Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic invalidation of Lp-PLA2 as a therapeutic target: Large-scale study of five functional Lp-PLA2-lowering alleles

Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA2 enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA2. We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA2 activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA2-lowering alleles. Results Lp-PLA2 activity was decreased by 64% (p = 2.4 × 10–25) with carriage of any of the four loss-of-function variants, by 45% (p < 10–300) for every allele inherited at Val279Phe, and by 2.7% (p = 1.9 × 10–12) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA2 activity by 65% (p < 10–300). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA2 activity were: 0.95 (0.88–1.03) with Val279Phe; 0.92 (0.74–1.16) with carriage of any loss-of-function variant; 1.01 (0.68–1.51) with Val379Ala; and 0.95 (0.89–1.02) with darapladib treatment. Conclusions In a large-scale human genetic study, none of a series of Lp-PLA2-lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA2 is unlikely to be a causal risk factor.
Lymphatic vessel diameter in female pelvic cancer‐related lower extremity lymphedematous limbs

Lymphaticovenular anastomosis (LVA) has become one of the useful surgical treatments for compression‐refractory lower extremity lymphedema (LEL). It is important to anastomose larger lymphatic vessels with abundant lymph flows in LVA surgery. This study aimed to clarify factors associated with lymphatic vessel diameter.
Different times of day do not change heart rate variability recovery after light exercise in sedentary subjects: 24 hours Holter monitoring

ABSTRACT Incidence of cardiovascular events follows a circadian rhythm with peak occurrence during morning. Disturbance of autonomic control caused by exercise had raised the question of the safety in morning exercise and its recovery. Furthermore, we sought to investigate whether light aerobic exercise performed at night would increase HR and decrease HRV during sleep. Therefore, the aim of this study was to test the hypothesis that morning exercise would delay HR and HRV recovery after light aerobic exercise, additionally, we tested the impact of late night light aerobic exercise on HR and HRV during sleep in sedentary subjects. Nine sedentary healthy men (age 24 ± 3 yr; height 180 ± 5 cm; weight 79 ± 8 kg; fat 12 ± 3%; mean±SD) performed 35 min of cycling exercise, at an intensity of first anaerobic threshold, at three times of day (7 a.m., 2 p.m. and 11 p.m.). R-R intervals were recorded during exercise and during short-time (60 min) and long-time recovery (24 hours) after cycling exercise. Exercise evoked increase in HR and decrease in HRV, and different times of day did not change the magnitude (p < 0.05 for time). Morning exercise did not delay exercise recovery, HR was similar to rest after 15 minutes recovery and HRV was similar to rest after 30 minutes recovery at morning, afternoon, and night. Low frequency power (LF) in normalized unites (n.u.) decreased during recovery when compared to exercise, but was still above resting values after 60 minutes of recovery. High frequency power (HF-n.u.) increased after exercise cessation (p < 0.05 for time) and was still below resting values after 60 minutes of recovery. The LF/HF ratio decreased after exercise cessation (p < 0.05 for time), but was still different to baseline levels after 60 minutes of recovery. In conclusion, morning exercise did not delay HR and HRV recovery after light aerobic cycling exercise in sedentary subjects. Additionally, exercise performed in the night did change autonomic control during the sleep. So, it seems that sedentary subjects can engage physical activity at any time of day without higher risk.
Incidence Of The Oxygen Plateau at VO2max During Exercise Testing To Volitional Fatigue

The purpose of this study was to better clarify the VO2 response to exercise to VO2max by comparing data derived from different time averaging intervals and exercise protocols. Sixteen active subjects (12 men and 4 women, mean age, height, weight, and VO2max = 31.6±8.9 yr, 172.0±6.6 cm, 70.8±12.7 kg, 3,212±652 mL/min) completed three different VO2max tests on a cycle ergometer (a 25 Watt/min ramp protocol (R), a 75 Watt/3 min step protocol (S), and a 25 Watt/min ramp protocol (H) under hypoxic conditions (FIO2 = 15%, P B = 635 mm Hg) on separate days. During each test, subjects breathed humidified air from a Tissot tank, and breath-by-breath gas exchange was obtained by a Medical Graphics metabolic cart. All breath-by-breath data were smoothed using an 11-breath moving average. These data were then time-averaged into 15, 30, and 60 s sampling intervals. Criteria for attainment of VO 2max included two of the following: RER ≥ 1.1, maximal heart rate (HR) within 10 b/min of the calculated value, or an O2 plateau (ΔVO2 ≤ 50 mL/min) with an increase in power output. Average VO2max was significantly lower (F (2, 30) = 84.37, p < . 001) for the H (2,532±562 mL/min) compared to the S (3,112±660 mL/min) and R (3,212±651 mL/min) protocols. Average maximal RER was significantly different (F (2, 30) = 3.77, p < . 05) across protocols, however no differences were exhibited between means. Average HR at VO2max was significantly lower (F (2, 30) = 12.26, p < . 001) during the H trial (169±13 b/min) compared to the R (176±9 b/min) and S (178±9 b/min) protocols. The incidence at which subjects demonstrated a plateau in VO2 for all protocols combined were 100, 100, 57 and 8% for the 11 breath, 15 s, 30 s and 1 min averaging, respectively. Data of the change in VO2 between VO2max and the closest neighboring data point revealed that variability was greatest for the longer time averaged data. This response was similar for each protocol. These findings show that shorter sampling intervals (breath-by-breath and 15 s) are most suitable for the detection of the VO2 plateau during progressive exercise to VO 2max. In addition, ramp and step protocols produce similar results, and acute normobaric hypoxia does not decrease the incidence of a VO2 plateau at VO2max using 11 breath or 15 s time averaging procedures.
The Impact of Strong for Life on the Physical Functioning and Health of Older Adults Receiving Home and Community-Based Services.

BACKGROUND/OBJECTIVES To test the effects of Strong for Life (SFL) on the physical performance and self-rated health of older adults receiving Home and Community-Based Services (HCBS). DESIGN Randomized, two-group trial with pre-post measures. SETTING In-home exercise program. PARTICIPANTS Clients aged 65-95 (n=42) and their Home Care Aide (HCA) (n=32) were randomly assigned to a usual care and SFL intervention or usual care control group. INTERVENTION Clients were instructed in SFL by their HCA and completed SFL 3 times per week for 12-weeks. MEASUREMENTS Outcomes included grip and quadriceps strength, Timed Up and Go, gait speed, Self-Efficacy for Exercise, pain, and PROMIS-global health measured at baseline and immediately following the intervention. Clients completed opened ended survey items on SFL program evaluation. RESULTS Effect sizes were moderate for grip strength (d= .38), pain (d= .34), and PROMIS-global health (d= .27). Small effect sizes were found for all other measures. Median quadriceps and TUG scores differentially improved among intervention participants versus controls. No adverse health events and high program satisfaction were reported. Frailty prevalence in the control group increased between baseline and post-test while frailty prevalence in the intervention group decreased during the same time period. CONCLUSION Strong for Life has the potential to improve the strength, mobility, health, and frailty of older adults receiving HCBS. This study provides initial evidence of the impact of SFL for older adults receiving HCBS, as well as the safety of the intervention evidenced by the lack of reported adverse events.
Monocrystalline iron oxide nanocompounds (MION): Physicochemical properties

We have previously described a novel monocrystalline iron oxide nanocompound (MION), a stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using a variety of analytical techniques. High resolution electron microscopy indicates that a MION consists of hexagonal shaped electron‐dense cores of 4.6 ± 1.2 nm in diameter. This iron oxide core has an inverse spinel crystal structure which was confirmed by x‐ray powder diffraction. Chemical analysis showed that each core has 25 ± 6 dextran molecules (10 kD) attached, resulting in a unimodal hydrodynamic radius of 20 nm by laser light scattering. Because of the flexibillity of the dextran layer, the radius is only 8 nm in nonaqueous reverse micelles. At room temperature, MION exhibit superparamagnetic behavior with an induced magnetization of 68 emu/g Fe at 1.5 T. Mössbauer studies show that the saturation internal magnetic field is 505 KOe, and blocking temperature is at 100 K. The R1 relaxivity of MION is 16.5 (mM‐sec)‐1 and the R2 relaxivity is 34.8 (mM‐sec)‐1 in aqueous solution at 37°C and 0.47 T. In vitro phantom studies show that the detectability of MION in liver tissue is less than 50 nmol Fe/g tissue using gradient echo imaging techniques.
1 Determinants and quasinormal modes

We derive an expression for functional determinants in thermal spacetimes as a product over the corresponding quasinormal modes. As simple applications we give efficient computations of scalar determinants in thermal AdS, BTZ black hole and de Sitter spacetimes. We emphasize the conceptual utility of our formula for discussing ‘1/N ’ corrections to strongly coupled field theories via the holographic correspondence. 1 Determinants and quasinormal modes In a semiclassical quantisation of gravity the partition function can be written schematically as Z = ∑ g⋆ det ( −∇2g⋆ )±1 e−SE [g⋆] . (1) Here g⋆ are saddle points of the Euclidean gravitational action SE. We use g⋆ to collectively denote the metric and any other nonzero fields. The det ( −∇g⋆ ) term schematically denotes the product of determinants of all the operators controlling fluctuations about the background solution g⋆. As usual, the determinants appear on the numerator or denominator depending on whether the fluctuations are fermionic or bosonic respectively. This formula is readily generalised to correlators of operators by including appropriate sources in the gravitational action. Originally developed with a view to elucidating quantum gravitational effects in our universe [1], the semiclassical approach to quantum gravity has gained a new lease of life through the holographic correspondence [2, 3]. This is because the semiclassical limit in gravity corresponds to the large N limit of a dual gauge theory. Almost all works have restricted attention to the leading order large N result, the exponent in (1). Exceptions to this last statement include [4, 5, 6, 7] who studied an effect due to the determinant term in pure Anti-de Sitter space. In our recent paper [8] we have stressed the fact that the semiclassical determinant term in (1), a 1/N# correction, will be important in the framework of ‘applied holography’. This is the case because there are interesting effects, in for instance thermodynamics and transport, which are either entirely absent at leading order or else swamped by physical processes that are not those of prime relevance. In general it is technically challenging to compute determinants in nontrivial background spacetimes. Even when the Euclidean saddles are homogeneous the calculation can be involved. For example, [9] computed the gravitational determinant on S2 × S2 to obtain the semiclassical rate of nucleation of black holes in de Sitter spacetime. For most cases of interest, often black hole spacetimes, the eigenvalues of the fluctuation operator cannot be determined explicitly and an evaluation of the determinant is difficult without resort to WKB or other approximations (although see for instance [10] and citations thereof). In this paper we present and derive a formula for determinants in black hole backgrounds, indeed finite temperature spacetimes more generally, in terms of the quasinormal modes of the spacetime. For (complex) bosonic fields the expression appears in section 3, equation (40), and takes the form 1 det ( −∇g⋆ ) = e ∏
Evaluation of Multi-Core Programming Models

With the advent of multi-core processing in personal computing systems, the demand for concurrent software has increased far beyond its original niche. The conventional model of lock-based concurrency for writing such software is di cult in use, error-prone and does not always lead to e cient use of the available resources. In this paper we shall evaluate several alternative models, namely the Actor Model, the Join-Calculus, Software Transactional Memory and Runtime Scheduling and compare them to the conventional one, to determine whether they provide superior means of writing concurrent software.
Biological and clinical implications of telomere dysfunction in myeloid malignancies

Telomeres at the ends of linear chromosomes protect the genome. Telomeres shorten with each round of cell division, placing a finite limit on cell growth. Telomere attrition is associated with cell senescence and apoptosis. Telomerase, a specialized ribonucleoprotein complex, maintains telomeres homeostasis through repeat addition of telomere sequences to the 3′ telomeric overhang. Telomere biology is closely related to cancer and normal aging. Upregulation of telomerase or activation of the alternative pathway of telomere lengthening is a hallmark of cancer cells, making telomerase an attractive target for cancer therapeutics. In this review, we will discuss telomere biology and the prognostic implications of telomere length in acute myeloid leukemia, and review exciting new investigational approaches using telomerase inhibitors in acute myeloid leukemia and other myeloid malignancies.
Comparison of a Population-Based Sample of “Risky Drinking” Smokers and Groups Consuming Just One Substance

This population-based study compares a group of “risky drinking” smokers (n = 137) with groups of either smokers (n = 760) or “risky drinkers” (n = 173) regarding sociodemographic, behavioral and motivational variables. The study took place in a rural and urban region of Germany in 1997. No differences were found in sociodemographics, nicotine-related variables, frequency of alcohol consumption, and most alcohol-related diagnoses. People who drink and smoke show a higher proportion of alcohol dependence (ES: h =. 20), drink more alcohol per occasion (ES: d =. 39), and are more motivated to decrease alcohol consumption (ES: h =. 45). The data suggest focusing research in more alcohol-related clinical settings and examining the relationship between smoking cessation and alcohol reduction.
Proteome‐wide analysis of the serological response to vaccinia and smallpox

The eradication of smallpox by vaccination with vaccinia virus was probably one of the greatest achievements of vaccinology. However, the immunological basis of this protection is not fully understood. To this end, we have used protein microarrays of the vaccinia (Western Reserve, WR) proteome to profile antibody reactivities after primary infection or boosting with the licensed smallpox vaccine, Dryvax®, and with archival convalescent smallpox sera. Some 25 antigens were consistently recognized by Dryvax® sera, of which half were envelope proteins (notably, H3, A13, B5, and D8). The remainder consisted mainly of core proteins (e.g. A10, L4, and I1), proteins involved in intracellular morphogenesis (A11, D13), and the A‐type inclusion protein, WR148. Convalescent smallpox sera also detected vaccinia antigens on the array, consistent with the notion that there is serological cross‐reactivity between these two orthopox species that underlies protection. Moreover, the profiles of immunodominant antigens recognized by variola‐infected individuals and Dryvax® vaccinees were indistinguishable. This is the first description of antibody‐specificity profiles induced after smallpox infection. The array data indicate that a significant component of the antibody response is not involved in virus neutralization, although these antigens should be considered alongside the envelope proteins as potential candidates for diagnostic and vaccine applications.
Relationships between Objective Assessment of Ligament Stability and Subjective Assessment of Symptoms and Function after Anterior Cruciate Ligament Reconstruction

Background Relationships between objective assessment of ligament stability and subjective assessment of symptoms and function after anterior cruciate ligament reconstruction have not been established. Hypothesis Relationships exist between objective and subjective assessments after anterior cruciate ligament reconstruction. Study Design Case series. Methods Patients (N = 202) undergoing anterior cruciate ligament reconstruction with 2-year minimum follow-up were studied. Objective variables of ligament stability at follow-up included instrumented laxity, Lachman examination, and pivot-shift examination. Subjective variables of symptoms at follow-up included pain, swelling, giving way, locking, crepitus, stiffness, and limping. Subjective function at follow-up included walking, squatting, stair climbing, running, cutting, jumping, twisting, activity limitation, sports level, activities of daily living level, work level, knee function, sports participation, Lysholm score, and satisfaction withoutcome. Results Instrumented knee laxity and Lachman examination had no significant (P> .05) relationships with any subjective variables of symptoms and function. Pivot-shift examination had significant associations with satisfaction (P= .03), partial giving way (P= .01), full giving way (P= .01), difficulty cutting (P= .01), difficulty twisting (P= .01), activity limitation (P= .01), overall knee function (P= .03), sports participation (P= .02), and Lysholm score (P= .01). Conclusions The pivot-shift examination may be a better measure of “functional instability” than instrumented knee laxity or Lachman examination after anterior cruciate ligament reconstruction.
Human activity recognition using neural networks

This paper presents research made for independent daily life assistance of elderly or persons with disabilities using IoT technologies. Our scope is to develop a system that allows living for as long as possible in familiar environment. This will be possible by wider spread of assistive technologies and the internet of things (IoT). We aim to bring together latest achievements in domain of Internet of things and assistive technologies in order to develop a complex assistive system with adaptive capability and learning behavior. We can use IoT technologies to monitor in real time the state of a patient or to get sensitive data in order to be subsequently analyzed for a medical diagnosis. We present the state of our work related to the development of an assistive assembly consisting of a smart and assistive environment, a human activity and health monitoring system, an assistive and telepresence robot, together with the related components and cloud services.
Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet.

Article de synthese sur la regulation de la transcription des genes qui codent les molecules de classe II: regulation de l'expression de ces molecules dans les lymphocytes B et T, les macrophages, les autres cellules qui presentent l'antigene, et dans quelques cellules de divers types dans differents tissus; description des sequences d'ADN impliquees dans l'activite du promoteur de transcription et des sequences activatrices en amont; description des proteines regulatrices qui reagissent avec ces elements d'ADN
Single Server Queueing-Location Models with Rejection

This paper considers the problem of locating a single server on a network while explicitly accounting for queueing of calls for service. Calls from a node can either all be accepted or all be rejected by the service system. Two models are considered. In the first model a call can be rejected independent of the state of the system when the call arrives. In the second model, an arriving call can be rejected only if it finds the server busy. The queueing systems are analyzed for both models. A greedy heuristic is developed which, parametrically in the arrival rate of calls, determines the location of the server and the rejection strategies at nodes. Extreme case analysis with respect to the arrival rate is investigated. A numerical example illustrates our results. Our major observation is that the rejection strategies for calls are dependent on the arrival rate, and the choice of model.
A Society of Devices: Integrating Intelligent Distributed Resources with Transactive Energy

Secure, Clean, and Efficient Energy is one of the great societal challenges of our time. Electricity as a sustainable energy carrier plays a central role in the most effective transition scenarios toward sustainability. To harness this potential, the current electricity infrastructure needs to be rigorously re-engineered into an integrated and intelligent electricity system: the smart grid. Key elements of the smart grid vision are the coordination mechanisms. In such a system, vast numbers of devices, currently just passively connected to the grid, will become actively involved in system-wide and local coordination tasks. In this light, transactive energy (TE ) is emerging as a strong contender for orchestrating the coordinated operation of so many devices.
Comparison of a Linear and a Hybrid Adaptive Cruise Controller for a S MART Daniele Corona and

An adaptive cruise controller (ACC) is a device used in modern automotive applications that aims to achieve the tracking of a leading vehicle, allowing safety, comfort driving and overall improvement of traffic streams. Through appropriate modeling and design it permits also to address other tasks such as energy saving, environmental protection and reduction of the mechanical stress. For a type of small car, a SMART, we propose the design of an ACC using control methods based on tuned proportional-integral (PI) action and on model predictive control (MPC), developed for linear and piecewise affine (PWA) systems. We implement these controllers and compare the main properties and strong/weak points of each method, collecting the comparison keys in a table. The trade-off between complexity and accuracy of the solutions is also discussed.
Ultra-wideband components using a microstrip-to-CPS balun

Various types of ultra-wideband components with 10's of GHz bandwidth have been developed utilizing a uniplanar ultra-wideband balun, which is a simple microstrip-to-coplanar stripline (CPS) transition structure with the operating frequency range from near DC to over 40 GHz. Developed ultra-wideband components include antennas, mixers, doublers and detectors in a carrier type or in a surface mountable type. These high-performance, low-cost ultra-wideband components may replace expensive conventional components, and also can be used to develop new multi-GHz UWB application areas.