bluuebunny/crossref_metadata_2025 huggingface dataset:
SUPREME LOCAL LYAPUNOV EXPONENTS AND CHAOTIC IMPULSIVE SYNCHRONIZATION
Authors: CHEN SHENGYAO , XI FENG , LIU ZHONG
Published: October 2013

Impulsively synchronized chaos with criterion from conditional Lyapunov exponent is often interrupted by desynchronized bursts. This is because the Lyapunov exponent cannot characterize local instability of synchronized attractor. To predict the possibility of the local instability, we introduce a concept of supreme local Lyapunov exponent (SLLE), which is defined as supremum of local Lyapunov exponents over the attractor. The SLLE is independent of the system trajectories and therefore, can characterize the extreme expansion behavior in all local regions with prescribed finite-time interval. It is shown that the impulsively synchronized chaos can be kept forever if the largest SLLE of error dynamical systems is negative and then the burst behavior will not appear. In addition, the impulsive synchronization with negative SLLE allows large synchronizable impulsive interval, which is significant for applications.
A CLASS OF FRACTIONAL BROWNIAN FIELDS FROM BRANCHING SYSTEMS AND THEIR REGULARITY PROPERTIES
Authors: LI YUQIANG , XIAO YIMIN
Published: October 2013

In this paper, the smoothness and exact modulus of continuity of a class of fractional Brownian fields are studied. These Gaussian random fields satisfy a kind of operator-scaling property and, depending on the choice of their parameters, may share similar fractal properties as those of fractional Brownian sheets or may be smooth in some (or all) directions. It is proved that these Gaussian random fields satisfy the property of sectorial local nondeterminism which is useful for further studying their sample path properties. In addition, the link between these Gaussian random fields and the functional fluctuation limits of branching particle systems is studied.
ON A SYSTEM OF MEASUREMENTS WHICH IS COMPLETE IN A STATISTICAL SENSE
Authors: KOMISARSKI ANDRZEJ , PASZKIEWICZ ADAM
Published: October 2013

We show that if H = ℂd then there exists a system of d + 1 measurements which allows to recover an unknown state ρ on H from the probabilities of results of these measurements. Moreover, we show that a randomly chosen system of d + 1 measurements has the above property with probability 1. We also present some novel properties of known mutually unbiased bases.
A NEW METHOD TO MEASURE EFFICIENCY IN PARALLEL PRODUCTION SYSTEMS WITH SHARED SOURCES IN NATURAL LIFE
Authors: KORDROSTAMI S. , BIJARKANI Z. BAKHODA
Published: October 2013

A few models in data envelopment analysis (DEA) have been proposed to evaluate performance of production systems which are composed of independent parallel production units. In this paper, we have developed a parallel DEA model for production systems which are composed of independent parallel subunits, so that each subunit uses its own inputs and a portion of the shared inputs to produce final outputs. Also, we will propose the models to calculate the efficiency of the whole system along with the efficiencies of its subunits. In addition to theoretical derivations, a case of 25 areas of Iran's Bank is used as an example to illustrate the whole idea.
AN IMPROVED COURNOT COMPETITION MODEL: CONSIDERATION OF MARKET SHARE OBJECTIVE
Authors: LI TONGYANG
Published: October 2013

Cournot competition model calculates profit by company's product quantity, but it does not take market share objective into consideration. It has obstacles of considering nonlinear aspects because the partial derivative equations are very hard to solve. Our algorithm both improves Cournot's model with consideration of market share ratio, and avoids the difficulty of solving several partial derivative equations directly. In our algorithm, we give a parameter σ to describe a company's consideration of market share objective, formulate the competition between companies, and calculate new market share ratio using parameter σ. We consider two network structures in our model: complete graph network and star graph network. For complete graph network, our calculation and numerical analysis is based on the case of 3 companies, but the result for general number of companies, n, is also discussed. We give a series of numerical results of new market share ratio after given the initial market share ratio and the parameter σ, and show that the initial market share ratio and new market share ratio are highly linear. Another important property in this network is the convergence of market share ratio when n goes to infinity. For star graph network, we give calculation for general cases and show that n = 3, 4 are the only numbers of companies that have positive increase of the market share ratio of the company.
Target DNA detection and quantitation on a single cell with single base resolution
Authors: Konry Tania , Lerner Adam , Yarmush Martin L. , Smolina Irina V.
Published: October 2013

In this report, we present a new method for sensitive detection of short DNA sites in single cells with single base resolution. The method combines peptide nucleic acid (PNA) openers as the tagging probes, together with isothermal rolling circle amplification (RCA) and fluorescence-based detection, all performed in a cells-in-flow format. Bis-PNAs provide single base resolution, while RCA ensures linear signal amplification. We applied this method to detect the oncoviral DNA inserts in cancer cell lines using a flow-cytometry system. We also demonstrated quantitative detection of the selected signature sites within single cells in microfluidic nano-liter droplets. Our results show single-nucleotide polymorphism (SNP) discrimination and detection of copy-number variations (CNV) under isothermal non-denaturing conditions. This new method is ideal for many applications in which ultra-sensitive DNA characterization with single base resolution is desired on the level of single cells.
Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction
Authors: Sheffer-Babila Sharone , Sun Yan , Israel Davelene D. , Liu Shun-Mei , Neal-Perry Genevieve , Chua Streamson C.
Published: October 2013

Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant ( Lepr db/db ) females result in restoration of fertility and lactation despite the persistence of obesity and insulin resistance. The overarching hypothesis in the present study is that the absence or reduction of leptin's inhibition of AGRP/NPY neurons leads to suppression of GnRH release in cases of leptin signaling deficiency. Since TAC2 (NKB)-TAC3R signaling plays a role in puberty maturation and is modulated by metabolic status, the other aim of this study is to test whether TAC2/NKB neurons in ARC regulated by melanocortinergic signals herein affect leptin's action on puberty and reproduction. Our data showed that AGRP deficiency in Lepr db/db females restores normal timing of vaginal opening and estrous cycling, although uterine weight gain and mammary gland development are morphologically delayed. Nonetheless, Agrp−/− Lepr db/db females are fertile and sustain adequate nutrition of pups with lactation to weaning age. AGRP deficiency results in advanced vaginal opening in wild-type female mice. The postpubertal increase in hypothalamic TAC2 mRNA was not observed in Lepr db/db females, whereas AGRP deficiency restored it in Lepr db/ db females. Additionally, MC4R activation with MTII induced FOS expression in TAC2 neurons, supporting the concept of melanocortinergic regulation of TAC2 neurons. These studies suggest that AGRP imposes an inhibitory effect on puberty and that TAC2 neurons may transmit melanocortinergic inhibition of GnRH neurons.
Divergent compensatory responses to high-fat diet between C57BL6/J and C57BLKS/J inbred mouse strains
Authors: Sims Emily K. , Hatanaka Masayuki , Morris David L. , Tersey Sarah A. , Kono Tatsuyoshi , Chaudry Zunaira Z. , Day Kathleen H. , Moss Dan R. , Stull Natalie D. , Mirmira Raghavendra G. , Evans-Molina Carmella
Published: October 2013

Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to diet- and genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18% kcal from fat), high-fat diet (HFD; 42% kcal from fat), or HFD supplemented with the PPARγ agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment.
Canthaxanthin Retinopathy with Visual Loss: A Case Report and Review
Authors: Beaulieu Robert A. , Warwar Ronald E. , Buerk Bruce M.
Published: October 2013

Canthaxanthin is a naturally occurring chemical, which is most commonly utilized as a colorant for food and dyes or a skin bronzing agent. Its most prevalent impact on human health is canthaxanthin retinopathy, which appears as birefringent, yellow to red crystals surrounding the macula. This occurs with increasing, dose-dependent exposure. Generally, patients remain asymptomatic and findings may only be evident on funduscopic examination. Cessation of canthaxanthin ingestion appears to reverse the retinopathy, but the time until crystal disappearance is variable. Despite a usually favorable outcome, long-standing visual changes may occur. We report a case of an 84-year-old woman with significant visual loss secondary to canthaxanthin retinopathy that ultimately improved upon cessation of the drug.
Modelling of Hybrid Materials and Interface Defects through Homogenization Approach for the Prediction of Effective Thermal Conductivity of FRP Composites Using Finite Element Method
Authors: Mahesh C. , Govindarajulu K. , Balakrishna Murthy V.
Published: October 2013

Finite element method is effectively used to homogenize the thermal conductivity of FRP composites consisting of hybrid materials and fibre-matrix debonds at some of the fibres. The homogenized result at microlevel is used to determine the property of the layer using macromechanics principles; thereby, it is possible to minimize the computational efforts required to solve the problem as in state through only micromechanics approach. The working of the proposed procedure is verified for three different problems: (i) hybrid composite having two different fibres in alternate layers, (ii) fibre-matrix interface debond in alternate layers, and (iii) fibre-matrix interface debond at one fibre in a group of four fibres in one unit cell. It is observed that the results are in good agreement with those obtained through pure micro-mechanics approach.
NSOM/QD-Based Visualization of GM1 Serving as Platforms for TCR/CD3 Mediated T-Cell Activation
Authors: Zhong Liyun , Zhang Zhun , Lu Xiaoxu , Liu Shengde , Chen Crystal Y. , Chen Zheng W.
Published: October 2013

Direct molecular imaging of nanoscale relationship between T-cell receptor complexes (TCR/CD3) and gangliosidosis GM1 before and after T-cell activation has not been reported. In this study, we made use of our expertise of near-field scanning optical microscopy(NSOM)/immune-labeling quantum dots- (QD-)based dual-color imaging system to visualize nanoscale profiles for distribution and organization of TCR/CD3, GM1, as well as their nanospatial relationship and their correlation with PKCθsignaling cascade during T-cell activation. Interestingly, after anti-CD3/anti-CD28 Ab co-stimulation, both TCR/CD3 and GM1 were clustered to form nanodomains; moreover, all of TCR/CD3 nanodomains were colocalized with GM1 nanodomains, indicating that the formation of GM1 nanodomains was greatly correlated with TCR/CD3 mediated signaling. Specially, while T-cells were pretreated with PKCθsignaling inhibitor rottlerin to suppress IL-2 cytokine production, no visible TCR/CD3 nanodomains appeared while a lot of GM1 nanodomains were still observed. However, while T-cells are pretreated with PKCαβsignaling inhibitor GÖ6976 to suppress calcium-dependent manner, all of TCR/CD3 nanodomains were still colocalized with GM1 nanodomains. These findings possibly support the notion that the formation of GM1 nanodomains indeed serves as platforms for the recruitment of TCR/CD3 nanodomains, and TCR/CD3 nanodomains are required for PKCθsignaling cascades and T-cell activation
Trends of Dust Transport Episodes in Cyprus Using a Classification of Synoptic Types Established with Artificial Neural Networks
Authors: Michaelides S. , Tymvios F. , Athanasatos S. , Papadakis M.
Published: October 2013

The relationship between dust episodes over Cyprus and specific synoptic patterns has long been considered but also further supported in recent studies by the authors. Having defined a dust episode as a day when the average PM10 measurement exceeds the threshold of 50 mg/(m3 day), the authors have utilized Artificial Neural Networks and synoptic charts, together with satellite and ground measurements, in order to establish a scheme which links specific synoptic patterns with the appearance of dust transport over Cyprus. In an effort to understand better these complicated synoptic-scale phenomena and their associations with dust transport episodes, the authors attempt in the present paper a followup of the previous tasks with the objective to further investigate dust episodes from the point of view of their time trends. The results have shown a tendency for the synoptic situations favoring dust events to increase in the last decades, whereas, the synoptic situations not favoring such events tend to decrease with time.
Near Infrared Lateral Photovoltaic Effect in LaTiO3Films
Authors: Jin Wujun , Zhang Shasha , Ni Hao , Xiang Wenfeng , Xi Jianfeng , Feng Xin , Zhao Kun
Published: October 2013

We have reported on the lateral photovoltaic effect of LaTiO3films epitaxially grown on (100) SrTiO3substrates. Under illumination of continuous 1064 nm laser beam on the LaTiO3film through SrTiO3substrate, the open-circuit photovoltage depended linearly on the illuminated position. The photosensitivity can be modified by bias current. These results indicated that the LaTiO3films give rise to a potentially photoelectronic device for near infrared position-sensitive detection.
Obesity and the Endometrium: Adipocyte-Secreted Proinflammatory TNFαCytokine Enhances the Proliferation of Human Endometrial Glandular Cells
Authors: Nair Sangeeta , Nguyen HoVan , Salama Salama , Al-Hendy Ayman
Published: October 2013

Obesity, a state of chronic inflammation, is associated with poor fertility and low implantation rates and is a well-documented risk factor for endometrial cancer. Adipokines, such as tumor necrosis factor alpha, play an important role in initiation of endometrial cancer. The aim of this study is to evaluatein vitroeffects of human adipocyte cells (SW872) on growth of endometrial glandular epithelial cells (EGE).Methods.We measured cell proliferation and expression of cell-growth proteins—proliferating cell nuclear antigen, cyclin D1, cyclin-dependent kinase-1, and apoptotic markers (BCL-2 and BAK) in human EGE cells cocultured with SW872 cells. EGE cells were also evaluated in SW872-conditioned media neutralized with anti-TNFαantibody.Results.A significant increase in EGE cell proliferation was observed in both SW872-conditioned media and in coculture (P<0.05). We observed an upregulation of proliferation markers PCNA, cyclin D1, CDK-1, and BCL-2 and decrease in BAK (P<0.05). Neutralization of SW872-conditioned media using anti-TNFαantibodies reversed EGE cell proliferation as indicated by BCL-2 expression.Conclusions.Adipocytes have potent proliferative paracrine effect on EGE cells which may be, in part, mediated via TNFα. Further understanding of the role of obesity in endometrial carcinogenesis should lead to better preventative and therapeutic strategies.
Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis
Authors: Tabata Taku , Kamisawa Terumi , Kuruma Sawako , Chiba Kazuro , Iwasaki Susumu , Kuwata Go , Fujiwara Takashi , Egashira Hideto , Koizumi Satomi , Endo Yuka , Koizumi Koichi , Fujiwara Junko , Arakawa Takeo , Momma Kumiko
Published: October 2013

