Interstitial Electronic Localization

We investigate the ground-state properties of a collection of \textit{N} non-interacting electrons in a macroscopic volume $\Omega$ also containing a crystalline array of \textit{N} spheres of radius $r_c$ each taken as largely impenetrable to electrons and with proximity of neighboring excluding regions playing a key physical role. The sole parameter of this quantum system is the ratio $r_c/r_s$, where $r_s$ is the Wigner- Seitz radius. Two lattices (FCC and BCC) are selected to illustrate the behavior of the system as a function of $r_c/r_s$. As this ratio increases valence electrons localize in the interstitial regions and the relative band-width $\epsilon_F/\epsilon_F^0$ is found to decrease monotonically for both. The system is motivated by the behavior of the alkali metals at significant compression. It accounts for band narrowing, leads to electronic densities with interstitially centered maxima, and can be taken as a model which clearly may be improved upon by perturbation and other methods.Comment: 11 pages, 5 figure

Splicing mutation analysis reveals previously unrecognized pathways in lymph node-invasive breast cancer.

Somatic mutations reported in large-scale breast cancer (BC) sequencing studies primarily consist of protein coding mutations. mRNA splicing mutation analyses have been limited in scope, despite their prevalence in Mendelian genetic disorders. We predicted splicing mutations in 442 BC tumour and matched normal exomes from The Cancer Genome Atlas Consortium (TCGA). These splicing defects were validated by abnormal expression changes in these tumours. Of the 5,206 putative mutations identified, exon skipping, leaky or cryptic splicing was confirmed for 988 variants. Pathway enrichment analysis of the mutated genes revealed mutations in 9 NCAM1-related pathways, which were significantly increased in samples with evidence of lymph node metastasis, but not in lymph node-negative tumours. We suggest that comprehensive reporting of DNA sequencing data should include non-trivial splicing analyses to avoid missing clinically-significant deleterious splicing mutations, which may reveal novel mutated pathways present in genetic disorders

IQ and Blood Lead from 2 to 7 Years of Age: Are the Effects in Older Children the Residual of High Blood Lead Concentrations in 2-Year-Olds?

Increases in peak blood lead concentrations, which occur at 18–30 months of age in the United States, are thought to result in lower IQ scores at 4–6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20–44 μg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed

Prevalence and co-infection of Toxoplasma gondii and Neospora caninum in Apodemus sylvaticus in an area relatively free of cats

The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%–47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%–67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses frompregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%–6·66%); M. domesticus: 3·08% (95% CI: 0·11%–6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems

Urine Biomarkers of Risk in the Molecular Etiology of Breast Cancer

Endogenous estrogens can be bio-activated to endogenous carcinogens via formation of estrogen quinones. Estrogen-3,4-quinones react with DNA to form mutagenic depurinating estrogen-DNA adducts. The carcinogenicity of endogenous estrogens is related to unbalanced estrogen metabolism leading to excess estrogen quinones and formation of depurinating DNA adducts. The present studies were initiated to confirm that relatively high levels of depurinating estrogen-DNA adducts are present in women at high risk for breast cancer or diagnosed with the disease. These adducts may be biomarkers for early detection of breast cancer risk. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry to analyze urine samples from 40 healthy control women, 40 high-risk women and 40 women with newly diagnosed breast cancer. Estrogen metabolism was shifted from protective methoxylation and conjugation pathways in healthy control women towards activating pathways leading to formation of depurinating DNA adducts in women at high risk or with breast cancer. These results support the hypothesis that breast cancer is initiated by mutations derived from depurination of estrogen-DNA adducts. Therefore, relative levels of depurinating estrogen-DNA adducts could become biomarkers for early detection of breast cancer risk and aid in determining preventive strategies

Optimal statistic for detecting gravitational wave signals from binary inspirals with LISA

A binary compact object early in its inspiral phase will be picked up by its nearly monochromatic gravitational radiation by LISA. But even this innocuous appearing candidate poses interesting detection challenges. The data that will be scanned for such sources will be a set of three functions of LISA's twelve data streams obtained through time-delay interferometry, which is necessary to cancel the noise contributions from laser-frequency fluctuations and optical-bench motions to these data streams. We call these three functions pseudo-detectors. The sensitivity of any pseudo-detector to a given sky position is a function of LISA's orbital position. Moreover, at a given point in LISA's orbit, each pseudo-detector has a different sensitivity to the same sky position. In this work, we obtain the optimal statistic for detecting gravitational wave signals, such as from compact binaries early in their inspiral stage, in LISA data. We also present how the sensitivity of LISA, defined by this optimal statistic, varies as a function of sky position and LISA's orbital location. Finally, we show how a real-time search for inspiral signals can be implemented on the LISA data by constructing a bank of templates in the sky positions.Comment: 22 pages, 15 eps figures, Latex, uses iopart style/class files. Based on talk given at the 8th Gravitational Wave Data Analysis Workshop, Milwaukee, USA, December 17-20, 2003. Accepted for publication in Class. Quant. Gra

Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning.

Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n = 31 genes) or gemcitabine (n = 18) were analyzed. A multi-factorial, principal component analysis (MFA) indicated expression was the strongest indicator of sensitivity for paclitaxel, and copy number and expression were informative for gemcitabine. The factors were combined using support vector machines (SVM). Expression of 15 genes (ABCC10, BCL2, BCL2L1, BIRC5, BMF, FGF2, FN1, MAP4, MAPT, NFKB2, SLCO1B3, TLR6, TMEM243, TWIST1, and CSAG2) predicted cell line sensitivity to paclitaxel with 82% accuracy. Copy number profiles of 3 genes (ABCC10, NT5C, TYMS) together with expression of 7 genes (ABCB1, ABCC10, CMPK1, DCTD, NME1, RRM1, RRM2B), predicted gemcitabine response with 85% accuracy. Expression and copy number studies of two independent sets of patients with known responses were then analyzed with these models. These included tumor blocks from 21 patients that were treated with both paclitaxel and gemcitabine, and 319 patients on paclitaxel and anthracycline therapy. A new paclitaxel SVM was derived from an 11-gene subset since data for 4 of the original genes was unavailable. The accuracy of this SVM was similar in cell lines and tumor blocks (70-71%). The gemcitabine SVM exhibited 62% prediction accuracy for the tumor blocks due to the presence of samples with poor nucleic acid integrity. Nevertheless, the paclitaxel SVM predicted sensitivity in 84% of patients with no or minimal residual disease

Global priorities for reduction of cetacean bycatch. Scientific Committee document SC/56/BC2, International Whaling Commission, July 2004, Sorrento, Italy

Progress at reducing the scale and conservation impact of cetacean bycatch has been slow, sporadic and limited to a few specific fisheries or circumstances. As a result bycatch remains perhaps the greatest immediate and well-documented threat to cetacean populations globally. Having recognized the critical importance of reducing bycatch levels to prevent the depletion, and in some cases extinction, of cetacean populations, World Wildlife Fund-US launched a global bycatch initiative early in 2002. Their strategy calls on governmental and non-governmental bodies to move quickly, cooperatively and thoughtfully to achieve bycatch reduction. As a supportive step a working group was established to identify priorities and provide guidance on how financial and other resources should be invested to address bycatch issues. The group will conduct a global survey of cetacean bycatch problems, classify and rank those problems according to an agreed set of criteria and provide a clear rationale for each problem assigned high priority for funding and intervention. The working group will emphasise: (1) situations that are especially critical (e.g. a species’ or population’s survival is immediately at risk from bycatch) and are not being addressed adequately; (2) circumstances where rapid progress could be made with a modest investment of resources; (3) situations in which bycatch is believed to pose a threat to cetaceans but a quantitative assessment is needed to verify the risk; and (4) fisheries in which a currently available solution (technical, socioeconomic or a combination) appears feasible. The report of the working group will be directed at governmental decision makers, aid agencies, nongovernmental organizations and related audiences