bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Emission and Performance of Diesel Engine Using Castor Biodiesel
Authors: Islam Md. Saiful , Ahmed Abu Saleh , Islam Aminul , Abdul Aziz Sidek , Xian Low Chyi , Mridha Moniruzzaman
Published: February 2014

This paper presents the result of investigations carried out in studying the emission and performance of diesel engine using the castor biodiesel and its blend with diesel from 0% to 40% by volume. The acid-based catalyzed transesterification system was used to produce castor biodiesel and the highest yield of 82.5% was obtained under the optimized condition. The FTIR spectrum of castor biodiesel indicates the presence of C=O and C–O functional groups, which is due to the ester compound in biodiesel. The smoke emission test revealed that B40 (biodiesel blend with 40% biodiesel and 60% diesel) had the least black smoke compared to the conventional diesel. Diesel engine performance test indicated that the specific fuel consumption of biodiesel blend was increased sufficiently when the blending ratio was optimized. Thus, the reduction in exhaust emissions and reduction in brake-specific fuel consumption made the blends of caster seed oil (B20) a suitable alternative fuel for diesel and could help in controlling air pollution.
Evaluation of the Cytotoxic Effects of CAM Therapies: AnIn VitroStudy in Normal Kidney Cell Lines
Authors: Arora Shagun , Tandon Chanderdeep , Tandon Simran
Published: February 2014

The purpose of this current study was to justify the incorporation of complementary and alternate medicine (CAM) in current cancer treatments. The major drawback of anticancer drugs is their nonselective killing, which ultimately leads to attrition of normal cells. Keeping this as the foundation of our study, we made an effort to compare the cytotoxicity associated with a known chemotherapeutic drug 5-Fluorouracil (5-FU), with certain CAM therapies previously reported to have anticancer activity. The parameters chosen for the study were based on antiproliferative and cytotoxic effects on normal, kidney epithelial cells (NRK-52E). The MTT assay, colony formation assay, DNA fragmentation, and differential staining using AO/EB, following treatment with either 5-FU or CAM therapies, were performed. The CAM therapies under study were various extracts of wheatgrass, roots ofAchyranthes aspera(AA), mushroom extracts (Pleurotus ostreatus, Macrolepiota procera,andAuricularia polytricha), and a homeopathic drug,Ruta graveolens(Ruta). The results showed that treatment of normal cells with the CAM therapies led to minimum cell damage in comparison to 5-FU. This evidence-based study will lead to greater acceptance of alternative therapies against cancer.
Bifurcation Analysis for Phage Lambda with Binding Energy Uncertainty
Authors: Xu Ning , Lei Xue , Ao Ping , Zhang Jun
Published: February 2014

In a phageλgenetic switch model, bistable dynamical behavior can be destroyed due to the bifurcation caused by inappropriately chosen model parameters. Since the values of many parameters with biological significance often cannot be accurately acquired, it is thus of fundamental importance to analyze how and to which extent the system dynamics is influenced by model parameters, especially those parameters pertaining to binding energies. In this paper, we apply a Jacobian method to investigate the relation between bifurcation and parameter uncertainties on a phageλOR model. By introducing bistable range as a measure of system robustness, we find that RNA polymerase binding energies have the minimum bistable ranges among all the binding energies, which implies that the uncertainties on these parameters tend to demolish the bistability more easily. Moreover, parameters describing mutual prohibition between proteins Cro and CI have finite bistable ranges, whereas those describing self-prohibition have infinity bistable ranges. Hence, the former are more sensitive to parameter uncertainties than the latter. These results help to understand the influence of parameter uncertainties on the bifurcation and thus bistability.
Agent Orange Footprint Still Visible in Rural Areas of Central Vietnam
Authors: Banout Jan , Urban Ondrej , Musil Vojtech , Szakova Jirina , Balik Jiri
Published: February 2014

Levels of polychlorinated dioxins/furans (PCDD/PCDF) in selected environmental samples (soils, sediments, fish, and farm animals) were analyzed from the area of Phong My commune (Thua Thien-Hue province, Vietnam). This area was affected by Agent Orange spraying during the Vietnam war (1968–1971). Whereas PCDD/PCDF content in soil and sediment samples is relatively low and ranges between 0.05 and 5.1 pg WHO-TEQ/g for soils and between 0.7 and 6.4 pg WHO-TEQ/g for sediments, the PCDD/PCDF content in poultry muscle and liver in most cases exceeded the maximum permissible limit of dioxin content per unit fat mass. In some cases of soil and sediments samples, 2,3,7,8-TCDD represented more than 90% of the total PCDD/PCDF, which indicates Agent Orange as the main source.
Design and Analysis of a Novel Dual Band-Notched UWB Antenna
Authors: Shi Ronghua , Xu Xi , Dong Jian , Luo Qingping
Published: February 2014

