bluuebunny/crossref_metadata_2025 huggingface dataset:
Transepidermal water loss in cats: comparison of three differently clipped sites to assess the influence of hair coat on transepidermal water loss values
Authors: Momota Yutaka , Shimada Kenichiroh , Takami Akina , Akaogi Harumi , Takasaki Mariko , Mimura Kana , Azakami Daigo , Ishioka Katsumi , Nakamura Yuka , Sako Toshinori
Published: June 2013

Background

The measurement of transepidermal water loss (TEWL) is one of the parameters that can be used to assess skin barrier function. The variability and reliability of TEWL measurements in dogs have been controversial, and the hair coat has been considered as one of the factors that may cause variation of TEWL values.

Hypothesis/Objectives

The aims of the study were to establish a suitable procedure for measuring feline TEWL, to evaluate the influence of hair coat on TEWL measurements and to assess variations of TEWL at different anatomical sites.

Methods

Transepidermal water loss was measured using a closed‐chamber evaporimeter, the VapoMeter®. We compared three adjacent sites in the groin area of 10 clinically normal, domestic short hair cats. One site was unclipped, the second was trimmed with scissors and the third was shaved using electric clippers. Values of TEWL were obtained for 48 h after trimming with scissors and clippers. Five sites were clipped (upper back, lumbar back, lateral thigh, axillae and groin), and the TEWL was measured.

Results

The mean and SD of TEWL values of the clipper‐trimmed site were the smallest, followed in order by the site trimmed with scissors and the unclipped site. The TEWL values were statistically constant in the clipper‐trimmed site, while the values in the unclipped sites were not. There was no statistically significant difference in TEWL values between all of the anatomical sites except for the axillae.

Conclusions and clinical importance

Hair clipping of sites with electric clippers is recommended for TEWL measurement in cats.
One-Dimensional Transient Heat Conduction in Composite Living Perfuse Tissue
Authors: Becker S. M.
Published: June 2013

Modeling the conduction of heat in living tissue requires the consideration of sudden spatial discontinuities in property values as well as the presence of the body's circulatory system. This paper presents a description of the separation of variables method that results in a remarkably simple solution of transient heat conduction in a perfuse composite slab for which at least one of the layers experiences a zero perfusion rate. The method uses the natural analytic approach and formats the description so that the constants of integration of each composite layer are expressed in terms of those of the previous layer's eigenfunctions. This allows the solution to be “built” in a very systematic and sequential manner. The method is presented in the context of the Pennes bioheat equation for which the solution is developed for a system composed of any number of N layers with arbitrary initial conditions.
Whole-Genome Sequences of Four Clinical Isolates of Mycobacterium tuberculosis from Tamil Nadu, South India
Authors: Narayanan Sujatha , Deshpande Uday
Published: June 2013

We report the annotated genome sequences of four clinical isolates of
Mycobacterium tuberculosis
from Tamil Nadu, India.
Genome Sequence of Mink Enteritis Virus Strain SD 12/01, Isolated from a Mink with Severe Diarrhea in China
Authors: Wang Jianke , Zhao Hang , Cheng Yuening , Yi Li , Cheng Shipeng
Published: June 2013

The mink enteritis virus (MEV) SD12/01 strain was isolated from a mink showing clinical and pathological signs of enteritis in Shandong, China, in 2012. The genome of MEV SD12/01 was sequenced and analyzed, which will promote a better understanding of the molecular epidemiology and genetic diversity of MEV field isolates in northern China.
Genome Sequence of Methicillin-Resistant Staphylococcus pseudintermedius Sequence Type 233 (ST233) Strain K7, of Human Origin
Authors: Youn Jung-Ho , Moodley Arshnee , Park Yong Ho , Sugimoto Chihiro
Published: June 2013

We report the genome sequence of the methicillin-resistant
Staphylococcus pseudintermedius
strain K7, isolated from the nares of a veterinarian in Seoul, South Korea.
Draft Genome Sequence and Annotation of the Entomopathogenic Bacterium Xenorhabdus nematophila Strain F1
Authors: Lanois Anne , Ogier Jean-Claude , Gouzy Jérome , Laroui Christine , Rouy Zoé , Givaudan Alain , Gaudriault Sophie
Published: June 2013

We report the 4.3-Mb genome sequence of
Xenorhabdus nematophila
strain F1, a Gram-negative bacterium that is a symbiont of the entomopathogenic nematode
Steinernema carpocapsae
and pathogenic by direct injection for a wide variety of insects.
Draft Genome Sequence of Methylobacterium mesophilicum Strain SR1.6/6, Isolated from
Citrus sinensis
Authors: Marinho Almeida Diogo , Dini-Andreote Francisco , Camargo Neves Aline Aparecida , Jucá Ramos Rommel Thiago , Andreote Fernando Dini , Carneiro Adriana Ribeiro , Oliveira de Souza Lima André , Caracciolo Gomes de Sá Pablo Henrique , Ribeiro Barbosa Maria Silvanira , Araújo Welington Luiz , Silva Artur
Published: June 2013

Methylobacterium mesophilicum
strain SR1.6/6 is an endophytic bacterium isolated from a surface-sterilized
Citrus sinensis
branch. Ecological and biotechnological aspects of this bacterium, such as the genes involved in its association with the host plant and the primary oxidation of methanol, were annotated in the draft genome.
Draft Genome Sequence of the Antarctic Psychrophilic Bacterium Pseudomonas syringae Strain Lz4W
Authors: Pandiyan Apuratha , Ray Malay K.
Published: June 2013

The psychrophilic bacterium
Pseudomonas syringae
strain Lz4W was isolated from soil samples from Antarctica to decipher the mechanisms of low-temperature adaptation. We report here the 4.982-Mb draft genome sequence of
P. syringae
Lz4W. This sequence will provide insights into the genomic basis of the psychrophilicity of this bacterium.
The experiences of adults with learning disabilities attending a sexuality and relationship group:“I want to get married and have kids”
Authors: Box Matthew , Shawe Jill
Published: June 2013

Background

People with learning disabilities are frequently denied or restricted in their right to express their sexuality by restrictive policies, negative attitudes or lack of awareness of their needs. They also tend to have differing and unrecognised sexual health needs to those of the general population. Evidence suggests that acquiring a greater knowledge and awareness of sexuality and relationship issues helps to decrease these disadvantages and to promote a greater sense of well-being for this group.

Methods

The experiences of eight adults with learning disabilities attending a sexuality and relationship group, based on a mixture of validated and established sexuality and relationship programmes, were explored using a case study approach. Participants’ experiences were gathered through semi-structured interviews and analysed using qualitative content analysis supported by participant observation and pre- and post-group assessment of knowledge.

Results

Participant experiences were unique and individual, with few shared opinions. All participants demonstrated increases in their total knowledge scores in the post-group assessment and felt that attending the group had changed their views on relationships; they felt that they were more able to talk to others, to trust someone, to feel confident to want longer relationships and to be married with children.

Conclusions

Sexuality and relationship groups can offer participants a beneficial and positive experience to explore such issues. The experiences of participants could be enhanced through adopting a person-centred approach and through recognising that participants have individual experiences that may not be shared within the group environment.
High rates of unprotected anal intercourse with regular and casual partners and associated risk factors in a sample of ethnic Malay men who have sex with men (MSM) in Penang, Malaysia
Authors: Lim Sin How , Bazazi Alexander Reza , Sim Clarence , Choo Martin , Altice Frederick L , Kamarulzaman Adeeba
Published: June 2013

Objective

To assess the prevalence of unprotected anal intercourse (UAI) and its correlates among ethnic Malay men who have sex with men (MSM).

Methods

In 2010, a convenience sample of 350 MSM in Penang were recruited to participate in an anonymous, computerised survey with rapid HIV testing. Participants who were not of Malay ethnicity (n=44) or who did not report sex with another man in the previous 12 months (n=22) were excluded, resulting in 284 participants in the final analysis. Correlates of UAI were examined separately for regular and casual partnerships using bivariate and multivariate logistic regression.

Results

Four men (1.9%) tested HIV positive. In the past 12 months, 64.7% of participants had regular sexual partners, 77.1% had casual sexual partners and 41.9% had both. Most participants (83.1%) reported UAI, which was more common in regular partnerships. Over two-thirds of participants had never been tested for HIV. In multivariate analysis, agreement about sexual risk reduction practices was associated with a reduction in UAI with regular partners (adjusted OR (AOR)=0.14, 95% CI 0.05 to 0.40). Reporting difficulty in using condoms was associated with an increase in UAI with casual partners (AOR=9.07, 95% CI 3.35 to 24.5), and any exposure to HIV prevention was associated with a decrease in UAI with casual partners (AOR=0.22, 95% CI 0.09 to 0.54).

Conclusions

Despite highly prevalent HIV risk behaviours, HIV seropositivity and prior HIV testing were low. Increasing sexual negotiation skills and access to HIV testing and other prevention services may improve future prevention efforts.
Multivariate distribution for undrained shear strengths under various test procedures
Authors: Ching Jianye , Phoon Kok-Kwang
Published: June 2013

The undrained shear strength (su) of a clay is not a constant. In particular, suvalues of a clay evaluated by different test procedures are different because these tests may have different stress states, stress histories, degrees of sampling disturbance, and strain rates. This study constructs the multivariate probability distribution of sufrom various test procedures based on a large clay database. This multivariate distribution provides an estimation of the normalized undrained shear strength based on four factors: test mode, overconsolidation ratio, strain rate, and plasticity. Once this multivariate distribution is constructed, interesting questions can be answered systematically using simple Bayesian analysis, e.g., given the suvalue for one test procedure, what is the updated mean and coefficient of variation of the suvalue for another test procedure?
Spring-loaded reproduction: effects of body condition and population size on fertility in migratory caribou (Rangifer tarandus)
Authors: Pachkowski M. , Côté S.D. , Festa-Bianchet M.
Published: June 2013

In many ungulates, female fecundity is affected by body condition and has important effects on population dynamics. In some species, females adopt a conservative strategy, reducing reproductive effort when population density is high. We investigated what factors affect the probability of gestation in adult female caribou (Rangifer tarandus (L., 1758)) from the Rivière-George herd in northern Quebec and Labrador over 5 years that spanned various population sizes and trends. Similar to other populations of migratory caribou, the probability that a female was pregnant in spring increased with body mass and percent body fat. The probability of gestation appeared to be reduced by high infestation of warbles (Hypoderma tarandi (L., 1758)). The proportion of females pregnant varied between years and was lower at high population size. Females of similar mass, however, were pregnant regardless of whether the population was increasing at low density, had reached a peak, or was declining. Compared with other ungulates that reduce maternal expenditure at high density, female caribou of the Rivière-George herd may have a risk-prone reproductive strategy.
The gigantic Seymareh (Saidmarreh) rock avalanche, Zagros Fold–Thrust Belt, Iran
Authors: Roberts Nicholas J. , Evans Stephen G.
Published: June 2013

The Seymareh rock avalanche, first described by J. V. Harrison and N. L. Falcon in the 1930s, is the largest known subaerial non-volcanic landslide on Earth. The volume of its debris (44 Gm
3
) is approximately equal to that of the largest known subaerial landslide of any kind, the 100 ka collapse of Mount Shasta volcano (45 Gm
3
) and approaches those of gigantic landslides on Mars. Using satellite imagery, SRTM-3 data, and detailed field investigations, we gain a new understanding of the gigantic rock avalanche. The initial failure (38 Gm
3
), involving a dip slope consisting of a relatively weak interbedded limestone–mudrock sequence capped by resistant Asmari Limestone, had an average thickness of 410 m along a 15.5 km width of the Kabir Kuh anticline. The rockslide transformed into a rock avalanche that travelled 19.0 km with a
fahrböschung
(the angle between the highest point of the pre-landslide source area topography and the distal limit of the debris) of only 3.6°. Initial failure involved complex planar sliding dictated by four structural elements: (1) bedding-parallel shears and (2) across-bedding break-throughs combined to produce a low-angle (11°) overall sliding surface that (3) broke out through the Asmari carapace at the toe of the failed slope while (4) tectonically weakened bedding-normal joints provided lateral release surfaces. Nine discrete bedding-parallel basal sliding surfaces divided the detached mass into nine stacked plates. The upper plate (23 Gm
3
) included 20.7 Gm
3
of Asmari Limestone. Analysis of accelerator mass spectrometry radiocarbon dates from this study and by others indicates that the rock avalanche occurred between
c
. 8710 and 9800
14
C years BP.

Supplementary material:

A summary of the tectonics, stratigraphy and physiography of the Zagros Fold–Thrust belt together with a description of surficial gravity collapse structures in the region (Harrison & Falcon 1934, 1936) is available at
www.geolsoc.org.uk/SUP18612
.
Quantifying rates of detachment faulting and erosion in the central Menderes Massif (western Turkey) by thermochronology and cosmogenic
10
Be
Authors: Buscher J. T. , Hampel A. , Hetzel R. , Dunkl I. , Glotzbach C. , Struffert A. , Akal C. , Rätz M.
Published: June 2013

Exhumation of rocks in extensional tectonic settings results from a combination of normal faulting and erosion but the relative contribution of these processes has rarely been quantified. Here we present new low-temperature thermochronological data and the first
10
Be-based catchment-wide erosion rates from the Boz Dağ region in the central Menderes Massif, which has experienced NNE–SSW extension since the Miocene. The slip rate of the shallow-dipping Gediz detachment fault, which defines the northern flank of the Boz Dağ block, is 4.3 (+3.0/−1.2) mm a
−1
, as constrained by zircon (U–Th)/He ages of
c
. 4–2 Ma in the footwall. Apatite and zircon (U–Th)/He and fission-track ages from the northern flank of the Boz Dağ block yield exhumation rates of 0.6–2 km Ma
−1
beneath the Gediz detachment, whereas those on the southern flank are only 0.2–0.6 km Ma
−1
. Erosion of catchments on the northern and southern flanks proceeds at rates of 80–180 and 330–460 mm ka
−1
, respectively. This marked contrast is a combined effect of the topographic asymmetry of the Boz Dağ block and differences in rock erodibility. If these erosion rates persisted in the past, rock exhumation on the northern flank occurred predominantly by tectonic denudation, whereas rocks on the southern flank were mainly exhumed by erosion.
Issues in dating young rocks from another planet: Martian shergottites
Authors: Park Jisun , Bogard Donald D. , Nyquist Laurence E. , Herzog G. F.
Published: June 2013

The
40
Ar/
39
Ar ages of a group of Martian meteorites called shergottites are systematically older by about 25% or more than ages obtained using Sm–Nd and other radiometric dating methods. The older
40
Ar/
39
Ar ages indicate the presence of
40
Ar not derived
in situ
from the radiogenic decay of
40
K. The ‘excess’ argon can be associated with several different components, including the Martian atmosphere and mantle. We discuss the sources of Ar in shergottites, and the methods used to separate and identify them.
A laser probe
40
Ar/
39
Ar investigation of poikilitic shergottite NWA 4797: implications for the timing of shock metamorphism
Authors: Walton Erin L. , Kelley Simon , Herd Christopher D. K. , Irving Anthony J.
Published: June 2013

Spatially resolved argon isotope measurements have been performed on neutron-irradiated samples of NW Africa (NWA) 4797. Shock heating of NWA 4797 completely melted and vesiculated precursor igneous plagioclase, which cooled to an assemblage of plagioclase crystals with interstitial glasses of variable composition (Ca/K ratios). Using a focused ultraviolet laser beam, is has been possible to distinguish between argon isotopic signatures from groundmass minerals (igneous olivine + pyroxene), plagioclase and a shock vein. This study focuses on the potential for this meteorite to shed light on shock ages of shergottites.

Apparent
40
Ar/
39
Ar ages of groundmass minerals show that there are large amounts of excess argon in this phase, yielding a wide range of calculated ages from 690 ± 30 Ma to several apparent ages older than 4.5 Ga. A traverse of laser-probe extractions across the 1 mm-diameter shock vein in NWA 4797 yielded apparent
40
Ar/
39
Ar ages younger than the groundmass. A signature of the Martian atmosphere, identified by
40
Ar/
36
Ar ratios of 1600–1900, was not found in the NWA 4797 shock vein. This is distinct from other shergottites where the products of shock melting contain a nearly pure sample of Martian atmosphere. We attribute this to a distinct formation mechanism, and hence gas-trapping mechanism, of the NWA 4797 shock vein.

We undertook 44 analyses of plagioclase areas identified by SEM analysis. Ages ranged from 45 ± 27 to 3771 ± 109 Ma and yield an average age of 375 ± 77 Ma, considerably younger than ages obtained in this study from either the groundmass or the shock vein. A plot of age v.
37
Ar/
39
Ar for plagioclase showed a continuum of ages from the oldest to youngest ages measured. Older ages are correlated with higher Ca/K ratios of plagioclase, indicating contamination from groundmass minerals rich in excess argon. The youngest ages correlate to plagioclase extractions with the lowest Ca/K ratios, interpreted to have crystallized from a nearly pure plagioclase melt with contributions from a K-rich mesostasis. We see no evidence for multiple shock events in NWA 4797. Rather, we favour the interpretation that the cosmic-ray exposure (CRE) age of 3.0±0.5 Ma, obtained on NWA 4797 in this study using cosmogenic
38
Ar, approximates the timing of shock melting in this meteorite.

Supplementary material:

Laser probe argon isotopic data for NWA 4797 obtained in this study are available at
http://www.geolsoc.org.uk/SUP18602
.
In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a β-adrenergic-related pathway and nitric oxide
Authors: Grossini Elena , Surico Daniela , Mary David A. S. G. , Molinari Claudio , Surico Nicola , Vacca Giovanni
Published: June 2013

Human chorionic gonadotropin (hCG) is not only responsible for numerous pregnancy-related processes, but can affect the cardiovascular system as well. So far, however, information about any direct effect elicited by hCG on cardiac function, perfusion, and the mechanisms involved has remained scarce. Therefore, the present study aimed to determine the primary in vivo effect of hCG on cardiac contractility and coronary blood flow and the involvement of autonomic nervous system and nitric oxide (NO). Moreover, in coronary endothelial cells (CEC), the intracellular pathways involved in the effects of hCG on NO release were also examined. In 25 anesthetized pigs, intracoronary 500 mU/ml hCG infusion at constant heart rate and aortic blood pressure increased coronary blood flow, maximum rate of change of left ventricular systolic pressure, segmental shortening, cardiac output, and coronary NO release ( P < 0.0001). These hemodynamic responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoceptors ( n = 5) and of α-adrenoceptors ( n = 5) did not abolish the observed responses, β1-adrenoceptors blocker ( n = 5) prevented the effects of hCG on cardiac function. In addition, β2-adrenoceptors ( n = 5) and NO synthase inhibition ( n = 5) abolished the coronary response and the effect of hCG on NO release. In CEC, hCG induced the phosphorylation of endothelial NO synthase through cAMP/PKA signaling and ERK1/2, Akt, p38 MAPK involvement, which were activated as downstream effectors of β2-adrenoceptor stimulation. In conclusion, in anesthetized pigs, hCG primarily increased cardiac function and perfusion through the involvement of β-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.
Direct and indirect lactate oxidation in trained and untrained men
Authors: Emhoff Chi-An W. , Messonnier Laurent A. , Horning Michael A. , Fattor Jill A. , Carlson Thomas J. , Brooks George A.
Published: June 2013

Lactate has been shown to be an important oxidative fuel. We aimed to quantify the total lactate oxidation rate (Rox) and its direct vs. indirect (glucose that is gluconeogenically derived from lactate and subsequently oxidized) components (mg·kg−1·min−1) during rest and exercise in humans. We also investigated the effects of endurance training, exercise intensity, and blood lactate concentration ([lactate]b) on direct and indirect lactate oxidation. Six untrained (UT) and six trained (T) men completed 60 min of constant load exercise at power outputs corresponding to their lactate threshold (LT). T subjects completed two additional 60-min sessions of constant load exercise at 10% below the LT workload (LT−10%), one of which included a lactate clamp (LC; LT−10%+LC). Roxwas higher at LT in T [22.7 ± 2.9, 75% peak oxygen consumption (V̇o2peak)] compared with UT (13.4 ± 2.5, 68% V̇o2peak, P < 0.05). Increasing [lactate]b(LT−10%+LC, 67% V̇o2peak) significantly increased lactate Rox(27.9 ± 3.0) compared with its corresponding LT−10% control (15.9 ± 2.2, P < 0.05). Direct and indirect Roxincreased significantly from rest to exercise, and their relative partitioning remained constant in all trials but differed between T and UT: direct oxidation comprised 75% of total lactate oxidation in UT and 90% in T, suggesting the presence of training-induced adaptations. Partitioning of total carbohydrate (CHO) use showed that subjects derived one-third of CHO energy from blood lactate, and exogenous lactate infusion increased lactate oxidation significantly, causing a glycogen-sparing effect in exercising muscle.
Transcription Poisoning by Topoisomerase I Is Controlled by Gene Length, Splice Sites, and miR-142-3p
Authors: Solier Stéphanie , Ryan Michael C. , Martin Scott E. , Varma Sudhir , Kohn Kurt W. , Liu Hongfang , Zeeberg Barry R. , Pommier Yves
Published: June 2013

Topoisomerase I (Top1) relaxes DNA supercoiling by forming transient cleavage complexes (Top1cc) up- and downstream of transcription complexes. Top1cc can be trapped by carcinogenic and endogenous DNA lesions and by camptothecin, resulting in transcription blocks. Here, we undertook genome-wide analysis of camptothecin-treated cells at exon resolution. RNA samples from HCT116 and MCF7 cells were analyzed with the Affy Exon Array platform, allowing high-resolution mapping along 18,537 genes. Long genes that are highly expressed were the most susceptible to downregulation, whereas short genes were preferentially upregulated. Along the body of genes, downregulation was most important toward the 3′-end and increased with the number of exon–intron junctions. Ubiquitin and RNA degradation-related pathway genes were selectively downregulated. Parallel analysis of microRNA with the Agilent miRNA microarray platform revealed that miR-142-3p was highly induced by camptothecin. More than 10% of the downregulated genes were targets of this p53-dependent microRNA. Our study shows the profound impact of Top1cc on transcription elongation, especially at intron–exon junctions and on transcript stability by microRNA miR-142-3p upregulation. Cancer Res; 73(15); 4830–9. ©2013 AACR.
Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma
Authors: Liao Rachel G. , Jung Joonil , Tchaicha Jeremy , Wilkerson Matthew D. , Sivachenko Andrey , Beauchamp Ellen M. , Liu Qingsong , Pugh Trevor J. , Pedamallu Chandra Sekhar , Hayes D. Neil , Gray Nathanael S. , Getz Gad , Wong Kwok-Kin , Haddad Robert I. , Meyerson Matthew , Hammerman Peter S.
Published: June 2013

A comprehensive description of genomic alterations in lung squamous cell carcinoma (lung SCC) has recently been reported, enabling the identification of genomic events that contribute to the oncogenesis of this disease. In lung SCC, one of the most frequently altered receptor tyrosine kinase families is the fibroblast growth factor receptor (FGFR) family, with amplification or mutation observed in all four family members. Here, we describe the oncogenic nature of mutations observed in FGFR2 and FGFR3, each of which are observed in 3% of samples, for a mutation rate of 6% across both genes. Using cell culture and xenograft models, we show that several of these mutations drive cellular transformation. Transformation can be reversed by small-molecule FGFR inhibitors currently being developed for clinical use. We also show that mutations in the extracellular domains of FGFR2 lead to constitutive FGFR dimerization. In addition, we report a patient with an FGFR2-mutated oral SCC who responded to the multitargeted tyrosine kinase inhibitor pazopanib. These findings provide new insights into driving oncogenic events in a subset of lung squamous cancers, and recommend future clinical studies with FGFR inhibitors in patients with lung and head and neck SCC. Cancer Res; 73(16); 5195–205. ©2013 AACR.
The DREAM Complex Mediates GIST Cell Quiescence and Is a Novel Therapeutic Target to Enhance Imatinib-Induced Apoptosis
Authors: Boichuk Sergei , Parry Joshua A. , Makielski Kathleen R. , Litovchick Larisa , Baron Julianne L. , Zewe James P. , Wozniak Agnieszka , Mehalek Keith R. , Korzeniewski Nina , Seneviratne Danushka S. , Schöffski Patrick , Debiec-Rychter Maria , DeCaprio James A. , Duensing Anette
Published: June 2013

Gastrointestinal stromal tumors (GIST) can be successfully treated with imatinib mesylate (Gleevec); however, complete remissions are rare and patients frequently achieve disease stabilization in the presence of residual tumor masses. The clinical observation that discontinuation of treatment can lead to tumor progression suggests that residual tumor cells are, in fact, quiescent and, therefore, able to re-enter the cell-division cycle. In line with this notion, we have previously shown that imatinib induces GIST cell quiescence in vitro through the APCCDH1–SKP2–p27Kip1 signaling axis. Here, we provide evidence that imatinib induces GIST cell quiescence in vivo and that this process also involves the DREAM complex, a multisubunit complex that has recently been identified as an additional key regulator of quiescence. Importantly, inhibition of DREAM complex formation by depletion of the DREAM regulatory kinase DYRK1A or its target LIN52 was found to enhance imatinib-induced cell death. Our results show that imatinib induces apoptosis in a fraction of GIST cells while, at the same time, a subset of cells undergoes quiescence involving the DREAM complex. Inhibition of this process enhances imatinib-induced apoptosis, which opens the opportunity for future therapeutic interventions to target the DREAM complex for more efficient imatinib responses. Cancer Res; 73(16); 5120–9. ©2013 AACR.
Controlled Local Delivery of CTLA-4 Blocking Antibody Induces CD8+ T-Cell–Dependent Tumor Eradication and Decreases Risk of Toxic Side Effects
Authors: Fransen Marieke F. , van der Sluis Tetje C. , Ossendorp Ferry , Arens Ramon , Melief Cornelis J.M.
Published: June 2013

Purpose: Blockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with CTLA-4 blocking antibodies is associated with autoimmune and inflammatory side effects. In this study, we propose a novel administration method for CTLA-4 blocking antibodies as monotherapy.

Experimental Design: We use different preclinical mouse models of cancer to investigate the local administration of CTLA-4 blocking antibody and its effect on cancer progression and the antitumor T-cell response.

Results: By injecting the antibodies in a subcutaneous slow-release delivery formulation in the tumor area, we show that an eight-fold lower dose of antibody is as effective in inducing tumor eradication as systemic delivery. A lower dose and slow release of the antibody results in thousand-fold decreased levels of antibody in the serum, reducing adverse events and the risk of autoimmunity. The main target and effector cells of the CTLA-4 blockade treatment in the studied tumor models are tumor-specific endogenous CD8+ T cells that are capable of eradicating also distant tumors, whereas CD4+ T cells do not play a prominent role in the antibody-mediated tumor eradication.

Conclusions: Injecting CTLA-4 blocking antibody in a slow-release formulation close to the tumor is an effective way of activating the antitumor T-cell response. This administration method is associated with very low serum levels of antibody, which decreases the risk of treatment-induced side effects. These results call for exploration of a similar delivery principle in clinical settings. Clin Cancer Res; 19(19); 5381–9. ©2013 AACR.
The Role of Inflammatory Pathways in Cancer-Associated Cachexia and Radiation Resistance
Authors: Laine Aaron , Iyengar Puneeth , Pandita Tej K.
Published: June 2013

Dysregulated inflammatory responses are key contributors to a multitude of chronic ailments, including cancer. Evidence indicates that disease progression in cancer is dependent on the complex interaction between the tumor and the host microenvironment. Most recently, the inflammatory response has been suggested to be critical, as both the tumor and microenvironment compartments produce cytokines that act on numerous target sites, where they foster a complex cascade of biologic outcomes. Patients with cancer-associated cachexia (CAC) suffer from a dramatic loss of skeletal muscle and adipose tissue, ultimately precluding them from many forms of therapeutic intervention, including radiotherapy. The cytokines that have been linked to the promotion of the cachectic response may also participate in radiation resistance. The major changes at the cytokine level are, in part, due to transcriptional regulatory alterations possibly due to epigenetic modifications. Herein we discuss the role of inflammatory pathways in CAC and examine the potential link between cachexia induction and radiation resistance. Mol Cancer Res; 11(9); 967–72. ©2013 AACR.
Inducible
Apoe
Gene Repair in Hypomorphic ApoE Mice Deficient in the Low-Density Lipoprotein Receptor Promotes Atheroma Stabilization with a Human-Like Lipoprotein Profile
Authors: Eberlé Delphine , Luk Fu Sang , Kim Roy Y. , Olivas Victor R. , Kumar Nikit , Posada Jessica M. , Li Kang , Gaudreault Nathalie , Rapp Joseph H. , Raffai Robert L.
Published: June 2013

Objective—

To study atherosclerosis regression in mice after plasma lipid reduction to moderately elevated apolipoprotein B (apoB)–lipoprotein levels.

Approach and Results—

Chow-fed hypomorphic Apoe mice deficient in low-density lipoprotein receptor expression (
Apoe

h/h

Ldlr

–/–

Mx1-cre
mice) develop hyperlipidemia and atherosclerosis. These mice were studied before and after inducible cre-mediated
Apoe
gene repair. By 1 week, induced mice displayed a 2-fold reduction in plasma cholesterol and triglyceride levels and a decrease in the non–high-density lipoprotein:high-density lipoprotein-cholesterol ratio from 87%:13% to 60%:40%. This halted atherosclerotic lesion growth and promoted macrophage loss and accumulation of thick collagen fibers for up to 8 weeks. Concomitantly, blood Ly-6C
high
monocytes were decreased by 2-fold but lesional macrophage apoptosis was unchanged. The expression of several genes involved in extracellular matrix remodeling and cell migration was changed in lesional macrophages 1 week after
Apoe
gene repair. However, mRNA levels of numerous genes involved in cholesterol efflux and inflammation were not significantly changed at this time point.

Conclusions—

Restoring apoE expression in
Apoe

h/h

Ldlr

–/–

Mx1-cre
mice resulted in lesion stabilization in the context of a human-like ratio of non–high-density lipoprotein:high-density lipoprotein-cholesterol. Our data suggest that macrophage loss derived in part from reduced blood Ly-6C
high
monocytes levels and genetic reprogramming of lesional macrophages.
Ezekiel 29:3 and Its Ancient Near Eastern Context
Authors: Yoder Tyler R.
Published: June 2013

Abstract

The chief aim of this essay is to posit a well-known Mesopotamian royal and divine epithet, ušumgallu “great dragon,” as the source behind Ezekiel’s enigmatic description of Pharaoh in 29.3, hattannīn haggādôl, “the great dragon.” This relationship sheds new light and meaning on an old problem: why does Ezekiel refer to Pharaoh as a dragon? Rather than viewing this prophetic expression as a pejorative, the cognate evidence argues for the converse by rooting it in an enduring tradition of regal titles. Replicating Akkadian ušumgallu (Sumerian UŠUM.GAL) as efficiently as possible and drawing upon Israelite cosmological history (viz. Gen. 1.21a), Ezekiel feigned including Pharaoh within a venerable, long line of Mesopotamian kings and deities to receive this title. Instead, and as is characteristic of Ezekiel’s rhetoric, he upended the putative associations of the “great dragon,” thereby exposing its true subordinate position under the hegemony of YHWH.
Global Discourse, Local Practice: Female Circumcision and Inter-Generational Conflict in a Somali Diaspora Community
Authors: Abubakar Nasra
Published: June 2013

Abstract

The purpose of this research is to contribute to ongoing efforts to eradicate the practice of female circumcision worldwide. To fully eliminate this practice we need to deeply understand the reasoning behind it. And so this work integrates global discussion and local practice, extending the dialogue about female circumcision beyond the realm of academics to include people for whom FC is a part of their daily lives. Through focus group sessions with members of the Somali diaspora in the US, I find a pronounced generational divide on opinions relating to FC, with the younger generation expressing adamant opposition to the practice. The views of the younger generation reflect a higher status for women of the Somali diaspora, which is borne out of a struggle with adjustment to a new culture.
Inbreeding depression in intraspecific metabolic scaling
Authors: Ketola Tarmo , Kotiaho Janne S. , Mazzi Dominique , Puurtinen Mikael
Published: June 2013

Metabolic scaling (i.e., the relationship between the size and metabolic rate of organisms) has been suggested to explain a large variety of biological patterns from individual growth to species diversity. However, considerable disagreement remains regarding the underlying causes of metabolic scaling patterns, and what these patterns are. As in all biology, understanding metabolic scaling will require understanding its evolution by natural selection. We searched for evidence of natural selection on metabolic scaling indirectly by manipulating the genetic quality of male and female Drosophila montana flies with induced mutations and inbreeding, building on the notion that mutations and inbreeding will cause predictable changes in characters under directional selection. Irradiation-induced mutations had no effect on the examined traits, most likely because of purging at an early stage. However, inbreeding increased the energy use of larger females, suggesting that selection has favoured low metabolic scaling in females. Inbreeding did not affect metabolic scaling of males. Together, our results suggest that natural selection on metabolic scaling acts differently on the sexes, depending on the relative importance of body size and energetic efficiency to individual fitness. The results call attention to the important notion that size-specific energy use can be an evolutionarily malleable trait.
New Operations - New Attitudes? Are Soldiers’ Attitudes Influenced by the Objectives of Peace Operations?
Authors: Kold Claus
Published: June 2013

This article first presents central theories of military sociology about soldiers’ developing of certain military values, attitudes and identities in war operations This question and the factors related to it are then used to ask if soldiers deployed in peace operations develop different military attitudes. The question is then confronted by observations of the practices in a Danish Battalion in KFOR. The field observations found that the Danish soldiers were struggling with competing attitudes originating from both the military training and the objective of the peace operation. It is observed that new concepts and attitudes are in the making such as a new ‘mediator identity’, but that the warrior identity still dominates due to the varied intertwined processes of the daily practices of the military organization.
Fear, Transition and Democracy in the Balkans
Authors: Losoncz Alpar
Published: June 2013

The article puts emphasis on the fact that fear is to be articulated in the intersection between the universal structure of modernity and the particular historical narrations of the Balkans. The interpretation of history and the relationship with hope determine the meanings of fear. Fear is treated as the imagining of threats based on the re-memorization of the past and the experience of a fragile future. Hope is a positive anticipation or expectation concerning the future but exposed to the possibility of frustration. These moments are analyzed in the context of transition from the single-party based “socialism” to capitalism. The countries of the Balkans represented variations on the authoritarian welfare state project that entered crises at the end of 1960s. Ethnic conflicts in this part of Europe have been intensified under the increased economic pressures that had been latent for decades. Therefore, the fear of declassation that the middle class is experiencing has resulted in the fact that we cannot understand different national conflicts explaining the actual fears of middle class. Hence, it is necessary here to determine the structural basis of fear and hope. In order to understand the fears of the Balkans we need to reflect on the capitalism created in the meantime. It is noticed that the restorative orientation followed by the political elites during the transition causes the formation of fear axes regarding the understanding of national identity, as well as fear related to the preservation of national determination.
Islam, the State, and the Law in Europe
Authors: Varon Ari
Published: June 2013

The article presents the intricacies of an intra-Islamic debate within Europe today discussing multiple Islamic perspectives of religion, the state and the law. Analyzing the ideas of four contemporary European Muslim intellectuals the article reveals variations on how Muslims in Europe view the concept of secularism, the role of the state and the guidelines of Islamic religious practice. Through a comparative discourse analysis the article identities four distinct Islamic discourses that are compared and contrasted with each other and juxtaposed with European theory about religion, the state and the law.

As Muslims in Europe gradually overcome social cleavages and ethnic differences they at times challenge the secular nature and religious neutrality of Europe’s religious, cultural and humanist inheritance. Understanding the distinctions between the Islamic discourses elaborates the trends and ramifications the political mobilization Muslims living in Europe might have on the status quo definitions of European society; some Islamic discourses represent a direct confrontation to the construct secular identity; others suggest full integration into European society. All four are present in Europe today. Recognizing the differences between the Islamic discourses can rearrange the principles in which Europe perceives Islam while enlightening the politically sensitive and complex subject relating to the formation of an Islamic European identity.
Uncovering French and Belgian Face Covering Bans
Authors: Brems Eva , Brems Eva , Vrielink Jogchum , Brems Eva , Vrielink Jogchum , Ouald Chaib Saïla
Published: June 2013

This paper analyses the French and Belgian bans on face covering by taking a close look at the aims they are intended to serve in the eyes of the legislators in the two countries. These stated aims are the basis for a critical assessment of the bans from a human rights perspective. The authors conclude that the reasons proffered for the prohibition can legitimize at most a limited set of contextual bans, not the broad nationwide bans that are in place.
A Network Model for Human Interoperability
Authors: Handley Holly A. H.
Published: June 2013

Objective:

The objective is to demonstrate how the Human View architecture can be used to define and evaluate the human interoperability capabilities of a net-centric system. Human interoperability strives to understand the types of system relationships that affect collaboration across networked environments.

Background:

The Human View was developed as an additional system architectural viewpoint to focus on the human component of a system by capturing data on human roles, tasks, constraints, interactions, and metrics. This framework can be used to collect and organize social system parameters to facilitate the way that humans interact across organizational boundaries.

Method:

By mapping the Human View elements to organizational relationships defined in the domain of network theory, a network model of the Human View can be developed. This representation can then be aligned with a Layers of Interoperability model for collaborative systems. The model extends traditional technical interoperability to include organizational aspects important for human interoperability. The resulting composite model can be used to evaluate the human interoperability capability of network-enabled systems.

Results:

An interagency response to a crisis situation is an example where increased levels of human interoperability can affect the effectiveness of the organizational interactions. The existing Human View products representing the interagency capabilities were evaluated using the network model to demonstrate how the social system variables can be identified and evaluated to improve the system design.

Conclusion:

By understanding and incorporating human interoperability requirements, the resulting system design can more effectively support collaborative tasks across technological environments to facilitate timely responses to events.
Preventive psychiatry: Concept appraisal and future directions
Authors: Trivedi Jitendra K , Tripathi Adarsh , Dhanasekaran Saranya , Moussaoui Driss
Published: June 2013

Preventive psychiatry is a branch of psychiatry that aims at health promotion, protection from specific mental illnesses, early diagnosis, effective treatment, disability limitation and rehabilitation. Prevention of neuropsychiatric illnesses as compared to other illnesses is particularly important as they run a chronic course and cause substantial disability. Preventive measures have been found to be effective in reducing incidence and disability in a wide range of mental illnesses such as depression, psychosis, anxiety and conduct disorders. The need of the hour is to translate advances in our understanding of mental illness into effective intervention programmes for the prevention of mental illness and the promotion of positive mental health.
Clinicians’ versus caregivers’ ratings of burden in patients with schizophrenia and bipolar disorder
Authors: Grover Sandeep , Chakrabarti Subho , Ghormode Deepak , Dutt Alakananda , Kate Natasha , Kulhara Parmanand
Published: June 2013

Background:

Only a few studies have evaluated the similarities and differences between clinicians’ and caregivers’ rating of burden of caring for a person with chronic mental illness.

Aim:

To compare clinician-rated and caregiver-rated burden in a population of patients with either schizophrenia or bipolar disorder, using two different scales to measure caregiver burden.

Methodology:

Caregivers of patients with schizophrenia ( n = 65) or bipolar disorder ( n = 57) completed the Hindi version of the Involvement Evaluation Questionnaire (Hindi-IEQ) by themselves. Clinicians rated the burden on the Family Burden Interview Schedule (FBI) based on semi-structured interview with the same caregivers.

Results:

Both total objective and subjective burden on the FBI (clinician ratings) demonstrated significant positive correlations with the total Hindi-IEQ (caregiver ratings) scores. Most areas of burden on the FBI correlated positively with the tension and the worrying-urging II subscales, as well as the total Hindi-IEQ scores. According to clinicians, a significantly higher percentage of caregivers of patients with schizophrenia were experiencing a moderate to severe degree of subjective burden; objective burden in this group was also significantly higher in the domains of effect on the mental health of caregivers. Contrastingly, caregivers of patients with bipolar disorder judged burden to be higher in this group than schizophrenia.

Conclusions:

There were many areas of agreement as well as some significant discrepancies between clinicians’ and caregivers’ assessment of burden in this population of patients. This suggests that a comprehensive evaluation of burden should include assessments by both clinicians and caregivers of patients.
Stigma and discrimination against people with schizophrenia related to medical services
Authors: Harangozo J , Reneses B , Brohan E , Sebes J , Csukly G , López-Ibor JJ , Sartorius N , Rose D , Thornicroft G
Published: June 2013

Objective:

To investigate whether people with schizophrenia experience discrimination when using health care services.

Methods:

A cross-sectional survey in 27 countries in centres affiliated to the INDIGO Research Network, using face-to-face interviews with 777 participants with schizophrenia (62% male and 38% female). We analysed the data related to health issues, including health care, disrespect of mental health staff, and also personal privacy, safety and security, starting a family, pregnancy and childbirth. Discrimination was measured by the Discrimination and Stigma Scale (DISC), which consists of 36 items comprising three sub-scales: positive experienced discrimination; negative experienced discrimination; and anticipated discrimination.

Results:

More than 17% of patients experienced discrimination when treated for physical health care problems. More than 38% of participants felt disrespected by mental health staff, with higher ratings in the post-communist countries.

Conclusions:

Mental health service providers have a key role in decreasing stigma in their provision of health care, and by doing more against stigmatizing and discriminating practices on the therapeutic and organizational level. This will require a change of attitudes and practices among mental and physical health care staff.