bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Underground Zinc Mine Investment Based on Fuzzy-Interval Grey System Theory and Geometric Brownian Motion
Authors: Gligoric Zoran , Kricak Lazar , Beljic Cedomir , Lutovac Suzana , Milojevic Jelena
Published: July 2014

Underground mine projects are often associated with diverse sources of uncertainties. Having the ability to plan for these uncertainties plays a key role in the process of project evaluation and is increasingly recognized as critical to mining project success. To make the best decision, based on the information available, it is necessary to develop an adequate model incorporating the uncertainty of the input parameters. The model is developed on the basis of full discounted cash flow analysis of an underground zinc mine project. The relationships between input variables and economic outcomes are complex and often nonlinear. Fuzzy-interval grey system theory is used to forecast zinc metal prices while geometric Brownian motion is used to forecast operating costs over the time frame of the project. To quantify the uncertainty in the parameters within a project, such as capital investment, ore grade, mill recovery, metal content of concentrate, and discount rate, we have applied the concept of interval numbers. The final decision related to project acceptance is based on the net present value of the cash flows generated by the simulation over the time project horizon.
A Transient Queuing Model for Analyzing and Optimizing Gate Congestion of Railway Container Terminals
Authors: Zeng Ming , Cheng Wenming , Guo Peng
Published: July 2014

As the significant connection between the external and internal of the railway container terminal, the operation performance of the gate system plays an important role in the entire system. So the gate congestion will bring many losses to the railway container terminal, even the entire railway container freight system. In this paper, the queue length and the average waiting time of the railway container terminal gate system, as well as the optimal number of service channels during the different time period, are investigated. An M/Ek/n transient queuing model is developed based on the distribution of the arrival time interval and the service time; besides the transient solutions are acquired by the equally likely combinations (ELC) heuristic method. Then the model is integrated into an optimization framework to obtain the optimal operation schemes. Finally, some computational experiments are conducted for model validation, sensitivity testing, and system optimization. Experimental results indicate that the model can provide the accurate reflection to the operation situation of the railway container terminal gate system, and the approach can yield the optimal number of service channels within the reasonable computation time.
A Note on the Normal Index and thec-Section of Maximal Subgroups of a Finite Group
Authors: Tang Na , Li Xianhua
Published: July 2014

LetMbe a maximal subgroup of finite groupG. For each chief factorH/KofGsuch thatK≤MandG=MH, we called the order ofH/Kthe normal index ofMandM∩H/Ka section ofMinG. Using the concepts of normal index andc-section, we obtain some new characterizations ofp-solvable, 2-supersolvable, andp-nilpotent.
Peritoneal Air Exposure Elicits an Intestinal Inflammation Resulting in Postoperative Ileus
Authors: Tan Shanjun , Yu Wenkui , Lin Zhiliang , Chen Qiyi , Shi Jialiang , Dong Yi , Duan Kaipeng , Bai Xiaowu , Xu Lin , Li Jieshou , Li Ning
Published: July 2014

Background.The pathogenesis of postoperative ileus (POI) is complex. The present study was designed to investigate the effects of peritoneal air exposure on the POI intestinal inflammation and the underlying mechanism.Methods.Sprague-Dawley rats were randomized into five groups (6/group): the control group, the sham group, and three exposure groups with peritoneal air exposure for 1, 2, or 3 h. At 24 h after surgery, we analyzed the gastrointestinal transit, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10, the myeloperoxidase activity, and the levels of TNF-α, IL-1β, IL-6, and IL-10 in the ileum and colon. The oxidant and antioxidant levels in the ileum and colon were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC).Results.Peritoneal air exposure caused an air-exposure-time-dependent decrease in the gastrointestinal transit. The length of peritoneal air exposure is correlated with the severity of both systemic and intestinal inflammations and the increases in the levels of MDA, SOD, GSH-Px, and T-AOC.Conclusions.The length of peritoneal air exposure is proportional to the degree of intestinal paralysis and the severity of intestinal inflammation, which is linked to the oxidative stress response.
Prevention and Restoration of Hearing Loss Associated with the Use of Cisplatin
Authors: Chirtes Felician , Albu Silviu
Published: July 2014

Background. Cisplatin is a well known platinum-based chemotherapeutic agent used for the treatment of various malignant tumours. A frequent side effect of cisplatin therapy is ototoxicity. Unfortunately, currently there are no available treatments.Material and Methods. Experimental, clinical studies and reviews published between 2004 and 2014 in the English medical literature concerning ototoxicity were selected using Medline, PubMed, and Google Scholar databases. Inclusion criteria were cisplatin-induced ototoxicity and therapy aimed at preventing or curing this disorder. Molecular mechanisms and clinical, audiological, and histological markers of cisplatin-induced ototoxicity are described. Moreover, experimental and clinical strategies for prevention or treatment of hearing loss were also reviewed.Results and Discussion. Experimental studies demonstrate a wide range of otoprotective molecules and strategies efficient against cisplatin-induced hearing loss. However, only dexamethasone proved a slight otoprotective effect in a clinical study.Conclusion. Further research must be completed to bring future therapeutic options into clinical setting.
A Newton-Based Extremum Seeking MPPT Method for Photovoltaic Systems with Stochastic Perturbations
Authors: Li Heng , Peng Jun , Liu Weirong , Huang Zhiwu , Lin Kuo-Chi
Published: July 2014

Microcontroller based maximum power point tracking (MPPT) has been the most popular MPPT approach in photovoltaic systems due to its high flexibility and efficiency in different photovoltaic systems. It is well known that PV systems typically operate under a range of uncertain environmental parameters and disturbances, which implies that MPPT controllers generally suffer from some unknown stochastic perturbations. To address this issue, a novel Newton-based stochastic extremum seeking MPPT method is proposed. Treating stochastic perturbations as excitation signals, the proposed MPPT controller has a good tolerance of stochastic perturbations in nature. Different from conventional gradient-based extremum seeking MPPT algorithm, the convergence rate of the proposed controller can be totally user-assignable rather than determined by unknown power map. The stability and convergence of the proposed controller are rigorously proved. We further discuss the effects of partial shading and PV module ageing on the proposed controller. Numerical simulations and experiments are conducted to show the effectiveness of the proposed MPPT algorithm.
A Method for Distributed Pipeline Burst and Leakage Detection in Wireless Sensor Networks Using Transform Analysis
Authors: Rashid Sidra , Qaisar Saad , Saeed Husnain , Felemban Emad
Published: July 2014

Bursts and leakages have turned out to be one of the most frequent malfunctions in liquid pipeline distribution systems. In recent years, the issue has gained a lot of attention in research community due to associated financial costs, environmental hazards, and safety considerations. Wireless sensor network (WSN) based leakage detection and localization can provide an exceptional level of operational efficiency, safety assurance, and real-time parametric view of the entire pipeline network. In this paper, we propose a transient pressure wave based technique coupled with wavelet analysis to achieve reliable detection and localization of abrupt bursts and leakages. The presented technique uses the information carried in the transient pressure signal. A specific pattern is induced on the pressure traces within the pipeline due to leak; we use wavelet analysis to detect these local singularities. The proposed algorithm is distributed in nature and run on low power sensor nodes. The algorithm is deployed in field on a custom pipeline test bed and performance results are documented for various testing scenarios. A comparison of proposed wavelet technique with other widely used methods has been carried out. The technique provides more than 90% accuracy in a number of deployment scenarios for high noise generating long pipeline networks.
Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering
Authors: Ansari Sahar , Freire Marcelo O. , Pang Eun-Kyoung , Abdelhamid Alaa I. , Almohaimeed Mohammad , Zadeh Homayoun H.
Published: July 2014

Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks,de novobone formation was assessed using micro-CT and histomorphometric analyses. Results showedde novobone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffoldsviaAMOR.
Stability and Dynamical Analysis of a Biological System
Authors: Pan Xinhong , Zhao Min , Wang Yapei , Yu Hengguo , Ma Zengling , Wang Qi
Published: July 2014

This study considers the spatiotemporal dynamics of a reaction-diffusion phytoplankton-zooplankton system with a double Allee effect on prey under a homogeneous boundary condition. The qualitative properties are analyzed, including the local stability of all equilibria and the global asymptotic property of the unique positive equilibrium. We also discuss the Hopf bifurcation and the steady state bifurcation of the system. These results are expected to help understand the complexity of the Allee effect and the interaction between phytoplankton and zooplankton.
IL-10 Counteracts Proinflammatory Mediator Evoked Oxidative Stress in Caco-2 Cells
Authors: Latorre Eva , Matheus Nyurky , Layunta Elena , Alcalde Ana Isabel , Mesonero José Emilio
Published: July 2014

Oxidative stress is thought to play a key role in the development of intestinal damage in intestinal inflammatory diseases. Several molecules are involved in the intestinal inflammation, either as pro- or anti-inflammatory factors; however, their effects on intestinal oxidative stress seem to be controversial. This work analyzes the contribution of pro- and anti-inflammatory molecules to the balance of oxidative damage in intestinal epithelial cells, as well as their effects on cellular antioxidant enzyme activity. With this purpose, the lipid and protein oxidation, together with the activity of catalase, superoxide dismutase, and glutathione peroxidase, were determined in the Caco-2 cells treated with serotonin, adenosine, melatonin, and TNFα, as proinflammatory factors, and IL-10, as an anti-inflammatory cytokine. The results have shown that all the proinflammatory factors assayed increased oxidative damage. In addition, these factors also inhibited the activity of antioxidant enzymes in the cells, except melatonin. In contrast, IL-10 did not alter these parameters but was able to reduce the prooxidant effects yielded by serotonin, adenosine, melatonin, or TNFα, in part by restoring the antioxidant enzymes activities. In summary, proinflammatory factors may induce oxidative damage in intestinal epithelial cells, whereas IL-10 seems to be able to restore the altered redox equilibrium in Caco-2 cells.
A Stochastic Integer Programming Model for Minimizing Cost in the Use of Rain Water Collectors for Firefighting
Authors: Rivera-Morales Luis A. , Smith Neale R. , Manzano Mario G. , Garza-Ramírez David
Published: July 2014

In this paper we propose a stochastic integer programming optimization model to determine the optimal location and number of rain water collectors (RWCs) for forest firefighting. The objective is to minimize expected total cost to control forest fires. The model is tested using a real case and several additional realistic scenarios. The impact on the solution of varying the limit on the number of RWCs, the RWC water capacity, the aircraft capacity, the water demands, and the aircraft operating cost is explored. Some observations are that the objective value improves with larger RWCs and with the use of aircraft with greater capacity.
The Weight-Inclusive versus Weight-Normative Approach to Health: Evaluating the Evidence for Prioritizing Well-Being over Weight Loss
Authors: Tylka Tracy L. , Annunziato Rachel A. , Burgard Deb , Daníelsdóttir Sigrún , Shuman Ellen , Davis Chad , Calogero Rachel M.
Published: July 2014

Using an ethical lens, this review evaluates two methods of working within patient care and public health: theweight-normative approach(emphasis on weight and weight loss when defining health and well-being) and theweight-inclusive approach(emphasis on viewing health and well-being as multifaceted while directing efforts toward improving health access and reducing weight stigma). Data reveal that the weight-normative approach is not effective for most people because of high rates of weight regain and cycling from weight loss interventions, which are linked to adverse health and well-being. Its predominant focus on weight may also foster stigma in health care and society, and data show that weight stigma is also linked to adverse health and well-being. In contrast, data support a weight-inclusive approach, which is included in models such as Health at Every Size for improving physical (e.g., blood pressure), behavioral (e.g., binge eating), and psychological (e.g., depression) indices, as well as acceptability of public health messages. Therefore, the weight-inclusive approach upholds nonmaleficience and beneficience, whereas the weight-normative approach does not. We offer a theoretical framework that organizes the research included in this review and discuss how it can guide research efforts and help health professionals intervene with their patients and community.
Gossypol Promotes Degeneration of Ovarian Follicles in Rats
Authors: Gadelha Ivana Cristina Nunes , Fernandes de Macedo Michelly , Oloris Sílvia Catarina Salgado , Melo Marilia Martins , Soto-Blanco Benito
Published: July 2014

The present study aimed to determine if gossypol interferes with ovarian follicles in rats. Twenty-four female Wistar rats were assigned to two equal groups: one control group and the other dosed with gossypol (25 mg/kg/day, subcutaneously) for 15 days. Ovarian follicles were histologically classified according to the stage of development and as normal or atretic. Gossypol treatment reduced the length of estrous with an increase in the duration of the diestrus phase. This compound was responsible for reduced serum levels of T4 and progesterone. Treatment with gossypol was responsible for a significant reduction in the number of normal ovarian follicles and a significant increase in the number of atretic follicles, both in all stages of development. Thus, treatment of rats with gossypol was responsible for reduction in the number of viable follicles and changes in hormone levels that resulted in interference of the estrous cycle.
Challenges and Frugal Remedies for Lowering Facility Based Neonatal Mortality and Morbidity: A Comparative Study
Authors: Amadi Hippolite O. , Osibogun Akin O. , Eyinade Olateju , Kawuwa Mohammed B. , Uwakwem Angela C. , Ibekwe Maryann U. , Alabi Peter , Ezeaka Chinyere , Eleshin Dada G. , Ibadin Mike O.
Published: July 2014