A novel ultrawide band (UWB) antenna with dual band-notched characteristics is presented. The first band rejection is provided by an arc H-shaped slot on the radiating patch. The parametric study of the arc H-shaped slot shows that this structure enables rejectband characteristic with improved control compared to traditional H-shaped slot. Based on the single band-notched UWB antenna, the second notched band is realized by etching narrow slots on the ground plane. By tuning the parameters of these slots, the proposed UWB antenna can operate from 2.9 GHz to above 10 GHz, except for the bandwidth of 3.3–3.6 GHz for WiMAX application and 5.1–5.9 GHz for WLAN application. Simulated and measured results show that the proposed antenna provides excellent band rejection and is a good candidate for future UWB application.
Prognostic Significance of Circulating and Endothelial Progenitor Cell Markers in Type 2 Diabetic Foot
Authors: Sambataro Maria , Seganfreddo Elena , Canal Fabio , Furlan Anna , del Pup Laura , Niero Monia , Paccagnella Agostino , Gherlinzoni Filippo , dei Tos Angelo Paolo
Published: February 2014

Objective. We studied circulating precursor cells (CPC) in type 2 diabetes mellitus (T2DM) with neuropathic foot lesions with or without critical limb ischemia and relationships between endothelial precursor cells (EPC) and peripheral neuropathy.Methods and Subjects. We measured peripheral blood CD34, CD133, and CD45 markers for CPC and KDR, CD31 markers for EPC by citofluorimetry and systemic neural nociceptor CGRP (calcitonin gene related protein) by ELISA in 8 healthy controls (C) and 62 T2DM patients: 14 with neuropathy (N), 20 with neuropathic foot lesions (N1), and 28 with neuroischemic recent revascularized (N2) foot lesions. Timing of lesions was: acute (until 6 weeks), healed, and not healed.Results. CD34+ and CD133+ were reduced in N, N1, and N2 versus C, and CD34+ were lower in N2 versus N1 (P=0.03). In N2 CD34+KDR+ remain elevated in healed versus chronic lesions and, in N1 CD133+31+ were elevated in acute lesions. CGRP was reduced in N2 and N1 versus C (P<0.04versus C26±2 pg/mL). CD34+KDR+ correlated in N2 with oximetry and negatively in N1 with CGRP.Conclusions. CD34+ CPC are reduced in diabetes with advanced complications and diabetic foot. CD34+KDR+ and CD31+133+ EPC differentiation could have a prognostic and therapeutic significance in the healing process of neuropathic and neuroischemic lesions.
A Stochastic Total Least Squares Solution of Adaptive Filtering Problem
Authors: Javed Shazia , Ahmad Noor Atinah
Published: February 2014

An efficient and computationally linear algorithm is derived for total least squares solution of adaptive filtering problem, when both input and output signals are contaminated by noise. The proposed total least mean squares (TLMS) algorithm is designed by recursively computing an optimal solution of adaptive TLS problem by minimizing instantaneous value of weighted cost function. Convergence analysis of the algorithm is given to show the global convergence of the proposed algorithm, provided that the stepsize parameter is appropriately chosen. The TLMS algorithm is computationally simpler than the other TLS algorithms and demonstrates a better performance as compared with the least mean square (LMS) and normalized least mean square (NLMS) algorithms. It provides minimum mean square deviation by exhibiting better convergence in misalignment for unknown system identification under noisy inputs.
Comparative Study of the Prevalence of Intestinal Parasites in Low Socioeconomic Areas from South Chennai, India
Authors: Dhanabal Jeevitha , Selvadoss Pradeep Pushparaj , Muthuswamy Kanchana
Published: February 2014

Intestinal parasites cause one of the most important health problems through their effects in causing undernourishment morbidity and incapacitation due to their behavior particularly in children compared to adults. This study was intended to state the prevalence of intestinal parasites between the slum dwellers of different areas in south Chennai. Among the total of 256 samples collected between the ages of 0–50 yrs, 194 samples were positive. Standard laboratory techniques for parasitological diagnosis were carried out for each sample.Entamoeba coli(23%),Cyclosporasp. (22.2%),Entamoeba histolytica(21.8%),Giardia intestinalis(14.4%),Ascaris lumbricoides(6.2%),Trichuris trichiura(1.1%), andHymenolepis nana(2.7%) were found in the dwellers of low socioeconomic areas. The data on the prevalence of parasites with respect to sex and age showed that the females harbored more numbers of parasites when compared to males. Further, with respect to age, children and teenagers had surplus parasites compared to old age groups. The percentage of educational status showed a reduction in the number of parasites in the higher education dwellers. These parasites could be prevented by possible grouping of better ecological design and hygiene. Conclusively, the examination of personal hygiene as well as routine medical examination and treatment is strongly recommended in the low socio-economic areas.
Validation of the Antidiabetic and Hypolipidemic Effects of Clitocybe nuda by Assessment of Glucose Transporter 4 and Gluconeogenesis and AMPK Phosphorylation in Streptozotocin‐Induced Mice
Authors: Shih Chun-Ching , Chen Mei-Hsing , Lin Cheng-Hsiu
Published: February 2014

The study was designed to investigate the effects of extract of Clitocybe nuda (CNE) on type 1 diabetes mellitus and dyslipidemia in streptozotocin‐ (STZ‐) induced diabetic mice. Diabetes was induced by injection of STZ. Diabetic mice were randomly divided into five groups and given orally CNE (C1: 0.2, C2: 0.5, and C3: 1.0 g/kg body weight) or metformin (Metf) or vehicle for 4 weeks. STZ induction decreased in the levels of insulin, body weight, and the weight of skeletal muscle, whereas the levels of blood glucose, hemoglobin nonenzymatically (percent HbA1c), and circulating triglyceride (P < 0.001, P < 0.001, and P < 0.01, resp.) were increased. CNE decreased the levels of blood glucose, HbA1c, and triglyceride levels, whereas it increased the levels of insulin and leptin compared with the vehicle‐treated STZ group. STZ induction caused a decrease in the protein contents of skeletal muscular and hepatic phosphorylation of AMP‐activated protein kinase (phospho‐AMPK) and muscular glucose transporter 4 (GLUT4). Muscular phospho‐AMPK contents were increased in C2‐, C3‐, and Metf‐treated groups. CNE and Metf significantly increased the muscular proteins of GLUT4. Liver phospho‐AMPK showed an increase in all CNE‐ and Metf‐treated groups combined with the decreased hepatic glucose production by decreasing phosphenolpyruvate carboxykinase (PEPCK), glucose‐6‐phosphatase (G6Pase), and 11beta hydroxysteroid dehydroxygenase (11β‐HSD1) gene, which contributed to attenuating diabetic state. The study indicated that the hypoglycemic properties of CNE were related to both the increased muscular glucose uptake and the reduction in hepatic gluconeogenesis. CNE exerts hypolipidemic effect by increasing gene expressions of peroxisome proliferator‐activated receptor α (PPARα) and decreasing expressions of fatty acid synthesis, including acyl‐coenzyme A: diacylglycerol acyltransferase (DGAT) 2. Therefore, amelioration of diabetic and dyslipidemic state by CNE in STZ‐induced diabetic mice occurred by regulation of GLUT4, PEPCK, DGAT2, and AMPK phosphorylation.
The Pink Rim Sign: Location of Pink as an Indicator of Melanoma in Dermoscopic Images
Authors: Rader Ryan K. , Payne Katie S. , Guntupalli Uday , Rabinovitz Harold S. , Oliviero Maggie C. , Drugge Rhett J. , Malters Joseph J. , Stoecker William V.
Published: February 2014

Background. In dermoscopic images, multiple shades of pink have been described in melanoma without specifying location of these areas within the lesion.Objective. The purpose of this study was to determine the statistics for the presence of centrally and peripherally located pink melanoma and benign melanocytic lesions.Methods. Three observers, untrained in dermoscopy, each retrospectively analyzed 1290 dermoscopic images (296 melanomas (170in situand 126 invasive), 994 benign melanocytic nevi) and assessed the presence of any shade of pink in the center and periphery of the lesion.Results. Pink was located in the peripheral region in 14.5% of melanomas and 6.3% of benign melanocytic lesions, yielding an odds ratio of 2.51 (95% CI: 1.7–3.8,P<0.0001). Central pink was located in 12.8% of melanomas and 21.8% of benign lesions, yielding an odds ratio of 0.462 (95% CI: 0.67,P=0.204). Pink in melanomain situtended to be present throughout the lesion (68% of pink lesions). Pink in invasive melanoma was present in 17% of cases, often presenting as a pink rim.Conclusions. The presence of pink in the periphery or rim of a dermoscopic melanocytic lesion image provides an indication of malignancy. We offer the “pink rim sign” as a clue to the dermoscopic diagnosis of invasive melanoma.
Analysis of Population Diversity of Dynamic Probabilistic Particle Swarm Optimization Algorithms
Authors: Ni Qingjian , Deng Jianming
Published: February 2014

In evolutionary algorithm, population diversity is an important factor for solving performance. In this paper, combined with some population diversity analysis methods in other evolutionary algorithms, three indicators are introduced to be measures of population diversity in PSO algorithms, which are standard deviation of population fitness values, population entropy, and Manhattan norm of standard deviation in population positions. The three measures are used to analyze the population diversity in a relatively new PSO variant—Dynamic Probabilistic Particle Swarm Optimization (DPPSO). The results show that the three measure methods can fully reflect the evolution of population diversity in DPPSO algorithms from different angles, and we also discuss the impact of population diversity on the DPPSO variants. The relevant conclusions of the population diversity on DPPSO can be used to analyze, design, and improve the DPPSO algorithms, thus improving optimization performance, which could also be beneficial to understand the working mechanism of DPPSO theoretically.
Comparative Study of Antioxidant Status in Androgenic Embryos ofAesculus hippocastanumandAesculus flava
Authors: Štajner Dubravka , Popović Boris M. , Ćalić Dušica , Štajner Marijana
Published: February 2014

In vivo(leaves and seed embryos) andin vitro(androgenic embryos) antioxidant scavenging activity ofAesculus hippocastanumandAesculus flavamedical plants was examined. Here we report antioxidant enzyme activities of superoxide dismutase, catalase, guaiacol peroxidase and glutathione peroxidase, reduced glutathione quantity, flavonoids, soluble protein contents, quantities of malondialdehyde, and•OH radical presence in the investigated plant samples. Total antioxidant capacity of all the samples ofA. hippocastanumandA. flavawas determined using FRAP, DPPH, and NO•radical scavenger capacity. The leaves ofA. flavacollected from the botanical garden exhibited stronger antioxidant activity (higher activities of SOD, and higher quantities of GSH, TSH, TPC, and scavenging abilities of DPPH and NO•, and higher FRAP values and lowest quantities of•OH and MDA) thanin vitroobtained cultures. However, the leaves ofA. flavashowed higher antioxidant activity than the leaves ofA. hippocastanum, and therefore they have a stronger tolerance of oxidative stress. Androgenic embryos of both species had low amount of antioxidants due to controlledin vitroenvironmental conditions (T, photoperiod, humidity, nutritive factors, and pathogen-free). Our results confirmed that we found optimalin vitroconditions for producing androgenic embryos of bothAesculusspecies. Also, we assume that horse chestnut androgenic embryos can be used as an alternative source for large-scale aescin production.
Notes on the Biology of the Cixiid PlanthopperCixius meridionalis(Hemiptera: Fulgoroidea)
Authors: Bowser M. L.
Published: February 2014

With the exception of a handful of economically important species, the biology of cixiid planthoppers (Hemiptera: Fulgoroidea: Cixiidae) is poorly known. The host plants and life history ofCixius meridionalisBeirne were investigated in a wetland in Soldotna, Alaska. Specimens were collected over the course of the growing season by hand, aspirator, Berlese funnel, and sweep net. A handful of live nymphs were placed in a terrarium containing potential host plants for direct observation of feeding.C. meridionaliswas found to feed on roots ofPicea mariana(Mill.) Britton, Sterns & Poggenb,Empetrum nigrumL.,Chamaedaphne calyculata(L.) Moench, andVaccinium vitis-idaeaL. At least within the study area,C. meridionalisappears to require multiple years to reach adulthood, with overwintering in nymphal instars.C. meridionaliswas occasionally tended byMyrmica alaskensisWheeler.
The Cauchy Problem for a Weakly Dissipative 2‐Component Camassa‐Holm System
Authors: Ming Sen , Yang Han , Wu Yonghong
Published: February 2014

The weakly dissipative 2‐component Camassa‐Holm system is considered. A local well‐posedness for the system in Besov spaces is established by using the Littlewood‐Paley theory and a priori estimates for the solutions of transport equation. The wave‐breaking mechanisms and the exact blow‐up rate of strong solutions to the system are presented. Moreover, a global existence result for strong solutions is derived.
A Supervised Network Analysis on Gene Expression Profiles of Breast Tumors Predicts a 41-Gene Prognostic Signature of the Transcription FactorMYBacross Molecular Subtypes
Authors: Liu Li-Yu D. , Chang Li-Yun , Kuo Wen-Hung , Hwa Hsiao-Lin , Chang King-Jen , Hsieh Fon-Jou
Published: February 2014

Background. MYBis predicted to be a favorable prognostic predictor in a breast cancer population. We proposed to find the inferred mechanism(s) relevant to the prognostic features ofMYBvia a supervised network analysis.Methods. Both coefficient of intrinsic dependence (CID) and Galton Pierson’s correlation coefficient (GPCC) were combined and designated as CIDUGPCC. It is for the univariate network analysis. Multivariate CID is for the multivariate network analysis. Other analyses using bioinformatic tools and statistical methods are included.Results. ARNT2is predicted to be the essential gene partner ofMYB. We classified four prognostic relevant gene subpools in three breast cancer cohorts as feature types I–IV. Only the probes in feature type II are the potential prognostic feature ofMYB. Moreover, we further validated 41 prognosis relevant probes to be the favorable prognostic signature. Surprisingly, two additional family members ofMYBare elevated to promote poor prognosis when both levels ofMYBandARNT2decline. BothMYBL1andMYBL2may partially decrease the tumor suppressive activities that are predicted to be up-regulated byMYBandARNT2.Conclusions. The major prognostic feature ofMYBis predicted to be determined by theMYBsubnetwork (41 probes) that is relevant across subtypes.
Surgical Management of Malignant Pleural Mesothelioma: Impact of Surgery on Survival and Quality of Life—Relation to Chemotherapy, Radiotherapy, and Alternative Therapies
Authors: Papaspyros Sotiris , Papaspyros Sayonara
Published: February 2014

Introduction. Malignant pleural mesothelioma (MPM) is an aggressive cancer arising from pleural mesothelium. Surgery aims to either cure the disease or control the symptoms. Two surgical procedures exist: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). In this systematic review we assess current evidence on safety and efficacy of surgery. Methods. Five electronic databases were reviewed from January 1990 to January 2013. Studies were selected according to a predefined protocol. Primary endpoint was overall survival. Secondary endpoints included quality of life, disease-free survival, disease recurrence, morbidity, and length of hospital stay. Results. Sixteen studies were included. Median survival ranged from 8.1 to 32 months for P/D and from 6.9 to 46.9 months for EPP. Perioperative mortality was 0%–9.8% and 3.2%–12.5%, respectively. Perioperative morbidity was 5.9%–55% for P/D and 10%–82.6% for EPP. Average length of stay was 7 days for P/D and 9 days for EPP. Conclusion. Current evidence cannot definitively answer which procedure (EPP or P/D) is more beneficial in terms of survival and operative risks. This systematic review suggests that surgery in the context of trimodality therapy offers acceptable perioperative outcomes and long-term survival. Centres specialising in MPM management have better results.
Multiyear Measurements of the Aerosol Absorption Coefficient Near the Surface in a Small-Sized Urban Area in Portugal
Authors: Nepomuceno Pereira Sérgio , Wagner Frank , Silva Ana Maria
Published: February 2014

Measurements of the aerosol absorption coefficient, between 2007 and 2013, were made at the ground level in Évora, a Portuguese small town located in the southwestern Iberia Peninsula. Such a relatively long time series of absorbing aerosols is unique in Portugal and uncommon elsewhere. The average aerosol absorption coefficient was close to 9 Mm−1and clear cycles at both daily and seasonal time scales were found. An average increase by a factor of two (from 6 to 12 Mm−1) was observed in winter if compared to summer season. The daily variations were similarly shaped for all seasons, with two morning and afternoon peaks, but with magnitudes modulated by the seasonal evolution. That was not the case if Sundays were considered. These variations can be explained in terms of the impact of local particle sources, related mainly to traffic and biomass burning and upward mixing of the aerosol due to variable mixing layer heights, either daily or seasonally. Also, a strong negative correlation between the aerosol absorption coefficient and the wind speed was verified, and an exponential decay function was found to fit very well to the data. The wind direction seems to be not correlated with the aerosol absorption coefficient.
Effects ofMomordica charantiaL. on the Blood Rheological Properties in Diabetic Patients
Authors: França Eduardo Luzía , Ribeiro Elton Brito , Scherer Edson Fredulin , Cantarini Déborah Giovanna , Pessôa Rafael Souza , França Fernando Luzía , Honorio-França Adenilda Cristina
Published: February 2014

An evaluation of the rheological properties and the effects ofMomordica. charantiaL. (M. charantia) nanoparticles and polyethylene glycol (PEG) microspheres adsorbed withM. charantiananoparticles on the blood of hyperglycemic patients is presented. Blood samples were collected according to glycemic status: normoglycemic(N=56)and hyperglycemic(N=26). General and hematological characteristics were determined. Blood rheological parameters were determined at room temperature and under a temperature scan. We determined the effects on whole blood viscosity of treatment with an extract ofM. charantia, PEG, or PEG microspheres adsorbed with plant extract. The viscosity of the blood of hyperglycemic patients is greater than that of normoglycemic patients. Nanoparticles ofM. charantiaextracts lowered blood viscosity at equivalent rates in normo- and hyperglycemic individuals. PEG microspheres did not reduce blood viscosity in hyperglycemic individuals. However, PEG microspheres adsorbed with nanofraction extracts ofM. charantiareduced blood viscosity. These data suggest that the effects of diabetes on the viscosity of the blood should be considered. The use of a nanoparticles extract ofM. charantiaand its adsorption on PEG microspheres may represent an alternative for the control and treatment of blood disorders in diabetic patients.
Effect of the Independent Acid Base Variables on Anion Gap Variation in Cardiac Surgical Patients: A Stewart-Figge Approach
Authors: Agrafiotis Michalis , Keklikoglou Ilias , Papoti Sofia , Diminikos George , Diplaris Konstantinos , Michaelidis Vassileios
Published: February 2014

Purpose. To determine the effect of each of independent acid base variables on the anion gap (AG) value in cardiac surgical patients.Methods. This retrospective study involved 128 cardiac surgical patients admitted for postoperative care. The variation of AG (AGvar) between the day of admission and the first postoperative day was correlated via a multiple linear regression model with the respective variations of the independent acid base variables, that is, apparent strong ion difference (SIDa), strong ion gap (SIG), carbon dioxide (PCO2), and albumin and phosphate concentrations.Results. The variations of all the above variables contributed significantly to the prediction ofAGvar(adjustedR2=0.9999,F=201890.24, andP<0.001). According to the standardized coefficients (β),  SIGvar(β= 0.948,P<0.001),[Albumin]var(β= 0.260,P<0.001), and[Phosphate]var(β= 0.191,P<0.001) were the major determinants ofAGvarwith lesser contributions fromSIDa, var(β= 0.071,P<0.001) andPCO2, var(β= −0.067,P<0.001).Conclusions. All the independent acid base variables contribute to the prediction of the AG value. However, albumin and phosphate and SIG variations seem to be the most important predictors, while AG appears to be rather stable with changes in PCO2andSIDa.
Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension
Authors: Molin Mikael , Demir Ayse Banu
Published: February 2014

Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.
90Y-DOTA-CHS Microspheres for Live Radiomicrosphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies
Authors: Amor-Coarasa Alejandro , Milera Andrew , Carvajal Denny , Gulec Seza , McGoron Anthony J.
Published: February 2014

Chitosan (CHS) is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected) in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine.
Review on Cold-Formed Steel Connections
Authors: Lee Yeong Huei , Tan Cher Siang , Mohammad Shahrin , Md Tahir Mahmood , Shek Poi Ngian
Published: February 2014

The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed.
Dynamic Scene Stitching Driven by Visual Cognition Model
Authors: Zou Li-hui , Zhang Dezheng , Wulamu Aziguli
Published: February 2014

Dynamic scene stitching still has a great challenge in maintaining the global key information without missing or deforming if multiple motion interferences exist in the image acquisition system. Object clips, motion blurs, or other synthetic defects easily occur in the final stitching image. In our research work, we proceed from human visual cognitive mechanism and construct a hybrid-saliency-based cognitive model to automatically guide the video volume stitching. The model consists of three elements of different visual stimuli, that is, intensity, edge contour, and scene depth saliencies. Combined with the manifold-based mosaicing framework, dynamic scene stitching is formulated as a cut path optimization problem in a constructed space-time graph. The cutting energy function for column width selections is defined according to the proposed visual cognition model. The optimum cut path can minimize the cognitive saliency difference throughout the whole video volume. The experimental results show that it can effectively avoid synthetic defects caused by different motion interferences and summarize the key contents of the scene without loss. The proposed method gives full play to the role of human visual cognitive mechanism for the stitching. It is of high practical value to environmental surveillance and other applications.
A Transgenic Mouse Model for Early Prostate Metastasis to Lymph Nodes
Authors: Ko Hyun-Kyung , Akakura Shin , Peresie Jennifer , Goodrich David W. , Foster Barbara A. , Gelman Irwin H.
Published: February 2014

The emergence of recurrent, metastatic prostate cancer following the failure of androgen-deprivation therapy represents the lethal phenotype of this disease. However, little is known regarding the genes and pathways that regulate this metastatic process, and moreover, it is unclear whether metastasis is an early or late event. The individual genetic loss of the metastasis suppressor, SSeCKS/Gravin/AKAP12 or Rb, genes that are downregulated or deleted in human prostate cancer, results in prostatic hyperplasia. Here, we show that the combined loss of Akap12 and Rb results in prostatic intraepithelial neoplasia (PIN) that fails to progress to malignancy after 18 months. Strikingly, 83% of mice with PIN lesions exhibited metastases to draining lymph nodes, marked by relatively differentiated tumor cells expressing markers of basal (p63, cytokeratin 14) and luminal (cytokeratin 8 and androgen receptor) epithelial cells, although none expressed the basal marker, cytokeratin 5. The finding that PIN lesions contain increased numbers of p63/AR-positive, cytokeratin 5-negative basal cells compared with WT or Akap12−/− prostate lobes suggests that these transitional cells may be the source of the lymph node metastases. Taken together, these data suggest that in the context of Rb loss, Akap12 suppresses the oncogenic proliferation and early metastatic spread of basal-luminal prostate tumor cells. Cancer Res; 74(3); 945–53. ©2014 AACR.
Combination of YM155, a Survivin Suppressant, with Bendamustine and Rituximab: A New Combination Therapy to Treat Relapsed/Refractory Diffuse Large B-cell Lymphoma
Authors: Kaneko Naoki , Mitsuoka Keisuke , Amino Nobuaki , Yamanaka Kentaro , Kita Aya , Mori Masamichi , Miyoshi Sosuke , Kuromitsu Sadao
Published: February 2014

Purpose: There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to evaluate the therapeutic potential of sepantronium bromide (YM155), a survivin suppressant, in combination with either bendamustine or both bendamustine and rituximab using DLBCL models.

Experimental Design: Human DLBCL cell lines, DB, SU-DHL-8, and WSU-DLCL2, were treated with YM155 in combination with bendamustine. Cell viability, apoptosis induction, protein expression, and cell-cycle distribution were evaluated. Furthermore, antitumor activities of YM155, in combination with bendamustine or both bendamustine and rituximab, were evaluated in mice bearing human DLBCL xenografts.

Results: The combination of YM155 with bendamustine showed greater cell growth inhibition and sub-G1 population than either agent alone. YM155 inhibited bendamustine-induced activation of the ATM pathway and accumulation of survivin at G2–M phase, with greater DNA damage and apoptosis than either single agent alone. In a DLBCL DB murine xenograft model, YM155 enhanced the antitumor activity of bendamustine, resulting in complete tumor regression without affecting body weight. Furthermore, YM155 combined with bendamustine and rituximab, decreased FLT-PET signals in lymph nodes and prolonged overall survival of mice bearing disseminated SU-DHL-8, an activated B-cell–like (ABC)-DLBCL xenografts when compared with the combination of either rituximab and bendamustine or YM155 with rituximab.

Conclusions: These results support a clinical trial of the combination of YM155 with bendamustine and rituximab in relapsed/refractory DLBCL. Clin Cancer Res; 20(7); 1814–22. ©2014 AACR.
Hypoxia-Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients
Authors: Dekervel Jeroen , Hompes Daphne , van Malenstein Hannah , Popovic Dusan , Sagaert Xavier , De Moor Bart , Van Cutsem Eric , D'Hoore André , Verslype Chris , van Pelt Jos
Published: February 2014

Purpose: Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.

Experimental Design: Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray datasets. These datasets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin-embedded material of 126 patients with colon cancer treated in our center.

Results: In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected P ≤ 0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n = 224). With a fourth published dataset (n = 177), the six-gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease-free survival at three years (77.3%) compared with high CCHS patients (46.4%; log-rank, P = 0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs. 52.2%; P = 0.001).

Conclusions: Hypoxia-driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A six-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledge on molecular classification of colon cancer. Clin Cancer Res; 20(8); 2159–68. ©2014 AACR.
Establishing a Diagnostic Road Map for MUTYH-Associated Polyposis
Authors: Borras Ester , Taggart Melissa W. , Lynch Patrick M. , Vilar Eduardo
Published: February 2014

The analysis of MUTYH-associated polyposis cases of the EPIPOLIP cohort confirms the importance of including serrated polyps in the diagnostic work-up of patients with oligopolyposis, suggests a role for screening polyps for the somatic c.34G>T KRAS mutation, and allows the implementation of a genetic testing strategy based on population data. Clin Cancer Res; 20(5); 1061–3. ©2014 AACR.
How Can We Improve Transfer of Outcomes from Randomized Clinical Trials to Clinical Practice with Disease-Modifying Drugs in Alzheimer's Disease?
Authors: Gauthier S. , Leuzy A. , Rosa-Neto P.
Published: February 2014

Background: Randomized clinical trials (RCTs) for putative disease-modifying drugs in Alzheimer's disease (AD) are using cognitive outcomes, such as the Alzheimer's Disease Assessment Scale - cognitive subscale, activities of daily living scales, such as the Alzheimer's Disease Cooperative Study Activities of Daily Living, and time from mild cognitive impairment to AD dementia. Objective: It was the aim of this study to build clinically relevant outcomes for future use in clinical practice into RCT designs and help third-party payers to measure benefit. Methods: We used a literature review for analysis. Results: The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) appears to be the most reliable primary outcome for RCT at different stages of AD, with the Relevant Outcome Scale for Alzheimer's Disease (ROSA) as a suitable alternative. The importance of current AD biomarkers vis-à- vis determination of efficacy of disease-modifying drugs has yet to be established; however, it is likely that at least one amyloid-specific test will be required prior to treatment with a drug acting predominantly on β-amyloid (Aβ42). Furthermore, serial MRI may be required to monitor adverse side effects associated with such drugs. Conclusions: Global clinical scales such as CDR-SB and ROSA should be considered for use with treatments aiming at slowing disease progression.
Inhibition of Amyloid Precursor Protein Processing Leads to Downregulation of Apoptotic Genes in Alzheimer's Disease Animal Models
Authors: Rabinovich-Nikitin Inna , Solomon Beka
Published: February 2014

Background and Methods: We previously reported the development of site-directed monoclonal antibodies able to inhibit the initiation of the amyloid precursor protein (APP) processing site, named ‘blocking β site 1' (BBS1). The beneficial effect of intracerebroventricular administration of these antibodies in the triple transgenic mouse model of Alzheimer's disease (AD) showed improvement in cognitive functions and reduction in tau and amyloid pathology. Amyloid-β may not be the only active component of AD neurotoxicity and may involve other proteolytic APP fragments such as the APP intracellular domain, proposed to work as a transcription factor involved in the regulation of p53 and glycogen synthase kinase 3β (GSK3β) as well as affecting several physiological processes contributing to AD pathology. Results: We show that inhibition of the β-secretase cleavage site via site-directed antibodies resulted in a major reduction in phosphorylated GSK3β levels, which is the active form of GSK3β, as well as in p53 levels. Conclusion: A therapy that is capable of reducing not only the direct hallmarks of AD but also the components that lead to neuronal apoptosis might have neuroprotective potential in AD treatment.
MRI for Iron Mapping in Alzheimer's Disease
Authors: Langkammer Christian , Ropele Stefan , Pirpamer Lukas , Fazekas Franz , Schmidt Reinhold
Published: February 2014

Background: Monitoring iron deposition became possible with new dedicated quantitative MRI sequences. These sequences hold promise to determine the role of iron in Alzheimer's disease (AD). It is currently unclear as to whether iron accumulation is pathogenically involved in AD or solely represents an epiphenomenon of the neurodegenerative process. Objective: We discuss currently available MR methods for quantitative iron mapping in the brain and provide an overview of results in animal models as well as in AD patients. Methods: A short literature review was used for analysis. Results: R2*-based imaging is the best validated technique for iron detection. Current research applications include amyloid plaque detection in postmortem brains and in transgenic animal models and quantitative iron mapping in gray matter. AD patients have increased iron levels in the putamen, pulvinar thalamus, red nucleus, hippocampus, and temporal cortex. The clinical consequences of this finding and the dynamics of iron accumulation in AD are widely unknown. Conclusions: MRI allows to quantitatively map iron accumulation in the brain. The clinical significance of increased iron levels in AD needs to be determined in both cross-sectional and longitudinal studies. The advent of ultra-high field imaging in clinical applications will increase image resolution and will allow in vivo iron detection in neocortical structures in AD patients both cross-sectionally and longitudinally.
The European Union Policy in the Field of Rare Diseases
Authors: Montserrat Moliner A. , Waligóra J.
Published: February 2014

Background: Rare diseases (RDs), including those of genetic origin, are defined by the European Union (EU) as life-threatening or chronically debilitating diseases, which are of low prevalence (fewer than 5 per 10,000). The specificities of RDs - a limited number of patients and scarcity of relevant knowledge and expertise - single them out as a unique domain of a very high European added value. Methods: Legal instruments at the disposal of the EU, in terms of Article 152 of the Treaties, are very limited. However, a combination of instruments using the research and the pharmaceutical legal regulations, an intensive and creative use of funding from the Second Health Programme, the adoption of the Commission Communication in November 2008, the Council Recommendation in June 2009, and the Directive on cross-border healthcare in 2011 have permitted the creation of a solid basis that Member States have considered as sufficient to place RDs in a privileged position in the health agenda. Results: As a result, an operational framework to act in the field of RDs with European coordination in several areas would be possible (orphan medicinal products, national plans on rare diseases, ICD-10 revision, European Reference Networks, European Platform for Rare Diseases registration, IRDiRC, European Committee of Experts, etc.). Conclusion: RDs is a field with an enormous potential for European cooperation.
Biomarkers in Rare Diseases
Authors: Ferlini A. , Scotton C. , Novelli G.
Published: February 2014

Background: Nowadays 7,000 rare diseases (RDs) have been identified with a prevalence less than 5/10,000. Despite of the enormous effort the European Union (EU) has already invested in this field, still 4,000 RDs remain orphan of genetic diagnosis and causative gene identification. The genetic definition of RDs represents a prerequisite for being diagnosed, for having a robust prevention, for entering in a specific standard of care, and ultimately, for being included in clinical trials, often via personalized medicine. It is well established that biomarkers can offer a way to speed up research by understanding the pathophysiological mechanisms of diseases. In particular, biomarkers will offer an invaluable tool for monitoring disease progression, prognosis and response to drug treatment. Methods: In this review, we summarize the different types of biomarkers and their importance as well as their translational applications in RDs. We have reviewed the current knowledge on biomarkers state-of-the-art via literature data, specific websites and EU sources regarding past, pending and current projects. Results: Here we provide a comprehensive scenario of biomarkers research, its applications in clinical practice, with special emphasis on translational research applicable to diagnostic and clinical trials. The experience of the EU project BIO-NMD is also mentioned. Conclusion: Biomarkers represent key features in both diagnostics and research on rare diseases and will encounter wide exploitation in translational and personalized medicine.
Clinical Trial Transparency and Orphan Drug Development: Recent Trends in Data Sharing by the Pharmaceutical Industry
Authors: So D. , Joly Y. , Knoppers B.M.
Published: February 2014

Background: Data sharing from clinical trials can be key to the development and approval of medicines for rare diseases. Many events during the first half of 2013 have contributed to the movement for increased transparency. These include the development of the European Medicines Agency's new data publication policy, the creation of the AllTrials petition and GlaxoSmithKline's choice to sign it, the launch of GlaxoSmithKline's system for access to patient-level clinical trial data and Roche's commitment to create a similar system, the release of results from the Yale University Open Data Access project's first medicine analysis for Medtronic, and the creation of the Reg4All website. Aims/Objectives: This paper summarises major developments in clinical trial transparency between January and June 2013 and analyses the composition of datasets released by GlaxoSmithKline. Methods: GlaxoSmithKline's database of available trials was tabulated and graphs of relevant trial characteristics were produced. Results/Conclusions: Due to current transparency initiatives, it is likely that much more data will be made available over the next few years through systems similar to GlaxoSmithKline's. Although some aspects of GlaxoSmithKline's model could limit its usefulness, the data currently listed is diverse and could be promising for researchers interested in rare disease treatment.