bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression
Authors: Mars Ruben A. T. , Nicolas Pierre , Denham Emma L. , van Dijl Jan Maarten
Published: October 2016

Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include
trans
-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as
Escherichia coli
and
Salmonella
. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium
Bacillus subtilis
. A recent study identified 1,583 putative regulatory RNAs in
B. subtilis
, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in
B. subtilis
, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in
B. subtilis
mostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in
B. subtilis
. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in
B. subtilis
.
Factors associated with the difficulty in hospital acceptance at the scene by emergency medical service personnel: a population-based study in Osaka City, Japan
Authors: Katayama Yusuke , Kitamura Tetsuhisa , Kiyohara Kosuke , Iwami Taku , Kawamura Takashi , Hayashida Sumito , Yoshiya Kazuhisa , Ogura Hiroshi , Shimazu Takeshi
Published: October 2016

Objectives

To investigate the association between the difficulty in hospital acceptance at the scene by emergency medical service (EMS) personnel and prehospital demographic factors and reasons for EMS calls.

Design

A retrospective, observational study.

Setting

Osaka City, Japan.

Participants

A total of 100 649 patients transported to medical institutions by EMS from January 2013 to December 2013.

Primary outcome measurements

The definition of difficulty in hospital acceptance at the scene was EMS personnel making ≥5 phone calls to medical institutions until a decision to transport was determined. Multivariable analysis was used to assess the relationship between difficulty in hospital acceptance and prehospital factors and reasons for EMS calls.

Results

Multivariable analysis showed the elderly, foreigners, loss of consciousness, holiday/weekend, and night-time to be positively associated with difficulty in hospital acceptance at the scene. As reasons for EMS calls, gas poisoning (adjusted OR 3.281, 95% CI 1.201 to 8.965), trauma by assault (adjusted OR 2.662, 95% CI 2.390 to 2.966), self-induced drug abuse/gas poisoning (adjusted OR 4.527, 95% CI 3.921 to 5.228) and self-induced trauma (adjusted OR 1.708, 95% CI 1.369 to 2.130) were positively associated with the difficulty in hospital acceptance at the scene.

Conclusions

Ambulance records in Osaka City showed that certain prehospital factors such as night-time were positively associated with difficulty in hospital acceptance at the scene, and reasons for EMS calls, such as self-induced drug abuse/gas poisoning, were also positive predictors for difficulty in hospital acceptance at the scene.
Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears
Authors: Lithwick-Yanai Gila , Dromi Nir , Shtabsky Alexander , Morgenstern Sara , Strenov Yulia , Feinmesser Meora , Kravtsov Vladimir , Leon Marino E , Hajdúch Marián , Ali Syed Z , VandenBussche Christopher J , Zhang Xinmin , Leider-Trejo Leonor , Zubkov Asia , Vorobyov Sergey , Kushnir Michal , Goren Yaron , Tabak Sarit , Kadosh Etti , Benjamin Hila , Schnitzer-Perlman Temima , Marmor Hagai , Motin Maria , Lebanony Danit , Kredo-Russo Sharon , Mitchell Heather , Noller Melissa , Smith Alexis , Dattner Olivia , Ashkenazi Karin , Sanden Mats , Berlin Kenneth A , Bar Dganit , Meiri Eti
Published: October 2016

Aims

The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears.

Methods

A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR.

Results

Test performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%).

Conclusions

A novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.
My working week: Padraig Egan
Authors: Egan Padraig
Published: October 2016

Padraig Egan is a surgical resident at Fitzpatrick Referrals in Surrey. Here, he describes a week on‐call.
Controlling the stereoselectivity of glycosylation via solvent effects
Authors: Kafle Arjun , Liu Jun , Cui Lina
Published: October 2016

This review covers a special topic in carbohydrate chemistry — solvent effects on the stereoselectivity of glycosylation reactions. Obtaining highly stereoselective glycosidic linkages is one of the most challenging tasks in organic synthesis, as it is affected by various controlling factors. One of the least understood factors is the effect of solvents. We have described the known solvent effects while providing both general rules and specific examples. We hope this review will not only help fellow researchers understand the known aspects of solvent effects and use that in their experiments, but moreover, we expect that more studies on this topic will be started and continued to expand our understanding of the mechanistic aspects of solvent effects in glycosylation reactions.
Dynamical Analysis and Big Bang Bifurcations of 1D and 2D Gompertz's Growth Functions
Authors: Rocha J. Leonel , Taha Abdel-Kaddous , Fournier-Prunaret D.
Published: October 2016

In this paper, we study the dynamics and bifurcation properties of a three-parameter family of 1D Gompertz's growth functions, which are defined by the population size functions of the Gompertz logistic growth equation. The dynamical behavior is complex leading to a diversified bifurcation structure, leading to the big bang bifurcations of the so-called “box-within-a-box” fractal type. We provide and discuss sufficient conditions for the existence of these bifurcation cascades for 1D Gompertz's growth functions. Moreover, this work concerns the description of some bifurcation properties of a Hénon's map type embedding: a “continuous” embedding of 1D Gompertz's growth functions into a 2D diffeomorphism. More particularly, properties that characterize the big bang bifurcations are considered in relation with this coupling of two population size functions, varying the embedding parameter. The existence of communication areas of crossroad area type or swallowtails are identified for this 2D diffeomorphism.
How Agile Developers Integrate User-Centered Design Into Their Processes: A Literature Review
Authors: Caballero Leydi , Moreno Ana M. , Seffah Ahmed
Published: October 2016

The lack of user engagement, the absence of user feedback, incomplete and continuously changing user requirements are among the critical concerns that cause projects to fail. User-centered design (UCD) and agile software development are two iterative approaches that have been proposed to overcome such concerns. UCD is a design process focusing on user research, user interface design and usability evaluation. Introduced by software engineering practitioners, agile refers to a number of iterative and incremental software development practices that emphasize people’s needs, communication between developers and stakeholders and the ability to adapt to change. In both the agile and UCD communities, however, a full understanding of user requirements is often seen as incompatible with early and quick development iterations. We performed a literature review aiming to identify how agile teams have integrated UCD tools into their agile software development process to a better understanding of the user requirements without losing sight of the agile values and principles. UCD tools adaptations and minimal-up-front design applied in agile development are among the approaches discovered in this study. The findings could lead to a comprehensive user-centric software engineering that will overcome inherent problems faced by agile teams to understand user needs, priorities and goals.
COURSR2: An Integrated Time Management System for Lifelong Learners
Authors: Agnantis Konstantinos , Alexiadis Anastasios , Refanidis Ioannis
Published: October 2016

This article presents COURSR2, an intelligent system aiming at managing the personal time of lifelong learners in an integrated way. Lifelong learners usually try to combine learning with their professional and family duties. Taking in advance informative decisions about whether they have the necessary time resources to devote to a learning object is crucial, both for psychological and for financial reasons. COURSR2 encompasses information for all temporal aspects of a learning object. For example, a course may have lectures, with cardinality constraints over attending them, labs, mid-term exams, final exams, homework, projects and home reading. The user can also represent his non-educational activities, using the general purpose ontology of the SELFPLANNER intelligent calendar application. By subscribing to a learning object through COURSR2, the scheduling engine of SELFPLANNER’s is employed to find viable plans, allowing rescheduling of existing activities. Thus, the learner is able to perform what-if analysis about whether a set of learning objects is compatible with each other, as well as with his other commitments. The latest version of COURSR2 has been deployed and evaluated using real users.
Improved quantum dilation and erosion operations
Authors: Yuan Suzhen , Mao Xia , Chen Lijiang , Wang Xiaofa
Published: October 2016

To reduce the time complexity of quantum morphology operations, two kinds of improved quantum dilation and erosion operations are proposed. Quantum parallelism is well used in the design of these operations. Consequently, the time complexity is greatly reduced compared with the previous quantum dilation and erosion operations. The neighborhood information of each pixel is needed in the process of designing quantum dilation and erosion operations. In order to get the neighborhood information, quantum position shifting transformation is utilized, which can make the neighborhood information store in a quantum image set. In this image set, the neighborhood information of pixel at location ([Formula: see text], [Formula: see text]) is stored at the same location ([Formula: see text], [Formula: see text]) of other images in the image set. All the pixels will be processed simultaneously, which is the performance of quantum parallelism. The time complexity analysis shows that these quantum operations have polynomial-time complexity which is much lower than the exponential-time complexity of the previous version.
Innovation Intermediaries in Technological Alliances
Authors: Weng Calvin S.
Published: October 2016

Technological alliances play an important role in generating innovations but face the challenge of effective matchmaking when finding suitable partners in “open innovation” among networks of innovating firms. Intermediaries refer to those external mechanisms/institutions that can appropriately support companies in their innovation-related activities. They are frequently used to build a bridge between different competency constraints among companies. The purpose of this paper was to try to understand the role of a firm’s alliances within the context of open innovation. What do innovation intermediaries of collaborative partners contribute?

Using the “Strategic Alliance Database” established by the National Science Council (NSC) in Taiwan as a basis, this study empirically explored the brokerage roles in the alliance that intermediaries take on to facilitate technological innovation and an innovation process. By using the technique of two-mode network analysis for social network analysis, this research focused on the question of how a technological alliance creates a platform for firms to execute matchmaking for new and/or relevant partners. The results presented here reveal that brokerage roles can be used to develop collaborations. The strategic position of the intermediary can activate different resources from the ones embedded in an alliance network.
Pathways for Transformation: Disaster Risk Management to Enhance Resilience to Extreme Events
Authors: Gibson T. D. , Pelling M. , Ghosh A. , Matyas D. , Siddiqi A. , Solecki W. , Johnson L. , Kenney C. , Johnston D. , Du Plessis R.
Published: October 2016

Disaster risk from extreme events and development are intimately linked. Disaster risk management influences and is affected by local development strategies. Trade-offs made in policy and implementation determine winners and losers on the basis of unequal capacity, susceptibility and hazard exposure. Transformation has been introduced as a concept opening new policy space for fundamental shifts in development trajectories. Though policy neutral, when combined with normative frameworks such as the Sustainable development goals it can open up leverage points for determining development trajectories. There is limited empirical evidence on which to base understanding of transformative disaster risk management policy though some work has been done in sister domains such as climate change mitigation and adaptation. This study asks whether transformation pathways for disaster risk management can be observed, offering an initial qualitative analysis to inform policy development. It is based on five case studies drawn from diverse locations exposed to a range of extreme events, examined through a conceptual framework offering five indicators of transformation to aid analysis: intense interaction between actors; the intervention of external actors; system level change extending beyond efficiency to governance and goals; behavior beyond established coping strategies; and behavior extending beyond established institutions. Core characteristics of transformative pathways for disaster risk reduction are identified, including pathway competition, pathway experimentation, pathway scale effects and pathway lock-in. These characteristics are seen to determine the extent to which the disruption consequent on extreme events leads to either transformatory change or relative stasis. The study concludes that transformative disaster risk management, both intentional and incidental can be observed. It is seen that transformations occur primarily at local level. Where policy level change occurs this generally played out at local level too. The particular insight of the study is to suggest that most often the burden of transformation is carried at the local level through the behavior of individuals, populations and civil society. This observation raises an important question for further work: How can the burden of undertaking transformation be shared across scales?
Design without a future
Authors: Sayers Jentery
Published: October 2016

This forum highlights conversations at the intersection of design methods and social studies of technology. By highlighting a diversity of perspectives on design interventions and programs, we aim to forge new connections between HCI design and communication, science and technology studies, and media studies scholarship.
--- Daniela Rosner, Editor
Oxyradical stress increases the biosynthesis of 2-arachidonoylglycerol: involvement of NADPH oxidase
Authors: Matthews Anberitha T. , Lee Jung Hwa , Borazjani Abdolsamad , Mangum Lee C. , Hou Xiang , Ross Matthew K.
Published: October 2016

NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-β (DAGL-β), the 2-AG biosynthetic enzyme. To test this idea, we challenged macrophage cell lines and murine primary macrophages with a xanthine oxidase system or with nonphysiological and physiological Nox stimulants [phorbol 12-myristate 13-acetate (PMA) and arachidonic acid (AA)]. Each stressor increased cellular superoxide levels and enhanced 2-AG biosynthetic activity in a Nox-dependent manner. Levels of cytosolic phospholipase A2-dependent AA metabolites (eicosanoids) in primary macrophages were also dependent on Nox-mediated ROS. In addition, 2-AG levels in DAGL-β-overexpressing COS7 cells were attenuated by inhibitors of Nox and DAGL-β. Furthermore, ROS induced by menadione (a redox cycling agent) or PMA could be partially attenuated by the cannabinoid 1/2 receptor agonist (WIN 55,212-2). Finally, cells that overexpress Nox2 components (Phox-COS7) synthesized larger amounts of 2-AG compared with the parental COS7 cells. Together, the results suggest a positive correlation between heightened oxygen radical flux and 2-AG biosynthesis in macrophage cell lines and primary macrophages. Because of the antioxidant and anti-inflammatory effects associated with 2-AG, the increased levels of this bioactive lipid might be an adaptive response to oxidative stress. Thus oxyradical stress may be counteracted by the enhanced endocannabinoid tone.
Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction
Authors: Hirai Daniel M. , Zelt Joel T. , Jones Joshua H. , Castanhas Luiza G. , Bentley Robert F. , Earle Wendy , Staples Patti , Tschakovsky Michael E. , McCans John , O’Donnell Denis E. , Neder J. Alberto
Published: October 2016

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.
Effect of N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan on Opioid Analgesia in Pediatric Intensive Care Unit
Authors: Naeem Mohammed , Al Alem Hala , Al Shehri Ali , Al-Jeraisy Majed
Published: October 2016

Objective. Pain control is an essential goal in the management of critical children. Narcotics are the mainstay for pain control. Patients frequently need escalating doses of narcotics. In such cases an adjunctive therapy may be beneficial. Dextromethorphan (DM) is NMDA receptor antagonist and may prevent tolerance to narcotics; however, its definitive role is still unclear. We sought whether dextromethorphan addition could decrease the requirements of fentanyl to control pain in critical children.Design. Double-blind, randomized control trial (RCT).Setting. Pediatric multidisciplinary ICU in tertiary care center.Patients. Thirty-six pediatric patients 2–14 years of age in a multidisciplinary PICU requiring analgesia were randomized into dextromethorphan and placebo. The subjects in both groups showed similarity in most of the characteristics.Interventions. Subjects while receiving fentanyl for pain control received dextromethorphan or placebo through nasogastric/orogastric tubes for 96 hours. Pain was assessed using FLACC and faces scales.Measurements and Main Results. This study found no statistical significant difference in fentanyl requirements between subjects receiving dextromethorphan and those receiving placebo (p=0.127).Conclusions. Dextromethorphan has no effect on opioid requirement for control of acute pain in children admitted with acute critical care illness in PICU. The registration number for this trial isNCT01553435.
Warm Dark Matter Sterile Neutrinos in Electron Capture and Beta Decay Spectra
Authors: Moreno O. , de Guerra E. Moya , Medrano M. Ramón
Published: October 2016

We briefly review the motivation to search for sterile neutrinos in the keV mass scale, as dark matter candidates, and the prospects to find them in beta decay or electron capture spectra, with a global perspective. We describe the fundamentals of the neutrino flavor-mass eigenstate mismatch that opens the possibility of detecting sterile neutrinos in such ordinary nuclear processes. Results are shown and discussed for the effect of heavy neutrino emission in electron capture in Holmium 163 and in two isotopes of Lead, 202 and 205, as well as in the beta decay of Tritium. We study the deexcitation spectrum in the considered cases of electron capture and the charged lepton spectrum in the case of Tritium beta decay. For each of these cases, we define ratios of integrated transition rates over different regions of the spectrum under study and give new results that may guide and facilitate the analysis of possible future measurements, paying particular attention to forbidden transitions in Lead isotopes.
Association of Tissue Transglutaminase Antibody Titer with Duodenal Histological Changes in Children with Celiac Disease
Authors: Hawamdeh Hasan , Al-Zoubi Basim , Al Sharqi Yasameen , Qasrawi Ayman , Abdelaziz Yousef , Barbar Maha
Published: October 2016

Celiac disease is usually diagnosed by demonstrating gluten enteropathy in small bowel biopsy. Celiac specific antibodies are used as an initial screening test. The goal of this study is to test the relationship of the anti-tTG titer and severity of histological changes in Jordanian children with celiac disease. Method. The medical records of 81 children who had elevated anti-tTG titer and had duodenal biopsies available were retrospectively reviewed. Result. Assessing the association of anti-tTG titer with duodenal histopathological changes, 94% of those with high anti-tTG titer (≥180 U/mL) had histological evidence of celiac disease. There was statistically significant positive association between high anti-tTG titer and Marsh grading as 82% of patients with Marsh III had high anti-tTG titer (Chi2 18.5; P value 0.00; Odds Ratio 8.5). The fraction of patients with Marsh III who were correctly identified as positive by anti-tTG titer ≥ 180 U/mL was high (sensitivity = 81.6). Moreover, the fraction of patients with anti-tTG titer ≥ 180 U/mL who had Marsh III was also high (positive predictive value = 78.4). Conclusion. Anti-tTG titer ≥ 180 U/mL had significant positive association with Marsh III histopathological changes of celiac disease.
Adequate Vitamin D Intake but Low Serum Levels in Pediatric Asthma Patients: A Pilot Study, Alberta Children’s Hospital
Authors: Howe McKenna Sarah , Fenton Tanis R. , Noseworthy Mary , Anselmo Mark
Published: October 2016

Background. We assessed vitamin D intakes and serum 25(OH) vitamin D levels in pediatric asthma patients on moderate-to-high dose inhaled steroids and compared them to published findings of healthy children in our city.Methods. Parents and/or patients were interviewed to estimate the children’s vitamin D intakes from foods and supplements (using an adapted validated food frequency questionnaire) and asthma duration and management. Vitamin D status: serum 25-hyroxy vitamin D (25(OH)D) was obtained from the medical records.Results. Vitamin D intakes from food and supplements of the asthma patients (n=20, 742 ± 185 IU/day) were significantly higher compared to healthy Canadian children (n=1442, 229 ± 121 IU/day). Despite higher vitamin D intakes, the children had nonsignificantly lower serum 25(OH) vitamin D levels compared to the comparison group. Serum 25(OH)D levels increased by 3.6 nmol/L with each 100 IU of vitamin D intake (95% Confidence interval = 2.0–4.0,R2= 0.931, andp=0.001).Conclusion. Since adequate vitamin D status in asthma patients is necessary to support bone mineral accretion, it is important to achieve adequate vitamin D status by checking serum 25(OH)D status and supplement accordingly.
A New Hybrid Approach for Wind Speed Prediction Using Fast Block Least Mean Square Algorithm and Artificial Neural Network
Authors: Filik Ummuhan Basaran
Published: October 2016

A new hybrid wind speed prediction approach, which uses fast block least mean square (FBLMS) algorithm and artificial neural network (ANN) method, is proposed. FBLMS is an adaptive algorithm which has reduced complexity with a very fast convergence rate. A hybrid approach is proposed which uses two powerful methods: FBLMS and ANN method. In order to show the efficiency and accuracy of the proposed approach, seven-year real hourly collected wind speed data sets belonging to Turkish State Meteorological Service of Bozcaada and Eskisehir regions are used. Two different ANN structures are used to compare with this approach. The first six-year data is handled as a train set; the remaining one-year hourly data is handled as test data. Mean absolute error (MAE) and root mean square error (RMSE) are used for performance evaluations. It is shown for various cases that the performance of the new hybrid approach gives better results than the different conventional ANN structure.
Basic Principles and Practical Applications of the Cahn–Hilliard Equation
Authors: Kim Junseok , Lee Seunggyu , Choi Yongho , Lee Seok-Min , Jeong Darae
Published: October 2016

The celebrated Cahn–Hilliard (CH) equation was proposed to model the process of phase separation in binary alloys by Cahn and Hilliard. Since then the equation has been extended to a variety of chemical, physical, biological, and other engineering fields such as spinodal decomposition, diblock copolymer, image inpainting, multiphase fluid flows, microstructures with elastic inhomogeneity, tumor growth simulation, and topology optimization. Therefore, it is important to understand the basic mechanism of the CH equation in each modeling type. In this paper, we review the applications of the CH equation and describe the basic mechanism of each modeling type with helpful references and computational simulation results.
Alox5 Blockade Eradicates JAK2V617F-Induced Polycythemia Vera in Mice
Authors: Chen Yaoyu , Shan Yi , Lu Min , DeSouza Ngoc , Guo Zhiru , Hoffman Ronald , Liang Aibin , Li Shaoguang
Published: October 2016

Myeloproliferative neoplasms such as polycythemia vera (PV), which are associated with the JAK mutation V617F, remain incurable despite progress in the use of JAK2 inhibitors for treatment of some of these diseases. In this study, we employed mice that undergo JAK2V617F-induced PV as a tool to explore new candidate targets for therapy. Our investigations focused on the lipid metabolic enzyme arachidonate 5-lipoxygenase (Alox5), which we found to be strongly upregulated by JAK2V617F in hematopoietic cells in vitro and in vivo. Notably, genetic deletion of Alox5 or its inhibition in mice with a bioactive small-molecule inhibitor was sufficient to attenuate PV development. This therapeutic effect was associated with induction of a blockade in cell-cycle progression and also with apoptosis in PV cells. Genetic loss exerted an inhibitory effect on PV-initiating cells. Similarly, Alox5 inhibition was sufficient to suppress colony formation in human JAK2V617F-expressing CD34+ cells. Mechanistic investigations showed that Alox5 inhibition reduced AKT activation and decreased β-catenin expression in JAK2V617F-expressing cells. Together, our results define Alox5 as a key genetic effector of JAK2V617F in driving PV, and they identify this enzyme as a candidate therapeutic target to treat this refractory myeloproliferative neoplasm. Cancer Res; 77(1); 164–74. ©2016 AACR.
Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality
Authors: Eisfeld Ann-Kathrin , Kohlschmidt Jessica , Mrózek Krzysztof , Volinia Stefano , Blachly James S. , Nicolet Deedra , Oakes Christopher , Kroll Karl , Orwick Shelley , Carroll Andrew J. , Stone Richard M. , Byrd John C. , de la Chapelle Albert , Bloomfield Clara D.
Published: October 2016

Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients ≥60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients ≥60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole -7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. Cancer Res; 77(1); 207–18. ©2016 AACR.
Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer
Authors: Schelhaas Sonja , Held Annelena , Wachsmuth Lydia , Hermann Sven , Honess Davina J. , Heinzmann Kathrin , Smith Donna-Michelle , Griffiths John R. , Faber Cornelius , Jacobs Andreas H.
Published: October 2016

3′-Deoxy-3′-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) and diffusion-weighted MRI (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models, uptake of [18F]FLT was significantly reduced 6 hours after drug administration. On the basis of the gemcitabine concentration and [18F]FLT excretion measured, this was presumably related to a direct competition of gemcitabine with the radiotracer for cellular uptake. On day 1 after therapy, [18F]FLT uptake was increased in both models, which was correlated with thymidine kinase 1 (TK1) expression. Two and 3 days after drug administration, [18F]FLT uptake as well as TK1 and Ki67 expression were unchanged. A reduction in [18F]FLT in the responsive H1975 xenografts could only be noted on day 5 of therapy. Changes in ADCmean in A549 xenografts 1 or 2 days after gemcitabine did not seem to be of therapy-related biological relevance as they were not related to cell death (assessed by caspase-3 IHC and cellular density) or tumor therapy response. Taken together, in these models, early changes of [18F]FLT uptake in tumors reflected mechanisms, such as competing gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected growth-inhibitory effects at a later time point. Hence, the time point for [18F]FLT-PET imaging of tumor response to gemcitabine is of crucial importance. Cancer Res; 76(24); 7096–105. ©2016 AACR.
The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development
Authors: Liu Shuang , Mitra Ramkrishna , Zhao Ming-Ming , Fan Wenhong , Eischen Christine M. , Yin Feng , Zhao Zhongming
Published: October 2016

Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA–mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB–EPHB, p75-mediated signaling, TNFα/NF-κB, and ErbB2/ErbB3 signaling pathways might be altered in glioblastoma. Specifically, lncRNA RAMP2-AS1 had significant decrease of expression in glioblastoma tissues and showed coexpressional relationship with NOTCH3, an important tumor promoter in many neoplastic diseases. Our follow up experiment indicated that (i) an overexpression of RAMP2-AS1 reduced glioblastoma cell proliferation in vitro and also reduced glioblastoma xenograft tumors in vivo; (ii) NOTCH3 and RAMP2-AS1 coexpression rescued the inhibitory action of RAMP2-AS1 in glioblastoma cells; and (iii) RNA pull-down assay revealed a direct interaction of RAMP2-AS1 with DHC10, which may consequently inhibit, as we hypothesize, the expression of NOTCH3 and its downstream signaling molecule HES1 in glioblastoma. Taken together, our data revealed that lncRNA expression profile in glioblastoma tissue was significantly altered; and RAMP2-AS1 might play a tumor suppressive role in glioblastoma through an indirect inhibition of NOTCH3. Our results provided some insights into understanding the key roles of lncRNA–mRNA coregulation in human glioblastoma and the mechanisms responsible for glioblastoma progression and pathogenesis. Mol Cancer Ther; 15(12); 2977–86. ©2016 AACR.
Blood Pressure Reduction is Associated With the Changes in Oxidative Stress and Endothelial Activation in Hypertension, Regardless of Antihypertensive Therapy
Authors: Mihalj Martina , Tadzic Refmir , Vcev Aleksandar , Rucevic Silvija , Drenjancevic Ines
Published: October 2016

Background/Aims: Hypertensive patients present with increased oxidative stress and frequently receive angiotensin II (ANGII) receptor type I blockers (ARB) for blood pressure (BP) reduction. Recent studies revealed an important role of ANGII in maintaining vascular oxidative homeostasis, including sustaining normal sodium dismutase activity. This study aimed to investigate the effects of antihypertensive therapy and also vitamin C/E supplementation on BP, oxidative stress and endothelial activation in patients with essential hypertension. Methods: Newly discovered patients received ARB/olmesartan or the Ca2+-channel blocker (CCB)/amlodipine, and additionally vitamin C/E or placebo throughout weeks 9-16. ELISA was used to determine 8-iso-prostaglendin F2-alpha (8iPGF2α) and endothelial activation markers. Results: In both groups BP was normalized during first 8 weeks of therapy. Vitamins C/E had no additional BP-lowering effect. The vitamins C/E supplementation was not effective in reducing absolute values of 8iPGF2α; however; the magnitude of 8iPGF2α reduction was significantly greater in patients taking vitamins C/E in the CCB group. Although plasma 8iPGF2α positively correlated to BP, a significant decrease occurred during an additional 8 weeks of treatment. There were no changes in endothelial activation markers related to the specific action of ARB or CCB. Conclusions: Present study suggests that observed oxidative stress is a consequence of hypertension. BP reduction is associated with the observed decrease in oxidative stress and changes in endothelial activation regardless of antihypertensive therapy.
Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis
Authors: Piñeiro Gastón J. , Arrizabalaga Pilar , Solé Manel , Abellana Rosa M. , Espinosa Gerard , Cervera Ricard
Published: October 2016

Background: How one responds to treatment of lupus nephritis (LN) is based on clinical features, but the activity in renal biopsy (RB) is uncertain. We have described the therapeutic decisions after performing a repeated RB on the assessment of response to intravenous cyclophosphamide (IC) and the possible prognostic role of this repeated RB. Methods: Clinical, laboratory and histological features at the initial RB and repeated RB were analyzed in 35 patients. Results: Data in the initial versus the repeated RB were serum creatinine 1.23 ± 1.08 and 0.96 ± 0.45 mg/dl (p < 0.05), glomerular filtration rate <60 ml/min in 12 and 5% patients and proteinuria 4.1 ± 2.8 vs. 0.6 1.1 g/day (p < 0.05). Significant differences were detected in hematuria, nephrotic syndrome and serological immune features. Complete renal remission was reached in 60% (n = 21) at the time of the repeated RB, partial remission in 31.4% (n = 11), and no response IC in 8.6% (n = 3). Nine patients showed proliferative forms in the repeated RB, 3 of them had proteinuria <1 g/day. Just after the repeated RB, 34.3% increased or started a new immunosuppressive therapy, 17.1% remained with the same complementary IST, and 14.3% decreased or stopped it. In the follow-up post repeated RB, 34.5% without active lesions showed a renal flare versus 77.8% with active lesions (p = 0.04). The mean time was 120 and 45 months, respectively. Conclusion: A repeated biopsy in LN distinguishes patients in true remission from those in apparent remission. By doing this, we can identify patients who could benefit from intensified treatment and for whom unnecessary treatment methods can be modified or eliminated.
Consumption of alcohol and tobacco in adolescentes
Authors: Rodríguez Puente Linda Azucena , Alonso Castillo Bertha Alicia , Alonso Castillo Marìa Magdalena , Alonso Castillo Marìa Teresa , Armendàriz Garcìa Nora Angèlica , Oliva Rodrìguez Nora Nelly
Published: October 2016

O objetivo foi identificar o consumo de álcool e o tabaco entre os adolescentes. Trata-se de um estudo descritivo e a população foi constituída por 386 indivíduos com 15 a 20 anos de uma escola de ensino médio de Monterrey, Nuevo León. Os participantes responderam a um questionário sociodemográfico e o AUDIT. Os resultados mostram que o número de bebidas consumidas em um dia típico foi de 6 bebidas padrão (DE= 6.6) e consumiu uma média de 2 cigarros por ocasião de beber (DE= 2.4). Índice de bebidas alcoólicas U= 15682; = 4.33 (p= 0.006) e o número de cigarros U= 16197; = 1.01 (p= 0.007) é maior em homens do que em mulheres
Aniba inaequabilis (Lauraceae), a new species from Peru
Authors: MATTA ALYSSON DA , CARVALHO RANGEL BATISTA DE , VICENTINI ALBERTO
Published: October 2016

A new plant species from the Amazon in Peru, Aniba inaequabilis, is here described. The new species belongs to a group of Aniba species that has papillose leaves, but differs from all the species described in this group by the combination of stamens with few sparse hairs, stamens of whorl I and II with different shapes and the glands at the base of the inner stamens fused. In this paper the new species is described and illustrated and its relationship with other species of Aniba with papillose leaves is discussed.
Spelaeonaias gen. nov., a new true-branched cyanobacterium from Cave Vlychada (Diros, Peloponnese, Greece)
Authors: LAMPRINOU VASILIKI , CHRISTODOULOU MARIA , HERNANDEZ-MARINE MARIONA , PARMAKELIS ARISTEIDIS , ECONOMOU-AMILLI ATHENA
Published: October 2016

Based on aspects of the classical LM morphology, and a combination of ultrastructural and molecular data, a new true-branched cyanobacterium, i.e. Spelaeonaias floccida Lamprinou, Christodoulou, Hernández-Mariné et Economou-Amilli, gen. nov. sp. nov., is described from the Greek cave Vlychada (part of the ‘Diros’ cave complex, Peloponnese, Greece). The new monospecific genus bears a Y-like type of branching, intercalary heterocytes and terminal heterocytes at the ensheathed hormogonia, thus morphologically resembling Symphyonemopsis. The subaerophytic growth of the ensheathed hormogonia is considered as the autapomorphic feature for Spelaeonaias. The 16S rRNA sequencing revealed that S. floccida forms a well congruent monophyletic cluster along with two stigonematalean strains SA1301 and SP302 from Maltese catacombs (GenBank: HQ917695 and HQ917696 respectively).
Aspidoglossum albocoronatum (Apocynaceae, Asclepiadoideae), a new species with a remarkable petaloid corona from the northern provinces of South Africa
Authors: BESTER STOFFEL P. , NICHOLAS ASHLEY
Published: October 2016

Aspidoglossum albocoronatum Bester & Nicholas is a unique species from Sekhukhuneland in Mpumalanga and southern Leolo Mountains in Limpopo, South Africa. In morphological character it belongs to the southern African Schizoglossum complex (which includes the genera Aspidoglossum, Schizoglossum s.s. and Miraglossum). A description, line drawings and a comparative table to its related genera are presented.
The Influence of Urban Surface Expansion in China on Regional Climate
Authors: Zhao Deming , Wu Jian
Published: October 2016

Incorporating satellite-based urban surface data for the 1980s, 1990s, 2000s, and 2010s in China, contributions to regional warming, and changes in the precipitation due to urban surface expansion were explored using the nested Fifth-generation Pennsylvania State University–NCAR Mesoscale Model version 3.7 (MM5V3.7) with urban effects considered. The impact on surface air temperature at 2 m (SAT) due to urban surface expansion between the 1980s and the 2010s revealed that annual urban-related warming was lower over East Asia (0.031°C) and China (0.075°C) but higher in eastern China (0.14°C), which experienced dramatic urbanization. Greater warming could be detected over urban surface areas in the three city clusters [Beijing–Tianjin–Hebei (BTH) and the Yangtze and Pearl River deltas (YRD and PRD, respectively)], which reached 1.06°, 0.84°, and 0.92°C, respectively. Urban-related warming was not limited to a single city or city clusters but extended over a SAT-increased belt that covered the eastern coast of China. Further analysis showed that urban-surface-expansion-induced changes in albedo and the total cloud amount contributed to the changes in the radiation budget, which resulted in strong surface radiative forcings in the urban surface (14.5, 11.2, and 11.7 W m−2 for BTH, YRD, and PRD, respectively). However, significant differences could be detected for the transition from nonurban to urban land use compared to those that were classified as urban in both time periods because of the varied albedo changes. The urbanization-related warming, especially in the city cluster areas, also had a further effect on the large-scale circulation and precipitation. The precipitation was weakened in northeastern and northern China but intensified in eastern and southern China, which resulted in the strengthened precipitation over China (0.016 mm day−1, 0.65%) and East Asia (0.011 mm day−1, 0.28%). Therefore, subregional characteristics with marked seasonal, interannual, and decadal variations were detected for the influence of the urban surface expansion.
His or her work–life balance? Experiences of self-employed immigrant parents
Authors: Munkejord Mai Camilla
Published: October 2016

The question of how to achieve ‘work–life balance’ has been a central debate for several decades. Hitherto, this subject has primarily been explored in organizational contexts; less is known in the context of self-employment. This article advances our understanding of work–life balance by analysing the everyday stories of self-employed immigrant parents in Norway. In this study, work–life balance is constructed in contrasting ways between mothers and fathers on the individual level and simultaneously in binary and potentially competing ways on the couple level. Hence, through an analysis of the participants’ work and family availabilities, this study sheds light on how gender relations may be shaped at the micro level within the Nordic dual-earner family model.