bluuebunny/crossref_metadata_2025 huggingface dataset:
Enriching Documents with Examples
Authors: Kim Jinhan , Lee Sanghoon , Hwang Seung-Won , Kim Sunghun
Published: February 2013

Software developers increasingly rely on information from the Web, such as documents or code examples on application programming interfaces (APIs), to facilitate their development processes. However, API documents often do not include enough information for developers to fully understand how to use the APIs, and searching for good code examples requires considerable effort.

To address this problem, we propose a novel code example recommendation system that combines the strength of browsing documents and searching for code examples and returns API documents embedded with high-quality code example summaries mined from the Web. Our evaluation results show that our approach provides code examples with high precision and boosts programmer productivity.
Durability with BookKeeper
Authors: Junqueira Flavio P. , Kelly Ivan , Reed Benjamin
Published: February 2013

Practical systems must often guarantee that changes to the system state are durable. Examples of such systems are databases, file systems, and messaging middleware with guaranteed delivery. One common way of implementing durability while keeping performance high is to use a log to persist updates to the system state. Such systems use the log to reconstruct the system state in the event of a crash. When implementing such a log, if the log is only stored locally, the system state is permanently lost when the server writing the log experiences a permanent hardware failure. BookKeeper is a system that exposes a log abstraction for building high performance, highly available distributed systems. BookKeeper transparently implements replication for high availability and striping for high performance. A Book- Keeper deployment comprises storage servers called bookies, which are designed to serve a large number of concurrent ledgers. BookKeeper is currently an open-source project and is in production use at Yahoo!
Using of Microsilica for Strength Improvement of Fiber Reinforced Cementitious Surface Compounds
Authors: Shebl S. S. , Khalil Ibrahim S. , Shoukry H.
Published: February 2013

This study represents an extension work to investigate the role of ultra fine sand (UFS) in enhancing the mechanical properties of fiber reinforced cementitious compounds. The micro-structural origins were identified by scanning electron microscope (SEM). About 50% of UFS had a diameter of less than 20 μm. Ordinary Portland Cement (OPC) was partially substituted by UFS at 3, 5, 7 and 10% by weight of binder. It was found that as UFS loadings increase, the flexural, compressive, and tensile strengths increased up to about 5% UFS loading by 12.9, 15.7 and 30.1%, respectively, thereafter, a decrease in these properties was observed. This can be attributed to the pozzolanic effect besides the filling effect of UFS resulting in enhancing the interfacial bonds between the sand grains and hydration products that makes the paste more homogeneous and dense. The effect of both short natural and artificial fiber loadings on the structural performance of compounds was also studied. Loadings of 2%, by weight, of short natural date palm leaves’ midribs fibers (DP) and artificial polypropylene fibers (PP) were added to the 5% UFS blended mix. An increase in both flexural and tensile strength was achieved, while a decrease in the compressive strength was observed.
Medical Practices and Attitudes of Dual-Licensed Medical Doctors in Korea
Authors: Ryu Jiseon , Choi Byunghee , Lim Byungmook , Kim Sina , Yun Youngju
Published: February 2013

Unique dual medical system in Korea has resulted in the emergence of dual-licensed medical doctors (DLMDs) who have both traditional Korean medicine (KM) and Western medicine (WM) licenses. There have been few studies on DLMDs in spite of their growing number and importance within the medical system. We surveyed the current status and attitudes of DLMD to assess their role in integrative medicine. Questionnaires were administered to the members of the association of DLMD. Data from 103 DLMD were collected and statistically analyzed. 41.4% of DLMD were copracticing both WM and KM at a single clinic, preferring the WM approach for physical examinations, laboratory tests, and education for patients—and the KM approach for treatment and prescription. Musculoskeletal, gastroenterologic, and allergic diseases were considered to be effectively treated with co-practice. DLMD highly agreed on the efficiency of copractice for disease control and patients’ satisfaction. On the other hand, they regarded the lack of health insurance coverage for copractice and increased medical expenditure as major problems in providing co-practice. To expand the role of DLMD as mediators of integration in primary health care, the effectiveness of their co-practice should be evaluated and a corresponding health insurance reimbursement system should be established.
Ubiquitination of Neurotransmitter Receptors and Postsynaptic Scaffolding Proteins
Authors: Lin Amy W. , Man Heng-Ye
Published: February 2013

The human brain is made up of an extensive network of neurons that communicate by forming specialized connections called synapses. The amount, location, and dynamic turnover of synaptic proteins, including neurotransmitter receptors and synaptic scaffolding molecules, are under complex regulation and play a crucial role in synaptic connectivity and plasticity, as well as in higher brain functions. An increasing number of studies have established ubiquitination and proteasome-mediated degradation as universal mechanisms in the control of synaptic protein homeostasis. In this paper, we focus on the role of the ubiquitin-proteasome system (UPS) in the turnover of major neurotransmitter receptors, including glutamatergic and nonglutamatergic receptors, as well as postsynaptic receptor-interacting proteins.
Structure of Intuitionistic Fuzzy Sets inΓ-Semihyperrings
Authors: Ersoy Bayram Ali , Davvaz Bijan
Published: February 2013

As we know, intuitionistic fuzzy sets are extensions of the standard fuzzy sets. Now, in this paper, the basic definitions and properties of intuitionistic fuzzy Γ-hyperideals of a Γ-semihyperring are introduced. A few examples are presented. In particular, some characterizations of Artinian and Noetherian Γ-semihyperring are given.
New Subclasses of Analytic Functions with Respect to Symmetric and Conjugate Points
Authors: Tang Huo , Deng Guan-Tie
Published: February 2013

We introduce new subclasses of close-to-convex and quasiconvex functions with respect to symmetric and conjugate points. The coefficient estimates for functions belonging to these classes are obtained.
Evaluation of Antioxidant and Wound Healing Potentials ofSphaeranthus amaranthoidesBurm.f.
Authors: Geethalakshmi R. , Sakravarthi C. , Kritika T. , Arul Kirubakaran M. , Sarada D. V. L.
Published: February 2013

Background.Sphaeranthus amaranthoidescommonly known as sivakaranthai is used in folklore medicine for the treatment of skin diseases.Methods. The antioxidant activity of the extract and its fraction was evaluated by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, total antioxidant capacity, and total phenolic content. The tested plant extracts showed variable degrees of antioxidant activity. In the present study, methanolic extract of the whole plant ofS. amaranthoidesand a flavonoid fraction obtained from column chromatography were studied for wound healing activity by incorporating the sample in simple ointment base. Wound healing activity was studied in excision wound model in rats, following which, wound contraction, period of epithelization, hydroxyproline content, and collagen levels in the scab were studied.Results. Methanolic extract showed the highest antioxidant effect (72.05%) and diethyl ether extract has the least (29.34%) compared to the standard (74.53%). Treatment of wound with ointment containing 5% (w/w) methanolic extract and 5% (w/w) flavonoid fraction exhibited better wound healing activity than positive control (silver sulfadiazine). Finally, histopathology studies conformed wound healing activity inSphaeranthus amaranthoides. The methanolic extract and flavonoid fraction exhibited good wound healing activity probably due to the presence of phenolic and flavonoid constituents. The methanolic extract and flavonoid fraction significantly enhanced the rate of wound contraction and the period of epithelialization comparable to silver sulfadiazine.
Optimal Variational Method for Truly Nonlinear Oscillators
Authors: Marinca Vasile , Herişanu Nicolae
Published: February 2013

The Optimal Variational Method (OVM) is introduced and applied for calculating approximate periodic solutions of “truly nonlinear oscillators”. The main advantage of this procedure consists in that it provides a convenient way to control the convergence of approximate solutions in a very rigorous way and allows adjustment of convergence regions where necessary. This approach does not depend upon any small or large parameters. A very good agreement was found between approximate and numerical solution, which proves that OVM is very efficient and accurate.
Epigenetic Influences in the Aetiology of Cancers Arising from Breast and Prostate: A Hypothesised Transgenerational Evolution in Chromatin Accessibility
Authors: Martin Francis L.
Published: February 2013

Epidemiological studies have consistently supported the notion that environmental and/or dietary factors play a central role in the aetiology of cancers of the breast and prostate. However, for more than five decades investigators have failed to identify a single cause-and-effect factor, which could be implicated; identification of a causative entity would allow the implementation of an intervention strategy in at-risk populations. This suggests a more complex pathoaetiology for these cancer sites, compared to others. When one examines the increases or decreases in incidence of specific cancers amongst migrant populations, it is notable that disease arising in colon or stomach requires one or at most two generations to exhibit a change in incidence to match that of high-incidence regions, whereas for breast or prostate cancer, at least three generations are required. This generational threshold could suggest a requirement for nonmutation-driven epigenetic alterations in the F0/F1 generations (parental/offspring adopting a more westernized lifestyle), which then predisposes the inherited genome of subsequent generations to mutagenic/genotoxic alterations leading to the development of sporadic cancer in these target sites. As such, individual susceptibility to carcinogen insult would not be based per se on polymorphisms in activating/detoxifying/repair enzymes, but on elevated accessibility of crucial target genes (e.g., oncogenes, tumour suppressor genes) or hotspots therein to mutation events. This could be termed a genomic susceptibility organizational structure (SOS). Several exposures including alcohol and heavy metals are epigens (i.e., modifiers of the epigenome), whereas others are mutagenic/genotoxic, for example, heterocyclic aromatic amines; humans are continuously and variously exposed to mixtures of these agents. Within such a transgenerational multistage model of cancer development, determining the interaction between epigenetic modification to generate a genomic SOS and genotoxic insult will facilitate a new level of understanding in the aetiology of cancer.
Synthesis, Characterization, and Photocatalytic Activity of N-Doped ZnO/ZnS Composites
Authors: Ma Hongchao , Cheng Xiaohong , Ma Chun , Dong Xiaoli , Zhang Xinxin , Xue Mang , Zhang Xiufang , Fu Yinghuan
Published: February 2013

The aim of the present study is to enhance photocatalytic performance of ZnO semiconductor by comodification with doping of nonmetal ions and coupling with another semiconductor. Therefore, we synthesized the N-doped ZnO/ZnS photocatalysts via a simple heat-treatment approach using L-cysteine as N and S source in this work. Anthraquinone dye (reactive brilliant blue KNR) is employed as the model contaminants to evaluate the photocatalytic activity of as-synthesized samples under sunlight illumination. The N-doped ZnO/ZnS synthesized by this method shows better photocatalytic activity as compared to that of pure ZnO. The enhanced photocatalytic activity of the N-doped ZnO/ZnS composites may be related to the existence of N doping, ZnS/ZnO heterostructure, and covered abundant carbon species on the photocatalyst surface, which causing high absorption efficiency of light, efficient separation of electron-hole pairs, and quick surface reaction in doped ZnO.
Mayer-Rokitansky-Kuster-Hauser Syndrome: Embryology, Genetics and Clinical and Surgical Treatment
Authors: Pizzo Alfonsa , Laganà Antonio Simone , Sturlese Emanuele , Retto Giovanni , Retto Annalisa , De Dominici Rosanna , Puzzolo Domenico
Published: February 2013

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a pathological condition characterized by primary amenorrhea and infertility and by congenital aplasia of the uterus and of the upper vagina. The development of secondary sexual characters is normal as well as that the karyotype (46,XX). Etiologically, this syndrome may be caused by the lack of development of the Müllerian ducts between the fifth and the sixth weeks of gestation. To explain this condition, it has been suggested that in patients with MRKH syndrome, there is a very strong hyperincretion of Müllerian-inhibiting factor (MIF), which would provoke the lack of development of the Müllerian ducts from primitive structures (as what normally occurs in male phenotype). These alterations are commonly associated with renal agenesis or ectopia. Specific mutations of several genes such as WT1, PAX2, HOXA7-HOXA13, PBX1, and WNT4 involved in the earliest stages of embryonic development could play a key role in the etiopathogenesis of this syndrome. Besides, it seems that the other two genes, TCF2 (HNF1B) and LHX1, are involved in the determinism of this pathology. Currently, the most widely nonsurgical used techniques include the “Frank’s dilators method,” while the surgical ones most commonly used are those developed by McIndoe, Williams, Vecchietti, Davydov, and Baldwin.
Preparation of Ultrahigh Potential Gradient of ZnO Varistors by Rare-Earth Doping and Low-Temperature Sintering
Authors: Ke Lei , Hu Ming , Ma Xueming
Published: February 2013

The effects of rare-earth doping and low-temperature sintering on electrical properties of ZnO varistors were investigated. The potential gradient(E1mA)of the ZnO varistors increased significantly to 2247.2 V/mm after doping 0.08 mol% of Y2O3and sintering at 800°C for 2 h. The notable decrease of the grain size with the given experimental conditions was the origin for the increase inE1mA. During the process of high-temperature sintering, both the oxygen at the grain boundary interface and the neutralisation of the ions on the depletion layer were directly reduced, which caused the weight loss and the internal derangement of double Schottky barriers.
Assessing Adipogenic Potential of Mesenchymal Stem Cells: A Rapid Three-Dimensional Culture Screening Technique
Authors: Welter Jean F. , Penick Kitsie J. , Solchaga Luis A.
Published: February 2013

Bone-marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into a number of phenotypes, including adipocytes. Adipogenic differentiation has traditionally been performed in monolayer culture, and, while the expression of a fat-cell phenotype can be achieved, this culture method is labor and material intensive and results in only small numbers of fragile adherent cells, which are not very useful for further applications. Aggregate culture is a cell-culture technique in which cells are induced to form three-dimensional aggregates; this method has previously been used successfully, among others, to induce and study chondrogenic differentiation of MSCs. We have previously published an adaptation of the chondrogenic aggregate culture method to a 96-well plate format. Based on the success of this method, we have used the same format for the preparation of three-dimensional adipogenic cultures. The MSCs differentiate rapidly, the aggregates can be handled and processed for histologic and biochemical assays with ease, and the format offers significant savings in supplies and labor. As a differentiation assay, this method can distinguish between degrees of senescence and appears suitable for testing medium or drug formulations in a high-volume, high-throughput fashion.
Consumption of Chinese Tea‐Flavor Liquor Improves Circulating Insulin Levels without Affecting Hepatic Lipid Metabolism‐Related Gene Expression in Sprague‐Dawley Rats
Authors: Zheng Ju-Sheng , Fu Yuan-Qing , Chen Qi , Huang Tao , Yang Jing , Li Duo
Published: February 2013

Objective. To examine the effect of two Chinese liquors with quite different nonalcoholic components on insulin sensitivity, tissue polyunsaturated fatty acids (PUFA), and hepatic lipid metabolism in SD rats. Methods. Thirty‐three SD rats were randomized into four groups and maintained in each treatment for 10 weeks: Chinese tea‐flavor liquor (TFL, n = 9), traditional Chinese liquor (TCL, n = 8), ethanol control (EC, n = 8), and water control (WC, n = 8). Results. TFL significantly decreased plasma insulin (P = 0.009) and marginally decreased Homeostatic Model Assessment‐Insulin Resistance (HOMA‐IR) (P = 0.05), compared with WC. Hepatic total and n‐6 PUFA compositions were significantly decreased in TFL, TCL, and EC groups compared with WC group (P < 0.05). TFL significantly increased kidney n‐6 PUFA (P = 0.05) and total PUFA (P = 0.039), compared with EC group. EC group showed significant higher gene expressions of acetyl‐CoA carboxylase and steroid response element‐binding protein (1c and 2), while there were no significant differences of these gene expressions in TFL or TCL group compared with WC. Conclusions. TFL has a beneficial effect on metabolic disorder in relation to improved circulating insulin levels without affecting hepatic lipid metabolism‐related gene expressions in rats.
Tumor-Specific Expression of Organic Anion-Transporting Polypeptides: Transporters as Novel Targets for Cancer Therapy
Authors: Buxhofer-Ausch Veronika , Secky Lena , Wlcek Katrin , Svoboda Martin , Kounnis Valentinos , Briasoulis Evangelos , Tzakos Andreas G. , Jaeger Walter , Thalhammer Theresia
Published: February 2013

