An efficient basis set representation for calculating electrons in molecules

The method of McCurdy, Baertschy, and Rescigno, J. Phys. B, 37, R137 (2004) is generalized to obtain a straightforward, surprisingly accurate, and scalable numerical representation for calculating the electronic wave functions of molecules. It uses a basis set of product sinc functions arrayed on a Cartesian grid, and yields 1 kcal/mol precision for valence transition energies with a grid resolution of approximately 0.1 bohr. The Coulomb matrix elements are replaced with matrix elements obtained from the kinetic energy operator. A resolution-of-the-identity approximation renders the primitive one- and two-electron matrix elements diagonal; in other words, the Coulomb operator is local with respect to the grid indices. The calculation of contracted two-electron matrix elements among orbitals requires only O(N log(N)) multiplication operations, not O(N^4), where N is the number of basis functions; N = n^3 on cubic grids. The representation not only is numerically expedient, but also produces energies and properties superior to those calculated variationally. Absolute energies, absorption cross sections, transition energies, and ionization potentials are reported for one- (He^+, H_2^+ ), two- (H_2, He), ten- (CH_4) and 56-electron (C_8H_8) systems.Comment: Submitted to JC

Effect of Meal Size and Test Duration on Gastric Emptying and Gastric Myoelectrical Activity as Determined with Simultaneous [13C]Octanoate Breath Test and Electrogastrography in Normal Subjects Using a Muffin Meal

Our purpose was to determine the effect of meal size on gastric emptying (GE) as measured by octanoate breath test (OBT), to determine the effect of the duration of breath collections on assessment of GE by OBT, and to determine the effect of meal size on gastric myoelectrical activity as measured by electrogastrography (EGG). Fourteen normal subjects underwent two modified [ 13 C]OBTs using muffin meals of 250 or 350 kcal mixed with 100 mg [ 13 C]sodium octanoate. T 1/2 for GE was determined for both the entire postprandial 6-hr breath collection and a truncated initial 4-hr data set. EGG was recorded for 30 min prior to the muffin meal and 4 hr postprandially. Using the 6-hr breath collection data, the T 1/2 was 177 ± 7 (mean ± sem) for the 350-kcal meal compared to 153 ± 7 min ( P < 0.01) for the 250-kcal meal. Using the 4-hr data, the T 1/2 for the 350-kcal meal was 244 ± 32 min compared to 165 ± 12 min ( P < 0.05) for the 250-kcal meal. The ratio of postprandial to fasting EGG power of the dominant frequency for the 350-kcal meal (1.9 ± 0.4) was higher than that for the 250-kcal meal (1.3 ± 0.6). T 1/2 for the 350-kcal meal using 4- and 6-hr data was significantly correlated with the 4-hr power ratio ( r = 0.68 and 0.67; P < 0.05, respectively), but poorly correlated for the 250-kcal meal. In conclusions, GE and EGG are affected by meal size. Using the muffin-based [ 13 C]OBT, T 1/2 for the 350-kcal meal was significantly longer than for a 250-kcal meal. Longer T 1/2 values were obtained with shorter breath sampling durations. The postprandial to fasting power ratio for the 350-kcal meal was greater than that for the 250-kcal meal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44429/1/10620_2004_Article_364228.pd

Metabolic and Immune Activation Effects of Treatment Interruption in Chronic HIV-1 Infection: Implications for Cardiovascular Risk

Background: Concern about costs and antiretroviral therapy (ART)-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI). Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk. Methodology: ACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with &lt;200 HIV RNA copies/mL and CD4 cell count ≥500 cells/µL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2) (cycle = 4.5 million IU sc BID x 5 days every 8 weeks). After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/µL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels. Principal Findings: By week 8 of TI, levels of total cholesterol (TC) (median (Q1, Q3) (−0.73 (−1.19, −0.18) mmol/L, p&lt;0.0001), LDL, HDL cholesterol (−0.36(−0.73,−0.03)mmol/L, p = 0.0007 and −0.05(−0.26,0.03), p = 0.0033, respectively) and triglycerides decreased (−0.40 (−0.84, 0.07) mmol/L, p = 0.005). However the TC/HDL ratio remained unchanged (−0.09 (−1.2, 0.5), p = 0.2). Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively). After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43), p&lt;0.0001) and soluble TNFR2 (1089 ng/L (−189, 1655), p = 0.0008) coinciding with the rebound of HIV viremia. Conclusions: Our data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD) risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic inflammatory responses associated with recrudescent HIV viremia may provide a more cogent explanation for the increased cardiovascular risk associated with treatment interruption and HIV infection. Trial Registration: ClinicalTrials.gov NCT0001570

Time Out of Joint: Hamlet and the Pure Form of Time

The aim of this paper is to explore why Deleuze takes up Hamlet’s claim that ‘time is out of joint’. In the first part of this paper, I explore this claim by looking at how Deleuze relates it to Plato’s Timaeus and its conception of the relationship between movement and time. Once we have seen how time functions when it is ‘in joint’, I explore what it would mean for time to no longer be understood in terms of an underlying rational structure. The claim can be understood as about a relationship between time and action. In the second part of this paper, I want to relate this new understanding of time to Hamlet itself, in order to see how temporality operates within the play. I will conclude by relating these two different conceptions of time out of joint to one another through Nietzsche’s Eternal Return

DIAPH3 Governs the Cellular Transition to the Amoeboid Tumour Phenotype

Therapies for most malignancies are generally ineffective once metastasis occurs. While tumour cells migrate through tissues using diverse strategies, the signalling networks controlling such behaviours in human tumours are poorly understood. Here we define a role for the Diaphanous-related formin-3 (DIAPH3) as a non-canonical regulator of metastasis that restrains conversion to amoeboid cell behaviour in multiple cancer types. The DIAPH3 locus is close to RB1, within a narrow consensus region of deletion on chromosome 13q in prostate, breast and hepatocellular carcinomas. DIAPH3 silencing in human carcinoma cells destabilized microtubules and induced defective endocytic trafficking, endosomal accumulation of EGFR, and hyperactivation of EGFR/MEK/ERK signalling. Silencing also evoked amoeboid properties, increased invasion and promoted metastasis in mice. In human tumours, DIAPH3 down-regulation was associated with aggressive or metastatic disease. DIAPH3-silenced cells were sensitive to MEK inhibition, but showed reduced sensitivity to EGFR inhibition. These findings have implications for understanding mechanisms of metastasis, and suggest that identifying patients with chromosomal deletions at DIAPH3 may have prognostic value

Mapping of the SZ effect in the cluster Cl 0016+16 with the Ryle Telescope

We have mapped the high-redshift (z = 0.546) cluster Cl 0016+16 with the Ryle Telescope at 15 GHz. The Sunyaev-Zel'dovich decrement is clearly detected, and resolved. We combine our data with an X-ray image from ROSAT, and a gas temperature from ASCA to estimate the Hubble Constant H0 = 69 +21/-16 km/s/Mpc for an Omega_M=1.0 cosmology or H0 = 84 +25/-19 km/s/Mpc for Omega_M=0.3 and Omega_Lambda=0.7.Comment: 10 pages, 2 tables, 6 figures Submitted to MNRA