bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical pulse stimulation: an in vitro exercise model for the induction of human skeletal muscle cell hypertrophy. A proof‐of‐concept study
Authors: Tarum Janelle , Folkesson Mattias , Atherton Philip J. , Kadi Fawzi
Published: September 2017

New Findings

What is the central question of this study?

Is electrical pulse stimulation (EPS) an in vitro exercise model able to elicit the hypertrophy of human muscle cells?

What is the main finding and its importance?

The addition of a restitution period of 8 h after EPS induces the enlargement of human muscle cells, a major physiological end‐point to resistance exercise. This is supported by downregulation of myostatin, a negative regulator of muscle mass, and increased phosphorylated mTOR and 4E‐BP1, key factors in the growth cascade. This proof‐of‐concept study provides a model of physiologically mediated muscle growth, which will be the basis for future studies aiming to depict molecular events governing the hypertrophy of human muscle cells.

Electrical pulse stimulation (EPS) of muscle cells has previously been used as an in vitro exercise model. The present study aimed to establish an EPS protocol promoting the hypertrophy of human muscle cells, which represents a major physiological end‐point to resistance exercise in humans. We hypothesized that adding a resting period after EPS would be crucial for the occurrence of the morphological change. Myoblasts obtained from human muscle biopsies (n = 5) were differentiated into multinucleated myotubes and exposed to 8 h of EPS consisting of 2 ms pulses at 12 V, with a frequency of 1 Hz. Myotube size was assessed using immunohistochemistry immediately, 4 and 8 h after completed EPS. Gene expression and phosphorylation status of selected markers of hypertrophy were assessed using RT‐PCR and Western blotting, respectively. Release of the myokine interleukin‐6 in culture medium was measured using enzyme‐linked immunosorbent assay. We demonstrated a significant increase (31 ± 14%; P = 0.03) in the size of myotubes when EPS was followed by an 8 h resting period, but not immediately or 4 h after completion of EPS. The response was supported by downregulation (P = 0.04) of the gene expression of myostatin, a negative regulator of muscle mass, and an increase in phosphorylated mTOR (P = 0.03) and 4E‐BP1 (P = 0.01), which are important factors in the cellular growth signalling cascade. The present work demonstrates that EPS is an in vitro exercise model promoting the hypertrophy of human muscle cells, recapitulating a major physiological end‐point to resistance exercise in human skeletal muscle.
Modeling and Analysis of Parallel Mechanisms With Both Kinematic and Actuation Redundancies Via Screw Theory
Authors: Kang Long , Kim Wheekuk , Yi Byung-Ju
Published: September 2017

Two kinds of mechanical redundancies, namely kinematic redundancy and actuation redundancy, have been extensively studied due to their advantageous features in autonomous industry. Screw theory has been successfully applied to develop an analytical Jacobian of nonredundant parallel manipulators (PMs). However, to the best of our knowledge, screw theory has not been attempted for modeling of PMs with kinematic redundancies. Thus, first, through the mobility analysis of a simple nonredundant planar PM and its variations, this paper reviews kinematic and actuation redundancy systematically. Then, we demonstrated how to derive analytical Jacobian and also static force relationship for a PM with both kinematic and actuation redundancies by using the screw theory. Finally, simulations were performed to demonstrate the advantageous features of kinematic and actuation redundancies.
Buckling of Cylindrical Steel Tanks With Oblique Body Imperfection Under Uniform External Pressure
Authors: Rastgar Mehdi , Showkati Hossein
Published: September 2017

Shell structures are built using a number of welded curved panel parts. Hence, some geometrical imperfections emerge. These imperfections have a direct impact on structural behavior of shells during the external compressive loading. In this research, a field study was accomplished on the implementation of the storage tanks in a refinery site, and then the resulted imperfections were identified and categorized. The survey of imperfections revealed that imperfection resulted from deviation with respect to the vertical direction has the highest number in tank bodies. This imperfection experimentally modeled, and the buckling behavior of these tanks was evaluated under uniform external pressure. The cylindrical tanks were examined using finite element analysis, and results obtained were compared with experimental results. Investigation of finding results demonstrated that such imperfection has a significant role in reducing the number of circumferential waves in body of the tanks under uniform external pressure. Comparing the results obtained by estimation, American Society of Mechanical Engineers (ASME) code, experimental research, and finite element method (FEM) represented a considerable difference in the amount of buckling load. Results show that tanks with oblique body imperfections exhibit high initial strength against buckling due to the uniform external pressure.
Molecular Dynamic Simulation of Hydrogen Production by Catalytic Gasification of Key Intermediates of Biomass in Supercritical Water
Authors: Jin Hui , Chen Bin , Zhao Xiao , Cao Changqing
Published: September 2017

Supercritical water gasification (SCWG) is an efficient and clean conversion of biomass due to the unique chemical and physical properties. Anthracene and furfural are the key intermediates in SCWG, and their microscopic reaction mechanism in supercritical water may provide information for reactor optimization and selection of optimal operating condition. Density functional theory (DFT) and reactive empirical force fields (ReaxFF) were combined to investigate the molecular dynamics of catalytic gasification of anthracene and furfural. The simulation results showed that Cu and Ni obviously increased the production of H radicals, therefore the substance SCWG process. Ni catalyst decreased the production of H2 with the residence time of 500 ps while significantly increased CO production and finally increased the syngas production. Ni catalyst was proved to decrease the free carbon production to prohibit the carbon deposition on the surface of active sites; meanwhile, Cu catalyst increased the production of free carbon.
Effects of noise suppression and envelope dynamic range compression on the intelligibility of vocoded sentences for a tonal language
Authors: Chen Fei , Zheng Dingchang , Tsao Yu
Published: September 2017

Vocoder simulation studies have suggested that the carrier signal type employed affects the intelligibility of vocoded speech. The present work further assessed how carrier signal type interacts with additional signal processing, namely, single-channel noise suppression and envelope dynamic range compression, in determining the intelligibility of vocoder simulations. In Experiment 1, Mandarin sentences that had been corrupted by speech spectrum-shaped noise (SSN) or two-talker babble (2TB) were processed by one of four single-channel noise-suppression algorithms before undergoing tone-vocoded (TV) or noise-vocoded (NV) processing. In Experiment 2, dynamic ranges of multiband envelope waveforms were compressed by scaling of the mean-removed envelope waveforms with a compression factor before undergoing TV or NV processing. TV Mandarin sentences yielded higher intelligibility scores with normal-hearing (NH) listeners than did noise-vocoded sentences. The intelligibility advantage of noise-suppressed vocoded speech depended on the masker type (SSN vs 2TB). NV speech was more negatively influenced by envelope dynamic range compression than was TV speech. These findings suggest that an interactional effect exists between the carrier signal type employed in the vocoding process and envelope distortion caused by signal processing.
The
Drosophila
embryo at single-cell transcriptome resolution
Authors: Karaiskos Nikos , Wahle Philipp , Alles Jonathan , Boltengagen Anastasiya , Ayoub Salah , Kipar Claudia , Kocks Christine , Rajewsky Nikolaus , Zinzen Robert P.
Published: September 2017

3D gene expression blueprint of the fly

When looking at populations of cells, features such as cell heterogeneity and localization are masked. However, single-cell sequencing reveals cellular heterogeneity and rare cell types. At the onset of gastrulation, the fly embryo consists of about 6000 cells with distinct gene expression profiles. Karaiskos
et al.
developed an algorithm to generate an interactive three-dimensional (3D) “virtual embryo,” with the expression of more than 8000 genes per cell measured for most cells (see the Perspective by Stadler and Eisen). The virtual embryo offers insights into developmental mechanisms—from local expression of regulators such as transcription factors and long noncoding RNAs to spatial modulation of signaling pathways.

Science
, this issue p.
194
; see also p.
172
Protecting unauthorized immigrant mothers improves their children’s mental health
Authors: Hainmueller Jens , Lawrence Duncan , Martén Linna , Black Bernard , Figueroa Lucila , Hotard Michael , Jiménez Tomás R. , Mendoza Fernando , Rodriguez Maria I. , Swartz Jonas J. , Laitin David D.
Published: September 2017

Life under threat of deportation

What is the effect on a child of having parents who are at risk of deportation as unauthorized immigrants? Hainmueller
et al.
developed a quasi-experimental protocol to address this complicated question. They selected mothers who had birthdates either just before or just after the cutoff for the United States' Deferred Action for Childhood Arrivals (DACA) program. Children whose mothers were protected from deportation by DACA had 50% fewer diagnoses of adjustment and anxiety disorder than children with mothers whose birthdates, by coincidence, preceded the cutoff and who thus were not protected.

Science
, this issue p.
1041
Nanophotonic rare-earth quantum memory with optically controlled retrieval
Authors: Zhong Tian , Kindem Jonathan M. , Bartholomew John G. , Rochman Jake , Craiciu Ioana , Miyazono Evan , Bettinelli Marco , Cavalli Enrico , Verma Varun , Nam Sae Woo , Marsili Francesco , Shaw Matthew D. , Beyer Andrew D. , Faraon Andrei
Published: September 2017

A rare-earth quantum memory

The development of global quantum networks will require chip-scale optically addressable quantum memories for quantum state storage, manipulation, and state swapping. Zhong
et al.
fabricated a nanostructured photonic crystal cavity in a rare-earth-doped material to form a high-fidelity quantum memory (see the Perspective by Waks and Goldschmidt). The cavity enhanced the light-matter interaction, allowing quantum states to be stored and retrieved from the memory on demand. The high fidelity and small footprint of the device offer a powerful building block for a quantum information platform.

Science
, this issue p.
1392
; see also p.
1354
Draft Genome Sequence of the Phytopathogenic FungusFusarium euwallaceae, the Causal Agent ofFusariumDieback
Authors: Ibarra-Laclette Enrique , Sánchez-Rangel Diana , Hernández-Domínguez Eric , Pérez-Torres Claudia-Anahí , Ortiz-Castro Randy , Villafán Emanuel , Alonso-Sánchez Alexandro , Rodríguez-Haas Benjamín , López-Buenfil Abel , García-Avila Clemente , Ramírez-Pool José-Abrahán
Published: September 2017

Here, we report the genome ofFusarium euwallaceaestrain HFEW-16-IV-019, an isolate obtained from Kuroshio shot hole borer (aEuwallaceasp.). These beetles were collected in Tijuana, Mexico, from elm trees showing typical symptoms ofFusariumdieback. The final assembly consists of 287 scaffolds spanning 48,274,071 bp and 13,777 genes.
Complete Genome Sequence of Lumpy Skin Disease Virus Isolate SERBIA/Bujanovac/2016, Detected during an Outbreak in the Balkan Area
Authors: Toplak Ivan , Petrović Tamaš , Vidanović Dejan , Lazić Sava , Šekler Milanko , Manić Marija , Petrović Miloš , Kuhar Urška
Published: September 2017

The lumpy skin disease virus (LSDV) isolate SERBIA/Bujanovac/2016 consists of 150,661 nucleotides and has a 99.95% nucleotide identity with the Neethling Warmbaths LW strain isolated in South Africa in 1999. This is the first complete LSDV genome determined in Serbia and also in the Balkan area.
Whole-Genome Sequence of Bacillus cereus AR156, a Potential Biocontrol Agent with High Soilborne Disease Biocontrol Efficacy and Plant Growth Promotion
Authors: Jiang Chun-Hao , Chen Yun , Yan Fang , Fan Zhi-Hang , Guo Jian-Hua
Published: September 2017

Bacillus cereus
AR156 was originally isolated from the forest soil of Zhenjiang, a city in China. To shed new light on the molecular mechanisms underlying the biological control of soilborne pathogens, the whole genome of this strain was sequenced. Here, we report the draft genome sequence of this strain, consisting of a single circularized contig measuring 5.66 Mb, with an average GC content of 35.5% and 5,367 open reading frames.
Draft Genome Sequences of the Oomycete
Pilasporangium apinafurcum
Strains JCM 30513 and JCM 30514, Formerly Classified as
Pythium apinafurcum
Authors: Uzuhashi Shihomi , Endoh Rikiya , Manabe Ri-ichiroh , Ohkuma Moriya
Published: September 2017

Pilasporangium apinafurcum
, formerly classified as
Pythium apinafurcum
, is a unique oomycete that infects plants asymptomatically. Here, we present the draft genome sequences of two variants of
P. apinafurcum
, JCM 30513 and JCM 30514, isolated from uncultivated field soil in Wakayama Prefecture, Japan.
Whole-Genome Sequence and Methylome Analysis of the Freshwater Colorless Sulfur Bacterium
Thioflexothrix psekupsii
D3
Authors: Fomenkov Alexey , Vincze Tamas , Grabovich Margarita Y. , Dubinina Galina , Orlova Maria , Belousova Elena , Roberts Richard J.
Published: September 2017

In this report, we announce the availability of a whole-genome sequence and methylome analysis of
Thioflexothrix psekupsii
strain D3.
High-Quality Draft Genome Sequences for Four Drug-Resistant or Outbreak-Associated Shigella sonnei Strains Generated with PacBio Sequencing and Whole-Genome Maps
Authors: Lindsey Rebecca L. , Batra Dhwani , Rowe Lori , N. Loparev Vladimir , Juieng Phalasy , Garcia-Toledo Lisley , Bicknese Amelia , Stripling Devon , Martin Haley , Chen Jessica , Strockbine Nancy , Trees Eija
Published: September 2017

Drug-resistant
Shigella sonnei
poses a clinical and public health challenge. We report here the high-quality draft whole-genome sequences of four outbreak-associated
S. sonnei
isolates; three were resistant to two or more antibiotics, and one was resistant to streptomycin only.
Complete Genome Sequence of the Pathogenic Vibrio vulnificus Type Strain ATCC 27562
Authors: Rusch Douglas B. , Rowe-Magnus Dean A.
Published: September 2017

Vibrio vulnificus
has the highest death rate and economic burden per case of any foodborne pathogen in the United States. A complete genome sequence of the type strain promotes comparative analyses with other clinical and environmental isolates, improving our understanding of this important human pathogen and successful environmental organism.
Complete Genome Sequence of
Nectarine stem pitting-associated virus
, Isolated from
Prunus persica
in Cheongdo County, South Korea
Authors: Igori Davaajargal , Baek Dasom , Kim San Yeong , Seo Euncheol , Lee Su-Heon , Jeong Rae-Dong , Yi Seung-In , Bong Jin-Jong , Moon Jae Sun
Published: September 2017

We report here the first complete genome sequence of a South Korean isolate of
Nectarine stem pitting-associated virus
(NSPaV) from peach and compare it with previously described complete NSPaV genome sequences. The highest whole-genome nucleotide sequence identity was 95.3% with GenBank accession no. KT273409 (NSPaV) from the United States.
Complete Genome Sequence of Bacillus velezensis GQJK49, a Plant Growth-Promoting Rhizobacterium with Antifungal Activity
Authors: Ma Jinjin , Liu Hu , Liu Kai , Wang Chengqiang , Li Yuhuan , Hou Qihui , Yao Liangtong , Cui Yanru , Zhang Tongrui , Wang Haide , Wang Beibei , Wang Yun , Ge Ruofei , Xu Baochao , Yao Gan , Xu Wenfeng , Fan Lingchao , Ding Yanqin , Du Binghai
Published: September 2017

Bacillus velezensis
GQJK49 is a plant growth-promoting rhizobacterium with antifungal activity, which was isolated from
Lycium barbarum
L. rhizosphere. Here, we report the complete genome sequence of
B. velezensis
GQJK49. Twelve gene clusters related to its biosynthesis of secondary metabolites, including antifungal and antibacterial antibiotics, were predicted.
Genome Sequence of Rhizobium esperanzae Type Strain CNPSo 668, Isolated from Phaseolus vulgaris Nodules in Mexico
Authors: Helene Luisa Caroline Ferraz , Ribeiro Renan Augusto , Hungria Mariangela
Published: September 2017

Rhizobium esperanzae
CNPSo 668
T
is a nitrogen-fixing symbiont of
Phaseolus vulgaris
isolated from Mexican soils. Its genome is estimated at 6,294,057 bp, with 6,219 coding sequences (CDSs) showing higher similarity (92.9%) with
Rhizobium etli
. Three copies of the regulatory
nodD
, in addition to other nodulation genes, should define its host specificity.
Comparative analysis of gender differences in outcomes after trauma in India and the USA: case for standardised coding of injury mechanisms in trauma registries
Authors: Dasari Mohini , David Siddarth D , Miller Elizabeth , Puyana Juan Carlos , Roy Nobhojit
Published: September 2017

Introduction

While females generally have better outcomes than males after traumatic injury, higher mortality has been shown to occur in females after intentional trauma in lower-income countries. However, gender differences in trauma outcomes in different countries have not been previously compared. We conducted a two-country comparative analysis to characterise gender differences in mortality for different mechanisms of injury.

Methods

Two urban trauma databases were analysed from India and the USA for fall, motor vehicle collision (MVC) and assault patients between 2013 and 2015. Coarsened exact matching was used to match the two groups based on gender, age, injury severity score, Glasgow Coma Score and type of injury (blunt vs penetrating). The primary outcome of mortality was studied by using logistic regression to calculate the odds of death in the four country/gender subgroups.

Results

A total of 10 089 and 14 144 patients were included from the Indian and US databases, respectively. After matching on covariates, 7505 and 9448 patients were included in the logistic regression. Indian males had the highest odds of death compared with US males, US females and Indian females for falls, MVC and assaults. Indian females had over 7 times the odds of dying after falls, 5 times the odds of dying for MVC and 40 times the odds of dying after assaults when compared with US females.

Conclusion

The high odds of death for Indian females compared with US females suggests that there are other injury and systemic factors that contribute to this discrepancy in mortality odds. This same mortality pattern and implication is seen for Indian males compared with all subgroups. Standardised coding of injury mechanism in trauma registries, in addition to intentionality of injury, can help further characterise discrepancies in outcomes by gender and country, to guide targeted injury prevention and care.
Development and validation of hospital information system-generated indicators of the appropriateness of oral anticoagulant prescriptions in hospitalised adults: the PACHA study protocol
Authors: Petit-Monéger Aurélie , Thiessard Frantz , Jouhet Vianney , Noize Pernelle , Berdaï Driss , Kret Marion , Sitta Rémi , Salmi Louis-Rachid , Saillour-Glénisson Florence
Published: September 2017

Introduction

The appropriateness of oral anticoagulant prescriptions is a major challenge to improve quality and safety of care. As indicators of the appropriateness of oral anticoagulant prescriptions are lacking, the aim of the study is to develop and validate a panel of such indicators, in hospitalised adults, from the hospital information system of two university hospitals in France.

Methods and analysis

The study will be carried out in four steps: (1) a literature review to identify indicators of the appropriateness of oral anticoagulant prescriptions and their conditions of appropriateness; (2) a Delphi consensus method to assess the potential utility and operational implementation of the selected indicators; (3) techniques of medical data search to implement indicators from the hospital information system and; (4) a cross-sectional study to assess the ability of indicators to detect inappropriate oral anticoagulant prescriptions, performance of medical data search techniques for tracking or retrieving information and the ability of tools to be transferred into other institutions. The fourth step will include up to 80 patient hospital stays for each indicator, depending on the prevalence of inappropriate prescriptions estimated in interim analyses.

Ethics and dissemination

This work addresses the current lack of quality indicators of the appropriateness of oral anticoagulant prescriptions. We aim to develop and validate such indicators for integrating them into hospital clinical practice, as part of a structured approach to improve quality and safety of care. As each hospital information system is different, we will propose tools transferable to other healthcare institutions to allow an automated construction of these indicators. The PACHA study protocol was approved by institutional review boards and ethics committees (CPP Sud-Ouest et Outre Mer III—DC 2016/119; CPP Ile-de-France II—CDW_2016_0014).

Registration details

Clinical Trial.gov registration:NCT02898090.
Can more appropriate support and services be provided for people who attend the emergency department frequently? National Health Service staff views
Authors: Ablard Suzanne , Coates Elizabeth , Cooper Cindy , Parry Glenys , Mason Suzanne M
Published: September 2017

Background

Interventions designed to help Emergency Department (ED) staff manage frequent attenders are labour-intensive and only benefit a small sample of frequent attenders. We aimed to use the in-depth knowledge of health professionals with experience of working with ED frequent attenders to understand the challenges of managing this group of patients and their opinions on providing more appropriate support.

Methods

Semi-structured interviews were conducted with medical and nursing ED staff, mental health liaison nurses and general practitioners (GPs). Interviews covered the following: definitions and experiences of treating frequent attenders and thoughts on alternative service provision. Vignettes of frequent attenders were used to elicit discussions on these topics. Thematic analysis of transcribed interviews was undertaken.

Results

Twelve health professionals were interviewed. Three groups of frequent attenders were identified: people with long-term physical conditions, mental health problems and health-related anxiety. Underlying reasons for attendance differed between the groups, highlighting the need for targeted interventions. Suggested interventions included improving self-management of long-term physical conditions; creating a ‘go-to’ place away from the ED for patients experiencing a mental health crisis; increasing the provision of mental health liaison services; and for patients with health-related anxiety, the role of the GP in the patients’ care pathway was emphasised, as were the benefits of providing additional training for ED staff to help identify and support this group.

Conclusion

Interventions to address frequent attendance should focus on redirection to and liaison with more appropriate services, located on the hospital site or in the community, tailored to each identified patient group.
Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas
Authors: Lin De-Chen , Dinh Huy Q , Xie Jian-Jun , Mayakonda Anand , Silva Tiago Chedraoui , Jiang Yan-Yi , Ding Ling-Wen , He Jian-Zhong , Xu Xiu-E , Hao Jia-Jie , Wang Ming-Rong , Li Chunquan , Xu Li-Yan , Li En-Min , Berman Benjamin P , Phillip Koeffler H
Published: September 2017

Objectives

Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number of clinical and epidemiological characteristics, complicating the design of clinical trials and biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, and biological and clinical significance.

Design

Previously exome-sequenced samples were re-analysed to identify significantly mutated genes (SMGs) and mutational signatures. The biological functions of novel SMGs were investigated using cell line and xenograft models. We further performed whole-genome bisulfite sequencing and chromatin immunoprecipitation (ChIP)-seq to characterise epigenetic alterations.

Results

OSCC and OAC displayed nearly mutually exclusive sets of driver genes, indicating that they follow independent developmental paths. The combined sample size allowed the statistical identification of a number of novel subtype-specific SMGs, mutational signatures and prognostic biomarkers. Particularly, we identified a novel mutational signature similar to Catalogue Of Somatic Mutations In Cancer (COSMIC)signature 16, which has prognostic value in OSCC. Two newly discovered SMGs,
CUL3
and
ZFP36L2
, were validated as important tumour-suppressors specific to the OSCC subtype. We further identified their additional loss-of-function mechanisms.
CUL3
was homozygously deleted specifically in OSCC and other squamous cell cancers (SCCs). Notably,
ZFP36L2
is associated with super-enhancer in healthy oesophageal mucosa; DNA hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancer-associated SCC suppressor.

Conclusions

These data comprehensively contrast differences between OSCC and OAC at both genomic and epigenomic levels, and reveal novel molecular features for further delineating the pathophysiological mechanisms and treatment strategies for these cancers.
Book your place at the BVA Gala Dinner
Authors: Dingle Helen
Published: September 2017

Helen Dingle, BVA CPD and Events Officer, highlights the excitement to come at the BVA Gala Dinner.
Making animal welfare education fun for children
Authors: Duggal Girija
Published: September 2017

Girija Duggal, BVA Media Officer, explains how to make learning about animal welfare fun for all ages.
The Need for Affective Trust Applied to Trust and Reputation Models
Authors: Granatyr Jones , Osman Nardine , Dias João , Nunes Maria Augusta Silveira Netto , Masthoff Judith , Enembreck Fabrício , Lessing Otto Robert , Sierra Carles , Paiva Ana Maria , Scalabrin Edson Emílio
Published: September 2017

Trust allows the behavior evaluation of individuals by setting confidence values, which are used in decisions about whether or not to interact. They have been used in several fields, and many trust and reputation models were developed recently. We perceived that most of them were built upon the numeric and cognitive paradigms, which do not use affective aspects to build trust or help in decision making. Studies in psychology argued that personality, emotions, and mood are important in decision making and can change the behaviors of individuals. Based on that, we present links between trust and affective computing, showing relations of trust dimensions found in trust models with affective aspects, and presenting why affective computing approaches fit trust issues often addressed by research in this field. We also discuss trust relationships and decision making, emotions, and personality. Affective computing concepts have been used in a dispersed way and specifically in some models, so we aim to bring them together to encourage the growth of fuller trust models similar to those used by humans. We aim to find relations between both fields so it will be possible to employ such concepts to develop trust models using this new paradigm, defined as the affective paradigm.
Optimal Don’t Care Filling for Minimizing Peak Toggles During At-Speed Stuck-At Testing
Authors: Trinadh A. Satya , Potluri Seetal , Ch. Sobhan Babu , Kamakoti V. , Singh Shiv Govind
Published: September 2017

Due to the increase in manufacturing/environmental uncertainties in the nanometer regime, testing digital chips under different operating conditions becomes mandatory. Traditionally, stuck-at tests were applied at slow speed to detect structural defects and transition fault tests were applied at-speed to detect delay defects. Recently, it was shown that certain cell-internal defects can only be detected using
at-speed stuck-at testing
. Stuck-at test patterns are power hungry, thereby causing excessive voltage droop on the power grid, delaying the test response, and finally leading to false delay failures on the tester. This motivates the need for peak power minimization during at-speed stuck-at testing. In this article, we use input toggle minimization as a means to minimize a circuit’s power dissipation during at-speed stuck-at testing under the Combinational State Preservation scan (CSP-scan) Design-For-Testability (DFT) scheme. For circuits whose test sets are dominated by don’t cares, this article maps the problem of optimal X-filling for peak input toggle minimization to a variant of the interval coloring problem and proposes a Dynamic Programming (DP) algorithm (DP-fill) for the same along with a theoretical proof for its optimality. For circuits whose test sets are not dominated by don’t cares, we propose a max scatter Hamiltonian path algorithm, which ensures that the ordering is done such that the don’t cares are evenly distributed in the final ordering of test cubes, thereby leading to better input toggle savings than DP-fill. The proposed algorithms, when experimented on ITC99 benchmarks, produced peak power savings of up to 48% over the best-known algorithms in literature. We have also pruned the solutions thus obtained using Greedy and Simulated Annealing strategies with iterative 1-bit neighborhood to validate our idea of optimal input toggle minimization as an effective technique for minimizing peak power dissipation during at-speed stuck-at testing.
DBpedia-Based Entity Linking via Greedy Search and Adjusted Monte Carlo Random Walk
Authors: Liu Ming , Chen Lei , Liu Bingquan , Zheng Guidong , Zhang Xiaoming
Published: September 2017

Facing a large amount of entities appearing on the web, entity linking has recently become useful. It assigns an entity from a resource to one name mention to help users grasp the meaning of this name mention. Unfortunately, many possible entities can be assigned to one name mention. Apparently, the usually co-occurring name mentions are related and can be considered together to determine their best assignments. This approach is called collective entity linking and is often conducted based on entity graph. However, traditional collective entity linking methods either consume much time due to the large scale of entity graph or obtain low accuracy due to simplifying graph. To improve both accuracy and efficiency, this article proposes a novel collective entity linking algorithm. It first constructs an entity graph by connecting any two related entities, and then a probability-based objective function is proposed on this graph to ensure the high accuracy of the linking result. Via this function, we convert entity linking to the process of finding the nodes with the highest PageRank Values. Greedy search and an adjusted Monte Carlo random walk are proposed to fulfill this work. Experimental results demonstrate that our algorithm performs much better than traditional linking methods.
Non-GPS Positioning Systems
Authors: Tariq Zain Bin , Cheema Dost Muhammad , Kamran Muhammad Zahir , Naqvi Ijaz Haider
Published: September 2017

An enormous amount of research has been conducted in the area of positioning systems and thus it calls for a detailed literature review of recent localization systems. This article focuses on recent developments of non-Global Positioning System (GPS) localization/positioning systems. We have presented a new hierarchical method to classify various positioning systems. A comprehensive performance comparison of the techniques and technologies against multiple performance metrics along with the limitations is presented. A few indoor positioning systems have emerged as more successful in particular application environments than others, which are presented at the end.
Cognitive Dysfunctions in Intellectual Disabilities: The Contributions of the Ras-MAPK and PI3K-AKT-mTOR Pathways
Authors: Borrie Sarah C. , Brems Hilde , Legius Eric , Bagni Claudia
Published: September 2017

The Ras-MAPK and PI3K-AKT-mTOR signaling cascades were originally identified as cancer regulatory pathways but have now been demonstrated to be critical for synaptic plasticity and behavior. Neurodevelopmental disorders arising from mutations in these pathways exhibit related neurological phenotypes, including cognitive dysfunction, autism, and intellectual disability. The downstream targets of these pathways include regulation of transcription and protein synthesis. Other disorders that affect protein translation include fragile X syndrome (an important cause of syndromal autism), and other translational regulators are now also linked to autism. Here, we review how mechanisms of synaptic plasticity have been revealed by studies of mouse models for Ras-MAPK, PI3K-AKT-mTOR, and translation regulatory pathway disorders. We discuss the face validity of these mouse models and review current progress in clinical trials directed at ameliorating cognitive and behavioral symptoms.
Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits
Authors: Florova Galina , Azghani Ali O. , Karandashova Sophia , Schaefer Chris , Yarovoi Serge V. , Declerck Paul J. , Cines Douglas B. , Idell Steven , Komissarov Andrey A.
Published: September 2017

Elevated active plasminogen activator inhibitor-1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. To enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and monoclonal antibody (mAb)-mediated PAI-1 inactivation. Removing positively charged residues at the “PAI-1 docking site” (179RHRGGS184→179AAAAAA184) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1. Mutant prourokinase (0.0625–0.5 mg/kg; n = 12) showed efficacy comparable to wild-type scuPA and did not change IPFT outcomes ( P > 0.05). Notably, the rate of PAI-1-independent intrapleural inactivation of mutant uPA was 2 times higher ( P < 0.05) than that of the wild-type enzyme. Trapping PAI-1 in a “molecular sandwich”-type complex with catalytically inactive two-chain urokinase with Ser195Ala substitution (S195A-tcuPA; 0.1 and 0.5 mg/kg) did not improve the efficacy of IPFT with scuPA (0.0625–0.5 mg/kg; n = 11). IPFT failed in the presence of MA-56A7C10 (0.5 mg/kg; n = 2), which forms a stable intrapleural molecular sandwich complex, allowing active PAI-1 to accumulate by blocking its transition to a latent form. In contrast, inactivation of PAI-1 by accelerating the active-to-latent transition mediated by mAb MA-33B8 (0.5 mg/kg; n = 2) improved the efficacy of IPFT with scuPA (0.25 mg/kg). Thus, under conditions of slow (4–8 h) fibrinolysis in tetracycline-induced pleural injury in rabbits, only the inactivation of PAI-1, but not a decrease in the rate of its reaction with uPA, enhances IPFT. Therefore the rate of fibrinolysis, which varies in different pathologic states, could affect the selection of PAI-1 inhibitors to enhance fibrinolytic therapy.
The endothelium in hypoxic pulmonary vasoconstriction
Authors: Grimmer Benjamin , Kuebler Wolfgang M.
Published: September 2017

Hypoxic pulmonary vasoconstriction (HPV) in combination with hypercapnic pulmonary vasoconstriction redistributes pulmonary blood flow from poorly aerated to better ventilated lung regions by an active process of local vasoconstriction. Impairment of HPV results in ventilation-perfusion mismatch and is commonly associated with various lung diseases including pneumonia, sepsis, or cystic fibrosis. Although several regulatory pathways have been identified, considerable knowledge gaps persist, and a unifying concept of the signaling pathways that underlie HPV and their impairment in lung diseases has not yet emerged. In the past, conceptual models of HPV have focused on pulmonary arterial smooth muscle cells (PASMC) acting as sensor and effector of hypoxia in the pulmonary vasculature. In contrast, the endothelium was considered a modulating bystander in this scenario. For an ideal design, however, the oxygen sensor in HPV should be located in the region of gas exchange, i.e., in the alveolar capillary network. This concept requires the retrograde propagation of the hypoxic signal along the endothelial layer of the vascular wall and subsequent contraction of PASMC in upstream arterioles that is elicited via temporospatially tightly controlled endothelial-smooth muscle cell crosstalk. The present review summarizes recent work that provides proof-of-principle for the existence and functional relevance of such signaling pathway in HPV that involves important roles for connexin 40, epoxyeicosatrienoic acids, sphingolipids, and cystic fibrosis transmembrane conductance regulator. Of translational relevance, implication of these molecules provides for novel mechanistic explanations for impaired ventilation/perfusion matching in patients with pneumonia, sepsis, cystic fibrosis, and presumably various other lung diseases.
Laser Peripheral Iridotomy versus Trabeculectomy as an Initial Treatment for Primary Angle-Closure Glaucoma
Authors: Chen Yan Yun , Fan Su Jie , Liang Yuan Bo , Rong Shi Song , Meng Hai Lin , Wang Xing , Thomas Ravi , Wang Ning Li
Published: September 2017

Purpose. To compare laser peripheral iridotomy (LPI) with trabeculectomy as an initial treatment for primary angle-closure glaucoma (PACG) with peripheral anterior synechiae (PAS) ≥ 6 clock hours. Methods. Patients were drawn from two randomized controlled trials. 38 eyes of 38 patients (PAS ≥ 6 clock hours) were treated with LPI (group 1) while 111 eyes of 111 PACG patients (PAS ≥ 6 clock hours) underwent primary trabeculectomy (group 2). All patients underwent a comprehensive ophthalmic examination at baseline and at postoperative visits and were followed up for a minimum of one year. Results. Group 2 had higher baseline IOP (45.7 ± 14.8 mmHg versus 34.3 ± 14.3 mmHg) than group 1 and more clock hours of PAS (10.4 ± 1.9 versus 9.0 ± 2.2). IOPs at all postoperative visits were significantly lower in group 2 than in group 1 (p=0.000). Five eyes in group 1 required trabeculectomy. 17 of the 38 eyes in group 1 (44.7%) required IOP-lowering medications as compared to seven of the 111 eyes in group 2 (6.3%). Cataract progression was documented in 2 eyes (5.3%) in group 1 and 16 eyes (14.4%) in group 2. Conclusions. Primary trabeculectomy for PACG (PAS ≥ 6 clock hours) is more effective than LPI in lowering IOP.
The Neuroprotective Effects of SIRT1 on NMDA‐Induced Excitotoxicity
Authors: Yang Xiaorong , Si Peipei , Qin Huaping , Yin Litian , Yan Liang-Jun , Zhang Ce
Published: September 2017

Silent information regulator 1 (SIRT1), an NAD+‐dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA‐mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV) in cultured cortical neurons or by overexpression of SIRT1 in SH‐SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA‐induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA‐induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH) release, and a decrease in the number of living cells as measured by CCK‐8 assay, LDH test, and Calcein‐AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA‐induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA‐induced neurotoxicity.
From Famine to Feast: Developing Early-Phase Combination Immunotherapy Trials Wisely
Authors: Day Daphne , Monjazeb Arta M. , Sharon Elad , Ivy S. Percy , Rubin Eric H. , Rosner Gary L. , Butler Marcus O.
Published: September 2017

Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes. Clin Cancer Res; 23(17); 4980–91. ©2017 AACR.

See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era.”
Immuno-oncology Clinical Trial Design: Limitations, Challenges, and Opportunities
Authors: Baik Christina S. , Rubin Eric H. , Forde Patrick M. , Mehnert Janice M. , Collyar Deborah , Butler Marcus O. , Dixon Erica L. , Chow Laura Q.M.
Published: September 2017

Recent advances in immuno-oncology and regulatory approvals have been rapid and paradigm shifting in many difficult-to-treat malignancies. Despite immune checkpoint inhibitor therapy becoming the standard of care across multiple tumor types, there are many unanswered questions that need to be addressed before this therapeutic modality can be fully harnessed. Areas of limitations include treatment of patients not sufficiently represented in clinical trials, uncertainty of the optimal treatment dosing and duration, and lack of understanding regarding long-term immune related toxicities and atypical tumor responses. Patients such as those with autoimmune disease, chronic viral infections, limited performance status, and brain metastases were often excluded from initial trials due to concerns of safety. However, limited data suggest that some of these patients can benefit from therapy with manageable toxicities; thus, future studies should incorporate these patients to clearly define safety and efficacy. There are still controversies regarding the optimal dosing strategy that can vary from weight-based to flat dosing, with undefined treatment duration. Further elucidation of the optimal dosing approach and evaluation of predictive biomarkers should be incorporated in the design of future trials. Finally, there are long-term immune-mediated toxicities, atypical tumor responses such as pseudoprogression and endpoints unique to immuno-oncology that are not adequately captured by traditional trial designs; thus, novel study designs are needed. In this article, we discuss in detail the above challenges and propose needed areas of research for exploration and incorporation in the next generation of immuno-oncology clinical trials. Clin Cancer Res; 23(17); 4992–5002. ©2017 AACR.

See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era.”
Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review
Authors: Himbert Caroline , Delphan Mahmoud , Scherer Dominique , Bowers Laura W. , Hursting Stephen , Ulrich Cornelia M.
Published: September 2017

Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiologic, clinical, and preclinical data suggest that within the growth-promoting, proinflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct “crosstalk” between adipose tissue and carcinomas in humans. We identified 4,641 articles with n = 20 human clinical studies, which are summarized as: (i) breast (n = 7); (ii) colorectal (n = 4); (iii) esophageal (n = 2); (iv) esophageal/colorectal (n = 1); (v) endometrial (n = 1); (vi) prostate (n = 4); and (vii) ear-nose-throat (ENT) cancer (n = 1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL6, TNFα, and other mechanisms. Moreover, visceral white adipose tissue plays a more central role, as it is more bioenergetically active and is associated with a more procancer secretome than subcutaneous adipose tissue. Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers. Cancer Prev Res; 10(9); 494–506. ©2017 AACR.
Infections of Intrathecal Baclofen Delivery Systems and Ventriculoperitoneal Shunting Systems: Clinical Series Discussion
Authors: Abousamra Oussama , Duque Orozco Maria del Pilar , Rogers Kenneth J. , Miller Freeman , Sees Julieanne P.
Published: September 2017

Background/Aims: The physiological interaction between the intrathecal baclofen (ITB) delivery system and the ventriculoperitoneal (VP) shunting system in a patient who had both systems implanted has not been reported previously. The aim of our report is to evaluate the effect that one system's infection might have on the other. Methods: Records of children who were followed at our institution between 2004 and 2015 for management of their ITB systems were reviewed. In this group, children who had VP shunts were identified, and those who had any of their ITB or VP systems infected were included. Results: Out of 313 children managed with ITB therapy at our institution, 31 (24%) children had VP shunts. Two patients had infection in both systems, and 3 patients had infection in 1 system. Conclusion: This report suggests that if aspiration from both systems showed positive cultures, the treatment would be removal of both systems. If the primarily not infected system does not show positive cultures, it does not need to be removed. Close follow-up is recommended, and any sign of infection or malfunction of the primarily not infected device should be approached with a high level of suspicion.