm Cory Julian , Garbrecht Erika L. , Wood Jeff , Bocklage Therese
Published: December 2015

Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone.
Epidemiology, Etiology, and Prevention of Late IOL-Capsular Bag Complex Dislocation: Review of the Literature
Authors: Ascaso Francisco J. , Huerva Valentín , Grzybowski Andrzej
Published: December 2015

Posterior chamber intraocular lens (PC-IOL) subluxation is uncommon but represents one of the most serious complications following phacoemulsification. Late spontaneous IOL-capsular bag complex dislocation is defined as occurring three months or later following cataract surgery. Unlike early IOL dislocation, late spontaneous IOL dislocation is due to a progressive zonular dehiscence and contraction of the capsular bag many years what seemed to be uneventful surgery. In recent years, late in-the-bag IOL subluxation or dislocation has been reported with increasing frequency, having a cumulative risk of IOL dislocation following cataract extraction of 0.1% after 10 years and 1.7% after 25 years. A predisposition to zonular insufficiency and capsular contraction is identified in 90% of reviewed cases. Multiple conditions likely play a role in contributing to this zonular weakness and capsular contraction. Pseudoexfoliation is the most common risk factor, accounting for more than 50% of cases. Other associated conditions predisposing to zonular dehiscence are aging, high myopia, uveitis, trauma, previous vitreoretinal surgery, retinitis pigmentosa, diabetes mellitus, atopic dermatitis, previous acute angle-closure glaucoma attack, and connective tissue disorders. The recognition of these predisposing factors suggests a modified approach in cases at risk. We review certain measures to prevent IOL-bag complex luxation that have been proposed.
The Skin as an Early Expression of Malignancies in the Neonatal Age: A Review of the Literature and a Case Series
Authors: Mondì Vito , Piersigilli Fiammetta , Salvatori Guglielmo , Auriti Cinzia
Published: December 2015

Skin lesions are a frequent finding in childhood, from infancy throughout adolescence. They can arise from many conditions, including infections and inflammation. Most neonatal rashes are benign and self-limiting and require no treatment. Other conditions may be an expression of malignancy or may be a marker for other abnormalities, such as neural tube defects. Therefore, skin lesions require an extensive evaluation and close follow-up to ensure the best possible outcome. This paper briefly reviews the main tumor types presenting with cutaneous involvement in neonates, followed by the description of some patients admitted to our Neonatal Intensive Care Unit with an early skin expression of malignancies.
The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control
Authors: Murakami Shinnosuke , Goto Yasuaki , Ito Kyo , Hayasaka Shinya , Kurihara Shigeo , Soga Tomoyoshi , Tomita Masaru , Fukuda Shinji
Published: December 2015

Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW) or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.
Septic Shock Induced by Bacterial Prostatitis withMorganella morganiisubsp.morganiiin a Posttransplantation Patient
Authors: Li Xiaofan , Chen Jianhui
Published: December 2015

Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT).Morganella morganiiis ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showedMorganella morganiisubsp.morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showedMorganella morganiisubsp.morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together,Morganella morganiishould be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced byMorganella morganiisubsp.morganiiin a posttransplantation patient.
Efficacy and Safety of Topical Timolol Eye Drops in the Treatment of Myopic Regression after Laser In Situ Keratomileusis: A Systematic Review and Meta-Analysis
Authors: Wang Xiaochen , Zhao Guiqiu , Lin Jing , Jiang Nan , Wang Qian , Xu Qiang
Published: December 2015

Aims. The aim of this study was to assess the efficacy and safety of timolol in the treatment of myopic regression after laser in situ keratomileusis (LASIK).Methods. We searched MEDLINE, CENTRAL, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) from the inception to July 2015 for relevant randomized controlled trials that examined timolol therapy for myopic regression. The methodological quality of the studies included was assessed using the Revman 5.3 software.Results. We included six clinical trials involving 483 eyes in this review, including 246 eyes in treated group and 237 eyes in controlled group. We observed statistically significant improvements on the postoperative SE in the 3 months. However, the change of CCT was not statistically different between the control group and the experimental group. There were fewer cases of IOP, UDVA, and CDVA in treated group having significant difference from the controlled group.Conclusions. Topical timolol could be an effective treatment for reduction of myopic regression especially the spherical errors after myopic LASIK. Further RCTs with larger sample sizes for these trials are warranted to determine the efficacy and limitation for myopic regression after LASIK.
t‐BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO‐1 Pathway
Authors: Ye Fang , Li Xiaoyi , Li Lili , Yuan Jing , Chen Jun
Published: December 2015

The neurotoxicity of lead has been well established, and oxidative stress is strongly associated with lead‐induced neurotoxicity. Nrf2 is important for protection against oxidative stress in many disease models. We applied t‐BHQ, which is an Nrf2 activator, to investigate the possible role of Nrf2 in the protection against lead neurotoxicity. t‐BHQ significantly attenuated the oxidative stress in developmental rats by decreasing MDA level, as well as by increasing SOD activity and GSH content, in the hippocampus and frontal cortex. Furthermore, neuronal apoptosis was detected by Nissl staining, and Bax expression was inhibited in the t‐BHQ‐treated group. Results showed that t‐BHQ suppressed ROS production and caspase 3/7 activity but increased intracellular GSH content, in SH‐SY5Y cells under lead exposure. Moreover, in vivo and in vitro, t‐BHQ enhanced the nuclear translocation of Nrf2 and binding to ARE areas but did not induce Nrf2 transcription. These phenomena were confirmed using RT‐PCR, EMSA, Western blot, and immunofluorescence analyses. Subsequent upregulation of the expression of HO‐1, NQO1, and GCLC was observed. However, knockdown of Nrf2 or HO‐1 adversely affected the protective effects of t‐BHQ against lead toxicity in SH‐SY5Y cells. Thus, t‐BHQ can protect against lead neurotoxicity, depending on the Nrf2/HO‐1 pathway.
Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer
Authors: Matos Andreia , Castelão Cindy , Pereira da Silva Alda , Alho Irina , Bicho Manuel , Medeiros Rui , Clara Bicho Maria
Published: December 2015

There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone‐sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903) and COMT (rs4680) polymorphisms in 130 cervical cancer cases (c‐cancer) and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c‐cancer (OR = 0.39, p = 0.002). The allele C of CYP1A1 was a risk for c‐cancer (OR = 2.29, p = 0.002). Women with COMT LL genotype had a higher risk of developing c‐cancer (OR = 4.83, p < 0.001). For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c‐cancer (OR = 6.07, p = 0.006) and TT&HL genotypes had a protection effect (OR = 0.24, p < 0.001). The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c‐cancer (p < 0.001 and p = 0.037, resp.). C‐cancer is associated with less production of 2‐methoxy‐estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16‐OH‐estrone that is more proliferative.
Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy
Authors: Tricò Domenico , Baldi Simona , Frascerra Silvia , Venturi Elena , Marraccini Paolo , Neglia Danilo , Natali Andrea
Published: December 2015

Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites duringRest,Pacing(at 130 b/min), andRecovery. Myocardial lactate exchange and oleate oxidation were also measured. AtRest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response toPacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g,p<0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2equivalents,p<0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.govNCT02440217.
Microoxygraph Device for Biosensoristic Applications
Authors: Aloisi A. , Tarentini E. , Ferramosca A. , Zara V. , Rinaldi R.
Published: December 2015

Oxygen consumption rate (OCR) is a significant parameter helpful to determinein vitrorespiratory efficiency of living cells. Oxygen is an excellent oxidant and its electrocatalytic reduction on a noble metal allows accurately detecting it. By means of microfabrication technologies, handy, low-cost, and disposable chip can be attained, minimizing working volumes and improving sensitivity and response time. In this respect, here is presented a microoxygraph device (MOD), based on Clark’s electrode principle, displaying many advantageous features in comparison to other systems. This lab-on-chip platform is composed of a three-microelectrode detector equipped with a microgrooved electrochemical cell, sealed with a polymeric reaction chamber. Au working/counter electrodes and Ag/AgCl reference electrode were fabricated on a glass slide. A microchannel was realized by photoresist lift-off technique and a polydimethylsiloxane (PDMS) nanoporous film was integrated as oxygen permeable membrane (OPM) between the probe and the microreaction chamber. Electrochemical measurements showed good reproducibility and average response time, assessed by periodic injection and suction of a reducing agent. OCR measurements on 3T3 cells, subjected, in real time, to chemical stress on the respiratory chain, were able to show that this chip allows performing consistent metabolic analysis.
Neurosphere Based Differentiation of Human iPSC Improves Astrocyte Differentiation
Authors: Zhou Shuling , Szczesna Karolina , Ochalek Anna , Kobolák Julianna , Varga Eszter , Nemes Csilla , Chandrasekaran Abinaya , Rasmussen Mikkel , Cirera Susanna , Hyttel Poul , Dinnyés András , Freude Kristine K. , Avci Hasan X.
Published: December 2015

Neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) are traditionally maintained and proliferated utilizing two‐dimensional (2D) adherent monolayer culture systems. However, NPCs cultured using this system hardly reflect the intrinsic spatial development of brain tissue. In this study, we determined that culturing iPSC‐derived NPCs as three‐dimensional (3D) floating neurospheres resulted in increased expression of the neural progenitor cell (NPC) markers, PAX6 and NESTIN. Expansion of NPCs in 3D culture methods also resulted in a more homogenous PAX6 expression when compared to 2D culture methods. Furthermore, the 3D propagation method for NPCs resulted in a significant higher expression of the astrocyte markers  GFAP and aquaporin 4 (AQP4) in the differentiated cells. Thus, our 3D propagation method could constitute a useful tool to promote NPC homogeneity and also to increase the differentiation potential of iPSC towards astrocytes.
Hydrogen‐Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model
Authors: Tamaki Naofumi , Orihuela-Campos Rita Cristina , Fukui Makoto , Ito Hiro-O
Published: December 2015

The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen‐rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing‐associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen‐rich water or distilled water was consumed. In the drinking hydrogen‐rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen‐rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing‐associated factors in rat palatal tissue. In conclusion, hydrogen‐rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen‐rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.
Application of X-Band Wave Radar for Coastal Dynamic Analysis: Case Test of Bagnara Calabra (South Tyrrhenian Sea, Italy)
Authors: Punzo Michele , Lanciano Chiara , Tarallo Daniela , Bianco Francesco , Cavuoto Giuseppe , De Rosa Rosanna , Di Fiore Vincenzo , Cianflone Giuseppe , Dominici Rocco , Iavarone Michele , Lirer Fabrizio , Pelosi Nicola , Giordano Laura , Ludeno Giovanni , Natale Antonio , Marsella Ennio
Published: December 2015

Sea state knowledge has a key role in evaluation of coastal erosion, the assessment of vulnerability and potential in coastal zone utilization, and development of numerical models to predict its evolution. X-band radar measurements were conducted to observe the spatial and temporal variation of the sea-state parameters along a 3 km long sandy-gravelly pocket beaches forming a littoral cell on Bagnara Calabra. We produced a sequence of 1000 images of the sea state extending offshore up to 1 mile. The survey has allowed monitoring the coastline, the directional wave spectra, the sea surface current fields, and the significant wave heights and detecting strong rip currents which cause scours around the open inlets and affect the stability of the submerged reef-type breakwaters. The possibility to validate the data acquired with other datasets (e.g., LaMMA Consortium) demonstrates the potential of the X-band radar technology as a monitoring tool to advance the understanding of the linkages between sea conditions, nearshore sediment dynamics, and coastal change. This work proves the possibility to obtain relevant information (e.g., wave number, period, and direction) for evaluation of local erosion phenomena and of morphological changes in the nearshore and surf zone.
Glycaemic Control and Associated Self-Management Behaviours in Diabetic Outpatients: A Hospital Based Observation Study in Lusaka, Zambia
Authors: Musenge Emmanuel Mwila , Michelo Charles , Mudenda Boyd , Manankov Alexey
Published: December 2015

Background. The control ofdiabetes mellitusdepends on several factors that also include individual lifestyles. We assessed glycaemic control status and self-management behaviours that may influence glycaemic control among diabetic outpatients.Methods. This cross-sectional study among 198 consenting randomly selected patients was conducted at the University Teaching Hospital diabetic clinic between September and December 2013 in Lusaka, Zambia. A structured interview schedule was used to collect data on demographic characteristics, self-management behaviours, and laboratory measurements. Binary logistic regression analysis using IBM SPSS for Windows version 20.0 was carried out to predict behaviours that were associated with glycaemic control status.Results. The proportion of patients that had good glycaemic control status (HbA1c≤48 mmol/mol) was 38.7% compared to 61.3% that had poor glycaemic control status (HbA1c≥49 mmol/mol). Adherence to antidiabetic treatment and fasting plasma glucose predicted glycaemic control status of the patients. However, self-blood glucose monitoring, self-blood glucose monitoring means and exercise did not predict glycaemic control status of the patients.  Conclusion. We find evidence of poor glycaemic control status among most diabetic patients suggesting that health promotion messages need to take into account both individual and community factors to promote behaviours likely to reduce nonadherence.
Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity
Authors: Jacobsen Mette J. , Mentzel Caroline M. Junker , Olesen Ann Sofie , Huby Thierry , Jørgensen Claus B. , Barrès Romain , Fredholm Merete , Simar David
Published: December 2015

Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.
Comparison of the Effects of Continuous Subcutaneous Insulin Infusion and Add-On Therapy with Sitagliptin in Patients with Newly Diagnosed Type 2 Diabetes Mellitus
Authors: Wan Heng , Zhao Defu , Shen Jie , Lu Lu , Zhang Tong , Chen Zhi
Published: December 2015

To identify a new regimen to optimize treatment for patients with newly diagnosed type 2 diabetes (T2DM) by short-term continuous subcutaneous insulin infusion (CSII) alone.Methods.60 patients with newly diagnosed T2DM were randomized into two groups (n=30each) and treated for 2 weeks with CSII alone (CSII group) or with CSII plus sitagliptin (CSII + Sig group). The glycemic variability of the patients was measured using a continuous glucose monitoring system (CGMS) for the last 72 hours. A standard meal test was performed before and after the interventions, and the levels of glycated albumin, fasting glucose, fasting C-peptide, postprandial 2 h blood glucose, and postprandial 2 h C-peptide were examined.Results.Compared with the CSII group, the indicators of glycemic variability, such as the mean amplitude of glycemic excursion (MAGE) and the standard deviation of blood glucose (SDBG), were decreased significantly in the CSII + Sig group. The changes before and after treatment in the C-peptide reactivity index (ΔCPI) and the secretory unit of islet in transplantation index (ΔSUIT) indicated a significant improvement in the CSII + Sig group.Conclusions.Add-on therapy with sitagliptin may be an optimized treatment for patients with newly diagnosed T2DM compared with short-term CSII alone.
Patient Mobility in Times of Austerity: A Legal and Policy Analysis of the Petru Case
Authors: Frischhut Markus , Fahy Nick
Published: December 2015

The case-law of the Court of Justice (ecj ) on patient mobility was recently challenged by a ruling that a patient could go to Germany for treatment when facilities in Romanian hospitals were inadequate. Given the reported impact of austerity measures in the field of health care this raises the question; what is the impact of the ecj ’s ruling on how Member States can manage expenditure and limit outflows of patients and how should such measures be legally evaluated? The objective of this article is to analyse potential impact on health systems in the context of increasing pressure on public financing for health. While the ecj mainly referred to the requirement of treatment in due time, we also analyse possible austerity reductions of the basket of care against the background of eu law (i.e., ecj case-law, patient mobility directive, Charter of Fundamental rights and social security regulation).
A new species of the leafhopper genus Naevus Knight, 1970 (Hemiptera: Cicadellidae: Deltocephalinae: Opsiini), from Saudi Arabia
Authors: EL-SONBATI SAAD A. , WILSON MICHAEL R. , DHAFER HATHAL M. AL
Published: December 2015

The genus Naevus Knight, 1970 is recorded from the mountains of southwestern Saudi Arabia, the first record from the Arabian Peninsula. A new species, Naevus hathali El-Sonbati & Wilson sp. n. is described here, which appears to have an asymmetric aedeagus. An illustrated key to Naevus species is presented to facilitate identification.
Insights on the identities of sharks of the Rhizoprionodon acutus (Elasmobranchii: Carcharhiniformes) species complex based on
three new species of Phoreiobothrium (Cestoda: Onchoproteocephalidea)
Authors: CAIRA J. N. , JENSEN K.
Published: December 2015

Recent molecular work on milk sharks (Rhizoprionodon acutus [Rüppell]) suggests that, rather than a single widely distributed species, R. acutus represents a complex of four narrowly distributed cryptic species. Examination of the cestodes in three of the four members of that complex globally led to the discovery and description of three new species in the onchoproteocephalidean genus Phoreiobothrium Linton, 1889. The host associations and geographic distributions of the new species are fully congruent with the geographic distributions and species boundaries inferred for the sharks from molecular data: Phoreiobothrium jahki n. sp. parasitizes Rhizoprionodon cf. acutus 3 off Borneo, P. nadiae n. sp. parasitizes R. cf. acutus 1 off Senegal, and P. swaki n. sp. parasitizes R. cf. acutus 2 off northern Australia. The new cestodes differ from one another and from their 11 valid congeners in morphological features such as sublocular configuration and number, hook size, and testis number. Given the notoriously oioxenous nature of elasmobranch-hosted onchoproteocephalidean cestodes, these results provide further support for recognition of the milk shark species complex. This work also raises questions about the Phoreiobothrium species reported in cursory descriptions from India; further examination of these cestodes is key because they are potentially hosted by the fourth member of the R. acutus complex. To encourage future taxonomic work on the morphology of sharks in this complex, comparative photographs of representatives of the four potential host species are provided.
Extrapolating Satellite Winds to Turbine Operating Heights
Authors: Badger Merete , Peña Alfredo , Hahmann Andrea N. , Mouche Alexis A. , Hasager Charlotte B.
Published: December 2015

Ocean wind retrievals from satellite sensors are typically performed for the standard level of 10 m. This restricts their full exploitation for wind energy planning, which requires wind information at much higher levels where wind turbines operate. A new method is presented for the vertical extrapolation of satellite-based wind maps. Winds near the sea surface are obtained from satellite data and used together with an adaptation of the Monin–Obukhov similarity theory to estimate the wind speed at higher levels. The thermal stratification of the atmosphere is taken into account through a long-term stability correction that is based on numerical weather prediction (NWP) model outputs. The effect of the long-term stability correction on the wind profile is significant. The method is applied to Envisat Advanced Synthetic Aperture Radar scenes acquired over the south Baltic Sea. This leads to maps of the long-term stability correction and wind speed at a height of 100 m with a spatial resolution of 0.02°. Calculations of the corresponding wind power density and Weibull parameters are shown. Comparisons with mast observations reveal that NWP model outputs can correct successfully for long-term stability effects and also, to some extent, for the limited number of satellite samples. The satellite-based and NWP-simulated wind profiles are almost equally accurate with respect to those from the mast. However, the satellite-based maps have a higher spatial resolution, which is particularly important in nearshore areas where most offshore wind farms are built.
Multiscale Interactions in an Idealized Walker Cell: Analysis with Isentropic Streamfunctions
Authors: Slawinska Joanna , Pauluis Olivier , Majda Andrew J. , Grabowski Wojciech W.
Published: December 2015

A new approach for analyzing multiscale properties of the atmospheric flow is proposed in this study. For that, the recently introduced isentropic streamfunctions are employed here for scale decomposition with Haar wavelets. This method is applied subsequently to a cloud-resolving simulation of a planetary Walker cell characterized by pronounced multiscale flow. The resulting set of isentropic streamfunctions—obtained at the convective, meso-, synoptic, and planetary scales—capture many important features of the across-scale interactions within an idealized Walker circulation. The convective scale is associated with the shallow, congestus, and deep clouds, which jointly dominate the upward mass flux in the lower troposphere. The synoptic and planetary scales play important roles in extending mass transport to the upper troposphere, where the corresponding streamfunctions mainly capture the first baroclinic mode associated with large-scale overturning circulation. The intermediate-scale features of the flow, such as anvil clouds associated with organized convective systems, are extracted with the mesoscale and synoptic-scale isentropic streamfunctions. Multiscale isentropic streamfunctions are also used to extract salient mechanisms that underlie the low-frequency variability of the Walker cell. In particular, the lag of a few days of the planetary scale behind the convective scale indicates the importance of the convective scale in moistening the atmosphere and strengthening the planetary-scale overturning circulation. Furthermore, the mesoscale and synoptic scale lags behind the planetary scale reflect the strong dependence of convective organization on the background shear.
Who wants to move? The role of neighbourhood change
Authors: Clark William AV , Coulter Rory
Published: December 2015

There is growing interest in how, when and where neighbourhoods affect individual behaviours and outcomes. In Britain, falling levels of owner-occupation and the growth of ethnic minority populations have sparked a debate about how neighbourhood characteristics and neighbourhood change intersect with the decision to move. In this paper we investigate how mobility preferences vary with neighbourhood characteristics and neighbourhood change. We use multilevel logistic regression models to test whether this is configured by personal attributes or attachment to one's neighbourhood and perceived similarity to one's neighbours. The results show that neighbourhood deprivation, changes in neighbourhood ethnic composition and changes in tenure mix are associated with preferring to move. Importantly, we show that a feeling of belonging to the neighbourhood or feeling similar to others in the neighbourhood significantly reduces the desire to move.