The Antikythera mechanism and the mechanical universe

Astronomers have two approaches to trying to determine the age of the Universe. They can estimate the ages of individual objects in the Universe and specifically in our Galaxy. These estimates use either the observed properties of stars and theoretical ideas concerning stellar evolution or the abundances of long-lived radioactive isotopes and their decay products. Alternatively they can use cosmological theories and observations to try to determine the age of the entire Universe. Obviously the Universe must be older than its component parts but neither of the above methods is sufficiently reliable that this is true of the deduced ages. As a result, it is from time to time reported that some object in the Universe is older than the Universe itself. In this article we discuss the methods that are currently being used to determine the age and we emphasize the problems in obtaining reliable results. It is not at present possible to provide a definite value for the age of the Universe.     

On commutation semigroups of dihedral groups

For any group G with g∈G, the right and left commutation semigroups associated with g are the mappings ρ(g) and λ(g) from G to G defined as (x)ρ(g)=[x,g] and (x)λ(g)=[g,x]. The set M(G) of all mappings from G to G forms a semigroup under composition of mappings. The right and left commutation semigroups of G, denoted P(G) and Λ(G), are the subsemigroups of M(G) generated by {ρ(g):g∈G} and {λ(g):g∈G}, respectively. In this paper, we develop explicit formulas for the orders of P(G) and Λ(G) when G=D _m , the dihedral group of order 2m. We apply these formulas to address the problems of determining when |P(G)|=|Λ(G)| and P(G)?Λ(G) and to derive proofs of several previous results of James Countryman (Ph.D. Thesis, University of Notre Dame, 1970) on commutation semigroups of pq groups.     

An algorithm for the mixed-integer nonlinear bilevel programming problem

The bilevel programming problem (BLPP) is a two-person nonzero sum game in which play is sequential and cooperation is not permitted. In this paper, we examine a class of BLPPs where the leader controls a set of continuous and discrete variables and tries to minimize a convex nonlinear objective function. The follower's objective function is a convex quadratic in a continuous decision space. All constraints are assumed to be linear. A branch and bound algorithm is developed that finds global optima. The main purpose of this paper is to identify efficient branching rules, and to determine the computational burden of the numeric procedures. Extensive test results are reported. We close by showing that it is not readily possible to extend the algorithm to the more general case involving integer follower variables.This work was supported by a grant from the Advanced Research Program of the Texas Higher Education Coordinating Board.     

ONIOM investigation of nucleotide selectivity in phosphodiesterases 3 and 4

The cyclic nucleotide phosphodiesterases (PDEs) are drug‐targeted enzymes that down regulate cyclic nucleotide concentrations in the cell by catalyzing the hydrolysis of the O3′‐phosphorous bond, yielding the noncyclic nucleotides. Selectivity for cAMP versus cGMP (cyclic 3′,5′‐adenosine/‐guanosine monophosphate) as the favored substrate is primarily attributed to the orientation of a conserved glutamine residue which binds to the adenine/guanine ring. We use ONIOM hybrid quantum methods to accurately describe substrate binding within the catalytic sites of the cAMP‐specific PDE4 and the cGMP‐inhibited, dual‐specific PDE3 in order to understand subtle aspects of substrate selectivity. We estimate PDE4's net preference for cAMP binding to be about 16 kcal/mol; the cause of cAMP's known preference resides both in its fixed glutamine orientation (Gln 369 in PDE4D) and in the differential free energy of solvation, which disfavors the binding of cGMP relative to cAMP by about 15 kcal/mol. Also, we discuss the contributing role played by Asn 321, held in place by a partner Asp 167, in the deselection of cGMP by PDE4. PDE3's conserved glutamine (Gln 988 in PDE3B) is free to take on either a cGMP‐favorable or cAMP‐favorable orientation. We find that enthalpies of binding favor cGMP for PDE3, but only by the same amount as free energies of solvation disfavor cGMP binding. Comparison of the PDE3‐cAMP and ‐cGMP complexes and energetics reveals cAMP to be more susceptible to the attack of the hydroxide nucleophile in PDE3. We identify a key threonine residue (Thr 952) as responsible for PDE3's kinetic relative disfavor of cGMP hydrolysis by causing Gln 988 to tilt out of cGMP's purine plane. Our results are consistent with the PDE3's kinetic specificity for cAMP hydrolysis and the known competitive inhibition of PDE3 by cGMP. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

A Simple Preparative Method for tert-Butyl Protection of Aminocephalosporanic Acid

A convenient and effective synthesis of the tert-butyl esters of 7-aminocephalosporanic acid, 7-aminodeacetoxycephalosporanic acid and 6-aminopenicillanic acid using tert-butylacetate and boron trifluoride etherate is described.     

A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized <Emphasis Type="SmallCaps">l</Emphasis>-arginine,symmetric dimethylarginine,and asymmetric dimethylarginine and establishment of the reference ranges

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an established biomarker for endothelial function, while symmetric dimethylarginine (SDMA), an emerging biomarker for renal function, has been shown to outperform creatinine-based equations for estimated glomerular filtration rate. In order to study these analytes for clinical research, a fast and simple method for measuring arginine (ARG), SDMA, and ADMA in plasma by liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been developed. Plasma (50 μL) was mixed with 50 μL of internal standard of ¹³C-arginine and d₇-ADMA followed by protein precipitation with methanol containing 1% ammonium acetate (300 μL). After centrifugation, the supernatant (100 μL) was mixed with 300 μL of acetonitrile with 1% formic acid, and the mixture was injected onto a silica column monitored by a mass spectrometer. The analytical cycle time was 5.0 min. The method was linear from 5.7 to 489.7 μM for ARG, 0.06 to 5.15 μM for SDMA, and from 0.34 to 5.65 μM for ADMA, with an accuracy of 99.0–120.0%. Total coefficients of variation for all analytes ranged from 2.7% to 7.7% for three concentration levels. The effects of hemolysis, lipemia, uremia, icterus, specimen tube types, storage at different temperature, and freeze/thaw were thoroughly investigated. Reference ranges were established using 51 well-defined reference subjects (12 men and 39 women, age 19–64 years): 53.1–129.7 μM for ARG, 0.32–0.65 μM for SDMA, and 0.36–0.67 μM for ADMA. In conclusion, the validated LC-MS/MS method described here offers a fast and reliable ARG, SDMA, and ADMA quantitation in plasma with minimum sample preparation.     

First measurements of inclusive muon neutrino charged current differential cross sections on argon

The ArgoNeuT Collaboration presents the first measurements of inclusive muon neutrino charged current differential cross sections on argon. Obtained in the NuMI neutrino beam line at Fermilab, the flux-integrated results are reported in terms of outgoing muon angle and momentum. The data are consistent with the Monte Carlo expectation across the full range of kinematics sampled, 0°<θ(μ)<36° and 0相似文献   

Synthesis and cytotoxicity of silylalkylthio‐substituted N‐heterocycles and their hydroselenites

New hydroselenites of the different silylalkylthio‐substituted N‐heterocycles have been prepared by the reaction of selenium dioxide with N‐heterocycles in an aqueous medium. Their structure was confirmed by ¹H, ¹³C, and ⁷⁷Se NMR data. Most of these silylalkylthio‐substituted N‐heterocycles and their hydroselenites have an expressed cytotoxic activity on the MG‐22A (mouse hepatoma), HT‐1080 (human fibrosarcoma), B16 (mouse melanoma), and Neuro 2A (mouse neuroblastoma) cell lines. Some of the hydroselenites exhibit free‐radical protection simultaneously with a high cytotoxic effect. The substances studied were also active in vivoagainst sarcoma S‐180. Copyright © 2003 John Wiley & Sons, Ltd.