Computational Studies of Protein Folding

Proteins are known to fold into tertiary structures that determine their functionality in living organisms. The goal of our research is to better understand the protein folding process. Using MATLAB, we created an algorithm that models the folding process via a Monte Carlo time step approach. Specifically, amino acids in the chain at each time step are allowed to fold to certain locations according to a set of rules. These rules are based on two main criteria: folds must maintain bond length and should be thermally and energetically favorable. One central goal of our research is to examine whether the folding process can be viewed through the lens of self-organized criticality. In particular we are interested in whether there are features of the folding process that are independent of the size of the protein

The long-term prognostic significance of 6-minute walk test distance in patients with chronic heart failure

Background. The 6-minute walk test (6-MWT) is used to assess patients with chronic heart failure (CHF). The prognostic significance of the 6-MWT distance during long-term followup ( > 5 years) is unclear. Methods. 1,667 patients (median [inter-quartile range, IQR]) (age 72 [65-77] ; 75% males) with heart failure due to left ventricular systolic impairment undertook a 6-MWT as part of their baseline assessment and were followed up for 5 years. Results. At 5 years' followup, those patients who died (n = 959) were older at baseline and had a higher log NT pro-BNP than those who survived to 5 years (n = 708). 6-MWT distance was lower in those who died [163 (153) m versus 269 (160) m; P 360 m. 6-MWT distance was a predictor of all-cause mortality (HR 0.97; 95% CI 0.96-0.97; Chi-square = 184.1; P < 0.0001). Independent predictors of all-cause mortality were decreasing 6-MWT distance, increasing age, increasing NYHA classification, increasing log NT pro-BNP, decreasing diastolic blood pressure, decreasing sodium, and increasing urea. Conclusion. The 6-MWT is an important independent predictor of all-cause mortality following long-term followup in patients with CHF. © 2014 Lee Ingle et al

Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions-Part II: Combination Therapy

Purpose of Review Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion loop diuretics-has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and current trial evidence for different diuretic strategies and explore potential future directions of research. Recent Findings We will assess recent trials, including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF, and assess how these may influence current practice and future research. Summary There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for high-dose loop diuretic treatment over low-dose treatment for patients admitted to hospital with HF, yet this is not reflected in guidelines. There is an urgent need for more and better research on different diuretic strategies in patients with HF

On the shot-noise limit of a thermal current

The noise power spectral density of a thermal current between two macroscopic dielectric bodies held at different temperatures and connected only at a quantum point contact is calculated. Assuming the thermal energy is carried only by phonons, we model the quantum point contact as a mechanical link, having a harmonic spring potential. In the weak coupling, or weak-link limit, we find the thermal current analog of the well-known electronic shot-noise expression.Comment: 4 pages, 1 figur

Prevention or procrastination for heart failure?: Why we need a universal definition of heart failure

No abstract available

Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure

Objective: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. Methods: Retrospective analysis of patient records at the Department of Cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients [median (25th-75th percentile)] [age 65 (56-72) years; 79% males; LVEF 34 (31-37) %] were included. Patients underwent a symptomlimited, maximal CPET on a treadmill. During a median follow up of 8.6 ± 2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. Results: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrell’s C-statistic, but the optimal combination of EOV + VE/VCO2 slope + OUES + VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the Heart Failure Survival Score (AUC=0.70;

Cardiorespiratory requirements of the 6-min walk test in patients with left ventricular systolic disfunction and no major structural heart disease

The six-minute walk test (6-MWT) is widely used to assess functional status in patients with chronic heart failure (CHF). The aims of the present study were: (1) to compare metabolic gas exchange during the 6-MWT in older patients with left ventricular systolic dysfunction (LVSD) and in breathless patients with no major structural heart disease (MSHD); (2) to determine the exercise intensity of the 6-MWT relative to peak oxygen uptake; (3) to establish the accuracy and reproducibility of the Metamax 3B ergospirometer during an incremental workload. Twenty four older patients with LVSD (19 male; age 76 ± 5 years; BMI 27 ± 4), and 18 patients with no MSHD (12 male; age 75 ± 8 years; BMI 27 ± 4) attended on consecutive days at the same time. Patients completed a 6-MWT with metabolic gas exchange measurements using the Metamax 3B portable ergospirometer, and an incremental cycle ergometry test using both the Metamax 3B and Oxycon Pro metabolic cart. Patients returned and performed a second 6-MWT and an incremental treadmill test, metabolic gas exchange was measured with the Metamax 3B. In patients with LVSD, the 6-MWT was performed at a higher fraction of maximal exercise capacity (p = 0.02). The 6-MWT was performed below the anaerobic threshold in patients with LVSD (83 %) and in patients with no MSHD (61 %). The Metamax 3B showed satisfactory to high accuracy at 10 W and 20 W in patients with LVSD (r = 0.77 - 0.97, p < 0.05), and no MSHD (r = 0.76 - 0.94, p < 0.05). Metabolic gas exchange variables measured during the 6-MWT showed satisfactory to high day-to-day reproducibility in patients with LVSD (ICC = 0.75 - 0.98), but a higher variability was evident in participants with no MSHD (ICC = 0.62 - 0.97). The Metamax 3B portable ergospirometer is an accurate and reproducible device during submaximal, fixed rate exercise in older patients with LVSD and no MSHD. In elderly patients with LVSD and no MSHD, the 6-MWT should not be considered a maximal test of exercise capacity but rather a test of submaximal exercise performance. Our study demonstrates that the 6-MWT takes place at a higher proportion of peak oxygen uptake in patients with LVSD compared to those with no MSHD, and may be one reason why fatigue is a more prominent symptom in these patients