Discussion of "EQUI-energy sampler" by Kou, Zhou and Wong

Novel sampling algorithms can significantly impact open questions in computational biology, most notably the in silico protein folding problem. By using computational methods, protein folding aims to find the three-dimensional structure of a protein chain given the sequence of its amino acid building blocks. The complexity of the problem strongly depends on the protein representation and its energy function. The more detailed the model, the more complex its corresponding energy function and the more challenge it sets for sampling algorithms. Kou, Zhou and Wong [math.ST/0507080] have introduced a novel sampling method, which could contribute significantly to the field of structural prediction.Comment: Published at http://dx.doi.org/10.1214/009053606000000470 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Direct enhancement of nuclear singlet order by dynamic nuclear polarization

Hyperpolarized singlet order is available immediately after dissolution DNP, avoiding need for additional preparation steps. We demonstrate this procedure on a sample of [1,2–13C2]pyruvic aci

Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.MethodsMedications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks.ResultsUse of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02).ConclusionsConcomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

Background:Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). Objective:To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. Design:Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. Setting:44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Patients:644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. Measurements:Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. Methods:We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. Results:Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). Limitations:Sample size, lack of urine output data, and prehospitalization baseline creatinine. Conclusion:Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI

Using error correction to determine the noise model

Quantum error correcting codes have been shown to have the ability of making quantum information resilient against noise. Here we show that we can use quantum error correcting codes as diagnostics to characterise noise. The experiment is based on a three-bit quantum error correcting code carried out on a three-qubit nuclear magnetic resonance (NMR) quantum information processor. Utilizing both engineered and natural noise, the degree of correlations present in the noise affecting a two-qubit subsystem was determined. We measured a correlation factor of c=0.5+/-0.2 using the error correction protocol, and c=0.3+/-0.2 using a standard NMR technique based on coherence pathway selection. Although the error correction method demands precise control, the results demonstrate that the required precision is achievable in the liquid-state NMR setting.Comment: 10 pages, 3 figures. Added discussion section, improved figure

Projective structures, grafting, and measured laminations

We show that grafting any fixed hyperbolic surface defines a homeomorphism from the space of measured laminations to Teichmuller space, complementing a result of Scannell-Wolf on grafting by a fixed lamination. This result is used to study the relationship between the complex-analytic and geometric coordinate systems for the space of complex projective (\CP^1) structures on a surface. We also study the rays in Teichmuller space associated to the grafting coordinates, obtaining estimates for extremal and hyperbolic length functions and their derivatives along these grafting rays.Comment: 31 pages, 4 figure

The Influence of Physical Activity on Monocyte Phenotype on Circulating Platelet-Monocyte Complexes in Overweight/Obese Persons

Elevated platelet-monocyte complexes (PMC) promote atherosclerosis and are associated with cardiovascular disease. It is unknown whether consistent physical activity (PA) decreases circulating PMCs. Additionally, no one has determined the monocyte phenotype most associated with PMCs. Purposes: 1) to examine the influence of PA on PMCs and their association with inflammatory /prothrombotic markers such as C-reactive protein (CRP), L-selectin (LS), platelet factor 4 (PF4), von Willebrand Factor (vWF), and hemoglobin A1C (HbA1c) and 2) to determine the monocyte phenotype most likely to form PMCs. Methods: Thirty-one overweight/obese subjects (44±5yr, BMI 34.2±5 kg×m2) were divided into two groups: sedentary (SED, n=17) and physically active (PA, n=14) based on physical activity logs. SED participated in \u3c 1 h of formal exercise while PA participated in moderate-high intensity exercise at least 3 h per week. Flow cytometry was used to identify PMCs on the monocyte phenotypes: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14+CD16++). Platelets were identified using the marker CD42a. Results: Percentage of circulating PMCs and median fluorescence intensity of CD42a (MedFI; marker of platelet density per monocyte) were not different between groups; however, monocyte phenotype significantly impacted PMC percentage and MedFI where the lower the CD16 expression, the greater the adhesion of platelets. Classical monocytes (CD16-) had the highest % of PMC, etc. (Fig 1). HbA1c was greater (p=0.031) and LS (p=0.019) was lower in SED compared to PA (Fig. 2). There were no significant associations between any blood marker and PMC percentage, but PF4 was correlated with percent of CD16 -(r= -0.482, p=0.031) and CD16+(r= 0.473, p=0.035) monocytes. Conclusions: The absence of a separation between groups in VO2max may partially explain the lack of a difference in PMCs between groups. Regarding our second aim, classical monocytes appear to be more involved in PMC formation than do CD16+ monocytes with CD16++ having the lowest percentage of cells with platelets adhered (PMC). This observation may be due to the shedding of adhesion molecules from platelets and monocytes during activation from classical (CD16-) to a more inflammatory state (ie. CD16+)

HIT vs. LSD: Four Days of Intensive Training does not Influence Lactoferrin, but LSD Increases Resting IL-6 while Attenuating the Acute Exercise Response, yet HIT Elevates Salivary Cortisol Levels

High intensity training programs (HIT) induce comparable endurance performance adaptations to those of continuous long slow distance training (LSD). HIT has increased, as athletes are able to maintain their VO2 max or performance with less time, and reduced training volume. High training volume may be immunosuppressive. PURPOSE: To examine a major mucosal immune component (salivary lactoferrin), the circulating cytokines (IL-6, IL-8, TNF-α), and cortisol response to HIT and LSD during 4 days of intensified training (IT). METHODS: Eight endurance-trained males (23.1±2.0yr,VO2 max 53.9±5.3 ml×kg-1×min-1) performed two, 4-day IT protocols: HIT and LSD conditions (separated by ³ 21 days). Both conditions included 2 exercise sessions / day (morning (AM) and late afternoon (PM)). LSD consisted of 50 min cycle ergometery in the AM (70% VO2max) and 90 min running in the PM (70% VO2max). The AM HIT session included 8 all-out, 30 sec cycling sprints (resistance=0.075kg×kg-1 body mass) with 4.5-8.5 min active recovery. The PM HIT session was the same as that for LSD. Blood and saliva samples were obtained at various time points based on the dependent variable. Plasma cytokines and creatine kinase (CK) activity were assessed both before and after the AM exercise sessions (pre-(PR), post(PO)-exercise) in both conditions on the first (before training; BT) and fourth (after training; AT) day of IT. Creatine kinase activity and cytokines were assessed in plasma. Salivary lactoferrin, and cortisol were assessed at 3 time points on days 1, 2 and 4 (PR and PO for AM, and PR for PM) in UHIT and LSD. Additionally, saliva was also collected at one time point (PR for the AM session) on the third and fifth day. RESULTS: Values above are listed as IL-6 (pg·mL-1), CK (U/L). BT= Day 1, AT= Day 4. Same letters indicate differences between time points for IL-6 serum levels (p\u3c0.05). Same numbers indicate differences between time points for CK activity (p\u3c0.05). Additionally, a significant time x day interaction occurred for lactoferrin secretion rate (PO\u3ePR on days 1 and 4, 1735\u3e5639 and 2290\u3e5663 ng·min-1, respectively; p=0.032). Moreover, a significant condition x time interaction occurred for lactoferrin secretion rate (p=0.047). A main effect for condition revealed that salivary cortisol was greater in HIT vs. LSD (p=0.028). CONCLUSION: Four days of IT did not attenuate the lactoferrin response to acute exercisese. LSD resulted in elevated resting IL-6, which may be responsible for the attenuation of the IL-6 response to acute exercise in this condition due to a feedback inhibition mechanism. Cortisol response is frequently linked to that of Il-6. Il-6 response to acute exercise was maintained in HIT, which may explain the elevated cortisol levels