Lattice QCD Matrix Elements for the B_{s}

Predicting the B_{s}^{0}-B[over ¯]_{s}^{0} width difference ΔΓ_{s} relies on the heavy quark expansion and on hadronic matrix elements of ΔB=2 operators. We present the first lattice QCD results for matrix elements of the dimension-7 operators R_{2,3} and linear combinations R[over ˜]_{2,3} using nonrelativistic QCD for the bottom quark and a highly improved staggered quark (HISQ) action for the strange quark. Computations use MILC Collaboration ensembles of gauge field configurations with 2+1+1 flavors of sea quarks with the HISQ discretization, including lattices with physically light up or down quark masses. We discuss features unique to calculating matrix elements of these operators and analyze uncertainties from series truncation, discretization, and quark mass dependence. Finally we report the first standard model determination of ΔΓ_{s} using lattice QCD results for all hadronic matrix elements through O(1/m_{b}). The main result of our calculations yields the 1/m_{b} contribution ΔΓ_{1/m_{b}}=-0.022(10) ps^{-1}. Adding this to the leading order contribution, the standard model prediction is ΔΓ_{s}=0.092(14) ps^{-1}.

Strong-Isospin-Breaking Correction to the Muon Anomalous Magnetic Moment from Lattice QCD at the Physical Point.

All lattice-QCD calculations of the hadronic-vacuum-polarization contribution to the muon's anomalous magnetic moment to date have been performed with degenerate up- and down-quark masses. Here we calculate directly the strong-isospin-breaking correction to a_{µ}^{HVP} for the first time with physical values of m_{u} and m_{d} and dynamical u, d, s, and c quarks, thereby removing this important source of systematic uncertainty. We obtain a relative shift to be applied to lattice-QCD results obtained with degenerate light-quark masses of δa_{µ}^{HVP,m_{u}≠m_{d}}=+1.5(7)%, in agreement with estimates from phenomenology.

-1 V bias 67 GHz bandwidth Si-contacted germanium waveguide p-i-n photodetector for optical links at 56 Gbps and beyond.

We demonstrate a 67 GHz bandwidth silicon-contacted germanium waveguide p-i-n photodetector operating at -1 V with 6.8 fF capacitance. The dark current is below 4 nA. The responsivity is 0.74 A/W at 1550 nm and 0.93 A/W at 1310 nm wavelength. 56 Gbps on-off-keying data reception is demonstrated with clear open eye diagrams in both the C-band and O-band.

High sensitivity 10Gb/s Si photonic receiver based on a low-voltage waveguide-coupled Ge avalanche photodetector.

We demonstrate low-voltage germanium waveguide avalanche photodetectors (APDs) with a gain × bandwidth product above 100GHz. A photonic receiver based on such a Ge APD, including a 0.13µm SiGe BiCMOS low-noise trans-impedance amplifier and a limiting amplifier, is realized. A 5.8dB sensitivity improvement is demonstrated at -5.9V bias at an avalanche gain of 6 through bit error ratio measurements. The absolute sensitivity in avalanche mode is -23.4dBm and -24.4dBm at a bit error ratio of 1 × 10(-12) and 1 × 10(-9) respectively.

Narrow-linewidth short-pulse III-V-on-silicon mode-locked lasers based on a linear and ring cavity geometry.

Picosecond-pulse III-V-on-silicon mode-locked lasers based on linear and ring extended cavity geometries are presented. In passive mode-locked operation a 12 kHz -3dB linewidth of the fundamental RF tone at 4.7 GHz is obtained for the linear cavity geometry and 16 kHz for the ring cavity geometry. Stabilization of the repetition rate of these devices using hybrid mode-locking is also demonstrated.

III-V-on-silicon anti-colliding pulse-type mode-locked laser.

An anti-colliding pulse-type III-V-on-silicon passively mode-locked laser is presented for the first time based on a III-V-on-silicon distributed Bragg reflector as outcoupling mirror implemented partially underneath the III-V saturable absorber. Passive mode-locking at 4.83 GHz repetition rate generating 3 ps pulses is demonstrated. The generated fundamental RF tone shows a 1.7 kHz 3 dB linewidth. Over 9 mW waveguide coupled output power is demonstrated.

Demonstration of Silicon-on-insulator mid-infrared spectrometers operating at 3.8 µm.

The design and characterization of silicon-on-insulator mid-infrared spectrometers operating at 3.8 µm is reported. The devices are fabricated on 200 mm SOI wafers in a CMOS pilot line. Both arrayed waveguide grating structures and planar concave grating structures were designed and tested. Low insertion loss (1.5-2.5 dB) and good crosstalk characteristics (15-20 dB) are demonstrated, together with waveguide propagation losses in the range of 3 to 6 dB/cm.

Standard model predictions for B→Kℓ(+)ℓ- with form factors from lattice QCD.

We calculate, for the first time using unquenched lattice QCD form factors, the standard model differential branching fractions dB/dq2(B→Kℓ(+)ℓ(-)) for ℓ=e, µ, τ and compare with experimental measurements by Belle, BABAR, CDF, and LHCb. We report on B(B→Kℓ(+)ℓ(-)) in q2 bins used by experiment and predict B(B→Kτ(+)τ(-))=(1.41±0.15)×10(-7). We also calculate the ratio of branching fractions R(e)(µ)=1.00029(69) and predict R(ℓ)(τ)=1.176(40), for ℓ=e, µ. Finally, we calculate the "flat term" in the angular distribution of the differential decay rate F(H)(e,µ,τ) in experimentally motivated q2 bins.

High-efficiency fiber-to-chip grating couplers realized using an advanced CMOS-compatible silicon-on-insulator platform.

A new generation of Silicon-on-Insulator fiber-to-chip grating couplers which use a silicon overlay to enhance the directionality and thereby the coupling efficiency is presented. Devices are realized on a 200 mm wafer in a CMOS pilot line. The fabricated fiber couplers show a coupling efficiency of -1.6 dB and a 3 dB bandwidth of 80 nm.

Precise charm to strange mass ratio and light quark masses from full lattice QCD.

By using a single formalism to handle charm, strange, and light valence quarks in full lattice QCD for the first time, we are able to determine ratios of quark masses to 1%. For m(c)/m(s) we obtain 11.85(16), an order of magnitude more precise than the current PDG average. Combined with 1% determinations of the charm quark mass now possible this gives m(s)(2 GeV)=92.4(1.5) MeV. The MILC result for m(s)/m(l)=27.2(3) yields m(l)(2 GeV)=3.40(7) MeV for the average of u and d quark masses.

Prediction of the B{c}{*} mass in full lattice QCD.

By using the highly improved staggered quark formalism to handle charm, strange, and light valence quarks in full lattice QCD, and NRQCD to handle bottom valence quarks, we are able to determine accurately ratios of the B meson vector-pseudoscalar mass splittings, in particular, [m(B{c}{*})-m(B{c})]/[m(B{s}{*})-m(B{s})]. We find this ratio to be 1.15(15), showing the "light" quark mass dependence of this splitting to be very small. Hence we predict m(B{c}{*})=6.330(7)(2)(6) GeV, where the first two errors are from the lattice calculation and the third from existing experiment. This is the most accurate prediction of a gold-plated hadron mass from lattice QCD to date.

Epidermal growth factor-induced neuroendocrine differentiation and apoptotic resistance of androgen-independent human prostate cancer cells.

Neuroendocrine differentiation (NED) has been implicated in prostate cancer progression and hormone-therapy failure. Neuroendocrine cells are non-proliferating and escape apoptotic cell death, although their origin and the causes of their apoptotic resistance have as yet been poorly elucidated. This study demonstrates a new mechanism involved in controlling NED. We report that epidermal growth factor (5-50 ng/ml) promotes neuroendocrine-like differentiation of androgen-independent DU145 prostate cancer cells. This differentiation is associated with an increase in the expression of Neuron Specific Enolase (NSE) and a reduction in cell proliferation and is blocked by inhibiting tyrosine kinase activity with genistein and with compound 56 (C56). An increase in the cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100 microM), does not promote NED by itself, but does increase the effect of EGF on NED. In addition, EGF-induced NED protects cells from apoptosis induced with thapsigargin (1 microM) by reducing the thapsigargin-induced cytosolic calcium overload. In order to describe how EGF-induced NED protects cells against thapigargin-induced calcium overload we investigated the spatiotemporal calcium signalling linked to apoptosis. By using thapsigargin in various conditions on DU145 cells and using micro-fluorimetric calcium measurements, we show that depletion of intracellular calcium store induces apoptosis and that the amplitude and duration of the capacitive calcium entry are two apoptosis-modulating parameters. We show that protection against thapsigargin-induced apoptosis conferred by NED is achieved by reducing the amount and the speed of calcium that can be released from calcium pools, as well as modulating the amplitude of the subsequent calcium entry.

Resistance to 9-beta-D-arabinofuranosyladenine in murine tumor cells.

Two lines of the 6C3HED (Gardner lymphosarcoma), 6C3HED-LeP and 6C3HED-ADL, were studied. The former is exquisitely sensitive to 9-beta-D-arabinofuranosyladenine (ara-A) and the latter is resistant. Cytological examinations and strain specificity tests indicated that they are both 6C3HED. DNA synthesis in the sensitive line was found to be more sensitive to ara-A in whole-cell incubations than it was in the resistant line. In cell-free extracts, the DNA synthesis of the sensitive line showed greater inhibition by 9-beta-D-arabinofuranosyladenine 5'-triphosphate. Lower ability to form 9-beta-D-arabinofuranosyladenine 5'-triphosphate or to allow access to the intracellular space was eliminated as an explanation for the resistance. Cells from an ara-A-resistant human leukemia were tested, and the DNA synthesis of the cells, in either whole cells or cell-free extract, was unaffected by ara-A or 9-beta-D-arabinofuranosyladenine 5'-triphosphate, respectively. This suggests that resistance has emerged by reason of change in the DNA polymerase(s) and that the finding may be important in the clinical use of ara-A.

Inhibition of DNA chain growth by alpha-2'-deoxythioguanosine.

Mecca lymphosarcoma cells were incubated with (35-S)-alpha-2'-deoxythioguanosine for 8 hr and DNA was analyzed in alkaline sucrose gradients. 35-S radioactivity was found exclusively in a low-molecular-weight fraction. Pulse-chase experiments showed that 35-S-containing DNA fragments formed during the pulse were not incorporated into high-molecular-weight DNA following the chase. These results, together with the previous observation that (35-S)-alpha-2'-deoxythioguanosine was found predominantly in the terminal nucleoside position of DNA chains, suggested that alpha-2'deoxythioguanosine, once incorporated, terminates chain elongation.

Growth characteristics and drug responses of a murine lung carcinoma in vitro and in vivo.

Cells obtained from the Nettesheim lung carcinoma of DBA/2 mice, a heterogenous population grown s.c., were cultured as monolayers. These cells were serially subcultured and cloned twice, and a clone was selected for further study. This clone produced malignant tumors at the injected site when injected s.c. into male DBA/2 or C57BL/L x DBA/2 F1 mice. Referred as KLN205, this cell line had the highest rate of lung colony formation on i.v. injection. It was subcultured for over 15 generations, and its cytological characteristics were investigated. The s.c. and lung colony growth were examined histologically. The effects of treatment with two antimetabolite drugs, arabinosyl-6-mercaptopurine (NSC 406021) and 6-selenoguanosine (NSC 137679) were determined in culture and in vivo. The former was relatively ineffective; the latter was very effective both in vivo and in vitro. Several drugs used clinically for the treatment of lung cancer were also tested. This established and characterized cell line is proposed as a potential model for testing other chemotherapeutic treatments.

Enhancement of the antitumor activity of arabinofuranosyladenine of 2'-deoxycoformycin.

The 6C3HED lymphosarcoma, a tumor cell line very sensitive to 9-beta-D-arabinofuranosyladenine (ara-A), and 6C3HED/ara-A, a line resistant to ara-A, were studied. Both were responsive to 9-beta-D-arabinofuranosylcytosine (ara-C). Two lines of cells. L1210 and L1210/ara-C, are both resistant to ara-A and have very high levels of the deaminase that inactivates ara-A. When an effective inhibitor of the deaminase, 2'-deoxycoformycin, was combined with ara-A in the treatment of mice bearing L1210 or L1210/ara-C tumors, both became responsive to ara-A. Studies are reported on the extent of effects of 2'-deoxycoformycin at several dose levels and the duration of its effect in tumor cells and normal tissues. Single doses produce essentially complete inhibition of the deaminase, and little recovery was seen before 24 hr. However, DNA synthesis in normal tissues recovered more quickly. It is suggested that ara-A and ara-C, the former as a new derivative (9-beta-D-arabinofuranosyladenine 5'-phosphate) and possibly combined with 2'-deoxycoformycin, be regarded as potentially alternative drugs for the treatment of neoplasms.

9-beta-D-arabinofuranosyladenine 5'-phosphate metabolism and excretion in humans.

9-beta-D-Arabinofuranosyladenine (ara-A) was converted chemically to the 9-beta-D-arabinofuranosyladenine 5'-phosphate (ara-A-5'-P) and administered i.v. to four cancer patients in seven experiments. Urinary excretion and plasma levels of radioactivity were monitored for 24 hr in each case. Radioactivity present as unchanged ara-A-5'-P, ara-A, and the deamination product of ara-A, 9-beta-D-arabinofuranosylhypoxanthine, was determined. Excretion was, as in earlier studies with ara-A, given i.v., largely as 6-beta-D-arabinofuranosylhypoxanthine. However, in contrast to the 88 to 97% excretion of ara-A and products in 24 hr when ara-A was given by i.v. push, excretion was 41.47 to 79.1% in 24 hr when ara-A-5'-P was given. With the exception of one experiment at a low dose, where plasma ara-A levels were significant for 6 hr, the plasma levels of ara-A were sustained at significant levels for 24 hr after a single dose of ara-A-5'-P. The doses of ara-A-5'-P given were well tolerated by the four patients. Indications are that this derivative provides important advantages (solubility and sustained blood levels) over ara-A.

Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.

Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant, swelling-activated Cl- current (I(Cl,swell)), associated with NE differentiation of androgen-dependent LNCaP prostate cancer epithelial cells. NE-differentiating regimens, namely, chronic cAMP elevation or androgen deprivation, resulted in generally augmented I(Cl,swell) and enhanced RVD. This occurred as a result of both the increased endogenous expression of ClC-3, which is a volume-sensitive Cl- channel involved, as we show, in I(Cl,swell) in LNCaP (lymph-node carcinoma of the prostate) cells and the weaker negative I(Cl,swell) control from Ca2+ entering via store-dependent pathways. The changes in the RVD of NE-differentiated cells generally mimicked those reported for Bcl-2-conferred apoptotic resistance. Our results suggest that strengthening the mechanism that helps to maintain volume constancy may contribute to better survival rates of apoptosis-resistant NE cells.

Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells.

Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. NE tumor cells are nonproliferating and escape apoptotic cell death; therefore, an understanding of the apoptotic status of the NE phenotype is imperative for the development of new therapies for prostate cancer. Here, we report for the first time on alterations in intracellular Ca(2+) homeostasis, which is a key factor in apoptosis, caused by NE differentiation of androgen-dependent prostate cancer epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen deprivation, resulted in a reduced endoplasmic reticulum Ca(2+)-store content due to both SERCA 2b Ca(2+) ATPase and luminal Ca(2+) binding/storage chaperone calreticulin underexpression, and to a downregulated store-operated Ca(2+) current. NE-differentiated cells showed enhanced resistance to thapsigargin- and TNF-alpha-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein overexpression. Our results suggest that targeting the key players determining Ca(2+) homeostasis in an attempt to enhance the proapoptotic potential of malignant cells may prove to be a useful strategy in the treatment of advanced prostate cancer.

The potential of the hydrocarbon breath test as a measure of lipid peroxidation.

The straight chain aliphatic hydrocarbons ethane and pentane have been advocated as noninvasive markers of free-radical induced lipid peroxidation in humans. In in vitro studies, the evolution of ethane and pentane as end products of n-3 and n-6 polyunsaturated fatty acids, respectively, correlates very well with other markers of lipid peroxidation and even seems to be the most sensitive test available. In laboratory animals the use of both hydrocarbons as in vivo markers of lipid peroxidation has been validated extensively. Although there are other possible sources of hydrocarbons in the body, such as protein oxidation and colonic bacterial metabolism, these apparently are of limited importance and do not interfere with the interpretation of the hydrocarbon breath test. The production of hydrocarbons relative to that of other end products of lipid peroxidation depends on variables that are difficult to control, such as the local availability of iron(II) ions and dioxygen. In addition, hydrocarbons are metabolized in the body, which especially influences the excretion of pentane. Because of the extremely low concentrations of ethane and pentane in human breath, which often are not significantly higher than those in ambient air, the hydrocarbon breath test requires a flawless technique regarding such factors as: (1) the preparation of the subject with hydrocarbon-free air to wash out ambient air hydrocarbons from the lungs, (2) the avoidance of ambient air contamination of the breath sample by using appropriate materials for sampling and storing, and (3) the procedures used to concentrate and filter the samples prior to gas chromatographic determination. For the gas chromatographic separation of hydrocarbons, open tubular capillary columns are preferred because of their high resolution capacity. Only in those settings where expired hydrocarbon levels are substantially higher than ambient air levels might washout prove to be unnecessary, at least in adults. Although many investigators have concentrated on one marker, it seems preferable to measure both ethane and pentane concurrently. The results of the hydrocarbon breath test are not influenced by prior food consumption, but both vitamin E and beta-carotene supplementation decrease hydrocarbon excretion. Nevertheless, the long-term use of a diet high in polyunsaturated fatty acids, such as in parenteral nutrition regimens, may result in increased hydrocarbon exhalation. Hydrocarbon excretion slightly increases with increasing age. Short-term increases follow physical and intellectual stress and exposure to hyperbaric dioxygen.(ABSTRACT TRUNCATED AT 400 WORDS)