bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative evaluation of cultural heritage information modeling techniques
Authors: Hug Charlotte , Gonzalez-Perez Cesar
Published: August 2012

In this article we evaluate three modeling techniques coming from information system engineering to represent cultural heritage domain concepts. Evaluations of the modeling techniques were performed by carrying out experiments with cultural heritage specialists. The first experiment consisted in evaluating UML class diagrams and a conceptual graph. The second experiment evaluated a value cluster modeling approach. These qualitative evaluations were conducted using focus groups composed of cultural heritage specialists. We evaluated the perceived ease of use, the perceived usefulness, and the intention to use of the three techniques (UML class diagrams, conceptual graphs, and the value cluster approach). Thanks to these evaluations, we will be able to propose a combined approach using value cluster modeling and UML class diagraming techniques to describe cultural heritage information.
An essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells
Authors: Gao Xiaohua , Yu Linda , Castro Lysandra , Tucker Charles J. , Moore Alicia B. , Xiao Hang , Dixon Darlene
Published: August 2012

Previously, we reported that fenvalerate (Fen) promotes proliferation of human uterine leiomyoma (UtLM) cells by enhancing progression of cells from G0-G1to S phase through molecular mechanisms independent of estrogen receptor-α and -β. The cyclin-dependent kinase (CDK) inhibitor p27, which blocks G1to S phase transitions and is an important regulator of CDK2, is often decreased in hormonally regulated diseases, including uterine leiomyomas. Therefore, we were interested in whether Fen could regulate the expression of p27 and whether p27 might play a role in Fen-induced cell proliferation. Expression of p27 in Fen-treated UtLM and uterine smooth muscle cells (UtSMCs) was examined. We found that p27 mRNA was significantly downregulated and that protein levels were decreased in both cell types treated with 10 μM Fen for 24 h compared with respective controls. Overexpression of p27 in UtLM cells and UtSMCs using an adenovirus doxycycline (Dox)-regulated Tet-off system abrogated the proliferative effects of Fen, as evidenced by decreased total cell numbers and BrdU incorporation. Fen treatment increased CDK2 mRNA expression levels; however, overexpression of p27 also abolished this effect. In contrast, Dox treatment dramatically restored the above muted responses. Finally, we utilized siRNA to knock down p27 expression. After transfection, mRNA levels of p27 were downregulated in UtLM cells and UtSMCs and total cell numbers and BrdU incorporation increased significantly compared with nontransfected cells. Fen treatment in the presence of p27 silencing enhanced the increased cell counts and BrdU labeling in UtLM cells and UtSMCs. Taken together, these results indicate that p27 downregulation is critical for Fen-induced cell proliferation.
Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess
Authors: Liu Jiarong , Zhang Wei , Chuang Gin C. , Hill Helliner S. , Tian Ling , Fu Yuchang , Moellering Douglas R. , Garvey W. Timothy
Published: August 2012

We have suggested previously that Tribbles homolog 3 (TRIB3), a negative regulator of Akt activity in insulin-sensitive tissues, could mediate glucose-induced insulin resistance in muscle under conditions of chronic hyperglycemia (Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT. Am J Physiol Endocrinol Metab 298: E565–E576, 2010). In the current study, we have assessed short-term physiological regulation of TRIB3 in skeletal muscle and adipose tissues by nutrient excess and fasting as well as TRIB3's ability to modulate glucose transport and mitochondrial oxidation. In Sprague-Dawley rats, we found that short-term fasting enhanced insulin sensitivity concomitantly with decrements in TRIB3 mRNA (66%, P < 0.05) and protein (81%, P < 0.05) in muscle and increments in TRIB3 mRNA (96%, P < 0.05) and protein (∼10-fold, P < 0.05) in adipose tissue compared with nonfasted controls. On the other hand, rats fed a Western diet for 7 days became insulin resistant concomitantly with increments in TRIB3 mRNA (155%, P < 0.05) and protein (69%, P = 0.0567) in muscle and a decrease in the mRNA (76%, P < 0.05) and protein (70%, P < 0.05) in adipose. In glucose transport and mitochondria oxidation studies using skeletal muscle cells, we found that stable TRIB3 overexpression impaired insulin-stimulated glucose uptake without affecting basal glucose transport and increased both basal glucose oxidation and the maximal uncoupled oxygen consumption rate. With stable knockdown of TRIB3, basal and insulin-stimulated glucose transport rates were increased, whereas basal glucose oxidation and the maximal uncoupled oxygen consumption rate were decreased. In conclusion, TRIB3 impacts glucose uptake and oxidation oppositely in muscle and fat according to levels of nutrient availability. The above data for the first time implicate TRIB3 as a potent physiological regulator of insulin sensitivity and mitochondrial glucose oxidation under conditions of nutrient deprivation and excess.
Mechanisms of action of islet neogenesis-associated protein: comparison of the full-length recombinant protein and a bioactive peptide
Authors: Petropavlovskaia Maria , Daoud Jamal , Zhu Jonathan , Moosavi Mandana , Ding Jieping , Makhlin Julia , Assouline-Thomas Beatrice , Rosenberg Lawrence
Published: August 2012

