bluuebunny/crossref_metadata_2025 huggingface dataset:
High resolution soft mold for UV-curing nanoimprint lithography using an oxygen insensitive degradable material
Authors: Hu Xin , Huang Jingrui , Gu Ronghua , Cui Yushuang , Yuan Changsheng , Ge Haixiong , Chen Yanfeng
Published: November 2014

Soft nanoimprint lithography has been developed to overcome the disadvantages of conventional nanoimprint lithography based on rigid molds. Hybrid nanoimprint-soft lithography mold is an efficient strategy to improve the resolution of soft nanoimprint because a rigid UV-curable material is used as the structural layer. In this paper, the authors design a novel UV-curable material for hybrid soft mold fabrication, which is degradable under mild acidic conditions and insensitive to oxygen during photopolymerization. The material comprises an acid-degradable cross-linker, 2,10-diacryloyloxymethyl-1,4,9,12-tetraoxaspiro[4.2.4.2] tetradecane, and an acyrlated polysiloxane, poly[(mercaptopropyl)methylsiloxane]. Oxygen sensitivity of acrylate groups during UV curing is avoided due to the cross-linking mechanism based on thiol-ene chemistry. The cured material can be decomposed into linear chains through the cleavage of acid-labile ketal links and dissolved in organic solvent when heated in an acidic solution. The material possesses necessary properties for mold fabrication and imprinting, including low shrinkage (about 5%), high modulus (1.4 GPa), high thermal stability, high UV transparency and stability in normal environment. Furthermore, since the cured material is degradable in acidic media, the stained master can be renewed in a mild condition. Various nanoscaled patterns are fabricated on planar and curved substrates via UV-nanoimprint when the same material is used as a patterning layer.
Semi-analytical computation of acoustic scattering by spheroids and disks
Authors: Adelman Ross , Gumerov Nail A. , Duraiswami Ramani
Published: November 2014

Analytical solutions to acoustic scattering problems involving spheroids and disks have long been known and have many applications. However, these solutions require special functions that are not easily computable. Therefore, their asymptotic forms are typically used instead since they are more readily available. In this paper, these solutions are explored, and computational software is provided for calculating their nonasymptotic forms, which are accurate over a wide range of frequencies and distances. This software, which runs in MATLAB, computes the solutions to acoustic scattering problems involving spheroids and disks by semi-analytical means, and is freely available from the authors' webpage.
Solar nebula magnetic fields recorded in the Semarkona meteorite
Authors: Fu Roger R. , Weiss Benjamin P. , Lima Eduardo A. , Harrison Richard J. , Bai Xue-Ning , Desch Steven J. , Ebel Denton S. , Suavet Clément , Wang Huapei , Glenn David , Le Sage David , Kasama Takeshi , Walsworth Ronald L. , Kuan Aaron T.
Published: November 2014

Magnetic fields are proposed to have played a critical role in some of the most enigmatic processes of planetary formation by mediating the rapid accretion of disk material onto the central star and the formation of the first solids. However, there have been no experimental constraints on the intensity of these fields. Here we show that dusty olivine-bearing chondrules from the Semarkona meteorite were magnetized in a nebular field of 54 ± 21 microteslas. This intensity supports chondrule formation by nebular shocks or planetesimal collisions rather than by electric currents, the x-wind, or other mechanisms near the Sun. This implies that background magnetic fields in the terrestrial planet-forming region were likely 5 to 54 microteslas, which is sufficient to account for measured rates of mass and angular momentum transport in protoplanetary disks.
Pacui Virus, Rio Preto da Eva Virus, and Tapirape Virus, Three Distinct Viruses within the Family
Bunyaviridae
Authors: Rodrigues Daniela Sueli Guerreiro , Medeiros Daniele Barbosa de Almeida , Rodrigues Sueli Guerreiro , Martins Livia Caricio , de Lima Clayton Pereira Silva , de Oliveira Layanna Freitas , de Vasconcelos Janaina Mota , Da Silva Daisy Elaine , Cardoso Jedson Ferreira , da Silva Sandro Patroca , Vianez-Júnior João Lídio da Silva Gonçalves , Nunes Márcio Roberto Teixeira , Vasconcelos Pedro Fernando da Costa
Published: November 2014

Nearly complete genome sequences for three ungrouped viruses, Pacui virus (BEAN27326), Rio Preto da Eva virus (BEAR540870), and Tapirape virus (BEAN767592) isolated in the Amazon region are reported here. All three genomic segments (small, medium and large RNA) were recovered and were similar to members of the genus
Orthobunyavirus
.
Draft Genome Sequence of Bacillus megaterium Type Strain ATCC 14581
Authors: Arya Gitanjali , Petronella Nicholas , Crosthwait Jennifer , Carrillo Catherine D. , Shwed Philip S.
Published: November 2014

