bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Object Tracking Using an Enhanced Mean Shift Method Based on Perceptual Spatial-Space Generation Model
Authors: Han Pengcheng , Du Junping , Fang Ming
Published: April 2013

Object tracking is one of the fundamental problems in computer vision, but existing efficient methods may not be suitable for spatial object tracking. Therefore, it is necessary to propose a more intelligent mathematical model. In this paper, we present an intelligent modeling method using an enhanced mean shift method based on a perceptual spatial-space generation model. We use a series of basic and composite graphic operators to complete signal perceptual transformation. The Monte Carlo contour detection method could overcome the dimensions problem of existing local filters. We also propose the enhanced mean shift method with estimation of spatial shape parameters. This method could adaptively adjust tracking areas and eliminate spatial background interference. Extensive experiments on a variety of spatial video sequences with comparison to several state-of-the-art methods demonstrate that our method could achieve reliable and accurate spatial object tracking.
Weight Loss Maintenance in African American Women: A Systematic Review of the Behavioral Lifestyle Intervention Literature
Authors: Tussing-Humphreys Lisa M. , Fitzgibbon Marian L. , Kong Angela , Odoms-Young Angela
Published: April 2013

We performed a systematic review of the behavioral lifestyle intervention trials conducted in the United States published between 1990 and 2011 that included a maintenance phase of at least six months, to identify intervention features that promote weight loss maintenance in African American women. Seventeen studies met the inclusion criteria. Generally, African American women lost less weight during the intensive weight loss phase and maintained a lower % of their weight loss compared to Caucasian women. The majority of studies failed to describe the specific strategies used in the delivery of the maintenance intervention, adherence to those strategies, and did not incorporate a maintenance phase process evaluation making it difficult to identify intervention characteristics associated with better weight loss maintenance. However, the inclusion of cultural adaptations, particularly in studies with a mixed ethnicity/race sample, resulted in less % weight regain for African American women. Studies with a formal maintenance intervention and weight management as the primary intervention focus reported more positive weight maintenance outcomes for African American women. Nonetheless, our results present both the difficulty in weight loss and maintenance experienced by African American women in behavioral lifestyle interventions.
Cosmetotextiles with Gallic Acid: Skin Reservoir Effect
Authors: Martí Meritxell , Alonso Cristina , Martínez Vanessa , Lis Manel , de la Maza Alfons , Parra José L. , Coderch Luisa
Published: April 2013

The antioxidant gallic acid (GA) has been incorporated into cotton (CO) and polyamide (PA) through two different vehicles, that is, liposomes and mixed micelles, and their respective absorption/desorption processes have been studied. Moreover, in vitro percutaneous absorption tests of different cosmetotextiles have been performed to demonstrate antioxidant penetration within the layers of the skin. When GA was embedded into the cosmetotextiles, it always promoted a reservoir effect that was much more marked than that observed for polyamide. Similar penetration was observed in the textiles treated with GA in mixed micelles or liposomes in such compartments of the skin as the stratum corneum, epidermis, and even the dermis. GA was detected in receptor fluid only when CO was treated with MM. This methodology may be useful in verifying how encapsulated substances incorporated into textile materials penetrate human skin. Indeed, such materials can be considered strategic delivery systems that release a given active compound into the skin at specific doses.
Potential of Immunoglobulin A to Prevent Allergic Asthma
Authors: Gloudemans Anouk K. , Lambrecht Bart N. , Smits Hermelijn H.
Published: April 2013

Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.
No Refund or Full Refund: When Should a Fashion Brand Offer Full Refund Consumer Return Service for Mass Customization Products?
Authors: Choi Tsan-Ming , Liu Na , Ren Shuyun , Hui Chi-Leung
Published: April 2013

We analytically explore in this paper the consumer return policy under fashion mass customization (MC) program. To be specific, we model the stochastic fashion MC program with the consideration of consumer demand uncertainty. If a consumer return policy is implemented, we further consider return uncertainty. By modeling the optimization objective of the risk averse MC fashion brand via a mean-variance approach, we derive the closed-form optimal solution under each case. We then conduct both analytical and numerical sensitivity analyses. For the scenario with full refund and return, we reveal the analytical conditions under which the optimal retail price and the optimal number of options available for customization (called the “optimal modularity level”) vary monotonically with respect to the salvage value and the return service charge. For the scenario when there is no refund and return, we show that the optimal retail price and the optimal modularity level are decreasing in the MC fashion brand's degree of risk aversion, the demand uncertainty, and the price-demand sensitivity coefficient. In addition, our numerical analysis indicates that whether the risk averse MC fashion brand would prefer offering consumer return with full refund to no return depends heavily on the demand-return correlation (DRC) parameter.
Exploratory Bioinformatics Study of lncRNAs in Alzheimer’s Disease mRNA Sequences with Application to Drug Development
Authors: Holden T. , Nguyen A. , Lin E. , Cheung E. , Dehipawala S. , Ye J. , Tremberger G. , Lieberman D. , Cheung T.
Published: April 2013

