bluuebunny/crossref_metadata_2025 huggingface dataset:
An overview of peanut and its wild relatives
Authors: Bertioli David J. , Seijo Guillermo , Freitas Fabio O. , Valls José F. M. , Leal-Bertioli Soraya C. M. , Moretzsohn Marcio C.
Published: January 2011

The legumeArachis hypogaea, commonly known as peanut or groundnut, is a very important food crop throughout the tropics and sub-tropics. The genus is endemic to South America being mostly associated with the savannah-like Cerrado. All species in the genus are unusual among legumes in that they produce their fruit below the ground. This profoundly influences their biology and natural distributions. The species occur in diverse habitats including grasslands, open patches of forest and even in temporarily flooded areas. Based on a number of criteria, including morphology and sexual compatibilities, the 80 described species are arranged in nine infrageneric taxonomic sections. While most wild species are diploid, cultivated peanut is a tetraploid. It is of recent origin and has an AABB-type genome. The most probable ancestral species areArachis duranensisandArachis ipaënsis, which contributed the A and B genome components, respectively. Although cultivated peanut is tetraploid, genetically it behaves as a diploid, the A and B chromosomes only rarely pairing during meiosis. Although morphologically variable, cultivated peanut has a very narrow genetic base. For some traits, such as disease and pest resistance, this has been a fundamental limitation to crop improvement using only cultivated germplasm. Transfer of some wild resistance genes to cultivated peanut has been achieved, for instance, the gene for resistance to root-knot nematode. However, a wider use of wild species in breeding has been hampered by ploidy and sexual incompatibility barriers, by linkage drag, and historically, by a lack of the tools needed to conveniently confirm hybrid identities and track introgressed chromosomal segments. In recent years, improved knowledge of species relationships has been gained by more detailed cytogenetic studies and molecular phylogenies. This knowledge, together with new tools for genetic and genomic analysis, will help in the more efficient use of peanut's genetic resources in crop improvement.
Recent development in Kirkpatrick–Baez focusing systems at the ESRF
Authors: Baker R. , Barrett R. , Dabin Y. , Gregoire J. , Malandrino G. , Manning T. , Vivo A. , Zhang L.
Published: January 2011

European Synchrotron Radiation Facility (ESRF) in-house designed Kirkpatrick–Baez (KB) focusing systems have been extensively used for high efficiency beam focusing over the past years. More recently however, increasing interest in nanofocusing techniques has directed our development efforts towards more compact, higher stability designs for dynamic focusing systems in which the optimization of numerous parameters enables mirror bending approaching its mechanical limits. Simultaneously, progress in fixed focus mirror fabrication techniques – notably ion beam figuring, differential deposition and elastic emission machining – now make the fabrication of highly elliptical, fixed focus X-ray optics an interesting option. This has simplified conception (no bending mechanics) which in turn has led to the design of miniaturized KBs.

A general overview of these recent developments in both dynamic bending and fixed focus KB systems is presented.
Er L3-edge resonant elastic X-ray scattering study of orbital ordering in ErVO3
Authors: Ikeuchi K. , Nakao H. , Murakami Y. , Miyasaka S. , Tokura Y.
Published: January 2011

Resonant elastic X-ray scattering (RXS) at the erbium absorption edge was investigated in the orbital-ordered compound ErVO3. An RXS signal resonating near the Er L3-edge was clearly observed at (1 0 0). Using this signal, we studied the relation between the anisotropy of the Er 5d orbital and the V 3d orbital ordering because the covalency between the Er 5d and V 3d orbitals is expected to stabilize the C-type orbital ordering of the V 3d electrons.
Wnt signalling: the case of the ‘missing’ G-protein
Authors: Malbon Craig C.
Published: January 2011

Wnt signalling remains a hot topic for cell signalling sleuthhounds. The trail of signalling downstream of the seven-transmembrane segment Frizzleds, which bind Wnt ligands, is replete of clues [e.g. LPR5/6 (lipoprotein receptor-related protein 5/6), G-proteins or Dishevelled] and yet remains the ‘final problem’. Although the heptahelical nature of Frizzleds places them well within a populous family of G-protein-coupled receptors, resistance to this theme has waxed and waned amid increasing demands for ‘proof’. The Wnt Homepage (http://www.stanford.edu/group/nusselab/cgi-bin/wnt/) has acted as a dynamic real-time arbiter of the controversy, highlighted by the appearance and later the disappearance of the G-protein from its central diagramming and tabulations. A recent publication in this issue of the Biochemical Journal offers a solution to the ‘final problem’, demonstrating under native conditions that Frizzleds expressed in mammalian brain preparations act functionally to catalyse guanine-nucleotide exchange in response to stimulation with Wnt3a. Lensed from the fictional character of Sherlock Holmes, The Case of the Missing G-Protein is investigated.
A pipeline for RNA-seq data processing and quality assessment
Authors: Goncalves Angela , Tikhonov Andrew , Brazma Alvis , Kapushesky Misha
Published: January 2011

Summary: We present an R based pipeline, ArrayExpressHTS, for pre-processing, expression estimation and data quality assessment of high-throughput sequencing transcriptional profiling (RNA-seq) datasets. The pipeline starts from raw sequence files and produces standard Bioconductor R objects containing gene or transcript measurements for downstream analysis along with web reports for data quality assessment. It may be run locally on a user's own computer or remotely on a distributed R-cloud farm at the European Bioinformatics Institute. It can be used to analyse user's own datasets or public RNA-seq datasets from the ArrayExpress Archive.

Availability: The R package is available at www.ebi.ac.uk/tools/rcloud with online documentation at www.ebi.ac.uk/Tools/rwiki/, also available as supplementary material.

Contact:  angela.goncalves@ebi.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Chlamydia trachomatis secretion of hypothetical protein CT622 into host cell cytoplasm via a secretion pathway that can be inhibited by the type III secretion system inhibitor compound 1
Authors: Gong Siqi , Lei Lei , Chang Xiaotong , Belland Robert , Zhong Guangming
Published: January 2011

Using antibodies raised with C. trachomatis fusion proteins, we localized a hypothetical protein encoded by the ORF ct622 in the cytoplasm of C. trachomatis-infected mammalian cells. The detection was specific since the antibody labelling of CT622 protein was removed by preabsorption with CT622 but not other fusion proteins. We similarly confirmed that CT621, a known secretion protein encoded by a hypothetical ORF downstream of ct622, was secreted into host cell cytosol. Proteins CT622 and CT621 displayed a similar secretion pattern, with both intra-inclusion and host cell cytosol localization, that was distinct from that of CPAF (chlamydial protease/proteasome-like activity factor). However, the expression and secretion kinetics differed significantly between CT622 and CT621: CT622 mRNA was detected at 2 h, protein at 6 h and secretion of protein into host cell cytoplasm at 36 h post-infection, while CT621 mRNA was detected at 8 h, protein at 16 h and secretion at 24 h. The secretion of both CT622 and CT621 was blocked by N′-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide (compound 1), an inhibitor known to target the type III secretion system of bacteria. These results suggest that CT621 and CT622 may fulfil different functions during chlamydial intracellular growth. Further characterization of these proteins may generate important information for understanding chlamydial pathogenesis.
Structures of two new high-pressure forms of AlPO4by X-ray powder diffraction and NMR spectroscopy
Authors: Kanzaki Masami , Xue Xianyu , Reibstein Sindy , Berryman Eleanor , Namgung Seonyi
Published: January 2011

The crystal structures of two new high-pressure AlPO4phases are reported. One phase synthesized at 6 GPa and 1523 K is triclinic (P\bar 1) whilst the other phase synthesized at 7 GPa and 1773 K is monoclinic (P2_1/c).31P MAS (magic-angle spinning) NMR suggests three tetrahedral P sites with equal abundance in both phases.27Al 3Q MAS NMR spectra provided evidence for two octahedral sites and one five-coordinated Al site in each phase. The crystal structures were solved using anab initiostructure determination technique from synchrotron powder X-ray diffraction data utilizing the local structural information from NMR, and were further refined by the Rietveld method. Both phases contain doubly bent chains made of six edge-shared Al polyhedra (including five-coordinated Al), which are joined by PO4tetrahedra. The P\bar{1} phase is isostructural with FeVO4and AlVO4. The two phases differ in the packing manner of the chains. This study has demonstrated that the combined application ofab initiostructure determinationviaX-ray powder diffraction and solid-state NMR spectroscopy is a powerful approach to the rapid solution of complex inorganic crystal structures.
Inhibition of paracetamol glucuronidation by tyrosine kinase inhibitors
Authors: Liu Yong , Ramírez Jacqueline , Ratain Mark J.
Published: January 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Clinical cases reported that fatal acute liver failure occurred when paracetamol (acetaminophen) was co‐administrated with some tyrosine kinase inhibitors (TKIs). The direct inhibition of UDP‐glucuronosyltransferase activities has been identified as a mechanism of potentiation of paracetamol hepatotoxicity. However, the effects of TKIs on paracetamol glucuronidation are not known.

WHAT THIS STUDY ADDS

• The TKIs, sorafenib, dasatinib and imatinib exhibited potent mixed inhibition against paracetamol glucuronidation in pooled human liver microsomes, implying a possible increase in paracetamol hepatotoxicity when they are co‐administrated with paracetamol.

AIMSWe aimed to investigate the effects of tyrosine kinase inhibitors (TKIs) on paracetamol (acetaminophen) glucuronidation.

METHODSThe inhibition of nine small molecule TKIs on paracetamol glucuronidation was investigated in human liver microsomes (HLMs) and recombinant human UDP‐glucuronosyltransferases (UGTs).

RESULTSSorafenib, dasatinib and imatinib exhibited mixed inhibition against paracetamol glucuronidation in pooled HLMs, and potent inhibition in UGT1A9 and UGT2B15. Dasatinib and imatinib also inhibited UGT1A1‐mediated paracetamol glucuronidation. Axitinib, erlotinib, gefitinib, lapatinib, nilotinib and vandetanib exhibited weak inhibition of paracetamol glucuronidation activity in HLMs.

CONCLUSIONSThe inhibition of paracetamol glucuronidation by TKIs might be of particular concern when they are co‐administered.
Are we closer to understanding the pathophysiology of chronic rhinosinusitis?
Authors: Ling M. , Hamilos D. L.
Published: January 2011

Cite this as: M. Ling and D. L. Hamilos, Clinical & Experimental Allergy, 2011 (41) 144–146.
Induction of β-defensins byl-isoleucine as novel immunotherapy in experimental murine tuberculosis
Authors: Rivas-Santiago C E , Rivas-Santiago B , León D A , Castañeda-Delgado J , Hernández Pando R
Published: January 2011

Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription–quantitative polymerase chain reaction (RT–qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease.
Epithelial transport and deamidation of gliadin peptides: a role for coeliac disease patient immunoglobulin A
Authors: Rauhavirta T , Qiao S-W , Jiang Z , Myrsky E , Loponen J , Korponay-Szabó I R , Salovaara H , Garcia-Horsman J A , Venäläinen J , Männistö P T , Collighan R , Mongeot A , Griffin M , Mäki M , Kaukinen K , Lindfors K
Published: January 2011

In coeliac disease, the intake of dietary gluten induces small-bowel mucosal damage and the production of immunoglobulin (Ig)A class autoantibodies against transglutaminase 2 (TG2). We examined the effect of coeliac patient IgA on the apical-to-basal passage of gluten-derived gliadin peptides p31–43 and p57–68 in intestinal epithelial cells. We demonstrate that coeliac IgA enhances the passage of gliadin peptides, which could be abolished by inhibition of TG2 enzymatic activity. Moreover, we also found that both the apical and the basal cell culture media containing the immunogenic gliadin peptides were able to induce the proliferation of deamidation-dependent coeliac patient-derived T cells even in the absence of exogenous TG2. Our results suggest that coeliac patient IgA could play a role in the transepithelial passage of gliadin peptides, a process during which they might be deamidated.
Intentional Relations and the Sideways‐on View: On McDowell's Critique of Sellars
Authors: Shapiro Lionel
Published: January 2011

Abstract: McDowell opposes the view that the intentionality of language and thought remains mysterious unless it can be understood ‘from outside the conceptual order’. While he thinks the demand for such a ‘sideways‐on’ understanding can be the result of ‘scientistic prejudice’, he points to Sellars's thought as exhibiting a different source: a distortion of our perspective ‘from within the conceptual order’. The distortion involves a failure on Sellars's part to see how descriptions from within the conceptual order can present expressions and mental acts as related to extra‐conceptual objects (a failure in turn explained by his failure to see how such relations could have normative import). In this paper, I argue that Sellars's thought suffers from no such distortion. If that is right, McDowell's examination of Sellars has not uncovered a disorder whose treatment might help relieve the desire for a sideways‐on view.
High rates of anaerobic methanotrophy at low sulfate concentrations with implications for past and present methane levels
Authors: BEAL E. J. , CLAIRE M. W. , HOUSE C. H.
Published: January 2011

Despite the importance of the anaerobic oxidation of methane (AOM) to global biogeochemical cycles, the relationship between sulfate concentration and the rate of AOM has not been previously experimentally constrained. Here, we present measurements showing substantial methane oxidation at low sulfate concentrations, with no significant decrease in the rate of AOM until sulfate levels are well below 1 mm. At sulfate levels below 1 mm, there appears to be a strong decoupling of AOM and sulfate reduction, with a 13C‐label transferred from methane to carbon dioxide occurring at a rate almost an order of magnitude faster than the observed rate of sulfate reduction. These results allow for the possibility that high rates of AOM occurred in the Archean oceans and that high rates of AOM may be found in freshwater environments (lakes, rivers, etc.) and deep ocean sediments today.
Retracted: Role of hypoxia‐inducible factors in the dexrazoxane‐mediated protection of cardiomyocytes from doxorubicin‐induced toxicity
Authors: Spagnuolo RD , Recalcati S , Tacchini L , Cairo G
Published: January 2011

BACKGROUND AND PURPOSE

Iron aggravates the cardiotoxicity of doxorubicin, a widely used anticancer anthracycline, and the iron chelator dexrazoxane is the only agent protecting against doxorubicin cardiotoxicity; however, the mechanisms underlying the role of iron in doxorubicin‐mediated cardiotoxicity and the protective role of dexrazoxane remain to be established. As iron is required for the degradation of hypoxia‐inducible factors (HIF), which control the expression of antiapoptotic and protective genes, we tested the hypothesis that dexrazoxane‐dependent HIF activation may mediate the cardioprotective effect of dexrazoxane.

EXPERIMENTAL APPROACH

Cell death, protein levels (by immunoblotting) and HIF‐mediated transcription (using reporter constructs) were evaluated in the rat H9c2 cardiomyocyte cell line exposed to low doses of doxorubicin with or without dexrazoxane pretreatment. HIF levels were genetically manipulated by transfecting dominant‐negative mutants or short hairpin RNA.

KEY RESULTS

Treatment with dexrazoxane induced HIF‐1α and HIF‐2α protein levels and transactivation capacity in H9c2 cells. It also prevented the induction of cell death and apoptosis by exposure of H9c2 cells to clinically relevant concentrations of doxorubicin. Suppression of HIF activity strongly reduced the protective effect of dexrazoxane. Conversely, HIF‐1α overexpression protected against doxorubicin‐mediated cell death and apoptosis also in cells not exposed to the chelator. Exposure to dexrazoxane increased the expression of the HIF‐regulated, antiapoptotic proteins survivin, Mcl1 and haem oxygenase.

CONCLUSIONS AND IMPLICATIONS

Our results showing HIF‐dependent prevention of doxorubicin toxicity in dexrazoxane‐treated H9c2 cardiomyocytes suggest that HIF activation may be a mechanism contributing to the protective effect of dexrazoxane against anthracycline cardiotoxicity.
Role of the endothelin axis and its antagonists in the treatment of cancer
Authors: Bagnato A , Loizidou M , Pflug BR , Curwen J , Growcott J
Published: January 2011

The endothelins (ET) are a group of proteins that act through G‐protein coupled receptors. Endothelin‐1 (ET‐1) was initially identified as a potent vasoconstrictor and dysregulation of the ET axis contributes to pathological processes responsible for cardiovascular disease states. More recently, the ET axis, in particular ET‐1 acting through the endothelin A receptor (ETA), has been implicated in the development of several cancers through activation of pathways involved in cell proliferation, migration, invasion, epithelial‐mesenchymal transition, osteogenesis and angiogenesis. The endothelin B receptor (ETB) may counter tumour progression by promoting apoptosis and clearing ET‐1; however, it has recently been implicated in the development of some tumour types including melanomas and oligodendrogliomas. Here, we review emerging preclinical and clinical data outlining the role of the ET axis in cancer, and its antagonism as an attractive and challenging approach to improve clinical cancer management. Clinical data of ETAantagonists in patients with prostate cancer are encouraging and provide promise for new ETAantagonist‐based treatment strategies. Given the unexpected opportunities to affect pleiotrophic tumorigenic signals by targeting ETA‐mediated pathways in a number of cancers, the evaluation of ET‐targeted therapy in cancer warrants further investigation.
bPiDI: a novel selective α6β2* nicotinic receptor antagonist and preclinical candidate treatment for nicotine abuse
Authors: Wooters Thomas E , Smith Andrew M , Pivavarchyk Marharyta , Siripurapu Kiran B , McIntosh J Michael , Zhang Zhenfa , Crooks Peter A , Bardo Michael T , Dwoskin Linda P
Published: January 2011

BACKGROUND AND PURPOSE

Nicotinic acetylcholine receptors (nAChRs) containing α6β2 subunits expressed by dopamine neurons regulate nicotine‐evoked dopamine release. Previous results show that the α6β2* nAChR antagonist,N,N′‐dodecane‐1,12‐diyl‐bis‐3‐picolinium dibromide (bPiDDB) inhibits nicotine‐evoked dopamine release from dorsal striatum and decreases nicotine self‐administration in rats. However, overt toxicity emerged with repeated bPiDDB treatment. The current study evaluated the preclinical pharmacology of a bPiDDB analogue.

EXPERIMENTAL APPROACH

The C10analogue of bPiDDB,N,N‐decane‐1,10‐diyl‐bis‐3‐picolinium diiodide (bPiDI), was evaluated preclinically for nAChR antagonist activity.

KEY RESULTS

bPiDI inhibits nicotine‐evoked [3H]dopamine overflow (IC50 = 150 nM,Imax = 58%) from rat striatal slices. Schild analysis revealed a rightward shift in the nicotine concentration–response curve and surmountability with increasing nicotine concentration; however, the Schild regression slope differed significantly from 1.0, indicating surmountable allosteric inhibition. Co‐exposure of maximally inhibitory concentrations of bPiDI (1 µM) and the α6β2* nAChR antagonist α‐conotoxin MII (1 nM) produced inhibition not different from either antagonist alone, indicating that bPiDI acts at α6β2* nAChRs. Nicotine treatment (0.4 mg·kg−1·day−1, 10 days) increased more than 100‐fold the potency of bPiDI (IC50 = 1.45 nM) to inhibit nicotine‐evoked dopamine release. Acute treatment with bPiDI (1.94–5.83 µmol·kg−1, s.c.) specifically reduced nicotine self‐administration relative to responding for food. Across seven daily treatments, bPiDI decreased nicotine self‐administration; however, tolerance developed to the acute decrease in food‐maintained responding. No observable body weight loss or lethargy was observed with repeated bPiDI.

CONCLUSIONS AND IMPLICATIONS

These results are consistent with the hypothesis that α6β2* nAChR antagonists have potential for development as pharmacotherapies for tobacco smoking cessation.
A Methodology for Modeling Regional Terrorism Risk
Authors: Chatterjee Samrat , Abkowitz Mark D.
Published: January 2011

Over the past decade, terrorism risk has become a prominent consideration in protecting the well‐being of individuals and organizations. More recently, there has been interest in not only quantifying terrorism risk, but also placing it in the context of an all‐hazards environment in which consideration is given to accidents and natural hazards, as well as intentional acts. This article discusses the development of a regional terrorism risk assessment model designed for this purpose. The approach taken is to model terrorism risk as a dependent variable, expressed in expected annual monetary terms, as a function of attributes of population concentration and critical infrastructure. This allows for an assessment of regional terrorism risk in and of itself, as well as in relation to man‐made accident and natural hazard risks, so that mitigation resources can be allocated in an effective manner. The adopted methodology incorporates elements of two terrorism risk modeling approaches (event‐based models and risk indicators), producing results that can be utilized at various jurisdictional levels. The validity, strengths, and limitations of the model are discussed in the context of a case study application within the United States.
Activation of NMDA Receptors in Lumbar Spinothalamic Cells is Required for Ejaculation
Authors: Staudt Michael D. , de Oliveira Cleusa V.R. , Lehman Michael N. , McKenna Kevin E. , Coolen Lique M.
Published: January 2011

Introduction

The sexual reflex ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord. A population of spinothalamic (LSt) neurons forms a key component of this generator, as manipulations of LSt cells either block or trigger ejaculation. However, it is currently unknown which afferent signals contribute to the activation of LSt cells and ejaculation.

Aim

The current study tested the hypothesis that glutamate, via activation of N-Methyl-D-aspartic acid (NMDA) receptors in LSt cells, is a key regulator of ejaculation.

Methods

Expression of phosphorylated NMDA receptor subunit 1 (NR1) was investigated following mating, or following ejaculation induced by electrical stimulation of the dorsal penile nerve (DPN) in anesthetized, spinalized male rats. Next, the effects of intraspinal delivery of NMDA receptor antagonist AP-5 on DPN stimulation-induced ejaculation were examined. Moreover, the ability of intraspinal delivery of NMDA to trigger ejaculation was examined. Finally, the site of action of NMDA was determined by studying effects of NMDA in male rats with LSt cell-specific lesions.

Main Outcome Measures

Expression of NR1 and phosphorylated NR1 in LSt cells was analyzed. Electromyographic recordings of the bulbocavernosus muscle (BCM) were recorded in anesthetized, spinalized rats following stimulation of the DPN and delivery of AP-5 or NMDA.

Results

Results indicate that the NR1 receptors are activated in LSt cells following ejaculation in mating animals or induced by DPN stimulation in anesthetized, spinalized animals. Moreover, NR1 activation in LSt cells is an essential trigger for rhythmic BCM bursting, as DPN stimulation-induced reflexes were absent following administration of NMDA receptor antagonist in the L3-L4 spinal area, and were triggered by NMDA. NMDA effects were dependent on intact LSt cells and were absent in LSt-lesioned males.

Conclusion

These results demonstrate that glutamate, via activation of NMDA receptors in LSt cells, is a key afferent signal for ejaculation.
Programming Effects of Antenatal Corticosteroids Exposure in Male Sexual Behavior
Authors: Oliveira Mário , Leão Pedro , Rodrigues Ana-João , Pêgo José-Miguel , Cerqueira João-José , Sousa Nuno
Published: January 2011

Introduction

Brain regions implicated in sexual behavior begin to differentiate in the last trimester of gestation. Antenatal therapy with corticosteroids is often used in clinical practice during this period to accelerate lung maturation in preterm-risk pregnancies. Clinical and animal studies highlighted major behavioral impairments induced later in life by these treatments, especially when synthetic corticosteroids are used.

Aim

To evaluate the implications of acute prenatal treatment with natural vs. synthetic corticosteroids on adult male rat sexual behavior and its neurochemical correlates.

Methods

Twelve pregnant Wistar rats were injected with dexamethasone (DEX—1 mg/kg), corticosterone (CORT—25 mg/kg), or saline on late gestation (pregnancy days 18 and 19). Following this brief exposure to corticosteroids, we assessed the sexual behavior of the adult male progeny and subsequently associated these behaviors with the levels of catecholamines and mRNA of dopamine and androgen receptors (AR) in brain regions relevant for sexual behavior.

Main Outcome Measures

Sexual behavior of adult male offspring was assessed by exposure to receptive females. This was associated with serum testosterone levels and levels of catecholamines (determined by high-performance liquid chromatography) and dopamine and AR mRNA expression (real-time polymerase chain reaction [PCR]) in brain regions implicated in sexual behavior.

Results

Prenatal DEX exposure resulted in a decreased number and increased mounts and intromissions latencies in adulthood. These findings were associated with decreased levels of serum testosterone and increased hypothalamic expression of AR mRNA. DEX animals also displayed lower dopamine levels and higher dopamine receptor mRNA expression both in hypothalamus and nucleus accumbens (NAcc). The milder phenotype of CORT animals was associated only with decreased dopamine levels in NAcc.

Conclusion

Antenatal corticotherapy programs adult male sexual behavior through changes in specific neuronal and endocrine mediators. Importantly, equipotent doses of CORT trigger less detrimental consequences than DEX, emphasizing the differential impact of activation of the different corticosteroid receptors.
PARP Inhibition Restores Erectile Function by Suppressing Corporal Smooth Muscle Apoptosis in Diabetic Rats
Authors: Li Wen Ji , Zhou Juan , Li Bao , Wang Hao , Peng Yu Bing , Wang Zhong
Published: January 2011

Introduction

An important mechanism suggested to be responsible for diabetes-associated erectile dysfunction (ED) involves increased apoptosis, increased collagen deposition, and reduced smooth muscle content in the corpus cavernosum.

Aim

To determine whether the activation of the pro-apoptotic poly(adenosine diphosphate ribose) polymerase (PARP) pathway is involved in the induction of corporal apoptosis, and whether the administration of 3-aminobenzamide (3-AB), a specific PARP inhibitor, could ameliorate ED in diabetic rats.

Methods

Male Sprague-Dawley rats (8-weeks-old) were randomly divided into three groups: age-matched controls (C), diabetic controls (DM), and 3-AB-treated diabetic group (DM + 3-AB). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg). Eight weeks after the induction of diabetes, DM + 3-AB group treated with 3-AB (30 mg/kg/day, ip) for 4 weeks.

Main Outcome Measures

At 12 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis, Masson’s trichrome stain and immunohistochemical analysis for smooth muscle alpha actin. Expression of poly(ADP-ribose), phospho-protein kinase B (Akt), phospho-Bcl-2-associated death promoter (Bad), B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and apoptosis-inducing factor (AIF) were evaluated by Western blot. Caspase-3 activity and malondialdehyde (MDA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD+) concentrations were also determined.

Results

DM group showed impaired erectile function, increased PARP activity and corporal apoptosis, and decreased smooth muscle contents. Expression of phospho-Akt, phospho-Bad, Bcl-2, and concentrations of ATP and NAD+ were decreased in the DM group, whereas concentrations of MDA, expression of Bax, nuclear translocation of AIF, and caspase-3 activity were increased. Treatment with 3-AB restored erectile function and significantly reversed all molecular and histological alterations except for the increased MDA.

Conclusions

Over-activation of penile PARP pathway in diabetic rats enhances corporal apoptosis via energy depletion, suppression of Akt phosphorylation, and activation of the mitochondrial apoptotic pathway, which results in ED; these event could be prevented by treatment with 3-AB.
Injection System for Multiwell Injection Using a Single Pump
Authors: Wovkulich Karen , Stute Martin , Protus Thomas J. , Mailloux Brian J. , Chillrud Steven N.
Published: January 2011

Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a 3‐month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over 3 months; an even distribution of flow to each injection well was maintained (RSD < 4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air‐stable liquids to multiple injection points with a single pump.
The Management of Hypertension for Primary Stroke Prevention: A Proposed Approach
Authors: Sharma Mukul , Hakim Antoine M.
Published: January 2011

The prevalence of hypertension in society is high and increasing. Untreated hypertension results in stroke, dementia, and damage to major organs. This article reviews the risks that hypertension causes and the issues now generally accepted as playing a role in the low level of hypertension control. These include lack of public awareness of the significance of elevated blood pressure, lack of impetus to measure blood pressure, lack of sites to perform the measurements, occasional therapeutic inertia on the part of the medical community, and poor compliance with treatment on the part of affected individuals. Innovative measures that may result in improved management of this risk factor are discussed. These include ubiquitous blood pressure measurement sites, expanding therapeutic potential by involving allied health professionals, and offering rewards for treatment and for compliance. The article also emphasises that the ideal blood pressure target for the primary prevention of stroke remains unclear.
GGR Biennial Review: Reference Materials in Geoanalytical and Environmental Research – Review for 2008 and 2009
Authors: Jochum Klaus Peter , Enzweiler Jacinta , Mertz‐Kraus Regina , Wang Xiaohong
Published: January 2011

This review gives an overview of the literature on reference materials of geochemical and environmental interest for the two‐year period 2008–2009. Reference materials play an increasingly important role in all fields of geoanalytical research. This is demonstrated by the large number of publications containing data on reference materials. Although many reference materials exist, there is still a great need for certified samples, so‐called delta zero materials for stable isotopic work and homogeneous microanalytical reference materials. This review focuses on six topics: developments of certification processes of reference materials mainly postulated in ISO guidelines and the IAG protocol, new developments of the GeoReM database, investigations of powdered rock reference materials, Chinese reference materials published in Chinese journals, microanalytical reference materials and isotopic reference materials.
Long‐term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age‐related macular degeneration in the EXTEND‐I study
Authors: Tano Yasuo , Ohji Masahito ,   on behalf of the EXTEND‐I Study Group
Published: January 2011

Purpose:  To evaluate the long‐term efficacy and safety of ranibizumab administered pro re nata (PRN) in Japanese patients with choroidal neovascularization secondary to age‐related macular degeneration during the extension phase of the EXTEND‐I study.

Methods:  EXTEND‐I, an open‐label, multicenter, Phase I/II study comprised: a single‐injection (Group A); a multiple‐injection (Groups A and B; the latter consisted of patients who did not participate in the single‐injection phase); and an extension phase. In the extension phase, a PRN regimen of ranibizumab (0.3 or 0.5 mg) guided by monthly best‐corrected visual acuity (BCVA) score and other ophthalmic examinations was employed. The efficacy variables included the mean BCVA change from Month 12 to the last visit in Group B. Safety was assessed in all patients.

Results:  In the extension phase, efficacy was assessed only in Group B patients. The number of ranibizumab injections per year in the 0.3 and 0.5 mg Group B patients was 4.19 and 4.27, respectively. The mean BCVA change (SD) from Month 12 to the last visit was −3.6 (14.82) letters for 0.3 mg (n = 28) and −2.2 (7.92) letters for 0.5 mg groups (n = 33) in Group B. Conjunctival haemorrhage and nasopharyngitis were the most commonly reported adverse events. Of the 13 serious adverse events reported, cerebral infarction (two incidences) was suspected to be study‐drug related.

Conclusions:  Pro re nata regimen of ranibizumab guided by monthly BCVA and other ophthalmic examinations appears effective in sustaining the BCVA gained with 12 monthly injections while reducing the number of injections during the extension phase. Ranibizumab was well tolerated during the extension phase.
The predictive value of subjective symptoms and clinical signs for the presence of treatment‐requiring exudative age‐related macular degeneration
Authors: Hessellund Anders , Larsen Dorte Ancher , Bek Toke
Published: January 2011

Purpose:  The introduction of vascular endothelial growth factor inhibitors for the treatment of exudative age‐related macular degeneration (AMD) has increased the referral rates of AMD patients with visual symptoms to treating centres considerably. However, a large proportion of the referred patients do not qualify for treatment implying that considerable resources could be saved if these patients could be identified on the basis of the clinical data available in the referring nonspecialized setting.

Methods:  A prospective observational study of 1682 consecutive patients referred with suspicion of exudative AMD qualifying for intravitreal angiostatic treatment. On the basis of the structured interviewing about symptoms, ophthalmoscopy, optical coherence tomography scanning, and fluorescein angiography, the patients were divided into two groups: one qualifying for and another not qualifying for treatment. Multiple logistic regression was used to identify independent parameters predicting the need for treatment.

Results:  The presence of metamorphopsia, dyschromatopsia, retinal haemorrhages and exudates, central retinal thickness, and the absence of micropsia were highly significant individual determinants of treatment‐requiring AMD. Sudden onset and worsening of symptoms and the presence of a central dark spot covaried with the occurrence of retinal haemorrhages, whereas reduced visual acuity and blurred vision covaried with the presence of both haemorrhages and exudates.

Conclusion:  Patients with treatment‐requiring AMD can be reliably identified by questioning about the presence of metamorphopsia and dyschromatopsia and the absence of micropsia, combined with ophthalmoscopical detection of retinal haemorrhages and exudates. This information may improve the triage of patients considered for referral.
Incorrect drug selection at the point of dispensing: a study of potential predisposing factors
Authors: Anto Berko , Barlow David , Oborne C Alice , Whittlesea Cate
Published: January 2011

Objective

To determine potential predisposing factors to medication errors involving confusion between drug names, strengths and dosage forms.

Methods

The study analysed medication errors reported over the period January 2005 to December 2008 from the two main dispensaries of a 1200-bed NHS Foundation Hospital Trust in London. Dispensing incidents considered for analysis included all incidents involving drug name, strength and dosage label and content errors. Statistical analyses were performed using Statistica. Dispensing frequencies of the prescribed and wrongly dispensed drugs were compared by means of Wilcoxon signed-rank test, and the extent of correlation between dispensing frequency and error frequency was assessed using Spearman's rank correlation coefficient.

Key findings

The Trust recorded a total of 911 dispensing errors between 2005 and 2008. The most significant category, which accounted for 211 (23.2%) of the reported errors, involved errors in drug selection. Drug-selection errors were not random events because the plot of error frequency against the average yearly dispensing frequency for the 1000 most issued drugs showed little evidence of association (r = 0.19, P(α) = 0.03). There was, however, an increased likelihood of drug-selection errors occurring when the prescribed drug was dispensed with relatively low frequency and shows a significant orthographic similarity to another drug which has a higher dispensing frequency.

Conclusion

The majority of drug-selection errors would seem to be caused by insufficient attention paid to the specified drug strength. Dispensing frequency is an important factor influencing the likelihood of a drug-selection errors occurring, but it is also shown here that a large proportion of the drug-selection errors involved specifications exhibiting high orthographic similarity.
An explanatory policy analysis of legislative change permitting pharmacists in Alberta, Canada, to prescribe
Authors: MacLeod-Glover Nora
Published: January 2011

Objectives

This paper provides an explanatory policy analysis of the new legislation which permits pharmacist prescribing in Alberta, Canada: the Pharmacists Profession Regulations (2006) to the Health Professions Act (1999). Its purpose is to provide useful insights for pharmacy regulatory bodies in other jurisdictions internationally that are in a position to pursue similar opportunities.

Methods

A search for government and regulatory body documents related to Alberta healthcare system and pharmacist prescribing was performed. Correspondence was initiated with authors and regulators to clarify or obtain current data.

Key findings

Research to support policy change recommendations and communication among healthcare professionals, regulators and other stakeholders is essential for developing and implementing legislative change regarding health professionals' scopes of practice at a time when legislative change is possible. Stakeholder barriers to implementation need to be identified early to provide opportunity to address and resolve.

Conclusions

Collaboration between healthcare professionals, regulators and other stakeholders is essential to developing a prescribing model that can be successfully implemented when there is the opportunity for legislative change related to health professionals' scope of practice.
Enhancement and Prediction of Heat Transfer Rate in Turbulent Flow Through Tube With Perforated Twisted Tape Inserts: A New Correlation
Authors: Ahamed J. U. , Wazed M. A. , Ahmed S. , Nukman Y. , Ya T. M. Y. S. Tuan , Sarkar M. A. R.
Published: January 2011

An experimental investigation has been carried out for turbulent flow in a tube with perforated twisted tape inserts. The mild steel twisted tape inserts with circular holes of different diameters (i.e., perforation) are used in the flow field. An intensive laboratory study is conducted for heat transfer and pressure drop characteristics in the tubes for turbulent flow with various airflow rates. Heat transfer and pressure drop data are engendered for a wide range Reynolds number (1.3×104–5.2×104). Tube wall temperature, pressure drop, air velocity, and its temperature are measured both for plain tube and for tube with perforated twisted tape inserts. Heat transfer coefficients, Nusselt number, pumping power, and heat transfer effectiveness are calculated for both cases. Experimental results showed that perforated twisted inserts of different geometry in a circular tube enhanced the heat transfer rate with an increase in friction factor and pumping power for turbulent flow. The pumping power, heat transfer coefficient, and effectiveness in the tube with the twisted tape inserts are found to increase up to 1.8, 5.5, and 4.0 times of those for the plain tube for same Reynolds number, respectively. Finally, a correlation is developed for prediction of the heat transfer rate for turbulent flow through a circular tube with perforated twisted tape inserts.
Maximally Regular T2R1-Type Parallel Manipulators With Bifurcated Spatial Motion
Authors: Gogu Grigore
Published: January 2011

This paper presents a new family of maximally regular T2R1-type parallel manipulators with bifurcated spatial motion. In each branch, the moving platform has two independent translations (T2) and one rotation (R1) driven by three actuators mounted on the fixed base. The rotation axis is situated in the plane of translation and can bifurcate in two orthogonal directions. This bifurcation occurs in a constraint singularity in which the connectivity between the moving and fixed platforms increases instantaneously, incurring no change in limb connectivity. The Jacobian matrix of the maximally regular solutions presented in this paper is a 3×3 identity matrix in the entire workspace of each branch. This paper presents for the first time a family of maximally regular T2R1-type parallel manipulators with bifurcated spatial motion of the moving platform along with solutions using uncoupled motions.
Effect of Biodiesel, JP-8 and Ultra Low Sulfur Diesel Fuel on Autoignition, Combustion, Performance and Emissions in a Single Cylinder Diesel Engine
Authors: Jayakumar Chandrasekharan , Nargunde Jagdish , Sinha Anubhav , Bryzik Walter , Henein Naeim A. , Sattler Eric
Published: January 2011

Concern about the depletion of petroleum reserves, rising prices of conventional fuels, security of supply and global warming have driven research toward the development of renewable fuels for use in diesel engines. These fuels have different physical and chemical properties that affect the diesel combustion process. This paper compares between the autoignition, combustion, performance and emissions of soybean derived biodiesel, JP-8 and ultra low sulfur diesel (ULSD) in a high speed single-cylinder research diesel engine equipped with a common rail injection system. Tests were conducted at steady state conditions at different injection pressures ranging from 600 bar to 1200 bar. The ‘rate of heat release’ traces are analyzed to determine the effect of fuel properties on the ignition delay, premixed combustion fraction and mixing and diffusion controlled combustion fractions. Biodiesel produced the largest diffusion controlled combustion fraction at all injection pressures compared to ULSD and JP-8. At 600 bar injection pressure, the diffusion controlled combustion fraction for biodiesel was 53% whereas both JP-8 and ULSD produced 39%. In addition, the effect of fuel properties on engine performance, fuel economy, and engine-out emissions is determined. On an average JP-8 produced 3% higher thermal efficiency than ULSD. Special attention is given to the NOx emissions and particulate matter characteristics. On an average biodiesel produced 37% less NOx emissions compared to ULSD and JP-8.