bluuebunny/crossref_metadata_2025 huggingface dataset:
PGC-1α controls hepatitis B virus through nutritional signals
Authors: Shlomai Amir , Paran Nir , Shaul Yosef
Published: October 2006

Hepatitis B virus (HBV) is a 3.2-kb DNA virus that replicates preferentially in the liver. Liver-enriched nuclear receptors (NRs) play a major role in the HBV life cycle, operating as essential transcription factors for viral gene expression. Notably, these NRs are also key players in metabolic processes that occur in the liver, serving as central transcription factors for key enzymes of gluconeogenesis, fatty acid β-oxidation, and ketogenesis. However, the association between these metabolic events and HBV gene expression is poorly understood. Here we show that peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a major metabolic regulator and a coactivator of key gluconeogenic genes, robustly coactivates HBV transcription. We further demonstrate that the liver-enriched NR hepatocyte nuclear factor 4α that binds HBV plays an important role in this process. Physiologically, we show that a short-term fast that turns on the gluconeogenic program robustly induces HBV gene expression
in vivo
. This induction is completely reversible by refeeding and depends on PGC-1α. We conclude that HBV is tightly regulated by changes in the body's nutritional state through the metabolic regulator PGC-1α. Our data provide evidence for nutrition signaling to control viral gene expression and life cycle and thus ascribe to metabolism an important role in virus–host interaction.
Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes
Authors: Szöőr Balázs , Wilson Jude , McElhinney Helen , Tabernero Lydia , Matthews Keith R.
Published: October 2006

Differentiation in African trypanosomes (Trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to procyclic forms that inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase (TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor profile, and its activity is impaired by reversible oxidation. TbPTP1 inactivation in monomorphic bloodstream trypanosomes by RNA interference or pharmacological inhibition triggers spontaneous differentiation to procyclic forms in a subset of committed cells. Consistent with this observation, homogeneous populations of stumpy forms synchronously differentiate to procyclic forms when tyrosine phosphatase activity is inhibited. Our data invoke a new model for trypanosome development in which differentiation to procyclic forms is prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to use PTP1B inhibitors to block trypanosomatid transmission.
Darkness descends with two Rabs
Authors: Marks Michael S.
Published: October 2006

Over 60 distinct Rab GTPases regulate specific vesicular transport steps in the mammalian central vacuolar system. Wasmeier et al. (this issue, p. 271) reveal a redundant role for two tissue-specific Rab proteins in regulating transport to a tissue-specific lysosome-related organelle, the melanosome.
Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease
Authors: Bilodeau Steve , Vallette-Kasic Sophie , Gauthier Yves , Figarella-Branger Dominique , Brue Thierry , Berthelet France , Lacroix André , Batista Dalia , Stratakis Constantine , Hanson Jeanette , Meij Björn , Drouin Jacques
Published: October 2006

Negative feedback regulation of the proopiomelanocortin (POMC) gene by the glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo–pituitary–adrenal axis, and it is in part exerted by trans-repression between GR and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and activator at the promoter and chromatin modification jointly contribute to trans-repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1 or HDAC2 should therefore produce Gc resistance, and we show that ∼50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark of Cushing disease, are deficient in nuclear expression of either protein. In addition to providing a molecular basis for Gc resistance, these deficiencies may also contribute to the tumorigenic process.
Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain
Authors: Wu Mei-Yi , Tsai Ting-Fen , Beaudet Arthur L.
Published: October 2006

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by deficiency of imprinted gene expression from paternal or maternal chromosome 15q11–q13, respectively. Genomic imprinting of the PWS/AS domain is regulated through a bipartite cis-acting imprinting center (PWS-IC/AS-IC) within and upstream of the SNRPN promoter. Here, we show that two Rb-binding protein-related genes, Rbbp1/Arid4a and Rbbp1l1/Arid4b, are involved in the regulation of imprinting of the IC. We recovered these two genes from gene trap mutagenesis selecting for altered expression of an Snrpn-EGFP fusion gene strategy. RBBP1/ARID4A is an Rb-binding protein. RBBP1/ARID4A interacts with RBBP1L1/ARID4B and with the Snrpn promoter, implying that both are part of a protein complex. To further elucidate their roles on regulation of imprinting, we deleted the Rbbp1/Arid4a and Rbbp1l1/Arid4b genes in mice. Combined homozygous deficiency for Rbbp1/Arid4a and heterozygous deficiency for Rbbp1l1/Arid4b altered epigenetic modifications at the PWS-IC with reduced trimethylation of histone H4K20 and H3K9 and reduced DNA methylation, changing the maternal allele toward a more paternal epigenotype. Importantly, mutations of Rbbp1/Arid4a, Rbbp1l1/Arid4b, or Rb suppressed an AS imprinting defect caused by a mutation at the AS-IC. These data identify Rbbp1/Arid4a and Rbbp1l1/Arid4b as new members of epigenetic complexes regulating genomic imprinting at the PWS/AS domain.
Water status and growth phenology of a Saharan shrub in north Africa
Authors: Abdallah Lotfi , Chaieb Mohamed
Published: October 2006

