69 research outputs found
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Competition between B-Z and B-L transitions in a single DNA molecule: Computational studies
Under negative torsion, DNA adopts left-handed helical forms, such as Z-DNA and L-DNA. Using the random copolymer model developed for a wormlike chain, we represent a single DNA molecule with structural heterogeneity as a helical chain consisting of monomers which can be characterized by different helical senses and pitches. By Monte Carlo simulation, where we take into account bending and twist fluctuations explicitly, we study sequence dependence of B-Z transitions under torsional stress and tension focusing on the interaction with B-L transitions. We consider core sequences, (GC)(n) repeats or (TG)(n) repeats, which can interconvert between the right-handed B form and the left-handed Z form, imbedded in a random sequence, which can convert to left-handed L form with different (tension dependent) helical pitch. We show that Z-DNA formation from the (GC)(n) sequence is always supported by unwinding torsional stress but Z-DNA formation from the (TG)(n) sequence, which are more costly to convert but numerous, can be strongly influenced by the quenched disorder in the surrounding random sequence.National Research Foundation NRF-2012 R1A1A3013044 NRF-2014R1A1A2055681NRF-2012R1A1A2021736IBS-R023-D1NRF-2015R1A2A2A01005916Chemistr
Human cell-camouflaged nanomagnetic scavengers restore immune homeostasis in a rodent model with bacteremia
Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here, scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs) are reported, which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. It is quantitatively revealed that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR) Escherichia coli, and extended-spectrum beta-lactamases-positive (ESBL-positive) E. coli, vancomycin-intermediate Staphylococcus aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within 7 days by treating them twice in series. It is also validated that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment
Effect of FIXed-dose combination of ARb and statin on adherence and risk factor control: The randomized FIXAR study
Background: The efficacy of fixed-dose combinations (FDCs) in improving adherence and risk factor control for cardiovascular disease has not been reported consistently. Here, we compared adherence and efficacy between an olmesartan/rosuvastatin FDC and the usual regimen.
Methods: In this 6-month, open-label, randomized, active-control study, we screened 154 patients; of these, 150 were randomly assigned to receive either olmesartan/rosuvastatin FDC or the usual regimen with separate angiotensin receptor blockers and statins. In total, 135 patients completed the study (median age: 68 years; male: 68.9%). The primary outcome was patients’ adherence; the secondary outcomes were changes in blood pressure (BP) and lipid parameters.
Results: During follow-up, adherence in both groups was high and similar between the groups (98.9% and 98.3% in the FDC and usual regimen groups, respectively, p = 0.328). Changes in systolic (–8 and –5 mmHg, respectively, p = 0.084) and diastolic BP (–5 and –2 mmHg, p = 0.092) did not differ significantly, although they were numerically greater in the FDC group. Changes in low-density lipoprotein cholesterol (LDL-C) were greater in the FDC group (–13 and –4 mg/dL, respectively, p = 0.019), whereas changes in other lipid parameters were similar between the groups. The test drugs were well tolerated, showing no difference in safety between the groups.
Conclusions: Patients’ adherence was excellent and similar in the groups, whereas the reduction in the LDL-C level was greater in the FDC group. We provide comprehensive information on the adherence and efficacy of an FDC compared to the usual regimen in Korean patients with high cardiovascular risk
Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012–2014
AbstractBackgroundThis study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3–18 year-old Korean children and adolescents.Materials and methodsWe used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012–2014 and identified 2388 children and adolescents aged 3–18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father’s education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times.ResultsThe median levels of blood lead and mercury, as well as urinary cadmium were 1.23μg/dL, 1.80μg/L, and 0.40μg/L (95% CIs, 1.21–1.25, 1.77–1.83, and 0.39–0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010.ConclusionSociodemographic factors, including age, sex, and father’s education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population
Automatically Harnessing Sparse Acceleration
Sparse linear algebra is central to many scientific programs, yet compilers
fail to optimize it well. High-performance libraries are available, but
adoption costs are significant. Moreover, libraries tie programs into
vendor-specific software and hardware ecosystems, creating non-portable code.
In this paper, we develop a new approach based on our specification Language
for implementers of Linear Algebra Computations (LiLAC). Rather than requiring
the application developer to (re)write every program for a given library, the
burden is shifted to a one-off description by the library implementer. The
LiLAC-enabled compiler uses this to insert appropriate library routines without
source code changes.
LiLAC provides automatic data marshaling, maintaining state between calls and
minimizing data transfers. Appropriate places for library insertion are
detected in compiler intermediate representation, independent of source
languages.
We evaluated on large-scale scientific applications written in FORTRAN;
standard C/C++ and FORTRAN benchmarks; and C++ graph analytics kernels. Across
heterogeneous platforms, applications and data sets we show speedups of
1.1 to over 10 without user intervention.Comment: Accepted to CC 202
Toward compiler-driven adaptive execution and its application to GPU architectures
A major shift in technology from maximizing single-core performance to integrating multiple cores has introduced a new, heterogeneous arena to high-performance computing communities. Among several new parallel platforms, hardware accelerators, such as General-Purpose Graphics Processing Units (GPGPUs), have emerged as promising alternatives for high-performance computing. While a GPGPU provides an inexpensive, highly parallel system to application developers, its programming complexity poses significant challenges for developers. This dissertation explores compile-time and runtime techniques to improve programmability and to enable adaptive execution of programs in such architectures. First, this dissertation examines the possibility of exploiting OpenMP shared memory programming model on stream architectures such as GPGPUs. This dissertation presents a compiler framework for automatic translation and optimization of standard OpenMP applications for executing on GPGPUs. Second, this dissertation studies runtime tuning systems to adapt applications dynamically. In preliminary work, an adaptive runtime tuning system with emphasis on parallel irregular applications has been proposed. Third, this dissertation focuses on creating an integrated framework where both the compiler framework and the tuning system are synergistically combined, such that compiler-translated GPGPU applications will be seamlessly adapted for the underlying system. For this goal, a new programming interface, called OpenMPC - OpenMP extended for CUDA, is proposed. OpenMPC provides an abstraction of the complex CUDA programming model and offers high-level control over the involved parameters and optimizations. We have developed a fully automatic compilation and user-assisted tuning system supporting OpenMPC. Experiments on various programs demonstrate that the proposed system achieves performance comparable to hand-coded CUDA programs
OpenMPC: Extended OpenMP Programming and Tuning for GPUs
General-Purpose Graphics Processing Units (GPGPUs) are promising parallel platforms for high performance computing. The CUDA (Compute Unified Device Architecture) programming model provides improved programmability for general computing on GPGPUs. However, its unique execution model and memory model still pose significant challenges for developers of efficient GPGPU code. This paper proposes a new programming interface, called OpenMPC, which builds on OpenMP to provide an abstraction of the complex CUDA programming model and offers high-level controls of the involved parameters and optimizations. We have developed a fully automatic compilation and user-assisted tuning system supporting OpenMPC. In addition to a range of compiler transformations and optimizations, the system includes tuning capabilities for generating, pruning, and navigating the search space of compilation variants. Our results demonstrate that OpenMPC offers both programmability and tunability. Our system achieves 88% of the performance of the hand-coded CUDA programs
OpenMPC: extended OpenMP for efficient programming and tuning on GPUs
General-purpose graphics processing units (GPGPUs) provide inexpensive, high performance platforms for compute-intensive applications. However, their programming complexity poses a significant challenge to developers. Even though the compute unified device architecture (CUDA) programming model offers better abstraction, developing efficient GPGPU code is still complex and error-prone. This paper proposes a directive-based, high-level programming model, called OpenMPC, which addresses both programmability and tunability issues on GPGPUs. We have developed a fully automatic compilation and user-assisted tuning system supporting OpenMPC. In addition to a range of compiler transformations and optimisations, the system includes tuning capabilities for generating, pruning, and navigating the search space of compilation variants. Evaluation using 14 applications shows that our system achieves 75% of the performance of the hand-coded CUDA programmes (92% if excluding one exceptional case)
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