Long noncoding RNA (lncRNA) within mRNA sequences of Alzheimer’s disease genes, namely, APP, APOE, PSEN1, and PSEN2, has been analyzed using fractal dimension (FD) computation and correlation analysis. We examined lncRNA by comparing mRNA FD to corresponding coding DNA sequences (CDSs) FD. APP, APOE, and PSEN1 CDSs select slightly higher FDs compared to the mRNA, while PSEN2 CDSs FDs are lower. The correlation coefficient for these sequences is 0.969. A comparative study of differentially expressed MAPK signaling pathway lncRNAs in pancreatic cancer cells shows a correlation of 0.771. Selection of higher FD CDSs could indicate interaction of Alzheimer’s gene products APP, APOE, and PSEN1. Including hypocretin sequences (where all CDSs have higher fractal dimensions than mRNA) in the APP, APOE, and PSEN1 sequence analyses improves correlation, but the inclusion of erythropoietin (where all CDSs have higher FD than mRNA) would suppress correlation, suggesting that HCRT, a hypothalamus neurotransmitter related to the wake/sleep cycle, might be better when compared to EPO, a glycoprotein hormone, for targeting Alzheimer’s disease drug development. Fractal dimension and entropy correlation have provided supporting evidence, consistent with evolutionary studies, for using a zebrafish model together with a mouse model, in HCRT drug development.
Cloning, Expression, and Purification of Nucleoside Diphosphate Kinase fromAcinetobacter baumannii
Authors: Sikarwar Juhi , Kaushik Sanket , Sinha Mau , Kaur Punit , Sharma Sujata , Singh Tej P.
Published: April 2013

Acinetobacter baumanniiis a multidrug resistant pathogenic bacteria associated with hospital acquired infections. This bacterium possesses a variety of resistance mechanisms which makes it more difficult to control the bacterium with conventional drugs, and, so far no effective drug treatment is available against it. Nucleoside diphosphate kinase is an important enzyme, which maintains the total nucleotide triphosphate pool inside the cell by the transfer ofγ-phosphate from NTPs to NDPs. The role of nucleoside diphosphate kinase (Ndk) has also been observed in pathogenesis in other organisms. However, intensive studies are needed to decipher its other putative roles inAcinetobacter baumannii. In the present study, we have successfully cloned the gene encoding Ndk and achieved overexpression in bacterial host BL-21 (DE3). The overexpressed protein is further purified by nickel-nitrilotriacetic acid (Ni-NTA) chromatography.
A Self-Adaptive Frequency Response Compensation Method for a TIADC System
Authors: Ye Peng , Pan Huiqing , Zeng Hao , Li Min , Huang Wuhuang
Published: April 2013

Time interleaving is one of the most efficient techniques employed in high-speed sampling systems. However, the frequency response mismatch among different channels will create distortion tones that degrade the system performance. In this paper, a self-adaptive frequency response mismatch compensation method is presented, where the design of compensation filter is optimized with a self-adapting strategy. This digital postprocessing technique realizes the compensation of frequency response effectively and also the increase of the digital bandwidth of the acquisition system. MATLAB-based simulation and an actual two-channel acquisition system test verify the effectiveness of the algorithm.
Outcome and Challenges of Kidney Transplant in Patients with Sickle Cell Disease
Authors: Okafor U. H. , Aneke E.
Published: April 2013

Sickle cell nephropathy is a common presentation in patients with sickle cell disease. End-stage kidney disease is the most severe presentation of sickle cell nephropathy in terms of morbidity and mortality. Sickle cell disease patients with end-stage kidney disease are amenable to renal replacement therapy including kidney transplant. Kidney transplant in these patients has been associated with variable outcome with recent studies reporting short- and long-term outcomes comparable to that of patients with HbAA. Sickle cell disease patients are predisposed to various haematological, cardiorespiratory, and immunological challenges. These challenges have the potential to limit, delay, or prevent kidney transplant in patients with sickle cell disease. There are few reports on the outcome and challenges of kidney transplant in this group of patients. The aim of this review is to highlight the outcome and challenges of kidney transplant in patients with sickle cell disease.
Melanoma M (Zero): Diagnosis and Therapy
Authors: Rastrelli Marco , Alaibac Mauro , Stramare Roberto , Chiarion Sileni Vanna , Montesco Maria Cristina , Vecchiato Antonella , Campana Luca Giovanni , Rossi Carlo Riccardo
Published: April 2013

This paper reviews the epidemiology, diagnosis, and treatment of M zero cutaneous melanoma including the most recent developments. This review also examined the main risk factors for melanoma. Tumor thickness measured according to Breslow, mitotic rate, ulceration, and growth phase has the greatest predictive value for survival and metastasis. Wide excision of the primary tumor is the only potentially curative treatment for primary melanoma. The sentinel node biopsy must be performed on all patients who have a primary melanoma with a Breslow thickness > 1 mm, or if the melanoma is from 0,75 mm to 1 mm thick but it is ulcerated and/or the mitotic index is ≥1. Total lymph node dissection consists in removing the residual lymph nodes in patients with positive sentinel node biopsy, or found positive on needle aspiration biopsy, without radiological evidence of spread. Isolated limb perfusion and isolated limb infusion are employed in patients within transit metastases with a rate of complete remission in around 50% and 38% of cases. Electrochemotherapy is mainly indicated for palliation in cases of metastatic disease, though it may sometimes be useful to complete isolated limb perfusion. The only agent found to affect survival as an adjuvant treatment is interferon alpha-2. Adjuvant radiotherapy improves local control of melanoma in patients at a high risk of recurrence after lymph node dissection.
A Comparison of Field-Based and Lab-Based Experiments to Evaluate User Experience of Personalised Mobile Devices
Authors: Sun Xu , May Andrew
Published: April 2013

There is a growing debate in the literature regarding the tradeoffs between lab and field evaluation of mobile devices. This paper presents a comparison of field-based and lab-based experiments to evaluate user experience of personalised mobile devices at large sports events. A lab experiment is recommended when the testing focus is on the user interface and application-oriented usability related issues. However, the results suggest that a field experiment is more suitable for investigating a wider range of factors affecting the overall acceptability of the designed mobile service. Such factors include the system function and effects of actual usage contexts aspects. Where open and relaxed communication is important (e.g., where participant groups are naturally reticent to communicate), this is more readily promoted by the use of a field study.
Single-Channel Data Broadcasting under Small Waiting Latency
Authors: Yu Hsiang-Fu
Published: April 2013

Due to the advancement of network technology, video-on-demand (VoD) services are growing in popularity. However, individual stream allocation for client requests easily causes a VoD system overload; when its network and disk bandwidth cannot match client growth. This study thus presents a fundamentally different approach by focusing solely on a class of applications identified as latency tolerant applications. Because video broadcasting does not provide interactive (i.e., VCR) functions, a client is able to tolerate playback latency from a video server. One efficient broadcasting method is periodic broadcasting, which divides a video into smaller segments and broadcasts these segments periodically on multiple channels. However, numerous practical systems, such as digital video broadcasting-handheld (DVB-H), do not allow clients to download video data from multiple channels because clients usually only have one tuner. To resolve this problem in multiple-channel broadcasting, this study proposes a novel single-channel broadcasting scheme, which leverages segment-broadcasting capability further for more efficient video delivery. The comparison results show that, with the same settings of broadcasting bandwidth, the proposed scheme outperforms the alternative broadcasting scheme, the hopping insertion scheme, SingBroad, PAS, and the reverse-order scheduling scheme for the maximal waiting time.
Use of Animal Models to Investigate Major Allergens Associated with Food Allergy
Authors: Van Gramberg Jenna L. , de Veer Michael J. , O'Hehir Robyn E. , Meeusen Els N. T. , Bischof Robert J.
Published: April 2013

Food allergy is an emerging epidemic that affects all age groups, with the highest prevalence rates being reported amongst Western countries such as the United States (US), United Kingdom (UK), and Australia. The development of animal models to test various food allergies has been beneficial in allowing more rapid and extensive investigations into the mechanisms involved in the allergic pathway, such as predicting possible triggers as well as the testing of novel treatments for food allergy. Traditionally, small animal models have been used to characterise immunological pathways, providing the foundation for the development of numerous allergy models. Larger animals also merit consideration as models for food allergy as they are thought to more closely reflect the human allergic state due to their physiology and outbred nature. This paper will discuss the use of animal models for the investigation of the major food allergens; cow's milk, hen's egg, and peanut/other tree nuts, highlight the distinguishing features of each of these models, and provide an overview of how the results from these trials have improved our understanding of these specific allergens and food allergy in general.
Autonomic Nervous System in the Control of Energy Balance and Body Weight: Personal Contributions
Authors: Messina G. , De Luca V. , Viggiano An. , Ascione A. , Iannaccone T. , Chieffi S. , Monda M.
Published: April 2013

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a “pandemia” in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the “Mona Lisa Hypothesis,” an acronym for “most obesities known are low in sympathetic activity.” Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.
A Comparative Analysis of the Mechanical Role of Leaf Sheaths of Poaceae, Juncaceae, and Cyperaceae
Authors: Kempe Andreas , Sommer Martin , Neinhuis Christoph
Published: April 2013

Similarities in structural organization of the culm in Poaceae, Juncaceae, and Cyperaceae such as leaf sheaths and the presence of intercalary meristems at every node suggest the same mechanical properties and, accordingly, the same functionality. Meristems are zones of tissue formation, which constitute areas of weakness along the entire culm and provide the basis for rapid shoot elongation. Leaf sheaths clasp the culm preventing the shoot from breaking, ensuring the rigidity to grow erectly and to avoid damage of the meristematic tissue. The mechanical influence of leaf sheaths was investigated in members of Poaceae, Juncaceae, and Cyperaceae in the flowering stage. Mechanical properties of Poa araratica, Bromus erectus, Arrhenatherum elatius (Poaceae), Luzula nivea (Juncaceae), and Carex arctata (Cyperaceae) were determined in three-point bending before and after the removal of leaf sheaths. The presence of leaf sheaths results in smoothing the distribution of flexural rigidity and therefore avoids stress peaks. The achieved maxima of relative contribution of leaf sheaths to entire flexural rigidity ranged from 55% up to 81% for Poaceae, 72% for C. arctata, and 40% for L. nivea. Across the investigated families, the mechanical role of leaf sheaths could be verified as essential for culm stability during development and beyond.
Vegetation Structure and Composition across Different Land Uses in a Semiarid Savanna of Southern Zimbabwe
Authors: Zisadza-Gandiwa Patience , Mabika Cheryl T. , Kupika Olga L. , Gandiwa Edson , Murungweni Chrispen
Published: April 2013

