bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of catalytic activity and structure of selenocysteine‐containing hGSTZ1c‐1c based on site‐directed mutagenesis and computational analysis
Authors: Yu Yang , Song Jian , Song Yang , Guo Xiao , Han Yiding , Wei Jingyan
Published: January 2013

Human glutathione transferase zeta 1c‐1c (hGSTZ1c‐1c) is one of the glutathione transferase isoenzymes and considered to be a protein scaffold to imitate glutathione peroxidase (GPX) owing to the natural binding site of glutathione (GSH). In this report, several residues near GSH were mutated to selenocysteine (Sec) or cysteine (Cys) residues and the impacts of the substitutions on different activities were discussed. Mutations of Ser‐14 or/and Ser‐15 to Cys or Sec residues resulted in dramatic loss of catalytic activity of hGSTZ1c‐1c with chlorofluoroacetic acid as substrate, which indicated the importance of the hydroxyl groups in Ser‐14 and Ser‐15. And subsequent study by molecular modeling suggested that Ser‐15 was probably involved in catalysis, while Ser‐14 may play a crucial role in binding and orientation of GSH and possibly had a synergistic effect with Ser‐15 in catalysis. On the contrary, the result of converting Cys‐16 to Ser indicated its trivial role in catalysis. The investigations of the selenocysteine‐containing hGSTZ1c‐1c (seleno‐hGSTZ1c‐1c) and the mutant S17C implied that the substitutions of multi‐Sec for Cys residues at position 16, 137, and 205 could lead to subtle change in the structure of the protein molecule and concomitant change in catalytic activity as a direct result. This finding provides overwhelming evidence that the protein scaffold containing fewer cysteines should be chosen for imitating GPX using cysteine auxotrophic strain system to avoid unexpected structural changes. © 2013 IUBMB Life, 65(2)163–170, 2013
Goal-directed treatment of osteoporosis
Authors: Cummings Steven R , Cosman Felicia , Eastell Richard , Reid Ian R , Mehta Mona , Lewiecki E Michael
Published: January 2013

Drug treatment for osteoporosis typically begins with an oral bisphosphonate, regardless of initial bone mineral density (BMD) or fracture risk, and decisions to continue or change treatment are often based on evidence of response to treatment based on changes in BMD, bone turnover markers, and occurrence of fractures. This pattern differs from preventive therapy for other conditions, such as hypertension, where treatment is based on achieving a goal. We propose that a goal be established to guide treatments to reduce fracture risk. The goal could be a certain risk of fracture or level of BMD. Goal-directed treatment would individualize the initial choice of treatment based on the probability that alternatives would achieve the patient's goal. In contrast to changing treatments based on years of use or failure to respond, the patient's BMD and risk would be reassessed periodically and decisions to stop or change treatment would be based on achieving or maximizing the chance of reaching an acceptable level of fracture risk or BMD. The acceptance of goal-directed treatment and application to practice will require a consensus on a number of issues about goals along with models of fracture risk while on treatment and probabilities of achieving goals. The result could be more rational and effective use of the expanding array of treatments for osteoporosis. © 2013 American Society for Bone and Mineral Research.
Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese-American and white women
Authors: Walker Marcella D , Liu X Sherry , Zhou Bin , Agarwal Shivani , Liu George , McMahon Donald J , Bilezikian John P , Guo X Edward
Published: January 2013

Compared to white women, premenopausal Chinese-American women have more plate-like trabecular (Tb) bone. It is unclear whether these findings are relevant to postmenopausal women and if there are racial differences in the deterioration of bone microarchitecture with aging. We applied individual trabecula segmentation and finite element analysis to high-resolution peripheral quantitative computed tomography images in premenopausal and postmenopausal Chinese-American and white women to quantify within-race age-related differences in Tb plate-versus-rod microarchitecture and bone stiffness. Race–menopause status interactions were assessed. Comparisons between races within menopause status were adjusted for age, height and weight. Comparisons between premenopausal and postmenopausal women were adjusted for height and weight. Adjusted analyses at the radius indicated that premenopausal Chinese-Americans had a higher plate bone volume fraction (pBV/TV), Tb plate-to-rod ratio (P-R ratio), and greater plate-plate junction densities (P-P Junc.D) versus white women (all p < 0.01), resulting in 27% higher Tb stiffness (p < 0.05). Greater cortical thickness and density (Ct.Th and Dcort) and more Tb plates led to 19% greater whole bone stiffness (p < 0.05). Postmenopausal Chinese-Americans had similar pBV/TV and P-P Junc.D, yet a higher P-R ratio versus white women. Postmenopausal Chinese-American versus white women had greater Ct.Th, Dcort, and relatively intact Tb plates, resulting in similar Tb stiffness but 12% greater whole bone stiffness (p < 0.05). In both races, Ct.Th and Dcort were lower in postmenopausal versus premenopausal women and there were no differences between races. Tb plate parameters were also lower in postmenopausal versus premenopausal women, but age-related differences in pBV/TV, P-R ratio, and P-P Junc D were greater (p < 0.05) in Chinese-Americans versus white women. There are advantages in cortical and Tb bone in premenopausal Chinese-American women. Within-race cross-sectional differences between premenopausal and postmenopausal women suggest greater loss of plate-like Tb bone with aging in Chinese-Americans, though thicker cortices and more plate-like Tb bone persists.
Intrapancreatic gastric duplication cyst—a rare cause of chronic abdominal pain in childhood
Authors: Lee Chiew Leng , Daud Che Zubaidah binti Che , Ismail Rohazly binti
Published: January 2013

We report a rare case of a gastric duplication cyst in the tail of the pancreas in a child presenting with chronic abdominal pain which was cured by excision of the cyst and adjacent pancreas. This case report highlights the role of sonography as an excellent imaging tool for depiction of the bowel wall and, hence, in aiding diagnosis even when clinical picture and findings of other modalities are nonspecific. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:42–44, 2014
INVESTING AND REINVESTING IN SOCIAL CAPITAL: THE SPILL‐OVER EFFECTS OF SOCIAL CAPITAL IN SELF‐HELP GROUPS
Authors: Knowles Gordon , Luke Belinda , Barraket Jo
Published: January 2013

Social capital is considered fundamental to microfinance programmes adopting a self‐help group (SHG) model and in facilitating community development. This report examines the collective benefits of social capital facilitated through SHGs within the broader (local) community. Findings highlight that social capital initially developed within SHGs resulted in a number of collaborative community projects. Although these projects developed tangible community assets, they also created social value through the underlying processes of joint activity and collaboration. This ‘spill‐over’ of social capital reflects a re‐investment of social capital generated from microfinance programmes, with important implications for collective poverty alleviation initiatives. Copyright © 2013 John Wiley & Sons, Ltd.
Orthogonal organic and aqueous‐based washes of tissue sections to enhance protein sensitivity by MALDI imaging mass spectrometry
Authors: Thomas Aurélien , Patterson Nathan Heath , Laveaux Charbonneau Jade , Chaurand Pierre
Published: January 2013

Imaging mass spectrometry (IMS) is an emergent and innovative approach for measuring the composition, abundance and regioselectivity of molecules within an investigated area of fixed dimension. Although providing unprecedented molecular information compared with conventional MS techniques, enhancement of protein signature by IMS is still necessary and challenging. This paper demonstrates the combination of conventional organic washes with an optimized aqueous‐based buffer for tissue section preparation before matrix‐assisted laser desorption/ionization (MALDI) IMS of proteins.

Based on a 500 mM ammonium formate in water–acetonitrile (9:1; v/v, 0.1% trifluororacetic acid, 0.1% Triton) solution, this buffer wash has shown to significantly enhance protein signature by profiling and IMS (~fourfold) when used after organic washes (70% EtOH followed by 90% EtOH), improving the quality and number of ion images obtained from mouse kidney and a 14‐day mouse fetus whole‐body tissue sections, while maintaining a similar reproducibility with conventional tissue rinsing. Even if some protein losses were observed, the data mining has demonstrated that it was primarily low abundant signals and that the number of new peaks found is greater with the described procedure. The proposed buffer has thus demonstrated to be of high efficiency for tissue section preparation providing novel and complementary information for direct on‐tissue MALDI analysis compared with solely conventional organic rinsing. Copyright © 2013 John Wiley & Sons, Ltd.
Development of an analytical method for yam saponins using HPLC with pulsed amperometric detection at different column temperatures
Authors: Kwon Ha‐Jeong , Choi Seung‐Hee , Yoo Chang‐Seon , Choi Hwa‐Young , Lee Soo‐Eon , Park Yong‐Duk
Published: January 2013

Yam saponins (dioscin, gracillin, protodioscin, and protogracillin) were analyzed with three different C18 columns at incremental column temperatures from 15 to 45°C to investigate the effect of temperature on the retention and resolution of yam saponins. At low temperature, yam saponins showed decreased retention times and improved resolutions in the C18 columns. In the Kinetex C18 column at 15°C, the four saponins achieved baseline separation (Rs > 1.5) within 30 min. Pulsed amperometric detection was used to identify saponins with high sensitivity. The limits of detection and quantification of saponins were 0.11–0.31 and 0.33–0.95 ng, respectively. The correlation coefficients ranged 0.9986–1.0000. Intra‐ and inter‐day precisions were <4.2% of retention times and <9.5% of the calculated contents. Average recoveries ranged from 92.18 to 105.98%. Saponin contents in Dioscorea nipponica tubers and commercial yam foods were determined without sample purification or concentration. Among the ten commercial yam foods investigated, only three showed significant saponin contents.
Ionic liquid‐based microwave‐assisted surfactant‐improved dispersive liquid–liquid microextraction and derivatization of aminoglycosides in milk samples
Authors: Xu Xu , Liu Zhuang , Zhao Xin , Su Rui , Zhang Yupu , Shi Jiayuan , Zhao Yajing , Wu Lijie , Ma Qiang , Zhou Xin , Zhang Hanqi , Wang Ziming
Published: January 2013

A green and simple method, ionic liquid‐based microwave‐assisted surfactant‐improved dispersive liquid–liquid microextraction and derivatization was developed for the determination of aminoglycosides in milk samples. Nonionic surfactant Triton X‐100 and ionic liquid 1‐hexyl‐3‐methylimidazolium hexafluorophosphate were used as the disperser and extraction solvent, respectively. Extraction, preconcentration, and derivatization of aminoglycosides were carried out in a single step. Several experimental parameters, including type and volume of extraction solvent, type and concentration of surfactant, microwave power and irradiation time, concentration of derivatization reagent, and pH value and volume of buffer were investigated and optimized. Under the optimum experimental conditions, the linearities for determining the analytes were in the range 0.4–10.0 ng/mL for tobramycin, 1.0–25.0 ng/mL for neomycin, and 2.0–50.0 ng/mL for gentamicin, with the correlation coefficients ranging from 0.9991 to 0.9998. The LODs for the analytes were between 0.11 and 0.50 ng/mL. The present method was applied to the analysis of different milk samples, and the recoveries of aminoglycosides obtained were in the range 96.4–105.4% with the RSDs lower than 5.5%. The results showed that the present method was a rapid, convenient, and environmentally friendly method for the determination of aminoglycosides in milk samples.
Novel linear and step‐gradient counter‐current chromatography for bio‐guided isolation and purification of cytotoxic podophyllotoxins from Dysosma versipellis (Hance)
Authors: Yang Zhi , Liu Xiaoman , Wang Kuiwu , Cao Xiaoji , Wu Shihua
Published: January 2013

Dysosma versipellis (Hance) is a famous traditional Chinese medicine for the treatment of snakebite, weakness, condyloma accuminata, lymphadenopathy, and tumors for thousands of years. In this work, four podophyllotoxin‐like lignans including 4′‐demethylpodophyllotoxin (1), α‐peltatin (2), podophyllotoxin (3), β‐peltatin (4) as major cytotoxic principles of D. versipellis were successfully isolated and purified by several novel linear and step gradient counter‐current chromatography methods using the systems of hexane/ethyl acetate/methanol/water (4:6:3:7 and 4:6:4:6, v/v/v/v). Compared with isocratic elution, linear and step‐gradient elution can provide better resolution and save more time for the separation of photophyllotoxin and its congeners. Their cytotoxicities were further evaluated and their structures were validated by high‐resolution electrospray TOF MS and nuclear magnetic resonance spectra. All components showed potent anticancer activity against human hepatoma cells HepG2.
Selective separation and enrichment of glibenclamide in health foods using surface molecularly imprinted polymers prepared via dendritic grafting of magnetic nanoparticles
Authors: Wang Ruoyu , Wang Yang , Xue Cheng , Wen Tingting , Wu Jinhua , Hong Junli , Zhou Xuemin
Published: January 2013

In this paper, the novel surface molecularly imprinted polymers based on dendritic‐grafting magnetic nanoparticles were developed to enrich and separate glibenclamide in health foods. The density functional theory method was used to give theoretical directions to the synthesis of molecularly imprinted polymers. The polymers were prepared by using magnetic nanoparticles as supporting materials, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross‐linker. The characteristics of magnetic nanoparticles and polymers were measured by transmission electron microscope and SEM, respectively. The enriching ability of molecularly imprinted polymers was measured by Freundlich Isotherm. The molecularly imprinted polymers were used as dispersive SPE materials to enrich, separate, and detect glibenclamide in health foods by HPLC. The average recoveries of glibenclamide in spiked health foods were 81.46–93.53% with the RSD < 4.07%.
Detection of paranasal ectopic adrenocorticotropic hormone‐secreting pituitary adenoma by Ga‐68‐DOTANOC positron‐emission tomography–computed tomography
Authors: Veit Johannes A. , Boehm Bernhard , Luster Markus , Scheuerle Angelika , Rotter Nicole , Rettinger Gerhard , Scheithauer Marc
Published: January 2013

Ectopic adrenocorticotropic hormone (ACTH)‐secreting tumors account for approximately 10% of Cushing's syndrome (CS). We present an extremely rare case of a patient with CS caused by an ectopic ACTH‐secreting pituitary adenoma (EAPA) of the ethmoid sinus. The tumor was identified by positron‐emission tomography–computed tomography (PET/CT) using the somatostatin receptor analogue Ga‐68‐DOTANOC. Transnasal endoscopic resection was performed and the patient showed significant clinical improvement with normalization of the endocrine pituitary axis. Immunostaining showed a somatostatin receptor 2 and 5‐positive ACTH‐producing adenoma. In patients with ectopic ACTH secretion, Ga‐68‐DOTANOC‐PET/CT may play an important role in the localization of EAPA. Transnasal endoscopic resection is the therapy of choice.
From the operating room to the courtroom
Authors: Svider Peter F. , Keeley Brieze R. , Zumba Osvaldo , Mauro Andrew C. , Setzen Michael , Eloy Jean Anderson
Published: January 2013

Objectives/Hypothesis

Malpractice litigation has increased in recent decades, contributing to higher health‐care costs. Characterization of complications leading to litigation is of special interest to practitioners of facial plastic surgery procedures because of the higher proportion of elective cases relative to other subspecialties. In this analysis, we comprehensively examine malpractice litigation in facial plastic surgery procedures and characterize factors important in determining legal responsibility, as this information may be of great interest and use to practitioners in several specialties.

Study Design

Retrospective analysis.

Methods

The Westlaw legal database was examined for court records pertaining to facial plastic surgery procedures. The term “medical malpractice” was searched in combination with numerous procedures obtained from the American Academy of Facial Plastic and Reconstructive Surgery website.

Results

Of the 88 cases included, 62.5% were decided in the physician's favor, 9.1% were resolved with an out‐of‐court settlement, and 28.4% ended in a jury awarding damages for malpractice. The mean settlement was $577,437 and mean jury award was $352,341. The most litigated procedures were blepharoplasties and rhinoplasties. Alleged lack of informed consent was noted in 38.6% of cases; other common complaints were excessive scarring/disfigurement, functional considerations, and postoperative pain.

Conclusions

This analysis characterized factors in determining legal responsibility in facial plastic surgery cases. Several factors were identified as potential targets for minimizing liability. Informed consent was the most reported entity in these malpractice suits. This finding emphasizes the importance of open communication between physicians and their patients regarding expectations as well as documentation of specific risks, benefits, and alternatives. Laryngoscope, 123:1849–1853, 2013
A new strategy for edible vegetable oil production
Authors: Turkay Selma , Gurbuz Hale
Published: January 2013

Consumer preference has changed rapidly from refined oils towards virgin oils in recent years. Virgin oils are edible vegetable oils obtained by mechanical procedures, such as expelling or pressing from oil seeds, and are consumed without being refined. Such oils are considered as specialty oils, because only small and medium size mills produce them in small amounts for gourmet and health markets from very different oil seeds. To meet consumer demands, bulk production of virgin oils should be accomplished from commodity oil seeds, such as rapeseeds, at reasonable prices. For this purpose two challenges have to be solved: production of high quality oil seeds, and production of virgin oils with a higher oil yield. In this article we focus on the pre‐treatment processes of oil seeds to increase oil yield, and describe a new alternative process, ultrasound‐assisted alcoholic treatment of oil seeds.
Successful Application of an Ionic Liquid Carrying the Fluoride Counter‐ion in Biomacromolecular Chemistry: Microwave‐Assisted Acylation of Cellulose in the Presence of 1‐Allyl‐3‐methylimidazolium Fluoride/DMSO Mixtures
Authors: Casarano Romeu , El Seoud Omar A.
Published: January 2013

The use of ionic liquids with fluoride anion (IL‐F) is challenging because of side reactions. Neat 1‐allyl‐3‐methylimidazolium fluoride (AlMeImF) is used as a solvent in microwave‐assisted acylation of cellulose. The results are disappointing due to side reactions in the IL proper, and F–‐mediated hydrolysis of the produced ester. A dramatic improvement is observed, when AlMeImF/DMSO mixture is employed. The results are comparable to those obtained when pure 1‐allyl‐3‐methylimidazolium chloride is employed. FTIR spectroscopy shows that dissolving a carboxylic acid anhydride in IL‐F leads to the formation of acyl fluoride. Thus ILs are far from being “spectator” solvents. The new approach (use of IL‐F/DMSO) is attractive because of its efficiency, low cost, and applicability to the derivatization of any polymer.

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A Serum‐Tolerant Hydroxyl‐Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA
Authors: Dong Xuan , Lin Lin , Chen Jie , Guo Zhaopei , Tian Huayu , Li Yuce , Wei Yen , Chen Xuesi
Published: January 2013

The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris(hydroxymethyl) acrylamidomethane via the Michael addition. These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges. The PTns show lower cytotoxicity and better serum‐resistant capacity than PEI25k. Specially, the transfection efficiency of PT26/DNA is 29‐fold higher than that of PEI25k in HeLa cells in serum‐containing medium. The PTn/siRNA complexes show superior knockdown effect in CT26 cells in serum‐containing medium. In addition, flow cytometry analysis shows that the PTns can efficiently mediate the entry of nucleic acids into the cell. Thus, PTns are potentially applicable as non‐viral carriers of nucleic acids and warrant further development for use in gene therapy.

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A high resolution NV/TVD Hermite polynomial upwind scheme for convection‐dominated problems
Authors: Gao Wei , Li Hong , Liu Yang
Published: January 2013

A high‐order convection‐bounded scheme is constructed by combining the total variational diminishing constraint and convection boundedness criterion condition in the normalized variable formulation. It employs the Hermite polynomial interpolation to design its characteristic line in the normalized variable diagram. Numerical results of the convection‐dominated problems with smooth or discontinuous initial distributions demonstrate the present scheme possesses high resolution and good robustness. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of extensive surgery in multidisciplinary approach of pterygopalatine/infratemporal fossa soft tissue sarcoma
Authors: Minard‐Colin Véronique , Kolb Frédéric , Saint‐Rose Christian , Fayard Florence , Janot François , Rey Annie , Canale Sandra , Julieron Morbize , Corradini Nadège , Raquin Marie‐Anne , Habrand Jean‐Louis , Grill Jacques , George Bernard , Ba Huy Patrice Tran , Couloignier Vincent , Terrier‐Lacombe Marie‐José , Luboinski Bernard , Valteau‐Couanet Dominique , Oberlin Odile
Published: January 2013

Background

To evaluate a strategy whereby extensive surgery ± external radiotherapy (RT) could improve local control in pterygopalatine/infratemporal fossa (PIF) sarcoma.

Procedure

Forty‐one patients with a diagnosis of sarcoma involving the PIF and referred to our Institute from 1984 to 2009 were included in the analysis. Patients received multidrug chemotherapy and radiotherapy ± surgery, depending on the period of treatment.

Results

The median age at diagnosis was 7.6 years (range: 0.1–22 years). There were 36 RMS, 3 undifferentiated sarcoma and 2 other soft‐tissue sarcomas. Sixty‐eight percent of patients had meningeal risk factors at diagnosis. Local treatment consisted of RT alone in 19 patients, surgery in combination to RT in 19 patients and surgery alone in 3 patients. The local progression rate (LPR) at 5 years was 45% for the entire population, 59% for the 19 patients treated with RT alone and 34% for the 22 patients who had surgery as part of their treatment. All locoregional failures after extensive surgery occurred at the skull base and/or in leptomeningeal spaces.

Conclusions

Multidisciplinary approach including extensive surgery for PIF sarcoma is feasible and yields good local control with 15/22 patients in local complete remission. Future studies are warranted to confirm these promising results, to evaluate the possibility of avoiding RT or limiting the RT field, and to extend the indication for extensive surgery to other “worse” sites of PM sarcoma such as the paranasal sinuses. Pediatr Blood Cancer 2013; 60: 928–934. © 2013 Wiley Periodicals, Inc.
Prognostic factors and long‐term outcomes of nasopharyngeal carcinoma in children and adolescents
Authors: Hu Songliu , Xu Xiangying , Xu Jianyu , Xu Qingyong , Liu Shanshan
Published: January 2013

Background

Nasopharyngeal carcinoma (NPC) is a rare malignancy in children and adolescents, and the optimal treatment modality in youths has not been established. The aim of this study was to evaluate the long‐term treatment outcomes and complications associated with childhood and adolescent NPC.

Procedure

From January 1985 to December 2004, the records of 95 patients with NPC and younger than 20 years of age were reviewed. All of the records were confirmed based on pathology via biopsy. The radiation doses to the primary tumors ranged from 64 to 80 Gy. The radiation doses to the metastatic cervical lymph nodes ranged from 60 to 74 Gy. The fractionated doses ranged from 1.8 to 2.0 Gy at 5 fractions/week. A total of 36 patients received chemotherapy before radiotherapy.

Results

The 1‐, 3‐, 5‐, 10‐, and 15‐year overall survival (OS) rates were 92.6%, 63.2%, 54.7%, 46.8%, and 42.6%, respectively. The 1‐, 3‐, 5‐, 10‐, and 15‐year disease‐free survival (DFS) rates were 73.7%, 51.3%, 49.1%, 44.6%, and 42.6%, respectively. The clinical stage had a significant impact on OS (P = 0.007) and DFS (P = 0.012). Complete responders to therapy had superior OS (P < 0.001) and DFS (P < 0.001). Patients >12 years of age had better OS (P = 0.026) and DFS (P = 0.037).

Conclusions

Children and adolescents with advanced NPC had a relatively good rate of long‐term survival. However, 28% of the survivors had serious long‐term treatment‐related morbidities. In addition to clinical stage and complete response or partial response, age was an independent prognostic factor in pediatric and adolescent NPC. Pediatr Blood Cancer 2013; 60: 1122–1127. © 2012 Wiley Periodicals, Inc.
Magnesium homeostasis and hypomagnesemia in children with malignancy
Authors: Kaplinsky Chaim , Alon Uri S.
Published: January 2013

Hypomagnesemia is not uncommon among children with malignancies. It is especially seen in association with certain medications and can be further complicated by the presence of diarrhea and malnutrition. Severe hypomagnesemia may cause disturbances in the neuromuscular and cardiovascular systems. All patients with hypomagnesemia should be supplemented with the mineral, and urgent treatment is indicated when serum magnesium decreases below 1.0 mg/dl, a level under which symptoms may develop. This review addresses the essentials of magnesium physiology, and pathophysiology of hypomagnesemia, its etiologies, clinical manifestations and ways to treat it, with an emphasis on the child with hematologic/oncologic disorders. Pediatr Blood Cancer 2013; 60: 734–740. © 2013 Wiley Periodicals, Inc.
A proposed modification to Hy's law and Edish criteria in oncology clinical trials using aggregated historical data
Authors: Parks Daniel , Lin Xiwu , Painter Jeffery L. , Cheng Jie , Hunt Christine M. , Spraggs Colin F. , Nelson Jeanenne J. , Curtis Lloyd , Menius J. Alan , Lee Kwan R.
Published: January 2013

Purpose

Identifying drug‐induced liver injury is a critical task in drug development and postapproval real‐world care. Severe liver injury is identified by the liver chemistry threshold of alanine aminotransferase (ALT) >3× upper limit of normal (ULN) and bilirubin >2× ULN, termed Hy's law by the Food and Drug Administration. These thresholds require discontinuation of the causative drug and are seldom exceeded in most patient populations. However, because maintenance of therapy is critical in the treatment of advanced cancer, customized thresholds may be useful in oncology patient populations, particularly for those with baseline liver chemistries elevations.

Methods

Liver chemistry data from 31 aggregated oncology clinical trials were modeled through a truncated robust multivariate outlier detection (TRMOD) method to develop the decision boundary or threshold for examining liver injury in oncology clinical trials.

Results

The boundary of TRMOD identified outliers with an ALT limit 5.0× ULN and total bilirubin limit 2.7× ULN. In addition, TRMOD was applied to the aggregated oncology data to examine fold‐baseline ALT and total bilirubin, revealing limits of ALT 6.9× baseline and bilirubin 6.5× baseline. Similar ALT and bilirubin threshold limits were observed for oncology patients both with and without liver metastases.

Conclusions

These higher liver chemistry thresholds examining fold‐ULN and fold‐baseline data may be valuable in identifying potential severe liver injury and detecting liver safety signals of clinical concern in oncology clinical trials and postapproval settings while helping to avoid premature discontinuation of curative therapy. Copyright © 2013 John Wiley & Sons, Ltd.
Bold, smart, dangerous and evil: Perceived correlates of core psychopathic traits among jury panel members
Authors: Edens John F. , Clark John , Smith Shannon Toney , Cox Jennifer , Kelley Shannon E.
Published: January 2013

Relatively few studies have investigated how laypersons perceive psychopathy, what factors they believe to be commonly associated with this disorder, or what rater personality characteristics might predict perceived psychopathic traits of the target person. An ethnically diverse sample of 285 US community members attending jury duty reviewed a case vignette regarding a capital murder trial and then rated (1) their perceptions of the defendant's psychopathic characteristics loosely based on trait indicators from the Psychopathy Checklist‐Revised; (2) other characteristics of the defendant that might be associated with psychopathy (e.g. intelligence, violence potential); and (3) their own personality, using a very brief measure of Five Factor traits. Multivariate regression analyses indicated that participant ratings of psychopathy pertaining to the defendant were strongly associated with ratings on measures of his perceived boldness (i.e. social dominance and fearlessness), intelligence, violence potential, and perceptions that he was ‘evil’. Big Five personality characteristics of the layperson raters, however, were only modestly associated with their ratings of psychopathy for the defendant. We review these results in terms of the potential stigmatization of individuals labelled as ‘psychopaths’ in forensic settings. Copyright © 2013 John Wiley & Sons, Ltd.
Liquid ammonia treatment of (cationic) nanofibrillated cellulose/vermiculite composites
Authors: Thao Ho Thi Thu , Zimmermann Tanja , Caseri Walter Remo , Smith Paul
Published: January 2013

Liquid ammonia was used to treat films of nanofibrillated cellulose (NFC), trimethylammonium‐modified NFC (TMA‐NFC), and their composites with vermiculite. Crystal structure, mechanical properties, water vapor permeation and water vapor adsorption of the resulting materials were investigated. Upon treatment, the crystal structure of (TMA‐)NFC both in presence and absence of vermiculite changed from cellulose I to III. With the exception of TMA‐NFC/vermiculite composites, pronounced effects on the addressed mechanical properties arose after exposure of the materials to ammonia. Furthermore, treatment of composite films with ammonia led to a distinct decrease in water vapor permeation. Remarkably, TMA‐NFC/vermiculite composites films show the best water vapor barrier properties, highest tensile strength and highest elastic modulus after treatment with liquid ammonia. This is regarded to be at least partially a consequence of electrostatic attraction between the positively charged ammonium groups in TMA‐NFC and the anionic silicate layers of vermiculite. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Miscibility in crystalline/amorphous blends of poly(3‐hydroxybutyrate)/DGEBA
Authors: Silva Leonel , Tognana Sebastián , Salgueiro Walter
Published: January 2013

A differential scanning calorimetry (DSC) and small‐angle X‐ray scattering (SAXS) study of miscibility in blends of the semicrystalline polyester poly(3‐hydroxybutyrate) (PHB) and amorphous monomer epoxy DGEBA (diglycidyl ether of bisphenol A) was performed. Evidence of the miscibility of PHB/DGEBA in the molten state was found from a DSC study of the dependence of glass transition temperature (Tg) as a function of the blend composition and isothermal crystallization, analyzing the melting point (Tm) as a function of blend composition. A negative value of Flory–Huggins interaction parameter χPD was obtained. Furthermore, the lamellar crystallinity in the blend was studied by SAXS as a function of the PHB content. Evidence of the segregation of the amorphous material out of the lamellar structure was obtained. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Feasibility Study of Virtual Target Scoring Using High‐Speed Imaging Techniques
Authors: Biswal Tapan K. , Sarkar Sumit , Adhikary Munesh
Published: January 2013

Measurements of consistency and accuracy are standard techniques to assess the performance of a weapon in case of direct fire kill mechanism. It is often determined from the scoring pattern of a witnessing target erected at a known distance in an open range making use of an in‐line CCD camera with suitable long‐range optics or using an array of acoustic/optical sensors in the close vicinity of the target. In the case of indoor range, acoustic and optical sensors are used to determine the same preferably for small‐caliber ammunitions. However, all these indirect methods are subjected to the constraint of triangulation error. In case of high‐caliber ammunitions, especially fired from tank guns, witnessing targets and acoustics methods are used although it is time‐consuming and labor‐intensive in nature. To overcome these difficulties a virtual scoring method is proposed. Herein, a high‐speed video camera is used for in‐line image acquisition of the projectile at the desired distance using long‐range optics. The virtual target is defined making use of an optical detector placed at the target distance and under the trajectory, where a trigger is generated when the projectile passes over it. This hardware trigger is sent to the high‐speed video camera and then the spatial coordinates of the projectile in the virtual plane is determined off‐line making use of necessary image processing and image analysis. A feasibility study of this technique was performed in a scaled‐down model and laid down in greater details.
Expectations of Being Helped in Return for Helping – Citizens, the State and the Local Area
Authors: Purdam Kingsley , Tranmer Mark
Published: January 2013

Citizens are increasingly being encouraged to take on new voluntary roles and responsibilities, such as, for example, looking after their local area and being involved in decision making. This move towards responsible citizenship is linked to the changing role of government, and the scaling down of the public services provided by the post war welfare state in many Western democracies.

In order to develop our understanding of why certain people are more likely to help than others in different circumstances, we examine people's expectations of help in return for helping at the individual, local, and national level. Our analysis suggests that across Europe younger people compared with older people are more likely to expect help in return for helping. Men are more likely than women to expect help in return for helping. In terms of helping values and behaviour, people who see helping others as important and also those who report helping other people in practice are less likely to expect help in return. There are also considerable differences between countries in reported rates of expecting help in return for helping. The perceived local context of help is important, such that people are more likely to expect help in return for helping where their perception of people helping each other in the local area is low. Policies aimed at encouraging citizens to take on new responsibilities need to take account of how citizens view their reciprocal relationships with fellow citizens as well as the local context and the state infrastructure.

Copyright © 2013 John Wiley & Sons, Ltd.
Crystal structure and phase transition in the doped super‐ionic conductor bismuth vanadate Bi4(V,Fe)2O11 revealed by neutron diffraction
Authors: Golosovsky I. V. , Golubko N. V. , Mosunov A. V. , Politova E. D. , Murasheva V. V. , Fortalnova E. A. , Rusakov V. S. , André G. , Porcher F.
Published: January 2013

Bismuth vanadate Bi4V2O11−y doped with Fe was studied by neutron diffraction. It was shown that Fe substitutes V only partially and the redundant iron forms an impurity hematite phase. In the sample with nominal content Bi4(V0.96Fe0.04)2O11−y a new phase transition within the frame of the monoclinic structure with the appearing of inversion center was discovered in the temperature region 200–300 °C. This transition was also confirmed by DTA experiments. Slow stabilization of the crystal structure with stabilization times of the order of hours, accompanied by a decrease of the unit cell volume, was observed. At high level of Fe doping, in addition to the dominant tetragonal γ‐phase some amount of the nanosized monoclinic α‐phase was detected.
The cluster‐size dependence of self‐diffusion behavior: A single Re adatom on a hexahedral surface
Authors: Dai Xiongying , Hu Wangyu , Yang Jianyu
Published: January 2013

The self‐diffusion of a single Re adatom on the Re clusters with 967–8263 atoms is studied. The minimum‐energy diffusion paths and the corresponding energy barriers for adatom diffusion on the Re hexahedral structure clusters surfaces are determined through a combination of the quenched molecular dynamics (MD) and nudged elastic bands (NEB) methods. Within the studied cluster size range, the ES barriers for an adatom across the step from a (0001) facet to a neighboring ($1{\bar {1}}01$) facet are the same. This means that the ES barriers are independent of the size of the clusters, while, the ES barriers for an adatom across the step between two ($1{\bar {1}}01$) facet have some dependence on the number of the shell (k). The ES barriers of the clusters with k = even number is lower than that of the clusters with k = odd number. For the former, the ES barriers decrease with increasing cluster size.
Probing factors affecting the Raman modes and structural collapse of single‐walled carbon nanotubes under pressure
Authors: Yao Mingguang , Lu Shuangchen , Xiao Junping , Yao Zhen , Jiang Linhai , Cui Tian , Liu Bingbing
Published: January 2013

Raman spectra of single‐walled carbon nanotubes (SWNTs) with diameter distribution of 0.6–1.6 nm have been studied under high pressure. We focused on the dependence of radial R‐band frequency (associated with the radial breathing mode, RBM) on pressure, dωRBM/dP, and studied the effect of experimental factors on the structural changes of nanotubes under pressure. We found that the nanotube diameter and the pressure transmission medium (PTM) strongly affect the dωRBM/dP dependence of a nanotube in the experiments with PTMs, while the nanotube diameter and the intertube interactions between the tube walls play a dominant role on the upshift of RBMs for nanotubes without a PTM. These results are in line with the theoretical predictions that PTMs have a strong effect on the pressure‐induced shift in the R‐bands of SWNTs. In addition, we found that the collapse of nanotubes and their reversibility depend not only on diameter and pressure environment but also on the sample quality. This could explain that there have been different results reported by different groups even for nanotubes with the same diameter distribution.
A survey on mining multiple data sources
Authors: Ramkumar T. , Hariharan S. , Selvamuthukumaran S.
Published: January 2013

Advancements in computer and communication technologies demand new perceptions of distributed computing environments and development of distributed data sources for storing voluminous amount of data. In such circumstances, mining multiple data sources for extracting useful patterns of significance is being considered as a challenging task within the data mining community. The domain, multi‐database mining (MDM) is regarded as a promising research area as evidenced by numerous research attempts in the recent past. The methods exist for discovering knowledge from multiple data sources, they fall into two wide categories, namely (1) mono‐database mining and (2) local pattern analysis. The main intent of the survey is to explain the idea behind those approaches and consolidate the research contributions along with their significance and limitations.

This article is categorized under:

Fundamental Concepts of Data and Knowledge > Data Concepts

Fundamental Concepts of Data and Knowledge > Motivation and Emergence of Data Mining
Large‐scale data mining using genetics‐based machine learning
Authors: Bacardit Jaume , Llorà Xavier
Published: January 2013

In the last decade, genetics‐based machine learning methods have shown their competence in large‐scale data mining tasks because of the scalability capacity that these techniques have demonstrated. This capacity goes beyond the innate massive parallelism of evolutionary computation methods by the proposal of a variety of mechanisms specifically tailored for machine learning tasks, including knowledge representations that exploit regularities in the datasets, hardware accelerations or data‐intensive computing methods, among others. This paper reviews different classes of methods that alone or (in many cases) combined accelerate genetics‐based machine learning methods. © 2013 Wiley Periodicals, Inc.

This article is categorized under:

Technologies > Classification

Technologies > Computational Intelligence
Gain‐of‐function mutation in the KlPDR1 gene encoding multidrug resistance regulator in Kluyveromyces lactis
Authors: Balazfyova Zuzana , Hervay Nora Toth , Gbelska Yvetta
Published: January 2013

KlPdr1p is a single Kluyveromyces lactis homologue of Saccharomyces cerevisiae ScPdr1p/ScPdr3p, the main transcriptional regulators of genes involved in S. cerevisiae multidrug resistance. KlPDR1 deletion leads to a sharp increase in K. lactis drug susceptibility. The presence of putative PDRE and YRE regulatory elements in the KlPDR1 gene promoter suggests an autoregulation of its transcription as well as its control by KlYap1p, the transcription factor involved in oxidative stress response. In this study, one plasmid‐borne Klpdr1‐1 allele that led to amino acid substitution (L273P) in the KlPdr1p was isolated. Overexpression of the Klpdr1‐1 allele from a multicopy plasmid in the K. lactis wild‐type and Klpdr1Δ mutant strain increased the tolerance of transformants to oligomycin. The plasmid‐borne Klpdr1‐1 allele increased the activation of the ScPDR5 promoter and complemented the drug hypersensitivity of the S. cerevisiae pdr1Δ pdr3Δ mutant strain. The results indicate that L273P amino acid substitution is the result of a gain‐of‐function mutation in the KlPDR1 gene that confers KlPdr1p hyperactivity, as revealed by a high expression of the ABC transporter gene KlPDR5, leading to multidrug resistance and rhodamine 6G efflux out of the cells. Copyright © 2013 John Wiley & Sons, Ltd.
Intra‐arterial Allogeneic Mesenchymal Stem Cells for Critical Limb Ischemia are Safe and Efficacious: Report of a Phase I Study
Authors: Das Anjan Kumar , Abdullah Basri Johan Jeet Bin , Dhillon S. S. , Vijanari A. , Anoop C. H. , Gupta Pawan Kumar
Published: January 2013

Background

Critical limb ischemia (CLI) caused by peripheral arterial disease is associated with significant morbidity and mortality. This condition is associated with a 30 % amputation rate as well as mortality levels which might be as high as 25 %. There is no pharmacological therapy available, but several reports have suggested that mesenchymal stem cells (MSCs) may be a useful therapeutic option.

Methods

This study, done at a university hospital, evaluated 13 patients for a phase I trial to investigate the safety and efficacy of intra‐arterial MSCs in CLI patients. Eight patients with ten affected limbs were recruited for the study. As two patients (three limbs) died of ischemic cardiac events during the 6‐month follow‐up period, seven limbs were finally evaluated for the study.

Results

There was significant pain relief. Visual analog scale (VAS) scores decreased from 2.29 ± 0.29 to 0.5 ± 0.34 (p < 0.05), ankle brachial pressure index (ABPI) increased significantly from 0.56 ± 0.02 to 0.67 ± 0.021 (p < 0.01), and transcutaneous oxygen pressure (TcPO2) also increased significantly in the foot from 13.57 ± 3.63 to 38 ± 3.47. Similar improvement was seen in the leg as well as the thigh. There was 86 % limb salvage and six of seven ulcers showed complete or partial healing.

Conclusion

It was concluded that intra‐arterial MSCs could be safely administered to patients with CLI and was associated with significant therapeutic benefits.
Physically Consistent Responses of the Global Atmospheric Hydrological Cycle in Models and Observations
Authors: Allan Richard P. , Liu Chunlei , Zahn Matthias , Lavers David A. , Koukouvagias Evgenios , Bodas-Salcedo Alejandro
Published: January 2013

Robust and physically understandable responses of the global atmospheric water cycle to a warming climate are presented. By considering interannual responses to changes in surface temperature (T), observations and AMIP5 simulations agree on an increase in column integrated water vapor at the rate 7 %/K (in line with the Clausius–Clapeyron equation) and of precipitation at the rate 2–3 %/K (in line with energetic constraints). Using simple and complex climate models, we demonstrate that radiative forcing by greenhouse gases is currently suppressing global precipitation (P) at ∼−0.15 %/decade. Along with natural variability, this can explain why observed trends in global P over the period 1988−2008 are close to zero. Regional responses in the global water cycle are strongly constrained by changes in moisture fluxes. Model simulations show an increased moisture flux into the tropical wet region at 900 hPa and an enhanced outflow (of smaller magnitude) at around 600 hPa with warming. Moisture transport explains an increase in P in the wet tropical regions and small or negative changes in the dry regions of the subtropics in CMIP5 simulations of a warming climate. For AMIP5 simulations and satellite observations, the heaviest 5-day rainfall totals increase in intensity at ∼15 %/K over the ocean with reductions at all percentiles over land. The climate change response in CMIP5 simulations shows consistent increases in P over ocean and land for the highest intensities, close to the Clausius−Clapeyron scaling of 7 %/K, while P declines for the lowest percentiles, indicating that interannual variability over land may not be a good proxy for climate change. The local changes in precipitation and its extremes are highly dependent upon small shifts in the large-scale atmospheric circulation and regional feedbacks.