An experimental study of the relationship between the phenological phases, water relations and climatic conditions was conducted on one shrub species, Spartidium saharae, in Saharan ecosystem of southern Tunisia. The results show that the water potential remained significantly higher than that recorded in other desert shrubs. However, a relationship between the water potential of S. saharae and precipitation was not evident suggesting that access to permanent ground water may be a factor of this decoupling. Although shoot elongation of the species occurred outside the wet season, water shortage induced a decrease in fruit production.
Assessment of α1‐adrenoceptor antagonists in benign prostatic hyperplasia based on the receptor occupancy theory
Authors: Ito Kaori , Ohtani Hisakazu , Sawada Yasufumi
Published: October 2006

Aims

To assess the mechanistic relationship between doxazosin (α1‐receptor antagonist) and receptor occupancy and a measure of pharmacological effect (Qmax, the maximum urinary flow rate) and to compare the mean receptor occupancy ratio at clinical doses of doxazosin, tamsulosin, terazosin and prazosin in benign prostatic hyperplasia (BPH).

Methods

A ternary complex model, which described the mechanism of α1‐receptor antagonists, was fitted to the pharmacological effects and receptor occupancy ratio data for doxazosin (standard tablet). In addition, mean receptor occupancy was calculated for other α1‐receptor antagonists and the optimal receptor occupancy was evaluated. The clinical pharmacological effects of the controlled release formulation of doxazosin (doxazosin GITS) were estimated based on the receptor occupancy.

Results

The mechanistic based model was able to describe the pharmacological effects of doxazosin. Regardless of the plasma concentrations or clinical dose of each drug, the results suggest that receptor occupancy is useful to assess quantitatively and compare the pharmacological effects of drugs with similar mechanisms of action. The clinical dosage for doxazosin GITS was estimated to be at least 8 mg and the stable pharmacological effect is expected based on the estimated receptor occupancy.

Conclusions

A model for Qmax improvement in BPH based on the receptor occupancy theory was able to describe the clinical effects of the α1‐receptor antagonists. Receptor occupancy is a useful index for predicting the clinical effects of α1‐receptor antagonists.
Herbivory and plant growth rate determine the success of El Niño Southern Oscillation‐driven tree establishment in semiarid South America
Authors: HOLMGREN MILENA , LÓPEZ BERNAT C. , GUTIÉRREZ JULIO R. , SQUEO FRANCISCO A.
Published: October 2006

While climatic extremes are predicted to increase with global warming, we know little about the effect of climatic variability on biome distribution. Here, we show that rainy El Niño Southern Oscillation (ENSO) events can enhance tree recruitment in the arid and semiarid ecosystems of north‐central Chile and northwest Peru. Tree‐ring studies in natural populations revealed that rainy El Niño episodes have triggered forest regeneration in Peru. Field experiments indicate that tree seedling recruitment in Chile is much less successful than in Peru due mostly to larger mortality caused by herbivores. The dramatic impact of herbivores in Chile was derived from the combined result of slower plant growth and the presence of exotic herbivores (European rabbits and hares). The interplay of herbivory and climatic effects we demonstrated implies that rainy ENSO events may represent ‘windows of opportunity’ for forest recovery if herbivore pressure is minimized at the right moment.
Schistosoma japonicum egg antigens stimulate CD4+ CD25+ T cells and modulate airway inflammation in a murine model of asthma
Authors: Yang Jianghua , Zhao Jiaqing , Yang Yanfeng , Zhang Lei , Yang Xue , Zhu Xiang , Ji Minjun , Sun Nanxiong , Su Chuan
Published: October 2006

A number of epidemiological and clinical studies have suggested an inverse association between allergy and helminth infection, such as Schistosomiasis. Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4+ CD25+ T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development. The frequency of CD4+ CD25+ T cells was determined by flow cytometry for mice treated with ovalbumin (OVA), CD25+ depletion/OVA, schistosome egg antigens, schistosome egg antigens/OVA and for control mice. The ability of CD25+ T cells from these mice to suppress T‐cell proliferation and cytokine production was investigated both in vivo and in vitro. Results showed that the CD4+ CD25+ T cells of OVA‐treated mice exhibited impaired control of dysregulated mucosal T helper 2 responses compared to the controls (P < 0·05). Depletion of CD25+ cells accelerated OVA‐induced airway inflammation and increased the expression of interleukin (IL)‐5 and IL‐4. Treatment with schistosome egg antigens increased the number and suppressive activity of CD4+ CD25+ T cells, which made IL‐10, but little IL‐4. In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen‐induced airway inflammation, and inhibited asthma development. Thus, we provided evidence that S. japonicum egg antigens induced the production of CD4+ CD25+ T cells, resulting in constitutive immunosuppressive activity and inhibition of asthma development. These results reveal a novel form of protection against asthma and suggest a mechanistic explanation for the protective effect of helminth infection on the development of allergy.
Feeding and indoor resting behaviour of the mosquito Anopheles longipalpis in an area of hyperendemic malaria transmission in southern Zambia
Authors: KENT R. J. , COETZEE M. , MHARAKURWA S. , NORRIS D. E.
Published: October 2006

Abstract Anopheles longipalpis (Theobald) (Diptera: Culicidae) is a predominantly zoophilic mosquito that has not been implicated in malaria transmission. However, this species was collected indoors with An. funestus s.l. in southern Zambia, where transmission of Plasmodium falciparum is hyperendemic, and we initially misidentified it morphologically and molecularly as An. funestus s.l. The indoor resting density and blood‐feeding behaviour of An. longipalpis were investigated during the 2004‐05 and 2005‐06 transmission seasons in Mufwafwi village in southern Zambia. Numbers of endophilic An. longipalpis increased towards the end of the rainy season. Although specimens were collected during human landing catches, the feeding behaviour of An. longipalpis was significantly biased towards cattle (88.7%), with other bloodmeals originating from dogs, goats and chickens. None of the 177 specimens of An. longipalpis were infected with P. falciparum. These data are consistent with existing reports that An. longipalpis is not involved in malaria transmission. However, more extensive sampling is necessary. Importantly, the correct identification of An. longipalpis is crucial for malaria control programmes in areas where An. funestus s.l and An. longipalpis exist sympatrically so that scarce resources are not wasted on the control of a non‐vector.
Species dependent expression of intestinal smooth muscle mechanosensitive sodium channels
Authors: Strege P. R. , Mazzone A. , Kraichely R. E. , Sha L. , Holm A. N. , Ou Y. , Lim I. , Gibbons S. J. , Sarr M. G. , Farrugia G.
Published: October 2006

Abstract  A mechanosensitive Na+ current carried by Nav1.5 is present in human intestinal circular smooth muscle and contributes to regulation of intestinal motor function. Expression of this channel in different species is unknown. Our aim was to determine if Na+ currents and message for the α subunit of the Na+ channel (SCN5A) are found in circular smooth muscle cells of human, dog, pig, mouse and guinea pig jejunum. Currents were recorded using patch clamp techniques. Message for SCN5A was investigated using laser capture microdissection and reverse transcription polymerase chain reaction (RT‐PCR). Na+ currents were identified consistently in human and dog smooth muscle cells; however, Na+ current was not found in pig (0/20) or guinea pig smooth muscle cells (0/21) and found only one mouse cell (1/21). SCN5A mRNA was found in circular muscle of human, dog, and mouse, but not in pig or guinea pig, and not in mouse longitudinal or mucosal layers. In summary, SCN5A message is expressed in, and Na+ current recorded from, circular muscle layer of human and dog but not from pig and guinea pig. These data show that there are species differences in expression of the SCN5A‐encoded Nav1.5 channel, suggesting species‐specific differences in the electrophysiological response to mechanical and depolarizing stimuli.
Micronutrient interventions and HIV infection: a review of current evidence
Authors: Friis Henrik
Published: October 2006

Objective  To review the current evidence on the role of micronutrient supplementation in HIV transmission and progression.

Method  Literature review.

Results  The importance of micronutrients in the prevention and treatment of childhood infections is well known, and evidence is emerging that micronutrient interventions may also affect HIV transmission and progression.

Conclusion  Interventions to improve micronutrient intake and status could contribute to a reduction in the magnitude and impact of the global HIV epidemic. However, more research is needed before specific recommendations can be made.
Changes of bispectral index during recovery from general anesthesia with 2% propofol and remifentanil in children
Authors: PARK HYE‐JIN , KIM YONG LAK , KIM CHONG SUNG , KIM SEONG DEOK , KIM HEE‐SOO
Published: October 2006

Background : The bispectral (BIS) index is a pharmacodynamic measure of the effect of anesthesia on the central nervous system. The aim of this study was to investigate the relationship between BIS index and predicted plasma concentration of propofol delivered by target controlled infusion (TCI) during emergence in children.

Methods : With approval of IRB, 30 patients (2–7 years) were included in this study. Anesthesia was with TCI propofol 3–5 μg·ml−1 and remifentanil 7.5 ng·ml−1 to maintain BIS 40–60 and the propofol concentration was fixed at 3 μg·ml−1 Remifentanil infusion was stopped 10 min before the end of surgery. BIS values were recorded after reducing propofol in decrement of 0.2 μg·ml−1. BIS values were checked when spontaneous respiration occurred and children were able to obey a command (eye opening or hand grasping).

Results : Spearman's correlation analysis showed negative correlation between BIS and propofol plasma concentration (r = −0.559, P < 0.001). When respiration returned, mean BIS was 77.2 ± 5.3 and propofol plasma concentration 1.6 ± 0.3 μg·ml−1 and when a verbal command was obeyed, BIS was 82.4 ± 5.6 and propofol plasma concentration 1.5 ± 0.3 μg·ml−1.

Conclusions : In preschool children, BIS moderately correlated with the predicted plasma concentration of propofol.
Headache Patients in Primary Care and a Tertiary Care Unit in Zürich, Switzerland
Authors: Gantenbein AR , Kozak S , Agosti F , Agosti R , Isler H
Published: October 2006

The Headache and Pain Clinic (HPC) is a unit of the Zürich Neurology Department, established in 1966. In the present study demographic features, clinical characteristics and medical management of primary and tertiary care patients were compared in two groups of 181 patients each, seen by general practitioners (GPs) or the HPC, respectively, for primary headaches in 1998. There was a preponderance of women and the socially underprivileged in both samples. Chronic headache was overrepresented in the HPC (44.7%). Loss of work for >2 months was found exclusively in the HPC (9.9%). Of the GP patients, 40% were using triptans and 26.5% in the HPC. One-third of both groups had had complementary and alternative medical treatment. Differences in management strategies reflected differences in headache severity and chronicity. Results indicated that remaining shortcomings of diagnosis and treatment of headache in primary care could be minimized by involving GPs in similar non-commercial studies.
Psychological Treatment of Recurrent Headache in Children and Adolescents - A Meta-Analysis
Authors: Trautmann E , Lackschewitz H , Kröner-Herwig B
Published: October 2006

Psychologically based interventions such as relaxation training, biofeedback and cognitive-behavioural therapy are increasingly discussed as options for the treatment of migraine and tension-type headache in children and adolescents. In order to determine the state of evidence regarding the efficacy of these treatments, a meta-analysis of randomized controlled studies was conducted. In a comprehensive literature search including data from 1966 to 2004, 23 studies were found meeting the inclusion criteria. Due to the application of the random effects model, generalization of the results is possible. Specific statistical procedures were used to account for a possible publication bias. Significantly more patients improved to a clinically relevant extent (headache reduction ≥50%) in treatment conditions compared with waiting list conditions (high effect sizes). Long-term stability was also confirmed. The analysed treatments lead to improvement (up to 1 year) in headache status in children and adolescents with primary headache. However, more well-designed studies are needed to support and consolidate the conclusions of this meta-analysis and to compare the effects of psychological treatment with those of prophylactic medical interventions (in migraine), to examine potential differences between treatments, to identify moderators of efficacy and to determine effects of treatment on other health- related variables such as quality of life.
Expression and prognostic significance of Stat5a and E‐cadherin in extramammary Paget’s disease
Authors: Liu Houjun , Urabe Kazunori , Uchi Hiroshi , Takeuchi Satoshi , Nakahara Takeshi , Dainichi Teruki , Tu Yating , Furue Masutaka , Moroi Yoichi
Published: October 2006

Background:  Stat5 has been shown to regulate the proliferation and inhibition of apoptosis in cancer cells. E‐cadherin plays an important role in maintaining epithelial stability and is widely regarded as a prognostic marker in many types of human cancers. The expression of Stat5 has not been investigated in extramammary Paget’s disease (EMPD).

Objectives:  To study the expression of Stat5a and E‐cadherin protein in EMPD and to evaluate the relationships between them.

Methods:  Thirty‐six tissue samples from 34 cases with primary EMPD were subjected to immunohistochemical staining for Stat5a and E‐cadherin.

Results:  Twenty‐nine of 30 in situ EMPD specimens were positive for Stat5a expression, and the staining pattern for Stat5a was mainly nuclear in the majority of Paget’s cells. All four invasive specimens and two metastatic lymph node specimens were negative for Stat5a. Twenty‐six of 30 in situ EMPD specimens expressed E‐cadherin in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed E‐cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one invasive specimen expressed E‐cadherin in less than 25% of tumor cells. Three invasive specimens and two metastatic lymph node specimens were negative, with occasional membranous staining for E‐cadherin. There is a significant correlation between the expression of Stat5a and E‐cadherin.

Conclusions:  Our results showed that these proteins were found in in situ lesions, and it is speculated that these proteins may play some role in the prognosis/invasion of EMPD.
Skeletal muscle regeneration: report of a case presenting as a cutaneous nodule following blunt trauma to the lip
Authors: Ghosn Samer H. , Radfar Arash , Stefanato Catherine M.
Published: October 2006

Abstract:  Skeletal muscle (SM) regeneration is a pleomorphic yet benign reaction pattern that follows injury to SM and has been reported to simulate histologically various malignancies such as squamous cell carcinoma and rhabdomyosarcoma.

A 61‐year‐old man presented with a 4‐month history of an enlarging nodule on the upper lip following blunt trauma. An initial punch biopsy was non‐diagnostic. A deeper biopsy revealed a multilobular proliferation of atypical and pleomorphic cells with vesicular nuclei, prominent nucleoli, and large amphophilic cytoplasm. Immunoperoxidase studies showed these cells to be positive for muscle‐specific actin and desmin and negative for S‐100 protein and smooth muscle actin. Based on these findings, a diagnosis of skeletal muscle regeneration (SMR) was made.

To our knowledge, this is the first report of SMR presenting clinically as a rapidly growing cutaneous nodule on the lip following blunt trauma.
Aggressive osteogenic desmoplastic melanoma: a case report
Authors: Emanuel Patrick O. , Idrees Muhammad T. , Leytin Anatoly , Kwon Eun Ji , Phelps Robert G.
Published: October 2006

A case of an osteogenic desmoplastic melanoma occurring on the sole of the foot of a 60‐year‐old African American man is described. The tumor measured 4.8 cm in greatest dimension, invaded to a thickness of 2.2 cm and metastasized to four of ten inguinal lymph nodes. The majority of the tumor had a classic desmoplastic phenotype with malignant spindle cells set in a sclerotic and myxoid matrix and foci of lymphocyte aggregation. In other areas, there were thick trabeculae of bone rimmed by malignant epithelioid melanocytes. There was a markedly atypical lentiginous hyperplasia in the overlying epidermis. Imaging showed no continuity with the underlying calcaneus. The tumor was characterized immunohistochemically by S100 positivity. Pathologists should be aware of this diagnosis and should differentiate it from osteosarcoma.
Human disturbance, climate and biodiversity determine biological invasion at a regional scale
Authors: ZHANG Zhibin , XIE Yan , WU Yuming
Published: October 2006

Many factors may affect biological invasion, but their effects have not been quantitatively calculated. Recent studies on the relationship between biodiversity and biological invasion are still controversial. Native biodiversity and alien species diversity are often positively correlated in large‐scale observation studies, but negatively correlated in small‐scale experimental studies. By using partial correlation and principal component regression methods, we found that human disturbance, climate, native biodiversity and their interactions explained, respectively, 30.3, 34.6, 26.4 and 4.4% of the variation in alien species diversity (ASD) and 50.3, 22.2, 10.8 and 5.5% of the variation in the relative invasibility of alien species (RIA = ASD/native biodiversity) at the regional scale in China. The correlation between ASD and native biodiversity is positive, but the correlation between RIA and native biodiversity is negative. Island and coastal provinces have suffered heavier biological invasions than inland provinces. These findings indicate that biological invasion is mostly determined by human disturbance and favorable climate, but less determined by native biodiversity. A disturbance‐dependent niche‐vacancy hypothesis is proposed to explain the contradictory observations in large‐and small‐scale studies.
Multidisciplinary consensus on the terminology and classification of complaints of the arm, neck and/or shoulder
Authors: Huisstede B M A , Miedema H S , Verhagen A P , Koes B W , Verhaar J A N
Published: October 2006

Background:There is no universally accepted way of labelling or defining upper-extremity musculoskeletal disorders. A variety of names are used and many different classification systems have been introduced.

Objective:To agree on an “unambiguous language” concerning the terminology and classification that can be used by all relevant medical and paramedical disciplines in the Netherlands.

Methods:A Delphi consensus strategy was initiated. The outcomes of a multidisciplinary conference were used as a starting point. In total, 47 experts in the field of upper-extremity musculoskeletal disorders were delegated by 11 medical and paramedical professional associations to form the expert panel for the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis and a feedback report.

Results:After three Delphi rounds, consensus was achieved. The experts reported the consensus in a model. This so-called CANS model describes the term, definition and classification of complaints of arm, neck and/or shoulder (CANS) and helps professionals to classify patients unambiguously. CANS is defined as “musculoskeletal complaints of arm, neck and/or shoulder not caused by acute trauma or by any systemic disease”. The experts classified 23 disorders as specific CANS, because they were judged as diagnosable disorders. All other complaints were called non-specific CANS. In addition, the experts defined “alert symptoms” on the top of the model.

Conclusions:The use of the CANS model can increase accurate and meaningful communication among healthcare workers, and may also have a positive influence on the quality of scientific research, by enabling comparison of data of different studies.
Occupational exposure to low frequency magnetic fields and dementia: a case–control study
Authors: Seidler Andreas , Geller Petra , Nienhaus Albert , Bernhardt Tanja , Ruppe Ingeburg , Eggert Siegfried , Hietanen Maila , Kauppinen Timo , Frölich Lutz
Published: October 2006

Background:Several studies point to a potential aetiological relevance to dementia of exposure to low-frequency magnetic fields, but the evidence is inconclusive.

Objective:To further examine the relationship between low frequency magnetic fields and dementia.

Methods:From 23 general practices, 195 patients with dementia were recruited. Of these, 108 had possible Alzheimer’s disease, 59 had possible vascular dementia and 28 had secondary or unclassified dementia. A total of 229 controls were recruited: 122 population controls and 107 ambulatory patients free from dementia. Data were gathered in a structured personal interview; in cases, the interview was administered to the next of kin. Exposure to low-frequency electromagnetic fields was assessed by expert rating. To identify occupations suspected to be associated with dementia, major occupations were a priori formed. Odds ratios were calculated using logistic regression, to control for age, region, sex, dementia in parents and smoking.

Results:Exposure to magnetic fields was not significantly associated with dementia; restriction of the analysis to cases with possible Alzheimer’s disease or possible vascular dementia did not lead to statistically significant results. We found an increased risk of dementia in blue-collar occupations (electrical and electronics workers, metal workers, construction workers, food and beverage processors and labourers).

Conclusions:Our study does not support a strong association between occupational exposure to low-frequency magnetic fields and dementia. Further studies should consider the relationship between blue-collar work and the late development of dementia.
VIRTUAL REALITY IN BRAIN INTERVENTION
Authors: NOWINSKI WIESLAW L.
Published: October 2006

After introduction to medical imaging, virtual reality (VR), and VR surgical simulation, the paper overviews our long-term efforts in human body modeling and development of VR-based applications for brain intervention. It describes construction, features, and applications of anatomical, functional, and vascular brain atlases. It also presents VR-based applications developed for stereotactic and functional neurosurgery (NeuroPlanner, NeuroBase, and BrainBench), interventional neuroradiology (NeuroCath and tele-NeuroCath), and tumor stereotaxis (VIVIAN). Finally, a vision of the future surgery (the DOTELL environment) is presented.
AUTHORSHIP ATTRIBUTION BASED ON FEATURE SET SUBSPACING ENSEMBLES
Authors: STAMATATOS EFSTATHIOS
Published: October 2006

Authorship attribution can assist the criminal investigation procedure as well as cybercrime analysis. This task can be viewed as a single-label multi-class text categorization problem. Given that the style of a text can be represented as mere word frequencies selected in a language-independent method, suitable machine learning techniques able to deal with high dimensional feature spaces and sparse data can be directly applied to solve this problem. This paper focuses on classifier ensembles based on feature set subspacing. It is shown that an effective ensemble can be constructed using, exhaustive disjoint subspacing, a simple method producing many poor but diverse base classifiers. The simple model can be enhanced by a variation of the technique of cross-validated committees applied to the feature set. Experiments on two benchmark text corpora demonstrate the effectiveness of the presented method improving previously reported results and compare it to support vector machines, an alternative suitable machine learning approach to authorship attribution.
CHARGED ANALOGUE OF FINCH–SKEA STARS
Authors: HANSRAJ S. , MAHARAJ S. D.
Published: October 2006

We present solutions to the Einstein–Maxwell system of equations in spherically symmetric gravitational fields for static interior space–times with a specified form of the electric field intensity. The condition of pressure isotropy yields three category of solutions. The first category is expressible in terms of elementary functions and does not have an uncharged limit. The second category is given in terms of Bessel functions of half-integer order. These charged solutions satisfy a barotropic equation of state and contain Finch–Skea uncharged stars. The third category is obtained in terms of modified Bessel functions of half-integer order and does not have an uncharged limit. The physical features of the charged analogue of the Finch–Skea stars are studied in detail. In particular, the condition of causality is satisfied and the speed of sound does not exceed the speed of light. The physical analysis indicates that this analogue is a realistic model for static charged relativistic perfect fluid spheres.
PARABOLOIDAL SPACE–TIMES AND RELATIVISTIC MODELS OF STRANGE STARS
Authors: JOTANIA KANTI , TIKEKAR RAMESH
Published: October 2006

The objective of this paper is to find out the suitability of an ansatz similar to that suggested by Vaidya–Tikekar, but prescribing paraboloidal geometry for the 3-space of the interior space–time of a relativistic spherical star in describing a family of physically viable models of superdense stars like Her X-1, SAX, and X-ray brust.
EFFECT OF PHYSICAL THERAPY ON WOMAC SCORES AND QUALITY OF LIFE IN PATIENTS WITH KNEE OSTEOARTHRITIS
Authors: Dinçer Fitnat , Erol Özlem , Atalay Ayçe
Published: October 2006

Objective: To assess effect of physical therapy including both physical agents and exercise on pain, physical functioning and quality of life in patients with knee osteoarthritis.

Methods: Twenty-seven patients (25 female and two male) with knee osteoarthritis were included in the study. Besides sociodemographic variables, presence of chronic diseases, analgesic use, recreational activites were recorded. A standard knee examination was performed and anteroposterior and lateral knee radiographs were obtained. Pain was measured using visual analogue scale (VAS), numeric scale and Likert scale. Pain, stiffness and physical function was assessed using Likert-scaled version of the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). For quality of life evaluation Medical Outcomes Study Short Form 36 (SF-36) was utilized. Evaluations were done at baseline and 1 month after completion of physical therapy sessions.

Results: Significant reduction of pain measurements namely VAS, numeric scale and Likert scale was observed as a result of physical treatment (p = 0.0001, p = 0.0001 and p = 0.001 respectively). In all 3 subscores of WOMAC (pain, stiffness and physical function) significant improvement was noted due to treatment (p = 0.0001, p = 0.012 and p = 0.0001 respectively). Similarly, physical functioning, role-physical, bodily pain and vitality and social functioning subscores demonstrated significant reductions after therapy. (p = 0.039, p = 0.001, p = 0.0001, p = 0.001 and p = 0.035 respectively).

Conclusion: Physical therapy including both physical agents and exercise leads to signifcant improvements in pain, physical functioning and quality of life. This change was demonstrated by both generic and disease specific outcome measures.
GEOMETRY OF FLAG MANIFOLDS
Authors: ARVANITOYEORGOS ANDREAS
Published: October 2006

A flag manifold is a homogeneous space M = G/K, where G is a compact semisimple Lie group, and K the centralizer of a torus in G. Equivalently, M can be identified with the adjoint orbit Ad (G)w of an element w in the Lie algebra of G. We present several aspects of flag manifolds, such as their classification in terms of painted Dynkin diagrams, T-roots and G-invariant metrics, and Kähler metrics. We give a Lie-theoretic expression of the Ricci tensor in M, hence reducing the Einstein equation on flag manifolds into an algebraic system of equations, which can be solved in several cases. A flag manifold is also a complex manifold, and this dual representation as a real and a complex manifold is related to a similar property of an infinite-dimensional manifold, the loop space, which in fact can be viewed as a "universal" flag manifold.
NANOTECHNOLOGY PATENT LANDSCAPE 2006
Authors: LEE LINDA L. , CHAN CASEY K. , NGIAM MICHELLE , RAMAKRISHNA SEERAM
Published: October 2006

Touted as the technological revolution of the 21st century, nanotechnology has already been the topic of numerous publications, patents and news stories. While the commercial applications of nanotechnology are still relatively few, they are beginning to attract the attention of the commercial sector. For successful commercialization of this emerging technology, patent protection is imperative. Patents are publicly available documents forming a rich repository of current knowledge. By a systematic method of collecting, organizing and analyzing these publicly available documents, valuable information can be distilled about the activities and opportunities within this emerging field. As this field is rapidly progressing, this paper provides a summary of current patent issues in nanotechnology, an overview of nanotechnology patent analyses and the latest update of the current landscape of nanotechnology patents.
Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor–Dependent Mechanism
Authors: Luther James M. , Gainer James V. , Murphey Laine J. , Yu Chang , Vaughan Douglas E. , Morrow Jason D. , Brown Nancy J.
Published: October 2006

This study tested the hypothesis that angiotensin promotes oxidative stress and inflammation in humans via aldosterone and the mineralocorticoid receptor. We measured the effect of intravenous aldosterone (0.7 μg/kg per hour for 10 hours followed by 0.9 μg/kg per hour for 4 hours) and vehicle in a randomized, double-blind crossover study in 11 sodium-restricted normotensive subjects. Aldosterone increased interleukin (IL)-6 (from 4.7±4.9 to 9.4±7.1 pg/mL; F=4.94;
P
=0.04) but did not affect blood pressure, serum potassium, or high-sensitivity C-reactive protein. We next conducted a randomized, double-blind, placebo-controlled, crossover study to measure the effect of 3-hour infusion of angiotensin II (2 ng/kg per minute) and norepinephrine (30 ng/kg per minute) on separate days after 2 weeks of placebo or spironolactone (50 mg per day) in 14 salt-replete normotensive subjects. Angiotensin II increased blood pressure (increase in systolic pressure: 13.7±7.5 and 15.2±9.4 mm Hg during placebo and spironolactone, respectively;
P
<0.001 for angiotensin II) and decreased renal plasma flow (−202±73 and −167±112 mL/min/1.73 kg/m
2
;
P
<0.001 for angiotensin II effect) similarly during placebo and spironolactone. Spironolactone enhanced the aldosterone response to angiotensin II (increase of 17.0±10.6 versus 9.0±5.7 ng/dL;
P
=0.002). Angiotensin II transiently increased free plasma F
2
-isoprostanes similarly during placebo and spironolactone. Angiotensin II increased serum IL-6 concentrations during placebo (from 1.8±1.1 to 2.4±1.4 pg/mL; F=4.5;
P
=0.04) but spironolactone prevented this effect (F=6.4;
P
=0.03 for spironolactone effect). Norepinephrine increased blood pressure and F
2
-isoprostanes but not aldosterone or IL-6. Aldosterone increases IL-6 in humans. These data suggest that angiotensin II induces IL-6 through a mineralocorticoid receptor–dependent mechanism in humans. In contrast, angiotensin II–induced oxidative stress, as measured by F
2
-isoprostanes, is mineralocorticoid receptor independent and may be pressor dependent.
Transcriptional Profiling in Coronary Artery Disease
Authors: Chittenden Thomas W. , Sherman Jonathan A. , Xiong Fei , Hall Amy E. , Lanahan Anthony A. , Taylor Jennifer M. , Duan Hangjun , Pearlman Justin D. , Moore Jason H. , Schwartz Stephen M. , Simons Michael
Published: October 2006

Background—

The development of collateral circulation plays an important role in protecting tissues from ischemic damage, and its stimulation has emerged as one of principal approaches to therapeutic angiogenesis. Clinical observations have documented substantial differences in the extent of collateralization among patients with coronary artery disease (CAD), with some individuals demonstrating marked abundance and others showing nearly complete absence of these vessels. Recent studies have suggested that circulating monocytes play a major role in collateral growth. The present study was undertaken to determine transcriptional profiles of circulating monocytes in CAD patients with different extents of collateral growth.

Methods and Results—

Monocyte transcriptomes from CAD patients with and without collateral vessels were obtained by use of high-throughput expression profiling. Using a newly developed redundancy-based data mining method, we have identified a set of molecular markers characteristic of a “noncollateralgenic” phenotype. Moreover, we show that these transcriptional abnormalities are independent of the severity of CAD or any other known clinical parameter thought to affect collateral development and correlated with protein expression levels in monocytes and plasma.

Conclusions—

Monocyte transcription profiling identifies sets of patients with extensive versus poorly developed collateral circulation. Thus, genetic factors may heavily influence coronary collateral vessel growth in CAD and affect prognosis and response to therapeutic interventions.
Hurricane Isabel (2003): New Insights into the Physics of Intense Storms. Part I: Mean Vortex Structure and Maximum Intensity Estimates
Authors: Montgomery Michael T. , Bell Michael M. , Aberson Sim D. , Black Michael L.
Published: October 2006

This study is an observational analysis of the inner-core structure, sea surface temperature, outflow layer, and atmospheric boundary layer of an intense tropical cyclone whose intensity and structure is consistent with recent numerical and theoretical predictions of superintense storms. The findings suggest new scientific challenges for the current understanding of hurricanes.

Unprecedented observations of the category-5 Hurricane Isabel (2003) were collected during 12–14 September. This two-part article reports novel dynamic and thermodynamic aspects of the inner-core structure of Isabel on 13 September that were made possible by analysis of these data. Here, a composite of the axisymmetric structure of the inner core and environment of Isabel is estimated using global positioning system dropwindsondes and in situ aircraft data. In Part II, an extreme wind speed observation on the same day is discussed in the context of this work.

The axisymmetric data composite suggests a reservoir of high-entropy air inside the low-level eye and significant penetration of inflowing near-surface air from outside. The analysis suggests that the low-level air penetrating the eye is enhanced thermodynamically by acquiring additional entropy through interaction with the ocean and replaces air mixed out of the eye. The results support the hypothesis that this high-entropy eye air “turboboosts” the hurricane engine upon its injection into the eyewall clouds. Recent estimates of the ratio of sea-to-air enthalpy and momentum exchange at high wind speeds are used to suggest that Isabel utilized this extra power to exceed the previously assumed intensity upper bound by 10–35 m s−1 for the given environmental conditions. Additional study with other datasets is encouraged to further test the superintensity hypothesis.
African Climate Change: Taking the Shorter Route
Authors: Washington Richard , Harrison Mike , Conway Declan , Black Emily , Challinor Andrew , Grimes David , Jones Richard , Morse Andy , Kay Gillian , Todd Martin
Published: October 2006

Numerous factors are associated with poverty and underdevelopment in Africa, including climate variability. Rainfall, and climate more generally, are implicated directly in the United Nations “Millennium Development Goals” to eradicate extreme poverty and hunger, and reduce child mortality and incidence of diseases such as malaria by the target date of 2015. But, Africa is not currently on target to meet these goals. We pose a number of questions from a climate science perspective aimed at understanding this background: Is there a common origin to factors that currently constrain climate science? Why is it that in a continent where human activity is so closely linked to interannual rainfall variability has climate science received little of the benefit that saw commercialization driving meteorology in the developed world? What might be suggested as an effective way for the continent to approach future climate variability and change? We make the case that a route to addressing the challenges of climate change in Africa rests with the improved management of climate variability. We start by discussing the constraints on climate science and how they might be overcome. We explain why the optimal management of activities directly influenced by interannual climate variability (which include the development of scientific capacity) has the potential to serve as a forerunner to engagement in the wider issue of climate change. We show this both from the perspective of the climate system and the institutions that engage with climate issues. We end with a thought experiment that tests the benefits of linking climate variability and climate change in the setting of smallholder farmers in Limpopo Province, South Africa.
GSWP-2: Multimodel Analysis and Implications for Our Perception of the Land Surface
Authors: Dirmeyer Paul A. , Gao Xiang , Zhao Mei , Guo Zhichang , Oki Taikan , Hanasaki Naota
Published: October 2006

Quantification of sources and sinks of carbon at global and regional scales requires not only a good description of the land sources and sinks of carbon, but also of the synoptic and mesoscale meteorology. An experiment was performed in Les Landes, southwest France, during May–June 2005, to determine the variability in concentration gradients and fluxes of CO2 The CarboEurope Regional Experiment Strategy (CERES; see also http://carboregional.mediasfrance.org/index) aimed to produce aggregated estimates of the carbon balance of a region that can be meaningfully compared to those obtained from the smallest downscaled information of atmospheric measurements and continental-scale inversions. We deployed several aircraft to sample the CO2 concentration and fluxes over the whole area, while fixed stations observed the fluxes and concentrations at high accuracy. Several (mesoscale) meteorological modeling tools were used to plan the experiment and flight patterns.

Results show that at regional scale the relation between profiles and fluxes is not obvious, and is strongly influenced by airmass history and mesoscale flow patterns. In particular, we show from an analysis of data for a single day that taking either the concentration at several locations as representative of local fluxes or taking the flux measurements at those sites as representative of larger regions would lead to incorrect conclusions about the distribution of sources and sinks of carbon. Joint consideration of the synoptic and regional flow, fluxes, and land surface is required for a correct interpretation. This calls for an experimental and modeling strategy that takes into account the large spatial gradients in concentrations and the variability in sources and sinks that arise from different land use types. We briefly describe how such an analysis can be performed and evaluate the usefulness of the data for planning of future networks or longer campaigns with reduced experimental efforts.