We compared the structure and composition of vegetation communities across different land uses in the northern Gonarezhou National Park and adjacent areas, southeast Zimbabwe. Vegetation data were collected from 60 sample plots using a stratified random sampling technique from April to May 2012. Stratification was by land use, and sample plots in all three strata occurred on predominantly siallitic soils. Our results show that the communal area had higher woody plant species diversity (H'=2.66) than the protected area (H'=1.78). However, the protected area had higher grass species richness per plot than the communal area and resettlement area. Overall, the protected area had more structural and compositional diversity than the other land use areas. These findings suggest that the areas adjacent to protected areas contribute to plant diversity in the greater ecosystem; hence conservation efforts should extend beyond the boundaries of protected areas. We recommend that protected area management should engage community-based institutions in neighbouring areas for effective monitoring of woody vegetation structure and composition.
Integrated Multiscale Latent Variable Regression and Application to Distillation Columns
Authors: Madakyaru Muddu , Nounou Mohamed N. , Nounou Hazem N.
Published: April 2013

Proper control of distillation columns requires estimating some key variables that are challenging to measure online (such as compositions), which are usually estimated using inferential models. Commonly used inferential models include latent variable regression (LVR) techniques, such as principal component regression (PCR), partial least squares (PLS), and regularized canonical correlation analysis (RCCA). Unfortunately, measured practical data are usually contaminated with errors, which degrade the prediction abilities of inferential models. Therefore, noisy measurements need to be filtered to enhance the prediction accuracy of these models. Multiscale filtering has been shown to be a powerful feature extraction tool. In this work, the advantages of multiscale filtering are utilized to enhance the prediction accuracy of LVR models by developing an integrated multiscale LVR (IMSLVR) modeling algorithm that integrates modeling and feature extraction. The idea behind the IMSLVR modeling algorithm is to filter the process data at different decomposition levels, model the filtered data from each level, and then select the LVR model that optimizes a model selection criterion. The performance of the developed IMSLVR algorithm is illustrated using three examples, one using synthetic data, one using simulated distillation column data, and one using experimental packed bed distillation column data. All examples clearly demonstrate the effectiveness of the IMSLVR algorithm over the conventional methods.
Efficacy and Tolerability of Peginterferonα-2a and Peginterferonα-2b, Both plus Ribavirin, for Chronic Hepatitis C: A Meta-Analysis of Randomized Controlled Trials
Authors: Yang Zongguo , Zhuang Liping , Yang Lei , Chen Xiaorong
Published: April 2013

Background. The efficacy and tolerability of peginterferonα-2a and peginterferonα-2b in chronic hepatitis C (CHC) patients remain controversial.Methods. PubMed, Ovid, and Cochrane libraries were electronically searched until August 30, 2012. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently.Results. The overall sustained virologic response (SVR) rate of the peginterferonα-2a group was significantly higher than that of the peginterferonα-2b group (46.7% versus 42.4%,Pvalue = 0.01). The same tendency was observed for naïve, genotype 1/4, and genotype 2/3 patients. The early virologic response (EVR) and end-of-treatment response (ETR) rates were significantly higher in the peginterferonα-2a group than in the peginterferonα-2b group (56.1% versus 49.8%,P<0.0001; 67.9% versus 56.6%,P<0.00001, resp.). Peginterferonα-2a had a significantly lower discontinuation rate than peginterferonα-2b (27.9% versus 33.9%,P<0.0001) in naïve patients. In both naïve CHC and hepatitis C virus genotype 1 patients, peginterferonα-2a had a higher relapse rate than peginterferonα-2b.Conclusions. Peginterferonα-2a has superior efficacy with higher EVR, ETR, and SVR than peginterferonα-2b for CHC patients, both plus ribavirin. Peginterferonα-2a might obtain a similar or even lower discontinuation rate than peginterferonα-2b. However, peginterferonα-2a had a higher relapse rate than peginterferonα-2b.
1,4-dihydroxy-2-naphthoic Acid Induces Apoptosis in Human Keratinocyte: Potential Application for Psoriasis Treatment
Authors: Mok Chong-Fai , Xie Chuan-Ming , Sham Kathy Wai-Yan , Lin Zhi-Xiu , Cheng Christopher Hon-Ki
Published: April 2013

Psoriasis, which affects approximately 1–3% of the population worldwide, is a chronic inflammatory skin disorder characterized by epidermal keratinocytes hyperproliferation, abnormal differentiation, and inflammatory infiltration. Decrease in keratinocyte apoptosis is a specific pathogenic phenomenon in psoriasis. Chinese herbs have been used for the treatment of psoriasis in China showing promising effect in clinical trials. A traditional Chinese medicine has relatively fewer side effects with longer remission time and lower recurrence rate. The extract ofRubia cordifoliaL. (EA) was previously found by us to induce HaCaT keratinocytes apoptosis. In this study we identified one of the components inRubia cordifoliaL., the anthraquinone precursor 1,4-dihydroxy-2-naphthoic acid (DHNA), induces HaCaT keratinocytes apoptosis through G0/G1 cell cycle arrest. We have also demonstrated that DHNA acts through both caspase-dependent and caspase-independent pathways. Besides, cytotoxicity and IL-1αrelease assays indicate that DHNA causes less irritation problems than dithranol, which is commonly employed to treat psoriasis in many countries. Since DHNA possesses similar apoptotic effects on keratinocytes as dithranol but causes less irritation, DHNA therefore constitutes a promising alternative agent for treating psoriasis. Our studies also provide an insight on the potential of using EA and DHNA, alternatively, as a safe and effective treatment modality for psoriasis.
Seismic Hazard of the Uttarakhand Himalaya, India, from Deterministic Modeling of Possible Rupture Planes in the Area
Authors: Joshi Anand , Kumar Ashvini , Castanos Heriberta , Lomnitz Cinna
Published: April 2013

This paper presents use of semiempirical method for seismic hazard zonation. The seismotectonically important region of Uttarakhand Himalaya has been considered in this work. Ruptures along the lineaments in the area identified from tectonic map are modeled deterministically using semi empirical approach given by Midorikawa (1993). This approach makes use of attenuation relation of peak ground acceleration for simulating strong ground motion at any site. Strong motion data collected over a span of three years in this region have been used to develop attenuation relation of peak ground acceleration of limited magnitude and distance applicability. The developed attenuation relation is used in the semi empirical method to predict peak ground acceleration from the modeled rupture planes in the area. A set of values of peak ground acceleration from possible ruptures in the area at the point of investigation is further used to compute probability of exceedance of peak ground acceleration of values 100 and 200 gals. The prepared map shows that regions like Tehri, Chamoli, Almora, Srinagar, Devprayag, Bageshwar, and Pauri fall in a zone of 10% probability of exceedence of peak ground acceleration of value 200 gals.
Electrodeposition, Characterization, and Corrosion Stability of Nanostructured Anodic Oxides on New Ti‐15Zr‐5Nb Alloy Surface
Authors: Calderon Moreno Jose M. , Vasilescu Cora , Drob Silviu Iulian , Popa Monica , Drob Paula , Vasilescu Ecaterina
Published: April 2013

A new Ti‐15Zr‐5Nb alloy with suitable microstructure and mechanical properties was processed by galvanostatic anodization in 0.3 M H3PO4 solution and a continuous nanostructured layer of protective TiO2 oxide was electrodeposited. The obtained anatase oxide layer has a nanotubes‐like porosity (SEM observations) and contains significant amount of phosphorus in phosphotitanate compound embedded in the oxide lattice (Raman, FT‐IR, SEM, and EDX analysis). This layer composition can stimulate the formation of the bone and its porosity can offer a good scaffold for bone cell adhesion. The electrochemical behaviour, corrosion stability, and variations of the open circuit potentials, Eoc, and corresponding open circuit potential gradients, ΔEoc, for 1500 soaking hours in Ringer solutions of 3.21, 7.58, and 8.91 pH values were studied. The anodized layer was more resistant, stable (from EIS spectra), and was formed from an inner barrier insulating layer that assures the very good alloy corrosion resistance and an outer porous layer that provides the good conditions for cell development. The nanostructured alloy has higher corrosion stability, namely, a more reduced quantity of ions released and a lower toxicity than that of the bare one. The monitoring of Eoc and ΔEoc showed the enhancement and stabilizing of the long‐term passive state of the anodized alloy and, respectively, no possibility at galvanic corrosion.
Animal Models of GWAS-Identified Type 2 Diabetes Genes
Authors: da Silva Xavier Gabriela , Bellomo Elisa A. , McGinty James A. , French Paul M. , Rutter Guy A.
Published: April 2013

More than 65loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notablyTCF7L2andZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.
Measurements and Design Calculations for a Deep Coaxial Borehole Heat Exchanger in Aachen, Germany
Authors: Dijkshoorn Lydia , Speer Simon , Pechnig Renate
Published: April 2013

This study aims at evaluating the feasibility of an installation for space heating and cooling the building of the university in the center of the city Aachen, Germany, with a 2500 m deep coaxial borehole heat exchanger (BHE). Direct heating the building in winter requires temperatures of 40°C. In summer, cooling the university building uses a climatic control adsorption unit, which requires a temperature of minimum 55°C. The drilled rocks of the 2500 m deep borehole have extremely low permeabilities and porosities less than 1%. Their thermal conductivity varies between 2.2 W/(m·K) and 8.9 W/(m·K). The high values are related to the quartzite sandstones. The maximum temperature in the borehole is 85°C at 2500 m depth, which corresponds to a mean specific heat flow of 85 mW/m2–90 mW/m2. Results indicate that for a short period, the borehole may deliver the required temperature. But after a 20-year period of operation, temperatures are too low to drive the adsorption unit for cooling. In winter, however, the borehole heat exchanger may still supply the building with sufficient heat, with temperatures varying between 25 and 55°C and a circulation flow rate of 10 m3/h at maximum.
Full-State Linearization and Stabilization of SISO Markovian Jump Nonlinear Systems
Authors: Lin Zhongwei , Liu Jizhen , Niu Yuguang
Published: April 2013

This paper investigates the linearization and stabilizing control design problems for a class of SISO Markovian jump nonlinear systems. According to the proposed relative degree set definition, the system can be transformed into the canonical form through the appropriate coordinate changes followed with the Markovian switchings; that is, the system can be full-state linearized in every jump mode with respect to the relative degree setn,…,n. Then, a stabilizing control is designed through applying the backstepping technique, which guarantees the asymptotic stability of Markovian jump nonlinear systems. A numerical example is presented to illustrate the effectiveness of our results.
The Dentato-Rubro-Olivary Tract: Clinical Dimension of This Anatomical Pathway
Authors: Khoyratty Fadil , Wilson Thomas
Published: April 2013

Symptomatic palatal tremor is potentially the result of a lesion in the triangle of Guillain-Mollaret (1931) and is associated with hypertrophic olivary degeneration (HOD) which has characteristic MR findings. The triangle is defined by dentate efferents ascending through the superior cerebellar peduncle and crossing in the decussation of the brachium conjunctivum inferior to the red nucleus, to finaliy reach the inferior olivary nucleus (ION) via the central tegmental tract. The triangle is completed by ION decussating efferents terminating on the original dentate nucleus via the inferior cerebellar peduncle. We can demonstrate the anatomy of this anatomical triangle using a clinical case of palatal tremor presenting with bilateral subjective pulsatile tinnitus along with the pathognomonic MR findings previously described. The hyperintense T2 signal in these patients may be permanent, but the hypertrophied olive normally regresses after 4 years. The temporal relationship between the evolution of the histopathology and the development of the palatal tremor remains unknown as does the natural history of the tremor. Botox injection at the level of tensor and levator veli palatini insertion have been used to treat patients with disabling tremor synchronous tinnitus. A lesion involving the triangle can have a quite varied clinical expression.
Fault Diagnosis of Complex Industrial Process Using KICA and Sparse SVM
Authors: Xu Jie , Zhao Jin , Ma Baoping , Hu Shousong
Published: April 2013

New approaches are proposed for complex industrial process monitoring and fault diagnosis based on kernel independent component analysis (KICA) and sparse support vector machine (SVM). The KICA method is a two-phase algorithm: whitened kernel principal component analysis (KPCA). The data are firstly mapped into high-dimensional feature subspace. Then, the ICA algorithm seeks the projection directions in the KPCA whitened space. Performance monitoring is implemented through constructing the statistical index and control limit in the feature space. If the statistical indexes exceed the predefined control limit, a fault may have occurred. Then, the nonlinear score vectors are calculated and fed into the sparse SVM to identify the faults. The proposed method is applied to the simulation of Tennessee Eastman (TE) chemical process. The simulation results show that the proposed method can identify various types of faults accurately and rapidly.
Structure-Specific Endonucleases Xpf and Mus81 Play Overlapping but Essential Roles in DNA Repair by Homologous Recombination
Authors: Kikuchi Koji , Narita Takeo , Pham Van T. , Iijima Junko , Hirota Kouji , Keka Islam Shamima , Mohiuddin  , Okawa Katsuya , Hori Tetsuya , Fukagawa Tatsuo , Essers Jeroen , Kanaar Roland , Whitby Matthew C. , Sugasawa Kaoru , Taniguchi Yoshihito , Kitagawa Katsumi , Takeda Shunichi
Published: April 2013

DNA double-strand breaks (DSB) occur frequently during replication in sister chromatids and are dramatically increased when cells are exposed to chemotherapeutic agents including camptothecin. Such DSBs are efficiently repaired specifically by homologous recombination (HR) with the intact sister chromatid. HR, therefore, plays pivotal roles in cellular proliferation and cellular tolerance to camptothecin. Mammalian cells carry several structure-specific endonucleases, such as Xpf-Ercc1 and Mus81-Eme1, in which Xpf and Mus81 are the essential subunits for enzymatic activity. Here, we show the functional overlap between Xpf and Mus81 by conditionally inactivating Xpf in the chicken DT40 cell line, which has no Mus81 ortholog. Although mammalian cells deficient in either Xpf or Mus81 are viable, Xpf inactivation in DT40 cells was lethal, resulting in a marked increase in the number of spontaneous chromosome breaks. Similarly, inactivation of both Xpf and Mus81 in human HeLa cells and murine embryonic stem cells caused numerous spontaneous chromosome breaks. Furthermore, the phenotype of Xpf-deficient DT40 cells was reversed by ectopic expression of human Mus81-Eme1 or human Xpf-Ercc1 heterodimers. These observations indicate the functional overlap of Xpf-Ercc1 and Mus81-Eme1 in the maintenance of genomic DNA. Both Mus81-Eme1 and Xpf-Ercc1 contribute to the completion of HR, as evidenced by the data that the expression of Mus81-Eme1 or Xpf-Ercc1 diminished the number of camptothecin-induced chromosome breaks in Xpf-deficient DT40 cells, and to preventing early steps in HR by deleting XRCC3 suppressed the nonviability of Xpf-deficient DT40 cells. In summary, Xpf and Mus81 have a substantially overlapping function in completion of HR. Cancer Res; 73(14); 4362–71. ©2013 AACR.
FGFR1 Is Essential for Prostate Cancer Progression and Metastasis
Authors: Yang Feng , Zhang Yongyou , Ressler Steven J. , Ittmann Michael M. , Ayala Gustavo E. , Dang Truong D. , Wang Fen , Rowley David R.
Published: April 2013

The fibroblast growth factor receptor 1 (FGFR1) is ectopically expressed in prostate carcinoma cells, but its functional contributions are undefined. In this study, we report the evaluation of a tissue-specific conditional deletion mutant generated in an ARR2PBi(Pbsn)-Cre/TRAMP/fgfr1loxP/loxP transgenic mouse model of prostate cancer. Mice lacking fgfr1, in prostate cells developed smaller tumors that also included distinct cancer foci still expressing fgfr1 indicating focal escape from gene excision. Tumors with confirmed fgfr1 deletion exhibited increased foci of early, well-differentiated cancer and phyllodes-type tumors, and tumors that escaped fgfr1 deletion primarily exhibited a poorly differentiated phenotype. Consistent with these phenotypes, mice carrying the fgfr1 null allele survived significantly longer than those without fgfr1 deletion. Most interestingly, all metastases were primarily negative for the fgfr1 null allele, exhibited high FGFR1 expression, and a neuroendocrine phenotype regardless of fgfr1 status in the primary tumors. Together, these results suggest a critical and permissive role of ectopic FGFR1 signaling in prostate tumorigenesis and particularly in mechanisms of metastasis. Cancer Res; 73(12); 3716–24. ©2013 AACR.
PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains
Authors: Picaud Sarah , Da Costa David , Thanasopoulou Angeliki , Filippakopoulos Panagis , Fish Paul V. , Philpott Martin , Fedorov Oleg , Brennan Paul , Bunnage Mark E. , Owen Dafydd R. , Bradner James E. , Taniere Philippe , O'Sullivan Brendan , Müller Susanne , Schwaller Juerg , Stankovic Tatjana , Knapp Stefan
Published: April 2013

Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. BET proteins are recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 and H4. Inhibition of the BET–histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer. Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target. Cancer Res; 73(11); 3336–46. ©2013 AACR.
NF-κB Regulates Radioresistance Mediated By β1-Integrin in Three-Dimensional Culture of Breast Cancer Cells
Authors: Ahmed Kazi Mokim , Zhang Hui , Park Catherine C.
Published: April 2013

β1-integrin induction enhances breast cancer cell survival after exposure to ionizing radiation (IR), but the mechanisms of this effect remain unclear. Although NF-κB initiates prosurvival signaling pathways post-IR, the molecular function of NF-κB with other key elements in radioresistance, particularly with respect to extracellular matrix-induced signaling, is not known. We discovered a typical NF-κB–binding site in the β1-integrin promoter region, indicating a possible regulatory role for NF-κB. Using three-dimensional laminin-rich extracellular matrix (3D lrECM) culture, we show that NF-κB is required for β1-integrin transactivation in T4-2 breast cancer cells post-IR. Inhibition of NF-κB reduced clonogenic survival and induced apoptosis and cytostasis in formed tumor colonies. In addition, T4-2 tumors with inhibition of NF-κB activity exhibit decreased growth in athymic mice, which was further reduced by IR with downregulated β1-integrin expression. Direct interactions between β1-integrin and NF-κB p65 were induced in nonmalignant breast epithelial cells, but not in malignant cells, indicating context-specific regulation. As β1-integrin also activates NF-κB, our findings reveal a novel forward feedback pathway that could be targeted to enhance therapy. Cancer Res; 73(12); 3737–48. ©2013 AACR.
YAP/TEAD–Mediated Transcription Controls Cellular Senescence
Authors: Xie Qi , Chen Jing , Feng Han , Peng Shengyi , Adams Ursula , Bai Yujie , Huang Li , Li Ji , Huang Junjian , Meng Songshu , Yuan Zengqiang
Published: April 2013

Transcription coactivator Yes-associated protein (YAP) plays an important role in the regulation of cell proliferation and apoptosis. Here, we identify a new role of YAP in the regulation of cellular senescence. We find that the expression levels of YAP proteins decrease following the replication-induced cellular senescence in IMR90 cells. Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53–dependent. Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP–TEAD complex. Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence. Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence. Taken together, our findings define the critical role of YAP in the regulation of cellular senescence and provide a novel insight into a potential chemotherapeutic avenue for tumor suppression. Cancer Res; 73(12); 3615–24. ©2013 AACR.
Threshold Levels of ABL Tyrosine Kinase Inhibitors Retained in Chronic Myeloid Leukemia Cells Determine Their Commitment to Apoptosis
Authors: O'Hare Thomas , Eide Christopher A. , Agarwal Anupriya , Adrian Lauren T. , Zabriskie Matthew S. , MacKenzie Ryan J. , LaTocha Dorian H. , Johnson Kara J. , You Huihong , Luo Jenny , Riddle Steven M. , Marks Bryan D. , Vogel Kurt W. , Koop Dennis R. , Apgar John , Tyner Jeffrey W. , Deininger Michael W. , Druker Brian J.
Published: April 2013

The imatinib paradigm in chronic myelogenous leukemia (CML) established continuous BCR-ABL inhibition as a design principle for ABL tyrosine kinase inhibitors (TKI). However, clinical responses seen in patients treated with the ABL TKI dasatinib despite its much shorter plasma half-life and the apparent rapid restoration of BCR-ABL signaling activity following once-daily dosing suggested acute, potent inhibition of kinase activity may be sufficient to irrevocably commit CML cells to apoptosis. To determine the specific requirements for ABL TKI-induced CML cell death for a panel of clinically important ABL TKIs (imatinib, nilotinib, dasatinib, ponatinib, and DCC-2036), we interrogated response of CML cell lines and primary CML cells following acute drug exposure using intracellular fluorescence-activated cell sorting and immunoblot analyses of BCR-ABL signaling, apoptosis measurements, liquid chromatography/tandem mass spectrometry of intracellular drug levels, and biochemical TKI dissociation studies. Importantly, significant intracellular TKI stores were detected following drug washout, levels of which tracked with onset of apoptosis and incomplete return of BCR-ABL signaling, particularly pSTAT5, to baseline. Among TKIs tested, ponatinib showed the most robust capacity for apoptotic commitment showing sustained suppression of BCR-ABL signaling even at low intracellular levels following extensive washout, consistent with high-affinity binding and slow dissociation from ABL kinase. Together, our findings suggest commitment of CML cells to apoptosis requires protracted incomplete restoration of BCR-ABL signaling mediated by intracellular retention of TKIs above a quantifiable threshold. These studies refine our understanding of apoptotic commitment in CML cells and highlight parameters important to design of therapeutic kinase inhibitors for CML and other malignancies. Cancer Res; 73(11); 3356–70. ©2013 AACR.
Hedgehog Signaling Alters Reliance on EGF Receptor Signaling and Mediates Anti-EGFR Therapeutic Resistance in Head and Neck Cancer
Authors: Keysar Stephen B. , Le Phuong N. , Anderson Ryan T. , Morton J. Jason , Bowles Daniel W. , Paylor Jeramiah J. , Vogler Brian W. , Thorburn Jackie , Fernandez Pamela , Glogowska Magdalena J. , Takimoto Sarah M. , Sehrt Daniel B. , Gan Gregory N. , Eagles-Soukup Justin R. , Serracino Hilary , Hirsch Fred R. , Lucia M. Scott , Thorburn Andrew , Song John I. , Wang Xiao-Jing , Jimeno Antonio
Published: April 2013

The EGF receptor (EGFR)-directed monoclonal antibody cetuximab is the only targeted therapy approved for the treatment of squamous cell carcinoma of the head and neck (HNSCC) but is only effective in a minority of patients. Epithelial-to-mesenchymal transition (EMT) has been implicated as a drug resistance mechanism in multiple cancers, and the EGFR and Hedgehog pathways (HhP) are relevant to this process, but the interplay between the two pathways has not been defined in HNSCC. Here, we show that HNSCC cells that were naturally sensitive to EGFR inhibition over time developed increased expression of the HhP transcription factor GLI1 as they became resistant after long-term EGFR inhibitor exposure. This robustly correlated with an increase in vimentin expression. Conversely, the HhP negatively regulated an EGFR-dependent, EMT-like state in HNSCC cells, and pharmacologic or genetic inhibition of HhP signaling pushed cells further into an EGFR-dependent phenotype, increasing expression of ZEB1 and VIM. In vivo treatment with cetuximab resulted in tumor shrinkage in four of six HNSCC patient-derived xenografts; however, they eventually regrew. Cetuximab in combination with the HhP inhibitor IPI-926 eliminated tumors in two cases and significantly delayed regrowth in the other two cases. Expression of EMT genes TWIST and ZEB2 was increased in sensitive xenografts, suggesting a possible resistant mesenchymal population. In summary, we report that EGFR-dependent HNSCC cells can undergo both EGFR-dependent and -independent EMT and HhP signaling is a regulator in both processes. Cetuximab plus IPI-926 forces tumor cells into an EGFR-dependent state, delaying or completely blocking tumor recurrence. Cancer Res; 73(11); 3381–92. ©2013 AACR.