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC.
Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach
Authors: Rodríguez-Cruz Maricela , Coral-Vázquez Ramón M. , Hernández-Stengele Gabriel , Sánchez Raúl , Salazar Emmanuel , Sanchez-Muñoz Fausto , Encarnación-Guevara Sergio , Ramírez-Salcedo Jorge
Published: October 2013

The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development.
Analysis on the Manufacturing of an AA5083 Straight Blade Previously ECAE Processed
Authors: Salcedo Daniel , Luis Carmelo , Puertas Ignacio , León Javier , Fuertes Juan Pablo , Luri Rodrigo
Published: October 2013

Over these past few years, there have been a large number of technical papers published related to the problem of improving the mechanical properties of materials obtained through severe plastic deformation. Nevertheless, the number of technical papers dealing with improvement in the mechanical properties of mechanical components manufactured from submicrometric grain size material has not been so proficient. Therefore, in this present research work, a straight blade has been manufactured starting from AA-5083 previously processed by ECAE twice (N2) with route C. This material will be manipulated so as to be isothermally forged at different temperature values. This present research work shows the results that are inherent in an improvement in the mechanical properties and the microstructure achieved in the thus obtained components, compared with the starting material. In addition, the optimum forging temperature to achieve these components will be determined. As shown in this research work, it is possible to obtain submicrometric grain size mechanical components with a higher mechanical strength than those obtained in nonultrafine grained materials. The originality of this research work lies in the manufacturing of actual mechanical components from ECAE processed material and the analysis of their properties.
A Proposed Model for Infant and Child Oral Health Promotion in India
Authors: Jawdekar Ashwin Muralidhar
Published: October 2013

Dental caries is an increasing burden in the developing countries. A proper budgetary allocation for treating dental diseases in an enormous population such as India is impractical, where resources are inadequate for major health challenges such as malnutrition and gastrointestinal and respiratory infections in children. An integrated, directed population approach targeting children is much needed. The existing machinery of successful public health campaigns such as the “Pulse Polio” and the “Mid-Day-Meals Scheme” of the Government of India can be used for oral health promotion for children. India has about 300 dental colleges and countrywide branches of the Indian Dental Association that can provide manpower for the program. An innovative, large-scale “Fit for School” program in Philippines is a model for an integrated approach for children’s health and has proved to be cost-effective and viable. A model for oral health promotion in infants and children of India, combining age-specific initiatives for health education, nutrition, hygiene, and fluoride use, is proposed. The model could be implemented to evaluate the oral health status of children, knowledge and knowledge gain of the community health workers, and acceptability and sustainability of the preventive programs (fluoride varnish and preschool and school tooth brushing) pragmatically.
Is Human Papillomavirus Associated with Prostate Cancer Survival?
Authors: Pascale Mariarosa , Pracella Danae , Barbazza Renzo , Marongiu Barbara , Roggero Enrico , Bonin Serena , Stanta Giorgio
Published: October 2013

The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years,P=0.0381). In multivariate analysis age (P<0.001), Gleason score (P<0.001), nuclear grading (P=0.002), and HPV status (P=0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.
Application of Genetic Algorithm for Discovery of Core Effective Formulae in TCM Clinical Data
Authors: Yang Ming , Poon Josiah , Wang Shaomo , Jiao Lijing , Poon Simon , Cui Lizhi , Chen Peiqi , Sze Daniel Man-Yuen , Xu Ling
Published: October 2013

Research on core and effective formulae (CEF) does not only summarize traditional Chinese medicine (TCM) treatment experience, it also helps to reveal the underlying knowledge in the formulation of a TCM prescription. In this paper, CEF discovery from tumor clinical data is discussed. The concepts of confidence, support, and effectiveness of the CEF are defined. Genetic algorithm (GA) is applied to find the CEF from a lung cancer dataset with 595 records from 161 patients. The results had 9 CEF with positive fitness values with 15 distinct herbs. The CEF have all had relative high average confidence and support. A herb-herb network was constructed and it shows that all the herbs in CEF are core herbs. The dataset was divided into CEF group and non-CEF group. The effective proportions of former group are significantly greater than those of latter group. A Synergy index (SI) was defined to evaluate the interaction between two herbs. There were 4 pairs of herbs with high SI values to indicate the synergy between the herbs. All the results agreed with the TCM theory, which demonstrates the feasibility of our approach.
Cidofovir: A Novel Antitumor Agent for Glioblastoma
Authors: Hadaczek Piotr , Ozawa Tomoko , Soroceanu Liliana , Yoshida Yasuyuki , Matlaf Lisa , Singer Eric , Fiallos Estefania , James C. David , Cobbs Charles S.
Published: October 2013

Purpose: Cidofovir (CDV) is an U.S. Food and Drug Administration (FDA)-approved nucleoside antiviral agent used to treat severe human cytomegalovirus (HCMV) infection. Until now, no clear therapeutic effects of CDV have been reported outside of the setting of viral infection, including a potential role for CDV as an antineoplastic agent for the treatment of brain tumors.

Experimental Design: We investigated the cytotoxicity of CDV against the glioblastoma cells, U87MG and primary SF7796, both in vitro and in vivo, using an intracranial xenograft model. Standard techniques for cell culturing, immunohistochemistry, Western blotting, and real-time PCR were employed. The survival of athymic mice (n = 8–10 per group) bearing glioblastoma tumors, treated with CDV alone or in combination with radiation, was analyzed by the Kaplan–Meier method and evaluated with a two-sided log-rank test.

Results: CDV possesses potent antineoplastic activity against HCMV-infected glioblastoma cells. This activity is associated with the inhibition of HCMV gene expression and with activation of cellular apoptosis. Surprisingly, we also determined that CDV induces glioblastoma cell death in the absence of HCMV infection. CDV is incorporated into tumor cell DNA, which promotes double-stranded DNA breaks and induces apoptosis. In the setting of ionizing radiotherapy, the standard of care for glioblastoma in humans, CDV augments radiation-induced DNA damage and, further, promotes tumor cell death. Combination therapy with CDV and radiotherapy significantly extended the survival of mice bearing intracranial glioblastoma tumors.

Conclusion: We have identified a novel antiglioma property of the FDA-approved drug CDV, which heightens the cytotoxic effect of radiotherapy, the standard of care therapy for glioblastoma. Clin Cancer Res; 19(23); 6473–83. ©2013 AACR.
Variations in Both α-Spectrin (SPTA1) and β-Spectrin (SPTB) in a Neonate with Prolonged Jaundice in a Family where Nine Individuals Had Hereditary Elliptocytosis
Authors: Christensen Robert D. , Nussenzveig Roberto H. , Reading N. Scott , Agarwal Archana M. , Prchal Josef T. , Yaish Hassan M.
Published: October 2013

We cared for a neonate who had problematic hyperbilirubinemia born into a family where nine first-degree relatives had hereditary elliptocytosis (HE). As neonates, the nine relatives did not have any significant jaundice or anemia that was recognizable. Blood films on the proband suggested a diagnosis of pyropoikilocytosis. Analysis of the α-spectrin gene (SPTA1) in the proband revealed two previously reported low-frequency heterozygous polymorphisms of unknown clinical significance and the αLELY allele. In addition, a novel heterozygous mutation was identified in exon 2 of the β-spectrin gene SPTB. No mutations were identified in ANK1 (ankyrin-1), SLC4A1 (band 3), EPB41 (band 4.1), or EPB42 (band 4.2).
Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Acute Kidney Injury in Patients with Morbid Obesity Who Underwent Bariatric Surgery
Authors: Koukoulaki Maria , Spyropoulos Charalampos , Hondrogiannis Panagiotis , Papachristou Evangelos , Mitsi Eleni , Kalfarentzos Fotios , Goumenos Dimitrios S.
Published: October 2013

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a biomarker of acute kidney injury (AKI) that could contribute to early diagnosis and effective management of AKI. The purpose of this study was to evaluate NGAL as a predictive marker of AKI in patients with clinically severe obesity (BMI >50) who underwent biliopancreatic diversion surgery. Patients and Methods: We prospectively studied 23 patients with clinically severe obesity who underwent biliopancreatic bypass surgery. NGAL was measured using chemiluminescent microparticle immunoassay in three urine samples collected from each patient before surgery (first sample), 2-6 h after surgery (second sample) and on the first postoperative day (third sample). Results: Renal function was evaluated using serum creatinine values, which were 0.91 ± 0.26 mg/dl before surgery, 0.87 ± 0.31 mg/dl immediately after surgery and 0.92 ± 0.62 mg/dl on the fifth postoperative day. During the immediate postoperative period, AKI was observed in 2 patients, one of whom required renal replacement therapy with hemodialysis. In both patients, urine NGAL increased within the first postoperative hours before the values of serum creatinine increased. Conclusion: Urine NGAL in patients with clinically severe obesity, which was surgically treated, might be a potential biomarker of early AKI detection. Further research is required in order to confirm these results observed in a small number of patients who developed postoperative AKI and make recommendations for predictive NGAL values in patients who underwent bariatric surgery.
The Role of Piloerection in Primate Thermoregulation
Authors: Chaplin George , Jablonski Nina G. , Sussman Robert W. , Kelley Elizabeth A.
Published: October 2013

The insulating properties of the primate integument are influenced by many factors, including piloerection, which raises the hair and insulates the body by creating motionless air near the skin's surface. The involuntary muscles that control piloerection, the musculi arrectores pilorum (MAP), are mostly absent except on the tail in most strepsirhines, and are entirely absent in tarsiers and some lorisids. The absence of piloerection and the reduced effectiveness of pilary insulation in preventing heat loss affected the evolution of behavior and metabolic thermoregulation in these animals. In lemurs, this situation contributed to the use of positional and social behaviors such as sunning and huddling that help maintain thermal homeostasis during day-night and seasonal temperature cycles. It also contributed in many lemurs and lorises to the evolution of a wide variety of activity patterns and energy-conserving metabolic patterns such as cathemerality, daily torpor, and hibernation. The absence of functional MAP in strepsirhines and tarsiers implies the absence of effective piloerection in early primates, and the reacquisition of whole-body MAP in ancestral anthropoids prior to the separation of platyrrhine and catarrhine lineages.
Relative Ratio and Level of Amyloid-β 42 Surrogate in Cerebrospinal Fluid of Familial Alzheimer Disease Patients with Presenilin 1 Mutations
Authors: Tagami Shinji , Okochi Masayasu , Yanagida Kanta , Kodama Takashi , Arai Tetsuaki , Kuwano Ryozo , Ikeuchi Takeshi , Takeda Masatoshi
Published: October 2013

Background: Presenilin 1 (PS1) mutations associated with familial Alzheimer disease (FAD) generally increase the amyloid-β 42 (Aβ42) to Aβ40 ratio secreted in cultured cells. Some of these mutants reduce the secretion of Aβ40 rather than increase that of Aβ42. Since it has been difficult to estimate Aβ42 secretion in brains of PS1-FAD patients due to substantial Aβ42 accumulation, it remains unknown whether the enhanced Aβ42 to Aβ40 ratio in brains of FAD patients is caused by elevated Aβ42 secretion or by reduced secretion of Aβ40. Objective/Methods: Cerebrospinal fluids (CSF) of PS1-FAD patients and neurological control patients (controls) were collected. Levels of CSF amyloid precursor-like protein-1-derived Aβ-like peptide (APL1β), including APL1β28, an Aβ42 surrogate marker, were quantified by liquid chromatography tandem mass spectrometry, and Aβ42 secretion in the brain was estimated. Results: The relative ratio of CSF APL1β28 to total APL1β was higher in PS1-FAD patients than in controls. Importantly, CSF APL1β28 was not significantly higher. However, C-terminally shorter CSF APL1β25 and APL1β27 were significantly lower in PS1-FAD patients and, as expected, so were CSF Aβ40 and Aβ42. Conclusion: A higher relative ratio of the CSF Aβ42 surrogate in PS1-FAD patients is not due to its increase in CSF, suggesting that massive Aβ42 accumulation in the PS1-FAD brain occurs without an apparent increase in Aβ42 secretion.
Gabapentinoid Abuse in Order to Potentiate the Effect of Methadone: A Survey among Substance Misusers
Authors: Baird Colin R.W. , Fox Pauline , Colvin Lesley A.
Published: October 2013

Background/Aims: There is emerging evidence of gabapentin and pregabalin (gabapentinoid) abuse, particularly in the substance misuse population, and some suggestion of gabapentinoids being abused alongside methadone. Methods: A questionnaire-based survey was carried out in six substance misuse clinics, looking for evidence of gabapentinoid abuse. Results: 22% (29/129) of respondents admitted to abusing gabapentinoids, and of these, 38% (11/29) abused gabapentinoids in order to potentiate the ‘high' they obtained from methadone. Conclusions: Gabapentinoid abuse along with methadone has not previously been described. These findings are of relevance to clinicians working within both substance misuse services and chronic pain services.
Seizures in Patients with Chronic Hepatitis C Treated with NS3/4A Protease Inhibitors: Does Pharmacological Interaction Play a Role?
Authors: Milazzo Laura , Falvella Felicia Stefania , Magni Carlo , Gervasoni Cristina , Peri Anna Maria , Cattaneo Dario , Antinori Spinello , Vidale Simone
Published: October 2013

The addition of NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (Peg-IFN)-α and ribavirin for the treatment of hepatitis C virus (HCV) genotype 1-infected patients has led to higher rates of virological response and adverse events. Among the several side effects of interferon, neuropsychiatric symptoms have been described, particularly depression and anxiety, occurring in about 25% of patients. Although seizures have been reported in interferon-treated patients with multiple sclerosis and in a variety of malignancies, the epileptogenic potential of interferon-α in the treatment of HCV infection is considered minimal. In this report we present a new onset of seizures occurring in 2 patients during anti-HCV therapy in association with Peg-IFN, ribavirin and HCV protease inhibitors.
Slight Changes in the Mechanical Stimulation Affects Osteoblast- and Osteoclast-Like Cells in Co-Culture
Authors: Kadow-Romacker Anke , Duda Georg N. , Bormann Nicole , Schmidmaier Gerhard , Wildemann Britt
Published: October 2013

SummaryBackground: Osteoblast- and osteoclast-like cells are responsible for coordinated bone maintenance, illustrated by a balanced formation and resorption. Both parameters appear to be influenced by mechanical constrains acting on each of these cell types individually. We hypothesized that the interactions between both cell types are also influenced by mechanical stimulation. Methods: Co-cultures of osteoblast- and osteoclast-like cells were stimulated with 1,100 µstrain, 0.1 or 0.3 Hz for 1-5 min/day over 5 days. Two different setups depending on the differentiation of the osteoclast-like cells were used: i) differentiation assay for the fusion of pre-osteoclasts to osteoclasts, ii) resorption assay to determine the activity level of osteoclast-like cells. Results: In the differentiation assay (co-culture of osteoblasts with unfused osteoclast precursor cells) the mechanical stimulation resulted in a significant decrease of collagen-1 and osteocalcin produced by osteoblast-like cells. Significantly more TRAP-iso5b was measured after stimulation for 3 min with 0.1 Hz, indicating enhanced osteoclastogenesis. In the resorption assay (co-culture of osteoblasts with fused osteoclasts) the stimulation for 3 min with 0.3 Hz significantly increased the resorption activity of osteoclasts measured by the pit formation and the collagen resorption. The same mechanical stimulation resulted in an increased collagen-1 production by the osteoblast-like cells. The ratio of RANKL/OPG was not different between the groups. Conclusion: These findings demonstrate that already small changes in duration or frequency of mechanical stimulation had significant consequences for the behavior of osteoblast- and osteoclast-like cells in co-culture, which partially depend on the differentiation status of the osteoclast-like cells.
Bioactive Factors in Platelet-Rich Plasma Obtained by Apheresis
Authors: Krüger Jan Philipp , Freymann Undine , Vetterlein Samuel , Neumann Katja , Endres Michaela , Kaps Christian
Published: October 2013

SummaryIntroduction: The use of platelet-rich plasma (PRP) in regenerative approaches in cartilage repair is becoming more common. Information about PRP composition and its content of putative bioactive chondrogenic growth factors (GF) that may support cartilage regeneration is scarce. Methods: GF composition of a pool of 6 PRP preparations was determined using Protein Antibody Membrane Arrays covering 507 GF, signaling molecules, and receptors. To verify the chondrogenic GF variability in PRP, Growth Factor Antibody Membrane Arrays covering 26 GF were applied to 6 individual PRP preparations. Selected GF involved in chondrogenic differentiation were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). Results: 417 out of 507 possible detectable proteins were present in the PRP pool, including 76 GF. Quantification of selected chondrogenic GF by ELISA showed an average of 0.31 ng/ml bone morphogenetic protein-2, 0.50 ng/ml connective tissue growth factor, 0.76 ng/ml fibroblast growth factor-2, and 0.59 ng/ml transforming growth factor-β3. Conclusion: PRP as a therapeutic option in regenerative cartilage repair strategies is a powerful tool for the local application of chondrogenic GF to the site of injury. Chondrogenic GF are present in PRP and may support cartilage repair by inducing cell differentiation and cartilage matrix formation.
Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease
Authors: Stacy Mitchel R. , Yu Da Yu , Maxfield Mark W. , Jaba Irina M. , Jozwik Bartosz P. , Zhuang Zhen W. , Lin Ben A. , Hawley Christi L. , Caracciolo Christopher M. , Pal Prasanta , Tirziu Daniela , Sampath Smita , Sinusas Albert J.
Published: October 2013

Background—

A standard quantitative imaging approach to evaluate peripheral arterial disease does not exist. Quantitative tools for evaluating arteriogenesis in vivo are not readily available, and the feasibility of monitoring serial regional changes in lower extremity perfusion has not been examined.

Methods and Results—

Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated after femoral artery occlusion in a porcine model using single photon emission tomography (SPECT)/CT imaging with postmortem validation of in vivo findings using gamma counting, postmortem imaging, and histological analysis. Hybrid
201
Tl SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately postocclusion, and at 1 and 4 weeks postocclusion. CT imaging was used to identify muscle regions of interest in the ischemic and nonischemic hindlimbs for quantification of regional changes in CT-defined arteriogenesis and quantification of
201
Tl perfusion. Four weeks postocclusion, postmortem tissue
201
Tl activity was measured by gamma counting, and immunohistochemistry was performed to assess capillary density. Relative
201
Tl retention (ischemic/nonischemic) was reduced immediately postocclusion in distal and proximal muscles and remained lower in calf and gluteus muscles 4 weeks later. Analysis of CT angiography revealed collateralization at 4 weeks within proximal muscles (
P
<0.05). SPECT perfusion correlated with tissue gamma counting at 4 weeks (
P
=0.01). Increased capillary density was seen within the ischemic calf at 4 weeks (
P
=0.004).

Conclusions—

201
Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion after limb ischemia. This approach may be effective for detection of disease and monitoring therapy in peripheral arterial disease.
Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non–ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization
Authors: Wallentin Lars , Lindholm Daniel , Siegbahn Agneta , Wernroth Lisa , Becker Richard C. , Cannon Christopher P. , Cornel Jan H. , Himmelmann Anders , Giannitsis Evangelos , Harrington Robert A. , Held Claes , Husted Steen , Katus Hugo A. , Mahaffey Kenneth W. , Steg Ph. Gabriel , Storey Robert F. , James Stefan K.
Published: October 2013

Background—

Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial.

Methods and Results—

Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (
P
<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group

Conclusions—

Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872.
Criscianthus, a new genus of Eupatorieae (Asteraceae) with a key to members of the tribe in Africa
Authors: Grossi Mariana Andrea , KATINAS LILIANA , NAKAJIMA JIMI N.
Published: October 2013

Stomatanthes zambiensis is segregated from the African genus Stomatanthes and raised as the only species of the new genus Criscianthus (Eupatorieae, Asteraceae). Criscianthus zambiensis is characterized by its verticillate phyllotaxy with three leaves per node, phyllaries with caudate apex, and an exclusive type of hair in its cypsela. A full description of the genus and its species, a morphological analysis, photographs, illustrations, and a distribution map are provided. A key to native and alien species of the tribe Eupatorieae in Africa is included.
Evaluation of Tropical Cyclones in the Canadian Global Modeling System: Sensitivity to Moist Process Parameterization
Authors: Zadra A. , McTaggart-Cowan R. , Vaillancourt P. A. , Roch M. , Bélair S. , Leduc A.-M.
Published: October 2013

Deep convection is one of various complex processes driving the evolution of tropical cyclones (TCs). The scales associated with deep convection are too small to be resolved by global NWP models. In the deep convection parameterization used by the Canadian Global Deterministic Prediction System (GDPS), the trigger function depends on various criteria, one of which is the adjustable “trigger velocity” parameter, a vertical velocity threshold used in the parcel stability test of the scheme. In this study, the sensitivity of the GDPS TC activity and precipitation distribution to convective triggering parameters is investigated by varying this threshold. Multiple basins are considered for three TC seasons, and the impacts of trigger velocity variations on TC statistics (forecast hits, bias, false alarms, and track and intensity errors) and on the model’s genesis potential index (GPI) are measured. It is shown that a reduction of the trigger velocity, from 0.05 to 0.01 m s−1, over the tropical oceans leads to increased convective stabilization of atmospheric columns, as well as an increase in convective precipitation amounts but a reduction in total (subgrid plus grid scale) precipitation accumulations. The trigger adjustment also yields a significant reduction of TC false alarm ratios, with no impact on forecast mean errors for true cyclones other than an expected deterioration of the intensity bias, and a systematic reduction of the average GPI over various basins at all lead times. A conceptual model is proposed to explain the relation between trigger adjustments and TC development.
Does Tourism Boost Criminal Activity? Evidence From a Top Touristic Country
Authors: Montolio Daniel , Planells-Struse Simón
Published: October 2013

The growth in the number of tourist arrivals in Spain in recent years has had significant economic repercussions; yet, little has been reported about its negative impact. This study goes some way to rectifying this by estimating the impact of tourist activity on crime rates in the Spanish provinces during the period 2000-2008. We use both 2-SLS and GMM techniques in a panel data framework to overcome the various challenges posed by estimating this relationship, namely, controlling for the unobserved characteristics of the provinces, and accounting for both the possible endogeneity of the tourist variable and the inertia of criminal activities. The results show that tourist arrivals have a positive and significant impact on crimes against both property and the person.