bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive familial intrahepatic cholestasis
Authors: Davit-Spraul Anne , Gonzales Emmanuel , Baussan Christiane , Jacquemin Emmanuel
Published: January 2009

Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births.

Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP). Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3), impair biliary phospholipid secretion resulting in PFIC3.

Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of hepatocellular carcinoma, especially in PFIC2 patients, should be offered from the first year of life. Hepatocyte transplantation, gene therapy or specific targeted pharmacotherapy may represent alternative treatments in the future.
Contralateral approach to a carotid bifurcation aneurysm in a case of multiple intracranial aneurysms: a case report
Authors: Tabatabai Seyed Ali F , Meybodi Ali Tayebi , Hashemi Mohammad , Habibi Zohreh
Published: January 2009

Background

Traditionally, surgery of the anterior circulation aneurysms of the cerebral vasculature is dictated by the site of the lesion, excluding such midline lesions as anterior communication artery aneurysms. Few reports address the issue of using a single craniotomy to obliterate multiple aneurysms located in both hemispheres.

Case presentation

A 51 year-old Caucasian right handed housewife lady (weight 61 kg, height 159 cm) presented with a headache of acute onset which proved to be caused by acute subarachnoid hemorrhage. Cerebral computed tomographic angiography revealed multiple aneurysms. The patient underwent a right pterional craniotomy to obliterate right middle cerebral, distal basilar and left carotid bifurcation aneurysms. The post-operative course was uneventful.

Conclusion

Despite technical difficulties of approaching cerebral vasculature through a contralateral craniotomy, this policy is advised in selected cases in which the benefits of unilateral craniotomy outweigh the risks of brain retraction.
Sedation practice in the intensive care unit: a UK national survey
Authors: Reschreiter Henrik , Maiden Matt , Kapila Atul
Published: January 2009

Introduction

The purpose of this study was to evaluate sedation practice in UK intensive care units (ICUs), particularly the implementation of daily sedation holding, written sedation guidelines, sedation scoring tools and choice of agents.

Methods

A national postal survey was conducted in all UK ICUs.

Results

A total of 192 responses out of 302 addressed units were received (63.5%). Of the responding ICUs, 88% used a sedation scoring tool, most frequently the Ramsey Sedation Scale score (66.4%). The majority of units have a written sedation guideline (80%), and 78% state that daily sedation holding is practiced. A wide variety of sedating agents is used, with the choice of agent largely determined by the duration of action rather than cost. The most frequently used agents were propofol and alfentanil for short-term sedation; propofol, midazolam and morphine for longer sedation; and propofol for weaning purposes.

Conclusions

Most UK ICUs use a sedation guideline and sedation scoring tool. The concept of sedation holding has been implemented in the majority of units, and most ICUs have a written sedation guideline.
Studying alternative splicing regulatory networks through partial correlation analysis
Authors: Chen Liang , Zheng Sika
Published: January 2009

Background

Alternative pre-mRNA splicing is an important gene regulation mechanism for expanding proteomic diversity in higher eukaryotes. Each splicing regulator can potentially influence a large group of alternative exons. Meanwhile, each alternative exon is controlled by multiple splicing regulators. The rapid accumulation of high-throughput data provides us with a unique opportunity to study the complicated alternative splicing regulatory network.

Results

We propose the use of partial correlation analysis to identify association links between exons and their upstream regulators or their downstream target genes (exon-gene links) and links between co-spliced exons (exon-exon links). The partial correlation analysis avoids taking the ratio of two noisy random variables, exon expression level and gene expression level, so that it achieves a higher statistical power. We named this analysis procedure pCastNet (partial Correlation analysis of splicing transcriptome Network). Through studies of known alternative exons, conservation patterns, relative positions, functional annotations, and RT-PCR experiments, we concluded that pCastNet can effectively identify exon-gene or exon-exon links. We further found that gene pairs with exon-gene or exon-exon links tend to have similar functions or are present in the same pathways. More interestingly, gene pairs with exon-gene or exon-exon links tend to share cis-elements in promoter regions and microRNA binding elements in 3' untranslated regions, which suggests the coupling of co-alternative-splicing, co-transcription-factor-binding, and co-microRNA-binding.

Conclusions

Alternative splicing regulatory networks reconstructed by pCastNet can help us better understand the coordinate and combinatorial nature of alternative splicing regulation. The proposed tool can be readily applied to other high-throughput data such as transcriptome sequencing data.
Insight into the molecular requirements for pathogenicity of Fusarium oxysporum f. sp. lycopersici through large-scale insertional mutagenesis
Authors: Michielse Caroline B , van Wijk Ringo , Reijnen Linda , Cornelissen Ben JC , Rep Martijn
Published: January 2009

Background

Fusarium oxysporum f. sp. lycopersici is the causal agent of vascular wilt disease in tomato. In order to gain more insight into the molecular processes in F. oxysporum necessary for pathogenesis and to uncover the genes involved, we used Agrobacterium-mediated insertional mutagenesis to generate 10,290 transformants and screened the transformants for loss or reduction of pathogenicity.

Results

This led to the identification of 106 pathogenicity mutants. Southern analysis revealed that the average T-DNA insertion is 1.4 and that 66% of the mutants carry a single T-DNA. Using TAIL-PCR, chromosomal T-DNA flanking regions were isolated and 111 potential pathogenicity genes were identified.

Conclusions

Functional categorization of the potential pathogenicity genes indicates that certain cellular processes, such as amino acid and lipid metabolism, cell wall remodeling, protein translocation and protein degradation, seem to be important for full pathogenicity of F. oxysporum. Several known pathogenicity genes were identified, such as those encoding chitin synthase V, developmental regulator FlbA and phosphomannose isomerase. In addition, complementation and gene knock-out experiments confirmed that a glycosylphosphatidylinositol-anchored protein, thought to be involved in cell wall integrity, a transcriptional regulator, a protein with unknown function and peroxisome biogenesis are required for full pathogenicity of F. oxysporum.
Porcine Marginal Mass Islet Autografts Resist Metabolic Failure Over Time and Are Enhanced by Early Treatment with Liraglutide
Authors: Emamaullee Juliet A. , Merani Shaheed , Toso Christian , Kin Tatsuya , Al-Saif Faisal , Truong Wayne , Pawlick Rena , Davis Joy , Edgar Ryan , Lock Jennifer , Bonner-Weir Susan , Knudsen Lotte B. , Shapiro A. M. James
Published: January 2009

Although insulin independence is maintained in most islet recipients at 1 yr after transplant, extended follow-up has revealed that many patients will eventually require insulin therapy. Previous studies have shown that islet autografts are prone to chronic failure in large animals and humans, suggesting that nonimmunological events contribute to islet graft functional decay. Early intervention with therapies that promote graft stability should provide a measurable benefit over time. In this study, the efficacy of the long-acting glucagon-like peptide-1 analog liraglutide was explored in a porcine marginal mass islet autograft transplant model. Incubation with liraglutide enhanced porcine islet survival and function after prolonged culture. Most vehicle-treated (83%) and liraglutide-treated (80%) animals became insulin independent after islet autotransplantation. Although liraglutide therapy did not improve insulin independence rates or blood glucose levels after transplant, a significant increase in insulin secretion and acute-phase insulin response was observed in treated animals. Surprisingly, no evidence for deterioration of graft function was observed in any of the transplanted animals over more than 18 months of follow-up despite significant weight gain; in fact, an enhanced response to glucose developed over time even in control animals. Histological analysis showed that intraportally transplanted islets remained highly insulin positive, retained α-cells, and did not form amyloid deposits. This study demonstrates that marginal mass porcine islet autografts have stable long-term function, even in the presence of an increasing metabolic demand. These results are discrepant with previous large animal studies and suggest that porcine islets may be resistant to metabolic failure.
Organizational Actions of Postnatal Estradiol in Female Sheep Treated Prenatally with Testosterone: Programming of Prepubertal Neuroendocrine Function and the Onset of Puberty
Authors: Jackson Leslie M. , Timmer Kathleen M. , Foster Douglas L.
Published: January 2009

Prenatal testosterone (T) exposure defeminizes reproductive neuroendocrine function in female sheep, although the LH surge dysfunctions are initially less severe in gonadally intact females than in females subject to neonatal ovariectomy and estradiol (E) replacement. Because prepubertal ovarian production of E differs quantitatively and qualitatively from chronic E replacement, we tested the hypothesis that postnatal E exacerbates the consequences of prenatal T on the positive, but not the negative, steroid feedback controls of GnRH secretion. Our approach was to characterize prepubertal sensitivity to E negative feedback, the onset and maintenance of progestagenic cycles, and the LH surge response in ovary intact, prenatally untreated (control), and T-treated (T) sheep that were exposed postnatally to only endogenous E, or exposed to excess E by sc implant. Sensitivity to E negative feedback was reduced in T females, but excess postnatal E did not further increase LH pulse frequency. Excess E prevented ovarian cycles in several control females, and increased cycle irregularity in T females. However, the LH surge mechanism was functional in all control females (regardless of postnatal E exposure) and in some T females without excess E, but nonfunctional in T females with excess E. These findings suggest that postnatal E does not program increased resistance to E negative feedback, but excess postnatal E does disrupt other mechanisms required for ovarian cyclicity. We conclude that in this precocial species, prenatal steroids are sufficient to program controls of tonic LH secretion, but the LH surge mechanism is susceptible to further programming by postnatal E.
MicroRNA 18 and 124a Down-Regulate the Glucocorticoid Receptor: Implications for Glucocorticoid Responsiveness in the Brain
Authors: Vreugdenhil Erno , Verissimo Carla S. L. , Mariman Rob , Kamphorst Jessica T. , Barbosa Joana S. , Zweers Thijs , Champagne Danielle L. , Schouten Theo , Meijer Onno C. , Ron de Kloet E. , Fitzsimons Carlos P.
Published: January 2009

