bluuebunny/crossref_metadata_2025 huggingface dataset:
The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function
Authors: Overgaard Christian E. , Schlingmann Barbara , Dorsainvil White StevenClaude , Ward Christina , Fan Xian , Swarnakar Snehasikta , Brown Lou Ann S. , Guidot David M. , Koval Michael
Published: April 2015

Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions (“spikes”) containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS.
Integrated Model of Joint Residence-Workplace Location Choice and Commute Behavior Using Latent Class and Mixed Logit Methods
Authors: Jiao Pengpeng , Liu Meiqi , Guo Jin
Published: April 2015

With the rapid development of urbanization and motorization, urban commute trips are becoming increasingly serious due to the unbalanced distribution of residence and workplace land-use types in most Chinese cities. To explore the inherent interrelations among residence location, workplace, and commute trip, an integrated model framework of joint residence-workplace location choice and commute behavior is put forward based on the personal trip survey data of Beijing in 2005. First, to extract households’ different choice characteristics, this paper presents a latent class model, clusters all households into several groups, and analyzes the conditional probability of each group. Second, the paper integrates the residence location and workplace together as the joint choice alternative, employs the socioeconomic factors, individual attributes, household attributes, and trip characteristics as explanatory variables, and formulates the joint residence-workplace location choice model using mixed logit method. Estimations of the latent class model show that four latent groups fit the data best. Further results of the joint residence-workplace location choice model indicate that there exist significantly different choice characteristics in each latent group. Generally, the integrated model framework outperforms traditional location choice methods.
Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice
Authors: Himeno Tatsuhito , Kamiya Hideki , Naruse Keiko , Cheng Zhao , Ito Sachiko , Shibata Taiga , Kondo Masaki , Kato Jiro , Okawa Tetsuji , Fujiya Atsushi , Suzuki Hirohiko , Kito Tetsutaro , Hamada Yoji , Oiso Yutaka , Isobe Kenichi , Nakamura Jiro
Published: April 2015

Background. Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells.Methods and Results. Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.Conclusions. These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy.
Forming High Ozone Concentration in the Ambient Air of Southern Taiwan under the Effects of Western Pacific Subtropical High
Authors: Lo Kuo-Cheng , Hung Chung-Hsuang
Published: April 2015

Due to the distinct geographical and meteorological conditions of Taiwan, air pollutants concentrations in the ambient air of it may vary with seasons. Accordingly, this study aimed to investigate the formation of high O3concentration in the ambient air of Southern Taiwan during summers. A high O3concentration case occurring between June 28 and July 2, 2013, was modeled and analyzed with WRF-Chem meteorological and air quality model. During the investigated period, a typical western Pacific subtropical high (WPSH) covered most East Asia, including Taiwan and its surrounding areas. The observations showed strong correlations between WPSH invasion and forming high O3concentrations. The dispersion of air pollutants in the ambient air is not sufficient to dilute their concentrations. In the afternoon of June 30, more than 60% of the air quality monitoring stations found O3concentrations exceeding 100 ppb, which were 2~3 times higher than their normal concentrations. Model simulation results verified that the presence of the WPSH hindered the dilution and transportation of air pollutants in ambient air. In addition, the air quality would be getting worse due to the leeward sides caused by the counter clockwise vertex formed in Southwestern Taiwan.
RNA Degradation inStaphylococcus aureus: Diversity of Ribonucleases and Their Impact
Authors: Bonnin Rémy A. , Bouloc Philippe
Published: April 2015

The regulation of RNA decay is now widely recognized as having a central role in bacterial adaption to environmental stress. Here we present an overview on the diversity of ribonucleases (RNases) and their impact at the posttranscriptional level in the human pathogenStaphylococcus aureus. RNases in prokaryotes have been mainly studied in the two model organismsEscherichia coliandBacillus subtilis. Based on identified RNases in these two models, putative orthologs have been identified inS. aureus. The main staphylococcal RNases involved in the processing and degradation of the bulk RNA are (i) endonucleases RNase III and RNase Y and (ii) exonucleases RNase J1/J2 and PNPase, having 5′ to 3′ and 3′ to 5′ activities, respectively. The diversity and potential roles of each RNase and of Hfq and RppH are discussed in the context of recent studies, some of which are based on next-generation sequencing technology.
A Study of Prisoner’s Dilemma Game Model with Incomplete Information
Authors: Deng Xiuqin , Deng Jiadi
Published: April 2015

Prisoners’ dilemma is a typical game theory issue. In our study, it is regarded as an incomplete information game with unpublicized game strategies. We solve our problem by establishing a machine learning model using Bayes formula. The model established is referred to as the Bayes model. Based on the Bayesian model, we can make the prediction of players’ choices to better complete the unknown information in the game. And we suggest the hash table to make improvement in space and time complexity. We build a game system with several types of game strategy for testing. In double- or multiplayer games, the Bayes model is more superior to other strategy models; the total income using Bayes model is higher than that of other models. Moreover, from the result of the games on the natural model with Bayes model, as well as the natural model with TFT model, it is found that Bayes model accrued more benefits than TFT model on average. This demonstrates that the Bayes model introduced in this study is feasible and effective. Therefore, it provides a novel method of solving incomplete information game problem.
Chinese Medicine Bu Xu Hua Yu Recipe for the Regulation of Treg/Th17 Ratio Imbalance in Autoimmune Hepatitis
Authors: Wang Lei , Du Huihui , Liu Yibo , Wang Lingtai , Ma Xiong , Zhang Wei
Published: April 2015

Objectives. The aim of this study is researching the role of the Regulatory T cell (Treg)/T helper cell-17 (Th17) cell ratio imbalance in the pathogenesis of autoimmune hepatitis (AIH) and the use of the “Bu Xu Hua Yu” recipe in the treatment of AIH.Materials and Methods. Sixty adult male C57/BL6 mice were divided into six different groups.α-Galcer was injected abdominally for production of the animal models. Liver function tests, histological examinations, liver tissue Regulatory T cell, and T helper cell-17 levels tests were carried out. TGF-β1, IL-10, IL-17, and expression of mRNA and protein levels of Foxp3 and ROR-γt were also assessed.Results. Bu Xu Hua Yu method increased the levels of Regulatory T cell, IL-10, and the expression of Foxp3 (P<0.05) in mice liver tissues. Furthermore, there were decreases in the levels of T helper cell-17, IL-17, and expression of RORγt mRNA and protein (P<0.05). The ratio of Treg/Th17 was increased (P<0.05).Conclusion. Mice with AIH have a Treg/Th17 ratio imbalance. Bu Xu Hua Yu method was able to restore the cellular balance of Treg/Th17 through the regulation of the expression of RORγt and Foxp3 and can play an important role in the treatment of AIH.
The Algorithm for Algorithms: An Evolutionary Algorithm Based on Automatic Designing of Genetic Operators
Authors: Jiang Dazhi , Fan Zhun
Published: April 2015

At present there is a wide range of evolutionary algorithms available to researchers and practitioners. Despite the great diversity of these algorithms, virtually all of the algorithms share one feature: they have been manually designed. A fundamental question is “are there any algorithms that can design evolutionary algorithms automatically?” A more complete definition of the question is “can computer construct an algorithm which will generate algorithms according to the requirement of a problem?” In this paper, a novel evolutionary algorithm based on automatic designing of genetic operators is presented to address these questions. The resulting algorithm not only explores solutions in the problem space like most traditional evolutionary algorithms do, but also automatically generates genetic operators in the operator space. In order to verify the performance of the proposed algorithm, comprehensive experiments on 23 well-known benchmark optimization problems are conducted. The results show that the proposed algorithm can outperform standard differential evolution algorithm in terms of convergence speed and solution accuracy which shows that the algorithm designed automatically by computers can compete with the algorithms designed by human beings.
Insulin Resistance and Skin Diseases
Authors: Napolitano Maddalena , Megna Matteo , Monfrecola Giuseppe
Published: April 2015

In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patient’s overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR‐associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism.
Validation of the New Algorithm for Rain Rate Retrieval from AMSR2 Data Using TMI Rain Rate Product
Authors: Zabolotskikh Elizaveta , Chapron Bertrand
Published: April 2015

A new algorithm is derived for rain rate (RR) estimation from Advanced Microwave Sounding Radiometer 2 (AMSR2) measurements taken at 6.9, 7.3, and 10.65 GHz. The algorithm is based on the numerical simulation of brightness temperatures (TB) for AMSR2 lower frequency channels, using a simplified radiation transfer model. Simultaneous meteorological and hydrological observations, supplemented with modeled values of cloud liquid water content and rain rate values, are used for the calculation of an ensemble of AMSR2TBs and RRs. Ice clouds are not taken into account. AMSR2 brightness temperature differences at C- and X-band channels are then used as inputs to train a neural network (NN) function for RR retrieval. Validation is performed against Tropical Rain Measurement Mission (TRMM) Microwave Instrument (TMI) RR products. For colocated AMSR2-TMI measurements, obtained within 10 min intervals, errors are about 1 mm/h. The new algorithm is applicable for RR estimation up to 20 mm/h. ForRR<2 mm/h the retrieval error is 0.3 mm/h. ForRR>10 mm/h the algorithm significantly underestimates TMI RR.
Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement
Authors: Araujo Bruno , Costa Francisco , Lopes Joanne , Castro Ricardo
Published: April 2015

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment.
Biomaterials for Pelvic Floor Reconstructive Surgery: How Can We Do Better?
Authors: Gigliobianco Giulia , Roman Regueros Sabiniano , Osman Nadir I. , Bissoli Julio , Bullock Anthony J. , Chapple Chris R. , MacNeil Sheila
Published: April 2015

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.
Clinically Relevant Molecular Subtypes in Leiomyosarcoma
Authors: Guo Xiangqian , Jo Vickie Y. , Mills Anne M. , Zhu Shirley X. , Lee Cheng-Han , Espinosa Inigo , Nucci Marisa R. , Varma Sushama , Forgó Erna , Hastie Trevor , Anderson Sharon , Ganjoo Kristen , Beck Andrew H. , West Robert B. , Fletcher Christopher D. , van de Rijn Matt
Published: April 2015

Purpose: Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.

Experimental Design: Ninety-nine cases of leiomyosarcoma were expression profiled with 3′end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.

Results: We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.

Conclusions: We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach. Clin Cancer Res; 21(15); 3501–11. ©2015 AACR.
Therapeutic Peptide Vaccine-Induced CD8 T Cells Strongly Modulate Intratumoral Macrophages Required for Tumor Regression
Authors: van der Sluis Tetje C. , Sluijter Marjolein , van Duikeren Suzanne , West Brian L. , Melief Cornelis J.M. , Arens Ramon , van der Burg Sjoerd H. , van Hall Thorbald
Published: April 2015

Abundant macrophage infiltration of solid cancers commonly correlates with poor prognosis. Tumor-promoting functions of macrophages include angiogenesis, metastasis formation, and suppression of Th1-type immune responses. Here, we show that successful treatment of cervical carcinoma in mouse models with synthetic long peptide (SLP) vaccines induced influx of cytokine-producing CD8 T cells that strongly altered the numbers and phenotype of intratumoral macrophages. On the basis of the expression of CD11b, CD11c, F4/80, Ly6C, Ly6G, and MHC II, we identified four myeloid subpopulations that increased in numbers from 2.0-fold to 8.7-fold in regressing tumors. These changes of the intratumoral myeloid composition coincided with macrophage recruitment by chemokines, including CCL2 and CCL5, and were completely dependent on a vaccine-induced influx of tumor-specific CD8 T cells. CD4 T cells were dispensable. Incubation of tumor cells with T cell–derived IFNγ and TNFα recapitulated the chemokine profile observed in vivo, confirming the capacity of antitumor CD8 T cells to mediate macrophage infiltration of tumors. Strikingly, complete regressions of large established tumors depended on the tumor-infiltrating macrophages that were induced by this immunotherapy, because a small-molecule drug inhibitor targeting CSF-1R diminished the number of intratumoral macrophages and abrogated the complete remissions. Survival rates after therapeutic SLP vaccination deteriorated in the presence of CSF-1R blockers. Together, these results show that therapeutic peptide vaccination could induce cytokine-producing T cells with strong macrophage-skewing capacity necessary for tumor shrinkage, and suggest that the development of macrophage-polarizing, rather than macrophage-depleting, agents is warranted. Cancer Immunol Res; 3(9); 1042–51. ©2015 AACR.
Insights into the All-trans-Retinoic Acid and Arsenic Trioxide Combination Treatment for Acute Promyelocytic Leukemia: A Meta-Analysis
Authors: Ma Hongbing , Yang Jing
Published: April 2015

Background: This study aimed to compare the curative effects of the combination therapy of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) with ATRA monotherapy on newly diagnosed acute promyelocytic leukemia (APL). Methods: The studies were retrieved from PubMed, EMBASE, Cochrane Library, ChinaInfo and China National Knowledge Infrastructure (CNKI) databases from the inception to June 20, 2014. Thereafter, the eligible studies were selected based on the predefined criteria, and the literature quality was assessed. The meta-analysis was conducted using Review Manager 5.2 software. The pooled effect size was relative risk (RR) and its 95% confidence interval (CI). Results: A total of 8 studies containing 480 cases were included, among which 264 were assigned to the ATRA + ATO group and the other 216 to the ATRA group. The meta-analysis showed that ATRA + ATO combination therapy significantly improved the complete remission (CR) rate (RR = 1.09, 95% CI = 1.03-1.16, p = 0.004), decreased the early mortality rate (RR = 0.42, 95% CI = 0.20-0.9, p = 0.03) and relapse rate (RR = 0.17, 95% CI = 0.07-0.42, p < 0.0001), but increased the high risk of liver dysfunction (RR = 2.43, 95% CI = 1.72-3.41, p < 0.00001), comparing with ATRA monotherapy. Conclusions: The ATRA + ATO combination therapy may be more effective for newly diagnosed APL with a higher CR rate but lower early mortality rate and relapse rate. However, the risks of liver damage should be of concern.
Role of Nuclear Factor Erythroid 2–Related Factor 2 in the Oxidative Stress–Dependent Hypertension Associated With the Depletion of DJ-1
Authors: Cuevas Santiago , Yang Yu , Konkalmatt Prasad , Asico Laureano D. , Feranil Jun , Jones John , Villar Van Anthony , Armando Ines , Jose Pedro A.
Published: April 2015

Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure (BP). We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) regulates the expression of several antioxidant genes. We tested the hypothesis that Nrf2 is involved in the renal DJ-1–mediated inhibition of reactive oxygen species production. We have reported that silencing dopamine 2 receptor in mouse renal proximal tubule cells decreases the expression of DJ-1. We now report that silencing DJ-1 or dopamine 2 receptor in mouse proximal tubule cells and mouse kidneys decreases Nrf2 expression and activity and increases reactive oxygen species production; BP is also increased in mice in which renal DJ-1 or dopamine 2 receptor is silenced.
DJ-1
−/−
mice have decreased renal
Nrf2
expression and activity and increased nitro-tyrosine levels and BP. Silencing
Nrf2
in mouse proximal tubule cells does not alter the expression of DJ-1 or dopamine 2 receptor, indicating that
Nrf2
is downstream of dopamine 2 receptor and DJ-1. An Nrf2 inducer, bardoxolone, normalizes the systolic BP and renal malondialdehyde levels in
DJ-1
−/−
mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in
DJ-1
−/−
mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and BP.
Brain Endoplasmic Reticulum Stress Mechanistically Distinguishes the Saline-Intake and Hypertensive Response to Deoxycorticosterone Acetate–Salt
Authors: Jo Fusakazu , Jo Hiromi , Hilzendeger Aline M. , Thompson Anthony P. , Cassell Martin D. , Rutkowski D. Thomas , Davisson Robin L. , Grobe Justin L. , Sigmund Curt D.
Published: April 2015

Endoplasmic reticulum stress has become an important mechanism in hypertension. We examined the role of endoplasmic reticulum stress in mediating the increased saline-intake and hypertensive effects in response to deoxycorticosterone acetate (DOCA)–salt. Intracerebroventricular delivery of the endoplasmic reticulum stress–reducing chemical chaperone tauroursodeoxycholic acid did not affect the magnitude of hypertension, but markedly decreased saline-intake in response to DOCA-salt. Increased saline-intake returned after tauroursodeoxycholic acid was terminated. Decreased saline-intake was also observed after intracerebroventricular infusion of 4-phenylbutyrate, another chemical chaperone. Immunoreactivity to CCAAT homologous binding protein, a marker of irremediable endoplasmic reticulum stress, was increased in the subfornical organ and supraoptic nucleus of DOCA-salt mice, but the signal was absent in control and CCAAT homologous binding protein–deficient mice. Electron microscopy revealed abnormalities in endoplasmic reticulum structure (decrease in membrane length, swollen membranes, and decreased ribosome numbers) in the subfornical organ consistent with endoplasmic reticulum stress. Subfornical organ-targeted adenoviral delivery of GRP78, a resident endoplasmic reticulum chaperone, decreased DOCA-salt–induced saline-intake. The increase in saline-intake in response to DOCA-salt was blunted in CCAAT homologous binding protein–deficient mice, but these mice exhibited a normal hypertensive response. We conclude that (1) brain endoplasmic reticulum stress mediates the saline-intake, but not blood pressure response to DOCA-salt, (2) DOCA-salt causes endoplasmic reticulum stress in the subfornical organ, which when attenuated by GRP78 blunts saline-intake, and (3) CCAAT homologous binding protein may play a functional role in DOCA-salt–induced saline-intake. The results suggest a mechanistic distinction between the importance of endoplasmic reticulum stress in mediating effects of DOCA-salt on saline-intake and blood pressure.
Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Dobre Mirela , Yang Wei , Pan Qiang , Appel Lawrence , Bellovich Keith , Chen Jing , Feldman Harold , Fischer Michael J. , Ham L. L. , Hostetter Thomas , Jaar Bernard G. , Kallem Radhakrishna R. , Rosas Sylvia E. , Scialla Julia J. , Wolf Myles , Rahman Mahboob ,   and the CRIC Study Investigators
Published: April 2015

Background

Serum bicarbonate varies over time in chronic kidney disease (
CKD
) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time‐updated longitudinal analysis to evaluate the association of serum bicarbonate with long‐term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [
eGFR
] or end‐stage renal disease), and mortality.

Methods and Results

Serum bicarbonate was measured annually, in 3586 participants with
CKD
, enrolled in the Chronic Renal Insufficiency Cohort (
CRIC
) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time‐dependent confounding. During the 6 years follow‐up, 512 participants developed congestive heart failure (26/1000 person‐years) and 749 developed renal events (37/1000 person‐years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow‐up (hazard ratio [
HR
] 1.66; 95% confidence interval [
CI
], 1.23 to 2.23, and
HR
1.36, 95%
CI
1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co‐morbidities, medications including diuretics,
eGFR,
and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2‐fold increased risk of renal disease progression (
HR
1.97; 95%
CI
, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L.

Conclusion

In this large
CKD
cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in
CKD
to prevent adverse clinical outcomes.
Androgen Deprivation Therapy Reversibly Increases Endothelium‐Dependent Vasodilation in Men With Prostate Cancer
Authors: Nguyen Paul L. , Jarolim Petr , Basaria Shehzad , Zuflacht Jonah P. , Milian Jessica , Kadivar Samoneh , Graham Powell L. , Hyatt Andrew , Kantoff Philip W. , Beckman Joshua A.
Published: April 2015

Background

Androgen deprivation therapy (
ADT
) is a standard treatment for patients with aggressive prostate cancer. Although
ADT
improves survival, it increases the risk of diabetes. Emerging evidence suggests that
ADT
increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that
ADT
may impair endothelium‐dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.

Methods and Results

We prospectively evaluated conduit artery endothelium‐dependent and ‐independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66±7 years; 25% with diabetes) with prostate cancer before and after 3 months of
ADT
. High‐resolution B‐mode ultrasound was used to assess flow‐mediated (endothelium‐dependent) and nitroglycerine‐mediated (endothelium‐independent) brachial artery vasodilation.
ADT
significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium‐dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively;
P
=0.046, allometric
P
=0.037). Nitroglycerine‐mediated vasodilation did not change from baseline (
P
>0.2). The subset of participants on
ADT
for 6 months returned for reevaluation at 1 year. In this group, endothelium‐dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively;
P
=0.05).

Conclusions

In contrast to our expectation,
ADT
improved endothelium‐dependent vasodilation and its cessation returned endothelium‐dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.
Review of the family Anthogonidae (Diplopoda, Chordeumatida), with descriptions of three new species from the Balkan Peninsula
Authors: ANTIĆ DRAGAN , DRAŽINA TVRTKO , RAÐA TONĆI , TOMIĆ VLADIMIR T. , MAKAROV SLOBODAN E.
Published: April 2015

Three new species of the family Anthogonidae are described from caves in Croatia and Montenegro, respectively: Egonpretneria vudutschajldi Antić & Dražina sp. n., Haasia jalzici Antić & Dražina sp. n., and Macrochaetosoma bertiscea Antić & Makarov sp. n. All three subfamilies within Anthogonidae are diagnosed, with brief discussion of relationships between genera and notes on their biogeography. A map of the global distribution of Anthogonidae is presented, as well as maps of the distribution of each species of Balkan anthogonids, including numerous new locality data. The first SEM images are provided for some representatives of this family. A key is given to all seven anthogonid genera. The subfamily Haasiinae Hoffman, 1980 is a new synonym of Anthogonidae, syn. n., while Macrochaetosoma bifurcatum Ćurčić & Makarov, 2001 becomes a new synonym for M. troglomontanum Absolon & Lang, 1933, syn. n..
Description of Danio absconditus, new species, and redescription of Danio feegradei (Teleostei: Cyprinidae), from the Rakhine Yoma hotspot in south-western Myanmar
Authors: KULLANDER SVEN O. , BRITZ RALF
Published: April 2015

Danio feegradei Hora is redescribed based on recently collected specimens from small coastal streams on the western slope of the Rakhine Yoma, ranging from the Thade River drainage southward to slightly north of Kyeintali. Danio absconditus, new species, is described from the Kyeintali Chaung and small coastal streams near Gwa, south of the range of D. feegradei. Both species are distinguished from other Danio by the presence of a dark, elongate or round spot at the base of the caudal fin and a cleithral marking composed of a small black spot margined by a much smaller orange spot. Danio feegradei is characterized by the colour pattern, with series of white spots along the otherwise dark side; D. absconditus by about 7-–11 dark vertical bars on the abdominal side. Within Danio, the presence of a complete lateral line, cleithral spot, and 14 circumpeduncular scales is shared with D. dangila and similar species, but these character states may be plesiomorphic as suggested by the shared presence of cleithral spot and complete lateral line in Devario and Betadevario. In other Danio the cleithral spot is absent, the lateral line is short or absent, and the circumpeduncular scale count is lower (10–12). Twenty teleost species are reported from streams on the western slope of the Rakhine Yoma, all probably endemic. The parapatric distribution of D. absconditus and D. feegradei is unique within the genus, and may be partly explained by changes in eustatic sea levels.
Establishing Best Practices to Improve Usefulness and Usability of Web Interfaces Providing Atmospheric Data
Authors: Oakley Nina S. , Daudert Britta
Published: April 2015

Accessing scientific data and information through an online portal can be a frustrating task, often because of the fact that they were not built with the user’s needs in mind. The concept of making web interfaces easy to use, known as “usability,” has been thoroughly researched in the field of e-commerce but has not been explicitly addressed in the atmospheric and most other sciences. As more observation stations are installed, satellites flown, models run, and field campaigns performed, data are continuously produced. Portals on the Internet have become the favored mechanisms for sharing this information and are ever increasing in number. Portals are often created without being explicitly tested for usability with the target audience though the expenses of testing are low and the returns high. To remain competitive and relevant in the provision of atmospheric information, it is imperative that developers understand design elements of a successful portal to make their product stand out among others. This work informs the audience of the benefits and basic principles of usability that can be applied to web pages presenting atmospheric information. We will also share some of the best practices and recommendations we have formulated from the results of usability testing performed on a data provision site designed for researchers in the Southwest Climate Science Center and hosted by the Western Regional Climate Center.
Sticky Thermals: Evidence for a Dominant Balance between Buoyancy and Drag in Cloud Updrafts
Authors: Romps David M. , Charn Alexander B.
Published: April 2015

The vertical velocities of convective clouds are of great practical interest because of their influence on many phenomena, including severe weather and stratospheric moistening. However, the magnitudes of forces giving rise to these vertical velocities are poorly understood, and the dominant balance is in dispute. Here, an algorithm is used to extract thousands of cloud thermals from a large-eddy simulation of deep and tropical maritime convection. Using a streamfunction to define natural boundaries for these thermals, the dominant balance in the vertical momentum equation is revealed. Cloud thermals rise with a nearly constant speed determined by their buoyancy and the standard drag law with a drag coefficient of 0.6. Contrary to suggestions that cloud thermals might be slippery, with a dominant balance between buoyancy and acceleration, cloud thermals are found here to be sticky, with a dominant balance between buoyancy and drag.
Scenario Changes of Atlantic Water in the Arctic Ocean
Authors: Long Zhenxia , Perrie Will
Published: April 2015

The authors explore possible temperature modifications of the Atlantic Water Layer (AWL) induced by climate change, performing simulations for 1970 to 2099 with a coupled ice–ocean Arctic model (CIOM). Surface fields to drive the CIOM were provided by the Canadian Regional Climate Model (CRCM), driven by outputs from the Canadian Centre for Climate Modelling and Analysis (CCCma) Coupled Global Climate Model, version 3 (CGCM3) following the A1B climate change scenario. In the present climate, represented as 1990–2009, the CIOM can reliably reproduce the AWL compared to Polar Science Center Hydrographic Climatology (PHC) data. For the future climate, assuming the A1B climate change scenario, there is a significant increase in water volume transport into the central Arctic Ocean through Fram Strait due to the weakened atmospheric high pressure system over the western Arctic and an intensified atmospheric low pressure system over the Nordic seas. The AWL temperature tends to decrease from 0.36°C in the 2010s to 0.26°C in the 2060s. In the vertical, the warm Atlantic water core slightly expands before the 2030s, significantly shrinks after the 2050s, and essentially disappears by 2070–99, in the southern Beaufort Sea. The temperature decrease after 2030 is mainly due to the reduced heat fluxes in the Kara and Barents Seas. In the northeastern Barents and Kara Seas, the loss of sea ice increases the heat loss from the Atlantic water and reduces the water temperature near the bottom, contributing to decreased heat fluxes into the central Arctic Ocean, as well as decreased AWL temperature at central Arctic Ocean intermediate layers. In addition, the vertically integrated heat loss also plays an important role in the AWL cooling process.
Effects of Increasing Horizontal Resolution in a Convection-Permitting Model on Flood Forecasting: The 2011 Dramatic Events in Liguria, Italy
Authors: Davolio Silvio , Silvestro Francesco , Malguzzi Piero
Published: April 2015

Coupling meteorological and hydrological models is a common and standard practice in the field of flood forecasting. In this study, a numerical weather prediction (NWP) chain based on the BOLogna Limited Area Model (BOLAM) and the MOdello LOCale in Hybrid coordinates (MOLOCH) was coupled with the operational hydrological forecasting chain of the Ligurian Hydro-Meteorological Functional Centre to simulate two major floods that occurred during autumn 2011 in northern Italy. Different atmospheric simulations were performed by varying the grid spacing (between 1.0 and 3.0 km) of the high-resolution meteorological model and the set of initial/boundary conditions driving the NWP chain. The aim was to investigate the impact of these parameters not only from a meteorological perspective, but also in terms of discharge predictions for the two flood events. The operational flood forecasting system was thus used as a tool to validate in a more pragmatic sense the quantitative precipitation forecast obtained from different configurations of the NWP system. The results showed an improvement in flood prediction when a high-resolution grid was employed for atmospheric simulations. In turn, a better description of the evolution of the precipitating convective systems was beneficial for the hydrological prediction. Although the simulations underestimated the severity of both floods, the higher-resolution model chain would have provided useful information to the decision-makers in charge of protecting citizens.
Using Microwave Satellite Data to Assess Changes in Storminess over the Pacific Ocean
Authors: Kruk Michael C. , Hilburn Kyle , Marra John J.
Published: April 2015

This study analyzes 25 years of Special Sensor Microwave Imager (SSM/I) retrievals of rain rate and wind speed to assess changes in storminess over the open water of the Pacific Ocean. Changes in storminess are characterized by combining trends in both the statistically derived 95th percentile exceedance frequencies of rain rate and wind speed (i.e., extremes). Storminess is computed annually and seasonally, with further partitioning done by phase of the El Niño–Southern Oscillation (ENSO) index and the Pacific decadal oscillation (PDO) index. Overall, rain-rate exceedance frequencies of 6–8 mm h−1 cover most of the western and central tropical Pacific, with higher values present around the Philippines, Japan, Mexico, and the northwest coast of Australia. Wind speed exceedance frequencies are a strong function of latitude, with values less (greater) than 12 m s−1 equatorward (poleward) of 30°N/S. Statistically significant increasing trends in rain rate were found in the western tropical Pacific near the Caroline Islands and the Solomon Islands, and in the extratropics from the Aleutian Islands down the coast along British Columbia and Washington State. Statistically significant increasing trends in wind speed are present in the equatorial central Pacific near Kiribati and the Republic of the Marshall Islands (RMI), and in the extratropics along the west coast of the United States and Canada. Thus, while extreme rain and winds are both increasing across large areas of the Pacific, these areas are modulated according to the phase of ENSO and the PDO, and their intersection takes aim at specific locations.
Applications of Positive Psychology in Counseling Psychology
Authors: Magyar-Moe Jeana L. , Owens Rhea L. , Scheel Michael J.
Published: April 2015

A distinctive feature and unifying theme of the work of counseling psychologists is a focus on client strengths, assets, and potentialities regardless of the degree of psychopathology. As such, positive psychology appears to have a natural home within counseling psychology. Evidence from content analyses of flagship journals of the field as well as from surveys of Members and Student Affiliates from the Society of Counseling Psychology (Division 17) of the American Psychological Association suggests, however, that a distinctive disconnect exists between the philosophical stance taken by many counseling psychologists toward strength-based approaches and knowledge and use of specific positive psychology theories and practices. The goals for the creation of this special issue are reported, and the articles that comprise the special issue are introduced.
Thomas Müntzer (c. 1489-1525)
Authors: Rowland Christopher
Published: April 2015

Thomas Münzter, who died in the Peasants’ Revolt in 1525, was remembered as the revolutionary firebrand of the Reformation. His theology is an important component of early modern theology, with its mix of the mystical and the apocalyptic, prioritising experience of God, and its subordination of Scripture and tradition to that experience. His legacy in terms of intellectual history has been more far-reaching than appears, evincing a pattern of religion which was to have a significant impact, albeit indirectly, on revolutionary theology in England in the seventeenth century and later.
Effectiveness and student perceptions of high-enrolment health studies online courses
Authors: Chen Ken-Zen , Lowenthal Patrick R , Bauer Christine
Published: April 2015

Objective:

In countries such as the USA, colleges and universities are focusing on how best to serve their students in tough fiscal times and a highly competitive marketplace. Boise State University has specifically focused on providing online courses as one option to meet student needs. However, more recently, the university has begun developing high-enrolment online courses to resolve bottlenecks in enrolments, while maintaining robust, interactive and engaging learning experiences.

Design:

Mixed-methods case study.

Setting:

Three high-enrolment health studies online courses offered at a 4-year university in Boise, Idaho, USA.

Method:

A systemic analysis of final course evaluations, student grades and course reports from the Learning Management System were examined to investigate the effectiveness and student perceptions of high-enrolment online courses.

Results:

Findings provide support for the premise that offering the high-enrolment courses met enrolment demand, provided high-quality instruction and maintained student satisfaction.

Conclusion:

Student perceptions of high-enrolment health studies online courses designed and implemented in the manner specified here can be positive. Lesson learned and suggestions for faculty members, instructional designers and administrators are identified.
IRF6 Is a Marker of Severity in Nonsyndromic Cleft Lip/Palate
Authors: Kerameddin S. , Namipashaki A. , Ebrahimi S. , Ansari-Pour N.
Published: April 2015

Nonsyndromic cleft lip with or without palate (CL/P) is thought to be caused by the interplay of genetic and environmental factors, and this has thus hindered the process of identifying genetic causative factors. Numerous studies in the past decade have implicated IRF6 in CL/P, but this has not often been replicated in other populations. In specific, the only etiologic single-nucleotide polymorphism (SNP) identified in the IRF6 locus (rs642961) has recently been shown not to be associated with CL/P in diverse populations. We therefore used a genewide tagging SNP (tagSNP) haplotyping approach (including rs642961 as a tagSNP) to detect all potential risk-conferring haplotypes and combined this with detailed subphenotyping of CL/P cases ( N = 150) according to severity. We observed a significant overrepresentation of a tagSNP haplotype carrying the rs642961 risk allele in the most severe subphenotype of CL/P (complete bilateral CL/P; P = 0.008, odds ratio = 4.97, 95% confidence interval = 1.33 to 18.46). It was recently shown that >80% of IRF6 mutations in syndromic CL/P occur on the same haplotype background. We therefore suggest that IRF6 is a marker of CL/P severity.