bluuebunny/crossref_metadata_2025 huggingface dataset:
Prion protein quantification in cerebrospinal fluid as a tool for prion disease drug development
Authors: Vallabh Sonia M , Nobuhara Chloe K , Llorens Franc , Zerr Inga , Parchi Piero , Capellari Sabina , Kuhn Eric , Klickstein Jacob , Safar Jiri , Nery Flavia , Swoboda Kathryn , Schreiber Stuart L , Geschwind Michael D , Zetterberg Henrik , Arnold Steven E , Minikel Eric Vallabh
Published: April 2018

Reduction of native prion protein (PrP) levels in the brain is an attractive and genetically validated strategy for the treatment or prevention of human prion diseases. However, clinical development of any PrP-reducing therapeutic will require an appropriate pharmacodynamic biomarker: a practical and robust method for quantifying PrP, and reliably demonstrating its reduction, in the central nervous system (CNS) of a living patient. Here we evaluate the potential of enzyme-linked immunosorbent assay (ELISA)-based quantification of human PrP in human cerebrospinal fluid (CSF) to serve as a biomarker for PrP-reducing therapeutics. We show that CSF PrP is highly sensitive to plastic adsorption during handling and storage, but its loss can be minimized by addition of detergent. We find that blood contamination does not affect CSF PrP levels, and that CSF PrP and hemoglobin are uncorrelated, together suggesting that CSF PrP is CNS-derived, supporting its relevance for monitoring the tissue of interest and in keeping with high PrP abundance in brain relative to blood. In a cohort with controlled sample handling, CSF PrP exhibits good within-subject test-retest reliability (mean coefficient of variation 13% in samples collected 8-11 weeks apart), a sufficiently stable baseline to allow therapeutically meaningful reductions in brain PrP to be readily detected in CSF. Together, these findings supply a method for monitoring the effect of a PrP-reducing drug in the CNS, enabling the development of prion disease therapeutics with this mechanism of action.
Optical mapping reveals a higher level of genomic architecture of chained fusions in cancer
Authors: Chan Eva K.F. , Cameron Daniel L. , Petersen Desiree C. , Lyons Ruth J. , Baldi Benedetta F. , Papenfuss Anthony T. , Thomas David M. , Hayes Vanessa M.
Published: April 2018

Genomic rearrangements are common in cancer, with demonstrated links to disease progression and treatment response. These rearrangements can be complex, resulting in fusions of multiple chromosomal fragments and generation of derivative chromosomes. Although methods exist for detecting individual fusions, they are generally unable to reconstruct complex chained events. To overcome these limitations, we adopted a new optical mapping approach, allowing megabase-length genome maps to be reconstructed and rearranged genomes to be visualized without loss of integrity. Whole-genome mapping (Bionano Genomics) of a well-studied highly rearranged liposarcoma cell line resulted in 3338 assembled consensus genome maps, including 72 fusion maps. These fusion maps represent 112.3 Mb of highly rearranged genomic regions, illuminating the complex architecture of chained fusions, including content, order, orientation, and size. Spanning the junction of 147 chromosomal translocations, we found a total of 28 Mb of interspersed sequences that could not be aligned to the reference genome. Traversing these interspersed sequences using short-read sequencing breakpoint calls, we were able to identify and place 399 sequencing fragments within the optical mapping gaps, thus illustrating the complementary nature of optical mapping and short-read sequencing. We demonstrate that optical mapping provides a powerful new approach for capturing a higher level of complex genomic architecture, creating a scaffold for renewed interpretation of sequencing data of particular relevance to human cancer.
Conflict perception: a new scale with evidence from Israel and Palestine
Authors: Khatib Ibrahim , Canetti Daphna , Rubin Aviad
Published: April 2018

Purpose

The current work aims to introduce the concept of conflict perception and construct a scale that measures individual differences in perceptions about conflicts along religious, national and material dimensions. The concept and the measure are developed in the context of the Israeli–Palestinian conflict.

Design/methodology/approach

The research design combines three methodological elements: 14 focus groups in Israel and the West Bank, which represent diversity in place of residence, religion, age and political background; an expert panel review; and a survey of 411 student respondents that was conducted between September 29 and October 9, 2013, among university students in Israel and Palestine.

Findings

The findings show that conflict perception is an individual’s subjective view regarding the essence of the conflict and its central issues, the identities of the parties involved and their motivations, which may include material, ideological or symbolic motives, or any combination thereof. A novel scale consisting of five statements that can measure conflict perception that was developed, validated and implemented via a survey sample showed that Palestinians in the West Bank and in Israel have a religious perception of the conflict, whereas Jews have a national perception of the conflict.

Originality/value

First, the paper introduces a new concept that sheds additional light on the micro foundations of peoples’ attitudes in conflict situations. Second, it develops and validates a measurement tool for conflict perception that may be usable, with necessary adjustments, in other conflicts. Third, it demonstrates that parties to the conflict do not necessarily share similar perceptions about the conflict, a finding with far-reaching consequences for conflict resolution at both the scholarly and policy levels.
Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes
Authors: Chang Wei‐Ting , Wu Sheng‐Nan
Published: April 2018

Telmisartan (TEL) is a non‐peptide blocker of angiotensin II type‐1 (AT1) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL‐1 cardiomyocytes. In whole‐cell recordings, addition of TEL stimulated the peak and late components of voltage‐gated Na+ currents (INa) with different potencies. The EC50 values required to achieve the stimulatory effect of this drug on peak and late INa were 0.2 and 1.2 μmol/L, respectively, and the current‐voltage relationship of peak INa shifted toward less‐depolarized potentials during exposure to TEL. Telmisartan not only increased peak INa but also prolonged the inactivation time course of late INa. Amiodarone (Amio) or ranolazine (Ran), but not angiotensin II, could reverse TEL‐mediated effects. The drug enhanced the recovery rate of INa inactivation and exerted an inhibitory effect on erg‐mediated K+ and L‐type Ca2+ currents. In whole‐cell current‐clamp recordings, addition of the drug resulted in prolongation of the duration of action potentials (APs) in a dose‐dependent manner in HL‐1 cells; Amio or Ran could reverse this increase in AP durations. Telmisartan‐mediated prolongation of AP was attenuated in KCNH2 siRNA‐transfected HL‐1 cells. In cultured smooth muscle cells of the human coronary artery, TEL enhanced INa amplitudes and slowed current inactivation. Stimulation by TEL of INa in HL‐1 cells did not simply increase current magnitude but altered current kinetics, thereby suggesting state‐dependent activation. Telmisartan may have greater affinity to the open/inactivated state than to the resting state residing in NaV channels. Collectively, TEL‐mediated stimulation of INa and inhibition of IK(erg) could be an important ionic mechanism underlying the increased cell excitability of HL‐1 cells; these actions, however, cannot be entirely explained by its blockade of AT1 receptor.
Transient antagonism of anti‐CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines
Authors: Zoellner Anna‐Katharina , Peter Nico , Zimmermann Yvonne , Hutter Grit , Hiddemann Wolfgang , Dreyling Martin
Published: April 2018

Introduction

PI3K inhibitors are evaluated for relapsed and refractory Diffuse large B‐cell lymphoma (DLBCL) patients.

Objective

As rituximab has shown to influence B‐cell receptor (BCR) signaling, we investigated the interaction of anti‐CD20 antibody rituximab and the new type II glycoengineered anti‐CD20 antibody obinutuzumab in combination with the PI3K delta inhibitor idelalisib.

Methods

Established DLBCL cell lines were treated with either rituximab or obinutuzumab alone or in combination with PI3K delta inhibitor idelalisib.

Results

Rituximab and to a lesser extent obinutuzumab monotherapy resulted in a temporary upregulation of p‐Akt, p42/44, and p38 signaling pathways.

Idelalisib reduced p‐Akt expression. Rituximab antagonized the p‐Akt downregulation at early time points, while obinutuzumab did not interfere with idelalisib's effects. In cell growth analysis, early antagonism could also be detected.

Conclusion

The combination of idelalisib with CD antibodies shows an initial antagonism of rituximab but not obinutuzumab in downregulation of PI3K‐signaling targets.
A novel type of +2‐base pair frameshift CALR mutation in a patient with myeloproliferative neoplasm
Authors: Kim Hyun‐Young , Kim Jong‐Won , Kim Sun‐Hee , Chang Myung Hee , Kim Hee‐Jin
Published: April 2018

Somatic CALR mutations have been identified in the majority of JAK2 mutation‐negative essential thrombocythaemia (ET) and primary myelofibrosis. Almost all CALR mutations have been reported to typically generate a +1‐base pair (bp) frameshift in the open reading frame. Here, we describe an ET patient with a +2‐bp frameshift CALR mutation. A 41‐year‐old man was admitted because of headache, and diagnosed as JAK2‐negative ET. After 4 years, his disease progressed to post‐ET myelofibrosis, and CALR mutation analysis demonstrated a +2‐bp frameshift CALR mutation caused by two different CALR mutations, c.1139_1151del and c.1211_1215delinsTTGA, on the same allele. The resultant mutant protein sequence shared 19 amino acids with those from type 1 and type 2 CALR mutations, but the downstream C‐terminal sequences were different. To our knowledge, CALR double mutations causing +2‐bp frameshift are extremely rare. Identification of this novel type of CALR mutation has potential implications for better understanding of CALR oncogenesis.
Prospective real‐world analysis of OnabotulinumtoxinA in chronic migraine post‐National Institute for Health and Care Excellence UK technology appraisal
Authors: Andreou A. P. , Trimboli M. , Al‐Kaisy A. , Murphy M. , Palmisani S. , Fenech C. , Smith T. , Lambru G.
Published: April 2018

Background and purpose

The National Institute for Health and Care Excellence (NICE) in the UK recommends the use of OnabotulinumtoxinA (BoNTA, Botox®) in the management of chronic migraine (CM) following specific guidelines within the National Health Service. In view of the lack of data on the efficacy of this therapy following implementation of these guidelines in clinical practice and on the evaluation of guidance compliance, we aimed to evaluate the effectiveness and safety of BoNTA in patients with CM following the NICE guidelines.

Methods

This was a prospective real‐life audit study.

Results

After two treatments, 127 of 200 patients (63.5%) obtained at least a 30% reduction in headache days. Those who continued the treatment up to 3 years reported a stable beneficial effect compared with baseline. Amongst responders, 68 patients (53.5%) were reclassified as episodic migraineurs. A total of 57 of these patients (83.8%) converted to an episodic migraine pattern at 6‐month follow‐up. The majority of those whose migraine became episodic after BoNTA extended the treatment intervals beyond 3 months (range 4–8 months) before noticing any worsening of headache. We observed no significant differences in the efficacy measures in patients treated with 155 U BoNTA compared with those treated with >155 U BoNTA.

Conclusions

When administered according to the NICE guidance, BoNTA produced a clinically meaningful effect in the long‐term management of CM with and without medication overuse headache. Treatment discontinuation when CM becomes episodic may be useful in clinical practice to identify those who may benefit from extended treatment intervals. Our clinical experience indicates a lack of additional benefit from using the ‘follow‐the‐pain’ paradigm.
PCSK9 plays a novel immunological role in oxidized LDL‐induced dendritic cell maturation and activation of T cells from human blood and atherosclerotic plaque
Authors: Liu A. , Frostegård J.
Published: April 2018

Background

Activated T cells and dendritic cells (DCs) occur in atherosclerotic plaques. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL‐receptor (LDLR) and results in increased LDL levels. We here investigate immune effects of PCSK9 on OxLDL induced DC maturation and T‐cell activation.

Methods

T cells were isolated from carotid specimens of patients undergoing carotid endarterectomy or from peripheral blood of healthy individuals. Human peripheral blood monocytes were differentiated into DCs. Naïve T cells were cocultured with pretreated DCs. The effects of PCSK9 and its inhibition by silencing were studied.

Results

OxLDL induced PCSK9 in DCs and promoted DC maturation with increased expressions of CD80, CD83, CD86 and HLA‐DR and the scavenger receptors LOX‐1 and CD36. T cells exposed to OxLDL‐treated DCs proliferated and produced IFN‐γ and IL‐17, thus with polarization to Th1 and/or Th17 subsets. Silencing of PCSK9 reversed the OxLDL effects on DCs and T cells. DC maturation was repressed, and the production of TNF‐α, IL‐1β and IL‐6 was limited, while TGF‐β and IL‐10 secretion and T regulatory cells were induced. OxLDL induced miRNA let‐7c, miR‐27a, miR‐27b, miR‐185. Silencing PCSK9 repressed miR‐27a and to a lesser extent let‐7c. PCSK9 silencing enhanced SOCS1 expression induced by OxLDL. Experiments on T cells from carotid atherosclerotic plaques or healthy individuals showed similar results.

Conclusions

We demonstrate immunological effects of PCSK9 in relation to activation and maturation of DCs and plaque T cells by OxLDL, a central player in atherosclerosis. This may directly influence atherosclerosis and cardiovascular disease, independent of LDL lowering.
Collections‐based science in the 21st Century
Authors: Funk Vicki A.
Published: April 2018

Discoveries from collections‐based science change the way we perceive ourselves, our environment, and our place in the universe. The 18thCentury saw the beginning of formal classification with Linnaeus proposing a system to classify all of life. The 19thCentury ushered in the age of exploration as naturalists undertook large‐scale collecting expeditions leading to major scientific advances (the founding of Physical Geography, Meteorology, Ecology, Biogeography, and Evolution) and challenging long held beliefs about nature. In the 20thCentury collections were central to paradigm shifts, including theories of Continental Drift and Phylogenetic Systematics; Molecular Phylogenetics added testable hypotheses, and computerized specimen records gave rise to the field of Biodiversity. In the first 15 years of the 21stCentury we have seen tree‐thinking pervade the life sciences, leading to the emergence of Evolutionary Medicine, Evolutionary Ecology, and new Food Safety methods. More advances are on the way: (i) Open access to large amounts of specimen data & images, (ii) Linking of collections and climate data to phylogenies on a global scale, and (iii) Production of vast quantities of genomic data allowing us to address big evolutionary questions. As a result of collections‐based science people see themselves not as the center of all things but rather as part of a complex universe. It is essential that we integrate new discoveries with knowledge from the past (e.g., collections) in order to understand this planet we all inhabit. To ensure the health of collections‐based science we must come together and plan for the future.
Internet addiction and attention‐deficit–hyperactivity disorder: Effects of anxiety, depression and self‐esteem
Authors: Kahraman Özlem , Demirci Esra Özdemir
Published: April 2018

Background

Attention‐deficit–hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood. Behavioral disinhibition, poor neurocognitive skills and immediate reward preference in children with ADHD have been suggested as risk factors for Internet addiction (IA). The aim of the present study was therefore to investigate the relationship between IA and depression, anxiety, and self‐esteem in adolescents with ADHD, and to identify the features of Internet use that predict IA.

Methods

We studied 111 patients with ADHD aged 12–18 years, and 108 healthy controls. The ADHD patients and controls were asked to complete a sociodemographic data form, the Internet Addiction Scale (IAS), Children's Depression Inventory, Childhood Screening Scale for Anxiety in Children, and the Rosenberg Self‐Esteem Scale.

Results

IAS total score in the adolescents with ADHD was significantly higher than in the control group. Compared with the control group, the ADHD group depression scale score was significantly higher, and self‐esteem score significantly lower (P < 0.05 for both). There was no difference between the groups in anxiety score. IAS score had a positive correlation with depression and anxiety scores, and a negative correlation with self‐esteem score.

Conclusion

The relationship between IA scale score and depression, anxiety and self‐esteem scale scores were similar in the ADHD and the control group. In addition, IAS subscale and total scores were significantly higher in the ADHD group than the control group, even after controlling for the effects of self‐esteem, depression and anxiety scores. Thus, ADHD is thought to be an independent risk factor for depression, anxiety and self‐esteem, and, hence, for IA.
Réformes électorales et changements institutionnels dans un contexte de démocratisation. Le choix du scrutin uninominal sous la Troisième République en France
Authors: Ehrhard Thomas , Passard Cédric
Published: April 2018

L'article étudie le choix du mode de scrutin uninominal sous la Troisième République à partir de l'analyse des débats parlementaires des trois lois électorales qui installent ou rétablissent ce mode de scrutin (1875, 1889 et 1927). Il interroge les intérêts électoraux des acteurs politiques avec les enjeux de la démocratisation et de l’évolution du régime politique.

Il montre que les réformes électorales sont utilisées stratégiquement pour tenter de limiter l'irruption de nouveaux acteurs politiques et pour rendre plus difficile la mise en cause de l’équilibre institutionnel. En profitant aux acteurs républicains notabilisés, le mode de scrutin uninominal, pourtant d'abord perçu comme un héritage des régimes autoritaires, favorise l'installation durable de la République. La démocratisation apparaît au final comme un processus qui ne s'appuie pas seulement sur des objectifs démocratiques.
Multicenter, randomized controlled, observer‐blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes—ProNOx1 study
Authors: Edmonds Michael E. , Bodansky Harvey J. , Boulton Andrew J.M. , Chadwick Paul J. , Dang Cuong N. , D'Costa Ryan , Johnston Atholl , Kennon Brian , Leese Graham , Rajbhandari Satyan M. , Serena Thomas E. , Young Matthew J. , Stewart Joanne E. , Tucker Arthur T. , Carter Marissa J.
Published: April 2018

The aim of this multicenter, prospective, observer‐blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting “real world” clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25–2,500 mm2 and either a palpable pedal pulse or ankle brachial pressure index > 0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12‐week follow‐up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110—75; Control—73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks in the intention‐to‐treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice.
Development of a large‐volume human‐derived adipose acellular allogenic flap by perfusion decellularization
Authors: Giatsidis Giorgio , Guyette Jacques P. , Ott Harald C. , Orgill Dennis P.
Published: April 2018

In reconstructive surgery, transfer of patients’ tissue (autologous flaps) is routinely used to repair large soft tissue defects caused by surgery, trauma, chronic diseases, or malformations; unfortunately, this strategy is not always possible and often creates a secondary defect in the donor site of the tissue. Tissue‐engineered synthetic flaps are currently unable to repair clinically‐relevant, large‐volume defects; allogenic flaps from cadaveric donors could provide a ready‐to‐use biological alternative if treated with methods to avoid the immune‐rejection of the donor's cells. Here, we describe the successful decellularization of a large (> 800 cc) human‐derived adipose flap through a perfusion apparatus; we demonstrate the complete removal of the immunogenic cellular components of the flap with the retention of its structural components and vascular network. Our aim is to obtain a universally compatible, off‐the‐shelf acellular allogenic flap that could be recellularized with cells from recipient patients to provide a tissue‐engineered allogenic/autologous alternative for reconstruction of large‐volume soft‐tissue defects.
Factoring as a Form of Financing Small and Medium-Sized Enterprises in ASEAN
Authors: Do Thi My Huong
Published: April 2018

Small and medium-sized enterprises have increasingly played very important roles, particularly in developing open economies and the ASEAN economic community. One of the biggest factors that hinders the growth of these firms is their lack of fund and limited access to financial sources. This writing, firstly, aims to illustrate that factoring can prove to be a popular tendency in fanancing small and medium enterprises in ASEAN by showing its considerable growing rate over the last two decades. In the second part, using the OLS, the paper also measures and discusses the determinants of factoring development in three financial markets including Malaysia, Thailand, Singapore.
Contribution to the knowledge of the oribatid mite genus Aokiella (Acari, Oribatida, Carabodidae)
Authors: Ermilov Sergey G.
Published: April 2018

A new species of the genus Aokiella (Oribatida, Carabodidae) is described from soil of Taiwan. Aokiella liaoi sp. nov. differs from Aokiella xuansoni Vu, Ermilov & Dao, 2010 in that notogastral setae c1 and c2 as well as da and la are similar in length, and the surface of the notogaster has small, sparse foveoles. A revised generic diagnosis, an identification key to known species, and data on the distribution and ecology of Aokiella are presented.
Mechanism of the 2015 volcanic tsunami earthquake near Torishima, Japan
Authors: Fukao Yoshio , Sandanbata Osamu , Sugioka Hiroko , Ito Aki , Shiobara Hajime , Watada Shingo , Satake Kenji
Published: April 2018

Anomalously large tsunamis generated by a submarine volcanic earthquake were recorded by an ocean bottom pressure gauge array.
Organic fertilizer as a vehicle for the entry of microplastic into the environment
Authors: Weithmann Nicolas , Möller Julia N. , Löder Martin G. J. , Piehl Sarah , Laforsch Christian , Freitag Ruth
Published: April 2018

Organic fertilizer from recycled biowaste was identified as a vehicle for entry of microplastic particles into the environment.
Draft Genome Sequence of Candida pseudohaemulonii Isolated from the Blood of a Neutropenic Patient
Authors: Mohd Tap Ratna , Kamarudin Nur Amalina , Ginsapu Stephanie Jane , Ahmed Bakri Ahmed Rafezzan , Ahmad Norazah , Amran Fairuz , Sipiczki Matthias
Published: April 2018

Candida pseudohaemulonii
is phylogenetically close to the
C. haemulonii
complex and exhibits resistance to amphotericin B and azole agents. We report here the draft genome sequence of
C. pseudohaemulonii
UZ153_17 isolated from the blood culture of a neutropenic patient. The draft genome is 3,532,003,666 bp in length, with 579,838 reads, 130 contigs, and a G+C content of 47.15%.
Challenges in screening for latent tuberculosis in inflammatory bowel disease prior to biologic treatment: a UK cohort study
Authors: Thi Aye Aye , Abbara Aula , Bouri Sonia , Collin Simon M , Wolfson Paul , Owen Leah , Buell Kevin G , John Laurence , Hart Ailsa L
Published: April 2018

Objective

The aim of this study was to determine the occurrence of latent tuberculosis infections (LTBI) and active TB in a cohort of patients with inflammatory bowel disease (IBD) treated with biologics. We also examined the effects of immunosuppressive drugs on indeterminate interferon-gamma release assays (IGRA) in LTBI screening.

Design

Retrospective study of patients treated with biologics between March 2007 and November 2015.

Setting

St Mark’s Hospital, North West London, UK.

Patients

732 patients with IBD who were screened for LTBI using either tuberculin skin test or IGRA before starting a biologic treatment.

Methods

Retrospective case note review of all patients with IBD who were screened for LTBI prior to initiating biologics. Patients who developed active TB were identified from the London TB register.

Results

Of 732 patients with IBD, 31 (4.2%) were diagnosed with and treated for LTBI with no significant side effects. Six of 596 patients (1.0%) who received biologic treatment developed active TB. There was a higher proportion of indeterminate IGRA in the immunosuppressive medication group compared with the non-immunosuppressive group (33% (59/181) compared with 9% (6/66), p<0.001). The combination of steroids and thiopurines had the highest proportion of indeterminate IGRA (64%, 16/25). High and low doses of steroids were equally likely to result in an indeterminate IGRA result (67% (8/12) and 57% (4/7), respectively).

Conclusions

This study highlights the challenges of LTBI screening prior to commencing biologic therapy and demonstrates the risk of TB in patients who have been screened and who are receiving prolonged and continuing doses of antitumour necrosis factor.
Bergamottin Inhibits Adipogenesis in 3T3-L1 Cells and Weight Regulation in Diet-Induced Obese Mice
Authors: Ko Jeong-Hyeon , Nam Dongwoo , Um Jae-Young , Jung Sang Hoon , Ahn Kwang Seok
Published: April 2018

Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text]). The expressions of target proteins such as adipocyte fatty acid-binding protein (aP2), adiponectin, and resistin were also decreased by BGM. It activated AMP-activated protein kinase (AMPK) by increasing phosphorylation of AMPK and the downstream target acetyl-CoA carboxylase (ACC), indicating that BGM exerted its antiadipogenic effect through AMPK activation. In the HFD-induced obese mouse model, BGM administration significantly reduced the weight and sizes of white adipose tissue as well as the weight gain of mice fed HFD. Moreover, UCP1 and PGC1[Formula: see text] expressions, well-known as brown adipocyte marker genes, were higher in the BGM-treated HFD mice than that in the HFD-induced obese mice. This study suggests that BGM suppress adipogenesis by AMPK activation in vitro and reduces body weight in vivo.
Semi-Deterministic Construction of Scale-Free Networks with Designated Parameters
Authors: TAKEUCHI NAOKI , FUJITA SATOSHI
Published: April 2018

Scale-free networks have several favorable properties as the topology of interconnection networks such as the short diameter and the quick message propagation. In this paper, we propose a method to construct scale-free networks in a semi-deterministic manner. The proposed algorithm extends the Bulut's algorithm for constructing scale-free networks with designated minimum degree k and maximum degree m, in such a way that: (1) it determines the ideal number of edges derived from the ideal degree distribution; and (2) after connecting each new node to k existing nodes as in the Bulut’s algorithm, it adjusts the number of edges to the ideal value by conducting add/removal of edges. We prove that such an adjustment is always possible if the number of nodes in the network exceeds [Formula: see text]. The performance of the algorithm is experimentally evaluated.
Channel Noise-Enhanced Synchronization Transitions Induced by Time Delay in Adaptive Neuronal Networks with Spike-Timing-Dependent Plasticity
Authors: Xie Huijuan , Gong Yubing , Wang Baoying
Published: April 2018

In this paper, we numerically study the effect of channel noise on synchronization transitions induced by time delay in adaptive scale-free Hodgkin–Huxley neuronal networks with spike-timing-dependent plasticity (STDP). It is found that synchronization transitions by time delay vary as channel noise intensity is changed and become most pronounced when channel noise intensity is optimal. This phenomenon depends on STDP and network average degree, and it can be either enhanced or suppressed as network average degree increases depending on channel noise intensity. These results show that there are optimal channel noise and network average degree that can enhance the synchronization transitions by time delay in the adaptive neuronal networks. These findings could be helpful for better understanding of the regulation effect of channel noise on synchronization of neuronal networks. They could find potential implications for information transmission in neural systems.
Electron Mobility Non-Damping Fluctuations in Semiconductors
Authors: Melkonyan Slavik V. , Zalinyan Tigran A. , Melkonyan Sargis S.
Published: April 2018

Equilibrium state disturbance and restoration processes of an electron gas interacting with phonon system in an equilibrium semiconductor have been investigated. Damping peculiarities of small deviations (fluctuations) of electron system from equilibrium state due to electron-acoustic phonon random scattering have been analyzed. A second-order linear partial differential equation for symmetric component of fluctuation of electron distribution function was obtained via linearization of the Boltzmann equation. This equation describes the chaotic movement of electrons along the energy axis, which can be interpreted as diffusion in momentum space. Another equation which describes the time dependence of electron lattice mobility fluctuations was obtained. It was shown that in the Boltzmann equation linearization approximation, lattice mobility fluctuations do not decay over time. The time dependence of the mobility fluctuations is described by stochastic harmonic function with random amplitude and random initial phase.
Decision Tree-Based Analytics for Reducing Air Pollution
Authors: Das Ajanta , Desarkar Anindita
Published: April 2018

Air pollution indicates contaminated air which arises due to the effect of physical, biological or chemical alteration to the air in the atmosphere applicable both for indoors and outdoors. This situation arises when poisonous gases, dust or smoke enter into the atmosphere and make the surroundings vulnerable for any living beings as well as difficult for them to survive. Large numbers of premature deaths happen across the globe if exposed to these pollutants on a long-term basis as major portion of the cities have the pollution level above the threshold determined by World Health Organization (WHO). So appropriate measures need to be taken on a priority basis to reduce air pollution as well as save our planet. This paper proposes a novel air pollution reduction approach which collects source pollution data. After extraction of source data, it uses various databases (DBs) and then different decisions or classes are created. The decision tree was created with the help of Iterative Dichotomiser 3 (ID3) algorithm to implement the rule base appropriately depending on the air pollution level and a bunch of rule sets were derived from the decision tree further.
A Methodology for Improving Vegetation Representation and Health Exploiting a Semantic Robotic System and Its Dynamic Stability Control
Authors: D’Auria Daniela , Persia Fabio
Published: April 2018

Precision farming technologies have been increasingly recognized for their potential ability for improving agricultural productivity, reducing production cost, and minimizing damage to the environment. In this context, the main goals of this paper are the following: First, we present a methodology that can be applied to extract semantic information, more specifically some vegetative indices, from plants, in order to further improve the vegetation representation and health by means of a specific semantic robotic system; then, we study in detail the tracked robot’s behavior, by emulating the real settings in a field and analytically analyze the simulation of the robot on an up and down slope path.
Software Product Line Engineering for Robotic Perception Systems
Authors: Brugali Davide , Hochgeschwender Nico
Published: April 2018

Control systems for autonomous robots are concurrent, distributed, embedded, real-time and data intensive software systems. A real-world robot control system is composed of tens of software components. For each component providing robotic functionality, tens of different implementations may be available. The difficult challenge in robotic system engineering consists in selecting a coherent set of components, which provide the functionality required by the application requirements, taking into account their mutual dependencies. This challenge is exacerbated by the fact that robotics system integrators and application developers are usually not specifically trained in software engineering. In various application domains, software product line (SPL) development has proven to be the most effective approach to face this kind of challenges. In a previous paper [D. Brugali and N. Hochgeschwender, Managing the functional variability of robotic perception systems, in First IEEE Int. Conf. Robotic Computing, 2017, pp. 277–283.] we have presented a model-based approach to the development of SPL for robotic perception systems, which integrates two modeling technologies developed by the authors: The HyperFlex toolkit [L. Gherardi and D. Brugali, Modeling and reusing robotic software architectures: The HyperFlex toolchain, in IEEE Int. Conf. Robotics and Automation, 2014, pp. 6414–6420.] and the Robot Perception Specification Language (RPSL) [N. Hochgeschwender, S. Schneider, H. Voos and G. K. Kraetzschmar, Declarative specification of robot perception architectures, in 4th Int. Conf. Simulation, Modeling, and Programming for Autonomous Robots, 2014, pp. 291–302.]. This paper extends our previous work by illustrating the entire development process of an SPL for robot perception systems with a real case study.
Enhanced Sound Beam from a Sonic Crystal Waveguide via a Self-Collimating Sonic Crystal
Authors: Liang Jin-Fu , Gong Lun-Xun
Published: April 2018

Two novel composite structures that couple a sonic crystal waveguide (SCW) to a self-collimating sonic crystal (SCSC) are proposed to control beam divergence and transmission. Finite element simulations indicate that an SCSC attached to the output of an SCW can reduce the half-power angular width by 48.81% and enhance the normal radiation intensity by 104.17%. This is due to both the high self-collimation properties and low interference of SCSCs. A composite consisting of four SCWs coupled via an SCSC exhibits high transmission with low cross talk when multiple signals are introduced. The proposed composites could be important in the SCW directional emission and SCW-based integrated circuit development.
Network Resilience and the Length-Bounded Multicut Problem
Authors: Kuhnle Alan , Crawford Victoria G. , Thai My T.
Published: April 2018

Motivated by networked systems in which the functionality of the network depends on vertices in the network being within a bounded distance
T
of each other, we study the length-bounded multicut problem: given a set of pairs, find a minimum-size set of edges whose removal ensures the distance between each pair exceeds
T
. We introduce the first algorithms for this problem capable of scaling to massive networks with billions of edges and nodes: three highly scalable algorithms with worst-case performance ratios. Furthermore, one of our algorithms is fully dynamic, capable of updating its solution upon incremental vertex / edge additions or removals from the network while maintaining its performance ratio. Finally, we show that unless
NP
⊆
BPP
, there is no polynomial-time, approximation algorithm with performance ratio better than $Ømega (T)$, which matches the ratio of our dynamic algorithm up to a constant factor.
Why Some Like It Loud
Authors: Islam Mohammad A. , Yang Luting , Ranganath Kiran , Ren Shaolei
Published: April 2018

The common practice of power infrastructure oversubscription in data centers exposes dangerous vulnerabilities to well-timed power attacks (i.e., maliciously timed power loads to overload the infrastructure capacity), possibly creating outages and resulting in multimillion-dollar losses. In this paper, we focus on the emerging threat of power attacks in a multi-tenant data center, where a malicious tenant (i.e., attacker) aims at compromising the data center availability through power attacks. We discover a novel acoustic side channel resulting from servers' cooling fan noise, which can help the attacker time power attacks at the moments when benign tenants' power usage is high. Concretely, we exploit the acoustic side channel by: (1) employing a high-pass filter to filter out the air conditioner's noise; (2) applying non-negative matrix factorization with sparsity constraint to demix the received aggregate noise and detect periods of high power usage by benign tenants; and (3) designing a state machine to guide power attacks. We run experiments in a practical data center environment as well as simulation studies, and demonstrate that the acoustic side channel can assist the attacker with detecting more than 50% of all attack opportunities, representing state-of-the-art timing accuracy.
SOAP
Authors: Scully Ziv , Harchol-Balter Mor , Scheller-Wolf Alan
Published: April 2018

We consider an extremely broad class of M/G/1 scheduling policies called SOAP: Schedule Ordered by Age-based Priority. The SOAP policies include almost all scheduling policies in the literature as well as an infinite number of variants which have never been analyzed, or maybe not even conceived. SOAP policies range from classic policies, like first-come, first-serve (FCFS), foreground-background (FB), class-based priority, and shortest remaining processing time (SRPT); to much more complicated scheduling rules, such as the famously complex Gittins index policy and other policies in which a job's priority changes arbitrarily with its age. While the response time of policies in the former category is well understood, policies in the latter category have resisted response time analysis. We present a universal analysis of all SOAP policies, deriving the mean and Laplace-Stieltjes transform of response time.
On a Class of Stochastic Multilayer Networks
Authors: Jiang Bo , Nain Philippe , Towsley Don , Guha Saikat
Published: April 2018

In this paper, we introduce a new class of stochastic multilayer networks. A stochastic multilayer network is the aggregation of
M
networks (one per layer) where each is a subgraph of a foundational network
G
. Each layer network is the result of probabilistically removing links and nodes from
G
. The resulting network includes any link that appears in at least
K
layers. This model is an instance of a non-standard site-bond percolation model. Two sets of results are obtained: first, we derive the probability distribution that the
M
-layer network is in a given configuration for some particular graph structures (explicit results are provided for a line and an algorithm is provided for a tree), where a configuration is the collective state of all links (each either active or inactive). Next, we show that for appropriate scalings of the node and link selection processes in a layer, links are asymptotically independent as the number of layers goes to infinity, and follow Poisson distributions. Numerical results are provided to highlight the impact of having several layers on some metrics of interest (including expected size of the cluster a node belongs to in the case of the line). This model finds applications in wireless communication networks with multichannel radios, multiple social networks with overlapping memberships, transportation networks, and, more generally, in any scenario where a common set of nodes can be linked via co-existing means of connectivity.
Working Set Size Estimation Techniques in Virtualized Environments
Authors: Nitu Vlad , Kocharyan Aram , Yaya Hannas , Tchana Alain , Hagimont Daniel , Astsatryan Hrachya
Published: April 2018

Energy consumption is a primary concern for datacenters? management. Numerous datacenters are relying on virtualization, as it provides flexible resource management means such as virtual machine (VM) checkpoint/restart, migration and consolidation. However, one of the main hindrances to server consolidation is physical memory. In nowadays cloud, memory is generally statically allocated to VMs and wasted if not used. Techniques (such as ballooning) were introduced for dynamically reclaiming memory from VMs, such that only the needed memory is provisioned to each VM. However, the challenge is to precisely monitor the needed memory, i.e., the working set of each VM. In this paper, we thoroughly review the main techniques that were proposed for monitoring the working set of VMs. Additionally, we have implemented the main techniques in the Xen hypervisor and we have defined different metrics in order to evaluate their efficiency. Based on the evaluation results, we propose Badis, a system which combines several of the existing solutions, using the right solution at the right time. We also propose a consolidation extension which leverages Badis in order to pack the VMs based on the working set size and not the booked memory. The implementation of all techniques, our proposed system, and the benchmarks we have used are publicly available in order to support further research in this domain.
Degree of Queue Imbalance
Authors: Zhou Xingyu , Wu Fei , Tan Jian , Srinivasan Kannan , Shroff Ness
Published: April 2018

Heavy-traffic delay optimality is considered to be an important metric in evaluating the delay performance of load balancing schemes. In this paper, we argue that heavy-traffic delay optimality is a coarse metric that does not necessarily imply good delay performance. Specifically, we show that any load balancing scheme is heavy-traffic delay optimal as long as it satisfies a fairly weak condition. This condition only requires that in the long-term the dispatcher favors, even slightly, shorter queues over longer queues. Hence, although a load balancing scheme could be heavy-traffic delay optimal, the empirical delay performance of heavy-traffic delay optimal schemes can range from very good (that of join-shortest-queue) to very bad (arbitrarily close to the performance of random routing). To overcome this limitation, we introduce a new metric called
degree of queue imbalance,
which measures the queue length difference between all the servers in steady-state. Given a heavy-traffic delay optimal load balancing scheme, we can characterize the resultant
degree of queue imbalance.
This, in turn, allows us to explicitly differentiate between good and poor load balancing schemes. Thus, this paper suggests that when designing good load balancing schemes, they should not only be heavy-traffic delay optimal, but also have a low degree of queue imbalance.
Organizing a large-scale Physiology Understanding (PhUn) Week event at a science center
Authors: VanRyn Valerie S. , Poteracki James M. , Balzer Micaela , Wehrwein Erica A.
Published: April 2018

For the past 6 yr, the Department of Physiology at Michigan State University (MSU) has partnered with Impression 5 Science Center in Lansing, MI. Together, we host a day-long community engagement event on a Saturday each year in early November coinciding with the American Physiological Society’s Physiology Understanding Week. The purpose was to provide a fun and memorable hands-on experience for children and families. This paper describes the detailed planning and logistics. The event takes place in the main exhibit space at the science center, generally has 15–17 physiology activities stations set up as booths run by volunteers, and the event runs as an open-house format. Three to five trained volunteers were needed per station for the full day. Since this was primarily based on undergraduate student volunteer involvement (a population already limited for time), morning, afternoon, and/or full-day shifts were offered to accommodate a variety of schedules. Additional set-up, clean-up, and general help was also recruited. Overall, ~100–150 MSU students, faculty, and staff members served as volunteers, alongside Impression 5 staff. Hosting the event at the science center generated a larger audience, aided in advertisement, and allowed for access to a large facility capable of handling the 600–1,000 attendees. The partnership facilitated the sharing of equipment and supplies for physiology demonstrations, allowed for activities on site in the chemistry laboratory space, and facilitated the growth of new community partnerships with local schools and groups who attended the event.