Glucocorticoids (GCs) exert profound effects on a variety of physiological processes, including adaptation to stress, metabolism, immunity, and neuronal development. Cellular responsiveness to GCs depends on numerous factors, including the amount of the glucocorticoid receptor (GR) protein. We tested the hypothesis that micro-RNAs (miRs), a recently discovered group of noncoding RNAs involved in mRNA translation, might control GR activity by reducing GR protein levels in neuronal tissues. We tested a panel of five miRs consisting of 124aa, 328, 524, 22, and 18. We found that miRs 18 and 124a reduced GR-mediated events in addition to decreasing GR protein levels. miR reporter assays revealed binding of miR-124a to the 3′ untranslated region of GR. In correspondence, the activation of the GR-responsive gene glucocorticoid-induced leucine zipper was strongly impaired by miR-124a and -18 overexpression. Although miR-18 is expressed widely throughout the body, expression of miR-124a is restricted to the brain. Endogenous miR-124a up-regulation during neuronal differentiation of P19 cells was associated with a decreasing amount of GR protein levels and reduced activity of luciferase reporter constructs bearing GR 3′ untranslated regions. Furthermore, we show that miR-124a expression varies over time during the stress hyporesponsive period, a neonatal period when GC signaling is modulated. Our findings demonstrate a potential role for miRs in the regulation of cell type-specific responsiveness to GCs, as may occur during critical periods of neuronal development. Ultimately, our results may provide a better understanding of the etiology of stress-related diseases as well as the efficacy of GC therapy.
RFamide-Related Peptide-3, a Mammalian Gonadotropin-Inhibitory Hormone Ortholog, Regulates Gonadotropin-Releasing Hormone Neuron Firing in the Mouse
Authors: Ducret Eric , Anderson Greg M. , Herbison Allan E.
Published: January 2009

The recent discovery that an RFamide termed gonadotropin-inhibitory hormone is likely to be a hypophysiotrophic gonadotropin release-inhibiting hormone in birds has generated interest into the role of LPXRFamide neuropeptides in the control of gonadotropin secretion in mammals. Recent immunocytochemical studies in birds and mammals have suggested that neurons expressing the mammalian LPXRFamides, RFamide-related peptides (RFRPs) 1 and 3, may innervate and regulate GnRH neurons directly. We used cell-attached electrophysiology in adult male and female GnRH-green fluorescent protein-tagged neurons to examine whether RFRP-3 modulated the electrical excitability of GnRH neurons. RFRP-3 was found to exhibit rapid and repeatable inhibitory effects on the firing rate of 41% of GnRH neurons. A small population of GnRH neurons (12%) increased their firing rate in response to RFRP-3, and the remainder was unaffected. No difference was detected in the RFRP-3 responses of GnRH neurons from male, diestrous, or proestrus female mice. The suppressive effect of RFRP-3 was maintained when amino acid transmission was blocked, suggesting a possible direct effect of RFRP-3 upon GnRH neurons. To evaluate the effects of other RFamide neuropeptides on GnRH neurons, we tested the actions of prolactin-releasing peptide-20 and -31. Neither compounds altered the firing rate of GnRH neurons. These studies demonstrate that RFRP-3 has a likely direct suppressive action on the excitability of GnRH neurons, indicating a role for RFRPs in the regulation of gonadotropin secretion in mammals through modulation of GnRH neuron activity.
Inhibition of Androgen Receptor Transcriptional Activity as a Novel Mechanism of Action of Arsenic
Authors: Rosenblatt Adena E. , Burnstein Kerry L.
Published: January 2009

Environmental sodium arsenite is a toxin that is associated with male infertility due to decreased and abnormal sperm production. Arsenic trioxide (ATO), another inorganic trivalent semimetal, is an effective therapy for acute promyelocytic leukemia, and there is investigation of its possible efficacy in prostate cancer. However, the mechanism of arsenic action in male urogenital tract tissues is not clear. Because the androgen receptor (AR) plays an important role in spermatogenesis and prostate cancer, we explored the possibility that trivalent arsenic regulates AR function. We found that arsenic inhibited AR transcriptional activity in prostate cancer and Sertoli cells using reporter gene assays testing several androgen response element-containing regions and by assessing native target gene expression. Arsenic inhibition of AR activity was not due to down-regulation of AR protein levels, decreased hormone binding to AR, disruption of AR nuclear translocation, or interference with AR-DNA binding in vitro. However, chromatin immunoprecipitation studies revealed that arsenic inhibited AR recruitment to an AR target gene enhancer in vivo. Consistent with a deficiency in AR-chromatin binding, arsenic disrupted AR amino and carboxyl termini interaction. Furthermore, ATO caused a significant decrease in prostate cancer cell proliferation that was more pronounced in cells expressing AR compared with cells depleted of AR. In addition, inhibition of AR activity by ATO and by the AR antagonist, bicalutamide, was additive. Thus, arsenic-induced male infertility may be due to inhibition of AR activity. Further, because AR is an important target in prostate cancer therapy, arsenic may serve as an effective therapeutic option.
Constitutive Somatostatin Receptor Activity Determines Tonic Pituitary Cell Response
Authors: Ben-Shlomo Anat , Zhou Cuiqi , Pichurin Oxana , Chesnokova Vera , Liu Ning-Ai , Culler Michael D. , Melmed Shlomo
Published: January 2009

Somatostatin (SRIF) binds G protein-coupled SRIF receptor subtypes (SST1, -2, -3, -4, and -5) to regulate cell secretion and proliferation. Hypothalamic SRIF inhibits pituitary growth hormone, thyroid stimulating hormone, and ACTH secretion. We tested SRIF-independent constitutive SST activity in AtT20 mouse pituitary corticotroph cells in which ACTH secretion is highly sensitive to SRIF action. Stable transfectants expressing SST2 or SST5 were sensitized to selective agonist action, and constitutive SST receptor activity was demonstrated by forskolin and pertussis toxin cAMP cell responses. Persistent constitutive SST activity decreased cell ACTH responses to CRH through decreased expression of CRH receptor subtype 1. Decreased dopamine receptor type 1 expression was associated with attenuated dopamine agonist action, whereas responses to isoproterenol were enhanced through increased β2-adrenoreceptor expression. Thus, integrated pituitary cell ACTH regulation is determined both by phasic SRIF action, as well as by tonic constitutive SST activity, independently of SRIF.
Factors associated with inappropriate inpatient prescribing of acid-suppressive therapy
Authors: Palkovic Lindsay B , Coley Kim C , Sokos Denise R
Published: January 2009

Objectives

Acid-suppressive therapy is used for 54–70% of inpatients, and is frequently prescribed for inappropriate indications. The objective of this study was to identify characteristics associated with inappropriate prescribing of acid-suppressive therapy.

Methods

A random sample of adult internal medicine inpatients admitted between 1 July 2005 and 30 June 2006 was screened for acid-suppressive therapy. Patients receiving such therapy without an accepted indication and those not prescribed acid-suppressive therapy were included in group 1 and group 2, respectively. Significant characteristics from separate univariate regression models were entered into a multivariate logistic regression to determine characteristics associated with inappropriate use. The setting was internal medicine units at a tertiary care academic medical centre.

Key findings

There were 108 patients in group 1 and 134 patients in group 2. Group 1 patients were older, had a longer median length of stay, a greater number of comorbidities, a greater median number of medications upon admission, and a higher rate of cirrhosis. Factors associated with use of acid-suppressive therapy without an accepted indication were use of a proton-pump inhibitor (odds ratio, 15.3; 95% confidence interval, 4.1–56.3) or histamine2 receptor antagonist (14.5; 2.8–74.8) prior to admission, cirrhosis (6.4; 1.02–39.5), use of inpatient anticoagulants (2.7; 1.4–5.2) and length of stay (1.1; 1.1-1.3).

Conclusions

The strongest factors associated with use of acid-suppressive therapy without an accepted indication were use of a proton-pump inhibitor or histamine2 receptor antagonist prior to admission, a diagnosis of cirrhosis and use of inpatient anticoagulants.
On modelling reusable components of change-capable manufacturing systems
Authors: Weston R H , Rahimifard A , Ajaefobi J O , Cui Z
Published: January 2009

New modelling constructs are defined to enable human, machine, and IT resource systems to be described coherently and explicitly as ‘reusable’, ‘change-capable’ ‘components’ of manufacturing enterprises. These components are referred to as ‘dynamic producer units’ or DPUs. DPU characterization is designed to facilitate: graphical representation of resource systems; explicit specification of resource systems; and implementation description of resource systems that can be computer executed within simulation modelling environments. Also described is a methodological use of the DPU modelling constructs, which shows how they can complement the use of ISO enterprise modelling and proprietary (discrete event and continuous) simulation software. By so doing, the modelling of responsive production systems is enabled, where such systems comprise user defined configurations of process networks, resource systems, and time-dependent flows of units of work. This modelling method enables decomposition and semantically rich representation of complex systems composed from interoperating DPUs that can be computer exercised within specific organizational contexts. This paper introduces the DPU and illustrates its systematic application when designing responsive production systems.
Recognizing shipbuilding parts using artificial neural networks and Fourier descriptors
Authors: Sanders D A
Published: January 2009

A pattern recognition system is described for recognizing shipbuilding parts using artificial neural networks and Fourier descriptors. The system uses shape contour information that is invariant of size, translation, and rotation. Fourier descriptors provide information, and the neural networks make decisions about the shapes. A brief review of the current state of the art is included, and results from testing show that the system distinguished between various shapes and proved to be a valid approach.
A study of multiple crack interaction at rolling contact fatigue loading of rails
Authors: Tillberg J , Larsson F , Runesson K
Published: January 2009

The objective of this paper is to investigate geometric and material parameters that affect the interaction of multiple pre-existing (initiated) cracks due to rolling contact fatigue (RCF) loading conditions. In particular, the behaviour of short cracks (head checks) in railway rail is studied. Parameters of interest are initial crack angle and spacing, distribution of initial crack lengths, width of the load/contact zone, and the material properties (in particular, the friction coefficient). Furthermore, the sensitivity of the finite element (FE)-mesh density is investigated. An open question of particular interest is the effect of crack interaction, e.g. shielding, on the prevailing crack spacing. In view of all uncertainties of the material model as well as the three-dimensional geometric complexity of the RCF problem, it is important to obtain a good understanding of the sensitivity of parameter changes. This is achieved in the presented investigation, although it is carried out using simplifying assumptions such as plane strain, linear elasticity, and Hertzian pressure distribution.
Intra-Molecular Cross-Linking of Acidic Residues for Protein Structure Studies
Authors: Novák Petr , Kruppa Gary H.
Published: January 2009

Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would help to develop structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine (lysine, the amino terminus) selective reagents. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution and solvent accessibility of the lysines in the protein sequence. To overcome these limitations, we have investigated the use of cross-linking reagents that can react with other reactive side chains in proteins. We used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E) and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO side chains can react to form “zero-length” cross-links with nearby primary amine containing residues, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO side chains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker arm of variable length. Using these reagents, we have found three new “zero-length” cross-links in ubiquitin consistent with its known structure (M1–E16, M1–E18 and K63–E64). Using the dihydrazide cross-linkers, we have identified two new cross-links (D21–D32 and E24–D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO–DEO cross-links of 5.8Å. These results show that additional structural information can be obtained by exploiting new cross-linker chemistry, increasing the probability that the protein target will yield sufficient distance constraints to develop a structural model.
Nano-Desorption Electrospray and Kinetic Method in Chiral Analysis of Drugs in Whole Human Blood Samples
Authors: Ranc Václav , Havlíček Vladimír , Bednar Petr , Lemr Karel
Published: January 2009

A home-made nano-desorption electrospray ionization (nano-DESI) device and the kinetic method were tested in chiral analysis of model clinical samples containing enantiomers of one of three pharmaceutically important compounds: dihydroxyphenylalanine (DOPA), ephedrine and ibuprofen. The initial evaluation of chiral systems was carried out by direct infusion of solution mixtures (analyte/central metal/chiral reference ligand) to a standard electrospray ionization (ESI) source. Cu(II) was used as a central metal for all analytes, l-phenylalanine was applied as a chiral reference ligand for DOPA, whereas l-tryptophan was used for the other two analytes. Then, the ESI source was substituted by a nano-DESI source and dried spots of 1 μL samples of whole human blood spiked with individual drugs were successfully analyzed without any pre-treatment. Irrespective of a laborious initial nano-DESI set-up, the combination of the kinetic method with nano-desorption electrospray has, for the first time, been demonstrated as a promising tool for chiral analysis of drugs in blood samples.
Deciphering Dorin M Glycosylation by Mass Spectrometry
Authors: Man Petr , Kovář Vojtěch , Štěrba Ján , Strohalm Martin , Kavan Daniel , Kopáček Petr , Grubhoffer Libor , Havlíček Vladimír
Published: January 2009

The soft tick, Ornithodoros moubata, is a vector of several bacterial and viral pathogens including Borrelia duttoni, a causative agent of relapsing fever and African swine fever virus. Previously, a sialic acid-specific lectin Dorin M was isolated from its hemolymph. Here, we report on the complete characterization of the primary sequence of Dorin M. Using liquid chromatography coupled to mass spectrometry, we identified three different glycopeptides in the tryptic digest of Dorin M. The peptide, as well as the glycan part of all glycopeptides, were further fully sequenced by means of tandem mass spectrometry (MS2) and multiple-stage mass spectrometry (MS3). Two classical N-glycosylation sites were modified by high-mannose-type glycans containing up to nine mannose residues. The third site bore a glycan with four to five mannose residues and a deoxyhexose (fucose) attached to the proximal N-acetylglycosamine. The microheterogeneity at each site was estimated based on chromatographic behavior of different glycoforms. The fourth, a non-classical N-glycosylation site (Asn–Asn–Cys), was not glycosylated, probably due to the involvement of the cysteine residue in a disulfide bridge.
Associations of Genetic Variants in ATP-Binding Cassette A1 and Cholesteryl Ester Transfer Protein and Differences in Lipoprotein Subclasses in the Multi-Ethnic Study of Atherosclerosis
Authors: Tsai Michael Y , Li Na , Sharrett A Richey , Shea Steven , Jacobs David R , Tracy Russell , Arnett Donna , Arends Valerie , Post Wendy
Published: January 2009

Background: ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied.

Methods: We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy.

Results: ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, −2505C/A AA, and −629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations.

Conclusions: Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes.
Determination of Selected Geotechnical Properties of Soil Using Electrical Conductivity Testing
Authors: Sebastian Bryson L. , Bathe Abhijit
Published: January 2009

The use of electrical conductivity measurements, at relatively low frequencies, has been shown to be an effective tool for characterizing soils for hydrogeological studies. Many of the properties that affect the hydraulic and mechanical behavior of a soil also affect the electrical response. Thus, there is a likelihood that electrical measurements of soils will provide useful information for predicting geotechnical parameters. This paper presents the results of efforts to develop an electrical conductivity testing system that can be used specifically to evaluate geotechnical properties of soils. The testing system consisted of a robust data acquisition and control system that allowed for autonomous testing of various sand-clay mixtures and a testing apparatus that was rugged enough to allow soil samples to be compacted directly into the cell. The testing apparatus utilized a multi-electrode configuration which facilitated the investigation of anisotropic electrical measurements of the compacted soil samples. The data obtained during the evaluation phase of this research showed that low-frequency electrical conductivity measurements are viable for evaluating and predicting geotechnical properties of soils such as void ratio and volumetric water content, and the use of the multi-electrode configuration is very promising for evaluating anisotropy in soils.
Ein Verfahren zur modellbasierten On-Board Diagnose von Drei-Wege-KatalysatorenA Method for Model-based On-board Diagnosis for Three-Way Catalytic Converters
Authors: Feßler Dirk K. , Krebs Volker
Published: January 2009

Dieser Beitrag beschreibt ein neues modellbasiertes On-Board Diagnoseverfahren für Drei-Wege-Katalysatoren, das Information über die Wärmeenergie nutzt, die durch die im Katalysator stattfindenden, stark exothermen chemischen Reaktionen entsteht. Bei diesem Verfahren kommt ein Sigma-Punkt-Kalman-Filter zum Einsatz, das fortlaufend den aktuellen Zustand des Katalysators schätzt. Erreicht dieser einen bestimmten Grenzwert, erfolgt eine Fehlermeldung. Das Filter basiert auf einem physikalischen Modell des Drei-Wege-Katalysators und verwendet als wesentliche Messgröße die Abgastemperatur am Ausgang des Katalysators.
Brennraumdruckbasierte Extremwertregelung für direkteinspritzende OttomotorenSelf-Tuning Extremum Control Based on Cylinder Pressure Sensors for Direct Injection Spark Ignition Engines
Authors: Kohlhase Martin , Isermann Rolf
Published: January 2009

Es wird eine brennraumdruckbasierte Extremwert-Regelung zur Online-Optimierung der Verbrennungsschwerpunktlage bzw. des Zündwinkels hinsichtlich maximaler Drehmomentabgabe bzw. maximalem indiziertem Mitteldruck vorgestellt. Die Regelung hält zylinder-individuell — unabhängig von Fertigungstoleranzen, Alterung und Sensorfehlern — den für den jeweiligen Motorbetriebspunkt optimalen Wert von Zündzeitpunkt bzw. Verbrennungsschwerpunktlage und regelt diese unabhängig von Störungen.
Looking inside the Burmese Military
Authors: Min Win
Published: January 2009

This article examines the internal dynamics of the Burmese military, focusing on struggles at the top level. It will explore the nature of and reasons for the struggles and assess the implications, especially for the current political impasse and possible changes in the future.
Burma and Asean: Estranged Bedfellows
Authors: McCarthy Stephen
Published: January 2009

Burma's relations with ASEAN have changed signifi cantly since 1997. This article examines how Burma-ASEAN relations have been influenced by intense international pressure and ASEAN's desire to maintain regional credibility. As ASEAN continues to redefine its position with Burma, the generals' relations elsewhere may continue to define it for them.
India's Ambitions in Burma: More Frustration Than Success?
Authors: Egreteau Renaud
Published: January 2009

India has been pursuing a new Burma policy since 1993 to meet its emerging strategic interests in the region. This article assesses 15 years of this “velvet policy” toward Burma's military regime and argues that New Delhi has faced more frustration than satisfaction in achieving its strategic objectives as a result of this shift in policy.
Burma's Insatiable State
Authors: Turnell Sean
Published: January 2009

The bounty presently accruing to Burma from rising exports of natural gas promises to transform the country's finances. Redeeming this promise, however, will require wholesale reform of Burma's fiscal and financial arrangements. Such reforms are unlikely. This article explores the financial potential of Burma's gas exports, the danger that they could yield a “resources curse,” and the extent to which the state's fiscal demands compromise Burma's economic development.
Gone Fishin'? Rossellini's Stromboli, Visconti's La Terra Trema
Authors: Thomas Paul
Published: January 2009

Rossellini's dramatic contrivances in Stromboli, especially the performance of Ingrid Bergman, contribute more authenticity to this picture of a fishing village than does Visconti's allegedly more documentary approach to the same subject.
The Lost Boys of Baltimore: Beauty and Desire in the Hood
Authors: Williams James S.
Published: January 2009

This article argues that despite the omnipresence of homophobia relayed linguistically and thematically in The Wire, the show also includes some remarkable instances of male homoeroticism in the way it visualizes “cinematically” its black male characters. The result is a groundbreaking exploration of the relations between race, television realism, and spectatorship.
Quality of life is reduced in patients with Klinefelter syndrome on androgen replacement therapy
Authors: de Ronde Willem , de Haan Anne , Drent Madeleine L
Published: January 2009

Context

Klinefelter syndrome (KS) is a genetic disorder, characterized by an XXY karyotype, hypergonadotrophic hypogonadism and infertility, which affects ∼1 in 700 men. KS has also been associated with neuropsychological alterations.

Objective

To investigate whether quality of life (QoL) is reduced in patients with KS on androgen treatment.

Design

Observational study.

Methods

Questionnaires (RAND-36) were sent to 46 KS patients on androgen treatment who regularly visit the outpatient clinic of an academic medical centre. QoL scores were compared with a Dutch male reference group.

Results

Forty (87%) questionnaires were returned which were suitable for evaluation. KS patients had significantly lower (worse) scores on eight of the nine domains of the RAND questionnaire compared with the male reference group. In KS patients, higher education was associated with significantly better QoL scores.

Conclusions

QoL is reduced in patients with KS on androgen treatment.
Screening for membrane hormone receptor expression in primary aldosteronism
Authors: Zwermann O , Suttmann Y , Bidlingmaier M , Beuschlein F , Reincke M
Published: January 2009

Objective

The investigation of expression and functional relevance of G-protein coupled receptors in primary aldosteronism (PA) by molecular and clinical studies.

Patients and methods

Tissues of 14 aldosterone-producing adenomas (APA), of one unilateral adrenal hyperplasia and of six healthy adult adrenal glands; 12 patients with confirmed PA due to APA; (n=5), idiopathic hyperaldosteronism (n=7) and 8 control subjects (C). The tissues were subjected to a quantitative PCR for determination of mRNA expression levels of AT2R1, GIPR, MC2R, GnRHR, LHR, TRHR, TSHR, glucagon-R, V1aR, V2R, and 5-HT4R. The patients and controls were enrolled in a test protocol consisting of stimulation by posture, mixed meal, ACTH, GnRH, TRH, glucagon, vasopressin, and metoclopramide (MCP). Three patients could be analyzed by both studies. A positive response was defined as an aldosterone increase of more than 50% following stimulation.

Results

All the tissues revealed AT2R1, MC2R, AVPR, and 5-HT4R mRNA expression. LHR mRNA was found in normal adrenals and 13 adrenal tumors. By contrast with normal adrenals tumorous adrenal tissue expressed GnRHR mRNA (4/15) and TSHR mRNA (1/15). Both the patients and controls responded to posture, ACTH, glucagon, AVP, and MCP. Specific responses were seen in one patient following TRH and three patients following GnRH stimulation.

Conclusions

We provide evidence for peptide hormone responsiveness to various peptide hormones in patients with PA, including GnRH and TRH. A good correlation between clinical and molecular testing could be observed, making an involvement of the receptor expressed in PA possible.
Hyperthyroidism and suicide: a retrospective cohort study in Sweden
Authors: Abraham-Nordling Mirna , Lönn Stefan , Wallin Göran , Yin Li , Nyren Olof , Tullgren Owe , Hall Per , Törring Ove
Published: January 2009

Objectives

Mental symptoms and impaired quality of life commonly occur in patients treated for hyperthyroidism. Our aim was to determine whether a history of hyperthyroidism implies an increased risk of suicide.

Design

Historic cohort study of 43 633 patients treated with radioiodine or surgery for hyperthyroidism between 1950 and 2005. The majority of the radioiodine-treated patients came from Stockholm. Two comparison cohorts consisted of 44 921 patients registered with an operation for atoxic nodular goitre between 1965 and 2005, and 354 861 patients with a cholecystectomy between 1965 and 2001.

Methods

Subjects were followed from the date of diagnosis until death, emigration or end of follow-up. Information on outcome was obtained from population and health registers.

Results

The number of observed suicide deaths was 134 in the study cohort. A naive comparison with the age-, sex- and calendar period-matched general Swedish population yielded a moderately increased standardized mortality ratio (SMR), but stratifications revealed that the excess was mainly driven by women from Stockholm, whose baseline suicide risk was higher than for women in the rest of Sweden. Using the population rates from Stockholm, the SMR among Stockholm women with Graves' disease was 1.14 (95% confidence intervals (CI) 0.66–1.86) and toxic goitre 0.99 (95% CI 0.51–1.72). A direct comparison between the study cohort and the combined comparison cohorts, with multiple adjustments (including adjustment for residence in Stockholm), yielded a relative risk of suicide of 0.93 (0.68–1.26).

Conclusions

This study did not confirm an increased risk of suicide among patients treated for hyperthyroidism.
Novel epididymal proteins as targets for the development of post-testicular male contraception
Authors: Sipilä P , Jalkanen J , Huhtaniemi I T , Poutanen M
Published: January 2009

Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the post-meiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags, in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genesin vivo. In this review, we summarize the current knowledge of several epididymal proteins shown eitherin vivoorin vitroto be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52, and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.
Electrochemical Applications of Acoustic Streaming Generated by a Focused Ultrasonic Source
Authors: Stefan Ionel C. , Greber Isaac , Zanelli Claudio I. , Scherson Daniel A.
Published: January 2009

Various aspects of mass transport toward a static disk electrode embedded in a planar surface in the presence of convective flow induced by a focused ultrasonic source have been examined by electrochemical means using the reduction of solution phase [Fe(CN)6]3‐− in an aqueous electrolyte as a probe redox reaction. Experiments were performed by placing the main axis of the acoustic transducer normal to the plane of disk electrodes of various radii. The results obtained revealed that the limiting current for the reduction of [Fe(CN)6]3‐− is proportional to the acoustic power, Pac to the 3/8 power, and also to the concentration of the redox active species in the electrolyte. Numerical calculations based on Kamakura's formalism (Kamakura, T. et al. J. Acoust. Soc. Am., 1995, 97, 2740–2746) have shown that the axial velocity induced at the focal point of the source is proportional to the square root of the acoustical pressure. On this basis, the behavior of the system under the conditions employed is analogous to that of the jet impinging electrode geometry in the wall jet regime.
Deposition of Gold Nanoparticles on Thin Polyaniline Films
Authors: Sheffer Marisa , Martina Virginia , Seeber Renato , Mandler Daniel
Published: January 2009

Local and bulk deposition of gold particles was accomplished by the spontaneous reaction between chemically reduced polyaniline (PAN) thin films and AuCl. PAN layers were deposited on glass, indium tin oxide (ITO), and glassy carbon (GC) by the Langmuir–Blodgett method and spin‐coating. Characterization of the PAN films was carried out by microscopy, UV–vis spectroscopy, and electrochemistry. We found that the nature of the gold deposit was greatly affected by the thickness of the PAN.

Scanning electrochemical microscopy was used as a means of locally depositing gold nanoparticles on an unbiased PAN film by anodically dissolving a gold micro‐electrode. This represents a generic approach whereby a variety of metal micro‐ and nanoparticles can be locally deposited on insulating supports.
Fatores de risco para transmissão da Hanseníase
Authors: Santos Andréia Soprani dos , Castro Denise Silveira de , Falqueto Aloísio
Published: January 2009

Estudo caso controle que objetivou identificar fatores individuais de risco relacionados à transmissão da doença. O grupo caso, composto por 90 pacientes de hanseníase notificados no SINAN entre 2003 e 2006; o grupo controle, constituído por 270 indivíduos sadios, pareados por sexo e faixa etária. Houve associação significativa entre a ocorrência da doença e a presença atual (OR= 2,9) e antiga (OR=5,0) de hanseníase entre parentes co-sangüíneos. Sabendo-se que o exame único dos contatos, no ato do diagnóstico, detecta uma parcela mínima dos casos, propõe-se a realização de exames periódicos dos contatos de hansenianos a fim de detectar os novos casos.
Argentina y Brasil en la Política Internacional: regionalismo y Mercosur (estrategias, cooperación y factores de tensión)
Authors: Bernal-Meza Raúl
Published: January 2009

Este artículo analiza la política de Brasil y Argentina en relación a los procesos de integración y cooperación regionales, en particular hacia el Mercosur. Se hace previamente una reflexión teórica sobre la regionalización o regionalismo, luego se presenta someramente el Mercosur para en seguida abordar las respectivas políticas exteriores. En Sudamérica el Mercosur coexiste hoy con otras dos iniciativas. Como nuevos escenarios de regionalización aparecen, desde diciembre de 2004 la Unasur (Unión Sudamericana de Naciones) como esquema de cooperación y concertación liderado por Brasil y, desde la misma época, ALBA (Alternativa Bolivariana de Integración) promovida por el presidente Chávez como proyecto contrario al Mercosur, al cual considera "neoliberal".