Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TOM complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

943 records · Page 53Linked to original sources
PubMed2005

An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk.

BACKGROUND: Alcoholism is a complex, genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk. One such intermediate phenotype is the low level of response (LR) to alcohol. This project used a case-control approach to search for genes that may contribute to LR. METHODS: Data were available from alcohol challenges at approximately age 20 and regarding the development of alcohol use disorders over the subsequent 20 years for 85 men, including 40 reported in a previous genetic analysis. LR was evaluated using oral consumption of 0.75 ml/kg of alcohol, after which changes in subjective feelings of intoxication and body sway were measured. Alcohol abuse and dependence were diagnosed by DSM-III-R criteria through structured interviews administered to both the participant and an informant (usually the spouse) 10, 15, and 20 years after initial testing. Four polymorphisms were evaluated, including the serotonin transporter HTTLPR promoter ins/del, GABAAalpha6 Pro385Ser, NPY Leu7Pro, and catalase 262C>T. Two of these, HTTLPR and GABAAalpha6 Pro385Ser, had been previously associated with LR and alcoholism in a preliminary study. RESULTS: The HTTLPR L allele was significantly related to both the LR and alcoholism in an allele-dosage (stepwise) manner. Furthermore, the association remained when L alleles were subdivided into recently reported functional subtypes: the lowest LR was associated with genotypes correlated with the highest serotonin transporter expression. The GABAAalpha6 Ser385 allele showed a nonsignificant trend for association to a low LR, as had been previously observed, although the Ser385 allele is uncommon, and only 18 heterozygotes were in the current group. However, the six men with both LL and Pro385/Ser385 genotypes had the lowest LR, and each had developed alcoholism during follow-up. Neither NPY nor catalase was associated with either LR or alcoholic outcomes, although the sample did not have sufficient power for definitive conclusions. CONCLUSIONS: This report strengthens the support for a relationship between the HTTLPR L and GABAAalpha6 Ser385 alleles to low alcohol LR and to alcoholism in a prospectively studied cohort evaluated for LR in young adulthood and before the onset of alcohol dependence.

Adult↗
PubMed2006

The 'human revolution' in lowland tropical Southeast Asia: the antiquity and behavior of anatomically modern humans at Niah Cave (Sarawak, Borneo).

Recent research in Europe, Africa, and Southeast Asia suggests that we can no longer assume a direct and exclusive link between anatomically modern humans and behavioral modernity (the 'human revolution'), and assume that the presence of either one implies the presence of the other: discussions of the emergence of cultural complexity have to proceed with greater scrutiny of the evidence on a site-by-site basis to establish secure associations between the archaeology present there and the hominins who created it. This paper presents one such case study: Niah Cave in Sarawak on the island of Borneo, famous for the discovery in 1958 in the West Mouth of the Great Cave of a modern human skull, the 'Deep Skull,' controversially associated with radiocarbon dates of ca. 40,000 years before the present. A new chronostratigraphy has been developed through a re-investigation of the lithostratigraphy left by the earlier excavations, AMS-dating using three different comparative pre-treatments including ABOX of charcoal, and U-series using the Diffusion-Absorption model applied to fragments of bones from the Deep Skull itself. Stratigraphic reasons for earlier uncertainties about the antiquity of the skull are examined, and it is shown not to be an 'intrusive' artifact. It was probably excavated from fluvial-pond-desiccation deposits that accumulated episodically in a shallow basin immediately behind the cave entrance lip, in a climate that ranged from times of comparative aridity with complete desiccation, to episodes of greater surface wetness, changes attributed to regional climatic fluctuations. Vegetation outside the cave varied significantly over time, including wet lowland forest, montane forest, savannah, and grassland. The new dates and the lithostratigraphy relate the Deep Skull to evidence of episodes of human activity that range in date from ca. 46,000 to ca. 34,000 years ago. Initial investigations of sediment scorching, pollen, palynomorphs, phytoliths, plant macrofossils, and starch grains recovered from existing exposures, and of vertebrates from the current and the earlier excavations, suggest that human foraging during these times was marked by habitat-tailored hunting technologies, the collection and processing of toxic plants for consumption, and, perhaps, the use of fire at some forest-edges. The Niah evidence demonstrates the sophisticated nature of the subsistence behavior developed by modern humans to exploit the tropical environments that they encountered in Southeast Asia, including rainforest.

Animals↗
PubMed2004

Multi-scale analysis of a household level agent-based model of landcover change.

Scale issues have significant implications for the analysis of social and biophysical processes in complex systems. These same scale implications are likewise considerations for the design and application of models of landcover change. Scale issues have wide-ranging effects from the representativeness of data used to validate models to aggregation errors introduced in the model structure. This paper presents an analysis of how scale issues affect an agent-based model (ABM) of landcover change developed for a research area in the Midwest, USA. The research presented here explores how scale factors affect the design and application of agent-based landcover change models. The ABM is composed of a series of heterogeneous agents who make landuse decisions on a portfolio of cells in a raster-based programming environment. The model is calibrated using measures of fit derived from both spatial composition and spatial pattern metrics from multi-temporal landcover data interpreted from historical aerial photography. A model calibration process is used to find a best-fit set of parameter weights assigned to agents' preferences for different landuses (agriculture, pasture, timber production, and non-harvested forest). Previous research using this model has shown how a heterogeneous set of agents with differing preferences for a portfolio of landuses produces the best fit to landcover changes observed in the study area. The scale dependence of the model is explored by varying the resolution of the input data used to calibrate the model (observed landcover), ancillary datasets that affect land suitability (topography), and the resolution of the model landscape on which agents make decisions. To explore the impact of these scale relationships the model is run with input datasets constructed at the following spatial resolutions: 60, 90, 120, 150, 240, 300 and 480 m. The results show that the distribution of landuse-preference weights differs as a function of scale. In addition, with the gradient descent model fitting method used in this analysis the model was not able to converge to an acceptable fit at the 300 and 480 m spatial resolutions. This is a product of the ratio of the input cell resolution to the average parcel size in the landscape. This paper uses these findings to identify scale considerations in the design, development, validation and application of ABMs of landcover change.

Agriculture↗
PubMed2004

Photoelectron spectroscopy of the doubly-charged anions [MIVO(mnt)2]2- (M = Mo, W; mnt = S2C2(CN)2(2-): access to the ground and excited states of the [MVO(mnt)2]- anion.

Photodetachment photoelectron spectroscopy was used to investigate the electronic structure of the doubly charged complexes [MIVO(mnt)2]2- (M = Mo, W; mnt = 1,2-dicyanoethenedithiolato). These dianions are stable in the gas phase and are minimal models for the active sites of the dimethyl sulfoxide reductase family of molybdenum enzymes and of related tungsten enzymes. Adiabatic and vertical electron binding energies for both species were measured, providing detailed information about molecular orbital energy levels of the parent dianions as well as the ground and excited states of the product anions [MVO(mnt)2]-. Density functional theory calculations were used to assist assignment of the detachment features. Differences in energy between these features provided the energies of ligand-to-metal charge-transfer transitions from S(pi) and S(sigma) molecular orbitals to the singly occupied metal-based orbital of the products [MVO(mnt)2]-. These unique data for the M(V) species were obtained at the C(2)(v)() geometry of the parent M(IV) dianions. However, theoretical calculations and available condensed phase data suggested that a geometry featuring differentially folded dithiolene ligands (Cs point symmetry) was slightly lower in energy. The driving force for ligand folding is a favorable covalent interaction between the singly occupied metal-based molecular orbital (a1 in C2v) point symmetry; highest occupied molecular orbital (HOMO)) and the least stable of the occupied sulfur-based molecular orbitals (b1 in C2v point symmetry, HOMO-1) that is only possible upon reduction to the lower symmetry. This ligand folding induces a large increase in the intensity predicted for the a' S(pi) --> a' dx2 - y2 charge-transfer transition originating from the HOMO-2 of [MVO(mnt)2](-) under Cs point symmetry. Electronic absorption spectra are available for the related species [MoVO(bdt)2]- (bdt = 1,2-benzenedithiolato) and for the oxidized form of dimethyl sulfoxide reductase. The intense absorptions at approximately 1.7 eV have been assigned previously to S(sigma) --> Mo transitions, assuming C2v geometry. The present work indicates that the alternative a' S(pi) --> a' dx2 - y2 of Cs geometry must be considered. Overall, this study confirms that the electronic structure of the M-dithiolene units are exquisitely sensitive to dithiolene ligand folding, reinforcing the proposal that these units are tunable conduits for electron transfer in enzyme systems.

Anions↗
PubMed2004

Prevention and treatment of erectile dysfunction using lifestyle changes and dietary supplements: what works and what is worthless, part II.

It seems naïve to believe that some plants or herbs do not contain specific compounds that could benefit patients with ED. Many supplements have not been investigated in a laboratory or clinical research setting before commercial sale, however,which creates a complex situation. If efficacy is or is not demonstrated through adequate research, then the benefit or lack thereof cannot be mentioned on the label. Furthermore, clinicians and the public cannot be made aware of which compounds or supplements are effective because no general standards for sale exist under the current guidelines. Dietary supplements have received a tremendous amount of publicity. The large and growing market for ED treatment seems to have contributed partly to the promotion of numerous supplements and their apparent benefits. Whether these dietary supplements have merit is questionable. Some supplements may produce results opposite to those advertised. Other supplements may be enjoying the benefits of the placebo effect. Because a placebo response of 25% to 50% has been recorded in clinical trials with effective agents, it is understandable that some supplements enjoy financial success despite the limited research espousing their use. If one to two of four individuals or one of three individuals who try a dietary supplement gain some benefit for their ED, the market for these supplements will remain extraordinary. On a larger scale, of 100,000 men who try a supplement, approximately 25,000 to 50,000 will claim some success. The challenge for clinicians is to discuss the placebo response properly and the need for good research before any intervention, especially supplements, can be advocated for general use. Table 2 summarizes some popular ED supplements and general conclusions that can be drawn from clinical investigations. Some dietary supplements may have an active ingredient that benefits patients with certain types of ED. An exciting area of future dietary supplement research is the ability of certain agents to have a synergistic effect with prescription agents for ED, thereby improving response rates in men that have failed approved ED therapy initially, especially with oral agents. Randomized clinical trials are the best method of determining which dietary supplements will become a part of conventional medicine. Therefore, more randomized trials for dietary supplements are needed so that they may have the opportunity to become a part of the mainstream milieu, which means that more funding needs to be made available for ED research. The coming years of research should bring enormous excitement and objectivity to this area of medicine.

Adult↗
PubMed2006

A new probabilistic seismic hazard assessment for greater Tokyo.

Tokyo and its outlying cities are home to one-quarter of Japan's 127 million people. Highly destructive earthquakes struck the capital in 1703, 1855 and 1923, the last of which took 105,000 lives. Fuelled by greater Tokyo's rich seismological record, but challenged by its magnificent complexity, our joint Japanese-US group carried out a new study of the capital's earthquake hazards. We used the prehistoric record of great earthquakes preserved by uplifted marine terraces and tsunami deposits (17 M approximately 8 shocks in the past 7000 years), a newly digitized dataset of historical shaking (10000 observations in the past 400 years), the dense modern seismic network (300,000 earthquakes in the past 30 years), and Japan's GeoNet array (150 GPS vectors in the past 10 years) to reinterpret the tectonic structure, identify active faults and their slip rates and estimate their earthquake frequency. We propose that a dislodged fragment of the Pacific plate is jammed between the Pacific, Philippine Sea and Eurasian plates beneath the Kanto plain on which Tokyo sits. We suggest that the Kanto fragment controls much of Tokyo's seismic behaviour for large earthquakes, including the damaging 1855 M approximately 7.3 Ansei-Edo shock. On the basis of the frequency of earthquakes beneath greater Tokyo, events with magnitude and location similar to the M approximately 7.3 Ansei-Edo event have a ca 20% likelihood in an average 30 year period. In contrast, our renewal (time-dependent) probability for the great M > or = 7.9 plate boundary shocks such as struck in 1923 and 1703 is 0.5% for the next 30 years, with a time-averaged 30 year probability of ca 10%. The resulting net likelihood for severe shaking (ca 0.9 g peak ground acceleration (PGA)) in Tokyo, Kawasaki and Yokohama for the next 30 years is ca 30%. The long historical record in Kanto also affords a rare opportunity to calculate the probability of shaking in an alternative manner exclusively from intensity observations. This approach permits robust estimates for the spatial distribution of expected shaking, even for sites with few observations. The resulting probability of severe shaking is ca 35% in Tokyo, Kawasaki and Yokohama and ca 10% in Chiba for an average 30 year period, in good agreement with our independent estimate, and thus bolstering our view that Tokyo's hazard looms large. Given 1 trillion US dollars estimates for the cost of an M approximately 7.3 shock beneath Tokyo, our probability implies a 13 billion US dollars annual probable loss.

Cities↗
PubMed2002

Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies.

Somatostatin and its analogues bind to somatostatin receptors (sst) 1 through 5 that are overexpressed in neuroendocrine neoplasms such as gastroenteropancreatic (GEP) malignancies. After ligand-receptor binding, a fraction of the ligand-receptor complexes internalize. This internalization process is an effective means of delivering cytotoxic radiolabeled somatostatin analogues, especially those emitting short-range decay particles such as Auger electrons, to the neoplastic cell nucleus. Indium-111-pentetreotide, an sst 2 preferring somatostatin analogue with gamma and Auger electron decay characteristics, is commonly used for the scintigraphic evaluation and management of neuroendocrine cancer patients. This clinical trial was performed to determine the effectiveness and tolerability of therapeutic doses of (111)In-pentetreotide in patients with GEP tumors. GEP tumor patients who had failed all forms of conventional therapy, with worsening of tumor-related signs and symptoms and/or radiographically documented progressive disease, an expected survival less than 6 months, and sst positivity as determined by the uptake on a 6.0 mCi (111)In-pentetreotide scan (OctreoScan; Mallinckrodt Medical, Inc, St. Louis, MO), were treated with at least 2 monthly 180-mCi intravenous injections of (111)In-pentetreotide. Baseline clinical assessments, serum chemistries, and plasma pancreastatin levels were measured and repeated before each (111)In-pentetreotide treatment. From February 1997 to February 1998, 27 GEP (24 carcinoid neoplasms with carcinoid syndrome and 3 pancreatic islet cells) patients were accrued, with 26 patients evaluable for clinical and radiographic responses, 21 patients evaluable for biochemical assessments, and 27 patients evaluable for survival analysis and safety. Toxicity was evaluated by using standard National Cancer Institute (NCI) Common Toxicity Criteria guidelines. Clinical benefit occurred in 16 (62%) patients. Pancreastatin levels decreased by 50% or more in 81% of the patients. Objective partial radiographic responses occurred in 2 (8%) patients, and significant tumor necrosis (defined by 20 Hounsfield units or greater decrease from baseline) developed in 7 (27%) patients. The following transient Grades 3/4 NCI Common Toxicity Criteria side effects were observed, respectively: leukocyte: 1/1; platelets: 0/2; hemoglobin: 3/0; bilirubin: 1/3; creatinine: 1/0; neurologic: 1/0. Myeloproliferative disease and/or myelodysplastic syndrome have not been observed in the 6 patients followed-up for 48+ months. The median survival was 18 months (range, 3-54+ mo). Two doses (180 mCi) of (111)In-pentetreotide are safe, well-tolerated, and improve symptoms in 62% of patients, decrease hormonal markers in 81% of patients, decrease Hounsfield units on computed tomography (CT) scans in 27% of patients, with 8% partial radiographic responses and increased expected survival in GEP cancer patients with somatostatin receptor-expressing tumors. The maximal tolerated dose of (111)In-pentetreotide and the optimal dosing schedules remain under investigation.

Adult↗