The balance of Polo-like kinase 1 in tumorigenesis

Polo-like kinase 1 (Plk1) belongs to a family of conserved serine/threonine kinases with a polo-box domain, which have similar but non-overlapping functions in the cell cycle progression. Plk1 plays a key role to ensure the normal mitosis. Interestingly, overexpression of Plk1 is associated with tumor development and could serve as a prognostic marker for many cancers. Due to Plk1 overexpression, several Plk1 inhibitors have been developed and tested for the cancer treatment. However, in a recent study, it has been suggested that down-regulation of Plk1 could also induce aneuploidy and tumor formation in vivo. Therefore, a normal level of Plk1 is important for mitosis. And caution should be taken when Plk1 inhibitors are used in the clinical trial and their side effects including tumorigenesis should be carefully evaluated

The Quasielastic 3He(e,e'p)d Reaction at Q^2 = 1.5 GeV^2 for Recoil Momenta up to 1 GeV/c

We have studied the quasielastic 3He(e,e'p)d reaction in perpendicular coplanar kinematics, with the energy and momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e'p)d cross section was measured for missing momenta up to 1000 MeV/c, while the A_TL asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the measured cross section is described well by calculations that use a variational ground-state wave function of the 3He nucleus derived from a potential that includes three-body forces. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A_TL asymmetry displays characteristic features of broken factorization, and is described reasonably well by available models.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, v3: changed conten

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q = 1502 MeV/c and omega = 840 MeV, respectively, for missing momenta p_m up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.Comment: 5 pages, 3 figures, updated to reflect published paper: minor text changes from previous version along with updated and added reference

Towards the development of a simulator for investigating the impact of people management practices on retail performance

               \ud           \ud 

The reaction dynamics of the 16O(e,e'p) cross section at high missing energies

We measured the cross section and response functions (R_L, R_T, and R_LT) for the 16O(e,e'p) reaction in quasielastic kinematics for missing energies 25 <= E_miss <= 120 MeV at various missing momenta P_miss <= 340 MeV/c. For 25 < E_miss < 50 MeV and P_miss \approx 60 MeV/c, the reaction is dominated by single-nucleon knockout from the 1s1/2-state. At larger P_miss, the single-particle aspects are increasingly masked by more complicated processes. For E_miss > 60 MeV and P_miss > 200 MeV/c, the cross section is relatively constant. Calculations which include contributions from pion exchange currents, isobar currents and short-range correlations account for the shape and the transversity but only for half of the magnitude of the measured cross section.Comment: 6 pages, 4 figures, submitted to Phys Rev Lett, formatting error fixe

Measurement of the Neutron Spin Structure Function g1ng_1^n with a Polarized ^3He Target

Results are reported from the HERMES experiment at HERA on a measurement of the neutron spin structure function $g_1^n(x,Q^2)$ in deep inelastic scattering using 27.5 GeV longitudinally polarized positrons incident on a polarized $^3$He internal gas target. The data cover the kinematic range $0.023<x<0.6$ and $1 (GeV/c)^2 < Q^2 <15 (GeV/c)^2$. The integral $\int_{0.023}^{0.6} g_1^n(x) dx$ evaluated at a fixed $Q^2$ of $2.5 (GeV/c)^2$ is $-0.034\pm 0.013(stat.)\pm 0.005(syst.)$. Assuming Regge behavior at low $x$, the first moment $\Gamma_1^n=\int_0^1 g_1^n(x) dx$ is $-0.037\pm 0.013(stat.)\pm 0.005(syst.)\pm 0.006(extrapol.)$.Comment: 4 pages TEX, text available at http://www.krl.caltech.edu/preprints/OAP.htm

Endocrine therapy in epithelial ovarian cancer

INTRODUCTION: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer

The Effective Temperatures of Hot Stars II. The Early-O Types

We derive the stellar parameters of a sample of Galactic early-O type stars by analysing their UV and Far-UV spectra from FUSE (905-1187A), IUE, HST-STIS and ORFEUS (1200-2000A). The data have been modeled with spherical, hydrodynamic, line-blanketed, non-LTE synthetic spectra computed with the WM-basic code. We obtain effective temperatures ranging from Teff = 41,000 K to 39,000 K for the O3-O4 dwarf stars, and Teff = 37,500 K for the only supergiant of the sample (O4 If+). Our values are lower than those from previous empirical calibrations for early-O types by up to 20%. The derived luminosities of the dwarf stars are also lower by 6 to 12%; however, the luminosity of the supergiant is in agreement with previous calibrations within the error bars. Our results extend the trend found for later-O types in a previous work by Bianchi & Garcia.Comment: Accepted for publication in The Astrophysical Journal. 38 pages (including 9 figures and 4 tables

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis