Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapyinduced leukemia

Glutathione S-transferases (GSTs) detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Functional polymorphisms exist in at least three genes that encode GSTs, including GSTM1, GSTT1, and GSTP1. We hypothesize, therefore, that polymorphisms in genes that encode GSTs alter susceptibility to chemotherapy-induced carcinogenesis, specifically to therapy-related acute myeloid leukemia (t-AML), a devastating complication of long-term cancer survival. Elucidation of genetic determinants may help to identify individuals at increased risk of developing t-AML. To this end, we have examined 89 cases of t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in GSTM1, GSTT1, and GSTP1. Gene deletion of GSTM1 or GSTT1 was not specifically associated with susceptibility to t-AML. Individuals with at least one GSTP1 codon 105 Val allele were significantly over-represented in t-AML cases compared with de novo AML cases [odds ratio (OR), 1.81; 95% confidence interval (CI), 1.11–2.94]. Moreover, relative to de novo AML, the GSTP1 codon 105 Val allele occurred more often among t-AML patients with prior exposure to chemotherapy (OR, 2.66; 95% CI, 1.39–5.09), particularly among those with prior exposure to known GSTP1 substrates (OR, 4.34; 95% CI, 1.43–13.20), and not among those t-AML patients with prior exposure to radiotherapy alone (OR,1.01; 95% CI, 0.50–2.07). These data suggest that inheritance of at least one Val allele at GSTP1 codon 105 confers a significantly increased risk of developing t-AML after cytotoxic chemotherapy, but not after radiotherapy

Organic Ring Oscillators with Sub-200 ns Stage Delay Based on a Solution-Processed p-type Semiconductor Blend

High-frequency ring oscillators with sub-microsecond stage delay fabricated from spin-coated films of a specially formulated small-molecule/host-polymer blend are reported. Contacts and interconnects are patterned by photolithography with plasma etching used for creating vias and removing excess material to reduce parasitic effects. The characteristics of transistors with 4.6 μm channel length scale linearly with channel width over the range 60�2160 μm. Model device parameters extracted using Silvaco's Universal Organic Thin Film Transistor (UOTFT) Model yield values of hole mobility increasing from 1.9 to 2.6 cm2 Vs�1 as gate voltage increased. Simulated and fabricated Vgs = 0 inverters predict that the technology is capable of fabricating 5-stage ring oscillators operating above 100 kHz. Initial designs operated mainly at frequencies in the range 250�300 kHz, due to smaller parasitic gate overlap capacitances and higher supply voltages than assumed in the simulations. A design incorporating graded inverter sizes operates at frequencies above 400 kHz with the best reaching 529 kHz. The corresponding stage delay of 189 ns is the shortest reported to date for a solution-processed p-type semiconductor and compares favorably with similar circuits based on evaporated small molecules. Significant further improvements are identified which could lead to the fabrication of digital circuits that operate at much higher bit rates than previously reported

Gravitational quasinormal modes of AdS black branes in d spacetime dimensions

The AdS/CFT duality has established a mapping between quantities in the bulk AdS black-hole physics and observables in a boundary finite-temperature field theory. Such a relationship appears to be valid for an arbitrary number of spacetime dimensions, extrapolating the original formulations of Maldacena's correspondence. In the same sense properties like the hydrodynamic behavior of AdS black-hole fluctuations have been proved to be universal. We investigate in this work the complete quasinormal spectra of gravitational perturbations of $d$-dimensional plane-symmetric AdS black holes (black branes). Holographically the frequencies of the quasinormal modes correspond to the poles of two-point correlation functions of the field-theory stress-energy tensor. The important issue of the correct boundary condition to be imposed on the gauge-invariant perturbation fields at the AdS boundary is studied and elucidated in a fully $d$-dimensional context. We obtain the dispersion relations of the first few modes in the low-, intermediate- and high-wavenumber regimes. The sound-wave (shear-mode) behavior of scalar (vector)-type low-frequency quasinormal mode is analytically and numerically confirmed. These results are found employing both a power series method and a direct numerical integration scheme.Comment: added references, typos corrected, minor changes, final version for JHE

Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt).

Transmembrane O-methyltransferase (TOMT / LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle

Black-hole quasinormal modes and scalar glueballs in a finite-temperature AdS/QCD model

We use the holographic AdS/QCD soft-wall model to investigate the spectrum of scalar glueballs in a finite temperature plasma. In this model, glueballs are described by a massless scalar field in an AdS_5 black hole with a dilaton soft-wall background. Using AdS/CFT prescriptions, we compute the boundary retarded Green's function. The corresponding thermal spectral function shows quasiparticle peaks at low temperatures. We also compute the quasinormal modes of the scalar field in the soft-wall black hole geometry. The temperature and momentum dependences of these modes are analyzed. The positions and widths of the peaks of the spectral function are related to the frequencies of the quasinormal modes. Our numerical results are found employing the power series method and the computation of Breit-Wigner resonances.Comment: Revision: Results unchanged. More discussions on the model and on the results. References added. 28 pages, 7 figures, 5 table

The dynamic floor of Yellowstone Lake, Wyoming, USA: The last 14 k.y. of hydrothermal explosions, venting, doming, and faulting

Hydrothermal explosions are significant potential hazards in Yellowstone National Park, Wyoming, USA. The northern Yellowstone Lake area hosts the three largest hydrothermal explosion craters known on Earth empowered by the highest heat flow values in Yellowstone and active seismicity and deformation. Geological and geochemical studies of eighteen sublacustrine cores provide the first detailed synthesis of the age, sedimentary facies, and origin of multiple hydrothermal explosion deposits.New tephrochronology and radiocarbon results provide a four-dimensional view of recent geologic activity since recession at ca. 15–14.5 ka of the \u3e1-km-thick Pinedale ice sheet. The sedimentary record in Yellowstone Lake contains multiple hydrothermal explosion deposits ranging in age from ca. 13 ka to ∼1860 CE. Hydrothermal explosions require a sudden drop in pressure resulting in rapid expansion of high-temperature fluids causing fragmentation, ejection, and crater formation; explosions may be initiated by seismicity, faulting, deformation, or rapid lake-level changes. Fallout and transport of ejecta produces distinct facies of subaqueous hydrothermal explosion deposits. Yellowstone hydrothermal systems are characterized by alkaline-Cl and/or vapor-dominated fluids that, respectively, produce alteration dominated by silica-smectite-chlorite or by kaolinite. Alkaline-Cl liquids flash to steam during hydrothermal explosions, producing much more energetic events than simple vapor expansion in vapor-dominated systems. Two enormous explosion events in Yellowstone Lake were triggered quite differently: Elliott’s Crater explosion resulted from a major seismic event (8 ka) that ruptured an impervious hydrothermal dome, whereas the Mary Bay explosion (13 ka) was triggered by a sudden drop in lake level stimulated by a seismic event, tsunami, and outlet channel erosion

Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

Pairing in two-dimensional boson-fermion mixtures

The possibilities of pairing in two-dimensional boson-fermion mixtures are carefully analyzed. It is shown that the boson-induced attraction between two identical fermions dominates the p-wave pairing at low density. For a given fermion density, the pairing gap becomes maximal at a certain optimal boson concentration. The conditions for observing pairing in current experiments are discussedComment: 10 pages, 5 figs, revtex

A CsI(Tl) Scintillating Crystal Detector for the Studies of Low Energy Neutrino Interactions

Scintillating crystal detector may offer some potential advantages in the low-energy, low-background experiments. A 500 kg CsI(Tl) detector to be placed near the core of Nuclear Power Station II in Taiwan is being constructed for the studies of electron-neutrino scatterings and other keV-MeV range neutrino interactions. The motivations of this detector approach, the physics to be addressed, the basic experimental design, and the characteristic performance of prototype modules are described. The expected background channels and their experimental handles are discussed.Comment: 34 pages, 11 figures, submitted to Nucl. Instrum. Method