bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ethics of Human Studies Research in the 21st Century
Authors: Murray John , Fairfield Joshua A. T.
Published: January 2014

Since 1979, the Belmont Report has been the core ethical guide for human and social research in academic and industrial studies, both in the United States and elsewhere. The report's guidelines now form the basis for such oversight in a variety of domains beyond its original purview in the biomedical and behavioral sciences. However, modern research environments introduce numerous new challenges, especially in relation to advanced communications and information technologies. Research in these fields today takes place in a transnational setting of ubiquitous computing and data acquisition in highly-interconnected networks, which are overlaid across varied, and often incompatible, legal regimes and social norms. In this talk, we explore these challenges, with emphasis on virtual worlds, augmented reality, and social networks, especially in an international context, and propose some innovative new opportunities for addressing them.
The efficacy of second-line hormone therapy for recurrence during adjuvant hormone therapy for breast cancer
Authors: Mori Ryutaro , Nagao Yasuko
Published: January 2014

Objectives:

The recurrence of breast cancer during adjuvant hormone therapy is often targeted by second-line hormone therapy. However, there has been a lack of prior success with such treatments. We retrospectively investigated the efficacy of subsequent hormone therapy.

Methods:

Patients who underwent breast cancer surgery between 2006 and 2012 at our institution were investigated.

Results:

A total of 20 patients developed recurrence during adjuvant hormone therapy. There were four patients with luminal A, seven with luminal B and six with luminal HER2 tumors, respectively. Twelve patients received subsequent hormone therapy, and eight patients received chemotherapy. Subsequent hormone therapy produced one partial response (PR), two long stable disease (SD), one SD and five progressive disease (PD). A clinical benefit (CB) was obtained by 33%. Subsequent chemotherapy produced one complete response (CR), two PRs, one long SD and two PD, resulting in a CB in 66%. Among those who received any hormone therapy, the best responses were two PR, three long SD and one SD. A CB was obtained by 38%, while seven patients did not have any CB from hormone therapy. Meanwhile, the best responses to chemotherapy were two CRs, four PRs, three SD and two PD, thus resulting in a CB in 72%. All luminal A cases obtained a long SD or SD with hormone therapy. However, the CB of hormone therapy for non-luminal A cases was only 30%.

Conclusions:

The efficacy of hormone therapy for recurrence during adjuvant hormone therapy is poor, and when selecting therapy for such patients, the breast cancer subtype should be taken into account.
Violent television program and ad memory: Respective roles of violence intensity and narrativity
Authors: Droulers Olivier , Roullet Bernard
Published: January 2014

For greater understanding of the influence of a violent program context on the memory for embedded commercials, three experiments were conducted. Taking as starting point a conceptual replication of Bushman and Bonacci’s (2002) study (Experiment 1), we investigated the influence of the level of violence contained in TV programs (Experiment 2) and the influence of the narrative continuity of the story present or not in the program (Experiment 3). Findings show that the intensity of violence is positively correlated with the free recall of commercials and that the program narrative continuity has no influence on ad memory. Finally, the role of program involvement – as a mediating variable between perceived violence and ad recall, moderated by gender and the viewer’s sensitivity – is highlighted.
Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study
Authors: Richardson Paul G. , Siegel David S. , Vij Ravi , Hofmeister Craig C. , Baz Rachid , Jagannath Sundar , Chen Christine , Lonial Sagar , Jakubowiak Andrzej , Bahlis Nizar , Song Kevin , Belch Andrew , Raje Noopur , Shustik Chaim , Lentzsch Suzanne , Lacy Martha , Mikhael Joseph , Matous Jeffrey , Vesole David , Chen Min , Zaki Mohamed H. , Jacques Christian , Yu Zhinuan , Anderson Kenneth C.
Published: January 2014

Key Points

Pomalidomide plus low-dose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma. Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.
Identification of miRNAs and their target genes in developing maize ears by combined small RNA and degradome sequencing
Authors: Liu Hongjun , Qin Cheng , Chen Zhe , Zuo Tao , Yang Xuerong , Zhou Huangkai , Xu Meng , Cao Shiliang , Shen Yaou , Lin Haijian , He Xiujing , Zhang Yinchao , Li Lujiang , Ding Haiping , Lübberstedt Thomas , Zhang Zhiming , Pan Guangtang
Published: January 2014

Background

In plants, microRNAs (miRNAs) are endogenous ~22 nt RNAs that play important regulatory roles in many aspects of plant biology, including metabolism, hormone response, epigenetic control of transposable elements, and stress response. Extensive studies of miRNAs have been performed in model plants such as rice and Arabidopsis thaliana. In maize, most miRNAs and their target genes were analyzed and identified by clearly different treatments, such as response to low nitrate, salt and drought stress. However, little is known about miRNAs involved in maize ear development. The objective of this study is to identify conserved and novel miRNAs and their target genes by combined small RNA and degradome sequencing at four inflorescence developmental stages.

Results

We used deep-sequencing, miRNA microarray assays and computational methods to identify, profile, and describe conserved and non-conserved miRNAs at four ear developmental stages, which resulted in identification of 22 conserved and 21-maize-specific miRNA families together with their corresponding miRNA*. Comparison of miRNA expression in these developmental stages revealed 18 differentially expressed miRNA families. Finally, a total of 141 genes (251 transcripts) targeted by 102 small RNAs including 98 miRNAs and 4 ta-siRNAs were identified by genomic-scale high-throughput sequencing of miRNA cleaved mRNAs. Moreover, the differentially expressed miRNAs-mediated pathways that regulate the development of ears were discussed.

Conclusions

This study confirmed 22 conserved miRNA families and discovered 26 novel miRNAs in maize. Moreover, we identified 141 target genes of known and new miRNAs and ta-siRNAs. Of these, 72 genes (117 transcripts) targeted by 62 differentially expressed miRNAs may attribute to the development of maize ears. Identification and characterization of these important classes of regulatory genes in maize may improve our understanding of molecular mechanisms controlling ear development.
Genomic comparison of sporeforming bacilli isolated from milk
Authors: Moreno Switt Andrea I , Andrus Alexis D , Ranieri Matthew L , Orsi Renato H , Ivy Reid , den Bakker Henk C , Martin Nicole H , Wiedmann Martin , Boor Kathryn J
Published: January 2014

Background

Sporeformers in the order Bacillales are important contributors to spoilage of pasteurized milk. While only a few Bacillus and Viridibacillus strains can grow in milk at 6°C, the majority of Paenibacillus isolated from pasteurized fluid milk can grow under these conditions. To gain a better understanding of genomic features of these important spoilage organisms and to identify candidate genomic features that may facilitate cold growth in milk, we performed a comparative genomic analysis of selected dairy associated sporeformers representing isolates that can and cannot grow in milk at 6°C.

Results

The genomes for seven Paenibacillus spp., two Bacillus spp., and one Viridibacillus sp. isolates were sequenced. Across the genomes sequenced, we identified numerous genes encoding antimicrobial resistance mechanisms, bacteriocins, and pathways for synthesis of non-ribosomal peptide antibiotics. Phylogenetic analysis placed genomes representing Bacillus, Paenibacillus and Viridibacillus into three distinct well supported clades and further classified the Paenibacillus strains characterized here into three distinct clades, including (i) clade I, which contains one strain able to grow at 6°C in skim milk broth and one strain not able to grow under these conditions, (ii) clade II, which contains three strains able to grow at 6°C in skim milk broth, and (iii) clade III, which contains two strains unable to grow under these conditions. While all Paenibacillus genomes were found to include multiple copies of genes encoding β-galactosidases, clade II strains showed significantly higher numbers of genes encoding these enzymes as compared to clade III strains. Genome comparison of strains able to grow at 6°C and strains unable to grow at this temperature identified numerous genes encoding features that might facilitate the growth of Paenibacillus in milk at 6°C, including peptidases with cold-adapted features (flexibility and disorder regions in the protein structure) and cold-adaptation related proteins (DEAD-box helicases, chaperone DnaJ).

Conclusions

Through a comparative genomics approach we identified a number of genomic features that may relate to the ability of selected Paenibacillus strains to cause spoilage of refrigerated fluid milk. With additional experimental evidence, these data will facilitate identification of targets to detect and control Gram positive spore formers in fluid milk.
Wireless home automation networks for indoor surveillance: technologies and experiments
Authors: Spadacini Milo , Savazzi Stefano , Nicoli Monica
Published: January 2014

The use of wireless technologies for critical surveillance and home automation introduces a number of opportunities as well as technological challenges. New emerging technologies give the opportunity to exploit the full potential of the internet of things paradigm by augmenting existing wired installations with smart wireless architectures. This work gives an overview of requirements, characteristics, and challenges of wireless home automation networks with special focus on intrusion detection systems. The proposed wireless network is based on several sensors that are deployed over a monitored area for detecting possible risky situations and triggering appropriate actions in response. The network needs to support critical traffic patterns with different characteristics and quality constraints. Namely, it should provide a periodic low-power monitoring service and, in case of intrusion detection, a real-time alarm propagation mechanism over inherently unreliable wireless links subject to fluctuations of the signal power. Following the guidelines introduced by recent standardization, this paper proposes the design of a wireless network prototype at 868 MHz which is able to satisfy the specifications of typical intrusion detection applications. A proprietary medium access control is developed based on the low-power SimpliciTI radio stack (Texas Instruments Incorporated, San Diego, CA, USA). Network performance is assessed by experimental measurements using a test-bed in an indoor office environment with severe multipath and nonline-of-sight propagation conditions. The measurement campaigns highlight the potential of the sub-GHz technology for cable replacing.
Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro
Authors: Aziz MohammedTalaat Abdel , El-Asmar Mohammed Farid , Rezq Ameen Mahmoud , Wassef MohammedAbdel Aziz , Fouad Hanan , Roshdy Nagwa Kamal , Ahmed Hanan Hosni , Rashed Laila Ahmed , Sabry Dina , Taha Fatma Mohammed , Hassouna Amira
Published: January 2014

Background

Hyperglycemia induces activation of the c-Jun N-terminal kinase (JNK) pathway, which suppresses insulin gene expression and reduces DNA binding of pancreatic and duodenal homeobox factor (PDX)-1. This study aims to investigate the effects of a novel curcumin derivative (NCD) on JNK signaling pathway on insulin synthesis and secretion in streptozotocin (STZ)-treated rat pancreatic islets in vitro.

Methods

Isolated rat pancreatic islets were divided into five groups: untreated control group; group treated with NCD (10 μM); group exposed to STZ (5 mM); group treated with NCD (10 μM) and then exposed to STZ (5 mM); and group exposed to STZ (5 mM) and then treated with NCD (10 μM). The pancreatic islets from all groups were used for DNA fragmentation assays and quantitative assessments of the JNK, Pdx1, glucose transporter-2 (GLUT2), heme oxygenase (HO)-1, transcription factor 7-like 2 (TCF7L2), and glucagon-like peptide (GLP)-1 gene expression levels. The intracellular calcium, zinc, and the phosphorylated and total JNK protein levels were assessed. The insulin (secreted/total) and C-peptide levels were examined in islet culture medium.

Results

NCD protected pancreatic islets against STZ-induced DNA damage, improved total insulin (P = 0.001), secreted insulin (P = 0.001), and C-peptide levels (P = 0.001), normalized mRNA expressions of insulin, Pdx1, and GLUT2 (P = 0.0001), and significantly elevated calcium and zinc levels (P = 0.0001). All effects were significant when islets were treated with NCD before STZ (P = 0.05). JNK gene overexpression and JNK protein levels induced by STZ were significantly inhibited after NCD treatment of islets ( P = 0.0001). NCD-treated islets showed significantly elevated gene expressions of HO-1, TCF7L2, and GLP-1 (P = 0.0001), and these upregulated gene expressions were more significantly elevated with NCD treatment before STZ than after STZ (P = 0.05).

Conclusions

NCD improved insulin synthesis and secretion in vitro in isolated pancreatic islets treated with STZ through inhibition of the JNK pathway, up-regulation of the gene expressions of HO-1, TCF7L2, and GLP-1 and enhancing effects on calcium and zinc levels.
Design and implementation of integrated solid wastes management pattern in industrial zones, case study of Shahroud, Iran
Authors: Saeid Nazemi , Roudbari Aliakbar , Yaghmaeian Kamyar
Published: January 2014

Background

The aim of the study was to design and implementation of integrated solid wastes management pattern in Shahroud industrial zone, evaluates the results and determine possible performance problems. This cross - sectional study was carried out for 4 years in Shahroud industrial zone and the implementation process included:1- Qualitative and quantitative analysis of all solid waste generated in the city, 2- determine the current state of solid waste management in the zone and to identify programs conducted, 3- Design and implementation of integrated solid wastes management pattern including design and implementation of training programs, laws, penalties and incentives and explain and implement programs for all factories and 4- The monitoring of the implementation process and determine the results.

Results

Annually, 1,728 tons of solid wastes generated in the town including 1603 tons of industrial wastes and 125 tons of municipal wastes. By implementing this pattern, the two separated systems of collection and recycling of domestic and industrial wastes was launched in this zone. Also consistent with the goals, the amount of solid wastes generated and disposed in 2009 was 51.5 and 28.6 kg per 100 million Rials production, respectively.

Conclusion

Results showed that implementation of pattern of separated collection, training programs, capacity building, providing technical services, completing chain of industries and strengthening the cooperation between industrial estate management and industrial units could greatly reduce the waste management problems.
Real-time in silico experiments on gene regulatory networks and surgery simulation on handheld devices
Authors: Alfaro Icíar , González David , Bordeu Felipe , Leygue Adrien , Ammar Amine , Cueto Elías , Chinesta Francisco
Published: January 2014

Simulation of all phenomena taking place in a surgical procedure is a formidable task that involves, when possible, the use of supercomputing facilities over long time periods. However, decision taking in the operating room needs for fast methods that provide an accurate response in real time. To this end, Model Order Reduction (MOR) techniques have emerged recently in the field of Computational Surgery to help alleviate this burden. In this paper, we review the basics of classical MOR and explain how a technique recently developed by the authors and coined as Proper Generalized Decomposition could make real-time feedback available with the use of simple devices like smartphones or tablets. Examples are given on the performance of the technique for problems at different scales of the surgical procedure, form gene regulatory networks to macroscopic soft tissue deformation and cutting.
The gray zone of the qualitative assessment of respiratory changes in inferior vena cava diameter in ICU patients
Authors: Duwat Antoine , Zogheib Elie , Guinot Pierre Grégoire , Levy Franck , Trojette Faouzi , Diouf Momar , Slama Michel , Dupont Hervé
Published: January 2014

Introduction

Transthoracic echocardiography (TTE) is a useful tool for minimally invasive hemodynamic monitoring in the ICU. Dynamic indices (such as the inferior vena cava distensibility index (dIVC)) can be used to predict fluid responsiveness in mechanically ventilated patients. Although quantitative use of the dIVC has been validated, the routinely used qualitative (visual) approach had not been assessed before the present study.

Methods

Qualitative and quantitative assessments of the dIVC were compared in a prospective, observational study. After operators with differing levels in critical care echocardiography had derived a qualitative dIVC, the last (expert) operator performed a standard, numeric measurement of the dIVC (referred to as the quantitative dIVC). Two groups of patients were separated into two groups: group (dIVC < 18%) and group (dIVC ≥ 18%).

Results

In total, 114 patients were assessed for inclusion, and 97 (63 men and 34 women) were included. The mean sensitivity and specificity values for qualitative assessment of the dIVC by an intensivist were 80.7% and 93.7%, respectively. A qualitative evaluation detected all quantitative dIVCs >40%. Most of the errors concerned quantitative dIVCs of between 15% and 30%. In the dIVC <18% group, two qualitative evaluation errors were noted for quantitative dIVCs of between 0 and 10%. The average of positive predictive values and negative predictive values for qualitative assessment of the dIVC by residents, intensivists and cardiologists were 83%, 83%, and 90%; and 92%, 94%, and 90%, respectively. The Fleiss kappa for all operators was estimated to be 0.68, corresponding to substantial agreement.

Conclusion

The qualitative dIVC is a rather easy and reliable assessment for extreme numeric values. It has a gray zone between 15% and 30%. The highest and lowest limitations of the gray area are rather tedious to define.

Despite reliability of the qualitative assessment when it comes to extreme to numerical values, the quantitative dIVC measurement must always be done within a hemodynamic assessment for intensive care patients. The qualitative approach can be easily integrated into a fast hemodynamic evaluation by using portable ultrasound scanner for out-of-hospital patients.
The ethical dimension in published animal research in critical care: the public face of science
Authors: Bara Meredith , Joffe Ari R
Published: January 2014

Introduction

The ethical quality of animal research is important for many reasons, including for maintaining public support. We aimed to determine the reported attention to the ethical dimensions of the 3Rs (Refinement, Reduction, and Replacement) in critical care animal research published in 2012.

Methods

A data-collection form and instruction manual were created based on published recommendations, and completed for all consecutive critical care animal research (using mammals) publications from January to June 2012 in three critical care journals. Predefined subgroups were by journal, sepsis model, and animal age, compared by using the χ2 statistic, with statistical significance accepted at P < 0.05.

Results

In total, 77 consecutive animal research publications were reviewed. Most studies did not report monitoring the level of anesthesia during invasive procedures, even when muscle paralytics were used, nor monitoring or treatment of expected pain. When euthanasia was used, the method was often not stated, and when stated, most methods were not appropriate for the species. A sample-size calculation was rarely used, and animal numbers were often poorly described. No studies performed a systematic review to ensure that the animal research would be useful and not simple repetition. Seventeen (22%) publications met the composite outcome of, if indicated, using anesthesia and pain control, and stating the method of euthanasia. Most studies were funded with public funds (foundation or government funding). Sepsis models less often met the composite outcome of, if indicated, using anesthesia and pain control, and stating the method of euthanasia (2 (7%) of 27 versus 15 (30%) of 50; P = 0.023). No other statistically significant differences were found in reporting of any criterion by animal age, sepsis model, or journal.

Conclusions

Reported (although not necessarily actual) ethical quality of animal research in three high-impact critical care journals during 6 months of 2012 was poor. This has important implications for the practice of critical care animal research.
Difference in mobilization of progenitor cells after myocardial infarction in smoking versus non-smoking patients: insights from the BONAMI trial
Authors: Lamirault Guillaume , Susen Sophie , Forest Virginie , Hemont Caroline , Parini Angelo , Corvoisier Philippe Le , Piot Christophe , Richard Marie-Jeanne , Delasalle Béatrice , Rouard Hélène , Sportouch Catherine , Persoons Virginie , Van Belle Eric , Roncalli Jérôme , Lemarchand Patricia
Published: January 2014

Introduction

Although autologous bone marrow cell (BMC) therapy has emerged as a promising treatment for acute myocardial infarction (AMI), trials reported mixed results. In the BONAMI trial, active smoking reduced cardiac function recovery after reperfused AMI. Therefore, we hypothesized that variability in the functionality of BMCs retrieved from patients with cardiovascular risk factors may partly explain these mixed results. We investigated the characteristics of progenitor cells in active smokers and non-smokers with AMI and their potential impact on BMC therapy efficacy.

Methods

Bone marrow and blood samples from 54 smoking and 47 non-smoking patients enrolled in the BONAMI cell therapy trial were analyzed.

Results

The white BMC and CD45dimCD34+ cell numbers were higher in active smokers (P = 0.001, P = 0.03, respectively). In marked contrast, either bone marrow or blood endothelial progenitor CD45dimCD34 + KDR + cells (EPCs) were decreased in active smokers (P = 0.005, P = 0.04, respectively). Importantly, a multivariate analysis including cardiovascular risk factors confirmed the association between active smoking and lower EPC number in bone marrow (P = 0.04) and blood (P = 0.04). Furthermore, baseline circulating EPC count predicted infarct size decrease at three months post-AMI in non-smokers (P = 0.01) but not in active smokers. Interestingly, baseline circulating EPCs were no longer predictive of cardiac function improvement in the BMC therapy group.

Conclusions

These data suggest that circulating EPCs play an important role in cardiac repair post-AMI only in non-smokers and that active smoking-associated EPC alterations may participate in the impairment of cardiac function recovery observed in smokers after AMI, an effect that was overridden by BMC therapy.
International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation
Authors: Palumbo Antonio , Rajkumar S. Vincent , San Miguel Jesus F. , Larocca Alessandra , Niesvizky Ruben , Morgan Gareth , Landgren Ola , Hajek Roman , Einsele Hermann , Anderson Kenneth C. , Dimopoulos Meletios A. , Richardson Paul G. , Cavo Michele , Spencer Andrew , Stewart A. Keith , Shimizu Kazuyuki , Lonial Sagar , Sonneveld Pieter , Durie Brian G.M. , Moreau Philippe , Orlowski Robert Z.
Published: January 2014

Purpose

To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation.

Methods

A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized.

Results

Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care.

Conclusion

These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice.
Nomogram to Predict Cycle-One Serious Drug-Related Toxicity in Phase I Oncology Trials
Authors: Hyman David M. , Eaton Anne A. , Gounder Mrinal M. , Smith Gary L. , Pamer Erika G. , Hensley Martee L. , Spriggs David R. , Ivy Percy , Iasonos Alexia
Published: January 2014

Purpose

All patients in phase I trials do not have equivalent susceptibility to serious drug-related toxicity (SDRT). Our goal was to develop a nomogram to predict the risk of cycle-one SDRT to better select appropriate patients for phase I trials.

Patients and Methods

The prospectively maintained database of patients with solid tumor enrolled onto Cancer Therapeutics Evaluation Program–sponsored phase I trials activated between 2000 and 2010 was used. SDRT was defined as a grade ≥ 4 hematologic or grade ≥ 3 nonhematologic toxicity attributed, at least possibly, to study drug(s). Logistic regression was used to test the association of candidate factors to cycle-one SDRT. A final model, or nomogram, was chosen based on both clinical and statistical significance and validated internally using a bootstrapping technique and externally in an independent data set.

Results

Data from 3,104 patients enrolled onto 127 trials were analyzed to build the nomogram. In a model with multiple covariates, Eastern Cooperative Oncology Group performance status, WBC count, creatinine clearance, albumin, AST, number of study drugs, biologic study drug (yes v no), and dose (relative to maximum administered) were significant predictors of cycle-one SDRT. All significant factors except dose were included in the final nomogram. The model was validated both internally (bootstrap-adjusted concordance index, 0.60) and externally (concordance index, 0.64).

Conclusion

This nomogram can be used to accurately predict a patient's risk for SDRT at the time of enrollment. Excluding patients at high risk for SDRT should improve the safety and efficiency of phase I trials.
Endothelin-1 Regulates H+-ATPase-Dependent Transepithelial H+ Secretion in Zebrafish
Authors: Guh Ying-Jey , Tseng Yung-Che , Yang Chao-Yew , Hwang Pung-Pung
Published: January 2014

Endothelin-1 (EDN1) is an important regulator of H+ secretion in the mammalian kidney. EDN1 enhances renal tubule H+-ATPase activity, but the underlying mechanism remains unclear. To further elucidate the role of EDN1 in vertebrates' acid-base regulation, the present study used zebrafish as the model to examine the effects of EDN1 and its receptors on transepithelial H+ secretion. Expression of EDN1 and one of its receptors, EDNRAa, was stimulated in zebrafish acclimated to acidic water. A noninvasive scanning ion-selective electrode technique was used to show that edn1 overexpression enhances H+ secretion in embryonic skin at 3 days post fertilization. EDNRAa loss of function significantly decreased EDN1- and acid-induced H+ secretion. Abrogation of EDN1-enhanced H+ secretion by a vacuolar H+-ATPase inhibitor (bafilomycin A1) suggests that EDN1 exerts its action by regulating the H+-ATPase-mediated H+ secretion. EDN1 does not appear to affect H+ secretion through either altering the abundance of H+-ATPase or affecting the cell differentiation of H+-ATPase-rich ionocytes, because the reduction in secretion upon ednraa knockdown was not accompanied by decreased expression of H+-ATPase or reduced H+-ATPase-rich cell density. These findings provide evidence that EDN1 signaling is involved in acid-base regulation in zebrafish and enhance our understanding of EDN1 regulation of transepithelial H+ secretion in vertebrates.
Differential Permeability of the Blood-Testis Barrier During Reinitiation of Spermatogenesis in Adult Male Rats
Authors: Haverfield Jenna T. , Meachem Sarah J. , Nicholls Peter K. , Rainczuk Katarzyna E. , Simpson Evan R. , Stanton Peter G.
Published: January 2014

The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV–VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility.
Effect of Bisphosphonates on the Rapidly Growing Male Murine Skeleton
Authors: Zhu Eric D. , Louis Leeann , Brooks Daniel J. , Bouxsein Mary L. , Demay Marie B.
Published: January 2014

Bisphosphonates are effective for preventing and treating skeletal disorders associated with hyperresorption. Their safety and efficacy has been studied in adults where the growth plate is fused and there is no longitudinal bone growth and little appositional growth. Although bisphosphonate use in the pediatric population was pioneered for compassionate use in the treatment of osteogenesis imperfecta, they are being increasingly used for the treatment and prevention of bone loss in children at risk of hyperresorptive bone loss. However, the effect of these agents on the growing skeleton in disorders other than osteogenesis imperfecta has not been systematically compared. Studies were, therefore, undertaken to examine the consequences of bisphosphonate administration on the growth plate and skeletal microarchitecture during a period of rapid growth. C57Bl6/J male mice were treated from 18 to 38 days of age with vehicle, alendronate, pamidronate, zoledronate, or clodronate at doses selected to replicate those used in humans. Treatment with alendronate, pamidronate, and zoledronate, but not clodronate, led to a decrease in the number of chondrocytes per column in the hypertrophic chondrocyte layer. This was not associated with altered hypertrophic chondrocyte apoptosis or vascular invasion at the growth plate. The effects of pamidronate on trabecular microarchitecture were less beneficial than those of alendronate and zoledronate. Pamidronate did not increase cortical thickness or cortical area/total area relative to control mice. These studies suggest that bisphosphonate administration does not adversely affect skeletal growth. Long-term investigations are required to determine whether the differences observed among the agents examined impact biomechanical integrity of the growing skeleton.
21-Hydroxylase-Derived Steroids in Follicles of Nonobese Women Undergoing Ovarian Stimulation for In Vitro Fertilization (IVF) Positively Correlate With Lipid Content of Luteinized Granulosa Cells (LGCs) as a Source of Cholesterol for Steroid Synthesis
Authors: Amin Marli , Simerman Ariel , Cho Michele , Singh Prapti , Briton-Jones Christine , Hill David , Grogan Tristan , Elashoff David , Clarke Nigel J. , Chazenbalk Gregorio D. , Dumesic Daniel A.
Published: January 2014

Context:

Mineralocorticoid synthesis by the nonhuman primate periovulatory follicle enhances luteinization. Whether a similar event occurs in women undergoing in vitro fertilization (IVF) is unknown.

Objective:

The objective of the study was to determine whether human luteinized granulosa cells (LGCs) produce mineralocorticoids derived from 21-hydroxylase activity and also express mRNA for 21-hydroxylase and the mineralocorticoid receptor.

Design:

This was a prospective cohort study.

Setting:

The study was conducted at an academic center.

Patients:

LGC lipid content and follicle fluid (FF) hormone analysis was performed on 27 nonobese IVF women. LGCs from six additional nonobese IVF women were used for gene expression studies.

Intervention:

At oocyte retrieval, FF was aspirated from the first follicle (≥16 mm in size) of each ovary and pooled LGCs were collected.

Main Outcome Measures:

FF steroid analysis was performed by liquid chromatography-tandem mass spectrometry. LGCs were stained with lipid fluorescent dye BODIPY FL C16 to estimate lipid content by confocal microscopy as a cholesterol source for steroidogenesis in vivo. Quantitative real-time PCR was performed using LGCs to detect 21-hydroxylase and mineralocorticoid receptor mRNA expression. Pearson correlation coefficients determined associations between FF steroid levels and LGC lipid content.

Results:

FF levels of the 21-hydroxylase-derived steroids, 11-deoxycorticosterone [DOC, 39.97, median (13.94–63.02) ng/mL] and 11-deoxycortisol [11DOC, 2.07 (0.69–5.01) ng/mL], along with the 21-hydroxylase precursor 17-hydroxyprogesterone [1268.21 (493.26–3558.39) ng/mL], positively correlated with LGC lipid content (84 ± 43 fluorescent units/sample) (P ≤ .05, all steroids). 21-Hydroxylase and mineralocorticoid receptor mRNA expression was detected in LGCs.

Conclusions:

Human LGCs likely synthesize 21-hydroxylase-derived mineralocorticoids from cholesterol-containing lipid in vivo to promote postovulatory luteinization via mineralocorticoid receptor-mediated events.
Empirically Based Composite Fracture Prediction Model From the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)
Authors: FitzGerald Gordon , Compston Juliet E. , Chapurlat Roland D. , Pfeilschifter Johannes , Cooper Cyrus , Hosmer David W. , Adachi Jonathan D. , Anderson Frederick A. , Díez-Pérez Adolfo , Greenspan Susan L. , Netelenbos J. Coen , Nieves Jeri W. , Rossini Maurizio , Watts Nelson B. , Hooven Frederick H. , LaCroix Andrea Z. , March Lyn , Roux Christian , Saag Kenneth G. , Siris Ethel S. , Silverman Stuart , Gehlbach Stephen H.
Published: January 2014

Context:

Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired.

Objective:

The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles.

Design:

This was a prospective, observational cohort study.

Setting:

The study was conducted at primary care practices in 10 countries.

Patients:

Women aged 55 years or older participated in the study.

Intervention:

Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures.

Main Outcome Measure:

The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age.

Results:

Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase.

Conclusions:

After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
The Von Hippel-Lindau Protein Suppresses Androgen Receptor Activity
Authors: Wang Jing , Zhang Wei , Ji Wei , Liu Xing , Ouyang Gang , Xiao Wuhan
Published: January 2014

The androgen receptor (AR) plays a pivotal role in prostate homeostasis and prostate cancer development. To understand the mechanism underlying the regulation of the AR holds a promise for developing novel therapeutic approaches for prostate cancer. Here, we show that the Von Hippel-Lindau gene product, pVHL, physically interacts with AR and inhibits AR transcription activity but does not induce AR turnover. Moreover, pVHL also suppresses androgen-induced cell proliferation, implicating a physiological role of pVHL in androgen-induced signaling pathway. In addition, we provide evidence to show that pVHL actually enhanced AR de-ubiquitination instead of inducing AR ubiquitination, uncovering a noncanonical role of pVHL in the ubiquitin proteasome pathway. Our data reveal a novel function of pVHL in the regulation of AR transcription activity, which may expand the scope of pVHL in tumor suppression and provide mechanistic insight into prostate cancer initiation and progression.
Regioselective Mono-Deprotection of Di-tert-butylsilylene Acetal Derived from 1,3-Diol with Ammonium Fluoride
Authors: Ohtawa Masaki , Tomoda Hiroshi , Nagamitsu Tohru
Published: January 2014

Here we report a novel and efficient method for the regioselective mono-deprotection of di-tert-butylsilylene acetals derived from 1,3-diols consisting of primary and secondary alcohols. The ammonium fluoride-mediated reactions of pyripyropene A derivative, thymidine and uridine derivatives, methyl β-d-glucofuranoside, and pyranoside derivatives each gave the corresponding primary alcohol with high regioselectivity.
Home, Parents, and Achievement Motivation: A Study of Key Home and Parental Factors that Predict Student Motivation and Engagement
Authors: Mansour Marianne , Martin Andrew J.
Published: January 2014

The home and parental factors that predict achievement motivation are an important focus in research, because they are a clear point for potential educational and psychological support for students. The present study investigates the achievement motivation of high school students, in the context of parental and home factors such as home resources, in- and out-of-home parental assistance, parenting style, and parental involvement in the school. Among a sample of 100 Australian high school students, hierarchal multiple linear regression analyses were performed in order to determine the relative salience of the proposed home and parental factors predicting students' achievement motivation. Results demonstrated that over and above demographic factors such as age, gender and ethnicity, home and parental factors do indeed play a critical function in predicting student motivation and engagement. Specifically, the study reveals that home resources and parenting style are the most salient home and parental factors associated with key aspects of achievement motivation and engagement (planning, task management, teacher–student relationships — positively, and self-handicapping — negatively). These findings affirm the role of the home and parents in students' academic development. Implications for future research and practice harnessing the present findings are discussed.
Discourse in a coma; A comment on a comma in the title of Jean-François Lyotard’s Discourse, Figure
Authors: Rubinstein Daniel
Published: January 2014

One of the key claims in Jean-Francois Lyotard’s “Discourse, Figure” is that the dialectical method (the backbone of Western philosophy) tends to obscure and hide all which is invisible, illegible and sensual. Lyotard’s strategy in exposing this rift within language (and philosophy) is by way of showing that the distance between the sign and the referent should not be thought of as negation but as a form of expression. Instead of the dialectical relation between the image and the object Lyotard proposes radical heterogeneity that he names ‘thickness’. This paper examines Lyotard’s non-dialectical approach in relation to the title of the book and argues that the comma is positioned as the sensual technology that creates the possibility of discursive continuity.
Pixelizing atrocity
Authors: Adelman Rebecca A.
Published: January 2014

A digital solution to the problems caused by US military personnel misusing their digital cameras, pixelization (the intentional post-production enlargement of pixels to obscure potentially disturbing content) has become a defining feature of newsmedia visualizations of American military atrocity during the War on Terror. Here, I consider the ethics and politics of pixelizing photographs depicting torture at Abu Ghraib, the exploits of the American ‘Kill Team’ in Afghanistan, and the carnality of US Marines urinating on the corpses of Taliban soldiers. Ostensibly, as a technique applied to those parts of the photograph that reveal the corporeal truth of war most graphically, such redaction is meant to protect the victims. But it also renders their appearance variable, subject to editorial whim, and pixelization alters not only the appearance of the photograph, but how it signifies. I query whether pixelization offers any meaningful redress for the victims and the extent to which it blunts photography’s capacity to document harm.
Photographically unconcealing the crimes: Christian Patterson’s Redheaded Peckerwood and Heidegger’s aletheia
Authors: Bennett Emma
Published: January 2014

Photographic truth has traditionally been theorized on the basis of ‘correctness’, whereby the image’s mechanically produced correspondence to reality guarantees its truth. This article suggests that Christian Patterson’s photobook Redheaded Peckerwood (2011) engages with a notion of photographic truth that can more usefully be understood in relation to Martin Heidegger’s descriptions of truth as aletheia or ‘unconcealing’. By including ambiguity, mystery and fiction in this nonetheless seemingly truthful retelling of historical events, the work suggests that a straightforward notion of the photograph’s transparency to the world is insufficient to explain the truth of photography.
La mujer en el subsector del alojamiento: el caso de la Costa Blanca (Alicante, España)
Authors: Sigüenza Poveda María Carmen
Published: January 2014

El artículo se acerca, desde la perspectiva de género, al mercado laboral general, y al relacionado con el alojamiento en particular, en la Costa Blanca (España). Dentro de la empresa hotelera, se centra en su organigrama y la integración por género de los diferentes departamentos que lo componen; también se analizará la integración horizontal y vertical, teniendo en cuenta la posición de las mujeres en los puestos operativos, intermedios y directivos. Este artículo propone el estudio de una serie de variables a investigar por medio de entrevistas a las trabajadoras de los hoteles costeros de diferentes localidades de la provincia de Alicante. Las variables del estudio son: la igualdad de oportunidades en la promoción de las mujeres del sector hotelero y el desarrollo profesional de estas, los obstáculos a la hora del desempeño profesional y las diferencias de género dentro del ámbito laboral y amparadas por el paraguas legal del Convenio Colectivo de la provincia. También se presta atención a temas como el absentismo laboral o el liderazgo dentro de los hoteles de la Costa Blanca.
Syngas Production from Reforming of Methane with CO2 and O2 over LaNi1–xCoxO3 Perovskites
Authors: Jahangiri Alireza , Aghabozorg Hamidreza , Pahlavanzadeh Hassan , Towfighi Jafar
Published: January 2014

The LaNi1–xCoxO3 (x = 0, 0.2, 0.4, 0.6, 0.8 and 1) perovskites were prepared by the citrate sol–gel method. The prepared compounds were characterized by using XRD, BET, ICP, SEM, EDS, TEM, TPR and TGA techniques, under the condition of as-synthesized and used samples. The results showed that the highly homogeneous and pure solids with particle sizes in the range of nanometers were obtained through this synthesis method. The XRD patterns of fresh catalysts indicated the formation of well-crystallized perovskite structure with LaNiO3 and LaCoO3 as the main phases present on the solids depending on the amount of Co-substitution. TPR analysis revealed that the reduction of the solids was more difficult when increasing the degree of substitution (x). The effects of the partial substitution of Ni by Co and reaction temperatures at atmospheric pressure were investigated in the combined reforming of methane with CO2 and O2 (CRM), after reduction of the samples under hydrogen. LaNiO3 exhibited high activity and selectivity without coke formation between all of the studied perovskites. For LaNi1–xCoxO3 perovskites, it was observed a trend to decrease the catalytic activity with increasing the Co-doping level.
Transesterification of Sunflower Oil in Microreactors
Authors: Bhoi Rohidas , Sen Nirvik , Singh K. K. , Mahajani Sanjay M. , Shenoy K. T. , Rao Hanmanth , Ghosh S. K.
Published: January 2014

KOH catalyzed transesterification of sunflower oil using methanol has been studied in different types of microreactors. All the microreactors consist of a serpentine microchannel etched in a glass chip but have different types of microfluidic junctions (dispersing devices). First microreactor consists of a T-type microfluidic junction. The second microreactor has a †-type microfluidic junction. The third microreactor uses a split and recombine micromixer to generate the dispersion. Effects of temperature, flow rate, and feed molar ratio on the conversion of triglyceride (TG) have been studied. In some cases, conversion of TG is not found to change monotonically with change in flow rate. An attempt has been made to explain this seemingly unusual trend, and the explanations are substantiated using the liquid–liquid two-phase flow patterns observed using a high-speed image acquisition system. The results from the experiments conducted in this study indicate that it is possible to get very high TG conversion (>90%) with residence time less than a minute.