Structure–activity relationship investigation of triazole-based kappa opioid receptor agonists

Select triazole-based small molecules possess potent and selective kappa opioid receptor (KOR) agonism. Here, we designed twenty new analogs to investigate the structure–activity relationship effects for all three functional groups attached to the triazole core. We identified specific groups that are critical for KOR potency and further extended the range of moieties explored. These efforts revealed analogs with potency on par with our lead triazole probe molecule, Triazole 1.1, in addition to analogs possessing a spectrum of less potent KOR agonist activity

Diffusion of particles moving with constant speed

The propagation of light in a scattering medium is described as the motion of a special kind of a Brownian particle on which the fluctuating forces act only perpendicular to its velocity. This enforces strictly and dynamically the constraint of constant speed of the photon in the medium. A Fokker-Planck equation is derived for the probability distribution in the phase space assuming the transverse fluctuating force to be a white noise. Analytic expressions for the moments of the displacement $$ along with an approximate expression for the marginal probability distribution function $P(x,t)$ are obtained. Exact numerical solutions for the phase space probability distribution for various geometries are presented. The results show that the velocity distribution randomizes in a time of about eight times the mean free time ($8t^*$) only after which the diffusion approximation becomes valid. This factor of eight is a well known experimental fact. A persistence exponent of $0.435 \pm 0.005$ is calculated for this process in two dimensions by studying the survival probability of the particle in a semi-infinite medium. The case of a stochastic amplifying medium is also discussed.Comment: 9 pages, 9 figures(Submitted to Phys. Rev. E

CDMS, Supersymmetry and Extra Dimensions

The CDMS experiment aims to directly detect massive, cold dark matter particles originating from the Milky Way halo. Charge and lattice excitations are detected after a particle scatters in a Ge or Si crystal kept at ~30 mK, allowing to separate nuclear recoils from the dominating electromagnetic background. The operation of 12 detectors in the Soudan mine for 75 live days in 2004 delivered no evidence for a signal, yielding stringent limits on dark matter candidates from supersymmetry and universal extra dimensions. Thirty Ge and Si detectors are presently installed in the Soudan cryostat, and operating at base temperature. The run scheduled to start in 2006 is expected to yield a one order of magnitude increase in dark matter sensitivity.Comment: To be published in the proceedings of the 7th UCLA symposium on sources and detection of dark matter and dark energy in the universe, Marina del Rey, Feb 22-24, 200

Temporal fluctuations of waves in weakly nonlinear disordered media

We consider the multiple scattering of a scalar wave in a disordered medium with a weak nonlinearity of Kerr type. The perturbation theory, developed to calculate the temporal autocorrelation function of scattered wave, fails at short correlation times. A self-consistent calculation shows that for nonlinearities exceeding a certain threshold value, the multiple-scattering speckle pattern becomes unstable and exhibits spontaneous fluctuations even in the absence of scatterer motion. The instability is due to a distributed feedback in the system "coherent wave + nonlinear disordered medium". The feedback is provided by the multiple scattering. The development of instability is independent of the sign of nonlinearity.Comment: RevTeX, 15 pages (including 5 figures), accepted for publication in Phys. Rev.

Big Bang nucleosynthesis and cosmic microwave background constraints on the time variation of the Higgs vacuum expectation value

We derive constraints on the time variation of the Higgs vacuum expectation value $$ through the effects on Big Bang nucleosynthesis (BBN) and the cosmic microwave background (CMB). In the former case, we include the (previously-neglected) effect of the change in the deuteron binding energy, which alters both the $^4$He and deuterium abundances significantly. We find that the current BBN limits on the relative change in \higgs are $-(0.6 - 0.7) \times 10^{-2} / < (1.5 - 2.0) \times 10^{-2}$, where the exact limits depend on the model we choose for the dependence of the deuteron binding energy on \higgs.The limits from the current CMB data are much weaker.Comment: 5 pages including 5 figures, accepted for publication in Phys. Rev.

Search for sterile neutrino oscillation using RENO and NEOS data

We present a reactor model independent search for sterile neutrino oscillation using 2\,509\,days of RENO near detector data and 180 days of NEOS data. The reactor related systematic uncertainties are significantly suppressed as both detectors are located at the same reactor complex of Hanbit Nuclear Power Plant. The search is performed by electron antineutrino\,($\overline{\nu}_e$) disappearance between six reactors and two detectors with baselines of 294\,m\,(RENO) and 24\,m\,(NEOS). A spectral comparison of the NEOS prompt-energy spectrum with a no-oscillation prediction from the RENO measurement can explore reactor $\overline{\nu}_e$ oscillations to sterile neutrino. Based on the comparison, we obtain a 95\% C.L. excluded region of $0.1<|\Delta m_{41}^2|<7$\,eV$^2$. We also obtain a 68\% C.L. allowed region with the best fit of $|\Delta m_{41}^2|=2.41\,\pm\,0.03\,$\,eV$^2$ and $\sin^2 2\theta_{14}$=0.08$\,\pm\,$0.03 with a p-value of 8.2\%. Comparisons of obtained reactor antineutrino spectra at reactor sources are made among RENO, NEOS, and Daya Bay to find a possible spectral variation.Comment: 6 pages, 5 figures: This manuscript has been significantly revised by the joint reanalysis by RENO and NEOS Collaborations. (In the previous edition, the RENO collaboration used publicly available NEOS data to evaluate the expected neutrino spectrum at NEOS.

qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Background: The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. Aims: We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. Methods: We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0–2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. Results: In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58–88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. Conclusion: qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let