A Molecular Platinum Cluster Junction: A Single-Molecule Switch

We present a theoretical study of the electronic transport through single-molecule junctions incorporating a Pt6 metal cluster bound within an organic framework. We show that the insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nano-metallic device with high conductance at the Fermi level and two sequential high on/off switching states. The origin of this property can be traced back to the existence of a HOMO which consists of two degenerate and asymmetric orbitals, lying close in energy to the Fermi level of the metallic leads. Their degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances which become pinned close to the Fermi level and display destructive interference.Comment: 4 pages, 4 figures. Reprinted (adapted) with permission from J. Am. Chem. Soc., 2013, 135 (6), 2052. Copyright 2013 American Chemical Societ

Inter-rater reliability of post-arrest cerebral performance category (CPC) scores.

PURPOSE: Cerebral Performance Category (CPC) scores are often an outcome measure for post-arrest neurologic function, collected worldwide to compare performance, evaluate therapies, and formulate recommendations. At most institutions, no formal training is offered in their determination, potentially leading to misclassification. MATERIALS AND METHODS: We identified 171 patients at 2 hospitals between 5/10/2005 and 8/31/2012 with two CPC scores at hospital discharge recorded independently - in an in-house quality improvement database and as part of a national registry. Scores were abstracted retrospectively from the same electronic medical record by two separate non-clinical researchers. These scores were compared to assess inter-rater reliability and stratified based on whether the score was concordant or discordant among reviewers to determine factors related to discordance. RESULTS: Thirty-nine CPC scores (22.8%) were discordant (kappa: 0.66), indicating substantial agreement. When dichotomized into favorable neurologic outcome (CPC 1-2)/ unfavorable neurologic outcome (CPC 3-5), 20 (11.7%) scores were discordant (kappa: 0.70), also indicating substantial agreement. Patients discharged home (as opposed to nursing/other care facility) and patients with suspected cardiac etiology of arrest were statistically more likely to have concordant scores. For the quality improvement database, patients with discordant scores had a statistically higher median CPC score than those with concordant scores. The registry had statistically lower median CPC score (CPC 1) than the quality improvement database (CPC 2); p\u3c0.01 for statistical significance. CONCLUSIONS: CPC scores have substantial inter-rater reliability, which is reduced in patients who have worse outcomes, have a non-cardiac etiology of arrest, and are discharged to a location other than home

The importance of high-throughput cell separation technologies for genomics/proteomics-based clinical diagnostics

Gene expression microarray analyses of mixtures of cells approximate a weighted average of the gene expression profiles (GEPs) of each cell type according to its relative abundance in the overall cell sample being analyzed. If the targeted subpopulation of cells is in the minority, or the expected perturbations are marginal, then such changes will be masked by the GEP of the normal/unaffected cells. We show that the GEP of a minor cell subpopulation is often lost when that cell subpopulation is of a frequency less than 30 percent. The GEP is almost always masked by the other cell subpopulations when that frequency drops to 10 percent or less. On the basis of these results one should always assume that the GEP of a given cell subpopulation is probably seriously affected by, the presence of significant numbers of other "contaminating" cell types. Several methodologies can be employed to enrich the target cells submitted for microarray analyses. These include magnetic sorting and laser capture microdissection. If a cell subpopulation of interest is small, very high-throughput cell separation technologies are needed to separate enough cells for conventional microarrays. However, high-throughput flow cytometry/cell sorting overcomes many restrictions of experimental enrichment conditions. This technology can also be used to sort smaller numbers of cells of specific cell subpopulations and subsequently amplify their mRNAs before microarray analyses. When purification techniques are applied to unfixed samples, the potential for changes in gene levels during the process of collection is an additional concern. Since RNA rapidly degrades, and specific mRNAs turn over in minutes or hours, the cell separation process must be very rapid. Hence, high-throughput cell separation (HTS) technologies are needed that can process the necessary number of cells expeditiously in order to avoid such uncontrolled changes in the target cells GEP. In cases where even the use of HTS yields only a small number of cells, the mRNAs (after reverse transcription to cDNA's) must be amplified to yield enough material for conventional microarray analyses. However, the problem of using "microamplification" PCR methods to expand the amount of cDNAs (from mRNAs) is that it is very difficult to amplify equally all of the mRNAs. Unequal amplification leads to a distorted gene expression profile on the microarray. Linear amplifications is difficult to achieve. Unfortunately, present-day gene-chips need to be about 100 times more sensitive than they are now to be able to do many biologically and biomedically meaningful experiments and clinical tests

Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine

Nanomedicine involves cell-by-cell regenerative medicine, either repairing cells one at a time or triggering apoptotic pathways in cells that are not repairable. Multilayered nanoparticle systems are being constructed for the targeted delivery of gene therapy to single cells. Cleavable shells containing targeting, biosensing, and gene therapeutic molecules are being constructed to direct nanoparticles to desired intracellular targets. Therapeutic gene sequences are controlled by biosensor-activated control switches to provide the proper amount of gene therapy on a single cell basis. The central idea is to set up gene therapy "nanofactories" inside single living cells. Molecular biosensors linked to these genes control their expression. Gene delivery is started in response to a biosensor detected problem; gene delivery is halted when the cell response indicates that more gene therapy is not needed

New Tetrahedral Global Minimum for the 98-atom Lennard-Jones Cluster

A new atomic cluster structure corresponding to the global minimum of the 98-atom Lennard-Jones cluster has been found using a variant of the basin-hopping global optimization algorithm. The new structure has an unusual tetrahedral symmetry with an energy of -543.665361, which is 0.022404 lower than the previous putative global minimum. The new LJ_98 structure is of particular interest because its tetrahedral symmetry establishes it as one of only three types of exceptions to the general pattern of icosahedral structural motifs for optimal LJ microclusters. Similar to the other exceptions the global minimum is difficult to find because it is at the bottom of a narrow funnel which only becomes thermodynamically most stable at low temperature.Comment: 3 pages, 2 figures, revte

Polytetrahedral Clusters

By studying the structures of clusters bound by a model potential that favours polytetrahedral order, we find a previously unknown series of `magic numbers' (i.e. sizes of special stability) whose polytetrahedral structures are characterized by disclination networks that are analogous to hydrocarbons.Comment: 4 pages, 4 figure

A floristic survey of Yucca Mountain and vicinity, Nye County, Nevada

A survey of the vascular flora of Yucca Mountain and vicinity, Nye County, Nevada, was conducted from March to June 1994. An annotated checklist of recorded taxa was compiled. Voucher plant specimens were collected and accessioned into the Herbarium at the University of Nevada, Las Vegas. Collection data accompanying these specimens were entered into that herbarium`s electronic data base. Combined results from this survey and the works of other investigators reveal the presence of a total of 325 specific and intraspecific taxa within the area, these allocated to 162 genera and 53 families. Owing to drought conditions prevalent throughout the area, the annual floristic component was largely absent during the period of study, and it is likely much under-represented in the tabulation of results. No taxon currently listed as threatened or endangered under the Endangered Species Act was encountered during this study. Several candidate species for listing under this Act were present, and distributional data for these were recorded. No change in the status of these candidate species is recommended as the result of this survey

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies.

Three mitochondria-encoded subunits form the catalytic core of cytochrome c oxidase, the terminal enzyme of the respiratory chain. COX1 and COX2 contain heme and copper redox centers, which are integrated during assembly of the enzyme. Defects in this process lead to an enzyme deficiency and manifest as mitochondrial disorders in humans. Here we demonstrate that COA6 is specifically required for COX2 biogenesis. Absence of COA6 leads to fast turnover of newly synthesized COX2 and a concomitant reduction in cytochrome c oxidase levels. COA6 interacts transiently with the copper-containing catalytic domain of newly synthesized COX2. Interestingly, similar to the copper metallochaperone SCO2, loss of COA6 causes cardiomyopathy in humans. We show that COA6 and SCO2 interact and that corresponding pathogenic mutations in each protein affect complex formation. Our analyses define COA6 as a constituent of the mitochondrial copper relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase deficiency