bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable presentations of TTR‐related familial amyloid polyneuropathy in seventeen patients
Authors: Cappellari Manuel , Cavallaro Tiziana , Ferrarini Moreno , Cabrini Ilaria , Taioli Federica , Ferrari Sergio , Merlini Giampaolo , Obici Laura , Briani Chiara , Fabrizi Gian Maria
Published: June 2011

Autosomal‐dominant transthyretin (TTR)‐related amyloidosis usually manifests in the second to fourth decade with a length‐dependent axonal neuropathy with prominent involvement of the small fibers and multi‐organ systemic failure. We retrospectively analyzed seventeen probands, including thirteen apparently isolated cases, carrying eight mutations of TTR gene (age of onset = 60.4 ± 13.5 years). Thirteen patients were initially un/misdiagnosed; interval from onset to definite diagnosis was 3.3 ± 2.3 years. Inaugural syndromes were a length‐dependent motor‐sensory neuropathy in seven cases, a sensory neuropathy in four, an isolated carpal tunnel syndrome in three, a pure dysautonomia in two, and a painful neuropathy in one. Atypical presentations included demyelinating nerve conduction changes with increased cerebrospinal fluid proteins resembling chronic inflammatory demyelinating polyradiculoneuropathy and a predominantly motor involvement resembling a motor neuron disorder. Misleading findings also included amyloid‐negative abdominal fat aspirate/biopsy, biclonal gammopathy, and hepatitis C virus (HCV) seropositivity. Sural nerve biopsy detected amyloid deposits in thirteen of fifteen patients, including one case with a previous negative biopsy. TTR‐immunohistochemistry was necessary to complete the diagnosis of primary amyloidosis light chain in a patient with biclonal gammopathy. A recurrent p.Phe64Leu mutation manifested in the seventh decade with painful motor‐sensory polyneuropathy, dysautonomia, bulbar palsies, and fasciculations. TTR should be tested in a wide clinical spectrum of cryptogenetic, progressive, and motor‐sensory neuropathies even manifesting with a very late onset.
Phenotype expression in women with CMT1X
Authors: Siskind Carly E. , Murphy Sinéad M. , Ovens Richard , Polke James , Reilly Mary M. , Shy Michael E.
Published: June 2011

Charcot‐Marie‐Tooth disease type 1X (CMT1X) is the second most common inherited peripheral neuropathy. Women with CMT1X typically have a less severe phenotype than men, perhaps because of X‐inactivation patterns. Our objective was to determine the phenotype of women with CMT1X and whether X‐inactivation patterns in white blood cells (WBCs) differ between females with CMT1X and controls. Thirty‐one women with CMT1X were evaluated using the CMT neuropathy score (CMTNS) and the CMT symptom score in cross‐sectional and longitudinal analyses. Lower scores correspond to less disability. WBCs were analyzed for X‐inactivation pattern by androgen receptor X‐inactivation assay in 14 patients and 23 controls. The 31 women's mean CMTNS was 8.35. Two‐thirds of the cohort had a mild CMTNS (mean 4.85) and one‐third had a moderate CMTNS (mean 14.73). Three patients had a CMTNS of 0. The pattern of X‐inactivation did not differ between the affected and control groups. Women with CMT1X presented with variable impairment independent of age, type of mutation, or location of mutation. No evidence supported the presence of a gap junction beta‐1 (GJB1) mutation affecting the pattern of X‐inactivation in blood. Further studies are planned to determine whether X‐inactivation is the mechanism for CMT1X females' variable phenotypes.
Novel treatment for immune neuropathies on the horizon
Authors: Hartung Hans‐Peter , Lehmann Helmar C. , Kieseier Bernd C. , Hughes Richard A. C.
Published: June 2011

Immune neuropathies represent a heterogeneous spectrum of acute and chronic peripheral nerve disorders of autoimmune origin. Despite the current available treatment options, immune neuropathies are still associated with severe neurological deficits and poor clinical prognosis. However, during the last years, significant advances have been made in unraveling some of the underlying pathomechanisms. The exploration of novel therapeutic approaches including monoclonal antibodies and oral immunosuppressants, known from other autoimmune disorders such as multiple sclerosis, suggests new approaches to treatment. Here, we review the available clinical data as well as the scientific rationale and expected benefits and risks for these strategies.
Anti‐inflammatory potential of allyl‐isothiocyanate – role of Nrf2, NF‐κB and microRNA‐155
Authors: Wagner Anika Eva , Boesch‐Saadatmandi Christine , Dose Janina , Schultheiss Gerhard , Rimbach Gerald
Published: June 2011

In this study, the underlying mechanisms of the potential anti‐inflammatory properties of allyl‐isothiocyanate (AITC) were analysed in vitro and in vivo. Murine RAW264.7 macrophages stimulated with lipopolysaccharide (LPS) were supplemented with increasing concentrations of AITC. In addition, C57BL/6 mice (n= 10 per group) were fed a pro‐inflammatory high‐fat diet and AITC was administered orally via gavage for 7 days. Biomarkers of inflammation were determined both in cultured cells and in mice. AITC significantly decreased tumour necrosis factor α mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro‐inflammatory markers including interleukin‐1β and inducible nitric oxide synthase were down‐regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF‐κB. Importantly, our data indicate that AITC significantly attenuated microRNA‐155 levels in LPS‐stimulated RAW264.7 macrophages in a dose‐dependent manner. The anti‐inflammatory effects of AITC were accompanied by an increase in Nrf2 nuclear translocation and consequently by an increase of mRNA and protein levels of the Nrf2 target gene heme‐oxygenase 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down‐regulating inflammation in LPS‐stimulated macrophages. A significant increase in nuclear Nrf2 and heme‐oxygenase 1 gene expression and only a moderate down‐regulation of interleukin‐1β and microRNA‐155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti‐inflammatory activity in cultured macrophages in vitro but has only little anti‐inflammatory activity in mice in vivo.
Detecting spatial patterns in species composition with multiple plot similarity coefficients and singularity measures
Authors: Jurasinski Gerald , Jentsch Anke , Retzer Vroni , Beierkuhnlein Carl
Published: June 2011

Recently, several multiple plot similarity indices have been presented that cure some of the problems associated with the approaches for the calculation of compositional similarity for groups of plots by averaging pairwise similarities. These new indices calculate the similarity between more than two plots whilst considering the species composition on all compared plots. The resulting similarity value is true for the whole group of plots considered (called neighborhood in the following). Here, we review the possibilities for multiple plot similarity calculation and additionally explore coefficients that examine multiple plot similarity between a reference plot (named focal plot in the following) and any number of surrounding plots. The latter represent measures of singularity. Further, we establish a framework for applying these two kinds of multiple plot measures to gridded data including an algorithm for testing the significance of calculated values against random expectations.

The capability of multiple plot measures for detecting species compositional gradients and local/regional hotspots within this framework is tested. For this purpose, several artificial data sets with known gradients in species composition (random, gradient, central hotspot, hotspot bottom right) are constructed on the basis of a real data set from a Tundra ecosystem in northern Sweden (Abisko). The coefficients that best reflect the positions of the plots on the realized gradients in species composition are considered as performing best with regard to pattern detection. The tested measures of multiple plot similarity and singularity produced considerably different results when applied to one real and 4 artificial data sets. The newly proposed symmetric singularity coefficient has the best overall performance which makes it suitable for local/regional hotspot detection and for incorporating local to regional similarity analyses in reserve selection procedures.
Energy, taxonomic aggregation, and the geography of ant abundance
Authors: Kaspari Michael , Weiser Michael D.
Published: June 2011

Ecological communities and their component populations vary geographically in abundance. Energy theory posits that abundance (the number of individuals area−1) should increase with the ratio of available energy (as net primary productivity, NPP) to individual energy use (i.e. metabolic rate). Most tests of energy theory evaluate the assumption that population abundance decreases as body mass−0.75 (a proxy of metabolic rate). Using 664 ant populations from 49 communities we examine how both NPP and body mass – individually and as a ratio – predict abundance (colonies m−2) at these different levels of taxonomic aggregation. Energy theory best predicts ant abundance when populations are aggregated into communities. At the population level, abundance formed a unimodal scatter plot vs all three drivers – colony mass, NPP, and NPP mass−0.75– suggesting that the majority of populations exist below energetic limits set by the ecosystem. At the community level, however, abundance scaled as predicted for mass−0.75 and NPP1.0, (b =−0.75 and 1.0, respectively) and was a positive decelerating function of their ratio (i.e. [NPP mass−0.75]0.61, r2= 0.68). Since geographic trends in colony mass and abundance are largely reciprocal – deserts tend to support few large colonies, and tropical rainforests support many small colonies – the geography of ant biomass (g m−2) is remarkably invariant.
Comparing survival among species with imperfect detection using multilevel analysis of mark—recapture data: a case study on bats
Authors: Papadatou Elena , Pradel Roger , Schaub Michael , Dolch Dietrich , Geiger Hartmut , Ibañez Carlos , Kerth Gerald , Popa‐Lisseanu Ana , Schorcht Wigbert , Teubner Jana , Gimenez Olivier
Published: June 2011

For comparative demography studies, 2 prerequisites are usually needed: 1) using typical parameter values for species, 2) correctly accounting for the uncertainty in the species specific estimates. However, although within‐species variability may be essential, it is typically not considered in analytical procedures, resulting in parameter estimates that may not be representative of the species. Further, data are analysed in 2 steps, first separately for each species, then estimates are compared among species. Accounting for the uncertainty in the species specific estimates is then difficult. Here we propose the application of multilevel Bayesian models on mark—recapture (MR) data for comparative studies on survival probabilities that solves these problems. Our models account for within‐species variability in space and time in the form of random effects. Models reflecting different biological predictions related to the species’ ecology and life‐history traits may further be contrasted. To illustrate our approach, we used long‐term data from 5 temperate tree‐roosting bat species and compared their survival probabilities. Results suggest that species foraging in open space, high reproductive output and short longevity records have lower survival than species foraging at short distances, with low reproductive output and high longevity records. Multilevel models provided relatively precise estimates, away from the edges of the parameter space, even for species with low encounter rates and short study duration. This is particularly valuable for less studied taxa such as bats for which available data are often more sparse. Our approach can be easily extended to include additional groups or levels of interest and effects at the individual level (e.g. sex or age). Different hypotheses regarding differences or similarities in parameters among species can be tested through the application of different models. Overall, it offers a flexible tool to ecologists, and population and evolutionary biologists for comparative studies, explicitly accounting for multilevel structures often encountered in MR data.
Tissue microarray analysis of RANKL in cutaneous lupus erythematosus and psoriasis
Authors: Toberer Ferdinand , Sykora Jaromir , Göttel Daniel , Ruland Vincent , Hartschuh Wolfgang , Enk Alexander , Luger Thomas A. , Beissert Stefan , Loser Karin , Joos Stefan , Krammer Peter H. , Kuhn Annegret
Published: June 2011

Abstract:  Recently, it was discovered that the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) is part of an important signal transduction pathway for tissue homoeostasis. Therefore, we were interested in investigating RANKL expression in the epidermis of skin lesions from patients with different subtypes of cutaneous lupus erythematosus (CLE) and psoriasis as well as normal healthy donors. Using the tissue microarray technique, skin biopsy specimens were evaluated by immunohistochemistry. RANKL showed a significantly increased expression in the epidermis of skin biopsy specimens from patients with psoriasis (median: 4, range: 0–5) compared to patients with CLE (median: 0, range: 0–4) (P < 0.001). No significant differences in epidermal RANKL expression between the CLE subtypes were detected. These data show a different expression of RANKL in the epidermis of skin lesions from patients with CLE compared to those with psoriasis suggesting that RANKL might play an important role in the pathogenesis of the disease.
Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof
Authors: Farwick Mike , Grether‐Beck Susanne , Marini Alessandra , Maczkiewitz Ursula , Lange Jennifer , Köhler Tim , Lersch Peter , Falla Tim , Felsner Ingo , Brenden Heidi , Jaenicke Thomas , Franke Susanne , Krutmann Jean
Published: June 2011

Abstract:  The ‘matrikine’ concept claims that processing of the precursors for collagen results in the formation of peptides such as KTTKS which in turn augments extracellular matrix (ECM) production. In the present study, we show the development of an anti‐ageing active from an in silico approach by molecular design resulting in the tetrapeptide GEKG derived from ECM proteins. The efficacy of the peptide to significantly induce collagen production of the protein level and mRNA level has been demonstrated in vitro in human dermal fibroblasts and in vivo in a double‐blind, randomized, placebo‐controlled study enroling 10 volunteers with an average age of 48.2 years. The effect of GEKG on facial wrinkles was studied in 30 volunteers using state of the art fringe projection, which allows determination of surface roughness in three‐dimensions. Here, only GEKG but not the placebo was able to significantly decrease skin roughness as a measure for wrinkles.
Fiscal Externalities of Becoming a Parent
Authors: Wolf Douglas A. , Lee Ronald D. , Miller Timothy , Donehower Gretchen , Genest Alexandre
Published: June 2011

Theoretical and empirical results suggest that there are externalities to childbearing, but those results usually assume that these externalities accrue uniformly within a homogeneous population. We advance this argument by developing separate estimates of the fiscal externalities associated with parents—those who devote time or material resources to minor children—and nonparents. Our analysis uses data from the US Panel Study of income Dynamics on the age profiles of taxes paid and publicly funded benefts consumed by parents and nonparents, together with a previously developed intertemporal economic‐demographic accounting model. The accounting framework takes into account the net fiscal impacts of future generations as well as the present population. Our findings indicate that, with a 3 percent discount rate, parents produce a substantial net fiscal externality, about $217,000 in 2009 dollars. This is equivalent to a lifetime annuity of nearly $8,100 per year beginning at age 18. The results are sensitive to both the discount rate used and the proportion of parents within the cohort.
Economic Recession and Fertility in the Developed World
Authors: Sobotka Tomáš , Skirbekk Vegard , Philipov Dimiter
Published: June 2011

This article reviews research on the effects of economic recessions on fertility in the developed world. We study how economic downturns, as measured by various indicators, especially by declining GDP levels, falling consumer confdence, and rising unemployment, were found to affect fertility. We also discuss particular mechanisms through which the recession may have influenced fertility behavior, including the effects of economic uncertainty, falling income, changes in the housing market, and rising enrollment in higher education, and also factors that influence fertility indirectly such as declining marriage rates. Most studies find that fertility tends to be pro‐cyclical and often rises and declines with the ups and downs of the business cycle. Usually, these aggregate effects are relatively small (typically, a few percentage points) and of short durations; in addition they often influence especially the timing of childbearing and in most cases do not leave an imprint on cohort fertility levels. Therefore, major long‐term fertility shifts often continue seemingly uninterrupted during the recession—including the fertility declines before and during the Great Depression of the 1930s and before and during the oil shock crises of the 1970s. Changes in the opportunity costs of childbearing and fertility behavior during economic downturn vary by sex, age, social status, and number of children; childless young adults are usually most affected. Furthermore, various policies and institutions may modify or even reverse the relationship between recessions and fertility. The first evidence pertaining to the recent recession falls in line with these findings. In most countries, the recession has brought a decline in the number of births and fertility rates, often marking a sharp halt to the previous decade of rising fertility rates.
Social Capital and Women's Reduced Vulnerability to HIV Infection in Rural Zimbabwe
Authors: Gregson Simon , Mushati Phyllis , Grusin Harry , Nhamo Mercy , Schumacher Christina , Skovdal Morten , Nyamukapa Constance , Campbell Catherine
Published: June 2011

Social capital—especially through its “network” dimension (high levels of participation in local community groups)—is thought to be an important determinant of health in many contexts. We investigate its effect on HIV prevention, using prospective data from a general population cohort in eastern Zimbabwe spanning a period of extensive behavior change (1998–2003). Almost half of the initially uninfected women interviewed were members of at least one community group. In an analysis of 88 communities, individuals with higher levels of community group participation had lower incidence of new HIV infections and more of them had adopted safer behaviors, although these effects were largely accounted for by differences in socio‐demographic composition. Individual women in community groups had lower HIV incidence and more extensive behavior change, even after controlling for confounding factors. Community group membership was not associated with lower HIV incidence in men, possibly refecting a propensity among men to participate in groups that allow them to develop and demonstrate their masculine identities—often at the expense of their health. Support for women's community groups could be an effective HIV prevention strategy in countries with large‐scale HIV epidemics.
What Works in Family Planning Interventions: A Systematic Review
Authors: Mwaikambo Lisa , Speizer Ilene S. , Schurmann Anna , Morgan Gwen , Fikree Fariyal
Published: June 2011

This study presents findings from a systematic review of evaluations of family planning interventions published between 1995 and 2008. Studies that used an experimental or quasi‐experimental design or used another approach to attribute program exposure to observed changes in fertility or family planning outcomes at the individual or population levels were included and ranked by strength of evidence. A total of 63 studies met the inclusion criteria. The findings from this review are summarized in tabular format by the type of intervention (classified as supply‐side or demand‐side). About two‐thirds of the studies found were evaluations of programs focusing on demand generation. Findings from all programs revealed significant improvements in knowledge, attitudes, discussion, and intentions. Program impacts on use of contraceptives and use of family planning services were less consistently found, and fewer than half of the studies that measured fertility or pregnancy‐related outcomes found an impact. Based on the review findings, we identify promising programmatic approaches and propose directions for future evaluation research of family planning interventions.
Normative Influence and Desired Family Size among Young People in Rural Egypt
Authors: Harbour Catherine
Published: June 2011

Research has identified the lack of acceptance of a two‐child‐family norm as the biggest obstacle to achieving replacement‐level fertility in Egypt. This analysis examines norms about desired family size for 1,366 males and 1,367 females aged 15–24 in 2004 in rural Minya governorate. Two‐level random‐effects multivariate logistic regression models, stratified by sex and grouped by neighborhood, are used to assess normative influence at the household and neighborhood levels, controlling for individual‐ and household‐level covariates. In the final model, young males in neighborhoods where more people desire a small family are 33 percent more likely to desire a small family than are young males in other neighborhoods. Young females in households with one or more adults preferring a small family are 78 percent more likely to desire a small family, and young females in households with one or more young people who prefer a small family are 37 percent more likely to desire a small family themselves, compared with those living with adults or with young people, respectively, who do not prefer a small family. Programs aiming to reduce fertility should be aware of gender differences in the sources of normative influence on desired family size.
Relationship Between Dual‐Domain Parameters and Practical Characterization Data
Authors: Flach Gregory P.
Published: June 2011

Dual‐domain solute transport models produce significantly improved agreement to observations compared to single‐domain (advection‐dispersion) models when used in an a posteriori data fitting mode. However, the use of dual‐domain models in a general predictive manner has been a difficult and persistent challenge, particularly at field‐scale where characterization of permeability and flow is inherently limited. Numerical experiments were conducted in this study to better understand how single‐rate mass transfer parameters vary with aquifer attributes and contaminant exposure. High‐resolution reference simulations considered 30 different scenarios involving variations in permeability distribution, flow field, mass transfer timescale, and contaminant exposure time. Optimal dual‐domain transport parameters were empirically determined by matching to breakthrough curves from the high‐resolution simulations. Numerical results show that mobile porosity increases with lower permeability contrast/variance, smaller spatial correlation length, lower connectivity of high‐permeability zones, and flow transverse to strata. A nonzero non‐participating porosity improves empirical fitting, and becomes larger for flow aligned with strata, smaller diffusion coefficient, and larger spatial correlation length. The non‐dimensional mass transfer coefficient or Damkohler number tends to be close to 1.0 and decrease with contaminant exposure time, in agreement with prior studies. The best empirical fit is generally achieved with a combination of macrodispersion and first‐order mass transfer. Quantitative prediction of ensemble‐average dual‐domain parameters as a function of measurable aquifer attributes proved only marginally successful.
Enzyme Stability of Microencapsulated Bifidobacterium animalis ssp. lactis Bb12 after Freeze Drying and during Storage in Low Water Activity at Room Temperature
Authors: Dianawati Dianawati , Shah Nagendra P.
Published: June 2011

Abstract:  Stability of enzymes such as β‐galactosidase (β‐gal), β‐glucosidase (β‐glu), lactate dehydrogenase (LDH), pyruvate kinase (PK), hexokinase (HK), and ATPase of microencapsulated Bifidobacterium animalis ssp. lactis Bb12 after freeze‐drying and after 10 wk of storage at low water activity (aw) at room temperature was studied. Bacteria were microencapsulated using alginate formulation with or without mannitol fortification (sodium alginate and mannitol [SAM] and sodium alginate [SA], respectively) by creating gel beads followed by freeze drying. Two types of dried gel beads were then stored at low aw, such as 0.07, 0.1, and 0.2; storage in an aluminum foil was used as control. All storage was carried out at room temperature of 25 °C for 10 wk. Measurement of β‐gal, β‐glu, LDH, PK, HK, and ATPase (with or without exposure to pH 2.0 for 2 h) activities was carried out before freeze drying, after freeze drying, and after 10 wk of storage. There was a significant decrease in almost all enzyme activities, except that of PK. SAM and SA showed no different effect on maintaining enzyme activities during freeze drying. Storage for 10 wk at room temperature at various low aw using SAM and SA system had a significant effect on retention of most enzymes studied, except that of PK and LDH. Storage at aw of 0.07 and 0.1 was more effective in maintaining enzyme activities than storage at aw of 0.2 and in an aluminum foil. However, mannitol fortification into alginate system did not significantly improve retention of enzymes during 10 wk of storage.
Self‐regulation following prostatectomy: Phase‐specific self‐efficacy beliefs for pelvic‐floor exercise
Authors: Burkert S , Knoll N , Scholz U , Roigas J , Gralla O
Published: June 2011

Objective. Beliefs in one's ability to perform a task or behaviour successfully are described as self‐efficacy beliefs (Bandura, 1977). Since individuals have to deal with differing demands during a behaviour‐change process, they form phase‐specific self‐efficacy beliefs directed at these respective challenges. The present study, based on the Health Action Process Approach (Schwarzer, 2001), examines the theoretical differentiation, relative importance, and differential effects of four phase‐specific self‐efficacy beliefs, including task self‐efficacy, preactional self‐efficacy, maintenance self‐efficacy, and recovery self‐efficacy.

Design. In a prospective longitudinal study, 112 prostatectomy‐patients received questionnaires at 2 days, 2 weeks, 1 month, and 6 months post‐surgery.

Methods. Participants provided data on phase‐specific self‐efficacies as well as phase indicators of health‐behaviour change, that is, intentions, planning, and pelvic‐floor exercise. Hierarchical regression analyses were conducted to test the study hypotheses.

Results. Task self‐efficacy was not uniquely associated with intentions. Preactional self‐efficacy was related to action planning. Maintenance self‐efficacy did not predict behaviour. Recovery self‐efficacy was associated with re‐uptake of pelvic‐floor exercise after relapses only.

Conclusion. Findings underline the importance of differentiating between task self‐efficacy and preactional self‐efficacy during early phases of behaviour change as well as of considering the occurrence of relapses as a moderator of potential effects of recovery self‐efficacy on the maintenance of behaviour change. Advanced knowledge on distinct, phase‐specific self‐efficacy beliefs may facilitate the design of effective tailored interventions for behaviour change.
Current Issues and Trends in Meshing and Geometric Processing for Computational Engineering Analyses
Authors: Shimada Kenji
Published: June 2011

This paper presents the current issues and trends in meshing and geometric processing, core tasks in the preparation stage of computational engineering analyses. In product development, computational simulation of product functionality and manufacturing process have contributed significantly toward improving the quality of a product, shortening the time-to-market and reducing the cost of the product and manufacturing process. The computational simulation can predict various physical behaviors of a target object or system, including its structural, thermal, fluid, dynamic, and electro-magnetic behaviors. In industry, the computer-aided engineering (CAE) software packages have been the driving force behind the ever-increasing usage of computational engineering analyses. While these tools have been improved continuously since their inception in the early 1960s, the demand for more complex computational simulation has grown significantly in recent years, creating some major shortfalls in the capability of current CAE tools. This paper first discusses the current trends of computational engineering analyses and then focuses on two areas of such shortfalls: meshing and geometric processing, critical tasks required in the preparation stage of engineering analyses that use common numerical methods such as the finite element method and the boundary element method.
Data-Driven Design Optimization for Composite Material Characterization
Authors: Michopoulos John G. , Hermanson John C. , Iliopoulos Athanasios , Lambrakos Samuel G. , Furukawa Tomonari
Published: June 2011

