bluuebunny/crossref_metadata_2025 huggingface dataset:
Parainfluenza virus‐3‐induced cytopathic effects on lung tissue and bronchoalveolar lavage fluid in a bone marrow transplant recipient
Authors: Pokharel Saraswati , Merickel C. Ryan , Alatassi Houda
Published: April 2013

Parainfluenza virus type 3(PIV‐3) commonly causes respiratory tract infections in hematopoietic stem cell transplant (HSCT) patients. The majority of PIV‐3 infections develop in patients who have undergone stem cell transplantation from unrelated donors. From these patients, bronchoalveolar lavage (BAL) fluid and/or lung biopsies are often collected and sent for evaluation of infectious processes. However, cytologic findings associated with a PIV‐3 infection in BAL fluid have not been reported in the literature. We describe BAL cytology and lung biopsy findings in a patient who received an HSCT from a related donor and subsequently developed a PIV‐3 infection. This patient was noted to have scattered reticular‐nodular opacities in both lungs on computed tomogram scan and underwent transbronchial biopsy and BAL of the left lower lobe. Examination of the BAL fluid revealed scattered multinucleated giant cells intermixed with inflammatory cells. The lung biopsy showed organizing pneumonia associated with several multinucleated respiratory epithelial cells containing rare intracytoplasmic inclusions. Gram, periodic acid Schiff, Gomori methenamine silver, and acid fast stains on the biopsy specimen failed to reveal microorganisms. A sample of the BAL fluid sent for respiratory viral culture grew PIV‐3. These findings suggest that the presence of giant cells in transplant patients with organizing pneumonia should raise suspicion of a PIV‐3 infection. Diagn. Cytopathol. 2014;42:521–524. © 2013 Wiley Periodicals, Inc.
Can we improve the positive predictive value of atypical glandular cells not otherwise specified?
Authors: Mariani Rachel , Grace Chelestes , Hughes Kathryn , Dietrich Ruth M. , Cabay Robert J. , David Odile
Published: April 2013

The category of atypical glandular cells (AGC) in gynecologic cytopathology presents many well‐documented diagnostic challenges, the most significant related to high interobserver variability, low specificity, and low positive predictive value. The current Bethesda System provides criteria for specific glandular categories including atypical endocervical cells not otherwise specified (AEC‐NOS), AEC favor neoplastic, and atypical endometrial cells. The Bethesda System does, however, acknowledge that in some cases AGC cannot be categorized based upon cell of origin, in which case the generic term “atypical glandular cells” (AGC) may be used. We sought to determine whether further refinement of the current Bethesda System criteria for AEC‐NOS might increase the positive predictive value of the general category of AGC. Fifty‐three cases of AGC with documented histologic follow‐up at the University of Illinois Hospital were reviewed. The cases were graded on each of the eight specific cytologic criteria recommended by the current Bethesda System for AEC‐NOS using a study‐developed three‐tier grading system. Multiple regression analysis showed that four of the cytologic criteria in combination—nuclear enlargement, nuclear pleomorphism, increased nuclear‐to‐cytoplasmic (N/C) ratio, and cells occurring in sheets and strips with cell crowding and nuclear overlap—discriminated positive histologic outcome slightly better than any single criterion alone. In addition, simple logistic regression analysis showed nuclear enlargement to have a marginal independent association with positive histologic outcome (P = 0.0566). No other criterion was independently associated with outcome. Ancillary methods seem indicated to increase the positive predictive value of AGC at this time. Diagn. Cytopathol. 2014;42:200–204. © 2013 Wiley Periodicals, Inc.
Mitigation measures for fish habitat improvement in Alpine rivers affected by hydropower operations
Authors: Person Emilie , Bieri Martin , Peter Armin , Schleiss Anton J.
Published: April 2013

In mountainous areas, high‐head‐storage hydropower plants produce peak load energy. The resulting unsteady water release to rivers, called hydropeaking, alters the natural flow regime. Mitigating the adverse impacts of hydropeaking on aquatic ecosystems has become a crucial step in recent water policies.

We developed a novel economic‐ecological diagnostic and intervention method to assess hydropeaking mitigation measures for fish habitat improvement. This method was applied to an Alpine river downstream of a complex storage hydropower scheme. The approach comprises (1) a hydropower operation model of flow regime generation and cost estimates for different mitigation measures, (2) a two‐dimensional hydrodynamic model to simulate the flow conditions in representative river reaches and (3) a dynamic fish habitat simulation tool to assess the sub‐daily changes in habitat conditions of three brown trout (Salmo trutta fario) life stages (adult, spawning and young‐of‐the‐year). Simulations showed that operational measures such as limiting maximum turbine discharge, increasing residual flow and limiting drawdown range incur high costs in relation to their ecological effectiveness. Compensation basins and powerhouse outflow deviation achieved the best cost–benefit ratio. Hydropeaking impact was strongly dependent on river morphology. Monotonous river reaches exhibited low habitat suitability for peak discharge, whereas a braided morphology provided high in‐stream structure and thus suitable habitat for unsteady flow conditions.

The interdisciplinary approach to economic and habitat rating informs decision makers regarding the effectiveness of measures implemented to mitigate the environmental impacts associated with fluctuating hydropower operations. Copyright © 2013 John Wiley & Sons, Ltd.
C–H Metalation Reaction of Diarylamine and Carbazole by Alkylaluminum Complexes at the Heteroatom‐Bridged Dimeric Aluminum Core
Authors: Yamamoto Koji , Shibata Yu , Kashiwa Yuki , Kondo Ai , Tsurugi Hayato , Mashima Kazushi
Published: April 2013

Direct metalation reactions of diphenylamine and carbazole by using an amido‐bridged dinuclear Al2 complex proceeded across two aluminum atoms while maintaining the dinuclear structure. In contrast, an aryloxido‐bridged dinuclear aluminium complex was inert to the C–H metalation reaction. Such different reactivity of the alkylaluminum complexes with an [Al2O2] or [Al2N2] core was attributed to the space available for the secondary amine substrates to approach the Al–Me moiety: the flexibility provided by the bridging amido ligand forms an Al2N2 core with both a planar and butterfly shape, which creates enough space for the Al–Me moiety to activate the amines.
Effect of support rotation on triple friction pendulum bearing behavior
Authors: Becker Tracy C. , Mahin Stephen A.
Published: April 2013

This paper presents numerical modeling techniques to capture the behavior of the triple friction pendulum (TFP) isolation bearing when rotation is permitted about the horizontal axes of the top and bottom components. This paper builds on a previous model for the TFP bearing presented by the authors that is based on the kinematic and constitutive relationships of the individual components of the TFP bearing. The effect of rotation on cyclic bearing behavior and seismic system behavior are investigated numerically for two cases: constant support rotation and variable support rotation. It is found that constant support rotations should be limited in amplitude to ensure standard TFP bearing behavior. Results suggest that flexible supports may not have a large effect on global structure performance as long as typical deformation limits for the supporting members are met. In cases of both constant support rotations and flexible supports, the hardening stages of TFP bearing behavior are diminished. Copyright © 2013 John Wiley & Sons, Ltd.
Pollution as a threat factor to urban food security in metropolitan Kano, Nigeria
Authors: Dawaki Mansur U. , Dikko Abubakar U. , Noma Samaila S. , Aliyu Umar A.
Published: April 2013

This study evaluated the potentials of pollution due to urban agriculture to pose risk to food security in Kano, Nigeria. Two sites irrigated with industrial and domestic wastewaters at Challawa and Jakara, respectively, were sampled for soil, water, and lettuce (Lactuca sativa L.). The samples were analyzed for Pb, Cd, Cr, and Cu being metals which when present in food may pose human health hazard. The values were compared with samples from a control site not associated with wastewater at Watari. The sites were each segmented into up, mid, and downstream sectors. Results showed that the two sites and the control were contaminated with Cu (pollution indexes [PI] = 0.14, 0.16, and 0.14, respectively). Domestic wastewater site was slightly polluted (PI = 1.09) while industrial wastewater site and the control were contaminated (PI = 0.8 and 0.54, respectively) with Pb. The two sites were excessively polluted with Cd and slightly polluted with Cr. The control was contaminated with both (PI = 0.74 and 0.06 for Cd and Cr, respectively). Metal levels in the waters of the sites and the control were higher than the recommended threshold for irrigation water. There was significant positive correlation between Pb, Cr, and Cd in water and in soil; while Cu in soil and in water negatively correlated. There was high metal transfer from soil to plants at the domestic wastewater site (Metal transfer factor Pb = 1.602, Cr = 1.126, and Cu = 1.834). Plants' accumulated concentrations were also high at the domestic wastewater site (Pb = 26.21 mg/kg, Cd = 1.03 mg/kg, Cr = 28.63, and Cu = 2.66 mg/kg). The plants' metal concentrations at the domestic wastewater site exceeded the allowable limits in vegetables. The human ingestion risk was in the order of Jakara > Challawa > Watari.
Legacy impacts of all‐time anthropogenic emissions on the global mercury cycle
Authors: Amos Helen M. , Jacob Daniel J. , Streets David G. , Sunderland Elsie M.
Published: April 2013

Elevated mercury (Hg) in marine and terrestrial ecosystems is a global health concern because of the formation of toxic methylmercury. Humans have emitted Hg to the atmosphere for millennia, and this Hg has deposited and accumulated into ecosystems globally. Here we present a global biogeochemical model with fully coupled atmospheric, terrestrial, and oceanic Hg reservoirs to better understand human influence on Hg cycling and timescales for responses. We drive the model with a historical inventory of anthropogenic emissions from 2000 BC to present. Results show that anthropogenic perturbations introduced to surface reservoirs (atmosphere, ocean, or terrestrial) accumulate and persist in the subsurface ocean for decades to centuries. The simulated present‐day atmosphere is enriched by a factor of 2.6 relative to 1840 levels, consistent with sediment archives, and by a factor of 7.5 relative to natural levels (2000 BC). Legacy anthropogenic Hg re‐emitted from surface reservoirs accounts for 60% of present‐day atmospheric deposition, compared to 27% from primary anthropogenic emissions, and 13% from natural sources. We find that only 17% of the present‐day Hg in the surface ocean is natural and that half of its anthropogenic enrichment originates from pre‐1950 emissions. Although Asia is presently the dominant contributor to primary anthropogenic emissions, only 17% of the surface ocean reservoir is of Asian anthropogenic origin, as compared to 30% of North American and European origin. The accumulated burden of legacy anthropogenic Hg means that future deposition will increase even if primary anthropogenic emissions are held constant. Aggressive global Hg emission reductions will be necessary just to maintain oceanic Hg concentrations at present levels.
210Pb and 137Cs in margin sediments of the Arctic Ocean: Controls on boundary scavenging
Authors: Kuzyk Zou Zou A. , Gobeil Charles , Macdonald Robie W.
Published: April 2013

210Pb and 137Cs were measured in 25 sediment cores collected during the International Polar Year from a transect spanning the North American Arctic margin, from the North Bering Sea to Baffin Bay/Davis Strait. Profiles and inventories of the radioisotopes were used to determine sediment mixing and accumulation at each site and to assess the intensity of scavenging and burial. Sediment accumulation rates derived from 210Pb and validated using 137Cs are between ≤0.04 and 0.23 g cm−2 yr−1. 210Pb cannot be used to derive sedimentation rates for vigorously biomixed sediments from the North Bering‐Chukchi shelf. Elevated 137Cs activities and inventories in recently deposited sediments imply delayed inputs of particle‐associated 137Cs to the sediments, likely transported from the watershed to the coast and subsequently redistributed to shelf/slope sediments. Inventories of 210Pbex in all cores meet or exceed the estimated supply of 210Pbex from atmospheric deposition and decay of 226Ra in the water column. This implies that in contrast to the deep Arctic Ocean basin, there is a sufficient supply of suspended particulates along the North American Arctic margin to scavenge the supply of 210Pbex. 210Pbex inventories in sediments are up to 21‐fold greater than the in situ supply at some sites. Large inventories of 210Pbex in sediments along the North Bering‐Chukchi shelf result primarily from focusing, while those along the north Chukchi slope (Barrow Canyon) and in Baffin Bay/Davis Strait reflect strong boundary scavenging, likely supported by lateral exchanges with deep/interior Atlantic‐origin waters.
Sex differences in the effect of four second‐generation antipsychotics on QTc interval in patients with schizophrenia
Authors: Suzuki Yutaro , Sugai Takuro , Fukui Naoki , Watanabe Junzo , Ono Shin , Tsuneyama Nobuto , Saito Mami , Someya Toshiyuki
Published: April 2013

Objective

We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia.

Methods

Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula.

Results

The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second‐generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007).

Conclusion

To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval. Copyright © 2013 John Wiley & Sons, Ltd.
Development of Infant Positive Emotionality: The Contribution of Maternal Characteristics and Effects on Subsequent Parenting
Authors: Bridgett David J. , Laake Lauren M. , Gartstein Maria A. , Dorn Danielle
Published: April 2013

The current study examined the influence of maternal characteristics on the development of infant smiling and laughter, a marker of early positive emotionality (PE) and how maternal characteristics and the development of infant PE contributed to subsequent maternal parenting. One hundred fifty‐nine mothers with 4‐month‐old infants participated. Maternal characteristics were assessed 4 months postpartum, infant smiling and laughter were assessed at 4, 6, 8, 10 and 12 months postpartum, and maternal negative parenting was assessed 18 months postpartum. Latent growth modelling was used to test hypotheses regarding the influence of maternal characteristics on the development of infant smiling and laughter, and the contribution of infant smiling and laughter to later maternal parenting. Higher maternal effortful control and PE predicted more initial infant smiling and laughter, whereas more maternal parenting stress predicted lower slopes of infant smiling and laughter. More frequent/intense symptoms of maternal depression predicted higher scores on a measure of negative parenting, whereas higher maternal PE and better effortful control predicted lower negative parenting scores. After accounting for maternal characteristics, higher intercepts and slopes of infant smiling and laughter predicted fewer reports of negative parenting practices. The implications of these findings for future research are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Mass Informatics: From Mass Spectrometry Peaks to Biological Pathways
Authors: Askenazi Manor , Linial Michal
Published: April 2013

In this review we will introduce the field of mass informatics, a branch of bioinformatics concerned with the analysis of data from mass spectrometry. As we shall demonstrate, this short definition hides a surprisingly diverse and challenging topic, driven by the remarkable versatility of the mass spectrometer. We first introduce the essential properties of the mass spectrum and highlight its key differences from the more common data types in high‐throughput bioinformatics (sequence, microarray and image data). We then explore the breadth of biochemistry accessible through the associated algorithmic challenge of spectral identification. Finally, we demonstrate instances where data‐mining techniques can be applied to large‐scale spectral libraries, thereby extracting latent biological insight.
Circadian events in human diseases and in cytochrome P450‐related drug metabolism and therapy
Authors: Košir Rok , Španinger Klemen , Rozman Damjana
Published: April 2013

The biochemical basis of the mammalian circadian clock can be described by transcriptional–translational feedback loops with a period of about 24 h. Crucial endogenous factors are under circadian control (i.e., body temperature, blood pressure, hormone secretion and metabolite levels). Also, drug metabolism, including phases I–III and the drug‐responsive nuclear receptors, is controlled by the clock. Disturbances in circadian rhythm in humans can lead to pathologies, which is exemplified by increased cancer risk in long‐term shift workers. On the other hand, best tolerability of drugs with minimum side effects can be achieved if the timing of drug treatment is synchronized with the patients' individual clock. The aim of this review is to underline the importance of accepting the individuals' endogenous clock which can contribute to personalized, patient‐friendly optimization of drug therapies. © 2013 IUBMB Life, 65(6)487:–496, 2013.
Homer Proteins in Ca2+ Entry
Authors: Jardin Isaac , López José J. , Berna‐Erro Alejandro , Salido Ginés M. , Rosado Juan A.
Published: April 2013

The Homer family of proteins consists of three adaptor proteins, Homer1, Homer2 and Homer3, each with various isoforms. Homer1 family presents an EVH1 domain, a coiled coil domain and two leucine zipper domains. Homer proteins regulate a number of Ca2+‐handling proteins, including transient receptor potential channels and other Ca2+‐permeable channels, ionotropic and metabotropic glutamate receptors, shank scaffolding proteins or endoplasmic reticulum Ca2+ release channels. This review article focuses on the association of Homer 1 proteins with Ca2+‐handling proteins and their role on intracellular Ca2+‐homeostasis. © 2013 IUBMB Life, 65(6):–, 2013
Osteogenic differentiation of human bone marrow mesenchymal stem cells in hydrogel containing nacre powder
Authors: Flausse Alicia , Henrionnet Christel , Dossot Manuel , Dumas Dominique , Hupont Sébastien , Pinzano Astrid , Mainard Didier , Galois Laurent , Magdalou Jacques , Lopez Evelyne , Gillet Pierre , Rousseau Marthe
Published: April 2013

Nacre (or mother of pearl) can facilitate bone cell differentiation and can speed up their mineralization. Here we report on the capability of nacre to induce differentiation of human bone marrow mesenchymal stem cells (hBM‐MSCs) and the production of extracellular matrix. hBM‐MSCs were encapsulated in an alginate hydrogel containing different concentrations of powdered nacre and cultured in the same environment until Day 28. Analysis of osteogenic gene expression, histochemistry, second harmonic generation (SHG) microscopy, and Raman scattering spectroscopy were used to characterize the synthesis of the extracellular matrix. In the presence of nacre powder, a significant increase in matrix synthesis from D21 in comparison with pure alginate was observed. Histochemistry revealed the formation of a new tissue composed of collagen fibers in the presence of nacre (immunostaining and SHG), and hydroxyapatite crystals (Raman) in the alginate beads. These results suggest that nacre is efficient in hBM‐MSCs differentiation, extracellular matrix production and mineralization in alginate 3D biomaterials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3211–3218, 2013.
Overexpressed nuclear BAG‐1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin
Authors: Ni Wenkai , Chen Buyou , Zhou Guoxiong , Lu Cuihua , Xiao Mingbing , Guan Chengqi , Zhang Yixing , He Song , Shen Aiguo , Ni Runzhou
Published: April 2013

Bcl‐2‐associated athanogene‐1 (BAG‐1) is a multifunctional anti‐apoptotic protein which regulates an array of cellular processes, including apoptosis, signaling, proliferation, transcription, and cell motility and has been reported to be over‐expressed in a number of human malignancies. To investigate the possible involvement of BAG‐1 in tumorigenesis of hepatocellular carcinoma (HCC), we performed Western blot analysis in eight paired samples of HCC and adjacent peritumoral tissues and immunohistochemistry in 65 paraffin sections of HCC, which both showed an enhanced expression of nuclear BAG‐1 isoform in HCC tissues. Statistical analysis confirmed that overexpression of nuclear BAG‐1 in HCC tissues was significantly associated with histological grading (P < 0.001), poor prognosis (P = 0.004), and was found to be an independent prognostic indicator for HCC (P = 0.023). We also noted that BAG‐1 was overexpressed in four HCC cell lines compared with a normal hepatocyte cell line, and BAG‐1 overexpression increased resistance of HCC cells to doxorubicin, a common chemotherapeutic agent for HCC. Furthermore, we observed that knock down of BAG‐1 with siRNA in HepG2 cells increased the chemosensitivity of cells, a process mediated through inhibition of doxorubicin‐triggered NF‐κB activation; and knock down of BAG‐1 suppressed proliferation and cell cycle transition of HepG2 cells. In consequence, our results for the first time indicated that BAG‐1 was dysregulated in HCC and suppression of BAG‐1 expression which resulted in inhibiting of NF‐κB signaling might be developed into a new strategy in HCC therapy. J. Cell. Biochem. 114: 2120–2130, 2013. © 2013 Wiley Periodicals, Inc.
The impact of penicillin skin testing on clinical practice and antimicrobial stewardship
Authors: Rimawi Ramzy H. , Cook Paul P. , Gooch Michael , Kabchi Badih , Ashraf Muhammad S. , Rimawi Bassam H. , Gebregziabher Mulugeta , Siraj Dawd S.
Published: April 2013

BACKGROUND

Penicillin skin testing (PST) is a simple and reliable way of diagnosing penicillin allergy. After being off the market for 4 years, penicilloyl‐polylysine was reintroduced in 2009 as PRE‐PEN. We describe the negative predictive value (NPV) of PST and the impact on antibiotic selection in a sample of hospitalized patients with a reported history of penicillin allergy.

METHODS

We introduced a quality improvement process at our 861‐bed tertiary care hospital that used PST to guide antibiotic usage in patients with a history consistent with an immunoglobulin E (IgE)‐mediated reaction to penicillin. Subjects with a negative PST were then transitioned to a β‐lactam agent for the remainder of their therapy. NPV of skin testing was established at 24‐hour follow‐up. We are reporting the result of 146 patients tested between March 2012 and July 2012.

RESULTS

A total of 146 patients with a history of penicillin allergy and negative PST were treated with β‐lactam antibiotics. Of these, only 1 subject experienced an allergic reaction to the PST. The remaining 145 patients tolerated a full course of β‐lactam therapy without an allergic response, giving the PST a 100% NPV. We estimated that PST‐guided antibiotic alteration for these patients resulted in an estimated annual savings of $82,000.

CONCLUSION

Patients with a history of penicillin allergy who have a negative PST result are at a low risk of developing an immediate‐type hypersensitivity reaction to β‐lactam antibiotics. The increased use of PST may help improve antibiotic stewardship in the hospital setting. Journal of Hospital Medicine 2013;8:341–345. © 2013 Society of Hospital Medicine
A typology for intraseasonal oscillations
Authors: Pohl Benjamin , Camberlin Pierre
Published: April 2013

This descriptive study attempts to document the diversity of intraseasonal oscillations (ISO) propagative and spatial patterns, as inferred from outgoing longwave radiation (OLR) variability. Main ISO events over the Indo‐Pacific Warm Pool are first extracted using a local mode analysis (LMA) applied on the 20–120‐d filtered OLR on the 1979–2008 period. One hundred and sixty‐nine individual ISO are detected. Their propagative patterns are then objectively regrouped into a few types using a hierarchical agglomerative classification. Three alternative partitionings are retained, depending on the level of details expected from the typology. ISO events first regroup naturally into two well‐separated classes, identifying boreal summer northward‐propagating events and boreal winter eastward‐propagating ones. Retaining a larger number of classes shows that the diversity of the ISO patterns is primarily modulated by the seasonal cycle, with the most pronounced convective perturbations roughly located at the latitude of the Inter‐tropical Convergence Zone in the tropics. When a sufficient number of types are considered, one can obtain several types of ISO events for a given season. Apart from seasonality, the variability in the ISO appears to be related to surface conditions, such as sea surface temperature. Analysis of the differences between the types suggests that the ‘canonical’ ISO, often considered in the literature, is actually rather rare and moderately representative of the propagative events taken individually.
A novel l‐isoleucine‐4′‐dioxygenase and l‐isoleucine dihydroxylation cascade in Pantoea ananatis
Authors: Smirnov Sergey V. , Sokolov Pavel M. , Kotlyarova Veronika A. , Samsonova Natalya N. , Kodera Tomohiro , Sugiyama Masakazu , Torii Takayoshi , Hibi Makoto , Shimizu Sakayu , Yokozeki Kenzo , Ogawa Jun
Published: April 2013

A unique operon structure has been identified in the genomes of several plant‐ and insect‐associated bacteria. The distinguishing feature of this operon is the presence of tandem hilA and hilB genes encoding dioxygenases belonging to the PF13640 and PF10014 (BsmA) Pfam families, respectively. The genes encoding HilA and HilB from Pantoea ananatis AJ13355 were cloned and expressed in Escherichia coli. The culturing of E. coli cells expressing hilA (E. coli‐HilA) or both hilA and hilB (E. coli‐HilAB) in the presence of l‐isoleucine resulted in the conversion of l‐isoleucine into two novel biogenic compounds: l‐4′‐isoleucine and l‐4,4′‐dihydroxyisoleucine, respectively. In parallel, two novel enzymatic activities were detected in the crude cell lysates of the E. coli‐HilA and E. coli‐HilAB strains: l‐isoleucine, 2‐oxoglutarate: oxygen oxidoreductase (4′‐hydroxylating) (HilA) and l‐4′‐hydroxyisoleucine, 2‐oxoglutarate: oxygen oxidoreductase (4‐hydroxylating) (HilB), respectively. Two hypotheses regarding the physiological significance of C‐4(4′)‐hydroxylation of l‐isoleucine in bacteria are also discussed. According to first hypothesis, the l‐isoleucine dihydroxylation cascade is involved in synthesis of dipeptide antibiotic in P. ananatis. Another unifying hypothesis is that the C‐4(4′)‐hydroxylation of l‐isoleucine in bacteria could result in the synthesis of signal molecules belonging to two classes: 2(5H)‐furanones and analogs of N‐acyl homoserine lactone.
A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3
Authors: Guimarães Rachel P. , D'Abreu Anelyssa , Yasuda Clarissa L. , França Marcondes C. , Silva Beatriz H. B. , Cappabianco Fabio A.M. , Bergo Felipe P.G. , Lopes‐Cendes Iscia T. , Cendes Fernando
Published: April 2013

Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically‐confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high‐resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3‐T scanner. We used Tract‐Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel‐based morphometry of infratentorial structures. T2‐relaxometry of cerebellum was performed with in‐house–developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel‐based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2‐relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients. © 2013 Movement Disorder Society
Numerical approaches to thermally coupled perfect plasticity
Authors: Bartels Sören , Roubíček Tomáš
Published: April 2013

The partial differential equations describing viscoelastic solids in Kelvin–Voigt rheology at small strains exhibiting also stress‐driven Prandtl‐Reuss perfect plasticity are considered and are coupled with a heat‐transfer equation through the dissipative heat produced by viscoplastic effects and through thermal expansion and corresponding adiabatic effects. Numerical discretization of the resulting thermodynamically consistent model is proposed by implicit time discretization, suitable regularization, and finite elements in space. Numerical stability is shown and computational simulations are reported to illustrate the practical performance of the method. In a quasistatic case, convergence is proved by careful successive limit passage. © 2013 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013
An efficient ETD method for pricing American options under stochastic volatility with nonsmooth payoffs
Authors: Yousuf M. , Khaliq A.Q.M.
Published: April 2013

Based on Cox and Matthews Exponential Time Differencing (ETD) approach, a fourth–order strongly–stable method having real distinct poles is developed and applied to solve American options under stochastic volatility with nonsmooth payoffs. A computationally efficient version of the method is constructed using partial fraction splitting technique. This approach requires to solve several backward Euler‐type linear systems at each time step. Numerical experiments are presented to demonstrate the computational efficiency, accuracy, and reliability of the method. © 2013 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013
Role of Interleukin‐1 Inhibitors in the Management of Gout
Authors: Tran Tran H. , Pham Jacqueline T. , Shafeeq Hira , Manigault Kendra R. , Arya Vibhuti
Published: April 2013

Interleukin‐1 (IL‐1) inhibitors potentially have a role as antiinflammatory agents in refractory gout or for patients who are unable to tolerate conventional therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or glucocorticoids, for acute attacks. Additionally, IL‐1 inhibitors may also help patients with polyarticular and tophaceous gout by making them less vulnerable to breakthrough attacks during initiation of chronic urate‐lowering treatment, the mainstay of gout therapy. Because evidence highlights the role of proinflammatory cytokine IL‐1 in the inflammation process during an acute gouty attack, IL‐1 inhibitors are used to modulate the pathogenesis of a variety of autoinflammatory diseases, providing support for its potential role in the inflammatory process of gout. After NSAIDs, colchicine, and steroids, IL‐1 inhibitors are beneficial as fourth‐line therapy for acute gout attacks due to their high cost and limited clinical experience. The IL‐1 inhibitors used in gout are anakinra, canakinumab, and rilonacept. Based on published evidence, anakinra has limited support in the form of anecdotal case reports to justify its use for treating gout. Canakinumab's toxic profile in clinical trials precludes its use in treating patients for gout, and rilonacept shows promise with a few well‐designed studies to support its use in gout patients initiating urate‐lowering treatment. When combined with current traditional therapies, these newer agents present clinicians and patients with more potential treatment options in the difficult‐to‐treat gout population.
Validation of a Novel Approach for Dose Individualization in Pharmacotherapy Using Gabapentin in a Proof of Principles Study
Authors: Blau Gary E. , Orcun Seza , Laínez José M. , Reklaitis Gintaras V. , Suvannasankha Attaya , Fausel Chris , Anaissie Elias J.
Published: April 2013

Study Objective

To demonstrate the premise of individualized dosing charts (IDCs) as a clinical‐bedside decision‐support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic (PK) behavior of the patient, to calculate the optimal sampling schedule (OSS), which minimizes the number of blood samples per patient. The approach is illustrated with available PK data for gabapentin.

Design

Retrospective proof of principles study using gabapentin PK data from a published clinical trial.

Patients

Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36 hours after administration of a single dose of gabapentin 400 mg, and plasma concentrations were determined at 14 time points.

Measurements and Main Results

When the PK profiles were different between subjects, the IDCs are dramatically different from each other and from the IDC for an “average” patient representing the patient population. The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range. An optimal sampling methodology based on the assumption‐free Bayesian approach is used to distinguish the PK profile of an individual patient from the patient population. In the case of gabapentin, only two optimally selected test blood samples, at 1.5 and 6 hours after administration of a single doses, were necessary. The average sensitivity and the average specificity of the OSS was 99% and 96%, respectively.

Conclusion

IDCs display the risk of a patient violating the target concentration range for any dosage regimen. They can be used as a clinical‐bedside decision‐support tool in a patient–physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance. By using the assumption‐free Bayesian approach and the OSS, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity. Prospective studies are being planned to validate the encouraging results. This approach can be extended to any drug if PK data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention.
Efficacy of a First‐Grade Responsiveness‐to‐Intervention Prevention Model for Struggling Readers
Authors: Gilbert Jennifer K. , Compton Donald L. , Fuchs Douglas , Fuchs Lynn S. , Bouton Bobette , Barquero Laura A. , Cho Eunsoo
Published: April 2013

This randomized control trial examined the efficacy of a multitiered supplemental tutoring program within a first‐grade responsiveness‐to‐intervention prevention model. Struggling first‐grade readers (n = 649) were screened and progress monitored at the start of the school year. Those identified as unresponsive to general education Tier 1 (n = 212) were randomly assigned to receive Tier 2 small‐group supplemental tutoring (n = 134) or to continue in Tier 1 (n = 78). Progress‐monitoring data were used to identify nonresponders to Tier 2 (n = 45), who were then randomly assigned to more Tier 2 tutoring (n = 21) or one‐on‐one Tier 3 tutoring (n = 24). Tutoring in Tier 3 was the same as in Tier 2 except for the delivery format and frequency of instruction. Results from a latent change analysis indicated nonresponders to Tier 1 who received supplemental tutoring made significantly higher word reading gains compared with controls who received reading instruction only in Tier 1 (effect size = 0.19). However, no differences were detected between nonresponders to Tier 2 who were assigned to Tier 3 versus more Tier 2. This suggests more frequent 1:1 delivery of a Tier 2 standard tutoring program may be insufficient for intensifying intervention at Tier 3. Although supplemental tutoring was effective in bolstering reading performance of Tier 1 nonresponders, only 40% of all Tier 2 students and 53% of Tier 2 responders were reading in the normal range by grade 3. Results challenge the preventive intent of short‐term, standard protocol, multitiered supplemental tutoring models.
A comparison of Bayesian hierarchical modeling with group‐based exposure assessment in occupational epidemiology
Authors: Xing Li , Burstyn Igor , Richardson David B. , Gustafson Paul
Published: April 2013

We build a Bayesian hierarchical model for relating disease to a potentially harmful exposure, by using data from studies in occupational epidemiology, and compare our method with the traditional group‐based exposure assessment method through simulation studies, a real data application, and theoretical calculation. We focus on cohort studies where a logistic disease model is appropriate and where group means can be treated as fixed effects. The results show a variety of advantages of the fully Bayesian approach and provide recommendations on situations where the traditional group‐based exposure assessment method may not be suitable to use. Copyright © 2013 John Wiley & Sons, Ltd.
A note on the evaluation of novel biomarkers: do not rely on integrated discrimination improvement and net reclassification index
Authors: Hilden Jørgen , Gerds Thomas A.
Published: April 2013

The ‘integrated discrimination improvement’ (IDI) and the ‘net reclassification index’ (NRI) are statistics proposed as measures of the incremental prognostic impact that a new biomarker will have when added to an existing prediction model for a binary outcome. By design, both measures were meant to be intuitively appropriate, and the IDI and NRI formulae do look intuitively plausible. Both have become increasingly popular. We shall argue, however, that their use is not always safe. If IDI and NRI are used to measure gain in prediction performance, then poorly calibrated models may appear advantageous, and in a simulation study, even the model that actually generates the data (and hence is the best possible model) can be improved on without adding measured information. We illustrate these shortcomings in actual cancer data as well as by Monte Carlo simulations. In these examples, we contrast IDI and NRI with the area under ROC and the Brier score. Unlike IDI and NRI, these traditional measures have the characteristic that prognostic performance cannot be accidentally or deliberately inflated. Copyright © 2013 John Wiley & Sons, Ltd.
Advanced Methods for Assessing the Melt‐Specific Creep Rupture Behavior of P91 Steel for Power Plants
Authors: Frolova Olga , Maile Karl
Published: April 2013

In systems that operate in the creep range, such as steam power plants, the life‐time assessment of highly loaded high‐temperature components poses an important task. The main problem in this context is the reliable detection and evaluation of specific material characteristics. First of all there are the strength properties that are the result of the multidimensional interdependences between the individual elements of the chemical composition, the heat treatment parameters and the production conditions. With the current state of knowledge and technology, melt‐specific creep rupture strength can only be determined experimentally. Modeling with neural network techniques therefore represents an alternative to analytical methods since multidimensional relationships can be taken into account. This work aims to identify and assess the potential for the application of artificial neural networks to the determination of relevant properties of selected high‐temperature resistant steels. The emphasis of the study is to determinate the position of the specific melts in the scatter band of creep rupture data as well as to assess/predict time‐to‐rupture for the given steel under consideration of all relevant technical data available and to find out an optimum of the creep rupture strength.
Ermüdungsverhalten kranspezifischer Kerbdetails – Untersuchungen im Kurzzeitfestigkeitsbereich
Authors: Herion Stefan , Ummenhofer Thomas , Hrabowski Jennifer
Published: April 2013

Die im Folgenden vorgestellten Ergebnisse experimenteller Untersuchungen sind Teil des nunmehr vierten Forschungsvorhabens, FOSTA P778 [1], das aus der Arbeitsgruppe “Krankerbdetails“ hervorgegangen ist. Die Arbeiten sind eine Fortführung der Projekte P293, P512 und LIFTHIGH sowie REFRESH ([2] bis [5]), die ausgewählte Details im Lastwechselbereich von ca. 40000 bis 5 Millionen Lastwechseln behandelten. Um die Wirtschaftlichkeit von Krankonstruktionen weiter erhöhen zu können, müssen auch stärkere Hubvorgänge nachweisbar sein, die noch höhere Beanspruchungen in der Konstruktion hervorrufen und damit zu geringeren Lebensdauern bzw. Lastwechselzahlen als in den bisherigen Untersuchungen führen. Dementsprechend wurde für die beiden typischen Kerbdetails – aufgeschweißte Längssteife und – querbelastete Stumpfnaht der Lastwechselbereich zwischen 10000 und 40000 Lastwechseln (Low Cycle Fatigue LCF) untersucht. Damit soll geklärt werden, ob und bis zu welcher Beanspruchung bzw. Lastwechselzahl die schon vorhandenen Wöhlerlinien linear in diesen LCF‐Bereich verlängert werden können. Untersuchungen wurden an Details aus den hochfesten Stahlsorten S690QL und S960QL sowie für die Stumpfnahtverbindungen zusätzlich aus S1100QL und S1300QL durchgeführt.

Fatigue behaviour of crane specific notch details – Investigations on low cycle fatigue. The following experimental investigations are part of the forth research project (FOSTA P778 [1]) which is initiated by the working group “Krankerbdetails” (working group on notch details in crane structures). They are an extension of the work carried out in projects P293, P512, LIFTHIGH and REFRESH ([2] to [5]) on specific notch details in the fatigue range of 40.000 to 5 million load cycles. To raise the economic efficiency, crane structures need to be designed also for higher loads respectively for a fatigue range below the load cycles investigated so far. Therefore, the two common notch details – longitudinal stiffener and – transverse loaded butt weld have been investigated in the fatigue range between 10.000 and 40.000 load cycles (LCF low cycle fatigue). For this reason, it will be determined if it is possible to extend the existing Wöhler lines into this range, and if so, up to which load this can be done. These investigations are carried out for high strength steels S690QL and S960QL, butt welded joints of steel grades S1100QL and S1300QL are additionally investigated.
Disease-Causing Mitochondrial Heteroplasmy Segregated Within Induced Pluripotent Stem Cell Clones Derived from a Patient with MELAS
Authors: Folmes Clifford D.L. , Martinez-Fernandez Almudena , Perales-Clemente Ester , Li Xing , Mcdonald Amber , Oglesbee Devin , Hrstka Sybil C. , Perez-Terzic Carmen , Terzic Andre , Nelson Timothy J.
Published: April 2013

Mitochondrial diseases display pathological phenotypes according to the mixture of mutant versus wild-type mitochondrial DNA (mtDNA), known as heteroplasmy. We herein examined the impact of nuclear reprogramming and clonal isolation of induced pluripotent stem cells (iPSC) on mitochondrial heteroplasmy. Patient-derived dermal fibroblasts with a prototypical mitochondrial deficiency diagnosed as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) demonstrated mitochondrial dysfunction with reduced oxidative reserve due to heteroplasmy at position G13513A in the ND5 subunit of complex I. Bioengineered iPSC clones acquired pluripotency with multilineage differentiation capacity and demonstrated reduction in mitochondrial density and oxygen consumption distinguishing them from the somatic source. Consistent with the cellular mosaicism of the original patient-derived fibroblasts, the MELAS-iPSC clones contained a similar range of mtDNA heteroplasmy of the disease-causing mutation with identical profiles in the remaining mtDNA. High-heteroplasmy iPSC clones were used to demonstrate that extended stem cell passaging was sufficient to purge mutant mtDNA, resulting in isogenic iPSC subclones with various degrees of disease-causing genotypes. On comparative differentiation of iPSC clones, improved cardiogenic yield was associated with iPSC clones containing lower heteroplasmy compared with isogenic clones with high heteroplasmy. Thus, mtDNA heteroplasmic segregation within patient-derived stem cell lines enables direct comparison of genotype/phenotype relationships in progenitor cells and lineage-restricted progeny, and indicates that cell fate decisions are regulated as a function of mtDNA mutation load. The novel nuclear reprogramming-based model system introduces a disease-in-a-dish tool to examine the impact of mutant genotypes for MELAS patients in bioengineered tissues and a cellular probe for molecular features of individual mitochondrial diseases.