bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression‐based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development
Authors: Roth Adrian , Boess Franziska , Landes Christian , Steiner Guido , Freichel Christian , Plancher Jean‐Marc , Raab Susanne , de Vera Mudry Cristina , Weiser Thomas , Suter Laura
Published: November 2010

We have analyzed gene expression and histopathology of rat liver treated with a histamine‐3 receptor inverse agonist under development for the treatment of obesity 24 h after a single acute administration. While histopathology did not identify a clear liver toxicity, analysis of gene changes strongly suggested the development of toxicity. This prediction was confirmed in a 2‐week repeat‐dose rat study where prominent liver pathology occurred, while gene changes that lead to the prediction persisted. A subset of these genes was analyzed in vitro in both rat and human hepatocytes to reveal the potential relevancy of the findings for the situation in humans. This comprehensive analysis of the development compound at the gene expression level allowed interpretation of findings of the follow‐up compound in a frontloaded 24‐h single‐dose acute study that was initiated before regular 2‐week repeat‐dose studies started. The high similarity of the follow‐up compound to the lead compound based on gene expression lead to the immediate termination of the development program for this compound series. Our data demonstrate the value of genomics‐based early toxicity prediction in short‐term in vivo studies for the characterization of compounds to allow prioritization and selection of suited candidates before compound‐, animal‐, and cost‐intensive longer term studies are undertaken. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:183–194, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20375
Extracellular‐superoxide dismutase expression during monocytic differentiation of U937 cells
Authors: Kamiya Tetsuro , Makino Junya , Hara Hirokazu , Inagaki Naoki , Adachi Tetsuo
Published: November 2010

Leukemic cell lines, such as U937, THP‐1, and HL60 cells, can differentiate into macrophages following exposure to various agents including 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in vitro. It is well known that TPA enhances reactive oxygen species (ROS) generation through the activation of NADPH oxidase (NOX), and ROS act as mediators in TPA signaling. Extracellular‐superoxide dismutase (EC‐SOD) is a major anti‐oxidative enzyme that protects the cells from damaging effects of superoxide. Recently, the reduction of Cu/Zn‐SOD and the induction of Mn‐SOD by TPA in leukemic cells have been reported; however, the regulation of EC‐SOD by TPA remains poorly understood. Here, we explored the regulation of EC‐SOD during the monocytic differentiation of U937 cells by TPA. We observed the reduction of EC‐SOD and Cu/Zn‐SOD, whereas the induction of Mn‐SOD during the differentiation of U937 cells. The reduction of EC‐SOD and Cu/Zn‐SOD was attenuated by pretreatments with GF109203X (an inhibitor of protein kinase C, PKC), diphenyleneiodonium (an inhibitor of NOX), and U0126 (an inhibitor of mitogen‐activated protein kinase kinase, MEK/extracellular‐signal regulated kinase, ERK). Interestingly, pretreatment with BAY11‐7082 (an inhibitor of nuclear factor‐κB, NF‐κB) suppressed the reduction of Cu/Zn‐SOD, but not of EC‐SOD. Furthermore, we also determined the involvement of newly synthesized protein and the instability of mRNA in the reduction of EC‐SOD. Overall, our results suggest that the expression of EC‐SOD is decreased by TPA through intracellular signaling consisting of PKC, NOX‐derived ROS and MEK/ERK, but not of NF‐κB signaling. J. Cell. Biochem. 112: 244–255, 2011. © 2010 Wiley‐Liss, Inc.
Cystic lymphangioma of the pancreas with congenital intrahepatic duct dilatation and choledochal cyst
Authors: Wang Yao , Tang Shao‐Shan , Ma Ying
Published: November 2010

Cystic lymphangioma of the pancreas is an extremely rare benign tumor of lymphatic origin. We report on a 68‐year‐old woman who had experienced epigastric abdominal distension and nausea for over 1 year. Sonography revealed a cystic‐solid mixed mass in the head of pancreas, with intrahepatic and extrahepatic duct dilatation. A diagnosis of cystic lymphangioma with congenital intrahepatic duct dilatation and choledochal cyst was made after excision and pathologic examination. Preoperative diagnosis of cystic lymphangioma of the pancreas is difficult, and carefulsonographic evaluation is required. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20763
Prenatal diagnosis of thoracic kidney in the 2nd trimester with delayed manifestation of associated diaphragmatic hernia
Authors: Athanasiadis Apostolos P. , Zafrakas Menelaos , Arnaoutoglou Christos , Karavida Aikaterini , Papasozomenou Panayiota , Tarlatzis Basil C.
Published: November 2010

Ectopic kidney is a rare congenital malformation, caused by renal malpositioning during embryogenesis. We report a rare case of ectopic kidney located in the left hemithorax of a male fetus. The unique features in this case were early sonographic prenatal diagnosis of thoracic kidney at 22 weeks' gestation, which was confirmed by fetal MRI, and delayed sonographic manifestation of the associated congenital diaphragmatic hernia at 27 weeks. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2011
Statistical approach to determine the effect of combined environmental parameters on conidial development of Trichoderma atroviride (T‐15603.1)
Authors: Schubert M. , Mourad S. , Schwarze F. W. M. R.
Published: November 2010

Trichoderma atroviride (T‐15603.1) is a promising fungal agent for biological control of wood decay fungi in urban tree wounds. The aim of this work was to determine the combined effects of water activity (aw, 0.998–0.892), temperature (10–30 °C) and pH (3–7) on the development of conidia on low‐nutrient agar (LNA). Lag phase prior to germination (h), germination rates (µm) and germ‐tube elongation were obtained at each set of conditions. The experimental data were used to fit a response surface model for predicting the germination rates of T‐15603.1 and to analyze the effect of the abiotic parameters tested. The polynomial response surface model was mathematically evaluated using graphical plots and several statistical indices (RMSE, %SEP, Af, Bf, pRE). Data analyses showed a highly significant effect on conidial development of aw and temperature (P < 0.001), whereas no significant effect of pH (P ≥ 0.05) was observed. The germination rate dropped and the lag prior to germination increased as the temperature and aw decreased, but T‐15603.1 appeared to be more sensitive to aw reduction than to temperature. The minimum aw level for germination was 0.910 at 15–25 °C, and maximum germination rates were obtained at aw = 0.998, 25–30 °C and pH 5. The response surface model was useful and widely accurate (R2 = 0.983) for predicting the germination rate of T‐15603.1 and complemented the experimental results. These findings contribute to better understanding how combined environmental factors affect the environmental parameter tolerance levels of T‐15603.1 and to the development of an adequate delivery system for optimized application of T‐15603. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Metabolic changes of Acidithiobacillus caldus under Cu2+ stress
Authors: Xia Lexian , Yin Chu , Cai Liyuan , Qiu Guanzhou , Qin Wenqing , Peng Bin , Liu Jianshe
Published: November 2010

Metabolic changes were investigated by measuring the depletion of dissolved oxygen and the enzymatic activities of sulfur metabolism in Acidithiobacillus caldus (A. caldus) before and after copper stress. The results showed that high concentrations of Cu2+ have an indirect negative effect on the sulfite oxidase and the APS reductase involved in sulfur metabolism when A. caldus is cultured in medium with elemental sulfur as its growth energy. This leads to a decrease in the respiration rate and the growth rate. The changes of activity are negatively correlated with the intracellular Cu2+ concentration through an indirect interaction mechanism. A. caldus was able to induce an efflux of copper ions by forming an ATPase‐dependent pump, which transported copper ions by consuming ATP. The negative effect of Cu2+ on the bacterial metabolism could be minimized by the copper efflux when the bacteria were adapted in medium containing Cu2+ for a long time. However, this bacterial rejuvenation became weaker when grown in medium containing higher concentrations of copper ions. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Anoxybacillus salavatliensis sp. nov., an α‐glucosidase producing, thermophilic bacterium isolated from Salavatli, Turkey
Authors: Cihan Arzu Coleri , Ozcan Birgul , Cokmus Cumhur
Published: November 2010

A novel moderately thermophilic, Gram‐positive staining, rod‐shaped, spore‐forming, motile, facultative anaerobic, and α‐glucosidase producing strain A343T, was isolated from a high temperature well‐pipeline sediment sample in Salavatli province of Aydin, Turkey. Growth was observed at 37–69 ºC (optimum 60 °C), at pH 5.5–9.5 (optimum 8.0–9.0) and at salinities from 0 to 4.5% (w/v) (optimum 2%). Strain A343T was able to grow on a wide range of carbon sources. Gelatin and starch utilization, amylase, catalase and oxidase activities, reduction of nitrate to nitrite were all positive. The G+C content of the genomic DNA was 45.1 mol%. The major menaquinone was MK‐7. The dominant cellular fatty acids were: iso‐C15:0, C16:0, and iso‐C17:0. The phylogenetic analysis based on the 16S rRNA gene sequence revealed that the strain A343T belonged to the genus Anoxybacillus. The 16S rRNA gene sequence similarity between strain A343T and the type strains of recognized Anoxybacillus species was ranged from 95.8 to 99.4%. DNA‐DNA hybridization revealed low homology with its closest relative Anoxybacillus kamchatkensis (49.7%). In addition to the total cell protein profiles, the Rep‐PCR and the intergenic 16S–23S rRNA gene fingerprinting profiles differentiated strain A343T from all of the reference Anoxybacillus species used. Based upon phenotypic, phylogenetic and chemotaxonomic evidence, strain A343T was assigned to a new species within the genus Anoxybacillus, A. salavatliensis sp. nov. (The type strain A343T= DSM 22626T = NCIMB 14579T). The 16S rRNA gene nucleotide sequence of strain A343T is available in the GenBank database under the accession number – EU326496. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Beryllium‐10 surface exposure dating of glacial successions in the Central Alaska Range
Authors: Dortch Jason M. , Owen Lewis A. , Caffee Marc W. , Li Dewen , Lowell Thomas V.
Published: November 2010

Glacial landforms and outwash terraces in the Nenana River valley, Reindeer Hills and Monahan Flat in the central Alaska Range were dated with 6010Be exposure ages to determine the timing of Late Pleistocene glaciation. In the Nenana River valley, glaciation occurred at 104–180 ka (Lignite Creek glaciation), ca. 55 ka (Healy glaciation), and ca. 16 ka (Carlo Creek phase); glaciers retreated in the Reindeer Hills and Monahan Flat by ca. 14 ka and ca. 13 ka, respectively. The Carlo Creek moraine is similar in age to at least six other moraines in the Alaska Range, Ahklun Mountains and Brooks Range. The new data suggest that post‐depositional geological processes limit the usefulness of10Be methods to the latter part (≤60 ka) of the late Quaternary in central Alaska. Ages on Healy and younger landforms cluster well, with the exception of Riley Creek moraines and Monahan Flat‐west sites, where boulders were likely affected by post‐depositional processes. Copyright © 2010 John Wiley & Sons, Ltd.
Ongoing exposure versus intense periodic exposure to military conflict and terror attacks in Israel
Authors: Lahad Mooli , Leykin Dmitry
Published: November 2010

The manifestation of posttraumatic stress disorder (PTSD) symptoms in two clinical samples in Israel (N = 212) was examined. Individuals suffering ongoing exposure to shelling were compared with subjects exposed to intense periodic exposure. Elevated arousal and avoidance symptoms, but not intrusion were reported in the ongoing exposure group. When compared by age, young participants in the ongoing exposure group had significantly lower PTSD scores, whereas no differences were found between participants among the intense periodic exposure age groups. No gender differences in symptoms were found among participants from intense periodic exposure, whereas in the other ongoing group the difference was in avoidance. Results are discussed in light of past research on exposure to terrorism.
A phase I study of zoledronic acid and low‐dose cyclophosphamide in recurrent/refractory neuroblastoma: A new approaches to neuroblastoma therapy (NANT) study
Authors: Russell Heidi V. , Groshen Susan G. , Ara Tasnim , DeClerck Yves A. , Hawkins Randy , Jackson Hollie A. , Daldrup‐Link Heike E. , Marachelian Araz , Skerjanec Andrej , Park Julie R. , Katzenstein Howard , Matthay Katherine K. , Blaney Susan M. , Villablanca Judith G.
Published: November 2010

Background

Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials.

Procedure

Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL‐6, and sIL‐6R were evaluated.

Results

Twenty‐one patients, median age 7.5 (range 0.8–25.6) years were treated with 2 mg/m2 (n = 4), 3 mg/m2 (n = 3), or 4 mg/m2 (n = 14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1–18) courses was given. Two dose limiting toxicities (grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other grades 3–4 toxicities included hypocalcemia (n = 2), elevated transaminases (n = 1), neutropenia (n = 2), anemia (n = 1), lymphopenia (n = 1), and hypokalemia (n = 1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3–18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL‐6 levels decreased with therapy.

Conclusions

Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days. Pediatr Blood Cancer 2011; 57: 275–282. © 2010 Wiley‐Liss, Inc.
The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort
Authors: Roumie Christianne L. , Huizinga Mary Margaret , Liu Xulei , Greevy Robert A. , Grijalva Carlos G. , Murff Harvey J. , Hung Adriana M. , Griffin Marie R.
Published: November 2010

Objective

Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12‐month lipid profiles among new OAD users.

Methods

We identified a retrospective cohort of 17 774 veterans who received care at Veterans Administration (VA) Mid‐South Network with a first OAD from 1 January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM at baseline, and 3871 (56%) had complete covariates. Incident users of sulfonylurea and combination metformin + sulfonylurea were compared to metformin users for time to LLM initiation. Incident users of these OADs and thiazolidendiones were included in comparison of 12‐month low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides (TGs), and total cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare utilization, and cardiovascular disease at baseline.

Results

The median time to starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin initiation and not statistically different for users of sulfonylureas, or combination OADs. Compared to metformin users, 12‐month HDL was 1.35 mg/dl (95%CI: −2.01, −0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl (95%CI: −19.9, −13.5) and 18.6 mg/dl (95%CI: −22.1, −15.1) lower than non‐statin users, respectively.

Conclusions

Time to LLM initiation was similar between OADs. Metformin use resulted in more favorable lipids at 12 months compared to sulfonylureas or thiazolidinediones. Copyright © 2010 John Wiley & Sons, Ltd.
Thermal, mechanical and acoustic damping properties of flexible open‐cell polyurethane/multi‐walled carbon nanotube foams: effect of surface functionality of nanotubes
Authors: Bandarian Maryam , Shojaei Akbar , Rashidi Ali Morad
Published: November 2010

This article demonstrates the properties of open‐cell flexible polyurethane foams incorporating multi‐walled carbon nanotubes. Three different types of highly functionalized nanotubes having carboxyl, hydroxyl and amide functional groups were synthesized. Neat polyurethane foam and three nanocomposite foams filled with 0.1 wt% of treated nanotubes were prepared. It was found that thermal stability, mechanical properties and acoustic damping were improved significantly by incorporation of small amounts of nanotubes. The nanotubes modified with carboxyl groups were found to have much more influence compared to the other two functional groups, possibly due to better interfacial interaction and improved dispersion. Scanning electron microscopy revealed micro‐cells with average diameters less than 5 µm in the skeleton of foams filled with nanotubes modified with hydroxyl and carboxyl, the formation of which was attributed to the generation of gaseous materials through the reaction with isocyanate. Such micro‐cells were found to be influential in improving mechanical and acoustic damping. Copyright © 2010 Society of Chemical Industry
Fabrication of photonic crystal structure on indium tin oxide electrode of GaN‐based light‐emitting diodes
Authors: Byeon Kyeong‐Jae , Park Hyoungwon , Cho Joong‐Yeon , Yang Ki‐Yeon , Baek Jong Hyeob , Jung Gun Young , Lee Heon
Published: November 2010

Wafer‐scale UV nanoimprint and dry etching processes were used to fabricate photonic crystal patterns on an indium tin oxide (ITO) top electrode of GaN‐based green light‐emitting diodes (LEDs). Photonic crystal patterns with pitches ranging from 600 to 900 nm were transferred to the entire 2‐inch LED wafer. Plasma damage in the GaN crystal of the LED device was avoided because the GaN was covered by ITO layer and was not exposed to the etching plasma during the ITO dry etching process. Consequently, the electroluminescence intensity of the patterned LED devices was enhanced up to 25% at 20 mA of driving current, compared to the nonpatterned LED device, while the forward voltage was similar.
Mode of action of peppermint oil and (‐)‐menthol with respect to 5‐HT3receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum
Authors: Heimes Katharina , Hauk Florian , Verspohl Eugen J.
Published: November 2010

Peppermint oil (Mentha×piperitaL. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (‐)‐menthol is the most important. Three differentin vitromodels were used to investigate the effects on 5‐HT3receptors (serotonin receptor subtype): [14C]guanidinium influx into N1E‐115 cells which express 5‐HT3receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5‐HT3receptor antagonist ([3H]GR65630) (3‐(5‐methyl‐1H‐imidazol‐4‐yl)‐1‐(1‐methyl‐1H‐indol‐3‐yl)‐1‐propanone). Both peppermint oil and (‐)‐menthol inhibited [14C]guanidinium influx through 5‐HT3receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (‐)‐menthol, however, was able to displace [3H]GR65630 from 5‐HT3binding sites. It may be concluded that peppermint oil and (‐)‐menthol exert their antiemetic effect at least partly by acting on the 5‐HT3receptor ion‐channel complex, probably by binding to a modulatory site distinct from the serotonin binding site. Copyright © 2010 John Wiley & Sons, Ltd.
Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice
Authors: Sampath C. , Holbik M. , Krenn L. , Butterweck V.
Published: November 2010

The purpose of this study was to characterize the putative anxiolytic‐like activity of fractions prepared from a hydroethanol extract of Passiflora incarnata L. using the elevated plus‐maze (EPM) in mice. The fractions were prepared as published recently, yielding a butanol, petroleum ether and chloroform fraction. From the tested fractions, the butanol fraction showed significant increases in the number of open arm entries in the EPM in concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of the original extract. The highest activity was found for the chloroform fraction in doses of 0.17 mg/kg (10.0 ± 1.9, p < 0.001) and 0.34 mg/kg (6.6 ± 0.86; p < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg, respectively. Interestingly, the petroleum ether fraction did not show any effects in the elevated plus maze. A sedative or stimulatory effect of each of the fractions could be excluded, since none of the compounds had an influence on the total distance that the animals covered during the observation period. The results suggest that the active principle of passion flower seems to be in the chloroform fraction and to a lower extent in the butanol fraction. Copyright © 2010 John Wiley & Sons, Ltd.
Surface energy balance and turbulence network during the Convective and Orographically‐induced Precipitation Study (COPS)
Authors: Eigenmann R. , Kalthoff N. , Foken T. , Dorninger M. , Kohler M. , Legain D. , Pigeon G. , Piguet B. , Schüttemeyer D. , Traulle O.
Published: November 2010

Experimental data of the energy balance and the turbulence network installed during the Convective and Orographically‐induced Precipitation Study (COPS) field campaign of 2007 are presented in this study. The network aims at providing continuous surface flux and other surface micrometeorological data of the required high accuracy and quality for further fundamental research. An overview of the turbulence data processing and data quality control, including footprint analysis and a check for internal boundary layers, is given. The consistently applied approach allows for a high comparability of the turbulent flux data of sensible and latent heat. The reaction of surface fluxes during the observed frontal passage during the Intensive Observation Period (IOP) 9c (20 July 2007) is presented. As surface fluxes were measured over different land‐use types and at different locations within the COPS area, the effect of land use and orography on turbulent fluxes is discussed with the help of IOP 8b (15 July 2007). The flux differences between individual sites due to varying surface characteristics are often larger than the flux differences with changing altitude. The oasis effect observed for the highly evapotranspirating maize fields is found to increase the residuum of the surface energy balance. At all sites and during both IOPs the occurrence of near‐ground free convection conditions (FCCs) is investigated. During the oasis effect, FCCs do not occur. Copyright © 2011 Royal Meteorological Society
Collapse resistance of unreinforced steel moment connections
Authors: Kim Taejin , Kim Un‐Suk , Kim Jinkoo
Published: November 2010

Experimental and analytical studies of steel moment connections in gravity load resisting systems were conducted to understand the connection behaviour under progressive collapse. An exterior beam–column assemblage was selected from the gravity load resisting system in a steel building. Two identical, full‐scale, unreinforced welded steel beam‐to‐column moment connection specimens were tested under monotonic and cyclic loading to investigate the effects of applied loading conditions on the connection rotation capacity. The beam web was connected to the column flange by bolting and the beam flanges were complete joint penetration welded to the column flange. The specimens failed by fracture in the beam flange CJP weld at story drifts of 9.2 % (specimen SP1 under monotonic loading) and 3.4% (specimen SP2 under cyclic loading). The maximum drift angle achieved in the monotonic test exceeded the General Service Administration criterion for welded unreinforced flange connections, and the amount of dissipated energy of SP1 turned out to be smaller than that of SP2. The finite element analysis of the test specimen was also conducted to validate the test results, and the analysis results matched well with those obtained from experiments. Copyright © 2010 John Wiley & Sons, Ltd.
Testicular torsion: a urological emergency
Authors: Thakare Niyukta , O'Flynn Kieran J. , Pearce Ian
Published: November 2010

Testicular torsion is an emergency that all health professionals should be aware of. The authors outline the presentation, differential diagnosis and need for rapid management. Copyright © 2010 Wiley Interface Ltd
Modeling Down syndrome screening performance using first‐trimester serum markers
Authors: Koster M. P. H. , Wortelboer E. J. , Stoutenbeek P. , Visser G. H. A. , Schielen P. C. J. I.
Published: November 2010

Objective

To evaluate the modeled predictive value of three current screening markers (pregnancy‐associated plasma protein‐A (PAPP‐A), free β‐human chorionic gonadotropin (free β‐hCG), and nuchal translucency (NT)) and four potential screening markers (a disintegrin and metalloprotease 12 (ADAM12), total hCG, placental protein 13 (PP13), and placental growth factor (PlGF)) for Down syndrome using different screening strategies.

Methods

All markers were measured in stored first‐trimester serum of 151 Down syndrome cases and 847 controls. All marker levels were expressed as gestational age‐specific multiples of the median (MoMs) and comparisons were made using the Mann‐Whitney U‐test. Detection rates (DRs) for fixed false‐positive rates (FPRs) were modeled using different screening strategies.

Results

Significantly different median MoMs for Down syndrome cases compared to controls were found for PAPP‐A (0.49 vs. 1.00; P < 0.0001), free β‐hCG (1.70 vs. 1.01; P < 0.0001), ADAM12 (0.89 vs. 1.00; P < 0.0001), total hCG (1.28 vs. 1.00; P < 0.0001), PlGF (0.80 vs. 1.00; P < 0.0001) and NT (1.74 vs. 1.01; P < 0.0001). The lower PP13 MoM in Down syndrome cases (0.91 vs. 1.00) was not statistically significant (P = 0.061). Adding the four new markers to the current screening strategy (i.e. first‐trimester combined test) led to an increase in DR from 77% to 80% at a 5% FPR. The modeled application of a two‐sample screening strategy (with some markers assessed early and others later in the first trimester) increased the DR to 89%. In a two‐step contingent screening model, using an intermediate risk range of 1 in 100 to 1 in 2000 at biochemical screening (using all markers), the overall DR was 77%, but it was predicted that only 33% of women would require referral for NT measurement.

Conclusions

First‐trimester Down syndrome screening may be improved by adding new markers to the current screening test and by applying different screening strategies. The application of a two‐sample screening model resulted in the highest predicted DR, but this should be confirmed in population‐based prospective studies. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
A contract-based approach to describe and deploy non-functional adaptations in software architectures
Authors: Loques Orlando , Sztajnberg Alexandre , Curty Romulo , Ansaloni Sidney
Published: November 2010

This paper presents a comprehensive approach to describe, deploy and adapt component-based applications having dynamic non-functional requirements. The approach is centered on high-level contracts associated to architectural descriptions, which allow the non-functional requirements to be handled separately during the system, design process. This helps to achieve separation of concerns facilitating the reuse of modules that implement the application in other systems. Besides specifying non-functional requirements, contracts are used at runtime to guide configuration adaptations required to enforce these requirements. The infrastructure required to manage the contracts follows an architectural pattern, which can be directly mapped to specific components included in a supporting reflective middleware. This allows designers to write a contract and to follow standard recipes to insert the extra code required to its enforcement in the supporting middleware.
An approach for reasoning and refining non-functional requirements
Authors: Rosa Nelson Souto , Freire Cunha Paulo Roberto , Ribeiro Justo George Roger
Published: November 2010

Non-functional requirements (NFRs) are rarely taken in account in most software development processes. There are some reasons that can help us to understand why these requirements are not explicitly dealt with: their complexity, NFRs are usually stated only informally, their high abstraction level and the rare support of languages, methodologies and tools. In this paper, we concentrate on defining how to reason and how to refine NFRs during the software development. Our approach is based on software architecture principles that guide the definition of the proposed refinement rules. In order to illustrate our approach, we adopt it to an appointmernt system.
A systematic approach for structuring exception handling in robust component-based software
Authors: Filho Fernando Castor , Guerra Paulo Asterio de C. , Pagano Vinicius Asta , Rubira Cecília Mary F.
Published: November 2010

Component-based development (CBD) is recognized today as the standard paradigm for structuring large software systems. However, the most popular component models and component-based development processes provide little guidance on how to systematically incorporate exception handling into component-based systems. The problem of how to employ language-level exception handling mechanisms to introduce redundancy in componentbased systems is recognized by CBD practitioners as very difficult and often not adequately solved. As a consequence, the implementation of the redundant exceptional behaviour causes a negative impact, instead of a positive one, on system and maintainability. In this paper, we propose an approach for the construction of dependable component-based systems that integrates two complementary strategies: (i) a global exception handling strategy for inter-component composition and (ii) a local exception handling strategy for dealing with errors in reusable components. A case study illustrates the application of our approach to a real software system.
Analyzing, modeling and predicting organizational effects in a distribuited sensor network
Authors: Horling Bryan , Lesser Victor
Published: November 2010

The organizational design of a distributed system defines how entities act and interact to achieve local and global objectives. We describe how a system employing different types of organizational techniques has been used to address the challenges posed by a distributed sensor network environment. The high-level, multi-agent architecture of this realworld system is given in detail, and we provide empirical results demonstrating the effects the organization has on the system’s performance across several different metrics. As with any design, the particular approach that is employed makes trade-offs, some of which are obvious and some more subtle. The presence of such trade-offs motivates the need for a better understanding of precisely how the organization influences large and small-scale behaviors. To address this need, we first demonstrate how a collection of analytic models can be developed to predict such effects. This experience is then used to ground the presentation of a more comprehensive, domain-independent organizational modeling language called ODML. The structure and capabilities of ODML are explained through the construction of a unified model of our sensor network organization. We then show that this model provides an accurate prediction of the original empirical results.
Systems of exchange values as tools for multi-agent organizations
Authors: Dimuro Gracaliz P. , Costa A. C. Rocha , Palazzo Luiz A. M.
Published: November 2010

This paper introduces systems of exchange values as tools for the organization of multi-agent systems. Systems of exchange values are defined on the basis of the theory of social exchanges, developed by Piaget and Homans. A model of social organization is proposed, where social relations are construed as social exchanges and exchange values are put into use in the support of the continuity of the performance of social exchanges. The dynamics of social organizations is formulated in terms of the regulation of exchanges of values, so that social equilibrium is connected to the continuity of the interactions. The concept of supervisor of social equilibrium is introduced as a centralized mechanism for solving the problem of the equilibrium of the organization The equilibrium supervisor solves such problem making use of a qualitative Markov Decision Process that uses numerical intervals for the representation of exchange values.
The use of an enterprise ontology to support knowledge management in software development environments
Authors: Villela Karina , Santos Gleison , Schnaider Lílian , Rocha Ana Regina , Travassos Guilherme Horta
Published: November 2010

Software engineering is knowledge-intensive activity and knowledge is thought to be the most important asset in an organization. Therefore this paper presents an approach to support Knowledge Management in Software Development Environments that is strongly based on ontologies: Enterprise Oriented Software Development Environments. After describing the components of such environments, this paper focuses on the Enterprise Ontology and on three tools developed based on this ontology: a ‘yellow pages’ tool which shows the distribution of competencies in the organization, a tool to support the allocation of people to software projects and a graphic tool for representing and visualizing organizational processes.
A fast and accurate approach for computing the dimensions of boxes from single perspective images
Authors: Fernandes Leandro A. F. , Oliveira Manuel M. , da Silva Roberto , Crespo Gustavo J.
Published: November 2010

This paper describes an accurate method for computing the dimensions of boxes directly from perspective projection images acquired by conventional cameras. The approach is based on projective geometry and computes the box dimensions using data extracted from the box silhouette and from the projection of two parallel laser beams on one of the imaged faces of the box. In order to identify the box silhouette, we have developed a statistical model for homogeneous-background-color removal that works with a moving camera, and an efficient voting scheme for the Hough transform that allows the identification of almost collinear groups of pixels. We demonstrate the effectiveness of the proposed approach by automatically computing the dimensions of real boxes using a scanner prototype that implements the algorithms and methods describe din the paper. We also present a discussion of the performed measurements, and an error propagation analysis that allows the method to estimate, from each single video frame, the uncertainty associated to all measurements made over thatframe, in real-time.
Muta-Pro: Towards the definition of a mutation testing process
Authors: Vincenzi A. M. R. , Simão A. S. , Delamaro M. E. , Maldonado J. C.
Published: November 2010

Mutation Testing originated from a classical method for digital circuit testing and today is used at program and specification levels. It can be used either to generate or to assess the quality of test sets. In spite of being very effective in detecting faults, Mutation Testing is usually considered a high cost criterion due to: i) the large number of generated mutants; ii) the time-consuming activity of determining equivalent mutants; and iii) the mutant execution time. Many initiatives aiming at reducing the Mutation Testing application cost have been conducted, most of them addressing one of the drawbacks mentioned above.

In this paper, we identify and summarize some of the most relevant researches and results related to Mutation Testing cost reduction, e.g., Constrained-Mutation, Constraint-Based Testing and Bayesian Learning. Moreover, we propose a Mutation Testing process, namedMuta-Pro, that synergetically integrates the related approaches and mechanisms. This process is intended to be incremental and tailorable to a specific application domain such as C programs or finite state machine models. The main ideas in this paper are illustrated using a UNIX utility program.

This process is being integrated in a Mutation Testing environment, based on the authors’ previous experience on implementing theProteum Familytools, aiming at promoting the technology transfer to industry and providing the basis for improving theMuta-Proprocess itself.
Plant effects on soil N mineralization are mediated by the composition of multiple soil organic fractions
Authors: Fornara Dario A. , Bardgett Richard , Steinbeiss Sibylle , Zak Donald R. , Gleixner Gerd , Tilman David
Published: November 2010

Despite the topic of soil nitrogen (N) mineralization being well‐studied, very few studies have addressed the relative contribution of different plant and soil variables in influencing soil N mineralization rates, and thus the supply of inorganic N to plants. Here, we used data from a well‐studied N‐limited grassland to address the relative effects of six plant and soil variables on net and on gross rates of soil N mineralization. We also addressed whether plant effects on soil N mineralization were mediated by changes in C and N concentrations of multiple soil organic matter (SOM) fractions. Regression analyses show that key plant traits (i.e., plant C:N ratios and total root mass) were more important than total C and N concentrations of bulk soil in influencing N mineralization. This was mainly because plant traits influenced the C and N concentration (and C:N ratios) of different SOM fractions, which in turn were significantly associated with changes in net and gross N mineralization. In particular, C:N ratios of a labile soil fraction were negatively related to net soil N mineralization rates, whereas total soil C and N concentrations of more recalcitrant fractions were positively related to gross N mineralization. Our study suggests that changes in belowground N‐cycling can be better predicted by simultaneously addressing how plant C:N ratios and root mass affect the composition and distribution of different SOM pools in N‐limited grassland systems.
Effect of Grape Seed Extracts on the Physicochemical and Sensory Properties of Corn Chips during Storage
Authors: Rababah Taha M. , Yücel Sevil , Ereifej Khalil I. , Alhamad Mohammad N. , Al‐Mahasneh Majdi A. , Yang Wade , Muhammad Al–u'datt H. , Ismaeal Khalid
Published: November 2010

This study evaluated the effectiveness of grape seed extracts (GSE) on lipid oxidation of corn chips stored for 90 days in comparison to tert‐butylhydroxytoluene (BHT). Proximate chemical analysis results showed that corn chips contained low moisture contents (less than 2%) and also that no significant differences were found in the dry matter values in ash, fat, protein, and fiber. Antioxidant activity of the GSE measured by an oxidative stability instrument ranged from 1.6 to 9.3 h of induction time, while BHT prevented oxidation by 18.8 h. GSE (800 ppm) increased the redness and decreased the brightness and yellowness of the corn chip samples, whereas no significant differences were observed for other concentrations of the GSE compared to the control. The peroxide values (PV) for the control and the lower concentration (200 ppm) of GSE increased from 4.5 to 32.7 mequiv/kg, and from 4.4 to18.7 mequiv/kg, respectively, while no increase in PV was found for the higher level (400 and 800 ppm) of GSE or BHT. These changes were observed after 90 days of storage. Descriptive and consumer results showed that the control and the low concentration of GSE were associated with an increase in rancidity and the appearance of off‐flavor, while no noticeable increase in either rancidity or off‐flavor was observed when using a higher concentration of GSE or BHT. GSE has great potential for use as a natural antioxidant to preserve the extruded corn chips.
Is Routine Histology Necessary in Circumcision?
Authors: McSorley A. , Nigam A.K.
Published: November 2010

Objective:

A retrospective audit of all patients circumcised during a calendar year (01/01/2008–31/12/2008) to determine whether routine specimen histology in circumcision is necessary.

Patients and methods:

The records of 114 patients (51 adult, 63 paediatric) circumcised in a year were retrospectively reviewed. Indications for circumcision were phimosis, recurrent balanoposthitis and suspected squamous cell carcinoma (SCC). Data were collected on the following areas: patient age, indication, pre-operative and histological diagnosis. Pre-operative diagnosis was compared with histological diagnosis to determine whether histology differed from the clinical impression.

Results:

A total of 31 patients had histologically confirmed lichen sclerosus (22 adult, 9 paediatric). Of these patients, 26 (84%) were predicted pre-operatively. There were three adult patients diagnosed with squamous cell carcinoma and all of these cases were predicted pre-operatively. There were no cases of SCC or lichen sclerosus diagnosed in patients clinically thought to have normal foreskin.

Conclusions:

The data indicate that routine histology is not necessary in adult and paediatric circumcision and should be reserved for patients with suspected lichen sclerosus or carcinoma.
POLICE BAIL WITHOUT CHARGE: THE HUMAN RIGHTS IMPLICATIONS
Authors: Cape Ed , Edwards Richard A.
Published: November 2010

Whilst the power of the police to release a person on bail prior to trial has existed for centuries, the power to release on bail a person suspected of but not charged with a criminal offence has been available to the police only since 1925. The power to attach conditions to pre-charge bail is of very recent origin, having been introduced for the first time in 2003 but rapidly expanded since then. Whilst imposing restrictions on the liberty of a person should, constitutionally, be reserved to the judiciary, the fact that it was originally conceived, in part at least, as a mechanism for enhancing liberty reduced the constitutional tension created by allowing members of the executive such powers. However, the changing role of arrest in the investigation of crime and the granting of extensive powers to the police to impose bail conditions means that the police now have the ability to place controls on people not charged with a criminal offence for extended periods of time. It is argued here that this is in breach of the right to liberty under Article 5 of the European Convention on Human Rights and, in practice, may also breach other Convention rights.
Living Truthfully: David Mamet's Practical Aesthetics
Authors: Collard Christophe
Published: November 2010

Although better known as a playwright and film-maker, David Mamet started his artistic career as a teacher of acting. In this essay Christophe Collard contextualizes the influences, evaluates the implications, and criticizes some of the implementations of his ‘Practical Aesthetics’ by bridging the divide between Mamet's aesthetic theory and its concretization in practice. Often mistaken for a disingenuous appropriation of the so-called ‘Stanislavsky System’, Mamet's derived ‘Method’ arguably is more functional than original. Nevertheless, Collard argues that his confusion between various interpretations of these precepts is deliberate and serves primarily a reflexive purpose, as illustrated here with an analysis of Mamet's rehearsal play A Life in the Theatre. Christophe Collard works as a research fellow in American theatre and drama at the Vrije Universiteit Brussel (Free University of Brussels), where he recently completed a doctorate about media and genre crossings in the work of David Mamet.
Reducing the computational cost of automatic calibration through model preemption
Authors: Razavi Saman , Tolson Bryan A. , Matott L. Shawn , Thomson Neil R. , MacLean Angela , Seglenieks Frank R.
Published: November 2010

Computational budget is frequently a limiting factor in both uncertainty‐based (e.g., through generalized likelihood uncertainty estimation (GLUE)) and optimization‐based (e.g., through least squares minimization) calibration of computationally intensive environmental simulation models. This study introduces and formalizes the concept of simulation model preemption during automatic calibration. The proposed “model preemption” method terminates a simulation model early to save computational budget if it is recognized through intermediate simulation model results that a given solution (model parameter set) is so poor that it will not benefit the search strategy. The methodology proposed here is referred to as deterministic model preemption because it leads to exactly the same calibration result as when deterministic preemption is not applied. As such, deterministic preemption–enabled calibration algorithms which make no approximations to the mathematical simulation model are a simple alternative to the increasingly common and more complex approach of metamodeling for computationally constrained model calibration. Despite its simplicity, the deterministic model preemption concept is a promising concept that has yet to be formalized in the environmental simulation model automatic calibration literature. The model preemption concept can be applied to a subset of uncertainty‐based and optimization‐based automatic calibration strategies using a variety of different objective functions. Results across multiple calibration case studies demonstrate actual preemption computational savings ranging from 14% to 49%, 34% to 59%, and 52% to 96% for the dynamically dimensioned search, particle swarm optimization, and GLUE automatic calibration methods, respectively.