bluuebunny/crossref_metadata_2025 huggingface dataset:
Integral equations method for the analysis and design of ELF conductive and magnetic shields
Authors: Lucca Giovanni
Published: December 2008

The need to shield ELF (extremely low frequency) magnetic fields generated by power and industrial installations arises for two main reasons: the first one is a typical EMC (electromagnetic compatibility) problem related to possible interference among electric and electronic devices while the second one is related to potential health effects due to magnetic field exposure. Different techniques exist to reduce the magnetic field mainly depending on the kind of source considered; here we treat only the shielding action offered by long and metallic structures like slabs, sheets, and foils with respect to the field produced by long sources like power cables, bus‐bars, and wires. In particular, we focus our attention on magnetic metallic shields where the shielding action is due to both ‘magnetic flux shunting’ and ‘eddy current cancellation’ mechanisms. From the design point of view, it is useful to have at disposal a calculation tool able to predict the magnetic field reduction, in a given region of space, as a function of the shield characteristics (geometry, material) and source characteristics (conductors disposition, distance from the shield). The typical calculation technique used in this kind of problem is based on the finite elements method (FEM) that is broadly described in the technical literature. Here, we want to propose a different approach that is based on integral equations (IE) and is able to model shields made by materials like iron, steel, and mumetal having both conductive and magnetic properties; nevertheless, as special cases, the algorithm is also able to deal with purely conductive shields like copper and aluminium, (frequently used in applications) where only the eddy current shielding action exists, and with purely magnetic shields, under the action of a d.c. source, where only the magnetic flux shunting effect is present. The main hypothesis that is necessary to adopt in the model is the linear behaviour of the magnetic material; such hypothesis is certainly reasonable in many real situations where the material is far from saturation. Copyright © 2008 John Wiley & Sons, Ltd.
A high‐resolution relative time scale for the Viséan Stage (Carboniferous) of the Kulm Basin (Rhenish Mountains, Germany)
Authors: Korn Dieter , Kaufmann Bernd
Published: December 2008

The Viséan (Carboniferous) sedimentary succession of the basinal Kulm facies (Rhenish Mountains) was investigated in detail in order to achieve a high‐resolution stratigraphic subdivision and correlation. Additionally, the ranges of fossil index taxa (ammonoids), fossil marker beds, volcaniclastic horizons and sedimentary features (e.g. colour changes) were integrated in the correlation. As a result, a comprehensive database was compiled, which contains 190 stratigraphic events of the Viséan interval of this area.

Several sections are almost completely composed of shales, which are regarded to represent a slow but constant basinal background sedimentation of the Kulm facies. The thickness of lithological homogeneous sections thus indicates an approximately linear record of time and the average thicknesses of biozones and positions of stratigraphic events can easily be calculated from the compiled database. The result is an approximately time‐linear biostratigraphic scale for the Viséan Stage of the Kulm Basin. Given a numerical length of the Viséan Stage of ca. 19 Ma, 190 stratigraphic events give a mean resolution of 100 000 years. This is unique in Palaeozoic stratigraphy. Copyright © 2008 John Wiley & Sons, Ltd.
P2 receptor‐mediated stimulation of the PI3‐K/Akt‐pathway in vivo
Authors: Franke H. , Sauer C. , Rudolph C. , Krügel U. , Hengstler J. G. , Illes P.
Published: December 2008

ATP acts as a growth factor as well as a toxic agent by stimulating P2 receptors. The P2 receptor‐activated signaling cascades mediating cellular growth and cell survival after injury are only incompletely understood. Therefore, the aim of the present study was to identify the role of the phosphoinositide 3 kinase (PI3‐K/Akt) and the mitogen‐activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) pathways in P2Y receptor‐mediated astrogliosis after traumatic injury and after microinfusion of ADPβS (P2Y1,12,13 receptor agonist) into the rat nucleus accumbens (NAc). Mechanical damage and even more the concomitant treatment with ADPβS, enhanced P2Y1 receptor‐expression in the NAc, which could be reduced by pretreatment with the P2X/Y receptor antagonist PPADS. Quantitative Western blot analysis indicated a significant increase in phosphorylated (p)Akt and pERK1/2 2 h after ADPβS‐microinjection. Pretreatment with PPADS or wortmannin abolished the up‐regulation of pAkt by injury alone or ADPβS‐treatment. The ADPβS‐enhanced expression of the early apoptosis marker active caspase 3 was reduced by PPADS and PD98059, but not by wortmannin. Multiple immunofluorescence labeling indicated a time‐dependent expression of pAkt and pMAPK on astrocytes and neurons and additionally the colocalization of pAkt, pMAPK, and active caspase 3 with the P2Y1 receptor especially at astrocytes. In conclusion, the data show for the first time the involvement of PI3‐K/Akt‐pathway in processes of injury‐induced astroglial proliferation and anti‐apoptosis via activation of P2Y1 receptors in vivo, suggesting specific roles of P2 receptors in glial cell pathophysiology in neurodegenerative diseases. © 2008 Wiley‐Liss, Inc.
The Alzheimer's disease drug memantine increases the number of radial glia‐like progenitor cells in adult hippocampus
Authors: Namba Takashi , Maekawa Motoko , Yuasa Shigeki , Kohsaka Shinichi , Uchino Shigeo
Published: December 2008

New neurons are continuously generated in the hippocampus of the adult mammalian brain, and N‐methyl‐D‐aspartate receptor (NMDA‐R) antagonists have been found to increase the number of newly generated neurons in the dentate gyrus (DG) of the adult hippocampus. In this study, we examined the effect of memantine, an NMDA‐R antagonist that is clinically used for the treatment of Alzheimer's disease, on primary progenitor cells exhibiting a radial glia‐like (RGL) morphology in the DG. We injected 3‐month‐old mice with memantine (50 mg/kg body weight, intraperitoneally [i.p.]); 3 days later, we injected the mice with 5‐bromo‐2‐deoxyuridine (BrdU; 75 mg/kg body weight, i.p.). We then counted the number of BrdU‐labeled RGL progenitor cells in the DG 1 or 7 days after the BrdU‐injection. The number of BrdU‐labeled RGL progenitor cells had increased significantly by 5.1‐fold on day 1 and by 13.7‐fold on day 7 after BrdU‐injection. Immunohistochemical staining revealed that the BrdU‐labeled RGL progenitor cells expressed two primary progenitor cell marker proteins, nestin and Sox2. These results clearly demonstrated that memantine promotes the proliferation of RGL progenitor cells. We also found that memantine increased the ratio of horizontally aligned RGL progenitor cells, which are probably produced by symmetric division. These findings suggest that memantine increases the proliferation of primary progenitor cells and expands the primary progenitor cell pool in the adult hippocampus by stimulating symmetric division. © 2008 Wiley‐Liss, Inc.
Patients' attitudes of dementia screening across the Atlantic
Authors: Justiss Michael D. , Boustani Malaz , Fox Chris , Katona Cornelius , Perkins Anthony J. , Healey Patrick J. , Sachs Greg , Hui Siu , Callahan Christopher M. , Hendrie Hugh C. , Scott Emma
Published: December 2008

Background

Dementia is a common and growing global public health problem. It leads to a high burden of suffering for society with an annual cost of $100 billion in the US and $10 billion in the UK. New strategies for both treatment and prevention of dementia are currently being developed. Implementation of these strategies will depend on the presence of a viable community or primary care based dementia screening and diagnosis program and patient acceptance of such a program.

Objective

To compare the acceptance, perceived harms and perceived benefits of dementia screening among older adults receiving their care in two different primary health care systems in two countries.

Design

A Cross‐sectional study.

Setting

Primary care clinics in Indianapolis, USA and Kent, UK.

Participants

A convenience sample of 245 older adults (Indianapolis, n = 125; Kent, n = 120).

Outcomes

Acceptance of dementia screening and its perceived harms and benefits as determined by a 52‐item questionnaire (PRISM‐PC questionnaire).

Results

Four of the five domains were significantly different across the two samples. The UK sample had significantly higher dementia screening acceptance scores (p < 0.05); higher perceived stigma scores (p < 0.05); higher perceived loss of independence scores (p < 0.01); and higher perceived suffering scores (p < 0.01) than the US sample. Both groups perceived dementia screening as beneficial (p = 0.218). After controlling for prior experience with dementia, acceptance and stigma were marginalized.

Conclusions

Older adults attending primary care clinics across the Atlantic value dementia screening but have significant concerns about dementia screening although these concerns differed between the two countries. Low acceptance rates and high rates of perceived harms might be a significant barrier for the introduction of treatment or preventive methods for dementia in the future. Copyright © 2008 John Wiley & Sons, Ltd.
Climate–river flow relationships across montane and lowland environments in northern Europe
Authors: Kingston Daniel G. , Hannah David M. , Lawler Damian M. , McGregor Glenn R.
Published: December 2008

To assess hydrological sensitivity to climate variability, improved understanding is needed of the process cascade linking large‐scale climate to river flow. For northern Europe such knowledge is limited, and is further complicated by mountainous terrain. This research gap is addressed through composite analysis of large‐scale climate drivers of monthly high and low river flow across northern Europe for the period 1968–1997. As an organizational framework for this investigation, the study is performed on a regional basis, using cluster analysis for identification of river flow regions. Results of the composite analysis show that the occurrence of high and low flow across northern Europe is associated with large‐scale patterns of temperature and precipitation variation. Especially in winter, these patterns are linked to changes in large‐scale geopotential height and wind fields, and in particular variation in the Azores High and Icelandic Low atmospheric centres of action. This is suggestive of a link between the North Atlantic Oscillation (NAO) and river flow, but is too complex to be described solely in terms of the NAO. Outside the winter half‐year, an inverse climate–river flow relationship is found between northern and southern Scandinavian river flow regions. This relationship is associated with differences in the relative contribution of meltwater to river flow between these regions, their latitudinal separation and orographic effects on precipitation distribution. Copyright © 2008 John Wiley & Sons, Ltd.
Glaciermelt of a small basin contributing to runoff under the extreme climate conditions in the summer of 2003
Authors: Koboltschnig Gernot R. , Schöner Wolfgang , Holzmann Hubert , Zappa Massimiliano
Published: December 2008

This paper gives an overview on the regional hydrological impact of the heatwave, which affected Europe in the summer of 2003. We investigated the small, glacierized Goldbergkees basin in the Austrian Alps, which is situated directly beneath the high Alpine Sonnblick observatory (3106 m a.s.l.). We analysed the long‐term air temperature time series and quantified the extreme anomaly of the mean summer (JJA) air temperature for 4·4 times the standard deviation of the long‐term mean (1886–2000). The mean summer air temperature was 4·7 °C. In 2003, the solid fraction of precipitation was only 35%. This was the lowest value observed from 1927 to 2005. To quantify the impact of the warm temperatures on the Goldbergkees glacier positive degree‐day sums were calculated. The ‘hot’ conditions of the summer of 2003 rapidly melted the snow covering the glacier and finally melted the ice beneath. The winter balance of the Goldbergkees did not show anomalies. The specific net balance of Goldbergkees was − 1·8 m water equivalent (w.e.) for the 2002/2003 period and has been the most negative observed. Snowmelt was accelerated by low albedo, which was a result of Sahara dust‐falls. The hydrological response unit (HRU)‐based model PREVAH was applied to simulate hourly runoff, which was observed at the outlet of this small and topographically heterogeneous basin. All components contributing to runoff were separated. The model was driven using hourly meteorological data gained from the Sonnblick observatory. Snow‐ and icemelt were modelled based on an advanced temperature index‐based approach. The model was validated using observed glacier mass balance data. The maximum simulated icemelt rate was 2·7 mm/h (4·9 mm/h assigned to the glacier surface). During August 2003, glaciermelt contributed 81% to the total runoff. Copyright © 2008 John Wiley & Sons, Ltd.
Analyses of seasonal snow disappearance in an alpine valley from micro‐ to meso‐scale (Loetschental, Switzerland)
Authors: Schmidt S. , Weber B. , Winiger M.
Published: December 2008

The seasonal snow cover duration depends on climatic conditions, vegetation and topography. Conventional approaches of snow cover monitoring, based on point measurements or remote sensing techniques, are not suitable for meso‐scale spatial and temporal observations, or for analyses of the snow extent. However, these meso‐scale analyses are the basis for an understanding of ecological, hydrological and climatic systems in high mountains. Therefore, new approaches are required to monitor and to analyse the meso‐scale spatial snow cover distribution.

In the presented study, we used 30 point measurement data and terrestrial images, which were taken by two digital cameras. The micro‐scale point measurements show the snow cover duration in several topographical positions. The terrestrial images monitor the variation of snow extent on a northwest and southeast‐facing slope. They provide a spatial resolution of 10 m, and due to bad weather conditions, a temporal resolution of 5 days. Both, the micro‐ as well as meso‐scale data enabled statistical analyses of the impact of topography on snow cover duration.

The combination of terrestrial images and point measurements facilitated the verification of the representativeness of point measurements as well as their extrapolation capabilities. One important conclusion of the presented study is that snow cover duration can be explained just partly by topographical features. Copyright © 2008 John Wiley & Sons, Ltd.
Using wind fields from a high‐resolution atmospheric model for simulating snow dynamics in mountainous terrain
Authors: Bernhardt M. , Zängl G. , Liston G. E. , Strasser U. , Mauser W.
Published: December 2008

Wind‐induced snow transport has remarkable effects on the snow cover spatial variability and on the temporal dynamics of snowmelt runoff. For accurate snow cover modelling, valid atmospheric forcing fields are essential. Since it is impossible to generate appropriate wind fields by a simple spatial interpolation of station data, a new approach was developed: A modified version of the Penn State University‐National Centre for Atmospheric Research (MM5) model was used to generate wind fields with 200‐m resolution. Because of the high computational costs of MM5, it was not practicable to include the wind field generation as an operational part of the snow cover modelling. Therefore, an archive consisting of 220 wind fields was generated prior to the simulation of the snow transport processes. These fields represent the most relevant synoptic situations for wind‐induced snow transport occurring at our test site. The criteria to generate which wind field to use in a specific snow model time step are mean wind speed and direction at the 700 hPa level derived from German Weather Service/Deutscher Wetterdienst (DWD) Lokalmodell (LM) analysis data. The wind field library provided physically derived wind speed and direction fields that were used to drive a snow transport model (SnowTran‐3D) in a high Alpine area in the Berchtesgaden National Park, Germany. In complex Alpine terrain, the procedure provides an alternative to simple interpolation methods, yielding improved physical realism at reasonable computational expense. Copyright © 2008 John Wiley & Sons, Ltd.
Assessment of operational strategies for logical and optimal use of irrigation water in a downstream control system
Authors: Ghumman A. R. , Khan M. Z. , Khan A. H. , Munir S.
Published: December 2008

Pakistan is endowed with one of the largest contiguous irrigation systems in the world. Considerable food production per unit area and per unit of water is inevitable to meet present‐day needs. The optimal use and effective management of water resources may lead to a significant increase in food production. The present study evaluates two different operational strategies for optimal and economical use of water in a downstream control irrigation system of the Upper Swat Canal in the North West Province (NWFP) of Pakistan. Firstly, the computerized weekly rotational scheduling was determined by using the Crop Based Irrigation Operation (CBIO) software developed by the International Water Management Institute (IWMI). Secondly, the application of CBIO coupled with closing the canals at night was simulated using the Canal Management Model (CanalMan).

Maps of the command area and primary data used for simulations were collected from various sources. Maps were digitized using a geographical information system to determine accurate data. It is observed that there is oversupply to the system as compared to the crop water requirements during periods of low demand. Significant savings of irrigation water were found by using CBIO and night‐time closure of canals. Copyright © 2008 John Wiley & Sons, Ltd.
The use of distribution factor technique for water allocation in rotational irrigation
Authors: Tongongar Belembaye , Chen Jin‐Hwa , Kan Chun‐E.
Published: December 2008

Yield failure is often caused by the uncertainty of supply or the shortage of water at the critical period of crop growth. This situation compels farmers and engineers to find ways to efficiently use the available resource. Reduction of irrigation depth or extension of irrigation interval are the methods commonly adopted. Another alternative is the application of the rotational irrigation technique instead of continuous irrigation. The question is how to adjust the water supply to minimize crop yield losses. Water supply itself is a dynamic parameter depending on farm size, canal capacity and crop growth stages. The distribution factor (DF) is a technique of water distribution based on the dynamic character of the supply over the growth stages. It allows categorization of the allocation of the available water in the farm within the limit of the channel capacity to satisfy crop water needs. The procedure was applied to a set of 24 farms in 2006 in the Chianan Irrigation Association which frequently experiences water shortages. The results showed that if a uniform reduction of water supply could be applied during moderate water shortages, DF made it possible to rationally distribute water among rotational groups in severe shortage conditions. Copyright © 2008 John Wiley & Sons, Ltd.
Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context
Authors: Hays Sean M. , Aylward Lesa L.
Published: December 2008

Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biological media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the US Centers for Disease Control and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This review describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value such as a tolerable daily intake or reference dose. The BE approach integrates available pharmacokinetic data to convert an existing exposure guidance value into an equivalent concentration in a biological medium. Key concepts regarding the derivation and communication of BE values resulting from an expert workshop held in 2007 are summarized. BE derivations for four case study chemicals (toluene, 2,4‐dichlorophenoxyacetic acid, cadmium and acrylamide) are presented, and the interpretation of biomonitoring data for these chemicals is presented using the BE values. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully developed physiologically based pharmacokinetic models, while useful, are not required. The resulting screening level evaluation can be used to classify these compounds into relative categories of low, medium and high priority for risk assessment follow‐up. Future challenges related to the derivation and use of BE values as tools in risk management are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Piperine activates testicular apoptosis in adult rats
Authors: D'Cruz Shereen Cynthia , Vaithinathan S. , Saradha B. , Mathur P. P.
Published: December 2008

Piperine, an alkaloid present in the fruits of commonly used spice pepper, is known to impair reproductive functions. In the present study, piperine was administered to adult male rats at the dose levels of 1, 10, and 100 mg/kg body weight for 30 days to evaluate its effects on the testis. A significant decrease in the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the testis was observed at 10 and 100 mg of piperine administration when compared with the controls. A dose‐dependent increase in lipid peroxidation and hydrogen peroxide generation was also observed. Sialic acid levels in the testis were also found to be decreased when piperine was administered at 10 and 100 mg dose levels. Immunofluorescence studies demonstrated a dose‐dependent increase in caspase 3 and Fas protein in testicular germ cells after piperine treatment. These observations indicate that piperine induces oxidative stress and thereby triggers apoptosis in the testis, contributing to hampered reproductive functions. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:382–388, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20251
Novel indoloquinoline derivative, IQDMA, inhibits STAT5 signaling associated with apoptosis in K562 cells
Authors: Yang Sheng‐Huei , Chien Ching‐Ming , Su Jung‐Chen , Chen Yeh‐Long , Chang Long‐Sen , Lin Shinne‐Ren
Published: December 2008

N′‐(11H‐indolo[3,2‐c]quinolin‐6‐yl)‐N,N‐dimethylethane‐1,2‐diamine (IQDMA), an indoloquinoline derivative, synthesized in our laboratory, has been demonstrated to be an effective antitumor agent in human leukemia cells. In the present study, treatment with IQDMA inhibited phosphorylation of epidermal growth factor receptor (EGFR), Src, Bcr‐Abl, and Janus‐activated kinase (JAK2) in a time‐dependent manner. IQDMA also degraded JAK2 protein. Moreover, signal transducer and activator of transcription 5 (STAT5) signaling were also blocked by IQDMA. However, IQDMA did not inhibit other oncogenic and tumor survival pathways such as those mediated by Akt and extracellular signal‐regulated kinase 1/2. Furthermore, IQDMA upregulated the expression of p21 and p27 and downregulated the expression of cyclin D1, myeloid cell leukemia‐1(Mcl‐1), Bcl‐XL, and vascular endothelial growth factor (VEGF). Taken together, these results indicate that IQDMA causes significant induction of apoptosis in K562 cells via downregulation of EGFR, Src, Bcr‐Abl, JAK2, and STAT5 signaling and modulation of p21, p27, cyclin D1, Mcl‐1, Bcl‐XL, and VEGF proteins. Thus, IQDMA appears to be a potential therapeutic agent for treating leukemia K562 cells. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:396–404, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20254
N‐nitrosodimethylamine changes the expression of glutathioneS‐transferase in the liver of male mice: The role of antioxidants
Authors: Sheweita S. A. , Mousa N. , Al‐Masry H. M.
Published: December 2008

The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)‐induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathioneS‐transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with low‐dose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low‐dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN‐treated groups. In addition, high‐dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN‐treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:389–395, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20255
Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis
Authors: Roy Madhuchhanda , Marchetti Dario
Published: December 2008

Heparan sulfate (HS) proteoglycans are essential components of the cell‐surface and extracellular matrix (ECM) which provide structural integrity and act as storage depots for growth factors and chemokines, through their HS side chains. Heparanase (HPSE) is the only mammalian endoglycosidase known that cleaves HS, thus contributing to matrix degradation and cell invasion. The enzyme acts as an endo‐β‐D‐glucuronidase resulting in HS fragments of discrete molecular weight size. Cell‐surface HS is known to inhibit or stimulate tumorigenesis depending upon size and composition. We hypothesized that HPSE contributes to melanoma metastasis by generating bioactive HS from the cell‐surface to facilitate biological activities of tumor cells as well as tumor microenvironment. We removed cell‐surface HS from melanoma (B16B15b) by HPSE treatment and resulting fragments were isolated. Purified cell‐surface HS stimulated in vitro B16B15b cell migration but not proliferation, and importantly, enhanced in vivo angiogenesis. Furthermore, melanoma cell‐surface HS did not affect in vitro endothelioma cell (b.End3) migration. Our results provide direct evidence that, in addition to remodeling ECM and releasing growth factors and chemokines, HPSE contributes to aggressive phenotype of melanoma by releasing bioactive cell‐surface HS fragments which can stimulate melanoma cell migration in vitro and angiogenesis in vivo. J. Cell. Biochem. 106: 200–209, 2009. © 2008 Wiley‐Liss, Inc.
Mechanisms of prostate cancer cell survival after inhibition of AR expression
Authors: Cohen Michael B. , Rokhlin Oskar W.
Published: December 2008

Recent reports have shown that the AR is the key determinant of the molecular changes required for driving prostate cancer cells from an androgen‐dependent to an androgen‐independent or androgen depletion‐independent (ADI) state. Several recent publications suggest that down‐regulation of AR expression should therefore be considered the principal strategy for the treatment of ADI prostate cancer. However, no valid data is available about how androgen‐dependent prostate cancer cells respond to apoptosis‐inducing drugs after knocking down AR expression and whether prostate cancer cells escape apoptosis after inhibition of AR expression. This review will focus on mechanisms of prostate cancer cell survival after inhibition of AR activity mediated either by androgen depletion or by targeting the expression of AR by siRNA. We have shown that knocking down AR expression by siRNA induced PI3K‐independent activation of Akt, which was mediated by calcium/calmodulin‐dependent kinase II (CaMKII). We also showed that the expression of CaMKII genes is under AR control: active AR in the presence of androgens inhibits CaMKII gene expression whereas inhibition of AR activity results in an elevated level of kinase activity and in enhanced expression of CaMKII genes. This in turn activates the anti‐apoptotic PI3K/Akt pathways. CaMKII also express anti‐apoptotic activity that is independent from the Akt pathway. This may therefore be an important mechanism by which prostate cancer cells escape apoptosis after androgen depletion or knocking down AR expression. In addition, we have found that there is another way to escape cell death after AR inhibition: DNA damaging agents cannot fully activate p53 in the absence of AR and as a result p53 down stream targets, for example, microRNA‐34, cannot be activated and induce apoptosis. This implies that there may be a need for re‐evaluation of the therapeutic approaches to human prostate cancer. J. Cell. Biochem. 106: 363–371, 2009. © 2008 Wiley‐Liss, Inc.
The truncated Hoxa1 protein interacts with Hoxa1 and Pbx1 in stem cells
Authors: Fernandez Cristina C. , Gudas Lorraine J.
Published: December 2008

Hox genes contain a homeobox encoding a 60‐amino acid DNA binding sequence. The Hoxa1 gene (Hox1.6, ERA1) encodes two alternatively spliced mRNAs that encode distinct proteins, one with the homeodomain (Hoxa1‐993), and another protein lacking this domain (Hoxa1‐399). The functions of Hoxa1‐399 are unknown. We detected Hoxa1‐993 and Hoxa1‐399 by immunoprecipitation using Hoxa1 antibodies. To assess whether Hoxa1‐399 functions in cellular differentiation, we analyzed Hoxb1, a Hoxa1 target gene. Hoxa1‐993 and its cofactor, Pbx1, bind to the Hoxb1 SOct‐R3 promoter to transcriptionally activate a luciferase reporter. Results from F9 stem cells that stably express ectopic Hoxa1‐399 (the F9‐399 line) show that Hoxa1‐399 reduces this transcriptional activation. Gel shift assays demonstrate that Hoxa1‐399 reduces Hoxa1‐993/Pbx1 binding to the Hoxb1 SOct‐R3 region. GST pull‐down experiments suggest that Hoxa1‐399, Hoxa1‐993, and Pbx1 form a trimer. However, the F9‐399 line exhibits no differences in RA‐induced proliferation arrest or endogenous Hoxb1, Pbx1, Hoxa5, Cyp26a1, GATA4, or Meis mRNA levels when compared to F9 wild‐type. J. Cell. Biochem. 106: 427–443, 2009. © 2008 Wiley‐Liss, Inc.
In silico prediction of drug solubility: 4. Will simple potentials suffice?
Authors: Lüder Kai , Lindfors Lennart , Westergren Jan , Nordholm Sture , Persson Rasmus , Pedersen Mikaela
Published: December 2008

In view of the extreme importance of reliable computational prediction of aqueous drug solubility, we have established a Monte Carlo simulation procedure which appears, in principle, to yield reliable solubilities even for complex drug molecules. A theory based on judicious application of linear response and mean field approximations has been found to reproduce the computationally demanding free energy determinations by simulation while at the same time offering mechanistic insight. The focus here is on the suitability of the model of both drug and solvent, i.e., the force fields. The optimized potentials for liquid simulations all atom (OPLS‐AA) force field, either intact or combined with partial charges determined either by semiempirical AM1/CM1A calculations or taken from the condensed‐phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field has been used. The results illustrate the crucial role of the force field in determining drug solubilities. The errors in interaction energies obtained by the simple force fields tested here are still found to be too large for our purpose but if a component of this error is systematic and readily removed by empirical adjustment the results are significantly improved. In fact, consistent use of the OPLS‐AA Lennard‐Jones force field parameters with partial charges from the COMPASS force field will in this way produce good predictions of amorphous drug solubility within 1 day on a standard desktop PC. This is shown here by the results of extensive new simulations for a total of 47 drug molecules which were also improved by increasing the water box in the hydration simulations from 500 to 2000 water molecules. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Predicting PH vibrations of gas phase molecules and surface‐adsorbed species using bond length‐frequency correlations
Authors: Das Ujjal , Raghavachari Krishnan
Published: December 2008

The high frequency XH (e.g., X = C, Si) stretching modes in small molecules are only slightly perturbed by other vibrational modes present in the system. The isolated frequencies, in these cases, exhibit a linear relationship with the corresponding bond lengths. Here, we study such a bond length‐frequency correlation in the case of PH stretching vibrations for molecules in the gas phase as well as for surface‐adsorbed species. Although a high degree of linear correlation is found, there is a small dependence on the local coordination around P, leading to significant deviations in some cases. By a careful analysis, we show that such correlations can be used to predict new surface frequencies without computing the Hessian matrix explicitly. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Electronic structures and optical properties of BiOX (X = F, Cl, Br, I) via DFT calculations
Authors: Huang Wen Lai
Published: December 2008

Based on the density functional theory (DFT), the lattice constants and atomic positions of BiOX (X = F, Cl, Br, I) species have been optimized, and the electronic and optical properties of the relaxed species have been calculated, with Bi 5d states considered or not. Relaxation generally results in the shrinkage in a and the expansion of c. Relaxed BiOCl, BiOBr, and BiOI present indirect band gaps, whereas BiOF exhibits a direct or somewhat indirect band‐gap feature corresponding to the relaxation and calculation with the Bi 5d states or not. The bottom of the conduction band is quite flat for relaxed BiOI, and apparently flat in BiOBr, and shows observable flatness in BiOCl as well when considering the Bi 5d states. The top of the valence band is rather even as well for some species. The obtained maximum gaps for relaxed BiOF, BiOCl, BiOBr, and BiOI are 3.34, 2.92, 2.65, and 1.75 eV, respectively. The density peak of X np states in the valence band shifts toward the valence band maximum with the increasing X atomic number. The bandwidths, atomic charges, bond orders, and orbital density have also been investigated along with some optical properties. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells
Authors: McCarty Rosa C. , Gronthos Stan , Zannettino Andrew C. , Foster Bruce K. , Xian Cory J.
Published: December 2008

Since discovery, significant interest has been generated in the potential application of mesenchymal stem cells or multipotential stromal cells (MSC) for tissue regeneration and repair, due to their proliferative and multipotential capabilities. Although the sheep is often used as a large animal model for translating potential therapies for musculoskeletal injury and repair, the characteristics of MSC from ovine bone marrow have been inadequately described. Histological and gene expression studies have previously shown that ovine MSC share similar properties with human and rodents MSC, including their capacity for clonogenic growth and multiple stromal lineage differentiation. In the present study, ovine bone marrow derived MSCs positively express cell surface markers associated with MSC such as CD29, CD44 and CD166, and lacked expression of CD14, CD31 and CD45. Under serum‐deprived conditions, proliferation of MSC occurred in response to EGF, PDGF, FGF‐2, IGF‐1 and most significantly TGF‐α. While subcutaneous transplantation of ovine MSC in association with a ceramic HA/TCP carrier into immunocomprimised mice resulted in ectopic osteogenesis, adipogenesis and haematopoietic‐support activity, transplantation of these cells within a gelatin sponge displayed partial chondrogenesis. The comprehensive characterisation of ovine MSC described herein provides important information for future translational studies involving ovine MSC. J. Cell. Physiol. 219: 324–333, 2009. © 2008 Wiley‐Liss, Inc.
Fifty hertz extremely low‐frequency magnetic field exposure elicits redox and trophic response in rat‐cortical neurons
Authors: Di Loreto Silvia , Falone Stefano , Caracciolo Valentina , Sebastiani Pierluigi , D'Alessandro Antonella , Mirabilio Alessandro , Zimmitti Vincenzo , Amicarelli Fernanda
Published: December 2008

Large research activity has raised around the mechanisms of interaction between extremely low‐frequency magnetic fields (ELF‐MFs) and biological systems. ELF‐MFs may interfere with chemical reactions involving reactive oxygen species (ROS), thus facilitating oxidative damages in living cells. Cortical neurons are particularly susceptible to oxidative stressors and are also highly dependent on the specific factors and proteins governing neuronal development, activity and survival. The aim of the present work was to investigate the effects of exposures to two different 50 Hz sinusoidal ELF‐MFs intensities (0.1 and 1 mT) in maturing rat cortical neurons' major anti‐oxidative enzymatic and non‐enzymatic cellular protection systems, membrane peroxidative damage, as well as growth factor, and cytokine expression pattern. Briefly, our results showed that ELF‐MFs affected positively the cell viability and concomitantly reduced the levels of apoptotic death in rat neuronal primary cultures, with no significant effects on the main anti‐oxidative defences. Interestingly, linear regression analysis suggested a positive correlation between reduced glutathione (GSH) and ROS levels in 1 mT MF‐exposed cells. On this basis, our hypothesis is that GSH could play an important role in the antioxidant defence towards the ELF‐MF‐induced redox challenge. Moreover, the GSH‐based cellular response was achieved together with a brain‐derived neurotrophic factor over‐expression as well as with the interleukin 1β‐dependent regulation of pro‐survival signaling pathways after ELF‐MF exposure. J. Cell. Physiol. 219: 334–343, 2009. © 2008 Wiley‐Liss, Inc.
Optimization of agro‐residual medium for α‐amylase production from a hyper‐producingBacillus subtilisKCC103 in submerged fermentation
Authors: Rajagopalan Gobinath , Krishnan Chandraraj
Published: December 2008

BACKGROUND:Although submerged fermentation (SmF) is the conventional method in industry, use of low‐cost agro‐residues for α‐amylase production in SmF has not been well established. Here we optimized agro‐residue‐based medium and culture conditions for α‐amylase production in SmF using a hyper‐producingBacillus subtilisKCC103.

RESULTS:B. subtilisKCC103 produced α‐amylase in SmF by utilizing agro‐residues. Wheat bran (WB) and sunflower oil cake (SFOC) were selected as the best substrates using shake flasks. Medium containing WB (carbohydrate rich) and SFOC (rich in protein and free amino acids) at 1:1 (w/w) ratio produced high levels (90 IU mL−1) of α‐amylase at 30–36 h in a shake flask. The α‐amylase yield was 14‐fold enhanced (1258 IU mL−1) by optimizing process parameters and medium composition following response surface methodology in a bioreactor. The optimal conditions were: WB 1.27%, SFOC 1.42%, pH 7, 37 °C and 10–12 h. Both in shake flask and bioreactor α‐amylase synthesis was not repressed by the release of simple sugars into the medium.

CONCLUSION:KCC103 with catabolite derepression and hyperproducing ability is useful for economic α‐amylase production using low‐cost agro‐residual substrates in conventional SmF. Since the production time (10–12 h) is much shorter than other strains this would improve productivity and further reduce the cost of α‐amylase production. Copyright © 2008 Society of Chemical Industry
Purification of glycerol/water solutions from biodiesel synthesis by ion exchange: sodium removal Part I
Authors: Carmona Manuel , Valverde José L. , Pérez Angel , Warchol Jolanta , Rodriguez Juan F.
Published: December 2008

BACKGROUND: In this study, equilibrium and kinetic data of the ion exchange of sodium from glycerol–water mixtures on the strong acid resin Amberlite‐252 were obtained. Basic parameters for the design of ion exchange units for the purification of the crude glycerol phase from biodiesel production have been determined.

RESULTS: Equilibrium uptake of sodium ions with the strong acid ion exchanger Amberlite‐252 was studied at three temperatures. The Langmuir equation and the mass action law model were used to fit the experimental equilibrium data. Equilibrium constants and thermodynamic parameters were obtained at each temperature. Kinetic experiments were carried out to evaluate the effective diffusion coefficients of sodium on the resin Amberlite‐252 in glycerine–water media.

CONCLUSIONS: Equilibrium results indicate that this process is favourable and also that its selectivity decreases with temperature increase from 303 to 333 K. Both models were able to fit the experimental equilibrium data. Kinetic experiments showed that the rate of mass transfer in this binary system is high. An Arrhenius type equation allowed the correlation of effective diffusion coefficients and temperature. The results indicate that the macroporous resin Amberlite‐252 could be useful for removal of sodium ions from glycerine/water solutions with a high salt concentration. Copyright © 2008 Society of Chemical Industry
Solvent‐free preparation of phytosteryl esters with fatty acids from butterfat in equimolecular conditions in the presence of a lipase from Candida rugosa
Authors: Torrelo Guzman , Torres Carlos F , Señorans F Javier , Blanco Rosa M , Reglero Guillermo
Published: December 2008

BACKGROUND: Enzymatic esterification of phytosterols with fatty acids from butterfat in equimolecular conditions to produce phytosteryl esters was performed in solvent‐free medium. Commercial and immobilized Candida rugosa lipases were used as biocatalysts for the reaction.

RESULTS: By this methodology, under simple and mild reaction conditions (without solvents, 50 °C and short reaction times), 94% and 99% (w/w) of phystosteroyl esters were obtained in 48 h and 9 h with the commercial and the immobilized lipase, respectively. The effects of temperature, fatty acid specificity, enzyme amount and residual activity of each lipase were also evaluated.

CONCLUSIONS: The phytosteryl esters from butterfat produced in this study are expected to have lower melting point, improved oil and fat solubility and bioavailability compared to that of their corresponding free phytosterols. Copyright © 2008 Society of Chemical Industry
Comparison of soybean peroxidase with laccase in the removal of phenol from synthetic and refinery wastewater samples
Authors: Steevensz Aaron , Al‐Ansari Mohammad Mousa , Taylor Keith E , Bewtra Jatinder K , Biswas Nihar
Published: December 2008

BACKGROUND: Several studies have demonstrated the feasibility of treating aqueous phenols and aromatic amines with oxidoreductases in synthetic wastewater samples. However, little work has been done on the effectiveness of enzymatic treatment on real wastewater. Here a comparison was made of the oxidative coupling of phenol catalyzed by laccase or soybean peroxidase (SBP) using synthetic and refinery wastewaters.

RESULTS: Optimization of pH, enzyme concentration, effect of polyethylene glycol (PEG) addition, and reducing anions were examined for a 3 h reaction time. Laccase had an optimum pH of 5.6–6.0, while SBP had a broad optimum from 6.0 to 8.0. In synthetic samples in tap water to achieve ≥ 95% removal of 1.0 mmol L−1 phenol in 3 h required 0.12 and 1.5 U mL−1 of catalytic activity of laccase and SBP, respectively. In refinery samples comparable removals required 1.2‐ to 1.8‐fold more enzyme than in synthetic tap water samples. Added PEG allowed for a small reduction in the SBP concentration for synthetic wastewater but was ineffective with either enzyme in treating refinery samples. Reducing ions increased the demand for oxidant but, with the exception of cyanide, phenol removal still occurred.

CONCLUSION: Both laccase and SBP were effective in removing phenol from aqueous refinery samples, albeit at slightly higher concentrations than required for the corresponding synthetic samples. Copyright © 2008 Society of Chemical Industry
Human beta‐defensin‐3 promotes wound healing in infected diabetic wounds
Authors: Hirsch Tobias , Spielmann Malte , Zuhaili Baraa , Fossum Magdalena , Metzig Marie , Koehler Till , Steinau Hans‐Ulrich , Yao Feng , Onderdonk Andrew Bruce , Steinstraesser Lars , Eriksson Elof
Published: December 2008

Background

Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta‐defensin (hBD)‐3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD‐3 expression in a model of infected diabetic wounds.

Methods

Excisional wounds were created on the backs of Yorkshire pigs and Ad5‐CMV‐hBD‐3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re‐epithelialization, wound contraction, wound fluid production and blood vessel formation.

Results

hBD‐3‐treated wounds showed a total bacterial load of 2.1 × 108 colony‐forming units (CFU)/g tissue, versus 1.3 × 109 CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re‐epithelialization showed 75 ± 15% wound closure for hBD‐3 expressing wounds and 50 ± 16% for controls (p < 0.01). hBD‐3 expression was in the range 15–20 ng/ml of wound fluid during day 1–4. The lower dose of 2 × 109 Ad5‐CMV‐hBD‐3 showed no effect, suggesting a dose dependency for hBD‐3.

Conclusions

In the present study, we show that hBD‐3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large‐animal model. Furthermore, a ten‐fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta‐defensin‐3 may play a major role in diabetic wound healing and wound infections. Copyright © 2008 John Wiley & Sons, Ltd.