Members of the organic anion transporter family (OATP) mediate the transmembrane uptake of clinical important drugs and hormones thereby affecting drug disposition and tissue penetration. Particularly OATP subfamily 1 is known to mediate the cellular uptake of anticancer drugs (e.g., methotrexate, derivatives of taxol and camptothecin, flavopiridol, and imatinib). Tissue-specific expression was shown for OATP1B1/OATP1B3 in liver, OATP4C1 in kidney, and OATP6A1 in testis, while other OATPs, for example, OATP4A1, are expressed in multiple cells and organs. Many different tumor entities show an altered expression of OATPs. OATP1B1/OATP1B3 are downregulated in liver tumors, but highly expressed in cancers in the gastrointestinal tract, breast, prostate, and lung. Similarly, testis-specific OATP6A1 is expressed in cancers in the lung, brain, and bladder. Due to their presence in various cancer tissues and their limited expression in normal tissues, OATP1B1, OATP1B3, and OATP6A1 could be a target for tumor immunotherapy. Otherwise, high levels of ubiquitous expressed OATP4A1 are found in colorectal cancers and their metastases. Therefore, this OATP might serve as biomarkers for these tumors. Expression of OATP is regulated by nuclear receptors, inflammatory cytokines, tissue factors, and also posttranslational modifications of the proteins. Through these processes, the distribution of the transporter in the tissue will be altered, and a shift from the plasma membrane to cytoplasmic compartments is possible. It will modify OATP uptake properties and, subsequently, change intracellular concentrations of drugs, hormones, and various other OATP substrates. Therefore, screening tumors for OATP expression before therapy should lead to an OATP-targeted therapy with higher efficacy and decreased side effects.
Antibiotic Resistance and Biofilm Production in Staphylococcus epidermidis Strains, Isolated from a Tertiary Care Hospital in Mexico City
Authors: Cabrera-Contreras Roberto , Morelos-Ramírez Rubén , Galicia-Camacho Ada Nelly , Meléndez-Herrada Enrique
Published: February 2013

Staphylococcus epidermidis strains isolated from nosocomial infections represent a serious problem worldwide. In various Mexican states several reports have shown isolates from hospitals with antibiotic resistance to methicillin. In Mexico City, there is scarce information on staphylococcal infections in hospitals. Here, our research findings are shown in a four-year period study (2006–2010) for Staphylococcus epidermidis strains. Susceptibility and/or resistance to antibiotics in SE strains were assessed by phenotypic and molecular methods as mecA gene by PCR, as well as the correlation with biofilm production for these isolates and the relationship to the infection site. Out of a total of 161 (66%) negative biofilm SE strains, just 103 (64%) SE strains were confirmed as MRSE by PCR to mecA gene. From 84 (34%) positive biofilm SE strains, 76 (91%) were confirmed as MRSE by PCR to mecA gene. Higher percentages of resistance to antibiotics and higher number of resistance markers were found in biofilm-forming clinical strains (9 to 14) than non-biofilm-forming SE strains (3 to 8). These research findings represent a guide to establish infection control programs for this hospital.
Severe Hyponatremia as the Initial Sign Preceding Guillain-Barré Syndrome, an Acute Inflammatory Demyelinating Polyneuropathy: A Case Report
Authors: Kloesel Benjamin , Hickson LaTonya J.
Published: February 2013

Guillain-Barré syndrome is an immune-mediated polyneuropathy that frequently presents with progressive muscle weakness. Hyponatremia has recently been described as a feature of this condition, generally appearing over the course of the illness and following the diagnosis of this demyelinating process. We report a case of Guillain-Barré syndrome presenting with severe hyponatremia that is further exacerbated by intravenous immune globulin therapy. Awareness should be raised for consideration of both Guillain-Barré syndrome and its treatment with intravenous immune globulin therapy as the cause of hyponatremia.
Experimental Study of Ignition over Impact-Driven Supersonic Liquid Fuel Jet
Authors: Matthujak Anirut , Pianthong Kulachate , Takayama Kazuyoshi , Milton B. E.
Published: February 2013

This study experimentally investigates the mechanism of the ignition of the supersonic liquid fuel jet by the visualization. N-Hexadecane having the cetane number of 100 was used as a liquid for the jet in order to enhance the ignition potential of the liquid fuel jet. Moreover, the heat column and the high intensity CO2 laser were applied to initiate the ignition. The ignition over the liquid fuel jet was visualized by a high-speed digital video camera with a shadowgraph system. From the shadowgraph images, the autoignition or ignition of the supersonic liquid fuel jet, at the velocity of 1,186 m/s which is a Mach number relative to the air of 3.41, did not take place. The ignition still did not occur, even though the heat column or the high intensity CO2 laser was alone applied. The attempt to initiate the ignition over the liquid fuel jet was achieved by applying both the heat column and the high intensity CO2 laser. Observing the signs of luminous spots or flames in the shadowgraph would readily indicate the presence of ignitions. The mechanism of the ignition and combustion over the liquid fuel jet was clearly clarified. Moreover, it was found that the ignition over the supersonic liquid fuel jet in this study was rather the force ignition than being the auto-ignition induced by shock wave heating.
Existence Solutions of Vector Equilibrium Problems and Fixed Point of Multivalued Mappings
Authors: Sitthithakerngkiet Kanokwan , Plubtieng Somyot
Published: February 2013

LetKbe a nonempty compact convex subset of a topological vector space. In this paper-sufficient conditions are given for the existence ofx∈Ksuch thatF(T)∩VEP(F)≠∅, whereF(T)is the set of all fixed points of the multivalued mappingTandVEP(F)is the set of all solutions for vector equilibrium problem of the vector-valued mappingF. This leads us to generalize and improve some existence results in the recent references.
A Novel Lightness Localization Algorithm Based on Anchor Nodes Equilateral Triangle Layout in WSNs
Authors: Li Dazhou , Zhao Hai , Zhu Jian , Bi Yuanguo
Published: February 2013

Localization, which determines the geographical locations of sensors, is a crucial issue in wireless sensor networks. In this paper, we propose a novel lightweight equilateral triangle localization algorithm (LETLA) that accurately localizes sensors and minimizes the power consumption. In the LETLA, the approximate coordinates substituted for the real coordinates of the unknown node, and the corresponding optimization problem is formulated to minimize the estimation error. With the sequences that represent the ranking of distances from the anchors to the unknown node, a simple and robust technique is developed to quickly and efficiently estimate a region containing the approximate coordinates, and a condition under which the approximate error can be minimized is given. This condition employs a new geometric construct of anchor layout called equilateral triangle diagrams. Extensive simulations show that the LETLA performs better than other state-of-the-art approaches in terms of energy consumption with the same localization precision.
Using Three‐Dimensional Computational Modeling to Compare the Geometrical Fitness of Two Kinds of Proximal Femoral Intramedullary Nail for Chinese Femur
Authors: Zhang Sheng , Zhang Kairui , Wang Yimin , Feng Wei , Wang Bowei , Yu Bin
Published: February 2013

Objective. The aim of this study was to use three‐dimensional (3D) computational modeling to compare the geometric fitness of these two kinds of proximal femoral intramedullary nails in the Chinese femurs. Computed tomography (CT) scans of a total of 120 normal adult Chinese cadaveric femurs were collected for analysis. With the three‐dimensional (3D) computational technology, the anatomical fitness between the nail and bone was quantified according to the impingement incidence, maximum thicknesses and lengths by which the nail was protruding into the cortex in the virtual bone model, respectively, at the proximal, middle, and distal portions of the implant in the femur. The results showed that PFNA‐II may fit better for the Chinese proximal femurs than InterTan, and the distal portion of InterTan may perform better than that of PFNA‐II; the anatomic fitness of both nails for Chinese patients may not be very satisfactory. As a result, both implants need further modifications to meet the needs of the Chinese population.
EGFR-TKI Resistance Due to BIM Polymorphism Can Be Circumvented in Combination with HDAC Inhibition
Authors: Nakagawa Takayuki , Takeuchi Shinji , Yamada Tadaaki , Ebi Hiromichi , Sano Takako , Nanjo Shigeki , Ishikawa Daisuke , Sato Mitsuo , Hasegawa Yoshinori , Sekido Yoshitaka , Yano Seiji
Published: February 2013

BIM (BCL2L11) is a BH3-only proapoptotic member of the Bcl-2 protein family. BIM upregulation is required for apoptosis induction by EGF receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in EGFR-mutant forms of non–small cell lung cancer (NSCLC). Notably, a BIM deletion polymorphism occurs naturally in 12.9% of East Asian individuals, impairing the generation of the proapoptotic isoform required for the EGFR-TKIs gefitinib and erlotinib and therefore conferring an inherent drug-resistant phenotype. Indeed, patients with NSCLC, who harbored this host BIM polymorphism, exhibited significantly inferior responses to EGFR-TKI treatment than individuals lacking this polymorphism. In an attempt to correct this response defect in the resistant group, we investigated whether the histone deacetylase (HDAC) inhibitor vorinostat could circumvent EGFR-TKI resistance in EGFR-mutant NSCLC cell lines that also harbored the BIM polymorphism. Consistent with our clinical observations, we found that such cells were much less sensitive to gefitinib-induced apoptosis than EGFR-mutant cells, which did not harbor the polymorphism. Notably, vorinostat increased expression in a dose-dependent manner of the proapoptotic BH3 domain-containing isoform of BIM, which was sufficient to restore gefitinib death sensitivity in the EGFR mutant, EGFR-TKI–resistant cells. In xenograft models, while gefitinib induced marked regression via apoptosis of tumors without the BIM polymorphism, its combination with vorinostat was needed to induce marked regression of tumors with the BIM polymorphism in the same manner. Together, our results show how HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI in cases of EGFR-mutant NSCLC where resistance to EGFR-TKI is associated with a common BIM polymorphism. Cancer Res; 73(8); 2428–34. ©2013 AACR.
Proteomic Analysis of Ubiquitin Ligase KEAP1 Reveals Associated Proteins That Inhibit NRF2 Ubiquitination
Authors: Hast Bridgid E. , Goldfarb Dennis , Mulvaney Kathleen M. , Hast Michael A. , Siesser Priscila F. , Yan Feng , Hayes D. Neil , Major Michael B.
Published: February 2013

Somatic mutations in the KEAP1 ubiquitin ligase or its substrate NRF2 (NFE2L2) commonly occur in human cancer, resulting in constitutive NRF2-mediated transcription of cytoprotective genes. However, many tumors display high NRF2 activity in the absence of mutation, supporting the hypothesis that alternative mechanisms of pathway activation exist. Previously, we and others discovered that via a competitive binding mechanism, the proteins WTX (AMER1), PALB2, and SQSTM1 bind KEAP1 to activate NRF2. Proteomic analysis of the KEAP1 protein interaction network revealed a significant enrichment of associated proteins containing an ETGE amino acid motif, which matches the KEAP1 interaction motif found in NRF2. Like WTX, PALB2, and SQSTM1, we found that the dipeptidyl peptidase 3 (DPP3) protein binds KEAP1 via an “ETGE” motif to displace NRF2, thus inhibiting NRF2 ubiquitination and driving NRF2-dependent transcription. Comparing the spectrum of KEAP1-interacting proteins with the genomic profile of 178 squamous cell lung carcinomas characterized by The Cancer Genome Atlas revealed amplification and mRNA overexpression of the DPP3 gene in tumors with high NRF2 activity but lacking NRF2 stabilizing mutations. We further show that tumor-derived mutations in KEAP1 are hypomorphic with respect to NRF2 inhibition and that DPP3 overexpression in the presence of these mutants further promotes NRF2 activation. Collectively, our findings further support the competition model of NRF2 activation and suggest that “ETGE”-containing proteins such as DPP3 contribute to NRF2 activity in cancer. Cancer Res; 73(7); 2199–210. ©2013 AACR.
Predation as a Determinant of Minimum Group Size in Baboons
Authors: Bettridge Caroline M. , Dunbar R.I.M.
Published: February 2013

Predation risk places a pressure on animals to adopt mechanisms by which they reduce their individual risk of being preyed on. However, a consensus on methods of determining predation risk has yet to be reached. One of the most widespread ways in which animals respond to predation risk is by living in groups. Minimum permissible group size is the smallest group size that animals are able to live in, given the habitat-specific predation risk they face. We explore ways in which predation risk can be measured and analyse its effect on minimum observed group size in baboons. Using data on predator density, habitat composition and baboon body size, we investigate the impact of the components of predation risk on baboon group size, and derive an equation that best predicts minimum group size. Minimum group size in baboons is related to predator density and female body mass. Both of these elements can, in turn, be estimated from environmental variables. These findings present support for the argument that group living in primates is a response to predation risk and offer potentially new ways of investigating carnivore and primate ecology.
Early Life Nutritional Programming of Obesity: Mother-Child Cohort Studies
Authors: Symonds Michael E. , Mendez Michelle A. , Meltzer Helle Margrete , Koletzko Berthold , Godfrey Keith , Forsyth Stewart , van der Beek Eline M.
Published: February 2013

Background: The obesity epidemic has resulted in more overweight/obese women before and during pregnancy. Their offspring tend to have higher birth weights and more body fat, and carry an increased risk of obesity later in life. These effects may partly be related to the heightened risk of gestational diabetes, occurring in at least 16% of all pregnancies irrespective of current body weight. Methods: An ILSI Europe workshop reviewed the key contributors leading to adverse outcomes in pregnancy and childhood, including gestational weight gain and nutrition. New research opportunities from prospective mother-child cohort studies were explored. Results: Simple measures of gestational weight gain provide insufficient detail of the underlying physiological and metabolic adaptations occurring in pregnancy, and should be complemented by measures of body composition, metabolic and endocrine responses. Recordings of maternal dietary intake and nutrient status are often limited and potential correlations with gestational weight gain have been poorly studied. Many pregnancies in overweight/obese women are uncomplicated and result in offspring of normal weight, leaving the main determinants of later adverse outcomes to be clarified. Conclusions: The workshop provided insights of primary measurements for the characterization of sustainable nutritional intervention strategies in the mother, infant and child for preventing obesity in later life.
Salvage External Beam Radiotherapy for Recurrent Prostate Adenocarcinoma after High-Intensity Focused Ultrasound as Primary Treatment
Authors: Munoz Fernando , Guarneri Alessia , Botticella Angela , Gabriele Pietro , Moretto Francesco , Panaia Rocco , Ruggieri Andrea , D'Urso Leonardo , Muto Giovanni , Filippi Andrea Riccardo , Ragona Riccardo , Ricardi Umberto
Published: February 2013

Introduction: The main objective was to evaluate feasibility, toxicity and biochemical control rates of salvage external beam radiotherapy (EBRT) in recurrent localized prostate cancer after high-intensity focused ultrasound (HIFU) as primary therapy. Patients and Methods: A total of 24 patients who underwent salvage EBRT after 1 or 2 HIFU sessions and with a minimum post-treatment follow-up of 24 months were retrospectively evaluated. Primary endpoints were toxicity and biochemical disease-free survival (bDFS, defined according to the ASTRO Phoenix definition). Results: Median follow-up was 40.3 months. Gastrointestinal toxicity was low. Acute genitourinary (GU) toxicity grade ≤II rate was 45.8%, with only few patients presenting grade III (8.3%) and grade IV (4.2%) toxicity. Late grade ≥III GU toxicity was registered in 16.7% of patients. The 3-year bDFS rate was 77.8%. Patients achieving a nadir prostate-specific antigen (nPSA) of ≤0.35 ng/ml after EBRT had significantly higher bDFS (3-year bDFS: 87.7 vs. 50%, respectively; p = 0.001). Achieving nPSA ≤0.35 ng/ml was the only factor independently associated to long-term bDFS both on univariate (p = 0.01) and multivariate analysis (HR 7.06, p = 0.039). Conclusions: Salvage EBRT after HIFU failure is feasible and allows to obtain satisfactory biochemical control rates, especially in patients attaining a nPSA ≤0.35 ng/ml after EBRT.
Breaking Haller's Rule: Brain-Body Size Isometry in a Minute Parasitic Wasp
Authors: van der Woude Emma , Smid Hans M. , Chittka Lars , Huigens Martinus E.
Published: February 2013

Throughout the animal kingdom, Haller's rule holds that smaller individuals have larger brains relative to their body than larger-bodied individuals. Such brain-body size allometry is documented for all animals studied to date, ranging from small ants to the largest mammals. However, through experimental induction of natural variation in body size, and 3-D reconstruction of brain and body volume, we here show an isometric brain-body size relationship in adults of one of the smallest insect species on Earth, the parasitic wasp Trichogramma evanescens. The relative brain volume constitutes on average 8.2% of the total body volume. Brain-body size isometry may be typical for the smallest species with a rich behavioural and cognitive repertoire: a further increase in expensive brain tissue relative to body size would be too costly in terms of energy expenditure. This novel brain scaling strategy suggests a hitherto unknown flexibility in neuronal architecture and brain modularity.
Comparison of Short-Term Surgical Outcomes after Single-Incision Laparoscopic versus Multiport Laparoscopic Right Colectomy: A Two-Center, Prospective Case-Controlled Study of 100 Patients
Authors: Velthuis Simone , van den Boezem Peter B. , Lips Daan J. , Prins Hubert A. , Cuesta Miguel A. , Sietses Colin
Published: February 2013

Background: Recent case studies have demonstrated the feasibility of single-incision laparoscopic colectomy (SILC). Few comparative studies for SILC and multiport laparoscopic colectomy (MLC) have been conducted. The aim of this case-controlled study was to compare the short-term surgical outcomes between SILC and MLC for right-sided colectomies. Methods: Between January 2010 and February 2012, data from the first 50 consecutive patients that underwent right SILS at one of the two institutions were compared with a group of 50 consecutive patients that underwent right MLC in the same period. Results: Median operative time was significantly shorter in SILC (97 vs. 112 min; p < 0.001). Between both groups, no statistically significant differences were found regarding number and nature of short-term complications, number of reoperations [4 (8%) vs. 6 (12%)], and mortality rate [1 (2%) vs. 2 (4%)]. Median postoperative hospital stay was 6 days for both groups. Conclusion: SILC is a safe and feasible procedure when performed by experienced laparoscopic surgeons. Length of hospital stay and overall complication rates are comparable with MLC. Until today, no clear advantages of SILC over MLC have been demonstrated. However, due to its smaller incisional trauma, SILC could be a major step in improving cosmetic outcomes.
Longitudinal Analysis of Vascular Function and Biomarkers of Metabolic Bone Disorders before and after Renal Transplantation
Authors: Yilmaz Mahmut Ilker , Sonmez Alper , Saglam Mutlu , Yaman Halil , Kilic Selim , Turker Turker , Unal Hilmi Umut , Gok Mahmut , Cetinkaya Hakki , Eyileten Tayfun , Oguz Yusuf , Caglar Kayser , Vural Abdulgaffar , Mallamaci Francesca , Zoccali Carmine
Published: February 2013

Background/Aims: The role of chronic kidney disease-mineral bone disorder (CKD-MBD) reversibility in the amelioration of vascular function and in the reduction of the risk for cardiovascular events after renal transplantation is still unknown. Methods: We investigated the longitudinal relationship between the main biomarkers of CKD-MBD and the evolution of vascular function [flow-mediated dilatation (FMD)] after transplantation in a series of 161 patients with kidney failure maintained on chronic dialysis (5D-CKD). Results: Before transplantation, FMD in patients was markedly lower (–40%, p < 0.001) than in well-matched healthy subjects and increased by 27% after transplantation (p = 0.001). Fibroblast growth factor 23 (FGF23), 25-hydroxy-vitamin D (25OHVD) and serum phosphate (p < 0.01) were independently associated with simultaneous changes in FMD. Changes in classical risk factors and in risk factors related to CKD like the glomerular filtration rate, serum albumin, C-reactive protein and insulin resistance failed to independently explain the variability in FMD changes after transplantation. Conclusion: Endothelium-dependent vasodilatation improves after kidney transplantation, which is parallel to the dramatic fall in FGF23, the reduction in serum phosphorus and the increase in 25OHVD levels. If these associations are causal, a part of decline in cardiovascular risk after transplantation is related to partial resolution of CKD-MBD.
Dystonia in a Patient with Melanoma Metastatic to the Brain Treated with High-Dose Interleukin-2, Radiation Therapy, and Levetiracetam
Authors: Sreenivasan Varun , Dudek Arkadiusz Z.
Published: February 2013

Dystonia has been described as a potential toxicity of radiation therapy. Management of this rare movement disorder is targeted in symptom improvement. We report a case of a 46-year-old female patient who developed dystonia during treatment of melanoma metastatic to the brain and discuss potential causes of and therapies for this rare complication.
Seasonal Blood Pressure Changes
Authors: Modesti Pietro Amedeo , Morabito Marco , Massetti Luciano , Rapi Stefano , Orlandini Simone , Mancia Giuseppe , Gensini Gian Franco , Parati Gianfranco
Published: February 2013

Seasonal blood pressure (BP) changes have been found to be related to either outdoor or indoor temperature. No information regarding the independent effects of temperature measured proximally to the patient, the personal-level environmental temperature (PET), is available. Inclusion of daylight hours in multivariate analysis might allow exploring the independent interaction of BP with seasonality. To investigate whether ambulatory BP monitoring is affected by PET or by seasonality, 1897 patients referred to our hypertension units underwent ambulatory BP monitoring with a battery-powered temperature data logger fitted to the carrying pouch of the monitor. Predictors of 24-hour daytime and nighttime BP and of morning BP surge were investigated with a multivariate stepwise regression model, including age, sex, body mass index, antihypertensive treatment, office BP, ambulatory heart rate, PET, relative humidity, atmospheric pressure, and daylight hours as independent variables. At adjusted regression analysis, daytime systolic BP was negatively related to PET (−0.14; 95% confidence interval, −0.25 to −0.02); nighttime BP was positively related to daylight hours (0.63; 0.37–0.90); and morning BP surge was negatively related to daylight hours (−0.54; −0.87 to −0.21). These results provide new evidence that PET and seasonality (daylight hours) are 2 independent predictors of ambulatory BP monitoring.
Teinobasis fatakula sp. nov. (Zygoptera: Coenagrionidae), found on ‘Eua Island, Kingdom of Tonga
Authors: MARINOV MILEN , DONNELLY THOMAS
Published: February 2013

A recent study of the 'Eua Island in the Kingdom of Tonga has yielded a small Odonata fauna including the new species Teinobasis fatakula (Holotype ♂: Kingdom of Tonga, ‘Eua Island, 21.3781o S, 174.9346o W, elevation 175 m; 14 July 2012, M. Marinov leg.). Because 'Eua has aquatic habitats unique within the Kingdom of Tonga, the new species is very likely endemic to that island and represents an extension of the verified range of the genus of at least 2800 km.
Global organizational communities of practice: The effects of nationality diversity, psychological safety, and media richness on community performance
Authors: Kirkman Bradley L , Cordery John L , Mathieu John , Rosen Benson , Kukenberger Michael
Published: February 2013

Organizational communities of practice (OCoPs) are used increasingly to capitalize on valuable distributed knowledge and to fully engage the innovation potential of employees. OCoPs have become increasingly global in their reach, relying of necessity on virtual forms of interaction to engage the participation and expertise of a global workforce. An unanswered question is whether the performance of such global OCoPs may be predicted to benefit or suffer owing to their nationality diversity. Using data from over 200 members of 30 global OCoPs in a Fortune 100 US-based multinational mining and minerals processing firm, we found that nationality diversity was curvilinearly (U-shaped) related to community performance. We also found that the curvilinear relationship was moderated by psychological safety and the extent of rich communication media use. Specifically, the arc relating nationality diversity and performance became more positive at the higher end, and less negative at the lower end, to the extent that communities reported higher psychological safety and richer communication media use.
Real-Time Warning Signs of Emerging and Collapsing Chinese House Price Bubbles
Authors: Chen Xi , Funke Michael
Published: February 2013

The recent increase in Chinese house prices has led to concerns that China is vulnerable to asset price shocks. In this paper, we apply recently developed recursive unit root tests to spot the beginning and the end of potential speculative bubbles in Chinese house price cycles. Overall, we find that except for 2009–10 actual house prices are not significantly disconnected from fundamentals. Thus, the evidence for speculative house price bubbles in China is in general weak.
Effect of halloysite nanotubes on curing behavior, mechanical, and microstructural properties of acrylonitrile–butadiene rubber nanocomposites
Authors: Ismail Hanafi , Ahmad Hazwani Syaza
Published: February 2013

Halloysite nanotubes (HNTs) have been used as a new type of filler for acrylonitrile–butadiene rubber (NBR) matrix. The NBR/HNT nanocomposites were prepared using a two-roll mill by adding 0–7 parts per hundred rubber (phr) HNTs, and the effect of the loading of HNTs on the curing behavior, mechanical, and microstructural properties were also investigated in this study. The cure characteristics showed that the cure time ( t90) and scorch time ( ts2) decreased, whereas the maximum torque ( MH) exhibited an increasing trend from 0 to 7 phr. The tensile properties improved until optimum loading of HNTs (5 phr) and thermal stability increased with increasing HNT loading. The morphological study revealed the HNTs homogeneously dispersed inside the NBR matrix and good interaction occurred between HNTs and NBR.
Extraverts Engage in More Interpersonal Citizenship When Motivated to Impression Manage
Authors: Chiaburu Dan S. , Stoverink Adam C. , Li Ning , Zhang Xin-an
Published: February 2013

Extraversion has exhibited inconsistent relationships with employees’ interpersonal citizenship. Across three studies, we integrate literature on personality with impression management and socioanalytic theories to propose that employees’ impression management motives act as a contingency, strengthening the relationship between extraversion and interpersonal citizenship. First, in Studies 1 and 2, across two settings (field and university) and two designs (nonexperimental and experimental), we confirm that extraverted individuals engage in citizenship to a greater extent when they are also either predisposed (Study 1) or cued (Study 2) to manage others’ impressions. In Study 3, we extend these findings by using a conditional mediation process model to develop and test the hypothesis that an individual’s strategy to get along serves as an explanatory mechanism to the interactive effect of extraversion and impression management motives on interpersonal citizenship. Overall, our results suggest that the prediction of interpersonal citizenship can be improved when considering the conjoint influence of employees’ extraversion and impression management motives.