bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a highly sensitive method for the determination of abiraterone in rat and human plasma by LC‐MS/MS‐ESI: application to a pharmacokinetic study
Authors: Gurav Sandip , Punde Ravindra , Farooqui Junaid , Zainuddin Mohd , Rajagopal Sriram , Mullangi Ramesh
Published: October 2011

A highly sensitive, rapid assay method has been developed and validated for the estimation of abiraterone (ART) in rat and human plasma with liquid chromatography coupled to tandem mass spectrometry and electrospray ionization in the positive‐ion mode. The assay procedure involves extraction of ART and phenacetin (internal standard, IS) from rat and human plasma with a simple protein precipitation extraction process. Chromatographic separation was achieved using an isocratic mobile (10 mm ammonium acetate:acetonitrile, 10:90, v/v) at a flow‐rate of 0.70 mL/min on an Atlantis dC18 column maintained at 40 °C with a total run time of 3.5 min. The MS/MS ion transitions monitored were 350.3 → 156.0 for ART and 180.2 → 110.1 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.20 ng/mL and the linearity range extended from 0.20 to 201 ng/mL. The intra‐ and inter‐day precisions were in the ranges 2.39–10.4 and 4.84–9.53% in rat plasma and 3.82–10.8 and 6.97–8.94% in human plasma. Copyright © 2011 John Wiley & Sons, Ltd.
Competitive no, co and hydrocarbon oxidation reactions over a diesel oxidation catalyst
Authors: AL‐Harbi Meshari , Hayes Robert , Votsmeier Martin , Epling William S.
Published: October 2011

The oxidation of NO, CO and hydrocarbons (HC) individually, in mixtures, and with NO2 were investigated over a monolith‐supported Pt/Al2O3 catalyst under oxidising conditions. Although competitive adsorption and inhibition by other species on oxidation reactions is a relatively well‐known phenomenon, this study represents a more comprehensive examination of such effects between key components in vehicle exhaust gases. NO2 was completely reduced by CO and C3H6, under NO2 limited conditions, at temperatures as low as 110°C and at temperatures above 140°C with dodecane and m‐xylene. NO2 was then again observed once the extent of oxidation of the other species by oxygen was significant. Under the conditions tested, NO, CO and HC oxidation was inhibited by NO2 in the feed gas mixture. HC were also found to inhibit the oxidation of NO and other HC species due to site adsorption competition. For CO, HC did not change the onset of oxidation, but did inhibit the extent after their light off began. At low temperatures, CO was initially found to inhibit NO oxidation, but at higher temperatures, once CO oxidation was significant, CO promoted NO conversion to NO2. The observed inhibition effects of the different gases on HC oxidation were not additive, indicating one species would cause inhibition, but once its inhibition ended, another species could still then cause inhibition. The combined effect of C3H6, NO and NO2 on CO conversion was found to be additive. This is because CO oxidation started prior C3H6. © 2011 Canadian Society for Chemical Engineering
Utilisation of immobilised activated sludge for the biosorption of chromium (VI)
Authors: Shams Khorramabadi Ghodratallah , Darvishi Cheshmeh Soltani Reza , Rezaee Abbas , Khataee Ali R. , Jonidi Jafari Ahmad
Published: October 2011

The objective of this investigation was to study the biosorption of Cr (VI) on immobilised activated sludge (IAS) and calcium alginate (CA) using batch system. The optimal pH for Cr (VI) biosorption by IAS and CA was 2.0 and 4.0, respectively. Equilibrium was attained at approximately 120 min for both biosorbents. For both biosorbents, the equilibrium biosorption capacity (mg/g) increased as the initial metal ion concentration increased and the concentration of biosorbent decreased.

The rate of biosorption onto IAS and pure CA (as mg/g) increased from 5.02 to 87.66 and 4.97 to 79.09 as the concentration of Cr (VI) ions increased from 10 to 1000 mg/L, respectively. In the case of biosorbent concentration, as the concentration of IAS and pure CA increased from 1 to 20 g/L, the equilibrium uptake (qe) decreased from 21.33 to 1.57 and 19.41 to 1.38 mg/g, respectively. The biosorption data showed that the Langmuir model was more suitable than the Freundlich model. Also, the results indicated that the pseudo‐second order model was the most suitable for Cr (VI) biosorption onto IAS and CA. © 2011 Canadian Society for Chemical Engineering
Cathepsin B cleavable novel prodrug Ac‐Phe‐Lys‐PABC‐ADM enhances efficacy at reduced toxicity in treating gastric cancer peritoneal carcinomatosis
Authors: Shao Li‐Hua , Liu Shao‐Ping , Hou Jin‐Xuan , Zhang Yan‐Hua , Peng Chun‐Wei , Zhong Yan‐Jun , Liu Xiong , Liu Xiu‐Li , Hong Ya‐Ping , Firestone Raymond A. , Li Yan
Published: October 2011

BACKGROUND:

Doxorubicin (Adriamycin) is effective in gastric cancer treatment, but with severe dose‐dependent toxicities. A novel prodrug of doxorubicin (Ac‐Phe‐Lys‐PABC‐ADM) is designed to deliver free doxorubicin relying on cathepsin B and reduce side effects. The authors examined the antitumor effect and toxicities of Ac‐Phe‐Lys‐PABC‐ADM against gastric cancer peritoneal carcinomatosis.

METHODS:

SGC‐7901 gastric cancer cell line was used for the study. The in vitro study investigated the effects of doxorubicin and Ac‐Phe‐Lys‐PABC‐ADM on cell growth dynamics and cell cycle. The in vivo study investigated the efficacy and toxicity of Ac‐Phe‐Lys‐PABC‐ADM on a nude mice model of peritoneal carcinomatosis, with doxorubicin as positive control.

RESULTS:

In the in vitro study, Ac‐Phe‐Lys‐PABC‐ADM had a lower dose‐dependent inhibitory effect on SGC‐7901 cells. In the in vivo study of control, doxorubicin, and Ac‐Phe‐Lys‐PABC‐ADM groups, the median experimental peritoneal carcinomatosis indexes were 6, 1.5, and 1, respectively (P = .004); the body weights were 24.32 ± 1.40 g, 18.40 ± 2.97 g, and 23.61 ± 0.80 g, respectively (P = .000). Biochemical studies showed that Ac‐Phe‐Lys‐PABC‐ADM had significantly lower toxicities on the bone marrow, liver, kidney, and particularly heart. Histopathological studies of the control, doxorubicin, and Ac‐Phe‐Lys‐PABC‐ADM groups found significant myocardium toxicities in 3, 7, and 4 animals, respectively.

CONCLUSIONS:

Ac‐Phe‐Lys‐PABC‐ADM could be an effective molecular targeting drug to treat gastric cancer peritoneal carcinomatosis with enhanced efficacy and reduced toxicity. Cancer 2011. © 2011 American Cancer Society.
Numerical simulation of a thermodynamically consistent four‐species tumor growth model
Authors: Hawkins‐Daarud Andrea , van der Zee Kristoffer G. , Tinsley Oden J.
Published: October 2011

In this paper, we develop a thermodynamically consistent four‐species model of tumor growth on the basis of the continuum theory of mixtures. Unique to this model is the incorporation of nutrient within the mixture as opposed to being modeled with an auxiliary reaction‐diffusion equation. The formulation involves systems of highly nonlinear partial differential equations of surface effects through diffuse‐interface models. A mixed finite element spatial discretization is developed and implemented to provide numerical results demonstrating the range of solutions this model can produce. A time‐stepping algorithm is then presented for this system, which is shown to be first order accurate and energy gradient stable. The results of an array of numerical experiments are presented, which demonstrate a wide range of solutions produced by various choices of model parameters.Copyright © 2011 John Wiley & Sons, Ltd.
Do infants show a cortisol awakening response?
Authors: Bright Melissa A. , Granger Douglas A. , Frick Janet E.
Published: October 2011

Upon awakening from sleep, combined processes of deactivation of the hippocampus and activation of suprachiasmatic nucleus result in a marked increase in cortisol release from structures within the hypothalamic–pituitary–adrenal axis. This phenomenon, termed the cortisol awakening response (CAR), has been studied extensively in adults. In the current study, we examine this phenomenon for the first time in infancy. Saliva samples were collected by 32 mothers from themselves and their infants (13 males; 7.8–17.4 months of age) at the infant's AM waking (and 30 min later), and upon waking from the infant's first nap (and 30 min later). In contrast to what has been observed with the CAR in adults, cortisol levels declined from AM waking to 30 min post‐waking. Moreover, cortisol levels did not significantly rise or fall following naps. Consistent with prior research, both group‐level and dyadic‐level analyses showed that cortisol levels for mother–infant dyads were associated. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 736–743, 2012.
Effect of CCL2 antisense oligodeoxynucleotides on bacterial translocation and subsequent sepsis in severely burned mice orally infected with Enterococcus faecalis
Authors: Shigematsu Kenji , Kogiso Mari , Kobayashi Makiko , Herndon David N. , Suzuki Fujio
Published: October 2011

Severely burned mice are susceptible to sepsis stemming from Enterococcus faecalis translocation due to the impaired generation of M1 macrophages (M1Mϕs) in local translocation sites. In our previous studies, CCL2 has been characterized as a major effector molecule on the burn‐associated generation of M2Mϕs, an inhibitor cell type for resident Mϕ conversion into M1Mϕs. In this study, we tried to protect burned mice orally infected with E. faecalis utilizing CCL2 antisense oligodeoxynucleotides (ODNs). We show that M2Mϕs in mesenteric lymph nodes (MLNs) were not demonstrated in burned mice treated with CCL2 antisense ODNs. M1Mϕs were not induced by heat‐killed E. faecalis from resident Mϕs transwell‐cultured with mesenteric lymph node macrophages (MLN‐Mϕs) from burned mice, while M1Mϕs were induced by the same antigen from resident Mϕs transwell‐cultured with Mϕs which were isolated from burned mice treated with CCL2 antisense ODNs. Bacterial growth in MLNs was shown in burned mice orally infected with a lethal dose of E. faecalis. However, after the same infection, sepsis did not develop in burned mice treated with CCL2 antisense ODNs. These results indicate that bacterial translocation and subsequent sepsis are controlled in burned mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing CCL2 antisense ODNs.
Monocytes link atherosclerosis and cancer
Authors: Pittet Mikael J. , Swirski Filip K.
Published: October 2011

From many perspectives, cardiovascular diseases and cancers are fundamentally different. On the one hand, atherosclerosis is a disease of lipid accumulation driven by diet and lifestyle, whereas cancer is an attack “from within” driven by mutations. Nevertheless, studies over the past 20 years have forced us to re‐evaluate such a view. We are learning that, among other factors, the immune system is indispensable for the development and progression of both diseases. Its components are not only reactive but can also orchestrate both tumor and atherosclerotic lesion growth. In this Viewpoint, we explore how monocytes, which are key constituents of the immune system, forge links between cardiovascular diseases and cancers.
Cancer‐promoting tumor‐associated macrophages: New vistas and open questions
Authors: Mantovani Alberto , Germano Giovanni , Marchesi Federica , Locatelli Marco , Biswas Subhra K.
Published: October 2011

Tumor‐associated macrophages (TAMs) are key components of the tumor macroenvironment. Cancer‐ and host cell‐derived signals generally drive the functions of TAMs towards an M2‐like polarized, tumor‐propelling mode; however, when appropriately re‐educated. TAMs also have the potential to elicit tumor destructive reactions. Here, we discuss recent advances regarding the immunobiology of TAMs and highlight open questions including the mechanisms of their accumulation (recruitment versus proliferation), their diversity and how to best therapeutically target these cells.
CE analysis and molecular characterisation of depurinated DNA samples
Authors: Fattorini Paolo , Marrubini Giorgio , Sorçaburu‐Cigliero Solange , Pitacco Paola , Grignani Pierangela , Previderè Carlo
Published: October 2011

A DNA sample was partially degraded by scalar heat‐acid treatments to study the extent of apurinic–apyrimidinic (A‐P) lesions produced along the molecule. A CE‐UV method allowed us to measure the rate of depurination at pH 5.0 and 70°C which was calculated to be 5.41×10−6 s−1 for adenine and 6.27×10−6 s−1 for guanine. CE identified depurination on treated samples when it occurred with a loss of >4% of the basic moieties. The molecular features of the A‐P enriched samples were investigated by using molecular assays (agarose gel electrophoresis, UV spectrophotometry and quantitative PCR) and the consistency of the results of the STR typing were compared with the degree of depurination of the PCR template. The treated DNA samples showed molecular features such as fragmentation, altered OD260/OD280 ratios and decreased ability of the quantitative PCR to synthesise the human target, related to the severity of depurination. A satisfactory correlation between the degree of damage and the amount of residual PCR‐sensitive target sequences was also demonstrated (r2=0.9717). The conventional and mini‐STR typing of the samples showed that the genetic outcome was influenced by a depurination damage that exceeded 4% when locus drop‐outs and artefactual PCR results were evident. As the success of STR typing depends on the integrity of the DNA recovered from the samples, the CE‐UV, physical and molecular assays described here are proposed as a set of useful methods in the analysis of certain forensic and clinical samples, for a critical evaluation of the outcome of the genetic testing.
Blinded study determination of high sensitivity and specificity microchip electrophoresis‐SSCP/HA to detect mutations in the p53 gene
Authors: Hestekin Christa N. , Lin Jennifer S. , Senderowicz Lionel , Jakupciak John P. , O'Connell Catherine , Rademaker Alfred , Barron Annelise E.
Published: October 2011

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single‐strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA‐based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor‐intensive, time‐consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here, we demonstrate the first blinded study using microchip electrophoresis (ME)‐SSCP/HA. We demonstrate the ability of ME‐SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5–9 in a blinded study in an analysis time of <10 min.
Copper removal from diluted cyanide wastewater by electrolysis
Authors: Pombo Felipe Ramalho , Dutra Achilles Junqueira Bourdot
Published: October 2011

Metal electroplating processes can use cyanide as reagent, generating large amounts of industrial wastewaters containing cyanide and heavy metals. These wastewaters are usually treated by chemical precipitation, generating toxic slugs consisting of metallic hydroxides and sulfides. This work aims at developing an electrolytic cell in order to recover the copper from diluted solutions simulating the wastewaters from the rinsing of copper electroplated disks, for coins manufactured in the Brazilian Mint, and, as a secondary target, to oxidize the free cyanide at the same time. The influence of some process variables was evaluated by thermodynamic and voltammetric studies. The solution flow rate and temperature increase favor copper deposition. It was also verified, by voltammetric and electrolytic tests, that the presence of copper oxide on the anode surface catalyses cyanide oxidation. The best results were obtained for a temperature of 50°C, a solution flow rate of 0.37 mL/s, and after a 3‐h electrolysis, when the copper and free cyanide concentrations were, respectively, 0.70 and 0.08 mg/L, for an electric current of 1.5 A, and, respectively, less than 0.50 and 0.08 mg/L, for an electric current of 2.0 A. © 2011 American Institute of Chemical Engineers Environ Prog, 32: 52–59, 2013.
The various aspects of an ecological house
Authors: Hacene M.A. Boukli , Sari N.E. Chabane
Published: October 2011

The total energy balance sheet of Algeria of the year 2009, shows that final energy consumption is evaluated to 30.98 million TEP (ton oil equivalent) [1], and emphasizes an prevalence of the energy consumption of the sector of the households is more than 41% compared with 19% for the sector from industry and 33% for that of transport (Figure 1). In this article, we present an analysis of the different balances sheets of a house in urban environment. We identified the energy sources of losses, as well as the possibilities of energy saving for this building. The results obtained are compared with the same house but built with more respectful ecological materials of the environment, the aim is to have an exact idea over the made savings, the needs for heating and cooling, the CO2 rejection, the carbon balance sheet and the time of damping. © 2011 American Institute of Chemical Engineers Environ Prog, 32: 109–114, 2013.
Microscale biopitting by the endolithic lichen Verrucaria baldensis and its proposed role in mesoscale solution basin development on limestone
Authors: McIlroy de la Rosa John P. , Warke Patricia A. , Smith Bernard J.
Published: October 2011

Data are reported demonstrating the potential role of microscale morphologies, induced by endolithic lichen communities, specifically Verrucaria baldensis, in the initiation and development of mesoscale solution basin formation on limestone in the Burren, County Clare. A biophysical model is proposed outlining the different microscale stages leading to solution basin initiation with a progression from initial lichen colonization and growth, associated perithecial biopitting followed by biopit coalescence to form biotroughs, their subsequent enlargement and eventual incipient solution basin formation. This model provides one explanation for solution basin development as this end state may also be achieved through simple solutional means without biological input. The complexity of interactions at the lichen–rock interface are identified with emphasis on the spatial and temporal variability of these underlining the point that, as with macrotopographies at the landscape scale, rock surface microtopographies also reflect historical weathering legacies. Copyright © 2011 John Wiley & Sons, Ltd.
The uplink coverage‐capacity trade‐off in CDMA‐based multihop cellular networks
Authors: Dawy Zaher
Published: October 2011

We propose a novel design for incorporating multihop transmission in code division multiple access‐based cellular systems to notably reduce the intercell interference in the network. Different design issues are considered such as the allowed number of hops, type of relay stations, relay selection, accessing scheme and duplexing mode. Numerical derivations demonstrate that the intercell interference can be significantly reduced. Moreover, a link budget analysis is performed to obtain coverage‐capacity trade‐off results. It is shown that with single user detection receivers at base stations, gains up to 100% in area coverage are achieved with moderate to low user loads. Furthermore, by deploying advanced interference cancellation receivers at base stations to combat intracell interference, the proposed multihop‐based design achieves very high gains in pole capacity and area coverage per cell. Additionally, practical implementation issues are addressed, and results are compared between omni‐directional and three‐sector network structures. Copyright © 2011 John Wiley & Sons, Ltd.
Cooperative wireless personal area network systems with partial best relay selection
Authors: Tsiftsis Theodoros A. , Kim Kyeong Jin , Kwak Kyung Sup
Published: October 2011

In this letter, cyclically prefixed cooperative wireless personal area network systems with partial best relay selection are studied. From the partial relay selection method, an upper bound on the achievable average rate is obtained. Moreover, an asymptotic outage diversity gain is also analysed at a high signal‐to‐noise ratio. Monte Carlo simulations verify the obtained achievable average rate and outage diversity. Copyright © 2011 John Wiley & Sons, Ltd.
A stabilized finite element method for transient Navier–Stokes equations based on two local Gauss integrations
Authors: Jiang Yu , Mei Liquan , Wei Huiming
Published: October 2011

On the basis of two local Gauss integrations, a stabilized finite element method for transient Navier–Stokes equations is presented, which is defined by the lowest equal‐order conforming finite element subspace such as (or ) elements. The best algorithmic feature of our method is using two local Gauss integrations to replace projection operator. The diffusion term in these equations is discretized by using finite element method, and the temporal differentiation and advection terms are treated by characteristic schemes. Moreover, we present some numerical simulations to demonstrate the effectiveness, good stability, and accuracy properties of our method. Especially, the rate of convergence study tells us that the stability still keeps well when the Reynolds number is increasing. Copyright © 2011 John Wiley & Sons, Ltd.
Der Schildkröten‐Code
Authors: Unterstell Rembert
Published: October 2011

Wenn das Besondere das Allgemeine erhellt: Der Paläontologe Walter Joyce blickt mit spektakulären Funden tief in die Evolutions‐ und Erdgeschichte / Von Yale nach Tübingen
Alte Seuchen in neuem Licht
Authors: Bramanti Barbara
Published: October 2011

Pest und Cholera: Die Infektions‐Pandemien früherer Jahrhunderte haben tiefe Spuren in der Evolutionsgeschichte hinterlassen. Aus den Skeletten der Opfer gewinnen Forscher heute altes DNA‐Material, dessen Analyse Aufschluss gibt über Krankheitsvirulenz und ‐resistenz.
Improving power and robustness for detecting genetic association with extreme‐value sampling design
Authors: Chen Hua Yun , Li Mingyao
Published: October 2011

Extreme‐value sampling design that samples subjects with extremely large or small quantitative trait values is commonly used in genetic association studies. Samples in such designs are often treated as “cases” and “controls” and analyzed using logistic regression. Such a case‐control analysis ignores the potential dose‐response relationship between the quantitative trait and the underlying trait locus and thus may lead to loss of power in detecting genetic association. An alternative approach to analyzing such data is to model the dose‐response relationship by a linear regression model. However, parameter estimation from this model can be biased, which may lead to inflated type I errors. We propose a robust and efficient approach that takes into consideration of both the biased sampling design and the potential dose‐response relationship. Extensive simulations demonstrate that the proposed method is more powerful than the traditional logistic regression analysis and is more robust than the linear regression analysis. We applied our method to the analysis of a candidate gene association study on high‐density lipoprotein cholesterol (HDL‐C) which includes study subjects with extremely high or low HDL‐C levels. Using our method, we identified several SNPs showing a stronger evidence of association with HDL‐C than the traditional case‐control logistic regression analysis. Our results suggest that it is important to appropriately model the quantitative traits and to adjust for the biased sampling when dose‐response relationship exists in extreme‐value sampling designs. Genet. Epidemiol. 2011.  © 2011 Wiley Periodicals, Inc.35:823‐830, 2011
Stereoselective synthesis of functional dehydrophenylalanine derivatives from novel β‐chloroamino esters
Authors: Ould Elemine Brahim , Ennigrou Mohamed Rached , Besbes Rafâa
Published: October 2011

New functional dehydrophenylalanines3were prepared from β‐amino alcohols1in a two‐step reaction sequence. The synthesis involved chlorination of the starting amino alcohols1to afford the intermediate erythro β‐chloroamines2. Treatment of the latter with an appropriate base led to a highly stereoselective elimination reaction, giving the corresponding (E)‐dehydrophenylalanine derivatives3in high yields. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:91–98, 2012; View this article online atwileyonlinelibrary.com. DOI 10.1002/hc.20756
Molecular biology of adenoid cystic carcinoma
Authors: Liu Jia , Shao Chunbo , Tan Marietta L. , Mu David , Ferris Robert L. , Ha Patrick K.
Published: October 2011

Background

Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy, has attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving ACC is quite rudimentary, due to the infrequent nature of its occurrence.

Methods

An extensive literature review was performed on salivary gland ACCs and basic science research findings.

Results

This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies.

Conclusion

Although there have been many discoveries, much still remains unknown about this rare malignancy. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection
Authors: Suneetha Pothakamuri Venkata , Pischke Sven , Schlaphoff Verena , Grabowski Jan , Fytili Paraskevi , Gronert Anna , Bremer Birgit , Markova Antoaneta , Jaroszewicz Jerzy , Bara Christoph , Manns Michael P. , Cornberg Markus , Wedemeyer Heiner
Published: October 2011

Hepatitis E virus (HEV) infection is usually self-limited but may lead to acute hepatitis and rarely to fulminant hepatic failure. Persistent HEV infections have recently been described in organ transplant recipients receiving immunosuppressive medications, suggesting that HEV is controlled by adaptive immune responses. However, only few studies have investigated HEV-specific T-cell responses and immune correlates for the failure to clear HEV infection have not been established so far. We investigated T-cell responses against HEV in 38 subjects including anti-HEV-positive (exposed, n = 9) and anti-HEV-negative (n = 10) healthy controls, 12 anti-HEV-positive but HEV RNA-negative organ transplant recipients, and seven transplant recipients with chronic hepatitis E. Proliferation as well as cytokine production of CD4+ and CD8+ T cells was studied after stimulation with overlapping peptides spanning all proteins encoded by HEV-open reading frame (ORF)2 and HEV-ORF3. We show that (1) strong and multispecific HEV-specific T-cell responses are present in exposed healthy controls, and to a lesser extent also in recovered patients after transplantation; (2) that these responses are absent in patients with chronic hepatitis E but become detectable after viral clearance; and (3) that HEV-specific T-cell responses can be restored

in vitro

by blocking the PD-1 or CTLA-4 pathways. However, a combination of PD-1 and CTLA-4 blockade had no synergistic effects. We conclude that chronic hepatitis E is associated with impaired HEV-specific T-cell responses and suggest that enhancing adaptive cellular immunity against HEV might prevent persistent HEV infections.
Biochemical and Immunologic Effects of Rituximab in Patients With Primary Biliary Cirrhosis and an Incomplete Response to Ursodeoxycholic Acid
Authors: Tsuda Masanobu , Moritoki Yuki , Lian Zhe-Xiong , Zhang Weici , Yoshida Katsunori , Wakabayashi Kanji , Yang Guo-Xiang , Nakatani Toshio , Vierling John , Lindor Keith , Gershwin Eric M. , Bowlus Christopher L.
Published: October 2011

The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment.

Conclusion :

These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (Hepatology 2012)
Rapid and Facile Access to Indeno[1,2‐d]imidazoles via a Tandem AdditionCyclization Reaction
Authors: Alizadeh Abdolali , Zarei Ameneh , Rezvanian Atieh
Published: October 2011

A novel and tandem synthesis of highly functionalized tetrahydroindeno[1,2‐d]imidazole is described. A one‐pot reaction between a primary amine, an aryl isothiocyanate, and ninhydrin leads to highly substituted indeno[1,2‐d]imidazoles under solvent‐free conditions in excellent yields (Scheme). Their structures were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS) and by elemental analyses.
A New Germanium Complex Containing Chelating Pyridinecarboxylate Ligands: cis‐Dihydroxybis(pyridine‐2‐carboxylato‐κN1,κO2)germanium Hydrate (1 : 2) (cis‐[Ge(pyca)2(OH)2]⋅2 H2O)
Authors: Shestopalov Michael A. , Efremova Olga A. , Smolentsev Anton I. , Mironov Yuri V. , Fedorov Vladimir E. , Song Yong‐Won
Published: October 2011

A new germanium complex, cis‐[Ge(pyca)2(OH)2]⋅2 H2O (1; pyca=pyridine‐2‐carboxylato), was synthesized by the reaction of [Ge(acac)2Cl2] (acac=acetylacetonato=pentane‐2,4‐dionato) with potassium pyridine‐2‐carboxylate (Kpyca) in H2O/THF. According to the single‐crystal X‐ray diffraction analysis, each Ge‐atom of 1 is coordinated by two pyca ligands and two OH− groups (Fig. 1). These molecules are bonded to each other via a system of H‐bonds resulting in a sheet‐like structure (Fig. 2). The complex is decomposed during heating with stepwise mass loss and formation of GeO2 as final product (Fig. 3).
Spatial variation in transient water table responses: differences between an upper and lower hillslope zone
Authors: Haught D. R. W. , van Meerveld H. J.
Published: October 2011

To better understand storage‐runoff dynamics, transient groundwater responses were examined in one of the steep watersheds in British Columbia's coastal mountains. Streamflow and piezometric data were collected for 1 year to determine the spatial and temporal relations between transient groundwater levels and discharge. Correlations between piezometer responses and lag‐time analysis were used to identify and better understand runoff generation mechanisms in this watershed. Results showed a large spatial and temporal variation in transient water table dynamics and indicated that two distinct zones existed: a lower hillslope zone and an upslope zone. Each zone was characterized by very different water table responses. The upper hillslope was disconnected from the stream for the majority of time, suggesting that during most events, it does not directly contribute to streamflow. Piezometers in the lower hillslope zone showed hydrologically limited responses, suggesting rapid subsurface flow, likely through the many macropores and soil pipes. The lag time between peak streamflow and peak groundwater level decreased with increasing antecedent moisture conditions and was more variable for piezometers further away from the stream than for piezometers close to the stream. The study results indicate that a single storage‐runoff model is not appropriate for this steep watershed and that a two‐ or three‐compartment model would be more suitable. Copyright © 2011 John Wiley & Sons, Ltd.
Assessment of the environmental fate and ecotoxicity of N,N-diethyl-m-toluamide (DEET)
Authors: Weeks JA , Guiney PD , Nikiforov AI
Published: October 2011

N,N-diethyl-m-toluamide (DEET) is a key active ingredient in many insect repellents available commercially throughout the world. Owing to its popularity among consumers for nearly 30 years, considerable work conducted in the past has demonstrated—and continues to demonstrate—that human exposure to DEET poses no significant health risk to the general population. The results of several studies reported in this paper describe more recent work to understand the environmental fate of DEET, particularly in surface waters and soil, and the potential hazards to aquatic and terrestrial organisms. In summary, DEET enters the environment through several pathways: directly into air during spray application; to surface water from overspray and indirectly via wastewater treatment plant (WTTP) discharges (as a result of washing of skin and laundering of clothing); or to soil via overspray and application of treated sewage as an amendment. Multimedia environmental fate modeling predicts that DEET entering the environment is retained either in receiving waters (∼79%) or in soil (∼21%). Based on its physicochemical properties, DEET is expected to be moderately mobile in the soil column. In surface waters and soil, DEET degrades at a moderate to rapid rate (its half-life is measured in days to weeks). The small amounts of DEET retained in air are subject to rapid photo-oxidation via hydroxyl radical–mediated degradation or, if in droplet form, gravitational settling to soil or water. DEET does not interfere with ozone formation in the upper atmosphere. The bioaccumulation potential of DEET is low; it is neither a persistent, bioaccumulative toxicant nor a persistent organic pollutant. Among aquatic species, acute effect concentrations range between 4 and 388 mg/L. The chronic no-observed effect concentrations (NOEC) for daphnids and green algae range from approximately 0.5 to 24 mg/L. Measured concentrations of DEET in surface waters are several hundreds to thousands of times lower than the lowest NOEC measured, and thus the probability for adverse effects to environmental species is low. A separate paper by Aronson et al. (this issue) supports this conclusion by quantitatively exploring the risks to the aquatic environment using a combination of monitoring data and exposure modeling. Integr Environ Assess Manag 2012;8:120–134. © 2011 SETAC
Links between mutant p53 and genomic instability
Authors: Hanel Walter , Moll Ute M.
Published: October 2011

The tumor suppressor p53 has long been known to play a central role in maintaining a stable genome in the face of toxic insults through its role in promoting cell‐cycle checkpoints, DNA repair, and apoptosis. However, p53 null cells still retain some function of certain checkpoint and repair processes, reducing the genomic changes that otherwise would occur if these mechanisms were absent. Accumulating evidence suggests that mutant forms of p53 proteins may drastically perturb these residual genome‐stabilizing mechanisms through gain‐of‐function interactions with multiple proteins leading to a higher level of genomic instability than in p53 null cells. This review summarizes the current body of evidence that mutp53 plays a role in promoting various forms of genomic instability and provides an overview of current mechanistic proposals. J. Cell. Biochem. 113: 433–439, 2012. © 2011 Wiley Periodicals, Inc.
Mechanical forces‐induced human osteoblasts differentiation involves MMP‐2/MMP‐13/MT1‐MMP proteolytic cascade
Authors: Barthelemi Stéphane , Robinet Julien , Garnotel Roselyne , Antonicelli Frank , Schittly Estelle , Hornebeck William , Lorimier Sandrine
Published: October 2011

Matrix metalloproteinase (MMP) family proteins play diverse roles in many aspects of cellular processes such as osteoblastic differentiation. Besides, mechanical forces that occur in 3D collagen gel promote the osteoblastic phenotype and accelerate matrix mineralization. Although MMPs have been involved in bone differentiation, the proteolytic cascades triggered by mechanical forces are still not well characterized. In this study, we have investigated the contribution of both proteolytic cascades, MMP‐3/MMP‐1 and MMP‐2/MMP‐13/MT1‐MMP in the differentiation of human osteoblasts cultured in a floating type I collagen lattice (FL) versus an attached collagen lattice (AL). Compared to AL, contraction of human osteoblasts‐populated FL led to a fast (1 day) induction of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteoprotegerin (OPG), and Runx‐2 expression. At day 4, osteocalcin (OC) overexpression preceded the formation of calcium‐containing nodule formation as assessed by X‐ray analyses. MMP‐1 and MMP‐3 were produced to similar extent by cells cultured in FL and AL, whereas contraction of collagen lattices triggered both mRNA overexpression of MMP‐2, MMP‐13, and MT1‐MMP (i.e., MMP‐14), and their activation as evidenced by Western blotting or zymographic analyses. Down‐regulating MT1‐MMP expression or activity either by siRNA transfection or supplementation of culture medium with TIMP‐1 or TIMP‐2 highlighted the contribution of that enzyme in OC, ALP, and OPG expression. MMP‐2 and MMP‐13 were more directly involved in BSP expression. So, these results suggest that the main proteolytic cascade, MMP‐2/MMP‐13/MT1‐MMP, and more particularly, its initial regulator MT1‐MMP is involved in osteoblast differentiation through mechanical forces. J. Cell. Biochem. 113: 760–772, 2012. © 2011 Wiley Periodicals, Inc.
Immunotherapy for metastatic melanoma
Authors: Zito Christopher R. , Kluger Harriet M.
Published: October 2011

Melanoma has traditionally been considered an immunogenic tumor. A number of approaches have been studied for enhancement of antitumor immunity. The first cytokine approved for the treatment of metastatic melanoma, interleukin‐2, has resulted in prolonged responses in a small subset of patients, providing hope that immunotherapy might be useful for this disease. Ipilimumab, a monoclonal antibody to CTLA‐4, was recently approved and a number of other promising investigational approaches are currently being pursued. This manuscript discusses more recent advances in the treatment of melanoma employing a variety of immune‐enhancing approaches. J. Cell. Biochem. 113: 725–734, 2012. © 2011 Wiley Periodicals, Inc.
Efficient transgene expression from naked DNA delivered into an arterio‐venous fistula model for kidney dialysis
Authors: Globerman Anat S. , Chaouat Malka , Shlomai Zippora , Galun Eithan , Zeira Evelyn , Zamir Gideon
Published: October 2011

Background

Patients with kidney failure frequently require the formation of an arterio‐venous fistula (AVF) in which a vein is connected to an artery resulting in arterialization of the vein to allow adequate blood flow into an external ‘artificial kidney’. In most patients, neo‐intimal hyperplasia (NIH) ensues, causing narrowing and subsequent occlusion of the vein, leading to significant morbidity. The cellular events causing venous NIH may serve as ideal targets for molecular‐based therapies. However, therapeutic gene delivery into the vascular system is seriously impeded by problems related to the low efficacy and toxicity of targeted viral vector delivery.

Materials and methods

To explore the feasibility of a plasmid‐based vascular gene delivery system, we established a rat AVF model that develops NIH. Plasmids encoding for reporter or therapeutic genes were delivered into the blood vessels at the time or after AVF formation.

Results

Intra‐luminal injection of plasmid into the AVF resulted in extensive and long‐term reporter gene expression at the venous limb mainly at the site of NIH formation. Transgene expression was confined to endothelial cells and myofibroblasts that migrate inwards from the adventitia and form the NIH lesion. There was no detrimental tissue reaction to plasmid delivery, contrasting with the severe inflammatory response observed after adenovirus infection. Intra‐vascular delivery of a plasmid carrying the endothelial nitric oxide synthase gene resulted in sustained production of nitric oxide, previously shown to mitigate NIH formation.

Conclusions

These findings open the possibility of vascular transduction with naked DNA bearing therapeutic genes in areas prone to NIH to ameliorate vein graft pathologies using simple and clinically applicable vector delivery methods. Copyright © 2011 John Wiley & Sons, Ltd.
MR in hypertension
Authors: Roditi Giles
Published: October 2011

Hypertension is a common systemic disorder affecting the cardiovascular system and kidneys with important morbidity and mortality. However, hypertension is often thought of by radiologists as an “invisible” disease. The aim of this article is to first review hypertension first in terms of its diagnosis, epidemiology and clinical importance. Second, those causes of secondary hypertension that may be diagnosed with MRI techniques are described along with the effects of hypertension on the cardiovascular system and kidneys that are demonstrable with MRI with particular emphasis on renovascular disease. Lastly the use of integrated MRI protocols to evaluate the hypertensive patient and areas for future research are considered. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
Physiological oxygen level is critical for modeling neuronal metabolism in vitro
Authors: Zhu Jing , Aja Susan , Kim Eun‐Kyoung , Park Min Jung , Ramamurthy Santosh , Jia Junling , Hu Xueying , Geng Ping , Ronnett Gabriele V.
Published: October 2011

In vitro models are important tools for studying the mechanisms that govern neuronal responses to injury. Most neuronal culture methods employ nonphysiological conditions with regard to metabolic parameters. Standard neuronal cell culture is performed at ambient (21%) oxygen levels, whereas actual tissue oxygen levels in the mammalian brain range from 1% to 5%. In this study, we examined the consequences of oxygen level on the viability and metabolism of primary cultures of cortical neurons. Our results indicate that physiological oxygen level (5% O2) has a beneficial effect on cortical neuronal survival and mitochondrial function in vitro. Moreover, oxygen level affects metabolic fluxes: glucose uptake and glycolysis was enhanced at physiological oxygen level, whereas glucose oxidation and fatty acid oxidation were reduced. Adenosine monophosphate‐activated protein kinase (AMPK) was more activated in 5% O2 and appears to play a role in these metabolic effects. Inhibiting AMPK activity with compound C decreased glucose uptake, intracellular ATP level, and viability in neurons cultured in 5% O2. These data indicate that oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro. © 2011 Wiley Periodicals, Inc.
Growth and development of pepper are affected by humic substances derived from composted sludge
Authors: Azcona Iñaki , Pascual Inmaculada , Aguirreolea Jone , Fuentes Marta , García‐Mina José María , Sánchez‐Díaz Manuel
Published: October 2011

A greenhouse experiment was conducted to evaluate the effects of humic substances extracted from composted sewage sludge on growth, phenological development, and photosynthetic activity of pepper (Capsicum annuum L. cv. Piquillo) plants. Humic substances derived from composted sludge (HSS) were compared with those derived from leonardite (HSL). Two doses of both humic substances were assayed (200 and 500 mg C [L substrate]–1) and compared with a control (C). HSS showed higher nitrogen content and a higher percentage of aliphatic carbon, as well as a lower content of aromatic and phenolic carbon than HSL. HSS significantly increased plant dry‐matter production (up to 560%), plant height (86%–151%), and leaf area (436%–1397%) during the early stages of pepper development. Net photosynthesis and stomatal conductance increased in the treatments with HSS (up to 48% and 63%, respectively) at the vegetative stage. In addition, HSS accelerated the phenological development of pepper plants, reducing significantly the number of days to flowering and ripening, which occurred 12 and 14 d earlier than in control plants, respectively. In general, the treatments with HSS and HSL did not markedly affect chlorophyll and nutrient concentrations in the leaves. At maturity, only small differences in total fruit yield, number of fruits per plant, and fruit size were observed between amended and control plants. The results suggest that the mechanisms through which HSS affected plant growth and development were not associated with an improved nutrient uptake. Although the identity of the growth‐promoting factors remains to be found, the results suggest that they may be linked to the chemical structure of the humic substances.
Compost and phosphorus amendments for stimulating microorganisms and growth of ryegrass in a Ferralsol and a Luvisol
Authors: Khan Khalid Saifullah , Joergensen Rainer Georg
Published: October 2011

A greenhouse pot experiment was carried out to investigate the effects of different P‐fertilizer application forms (triple superphosphate [TSP], compost + TSP, TSP‐enriched compost) on the growth of ryegrass and the soil microbial biomass. The fertilizers were applied at equivalent doses for all nutrients to a neutral Luvisol in comparison with an acidic Ferralsol. Fertilizer application led to significantly increased contents of microbial biomass C, N, and P. Furthermore, yields of shoot C and root C, and concentrations of P, Ca, Mg, K, Fe, and Mn in shoots and roots were significantly increased. These increases always followed the order TSP < compost + TSP < TSP‐enriched compost. Sole TSP application led only to maximum concentrations of N and S. In the Ferralsol, TSP had only minimal positive effect on the P concentration of the grass shoots. The positive effect of TSP‐enriched compost, i.e., incubating TSP together with compost for 24 h, did not differ between the neutral Luvisol and the acidic Ferralsol, i.e., the effect is independent of the soil type. Consequently, soluble inorganic P fertilizer should generally be mixed into an organic fertilizer before application to soil.