Ethyl 1-benzyl-1,2,3,3a,4,10b-hexa-hydro-pyrrolo-[2',3':3,4]pyrrolo-[1,2-a]benzimidazole-2-carboxyl-ate.

The title mol-ecule, C(22)H(23)N(3)O(2), was obtained via an intra-molecular cyclo-addition of an azomethine ylide and an alkene tethered by a benzimidazole unit. The benzoimidazole unit is essentially planar, with an r.m.s. deviation of 0.0087 Å from the nine constituent atoms. It has a cis fusion of the two pyrrolidine rings as well as a cis ester appendage. The two pyrrolidine rings rings have envelope conformations. The crystal packing is stabilized by aromatic π-π stacking of parallel benzimidazole ring systems, with a centroid-to-centroid distance of 3.518 (6) Å. Weak inter-molecular C-H⋯O contacts may also play a role in the stability of the packing

The Solid-Phase Part of Supported Small-Molecule Synthesis

The synthesis of small molecules on solid phase must not only address the vagaries of C–C-bond formation and functional-group manipulation, but must also take into account solid-support issues such as 'point of attachment', 'resin compatibility', 'reagent accesibility', and 'product liberation'. Hence, the resin plays a vital role in the solid-phase venture and the polymer advantages can be summarized as reactions can be driven to completion by addition of excess solution-phase reagents, reaction products are 'isolated' by filtration and washing, and multiple-step synthesis terminating with a 'selective' liberation step can deliver essentially pure product. These issues, as well as a number of strategies for the preparation and functionalization of resin supports, are discussed

Davis-Beirut reaction: route to thiazolo-, thiazino-, and thiazepino-2H-indazoles.

Methods for the construction of thiazolo-, thiazino-, and thiazepino-2H-indazoles from o-nitrobenzaldehydes or o-nitrobenzyl bromides and S-trityl-protected 1°-aminothioalkanes are reported. The process consists of formation of the requisite N-(2-nitrobenzyl)(tritylthio)alkylamine, subsequent deprotection of the trityl moiety with TFA, and immediate treatment with aq. KOH in methanol under Davis-Beirut reaction conditions to deliver the target thiazolo-, thiazino-, or thiazepino-2H-indazole in good overall yield. Subsequent S-oxidation gives the corresponding sulfone

Nuclear Parity Violation from Lattice QCD

The electroweak interaction at the level of quarks and gluons are well understood from precision measurements in high energy collider experiments. Relating these fundamental parameters to Hadronic Parity Violation in nuclei however remains an outstanding theoretical challenge. One of the most interesting observables in this respect is the parity violating hadronic neutral current: it is hard to measure in collider experiments and is thus the least constrained observable of the Standard Model. Precision measurements of parity violating transitions in nuclei can help to improve these constraints. In these systems however, the weak interaction is masked by effects of the seven orders of magnitude stronger non-perturbative strong interaction. Therefore, in order to relate experimental measurements of the parity violating pion-nucleon couplings to the fundamental Lagrangian of the SM, these non-perturbative effects have to be well understood. In this paper, we are going to present a Lattice QCD approach for computing the $\Delta I{=}2$ parity violating matrix element in proton proton scattering. This process does not involve disconnected diagrams in the isospin symmetric limit and is thus a perfect testbed for studying the feasibility of the more involved calculation of the parity violating pion-nucleon coupling.Comment: PoS Lattice 201

Two-nucleon scattering in multiple partial waves

We determine scattering phase shifts for S,P,D, and F partial wave channels in two-nucleon systems using lattice QCD methods. We use a generalization of Luscher's finite volume method to determine infinite volume phase shifts from a set of finite volume ground- and excited-state energy levels on two volumes, V=(3.4 fm)^3 and V=(4.5 fm)^3. The calculations are performed in the SU(3)-flavor limit, corresponding to a pion mass of approximately 800 MeV. From the energy dependence of the phase shifts we are able to extract scattering parameters corresponding to an effective range expansion.Comment: 7 pages, 11 figures. Proceedings of the 33rd International Symposium on Lattice Field Theory, July 14-18, 2015, Kobe, Japa

Two-nucleon higher partial-wave scattering from lattice QCD

We present a determination of nucleon-nucleon scattering phase shifts for l \u3e= 0. The S, P, D and F phase shifts for both the spin-triplet and spin-singlet channels are computed with lattice Quantum ChromoDynamics. For t \u3e 0, this is the first lattice QCD calculation using the Luscher finite-volume formalism. This required the design and implementation of novel lattice methods involving displaced sources and momentum-space cubic sinks. To demonstrate the utility of our approach, the calculations were performed in the SU(3)-flavor limit where the light quark masses have been tuned to the physical strange quark mass, corresponding to m(pi)=m(K)approximate to 800 MeV. In this work, we have assumed that only the lowest partial waves contribute to each channel, ignoring the unphysical partial wave mixing that arises within the finite-volume formalism. This assumption is only valid for sufficiently low energies; we present evidence that it holds for our study using two different channels. Two spatial volumes of V approximate to (3.5 fm)(3) and V approximate to (4.6 fm)(3) were used. The finite-volume spectrum is extracted from the exponential falloff of the correlation functions. Said spectrum is mapped onto the infinite volume phase shifts using the generalization of the Luscher formalism for two-nucleon systems. Published by Elsevier B.V

Generative replay underlies compositional inference in the hippocampal-prefrontal circuit

Human reasoning depends on reusing pieces of information by putting them together in new ways. However, very little is known about how compositional computation is implemented in the brain. Here, we ask participants to solve a series of problems that each require constructing a whole from a set of elements. With fMRI, we find that representations of novel constructed objects in the frontal cortex and hippocampus are relational and compositional. With MEG, we find that replay assembles elements into compounds, with each replay sequence constituting a hypothesis about a possible configuration of elements. The content of sequences evolves as participants solve each puzzle, progressing from predictable to uncertain elements and gradually converging on the correct configuration. Together, these results suggest a computational bridge between apparently distinct functions of hippocampal-prefrontal circuitry and a role for generative replay in compositional inference and hypothesis testing

The relationship of dieting severity and bulimic behaviors to alcohol and other drug use in young women

Patients with bulimia nervosa frequently have problems with alcoholism and other substance abuse. The goal of this study was to assess whether this relationship between eating abnormalities and substance abuse extends to subthreshold levels of dieting and substance use. A self-administered questionnaire assessing dieting and substance use (alcohol, cigarettes, and marijuana) was completed by 1,796 women prior to their freshman year in college. Using a scale derived from DSM-III-R criteria for bulimia nervosa and previous research in this population, subjects were categorized as nondieters, casual, intense, severe, at-risk, or bulimic dieters. The relationship between the dieting-severity category and frequency and intensity of alcohol use and frequency of marijuana and cigarette use was assessed. DSM-III-R criteria for bulimia nervosa were met by 1.6% of the women. Only 13.8% of these women were nondieters. Increasing dieting severity was positively associated with increasing prevalence of alcohol, cigarette, and marijuana use and with increasing frequency and intensity of alcohol use. The bulimic and at-risk dieters were similar in their alcohol and drug use. The relationship between eating disorders and alcoholism and other substance abuse noted in clinical populations extends in a continuous, graded manner to subthreshold levels of dieting and substance use behaviors. Dieting-related attitudes and behaviors in young women may be related to increased susceptibility to alcohol and drug abuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30340/1/0000742.pd

A Novel Combination of Serum Markers in a Multivariate Model to Help Triage Patients Into “Low-” and “High-Risk” Categories for Prostate Cancer

BACKGROUND: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies. MATERIALS AND METHODS: Serum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA). RESULTS: The data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log(10) IL-8, log(10) MCP-1, and log(10) tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA. CONCLUSIONS: The novel combination of serum markers identified in this study could be employed to help triage patients into “low-” and “high-risk” categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments