bluuebunny/crossref_metadata_2025 huggingface dataset:
Starvation Promotes REV1 SUMOylation and p53-Dependent Sensitization of Melanoma and Breast Cancer Cells
Authors: Shim Hong Seok , Wei Min , Brandhorst Sebastian , Longo Valter D.
Published: January 2015

Short-term starvation or fasting can augment cancer treatment efficacy and can be effective in delaying cancer progression in the absence of chemotherapy, but the underlying molecular mechanisms of action remain elusive. Here, we describe the role of REV1, a specialized DNA polymerase involved in DNA repair, as an important signaling node linking nutrient sensing and metabolic control to cell fate. We show that REV1 is a novel binding partner of the tumor suppressor p53 and regulates its activity. Under starvation, REV1 is modified by SUMO2/3, resulting in the relief of REV1′s inhibition of p53 and enhancing p53′s effects on proapoptotic gene expression and apoptosis in breast cancer and melanoma cells. Thus, fasting in part through its effect on REV1 is a promising nontoxic strategy to increase p53-dependent cell death and to enhance the efficacy of cancer therapies. Cancer Res; 75(6); 1056–67. ©2015 AACR.
Vemurafenib Resistance Signature by Proteome Analysis Offers New Strategies and Rational Therapeutic Concepts
Authors: Paulitschke Verena , Berger Walter , Paulitschke Philipp , Hofstätter Elisabeth , Knapp Bernhard , Dingelmaier-Hovorka Ruth , Födinger Dagmar , Jäger Walter , Szekeres Thomas , Meshcheryakova Anastasia , Bileck Andrea , Pirker Christine , Pehamberger Hubert , Gerner Christopher , Kunstfeld Rainer
Published: January 2015

The FDA-approved BRAF inhibitor vemurafenib achieves outstanding clinical response rates in patients with melanoma, but early resistance is common. Understanding the pathologic mechanisms of drug resistance and identification of effective therapeutic alternatives are key scientific challenges in the melanoma setting. Using proteomic techniques, including shotgun analysis and 2D-gel electrophoresis, we identified a comprehensive signature of the vemurafenib-resistant M24met in comparison with the vemurafenib-sensitive A375 melanoma cell line. The resistant cells were characterized by loss of differentiation, induction of transformation, enhanced expression of the lysosomal compartment, increased potential for metastasis, migration, adherence and Ca2+ ion binding, enhanced expression of the MAPK pathway and extracellular matrix proteins, and epithelial–mesenchymal transformation. The main features were verified by shotgun analysis with QEXACTIVE orbitrap MS, electron microscopy, lysosomal staining, Western blotting, and adherence assay in a VM-1 melanoma cell line with acquired vemurafenib resistance. On the basis of the resistance profile, we were able to successfully predict that a novel resveratrol-derived COX-2 inhibitor, M8, would be active against the vemurafenib-resistant but not the vemurafenib-sensitive melanoma cells. Using high-throughput methods for cell line and drug characterization may thus offer a new way to identify key features of vemurafenib resistance, facilitating the design of effective rational therapeutic alternatives. Mol Cancer Ther; 14(3); 757–68. ©2015 AACR.
A Genetic Platform to Model Sarcomagenesis from Primary Adult Mesenchymal Stem Cells
Authors: Guarnerio Jlenia , Riccardi Luisa , Taulli Riccardo , Maeda Takahiro , Wang Guocan , Hobbs Robin M. , Song Min Sup , Sportoletti Paolo , Bernardi Rosa , Bronson Roderick T. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Lunardi Andrea , Pandolfi Pier Paolo
Published: January 2015

The regulatory factors governing adult mesenchymal stem cell (MSC) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal forms of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here, we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSC transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF–DLK1–SOX9 pathway in the pathogenesis of undifferentiated sarcoma, with important therapeutic implications.

Significance: The paucity of therapeutic options for the treatment of sarcoma calls for a rapid and effective preclinical assessment of new therapeutic modalities. We have here developed a new platform to deconstruct the molecular genetics underlying the pathogenesis of sarcoma and to evaluatein vivo the efficacy of novel targeted therapies. Cancer Discov; 5(4); 396–409. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 333
Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies
Authors: Evans Elizabeth E. , Jonason Alan S. , Bussler Holm , Torno Sebold , Veeraraghavan Janaki , Reilly Christine , Doherty Michael A. , Seils Jennifer , Winter Laurie A. , Mallow Crystal , Kirk Renee , Howell Alan , Giralico Susan , Scrivens Maria , Klimatcheva Katya , Fisher Terrence L. , Bowers William J. , Paris Mark , Smith Ernest S. , Zauderer Maurice
Published: January 2015

Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 (PLXNB1) are broadly expressed in murine and human tumors, and their expression has been shown to correlate with invasive disease in several human tumors. SEMA4D normally functions to regulate the motility and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. In the setting of cancer, SEMA4D–PLXNB1 interactions have been reported to affect vascular stabilization and transactivation of ERBB2, but effects on immune-cell trafficking in the tumor microenvironment (TME) have not been investigated. We describe a novel immunomodulatory function of SEMA4D, whereby strong expression of SEMA4D at the invasive margins of actively growing tumors influences the infiltration and distribution of leukocytes in the TME. Antibody neutralization of SEMA4D disrupts this gradient of expression, enhances recruitment of activated monocytes and lymphocytes into the tumor, and shifts the balance of cells and cytokines toward a proinflammatory and antitumor milieu within the TME. This orchestrated change in the tumor architecture was associated with durable tumor rejection in murine Colon26 and ERBB2+ mammary carcinoma models. The immunomodulatory activity of anti-SEMA4D antibody can be enhanced by combination with other immunotherapies, including immune checkpoint inhibition and chemotherapy. Strikingly, the combination of anti-SEMA4D antibody with antibody to CTLA-4 acts synergistically to promote complete tumor rejection and survival. Inhibition of SEMA4D represents a novel mechanism and therapeutic strategy to promote functional immune infiltration into the TME and inhibit tumor progression. Cancer Immunol Res; 3(6); 689–701. ©2015 AACR.
Uterus Preserving Reposition of Non-Puerperal Uterine Inversion under Laparoscope: A Case Report and Literature Review
Authors: Zhang Xuyin , Sun Li , Chen Xiaojun , Hua Keqin
Published: January 2015

Non-puerperal uterine inversion is a rare clinical condition. Surgical procedures described in literature were mostly repositioning of the uterus followed by hysterectomy and laparotomy. In this paper, we reported a case of successful uterus preserving reposition of non-puerperal uterine inversion under laparoscopy. The patient, a 34-year-old, was presented with irregular vaginal bleeding with a mass protruding. On laparoscopy, the anterior wall of the uterus was opened longitudinally to release the thick ring of cervical tissue. The uterus was then repositioned and the anterior wall of the uterus was closed by stitches with two layers. Antibiotics was used for 6 days to prevent infection. The patient recovered well and retrieved menstruation 1 month after surgery.
Transglutaminase 2 Promotes PDGF-Mediated Activation of PDGFR/Akt1 and β-Catenin Signaling in Vascular Smooth Muscle Cells and Supports Neointima Formation
Authors: Nurminskaya Maria , Beazley Kelly E. , Smith Elizabeth P. , Belkin Alexey M.
Published: January 2015

Background: Phenotypic switch of vascular smooth muscle cells (VSMCs) accompanies neointima formation and associates with vascular diseases. Platelet-derived growth factor (PDGF)-induced activation of PDGFR/Akt1 and β-catenin signaling pathways in VSMCs has been implicated in vessel occlusion. Transglutaminase 2 (TG2) regulates these pathways and its levels are increased in the neointima. Objective: The aim of this study was to evaluate the role of TG2 in PDGF/β-catenin signaling cross-talk and assess its contribution to neointima. Methods: Aortic VSMCs from wild-type and TG2 knockout mice were tested in vitro for levels of VSMC markers, proliferation, migration and PDGF-induced activation of PDGFR/Akt1 and β-catenin pathways. Neointima in these mice was studied ex vivo in coronary vessels using a heart slice model and in vivo using a carotid artery ligation model. Results: Genetic deletion of TG2 attenuated the PDGF-induced phenotypic switch of aortic VSMCs, reduced their proliferation and migration rates, and inhibited PDGF-induced activation of PDGFR/Akt1 and β-catenin pathways in both ex vivo and in vivo neointima models. Importantly, genetic deletion of TG2 also markedly attenuated vessel occlusion. Conclusions: TG2 promotes neointima formation by mediating the PDGF-induced activation of the PDGFR/Akt1 and β-catenin pathways in VSMCs. This study identifies TG2 as a potential therapeutic target for blocking neointima in blood vessels.
Measures of Ventricles and Evans' Index: From Neonate to Adolescent
Authors: Sarı Erkan , Sarı Sebahattin , Akgün Veysel , Özcan Emrah , Ìnce Selami , Babacan Oğuzhan , Saldır Mehmet , Açıkel Cengizhan , Başbozkurt Gökalp , Yeşilkaya Şirzat , Kılıc Cenk , Kara Kemal , Vurucu Sebahattin , Kocaoğlu Murat , Yeşilkaya Ediz
Published: January 2015

Ventricle sizes are important for the early diagnosis of hydrocephalus or for follow-up after ventriculostomy. Diameters of ventricles may change, especially in childhood. This study aims to provide normative data about ventricle diameters. Among 14,854 cranial MRI performed between 2011 and 2013, 2,755 images of Turkish children aged 0-18 years were obtained. After exclusions, 517 images were left. Four radiologists were trained by a pediatric radiologist. Twenty images were assessed by all radiologists for a pilot study to see that there was no interobserver variation. There were 10-22 children in each age group. The maximum width of the third ventricle was 5.54 ± 1.29 mm in males in age group 1 and 4.98 ± 1.08 mm in females in age group 2. The Evans' index was <0.3 and consistent with the literature. The third ventricle/basilar artery width ratio was found to be >1 and <2 in all age groups and both gender groups. Our study showed the ventricle size data of children in various age groups from newborn to adolescent. The ventricle volume/cerebral parenchyma ratio seems to decrease with age. We think that these data can be applied in clinical practice, especially for the early diagnosis of hydrocephalus.
Bisphosphonate-Related Osteonecrosis of the Palatal Torus
Authors: Kaneko Kenichi , Takahashi Haruo
Published: January 2015

Background: Bisphosphonates are widely used for the treatment of osteoporosis and other bone-degrading disorders; however, bisphosphonate therapy is an important risk factor for osteonecrosis of the jaws. Methods: We report a rare case of bisphosphonate-related osteonecrosis of the palatal torus. Results: The patient was a 72-year-old woman with osteoporosis who had received 35 mg alendronate sodium hydrate once every week for 6 years. She had a 2-month history of oral pain because of intractable mucositis and ulceration of the palatal torus, with no history of malignant disease, radiation therapy, chemotherapy, steroid use, or recent dentoalveolar surgery. A CT scan showed a bony prominence at the midportion of the hard palate with erosion of its cortex. Her condition was diagnosed as stage 2 bisphosphonate-related osteonecrosis of the jaw caused by trauma, and she was advised to discontinue alendronate. She was prescribed oral antibiotics for 5 days and an oral antibacterial rinse. The mucositis with ulceration healed in approximately 10 weeks, but left a small scar. Conclusions: Although osteonecrosis of the palatal torus associated with bisphosphonate use is a rare condition, otolaryngologists should consider this condition in the differential diagnosis of intractable ulceration of the hard palate.
Fibrin, γ′-Fibrinogen, and Transclot Pressure Gradient Control Hemostatic Clot Growth During Human Blood Flow Over a Collagen/Tissue Factor Wound
Authors: Muthard Ryan W. , Welsh John D. , Brass Lawrence F. , Diamond Scott L.
Published: January 2015

Objective—

Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (Δ
P
) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin-mediated clot growth.

Approach and Results—

Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and Δ
P
, we found thrombin to be highly localized in the P-selectin
+
core of hemostatic clots. Increasing Δ
P
from 9 to 29 mm Hg (wall shear rate=400 s
−1
) reduced P-selectin
+
core size and total clot size because of enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mmol/L Gly-Pro-Arg-Pro dysregulated hemostasis by enhancing both P-selectin
+
core size and clot size at 400 s
−1
(20 mm Hg). For whole-blood flow (no Gly-Pro-Arg-Pro), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s
−1
, 20 mm Hg). Consistent with the antithrombin-1 activity of fibrin implicated with Gly-Pro-Arg-Pro, anti-γ′-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s
−1
) but not arterial wall shear rates (2000 s
−1
). Pathological shear (15 000 s
−1
) and Gly-Pro-Arg-Pro synergized to exacerbate clot growth.

Conclusions—

Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the transclot ΔP. Also, γ′-fibrinogen had a role in venous but not arterial conditions.
GATA-Binding Factor 6 Contributes to Atrioventricular Node Development and Function
Authors: Liu Fang , Lu Min Min , Patel Neil N. , Schillinger Kurt J. , Wang Tao , Patel Vickas V.
Published: January 2015

Background—

Several transcription factors regulate cardiac conduction system (CCS) development and function but the role of each in specifying distinct CCS components remains unclear. GATA-binding factor 6 (GATA6) is a zinc-finger transcription factor that is critical for patterning the cardiovascular system. However, the role of GATA6 in the embryonic heart and CCS has never been shown.

Methods and Results—

We report that
Gata6
is expressed abundantly in the proximal CCS during midgestation in mice. Myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
induces loss of hyperpolarizing cyclic nucleotide–gated channel, subtype 4 staining in the compact atrioventricular node with some retention of hyperpolarizing cyclic nucleotide–gated channel, subtype 4 staining in the atrioventricular bundle, but has no significant effect on the connexin-40–positive bundle branches. Furthermore, myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
alters atrioventricular conduction in postnatal life as assessed by surface and invasive electrophysiological evaluation, as well as decreasing the number of ventricular myocytes and inducing compensatory myocyte hypertrophy. Myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
is also associated with downregulation of the transcriptional repressor ID2 and the cardiac sodium–calcium exchanger NCX1 in the proximal CCS, where GATA6 transactivates both of these factors. Finally, carboxyl zinc-finger deletion of
Gata6
reduces cell-cycle exit of TBX3+ myocytes in the developing atrioventricular bundle during the period of atrioventricular node specification, which results in fewer TBX3+ cells in the proximal CCS of mature mutant mice.

Conclusions—

GATA6 contributes to the development and postnatal function of the murine atrioventricular node by promoting cell-cycle exit of specified cardiomyocytes toward a conduction system lineage.
Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke
Authors: Holliday Elizabeth G. , Traylor Matthew , Malik Rainer , Bevan Steve , Falcone Guido , Hopewell Jemma C. , Cheng Yu-Ching , Cotlarciuc Ioana , Bis Joshua C. , Boerwinkle Eric , Boncoraglio Giorgio B. , Clarke Robert , Cole John W. , Fornage Myriam , Furie Karen L. , Ikram M. Arfan , Jannes Jim , Kittner Steven J. , Lincz Lisa F. , Maguire Jane M. , Meschia James F. , Mosley Thomas H. , Nalls Mike A. , Oldmeadow Christopher , Parati Eugenio A. , Psaty Bruce M. , Rothwell Peter M. , Seshadri Sudha , Scott Rodney J. , Sharma Pankaj , Sudlow Cathie , Wiggins Kerri L. , Worrall Bradford B. , Rosand Jonathan , Mitchell Braxton D. , Dichgans Martin , Markus Hugh S. , Levi Christopher , Attia John , Wray Naomi R.
Published: January 2015

Background and Purpose—

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses.

Methods—

Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA–SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles.

Results—

High genetic correlation was identified between LAA and SVD using linear mixed models (
r
g
=0.96, SE=0.47,
P
=9×10
−4
) and profile scores (
r
g
=0.72; 95% confidence interval, 0.52–0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (
P
=1×10
−7
) for single nucleotide polymorphisms near the opioid receptor μ1 (
OPRM1
) gene.

Conclusions—

Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes.
Dimeria raviana (Poaceae: Panicoideae), a new species from Southern Western Ghats, India
Authors: S Kiran Raj M , M Sivadasan , Alfarhan Ahmed H , Frederik Veldkamp Jan Frederik
Published: January 2015

Dimeria raviana, a new species of Poaceae from the Southern Western Ghats of Kerala, India is described and illustrated. It closely resembles D. fuscescens, but strikingly differs in having a flattened and winged raceme rachis of 1.0–1.25 mm in width with smooth margins.
New botanical discoveries of Myrtaceae from Bolivia and notes on Psidium hians
Authors: Villarroel Daniel , Gomes-Bezerra Kadja
Published: January 2015

A new species, Myrcia proencana is described from eastern Bolivia. It is known from the Serranía de Huanchaca in the Noel Kempff Mercado National Park. M. proencana is compared with M. torta which is the species most similar. Also, we determined that Psidium hians should be considered as an accepted name, and P. nutans should be included in its synonymy. Additionally, Eugenia paranahybensis, E. pitanga, E. suberosa, Psidium misionum and P. myrsinites are reported as new records for the Bolivian flora.
A new species of Amphinemura (Plecoptera: Nemouridae) from the South of the Russian Far East
Authors: TESLENKO VALENTINA A.
Published: January 2015

A new species of Plecoptera, Amphinemura zwicki sp. n. from the Primorsky Region south of the Russian Far East, is described and illustrated. Relationships with its close relatives are discussed.
Brachiopods from off the San Bernardo Archipelago (Colombian Caribbean), with comments on specific synonymies in Tichosina Cooper, 1977
Authors: ROJAS ALEXIS , GRACIA ADRIANA , PATARROYO PEDRO
Published: January 2015

Colombian brachiopod faunas have not been studied extensively. Only three brachiopod species have been reported from the Colombian Caribbean Sea so far, namely Argyrotheca barrettiana (Davidson, 1866), Terebratulina latifrons Dall, 1920, and the cosmopolitan Platidia anomioides (Scacchi & Philippi, 1844). In this work, brachiopods collected from deep-water environments (90–250 m) off the San Bernardo Archipelago, collected during the MARCORAL cruise, are examined. The studied material consists of four species, two of which are new records for Colombia: Terebratulina cailleti Crosse, 1865 and Tichosina plicata Cooper, 1977. The genus Tichosina belongs to the family Terebratulidae and comprises twenty extant species occurring across the Caribbean. Based on a revision of published descriptions and illustrations, we synonymize Tichosina bullisi Cooper, 1977 and Tichosina dubia Cooper, 1977 with Tichosina plicata Cooper, 1977. Remarkably, apart from reports from southern Guiana, T. plicata is restricted to the margins of the Caribbean plate.
An Old Language with a New Status. Some Aspects of the Kvens’ Identity in the Borderland
Authors: Petryk Marta
Published: January 2015

An Old Language with a New Status. Some Aspects of the Kvens’ Identity in the BorderlandKvens are one of the groups which are recognized as minorities in Norway. In this article I will address the issue of language as an important identity creating factor. After I have given the most important informations about the hardly known minority group  I will present a short description of the Kven language’s classification and status in Norway – both earlier and nowadays. Then I want to present how the Kven language is used while creating the Kven identity. Stary język o nowym statusie. Kilka aspektów tożsamości Kvenów na PograniczuKvenowie są jedną z kilku grup uznawanych w Norwegii za mniejszości. Zarówno definicja jak i etnonim „Kven” budzą wiele kontrowersji. W myśl najpowszechniejszej definicji Kvenowie to potomkowie fińskich imigrantów w Norwegii. Jednakże trzeba pamiętać, że posługując się słowem „imigranci” możemy natrafić na sprzeciw, ponieważ w przypadku Kvenów mówimy często o migracjach na obszarze północnej Skandynawii wcześniejszych od ustanowienia dzisiejszych granic państwowych. Podobnie termin Finowie nie jest powszechnie akceptowany. Wątpliwości budzi on zwłaszcza wśród badaczy oraz tych członków grupy, którzy podkreślają zróżnicowanie etniczne dzisiejszej Finlandii. Mimo to wielu członków grupy nazywanej Kvenami uważa, że „Kven” i „Fin” oznaczają to samo. Protestują przy tym przeciwko nazywaniu ich Kvenami, ponieważ to niegdyś używane przez norweską większość słowo miało pejoratywny wydźwięk. Wśród współczesnych definicji kategorii „Kven” często pojawia się następująca: „Kvenowie to fińskojęzyczny lud przybyły do Norwegii przed rokiem 1900 oraz jego potomkowie” (Skarstein 2002: 85). Również i ta definicja może napotkać opór, ponieważ kveński uważany jest w Norwegii za odrębny język od roku 2005, a różnicę między kveńskim a fińskim bardzo wielu badaczy i użytkowników języka uważa za istotną. W niniejszym artykule zajmę się kwestią języka jako znaczącego czynnika tworzącego tożsamość. Przedstawię najważniejsze wiadomości o mało znanej mniejszości, a następnie omówię krótko klasyfikację i status języka kveńskiego w Norwegii, dawniej i dzisiaj. W końcu zajmę się kwestią wykorzystywania języka w procesie tworzenia tożsamości Kvenów.
How to Escape? The Trap of the Transition in the Recent Cinema of Bosnia and Herzegovina (2000-2012)
Authors: Rawski Tomasz , Roman Katarzyna
Published: January 2015

How to Escape? The Trap of the Transition in the Recent Cinema of Bosnia and Herzegovina (2000-2012)The paper concerns the latest cinema of Bosnia and Herzegovina (2000-2012). Focusing on the cinema of social criticism (represented by movies which try to rethink the new socio-political order gradually emerging in BiH after the war of 1992-95), the authors recognize the Bosnian society as a community captured in the trap of an unfinished system transition. The story of the Bosnian society, simultaneously stuck in a dysfunctional and oppressive state and completely devoid of any prospects for the improvement of this situation, seems to be dominated by several escape strategies into an alternative reality: the nostalgic past, the imagined present or the utopian future. In that sense, the Bosnian cinema of social criticism turns out to be a cinema of social escapism. Jak uciec? Pułapka transformacji w najnowszym kinie Bośni i Hercegowiny (2000-2012)Tekst dotyczy najnowszej kinematografii Bośni i Hercegowiny (2000-2012). Skupienie na nurcie kina krytycznego (do którego zaliczone zostały filmy, które próbują interpretować nowy porządek społeczno-polityczny powoli wyłaniający się w Bośni i Hercegowinie po wojnie z lat 1992-95) pozwala ukazać społeczeństwo Bośni i Hercegowiny jako znajdujące się w pułapce wciąż niedokończonej transformacji systemowej. Opowieść o społeczeństwie z jednej strony uwięzionym w dysfunkcjonalnym i opresyjnym państwie, a z drugiej całkowicie pozbawionym perspektyw i nadziei na poprawę sytuacji, zdominowana jest przez rozmaite strategie ucieczki w alternatywną rzeczywistość: nostalgiczną przeszłość, wyobrażoną teraźniejszość lub utopijną przyszłość. W tym sensie, bośniackie kino krytyczne jawi się jako kino eskapizmu społecznego.
Direct Radiative Effect by Multicomponent Aerosol over China*
Authors: Huang Xin , Song Yu , Zhao Chun , Cai Xuhui , Zhang Hongsheng , Zhu Tong
Published: January 2015

The direct radiative effect (DRE) of multiple aerosol species [sulfate, nitrate, ammonium, black carbon (BC), organic carbon (OC), and mineral aerosol] and their spatiotemporal variations over China were investigated using a fully coupled meteorology–chemistry model [Weather Research and Forecasting (WRF) Model coupled with Chemistry (WRF-Chem)] for the entire year of 2006. This study made modifications to improve the model performance, including updating land surface parameters, improving the calculation of transition-metal-catalyzed oxidation of SO2, and adding heterogeneous reactions between mineral dust aerosol and acid gases. The modified model generally reproduced the magnitude, seasonal pattern, and spatial distribution of the measured meteorological conditions, concentrations of PM10 and its components, and aerosol optical depth (AOD), although some low biases existed in modeled aerosol concentrations. A diagnostic iteration method was used to estimate the overall DRE of aerosols and contributions from different components. At the land surface, the incident net radiation flux was reduced by 10.2 W m−2 over China. Aerosols significantly warmed the atmosphere with the national mean DRE of +10.8 W m−2. BC was the leading radiative heating component (+8.7 W m−2), followed by mineral aerosol (+1.1 W m−2). At the top of the atmosphere (TOA), BC introduced the largest radiative perturbation (+4.5 W m−2), followed by sulfate (−1.4 W m−2). The overall perturbation of aerosols on radiation transfer is quite small over China, demonstrating the counterbalancing effect between scattering and adsorbing aerosols. Aerosol DRE at the TOA had distinct seasonality, generally with a summer maximum and winter minimum, mainly determined by mass loadings, hygroscopic growth, and incident radiation flux.
Monito-Ring: An original fiber optic system for morphing application
Authors: Ciminello Monica , Bettini Paolo , Ameduri Salvatore , Guerreschi Erika , Concilio Antonio , Sala Giuseppe
Published: January 2015

An original Monito-Ring system based on chirped fiber optic and draw tower grating array is presented. The target of this research activity is the realization of a device able to measure deformations of morphing structures which may show large, global displacements due to nonstandard architectures and materials adopted. The occurring strain field results, in turns, much more than the standard sensors can handle. Modulations are then necessary to keep the measured strain low. The proposed solution was conceived to overcome this limitation assuring a suitable reduction of the revealed strain. The concept is made of a flexible ring pinned on a certain number of points to the structural component of interest. The fiber optic is integrated within the ring, and depending on the angular position of the sensor, the ratio between the diameter elongation (i.e. structural strain) and the measured deformation (strain) can be almost arbitrarily set in a large range of values. From each spectrum provided by draw tower grating array, the corresponding unknown strain field is retrieved by applying an inverse technique obtaining an accurate continuous strain map. This article deals with a proof of concept analytical study first and then numerical and experimental validation.
Breathing difficulty in a middle-aged woman – a dangerous cause?
Authors: Wu Zhe , Rugg-Gunn Fergus
Published: January 2015

Lesson

Temporal lobe epilepsy is a rare but treatable cause of apnoea.
Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis
Authors: Wilkes David S. , Chew Terrence , Flaherty Kevin R. , Frye Sarah , Gibson Kevin F. , Kaminski Naftali , Klemsz Michael J. , Lange Wade , Noth Imre , Rothhaar Katia
Published: January 2015

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)).

Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period.

All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies.

IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)- reactive IPF patients.
Complicated grief after death of a relative in the intensive care unit
Authors: Kentish-Barnes Nancy , Chaize Marine , Seegers Valérie , Legriel Stéphane , Cariou Alain , Jaber Samir , Lefrant Jean-Yves , Floccard Bernard , Renault Anne , Vinatier Isabelle , Mathonnet Armelle , Reuter Danielle , Guisset Olivier , Cohen-Solal Zoé , Cracco Christophe , Seguin Amélie , Durand-Gasselin Jacques , Éon Béatrice , Thirion Marina , Rigaud Jean-Philippe , Philippon-Jouve Bénédicte , Argaud Laurent , Chouquer Renaud , Adda Mélanie , Dedrie Céline , Georges Hugues , Lebas Eddy , Rolin Nathalie , Bollaert Pierre-Edouard , Lecuyer Lucien , Viquesnel Gérard , Léone Marc , Chalumeau-Lemoine Ludivine , Garrouste Maïté , Schlemmer Benoit , Chevret Sylvie , Falissard Bruno , Azoulay Élie
Published: January 2015

An increased proportion of deaths occur in the intensive care unit (ICU).

We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months.

Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives).

End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.
Common fixed points of Caristi’s type mappings via w-distance
Authors: Sitthikul Kittipong , Saejung Satit
Published: January 2015

Motivated by fixed point theorems of Obama and Kuroiwa (Sci. Math. Jpn. 72(1), 41-48, 2010), we discuss their results with another, weaker assumption and obtain some estimating expressions. Furthermore, we also discuss the results with the lower semicontinuities of the dominated functions in place of the original orbital continuities of the mappings.
Factors affecting viability of Bifidobacterium bifidum during spray drying
Authors: Shokri Zahra , Fazeli Mohammad Reza , Ardjmand Mehdi , Mousavi Seyyed Mohammad , Gilani Kambiz
Published: January 2015

Background

There is substantial clinical data supporting the role of Bifidobacterium bifidum in human health particularly in benefiting the immune system and suppressing intestinal infections. Compared to the traditional lyophilization, spray-drying is an economical process for preparing large quantities of viable microorganisms. The technique offers high production rates and low operating costs but is not usually used for drying of substances prone to high temperature. The aim of this study was to establish the optimized environmental factors in spray drying of cultured bifidobacteria to obtain a viable and stable powder.

Methods

The experiments were designed to test variables such as inlet air temperature, air pressure and also maltodextrin content. The combined effect of these variables on survival rateand moisture content of bacterial powder was studied using a central composite design (CCD). Sub-lethal heat-adaptation of a B. bifidum strain which was previously adapted to acid-bile-NaCl led to much more resistance to high outlet temperature during spray drying. The resistant B. bifidum was supplemented with cost friendly permeate, sucrose, yeast extract and different amount of maltodextrin before it was fed into a Buchi B-191 mini spray-dryer.

Results

Second-order polynomials were established to identify the relationship between the responses andthe three variables. Results of verification experiments and predicted values from fitted correlations were in close agreement at 95% confidence interval. The optimal values of the variables for maximum survival and minimum moisture content of B. bifidum powder were as follows: inlet air temperature of 111.15°C, air pressure of 4.5 bar and maltodextrin concentration of 6%. Under optimum conditions, the maximum survival of 28.38% was achieved while moisture was maintained at 4.05%.

Conclusion

Viable and cost effective spray drying of Bifidobacterium bifidum could be achieved by cultivating heat and acid adapted strain into the culture media containing nutritional protective agents.
Angels in (Mexican) America
Authors: Stein Jordan Alexander
Published: January 2015

This essay posits that scholars interested in studying the history of secularism might avail themselves of the tools attendant upon the study of another well-worn historically important but empirically fraught object: literature. Precisely because secularism is a story—a bad alibi, a false descriptor, a failed promise, an expiring explanation of enduring historical transformations—literature may prove to be an exemplary domain for investigations into the historiography of secularism. Moreover, the study of literature at the present time is attentive not only to the form of a text—its language, tone, syntax, and style—but also to the technological and social mechanics of its circulation. The methodologies of literary studies may offer some inroads to the historical study of secularism, because secularism is like literature in the sense that each is reliant for its existence on material structures that its fictional narrative contents may belie, yet each is palpable in its purchase on the world just the same.
Women Working “Amidst the Mad”: Domesticity as Psychiatric Treatment in Nineteenth-Century Paris
Authors: Hewitt Jessie
Published: January 2015

This article examines the role of women in the direction of private mental institutions owned by the Brierre de Boismont family in nineteenth-century Paris, arguing that the cultural elevation of domesticity sanctioned the participation of Athalie Brierre de Boismont and her daughter, Marie Rivet, in asylum operations despite proscriptions against elite women’s labor. Alexandre Brierre de Boismont and his family lived alongside their patients and integrated them into the household routine in hopes that this would encourage those deemed insane to return to rationality. As exemplars of ideal womanhood, the Brierre de Boismont women were central to the enactment of the treatment process. While their activities in the family’s asylums often perpetuated gender values that naturalized the division of the public and private spheres, they also called attention to the artificiality of such beliefs by performing domesticity in an environment so unlike the typical bourgeois home.

Cet article examine le rôle des femmes dans la direction des institutions psychiatriques privées appartenant à la famille Brierre de Boismont à Paris au dix-neuvième siècle, en argumentant que la promotion culturelle de la domesticité a permis la participation d’Athalie Brierre de Boismont et sa fille, Marie Rivet, dans les opérations de l’asile malgré les proscriptions contre le travail imposées sur les femmes élites. Le médecin Alexandre Brierre de Boismont et sa famille habitaient aux côtés de leurs patients et les intégraient dans la routine ménagère quotidienne dans l’espoir que cela encouragerait ceux qui étaient jugés fous à revenir à la raison. En tant que modèles de la féminité idéale, Athalie Brierre de Boismont et sa fille étaient au centre de la mise en œuvre du processus de traitement. Même si leurs activités au sein des asiles dirigées par la famille perpétuaient souvent des valeurs sexuées naturalisant la division entre la sphère publique et la sphère privée, elles ont également mis l’accent sur le caractère artificiel de ces croyances en incarnant la domesticité dans un environnement si différent de celui de la maison bourgeoise typique.
Jag1b is essential for patterning inner ear sensory cristae by regulating anterior morphogenetic tissue separation and preventing posterior cell death
Authors: Ma Wei-Rui , Zhang Jian
Published: January 2015

The sensory patches of the vertebrate inner ear, which contain hair cells and supporting cells, are essential for hearing and balance functions. How the stereotypically organized sensory patches are formed remains to be determined. In this study, we isolated a zebrafish mutant in which the jag1b gene is disrupted by an EGFP insertion. Loss of Jag1b causes cell death in the developing posterior crista and results in downregulation of fgf10a in the posterior prosensory cells. Inhibition of FGFR activity in wild-type embryos also causes loss of the posterior crista, suggesting that Fgf10a mediates Jag1b activity. By contrast, in the anterior prosensory domain, Jag1b regulates separation of a single morphogenetic field into anterior and lateral cristae by flattening cells destined to form a nonsensory epithelium between the two cristae. MAPK activation in the nonsensory epithelium precursors is required for the separation. In the jag1b mutant, MAPK activation and cell flattening are extended to anterior crista primordia, causing loss of anterior crista. More importantly, inhibition of MAPK activity, which blocks the differentiation of nonsensory epithelial cells, generated a fused large crista and extra hair cells. Thus, Jag1b uses two distinct mechanisms to form three sensory cristae in zebrafish.
Communication between distant epithelial cells by filopodia-like protrusions during embryonic development
Authors: Sagar  , Pröls Felicitas , Wiegreffe Christoph , Scaal Martin
Published: January 2015

Long-range intercellular communication is essential for the regulation of embryonic development. Apart from simple diffusion, various modes of signal transfer have been described in the literature. Here, we describe a novel type of cellular extensions found in epithelial cells of the somites in chicken embryos. These filopodia-like protrusions span the subectodermal space overlying the dorsal surface of the somites and contact the ectoderm. We show that these protrusions are actin- and tubulin-positive and require Rac1 for their formation. The presence of glycophosphatidylinositol-anchored proteins and net retrograde trafficking of the transmembrane Wnt-receptor Frizzled-7 along the protrusions indicate their role in signal transport and distribution. Taken together, our data suggest a role of filopodia-like protrusions in mediating signaling events between distant epithelial cells during embryonic development.
Streamwise vortices destabilize swimming bluegill sunfish (Lepomis macrochirus)
Authors: Maia Anabela , Sheltzer Alex P. , Tytell Eric D.
Published: January 2015

In their natural environment, fish must swim stably through unsteady flows and vortices, including vertical vortices, typically shed by posts in a flow, horizontal cross-flow vortices, often produced by a step or a waterfall in a stream, and streamwise vortices, where the axis of rotation is aligned with the direction of the flow. Streamwise vortices are commonly shed by bluff bodies in streams and by ships' propellers and axial turbines, but we know little about their effects on fish. Here, we describe how bluegill sunfish use more energy and are destabilized more often in flow with strong streamwise vorticity. The vortices were created inside a sealed flow tank by an array of four turbines with similar diameter to the experimental fish. We measured oxygen consumption for seven sunfish swimming at 1.5 body lengths (BL) s−1 with the turbines rotating at 2 Hz and with the turbines off (control). Simultaneously, we filmed the fish ventrally and recorded the fraction of time spent maneuvering side-to-side and accelerating forward. Separately, we also recorded lateral and ventral video for a combination of swimming speeds (0.5, 1.5 and 2.5 BL s−1) and turbine speeds (0, 1, 2 and 3 Hz), immediately after turning the turbines on and 10 min later to test for accommodation. Bluegill sunfish are negatively affected by streamwise vorticity. Spills (loss of heading), maneuvers and accelerations were more frequent when the turbines were on than in the control treatment. These unsteady behaviors, particularly acceleration, correlated with an increase in oxygen consumption in the vortex flow. Bluegill sunfish are generally fast to recover from roll perturbations and do so by moving their pectoral fins. The frequency of spills decreased after the turbines had run for 10 min, but was still markedly higher than in the control, showing that fish partially adapt to streamwise vorticity, but not completely. Coping with streamwise vorticity may be an important energetic cost for stream fishes or migratory fishes.
Supply chain governance in the production systems of business clusters: The case of the footwear industry in Jaú
Authors: Brito Eliane Pereira Zamith , Carvalho Lilian Soares Pereira
Published: January 2015

This paper’s objective was to analyze the role of transaction costs in the longevity of Jaú footwear supply chain. Firms are configured in a cluster, and their level of coordination was investigated. The study data was collected via conducting interviews with the cluster’s agents, making direct observations during the field visits, and consulting secondary data emerging both from document analysis and from sources such as newspapers, sectoral studies, and previous academic studies. The data point to the intense frequency of transactions among firms and the low uncertainty of internal transactions within the cluster due to the extensive exchange of information among agents. The bonds of competition and coordination that are established among the firms both reduce transaction costs and make them more competitive. Both human asset specificity and site specificity are important factors in the longevity of Jaú’s footwear cluster.DOI: 10.12660/joscmv7n2p140-153URL: http://dx.doi.org/10.12660/joscmv7n2p140-153
TRANSIENT EXPERIMENTS IN ZED-2 TO INVESTIGATE THE IMPACT OF LEAKAGE ON REACTOR PHYSICS PHENOMENA
Authors: Zeller M.B. , Atfield J.E.
Published: January 2015

This paper describes an experimental approach where reactor kinetics experiments are used to study reactor physics phenomena that are normally investigated using static-measurement techniques. This approach provides validation data relating to these phenomena for a range of core reactivities, rather than only providing data at critical conditions. Sub-critical and super-critical transient measurements were performed in the ZED-2 reactor. The transients were analyzed using a point kinetics model to derive the reactivity states that induced the transients.

The reactor physics phenomenon of interest for the current study is Coolant Density Induced Reactivity. Initial measurements were performed using an air-cooled (i.e., voided) ZED-2 lattice; the measurements were then repeated using the same lattice cooled with light water. These measurements yielded reactivity values for both coolant conditions in the lattice for a range of super-critical and sub-critical states. This investigation avoids the inherent assumption of static-measurement analyses that the bias in predicting criticality for the two coolant conditions is identical to the bias in predicting the phenomenon of Coolant Density Induced Reactivity itself.

The measured reactivity values are compared with calculations employing the 3-D stochastic neutron transport reactor code MCNP.
In search of a new leadership currency
Authors: Ojo Olurotimi (Tim)
Published: January 2015

The radical proposals contained in the coalition government's White Paper ‘Equity and excellence: Liberating the NHS’, are the most significant shift in the tectonic plates of NHS top-down management structures ever to be contemplated. The implications of some of the governments’ intentions for health and social care delivery have transformative consequences for managerial and clinical leadership requirements. This article reviews relevant leadership literature with a view to exploring what existing leadership models tell us and how they can inform the strategic leadership thinking required to deliver the government's ambitions over the next few years.
Diabetes: pathogenesis and diagnosis
Authors: Forth Rachel , Jude Edward
Published: January 2015

Diabetes mellitus (DM) is one of the biggest challenges facing the NHS in terms of health care, with the number of individuals developing type 2 DM rising rapidly. In England alone there are over 2.2 million people with diabetes mellitus (DM). Uncontrolled DM, has a long list of sequelae linked with increased morbidity. In this first of a two part series, we will focus on the pathogenesis and the diagnosis of DM. The epidemiology of DM will also be addressed.