Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulating the dynamics of the mechanochemical cycle of myosin-V

Significance The free-energy landscape of the complete mechanochemical cycle of myosin-V is used in simulating the real-time features of the directional motion. The combination of Langevin dynamics simulations and time-dependent Monte Carlo simulations reproduces the observed trend in terms of stall force and force/velocity profile. The present study also addresses the role of the powerstroke and finds it to be the result of the complete free-energy landscape rather than the driving force of the energy conversion by the system. The detailed dynamics of the cycle of myosin-V are explored by simulation approaches, examining the nature of the energy-driven motion. Our study started with Langevin dynamics (LD) simulations on a very coarse landscape with a single rate-limiting barrier and reproduced the stall force and the hand-over-hand dynamics. We then considered a more realistic landscape and used time-dependent Monte Carlo (MC) simulations that allowed trajectories long enough to reproduce the force/velocity characteristic sigmoidal correlation, while also reproducing the hand-over-hand motion. Overall, our study indicated that the notion of a downhill lever-up to lever-down process (popularly known as the powerstroke mechanism) is the result of the energetics of the complete myosin-V cycle and is not the source of directional motion or force generation on its own. The present work further emphasizes the need to use well-defined energy landscapes in studying molecular motors in general and myosin in particular.
Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men.

BACKGROUND Interest in the development of dairy products naturally enriched in conjugated linoleic acid (CLA) exists. However, feeding regimens that enhance the CLA content of milk also increase concentrations of trans-18:1 fatty acids. The implications for human health are not yet known. OBJECTIVE This study investigated the effects of consuming dairy products naturally enriched in cis-9,trans-11 CLA (and trans-11 18:1) on the blood lipid profile, the atherogenicity of LDL, and markers of inflammation and insulin resistance in healthy middle-aged men. DESIGN Healthy middle-aged men (n = 32) consumed ultra-heat-treated milk, butter, and cheese that provided 0.151 g/d (control) or 1.421 g/d (modified) cis-9,trans-11 CLA for 6 wk. This was followed by a 7-wk washout and a crossover to the other treatment. RESULTS Consumption of dairy products enriched with cis-9,trans-11 CLA and trans-11 18:1 did not significantly affect body weight, inflammatory markers, insulin, glucose, triacylglycerols, or total, LDL, and HDL cholesterol but resulted in a small increase in the ratio of LDL to HDL cholesterol. The modified dairy products changed LDL fatty acid composition but had no significant effect on LDL particle size or the susceptibility of LDL to oxidation. Overall, increased consumption of full-fat dairy products and naturally derived trans fatty acids did not cause significant changes in cardiovascular disease risk variables, as may be expected on the basis of current health recommendations. CONCLUSION Dairy products naturally enriched with cis-9,trans-11 CLA and trans-11 18:1 do not appear to have a significant effect on the blood lipid profile.
A new anthropomorphic robotic hand

This paper presents the new robotic FRH-4 hand. The FRH-4 hand constitutes a new hybrid concept of an anthropomorphic five fingered hand and a three jaw robotic gripper. The hand has a humanoid appearance while maintaining the precision of a robotic gripper. Since it is actuated with flexible fluidic actuators, it exhibits an excellent power to weight ratio. These elastic actuators also ensure that the hand is safe for interacting with humans. In order to fully control the joints, it is equipped with position sensors on all of the 11 joints. The hand is also fitted with tactile sensors based on cursor navigation sensor elements, which allows it to have grasping feedback and the ability for exploration.
Interleukin-11 attenuates pulmonary inflammation and vasomotor dysfunction in endotoxin-induced lung injury.

Interleukin (IL)-11, like other members of the gp130 receptor class, possesses anti-inflammatory properties. We hypothesized that IL-11 pretreatment would attenuate endotoxin [lipopolysaccharide (LPS)]-induced lung inflammation and diminish injury to endothelium-dependent and -independent mechanisms of pulmonary vasorelaxation that require cGMP in Sprague-Dawley rats. LPS (20 mg/kg ip) increased lung tumor necrosis factor (TNF)-α compared with the saline control (0.7 ± 0.15 ng/g lung wet wt for control vs. 3.5 ± 0.09 ng/g lung wet wt for LPS; P < 0.05). IL-11 (200 mg/kg ip) injected 10 min before LPS administration attenuated the LPS-induced lung TNF-α levels (1.6 ± 0.91 ng/g lung wet wt; P < 0.05 vs. LPS). IL-11 also diminished LPS-induced lung neutrophil sequestration as assessed by myeloperoxidase units (2.1 ± 0.25 U/g lung wet wt for saline and 15.6 ± 2.02 U/g lung wet wt for LPS vs. 7.07 ± 1.65 U/g lung wet wt for LPS plus IL-11; P < 0.05). Similarly, TNF-α binding protein (175 mg/kg) attenuated LPS-induced myeloperoxidase activity (6.04 ± 0.14 U/g lung wet wt; P < 0.05). Both IL-11 and TNF-α binding protein similarly attenuated LPS-induced endothelium-dependent vasomotor dysfunction with improved relaxation responses to 10-7 and 10-6 M acetylcholine and A-23187 in phenylephrine-preconstricted isolated pulmonary artery rings ( P < 0.05 vs. LPS). Endothelium-independent relaxation responses to sodium nitroprusside were also improved after LPS at 10-6 M ( P < 0.05 vs. LPS). Moreover, IL-11 decreased endotoxin-induced mortality in CF1 mice from 90 to 50% ( P ≤ 0.05 vs. LPS). Therefore, IL-11 prevents LPS-induced lung TNF-α production, neutrophil sequestration, and pulmonary vasomotor dysfunction. We conclude that IL-11 possesses anti-inflammatory activity that protects against LPS-induced lung injury and lethality.
Enhancing gap junction coupling in reperfused myocardium

The work in this thesis sought to examine the effects of enhancing cardiac gap junction coupling using the pharmacological agent Rotigaptide in clinically applicable models of acute myocardial infarction (MI). Specifically, the studies in this thesis investigated the effect of Rotigaptide on ventricular arrhythmogenesis and structural remodelling of the reperfused substrate, with particular emphasis on the development, application and histological validation of diffusion tensor magnetic resonance imagine (DTI) as a novel imaging modality to describe and quantify structural remodelling post-infarction. An ex vivo rat model of acute regional ischaemia-reperfusion was characterised and used to study the effect of Rotigaptide on ventricular arrhythmogenesis during acute ischaemia and reperfusion. Arrhythmias occurred during ischaemia in a monomodal distribution with a peak incidence between 12-15 minutes after ischaemia. The incidence of reperfusion arrhythmias was dependent on the preceding duration of ischaemia with a progressive reduction as ischaemic time extended from 15 to 60 minutes. Rotigaptide pre-treatment afforded a significant reduction in ischaemia-induced arrhythmias compared to administration at the onset of ischaemia or at the time of reperfusion. An in vivo rat model of infarction-reperfusion, mimicking clinical reperfusion in the setting of acute MI was characterised and Rotigaptide administered prior to reperfusion and for a week post-MI. At four-weeks post-MI animals were studied with 6-lead ECG, ambulatory telemetry, programmed electrical simulation (PES), optical mapping, DTI and histology. Rotigaptide reduced the susceptibility to arrhythmias induced by PES and partially restored DTI-derived indices of tissue disruption in infarcted myocardium.
Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients.

BACKGROUND Oxidative stress associated with postprandial lipemia contributes to endothelial dysfunction, which shifts hemostasis to a more thrombogenic state. OBJECTIVE We investigated whether a high concentration of phenols in olive oil can partly reverse this phenomenon. DESIGN Twenty-one hypercholesterolemic volunteers received 2 breakfasts rich in olive oils with different phenolic contents (80 or 400 ppm) according to a randomized, sequential crossover design. Plasma concentrations of lipid fractions, factor VII antigen (FVIIag), activated factor VII (FVIIa), and plasminogen activator inhibitor-1 (PAI-1) activity were measured at baseline and postprandially. RESULTS Concentrations of FVIIa increased less (P = 0.018) and plasma PAI-1 activity decreased more (P = 0.021) 2 h after the high-phenol meal than after the low-phenol meal. FVIIa concentrations 120 min after intake of the olive oil with a high phenol content correlated positively with fasting plasma triacylglycerols (P = 0.001), area under the curve (AUC) of triacylglycerols (P = 0.001), and AUC of nonesterified fatty acids (P = 0.024) and negatively with hydroxytyrosol plasma concentrations at 60 min (P = 0.039) and fasting HDL-cholesterol concentrations (P = 0.005). PAI-1 positively correlated with homeostasis model assessment of insulin resistance (P = 0.005) and fasting triacylglycerols (P = 0.025) and inversely with adiponectin (P = 0.026). In a multivariate analysis, the AUCs of nonesterified fatty acids (R(2) = 0.467; beta: 0.787; SE: 0.02; P < 0.001) and adiponectin (R(2) = 0.232; beta: -1.594; SE: 0.629; P < 0.05) were the strongest predictors of plasma FVIIa and PAI-1, respectively. CONCLUSIONS A virgin olive oil with a high content of phenolic compounds changes the postprandial hemostatic profile to a less thrombogenic state.
Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection.

Whole-body protein metabolism was investigated in human immunodeficiency virus (HIV) infection by primed constant infusion of L-[1-13C]leucine in 8 control and 22 HIV-infected subjects (8 stage II; 14 stage IV disease), in postabsorptive and fed states. Postabsorptive leucine flux was increased 25% in subjects with stage IV HiV infection vs that in control subjects (130 +/- 13 vs 103 +/- 10 mumol leucine.kg-1.h-1, P < 0.001); both leucine disposal by protein synthesis (111.6 +/- 12.1 vs 82.3 +/- 9.2, P < 0.001) and release by protein degradation (129.7 +/- 13.1 vs 103.4 +/- 10.2, P < 0.001) were increased. No difference in leucine balance or oxidation was found but fat oxidation was greater in subjects with HIV infection (61.1 +/- 13.0% of energy) than in control subjects (47.6 +/- 13.7% of energy, P < 0.025). Stage II subjects had intermediate values of leucine flux, not significantly different from those of control subjects. Provision of parenteral nutrition for 4 h increased leucine flux with a switch in leucine balance from net loss to net gain; this response was quantitatively similar in all groups. HIV infection increases whole-body protein turnover but does not quantitatively impair the acute anabolic response to intravenous nutrition.
Three-Dimensional, Tomographic Super-Resolution Fluorescence Imaging of Serially Sectioned Thick Samples

Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 µm×50 µm×2.5 µm. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy.
New reference values for thyroid volume by ultrasound in iodine-sufficient schoolchildren: a World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group Report.

BACKGROUND Goiter prevalence in school-age children is an indicator of the severity of iodine deficiency disorders (IDDs) in a population. In areas of mild-to-moderate IDDs, measurement of thyroid volume (Tvol) by ultrasound is preferable to palpation for grading goiter, but interpretation requires reference criteria from iodine-sufficient children. OBJECTIVE The study aim was to establish international reference values for Tvol by ultrasound in 6-12-y-old children that could be used to define goiter in the context of IDD monitoring. DESIGN Tvol was measured by ultrasound in 6-12-y-old children living in areas of long-term iodine sufficiency in North and South America, central Europe, the eastern Mediterranean, Africa, and the western Pacific. Measurements were made by 2 experienced examiners using validated techniques. Data were log transformed, used to calculate percentiles on the basis of the Gaussian distribution, and then transformed back to the linear scale. Age- and body surface area (BSA)-specific 97th percentiles for Tvol were calculated for boys and girls. RESULTS The sample included 3529 children evenly divided between boys and girls at each year ( +/- SD age: 9.3 +/- 1.9 y). The range of median urinary iodine concentrations for the 6 study sites was 118-288 micro g/L. There were significant differences in age- and BSA-adjusted mean Tvols between sites, which suggests that population-specific references in countries with long-standing iodine sufficiency may be more accurate than is a single international reference. However, overall differences in age- and BSA-adjusted Tvols between sites were modest relative to the population and measurement variability, which supports the use of a single, site-independent set of references. CONCLUSION These new international reference values for Tvol by ultrasound can be used for goiter screening in the context of IDD monitoring.
Procedures in the 1st year of life for children with trisomy 13 and trisomy 18, a 25‐year, single‐center review

Care of the child born with trisomy 13 or 18 has evolved over the past few decades, leading to increased healthcare utilization. We hypothesized that there has been an increase in procedures across all intensity types, including major, invasive procedures. We performed a retrospective‐cohort study of children with trisomy 13 or 18 from 1990 to 2014 in a quaternary, free‐standing children's hospital. Children were identified using ICD‐9 billing diagnoses. Procedures were identified during these encounters and categorized by intensity (major, intermediate, or minor). One hundred thirty‐two children with trisomy 13 or 18 were identified. In children with trisomy 13, major procedures increased from period 1 (1990–1997) to period 3 (2006–2013) from 0.11 to 0.78 procedures per patient. For trisomy 18, the increase between the time periods was from 0.14 to 1.33 procedures per patient. By the end of the study period, nearly all trisomy 13 patients had a major procedure and the majority of those with trisomy 18 had undergone a major procedure. Estimated 1‐year survival for those with a major procedure was 30% and 22% for trisomies 13 and 18, respectively. In conclusion, there was an increasing rate of procedures per patient of all intensity levels over the 25‐year study period. Given differences in characteristics in those with trisomies 13 and 18, and effects of intervention on survival, an individualized approach to care of these patients should be employed by parents and healthcare providers, using factors such as trisomy type, infant gender, co‐morbidities, and parental preference. © 2016 Wiley Periodicals, Inc.
Cohort- and time-specific associations of CTLA4 genotypes with HIV-1 disease progression

Background:CTLA4 in the chromosome 2q33 region encodes cytotoxic T-lymphocyte (CTL) associated antigen 4, which downregulates CTL responses. We examined the relationships between common CTLA4 variants and several outcomes of HIV-1 infection in adults and adolescents. Methods:We studied 765 HIV-1-infected persons: 558 Caucasian seroconverters from three cohorts (MACS, ACS, and DCG) and 207 infected adolescents (mostly female) from another cohort (REACH) of mixed ethnicity. Single nucleotide polymorphisms in CTLA4 promoter (-1147C/T, -658C/T, -318C/T), coding sequence (49A/G) and the 3′ untranslated region (CT60A/G) were resolved by PCR-based techniques. Repeated measures and survival analyses were used to test allelic and haplotypic associations with HIV-1 viral load (VL) and time to AIDS, respectively. Results:Individuals carrying −318T or the (−1147) T-(−318) T haplotype had elevated HIV-1 VL in MACS and REACH but reduced VL in DCG and ACS participants. Time-dependent associations of CTLA4-318T with VL were observed in MACS and REACH (P = 0.03–0.09). In Cox regression models adjusted for age and established contributory markers in CCR5 and HLA class I genes, CTLA4-318T was associated with rapid progression to AIDS in MACS (relative hazard 1.69; 95% confidence interval, 1.15–2.49; P < 0.01) as opposed to a non-significant slower disease progression in ACS and no appreciable association in DCG. Conclusions:Association of CTLA4 genotypes with clinical and virological outcomes following HIV-1 infection appeared to vary with time and among the cohorts. Further analyses in conjunction with other biologically and positionally related genes, such as CD28 and ICOS, may help explain the disparate findings.
Adequate Intake levels of choline are sufficient for preventing elevations in serum markers of liver dysfunction in Mexican American men but are not optimal for minimizing plasma total homocysteine increases after a methionine load.

BACKGROUND An adequate intake of 550 mg choline/d was established for the prevention of liver dysfunction in men, as assessed by measuring serum alanine aminotransferase concentrations. OBJECTIVE This controlled feeding study investigated the influence of choline intakes ranging from 300 to 2200 mg/d on biomarkers of choline status. The effect of the methylenetetrahydrofolate reductase (MTHFR) C677T genotype on choline status was also examined. DESIGN Mexican American men (n = 60) with different MTHFR C677T genotypes (29 677TT, 31 677CC) consumed a diet providing 300 mg choline/d plus supplemental choline intakes of 0, 250, 800, or 1900 mg/d for total choline intakes of 300, 550, 1100, or 2200 mg/d, respectively, for 12 wk; 400 mug/d as dietary folate equivalents and 173 mg betaine/d were consumed throughout the study. RESULTS Choline intake affected the response of plasma free choline and betaine (time x choline, P < 0.001); the highest concentrations were observed in the 2200 mg/d group. Phosphatidylcholine (P = 0.026) and total cholesterol (P = 0.002) were also influenced by choline intake; diminished concentrations were observed in the 300 mg/d group. Phosphatidylcholine was modified by MTHFR genotype (P = 0.035; 677TT < 677CC). After a methionine load (100 mg/kg body wt), choline intakes of 1100 and 2200 mg/d attenuated (P = 0.016) the rise in plasma homocysteine, as did the MTHFR 677TT genotype (P < 0.001). Serum alanine aminotransferase was not influenced by the choline intakes administered in this study. CONCLUSIONS These data suggest that 550 mg choline/d is sufficient for preventing elevations in serum markers of liver dysfunction in this population under the conditions of this study; higher intakes may be needed to optimize other endpoints.
Fast Private Set Intersection from Homomorphic Encryption

Private Set Intersection (PSI) is a cryptographic technique that allows two parties to compute the intersection of their sets without revealing anything except the intersection. We use fully homomorphic encryption to construct a fast PSI protocol with a small communication overhead that works particularly well when one of the two sets is much smaller than the other, and is secure against semi-honest adversaries. The most computationally efficient PSI protocols have been constructed using tools such as hash functions and oblivious transfer, but a potential limitation with these approaches is the communication complexity, which scales linearly with the size of the larger set. This is of particular concern when performing PSI between a constrained device (cellphone) holding a small set, and a large service provider (e.g. WhatsApp), such as in the Private Contact Discovery application. Our protocol has communication complexity linear in the size of the smaller set, and logarithmic in the larger set. More precisely, if the set sizes are Ny < Nx, we achieve a communication overhead of O(Ny log Nx). Our running-time-optimized benchmarks show that it takes 36 seconds of online-computation, 71 seconds of non-interactive (receiver-independent) pre-processing, and only 12.5MB of round trip communication to intersect five thousand 32-bit strings with 16 million 32-bit strings. Compared to prior works, this is roughly a 38--115x reduction in communication with minimal difference in computational overhead.
Generalizability of the findings from a randomized controlled trial of a web‐based substance use disorder intervention

BACKGROUND AND OBJECTIVES There is growing concern regarding the generalizability of findings from randomized controlled trials (RCTs) of interventions for substance use disorders (SUDs). This study used a selection model approach to assess and improve the generalizability of an evaluation for a web-based SUD intervention by making the trial sample resemble the target population. METHODS The sample of the web-based SUD intervention (Therapeutic Education System vs. Treatment-as-usual; n = 507) was compared with the target population of SUD treatment-seeking individuals from the Treatment Episodes Data Set-Admissions (TEDS-A). Using weights based on the probabilities of RCT participation, we computed weighted treatment effects on retention and abstinence. RESULTS Substantial differences between the RCT sample and the target population was demonstrated in significant difference in the mean propensity scores (1.62 standard deviations at p < .001). The population effect on abstinence (12 weeks and 6 months) was statistically insignificant after weighting the data with the generalizability weight. DISCUSSIONS AND CONCLUSIONS Generalizability of the findings from the RCT could be limited when the RCT sample does not well represent the target population. SCIENTIFIC SIGNIFICANCE Application of generalizability weights can be a potentially useful tool to improve generalizability of RCT findings. (Am J Addict 2018;27:231-237).