The main goal of the present paper is to demonstrate the value of design optimization beyond its use for structural shape determination in the realm of the constitutive characterization of anisotropic material systems such as polymer matrix composites with or without damage. The approaches discussed are based on the availability of massive experimental data representing the excitation and response behavior of specimens tested by automated mechatronic material testing systems capable of applying multiaxial loading. Material constitutive characterization is achieved by minimizing the difference between experimentally measured and analytically computed system responses as described by surface strain and strain energy density fields. Small and large strain formulations based on additive strain energy density decompositions are introduced and utilized for constructing the necessary objective functions and their subsequent minimization. Numerical examples based on both synthetic (for one-dimensional systems) and actual data (for realistic 3D material systems) demonstrate the successful application of design optimization for constitutive characterization.
The Effect of Unequal Admission on the Performance and Loss Generation in a Double-Entry Turbocharger Turbine
Authors: Copeland Colin D. , Newton Peter J. , Martinez-Botas Ricardo , Seiler Martin
Published: June 2011

The current work investigates a circumferentially divided turbine volute designed such that each gas inlet feeds a separate section of the turbine wheel. Although there is a small connecting interspace formed between the nozzle and the mixed-flow rotor inlet, this design does well to preserve the exhaust gas energy in a pulsed-charged application by largely isolating the two streams entering the turbine. However, this type of volute design produces some interesting flow features as a result of unequal flows driving the turbine wheel. To investigate the influence of unequal flows, experimental data from the turbocharger facility at Imperial College have been gathered over a wide range of steady-state, unequal admission conditions. These test results show a significant drop in turbine performance with increasing pressure difference between inlets. In addition, the swallowing capacities of each gas inlet are interdependent, thus indicating some flow interaction between entries. To understand the flow physics driving the observed performance, a full 3D computational fluid dynamics (CFD) model of the turbine was created. Results show a highly disturbed flow field as a consequence of the nonuniform admission. From these results, it is possible to identify the regions of aerodynamic loss responsible for the measured performance decrease. Given the unequal flows present in a double-entry design, each rotor passage sees an abrupt change in flow conditions as it rotates spanning the two feeding sectors. This operation introduces a high degree of unsteady flow into the rotor passage even when it operates in steady conditions. The amplitude and frequency of this unsteadiness will depend both on the level of unequal admission and the speed of rotor rotation. The reduced frequency associated with this disturbance supports the evidence that the flow in the rotor passage is unsteady. Furthermore, the CFD model indicates that the blade passage flow is unable to fully develop in the time available to travel between the two different sectors (entries).
Numerical and Experimental Investigation of Turning Flow Effects on Innovative Pin Fin Arrangements for Trailing Edge Cooling Configurations
Authors: Bianchini C. , Facchini B. , Simonetti F. , Tarchi L. , Zecchi S.
Published: June 2011

The effect of the array configuration of circular pin fins is investigated from a numerical and experimental point of view reproducing a typical cooling scheme of a real high pressure aero-engine blade. The airstream enters the domain of interest radially from the hub inlet and exits axially from the trailing edge (TE) outlet section. More than 100 turbulators are inserted in the wedge-shaped TE duct to enhance the heat transfer: A reference array implementing seven rows of staggered pins is compared with an innovative pentagonal arrangement. Investigations were made considering real engine flow conditions: Both numerical calculations and experimental measurements were performed fixing Re=18,000 and Ma=0.3 in the TE throat section. The effect of the tip mass flow rate was also taken into account, investigating 0% and 25% of the TE mass flow rate. The experimental activity was aimed at obtaining detailed heat transfer coefficient maps over the internal pressure side (PS) surface by means of the transient technique with thermochromic liquid crystals. Particle image velocimetry measurements were performed and surface flow visualizations were made by means of the oil and dye technique on the PS surface. Steady-state Reynolds averaged Navier–Stokes simulations were performed with two different computational fluid dynamics (CFD) codes: the commercial software Ansys CFX®11.0 and an in-house solver based on the opensource toolbox OpenFOAM®, to compare the performance and predictive capabilities. Turbulence was modeled by means of the k−ω shear stress transport (SST) model with a hybrid near-wall treatment allowing strong clustering of the wall of interest as well as quite coarse refinement on the other viscous surfaces.
Novel IGV Designs for Centrifugal Compressors and Their Interaction With the Impeller
Authors: Mohseni Arman , Goldhahn Erik , Van den Braembussche René A. , Seume Joerg R.
Published: June 2011

In centrifugal compressors, variable inlet guide vanes (IGVs) are used to control the mass flow rate with negligible change in pressure ratio and shaft speed. The efficient operation of IGVs is limited to the range of aerodynamic stability of their vane profiles. Thin symmetric profiles, which are usually used, tend to exhibit flow separation already at low setting angles, resulting in a rapid decrease in the global efficiency. Three different guide vane profiles, including a symmetric reference profile, a two-piece tandem profile with a variable angle, and an s-cambered profile, together with two auxiliary profiles, were considered. These variants were numerically and experimentally investigated at different setting angles, covering negative and positive inlet swirls, and at different operating points. The results show that tandem and s-cambered vanes have superior aerodynamic performance in comparison with the symmetric reference profile and extend the operating range of the compressor over which the efficiency remains high. The tandem profile shows better aerodynamic performance than the s-cambered profile at negative inlet swirl, while the asymmetric s-cambered profile offers an extended range of high efficiency at positive preswirl. Considering manufacturing requirements and cost, the s-cambered profile is preferred for applications with positive preswirl.
Thermal Transport in Self-Assembled Conductive Networks for Thermal Interface Materials
Authors: Hu Lin , Evans William , Keblinski Pawel
Published: June 2011

