Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM.

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients

Long-term adherence to healthy dietary guidelines and chronic inflammation in the prospective Whitehall II study

Background Inflammation plays an important role in the cause of cardiovascular diseases and may contribute to the association linking an unhealthy diet to chronic age-related diseases. However, to date the long-term associations between diet and inflammation have been poorly described. Our aim was to assess the extent to which adherence to a healthy diet and dietary improvements over a 6-year exposure period prevented subsequent chronic inflammation over a 5-year follow-up in a large British population of men and women. Methods Data were drawn from 4600 adults (mean ± standard deviation, age 49.6 ± 6.1 years, 28% were women) from the prospective Whitehall cohort II study. Adherence to a healthy diet was measured using Alternative Healthy Eating Index (AHEI) scores in 1991-1993 (50.7 ± 11.9 points) and 1997-1999 (51.6 ± 12.4 points). Chronic inflammation, defined as average levels of serum interleukin-6 from 2 measures 5 years apart, was assessed in 1997-1999 and 2002-2004. Results After adjustment for sociodemographic factors, health behaviors, and health status, participants who maintained a high AHEI score (ie, a healthy diet, n = 1736, 37.7%) and those who improved this score over time (n = 681, 14.8%) showed significantly lower mean levels of interleukin-6 (1.84 pg/mL, 95% confidence interval [CI], 1.71-1.98 and 1.84 pg/mL, 95% CI, 1.70-1.99, respectively) than those who had a low AHEI score (n = 1594, 34.6%) over the 6-year exposure period (2.01 pg/mL, 95% CI, 1.87-2.17). Conclusions These data suggest that maintaining and improving adherence to healthy dietary recommendations may reduce the risk of long-term inflammation.</p

Generalization of one-center non orthogonal configuration interaction singles to open shell singlet reference states: Theory and application to valence-core pump-probe states in acetylacetone

We formulate a one-center non-orthogonal configuration interaction singles (1C-NOCIS) theory for the computation of core excited states of an initial singlet state with two unpaired electrons. This model, which we refer to as 1C-NOCIS two-electron open-shell (2eOS), is appropriate for computing the K-edge near-edge X-ray absorption spectra (NEXAS) of the valence excited states of closed-shell molecules relevant to pump-probe time-resolved (TR) NEXAS experiments. With inclusion of core hole relaxation effects and explicit spin adaptation, 1C-NOCIS 2eOS requires mild shifts to match experiment, is free of artifacts due to spin contamination, and can capture the high-energy region of the spectrum beyond the transitions into the singly occupied molecular orbitals (SOMO). Calculations on water and thymine illustrate the different key features of excited-state NEXAS, namely the core-to-SOMO transition as well as shifts and spin-splittings in the transitions analogous to those of the ground state. Finally, simulations of the TR-NEXAS of acetylacetone after excitation onto its pi to pi-star singlet excited state at the carbon K-edge - an experiment carried out recently - showcases the ability of 1C-NOCIS 2eOS to efficiently simulate NEXAS based on non-adiabatic molecular dynamics simulations.Comment: Manuscript: 42 pages, 6 figures. SI: 48 pages, 10 figure

Is Unaided Active Learning an Effective Teaching Method for Those with Learning Disabilities?

The work presented here aims to address a critical knowledge gap in the engineering education literature through a preliminary study meant to determine if active learning is more effective when students with learning disabilities are first front-loaded with information. These preliminary findings aimed at not only determining if the work should be continued in the future, but also at evaluating if frontloading resulted in: (1) increased student engagement and (2) increased learning effectiveness. Preliminary findings conclude that students with documented, and undocumented, learning disabilities did have an increased understanding of the course content as a result of combining frontloading and active learning

Spin Dependence of Massive Lepton Pair Production in Proton-Proton Collisions

We calculate the transverse momentum distribution for the production of massive lepton-pairs in longitudinally polarized proton-proton reactions at collider energies within the context of perturbative quantum chromodynamics. For values of the transverse momentum Q_T greater than roughly half the pair mass Q, Q_T > Q/2, we show that the differential cross section is dominated by subprocesses initiated by incident gluons, provided that the polarized gluon density is not too small. Massive lepton-pair differential cross sections should be a good source of independent constraints on the polarized gluon density, free from the experimental and theoretical complications of photon isolation that beset studies of prompt photon production. We provide predictions for the spin-averaged and spin-dependent differential cross sections as a function of Q_T at energies relevant for the Relativistic Heavy Ion Collider (RHIC) at Brookhaven, and we compare these with predictions for real prompt photon production.Comment: 34 pages, RevTeX including 17 figures in .ps file

Is native speaker intuition reliable for high-frequency context creation?

This study determined whether native speaker intuition could be relied upon to producecontextual content that mostly fell into what is considered high-frequency vocabulary. Native speakers wrote over 160,000 tokens worth of example sentences for high-frequency multi-word units derived from a corpus. The resulting database was examined to determine whether the content added by the native speakers mostly stayed within the high-frequency realm.Results showed that not only did the vast majority of native speakers\u27 tokens fall into the high-frequency realm, the percentage that fell into the high-frequency realm only dropped by 0.84 percent in comparison to the multi-word units alone despite the large amount of data beingadded. This study highlighted how the intuition of experienced ESL practitioners can be relied upon to produce high-frequency contextual content

Meta-analysis of Chromatin Programming by Steroid Receptors

Transcription factors (TFs) must access chromatin to bind to their response elements and regulate gene expression. A widely accepted model proposes that only a special subset of TFs, pioneer factors, can associate with condensed chromatin and initiate chromatin opening. We previously reported that steroid receptors (SRs), not considered pioneer factors, can assist the binding of an archetypal pioneer, the forkhead box protein 1 (FOXA1), at a subset of receptor-activated enhancers. These findings have been challenged recently, with the suggestion that newly acquired data fully support the prevailing pioneer model. Here, we reexamine our results and confirm the original conclusions. We also analyze and discuss a number of available datasets relevant to chromatin penetration by SRs and find a general consensus supporting our original observations. Hence, we propose that chromatin opening at some sites can be initiated by SRs, with a parallel recruitment of factors often treated as having a unique pioneer function.Fil: Paakinaho, Ville. University Of Eastern Finland.; FinlandiaFil: Swinstead, Erin E.. National Cancer Institute; Estados UnidosFil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Grøntved, Lars. Technical University of Denmark; DinamarcaFil: Hager, Gordon L.. National Cancer Institute; Estados Unido

Fantastical Excited State Optimized Structures and Where to Find Them

The quantum chemistry community has developed analytic forces for approximate electronic excited states to enable walking on excited state potential energy surfaces (PES). One can thereby computationally characterize excited state minima and saddle points. Always implicit in using this machinery is the fact that an excited state PES only exists within the realm of the Born-Oppenheimer approximation, where the nuclear and electronic degrees of freedom separate. This work demonstrates through ab initio calculations and simple nonadiabatic dynamics that some excited state minimum structures are fantastical: they appear to exist as stable configurations only as a consequence of the PES construct, rather than being physically observable. One such case is the S2 excited state of phosphine and a second case are local minima of a number of states of tris(bipyridine)ruthenium(II). Each fantastical structure exhibits an unphysically high predicted harmonic frequency and associated force constant. This fact can serve as a valuable diagnostic of when an optimized excited state structure is non-observable. Their origin lies in the coupling between different electronic states, and the resulting avoided crossings. The upper state may exhibit a minimum very close to the crossing, where the force constant relates to the strength of the electronic coupling rather than to any characteristic excited state vibration. Nonadiabatic dynamics results using a Landau-Zener model illustrate that fantastical excited state structures have extremely short lifetimes on the order of a few femtoseconds. Their appearance in a calculation signals the presence of a nearby avoided crossing or conical intersection through which the system will rapidly cross to a lower surface.Comment: 7 pages, 4 figure

Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins