bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
Authors: Filipek‐Górniok Beata , Holmborn Katarina , Haitina Tatjana , Habicher Judith , Oliveira Marta Bastos , Hellgren Charlotte , Eriksson Inger , Kjellén Lena , Kreuger Johan , Ledin Johan
Published: May 2013

Background:Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions.Results:Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes,chpf, is represented by two copies in the zebrafish genome,chpfaandchpfb, while the other five human CS/DS glycosyltransferasescsgalnact1, csgalnact2, chpf2, chsy1,andchsy3all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady‐state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation.Conclusions:There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.Developmental Dynamics 242:964–975, 2013. © 2013 Wiley Periodicals, Inc.
Improvement of the Caenorhabditis elegans growth and reproduction test to assess the ecotoxicity of soils and complex matrices
Authors: Huguier Pierre , Manier Nicolas , Méline Camille , Bauda Pascale , Pandard Pascal
Published: May 2013

A growth and reproduction test using the nematode Caenorhabditis elegans was recently standardized by the International Organization for Standardization (ISO). Performing the ISO 10872 protocol (2010) revealed some drawbacks when applied to soil or soil mixed with complex matrices. The authors propose some modifications to the current protocol to normalize the test conditions. An appropriate range of moisture conditions was determined as a percentage of the water-holding capacity (WHC) of the soil. According to the authors' results, C. elegans tests can be performed in the range of 60% to 100% WHC. To ensure that the modifications of the protocol did not affect the organisms' recovery, extraction ratios for the juveniles were subsequently estimated. The modified protocol was found to be as reliable as the standard one concerning recovery of juveniles (over 80%). The protocol was also applied to several chemicals to investigate their potential as reference chemicals for soil toxicity tests. Boric acid, copper chloride, and nickel sulfate showed deleterious effects in a concentration-dependent manner for the growth and reproduction of C. elegans. Finally, the modified protocol was used to assess the growth and reproduction of C. elegans in soil amended with a limed sewage sludge. The authors conclude that the C. elegans modified protocol is a promising tool for the assessment of soil toxicity as well as the toxicity of mixtures with complex matrices. Environ Toxicol Chem 2013;32:2100–2108. © 2013 SETAC
Polo-like kinase 2 is a mediator of hedgehog survival signaling in cholangiocarcinoma
Authors: Fingas Christian D. , Mertens Joachim C. , Razumilava Nataliya , Sydor Svenja , Bronk Steven F. , Christensen John D. , Rizvi Sumera H. , Canbay Ali , Treckmann Jürgen W. , Paul Andreas , Sirica Alphonse E. , Gores Gregory J.
Published: May 2013

Cholangiocarcinoma (CCA) cells paradoxically express the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and thus rely on potent survival signals to circumvent cell death by TRAIL. Hedgehog (Hh) signaling is an important survival pathway in CCA. Herein, we further examine the mechanisms whereby Hh signaling mediates apoptosis resistance in CCA, revealing a pivotal role for the cell division regulating serine/threonine kinase polo-like kinase 2 (PLK2). We employed 50 human CCA samples (25 intrahepatic and 25 extrahepatic CCA) as well as human KMCH-1, Mz-CHA-1, and HUCCT-1 CCA cells for these studies.

In vivo

experiments were conducted using a syngeneic rat orthotopic CCA model. In human samples, polo-like kinase (PLK)1/2/3-immunoreactive cancer cells were present in the preponderance of intra- and extrahepatic CCA specimens. Inhibition of Hh signaling by cyclopamine reduced PLK2, but not PLK1 or PLK3, messenger RNA and protein expression in vehicle-treated and sonic Hh–treated CCA cells, confirming our previous microarray study. PLK2 regulation by Hh signaling appears to be direct, because the Hh transcription factors, glioma-associated oncogene 1 and 2, bind to the PLK2 promotor. Moreover, inhibition of PLK2 by the PLK inhibitor, BI 6727 (volasertib), or PLK2 knockdown was proapoptotic in CCA cells. BI 6727 administration or PLK2 knockdown decreased cellular protein levels of antiapoptotic myeloid cell leukemia 1 (Mcl-1), an effect reversed by the proteasome inhibitor, MG-132. Finally, BI 6727 administration reduced Mcl-1 protein expression in CCA cells, resulting in CCA cell apoptosis and tumor suppression

in vivo

.

Conclusion

: PLK2 appears to be an important mediator of Hh survival signaling. These results suggest PLK inhibitors to be of therapeutic value for treatment of human CCA. (Hepatology 2013;58:1362–1374)
Radiological-pathological analysis of WHO, RECIST, EASL, mRECIST and DWI: Imaging analysis from a prospective randomized trial of Y90 ± sorafenib
Authors: Vouche Michael , Kulik Laura , Atassi Rohi , Memon Khairuddin , Hickey Ryan , Ganger Daniel , Miller Frank H. , Yaghmai Vahid , Abecassis Michael , Baker Talia , Mulcahy Mary , Nayar Ritu , Lewandowski Robert J. , Salem Riad
Published: May 2013

The aim of this study was to compare radiological and pathological changes and test the adjunct efficacy of Sorafenib to Y90 as a bridge to transplantation in hepatocellular carcinoma (HCC). 15 patients with 16 HCC lesions were randomized to Y90 without (Group A, n = 9) or with Sorafenib (Group B, n = 7). Size (WHO, RECIST), enhancement (EASL, mRECIST) and diffusion-weighted imaging criteria (apparent diffusion coefficient, ADC) measurements were obtained at baseline, then at 1 and every 3 months after treatment until transplantation. Percentage necrosis in explanted tumors was correlated with imaging findings. 100%, 50%-99% and <50% pathological necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in Group A and 3 (42%), 2 (28%), and 2 (28%) in Group B, respectively (

P

= 0.81). While ADC (

P

= 0.46) did not change after treatment, WHO (

P

= 0.06) and RECIST (

P

= 0.08) response at 1 month failed to reach significance, but significant responses by EASL (

P

< 0.01/0.03) and mRECIST (

P

< 0.01/0.03) at 1 and 3 months were observed. Response was equivalent by EASL or mRECIST. No difference in response rates was observed between groups A and B at 1 and 3 months by WHO, RECIST, EASL, mRECIST or ADC measurements. Despite failing to reach significance, smaller baseline size was associated with complete pathological necrosis (CPN) (RECIST:

P

= 0.07; WHO:

P

= 0.05). However, a cut-off size of 35 mm was predictive of CPN (

P

= 0.005). CPN could not be predicted by WHO (

P

= 0.25 and 0.62), RECIST (P = 0.35 and 0.54), EASL (

P

= 0.49 and 0.46), mRECIST (

P

= 0.49 and 0.60) or ADC (

P

= 0.86 and 0.93).

Conclusion:

The adjunct of Sorafenib did not augment radiological or pathological response to Y90 therapy for HCC. Equivalent significant reduction in enhancement at 1 and 3 months by EASL/mRECIST was noted. Neither EASL nor mRECIST could reliably predict CPN. (Hepatology 2013;58:1655–1666)
Microbiota-liver axis in hepatic disease
Authors: Chassaing Benoit , Etienne-Mesmin Lucie , Gewirtz Andrew T.
Published: May 2013

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive proinflammatory gene expression, thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease.
Nonsteroidal Anti-Inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma: The Egg of Columbus or Another Illusion?
Authors: Kim Amy K. , Dziura James , Strazzabosco Mario
Published: May 2013

Abstract

Background:

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated. Methods: We analyzed prospective data on 300 504 men and women aged 50 to 71 years in the National Institutes of Health–AARP Diet and Health Study cohort and linked self-reported aspirin and non-aspirin NSAID use with registry confirmed diagnoses of HCC and death due to CLD. We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.

Results:

Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of non-aspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI = 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use non-aspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of non-aspirin NSAIDs compared to non-users. Conclusions: Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.
The Reciprocal Relations of Pressure, Work/Family Interference, and Role Satisfaction: Evidence from a Longitudinal Study in Taiwan
Authors: Lu Luo , Kao Shu‐Fang
Published: May 2013

The aim of this longitudinal study was to explore reciprocal relationships between work/family pressure, work/family interference, and work/family satisfaction among Taiwanese employees (N = 310). All study variables were assessed three times. We found that within the work domain, earlier work pressure caused later work‐to‐family conflict (WFC), while earlier WFC reduced later job satisfaction. We also found that earlier WFC caused later work pressure, while earlier job satisfaction reduced later WFC. Similarly, we found that within the family domain, earlier family pressure caused later family‐to‐work conflict (FWC), while earlier FWC reduced later family satisfaction. We also found that earlier FWC caused later family pressure. In addition, family pressure and family satisfaction had reciprocal relationships over time. Together these longitudinal and reciprocal relations strongly support our hypothesized feedback loops linking pressure, work and family conflict, and role satisfaction, within each of the work and family domains. We made specific suggestions on breaking these vicious cycles to effectively manage both the work and family roles.
A goodness of fit measure related to r2 for model performance assessment
Authors: Bardsley William Earl
Published: May 2013

Checking the predictive worth of an environmental model inevitably includes a goodness of fit metric to quantify the degree of matching to recorded data, thereby giving a measure of model performance. Considerable analysis and discussion have taken place over fit indices in hydrology, but a neglected aspect is the degree of communicability to other disciplines. It is suggested that a fit index is best communicated to colleagues via reference to models giving unbiased predictions, because unbiased environmental models are a desirable goal across disciplines. That is, broad recognition of a fit index is aided if it simplifies in the unbiased case to a familiar and logical expression. This does not hold for the Nash–Sutcliffe Efficiency E which reduces to the somewhat awkward unbiased expression E = 2 – 1/r2, where r2 is the coefficient of determination. A new goodness of fit index V is proposed for model validation as V = r2/(2‐E), which simplifies to the easily communicated V = r4 in the unbiased case. The index is defined over the range 0 ≤ V ≤ 1, and it happens that V < E for larger values of E. Some synthetic and recorded data sets are used to illustrate characteristics of V in comparison to E. Copyright © 2013 John Wiley & Sons, Ltd.
The Structural Study of Copper‐binding Peptides: Implication in the Aggregation of Amyloid‐β Peptides
Authors: Lin Ren‐Jie , Jinn Tzyy‐Rong , Jang Soonmin , Mai Fur‐Der , Li Feng‐Yin
Published: May 2013

There is evidence that copper is bound to amyloid‐β peptide (Aβ) in senile plaque of Alzheimer's disease. Copper also plays a role in the neurotoxicity of the Aβ aggregates associated with free radical damage. In this study, we used L‐histidyl‐L‐histidine peptide (di‐histidine) to represent Aβ along with ab initio calculation to characterize the probable coordination between Cu(II) and Aβs to explore the Aβ aggregate structures. Sixteen models of copper‐di‐histidine complexes were proposed to investigate the copper‐induced aggregation of Aβs through copper ionic coordination. All structures of the proposed models were optimized at the M05‐2X/LanL2DZ level, and an Aβ aggregation formation mechanism was proposed.
Chirality Inversion Process of a Bulky Alkyl Group in the Crystalline State Photo‐Isomerization of Cobaloxime Complex Crystals
Authors: Takeoka Hiraku , Sekine Akiko , Uekusa Hidehiro , Ohashi Yuji
Published: May 2013

The complex of [(R)‐tert‐(butoxycarbonyl)ethyl][(S)‐1‐cyclohexylethylamine]bis(dimethylglyoximato)cobalt(III), (R‐bce)(S‐cha)cobaloxime, 1, showed a racemization of the R‐bce group on exposure to a xenon lamp with retention of the single crystal form. A part of the R‐bce groups gradually inverted to the opposite configuration in the P212121 cell. However, the inversion of the R‐bce group converged when the R:S ratio became ca.75:25. The shape of the reaction cavity for the disordered bce group became symmetric at the ratio. For the related complex crystal with pyridine as an axial ligand, (R‐bce)(py)cobaloxime, 2, there are two crystallographically independent molecules, A and B, which are related by a pseudo inversion center in the P21 cell. When the crystal was exposed to the xenon lamp, the R‐bce group of the A molecule was gradually inverted to the opposite configuration without decomposition of the single crystal form, whereas the R‐bce group of B remained unchanged. Finally the pseudo inversion center became a crystallographic one and the space group became P21/c. The third complex crystal with water as an axial ligand, (R‐bce)(aqua)cobaloxime, 3, showed no changed on exposure to the xenon lamp. This is well explained by the size and shape of the reaction cavities for the R‐bce groups in the three crystals.
Effects of noble metals doped on mesoporous LaAlNi mixed oxide catalyst and identification of carbon deposit for reforming CH4 with CO2
Authors: Arandiyan Hamidreza , Peng Yue , Liu Caixia , Chang Huazhen , Li Junhua
Published: May 2013

BACKGROUND

The effect of the B cation on the surface properties and catalytic activity in the dry reforming reaction over La0.4M0.6Al0.2Ni0.8O3 (M=noble metal) perovskite‐type oxides with surface area 3.26–4.14 m2 g–1 and rhombohedral structure was studied.

RESULTS

Among LaAlxNi1‐xO3 series, LaAl0.2Ni0.8O3 had the highest catalytic activity, but suffered a slow deactivation with time‐on‐stream (TOS). It is observed that all samples presented similar activity at low reaction temperatures (500–600°C), while at higher temperatures (600–850°C) the prepared solid was more active and perovskite phase was transformed into Ni0 or La2O2CO3. It was found that among the noble metal samples, La0.4Rh0.6Al0.2Ni0.8O3 possessed the highest surface area and surface oxygen concentration and the best low‐temperature reducibility. For the Rh catalyst the CH4 and CO2 conversions were 89.1 and 86.2%, which were the most resistant against coke deposition and showed very high stability without decrease in reforming and remained constant during the 3000 min TOS. The following order of activity was observed: La0.4Rh0.6Al0.2Ni0.8O3 > La0.4Ru0.6Al0.2Ni0.8O3 > LaAl0.2Ni0.8O3> La0.4Ir0.6Al0.2Ni0.8O3 ≥La0.4Pt0.6Al0.2Ni0.8O3 > La0.4Pd0.6Al0.2Ni0.8O3.

CONCLUSIONS

It is believed that the high surface area and surface oxygen concentration and good low‐temperature reducibility were responsible for the good catalytic performance of the La0.4Rh0.6Al0.2Ni0.8O3 sample. © 2013 Society of Chemical Industry
The nature of the plate interface and driving force of interseismic deformation in the New Zealand plate‐boundary zone, revealed by the continuous GPS velocity field
Authors: Lamb Simon , Smith Euan
Published: May 2013

New Zealand straddles the boundary between the Australian and Pacific plates. Cenozoic relative plate motion has resulted in a complex pattern of faulting and block rotation, with displacements on individual faults up to hundreds of kilometers. However, over periods of several years, GPS measurements show a remarkably smooth pattern of velocities. We show here using a new method of back slip analysis, that almost the entire plate‐boundary continuous GPS velocity field can be predicted within measurement error from a simple model of elastic distortion due to deep slip on a single plate interface (megathrust in the Hikurangi and Putsegur subduction zones or fault through continental lithosphere beneath the Southern Alps) at the relative plate motion rates. This suggests that the main driving force of plate‐boundary deformation is slip on the deeper moving part of the plate interface, without buried creep in localized shear zones beneath individual surface faults. The depth at which this deep slip terminates (locking point line) determines the width of deformation. Along the Hikurangi margin, there is also clockwise rotation of ~150 km long segment of the fore arc (Wairoa domain) at 4.5° ± 1 Ma, relative to the Australian Plate, about a pole in western North Island; model residuals in the velocity field are mainly a result of incomplete averaging of the cycle of slow slip events on the plate interface, downdip of the locking point.
Detection of short‐term slow slip events along the Nankai Trough, southwest Japan, using GNSS data
Authors: Nishimura Takuya , Matsuzawa Takanori , Obara Kazushige
Published: May 2013

We detected short‐term slow slip events (SSEs) previously observable only with tilt and strain data along the Nankai Trough, southwest Japan, using GNSS (Global Navigation Satellite System) data. Offsets detected in GNSS time series using Akaike's information criterion helped automatically identify 207 episodes with a motion direction opposite to that of the relative plate motion from June 1996 to January 2012. By nonlinear inversion of the detected displacement, we estimated rectangular fault models for 133 probable and 25 possible short‐term SSEs over 15 years. The SSE moment magnitudes range from 5.5 to 6.3. Most SSE fault models are located in a narrow band of non‐volcanic tremors on the interfaces of the subducting Philippine Sea Plate. Large SSEs (moment magnitude, Mw, ≥6) often occur in western and central Shikoku. The cumulative slip is distributed heterogeneously along the strike, generally decreasing eastward with the maximum slip (~50 cm) in western Shikoku. No definite short‐term SSEs were found in the Kii Channel, but several short‐term SSEs occurred in Ise Bay. Both regions are known as tremor gaps. The local maximum of the cumulative slip fills in the tremor gap located in Ise Bay. The long‐term rate of short‐term SSE cumulative moment increased by threefold around 2003 in eastern Shikoku, whereas it was almost constant in other regions. Comparison with short‐term SSE catalogues using tilt data suggests that both this study and previous studies missed some SSEs along the Nankai Trough. A combination of geodetic data is important in the monitoring of the spatiotemporal distribution of short‐term SSEs.
New constraints on dike injection and fault slip during the 1975–1984 Krafla rift crisis, NE Iceland
Authors: Hollingsworth J. , Leprince Sébastien , Ayoub François , Avouac Jean‐Philippe
Published: May 2013

Correlation of KH9 spy and SPOT5 satellite images, airphotos, digital elevation model differencing, electronic distance measurement, and leveling survey data is used to constrain the deformation resulting from the 1975–1984 Krafla rifting crisis. We find that diking typically extends to depths of 5 km, while the dike tops range from 0 km in the caldera region to 3 km at the northern end of the rift. Extension is accommodated by diking at depth and normal faulting in the shallowest crust. In the southern section of the Krafla rift, surface opening is 80% of the dike opening at depth. Over the 70–80 km length of the rift, the average dike opening was 4.3–5.4 m. From these estimates, we calculate the total geodetic moment released over the Krafla rift crisis, 4.4–9.0×1019 Nm, which is an order of magnitude higher than the seismic moment released over the same time period, ~5.8×1018 Nm. The total volume of magma added to the upper crust was 1.1–2.1×109m3. This study highlights how optical image correlation using inexpensive declassified spy satellite and airphotos, combined with simple models of crustal deformation, can provide important constraints on the deformation resulting from past earthquake and volcanic events.
Symmetry and the critical slip distance in rate and state friction laws
Authors: Rathbun Andrew P. , Marone Chris
Published: May 2013

We performed laboratory experiments to investigate the processes responsible for rate and state friction (RSF) behavior in fault rocks. We focused on the symmetry of the frictional constitutive response to velocity changes and the mechanics of the critical friction slip distance Dc. Experiments were conducted in double direct shear at 1 and 25 MPa normal stress, at room temperature, and for shearing velocity from 1 to 300 µm/s. We studied three granular materials and bare surfaces of Westerly granite. Ruina's law, which predicts frictional symmetry between velocity increases and decreases, better matches our data than Dieterich's law, which predicts that velocity decreases should evolve to steady state at a smaller displacement. However, for granular shear, in some cases Dc is smaller for velocity increases than for velocity decreases, contrary to expectations from either law. On bare granite surfaces, the frictional response is symmetric for velocity increases/decreases. Two distinct length scales for Dc and two‐state variables are required for granular shear in some cases. We hypothesize that asymmetry and two‐state behavior are caused by shear localization and changes in shear fabric in fault gouge. Our measurements show that during steady state frictional shear, dilation after a velocity increase is smaller than compaction after a decrease. Normal stress oscillations cause a marked decrease in Dc. Reduction of Dc reduces frictional stability, enhancing the possibility of seismic slip. Our experiments show that shear localization and fabric within the fault gouge can influence the RSF parameters that dictate earthquake nucleation and dynamic rupture.
Three‐dimensional tsunami propagation simulations using an unstructured mesh finite element model
Authors: Oishi Yusuke , Piggott Matthew D. , Maeda Takuto , Kramer Stephan C. , Collins Gareth S. , Tsushima Hiroaki , Furumura Takashi
Published: May 2013

Large‐scale tsunami propagation simulations from the fault region to the coast are conducted using a three‐dimensional (3‐D) parallel unstructured mesh finite element code (Fluidity‐ICOM). Unlike conventional 2‐D approximation models, our tsunami model solves the full 3‐D incompressible Navier‐Stokes (NS) equations. The model is tested against analytical solutions to simple dispersive wave propagation problems. Comparisons of our 3‐D NS model results with those from linear shallow water and linear dispersive wave models demonstrate that the 3‐D NS model simulates the dispersion of very short wavelength components more accurately than the 2‐D models. This improved accuracy is achieved using only a small number (three to five) of vertical layers in the mesh. The numerical error in the wave velocity compared with the linear wave theory is less than 3% up to kH = 40, where k is the wave number and H is the sea depth. The same 2‐D and 3‐D models are also used to simulate two earthquake‐generated tsunamis off the coast of Japan: the 2004 off Kii peninsula and the 2011 off Tohoku tsunamis. The linear dispersive and NS models showed good agreement in the leading waves but differed especially in their near‐source, short wavelength dispersive wave components. This is consistent with the results from earlier tests, suggesting that the 3‐D NS simulations are more accurate. The computational performance on a parallel computer showed good scalability up to 512 cores. By using a combination of unstructured meshes and high‐performance computers, highly accurate 3‐D tsunami simulations can be conducted in a practical timescale.
Biodistribution of 99mTc‐sunitinib as a potential radiotracer for tumor hypoxia imaging
Authors: Sakr T. M. , El‐Safoury D. M. , Awad Gehanne A. S. , Motaleb M. A.
Published: May 2013

Tyrosine kinases are groups of enzymes, which are over‐expressed in solid tumor cells, representing good targets for different drugs such as sunitinib (N‐[2‐(diethylamino)ethyl]‐5‐{[(3Z)‐5‐fluoro‐2‐oxo‐2,3‐dihydro‐1H‐indol‐3‐ylidene]methyl}‐2,4‐dimethyl‐1H‐pyrrole‐3‐carboxamide). The aim of this work was to design and synthesize 99mTc‐sunitinib radiotracer and to study its tumor binding specificity as a novel selective radiopharmaceutical for tumor hypoxia imaging. The in vivo biodistribution of 99mTc‐sunitinib in tumor bearing mice showed high target/non‐target (T/NT) ratio (T/NT ~ 3 at 60 min post injection). This preclinical high biological accumulation in tumor cells suggests that 99mTc‐sunitinib is ready to go through the clinical trials as a potential selective radiotracer able to image tumor hypoxia.
Molecular epidemiology of JCV genotypes in patients and healthy subjects from Northern Italy
Authors: Zanotta Nunzia , Delbue Serena , Rossi Tatiana , Pelos Giorgio , D'Agaro Pierlanfranco , Monasta Lorenzo , Ferrante Pasquale , Comar Manola
Published: May 2013

Very little is known about JCV infection and genotype distribution with respect to the different demographic and clinical characteristics of the Italian population. A cross‐sectional study was carried out on the prevalence of JCV genotypes in 323 Caucasian subjects (mean age: 37.5 years, range: 2–70 years). Urine samples from 200 immunocompromised patients, including patients affected by Multiple Sclerosis (MS), Human Immunodeficiency Virus (HIV), colon cancer, inflammatory diseases and Progressive Multifocal Leukoencephalopathy (PML), and 123 immunocompetent individuals were tested by quantitative real time PCR. Sequencing of the JCV viral protein 1 (VP1) and transcriptional control region (TCR) was performed. In this series, the overall prevalence of JCV excretion was 32.8% without significant differences between males and females. JCV was detected in 39.5% of patients and in 22% of healthy individuals (P = 0.004). The most prevalent JCV genotype excreted was genotype 1 (69.8%), followed by genotype 2 (22.6%) and genotype 4 (7.5%). Distribution of genotypes between patients and healthy subjects showed a statistically significant difference for the type 1 compared to the other variants (P < 0.01). Of note, JCV genotype 2 was found to be associated to young patients (P = 0.0001) and to patients treated with immunomodulator drugs (P = 0.0001), but not to PML subjects. The non‐pathogenic archetype IIS (singular, insert) form was present in all JCV strains detected. This result allows to hypothesize a possible JCV genotype selection in response to pressure by immunomodulatory drugs. J. Med. Virol. 85:1286–1292, 2013. © 2013 Wiley Periodicals, Inc.
Serum apolipoprotein B‐100 concentration predicts the virological response to pegylated interferon plus ribavirin combination therapy in patients infected with chronic hepatitis C virus genotype 1b
Authors: Yoshizawa Kai , Abe Hiroshi , Aida Yuta , Ishiguro Haruya , Ika Makiko , Shimada Noritomo , Tsubota Akihito , Aizawa Yoshio
Published: May 2013

Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg‐IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity‐determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg‐IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b‐infected patients to investigate whether the response to Peg‐IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B‐100 (apoB‐100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB‐100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046–2.456), alpha‐fetoprotein (OR, 0.764; 95% CI, 0.610–0.958), non‐wild‐type ISDR (OR, 5.617; 95% CI, 1.274–24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225–114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3‐log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB‐100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB‐100 concentrations could predict virological response to Peg‐IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype. J. Med. Virol. 85:1180–1190, 2013. © 2013 Wiley Periodicals, Inc.
Epidemiological and molecular analyses of a non‐seasonal outbreak of acute icteric hepatitis E in Bangladesh
Authors: Harun‐Or‐Rashid Mohammad , Akbar Sheikh Mohammad Fazle , Takahashi Kazuaki , Al‐Mahtab Mamun , Khan Mohammad Sakirul Islam , Alim Mohammad Abdul , Ekram A. R. M. Saifuddin , Khan Mohammad Mahbubur Rahman , Arai Masahiro , Mishiro Shunji
Published: May 2013

Acute hepatitis due to hepatitis E virus (HEV) is endemic in Bangladesh, but its epidemiological characteristics and virological features remain obscure. An outbreak of acute icteric hepatitis E occurred in Rajshahi, Bangladesh during 2010 when 200 patients with visible jaundice visited physicians within a period of 1 month (January–February). Clinical and epidemiological data were collected from these patients using questionnaires. Nucleic acids were isolated from 15 patients who were selected at random to ascertain their HEV genotypes. Near‐complete nucleotide sequences of the HEV genome were detected in two patients and partial ORF2 regions in the other 13 patients. All patients tested positive for IgM antibodies to HEV but negative for other hepatitis viruses. Most patients were icteric and complained of vomiting, fever, itching, and abdominal pain. All 15 HEV sequences formed a single cluster within genotype 1a. Two of the 7,186‐nt HEV sequences were 99.8% identical. This is the first study to report the clinical, epidemiological, and molecular characterization of an outbreak of acute hepatitis E in Bangladesh. J. Med. Virol. 85:1369–1376, 2013. © 2013 Wiley Periodicals, Inc.
The Crucial Role of Diffusional Limitations in Controlled Radical Polymerization
Authors: D'hooge Dagmar R. , Reyniers Marie‐Françoise , Marin Guy B.
Published: May 2013

The importance of diffusional limitations in controlled radical polymerization at laboratory scale and in homogeneous medium is highlighted using different diffusion models. In particular, a coupled ‘parallel’ encounter pair model is introduced which allows a rigorous description of the influence of diffusional limitations on the activation/deactivation process. Diffusional limitations on termination have a significant influence, whereas those on the activation/deactivation process can disturb the regular growth pattern at high conversion if the mediating agent is a sufficiently bulky species. Diffusional limitations on initiation are only important in case radical initiator is still present at high conversion.
Unedited in vivo detection and quantification of γ‐aminobutyric acid in the occipital cortex using short‐TE MRS at 3 T
Authors: Near Jamie , Andersson Jesper , Maron Eduard , Mekle Ralf , Gruetter Rolf , Cowen Philip , Jezzard Peter
Published: May 2013

Short‐TE MRS has been proposed recently as a method for the in vivo detection and quantification of γ‐aminobutyric acid (GABA) in the human brain at 3 T. In this study, we investigated the accuracy and reproducibility of short‐TE MRS measurements of GABA at 3 T using both simulations and experiments. LCModel analysis was performed on a large number of simulated spectra with known metabolite input concentrations. Simulated spectra were generated using a range of spectral linewidths and signal‐to‐noise ratios to investigate the effect of varying experimental conditions, and analyses were performed using two different baseline models to investigate the effect of an inaccurate baseline model on GABA quantification. The results of these analyses indicated that, under experimental conditions corresponding to those typically observed in the occipital cortex, GABA concentration estimates are reproducible (mean reproducibility error, <20%), even when an incorrect baseline model is used. However, simulations indicate that the accuracy of GABA concentration estimates depends strongly on the experimental conditions (linewidth and signal‐to‐noise ratio). In addition to simulations, in vivo GABA measurements were performed using both spectral editing and short‐TE MRS in the occipital cortex of 14 healthy volunteers. Short‐TE MRS measurements of GABA exhibited a significant positive correlation with edited GABA measurements (R = 0.58, p < 0.05), suggesting that short‐TE measurements of GABA correspond well with measurements made using spectral editing techniques. Finally, within‐session reproducibility was assessed in the same 14 subjects using four consecutive short‐TE GABA measurements in the occipital cortex. Across all subjects, the average coefficient of variation of these four GABA measurements was 8.7 ± 4.9%. This study demonstrates that, under some experimental conditions, short‐TE MRS can be employed for the reproducible detection of GABA at 3 T, but that the technique should be used with caution, as the results are dependent on the experimental conditions. Copyright © 2013 John Wiley & Sons, Ltd.
A new insight into the impact of different proteases on SILAC quantitative proteome of the mouse liver
Authors: Ma Jie , Li Wenbo , Lv Yongzhuang , Chang Cheng , Wu Songfeng , Song Lei , Ding Chen , Wei Handong , He Fuchu , Jiang Ying , Zhu Yunping
Published: May 2013

In this study, we examined the use of multiple proteases (trypsin, LysC, tandem LysC/trypsin) on both protein identification and quantification in the Lys‐labeled SILAC mouse liver. Our results show that trypsin and tandem LysC/trypsin digestion are superior to LysC in peptides and protein identification while LysC shows advantages in quantification of Lys‐labeled proteins. Combination of experimental results from different proteases (LysC and trypsin) enabled a significant increase in the number of identified protein and protein can be quantified. Thus, taking advantage of the complementation of different protease should be a good strategy to improve both qualitative and quantitative proteomics research.
Temperature responsive copolymers of N‐vinylcaprolactam and di(ethylene glycol) methyl ether methacrylate and their interactions with drugs
Authors: Zuber Stefanie , Landfester Katharina , Crespy Daniel , Popa Ana‐Maria
Published: May 2013

Poly(N‐vinylcaprolactam) (PVCL) and poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) are well known for their thermoresponsive behavior in aqueous solutions. Indeed, they display lower critical solution temperatures (LCST) in the physiological range, which makes them interesting for biomedical devices and use in drug delivery systems. Homopolymers of N‐vinylcaprolactam and di(ethylene glycol) methyl ether methacrylate as well as copolymers thereof were synthesized by solution and direct miniemulsion polymerizations. The cloud points of the copolymers in aqueous solution were investigated as a function of temperature, comonomer ratio, and in the presence of model pharmaceutical ingredients. By variation of the comonomer ratio, it was possible to control the cloud point temperature between 26 and 35 °C, which was found to be beneficial to attenuate the effect of the drugs that also altered the cloud points. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3308–3313
Viscoelastic phase diagram of fluorinated and grafted polymer films and proton‐exchange membranes for fuel cell applications
Authors: Leterrier Yves , Thivolle Jérémy , Oliveira Fabiane , Månson Jan‐Anders , Gubler Lorenz , Ben youcef Hicham , Bonorand Lukas , Scherer Günther
Published: May 2013

The influence of temperature and moisture activity on the viscoelastic behavior of fluorinated membranes for fuel cell applications was investigated. Uncrosslinked and crosslinked ethylene tetrafluoroethylene (ETFE)‐based proton‐conducting membranes were prepared by radiation grafting and subsequent sulfonation and their behavior was compared with ETFE base film and commercial Nafion® NR212 membrane. Uniaxial tensile tests and stress relaxation tests at controlled temperature and relative humidity (RH) were carried out at 30 and 50 °C for 10% < RH < 90%. Grafted films were stiffer and exhibited stronger strain hardening when compared with ETFE. Similarly, both uncrosslinked and crosslinked membranes were stiffer and stronger than Nafion®. Yield stress was found to decrease and moisture sensitivity to increase on sulfonation. The viscoelastic relaxation of the grafted films was found to obey a power‐law behavior with exponent equal to −0.04 ± 0.01, a factor of almost 2 lower than ETFE, weakly influenced by moisture and temperature. Moreover, the grafted films presented a higher hygrothermal stability when compared with their membranes counterparts. In the case of membranes, a power‐law behavior at RH < 60% was also observed. However, a markedly different behavior was evident at RH > 60%, with an almost single relaxation time exponential. An exponential decrease of relaxation time with RH from 60 s to 10 s was obtained at RH ≥ 70% and 30 °C. The general behavior of grafted films observed at 30 °C was also obtained at 50 °C. However, an anomalous result was noticed for the membranes, with a higher modulus at 50 °C when compared with 30 °C. This behavior was explained by solvation of the sulfonic acid groups by water absorption creating hydrogen bonding within the clusters. A viscoelastic phase diagram was elaborated to map critical conditions (temperature and RH) for transitions in time‐dependent behavior, from power‐law scaling to exponential scaling. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1139–1148
Recent advances in the use of the quartz crystal microbalance with dissipation for the study of the collapse of polyelectrolyte brushes
Authors: Moya Sergio Enrique , Irigoyen Joseba
Published: May 2013

The combination of Quartz Crystal Microbalance and ellipsometry to quantify polyelectrolyte brush hydration and how this impacts on the study of brush collapse is discussed here. Recent articles study collapse after quantifying hydration of poly (2‐methacryloyloxy ethyl trimethyl ammonium chloride) (PMETAC) and poly(potassium sulfo propyl methacrylate). Water lost increases with ionic strength but only a 50% of their water content is lost at 1 M NaCl. For PMETAC brushes the exchange of Cl− by ClO4− is more effective, causing 50% lost at 0.05 M. The hydration and water lost for PMETAC brushes synthesized from thiol monolayers with variable density of initiators from 1 to 100% show that the freely entrapped water of the brushes is around a 10%. Irrespectively of initiator percentage the brush does not lose at 1 M NaCl more than 50% of the original water content. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1068–1072
Exemption from prescription charges and prevalence of fraud
Authors: Chaplin Steve
Published: May 2013

A guide to when patients are exempt from paying prescription charges in England and the level of fraud.
Medicines optimisation reviews in patients taking PPIs
Authors: Spencer Mark
Published: May 2013

How targeting patients for medication review based on use of PPIs resulted in improved safety, reduced costs and improved patient satisfaction.
Ferumoxytol (Rienso): new intravenous iron preparation
Authors: Chaplin Steve , Brookes Matthew
Published: May 2013

Ferumoxytol (Rienso) is a new intravenous iron formulation for the treatment of iron‐deficiency anaemia in chronic kidney disease. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse events and Dr Matthew Brookes discusses its place in the treatment of iron‐deficiency anaemia.
Developments in the diagnosis and management of asthma
Authors: Thomson Neil C
Published: May 2013

Despite receiving asthma therapy, many patients have poorly controlled symptoms and experience frequent exacerbations. Our Drug review focusses on key points and recent advances in the diagnosis and management of asthma, followed by a review of the prescription data and sources of further information.
Dymista: first steroid plus antihistamine nasal spray
Authors: Chaplin Steve
Published: May 2013

Dymista is a new nasal spray containing fluticasone and azelastine. Our New products review considers the trial evidence for its efficacy and side‐effects and suggests its potential role in the treatment of allergic rhinitis.
Z drugs: their properties and use in treating insomnia
Authors: Chaplin Steve , Wilson Sue , Nutt David
Published: May 2013

Steve Chaplin, Sue Wilson and Professor David Nutt provide an overview of the properties of Z drugs and how they compare in the short‐term treatment of insomnia.
Invest to save: provision of a medicines management service
Authors: Bevan Beryl , Ibrahim Mohammed , Lane Vanessa
Published: May 2013

The authors describe an invest‐to‐save scheme involving three London PCTs with the aim of saving between £5 and £7 for every £1 invested in pharmacists working in practices to make savings on prescribing.
Inclusion of NICE guidance into local formularies
Authors: Hill Adam
Published: May 2013

Recent guidance from NICE requires that NICE‐approved medicines must be automatically included into local formularies.
The ‘Stayers’: Dynamics of Lifelong Sedentary Behaviour in an Urban Context
Authors: Hjälm Anna
Published: May 2013

Migration has, over the years, attracted infinitely more attention than non‐migration or staying. In this paper, the focus is set on those individuals who have demonstrated lifelong sedentary behaviour. The aim of the study is to scrutinise the ways in which people who have lived their entire life in the same place make sense of their sedentary, or immobile, lifestyle. The study builds upon semi‐structured interviews, conducted in 2011–2012, with persons aged 60 years and older who were living in an urban area in northern Sweden. Initially, the different definitions of staying are highlighted by the informants, and the flexibility of the concept is addressed. The findings indicate that even though reasons for staying might be harder to articulate than reasons for migration, the explanations given are still complex and multi‐layered. The findings also suggest that the decision to stay is not a choice made once and then never renegotiated but rather a decision made over and over again. Furthermore, the significance of intertwined lives, both with living relatives and with preceding and following generations, is analysed. Finally, the results from the study challenge earlier pictures of stayers – where they were portrayed as stigmatised – and highlight the need to consider staying, as well as moving, as a conscious choice in order that we may gain a better understanding of the dynamics of staying. Copyright © 2013 John Wiley & Sons, Ltd.
Sintering without grain growth for Mg2Si thermoelectric devices
Authors: Nakamura Shigeyuki , Mori Yoshihisa , Takarabe Ken'ichi
Published: May 2013

Mg2Si is expected as a candidate for environmental‐friendly material of a thermoelectric device. Nano‐crystallization is considered to be one of the most effective approaches to improve thermoelectric property. If grain grows up during sintering, we are afraid not to obtain nano‐effect. We have, therefore, investigated grain growth during sintering. We have found that grain growth is not observed if particle size distribution of starting powder is relatively uniform. On the contrary, grain growth is observed if it is relatively not uniform. We have concluded this may be due to un‐uniformly distributed current during sintering. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Forecast sensitivity to observations in the Met Office Global numerical weather prediction system
Authors: Lorenc Andrew C. , Marriott Richard T.
Published: May 2013

An adjoint‐based method for calculating the impacts of observations in the Met Office's global four‐dimensional variational assimilation (4D‐Var) system is documented. Our approach is novel, as we seek from the outset a linearized approximation to partition the finite impact from a batch of observations, but our method and results are very similar to those of other systems. The large beneficial impacts measured for satellite radiances and radiosonde soundings in our system are interesting results. We also identify areas for potential improvement, such as the assimilation of Northern Hemisphere stratospheric satellite radio occultation (GPSRO) observations, polar atmospheric motion vectors and tropical cyclone (TC) bogus observations synthesized automatically from tropical cyclone warning centre advisory messages.

We use a toy model to explain why only just over 50% of observations improve the forecast. Growing modes, observational errors and errors in the verifying forecast contribute approximately equally and we suggest that our necessarily imperfect knowledge of background‐error statistics also contributes.