Genomic and proteomic profiling of responses to toxic metals in human lung cells.

Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3 M Cd(II) (as cadmium chloride), 10 M Cr(VI) (as sodium dichromate), 3 g/cm2 Ni(II) (as nickel subsulfide), 5 M or 50 M As(III) (as sodium arsenite), or 1 M MMC for 4 hr. Expression changes were verified at the protein level for several genes. Only a small subset of genes was differentially expressed in response to each agent: Cd, Cr, Ni, As (5 M), As (50 M), and MMC each differentially altered the expression of 25, 44, 31, 110, 65, and 16 individual genes, respectively. Few genes were commonly expressed among the various treatments. Only one gene was altered in response to all four metals (hsp90), and no gene overlapped among all five treatments. We also compared low-dose (5 M, noncytotoxic) and high-dose (50 M, cytotoxic) arsenic treatments, which surprisingly, affected expression of almost completely nonoverlapping subsets of genes, suggesting a threshold switch from a survival-based biological response at low doses to a death response at high doses

Dirt Road Corrugations

WE CONSIDER FACTORS INFLUENCING the build-up of corrugations on dirt roads and the reactions of vehicles to them. We suggest that corrugations are (at least in part) a consequence of a natural tangential oscillation of the tread surface of the car lure that occurs when the vehicle is being driven or braked. Secondly, we suggest that the unpleasant vibration experienced by a vehicle passing over a corrugated road is the result of a beat produced by the difference of the frequency of oscillation of its own tyres and the frequency of the stimulation received by the vehicle due to passage over a corrugated road. We consider how this is affected by actions that the driver can take and conclude with some recommendations and observations of related effects

Perturbation expansions for a class of singular potentials

Harrell's modified perturbation theory [Ann. Phys. 105, 379-406 (1977)] is applied and extended to obtain non-power perturbation expansions for a class of singular Hamiltonians H = -D^2 + x^2 + A/x^2 + lambda/x^alpha, (A\geq 0, alpha > 2), known as generalized spiked harmonic oscillators. The perturbation expansions developed here are valid for small values of the coupling lambda > 0, and they extend the results which Harrell obtained for the spiked harmonic oscillator A = 0. Formulas for the the excited-states are also developed.Comment: 23 page

Modularity map of the network of human cell differentiation

Cell differentiation in multicellular organisms is a complex process whose mechanism can be understood by a reductionist approach, in which the individual processes that control the generation of different cell types are identified. Alternatively, a large scale approach in search of different organizational features of the growth stages promises to reveal its modular global structure with the goal of discovering previously unknown relations between cell types. Here we sort and analyze a large set of scattered data to construct the network of human cell differentiation (NHCD) based on cell types (nodes) and differentiation steps (links) from the fertilized egg to a crying baby. We discover a dynamical law of critical branching, which reveals a fractal regularity in the modular organization of the network, and allows us to observe the network at different scales. The emerging picture clearly identifies clusters of cell types following a hierarchical organization, ranging from sub-modules to super-modules of specialized tissues and organs on varying scales. This discovery will allow one to treat the development of a particular cell function in the context of the complex network of human development as a whole. Our results point to an integrated large-scale view of the network of cell types systematically revealing ties between previously unrelated domains in organ functions.Comment: 32 pages, 7 figure

Evaluation of mode equivalence of the MSKCC Bowel Function Instrument, LASA Quality of Life, and Subjective Significance Questionnaire items administered by Web, interactive voice response system (IVRS), and paper

To assess the equivalence of patient-reported outcome (PRO) survey responses across Web, interactive voice response system (IVRS), and paper modes of administration

Waist circumference predicts clustering of cardiovascular risk factors in older South Africans

Objecti~'eand design. A cross-sectional analytical study to determine the cardiovascular risk factor profile of older residents of fishing villages on the West Coast of South Africa, and to det.ermine which anthropometric measures are associated with risk factors. Subjects. A convenient community-based sample of 152 subjects of mixed ancestry aged 55 years and over was recruited door-to-door using an address list of ageeligible subjects provided by the local public health care clinics. Methods. Cardiovascular relationships were im'estigated between: (i) number of risk factors (hypertension, hypercholesterolaemia, diabetes) and body mass index (8MI), waist-to-hip ratio (WHR), and waist circumference; and (ii) continuous cardiovascular risk factor variables and physical activity, smoking, dietary intake, and 24-hour urinary sodium and potassium concentrationS. Results. The prevalence of hypertension (~ 160/95 mmHg) was 74.3% (95% CI: 67.2 - 81.4%). Neither 24- hour urinary sodium nor potassium concentrations was associated with blood pressure (BP). Past, but not present, moderate-intensity physical activity, particularly that associated with occupation, was negatively associated with systolic BP (r = -0.24, P < 0.05). The prevalence of diabetes and hypercholesterolaemia (serum cholesterol ~ 6.5 mmolll) was 24.6% (95% CI: 17.2 - 32%) and 40% (95% CI: 31.8 - 48.2%),respectively. The percentage of subjects with 0, 1, or 2 or more cardiovascular risk factors was 13.4%,44.1% and 42.5%, respectively. Subjects with a waist circumference ~ 92 em had a significantly higher number of cardiovascular risk factors than those with a waist circumference < 92 cm (Xl =9.29, P < 0.01), and this association remained significant even after controlling for age, sex and smoking (P < 0.05). Neither 8MI tertiles according to sex, nor a 8MI cut-point ~ 30, was significantly associated with a clustering of risk factors. COllclusioll. In a sample of older South Africans of ntlxed ancestry at high risk of cardiovascular disease, waist circumference ~ 92 em predicts clustering of risk factors, Independentl)' of BMI. This simple, populationspecific reference value may provide a useful screening tool to identify at-risk Individuals for targeted prevention for coronary heart disease and associated metabolic disorders

Generation of many-particle entanglement in an ion trap by adiabatic ground-state transitions

We discuss the creation of many-particle entanglement in an ion trap where all ions are simultaneously coupled to bichromatic laser fields. It is shown that in a time-averaged, coarse-grained picture the system can be mapped onto a spin ensemble with controllable collective interactions. An adiabatic change of laser parameters allows a transfer from separable to entangled eigenstates of the many-particle Hamiltonian. Of particular interest is a transition in the ground state which in some cases corresponds to a quantum phase transition. The influence of decoherence mechanisms can be substantially reduced if at all times a sufficiently large energy gap between the ground state and the first excited state is maintained.Comment: 4 pages, 3 figure

Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.

The biological processes controlling human growth are diverse, complex and poorly understood. Genetic factors are important and human height has been shown to be a highly polygenic trait to which common and rare genetic variation contributes. Weaver syndrome is a human overgrowth condition characterised by tall stature, dysmorphic facial features, learning disability and variable additional features. We performed exome sequencing in four individuals with Weaver syndrome, identifying a mutation in the histone methyltransferase, EZH2, in each case. Sequencing of EZH2 in additional individuals with overgrowth identified a further 15 mutations. The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies. Our data establish EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth