A parallel multistate framework for atomistic non-equilibrium reaction dynamics of solutes in strongly interacting organic solvents

We describe a parallel linear-scaling computational framework developed to implement arbitrarily large multi-state empirical valence bond (MS-EVB) calculations within CHARMM. Forces are obtained using the Hellman-Feynmann relationship, giving continuous gradients, and excellent energy conservation. Utilizing multi-dimensional Gaussian coupling elements fit to CCSD(T)-F12 electronic structure theory, we built a 64-state MS-EVB model designed to study the F + CD3CN -> DF + CD2CN reaction in CD3CN solvent. This approach allows us to build a reactive potential energy surface (PES) whose balanced accuracy and efficiency considerably surpass what we could achieve otherwise. We use our PES to run MD simulations, and examine a range of transient observables which follow in the wake of reaction, including transient spectra of the DF vibrational band, time dependent profiles of vibrationally excited DF in CD3CN solvent, and relaxation rates for energy flow from DF into the solvent, all of which agree well with experimental observations. Immediately following deuterium abstraction, the nascent DF is in a non-equilibrium regime in two different respects: (1) it is highly excited, with ~23 kcal mol-1 localized in the stretch; and (2) not yet Hydrogen bonded to the CD3CN solvent, its microsolvation environment is intermediate between the non-interacting gas-phase limit and the solution-phase equilibrium limit. Vibrational relaxation of the nascent DF results in a spectral blue shift, while relaxation of its microsolvation environment results in a red shift. These two competing effects result in a post-reaction relaxation profile distinct from that observed when DF vibration excitation occurs within an equilibrium microsolvation environment. The parallel software framework presented in this paper should be more broadly applicable to a range of complex reactive systems.Comment: 58 pages and 29 Figure

Risk map as a library management information dashboard: a case study in adapting a configural display

In this paper, we report on our application of Cognitive Work Analysis to create an Abstraction Hierarchy model that helps librarians identify key functional relationships for managing the overall performance of a library. By themselves, functional relationships are not as useful in providing insights into the reasons for good or poor performance. However, when these functional relationships are set against the context of system invariants and constraints, they can provide library managers information useful for diagnosis and localization of problems. We propose the Risk Map visualization technique as an information dashboard to cognitively access these functional relationships. Furthermore, when these functional relationships are portrayed over time, trends and patterns can be detected with relative ease

Life-Time Covariation of Major Cardiovascular Diseases: A 40-Year Longitudinal Study and Genetic Studies

BACKGROUND: It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs. METHODS: The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used. RESULTS: Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links. CONCLUSIONS: During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs

Left ventricular geometric patterns and adaptations to hemodynamics are similar in elderly men and women

<p>Abstract</p> <p>Background</p> <p>Common conditions such as obesity and hypertension result in hemodynamic alterations that will induce remodeling of the left ventricle (LV). However, differences between the genders in the relationship of hemodynamics to LV geometry are not well known.</p> <p>The present study aims to investigate differences between the genders in this respect, in a sample of elderly persons.</p> <p>Methods</p> <p>Echocardiography and Doppler was performed in a population-based sample aged 70 - The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 922).</p> <p>Hemodynamic patterns obtained by echocardiography and Doppler were evaluated in relation to four LV geometric groups (normal, concentric remodeling, eccentric hypertrophy and concentric hypertrophy).</p> <p>Results</p> <p>No significant difference between the genders was observed regarding the prevalence of the LV geometric groups.</p> <p>Mean values of most evaluated echocardiography and Doppler variables differed between men and women, such as LA, IVS, LVEDD and IVRT, but the relationship of hemodynamic variables to LV geometric groups did not differ between the genders.</p> <p>Conclusions</p> <p>Although mean values of many echocardiographic variables differed between men and women, the LV geometric adaptations to a given hemodynamic load appear similar in both genders.</p

A comparison of the nutritional qualities of supermarket's own and regular brands of bread in Sweden

Processed food is associated with unhealthy qualities such as higher content of harmful fats, sugars and salt. The aim of our study was to compare the nutritional qualities of supermarket's own brands and regular brands of bread sold in Sweden. Additionally, we compared the nutritional qualities of gluten-free and gluten-containing bread. We collected information from the labels of 332 bread products available in the largest grocery store chains. The Australian Health Star Rating (HSR) system was used to quantify the nutritional quality of each bread product. We compared all supermarket's own brand products to regular brand products, and gluten-free to gluten-containing bread. The mean HSR for the supermarket's own brands was lower than the regular brands (3.6 vs. 3.7; p = 0.046). For the regular brand products, the fibre, sugar and total fat content were greater (p < 0.001, p = 0.002 and p = 0.021, respectively), while less protein (p = 0.009) compared to regular bread products. Gluten-free bread had a lower HSR than gluten-containing bread (mean 3.5 vs. 3.8, respectively; p < 0.001). The regular brand products were slightly healthier than the supermarket's own brands, primarily as a result of a higher fibre content. Gluten-free bread products were slightly unhealthier due to a lower protein content

Tri-critical point and suppression of the Shastry-Sutherland phase in Ce2_{2}Pd2_{2}Sn by Ni doping

Structural, magnetization and heat capacity measurements were performed on Ce$_2$(Pd$_{1-x}$Ni$_x$)$_2$Sn ($0 \leq x \leq 0.25$) alloys, covering the full range of the Mo$_2$FeB$_2$ structure stability. In this system, the two transitions observed in Ce$_2$Pd$_2$Sn (at $T_N=4.8$\,K and $T_C=2.1$\,K respectively) converge into a tri-critical point at $T_{cr}\approx 3.4$\,K for $x\approx 0.3$, where the intermediate antiferromagnetic AF phase is suppressed. The $T_N(x)$ phase boundary decrease is due to an incipient Kondo screening of the Ce-4f moments and local atomic disorder in the alloy. Both mechanisms affect the formation of Ce-magnetic dimers on which the Shastry-Sutherland lattice (SSL) builds up. On the contrary, the $T_C(x)$ transition to the ferromagnetic ground state increases as a consequence of the weakening of the AF-SSL phase. Applied magnetic field also suppresses the AF phase like in the stoichiometric compound.Comment: 6 pages, 8 figure

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial

Importance: Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective: To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants: A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions: Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures: Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results: There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P <.001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. Conclusions and Relevance: These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02774460