Islet neogenesis-associated protein (INGAP) was discovered in the partially duct-obstructed hamster pancreas as a factor inducing formation of new duct-associated islets. A bioactive portion of INGAP, INGAP104–118peptide (INGAP-P), has been shown to have neogenic and insulin-potentiating activity in numerous studies, including recent phase 2 clinical trials that demonstrated improved glucose homeostasis in both type 1 and type 2 diabetic patients. Aiming to improve INGAP-P efficacy and to understand its mechanism of action, we cloned the full-length protein (rINGAP) and compared the signaling events induced by the protein and the peptide in RIN-m5F cells that respond to INGAP with an increase in proliferation. Here, we show that, although both rINGAP and INGAP-P signal via the Ras/Raf/ERK pathway, rINGAP is at least 100 times more efficient on a molar basis than INGAP-P. For either ligand, ERK1/2 activation appears to be pertussis toxin sensitive, suggesting involvement of a G protein-coupled receptor(s). However, there are clear differences between the peptide and the protein in interactions with the cell surface and in the downstream signaling. We demonstrate that fluorescent-labeled rINGAP is characterized by clustering on the membrane and by slow internalization (≤5 h), whereas INGAP-P does not cluster and is internalized within minutes. Signaling by rINGAP appears to involve Src, in contrast to INGAP-P, which appears to activate Akt in addition to the Ras/Raf/ERK1/2 pathway. Thus our data suggest that interactions of INGAP with the cell surface are important to consider for further development of INGAP as a pharmacotherapy for diabetes.
Role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
Authors: Aare Sudhakar , Radell Peter , Eriksson Lars I. , Chen Yi-Wen , Hoffman Eric P. , Larsson Lars
Published: August 2012

Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover, the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin-induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis, for 5 days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of >500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity, and transcriptional regulation. Genes involved in the regulation of the oxidative stress response and cytoskeletal/sarcomeric and heat shock proteins were on the other hand downregulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients, and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.
Decreased Skin-Mediated Detoxification Contributes to Oxidative Stress and Insulin Resistance
Authors: Liu Xing-Xing , Sun Chang-Bin , Yang Ting-Tong , Li Da , Li Chun-Yan , Tian Yan-Jie , Guo Ming , Cao Yu , Zhou Shi-Sheng
Published: August 2012

The skin, the body's largest organ, plays an important role in the biotransformation/detoxification and elimination of xenobiotics and endogenous toxic substances, but its role in oxidative stress and insulin resistance is unclear. We investigated the relationship between skin detoxification and oxidative stress/insulin resistance by examining burn-induced changes in nicotinamide degradation. Rats were divided into four groups: sham-operated, sham-nicotinamide, burn, and burn-nicotinamide. Rats received an intraperitoneal glucose injection (2 g/kg) with (sham-nicotinamide and burn-nicotinamide groups) or without (sham-operated and burn groups) coadministration of nicotinamide (100 mg/kg). The results showed that the mRNA of all detoxification-related enzymes tested was detected in sham-operated skin but not in burned skin. The clearance of nicotinamide andN1-methylnicotinamide in burned rats was significantly decreased compared with that in sham-operated rats. After glucose loading, burn group showed significantly higher plasma insulin levels with a lower muscle glycogen level than that of sham-operated and sham-nicotinamide groups, although there were no significant differences in blood glucose levels over time between groups. More profound changes in plasma H2O2and insulin levels were observed in burn-nicotinamide group. It may be concluded that decreased skin detoxification may increase the risk for oxidative stress and insulin resistance.
An M/M/2 Queueing System with Heterogeneous Servers Including One with Working Vacation
Authors: Krishnamoorthy A. , Sreenivasan C.
Published: August 2012

This paper analyzes an M/M/2 queueing system with two heterogeneous servers, one of which is always available but the other goes on vacation in the absence of customers waiting for service. The vacationing server, however, returns to serve at a low rate as an arrival finds the other server busy. The system is analyzed in the steady state using matrix geometric method. Busy period of the system is analyzed and mean waiting time in the stationary regime computed. Conditional stochastic decomposition of stationary queue length is obtained. An illustrative example is also provided.
Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93AMouse Model of Amyotrophic Lateral Sclerosis
Authors: Gifondorwa David J. , Jimenz-Moreno Ramon , Hayes Crystal D. , Rouhani Hesam , Robinson Mac B. , Strupe Jane L. , Caress James , Milligan Carol
Published: August 2012

A prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs). While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervation may improve quality of life by maintaining muscle control and slowing disease progression. The precise cause of MN dysfunction and denervation is not known, but several mechanisms have been proposed that involve potentially toxic intra- and extracellular changes. Many cells confront these changes by mounting a stress response that includes increased expression of heat shock protein 70 (Hsp70). MNs do not upregulate Hsp70, and this may result in a potentially increased vulnerability. We previously reported that recombinant human hsp70 (rhHsp70) injections delayed symptom onset and increased lifespan in SOD1G93Amice. The exogenous rhHsp70 was localized to the muscle and not to spinal cord or brain suggesting it modulates peripheral pathophysiology. In the current study, we focused on earlier administration of Hsp70 and its effect on initial muscle denervation. Injections of the protein appeared to arrest denervation with preserved large myelinated peripheral axons, and reduced glial activation.
Temporal Forecasting with a Bayesian Spatial Predictor: Application to Ozone
Authors: Dou Yiping , Le Nhu D. , Zidek James V.
Published: August 2012

This paper develops and empirically compares two Bayesian and empirical Bayes space-time approaches for forecasting next-day hourly ground-level ozone concentrations. The comparison involves the Chicago area in the summer of 2000 and measurements from fourteen monitors as reported in the EPA's AQS database. One of these approaches adapts a multivariate method originally designed for spatial prediction. The second is based on a state-space modeling approach originally developed and used in a case study involving one week in Mexico City with ten monitoring sites. The first method proves superior to the second in the Chicago Case Study, judged by several criteria, notably root mean square predictive accuracy, computing times, and calibration of 95% predictive intervals.
Chronic Condition Clusters and Polypharmacy among Adults
Authors: Vyas Ami , Pan Xiaoyun , Sambamoorthi Usha
Published: August 2012

Objective. The primary objective of the study was to estimate the rates of polypharmacy among individuals with multimorbidity defined as chronic condition clusters and examine their associations with polypharmacy. Methods. Cross-sectional analysis of 10,528 individuals of age above 21, with at least one physical condition in cardiometabolic (diabetes or heart disease or hypertension), musculoskeletal (arthritis or osteoporosis), and respiratory (chronic obstructive pulmonary disease (COPD) or asthma) clusters from the 2009 Medical Expenditure Panel Survey. Chi-square tests and logistic regressions were performed to analyze the association between polypharmacy and multimorbidity. Results. Polypharmacy rates varied from a low of 7.2% among those with respiratory cluster to a high of 64.1% among those with all three disease clusters. Among those with two or more disease clusters, the rates varied from 28.3% for musculoskeletal and respiratory clusters to 41.8% for those with cardiometabolic and respiratory clusters. Individual with cardiometabolic conditions alone or in combination with other disease clusters were more likely to have polypharmacy. Compared to those with musculoskeletal and respiratory conditions, those with cardiometabolic and respiratory conditions had 1.68 times higher likelihood of polypharmacy. Conclusions. Rates of polypharmacy differed by specific disease clusters. Individuals with cardiometabolic condition were particularly at high risk of polypharmacy, suggesting greater surveillance for adverse drug interaction in this group.
Intertrochanteric Fracture of the Ankylosed Hip Joint Treated by a Gamma Nail: A Case Report
Authors: Ishimaru Daichi , Nozawa Satoshi , Maeda Masato , Shimizu Katsuji
Published: August 2012

We herein report a rare case of an intertrochanteric fracture complicated with an ankylosed hip joint in a 76-year-old man. Generally, operative treatment is performed for elderly people with intertrochanteric fractures to prevent general complications, maintain mobility, and release pain. However, intertrochanteric fractures of ankylosed hip joints are rare, and the optimal surgery for this condition is unknown. In addition, surgical fracture repair is challenging because unusual instability of the fracture site is suspected owing to the long lever arm of the lower extremity. Nevertheless, we successfully treated this rare fracture using a gamma nail, which may be a useful implant with which to treat this type of fracture if the status of the arthrodesed hip joint allows.
Primary Leiomyosarcoma of Gallbladder: A Rare Diagnosis
Authors: Savlania Ajay , Behera Arunanshu , Vaiphei Kim , Singh Harjeet , Dhiman R. K. , Duseja Ajay , Chawla Y. K.
Published: August 2012

Leiomyosarcoma of the gallbladder is a rare entity, constituting about 1.4 per 1000 gallbladder malignancies. Literature review shows female preponderance in sixth decade of life, due to unknown reasons. We report one such rare case of a 50-year-old female admitted with pain in right upper abdomen. On examination, mass was felt in right hypochondrium. The ultrasound abdomen showed mass with loss of interface with liver and cholelithiasis. CECT abdomen showed polypoidal gallbladder malignancy with ill-defined interface with liver. She was operated upon with diagnosis of carcinoma gallbladder; extended cholecystectomy was done. Histopathological examination revealed spindle-cell proliferation and possibility of malignant tumor of mesenchymal origin was kept. This was later confirmed on immunohistochemistry.
Nothing as Practical as a Good Theory? The Theoretical Basis of HIV Prevention Interventions for Young People in Sub-Saharan Africa: A Systematic Review
Authors: Michielsen Kristien , Chersich Matthew , Temmerman Marleen , Dooms Tessa , Van Rossem Ronan
Published: August 2012

This paper assesses the extent to which HIV prevention interventions for young people in sub-Saharan Africa are grounded in theory and if theory-based interventions are more effective. Three databases were searched for evaluation studies of HIV prevention interventions for youth. Additional articles were identified on websites of international organisations and through searching references. 34 interventions were included; 25 mentioned the use of theory. Social Cognitive Theory was most prominent (n=13), followed by Health Belief Model (n=7), and Theory of Reasoned Action/Planned Behaviour (n=6). These cognitive behavioural theories assume that cognitions drive sexual behaviour. Reporting on choice and use of theory was low. Only three articles provided information about why a particular theory was selected. Interventions used theory to inform content (n=13), for evaluation purposes (n=4) or both (n=7). No patterns of differential effectiveness could be detected between studies using and not using theory, or according to whether a theory informed content, and/or evaluation. We discuss characteristics of the theories that might account for the limited effectiveness observed, including overreliance on cognitions that likely vary according to type of sexual behaviour and other personal factors, inadequately address interpersonal factors, and failure to account for contextual factors.
Severe Primary HSV-2 in a Perinatal HIV-Infected Woman with Advanced Immunosuppression
Authors: Lee Lana , Agwu Allison , Hutton Nancy
Published: August 2012

Herpes simplex virus type 2 (HSV-2) is most commonly associated with mucocutaneous manifestations; however, coinfections with HIV may be associated with atypical and more severe presentations of clinical disease. We present a case of a young woman with advanced perinatally acquired AIDS presenting with severe purulent pharyngitis, fevers, and toxic appearance with a subsequent diagnosis of disseminated primary HSV-2 infection in multiple noncontiguous mucocutaneous sites. This case highlights an unusual presentation of the protean nature of primary HSV infection and the potential severity of illness in patients with advanced immunosuppression.
C-Peptide Versus Insulin: Relationships with Risk Biomarkers of Cardiovascular Disease in Metabolic Syndrome in Young Arab Females
Authors: Abdullah A. , Hasan H. , Raigangar V. , Bani-Issa W.
Published: August 2012

Background. Obesity is a major health concern and is associated with metabolic syndrome (MetS) that increases the risk for cardiovascular disease (CVD). Since little is known about the relationships between MetS components and CVD in overweight/obese young Arab females, our study aimed at examining these relationships and further to explore the associations between connecting peptide (C-peptide) and insulin with these biomarkers.Subjects and Methods. In this cross-sectional study, 80 apparently healthy young Arab females were recruited and grouped by their body mass index (BMI) into normal-weight (GI) and overweight/obese (GII) groups.Results. The two groups significantly differed in BMI, waist circumference (WC) and values of biomarkers, namely, leptin, fasting insulin, uric acid (UA), insulin resistance (HOMA-IR), C-peptide, high-sensitivity C-reactive protein (hs-CRP), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). C-peptide significantly correlated with WC, leptin, UA, and HDL-C and was predicted by three biomarkers; UA, WC and HDL-C. Whereas, insulin significantly correlated with only two biomarkers including leptin and DBP and was predicted by UA and DBP.Conclusions. The present study highlighted the association between MetS and CVD in young Arab females and the possible role of C-peptide in the prediction of CVD.
Physical-Rules-Based Adaptive Neuro-Fuzzy Inferential Sensor Model for Predicting the Indoor Temperature in Heating Systems
Authors: Huang Liang , Liao Zaiyi , Zhao Lian
Published: August 2012

Previous research demonstrated that inferential sensors-based control technology can significantly improve the energy efficiency of space heating systems. However, the performance strongly relies on the accuracy and robustness of the dynamic model upon which the inferential model is built. Traditional methods, such as simplified physical model, adaptive neurofuzzy inferential sensor- (ANFIS-) based model, were developed and tested in this research. In attempt to improve both the accuracy and robustness of inferential model, this study aims to investigate how to improve the performance of inferential sensors using physical-rules-based ANFIS in prediction of the hydraulic system temperature in order to adapt the good power needed in the dwellings. This paper presents the structure of this innovative method. The performance is tested using experimental data and is compared with that of previous methods using three performance measures: RMSE, RMS, and [Formula: see text]. The results show that the physical-rule-based ANFIS inferential model is more accurate and robust. The impact of this improvement on the overall control performance is also discussed.
Spectral Properties of Non‐Self‐Adjoint Perturbations for a Spectral Problem with Involution
Authors: Kopzhassarova Asylzat A. , Lukashov Alexey L. , Sarsenbi Abdizhakhan M.
Published: August 2012

Full description of Riesz basis property for eigenfunctions of boundary value problems for first order differential equations with involutions is given.
On Generalized Localization of Fourier Inversion Associated with an Elliptic Operator for Distributions
Authors: Ashurov Ravshan , Butaev Almaz , Pradhan Biswajeet
Published: August 2012

We study the behavior of Fourier integrals summed by the symbols of elliptic operators and pointwise convergence of Fourier inversion. We consider generalized localization principle which in classical Lp spaces was investigated by Sjölin (1983), Carbery and Soria (1988, 1997) and Alimov (1993). Proceeding these studies, in this paper, we establish sharp conditions for generalized localization in the class of finitely supported distributions.
An Entropy-Based Multiobjective Evolutionary Algorithm with an Enhanced Elite Mechanism
Authors: Qin Yufang , Ji Junzhong , Liu Chunnian
Published: August 2012

Multiobjective optimization problem (MOP) is an important and challenging topic in the fields of industrial design and scientific research. Multi-objective evolutionary algorithm (MOEA) has proved to be one of the most efficient algorithms solving the multi-objective optimization. In this paper, we propose an entropy-based multi-objective evolutionary algorithm with an enhanced elite mechanism (E-MOEA), which improves the convergence and diversity of solution set in MOPs effectively. In this algorithm, an enhanced elite mechanism is applied to guide the direction of the evolution of the population. Specifically, it accelerates the population to approach the true Pareto front at the early stage of the evolution process. A strategy based on entropy is used to maintain the diversity of population when the population is near to the Pareto front. The proposed algorithm is executed on widely used test problems, and the simulated results show that the algorithm has better or comparative performances in convergence and diversity of solutions compared with two state-of-the-art evolutionary algorithms: NSGA-II, SPEA2 and the MOSADE.
Effects of Regional Magnetic Field on Rotating MHD Flow Field of Unity Magnetic Prandtl Number
Authors: Hung Sheng Lun , Leong Jik Chang
Published: August 2012

This work numerically studies the flow pattern of a magnetic fluid filled within an annulus whose inner cylinder is moving at a constant rotational speed, while the outer cylinder is stationary but under the influence of a nonuniform external magnetic field. The magnetic field consists of four basic configurations, that is, completely circular, semicircular, quarter circular, and alternately quarter circular. The strength of the external magnetic field is characterized using a reference Hartmann number. As the reference Hartmann number increases, the fluid elements need to overcome greater resistance to enter the region with magnetic field. Hence, there always exists an apparent recirculation cell within the region without externally applied magnetic field. The strength and size of the recirculation cell depend on the reference Hartmann number, the number and size of the discrete regions without external magnetic field. Only the shear stress on the moving cylinder always increases in magnitude with the reference Hartmann number and the span of the single external magnetic field region. Splitting and separating the external magnetic field may increase the magnitude of the shear stress on the moving inner cylinder but decrease that on the stationary outer cylinder. If the magnitude of the shear stress on the outer cylinder reduces beyond zero, a shear stress in the opposite sense will increase in magnitude with Hartmann number.
Aging, Neuromuscular Decline, and the Change in Physiological and Behavioral Complexity of Upper-Limb Movement Dynamics
Authors: Morrison S. , Newell K. M.
Published: August 2012

Aging is characterized by a general decline in physiological and behavioral function that has been widely interpreted within the context of the loss of complexity hypothesis. In this paper, we examine the relation between aging, neuromuscular function and physiological-behavioral complexity in the arm-hand effector system, specifically with reference to physiological tremor and isometric force production. Experimental findings reveal that the adaptive behavioral consequences of the aging-related functional decline in neurophysiological processes are less pronounced in simple motor tasks which provides support for the proposition that the motor output is influenced by both extrinsic (e.g., task related) and intrinsic (e.g., coordination, weakness) factors. Moreover, the aging-related change in complexity can be bidirectional (increase or decrease) according to the influence of task constraints on the adaptation required of the intrinsic properties of the effector system.
Hyperspherical Manifold for EEG Signals of Epileptic Seizures
Authors: Ahmad Tahir , Ramachandran Vinod
Published: August 2012

The mathematical modelling of EEG signals of epileptic seizures presents a challenge as seizure data is erratic, often with no visible trend. Limitations in existing models indicate a need for a generalized model that can be used to analyze seizures without the need for apriori information, whilst minimizing the loss of signal data due to smoothing. This paper utilizes measure theory to design a discrete probability measure that reformats EEG data without altering its geometric structure. An analysis of EEG data from three patients experiencing epileptic seizures is made using the developed measure, resulting in successful identification of increased potential difference in portions of the brain that correspond to physical symptoms demonstrated by the patients. A mapping then is devised to transport the measure data onto the surface of a high‐dimensional manifold, enabling the analysis of seizures using directional statistics and manifold theory. The subset of seizure signals on the manifold is shown to be a topological space, verifying Ahmad′s approach to use topological modelling.
Spark Plasma Sintering of Metals and Metal Matrix Nanocomposites: A Review
Authors: Saheb Nouari , Iqbal Zafar , Khalil Abdullah , Hakeem Abbas Saeed , Al Aqeeli Nasser , Laoui Tahar , Al-Qutub Amro , Kirchner René
Published: August 2012

Metal matrix nanocomposites (MMNCs) are those metal matrix composites where the reinforcement is of nanometer dimensions, typically less than 100 nm in size. Also, it is possible to have both the matrix and reinforcement phases of nanometer dimensions. The improvement in mechanical properties of MMNCs is attributed to the size and strength of the reinforcement as well as to the fine grain size of the matrix. Spark plasma sintering has been used extensively over the past years to consolidate wide range of materials including nanocomposites and was shown to be effective noneconventional sintering method for obtaining fully dense materials with preserved nanostructure features. The objective of this work is to briefly present the spark plasma sintering process and review published work on spark‐plasma‐sintered metals and metal matrix nanocomposites.
Embryonic Protein Nodal Promotes Breast Cancer Vascularization
Authors: Quail Daniela F. , Walsh Logan A. , Zhang Guihua , Findlay Scott D. , Moreno Juan , Fung Laura , Ablack Amber , Lewis John D. , Done Susan J. , Hess David A. , Postovit Lynne-Marie
Published: August 2012

Tumor vascularization is requisite for breast cancer progression, and high microvascular density in tumors is a poor prognostic indicator. Patients bearing breast cancers expressing human embryonic stem cell (hESC)-associated genes similarly exhibit high mortality rates, and the expression of embryonic proteins is associated with tumor progression. Here, we show that Nodal, a hESC-associated protein, promotes breast cancer vascularization. We show that high levels of Nodal are positively correlated with high vascular densities in human breast lesions (P = 0.0078). In vitro, we show that Nodal facilitates breast cancer–induced endothelial cell migration and tube formation, largely by upregulating the expression and secretion of proangiogenic factors by breast cancer cells. Using a directed in vivo angiogenesis assay and a chick chorioallantoic membrane assay, we show that Nodal promotes vascular recruitment in vivo. In a clinically relevant in vivo model, whereby Nodal expression was inhibited following tumor formation, we found a significant reduction in tumor vascularization concomitant with elevated hypoxia and tumor necrosis. These findings establish Nodal as a potential target for the treatment of breast cancer angiogenesis and progression. Cancer Res; 72(15); 3851–63. ©2012 AACR.
Autoregulatory Mechanisms of Phosphorylation of Checkpoint Kinase 1
Authors: Wang Jingna , Han Xiangzi , Zhang Youwei
Published: August 2012

Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, is centrally involved in cell-cycle checkpoints and cellular response to DNA damage. Phosphorylation of Chk1 at 2 Ser/Gln (SQ) sites, Ser-317 and Ser-345, by the upstream kinase ATR is critical for checkpoint activation. However, the precise molecular mechanisms controlling Chk1 phosphorylation and subsequent checkpoint activation are not well understood. Here, we report unique autoregulatory mechanisms that control protein phosphorylation of human Chk1, as well as checkpoint activation and cell viability. Phosphorylation of Ser-317 is required, but not sufficient, for maximal phosphorylation at Ser-345. The N-terminal kinase domain of Chk1 prevents Chk1 phosphorylation at the C-terminus by ATR in the absence of DNA damage. Loss of the inhibitory effect imposed by the N-terminus causes constitutive phosphorylation of Chk1 by ATR under normal growth conditions, which in turn triggers artificial checkpoints that suppress the S-phase progression. Furthermore, two point mutations were identified that rendered Chk1 constitutively active, and expression of the constitutively active mutant form of Chk1 inhibited cancer cell proliferation. Our findings therefore reveal unique regulatory mechanisms of Chk1 phosphorylation and suggest that expression of constitutively active Chk1 may represent a novel strategy to suppress tumor growth. Cancer Res; 72(15); 3786–94. ©2012 AACR.
ALKBH3 Contributes to Survival and Angiogenesis of Human Urothelial Carcinoma Cells through NADPH Oxidase and Tweak/Fn14/VEGF Signals
Authors: Shimada Keiji , Fujii Tomomi , Tsujikawa Kazutake , Anai Satoshi , Fujimoto Kiyohide , Konishi Noboru
Published: August 2012

Purpose: The role and function of a novel human AlkB homologue, ALKBH3, in human urothelial carcinoma development were examined.

Experimental design: Biologic roles of ALKBH3 were examined by gene silencing analysis using in vitro and in vivo siRNA transfection. Immunohistochemical analyses of ALKBH3 and the related molecules using human bladder cancer samples were conducted to estimate the association with clinicopathologic or prognostic parameters.

Results: ALKBH3 knockdown induced cell cycle arrest at the G1 phase through downregulation of NAD(P)H oxidase-2 (NOX-2)–mediated generation of reactive oxygen species (ROS). ALKBH3 knockdown reduced VEGF expression by reducing expression of tumor necrosis factor-like weak inducer of apoptosis (Tweak) and its receptor, fibroblast growth factor-inducible 14 (Fn14). Silencing of ALKBH3 or Tweak significantly suppressed invasion and angiogenesis of urothelial carcinoma in vivo as assessed both by a chorioallantoic membrane assay and in an orthotopic mouse model. Interestingly, not only urothelial carcinoma cells but also vascular endothelial cells within cancer foci expressed Fn14, which was strongly reduced by ALKBH3 and Tweak knockdown in vivo, suggesting that ALKBH3-dependent expression of Tweak stabilizes Fn14. Immunohistochemical examination showed high expression of ALKBH3, Tweak, and Fn14 in urothelial carcinoma, especially in high-grade, superficially, and deeply invasive carcinomas; moreover, Fn14-positive vessel counts within cancer foci were increased in invasive phenotypes.

Conclusions: ALKBH3 contributes to development of urothelial carcinomas by accelerating their survival, angiogenesis, and invasion through NOX-2-ROS and Tweak/Fn14-VEGF signals. Clin Cancer Res; 18(19); 5247–55. ©2012 AACR.
Issues, goals, and guidelines in selecting first-line drug therapy for hypertension.
Authors: Laragh J H
Published: August 2012

Modern antihypertensive therapy is enriched by an explosion in drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of hypertension and to pathophysiologically stratify the remaining cases of essential hypertension. Modern treatment can be much more specific than before. When long-term drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human hypertension. The first, renin-mediated vasoconstriction, is directly related to the plasma renin level. The second, sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal renin level and involves abnormal sodium retention and calcium transport. A baseline renin-sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--renovascular hypertension and primary aldosteronism. Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term drug therapy. The renin-sodium profile, used in conjunction with serum potassium and creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological vasoconstrictor mechanism that underlies the hypertension. Converting enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the hypertension of high- or medium-renin patients, whereas calcium antagonists, diuretic agents, or alpha-blockers alone are most effective against the low-renin form of vasoconstriction. In the large midzone of renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume therapies can be developed.
Traditional first-line therapy. Overview of medical benefits and side effects.
Authors: Gifford R W , Borazanian R A
Published: August 2012

When diuretic-based stepped care was first advocated for the treatment of hypertension, there were fewer classes of antihypertensive medication than there are today. In 1984, the third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC) for the first time suggested an alternative initial treatment with a beta-blocker in selected hypertensive patients, and the fourth JNC report has recommended the alternatives of calcium channel blockers or angiotensin converting enzyme inhibitors for step-one therapy as well. However, only the diuretic drugs and beta-blockers have been shown to reduce cardiovascular morbidity and mortality in prospective, long-term, controlled trials. Moreover, 30 years' experience with diuretic agents and 20 years' experience with beta-blockers have defined the advantages, disadvantages, and potential side effects of these drugs more precisely than is possible for newer agents. The diuretic drugs and beta-blockers remain excellent choices in the management of hypertension.
Angiotensin converting enzyme inhibitors. Present and future.
Authors: Frohlich E D
Published: August 2012

The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the "more local" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents.
Blood pressure as a risk factor for cardiovascular disease. The Framingham Study--30 years of follow-up.
Authors: Stokes J , Kannel W B , Wolf P A , D'Agostino R B , Cupples L A
Published: August 2012

Data from 30 years of follow-up of the original Framingham Study cohort of 5,070 men and women aged 30-62 years who were first examined during the period 1948-1952 and who were free of cardiovascular disease reveal that blood pressure is a strong and consistent predictor of the development of coronary heart disease, stroke, transient ischemic attack, and congestive heart failure. Other factors related to blood pressure like obesity, left ventricular hypertrophy as demonstrated on electrocardiograms, and heart enlargement as shown by x-ray radiography made several selective additional independent contributions to risk; heart enlargement by x-ray radiography was the best predictor of congestive heart failure.
Cost and quality trade-offs in the treatment of hypertension.
Authors: Stason W B
Published: August 2012

The cost-effectiveness of treatment for hypertension is positively related to the level of pretreatment blood pressure and to the level of success in achieving patient adherence to prescribed medical regimens. Opportunities to improve the cost-effectiveness of treatment include limiting treatment to patients with well-documented sustained increases in blood pressure, giving higher priority to the treatment of patients with diastolic blood pressures of 100 mm Hg and above, and relying on lower-cost medications if clinical responses to treatment permit. In patients with mild hypertension, a comparison of strategies for initiating pharmacological treatment that takes into account potential side effects as well as the costs of medications indicates a difference of $270/patient-yr between the least and most expensive alternatives. Whether the additional costs of more expensive treatment strategies are "worth it" depend on any additional health benefits actually conferred. Moreover, higher-cost strategies may have negative influences on patients' decisions to adhere to prescribed regimens or to continue in treatment. Cost is a particular problem for the treatment of chronic conditions like hypertension because of inadequate insurance coverage for medications, especially for the poor.
Choosing initial therapy for hypertension. A personal view.
Authors: Black H R
Published: August 2012

With numerous safe and effective antihypertensive drugs now available, the clinician should no longer choose only diuretic agents or beta-adrenergic receptor blockers (beta-blockers) as initial therapy. Five classes of agents, including angiotensin converting enzyme inhibitors, beta-blockers, calcium entry blockers, peripheral alpha 1-adrenergic receptor blockers, and thiazide diuretic agents, are all appropriate monotherapy in properly selected patients. The choice depends on efficacy, side effects, demography, comorbidity, dosage schedule, cost, mechanism of drug action, and the pathophysiology of the patient's hypertension. Extensive data are now available that will assist the clinician in choosing an agent that has the greatest probability of success without the need for extensive biochemical or hemodynamic evaluation.
Implications for research and policy in the treatment of hypertension. Medical considerations.
Authors: Horan M J
Published: August 2012

Hypertension, or high blood pressure, is a disease and a risk factor. Cardiovascular risk is directly proportional to the level of blood pressure. Current therapeutic approaches include the classical medical model of detection, evaluation, and drug treatment of high-risk patients who have elevated blood pressure and also a less-well-studied population approach that seeks to manipulate environmental variables in large groups of subjects to reduce blood pressure and subsequent cardiovascular risk. Future research should center on more precise delineation of cardiovascular risk, evaluation of alternative environmental manipulations to reduce blood pressure, enhanced understanding of the pathophysiological mechanisms of hypertension, better matching of antihypertensive drug therapy to pathophysiology, development of new drugs that not only lower blood pressure but also provide additional benefits with minimal side effects, and finally, investigations to further our understanding of the behavioral aspects of the physician-patient encounter, as well as studies on compliance and other issues that influence therapeutic outcome.
Risks of untreated hypertension. A discussion.
Authors: Wilhelmsen L
Published: August 2012

There is a strong and graded association between blood pressure and the incidence of major coronary heart disease manifestations, congestive heart failure, stroke, and total mortality. The risk of any of these manifestations is also modified by other risk factors. Tobacco smoking affects the risk for all of the previously mentioned end points. Generally, lipid disturbances are only important predictors of coronary heart disease and total mortality. Several facts indicate that elevated blood pressure is causally related to the end points. There are, however, positive relations between blood pressure levels and heart rate, serum cholesterol level, body mass index, and, according to some studies, glucose intolerance. Some more basic abnormality may be responsible for the blood pressure increase and the increases in these other factors. Hypothetically, this abnormality may be more fundamentally related to some of the end points than is hypertension itself. If that is the case, then the type of antihypertensive treatment may be of decisive importance. Different end points may be affected differently by antihypertensive drugs, a factor that may be essential in the choice of drug treatment. Proper management of other risk factors is also essential in the prevention of cardiovascular disease.