Millennium development goal target on infant mortality (MDG4) by 2015 would not be realised in some low-resource countries. This was in part due to unsustainable high-tech ideas that have been poorly executed. Prudent but high impact techniques could have been synthesised in these countries. A collaborative outreach was initiated to devise frugal measures that could reduce neonatal deaths in Nigeria. Prevailing issues of concern that could militate against neonatal survival within care centres were identified and remedies were proffered. These included application of (i) recycled incubator technology (RIT) as a measure of providing affordable incubator sufficiency, (ii) facility-based research groups, (iii) elective training courses for clinicians/nurses, (iv) independent local artisans on spare parts production, (v) power-banking and apnoea-monitoring schemes, and (v) 1/2 yearly failure-preventive maintenance and auditing system. Through a retrospective data analyses 4 outreach centres and one “control” were assessed. Average neonatal mortality of centres reduced from 254/1000 to 114/1000 whilst control remained at 250/1000. There was higher relative influx of incubator-dependent-neonates at outreach centres. It was found that 43% of mortality occurred within 48 hours of presentation (d48) and up to 92% of d48 were of very-low birth parameters. The RIT and associated concerns remedies have demonstrated the vital signs of efficiency that would have guaranteed MDG4 neonatal component in Nigeria.
Design Optimization of Composite Elliptical Deep-Submersible Pressure Hull for Minimizing the Buoyancy Factor
Authors: Fathallah Elsayed , Qi Hui , Tong Lili , Helal Mahmoud
Published: July 2014

The design of deep submersible pressure hull's structural is one of the core technologies of submersible development of human history. Submersible pressure hulls with fiber-reinforced multilayer constructions have been developed in the recent years as substitutes for classical metallic ring-stiffened pressure hulls; strength and stability are its top priority. This paper investigates the optimum design of a composite elliptical deep-submerged pressure hull under hydrostatic pressure to minimize the buoyancy factor of the submersible pressure hull under constraints on the failure criteria and the buckling strength of the hulls to reach the maximum operating depth. The thickness and the fiber orientation angles in each layer, the radii of the ellipse, and stringers dimensions were taken as design variables and determined in the design process. The optimization procedures are performed using commercial finite element analysis software ANSYS. Additionally, a sensitivity analysis is performed to study the influence of the design variables on the structural optimum design. Results of this study provide a valuable reference for designers of underwater vehicles.
Runx2 Is a Novel Regulator of Mammary Epithelial Cell Fate in Development and Breast Cancer
Authors: Owens Thomas W. , Rogers Renee L. , Best Sarah A. , Ledger Anita , Mooney Anne-Marie , Ferguson Alison , Shore Paul , Swarbrick Alexander , Ormandy Christopher J. , Simpson Peter T. , Carroll Jason S. , Visvader Jane E. , Naylor Matthew J.
Published: July 2014

Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here, we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differentiation in a manner that disrupted alveolar progenitor cell populations. Conversely, exogenous transgenic expression of Runx2 in mammary epithelial cells blocked milk production, suggesting that the decrease in endogenous Runx2 observed late in pregnancy is necessary for full differentiation. In addition, overexpression of Runx2 drove epithelial-to-mesenchymal transition–like changes in normal mammary epithelial cells, whereas Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor latency and enhanced overall survival in a mouse model of breast cancer, with Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our results establish a previously unreported function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions. Cancer Res; 74(18); 5277–86. ©2014 AACR.
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography
Authors: Iommelli Francesca , De Rosa Viviana , Gargiulo Sara , Panico Mariarosaria , Monti Marcello , Greco Adelaide , Gramanzini Matteo , Ortosecco Giovanni , Fonti Rosa , Brunetti Arturo , Del Vecchio Silvana
Published: July 2014

Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non–small cell lung cancer (NSCLC). Here, we tested whether 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.

Experimental Design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [18F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).

Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [18F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [18F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [18F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [18F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.

Conclusions: [18F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC. Clin Cancer Res; 20(18); 4806–15. ©2014 AACR.
BRCA2 and RAD51 Promote Double-Strand Break Formation and Cell Death in Response to Gemcitabine
Authors: Jones Rebecca M. , Kotsantis Panagiotis , Stewart Grant S. , Groth Petra , Petermann Eva
Published: July 2014

Replication inhibitors cause replication fork stalling and double-strand breaks (DSB) that result from processing of stalled forks. During recovery from replication blocks, the homologous recombination (HR) factor RAD51 mediates fork restart and DSB repair. HR defects therefore sensitize cells to replication inhibitors, with clear implications for cancer therapy. Gemcitabine is a potent replication inhibitor used to treat cancers with mutations in HR genes such as BRCA2. Here, we investigate why, paradoxically, mutations in HR genes protect cells from killing by gemcitabine. Using DNA replication and DNA damage assays in mammalian cells, we show that even short gemcitabine treatments cause persistent replication inhibition. BRCA2 and RAD51 are recruited to chromatin early after removal of the drug, actively inhibit replication fork progression, and promote the formation of MUS81- and XPF-dependent DSBs that remain unrepaired. Our data suggest that HR intermediates formed at gemcitabine-stalled forks are converted into DSBs and thus contribute to gemcitabine-induced cell death, which could have implications for the treatment response of HR-deficient tumors. Mol Cancer Ther; 13(10); 2412–21. ©2014 AACR.
Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer
Authors: Daige Christopher L. , Wiggins Jason F. , Priddy Leslie , Nelligan-Davis Terri , Zhao Jane , Brown David
Published: July 2014

miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. Mol Cancer Ther; 13(10); 2352–60. ©2014 AACR.
Redirected T-Cell Killing of Solid Cancers Targeted with an Anti-CD3/Trop-2–Bispecific Antibody Is Enhanced in Combination with Interferon-α
Authors: Rossi Edmund A. , Rossi Diane L. , Cardillo Thomas M. , Chang Chien-Hsing , Goldenberg David M.
Published: July 2014

Trop-2 has limited presence on normal tissues but is highly expressed in diverse epithelial cancers. (E1)-3s is a T-cell–redirecting trivalent bispecific antibody (bsAb), comprising an anti-CD3 scFv covalently linked to a stabilized dimer of a Trop-2–targeting Fab using Dock-and-Lock. We show for the first time that bsAb-mediated bidirectional trogocytosis occurs between target and T cells and involves immunologic synapses. We studied the effects of interferon-α (INFα) on (E1)-3s–mediated T-cell killing of human gastric and pancreatic cancer cell lines. T-cell activation, cytokine induction, and cytotoxicity were evaluated ex vivo using peripheral blood mononuclear cells (PBMC) or T cells with NCI-N87 gastric cancer as target cells. In vivo activity was assayed with NCI-N87 and Capan-1 (pancreatic) xenografts. In the presence of target cells and PBMCs, (E1)-3s did not cause excess cytokine production. When combined with (E1)-3s, peginterferonalfa-2a—which alone did not increase T-cell activation or raise cytokine levels over baseline—increased CD69 expression but did not significantly increase cytokine induction. (E1) 3s mediated a highly potent T-cell lysis of NCI-N87 target cells in vitro. Inclusion of peginterferonalfa-2a or a more potent form of INFα, 20*-2b, significantly potentiated the activity of (E1)-3s by more than 2.5- or 7-fold, respectively. In vivo, combining peginterferonalfa-2a with (E1)-3s delayed Capan-1 growth longer than each single agent. Similarly, combination therapy delayed tumor proliferation of NCI-N87 compared with (E1)-3s or peginterferonalfa-2a single-treatment groups. (E1)-3s effectively induced T-cell–mediated killing of Trop-2–expressing pancreatic and gastric cancers, which was enhanced with INFα. Mol Cancer Ther; 13(10); 2341–51. ©2014 AACR.
Inflammatory Myofibroblastic Tumours of the Urinary Bladder: Multi-Centre 18-Year Experience
Authors: Teoh Jeremy Yuen Chun , Chan Ning Hong , Mak Siu Ming , Lo Anthony Wing Ip , Leung Chung Ying , Hui Yin , Law In Chak , Fan Chi Wai , Cheung Fu Keung , Chan Steve Wai Hee , Yiu Ming Kwong , Man Chi Wai , So Hing Shing , Cheung Ho Yuen , Hou Simon See Ming , Ng Chi Fai
Published: July 2014

Objective: To review a series of inflammatory myofibroblastic tumours (IMTs) of the urinary bladder in 10 hospitals in Hong Kong. Methods: A database search in the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was performed using the key words ‘inflammatory myofibroblastic tumour', ‘inflammatory pseudotumour' and ‘spindle cell lesion'. Patient characteristics, clinical features, histological features, immunohistochemical staining results and treatment outcomes were reviewed. Results: Nine cases of IMT of the urinary bladder were retrieved. The mean age was 45.4 ± 22.8 years (range 11-78). Eight patients (88.9%) presented with haematuria and 5 patients (55.6%) had anaemia with a mean haemoglobin level of 6.8 ± 1.3 g/dl. Histologically, the majority of patients (77.8%) had a compact spindle cell pattern. Anaplastic lymphoma kinase staining was positive in 75% of cases. During a mean follow-up period of 43.4 months (range 8-94), none of them developed any local recurrence or distant metastasis. Conclusions: A high index of suspicion of IMT should be maintained for young patients presenting with bleeding bladder tumours and significant anaemia. IMTs of the urinary bladder run a benign disease course, and good prognosis can be achieved after surgical resection.
Urodynamic After-Contraction Waves: A Large Observational Study in an Adult Female Population and Correlation with Bladder and Ureter Emptying Functions in Women
Authors: Rodrigues Paulo , Hering Flávio , Campagnari João Carlos
Published: July 2014

Objective: To evaluate different patterns of after-contraction (A-C) waves detected during urodynamic evaluation in women. Patients and Methods: 4,110 women were prospectively observed regarding the presence of A-C waves upon urodynamic evaluation. Intravenous pyelography and ultrasound were requested. Paired t test, χ2 test, Wilcoxon's rank sum test and correlation analysis were performed with a 95% significance level. Results: There were three distinguishing patterns of A-C: type I - detrusor contraction after the regular voiding phase, type II - detrusor contraction persisting after the flow rate had stopped, and type III - rebound of the detrusor contraction after the flow. A-C was observed in 13.9% of the women. Type I A-C wave patterns were present in 68 patients (11.8%), type II A-C wave patterns in 477 patients (83.2%), and type III A-C wave patterns in 28 patients (10.3%). Studies with intravenous pyelography and ultrasound very frequently showed bladder mucosa, muscle thickening or trabeculation. Secondary ureterectasis related to A-C waves was also observed. Additionally, watts factor, maximum flow rate, detrusor pressure and opening detrusor pressure were markedly elevated in patients with type III A-C, suggesting enhanced detrusor contraction in these A-C waves. Conclusion: A-C waves are a real urodynamic entity with different patterns of presentation and with clinical and morphological alterations.
Behandlung von Infektionen mit Chlamydia trachomatis
Authors: Hammerschlag Margaret R.
Published: July 2014

Die Behandlung von Patienten mit C.-trachomatis-Infektion verhindert die weitere sexuelle Übertragung. Die Behandlung der Sexualpartner der infizierten Personen verhindert zugleich die Reinfektion des registrierten Falls und die nachfolgende Übertragung auf andere Sexualpartner. Die frühzeitige Behandlung von Chlamydien-Infektionen, insbesondere bei Frauen, verringert auch Komplikationen wie entzündliche Beckenerkrankungen. Die Behandlung von schwangeren Frauen verhindert die Übertragung der Infektion auf das Kind bei der Geburt, was in den USA zu einem drastischen Rückgang perinatal erworbener Chlamydien-Infektionen (Konjunktivitis, Pneumonie) geführt hat. Die Einführung von hochspezifischen Nukleinsäure-Amplifikationstests für den Nachweis von C. trachomatis und die gleichzeitige Verfügbarkeit einer wirksamen Einzeldosis-Antibiotikatherapie hat erhebliche Auswirkungen auf die Kontrolle von Chlamydien-Infektionen des Genitaltrakts. In diesem Kapitel werden die aktuellen Empfehlungen zur Behandlung von C.-trachomatis-Infektionen vorgestellt.
Hyperpigmentierung nach Behandlung einer frontalen fibrosierenden Alopezie
Authors: Pérez-Rodríguez Irma Margarita , García-Melendez Martha Elena , Eichelmann Kristian , Vázquez-Martínez Osvaldo , Ocampo-Candiani Jorge
Published: July 2014

Einleitung: Die frontale fibrosierende Alopezie (FFA) ist eine Narben bildende Form des Haarausfalls, die durch progressives Zurückweichen des frontotemporalen Haaransatzes gekennzeichnet ist. Die aktuelle Therapie zielt darauf ab, das Fortschreiten aufzuhalten; die wirksamste Behandlung ist eine Kombination aus Dutasterid und Pimecrolimus. Mit Dutasterid assoziierte Nebenwirkungen sind erektile Dysfunktion sowie Brustspannen und -vergrößerung; Pimecrolimus ruft Brennen hervor. Fallbericht: Wir präsentieren den Fall einer 57-jährigen postmenopausalen Frau mit 3-jähriger Vorgeschichte von plaqueförmiger vernarbender Alopezie in der Frontotemporalregion. Die FFA-Diagnose wurde durch Biopsie gesichert. Es wurde eine Therapie mit Dutasterid, 0,5 mg oral 1× täglich, eingeleitet, später wurde das Schema um topisches Pimecrolimus, 1% 2× täglich, erweitert. Acht Monate nach Behandlungsbeginn zeigte die Patientin Hyperpigmentierung an den Finger- und Fingergrundgelenken sowie auf den Wangen und am Kinn; Dutasterid und Pimecrolimus wurden abgesetzt. Bei der Nachuntersuchung nach 5 Monaten, während derer die Patientin lediglich Lichtschutz anwendete, hatte sich die Hyperpigmentierung um 80% gebessert. Fazit: Aufgrund des variablen klinischen Verlaufs der FFA ist das vorrangige Therapieziel die Eindämmung der Progression. Verschiedene medikamentöse Therapien sind erprobt worden; die Kombination aus Dutasterid und Pimecrolimus hat eine hohe Ansprechrate. Es liegen keine Berichte über Hyperpigmentierung in Verbindung mit dieser Wirkstoffkombination vor.
Molecular and Cytogenetic Analysis in Stillbirth: Results from 481 Consecutive Cases
Authors: Sahlin Ellika , Gustavsson Peter , Liedén Agne , Papadogiannakis Nikos , Bjäreborn Linus , Pettersson Karin , Nordenskjöld Magnus , Iwarsson Erik
Published: July 2014

Introduction: The underlying causes of stillbirth are heterogeneous and in many cases unexplained. Our aim was to conclude clinical results from karyotype and quantitative fluorescence-polymerase chain reaction (QF-PCR) analysis of all stillbirths occurring in Stockholm County between 2008 and 2012. By screening a subset of cases, we aimed to study the possible benefits of chromosomal microarray (CMA) in the analysis of the etiology of stillbirth. Methods: During 2008-2012, 481 stillbirths in Stockholm County were investigated according to a clinical protocol including karyotype or QF-PCR analysis. CMA screening was performed on a subset of 90 cases, corresponding to all stillbirths from 2010 without a genetic diagnosis. Results: Chromosomal aberrations were detected by karyotype or QF-PCR analysis in 7.5% of the stillbirths. CMA analysis additionally identified two known syndromes, one aberration disrupting a known disease gene, and 26 variants of unknown significance. Furthermore, CMA had a significantly higher success rate than karyotyping (100 vs. 80%, p < 0.001). Discussion: In the analysis of stillbirth, conventional karyotyping is prone to failure, and QF-PCR is a useful complement. We show that CMA has a higher success rate and aberration detection frequency than these methods, and conclude that CMA is a valuable tool for identification of chromosomal aberrations in stillbirth.
Brain Organization and Habitat Complexity in Anolis Lizards
Authors: Powell Brian J. , Leal Manuel
Published: July 2014

Across vertebrates, there is a broad correlation between neuroanatomy and the type of habitat preferred by a species. In general, species occupying habitats classified as more structurally complex have relatively larger brains and exaggerated structures related to navigating and exploiting those habitats. We empirically measured the structural habitat complexity of six species of Puerto Rican Anolis lizards, which have traditionally been classified as occupying three distinct habitat types. We also measured the volume of the whole brain as well as six structures putatively related to exploiting complex habitats in these species. We found a significant interspecific variation in structural habitat complexity, including a substantial variation between those belonging to the same ecomorph category. Despite this, we found no evidence to support the hypothesis that interspecific differences in habitat preferences, particularly differences in the relative structural complexity of those habitats, can favor a divergence in neuroanatomy. However, our findings indicate that, at a finer scale, species preferences for structural habitats vary greatly between Anolis species belonging to the same ecomorph category. This variation might contribute to the community structure of anoles by allowing multiple sympatric species of the same ecomorph category to occupy what, at a coarse scale, appears to be the same structural niche. We propose that, in the case of arboreal species, differences in the complexity of arboreal habitats alone may not be sufficient to favor divergent brain evolution.
Multiple Primary Acral Melanomas in Two Young Caucasian Patients
Authors: Lacruz Goretti , Cárdenas Isabel , Carrera Cristina , Díaz Alba , Puig-Butillè Joan Anton , Badenas Celia , Malvehy Josep , Puig Susana
Published: July 2014

Background: Acral melanoma (AM) is still one of the most poorly studied melanomas. It generally presents beyond the fifth decade of life and usually is a BRAF wild-type melanoma. Objective: To report the first cases of multiple primary AM in Caucasians. Methods: Clinical, dermoscopic, pathological and molecular profiles. Results: A healthy 34- year-old male presented an in situ subungual melanoma on his finger, and 22 months later a fast-growing nodular melanoma appeared in an existing nevus on the sole. Both melanomas carried the V600E BRAF mutation. A 19-year-old female patient presented 2 in situ melanomas on different parts of her left foot within a 6-year period of time. The patients have neither familiar melanoma nor germline mutations in CDKN2A/CDK4 genes. Conclusion: Multiple AM in Caucasians is very rare. BRAF mutations are possible, especially in a high-risk set of patients with multiple nevi. Specific acral examination must be recommended since AM still suffers delayed detection.
Pharmacological Characterization of a Highly Selective and Potent Partial Agonist of the MT2 Melatonin Receptor
Authors: Sakurai Taku , Koike Tatsuki , Nakayama Masaharu
Published: July 2014

Background/Aims: The MT2 melatonin receptor is a potential target for treating circadian rhythm sleep disorders. This study aims to characterize the recently identified MT2 melatonin receptor agonist. Methods: The pharmacological properties of the MT2 melatonin receptor-selective agonist as exemplified by compound 1 [N-(2-[7-benzyl-1,6-dihydro-2H-indeno(5,4-b)furan-8-yl]ethyl)acetamide] were evaluated by use of cell-free binding and cell-based functional assays. Results: Competition binding assays using 2-[125I]iodomelatonin revealed rapid, reversible, and high-affinity binding of compound 1 to human, mouse, and rat MT2 melatonin receptors. cAMP, ERK1/2, and PathHunter β-arrestin recruitment assays revealed partial agonist activities. However, compound 1 induced a more intense internalization of human MT2 melatonin receptor than melatonin. Based on studies using structurally related analogs of compound 1, we further demonstrated that the extent of internalization is independent of the intrinsic efficacy of agonists. Conclusion: These findings provide novel insights into the relationship between intrinsic agonist efficacy and agonist-induced internalization and demonstrate that compound 1 could serve as a pharmacological tool for future studies to elucidate the detailed molecular mechanism of MT2 receptor internalization.
Ein Fall von autosomal-rezessiver Hypotrichose mit Kräuselhaar mit veränderlichem Schweregrad: Verschlechterung und Verbesserung mit zunehmendem Alter
Authors: Matsuno Naoko , Kunisada Makoto , Kanki Haruhisa , Simomura Yutaka , Nishigori Chikako
Published: July 2014

Die autosomal-rezessiv vererbliche Hypotrichose mit Kräuselhaar (autosomal recessive woolly hair/hypotrichosis; ARWH/H) ist eine nichtsyndromale Haarwuchsanomalie, die durch spärliche, kurze, lockige Haare (WH/H) gekennzeichnet ist. Wir berichten über den Fall eines 3-jährigen Mädchens ohne Vorgeschichte von WH/H innerhalb der blutsverwandten Vorfahren. Bei der Geburt war der Haarwuchs unauffällig, dann entwickelte sich jedoch in den ersten 6 Monaten starker Haarausfall. Bis zur Vollendung des 3. Lebensjahrs hatte sich die Haardichte wieder etwas verbessert. In der Lichtmikroskopie war die Invagination von Haarschäften zu erkennen, und die Polarisationsmikroskopie deutete auf eine vollständige Disruption des Haarmarks hin. Eine direkte Sequenzanalyse von peripherem Blut ergab eine homozygote Missense-Mutation auf Exon 6 des Lipase-H-Gens (LIPH: c.736T>A, p.Cys246Ser); exakt dieselbe Mutation lag heterozygot auch bei beiden Eltern vor. Die anfängliche Verschlechterung und nachfolgende Verbesserung mit zunehmendem Lebensalter, die in diesem Fall zu beobachten waren, legen nahe, dass der klinische Verlauf der ARWH/H bei Patienten mit der hier vorliegenden LIPH-Mutation stark variieren kann, was wiederum darauf hindeutet, dass möglicherweise weitere Faktoren die Auswirkung von LIPH auf den Haarwuchs beeinflussen.
Identification of a Novel Nonsense Mutation in the Ligand-Binding Domain of the Vitamin D Receptor Gene and Clinical Description of Two Greek Patients with Hereditary Vitamin D-Resistant Rickets and Alopecia
Authors: Papadopoulou Anna , Bountouvi Evangelia , Gole Evangelia , Doulgeraki Artemis , Tournis Symeon , Papadimitriou Anastasios , Nicolaidou Polyxeni
Published: July 2014

Background/Aims: We analyzed the vitamin D receptor (VDR) gene in 2 Greek patients who exhibited the classical features of hereditary vitamin D-resistant rickets (HVDRR) type II, including severe bone deformities and alopecia. We also describe the clinical phenotypes and the response to treatment of our patients. Methods: Genomic DNA was extracted from peripheral blood samples of both patients. Coding region and flanking introns of VDR gDNA was amplified and direct sequenced. Results: A unique cytosine to thymine (C>T) transition was identified at nucleotide position 1066 (c.1066C>T) in the ligand-binding domain of the VDR gene of both patients, predicting the substitution of a glutamine to a terminal codon at position 356 (Gln356stop). Conclusions: The novel nonsense mutation c.1066C>T (Gln356stop) is expected to result in a VDR protein 71 amino acids shorter and thus to affect the normal VDR function. In particular, the missing protein part alters the VDR heterodimerization with the retinoid X receptor which has been correlated with the presence of alopecia. Both patients were introduced to treatment with supraphysiological doses of 1α-calcidiol which improved their clinical phenotypes except for alopecia.
An Uncommon Cause of Hypoglycemia: Insulin Autoimmune Syndrome
Authors: Savas-Erdeve Senay , Yılmaz Agladioglu Sebahat , Onder Asan , Peltek Kendirci Havva Nur , Bas Veysel Nijat , Sagsak Elif , Cetinkaya Semra , Aycan Zehra
Published: July 2014

Background: Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. Case Report: A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. Conclusion: In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out.
Using Daptomycin in Hospitalised Patients with cSSTI Caused by Staphylococcus aureus Has an Impact on Costs
Authors: Muszbek Noemi , Chapman Ruth , Browne Chantelle , Marsh Kevin , Gould Ian M. , Brown Ruth E. , Balp Maria-Magdelana , Allen Mike
Published: July 2014

Background: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. Methods: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. Results: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. Conclusions: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.