bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational photography comes into focus
Authors: Greengard Samuel
Published: January 2014

Advances in computational photography are making image capture the starting point. The technology is transforming the field.
Should
everybody
learn to code?
Authors: Shein Esther
Published: January 2014

Not everyone needs coding skills, but learning how to think like a programmer can be useful in many disciplines.
Clarifying human-computer interaction
Authors: Guo Philip
Published: January 2014

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Philip Guo teaches an undergrad through the use of examples.
Mars code
Authors: Holzmann Gerard J.
Published: January 2014

Redundant software (and hardware) ensured Curiosity reached its destination and functioned as its designers intended.
Report on the SIGIR 2013 workshop on modeling user behavior for information retrieval evaluation (MUBE 2013)
Authors: Clarke Charles L.A. , Freund Luanne , Smucker Mark D. , Yilmaz Emine
Published: January 2014

The SIGIR 2013 Workshop on Modeling User Behavior of Information Retrieval Evaluation brought together researchers interested in improving Cranfield-style evaluation of information retrieval through the modeling of user behavior. The workshop included two invited talks, ten short paper presentations, and breakout groups. Workshop participants brainstormed research questions of interest and formed breakout groups to explore these questions in greater depth. In addition to summarizing the invited talks and presentations, this report details the results of the breakout groups, which provide a set of research directions for the improvement of information retrieval evaluation.
Report on the SIGIR 2013 workshop on health search and discovery
Authors: White Ryen W. , Yom-Tov Elad , Horvitz Eric , Agichtein Eugene , Hersh William
Published: January 2014

The workshop brought together 40 researchers and practitioners from academia and industry to discuss search and discovery in the medical domain. Presentations and discussions spanned several challenging and important topics, including directions improving the accessibility of medical and health information for lay people (with associated enhancements to result ranking algorithms and search interfaces), and methods for discovering biomedical phenomena from the information that people seek online, as evidenced in query streams and other sources such as social and news media. A thread throughout the workshop was the opportunity for new methods and applications to enhance the quality of life of people suffering from medical disorders, carry out surveillance of emerging diseases and other threats, and, more generally, to improve the health and well-being of people via tools to support their health-related information behavior.
Report on the workshop on web archiving and digital libraries (WADL 2013)
Authors: Fox Edward A. , Farag Mohamed M.
Published: January 2014

This workshop explored the integration of Web archiving and digital libraries, so the complete life cycle involved is covered, from creation/authoring, uploading/publishing in the Web (including Web 2.0), (focused) crawling, curation, indexing, exploration (including searching and browsing), (text) analysis, archiving, and up through long-term preservation. It included particular coverage of current topics of interest: challenges facing archiving initiatives, archiving related to disasters, interaction with and use of archive data, applications on an international scale, working with big data, mobile Web archiving, temporal issues, Memento, and SiteStory.
Cryptography miracles, secure auctions, matching problem verification
Authors: Micali Silvio , Rabin Michael O.
Published: January 2014

A solution to the persistent problem of preventing collusion in Vickrey auctions.
The Role of Transforming Growth Factor-Beta in Diabetic Nephropathy
Authors: Braga Gomes Karina , Fontana Rodrigues Kathryna , Fernandes Ana Paula
Published: January 2014

Several studies have demonstrated that chronic and low-grade inflammation is closely linked to type 2 diabetes mellitus. The associated mechanisms are related to synthesis and release of proinflammatory and anti-inflammatory cytokines, mainly by the adipose tissue. Moreover, there are evidences that cytokines and adhesion molecules are important for development of diabetic nephropathy. Among the cytokines associated with inflammatory responses in type 2 diabetes mellitus, the transforming growth factor-β (TGF-β) has been recognized as a central player in the diabetic nephropathy being involved in the development of glomerulosclerosis and interstitial fibrosis, as observed in the course of end-stage renal disease. Although TGF-β1 is classically an anti-inflammatory immune mediator it has been shown that in the presence of IL-6, which increases before the onset of T2D, TGF-β1 favors the differentiation of T helper 17 (Th17) cells that are activated in many pro-inflammatory conditions. Since TGF-β1 mRNA and consequently serum TGF-β1 levels are under genetic control, this review aims to discuss the relationship of TGF-β1 levels and polymorphisms in the development of nephropathy in type 2 diabetes mellitus.
Residual HEMA and TEGDMA Release and Cytotoxicity Evaluation of Resin-Modified Glass Ionomer Cement and Compomers Cured with Different Light Sources
Authors: Botsali Murat Selim , Kuşgöz Adem , Altintaş Subutay Han , Ülker Hayriye Esra , Tanriver Mehmet , Kiliç Serdar , Başak Feridun , Ülker Mustafa
Published: January 2014

The purpose of this study was first to evaluate the elution of 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) monomers from resin-modified glass ionomer cement (RMGIC) and compomers cured with halogen and light-emitting diode (LED) light-curing units (LCUs). The effect of cured materials on the viability of L929 fibroblast cells was also evaluated. One RMGIC (Ketac N100) and two compomers (Dyract Extra and Twinkystar) were tested. Materials were prepared in teflon disks and light-cured with LED or halogen LCUs. The residual monomers of resin materials in solution were identified using high-performance liquid chromatography. The fibroblast cells’ viability was analyzed using MTT assay. The type of LCU did not have a significant effect on the elution of HEMA and TEGDMA. A greater amount of HEMA than TEGMDA was eluted. The amount of TEGDMA eluted from Twinkystar was greater than Dyract Extra (P<0.05) when cured with a halogen LCU. All material-LCU combinations decreased the fibroblast cells’ viability more than the control group (P<0.01), except for Dyract Extra cured with a halogen LCU (P>0.05). Curing with the LED LCU decreased the cells’ viability more than curing with the halogen LCU for compomers. For Ketac N100, the halogen LCU decreased the cells’ viability more than the LED LCU.
Diverse Effects of Lead Nitrate on the Proliferation, Differentiation, and Gene Expression of Stem Cells Isolated from a Dental Origin
Authors: Abdullah Mariam , Rahman Fazliny Abd. , Gnanasegaran Nareshwaran , Govindasamy Vijayendran , Abu Kasim Noor Hayaty , Musa Sabri
Published: January 2014

Lead (Pb2+) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb2+toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb2+concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb2+on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb2+treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb2+continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb2+exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.
Drug Resistance Mechanisms ofMycoplasma pneumoniaeto Macrolide Antibiotics
Authors: Liu Xijie , Jiang Yue , Chen Xiaogeng , Li Jing , Shi Dawei , Xin Deli
Published: January 2014

Throat swabs from children with suspectedMycoplasma pneumoniae(M. pneumoniae) infection were cultured for the presence ofM. pneumoniaeand its species specificity using the 16S rRNA gene. Seventy-sixM. pneumoniaestrains isolated from 580 swabs showed that 70 were erythromycin resistant with minimum inhibitory concentrations (MIC) around 32–512 mg/L. FiftyM. pneumoniaestrains (46 resistant, 4 sensitive) were tested for sensitivity to tetracycline, ciprofloxacin, and gentamicin. Tetracycline and ciprofloxacin had some effect, and gentamicin had an effect on the majority ofM. pneumoniaestrains. Domains II and V of the 23S rRNA gene and the ribosomal protein L4 and L22 genes, both of which are considered to be associated with macrolide resistance, were sequenced and the sequences were compared with the corresponding sequences in M129 registered with NCBI and the FH strain. The 70 resistant strains all showed a 2063 or 2064 site mutation in domain V of the 23S rRNA but no mutations in domain II. Site mutations of L4 or L22 can be observed in either resistant or sensitive strains, although it is not known whether this is associated with drug resistance.
Mortality in Levodopa-Treated Parkinson's Disease
Authors: Morgan John C. , Currie Lillian J. , Harrison Madaline B. , Bennett James P. , Trugman Joel M. , Wooten G. Frederick
Published: January 2014

Parkinson’s disease (PD) is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960’s, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers. We undertook this retrospective study of 211 deceased PD patients to determine the factors associated with mortality in levodopa-treated PD. Our findings confirm that PD is associated with increased mortality in both men and women. Unlike the majority of other mortality studies, we found that women have a greater reduction in lifespan compared to men. We also found that patients with early onset PD (onset at the age of 50 or before) have reduced survival relative to PD patients with later ages of onset. A final important finding is that survival is equal in PD patients treated with levodopa early (within 2 years or less of PD onset) versus later.
Automorphisms of Ordinary Differential Equations
Authors: Tryhuk Václav , Chrastinová Veronika
Published: January 2014

The paper deals with the local theory of internal symmetries of underdetermined systems of ordinary differential equations in full generality. The symmetries need not preserve the choice of the independent variable, the hierarchy of dependent variables, and the order of derivatives. Internal approach to the symmetries of one-dimensional constrained variational integrals is moreover proposed without the use of multipliers.
Carotid Intima Media Thickness Is Independently Associated with Male Gender, Middle Age, and IGF-1 in Metabolically Healthy Obese Individuals
Authors: Abd El-Hafez Hala , Elrakhawy Mohamed M. , El-Baiomy Azza A. , El-Eshmawy Mervat M.
Published: January 2014

Background/Aims. The effect of benign obesity on subclinical cardiovascular disease is still questionable. The purpose of this study was to assess carotid intima media thickness (CIMT), as a marker of subclinical atherosclerosis, and to evaluate its relation to age, sex, and IGF-1 in metabolically healthy obese (MHO) subjects. Methods. A total of 75 MHO subjects and 80 age, and sex matched healthy nonobese control subjects were included in the study. Body mass index (BMI), waist circumference (WC), blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, lipid profile, insulin like growth factor-1 (IGF-1), and CIMT were assessed in all subjects. Results. MHO subjects had significantly higher CIMT and lower IGF-1 than healthy nonobese controls. Mean CIMT was significantly higher in MHO men age subgroup range from 30 to 50 years than in their age range matched (premenopausal) MHO women subgroup. In MHO subjects, CIMT was positively correlated with age, BMI, WC, SBP, HOMA-IR, TG, and LDL-C, and negatively correlated with IGF-1. Regression analysis revealed that middle age, male sex and IGF-1 remained independently associated with CIMT in MHO subjects. Conclusion. CIMT is elevated and IGF-1 is reduced in MHO subjects, and CIMT is independently associated with male gender, middle age, and IGF-1. Definition of healthy obesity may be broadened to include IMT measurement.
The Association of Long-Functioning Hemodialysis Vascular Access with Prevalence of Left Ventricular Hypertrophy in Kidney Transplant Recipients
Authors: Kolonko Aureliusz , Kujawa-Szewieczek Agata , Szotowska Magdalena , Kuczera Piotr , Chudek Jerzy , Więcek Andrzej
Published: January 2014

Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%,P=0.02). OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76),P=0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.
Some Convergence and Stability Results for Two New Kirk Type Hybrid Fixed Point Iterative Algorithms
Authors: Gürsoy Faik , Karakaya Vatan
Published: January 2014

We introduce Kirk-multistep-SP and Kirk-S iterative algorithms and we prove some convergence and stability results for these iterative algorithms. Since these iterative algorithms are more general than some other iterative algorithms in the existing literature, our results generalize and unify some other results in the literature.
Knowledge of Acne among Medical Students: Pretest and Posttest Assessment
Authors: Shivaswamy Kanakapura Nanjundaswamy , Shyamprasad Arakali Lakshminarayana , Sumathy Tharayil Kunneth , Ranganathan Chandrashekaran , Kumar Shanmugan Praveen
Published: January 2014

Background. Acne vulgaris is a disorder of sebaceous glands mainly affecting the adolescent population. There are some misconceptions about acne not only in the general population but also among the medical students. Methods. Second year medical undergraduate students attending dermatology postings for the first time were included in the study. A questionnaire (in yes or no answer format) with 20 questions on acne, each carrying one mark, was to be answered by the students. The students were categorized into 4 grades based on the marks obtained: Grade I 90% marks and above, Grade II 75%–90%, Grade III 50%–74%, and Grade IV <50% marks obtained. Results. Of the 144 students of the batch, 95 (69.5%) completed both pretest and posttest questionnaires. The average pretest score was 14.1 and that of the posttest was 16.9. The percentage of improvement in mean score from pretest to posttest was 16.5. Fischer’s exact test was applied to analyze the improvement in scores between pretest and posttests which is significant at P=0.015 (P<0.05). In the paired t-test the improvement in mean scores between pretest and posttest was significant at P<0.001.
A Comparison of the South African and United States Models of Natural Areas Management
Authors: Licht Daniel S. , Kenner Brian C. , Roddy Daniel E.
Published: January 2014

In May-June of 2013 we visited several South African parks and reserves to learn about wildlife and natural areas management in that country. We focused our visit on parks and reserves that are of moderate size (5,000–100,00 ha), comprised of grassland/savanna habitats, located within agrarian landscapes, and enclosed with boundary fences, characteristics similar to several parks and reserves in the Northern Great Plains region of the United States. In this paper we compare the South African model of natural areas management to the United States model. We observed that South African parks and reserves with the aforementioned characteristics are more likely to (1) reintroduce and conserve small, nonviable wildlife populations, (2) reintroduce and conserve top-level predators, (3) have more intensive management of wildlife, (4) manage in partnership across multiple landowners, (5) engage local communities, (6) be self-funding, and (7) restrict visitor movement. The South African model is arguably more effective in conserving biodiversity as measured by conservation of apex predators and natural processes. The differences between the countries appear to be driven in large part by socioeconomic factors. Knowledge of natural areas management in other countries may lead to more innovative and creative models that could benefit biodiversity conservation.
Lifestyle Factors in Hypertension Drug Research: Systematic Analysis of Articles in a Leading Cochrane Report
Authors: Wilson Dan E. , Van Vlack Tashina , Schievink Brendin P. , Doak Eric B. , Shane Jason S. , Dean Elizabeth
Published: January 2014

Established standards for first-line hypertension management include lifestyle modification and behavior change. The degree to which and how lifestyle modification is systematically integrated into studies of first-line drug management for hypertension is of methodological and clinical relevance. This study systematically reviewed the methodology of articles from a recent Cochrane review that had been designed to inform first-line medical treatment of hypertension and was representative of high quality established clinical trials in the field. Source articles(n=34)were systematically reviewed for lifestyle interventions including smoking cessation, diet, weight loss, physical activity and exercise, stress reduction, and moderate alcohol consumption. 54% of articles did not mention lifestyle modification; 46% contained nonspecific descriptions of interventions. We contend that hypertension management research trials (including drug studies) need to elucidate the benefits and risks of drug-lifestyle interaction, to support the priority of lifestyle modification, and that lifestyle modification, rather than drugs, is seen by patients and the public as a priority for health professionals. The inclusion of lifestyle modification strategies in research designs for hypertension drug trials could enhance current research, from trial efficacy to clinical outcome effectiveness, and align hypertension best practices of a range of health professionals with evidence-based knowledge translation.
Arbuscular Mycorrhizal Colonization Enhanced Early Growth ofMallotus paniculatusandAlbizia samanunder Nursery Conditions in East Kalimantan, Indonesia
Authors: Wulandari Dewi , Saridi  , Cheng Weiguo , Tawaraya Keitaro
Published: January 2014

Forest over logging, forest fire, forest conversion, and opencast mining have promoted deforestation in Indonesia, and reforestation is needed immediately. However, reforestation is limited by low seedling quality and production, and slow seedling growth in nurseries. Native tropical tree and fast-growing species,Mallotus paniculatusandAlbizia saman, are potential to promote the first rotation of reforestation. Arbuscular mycorrhizal (AM) fungi are known to promote nutrient uptake and plant growth. We examined the effects of two native AM fungi,Gigaspora decipiensandGlomus clarum, on the growth ofM. paniculatusandA. samanseedlings under nursery conditions. At harvest, after six months, we determined AM colonization, shoot dry weight, and shoot N and P concentration. Approximately 90% and 50% ofM. paniculatusandA. samanroots, respectively, were colonized by AM fungi, without any difference between the inoculation treatments.G. decipiensandG. clarumincreased shoot height, leaf number, shoot dry weight, and shoot N and P uptake of both species. A positive correlation was observed between N and P uptake and shoot dry weight. These results suggest that AM fungi are effective in accelerating nutrient uptake and plant growth, which will, in turn, promote reforestation and sustainable forest timber production.
OnF-AlgebrasMp  (1<p<∞)of Holomorphic Functions
Authors: Meštrović Romeo
Published: January 2014

We consider the classesMp (1<p<∞)of holomorphic functions on the open unit disk𝔻in the complex plane. These classes are in fact generalizations of the classMintroduced by Kim (1986). The spaceMpequipped with the topology given by the metricρpdefined byρp(f,g)=f-gp=∫02π‍logp1+Mf-gθdθ/2π1/p, withf,g∈MpandMfθ=sup0⩽r<1⁡f(reiθ), becomes anF-space. By a result of Stoll (1977), the Privalov spaceNp (1<p<∞)with the topology given by the Stoll metricdpis anF-algebra. By using these two facts, we prove that the spacesMpandNpcoincide and have the same topological structure. Consequently, we describe a general form of continuous linear functionals onMp(with respect to the metricρp). Furthermore, we give a characterization of bounded subsets of the spacesMp. Moreover, we give the examples of bounded subsets ofMpthat are not relatively compact.
Effects of Direction and Index of Difficulty on Aiming Movements after Stroke
Authors: Ribeiro Coqueiro Paola , de Freitas Sandra Maria Sbeghen Ferreira , Assunção e Silva Cassandra Mendes , Alouche Sandra Regina
Published: January 2014

Background.Brain hemispheres play different roles in the control of aiming movements that are impaired after unilateral stroke. It is not clear whether those roles are influenced by the direction and the difficulty of the task.Objective.To evaluate the influence of direction and index of difficulty (ID) of the task on performance of ipsilesional aiming movements after unilateral stroke.Methods.Ten individuals with right hemisphere stroke, ten with left hemisphere stroke, and ten age- and gender-matched controls performed the aiming movements on a digitizing tablet as fast as possible. Stroke individuals used their ipsilesional arm. The direction (ipsilateral or contralateral), size (0.8 or 1.6 cm), and distance (9 or 18 cm) of the targets, presented on a monitor, were manipulated and determined to be of different ID (3.5, 4.5, and 5.5).Results.Individuals with right hemisphere lesion were more sensitive to ID of the task, affecting planning and final position accuracy. Left hemisphere lesion generated slower and less smooth movements and was more influenced by target distance. Contralateral movements and higher ID increased planning demands and hindered movement execution.Conclusion.Right and left hemisphere damages are differentially influenced by task constraints which suggest their complementary roles in the control of aiming movements.
Inclusion of Management Desirability and Risk in Service FMEA-Based Corrective Action Selection Methodology
Authors: Sutrisno Agung , Lee Tzong Ru (Jiun Shen) , Kwon Hyuck Moo
Published: January 2014

When selecting competing corrective actions on FMEA, decision makers may have a different desirability to target a certain improvement goal. Besides, once the corrective actions have been implemented, there may exist a considerable degree of risk due to the possible uncertainties of the outcome. This paper attempts to present FMEA-based corrective action prioritization, incorporating both management desirability and implementation relevant risk into the model. To reflect team desirability and risk attitude in estimating the attractiveness of corrective actions, the Derringer desirability and risk aversion factor are used. An illustrative example is provided to demonstrate the applicability of the proposed model.
New Strategies in Lung Cancer: Translating Immunotherapy into Clinical Practice
Authors: Forde Patrick M. , Kelly Ronan J. , Brahmer Julie R.
Published: January 2014

Recent breakthroughs in translating the early development of immunomodulatory antibodies into the clinic, notably with the anti–cytotoxic T-lymphocyte antigen-4 antibody, ipilimumab, have led to durable benefits and prolonged survival for a subgroup of patients with advanced melanoma. Subsequent studies have shown that related immune checkpoint antibodies, specifically those targeting the programmed death-1 pathway, have activity in non–small cell lung cancer. Non–small cell lung cancer is the commonest cause of cancer death worldwide and this exciting avenue of clinical investigation carries with it great promise and new challenges. In this article, we discuss recent developments in lung cancer immunotherapy, reviewing recent findings from therapeutic vaccine studies and in particular we focus on the refinement of immunomodulation as a therapeutic strategy in this challenging disease. Clin Cancer Res; 20(5); 1067–73. ©2014 AACR.
Phase Ib Study of Buparlisib plus Trastuzumab in Patients with HER2-Positive Advanced or Metastatic Breast Cancer That Has Progressed on Trastuzumab-Based Therapy
Authors: Saura Cristina , Bendell Johanna , Jerusalem Guy , Su Shaun , Ru Qinhua , De Buck Stefan , Mills David , Ruquet Sophie , Bosch Ana , Urruticoechea Ander , Beck Joseph T. , Di Tomaso Emmanuelle , Sternberg David W. , Massacesi Cristian , Hirawat Samit , Dirix Luc , Baselga Jose
Published: January 2014

Purpose: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2+) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose of this study was to determine the clinical activity of the PI3K inhibitor buparlisib (BKM120) in patients with HER2+ advanced/metastatic breast cancer resistant to trastuzumab-based therapy.

Experimental Design: In the dose-escalation portion of this phase I/II study, patients with trastuzumab-resistant locally advanced or metastatic HER2+ breast cancer were treated with daily oral doses of buparlisib and weekly intravenous trastuzumab (2 mg/kg). Dose escalation was guided by a Bayesian logistic regression model with overdose control.

Results: Of 18 enrolled patients, 17 received buparlisib. One dose-limiting toxicity of grade 3 general weakness was reported at the 100-mg/day dose level (the single-agent maximum tolerated dose) and this dose level was declared the recommended phase II dose (RP2D) of buparlisib in combination with trastuzumab. Common (>25%) adverse events included rash (39%), hyperglycemia (33%), and diarrhea (28%). The pharmacokinetic profile of buparlisib was not affected by its combination with trastuzumab. At the RP2D, there were two (17%) partial responses, 7 (58%) patients had stable disease (≥6 weeks), and the disease control rate was 75%. Pharmacodynamic studies showed inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways.

Conclusions: In this patient population, the combination of buparlisib and trastuzumab was well tolerated, and preliminary signs of clinical activity were observed. The phase II portion of this study will further explore the safety and efficacy of this combination at the RP2D. Clin Cancer Res; 20(7); 1935–45. ©2014 AACR.
RNA Helicase A Is a Downstream Mediator of KIF1Bβ Tumor-Suppressor Function in Neuroblastoma
Authors: Chen Zhi Xiong , Wallis Karin , Fell Stuart M. , Sobrado Veronica R. , Hemmer Marie C. , Ramsköld Daniel , Hellman Ulf , Sandberg Rickard , Kenchappa Rajappa S. , Martinson Tommy , Johnsen John I. , Kogner Per , Schlisio Susanne
Published: January 2014

Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis.

Significance: KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation. Cancer Discov; 4(4); 434–51. ©2014 AACR.

See related commentary by Bernards, p. 392

This article is highlighted in the In This Issue feature, p. 377
Is There an Appropriate Cutoff Age for Sampling the Endometrium in Premenopausal Bleeding?
Authors: Corbacioglu Esmer Aytul , Akbayir Ozgur , Goksedef Behiye Pinar Cilesiz , Gunduz Nermin , Kisacık Songul , Dagdeviren Hediye , Guraslan Birgul , Ark Cemal
Published: January 2014

Aim: To determine a cutoff age for endometrial evaluation in premenopausal abnormal uterine bleeding (AUB). Methods: Histopathology reports of endometrial sampling performed due to AUB in women aged 50 years or less were reviewed retrospectively. Histopathological findings were categorized into three groups as follows: group 1: hyperplasia without atypia + hyperplasia with atypia + malignancy, group 2: hyperplasia with atypia + malignancy, and group 3: malignancy. Results: Data from 2,516 patients were analyzed for this study. Overall, 13.5% of patients had endometrial hyperplasia without atypia, 1% of patients had hyperplasia with atypia and 0.6% of patients had malignant disease. Logistic regression revealed a significant difference in the odds ratios of group 1 in the age ranges of 40-45 and 45-50 years compared with <40 years (p = 0.001 and p = 0.01, respectively). There were no significant differences between the age groups for the odds ratio of group 2 and group 3. Conclusion: There is no cutoff age for sampling the endometrium in order to detect hyperplasia with atypia and cancer in premenopausal women with AUB. Therefore, the management of AUB should be tailored to each patient regardless of age, incorporating all risk factors for malignant disease.
Impact of S-Adenosylmethionine Decarboxylase 1 on Pulmonary Vascular Remodeling
Authors: Weisel Friederike Christine , Kloepping Christina , Pichl Alexandra , Sydykov Akylbek , Kojonazarov Baktybek , Wilhelm Jochen , Roth Markus , Ridge Karen Marie , Igarashi Kazuei , Nishimura Kazuhiro , Maison Wolfgang , Wackendorff Claudia , Klepetko Walter , Jaksch Peter , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Seeger Werner , Schermuly Ralph Theo , Weissmann Norbert , Kwapiszewska Grazyna
Published: January 2014

Background—

Pulmonary hypertension (PH) is a life-threatening disease characterized by vascular remodeling and increased pulmonary vascular resistance. Chronic alveolar hypoxia in animals is often used to decipher pathways being regulated in PH. Here, we aimed to investigate whether chronic hypoxia–induced PH in mice can be reversed by reoxygenation and whether possible regression can be used to identify pathways activated during the reversal and development of PH by genome-wide screening.

Methods and Results—

Mice exposed to chronic hypoxia (21 days, 10% O
2
) were reoxygenated for up to 42 days. Full reversal of PH during reoxygenation was evident by normalized right ventricular pressure, right heart hypertrophy, and muscularization of small pulmonary vessels. Microarray analysis from these mice revealed s-adenosylmethionine decarboxylase 1 (AMD-1) as one of the most downregulated genes. In situ hybridization localized AMD-1 in pulmonary vessels. AMD-1 silencing decreased the proliferation of pulmonary arterial smooth muscle cells and diminished phospholipase Cγ1 phosphorylation. Compared with the respective controls, AMD-1 depletion by heterozygous in vivo knockout or pharmacological inhibition attenuated PH during chronic hypoxia. A detailed molecular approach including promoter analysis showed that AMD-1 could be regulated by early growth response 1, transcription factor, as a consequence of epidermal growth factor stimulation. Key findings from the animal model were confirmed in human idiopathic pulmonary arterial hypertension.

Conclusions—

Our study indicates that genome-wide screening in mice from a PH model in which full reversal of PH occurs can be useful to identify potential key candidates for the reversal and development of PH. Targeting AMD-1 may represent a promising strategy for PH therapy.
Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation
Authors: Dörr Oliver , Liebetrau Christoph , Möllmann Helge , Lorenz Jakob , Gaede Luise , Troidl Christian , Rixe Johannes , Hamm Christian , Nef Holger
Published: January 2014

Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (
P
<0.001) as were ICAM-1 (
P
<0.001) and VCAM-1 levels (
P
<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718–0.921;
P
<0.001), 0.754 (0.654–0.854;
P
<0.001), and 0.684 (0.564–804;
P
=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation.
Bulbophyllum cherrapunjeensis (Orchidaceae), a new species from Meghalaya, India
Authors: Verma Durgesh , Barbhuiya Hussain Ahmed , Lavania Seshu
Published: January 2014

Bulbophyllum Petit-Thouars (1822: tab. 3) is the largest orchid genus, comprising about 1900 species, largely distributed in tropical areas of both New and Old Worlds (Chen & Vermeulen 2009). There are about 100 species in India and about 63 in northeastern India (Augustine et al 2001, Misra 2007). Kataki (1986) reported 28 species of Bulbophyllum from the state of Meghalaya. During our botanical exploration to Cherrapunjee, Meghalaya, in July 2013, we found a new species described below.
Updated list and community structure of Tettigonioidea and Acridoidea (Insecta: Orthoptera) of the Alta Murgia plateau (Italy)
Authors: LABADESSA ROCCO
Published: January 2014

Alta Murgia calcareous plateau (southeast Italy) is thought to represent one of the most important area for Orthoptera in southern Italy, both due to its biogeographical concern and its unique richness in semi-natural dry grasslands. Since the half of the last century, no recent synthesis has been proposed for the Orthopterofauna of this area and a revision of old observations was still needed. This paper propose a reviewed list of Tettigonioidea and Acridoidea species from the Alta Murgia plateau, also providing information on local community structure and ecology. Based on the revision of previously published lists of species and on data collected during recent field works, a number of 37 species of grasshoppers and katydids is reported. The majority of species found in literature were confirmed, and six species were recorded as new for the area. Data collected during recent field works also enable to provide information about community structure, with particular focus on grassland habitat. This study also gives suggestions for replicable monitoring of Orthoptera assemblages in this area, as it is a valuable information for habitat surveillance purposes and ecosystem conservation strategies.
Cyrtodactylus khelangensis, a new cave-dwelling Bent-toed Gecko (Squamata: Gekkonidae) from Lampang Province, northern Thailand
Authors: PAUWELS OLIVIER S. G. , SUMONTHA MONTRI , PANITVONG NONN , VARAGUTTANONDA VARAWUT
Published: January 2014

We describe Cyrtodactylus khelangensis sp. nov. from a limestone cave in Pratu Pha, Mae Mo District, Lampang Province, northern Thailand. It is characterized by a maximal known SVL of 95.3 mm; 16–20 longitudinal rows of dorsal tubercles; a continuous series of 37–40 enlarged femoroprecloacal scales, including six-seven pitted or pore-bearing scales (males) or one or two pitted scales (females) on each femur separated by a diastema from 2–6 pore-bearing precloacal scales (males and females); no precloacal groove nor depression; transversely enlarged subcaudal scales; and four irregular brown dorsal bands between nuchal loop and hind limb insertions.
Circulation and Modification of Warm Deep Water on the Central Amundsen Shelf
Authors: Ha H. K. , Wåhlin A. K. , Kim T. W. , Lee S. H. , Lee J. H. , Lee H. J. , Hong C. S. , Arneborg L. , Björk G. , Kalén O.
Published: January 2014

The circulation pathways and subsurface cooling and freshening of warm deep water on the central Amundsen Sea shelf are deduced from hydrographic transects and four subsurface moorings. The Amundsen Sea continental shelf is intersected by the Dotson trough (DT), leading from the outer shelf to the deep basins on the inner shelf. During the measurement period, warm deep water was observed to flow southward on the eastern side of DT in approximate geostrophic balance. A northward outflow from the shelf was also observed along the bottom in the western side of DT. Estimates of the flow rate suggest that up to one-third of the inflowing warm deep water leaves the shelf area below the thermocline in this deep outflow. The deep current was 1.2°C colder and 0.3 psu fresher than the inflow, but still warm, salty, and dense compared to the overlying water mass. The temperature and salinity properties suggest that the cooling and freshening process is induced by subsurface melting of glacial ice, possibly from basal melting of Dotson and Getz ice shelves. New heat budgets are presented, with a southward oceanic heat transport of 3.3 TW on the eastern side of the DT, a northward oceanic heat transport of 0.5–1.6 TW on the western side, and an ocean-to-glacier heat flux of 0.9–2.53 TW, equivalent to melting glacial ice at the rate of 83–237 km3 yr−1. Recent satellite-based estimates of basal melt rates for the glaciers suggest comparable values for the Getz and Dotson ice shelves.
Ponatinib efficiently kills imatinib-resistant chronic eosinophilic leukemia cells harboring gatekeeper mutant T674I FIP1L1-PDGFRα: roles of Mcl-1 and β-catenin
Authors: Jin Yanli , Ding Ke , Li Honglin , Xue Mengzhu , Shi Xiaoke , Wang Chengyan , Pan Jingxuan
Published: January 2014

Background

T674I FIP1L1-PDGFRα in a subset of chronic eosinophilic leukemia (CEL) is a gatekeeper mutation that is resistant to many tyrosine kinase inhibitors (TKIs) (e.g., imatinib, nilotinib and dasatinib), similar to T315I Bcr-Abl. Therefore, novel TKIs effective against T674I FIP1L1-PDGFRα are needed. Ponatinib (AP24534) is a novel orally bioavailable TKI against T315I Bcr-Abl, but it is not clear whether ponatinib is effective against T674I FIP1L1-PDGFRα. The purpose of this study was to examine the effect of ponatinib on T674I FIP1L1-PDGFRα.

Methods

Molecular docking analysis in silico was performed. The effects of ponatinib on PDGFRα signaling pathways, apoptosis and cell cycling were examined in EOL-1, BaF3 cells expressing either wild type (WT) or T674I FIP1L1-PDGFRα. The in vivo antitumor activity of ponatinib was evaluated with xenografted BaF3-T674I FIP1L1-PDGFRα cells in nude mice models.

Results

Molecular docking analysis revealed that ponatinib could bind to the DFG (Asp-Phe-Gly)-out state of T674I PDGFRα. Ponatinib potently inhibited the phosphorylation of WT and T674I FIP1L1-PDGFRα and their downstream signaling molecules (e.g., Stat3, Stat5). Ponatinib strikingly inhibited the growth of both WT and T674I FIP1L1-PDGFRα-carrying CEL cells (IC50: 0.004–2.5 nM). It induced apoptosis in CEL cells with caspase-3-dependent cleavage of Mcl-1, and inhibited tyrosine phosphorylation of β-catenin to decrease its stability and pro-survival functions. In vivo, ponatinib abrogated the growth of xenografted BaF3-T674I FIP1L1-PDGFRα cells in nude mice.

Conclusions

Ponatinib is a pan-FIP1L1-PDGFRα inhibitor, and clinical trials are warranted to investigate its efficacy in imatinib-resistant CEL.
What are the effects of agricultural management on soil organic carbon (SOC) stocks?
Authors: Söderström Bo , Hedlund Katarina , Jackson Louise E , Kätterer Thomas , Lugato Emanuele , Thomsen Ingrid K , Bracht Jørgensen Helene
Published: January 2014

Background

Changes in soil organic carbon (SOC) stocks significantly influence the atmospheric C concentration. Agricultural management practices that increase SOC stocks thus may have profound effects on climate mitigation. Additional benefits include higher soil fertility since increased SOC stocks improve the physical and biological properties of the soil. Intensification of agriculture and land-use change from grasslands to croplands are generally known to deplete SOC stocks. The depletion is exacerbated through agricultural practices with low return of organic material and various mechanisms, such as oxidation/mineralization, leaching and erosion. However, a systematic review comparing the efficacy of different agricultural management practices to increase SOC stocks has not yet been produced. Since there are diverging views on this matter, a systematic review would be timely for framing policies not only nationally in Sweden, but also internationally, for promoting long-term sustainable management of soils and mitigating climate change.

Methods

The systematic review will examine how changes in SOC are affected by a range of soil-management practices relating to tillage management, addition of crop residues, manure or other organic “wastes”, and different crop rotation schemes. Within the warm temperate and the snow climate zones, agricultural management systems in which wheat, barley, rye, oats, silage maize or oilseed rape can grow in the crop rotation will be selected. The review will exclusively focus on studies conducted over at least 10 years. Searches will be made in 15 publication databases as well as in specialist databases. Articles found will be screened using inclusion/exclusion criteria at title, abstract and full-text levels, and screening consistency will be evaluated using Kappa tests. Data from articles that remain after critical appraisal will be extracted using a predefined spreadsheet. Subgroup analyses will be undertaken to elucidate statistical relationships that are specific to particular type of management interventions. Meta-regression within subgroups will be performed as well as sensitivity analysis to investigate the impact of removing groups of studies with low or unclear quality.
Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants
Authors: Brooks Brandon , Firek Brian A , Miller Christopher S , Sharon Itai , Thomas Brian C , Baker Robyn , Morowitz Michael J , Banfield Jillian F
Published: January 2014

Background

The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life.

Results

Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed ‘expectation maximization iterative reconstruction of genes from the environment’ (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment.

Conclusions

We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut.