MDAN-21: A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys

MDAN-21, , a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice. Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors. The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral repertoire not unlike humans. With regard to opioids, this species usually better predicts clinical outcomes. MDAN-21 substituted for morphine in morphine-dependent monkeys in the remarkably low dose range 0.006–0.032 mg/kg, subcutaneously. Although MDAN-21 failed to produce reliable thermal analgesia in the dose range 0.0032–0.032 mg/kg, intramuscularly, it was active in the same dose range and by the same route of administration, in the capsaicin-induced thermal allodynia assay. The results suggest that MDAN-21 may be useful in the treatment of opioid dependence and allodynia. The data provide additional evidence that opioid withdrawal is associated with sensitized pain

Tkachenko modes as sources of quasiperiodic pulsar spin variations

We study the long wavelength shear modes (Tkachenko waves) of triangular lattices of singly quantized vortices in neutron star interiors taking into account the mutual friction between the superfluid and the normal fluid and the shear viscosity of the normal fluid. The set of Tkachenko modes that propagate in the plane orthogonal to the spin vector are weakly damped if the coupling between the superfluid and normal fluid is small. In strong coupling, their oscillation frequencies are lower and are undamped for small and moderate shear viscosities. The periods of these modes are consistent with the observed ~100-1000 day variations in spin of PSR 1828-11.Comment: 7 pages, 3 figures, uses RevTex, v2: added discussion/references, matches published versio

A Series of 2,4(1H,3H)-Quinazolinedione derivatives: Synthesis and biological evaluation as potential anticancer agents

A series of 6,7-disubstituted-3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline- 2,4(1H,3H)-dione derivatives (7-34) were synthesized and their structures were elucidated on the basis of analytical and spectral (UV, IR, 1H-NMR, 13C-NMR and MS) data. These synthesized compounds were evaluated for their in vitro cytotoxicities against a panel of three human cancer cell lines. According to the cytotoxicity screening results, 3-{2-[4-(4-chlorobenzyl)piperazin-1-yl]-2-oxoethyl} quinazoline-2,4(1H,3H)-dione (7) presented the highest activity against HUH-7, MCF-7 and HCT-116 cell line with the IC50 values of 2.5, 6.8 and 4.9 μM, respectively. © 2016 Bentham Science Publishers

Measurement of Charged Pion Production Yields off the NuMI Target

The fixed-target MIPP experiment, Fermilab E907, was designed to measure the production of hadrons from the collisions of hadrons of momenta ranging from 5 to 120 GeV/c on a variety of nuclei. These data will generally improve the simulation of particle detectors and predictions of particle beam fluxes at accelerators. The spectrometer momentum resolution is between 3 and 4%, and particle identification is performed for particles ranging between 0.3 and 80 GeV/c using $dE/dx$, time-of-flight and Cherenkov radiation measurements. MIPP collected $1.42 \times10^6$ events of 120 GeV Main Injector protons striking a target used in the NuMI facility at Fermilab. The data have been analyzed and we present here charged pion yields per proton-on-target determined in bins of longitudinal and transverse momentum between 0.5 and 80 GeV/c, with combined statistical and systematic relative uncertainties between 5 and 10%.Comment: 15 pages, 13 figure

Quartz Plate Calorimeter as SLHC Upgrade to CMS Hadronic EndCap Calorimeters

Due to an expected increase in radiation damage under super-LHC conditions, we propose to substitute the scintillator tiles in the original design of the hadronic endcap (HE) calorimeter with quartz plates. Quartz is proved to be radiation hard by the radiation damage tests with electron, proton, neutron and gamma beams. Using wavelength shifting fibers, it is possible to collect efficiently the Cherenkov light generated in quartz plates. This paper summarizes the results from various test beams, bench tests, and Geant4 simulations done on methods of collecting light from quartz plates, as well as radiation hardness tests on quartz material

Forward Neutron Production at the Fermilab Main Injector

We have measured cross sections for forward neutron production from a variety of targets using proton beams from the Fermilab Main Injector. Measurements were performed for proton beam momenta of 58 GeV/c, 84 GeV/c, and 120 GeV/c. The cross section dependence on the atomic weight (A) of the targets was found to vary as $A^(alpha)$ where $\alpha$ is $0.46\pm0.06$ for a beam momentum of 58 GeV/c and 0.54$\pm$0.05 for 120 GeV/c. The cross sections show reasonable agreement with FLUKA and DPMJET Monte Carlos. Comparisons have also been made with the LAQGSM Monte Carlo.Comment: Accepted for publication in Physical Review D. This version incorporates small changes suggested by referee and small corrections in the neutron production cross sections predicted by FLUK

The influence of nondipolar magnetic field and neutron star precession on braking indexes of radiopulsars

Some of radiopulsars have anomalous braking index values $n = \Omega \ddot{\Omega} / \dot{\Omega}^2 \sim \pm (10^3 \div 10^4)$. It is shown that such values may be related with nondipolar magnetic field. The precession of neutron star lead to rotation (in reference frame related with neutron star) of vector of angular velocity $\vec{\Omega}$ along direction of neutron star magnetic dipole moment $\vec{m}$ with angular velocity $\vec{\Omega}_{p}$. This process may cause the altering of electric current flow through inner gap and consequently the current losses with the same time scale as precession period $T_{p} = 2\pi / \Omega_{p}$. It occurs because of electric current in inner gaps is determined by Goldreich-Julian charge density $\rho_{GJ} = -\frac{\vec{\Omega} \cdot \vec{B}}{2\pi c}$, which are depend on angle between direction of small scale magnetic field and angular velocity $\vec{\Omega}$. It is essential that pulsar tubes nearby neutron star surface are curved. In current paper it is considered the only inner gaps with steady, electron charge limited flow regime.Comment: 11 pages, 17 figure

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

First observation of a narrow charm-strange meson DsJ(2632) -> Ds eta and D0 K+

We report the first observation of a charm-strange meson DsJ(2632) at a mass of 2632.6+/-1.6 MeV/c^2 in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, Ds eta and D0 K+. In the Ds eta decay mode we observe an excess of 49.3 events with a significance of 7.2sigma at a mass of 2635.9+/-2.9 MeV/c^2. There is a corresponding peak of 14 events with a significance of 5.3sigma at 2631.5+/-1.9 MeV/c^2 in the decay mode D0 K+. The decay width of this state is <17 MeV/c^2 at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(Dseta) is 0.16+/-0.06. The mechanism which keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the Ds eta decay mode.Comment: 5 pages, 3 included eps figures. v2 as accepted for publication by PR

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets