ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc).

Introduction: The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT interval in humans. In the original analysis of these data, QT, QTcB (Bazett model), QTcF (Fridericia model), and QTcQ (animal-specific model) were evaluated. We further evaluate the statistical properties of these measurements, using a method that can properly account for the sources of variability in the dataset.

Internal representations of smell in the Drosophila brain.

Recent advances in sensory neuroscience using Drosophila olfaction as a model system have revealed brain maps representing the external world. Once we understand how the brain's built-in capability generates the internal olfactory maps, we can then elaborate how the brain computes and makes decision to elicit complex behaviors. Here, we review current progress in mapping Drosophila olfactory circuits and discuss their relationships with innate olfactory behaviors.

Mediators of vascular remodelling co-opted for sequential steps in lung metastasis.

Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.

Electro-optic periodically poled lithium niobate Bragg modulator as a laser Q-switch.

We report an electro-optic Bragg modulator using a periodically poled lithium niobate (PPLN) crystal. We measured a half-wave voltage of 160 V when transmitting a 1064 nm laser through a 14.2 mm long, 780 microm thick, 20.

A map of olfactory representation in the Drosophila mushroom body.

Neural coding for olfactory sensory stimuli has been mapped near completion in the Drosophila first-order center, but little is known in the higher brain centers. Here, we report that the antenna lobe (AL) spatial map is transformed further in the calyx of the mushroom body (MB), an essential olfactory associated learning center, by stereotypic connections with projection neurons (PNs). We found that Kenyon cell (KC) dendrites are segregated into 17 complementary domains according to their neuroblast clonal origins and birth orders.

A reliable surface reconstruction system in biomedicine.

For common biomedical imaging facilities, such as CT, MRI, and confocal microscopy, the acquired scans are sequential parallel sections. The object of interest in each section image can be extracted by segmentation procedure to form serial parallel planar contours. How to reconstruct a trustworthy surface from these contours is a crucial issue in biomedical 3D visualization.

Obstructive sleep apnea and chronic intermittent hypoxia: a review.

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level.

Grafting of cyclopentadienyl ruthenium complexes on aminosilane linker modified mesoporous SBA-15 silicates.

Cyclopentadienyl ruthenium phosphane and carbene complexes are grafted on the surface of mesoporous SBA-15 molecular sieves through an aminosilane linker. The nature of the support after the grafting is examined by powder XRD, TEM and N(2) adsorption/desorption analysis. Elemental analysis, FT-IR, DRIFTS, TG-MS and MAS-NMR studies confirm the successful grafting of the complexes on the surface.

Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation.

A retrospective cohort of 163 children with 171 hematopoietic stem cell transplantation (HSCT) performed during Mar. 1992-Dec. 2005 were analyzed to evaluate the incidence, risk factors, management, and outcome of hemorrhagic cystitis (HC).

Antioxidant effects of black rice extract through the induction of superoxide dismutase and catalase activities.

Our ex vivo study revealed that BRE had significantly stronger ability to inhibit LDL oxidation than white rice extract (WRE). The purpose of this study was to investigate whether black rice extract (BRE) supplementation might ameliorate oxidative stress and enhance antioxidant enzyme activities in HepG2 cells and in C57BL/6 mice. In the cellular study, superoxide anions (O2*-) and reactive oxygen species (ROS) in the BRE group were significantly suppressed.

The ISNT rule and differentiation of normal from glaucomatous eyes.

Objective: To determine whether the ISNT rule (that normal eyes show a characteristic configuration for disc rim thickness of inferior > or = superior > or = nasal > or = temporal), widely used for clinical evaluation of the optic nerve head, can differentiate normal from glaucomatous eyes.

Methods: All subjects underwent complete eye examination, including achromatic automated perimetry, simultaneous stereoscopic disc photography, and confocal scanning laser ophthalmoscopy. Subjects with normal eyes had no evidence of glaucoma or ocular hypertension and had normal perimetry measurements.

Light-enhanced electro-optic spectral tuning in annealed proton-exchanged periodically poled lithium niobate channel waveguides.

We report the observation of light-enhanced electro-optic spectral tuning in annealed proton-exchanged, asymmetric domain-duty-cycle periodically poled lithium niobate (PPLN) channel waveguides for second-harmonic generation. The spectral tuning rate was increased rapidly from 0.07 nm/(kV/mm) to a saturated value of 0.

Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors.

Purpose: In patients whose lung adenocarcinomas harbor epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations, acquired resistance to the tyrosine kinase inhibitors (TKI) gefitinib (Iressa) and erlotinib (Tarceva) has been associated with a second-site EGFR mutation, which leads to substitution of methionine for threonine at position 790 (T790M). We aimed to elucidate the frequency and nature of secondary EGFR mutations in patients with acquired resistance to TKI monotherapy.

Experimental Design: Tumor cells from patients with acquired resistance were examined for secondary EGFR kinase domain mutations by molecular analyses.

Induction of cyclooxygenase-2 expression by manganese in cultured astrocytes.

Inflammatory and oxidative events are present in neurodegenerative disorders and appear to contribute to initiation and/or progression of the disease. Within the brain, redox-active metals, such as manganese, play an important role as components of proteins essential for neural function. However, increasing evidence implies its participation in neurodegenerative diseases involving immune modulation.

Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity.

Many neural progenitors, including Drosophila mushroom body (MB) and projection neuron (PN) neuroblasts, sequentially give rise to different subtypes of neurons throughout development. We identified a novel BTB-zinc finger protein, named Chinmo (Chronologically inappropriate morphogenesis), that governs neuronal temporal identity during postembryonic development of the Drosophila brain. In both MB and PN lineages, loss of Chinmo autonomously causes early-born neurons to adopt the fates of late-born neurons from the same lineages.

Fixation of greater tuberosity fractures: a biomechanical comparison of three techniques.

The fixation of displaced greater tuberosity fractures with 5-0 Fiberwire, Fiberwire tape, and 5-0 Ethibond sutures was compared in 12 pairs of cadaveric humeri. A simulated fracture was created and fixed with suture in a figure-of-eight pattern. The tuberosity was cyclically loaded and its displacement measured.

Parotid acinar cell carcinoma in a long-term survivor of childhood acute lymphoblastic leukemia.

Secondary malignancies are an important cause of morbidity and mortality in childhood cancer survivors. Salivary gland tumors account for about 6% of the second cancers. The majority of these are mucoepidermoid carcinomas (MEC) of the parotid gland.

Rapid synthesis of MFI zeolite nanocrystals.

A rapid synthesis procedure for nonagglomerated silicalite nanocrystals has been developed. This was achieved by concentrating the precursor sol before 10-12 h of aging at 80 degrees C, followed by hydrothermal synthesis at 175 degrees C for 90 min. The high silica concentration in the concentrated sol accelerated the aggregation of primary units that were present early in the system.

Single-longitudinal-mode, tunable dual-wavelength,CW Nd:YVO(4) laser.

We report a single-longitudinal-mode CW diode-pumped Nd:YVO(4) laser emitting at both 1064 and 1342 nm with 10% optical efficiency at 20-W pump power. The measured spectral widths at 1064 and 1342 nm were less than 450 MHz and 400 MHz, respectively. The two emission wavelengths can be independently tuned over the lasing bandwidths of the dual-wavelength laser.

Genome-wide identification of pseudogenes capable of disease-causing gene conversion.

Pseudogenes are remnants of gene duplication (nonprocessed pseudogenes) and retrotransposition (processed pseudogenes) events. This study describes methods for identifying gene conversion candidates from predicted pseudogenes. Pseudogenes may accumulate and harbor sequence variations over time that become disease-causing mutations when transferred to genes by gene conversion.

L-glutamate activates RhoA GTPase leading to suppression of astrocyte stellation.

The actin cytoskeleton is known to support cellular morphological changes. Rho family small GTPases function as switching molecules to promote the convergence of both extracellular and intracellular signals in regulating cytoskeletal organization. Evidence indicates that L-glutamate suppresses morphological changes of astrocytes over a broad spectrum.

A calmodulin-binding site on cyclin E mediates Ca2+-sensitive G1/s transitions in vascular smooth muscle cells.

Calcium transients are known to control several transition points in the eukaryotic cell cycle. For example, we have previously shown that a coordinate elevation in the intracellular free calcium ion concentration is required for G1- to S-phase cell cycle progression in vascular smooth muscle cells (VSMC). However, the molecular basis for this Ca2+ sensitivity was not known.

Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).

The identification of mutations in genes that cause human diseases has largely been accomplished through the use of positional cloning, which relies on linkage mapping. In studies of rare diseases, the resolution of linkage mapping is limited by the number of available meioses and informative marker density. One recent advance is the development of high-density SNP microarrays for genotyping.

A one-step approach to the analysis of the QT interval in conscious telemetrized dogs.

Introduction: To account for heart rate-induced changes in the QT interval, correction formulas are generally applied to normalize the QT interval for heart rate. None of these formulas is entirely accurate because correction or normalization of any parameter in biology may introduce an additional source of variation in estimating the parameter. In this article, a one-step approach for the statistical analysis of the QT interval was proposed based on modeling the functional relationship between the QT interval and heart rate.

Osteoporosis--diagnosis and treatment in a general practice population.

Background: Osteoporosis may be underdiagnosed and undertreated. General practitioners are best placed to redress this.

Methods: The research group invited all GPs in Bendigo (Victoria) (60) to attend an educational evening about osteoporosis, and also to engage in subsequent research involving data extraction from their electronic medical records for 2003.