We present a concept for development of high thermal conductivity thermal interface materials (TIMs) via a rapid formation of conductive network. In particular we use molecular dynamics simulations to demonstrate the possibility of a formation of a network of solid nanoparticles in liquid solution and establish wetting and volume fraction conditions required for a rapid formation of such network. Then, we use Monte-Carlo simulations to determine effective thermal conductivity of the solid/liquid composite material. The presence of a percolating network dramatically increases the effective thermal conductivity, as compared to values characterizing dispersed particle structures.
Correlation and prediction uncertainties in the CyberKnife Synchrony respiratory tracking system
Authors: Pepin Eric W. , Wu Huanmei , Zhang Yuenian , Lord Bryce
Published: June 2011

Purpose:

The CyberKnife uses an online prediction model to improve radiation delivery when treating lung tumors. This study evaluates the prediction model used by the CyberKnife radiation therapy system in terms of treatment margins about the gross tumor volume (GTV).

Methods:

From the data log files produced by the CyberKnife synchrony model, the uncertainty in radiation delivery can be calculated. Modeler points indicate the tracked position of the tumor and Predictor points predict the position about 115 ms in the future. The discrepancy between Predictor points and their corresponding Modeler points was analyzed for 100 treatment model data sets from 23 de‐identified lung patients. The treatment margins were determined in each anatomic direction to cover an arbitrary volume of the GTV, derived from the Modeler points, when the radiation is targeted at the Predictor points. Each treatment model had about 30 min of motion data, of which about 10 min constituted treatment time; only these 10 min were used in the analysis. The frequencies of margin sizes were analyzed and truncated Gaussian normal functions were fit to each direction's distribution. The standard deviation of each Gaussian distribution was then used to describe the necessary margin expansions in each signed dimension in order to achieve the desired coverage. In this study, 95% modeler point coverage was compared to 99% modeler coverage. Two other error sources were investigated: the correlation error and the targeting error. These were added to the prediction error to give an aggregate error for the CyberKnife during treatment of lung tumors.

Results:

Considering the magnitude of 2σ from the mean of the Gaussian in each signed dimension, the margin expansions needed for 95% modeler point coverage were 1.2 mm in the lateral (LAT) direction and 1.7 mm in the anterior–posterior (AP) direction. For the superior–inferior (SI) direction, the fit was poor; but empirically, the expansions were 3.5 mm. For 99% modeler point coverage, the AP margin was 3.6 mm and the lateral margin was 2.9 mm. The SI margins for 99% modeler point coverage were highly variable. The aggregate error at 95% was 6.9 mm in the SI direction, 4.6 mm in the AP direction, and 3.5 in the lateral direction.

Conclusions:

The Predictor points follow the Modeler points closely. Margins were found in each clinical direction that would provide 95% modeler point coverage for 95% of the models reviewed in this study. Similar margins were found in two clinical directions for 99% modeler point coverage in 95% of models. These results can offer guidance in the selection of CTV margins for treatment with the CyberKnife.
High dose per fraction dosimetry of small fields with Gafchromic EBT2 film
Authors: Hardcastle Nicholas , Basavatia Amar , Bayliss Adam , Tomé Wolfgang A.
Published: June 2011

Purpose:

Small field dosimetry is prone to uncertainties due to the lack of electronic equilibrium and the use of the correct detector size relative to the field size measured. It also exhibits higher sensitivity to setup errors as well as large variation in output with field size and shape. Radiochromic film is an attractive method for reference dosimetry in small fields due to its ability to provide 2D dose measurements while having minimal impact on the dose distribution. Gafchromic EBT2 has a dose range of up to 40 Gy; therefore, it could potentially be useful for high dose reference dosimetry with high spatial resolution. This is a requirement in stereotactic radiosurgery deliveries, which deliver high doses per fraction to small targets.

Methods:

Targets of 4 mm and 12 mm diameters were treated to a minimum peripheral dose of 21 Gy prescribed to 80% of the maximum dose in one fraction. Target doses were measured with EBT2 film (both targets) and an ion chamber (12 mm target only). Measured doses were compared with planned dose distributions using profiles through the target and minimum peripheral dose coverage.

Results:

The measured target doses and isodose coverage agreed with the planned dose within ±1 standard deviation of three measurements, which were 2.13% and 2.5% for the 4 mm and 12 mm targets, respectively.

Conclusions:

EBT2 film is a feasible dosimeter for high dose per fraction reference 2D dosimetry.
IPIP: A new approach to inverse planning for HDR brachytherapy by directly optimizing dosimetric indices
Authors: Siauw Timmy , Cunha Adam , Atamtürk Alper , Hsu I‐Chow , Pouliot Jean , Goldberg Ken
Published: June 2011

Purpose:

Many planning methods for high dose rate (HDR) brachytherapy require an iterative approach. A set of computational parameters are hypothesized that will give a dose plan that meets dosimetric criteria. A dose plan is computed using these parameters, and if any dosimetric criteria are not met, the process is iterated until a suitable dose plan is found. In this way, the dose distribution is controlled by abstract parameters. The purpose of this study is to develop a new approach for HDR brachytherapy by directly optimizing the dose distribution based on dosimetric criteria.

Methods:

The authors developed inverse planning by integer program (IPIP), an optimization model for computing HDR brachytherapy dose plans and a fast heuristic for it. They used their heuristic to compute dose plans for 20 anonymized prostate cancer image data sets from patients previously treated at their clinic database. Dosimetry was evaluated and compared to dosimetric criteria.

Results:

Dose plans computed from IPIP satisfied all given dosimetric criteria for the target and healthy tissue after a single iteration. The average target coverage was 95%. The average computation time for IPIP was 30.1 s on an Intel(R) CoreTM2 Duo CPU 1.67 GHz processor with 3 Gib RAM.

Conclusions:

IPIP is an HDR brachytherapy planning system that directly incorporates dosimetric criteria. The authors have demonstrated that IPIP has clinically acceptable performance for the prostate cases and dosimetric criteria used in this study, in both dosimetry and runtime. Further study is required to determine if IPIP performs well for a more general group of patients and dosimetric criteria, including other cancer sites such as GYN.
Inverse determination of the penalty parameter in penalized weighted least‐squares algorithm for noise reduction of low‐dose CBCT
Authors: Wang Jing , Guan Huaiqun , Solberg Timothy
Published: June 2011

Purpose:

A statistical projection restoration algorithm based on the penalized weighted least‐squares (PWLS) criterion can substantially improve the image quality of low‐dose CBCT images. The performance of PWLS is largely dependent on the choice of the penalty parameter. Previously, the penalty parameter was chosen empirically by trial and error. In this work, the authors developed an inverse technique to calculate the penalty parameter in PWLS for noise suppression of low‐dose CBCT in image guided radiotherapy (IGRT).

Methods:

In IGRT, a daily CBCT is acquired for the same patient during a treatment course. In this work, the authors acquired the CBCT with a high‐mAs protocol for the first session and then a lower mAs protocol for the subsequent sessions. The high‐mAs projections served as the goal (ideal) toward, which the low‐mAs projections were to be smoothed by minimizing the PWLS objective function. The penalty parameter was determined through an inverse calculation of the derivative of the objective function incorporating both the high and low‐mAs projections. Then the parameter obtained can be used for PWLS to smooth the noise in low‐dose projections. CBCT projections for a CatPhan® 600 and an anthropomorphic head phantom, as well as for a brain patient, were used to evaluate the performance of the proposed technique.

Results:

The penalty parameter in PWLS was obtained for each CBCT projection using the proposed strategy. The noise in the low‐dose CBCT images reconstructed from the smoothed projections was greatly suppressed. Image quality in PWLS‐processed low‐dose CBCT was comparable to its corresponding high‐dose CBCT.

Conclusions:

A technique was proposed to estimate the penalty parameter for PWLS algorithm. It provides an objective and efficient way to obtain the penalty parameter for image restoration algorithms that require predefined smoothing parameters.
The Role of Nogo and the Mitochondria–Endoplasmic Reticulum Unit in Pulmonary Hypertension
Authors: Sutendra Gopinath , Dromparis Peter , Wright Paulette , Bonnet Sébastien , Haromy Alois , Hao Zhengrong , McMurtry M. Sean , Michalak Marek , Vance Jean E. , Sessa William C. , Michelakis Evangelos D.
Published: June 2011

The endoplasmic reticulum stress protein Nogo is a culprit in the mitochondrial defects that characterize pulmonary hypertension, pointing to therapeutic drug targets.
Immunogenicity of the Tuberculosis Vaccine MVA85A Is Reduced by Coadministration with EPI Vaccines in a Randomized Controlled Trial in Gambian Infants
Authors: Ota Martin O. C. , Odutola Aderonke A. , Owiafe Patrick K. , Donkor Simon , Owolabi Olumuyiwa A. , Brittain Nathaniel J. , Williams Nicola , Rowland-Jones Sarah , Hill Adrian V. S. , Adegbola Richard A. , McShane Helen
Published: June 2011

Coadministration with standard vaccines may reduce immunogenicity of tuberculosis vaccine.
Fanning the Flames: Understanding Menopausal Hot Flushes
Authors: Farrell Ruth M.
Published: June 2011

A longitudinal study of middle-aged women defines duration of and risk factors for menopausal hot flushes.
Mastering Metabolic Pathways in Diabetes
Authors: Damani Samir
Published: June 2011

The transcription factor KLF14 is a master regulator of multiple genes linked to diabetes and key metabolic phenotypes.
A Hepatitis C Mouse Model That Isn’t Chopped Liver
Authors: Evans-Molina Carmella
Published: June 2011

Four human proteins render mouse hepatocytes susceptible to hepatitis C virus: a new humanized mouse model for hepatitis C infection.