bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery and origin of a Palaeogene smectite-bearing clay deposit in the SE Gobi (Mongolia)
Authors: Dill H. G. , Kaufhold S. , Khishigsuren S. , Bulgamaa J.
Published: October 2005

The smectite-bearing red bed series of the Palaeogene Ergeliin zoo Formation in Mongolia is part of an alluvial-fluvial fan prograding over prodelta/mudflat deposits. The series was investigated in the field (mapping and portable infrared (IR) spectrometry in the short wavelength (SW) range) and samples were analysed in the laboratory using thin sections, X-ray diffraction, X-ray fluorescence, cation exchange capacity and Fourier transform infrared spectrometry in the mid-IR range. Two reference sections are treated in more detail as to the environment of deposition and concentration of smectite. The deposits at Ulaan uul are representative of a distal fan section with prevalent mudflats, whereas Ulaan buur offers insight into a braided river drainage system. Metabasic rocks in the hinterland delivered mica and chlorite from which smectite originated during diagenesis under semi-arid climatic and surface-near conditions. Towards the basin edge, smectite is replaced by kaolinite. The prime area in which we were interested in the smectite is the most distal part of the alluvial-fluvial fan, which was the subject of a field-based IR survey. This exploration method is a valuable tool to obtain a quick overview of the mineral composition and reduce the number of samples in the field for follow-up analyses. Its weak and strong points are discussed.
Na-magadiite prepared in a water/alcohol medium: synthesis, characterization and use as a host material to prepare alkyltrimethylammonium- and Si-pillared derivates
Authors: Sassi M. , Miehé-Brendlé J. , Patarin J. , Bengueddach A.
Published: October 2005

Syntheses of Na-magadiite were performed under hydrothermal conditions in a water/alcohol medium. It is only possible to obtain a pure and well crystallized magadiite sample using a water/ethanol medium at a water/ethanol molar ratio of ∼0.12. As shown by thermal analysis and1H liquid nuclear magnetic resonance spectroscopy, ethanol is not incorporated into the magadiite. Intercalation of dodecyl- and hexadecyltrimethylammonium cations in the interlayer space of Na-magadiite at different theoretical ion-exchange rates shows that the experimental ion-exchange rates are in good agreement with the theoretical ones. However, scanning electron micrographs of the sample having a theoretical ion exchange rate of 25–75% shows that the exchanges are not homogeneous (both thin and thick platelets are present). Attempts to obtain a Si-pillared compound starting from C16TMA-magadiite as the host material leads to a microporous compound having a BET surface area of 778 m2g-1.
Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3b precursor
Authors: Perosa Federico , Favoino Elvira , Caragnano Maria Antonietta , Dammacco Franco
Published: October 2005

Heterogeneity of the effector functions displayed by rituximab and other anti-CD20 monoclonal antibodies (mAbs) apparently recognizing the same CD20 epitope suggests that additional mechanisms, probably related to mAb fine specificity, are responsible for B-cell depletion. To improve our understanding of rituximab's function, its fine specificity was investigated by means of phage display peptide library (PDPL)-expressing 7-mer cyclic (c7c) or 7-/12-mer linear peptides. Rituximab-specific c7c PDPL-derived clone insert sequences expressed the motif A(S)NPS overlapping the human CD20 170ANPS173. P172 was the most critical for rituximab binding, since its replacement with S172 (of mouse CD20) abolished the reactivity. The WPXWLE motif expressed by the linear PDPL-derived clone insert sequences could only be aligned to the reverse-oriented 161WPXWLE156 of acid sphingomyelinase-like phosphodiesterase 3b precursor (ASMLPD), though linear peptides bearing WPXWLE competed with cyclic ones for rituximab-paratope binding. Anti-CD20 mAb 1F5 only displayed a reactivity profile similar to that of rituximab, which also reacted with ASMLPD-derived peptides. Peptides induced antibodies with specificity and effector functions similar to those of rituximab. Our results show a unique fine specificity of rituximab, define the molecular basis for the lack of rituximab reactivity with mouse CD20 (mCD20), and the potential of targeting CD20 in an active immunotherapy setting. A possible rituximab interaction with ASMLPD is suggested.
Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720
Authors: Zemann Barbara , Kinzel Bernd , Müller Matthias , Reuschel Roland , Mechtcheriakova Diana , Urtz Nicole , Bornancin Frédéric , Baumruker Thomas , Billich Andreas
Published: October 2005

FTY720, a potent immunomodulatory drug in phase 2/3 clinical trials, induces rapid and reversible sequestration of lymphocytes into secondary lymphoid organs, thereby preventing their migration to sites of inflammation. As prerequisite for its function, phosphorylation of FTY720 to yield a potent agonist of the sphingosine-1-phosphate receptor S1P1 is required in vivo, catalyzed by an as-yet-unknown kinase. Here, we report on the generation of sphingosine kinase 2 (SPHK2) knockout mice and demonstrate that this enzyme is essential for FTY720 phosphate formation in vivo. Consequently, administration of FTY720 does not induce lymphopenia in SPHK2-deficient mice. After direct dosage of FTY720 phosphate, lymphopenia is only transient in this strain, indicating that SPHK2 is constantly required to maintain FTY720 phosphate levels in vivo.
Interaction between integrin α9β1 and vascular cell adhesion molecule-1 (VCAM-1) inhibits neutrophil apoptosis
Authors: Ross Ewan A. , Douglas Mike R. , Wong See Heng , Ross Emma J. , Curnow S. John , Nash Gerard B. , Rainger Ed , Scheel-Toellner Dagmar , Lord Janet M. , Salmon Mike , Buckley Christopher D.
Published: October 2005

According to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-β and provided an additive, increased delay in apoptosis when given in combination with IFN-β. VCAM-1 delivered its antiapoptotic effect through binding the integrin α9β1. The α9β1 signaling pathway shares significant features with the IFN-β survival signaling pathway, requiring PI3 kinase, NF-κB activation, as well as de novo protein synthesis, but the kinetics of NF-κB activation by VCAM-1 were slower and more sustained compared with IFN-β. This study demonstrates a novel functional role for α9β1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.
Relative contribution of G-protein-coupled pathways to protease-activated receptor-mediated Akt phosphorylation in platelets
Authors: Kim Soochong , Jin Jianguo , Kunapuli Satya P.
Published: October 2005

Protease-activated receptors (PARs) activate Gq and G12/13 pathways, as well as Akt (protein kinase B [PKB/Akt]) in platelets. However, the relative contribution of different G-protein pathways to Akt phosphorylation has not been elucidated. We investigated the contribution of Gq and G12/13 to Gi/Gz-mediated Akt phosphorylation downstream of PAR activation. Selective G12/13 activation failed to cause Akt phosphorylation in human and Gαq-deficient mouse platelets. However, supplementing Gi/Gz signaling to G12/13 caused significant increase in Akt phosphorylation, confirming that G12/13 potentiates Akt phosphorylation. Inhibition of PAR-mediated Akt phosphorylation in the presence of the Gq-selective inhibitor YM-254890 was restored to the normal extent achieved by PAR agonists if supplemented with Gi signaling, indicating that Gq does not have any direct effect on Akt phosphorylation. Selective G12/13 activation resulted in Src kinase activation, and Akt phosphorylation induced by costimulation of G12/13 and Gi/Gz was inhibited by a Src kinase inhibitor but not by a Rho kinase inhibitor. These data demonstrate that G12/13, but not Gq, is essential for thrombin-induced Akt phosphorylation in platelets, whereas Gq indirectly contributes to Akt phosphorylation through Gi stimulation by secreted ADP. G12/13 activation might mediate its potentiating effect through Src activation, and Src kinases play an important role in thrombin-mediated Akt phosphorylation.
Physiologic self antigens rapidly capacitate autoimmune disease-specific polyclonal CD4+CD25+ regulatory T cells
Authors: Setiady Yulius Y. , Ohno Katsuhiro , Samy Eileen T. , Bagavant Harini , Qiao Hui , Sharp Colin , She Jin Xiong , Tung Kenneth S. K.
Published: October 2005

Studies on CD4+CD25+ regulatory T cells (Tregs) with transgenic T-cell receptors indicate that Tregs may receive continuous antigen (Ag) stimulation in the periphery. However, the consequence of this Ag encounter and its relevance to physiologic polyclonal Treg function are not established. In autoimmune prostatitis (EAP) of the day-3 thymectomized (d3tx) mice, male Tregs suppressed EAP 3 times better than Tregs from female mice or male mice without prostates. Importantly, the superior EAP-suppressing function was acquired after a 6-day exposure to prostate Ag in the periphery, unaffected by sex hormones. Thus, a brief exposure of physiologic prostate Ag capacitates peripheral polyclonal Tregs to suppress EAP. In striking contrast, autoimmune ovarian disease (AOD) was suppressed equally by male and female Tregs. We now provide evidence that the ovarian Ag develops at birth, 14 days earlier than prostate Ag, and that male Tregs respond to neonatal ovarian Ag in the Treg recipients to gain AOD-suppressing capacity. When d3tx female recipients were deprived of ovarian Ag in the neonatal period, AOD was suppressed by female but not by male Tregs, whereas dacryoadenitis was suppressed by both. We conclude that the physiologic autoAg quickly and continuously enhances disease-specific polyclonal Treg function to maintain self-tolerance.
Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?
Authors: Halama Niels , Grauling-Halama Silke A , Daboul Isam
Published: October 2005

Background

Leiomyomatosis peritonealis disseminata (LPD) is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described.

Case presentation

We describe a Caucasian-American family in which six members (three men) are diagnosed with Leiomyomatosis peritonealis disseminata (LPD) and three deceased family members most likely had LPD (based on the autopsy reports). Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis.

Conclusion

Familial clustering of Leiomyomatosis peritonealis disseminata (LPD) has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms.
Validating a work group climate assessment tool for improving the performance of public health organizations
Authors: Perry Cary , LeMay Nancy , Rodway Greg , Tracy Allison , Galer Joan
Published: October 2005

Background

This article describes the validation of an instrument to measure work group climate in public health organizations in developing countries. The instrument, the Work Group Climate Assessment Tool (WCA), was applied in Brazil, Mozambique, and Guinea to assess the intermediate outcomes of a program to develop leadership for performance improvement. Data were collected from 305 individuals in 42 work groups, who completed a self-administered questionnaire.

Methods

The WCA was initially validated using Cronbach's alpha reliability coefficient and exploratory factor analysis. This article presents the results of a second validation study to refine the initial analyses to account for nested data, to provide item-level psychometrics, and to establish construct validity. Analyses included eigenvalue decomposition analysis, confirmatory factor analysis, and validity and reliability analyses.

Results

This study confirmed the validity and reliability of the WCA across work groups with different demographic characteristics (gender, education, management level, and geographical location). The study showed that there is agreement between the theoretical construct of work climate and the items in the WCA tool across different populations. The WCA captures a single perception of climate rather than individual sub-scales of clarity, support, and challenge.

Conclusion

The WCA is useful for comparing the climates of different work groups, tracking the changes in climate in a single work group over time, or examining differences among individuals' perceptions of their work group climate. Application of the WCA before and after a leadership development process can help work groups hold a discussion about current climate and select a target for improvement. The WCA provides work groups with a tool to take ownership of their own group climate through a process that is simple and objective and that protects individual confidentiality.
Seeking new methodology for palliative care research: challenging assumptions about studying people who are approaching the end of life
Authors: Hopkinson Jane B , Wright David NM , Corner Jessica L
Published: October 2005

Palliative care researchers face many ethical and practical challenges. In particular, recruitment has proven difficult. New methodologies and methods need to be developed if barriers are to be overcome. This paper presents an example of a participatory approach to research with people receiving palliative care services. The approach was used for recruitment into an in-depth multi-methods study of weight loss and eating difficulties experienced by people with advanced cancer. Methods included a survey of patients on the case-loads of two community palliative care teams working in the South of England in 2003. The questionnaire was returned by 199 patients, 58% of the total patient population under the care of the two teams.

Benefits of the approach taken are detailed, but also issues that emerged across the course of recruitment, thus highlighting points of interest for palliative care researchers. It is proposed that the success of the recruitment process can be attributed to the adoption of a context specific participatory approach. Successful recruitment into the study challenges the widely held belief that, for practical and ethical reasons, it is inappropriate to study people who are approaching the end of life. It demonstrates that a participatory approach enables clinical practice and research to share decision making and values, leading to a feasible and successful recruitment process that is acceptable to clinicians, researchers and patients.
Validation of the McGill Quality of Life Questionnaire in home hospice settings in Israel
Authors: Bentur Netta , Resnizky Shirli
Published: October 2005

Given that the meaning and significance of ‘quality of life’ can differ among language and cultural groups, it is incumbent upon researchers to assess whether the tool they have chosen is appropriate to the population under study. This study aimed to test the reliability and validity of the McGill Quality of Life Questionnaire (MQOL) translated into Hebrew for use with palliative care patients in Israel. In this, as in previous studies, the 16 questions of the tool clustered into four domains (physical, psychological, existential well-being and support), although the distribution of items among them differed somewhat. The existential well-being and psychological domains had an independent effect on the overall quality of life of patients in Israel, as in other countries. It seems that this tool produces similar responses in metastatic cancer patients around the world, and hence can be used to compare palliative care services in different countries.
Caregiving for the terminally ill: at what cost?
Authors: Aoun Samar M , Kristjanson Linda J , Currow David C , Hudson Peter L
Published: October 2005

This literature review exposes the nature and extent of physical and psychosocial morbidity and economic disadvantage, home palliative caregivers suffer as a direct result of their caregiving role. Research has demonstrated that caregivers providing support to individuals receiving palliative care report unmet needs for information, communication, service provision and support from health and community services. Three sets of challenges are highlighted in this literature review which help explain why the needs of home palliative caregivers are largely unmet: (i) barriers to seeking help; (ii) a dearth of research-based interventions focused on reducing the negative aspects of caregiving; and (iii) a number of impediments to effective policy and service development for family caregivers. Furthermore, invited submissions from caregivers echoed and confirmed the issues reported in the literature. Recommendations for enhancing caregiver support are outlined.
Estimating the size of a potential palliative care population
Authors: Rosenwax LK , McNamara B , Blackmore AM , Holman CDJ
Published: October 2005

Objectives: To develop a method for estimating the population who could potentially benefit from receiving palliative care in the last year of their lives, and then apply the estimates to the Western Australian population to ascertain characteristics of these people. Methods: Three estimates of the potential palliative care population, Minimal, Mid-range and Maximal, were developed through focus groups, interviews and the literature. These estimates were applied to the cohort of people who died in Western Australia between 1 July 2000 and 31 December 2002 by linking death records with hospital morbidity data through the Western Australian Data Linkage System. Results: Between 0.28% and 0.50% of people in the Western Australian population in any one year could potentially benefit from palliative care, many of whom die from conditions other than neoplasms. While neoplasms accounted for 59.5% of all underlying causes of deaths in the Minimal Estimate, heart failure (21.0%), renal failure (9.8%), chronic obstructive pulmonary disease (9.6%), Alzheimer’s disease (4.0%), liver failure (3.2%), Parkinson’s disease (1.3%), motor neurone disease (0.9%), HIV/AIDS (B-0.01%) and Huntington’s disease (B-0.01%) accounted for other conditions in this estimate. The study was expanded to include Mid-range and Maximal Estimates. Characteristics of the Western Australian population in these three estimates are described. Conclusions: Unlike traditional palliative care estimates that focus on malignant disease, this study included nonmalignant conditions in a set of three estimates of a potential palliative care population. By using population-based data to describe characteristics of people who compose palliative care populations, these results offer a tool for planning equitable healthcare services.
Utilization and costs of the introduction of system-wide palliative care in Alberta, 19932000
Authors: Fassbender Konrad , Fainsinger Robin , Brenneis Carleen , Brown Pam , Braun Ted , Jacobs Philip
Published: October 2005

Background: De-institutionalization of health care services provided to terminally ill cancer patients is a cost-effective strategy that underpins health care reforms in Canada. The objective of this study therefore is to evaluate the economic implications associated with Canadian innovations in the delivery of palliative care services. Methods: We identified 16 282 adults who died of cancer between 1993 and 2000 in two Canadian cities with newly introduced palliative care programs. Linkage of administrative databases was used to measure healthcare resource utilization. We sought to describe the utilization of palliative care services and its consequences for overall health care system costs. Results: Use of palliative services increased from 45 to 81% of cancer patients during the study period. Identifiable public health care services cost $28 093Cdn/patient (19 033US$, 11 508GB£, 17 778t) for terminally ill cancer patients in their last year of life. Acute care accounted for two-thirds (67%) of these costs; physician (10%), residential hospice care (8%), nursing homes (6%), home care (6%) and prescription medications (3%) comprise the remainder. Increased costs associated with the introduction of palliative care programs were offset by cost savings realized when terminally ill cancer patients spent less time in hospital. Palliative home care and residential hospice care accounted for the bulk of this substitution effect. Cost neutrality was observed from the public perspective. Discussion: These results demonstrate that the introduction of comprehensive and community-based palliative care services resulted in increased palliative care service delivery and cost neutrality, primarily achieved through a decreased use of acute care beds.
Painful bone metastases: a prospective observational cohort study
Authors: Clare Charlotte , Royle Deborah , Saharia Kirsten , Pearse Hazel , Oxberry Stephen , Oakley Kath , Allsopp Leslie , Rigby Alan S , Johnson Miriam J
Published: October 2005

Incident pain related to bone metastases is a problematic symptom to treat. The difficulty in treating this type of pain is reflected in the wide variety of treatment modalities recommended. The aims of this prospective observational study were to determine the patterns of pain severity at rest and on movement over time and which treatment modalities are employed. In addition, we were interested in ascertaining any correlations between bone pain at rest, bone pain on movement and functional ability.

Thirty-two patients were followed up for a mean of 22 weeks (range: 2-52). In total, there were 704 patient follow-up weeks. Patients were followed up for one year or until death. A total of 19 different treatment modalities were employed. There were strong correlations between pain at rest and pain on movement. There were no significant correlations between functional ability and pain at rest or movement.

Our study demonstrates the complex management of patients with bone pain. This is the first study that highlights the correlation between pain at rest and pain on movement in patients with bone metastases in a palliative care population. It highlights the need for intensive follow-up of these patients, as they require multiple interventions to help control their pain. These data can also be used to power further interventional studies.
Synthesis, Expression and Biological Activity of the Prohormone for Gastrin Releasing Peptide (ProGRP)
Authors: Dumesny Chelsea , Patel Oneel , Lachal Shamilah , Giraud Andrew S. , Baldwin Graham S. , Shulkes Arthur
Published: October 2005

Gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on endocrine and exocrine secretions and metabolism. The prohormone for GRP (ProGRP, 125 amino acids) is processed to the amidated, biologically active end products GRP1–27 and GRP18–27. Amidated forms of GRP are putative autocrine or paracrine growth factors in a number of cancers including colorectal cancer. However, the potential role and biological activity of proGRP has not been investigated. Using a newly developed antisera directed to the N terminus of human proGRP, proGRP immunoreactivity was detected in all of the endometrial, prostate, and colon cancer cell lines tested and in nine of 10 resected colorectal carcinomas. However, no amidated forms were detected, suggesting an attenuation of processing in tumors. Recombinant proGRP was expressed as a His-tag fusion protein and purified by metal affinity chromatography and HPLC. ProGRP stimulated proliferation of a colon cancer cell line and activated MAPK, but unlike GRP18–27amide had no effect on inositol phosphate production. ProGRP did not compete with iodinated bombesin in binding assays on Balb-3T3 cells transfected with the known GRP receptors, GRP-R or BRS-3. We conclude that proGRP is present in a number of cancer cell lines and in resected colorectal tumors and is biologically active. Our results suggest that antagonists to GRP precursors rather than the amidated end products should be developed as a treatment for colorectal and other cancers that express proGRP-derived peptides.
17β-Estradiol Induces Apoptosis in the Developing Rodent Prostate Independently of ERα or ERβ
Authors: Taylor R. A , Cowin P. , Couse J. F. , Korach K. S. , Risbridger G. P.
Published: October 2005

Estrogens induce both proliferative and antiproliferative responses in the prostate gland. To date, antiproliferative effects of estrogens are generally considered to be due to systemic antiandrogenic actions. However, estrogen action mediated through estrogen receptor (ER) β was recently suggested as another mechanism of induction of apoptosis in the prostate. This study aimed to explore the hypothesis that the antiproliferative effects of estrogen are directly mediated through ERβ using a prostate organ culture system. We previously reported effects of 17β-estradiol (E2) using rat ventral prostate (VP) tissues, and adapted the system for culturing mouse tissues. In both rat and mouse models, estrogen-induced apoptosis was detected that was spatially and regionally localized to the epithelium of the distal tips. Using organ cultures of αER knockout (αERKO) and βERKO prostates, we failed to demonstrate that apoptosis induced by E2 was mediated through either receptor subtype. Activation of ER-selective ligands (ERα, propyl pyrazole triol, ERβ, diaryl-proprionitrile, and 5α-androstane-3β,17β-diol) in organ culture experiments failed to induce apoptosis, as did the membrane impermeable conjugate E2:BSA, discounting the possibility of nongenomic effects. Consequently, E2 regulation of androgen receptor (AR) expression was examined and, in the presence of nanomolar testosterone levels, E2 caused a specific reduction in AR protein expression in wild-type, αERKO, and βERKO mice, particularly in the distal region where apoptosis was detected. This down-regulation of AR protein provides a possible mechanism for the proapoptotic action of E2 that is independent of ERs or nongenomic effects.
Targeted Disruption of the Type 1 Selenodeiodinase Gene (Dio1) Results in Marked Changes in Thyroid Hormone Economy in Mice
Authors: Schneider Mark J. , Fiering Steven N. , Thai B. , Wu Sing-yung , St. Germain Emily , Parlow Albert F. , St. Germain Donald L. , Galton Valerie Anne
Published: October 2005

The type 1 deiodinase (D1) is thought to be an important source of T3 in the euthyroid state. To explore the role of the D1 in thyroid hormone economy, a D1-deficient mouse (D1KO) was made by targeted disruption of the Dio1 gene. The general health and reproductive capacity of the D1KO mouse were seemingly unimpaired. In serum, levels of T4 and rT3 were elevated, whereas those of TSH and T3 were unchanged, as were several indices of peripheral thyroid status. It thus appears that the D1 is not essential for the maintenance of a normal serum T3 level in euthyroid mice. However, D1 deficiency resulted in marked changes in the metabolism and excretion of iodothyronines. Fecal excretion of endogenous iodothyronines was greatly increased. Furthermore, when compared with both wild-type and D2-deficient mice, fecal excretion of [125I]iodothyronines was greatly increased in D1KO mice during the 48 h after injection of [125I]T4 or [125I]T3, whereas urinary excretion of [125I]iodide was markedly diminished. From these data it was estimated that a majority of the iodide generated by the D1 was derived from substrates other than T4. Treatment with T3 resulted in a significantly higher serum T3 level and a greater degree of hyperthyroidism in D1KO mice than in wild-type mice. We conclude that, although the D1 is of questionable importance to the wellbeing of the euthyroid mouse, it may play a major role in limiting the detrimental effects of conditions that alter normal thyroid function, including hyperthyroidism and iodine deficiency.
Endoplasmic Reticulum Stress Increases Glucose-6-Phosphatase and Glucose Cycling in Liver Cells
Authors: Wang Dong , Wei Yuren , Schmoll Dieter , Maclean Kenneth N. , Pagliassotti Michael J.
Published: October 2005

Impaired regulation of hepatic glucose production is a characteristic feature of the metabolic syndrome, a cluster of diseases that includes obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. It has been proposed that sustained endoplasmic reticulum stress, which appears to occur in obesity and diabetes, modulates insulin action in the liver. In this study, we show that experimental induction of endoplasmic reticulum stress increases expression and activity of glucose-6-phosphatase and the capacity for glucose release and glucose cycling in primary rat hepatocytes and H4IIE liver cells. Increased expression of the catalytic subunit of glucose-6-phosphatase was largely a result of increased transcription. Deletion analysis of the glucose-6-phosphatase promoter identified an endoplasmic reticulum stress-responsive region located between −233 and −187 with respect to the transcriptional start site. Experimental induction of endoplasmic reticulum stress increased the activity of c-jun N-terminal kinase. Prevention of endoplasmic reticulum stress-mediated activation of c-jun N-terminal kinase reduced the expression of the catalytic subunit of glucose-6-phosphatase, glucose-6-phosphatase activity, glucose release, and glucose cycling. These data demonstrate that sustained endoplasmic reticulum stress in the hepatocyte provokes adaptations, mediated in part via activation of c-jun N-terminal kinase, that act to increase hepatocellular capacity for glucose release and glucose cycling.
Identification of Neuroactive Steroids and Their Precursors and Metabolites in Adult Male Rat Brain
Authors: Ebner M. J. , Corol D. I. , Havlíková H. , Honour J. W. , Fry J. P.
Published: October 2005

Steroids in the brain arise both from local synthesis and from peripheral sources and have a variety of effects on neuronal function. However, there is little direct chemical evidence for the range of steroids present in brain or of the pathways for their synthesis and inactivation. This information is a prerequisite for understanding the regulation and function of brain steroids. After extraction from adult male rat brain, we have fractionated free steroids and their sulfate esters and then converted them to heptafluorobutyrate or methyloxime-trimethylsilyl ether derivatives for unequivocal identification and assay by gas chromatography analysis and selected ion monitoring mass spectrometry. In the free steroid fraction, corticosterone, 3α,5α-tetrahydrodeoxycorticosterone, testosterone, and dehydroepiandrosterone were found in the absence of detectable precursors usually found in endocrine glands, indicating peripheral sources and/or alternative synthetic pathways in brain. Conversely, the potent neuroactive steroid 3α,5α-tetrahydroprogesterone (allopregnanolone) was found in the presence of its precursors pregnenolone, progesterone, and 5α-dihydroprogesterone. Furthermore, the presence of 3β-, 11β-, 17α-, and 20α-hydroxylated metabolites of 3α,5α-tetrahydroprogesterone implicated possible inactivation pathways for this steroid. The 20α-reduced metabolites could also be found for pregnenolone, progesterone, and 5α-dihydroprogesterone, introducing a possible regulatory diversion from the production of 3α,5α-tetrahydroprogesterone. In the steroid sulfate fraction, dehydroepiandrostrone sulfate was identified but not pregnenolone sulfate. Although pharmacologically active, identification of the latter appears to be an earlier methodological artifact, and the compound is thus of doubtful physiological significance in the adult brain. Our results provide a basis for elucidating the origins and regulation of brain steroids.
Expression and Function of Toll-Like Receptor 4 in the Endometrial Cells of the Uterus
Authors: Herath Shan , Fischer Deborah P. , Werling Dirk , Williams Erin J. , Lilly Sonia T. , Dobson Hilary , Bryant Clare E. , Sheldon I. Martin
Published: October 2005

Prostaglandins have a central role in many endocrine functions in mammals, including regulation of the life span of the corpus luteum by prostaglandin F2α (PGF) and prostaglandin E2 (PGE), which are secreted by the uterine endometrium. However, the uterus is readily infected with bacteria such as Escherichia coli, which disrupt luteolysis. Immune cells detect E. coli by Toll-like receptor 4 (TLR4) binding its pathogenic ligand, lipopolysaccharide (LPS), although signaling requires accessory molecules such as CD14. The objective of this study was to determine the effect of E. coli or LPS on the function of bovine endometrial cells, and whether purified populations of epithelial and stromal cells express the molecules involved in LPS recognition. In addition, because the female sex hormones estradiol and progesterone modify the risk of uterine infection, their effect on the LPS response was investigated. Endometrial explants produced prostaglandins in response to LPS, with an increased ratio of PGE to PGF. Addition of LPS or E. coli to stromal and epithelial cells stimulated production of PGE and PGF and increased their cyclooxygenase 2 mRNA expression. The production of prostaglandins was abrogated by an LPS antagonist. In addition, estradiol and progesterone inhibited the production of PGE and PGF in response to LPS, indicating a role for steroid hormones in the response to bacterial infection. For the first time, Toll-like receptor 4 mRNA and CD14 mRNA and protein were detected in bovine endometrial stromal and epithelial cells by RT-PCR and flow cytometry. In conclusion, epithelial and stromal cells detect and respond to bacteria, which modulate their endocrine function.
Semi‐implicit time‐integrators for a scalable spectral element atmospheric model
Authors: Giraldo Francis X.
Published: October 2005

The Naval Research Laboratory's spectral element atmospheric model (NSEAM) for scalable computer architectures is presented. This new dynamical core is based on a high‐order spectral element (SE) method in space and uses semi‐implicit methods in time based on either the traditional second‐order leapfrog (LF2) or second‐order backward difference formulas (BDF2). The novelties of NSEAM are: it is geometrically flexible and thereby can accommodate any type of grid; LF2 or BDF2 are used to construct the semi‐implicit method; and the horizontal operators are written, discretized, and solved in three‐dimensional Cartesian space. The semi‐implicit NSEAM is validated using: five baroclinic test cases; direct comparisons to the explicit version of NSEAM which has been extensively tested and the results previously reported in the literature; and comparisons with operational weather prediction and well‐established climate models. A comparison with the US Navy's spectral transform global forecast model illustrates that NSEAM is 60% faster on an IBM SP4 using 96 processors for the current operational resolution of T239 L30. However, NSEAM can accommodate many more processors while continuing to scale efficiently even at higher grid resolutions. In fact, we show that at T498 L60, NSEAM scales linearly up to 384 processors. Copyright © 2005 Royal Meteorological Society
Tropical plumes and extreme precipitation in subtropical and tropical West Africa
Authors: Knippertz Peter , Martin Jonathan E.
Published: October 2005

Three cases of extreme precipitation in October, January and March/April over subtropical north‐western and tropical West Africa have been selected in order to study the moisture transports, precipitation generation mechanisms and large‐scale dynamics involved. All cases show strong tropical–extratropical interactions and elongated cloud bands extending from the Tropics into the subtropics, usually referred to as tropical plumes (TPs). Investigations are based on observational data and high‐resolution output from simulations using the University of Wisconsin–Nonhydrostatic Modeling System. Trajectory analyses show that moisture is transported from the tropical easterly mid‐level flow, the monsoonal southerlies and the north‐easterly trade winds to provide precipitable water and potential instability at mid‐tropospheric levels. The instability is released through ascent related both to weak quasi‐geostrophic forcing to the east of an upper‐level trough and to the strong, inertially unstable and highly divergent upper‐level subtropical jet (STJ) accompanying the TP. In the January and March cases the passage of a precursor upper‐level trough over the same location precedes the development and initiates the moisture transport from the deep Tropics. The associated north‐westerly cold advection supports the generation of precipitation by triggering convection over the tropical Atlantic Ocean, whose outflow feeds into the STJ over Africa, and by enhancing the vertical mass transport within the intertropical discontinuity over and near West Africa. In October, when the still active African monsoon facilitates the extraction of tropical moisture, a wave in the tropical easterlies and strong trade winds from the southern hemisphere are dominant factors. Low‐level cyclogenesis and frontogenesis only play roles in the late stages of the developments. The elongated, mostly positively tilted potential‐vorticity (PV) streamers associated with the observed troughs form as a result of an equatorward transport of high‐PV air downstream of a large ridge over the North Atlantic. The rapid amplification of the ridge is achieved through a combination of negative horizontal PV advection and diabatic reduction of upper‐level PV through latent heating within a cloud band that forms in connection with an explosive baroclinic development near the east coast of North America. Copyright © 2005 Royal Meteorological Society
The diurnal variation of the marine surface wind in an offshore flow
Authors: A. Lapworth
Published: October 2005

Data from a number of light vessels moored off the English coast have been used to show that the marine near‐surface wind within a distance of 40 km to 80 km from the coast varies diurnally when the wind is blowing in an offshore direction and the sea is cooler than the maximum overland air temperature. This variation is such that the maximum wind speed is overnight while the minimum wind speed is during the afternoon. This is in distinction to overland surface winds where the diurnal maximum in the wind strength occurs during the afternoon. A numerical model of the stable boundary layer has been used to simulate the variation, and the mechanisms involved are compared with those operating in stable layers over the land. This gives evidence that the main reason for the variation is the difference in boundary‐layer temperature profiles between the daytime and night‐time offshore flows. During the day the stable layer formed advectively over the sea reduces downward momentum transfer and hence the surface wind. During the night the stable layer preformed over the land evolves during advection to form an elevated inversion over the sea which, for reasons discussed, causes the overnight maximum. As well as having implications for maritime forecasting, model results show that vertical wind shears in the stable layers affect the performance of sailing vessels. © Crown copyright, 2005. Royal Meteorological Society
The effect of the continental boundary layer on the dynamics of fronts in a 2D model of baroclinic instability. I: An insulated lower surface
Authors: Tory Kevin J. , Reeder Michael J.
Published: October 2005

The effect of boundary‐layer turbulence on the structure and evolution of the surface front that develops in the finite‐amplitude Eady wave is examined. A no‐slip condition is imposed at the lower boundary, and the boundary‐layer turbulence is parametrized using either the Blackadar scheme, the Mellor–Yamada 2¼ scheme or the ECMWF scheme. The study builds on the influential work of Keyser and Anthes. It is shown that the low‐level structure of the front, and especially the pre‐frontal updraught, is sensitive to the depth of the boundary layer. In particular, the pre‐frontal updraught intensifies when the boundary layer deepens because the vertically integrated cross‐isobaric mass flux increases. The numerical experiments also show that the frictionally induced convergence strengthens the cross‐front potential temperature gradient, and that the convergence itself is determined by the horizontal variation in net pressure gradient force (that part of the pressure gradient force not balanced by the Coriolis force). While surface sensible heat fluxes are neglected here, their effect is explored in a companion paper. Copyright © 2005 Royal Meteorological Society
The sting at the end of the tail: Model diagnostics of fine‐scale three‐dimensional structure of the cloud head
Authors: Clark P. A. , Browning K. A. , Wang C.
Published: October 2005

This is the second in a series of papers on ‘the sting at the end of the tail’—a mesoscale region of potentially damaging surface winds that can occur close to the evaporating tip of a cloud head wrapped around the bent‐back front of an extratropical cyclone. In the first paper the sting phenomenon was identified from a purely observational study of the great storm of October 1987. In the present paper an observationally validated forecast run from a high‐resolution numerical weather prediction model is used to examine the evolving three‐dimensional structure of the sting phenomenon. It is shown that the damaging surface winds in the October 1987 storm were due to a well‐defined mesoscale ‘sting jet’ (SJ), identifiable as a coherent ensemble of trajectories originating in cloudy air at about 650 hPa. There is evidence of multiple mesoscale slantwise circulations, and the SJ appears to form within the descending part of these circulations. Air within the SJ descends to the 900 hPa level over a period of about 4 h, during which time it accelerates from less than 20 to above 45 m s−1 with extremes greater than 50 m s−1. Although the wet‐bulb potential temperature of air in the SJ remains constant during its descent to 900 hPa, evaporation leads to a reduction of up to 5 K or more in dry‐bulb potential temperature in some parts of the jet. The SJ is situated behind the primary cold front, and is distinct from the associated warm‐conveyor‐belt low‐level jet; it is also distinct from the cold‐conveyor‐belt low‐level jet which remains below and behind it as the SJ skirts the bent‐back front. © Crown copyright, 2005.
Hydro Tasmania – Renewable Energy Drivers, Action and Plans
Authors: Gill Roger , Andrews Harry
Published: October 2005

In Tasmania, the island state of Australia, the generator, Hydro Tasmania, is pushing technical, environmental and business boundaries in its plans to integrate a relatively high proportion (up to 20 percent) of large wind generators into its current complex mix of large and small hydropower plants. Its plans include projects to increase the efficiency of its older hydropower equipment as it prepares to supply much needed peaking capacity to the market in southern Australia via the groundbreaking Basslink undersea cable, which is due for completion in November 2005. Taken as a package these developments are creating a globally significant reference site for renewable energy systems.

The paper will describe what is happening, and more importantly what is underpinning the developments, including:

the harnessing of Tasmania's world-class wind resource, where recently constructed 1.75 MW wind turbines are achieving capacity factors of over 45 percent – some of the best productivity in the world today; the application of leading environmental science measures to ensure the sustainability of both the new wind farm developments and the transformation of the hydropower system to meet peak capacity demands; the relevance of the existing large hydropower storages that can operate in synergy with the wind resource; the contribution of Australia's renewable energy certificate scheme, which is effectively doubling the value of new renewable energy developments compared with existing generation sources; the application of the latest technology in hydropower turbines, combined with power system expertise from the world's leading manufacturers, to increase the efficiency of older hydropower generators, thereby more effectively harnessing the existing environmental footprint; and the transformation of Hydro Tasmania's business into a significant supplier and trader of premium value peak energy into the sophisticated Australian National Electricity Market.
Transport and Energy Demand in the Developing World: The Urgent Alternatives
Authors: Bauer Mariano , Mar Elizabeth
Published: October 2005

The appeal of individual mobility provided today by automobiles and light trucks with internal combustion engines, makes transportation the sector most resilient to a fuel substitution away from its dependence on oil. While the number of vehicles per capita and the distance traveled per vehicle are approaching saturation levels in the industrialized countries (IEA 2002), increases in population and income per capita, economic reforms and industry globalization can result in an off-trend accelerated growth of vehicles in the economies in transition (FSU and EE) and in the developing world (China, India and Latin America, mainly). The corresponding world road use energy consumption could reach a 200 percent increase from present levels by the year 2020, instead of an already worrisome “business as usual” projection of 75 percent (BAUER 2003, 2004). This paper analyses the mitigation effect on world oil demand and on its environmental impact that a policy of leapfrogging towards energy efficient internal combustion technologies and/or alternative vehicles – hybrid or fully electric – could have.
Robust Control of Markov Decision Processes with Uncertain Transition Matrices
Authors: Nilim Arnab , El Ghaoui Laurent
Published: October 2005

Optimal solutions to Markov decision problems may be very sensitive with respect to the state transition probabilities. In many practical problems, the estimation of these probabilities is far from accurate. Hence, estimation errors are limiting factors in applying Markov decision processes to real-world problems.

We consider a robust control problem for a finite-state, finite-action Markov decision process, where uncertainty on the transition matrices is described in terms of possibly nonconvex sets. We show that perfect duality holds for this problem, and that as a consequence, it can be solved with a variant of the classical dynamic programming algorithm, the “robust dynamic programming” algorithm. We show that a particular choice of the uncertainty sets, involving likelihood regions or entropy bounds, leads to both a statistically accurate representation of uncertainty, and a complexity of the robust recursion that is almost the same as that of the classical recursion. Hence, robustness can be added at practically no extra computing cost. We derive similar results for other uncertainty sets, including one with a finite number of possible values for the transition matrices.

We describe in a practical path planning example the benefits of using a robust strategy instead of the classical optimal strategy; even if the uncertainty level is only crudely guessed, the robust strategy yields a much better worst-case expected travel time.