Bacillus megaterium
is a Gram-positive, rod-shaped, spore-forming bacterium of biotechnological importance. Here, we report a 5.7-Mbp draft genome sequence of
B. megaterium
ATCC 14581, which is the type strain of the species.
Exploring the Genome of Cheese Starter Lactic Acid Bacterium Lactococcus lactis subsp.
lactis
CECT 4433
Authors: Tschoeke Diogo Antonio , Moreira Ana Paula B. , Chimetto Tonon Luciane A. , de Mesquita Milene Miranda A. , Gregoracci Gustavo B. , Gomez-Gil Bruno , Valle Rogério , Thompson Cristiane C. , Thompson Fabiano L.
Published: November 2014

Here, we present the draft genome sequences of
Lactococcus lactis
subsp.
lactis
CECT 4433, a cheese fermentation starter strain. The genome provides further insight into the genomic plasticity, biocomplexity (including gene strain specifics), and evolution of these genera.
Draft Genome Sequences of Marine Flavobacterium Algibacter lectus Strains SS8 and NR4
Authors: Takatani Naoki , Nakanishi Masato , Meirelles Pedro , Mino Sayaka , Suda Wataru , Oshima Kenshiro , Hattori Masahira , Ohkuma Moriya , Hosokawa Masashi , Miyashita Kazuo , Thompson Fabiano L. , Niwa Ako , Sawabe Toko , Sawabe Tomoo
Published: November 2014

Here, we present the draft genome sequences of a zeaxanthin-producing flavobacterium,
Algibacter lectus
strains SS8 and NR4, isolated from coastal sediment and rock surfaces in Hakodate, Japan, respectively. This genomic information represents the first
Algibacter
genome sequences, which will help us to elucidate the biology and evolution of
Flavobacteriaceae
bacteria.
Draft Genome Sequence of Bacillus alcalophilus AV1934, a Classic Alkaliphile Isolated from Human Feces in 1934
Authors: Attie Oliver , Jayaprakash Anitha , Shah Hardik , Paulsen Ian T. , Morino Masato , Takahashi Yuka , Narumi Issay , Sachidanandam Ravi , Satoh Katsuya , Ito Masahiro , Krulwich Terry A.
Published: November 2014

Bacillus alcalophilus
AV1934, isolated from human feces, was described in 1934 before microbiome studies and recent indications of novel potassium ion coupling to motility in this extremophile. Here, we report draft sequences that will facilitate an examination of whether that coupling is part of a larger cycle of potassium ion-coupled transporters.
Genome Sequences of
Lactobacillus
sp. Strains wkB8 and wkB10, Members of the Firm-5 Clade, from Honey Bee Guts
Authors: Kwong Waldan K. , Mancenido Amanda L. , Moran Nancy A.
Published: November 2014

We sequenced two strains from the
Lactobacillus
Firm-5 clade, a dominant group of symbionts in the guts of honey bees and other social bees. The genome of strain wkB8, comprising a 1.93-Mb chromosome and a 6.4-kb plasmid, was fully closed, while strain wkB10 was assembled into 32 contigs. These genomes will provide insights into how gut symbionts evolve and interact with their host species.
Complete Genome Sequence of the Multiresistant Acinetobacter baumannii Strain AbH12O-A2, Isolated during a Large Outbreak in Spain
Authors: Merino M. , Alvarez-Fraga L. , Gómez M. J. , Aransay A. M. , Lavín J. L. , Chaves F. , Bou G. , Poza M.
Published: November 2014

We report the complete genome sequence of
Acinetobacter baumannii
strain AbH12O-A2, isolated during a large outbreak in Spain. The genome has 3,875,775 bp and 3,526 coding sequences, with 39.4% G+C content. The availability of this genome will facilitate the study of the pathogenicity of the
Acinetobacter
species.
The Draft Genome Sequence of
Sphingomonas
sp. Strain FukuSWIS1, Obtained from Acidic Lake Grosse Fuchskuhle, Indicates Photoheterotrophy and a Potential for Humic Matter Degradation
Authors: Salka Ivette , Srivastava Abhishek , Allgaier Martin , Grossart Hans-Peter
Published: November 2014

Sphingomonas
spp. are
Alphaproteobacteria
considered to be versatile bacteria that can utilize a variety of natural substrates available in terrestrial and aquatic systems.
Sphingomonas
sp
.
strain FukuSWIS1 was isolated from the eutrophic and acidic freshwater Lake Grosse Fuchskuhle in northeastern Germany. The strain has a genome size of 3.89 Mb, possesses a set of photosynthetic genes, and expresses photopigment BChl
a
under oxic conditions. Thus, this strain belongs to the aerobic anoxygenic phototrophic (AAP) bacteria, which are most likely involved in humic matter degradation as indicated by the presence of organic compound mineralizing genes.
High-Quality Draft Genome Sequence of
Babesia divergens
, the Etiological Agent of Cattle and Human Babesiosis
Authors: Cuesta Isabel , González Luis M. , Estrada Karel , Grande Ricardo , Zaballos Ángel , Lobo Cheryl A. , Barrera Jorge , Sanchez-Flores Alejandro , Montero Estrella
Published: November 2014

Babesia divergens
causes significant morbidity and mortality in cattle and splenectomized or immunocompromised individuals. Here, we present a 10.7-Mb high-quality draft genome of this parasite close to chromosome resolution that will enable comparative genome analyses and synteny studies among related parasites.
Draft Genome Sequence of
Bacillus
sp. Strain BSC154, Isolated from Biological Soil Crust of Moab, Utah
Authors: Bailey Alexis C. , Kellom Matthew , Poret-Peterson Amisha T. , Noonan Kathryn , Hartnett Hilairy E. , Raymond Jason
Published: November 2014

Bacillus
sp. BSC154 was isolated from a biological soil crust near Moab, Utah. The strain appears to be capable of chemotaxis and biofilm production. The BSC154 genome contains iron siderophore production, nitrate reduction, mixed acid-butanediol fermentation, and assimilatory and dissimilatory sulfate metabolism pathways.
Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary post-tonsillectomy haemorrhage
Authors: Fox Richard , Varadharajan Kiran , Patel Bhavesh , Beegun Issa
Published: November 2014

A 30-year-old male body builder and androgenic-anabolic steroid and insulin abuser was admitted for day case elective tonsillectomy (bipolar). He returned with primary post-tonsillectomy haemorrhage 18 h after the operation and required bipolar cautery to the multiple small bleeding points in the right and left tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary haemorrhage occurred 3 h post-operatively requiring immediate surgical intervention, removal of the inferior poles, precautionary throat packs, intubation and observation on the intensive treatment unit (ITU). Re-examination in theatre revealed a bleeding left superior pole that was under-run to achieve haemostasis and the patient returned to ITU. Hypertensive episodes were noted in the emergency department and intraoperatively including one recording >200 mm Hg. Haemostasis was eventually achieved once the blood pressure was adequately controlled. A slow wean of steroids was also instigated and the patient was managed on a surgical ward for 2 weeks post-tonsillectomy.
Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study
Authors: Rifbjerg-Madsen Signe , Christensen Anton Wulf , Boesen Mikael , Christensen Robin , Danneskiold-Samsøe Bente , Bliddal Henning , Bartels Else Marie , Locht Henning , Amris Kirstine
Published: November 2014

Introduction

Pain in rheumatoid arthritis (RA) is traditionally considered to be of inflammatory origin. Despite better control of inflammation, some patients still report pain as a significant concern, even when being in clinical remission. This suggests that RA may prompt central sensitisation—one aspect of chronic pain. In contrast, other patients report good treatment response, although imaging shows signs of inflammation, which could indicate a possible enhancement of descending pain inhibitory mechanisms.

When assessing disease activity in patients with central sensitisation, the commonly used disease activity scores (eg, DAS28-CRP (C reactive protein)) will yield constant high total scores due to high tender joint count and global health assessments, whereas MRI provides an isolated estimate of inflammation.

The objective of this study is, in patients with RA initiating anti-inflammatory treatment, to explore the prognostic value of a screening questionnaire for central sensitisation, hand inflammation assessed by conventional MRI, and the interaction between them regarding treatment outcome evaluated by clinical status (DAS28-CRP). For the purpose of further exploratory analyses, dynamic contrast-enhanced MRI (DCE-MRI) is performed.

Method and analysis

The painDETECT Questionnaire (PDQ), originally developed to screen for a neuropathic pain component, is applied to indicate the presence of central sensitisation. Adults diagnosed with RA are included when either (A) initiating disease-modifying antirheumatic drug treatment, or (B) initiating or switching to biological therapy.

We anticipate that 100 patients will be enrolled, tested and reassessed after 4 months of treatment.

Data collection includes

Clinical data, conventional MRI, DCE-MRI, blood samples and patient-reported outcomes.

Ethics and dissemination

This study aims at supporting rheumatologists to define strategies to reach optimal treatment outcomes in patients with RA based on chronic pain prognostics. The study has been approved by The Capital region of Denmark's Ethics Committee; identification number H-3-2013-049. The results will be published in international peer-reviewed journals.
Better-than-average and worse-than-average hospitals may not significantly differ from average hospitals: an analysis of Medicare Hospital Compare ratings
Authors: Paddock Susan M , Adams John L , Hoces de la Guardia Fernando
Published: November 2014

Background

Public report card designers aim to provide comprehensible provider performance information to consumers. Report cards often display classifications of providers into performance tiers that reflect whether performance is statistically significantly above or below average or not statistically significantly different from average. To further enhance the salience of public reporting to consumers, report card websites often allow a user to compare a subset of selected providers on tiered performance rather than direct statistical comparisons of the providers in a consumer's personal choice set.

Objective

We illustrate the differences in conclusions drawn about relative provider performance using tiers versus conducing statistical tests to assess performance differences.

Methods

Using publicly available cross-sectional data from Medicare Hospital Compare on three mortality and three readmission outcome measures, we compared each provider in the top or bottom performance tier with those in the middle tier and assessed the proportion of such comparisons that exhibited no statistically significant differences.

Results

Across the six outcomes, 1.3–6.1% of hospitals were classified in the top tier. Each top-tier hospital did not statistically significantly differ in performance from at least one mid-tier hospital. The percentages of mid-tier hospitals that were not statistically significantly different from a given top-tier hospital were 74.3–81.1%. The percentages of hospitals classified as bottom tier were 0.6–4.0%. Each bottom-tier hospital showed no statistically significant difference from at least one mid-tier hospital. The percentage of mid-tier hospitals that were not significantly different from a bottom-tier hospital ranged from 60.4% to 74.8%.

Conclusions

Our analyses illustrate the need for further innovations in the design of public report cards to enhance their salience for consumers.
The Usability of Noise Level from Rock Cutting for the Prediction of Physico-Mechanical Properties of Rocks
Authors: Delibalta M. S. , Kahraman S. , Comakli R.
Published: November 2014

Because the indirect tests are easier and cheaper than the direct tests, the prediction of rock properties from the indirect testing methods is important especially for the preliminary investigations. In this study, the predictability of the physico-mechanical rock properties from the noise level measured during cutting rock with diamond saw was investigated. Noise measurement test, uniaxial compressive strength (UCS) test, Brazilian tensile strength (BTS) test, point load strength (Is) test, density test, and porosity test were carried out on 54 different rock types in the laboratory. The results were statistically analyzed to derive estimation equations. Strong correlations between the noise level and the mechanical rock properties were found. The relations follow power functions. Increasing rock strength increases the noise level. Density and porosity also correlated strongly with the noise level. The relations follow linear functions. Increasing density increases the noise level while increasing porosity decreases the noise level. The developed equations are valid for the rocks with a compressive strength below 150 MPa. Concluding remark is that the physico-mechanical rock properties can reliably be estimated from the noise level measured during cutting the rock with diamond saw.
Stress intensity factors for part-elliptical cracks emanating from dimpled rivet holes
Authors: Wang Ailun , She Chongmin , Lin Gang , Zhou You , Guo Wanlin
Published: November 2014

Detailed investigations on the stress intensity factors (SIFs) for corner cracks emanated from interference fitted dimpled rivet holes are conducted using three-dimensional finite element method. The influences of the crack length a, elliptical shape factor t, far-end stress S and interference magnitude δ on the stress intensity factors are systematically studied. The SIFs for corner cracks emanated from open holes are also investigated for comparisons. An empirical formula of the normalized SIF is proposed by use of the least square method for convenience of the engineering application, which is a function of the crack length a, elliptical shape factor t, far-end stress S, interference magnitude δ and the normalized elliptical centrifugal angle φn. Based on the empirical formula, a crack growth simulation for a rivet filled hole is conducted, which shows a good agreement with the test data.
Volatiles in subduction zone magmatism
Authors: Zellmer Georg F. , Edmonds Marie , Straub Susanne M.
Published: November 2014

The volatile cycle at subduction zones is key to the petrogenesis, transport, storage and eruption of arc magmas. Volatiles control the flux of slab components into the mantle wedge, are responsible for melt generation through lowering the solidi of mantle materials, and influence the crystallizing phase assemblages in the overriding crust. Globally, magma ponding depths may be partially controlled by melt volatile contents. Volatiles also affect the rate and extent of degassing during magma storage and decompression, influence magma rheology and therefore control eruption style. The style of eruptions in turn determines the injection height of environmentally sensitive gases into the atmosphere and the impact of explosive arc volcanism. In this overview we summarize recent advances regarding the role of volatiles during slab dehydration, melt generation in the mantle wedge, magmatic evolution in the overriding crust, eruption triggering, and the release of some magmatic volatiles from volcanic edifices into the Earth's atmosphere.
Rediscovering geoheritage, reinventing geotourism: 200 years of experience from the Sudetes, Central Europe
Authors: Migoń Piotr
Published: November 2014

The Sudetes is a mountain range in Central Europe and an area of remarkable geodiversity. In recent years, the area has been promoted as a geotourist destination and various initiatives aimed at better understanding geoheritage have been implemented. An interest in scenic landscapes is not new however, and dates back to the end of the eighteenth century. Two areas within the Sudetes are cradles of local nature-based tourism. These are the granite massif of the Karkonosze in the west and the sandstone stepped plateau of Broumov Highland and Stołowe Mountains in the central part of the Sudetes. In both, physical access to the key geosites was provided as early as in the nineteenth century, while an interpretation component was added in the early twentieth century. A side-effect of political change following the end of World War II was the neglect and dilapidation of many sites, as well as the disappearance of geoheritage appreciation from the collective social memory. In the last decade many of those early achievements were rediscovered and provided the foundations for contemporary activities. An educational component based on modern science is now included in the features which were discovered as tourist attractions long ago.
Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs
Authors: Andres Sarah F. , Santoro M. Agostina , Mah Amanda T. , Keku J. Adeola , Bortvedt Amy E. , Blue R. Eric , Lund P. Kay
Published: November 2014

The insulin receptor (IR) regulates nutrient uptake and utilization in multiple organs, but its role in the intestinal epithelium is not defined. This study developed a mouse model with villin-Cre (VC) recombinase-mediated intestinal epithelial cell (IEC)-specific IR deletion (VC-IRΔ/Δ) and littermate controls with floxed, but intact, IR (IRfl/fl) to define in vivo roles of IEC-IR in mice fed chow or high-fat diet (HFD). We hypothesized that loss of IEC-IR would alter intestinal growth, biomarkers of intestinal epithelial stem cells (IESC) or other lineages, body weight, adiposity, and glucose or lipid handling. In lean, chow-fed mice, IEC-IR deletion did not affect body or fat mass, plasma glucose, or IEC proliferation. In chow-fed VC-IRΔ/Δ mice, mRNA levels of the Paneth cell marker lysozyme ( Lyz) were decreased, but markers of other differentiated lineages were unchanged. During HFD-induced obesity, IRfl/fl and VC-IRΔ/Δ mice exhibited similar increases in body and fat mass, plasma insulin, mRNAs encoding several lipid-handling proteins, a decrease in Paneth cell number, and impaired glucose tolerance. In IRfl/fl mice, HFD-induced obesity increased circulating cholesterol; numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC); and mRNAs encoding Chga, glucose-dependent insulinotrophic peptide ( Gip), glucagon ( Gcg), Lyz, IESC biomarkers, and the enterocyte cholesterol transporter Scarb1. All these effects were attenuated or lost in VC-IRΔ/Δ mice. These results demonstrate that IEC-IR is not required for normal growth of the intestinal epithelium in lean adult mice. However, our findings provide novel evidence that, during HFD-induced obesity, IEC-IR contributes to increases in EEC, plasma cholesterol, and increased expression of Scarb1 or IESC-, EEC-, and Paneth cell-derived mRNAs.
SCFA transport in rat duodenum
Authors: Kaji Izumi , Iwanaga Toshihiko , Watanabe Masahiko , Guth Paul H. , Engel Eli , Kaunitz Jonathan D. , Akiba Yasutada
Published: November 2014

Bacterial or ingested food-derived short-chain fatty acids (SCFAs) are present in the duodenal lumen. Acetate, the most abundant SCFA in the foregut lumen, is absorbed immediately after ingestion, although the mechanism by which this absorption occurs is not fully understood. We investigated the distribution and function of candidate SCFA transporters in rat duodenum. The Na+-coupled monocarboxylate transporter-1 (SMCT1) was localized to the brush border, whereas the pH-dependent monocarboxylate transporter (MCT) 1 and MCT4 were localized to the duodenocyte basolateral membrane. In Ussing chambered duodenal mucosa, luminal acetate dose-dependently increased short-circuit current ( Isc) in the presence of serosal bumetanide and indomethacin by a luminal Na+-dependent, ouabain-sensitive mechanism. The Isc response was inhibited dose-dependently by the SMCT1 nonsubstrate inhibitor ibuprofen, consistent with net electrogenic absorption of acetate via SMCT1. Other SCFAs and lactate also increased Isc. Furthermore, duodenal loop perfusion of acetate increased portal venous acetate concentration, inhibited by coperfusion of ibuprofen or a MCT inhibitor. Luminal acetate perfusion increased duodenal HCO3− secretion via capsaicin-sensitive afferent nerve activation and cyclooxygenase activity, consistent with absorption-mediated HCO3− secretion. These results suggest that absorption of luminal SCFA via SMCT1 and MCTs increases duodenal HCO3− secretion. In addition to SCFA sensing via free fatty acid receptors, the presence of rapid duodenal SCFA absorption may be important for the suppression of luminal bacterial colonization and implicated in the generation of functional dyspepsia due to bacterial overgrowth.
Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury
Authors: Mo Yiqun , Chen Jing , Humphrey David M. , Fodah Ramy A. , Warawa Jonathan M. , Hoyle Gary W.
Published: November 2014

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium.
Effect of body position and oxygen tension on foramen ovale recruitment
Authors: Moses Kayla L. , Beshish Arij G. , Heinowski Nicole , Baker Kim R. , Pegelow David F. , Eldridge Marlowe W. , Bates Melissa L.
Published: November 2014

While there is an increased prevalence of stroke at altitude in individuals who are considered to be low risk for thrombotic events, it is uncertain how venous thrombi reach the brain. The patent foramen ovale (PFO) is a recruitable intracardiac shunt between the right and left atrium. We aimed to determine whether body position and oxygen tension affect blood flow through the PFO in healthy adults. We hypothesized that hypoxia and body positions that promote right atrial filling would independently recruit the PFO. Subjects with a PFO ( n = 11) performed 11 trials, combining four different fractions of inhaled oxygen (FiO2) (1.0, 0.21, 0.15, and 0.10) and three positions (upright, supine, and 45° head down), with the exception of FiO2= 0.10, while 45° head down. After 5 min in each position, breathing the prescribed oxygen tension, saline bubbles were injected into an antecubital vein and a four-chamber echocardiogram was obtained to evaluate PFO recruitment. We observed a high incidence of PFO recruitment in all conditions, with increased recruitment in response to severe hypoxia and some contribution of body position at moderate levels of hypoxia. We suspect that increased pulmonary vascular pressure, secondary to hypoxia-induced pulmonary vasoconstriction, increased right atrial pressure enough to recruit the PFO. Additionally, we hypothesize that the minor increase in breathing resistance that was added by the mouthpiece, used during experimental trials, affected intrathoracic pressure and venous return sufficiently to recruit the PFO.
NMDA-type glutamate receptors participate in reduction of food intake following hindbrain melanocortin receptor activation
Authors: Campos Carlos A. , Ritter Robert C.
Published: November 2014

Hindbrain injection of a melanocortin-3/4 receptor agonist, MTII, reduces food intake primarily by reducing meal size. Our previously reported results indicate that N-methyl-d-aspartate-type glutamate receptors (NMDAR) in the nucleus of the solitary tract (NTS) play an important role in the control of meal size and food intake. Therefore, we hypothesized that activation of NTS NMDARs contribute to reduction of food intake in response to fourth ventricle or NTS injection of MTII. We found that coinjection of a competitive NMDAR antagonist (d-CPP-ene) with MTII into the fourth ventricle or directly into the NTS of adult male rats attenuated MTII-induced reduction of food intake. Hindbrain NMDAR antagonism also attenuated MTII-induced ERK1/2 phosphorylation in NTS neurons and prevented synapsin I phosphorylation in central vagal afferent endings, both of which are cellular mechanisms previously shown to participate in hindbrain melanocortinergic reduction of food intake. Together, our results indicate that NMDAR activation significantly contributes to reduction of food intake following hindbrain melanocortin receptor activation, and it participates in melanocortinergic signaling in NTS neural circuits that mediate reduction of food intake.
Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression
Authors: Raff Hershel , Gehrand Ashley , Bruder Eric D. , Hoffman Matthew J. , Engeland William C. , Moreno Carol
Published: November 2014

The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo ( Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland.
Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects
Authors: Rogers Robert S. , Beaudoin Marie-Soleil , Wheatley Joshua L. , Wright David C. , Geiger Paige C.
Published: November 2014

Heat treatments (HT) and the induction of heat shock proteins (HSPs) improve whole body and skeletal muscle insulin sensitivity while decreasing white adipose tissue (WAT) mass. However, HSPs in WAT have been understudied. The purpose of the present study was to examine patterns of HSP expression in WAT depots, and to examine the effects of a single in vivo HT on WAT metabolism. Male Wistar rats received HT (41°C, 20 min) or sham treatment (37°C), and 24 h later subcutaneous, epididymal, and retroperitoneal WAT depots (SCAT, eWAT, and rpWAT, respectively) were removed for ex vivo experiments and Western blotting. SCAT, eWAT, and rpWAT from a subset of rats were also cultured separately and received a single in vitro HT or sham treatment. HSP72 and HSP25 expression was greatest in more metabolically active WAT depots (i.e., eWAT and rpWAT) compared with the SCAT. Following HT, HSP72 increased in all depots with the greatest induction occurring in the SCAT. In addition, HSP25 increased in the rpWAT and eWAT, while HSP60 increased in the rpWAT only in vivo. Free fatty acid (FFA) release from WAT explants was increased following HT in the rpWAT only, and fatty acid reesterification was decreased in the rpWAT but increased in the SCAT following HT. HT increased insulin responsiveness in eWAT, but not in SCAT or rpWAT. Differences in HSP expression and induction patterns following HT further support the growing body of literature differentiating distinct WAT depots in health and disease.
Transient energy deficit induced by exercise increases 24-h fat oxidation in young trained men
Authors: Iwayama Kaito , Kawabuchi Ryosuke , Park Insung , Kurihara Reiko , Kobayashi Masashi , Hibi Masanobu , Oishi Sachiko , Yasunaga Koichi , Ogata Hitomi , Nabekura Yoshiharu , Tokuyama Kumpei
Published: November 2014

Whole body fat oxidation increases during exercise. However, 24-h fat oxidation on a day with exercise often remains similar to that of sedentary day, when energy intake is increased to achieve an energy-balanced condition. The present study aimed to examine a possibility that time of the day when exercise is performed makes differences in 24-h fat oxidation. As a potential mechanism of exercise affecting 24-h fat oxidation, its relation to exercise-induced transient energy deficit was examined. Nine young male endurance athletes underwent three trials of indirect calorimetry using a metabolic chamber, in which they performed a session of 100 min of exercise before breakfast (AM), after lunch (PM), or two sessions of 50 min of exercise before breakfast and after lunch (AM/PM) at 65% of maximal oxygen uptake. Experimental meals were designed to achieve individual energy balance. Twenty-four-hour energy expenditure was similar among the trials, but 24-h fat oxidation was 1,142 ± 97, 809 ± 88, and 608 ± 46 kcal/24 h in descending order of its magnitude for AM, AM/PM, and PM, respectively ( P < 0.05). Twenty-four-hour carbohydrate oxidation was 2,558 ± 110, 2,374 ± 114, and 2,062 ± 96 kcal/24 h for PM, AM/PM, and AM, respectively. In spite of energy-balanced condition over 24 h, exercise induced a transient energy deficit, the magnitude of which was negatively correlated with 24-h fat oxidation ( r = −0.72, P < 0.01). Similarly, transient carbohydrate deficit after exercise was negatively correlated with 24-h fat oxidation ( r = −0.40, P < 0.05). The time of the day when exercise is performed affects 24-h fat oxidation, and the transient energy/carbohydrate deficit after exercise is implied as a factor affecting 24-h fat oxidation.
Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia
Authors: Milne Elizabeth , Greenop Kathryn R. , Scott Rodney J. , Haber Michelle , Norris Murray D. , Attia John , Jamieson Sarra E. , Miller Margaret , Bower Carol , Bailey Helen D. , Dawson Somer , McCowage Geoffrey B. , de Klerk Nicholas H. , van Bockxmeer Frank M. , Armstrong Bruce K.
Published: November 2014

Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case–control study (2003–2007).

Methods: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case–parent trios were also analyzed.

Results: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39–0.91] and 0.64 (95% CI, 0.40–1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02–1.93) and 1.81 (95% CI, 1.06–3.07). ORs varied little by maternal folic acid supplementation.

Conclusions: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.

Impact: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results. Cancer Epidemiol Biomarkers Prev; 24(1); 48–56. ©2014 AACR.
Criminal Involvement and Crime Specialization Among Crack Users in the Netherlands
Authors: Oteo Pérez Alberto , Benschop Annemieke , Blanken Peter , Korf Dirk J.
Published: November 2014

Background/Aims: Crack users in the Netherlands are an ageing and diverse population with longstanding criminal careers. Our aim was to assess factors associated with current criminal involvement and specialization in selling drugs, property crime and violence. Method: A sample of 1,039 frequent crack users was recruited in three major Dutch cities, combining respondent-driven sampling with random institutional sampling. Bivariate and logistic regression analyses were performed to find factors associated with current criminality. Results: A total of 431 participants (41.5%) had engaged in crime in the past 30 days, mostly selling drugs (68.9%), followed by property crimes (34.4%) and a few cases of violent crime (9.7%). Younger age, homelessness, heavier patterns of use and a more prolific criminal justice history were associated with current criminality. Those receiving welfare benefits tended to be more likely to specialize only in selling drugs as opposed to (also) property crimes. Conclusion: Reducing drug use among criminally involved crack users and addressing their housing conditions could have a significant impact on reducing drug-related crime. Welfare benefits might act as protective factor against committing property crimes but not against the selling of drugs.
The Use of Bisphosphonates in Pediatrics
Authors: Baroncelli Giampiero I. , Bertelloni Silvano
Published: November 2014

Bisphosphonates are widely used for the prevention and treatment of osteoporosis in adulthood. In the last years, bisphosphonates have been increasingly used in pediatric patients for the treatment of a growing number of disorders associated with osteoporosis, resistant hypercalcemia or heterotopic calcifications. The use of bisphosphonates in pediatric patients has been proven safe; however, the risk of potential severe consequences into adulthood should be kept in mind. Well-defined criteria for bisphosphonates treatment in pediatric patients are not specified, therefore an accurate selection of patients who could benefit from bisphosphonates is mandatory. A strict follow-up of pediatric patients receiving long-term bisphosphonate therapy is strongly recommended. The purpose of this mini review is to provide a summary of current knowledge on some main general aspects of the structure, mechanisms of action, pharmacokinetics, and bioavailability of bisphosphonates, and to focus on the latest advances of bisphosphonate treatment in pediatric patients. Particular attention has been paid to the common and potential adverse effects of bisphosphonate treatment, and some suggestions concerning the clinical approach and general measures for bisphosphonate treatment in pediatric patients are reported.
The Study of Breast Milk IGF-1, Leptin, Ghrelin and Adiponectin Levels as Possible Reasons of High Weight Gain in Breast-Fed Infants
Authors: Kon Igor Ya , Shilina Natalia M. , Gmoshinskaya Maria V. , Ivanushkina Tatiana A.
Published: November 2014

