Adventures in Invariant Theory

We provide an introduction to enumerating and constructing invariants of group representations via character methods. The problem is contextualised via two case studies arising from our recent work: entanglement measures, for characterising the structure of state spaces for composite quantum systems; and Markov invariants, a robust alternative to parameter-estimation intensive methods of statistical inference in molecular phylogenetics.Comment: 12 pp, includes supplementary discussion of example

Spectral and Spin Measurement of Two Small and Fast-Rotating Near-Earth Asteroids

In May 2012 two asteroids made near-miss "grazing" passes at distances of a few Earth-radii: 2012 KP24 passed at nine Earth-radii and 2012 KT42 at only three Earth-radii. The latter passed inside the orbital distance of geosynchronous satellites. From spectral and imaging measurements using NASA's 3-m Infrared Telescope Facility (IRTF), we deduce taxonomic, rotational, and physical properties. Their spectral characteristics are somewhat atypical among near-Earth asteroids: C-complex for 2012 KP24 and B-type for 2012 KT42, from which we interpret the albedos of both asteroids to be between 0.10 and 0.15 and effective diameters of 20+-2 and 6+-1 meters, respectively. Among B-type asteroids, the spectrum of 2012 KT42 is most similar to 3200 Phaethon and 4015 Wilson-Harrington. Not only are these among the smallest asteroids spectrally measured, we also find they are among the fastest-spinning: 2012 KP24 completes a rotation in 2.5008+-0.0006 minutes and 2012 KT42 rotates in 3.634+-0.001 minutes.Comment: 4 pages, 3 figures, accepted for publication in Icaru

Nonlinear software sensor for monitoring genetic regulation processes with noise and modeling errors

Nonlinear control techniques by means of a software sensor that are commonly used in chemical engineering could be also applied to genetic regulation processes. We provide here a realistic formulation of this procedure by introducing an additive white Gaussian noise, which is usually found in experimental data. Besides, we include model errors, meaning that we assume we do not know the nonlinear regulation function of the process. In order to illustrate this procedure, we employ the Goodwin dynamics of the concentrations [B.C. Goodwin, Temporal Oscillations in Cells, (Academic Press, New York, 1963)] in the simple form recently applied to single gene systems and some operon cases [H. De Jong, J. Comp. Biol. 9, 67 (2002)], which involves the dynamics of the mRNA, given protein, and metabolite concentrations. Further, we present results for a three gene case in co-regulated sets of transcription units as they occur in prokaryotes. However, instead of considering their full dynamics, we use only the data of the metabolites and a designed software sensor. We also show, more generally, that it is possible to rebuild the complete set of nonmeasured concentrations despite the uncertainties in the regulation function or, even more, in the case of not knowing the mRNA dynamics. In addition, the rebuilding of concentrations is not affected by the perturbation due to the additive white Gaussian noise and also we managed to filter the noisy output of the biological systemComment: 21 pages, 7 figures; also selected in vjbio of August 2005; this version corrects a misorder in the last three references of the published versio

Preserving entanglement under decoherence and sandwiching all separable states

Every entangled state can be perturbed, for instance by decoherence, and stay entangled. For a large class of pure entangled states, we show how large the perturbation can be. Our class includes all pure bipartite and all maximally entangled states. For an entangled state, E, the constucted neighborhood of entangled states is the region outside two parallel hyperplanes, which sandwich the set of all separable states. The states for which these neighborhoods are largest are the maximally entangled ones. As the number of particles, or the dimensions of the Hilbert spaces for two of the particles increases, the distance between two of the hyperplanes which sandwich the separable states goes to zero. It is easy to decide if a state Q is in the neighborhood of entangled states we construct for an entangled state E. One merely has to check if the trace of EQ is greater than a constant which depends upon E and which we determine.Comment: Corrected first author's e-mail address. All the rest remains unchange

Elevated alpha-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells

We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson´s disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson´s disease progression, particularly in the context of bioenergetic dysfunction.Fil: Oliveira, L. M. A.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Botelho, M. G.. Max-Planck-Institut für biophysikalische Chemie; Alemania. Universidade Federal do Rio de Janeiro; BrasilFil: Lin, K. H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Wales, P.. Universität Göttingen; AlemaniaFil: Koch, J. C.. Universität Göttingen; AlemaniaFil: Gerhardt, Elizabeth. Universität Göttingen; AlemaniaFil: Taschenberger, H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Outeiro, T. F.. Universität Göttingen; AlemaniaFil: Lingor, P.. Universität Göttingen; AlemaniaFil: Schüele, B.. The Parkinson’s Institute; Estados UnidosFil: Arndt Jovin, D. J.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Jovin, T. M.. Max-Planck-Institut für biophysikalische Chemie; Alemani

Rational Moral Ignorance

Philosophy and Phenomenological Research, EarlyView

Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: A review of the National Cancer Database

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival

Internet Polling Development Report

This final report presents the system design, testing results and real-world production usage of the system. The copyrighted source code of all the programs is also included.This is the final report which documents the development of Internet-based data logger polling. The project consists of two main tasks: the development of automated polling procedures that can be launched remotely with no operator input, and the development of a polling engine to launch the above procedures and pass the data on to the database server. This final report describes the automated polling procedures that have been developed for Synergistic, Highland and ABB loggers. This report also describes the universal polling engine, which, in addition to launching polling and transferring data, is able to convert ABB data into Synergistic format (the format required to load the data into the LoanSTAR Informix database). The results of testing with Synergistic, Highland and ABB loggers are also described, as well as the real-world production use with ABB power meter loggers at West Texas A&M University

A pharmacodynamic analysis of resistance trends in pathogens from patients with infection in intensive care units in the United States between 1993 and 2004

<p>Abstract</p> <p>Background</p> <p>Increasing nosocomial pathogen resistance to available antimicrobial agents is of growing concern. While higher MICs can diminish antimicrobial effectiveness, dose adjustments often mitigate this effect. This study's objective was to ascertain whether MICs among major pathogens in the ICU to several commonly used agents have increased enough to significantly impact their ability to achieve bactericidal effect.</p> <p>Methods</p> <p>Cefepime, ceftriaxone, imipenem and piperacillin-tazobactam MICs were determined with 74,394 Gram-negative bacilli obtained from ICU patients with various infections in the US between 1993 and 2004. Results were grouped into four 3-year periods. The predicted cumulative fraction of response (CFR) was estimated based on patient-derived pharmacokinetic values and Monte Carlo simulation. Trends in CFR over the four study periods were assessed using the Cochran-Armitage test. The primary analysis included all organisms combined; <it>Pseudomonas aeruginosa </it>and <it>Acinetobacter </it>species were also evaluated individually.</p> <p>Results</p> <p>In the primary analysis, imipenem 500 mg q6h showed CFRs from 87% to 90% across all four study periods, with a trend toward slightly improved bactericidal target attainment (p < 0.01). CFRs for cefepime 2 g q12h and piperacillin-tazobactam 4.5 g q6h both declined by 2% (p < 0.01 and p < 0.05, respectively), reflecting upward shifts in the underlying MIC distributions. Ceftriaxone had <52% CFR for all regimens in all periods, with no significant trend. Against <it>P. aeruginosa</it>, significant declines in CFR were seen for (range, p-value): imipenem 1 g q8h (82%–79%, p < 0.01), cefepime 1 g q12h (70%–67%, p < 0.01), cefepime 2 g q12h (84%–82%, p < 0.05), piperacillin-tazobactam 3.375 g q6h (76%–73%, p < 0.01), piperacillin-tazobactam 4.5 g q8h (71%–68%, p < 0.01), and piperacillin-tazobactam 4.5 g q6h (80%–77%, p < .01). Against <it>Acinetobacter </it>spp., all regimens of imipenem, cefepime and piperacillin-tazobactam showed significant declines in CFR over time (p < 0.01).</p> <p>Conclusion</p> <p>Our observations suggest that as a result of increasing antimicrobial resistance among ICU pathogens in the US, drug effectiveness, assessed as a function of individual agents' ability to attain pharmacodynamic targets, has declined, especially with <it>P. aeruginosa </it>and <it>Acinetobacter </it>spp. Cefepime 2 g q8h and imipenem were the most potent agents against these species, respectively. More aggressive dosing of all of the agents characterized could preserve their clinical utility, but this must be balanced with safety and tolerability issues by the physician.</p