bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the performance of the ensemble Kalman filter for subsurface flow data integration under variogram uncertainty
Authors: Jafarpour B. , Tarrahi Mohammadali
Published: May 2011

The ensemble Kalman filter (EnKF) has recently been proposed as a promising parameter estimation approach for constraining the description of rock flow properties, such as permeability and porosity, to reproduce flow measurements that are modeled as nonlinear functions of these properties. One of the key factors that strongly affect the performance of the EnKF is the quality or representativeness of the prior ensemble of property fields used to initialize the EnKF assimilation procedure. The initial ensemble is commonly constructed by assuming a known geological continuity model such as a variogram. However, geologic continuity models are derived from incomplete information and imperfect modeling assumptions, which can introduce a significant level of uncertainty into the produced models. Neglecting this important source of uncertainty can lead to systematic errors and questionable estimation results. In this paper, we investigate the performance of the EnKF under varying levels of uncertainty in the variogram model parameters. We first attempt to directly estimate variogram model parameters from flow data and show that the complex and nonunique relation they have with the flow data provides little sensitivity for an effective inversion with the EnKF. We then assess the performance of the EnKF for estimation of permeability values under uncertain and incorrect initial variogram parameters and show that any bias in specifying variogram parameters tends to persist throughout the EnKF analysis even though locally reasonable permeability updates may be obtained near observation points. More importantly, we show that when variogram parameters are specified probabilistically to account for the full range of structural variability in the initial permeability ensemble, the EnKF update results are quite promising. The results suggest that under uncertain geologic continuity, the EnKF tends to perform better if a very diverse set of property fields is used to form the initial ensemble than when a deterministic and potentially erroneous variogram model is used. Therefore, in applying the EnKF to model calibration problems, it is preferable to overestimate the uncertainty in geologic continuity and to initialize the EnKF procedure with a wide range of variability in property description than to overlook the variogram uncertainty at the risk of introducing systematic bias that cannot be corrected by the EnKF updates. The practical implications of the results in this paper are significant for designing the EnKF for realistic ensemble model calibration problems where the level of uncertainty in the initial ensemble is usually not known a priori.
Quantitative MRI Reveals the Elderly Ischemic Brain is Susceptible to Increased Early Blood—Brain Barrier Permeability Following Tissue Plasminogen Activator Related to Claudin 5 and Occludin Disassembly
Authors: Kaur Jaspreet , Tuor Ursula I , Zhao Zonghang , Barber Philip A
Published: May 2011

Great uncertainty exists as to whether aging enhances the detrimental effects of tissue plasminogen activator (tPA) on vascular integrity of the ischemic brain. We hypothesized that tPA treatment would augment ischemic injury by causing increased blood-brain barrier (BBB) breakdown as determined by quantitative serial T1 and T2 magnetic resonance imaging (MRI), and the transfer constant for gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) from blood to brain in aged (18 to 20 months) compared with young (3 to 4 months) Wistar rats after middle cerebral artery occlusion, mediated through the acute disassembly of claudin 5 and occludin. Increased T2 values over the first hour of postreperfusion were independently augmented following treatment with tPA ( P < 0.001) and aging ( P < 0.01), supporting a synergistic effect of tPA on the aged ischemic brain. Blood-brain barrier permeability for Gd-DTPA ( KGd) was substantial following reperfusion in all animal groups and was exacerbated by tPA treatment in the elderly rat ( P < 0.001). The frequency of hematoma formation was proportionately increased in the elderly ischemic brain ( P < 0.05). Both tPA and age independently increased claudin 5 and occludin phosphorylation during ischemia. Early BBB permeability detected by quantitative MRI following ischemic stroke is enhanced by increased age and tPA and is related to claudin 5 and occludin phosphorylation.
Can Plant-Made Copper Chaperones Heal Early Alzheimer’s Disease?
Authors: Kastenholz Bernd , Horst Basil , Horst Jürgen
Published: May 2011

Commercially available medicinal plant extracts such as Ginkgo biloba leaf extract show no consistent pattern of clinical benefit for people with dementia or cognitive impairment, and have been suggested to be toxic to cells at higher doses. However, medicinal plants may contain other more efficient bioactive molecules apart from the well-known flavonoids and terpenoids. Therapeutic recombinant proteins, plant-made copper chaperone for superoxide dismutase (CCS) derived from Ginkgo biloba leaves, may establish and maintain physiologic Cu levels through restoration and modulation of biometal metabolism in organ systems of younger Alzheimer patients (> 50 years). Medications developed from plant-made copper chaperone proteins may delay progression during early disease stages or even be a basis for a possible causal treatment of preclinical stages of Alzheimer’s disease by preventing formation of A β plaques in the brain, a major putative factor involved in Alzheimer’s disease pathogenesis.
Hybrid organic/inorganic ambipolar thin film transistor chemical sensor
Authors: Dutta Soumya , Lewis Shannon D. , Dodabalapur Ananth
Published: May 2011

An ambipolar hybrid organic-inorganic thin film transistor, consisting of pentacene and zinc oxide as semiconductors, is reported. The current-voltage characteristics in different operational modes are studied. The transistor is employed as a chemical vapor sensor, operating at room temperature. In p-channel accumulation mode, which is dominated by hole transport, a decrease of current with the introduction of analyte is observed, while in the n-channel triode mode, in which the current is predominantly contributed by electron transport, an increase in current with analyte delivery is observed. A qualitative model based on dipole interaction is proposed to explain the sensing activity.
Effect of chemical doping on the thermoelectric properties of FeGa3
Authors: Haldolaarachchige N. , Karki A. B. , Phelan W. Adam , Xiong Y. M. , Jin R. , Chan Julia Y. , Stadler S. , Young D. P.
Published: May 2011

Thermoelectric properties of the chemically-doped intermetallic narrow-band semiconductor FeGa3 are reported. The parent compound shows semiconductor-like behavior with a small bandgap (Eg = 0.2 eV), a carrier density of ∼1018 cm−3, and a large n-type Seebeck coefficient (S ∼ − 400 μV/K) at room temperature. Hall effect measurements indicate that chemical doping significantly increases the carrier density, resulting in a metallic state, while the Seebeck coefficient still remains fairly large (∼− 150 μV/K). The largest power factor (S2/ρ = 62 μW/m K2) was observed for Fe0.99Co0.01(Ga0.997Ge0.003)3, and its corresponding figure of merit (ZT = 1.3 × 10−2) at 390 K improved by over a factor of 5 from the pure material.
Particle energization in 3D magnetic reconnection of relativistic pair plasmas
Authors: Liu Wei , Li Hui , Yin Lin , Albright B. J. , Bowers K. J. , Liang Edison P.
Published: May 2011

We present large scale 3D particle-in-cell simulations to examine particle energization in magnetic reconnection of relativistic electron-positron (pair) plasmas. The initial configuration is set up as a relativistic Harris equilibrium without a guide field. These simulations are large enough to accommodate a sufficient number of tearing and kink modes. Contrary to the non-relativistic limit, the linear tearing instability is faster than the linear kink instability, at least in our specific parameters. We find that the magnetic energy dissipation is first facilitated by the tearing instability and followed by the secondary kink instability. Particles are mostly energized inside the magnetic islands during the tearing stage due to the spatially varying electric fields produced by the outflows from reconnection. Secondary kink instability leads to additional particle acceleration. Accelerated particles are, however, observed to be thermalized quickly. The large amplitude of the vertical magnetic field resulting from the tearing modes by the secondary kink modes further help thermalizing the non-thermal particles generated from the secondary kink instability. Implications of these results for astrophysics are briefly discussed.
Modeling of carbon dioxide condensation in the high pressure flows using the statistical BGK approach
Authors: Kumar Rakesh , Li Zheng , Levin Deborah A.
Published: May 2011

In this work, we propose a new heat accommodation model to simulate freely expanding homogeneous condensation flows of gaseous carbon dioxide using a new approach, the statistical Bhatnagar-Gross-Krook method. The motivation for the present work comes from the earlier work of Li et al. [J. Phys. Chem. 114, 5276 (2010)] in which condensation models were proposed and used in the direct simulation Monte Carlo method to simulate the flow of carbon dioxide from supersonic expansions of small nozzles into near-vacuum conditions. Simulations conducted for stagnation pressures of one and three bar were compared with the measurements of gas and cluster number densities, cluster size, and carbon dioxide rotational temperature obtained by Ramos et al. [Phys. Rev. A 72, 3204 (2005)]. Due to the high computational cost of direct simulation Monte Carlo method, comparison between simulations and data could only be performed for these stagnation pressures, with good agreement obtained beyond the condensation onset point, in the farfield. As the stagnation pressure increases, the degree of condensation also increases; therefore, to improve the modeling of condensation onset, one must be able to simulate higher stagnation pressures. In simulations of an expanding flow of argon through a nozzle, Kumar et al. [AIAA J. 48, 1531 (2010)] found that the statistical Bhatnagar-Gross-Krook method provides the same accuracy as direct simulation Monte Carlo method, but, at one half of the computational cost. In this work, the statistical Bhatnagar-Gross-Krook method was modified to account for internal degrees of freedom for multi-species polyatomic gases. With the computational approach in hand, we developed and tested a new heat accommodation model for a polyatomic system to properly account for the heat release of condensation. We then developed condensation models in the framework of the statistical Bhatnagar-Gross-Krook method. Simulations were found to agree well with the experiment for all stagnation pressure cases (1-5 bar), validating the accuracy of the Bhatnagar-Gross-Krook based condensation model in capturing the physics of condensation.
A Fano-type interference enhanced quantum dot infrared photodetector
Authors: Vasinajindakaw Puminun , Vaillancourt Jarrod , Gu Guiru , Liu Runyu , Ling Yunfeng , Lu Xuejun
Published: May 2011

In this letter, we report a quantum dot photodetector enhanced by Fano-type interference in a metallic two-dimensional (2D) subwavelength hole array (2DSHA). The photocurrent enhancement wavelength shows an offset from the plasmonic resonant peak and corresponds to a dip in the transmission spectrum of the 2DSHA structure. The offset is attributed to the Fano-type interference in the 2DSHA structure. The asymmetric line shapes of the plasmonic resonance are analyzed and agree well with the two-peak Fano-type interference model. Over 100% enhancement in photodetectivity and photoresponsivity is achieved at the wavelength of the Fano dip of the first order plasmonic mode.
Direct measurement of the spin diffusion length by Andreev spectroscopy
Authors: Geresdi A. , Halbritter A. , Tanczikó F. , Mihály G.
Published: May 2011

The application of point contact Andreev spectroscopy for the measurement of the spin diffusion length is demonstrated by studying the spin relaxation in platinum thin films grown on the top of a ferromagnetic cobalt layer. Using this local probe technique, the temperature dependence of the spin diffusion length was determined, and various sources of the spin relaxation in platinum were identified. At low temperatures the spin lifetime is found to be three orders of magnitude larger than the momentum lifetime. The applied method is selectively sensitive to spin-flip processes even in the presence of a huge background of momentum scattering.
A carbon nanotube field emission multipixel x-ray array source for microradiotherapy application
Authors: Wang Sigen , Calderon Xiomara , Peng Rui , Schreiber Eric C. , Zhou Otto , Chang Sha
Published: May 2011

The authors report a carbon nanotube (CNT) field emission multipixel x-ray array source for microradiotherapy for cancer research. The developed multipixel x-ray array source has 50 individually controllable pixels and it has several distinct advantages over other irradiation source including high-temporal resolution (millisecond level), the ability to electronically shape the form, and intensity distribution of the radiation fields. The x-ray array was generated by a CNT cathode array (5×10) chip with electron field emission. A dose rate on the order of >1.2 Gy/min per x-ray pixel beam is achieved at the center of the irradiated volume. The measured dose rate is in good agreement with the Monte Carlo simulation result.
Half-metallicity of wurtzite NiO and w-NiO/ZnO (0001) interface: First principles simulation
Authors: Chen Zhongping , Miao Ling , Miao Xiangshui
Published: May 2011

First principles calculations based on density functional theory (DFT) are performed to investigate the structural, electronic and magnetic properties of wurtzite NiO (w-NiO) and w-NiO/ZnO (0001) interface. By applying DFT+U method we discover that wurtzite NiO retains the half-metallic behavior in the w-NiO/ZnO (0001) heterostructure. Through analyses of density of state, charge population and magnetic moments, we find the half-metallicity is weakened around the interface but the interface effect is quite localized. More over the interface configuration keeps a ferromagnetic ground state as bulk w-NiO does. Based on the simulations of epitaxial growth case, w-NiO is predicted to be a promising candidate for electrode injecting spin polarized currents.
Communication: Equation of state of hard oblate ellipsoids by replica exchange Monte Carlo
Authors: Odriozola G. , Guevara-Rodríguez F. de J.
Published: May 2011

We implemented the replica exchange Monte Carlo technique to produce the equation of state of hard 1:5 aspect-ratio oblate ellipsoids for a wide density range. For this purpose, we considered the analytical approximation of the overlap distance given by Bern and Pechukas and the exact numerical solution given by Perram and Wertheim. For both cases we capture the expected isotropic-nematic transition at low densities and a nematic-crystal transition at larger densities. For the exact case, these transitions occur at the volume fraction 0.341, and in the interval 0.584 − 0.605, respectively.
Inconsistent benefits of a freshwater protected area for artisanal fisheries and biodiversity in a South-east Asian wetland
Authors: Srinoparatwatana C. , Hyndes G.
Published: May 2011

Spatial closure management is a strategy used throughout the world for a range of goals, including protecting aquatic biodiversity and promoting fish production. However, benefits of freshwater protected areas (FPAs) have seldom been assessed. The present study is, therefore, one of the few that has compared the abundances, biomass and size structure of fish species between a FPA and the adjacent fished area. Fish assemblages in a large freshwater swamp (Beung Borapet) in Thailand were sampled with fish traps to test the hypothesis that the FPA would enhance fisheries production and biodiversity. Total densities and biomass of fish did not differ or were inconsistent between FPA and the fished area, and these patterns were inconsistent among several dominant species. Only one dominant species had higher densities and biomass in the FPA, which also did not appear to result in an increase in the size of fish. The benefits of the FPA for fisheries enhancement and conservation of biodiversity are inconsistent and appear to be compromised by a combination of non-selective fishing methods, illegal fishing activities and point-source impacts from other human disturbances. Spatial management therefore needs to be tailored to the socioeconomic structure of the community, resource availability for compliance, and multiple management-agency objectives.
A biophysical protein folding model accounts for most mutational fitness effects in viruses
Authors: Wylie C. Scott , Shakhnovich Eugene I.
Published: May 2011

Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and a mathematical portrait of robustness. Recent experiments on five viral species all revealed a characteristic bimodal-shaped DFE featuring peaks at neutrality and lethality. However, the phenotypic causes underlying observed fitness effects are still unknown and presumably, are thought to vary unpredictably from one mutation to another. By combining population genetics simulations with a simple biophysical protein folding model, we show that protein thermodynamic stability accounts for a large fraction of observed mutational effects. We assume that moderately destabilizing mutations inflict a fitness penalty proportional to the reduction in folded protein, which depends continuously on folding free energy (Δ
G
). Most mutations in our model affect fitness by altering Δ
G
, whereas based on simple estimates, ∼10% abolish activity and are unconditionally lethal. Mutations pushing Δ
G
> 0 are also considered lethal. Contrary to neutral network theory, we find that, in mutation/selection/drift steady state, high mutation rates (
m
) lead to less stable proteins and a more dispersed DFE (i.e., less mutational robustness). Small population size (
N
) also decreases stability and robustness. In our model, a continuum of nonlethal mutations reduces fitness by ∼2% on average, whereas ∼10–35% of mutations are lethal depending on
N
and
m
. Compensatory mutations are common in small populations with high mutation rates. More broadly, we conclude that interplay between biophysical and population genetic forces shapes the DFE.
Weakening of a thin shell structure by annihilating singularities
Authors: Walsh Lee , Meza Rubén , Hamm Eugenio
Published: May 2011

The strong deformation of a thin sheet or shell is characterized by the formation of sharp structures. In a shell that is forced to collapse, these features develop folds that make the process more efficient. On the other hand, in the crumpling of a membrane, the same features tend to stiffen the structure. We experimentally investigated a mechanism relevant in the collapse of shells and the early stages of crumpling, namely the mutual annihilation of vertex singularities. We show that the annihilation of two vertices in a displacement-controlled experiment is accompanied by a decrease of the forces at equilibrium. We propose a simple theoretical interpretation for this instability based on the near inextensibility of thin elastic sheets.
Infinite sequences of mutually non-conjugate surface braids representing same surface-links
Authors: Iwakiri Masahide
Published: May 2011

We give an infinite sequence of mutually non-conjugate surface braids with same degree representing the trivial surface-link with at least two components and a pair of non-conjugate surface braids with same degree representing a spun

(
2
,
t
)

(2,t)

-torus knot for

t
≥
3

t\geq 3

. To give these examples, we introduce new invariants of conjugacy classes of surface braids via colorings by Alexander quandles or core quandles of groups.
Homoclinic orbits of superlinear Hamiltonian systems
Authors: Chen Guanwei , Ma Shiwang
Published: May 2011

In this paper, we consider the first-order Hamiltonian system
\[

J

u
˙

(
t
)
+
∇
H
(
t
,
u
(
t
)
)
=
0
,

t
∈

R

.

J\dot {u}(t)+\nabla H(t,u(t))=0,\quad t\in \mathbb {R}.

\]
Here the classical Ambrosetti-Rabinowitz superlinear condition is replaced by a general super-quadratic condition. We will study the homoclinic orbits for the system. The main idea here lies in an application of a variant generalized weak linking theorem for a strongly indefinite problem developed by Schechter and Zou.
Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size
Authors: Antonescu Costin N. , Aguet François , Danuser Gaudenz , Schmid Sandra L.
Published: May 2011

Clathrin-mediated endocytosis (CME) is the major mechanism for internalization in mammalian cells. CME initiates by recruitment of adaptors and clathrin to form clathrin-coated pits (CCPs). Nearly half of nascent CCPs abort, whereas others are stabilized by unknown mechanisms and undergo further maturation before pinching off to form clathrin-coated vesicles (CCVs). Phosphatidylinositol-(4,5)-bisphosphate (PIP2), the main lipid binding partner of endocytic proteins, is required for CCP assembly, but little is currently known about its contribution(s) to later events in CCV formation. Using small interfering RNA (siRNA) knockdown and overexpression, we have analyzed the effects of manipulating PIP2 synthesis and turnover on CME by quantitative total internal reflection fluorescence microscopy and computational analysis. Phosphatidylinositol-4-phosphate-5-kinase cannot be detected within CCPs but functions in initiation and controls the rate and extent of CCP growth. In contrast, the 5′-inositol phosphatase synaptojanin 1 localizes to CCPs and controls early stabilization and maturation efficiency. Together these results suggest that the balance of PIP2 synthesis in the bulk plasma membrane and its local turnover within CCPs control multiple stages of CCV formation.
Egg mortality: predation and hydrography in the central Baltic
Authors: Voss Rüdiger , Hinrichsen Hans-Harald , Stepputtis Daniel , Bernreuther Matthias , Huwer Bastian , Neumann Viola , Schmidt Jörn O.
Published: May 2011

Voss, R., Hinrichsen, H-H., Stepputtis, D., Bernreuther, M., Huwer, B., Neumann, V., and Schmidt, J. O. 2011. Egg mortality: predation and hydrography in the central Baltic. – ICES Journal of Marine Science, 68: 1379–1390. Cod and sprat are the dominant fish species in the Baltic pelagic ecosystem, both of great economic importance and ecologically strongly interlinked. Management of both species is challenged by highly variable recruitment success. Recent studies have identified predation and hydrographic conditions during the egg phase to be of critical importance. Two years of extensive field investigations in the Bornholm Basin, central Baltic Sea, were undertaken. In 2002, a typical stagnation situation characterized by low salinity and poor oxygen conditions was investigated, and in early 2003, a major inflow of North Sea water completely changed the hydrographic conditions by increasing salinity and oxygen content, thereby altering ecological conditions. The goal was to quantify egg mortality caused by predation and hydrography, and to compare these estimates with independent estimates based on cohort analysis. Results indicated high intra-annual variability in egg mortality. Cod and sprat egg mortality responded differently to the major Baltic inflow: mortality related to hydrographic conditions increased for sprat and decreased for cod. On the other hand, predation mortality during peak spawning decreased for sprat and increased for cod.
Prevalence and Risk Factors for Hypovitaminosis D in Young Patients With Inflammatory Bowel Disease
Authors: Pappa Helen M. , Langereis Eveline J. , Grand Richard J. , Gordon Catherine M.
Published: May 2011

Vitamin D plays an important role in bone homeostasis. We aimed to report the prevalence of hypovitaminosis D in children with inflammatory bowel disease (IBD) and risk factors associated with low serum 25‐hydroxyvitamin D (25OHD) concentration in children with IBD.

Risk factors for deficiency of this vitamin are similar to those in healthy children, with the addition of higher erythrocyte sedimentation rate. Both patients with ulcerative colitis and Crohn disease are at risk for hypovitaminosis D.
Harry Elliot CBE. 28 June 1920 — 5 July 2009
Authors: Southwood David
Published: May 2011

Harry Elliot, a pioneer of British space science and known worldwide for his work on cosmic rays, passed away in July 2009. Coming from a farming family in the Anglo-Scottish borders, he entered Manchester University at the outbreak of war. After service in the Coastal Command of the Royal Air Force, he returned to Manchester to work with Patrick Blackett on the origin of primary cosmic rays, a scientific pursuit he followed for the rest of his career. In 1954 he moved with Blackett to Imperial College. After playing an important part in the International Geophysical Year, the dawn of the space age gave him the opportunity to be the originator of one of the major British space research groups. Subsequently, through his long-standing service at high level in the UK Science Research Council, the European Space Research Organisation and the European Space Agency, he played an important part in steering the development of British astronomical facilities as well as the evolution of European space science.
The mechanics and energetics of human walking and running: a joint level perspective
Authors: Farris Dominic James , Sawicki Gregory S.
Published: May 2011

Humans walk and run at a range of speeds. While steady locomotion at a given speed requires no net mechanical work, moving faster does demand both more positive and negative mechanical work per stride. Is this increased demand met by increasing power output at all lower limb joints or just some of them? Does running rely on different joints for power output than walking? How does this contribute to the metabolic cost of locomotion? This study examined the effects of walking and running speed on lower limb joint mechanics and metabolic cost of transport in humans. Kinematic and kinetic data for 10 participants were collected for a range of walking (0.75, 1.25, 1.75, 2.0 m s−1) and running (2.0, 2.25, 2.75, 3.25 m s−1) speeds. Net metabolic power was measured by indirect calorimetry. Within each gait, there was no difference in the proportion of power contributed by each joint (hip, knee, ankle) to total power across speeds. Changing from walking to running resulted in a significant (p= 0.02) shift in power production from the hip to the ankle which may explain the higher efficiency of running at speeds above 2.0 m s−1and shed light on a potential mechanism behind the walk–run transition.
The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells
Authors: Tirkkonen Laura , Halonen Heidi , Hyttinen Jari , Kuokkanen Hannu , Sievänen Harri , Koivisto Anna-Maija , Mannerström Bettina , Sándor George K. B. , Suuronen Riitta , Miettinen Susanna , Haimi Suvi
Published: May 2011

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3gpeak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d–1for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells.
Thatcher, Scientist
Authors: Agar Jon
Published: May 2011

This paper has two halves. First, I piece together what we know about Margaret Thatcher's training and employment as a scientist. She took science subjects at school; she studied chemistry at Oxford, arriving during World War II and coming under the influence (and comment) of two excellent women scientists, Janet Vaughan and Dorothy Hodgkin. She did a fourth-year dissertation on X-ray crystallography of gramicidin just after the war. She then gathered four years' experience as a working industrial chemist, at British Xylonite Plastics and at Lyons. Second, my argument is that, having lived the life of a working research scientist, she had a quite different view of science from that of any other minister responsible for science. This is crucial in understanding her reaction to the proposals—associated with the Rothschild reforms of the early 1970s—to reinterpret aspects of science policy in market terms. Although she was strongly pressured by bodies such as the Royal Society to reaffirm the established place of science as a different kind of entity—one, at least at core, that was unsuitable to marketization—Thatcher took a different line.
Diagnosis and management of anaemia of chronic disease: current status
Authors: Cullis Jonathan O.
Published: May 2011

Anaemia of chronic disease is the second most common form of anaemia worldwide, and is seen in a variety of inflammatory, infective and malignant diseases. Functional iron deficiency is fundamental to the pathogenesis of the anaemia, and the polypeptide, hepcidin, plays a key role. Diagnosis may be difficult, but new automated red cell indices, algorithms for detection of functional iron deficiency, and assays for hepcidin levels are being developed. Management of the causative disease process will usually improve haemoglobin levels, but where this is not possible, erythropoietic stimulating agents are often used, although there are still concerns about potential adverse effects, especially thromboembolism. There is increasing evidence that supplemental iron given parenterally can safely overcome the functional iron deficiency. Inhibitors of hepcidin, and various inflammatory modulators show promise for the future.
Modulation of CD4+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis
Authors: Hashimoto N , Shimoda S , Kawanaka H , Tsuneyama K , Uehara H , Akahoshi T , Kinjo N , Taketomi A , Shirabe K , Akashi K , Lleo A , Ansari A A , Gershwin M E , Maehara Y
Published: May 2011

Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV-related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV-related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4+ T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4+ T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4+ regulatory T cells and PD-L1- and PD-L2-expressing cells than controls. Blocking of PD-1/PD-1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)-γ to interleukin (IL)-10 and a reduction of PD-1-expressing CD4+ T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up-regulated expression of PD-1 ligands.
Determinants of plasma vitamin D levels in patients with acute coronary syndromes
Authors: Rodriguez Gabriella , Starr Aijing Z. , Czernuszewicz Grazyna Z. , Manhas Amit , Alhariri Ahmad , Willerson James T. , Reist Craig J. , Pieper Karen , Mahaffey Kenneth W. , Marian Ali J. , Kleiman Neal S.
Published: May 2011

Eur J Clin Invest 2011; 41 (12): 1299–1309

Background  Vitamin D is implicated in various biological functions ranging from cellular proliferation to immunity. Vitamin D deficiency is associated with an increased risk of several diseases including coronary atherosclerosis.

Materials and methods  We measured plasma 25(OH)D3 level in 224 patients with acute coronary syndromes (ACS) and 209 control individuals by ELISA. We genotyped the study populations for 11 single nucleotide polymorphisms (SNPs) in seven genes involved in vitamin D biosynthesis and metabolism by 5′ nuclease assays.

Results  The mean and median plasma 25(OH)D3 levels were not significantly different between patients with ACS and controls (median: 22·06 vs. 22·24 ng mL−1, respectively, P = 0·618). Plasma 25(OH)D3 level was < 20 ng mL−1 in 175/433 (40%) and < 30 ng mL−1 in 333/433 (77%) participants. Only four individuals had plasma 25(OH)D3 levels of above 60 ng mL−1. African‐American and Hispanic populations, women and those with diabetes mellitus had significantly lower plasma 25(OH)D3 levels. In multivariable regression analysis, age, sex, diabetes mellitus, body weight, rs2762933 (CYP24A1) and rs6055987 (PLCB1) SNPs were independent predictors of plasma 25(OH)D3 level in the Caucasian population.

Conclusions  We found no difference in mean plasma vitamin D levels between patients with ACS and controls. Differences in population characteristics between the two study groups including medications use and the lack of data on vitamin D, calcium and multivitamin supplements intake as well as the relatively small sample size of the populations could confound the results. Ethnic background, sex, age, body weight and SNPs in CYP24A1 and PLCB1 were independent determinants of plasma vitamin D levels.
In vitro responsiveness of human muscle cell peroxisome proliferator‐activated receptor δ reflects donors’ insulin sensitivity in vivo
Authors: Ordelheide Anna‐Maria , Heni Martin , Thamer Claus , Machicao Fausto , Fritsche Andreas , Stefan Norbert , Häring Hans‐Ulrich , Staiger Harald
Published: May 2011

Eur J Clin Invest 2011; 41 (12): 1323–1329

Background  Peroxisome proliferator‐activated receptor δ (PPARδ) activation enhances muscular fatty acid oxidation and oxidative phosphorylation, and muscle’s oxidative capacity positively associates with whole‐body insulin sensitivity. Therefore, we asked here whether human muscle cell PPARD expression is a determinant of donors’ insulin sensitivity.

Materials and methods  Skeletal muscle cells derived from 38 nondiabetic donors were differentiated in vitro to myotubes, and gene (mRNA) expression was quantified by real‐time RT–PCR. Donors’ insulin sensitivity was calculated from plasma insulin and glucose levels during oral glucose tolerance test (OGTT) and hyperinsulinemic‐euglycemic clamp.

Results  Basal myotube PPARD expression was closely related to the expression of its target genes PDK4 and ANGPTL4 (P = 0·0312 and P = 0·0003, respectively). Basal PPARD, PDK4 and ANGPTL4 expression levels were not associated with donors’ insulin sensitivity (P > 0·2, all). Treatment of myotubes with a selective high‐affinity PPARδ agonist (GW501516) did not change mean PPARD, but enhanced mean PDK4 and ANGPTL4 expression 13‐ and 16‐fold, respectively (P < 0·0001, both). The individual PDK4 and ANGPTL4 expression levels reached upon GW501516 treatment were associated with donors’ insulin sensitivity neither (P > 0·2, both). However, GW501516‐mediated fold increments in PDK4 and ANGPTL4 expression, reflecting PPARδ responsiveness, were positively associated with donors’ insulin sensitivity derived from OGTT (P = 0·0182 and P = 0·0231, respectively) and hyperinsulinemic‐euglycemic clamp (P = 0·0046 and P = 0·0258, respectively).

Conclusions  Using a highly selective pharmacological tool, we show here that the individual responsiveness of human muscle cell PPARδ, rather than the absolute PPARD expression level, represents a major determinant of insulin sensitivity.
Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours
Authors: Bush J. M. , Gardiner D. W. , Palmer J. S. , Rajpert‐De Meyts E. , Veeramachaneni D. N. R.
Published: May 2011

Unlike seminomas in humans, seminomas in animals are not typically sub‐classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated and characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model for this rare human neoplasm.
‘High‐tech’ home care: overview of professional care in patients on home parenteral nutrition and implications for nursing care
Authors: Huisman‐de Waal Getty , van Achterberg Theo , Jansen Jan , Wanten Geert , Schoonhoven Lisette
Published: May 2011

Aim.  The aim of this study is to describe the quality, quantity and content of care given to home parenteral nutrition‐dependent patients by various professionals in the Netherlands and to detect potential shortcomings.

Background.  Home parenteral nutrition is a lifesaving treatment for patients who cannot eat or cannot eat sufficiently. Very little is known about follow‐up care after hospital stay. Yet this is an important aspect of care as patients must cope with high‐tech skills at home. Also, complications and psychosocial complaints can occur.

Design.  Survey.

Methods.  A patient questionnaire was used to assess contacts with professionals and possible shortcomings in care. Nursing files from home parenteral nutrition nurses were reviewed for information from all contact moments. Home parenteral nutrition nurses and home care teams were interviewed to assess nursing care and to detect bottlenecks.

Results.  The nutrition support team was primarily responsible for the home parenteral nutrition care. Physical complaints like abdominal pain or nausea and venous access problems like fever were discussed most often. Patients were satisfied about the nutrition support team, but both the patients and the home parenteral nutrition nurses reported that relatively little attention was paid to psychosocial problems. Furthermore, the included patients visited their General Practitioner 11 times per year on average (range 1–104). Patients experienced a bottleneck with respect to the general practitioner’s knowledge of home parenteral nutrition‐related matters.

Conclusion.  Home parenteral nutrition patients visit the nutrition support team and their general practitioner most frequently and much attention is paid to medical and physical problems. Psychosocial problems, however, were only discussed in a minority of patients, and this was experienced as a shortcoming.

Relevance to clinical practice.  Both the patients and the home parenteral nutrition nurses reported that relatively little attention was paid to psychosocial problems. Patients’ concerns must be integrated in contact moments to enhance Quality of Life.
Nurses’ knowledge of heart failure education principles survey: a psychometric study
Authors: Hart Patricia L , Spiva LeeAnna , Kimble Laura P
Published: May 2011

Aims.  To compare the psychometric properties of the original dichotomously scored Nurses’ Knowledge of Heart Failure Self‐Management Education Principles Survey with a Likert scored version.

Background.  Nurses must be knowledgeable of HF self‐management principles to provide optimal education to patients. Psychometrically strong instruments to measure nurses’ knowledge of HF self‐management provide important insight into gaps of nurses’ knowledge.

Design.  This psychometric study had a two phase non‐experimental design comparing the psychometric characteristics of two versions of an existing survey in addition to test–retest reliability of the revised survey.

Methods.  A convenience sample of 122 nurses was recruited from a healthcare system located in the Southeastern USA. Data were collected from August 2006 through December 2006. Nurses completed the two versions of the survey.

Results.  The sample was predominantly Caucasian (76%), female (95%) with a mean age of 42 years (SD 11·4). Internal consistency reliability was 0·27 for the dichotomously scored version of the survey and 0·70 for the Likert scored version. The test–retest reliability of the Likert scored survey was r = 0·66. Data from individual Likert scored items indicated nurses were most knowledgeable about the need to continue daily weights even after HF symptoms are gone (mean = 4·43, SD 0·51) and least knowledgeable about how to advise asymptomatic patients to manage a low BP reading (mean = 2·11, SD 0·98).

Conclusion.  The Likert scored version of the Nurses’ Knowledge of Heart Failure Self‐Management Principles Survey was stronger psychometrically than the dichotomously scored version.

Relevance to clinical practice.  Teaching HF self‐management skills to patients is challenging and it is important to identify nurses’ gaps in knowledge of self‐management principles. The psychometrically sound Likert scored version of the survey potentially may be used to identify nurses’ knowledge gaps and inform staff development in‐services.
Quality circles for pharmacotherapy to modify general practitioners' prescribing behaviour for generic drugs
Authors: Spiegel Wolfgang , Mlczoch‐Czerny Marie‐Theres , Jens Rolf , Dowrick Christopher
Published: May 2011

Rationale, aims and objectives  In Austria, the participation of general practitioners (GPs) in so‐called ‘quality circles for pharmacotherapy’ (QCPs) was taken as a special approach to increase the use of generics and possibly, to improve the quality and efficiency of prescribing patterns in primary care. This study aimes at exploring GPs' perception of QCPs whether they think that taking part has helped to change their prescribing habits, their opinions on generics in general and the issues that arise for them in attempting to promote their use.

Methods  Qualitative analysis was used to evaluate QCP protocols for their potential to evoke discussion in the group and for their relevance to our study questions.

Results  Of the 821 self‐employed GPs in Vienna under contract with the Vienna District Health Insurance Fund 445 took part at least once in the study period. Seven main topics, which provide insight into various aspects of patient care in primary care, were identified: QCPs work, generic drug prescription, problems related to the sale of generics, patient counselling and education, therapy adherence, coordination of care, competence and medical education. From all prescribed drugs for which generics were available in the fourth quarter of the year 2003 GPs prescribed 33.91% generics, in the fourth quarter of 2004 43.97%, in the fourth quarter of 2005 46.31%, and in the fourth quarter of 2006 49.88%.

Conclusions  Peer review groups can be an important method of quality improvement in GPs' prescribing behaviour in favour of generics. QCPs also facilitate the exchange between GPs on problems encountered and provide feedback to policy makers.
The applicability of grading systems for guidelines
Authors: Baker Adrian , Potter Jonathan , Young Katharine , Madan Ira
Published: May 2011

Rationale  This study focused on factors that most concern specialist societies when choosing an evidence grading system, such as methodological strengths and weaknesses, applicability and ease of use. The grading systems chosen were the Scottish Intercollegiate Guidelines Network (SIGN), the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the National Service Framework for long‐term neurological conditions critical appraisal tool (NSF‐LTC).

Methodology  Twelve assessors, representing typical members of society‐based guideline development groups, graded papers and a recommendation using a key question as a guide. Key questions and recommendations were extracted from existing clinical guidelines representing a variety of research fields. Assessors were given 3 months to grade the papers using the grading systems and to complete a semi‐structured qualitative questionnaire. The results were independently assessed for emerging themes.

Results  Assessors felt all three systems had strengths and weaknesses depending on the type of evidence being graded. GRADE was seen as the most complex but rigorous system, while SIGN and NSF were seen as easier and more flexible to use, but less methodologically rigorous. In grading the evidence, 10% of assessors used GRADE incorrectly, 33% used SIGN incorrectly and 75% used NSF‐LTC incorrectly. In grading the recommendations, 60% used GRADE incorrectly, 50% used SIGN incorrectly and 50% used NSF‐LTC incorrectly.

Implications  It is recommended that specialist societies consider the type of evidence they will be evaluating and the research experience of the appraisers before selecting a grading system. Additionally, appraisers should have training in appraising and grading evidence using the system to be employed.
Mechanisms of Glucocorticoids in the Control of Neuroinflammation
Authors: Schweingruber N. , Reichardt S. D. , Lühder F. , Reichardt H. M.
Published: May 2011

Glucocorticoids (GCs) are widely used to treat inflammatory diseases such as multiple sclerosis (MS). They predominantly act through the GC receptor, a member of the nuclear receptor superfamily that controls transcription by several different mechanisms. Owing to its ubiquitous expression, there are a variety of cell types that could serve as GC targets in the pathogenesis and treatment of MS. This brings about a great diversity of mechanisms potentially involved in the modulation of neuroinflammation by GCs, including the induction of apoptosis, repression of pro‐inflammatory mediators and the expansion of myeloid‐derived suppressor cells. Nevertheless, it is not well understood which of these mechanisms are essential for therapeutic efficacy. In this review, we summarise findings made concerning the actions of GCs in MS and its animal model experimental autoimmune encephalomyelitis, and also elucidate current concepts and developments that pertain to this clinically highly relevant treatment regimen.