Background: Excessive consumption of protein that leads to increased blood levels of insulin-like growth factor-1 (IGF-1) is an important risk factor for high growth velocity and obesity in formula-fed infants. However, it is not clear whether these factors can explain the high growth velocity in breast-fed infants. Aim: To study the possible links between the growth velocity in breast-fed infants and the levels of protein, IGF-1 and other hormones, which regulate energy homeostasis, in mothers' breast milk. Methods: We studied 103 mother-infant pairs. Their daily breast milk intake and level of IGF-1, leptin, ghrelin, adiponectin, protein and fat in breast milk were measured at 1, 2 and 3 months of lactation. The infant group was divided into three subgroups of low, normal and high weight gain tertiles. Results: The breast milk consumed by the infants with high weight gain contained higher levels of IGF-1 than that consumed by those with low weight gain at all periods studied (p = 0.032 at 3 months of lactation), and ghrelin levels were higher at 1 and 2 months and leptin levels at 2 and 3 months of lactation (p < 0.05). A positive correlation was observed between the breast milk IGF-1 level and infant weight gain (r = 0.294, p = 0.043). Total daily breast milk, fat and hormone intake was also higher in the high weight gain group compared to the low weight gain group. Conclusion: One of the reasons for the high growth velocity in breast-fed infants may be the enhanced levels of the studied hormones in breast milk.
A Novel ERCC6 Splicing Variant Associated with a Mild Cockayne Syndrome Phenotype
Authors: Swartz Jonathan M. , Akinci Aysehan , Andrew Shayne F. , Siğirci Ahmet , Hirschhorn Joel N. , Rosenfeld Ron G. , Dauber Andrew , Hwa Vivian
Published: November 2014

Background: Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and photosensitivity. New genomic approaches offer improved molecular diagnostic potential. Methods: Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism. Results: We identified a novel homozygous ERCC6 variant at the donor splice site of intron 9 (c.1992 + 3A>G), which was predicted to only slightly perturb splicing efficiencies. Assessment of primary fibroblast-derived mRNAs, however, revealed a dominant splicing species that utilized an unsuspected putative donor splice site within exon 9, resulting in predicted early protein termination (p.Arg637Serfs*34). Conclusions: We describe a new splicing ERCC6 defect causal of Cockayne syndrome. The application of exome sequence analysis was integral to diagnosis, given the complexity of phenotypic presentation in the affected family members. The novel splicing defect, furthermore, illustrates how a seemingly minor change in the relative strength of a splice site can have significant biological consequences.
Effects of Ethnicity and Sex on the Pharmacokinetics and Pharmacodynamics of the Selective Sphingosine-1-Phosphate Receptor 1 Modulator Ponesimod: A Clinical Study in Japanese and Caucasian Subjects
Authors: Reyes Maribel , Hoch Matthias , Brossard Patrick , Dingemanse Jasper
Published: November 2014

Abstract: The aim of this study was to evaluate the relative pharmacokinetic (PK) and pharmacodynamic (PD) properties of a single dose of ponesimod, an oral and selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, in Japanese and Caucasian healthy subjects and explore the effects of sex on PK. Subjects received a single 40-mg dose of ponesimod in a single-centre, open-label, parallel-group study design. Ten Japanese and 10 Caucasian healthy subjects (age: 22-45 years, 1:1 sex ratio) participated in the study and were matched for body weight (w10%). Ponesimod concentration in plasma was determined by liquid chromatography tandem mass spectrometry, and PK parameters were obtained by non-compartmental analysis. Total lymphocyte count served as PD marker. Adverse events (AEs), laboratory values, electrocardiography (12-lead ECG), and vital signs were assessed for safety and tolerability. Administration of ponesimod resulted in similar PK parameters between the two ethnic groups, with a 16% higher exposure [AUC0-∞ of 7,368 ng · h/ml (95% CI: 6,059-8,962) vs. 6,353 ng · h/ml (4,950-8,154)] and a 17% longer terminal elimination half-life [32.9 h (30.1-36.0) vs. 28.1 h (23.4-33.6)] in Japanese compared to Caucasian subjects. Exposure was slightly higher in female subjects [7,488 ng · h/ml (5,983-9,371)] than in male subjects [6,252 ng · h/ml (5,031-7,771)]. The maximum mean lymphocyte count decrease from baseline, observed 6 h after receiving the dose in both groups, was similar in Japanese subjects (61.8%) and Caucasians (62.5%). The maximum mean heart rate (ECG) reduction from baseline was similar, with a difference of 4.2 bpm between Caucasian and Japanese subjects, observed 2.5 h after receiving the dose in both ethnic groups. There were no clinically relevant changes in other safety variables. No serious AEs were reported during the study. This study showed that the PK and PD profile of ponesimod was similar in Japanese and Caucasian subjects. No unexpected safety findings were reported. No dose adjustment is deemed necessary for Japanese subjects compared to Caucasians. i 2014 S. Karger AG, Basel