bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoimprint-induced orientation of localized wrinkles with SU-8
Authors: Steinberg Christian , Runkel Manuel , Papenheim Marc , Wang Si , Mayer Andre , Scheer Hella-Christin
Published: September 2016

With thermal processing of multilayer systems' prevention of wrinkling is challenging, but when wrinkling results in well-controlled patterns, this self-forming process is interesting for a lot of applications, in particular, when mechanically stable and transparent materials are involved. The authors use the widely used negative tone photoresist SU-8; the hard top layer is realized by vacuum ultraviolet-treatment. Applicability of the established wrinkling theories to this SU-8 system is verified. The control of wrinkling is provided by masked lithography and nanoimprint. In combination, these two techniques allow controlling the wrinkling area and, moreover, are capable of inducing anisotropy to the wrinkling pattern. An analytical calculation of the anisotropy is presented and compared to experimental results. The calculation is based on the bending stiffness of two orthogonal directions. Two types of imprinted line-structures are investigated, normal and inverted V-grooves. Wrinkling amplitudes and anisotropies found are in good accordance with theoretical results.
Versatile multicharacterization platform involving tailored superhydrophobic SU-8 micropillars for the investigation of breast cancer estrogen receptor isoforms
Authors: Accardo Angelo , Trevisiol Emmanuelle , Cerf Aline , Thibault Christophe , Laurell Henrik , Buscato Melissa , Lenfant Françoise , Arnal Jean-François , Fontaine Coralie , Vieu Christophe
Published: September 2016

Here, the authors report the fabrication of lotus-leaf-like tailored SU8 micropillars and their application in the context of a multitechnique characterization protocol for the investigation of the structural properties of the two estrogen receptors (ERα66/ERα46). ER (α) expression is undoubtedly the most important biomarker in breast cancer, as it provides the index for sensitivity to endocrine treatment. Beside the well-characterized ERα66 isoform, a shorter one (ERα46) is also expressed in ERα positive breast cancers and breast cancer cell lines. The superhydrophobic supports were developed by using a two-step approach including an optical lithography process and a plasma reactive ion roughening one. Upon drying on the micropillars, the biological samples resulted in stretched fibers of different diameters which were then characterized by synchrotron x-ray diffraction (XRD), Raman and Fourier-transform infrared spectroscopy. The evidence of both different spectroscopic vibrational responses and XRD signatures in the two estrogen receptors suggests the presence of conformational changes between the two biomarkers. The SU8 micropillar platform therefore represents a valid tool to enhance the discrimination sensitivity of structural features of this class of biomarkers by exploiting a multitechnique in situ characterization approach.
Design of broadband time-domain impedance boundary conditions using the oscillatory-diffusive representation of acoustical models
Authors: Monteghetti Florian , Matignon Denis , Piot Estelle , Pascal Lucas
Published: September 2016

A methodology to design broadband time-domain impedance boundary conditions (TDIBCs) from the analysis of acoustical models is presented. The derived TDIBCs are recast exclusively as first-order differential equations, well-suited for high-order numerical simulations. Broadband approximations are yielded from an elementary linear least squares optimization that is, for most models, independent of the absorbing material geometry. This methodology relies on a mathematical technique referred to as the oscillatory-diffusive (or poles and cuts) representation, and is applied to a wide range of acoustical models, drawn from duct acoustics and outdoor sound propagation, which covers perforates, semi-infinite ground layers, as well as cavities filled with a porous medium. It is shown that each of these impedance models leads to a different TDIBC. Comparison with existing numerical models, such as multi-pole or extended Helmholtz resonator, provides insights into their suitability. Additionally, the broadly-applicable fractional polynomial impedance models are analyzed using fractional calculus.
CHK1 as a therapeutic target to bypass chemoresistance in AML
Authors: David Laure , Fernandez-Vidal Anne , Bertoli Sarah , Grgurevic Srdana , Lepage Benoît , Deshaies Dominique , Prade Naïs , Cartel Maëlle , Larrue Clément , Sarry Jean-Emmanuel , Delabesse Eric , Cazaux Christophe , Didier Christine , Récher Christian , Manenti Stéphane , Hoffmann Jean-Sébastien
Published: September 2016

AML patients have new hope for overcoming resistance to therapy by inhibiting the DNA checkpoint kinase CHK1.
Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells
Authors: Blewett Megan M. , Xie Jiji , Zaro Balyn W. , Backus Keriann M. , Altman Amnon , Teijaro John R. , Cravatt Benjamin F.
Published: September 2016

Chemical proteomics analysis suggests the mechanism of action of a drug used to treat autoimmune diseases.
New connections: New hope for AML patients
Authors: Ferrarelli Leslie K.
Published: September 2016

New mechanistic insights into the development and therapeutic resistance of acute myeloid leukemia should help identify patients most likely to benefit from treatment.
Development of a Novel Collagen Wound Model To Simulate the Activity and Distribution of Antimicrobials in Soft Tissue during Diabetic Foot Infection
Authors: Price Bianca L. , Lovering Andrew M. , Bowling Frank L. , Dobson Curtis B.
Published: September 2016

Diabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robustPseudomonas aeruginosabiofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistantStaphylococcus aureusbiofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs.
In Vitro
Activity of Solithromycin against Bordetella pertussis, an Emerging Respiratory Pathogen
Authors: Hardy Dwight J. , Vicino David , Fernandes Prabhavathi
Published: September 2016

There has been an increase in the number of pertussis cases reported since the introduction of the acellular pertussis vaccine. While children that present with pertussis have a characteristic whooping cough, adults can simply have a persistent, nonspecific cough and remain undiagnosed. Macrolide antibiotics, such as azithromycin, are the currently recommended treatment for pertussis. Solithromycin is a new macrolide and the first fluoroketolide with broad activity against a wide spectrum of bacterial pathogens and has completed clinical development for community-acquired bacterial pneumonia. This study reports the potent
in vitro
activity of solithromycin against a collection of recent isolates of
Bordetella pertussis
.
PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally
Authors: Graci Jason D. , Jung Stephen P. , Pichardo John , Lahser Frederick , Tong Xiao , Gu Zhengxian , Colacino Joseph M.
Published: September 2016

PTC725 is a small molecule NS4B-targeting inhibitor of hepatitis C virus (HCV) genotype (gt) 1 RNA replication that lacks activity against HCV gt2. We analyzed the Los Alamos HCV sequence database to predict susceptible/resistant HCV gt's according to the prevalence of known resistance-conferring amino acids in the NS4B protein. Our analysis predicted that HCV gt3 would be highly susceptible to the activity of PTC725. Indeed, PTC725 was shown to be active against a gt3 subgenomic replicon with a 50% effective concentration of ∼5 nM.
De novo
resistance selection identified mutations encoding amino acid substitutions mapping to the first predicted transmembrane region of NS4B, a finding consistent with results for PTC725 and other NS4B-targeting compounds against HCV gt1. This is the first report of the activity of an NS4B targeting compound against HCV gt3. In addition, we have identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region.
mgrB
Mutations Mediating Polymyxin B Resistance in Klebsiella pneumoniae Isolates from Rectal Surveillance Swabs in Brazil
Authors: Aires Caio Augusto Martins , Pereira Polyana Silva , Asensi Marise Dutra , Carvalho-Assef Ana Paula D'Alincourt
Published: September 2016

We aimed to investigate polymyxin B (PMB) resistance and its molecular mechanisms in 126
Klebsiella pneumoniae
isolates from rectal swabs in Brazil. Ten isolates exhibited PMB resistance with interruption of
mgrB
gene by insertion sequences or missense mutations. Most of the PMB-resistant isolates harbored
bla
KPC-2
(
n
= 8) and belonged to clonal complex 258 (CC258) (
n
= 7). These results highlight the importance of monitoring the spread of polymyxin-resistant bacteria in hospitals, since few options remain to treat multidrug-resistant isolates.
Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin
Authors: Tronnet Sophie , Garcie Christophe , Rehm Nadine , Dobrindt Ulrich , Oswald Eric , Martin Patricia
Published: September 2016

The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by iron availability, we hypothesized that iron could also modulate the production of colibactin through the transcriptional regulation of
clbA
. This study revealed an increased transcription of
clbA
under iron-limiting conditions and a decrease of
clbA
expression in iron-rich media. We demonstrate that
clbA
transcription is regulated by both the ferric uptake regulator (Fur) and the small regulatory noncoding RNA RyhB. We evidenced that the regulation of the transcription of
clbA
by Fur and RyhB leads to the regulation of colibactin production. This work highlights the complex mechanism of regulation of an important virulence factor by the two major regulators of bacterial iron homeostasis, making iron a key environmental factor contributing to bacterial virulence and carcinogenesis.
Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster
Authors: Zhang Wenlong , Zhang Naisheng , Xie Xufeng , Guo Jian , Jin Xuemin , Xue Feng , Ding Zhuang , Cao Yongguo
Published: September 2016

Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after
Leptospira interrogans
serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.
Spontaneous Reversions of an Evolutionary Trait Loss Reveal Regulators of a Small RNA That Controls Multicellular Development in Myxobacteria
Authors: Yu Yuen-Tsu N. , Kleiner Manuel , Velicer Gregory J.
Published: September 2016

Lost traits can reevolve, but the probability of trait reversion depends partly on a trait's genetic complexity. Myxobacterial fruiting body development is a complex trait controlled by the small RNA (sRNA) Pxr, which blocks development under conditions of nutrient abundance. In developmentally proficient strains of
Myxococcus xanthus
, starvation relaxes the inhibition by Pxr, thereby allowing development to proceed. In contrast, the lab-evolved strain OC does not develop because it fails to relay an early starvation signal that alleviates inhibition by Pxr. A descendant of OC, strain PX, previously reevolved developmental proficiency via a mutation in
pxr
that inactivates its function. A single-colony screen was used to test whether reversion of OC to developmental proficiency occurs only by mutation of
pxr
or might also occur through alternative regulatory loci. Five spontaneous mutants of OC that exhibited restored development were isolated, and all five showed defects in Pxr synthesis, structure, or processing, including one that incurred an eight-nucleotide deletion in
pxr
. Two mutations occurred in the σ
54
response regulator (RR) gene
MXAN_1078
(named
pxrR
here), immediately upstream of
pxr
. PxrR was found to positively regulate
pxr
transcription, presumably via the σ
54
promoter of
pxr
. Two other mutations were identified in a histidine kinase (HK) gene (
MXAN_1077
; named
pxrK
here) immediately upstream of
pxrR
. Evolutionarily, the rate of trait restoration documented in this study suggests that reversion of social defects in natural microbial populations may be common. Molecularly, these results suggest a mechanism by which the regulatory functions of an HK-RR two-component signaling system and an sRNA are integrated to control initiation of myxobacterial development.

IMPORTANCE
Many myxobacteria initiate a process of multicellular fruiting body development upon starvation, but key features of the regulatory network controlling the transition from growth to development remain obscure. Previous work with
Myxococcus xanthus
identified the first small RNA (sRNA) regulator (Pxr) known to serve as a gatekeeper in this life history transition, as it blocks development when nutrients are abundant. In the present study, a screen for spontaneous mutants of
M. xanthus
was developed that revealed a two-component system operon (encoding a histidine kinase and a σ
54
response regulator) associated with the production and processing of Pxr sRNA. This discovery broadens our knowledge of early developmental gene regulation and also represents an evolutionary integration of two-component signaling and sRNA gene regulation to control a bacterial social trait.
The MarR-Type Regulator Rdh2R Regulates
rdh
Gene Transcription in Dehalococcoides mccartyi Strain CBDB1
Authors: Krasper Lydia , Lilie Hauke , Kublik Anja , Adrian Lorenz , Golbik Ralph , Lechner Ute
Published: September 2016

Reductive dehalogenases are essential enzymes in organohalide respiration and consist of a catalytic subunit A and a membrane protein B, encoded by
rdhAB
genes. Thirty-two
rdhAB
genes exist in the genome of
Dehalococcoides mccartyi
strain CBDB1. To gain a first insight into the regulation of
rdh
operons, the control of gene expression of two
rdhAB
genes (cbdbA1453/cbdbA1452 and cbdbA1455/cbdbA1454) by the MarR-type regulator Rdh2R (cbdbA1456) encoded directly upstream was studied using heterologous expression and
in vitro
studies. Promoter-
lacZ
reporter fusions were generated and integrated into the genome of the
Escherichia coli
host. The
lacZ
reporter activities of both
rdhA
promoters decreased upon transformation of the cells with a plasmid carrying the
rdh2R
gene, suggesting that Rdh2R acts as repressor, whereas the
lacZ
reporter activity of the
rdh2R
promoter was not affected. The transcriptional start sites of both
rdhA
genes in strain CBDB1 and/or the heterologous host mapped to a conserved direct repeat with 11- to 13-bp half-sites. DNase I footprinting revealed binding of Rdh2R to a ∼30-bp sequence covering the complete direct repeat in both promoters, including the transcriptional start sites. Equilibrium sedimentation ultracentrifugation revealed that Rdh2R binds as tetramer to the direct-repeat motif of the
rdhA
(cbdbA1455) promoter. Using electrophoretic mobility shift assays, a similar binding affinity was found for both
rdhA
promoters. In the presence of only one half-site of the direct repeat, the interaction was strongly reduced, suggesting a positive cooperativity of binding, for which unusual short palindromes within the direct-repeat half-sites might play an important role.

IMPORTANCE
Dehalococcoides mccartyi
strains are obligate anaerobes that grow by organohalide respiration. They have an important bioremediation potential because they are capable of reducing a multitude of halogenated compounds to less toxic products. We are now beginning to understand how these organisms make use of this large catabolic potential, whereby
D. mccartyi
expresses dehalogenases in a compound-specific fashion. MarR-type regulators are often encoded in the vicinity of reductive dehalogenase genes. In this study, we made use of heterologous expression and
in vitro
studies to demonstrate that the MarR-type transcription factor Rdh2R acts as a negative regulator. We identify its binding site on the DNA, which suggests a mechanism by which it controls the expression of two adjacent reductive dehalogenase operons.
Corrected Genome Annotations Reveal Gene Loss and Antibiotic Resistance as Drivers in the Fitness Evolution of Salmonella enterica Serovar Typhimurium
Authors: Paul Sandip , Sokurenko Evgeni V. , Chattopadhyay Sujay
Published: September 2016

Horizontal acquisition of novel chromosomal genes is considered to be a key process in the evolution of bacterial pathogens. However, the identification of gene presence or absence could be hindered by the inconsistencies in bacterial genome annotations. Here, we performed a cross-annotation of omnipresent core and mosaic accessory genes in the chromosome of
Salmonella enterica
serovar Typhimurium across a total of 20 fully assembled genomes deposited into GenBank. Cross-annotation resulted in a 32% increase in the number of core genes and a 3-fold decrease in the number of genes identified as mosaic genes (i.e., genes present in some strains only) by the original annotation. Of the remaining noncore genes, the vast majority were prophage genes, and 255 of the nonphage genes were actually of core origin but lost in some strains upon the emergence of the
S
. Typhimurium serovar, suggesting that the chromosomal portion of the
S
. Typhimurium genome acquired a very limited number of novel genes other than prophages. Only horizontally acquired nonphage genes related to bacterial fitness or virulence were found in four recently sequenced isolates, all located on three different genomic islands that harbor multidrug resistance determinants. Thus, the extensive use of antimicrobials could be the main selection force behind the new fitness gene acquisition and the emergence of novel
Salmonella
pathotypes.

IMPORTANCE
Significant discrepancies in the annotations of bacterial genomes could mislead the conclusions about evolutionary origin of chromosomal genes, as we demonstrate here via a cross-annotation-based analysis of
Salmonella
Typhimurium genomes from GenBank. We conclude that despite being able to infect a broad range of vertebrate hosts, the genomic diversity of
S
. Typhimurium strains is almost exclusively limited to gene loss and the transfer of prophage DNA. Only nonphage chromosomal genes acquired after the emergence of the serovar are linked to the genomic islands harboring multidrug resistance factors. Since the fitness factors could lead to increased virulence, this poses an important research question: could overuse or misuse of antimicrobials act as selection forces for the emergence of more pathogenic strains of
Salmonella
?
Boron isotopic discrimination for subduction-related serpentinites
Authors: Martin Céline , Flores Kennet E. , Harlow George E.
Published: September 2016

The Guatemala Suture Zone (GSZ), Guatemala, is a region that contains two distinct suture-related serpentinite mélanges straddling the Motagua fault and an ophiolitic complex paired with the northern mélange. The serpentinite matrix of the mélanges formed by subduction-fluid hydration of peridotite from the deep mantle wedge. The occurrence of serpentinite from both exhumed subduction channel mélange and ophiolite is not uncommon in paleo–suture zones, but distinguishing them and their tectonic origin can be difficult. A new method of discrimination, based on boron isotopes in serpentine from both mélanges and ophiolite, as well as on mica and pyroxene from the metamorphic and vein-rock blocks embedded within the mélanges, has been developed. The metamorphic and vein samples have mainly negative δ11B, ranging from –15.3‰ to +4.3‰, in the same range as the serpentine from the mélanges (–14.4‰ to +9.7‰). In addition to being the most negative δ11B values ever measured in serpentinite, comparable values from vein minerals indicate that the same fluid serpentinized the overlying mantle. In contrast, serpentine samples from the ophiolite have positive δ11B, in the range 0‰ to +18.0‰, consistent with hydration by seawater-derived fluids. As the GSZ displays two mélanges whose serpentinite originated from two different deep subductions and mantle hydration, we hypothesize that the negative signature of exhumed mélange serpentine is the norm and that the B isotopic signature can be a useful tool to discriminate the tectonic origin of serpentinization in paleo–suture zones.
How did a Housing First intervention improve health and social outcomes among homeless adults with mental illness in Toronto? Two-year outcomes from a randomised trial
Authors: O'Campo Patricia , Stergiopoulos Vicky , Nir Pam , Levy Matthew , Misir Vachan , Chum Antony , Arbach Bouchra , Nisenbaum Rosane , To Matthew J , Hwang Stephen W
Published: September 2016

Objectives

We studied the impact of a Housing First (HF) intervention on housing, contact with the justice system, healthcare usage and health outcomes among At Home/Chez Soi randomised trial participants in Toronto, a city with an extensive service network for social and health services for individuals who are experiencing homelessness and mental illness.

Methods

Participants identified as high needs were randomised to receive either the intervention which provided them with housing and supports by an assertive community treatment team (HF+ACT) or treatment as usual (TAU). Participants (N=197) had in-person interviews every 3 months for 2 years.

Results

The HF+ACT group spent more time stably housed compared to the TAU group with the mean difference between the groups of 45.8% (95% CI 37.1% to 54.4%, p<0.0001). Accounting for baseline differences, HF+ACT group showed significant improvements over TAU group for community functioning, selected quality-of-life subscales and arrests at some time points during follow-up. No differences between HF+ACT and TAU groups over the follow-up were observed for health service usage, community integration and substance use.

Conclusions

HF for individuals with high levels of need increased housing stability and selected health and justice outcomes over 2 years in a city with many social and health services.

Trial registration number

ISRCTN42520374.
Improving care for victims: a study protocol of the evaluation of a centre for sexual and family violence
Authors: Zijlstra E , LoFoWong S , Hutschemaekers G , Lagro-Janssen A
Published: September 2016

Introduction

Worldwide, sexual and family violence are highly prevalent problems. Victims of sexual and family violence often do not seek formal help in the acute phase. When they do seek help, they encounter a system of scattered care. For this reason, a centre for sexual and family violence was launched in Nijmegen, the Netherlands. The centre provides multidisciplinary care for victims of acute sexual and/or family violence. With the study described in this study protocol, we want to evaluate the implementation process and the reach of the Center for Sexual and Family Violence Nijmegen (CSFVN).

Methods and analysis

We will conduct a mixed-methods study including quantitative and qualitative methods of data collection and analysis. Data about the implementation process will be obtained via semistructured interviews and focus group discussions. Content analysis will be done in software program Atlas.ti. Analysis of file data will be undertaken to assess the reach of the CSFVN (patient characteristics and characteristics of the care they received). The data will be analysed in SPSS.

Ethics and dissemination

The Medical Ethics Committee of the Radboud University Nijmegen Medical Center approved the study protocol under file number 2012–1218. Dissemination will be done by submitting scientific articles to academic peer-reviewed journals. We will present the results at relevant international, national and local conferences and meetings. We will send press releases to relevant media. We will share the results with the network of assault centres in the Netherlands.
Evaluation of use and cost of medical care of common lumbar disorders in Korea: cross-sectional study of Korean Health Insurance Review and Assessment Service National Patient Sample data
Authors: Ahn Yong-Jun , Shin Joon-Shik , Lee Jinho , Lee Yoon Jae , Kim Me-Riong , Park Ki Byung , Lee Jun-Hwan , Shin Kyung-Min , Ha In-Hyuk
Published: September 2016

Objectives

To assess medical care and costs of the 3 highest prevalence lumbar disorders—non-specific low back pain (nLBP), intervertebral disc disorder (IDD) and spinal stenosis (SS)—from national billing data to provide basic information for standards of appropriate management.

Design

Retrospective analysis of National Health Insurance National Patient Sample data provided by the Korean Health Insurance Review and Assessment Service (HIRA).

Setting

2011 claims data from all medical institutions which filed billing statements to HIRA.

Participants

A total of 135 561 patients with lumbar disorder who received medical services during 2011.

Outcome measures

Patient characteristics, medical procedures, medication, cost, injection and surgery.

Results

In the nLBP and IDD groups, the 50–59 age range had the highest prevalence, whereas prevalence increased with age in SS. All 3 groups showed a higher percentage in women. The average treatment cost was 196 552 KRW in the nLBP and 362 050 KRW in the IDD group, and highest in the SS group at 439 025 KRW. While in the nLBP group women spent more on medical expenses, in the other 2 groups men showed higher expenditure. Expenditure grew with age in the nLBP and SS groups, whereas that of the IDD group peaked in their 40s. Analgesics were used in 73.43% of patients with nLBP, 82.64% of patients with IDD and 86.46% of patients with SS, and opioids in 4.12% of patients with IDD and 5.36% of patients with SS. Surgery rates were highest in the SS group at 4.85%, with 0.9% for nLBP and 4.59% for IDD. The most frequent injection code was lumbar/caudal epidural nerve block. Expenditure and surgery rates were higher in the injection than in the non-injection subgroup in all 3 groups.

Conclusions

Patterns of medical care of most frequent lumbar disorders from HIRA data showed significant difference between groups and provide a basic standard for future usual care guidelines linked with health policy and budget appropriation.
Association between aerobic exercise training effects of serum adropin level, arterial stiffness, and adiposity in obese elderly adults
Authors: Fujie Shumpei , Hasegawa Natsuki , Kurihara Toshiyuki , Sanada Kiyoshi , Hamaoka Takafumi , Iemitsu Motoyuki
Published: September 2016

Serum levels of adropin, which enhances endothelial cell release of nitric oxide (NO), are lower in obese patients. Although habitual aerobic exercise reduces arterial stiffness and adiposity, the relationship between these effects and circulating levels of adropin remains unclear. The purpose of this study was to determine if serum adropin level is associated with the effects of aerobic exercise training on arterial stiffness and adiposity in obese adults. In Experiment 1, we examined whether serum adropin levels are associated with cardiorespiratory fitness, carotid β-stiffness, plasma nitrite/nitrate (NOx) level, and abdominal visceral fat in 27 normal, 20 overweight, and 25 obese adults (age, 41–79 years). In Experiment 2, we examined the effects of an 8-week aerobic exercise training program on the relationship between serum adropin level and arterial stiffness or adiposity in 13 obese adults (age, 54–76 years). Serum adropin levels in normal, overweight, and obese adults negatively correlated with carotid β-stiffness and abdominal visceral fat, and positively correlated with plasma NOx level and cardiorespiratory fitness. After the 8-week exercise program, serum adropin levels in obese adults were elevated, and correlated with training-induced changes in carotid β-stiffness (r = –0.573, P < 0.05), plasma NOx level (r = 0.671, P < 0.05), and abdominal visceral fat (r = –0.585, P < 0.05). These findings suggest that the exercise training-induced increase in serum adropin may be related to the training effects of arterial stiffness and adiposity in obese adults.
New fossil Pinaceae from the Early Cretaceous of Mongolia
Authors: Herrera Fabiany , Leslie Andrew B. , Shi Gongle , Knopf Patrick , Ichinnorov Niiden , Takahashi Masamichi , Crane Peter R. , Herendeen Patrick S.
Published: September 2016

Exceptionally well-preserved pinaceous leaves and seed cones are abundant in unconsolidated Early Cretaceous lignites in central Mongolia. These fossils include two seed cones, both of which have helically arranged bract–scale complexes with two winged seeds on the adaxial surface. The larger of the two seed cones, described as Picea farjonii sp. nov., is cylindrical to ellipsoidal, and was borne terminally on a stout shoot. The bract is small and tridentate. Leaf bases on the shoots are helically arranged, and attached leaves are linear and flattened. In all of the morphological and anatomical features that are preserved, P. farjonii is very similar to extant Picea. The smaller seed cone, described as Pityostrobus stockeyae sp. nov., shows features of several genera of extant Pinaceae. This cone is ellipsoidal and was borne terminally on a long, slender shoot. The bract is thin and triangular proximally, but the distal portion is thicker, needle-like, and deciduous. Picea farjonii and Pityostrobus stockeyae were abundant in conifer-dominated swamps in Mongolia during the Aptian–Albian and provide further support for the importance of plants related to extant Pinaceae in the vegetation of the Northern Hemisphere at this time.
Effect of critical sub-system failures on the post-earthquake functionality of buildings: A case study for Montréal hospitals
Authors: Youance Suze , Nollet Marie-José , McClure Ghyslaine
Published: September 2016

When an earthquake occurs, hospitals are expected to remain functional as they play a crucial role in emergency care operations. This ability to ensure the continuity of quality operations while ensuring the safety of occupants during and after an earthquake defines the concept of post-earthquake functionality. Hospital functionality relies on the good performance of a large number of critical sub-systems, components and equipment. Although the global seismic performance of building structures and their nonstructural components was extensively observed in several post-disaster reconnaissance surveys, there is limited and incomplete information on the effect of building and nonstructural damage on post-earthquake functionality. The objective of this paper is to present a methodology for the assessment of post-earthquake functionality of existing Montréal hospitals using fault-tree analysis. The study shows that using specific and accurate information on the vulnerability and fragility of structural and critical nonstructural components, a probabilistic index of post-earthquake functionality of the entire facility is computed which informs mitigation action for the critical failure processes through the system.
Isotropic cosmological models in F(T,TG) theory
Authors: Sharif M. , Nazir Kanwal
Published: September 2016

This paper is devoted to study evolution of the isotropic universe models in the framework of [Formula: see text] gravity ([Formula: see text] represents torsion scalar and [Formula: see text] is the teleparallel equivalent of the Gauss–Bonnet (GB) term). We construct [Formula: see text] models by taking different eras of the universe like non-relativistic and relativistic matter eras, dark energy (DE) dominated era and their combinations. It is found that the reconstructed models indicate decreasing behavior for DE dominated era and its combination with other eras. We also discuss stability of each reconstructed model. Finally, we evaluate equation of state (EoS) parameter by considering two models and study its behavior graphically.
Solitons, Bäcklund transformation and Lax pair for a (2+1)-dimensional B-type Kadomtsev–Petviashvili equation in the fluid/plasma mechanics
Authors: Lan Zhong-Zhou , Gao Yi-Tian , Yang Jin-Wei , Su Chuan-Qi , Wang Qi-Min
Published: September 2016

Under investigation in this paper is a (2[Formula: see text]+[Formula: see text]1)-dimensional B-type Kadomtsev–Petviashvili equation for the shallow water wave in a fluid or electrostatic wave potential in a plasma. Bilinear form, Bäcklund transformation and Lax pair are derived based on the binary Bell polynomials. Multi-soliton solutions are constructed via the Hirota’s method. Propagation and interaction of the solitons are illustrated graphically: (i) Through the asymptotic analysis, elastic and inelastic interactions between the two solitons are discussed analytically and graphically, respectively. The elastic interaction, amplitudes, velocities and shapes of the two solitons remain unchanged except for a phase shift. However, in the area of the inelastic interaction, amplitudes of the two solitons have a linear superposition. (ii) Elastic interactions among the three solitons indicate that the properties of the elastic interactions among the three solitons are similar to those between the two solitons. Moreover, oblique and overtaking interactions between the two solitons are displayed. Oblique interactions among the three solitons and interactions among the two parallel solitons and a single one are presented as well. (iii) Inelastic–elastic interactions imply that the interaction between the inelastic region and another one is elastic.
Template-Based Bitmap View Selection for Optimizing Queries Over Tree Data
Authors: Wu Xiaoying , Theodoratos Dimitri
Published: September 2016

Developing and exploiting flexible techniques for optimizing the evaluation of queries over loosely structured data (e.g. tree or graph databases) is of crucial importance for modern database applications. In this context, we consider a new type of views which can be materialized as compressed bitmaps over tree data. We introduce the concept of view structural template to define classes of views. We then define and address a novel view selection problem (called view class selection (VCS) problem) where the goal is to select classes of bitmap views in order to optimize the overall evaluation cost of all tree pattern queries (TPQs) that can be issued against a database while satisfying a space constraint and ensuring that all the TPQs can be answered using exclusively the materialized views. We show that the VCS problem is NP-hard and we design two heuristic greedy algorithms which iteratively generate new batches of candidate view classes and make them available for selection. Each algorithm uses a different view class expansion technique to enable the systematic generation of candidate view classes from classes with smaller templates. We run extensive experiments to evaluate both the effectiveness of the algorithms and their efficiency on real, benchmark and synthetic datasets. Our algorithms are able to suggest high quality selections of view classes in a reasonable amount of time.
BUSINESS REGISTRATION AND FIRM PERFORMANCE: SOME LESSONS FROM INDIA
Authors: WILLIAMS COLIN C , KEDIR ABBI M.
Published: September 2016

The aim of this paper is to evaluate the impacts on future firm performance of a firm deciding to register from the outset of its operations. Until now, the assumption has been that starting up registered is linked to higher future firm performance. Reporting World Bank Enterprise Survey (WBES) data collected in 2014 on 9,281 formal enterprises in India, and controlling for other determinants of firm performance as well as the endogeneity of the registration decision, the finding is that formal enterprises that start up unregistered and spend longer unregistered have significantly higher subsequent annual sales and employment growth rates compared with those registered from the outset. When the number of years spent unregistered is included, there are also productivity gains from delaying registration. The tentative explanation is that in this weak institutional environment, the advantages of registering from the outset are outweighed by the benefits of deferring registration. Evaluating the policy implications, the argument is that there is a need to shift away from the conventional eradication approach toward unregistered startups based on the assumption they are unproductive, and toward a more facilitating approach that improves the benefits of being registered and tackles the systemic formal institutional deficiencies that lead entrepreneurs to delay their decision to register.
China’s 13th Five-Year Plan: Road Map for Social Development
Authors: ZHAO Litao
Published: September 2016

China’s 13th Five-Year Plan (FYP) maps out China’s economic and social development in the next five years under the guidelines of “innovative development”, “coordinated development”, “green development”, “open development” and “shared development”. It features a pro-active approach to programmes that are “social investment” in nature and a conservative approach to programmes seen as “social consumptions”. As the economy slows down, the 13th FYP period is likely to see social expenditures proceeding at a slower pace.
Understanding Chinese Meritocracy
Authors: GORE Lance L P
Published: September 2016

Many have problem reconciling China’s corruption-infested system with meritocracy. The survey study reported here indicates that Chinese cadres are eager to impress their superior, but what impresses the superior is increasingly along the line of competence and achievement. Even corrupt officials have to deliver and be competent, the bottom line that sets limits to patronage. The system may not always favour the most competent but it is geared towards performance.
Assessing China’s South China Sea Policy, 2009-2015
Authors: ZHANG Feng
Published: September 2016

This paper identifies three phases of China’s South China Sea policy since 2009: reactive assertiveness from 2009 to 2011, forceful response from 2012 to 2013, and proactive adjustment from 2014 to the present. These three distinct phases suggest that China does not have a grand strategy for the South China Sea. The paper also assesses the consequences of China’s island building in the South China Sea and the costs of its deliberate ambiguity on the international legal front.
Economic and Political Factors for the Fall of Japanese Foreign Direct Investment in China
Authors: XING Yuqing
Published: September 2016

Japanese direct investment in China fell sharply in 2013 and 2014. Both political and economic factors contributed to the fall. Political tensions between the two countries greatly exacerbated China risks as perceived by Japanese companies and dampened their confidence of investing in China. Additionally, China has lost its competitiveness of attracting export-oriented Japanese FDI because of the cumulative appreciation of the Yuan and rapid wage growth.
Scalar Implicatures and Their Interface with Grammar
Authors: Chierchia Gennaro
Published: September 2016

Scalar implicatures (SIs) and, more generally, quantity-based implicatures (QBIs) have been intensely investigated since Grice's seminal work. Recently, SIs and QBIs have been at the center of an intense debate. Some researchers, following Grice's original insight, argue that they should be captured solely in terms of principles of rational action (the pragmatic approach). Others argue that they cannot be analyzed in purely pragmatic terms but can only be properly understood in terms of a compositional semantic device, namely exhaustification (the grammatical approach). In this article, I review the key arguments in this debate, which is of interest not only to determine who is right but also because of the range of new phenomena that have come to light thanks to such a debate. My conclusion is that both conceptual and empirical reasons favor the grammatical approach.
How Baleen Whales Feed: The Biomechanics of Engulfment and Filtration
Authors: Goldbogen J.A. , Cade D.E. , Calambokidis J. , Friedlaender A.S. , Potvin J. , Segre P.S. , Werth A.J.
Published: September 2016

Baleen whales are gigantic obligate filter feeders that exploit aggregations of small-bodied prey in littoral, epipelagic, and mesopelagic ecosystems. At the extreme of maximum body size observed among mammals, baleen whales exhibit a unique combination of high overall energetic demands and low mass-specific metabolic rates. As a result, most baleen whale species have evolved filter-feeding mechanisms and foraging strategies that take advantage of seasonally abundant yet patchily and ephemerally distributed prey resources. New methodologies consisting of multi-sensor tags, active acoustic prey mapping, and hydrodynamic modeling have revolutionized our ability to study the physiology and ecology of baleen whale feeding mechanisms. Here, we review the current state of the field by exploring several hypotheses that aim to explain how baleen whales feed. Despite significant advances, major questions remain about the processes that underlie these extreme feeding mechanisms, which enabled the evolution of the largest animals of all time.
Precision Medicine in Myelodysplastic Syndromes and Leukemias: Lessons from Sequential Mutations
Authors: Nazha Aziz , Sekeres Mikkael A.
Published: September 2016

Precision medicine can be simply defined as the identification of personalized treatment that matches patient-specific clinical and genomic characteristics. Since the completion of the Human Genome Project in 2003, significant advances have been made in our understanding of the genetic makeup of diseases, especially cancers. The identification of somatic mutations that can drive cancer has led to the development of therapies that specifically target the abnormal proteins derived from these mutations. This has led to a paradigm shift in our treatment methodology. Although some success has been achieved in targeting some genetic abnormalities, several challenges and limitations exist when applying precision-medicine concepts in leukemia and myelodysplastic syndromes. We review the current understanding of genomics in myelodysplastic syndromes (MDS) and leukemias and the limitations of precision-medicine concepts in MDS.
Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward
Authors: Volkow Nora D. , Hampson Aidan J. , Baler Ruben D.
Published: September 2016

Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.
Challenges and Opportunities in Protease-Activated Receptor Drug Development
Authors: Hamilton Justin R. , Trejo JoAnn
Published: September 2016

Protease-activated receptors (PARs) are a unique class of G protein–coupled receptors (GPCRs) that transduce cellular responses to extracellular proteases. PARs have important functions in the vasculature, inflammation, and cancer and are important drug targets. A unique feature of PARs is their irreversible proteolytic mechanism of activation that results in the generation of a tethered ligand that cannot diffuse away. Despite the fact that GPCRs have proved to be the most successful class of druggable targets, the development of agents that target PARs specifically has been challenging. As a consequence, researchers have taken a remarkable diversity of approaches to develop pharmacological entities that modulate PAR function. Here, we present an overview of the diversity of therapeutic agents that have been developed against PARs. We further discuss PAR biased signaling and the influence of receptor compartmentalization, posttranslational modifications, and dimerization, which are important considerations for drug development.