Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysosomal Targeting and Trafficking of Acid Sphingomyelinase to Lipid Raft Platforms in Coronary Endothelial Cells

Objective—The purpose of this study was to determine whether lysosome trafficking and targeting of acid sphingomyelinase (ASMase) to this organelle contribute to the formation of lipid raft (LR) signaling platforms in the membrane of coronary arterial endothelial cells (CAECs). Methods and Results—By measurement of fluorescent resonance energy transfer (FRET), it was found that in FasL-stimulated CAECs, membrane lamp1 (a lysosome marker protein) or Fas and GM1 (a LR marker) were trafficking together. Cofocal colocalization assay showed that ceramide was enriched in these LR platforms. Further studies demonstrated that these ceramide molecules in LR platforms were colocalized with ASMase, a ceramide producing enzyme. Fluorescence imaging of living CAECs loaded with lysosomal specific dyes demonstrated that lysosomes fused with membrane on FasL stimulation. In the presence of lysosome function inhibitors, bafilomycin (Baf) or glycyl-l-phenylalanine-&bgr;-naphthylamide (GPN), these FasL-induced changes were abolished. Moreover, this FasL-induced formation of LR platforms was also blocked in ECs transfected with siRNA of sortilin, an intracellular transporter for targeting of ASMase to lysosomes. Functionally, FasL-induced impairment of vasodilator response was reversed by lysosomal inhibitors or sortilin gene silencing. Conclusions—Lysosomal trafficking and targeting of ASMase are importantly involved in LRs clustering in ECs membrane, leading to the formation of signaling platforms or signalosomes.
Cerebrospinal fl uid sphingolipids , b-amyloid , and tau in adults at risk for Alzheimer ’ s disease

Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Ab) and tau pathology but in vivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Ab1-42, AbX-38, AbX-40, and AbX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36e69 years, with a parental history of Alzheimer’s disease. The 18-carbon acyl chain length ceramide species was associated with AbX-38 (r 1⁄4 0.312, p 1⁄4 0.003), AbX-40 (r 1⁄4 0.327, p 1⁄4 0.002), and T-tau (r 1⁄4 0.313, p 1⁄4 0.003) but not with AbX-42 (r 1⁄4 0.171, p 1⁄4 0.106) or p-tau (r 1⁄4 0.086, p 1⁄4 0.418). All sphingomyelin species correlated (most p < 0.001) with all Ab species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest in vivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Ab and tau levels in cognitively normal individuals at increased risk for Alzheimer’s disease, indicating these sphingolipids may be associated with early pathogenesis. 2014 Elsevier Inc. All rights reserved.
Enabling accurate and efficient modeling-based CPU power estimation for smartphones

CPU is one of the most significant sources of power consumption on smartphones. Power modeling is a key technique and important tool for power estimation and management, both of which are critical for providing good QoS for smartphones. However, we find that existing CPU power models for smartphones are ill-suited for modern multicore CPUs: they can give high estimation errors (up to 34%) and high estimation accuracy variation (more than 30%) for different types of workloads on mainstream multicore smartphones. The cause is that the existing approaches do not appropriately consider the effects of CPU idle power states on smartphones CPU power modeling. Based on our extensive measurement experiments, we develop a new CPU power modeling approach that carefully considers the effects of CPU idle power states. We present the detailed design of our power modeling approach, and a prototype CPU power estimation system on commercial multicore smartphones. Evaluation results show that our approach consistently achieves higher power estimation accuracy and stability for various benchmarks programs and real apps than the existing approaches.
Hydrology and hillslope processes explain spatial variation in tree‐ring responses to the 1983 earthquake at Borah Peak, Idaho, USA

Dendrogeomorphic approaches have been used to identify tree‐ring responses to earthquakes, and have the potential to contribute new paleoseismic information. However, this potential is limited by the relatively low intensity of damage from earthquakes. In this paper, we present a comparison of tree‐ring responses in multiple species to the Mw 6.9 1983 Borah Peak, Idaho earthquake across three adjacent but distinct sites with different hydrologic settings, and different types and intensities of co‐seismic mass movement. We analyzed samples from 166 trees for a broad range of growth responses, including suppressions, releases, reaction wood, and traumatic resin ducts. The proportions of trees recording growth disturbances at the sites with clear hydrologic changes and/or co‐seismic mass movement were twice as high (39–42%) as the site where these processes were less evident (19%), and probability density functions of percentage change in growth for all crossdated trees echoed these results. Growth suppressions and reaction wood were common across sites, whereas traumatic resin ducts were only associated with rockfalls and landslides at one site. Growth releases were also primarily restricted to one site, and in contrast to previous studies, most of these probably reflected direct improvements in growing conditions via documented increased flow in springs and streams, rather than the indirect influence of reduced competition via the death of neighboring trees. These results highlight the importance of site selection in dendroseismology, and particularly suggest that focusing on sites with potential co‐seismic hydrologic changes and mass movement, sampling trees with and without external evidence of earthquake impacts, and understanding the connection between responses and site conditions may facilitate greater contributions of dendrogeomorphic approaches to paleoseismology. © 2018 John Wiley & Sons, Ltd.
Familiality and molecular genetics of attention networks in ADHD

Indices from a more elementary neuropsychological level might be useful in the search for genes for complex psychiatric disorders, such as ADHD. In this study we investigated systematically whether attentional performance as measured with the Attention Network Test (ANT) is suited for the identification of endophenotypes of ADHD. Attentional performance in affected sib pairs with ADHD (n = 181) was compared to unaffected control siblings (n = 121). Intrafamilial correlation patterns were calculated. In addition, linkage and association analyses were conducted between quantitative scores of attentional functions and dopamine receptor D4 (DRD4) and dopamine transporter (DAT1 or SLC6A3) gene variants. Only the executive attention network was significantly impaired in subjects with ADHD compared to controls (P < 0.05) and showed evidence for familiality in both affected and unaffected families. Linkage analyses revealed the highest LOD score for a severity score based on DSM‐IV inattentive symptoms in the DAT1 chromosomal region (LOD score 2.6 at 15 cM). However, a SNP (rs6350) at the DAT1 locus showed a tendency for association with both alerting performance (P = 0.02) and executive attention (P = 0.01) although it did not survive alpha adjustment for multiple testing. No evidence was found for association of any of the investigated phenotypes with the VNTR in the DRD4. Thus, our data suggest that the quantitative behavioral ratings of inattentive symptoms might be more useful when searching for new genes associated with ADHD, however, among the ANT measures the executive attention network seems to be best suited for further endophenotype analyses. © 2009 Wiley‐Liss, Inc.
Memory-efficient RNA energy landscape exploration

Motivation: Energy landscapes provide a valuable means for studying the folding dynamics of short RNA molecules in detail by modeling all possible structures and their transitions. Higher abstraction levels based on a macro-state decomposition of the landscape enable the study of larger systems; however, they are still restricted by huge memory requirements of exact approaches. Results: We present a highly parallelizable local enumeration scheme that enables the computation of exact macro-state transition models with highly reduced memory requirements. The approach is evaluated on RNA secondary structure landscapes using a gradient basin definition for macro-states. Furthermore, we demonstrate the need for exact transition models by comparing two barrier-based approaches, and perform a detailed investigation of gradient basins in RNA energy landscapes. Availability and implementation: Source code is part of the C++ Energy Landscape Library available at http://www.bioinf. uni-freiburg.de/Software/. Contact: mmann@informatik.uni-freiburg.de Supplementary information: Supplementary data are available at Bioinformatics online.
A comparison of continuous wavelet transform and modulus maxima analysis of characteristic ECG features

The continuous wavelet transform (CWT) offers a valuable tool for the analysis of signals as it provides precise location in time of high frequency components. The selection of a mother wavelet with high correlation with the signal under study provides a more accurate time-frequency analysis. Continuous wavelet transform modulus maxima (CWTMM) reduce the computational requirement by representing only the pertinent information contained within the scalogram obtained from continuous wavelet analysis. This new domain has an easy interpretation and offers a useful tool for the automatic characterization of the different components observed in the ECG in health and disease. The aim of this work was to compare the two time-frequency domains for ECG analysis: CWT and CWTMM, providing example applications of both methods
An Improved Array-Error Estimation Method for Constellation SAR Systems

In this letter, we consider the problem of estimating gain-phase and position errors for constellation synthetic aperture radar (SAR) systems. In the conventional method, the position error estimation is based on the first-order Taylor series expansion of the position-error exponential function. However, the first-order Taylor series expansion causes an approximation error, resulting in the inaccuracy of the estimation by the conventional method. In this letter, an improved method is developed to overcome this problem, based on the fact that the aforementioned approximation error decreases with the reduction in position errors. In the improved method, we first compensate the position error estimates obtained at the kth iteration in order to reduce the remaining position errors at the (k + 1) th iteration. Then, the position error estimates obtained at all iterations are summed as the estimates of the true position errors. In this way, the improved method removes the aforementioned approximation error, leading to estimates with high accuracy. Simulation results verify that the estimates by the improved method are closer to the true array errors than those by the conventional method. In addition, simulation results show that the improved method is more robust to position errors than the conventional method. Furthermore, the increase in the computational load of the improved method is negligible.
Solving online feasibility problem in constant amortized time per update

We present a deterministic algorithm for solving the two and three-dimensional online feasibility problem. Insertion of a new constraint is processed in constant amortized time. Our method is adapted from the offline linear deterministic Megiddo algorithm for linear programming. As in his prune and search technique, our method and its time bound extend to higher dimensions but involve the same large constant. Our online version that processes a feasibility problem achieves an optimal time bound relative to previous methods [2, 6, 8, 9]. As an application, it is well suited for the problem of digital object recognition.
Adopting an unconstrained ray model in light-field cameras for 3D shape reconstruction

Given the raising interest in light-field technology and the increasing availability of professional devices, a feasible and accurate calibration method is paramount to unleash practical applications. In this paper we propose to embrace a fully non-parametric model for the imaging and we show that it can be properly calibrated with little effort using a dense active target. This process produces a dense set of independent rays that cannot be directly used to produce a conventional image. However, they are an ideal tool for 3D reconstruction tasks, since they are highly redundant, very accurate and they cover a wide range of different baselines. The feasibility and convenience of the process and the accuracy of the obtained calibration are comprehensively evaluated through several experiments.
Aberrant Membranes and Double-Membrane Structures Accumulate in the Axons of Atg5-Null Purkinje Cells before Neuronal Death

Autophagy (macroautophagy) is an evolutionally conserved process by which cytoplasmic proteins and organelles are surrounded by unique double membranes and are subsequently degraded upon fusion with lysosomes. Many autophagy-related genes (Atg) have been identified in yeast; a ubiquitin-like Atg12-Atg5 system is also essential for the elongation of the isolation membrane in mammalian cells. Nevertheless, the regulation of autophagy in neurons remains largely unknown. In this study, we crossed conditional knockout mice Atg5flox/flox with pcp2-Cre transgenic mice, which express Cre recombinase through a Purkinje cell–specific promoter, pcp2. In Atg5flox/flox; pcp2-Cre mice, the Atg5 gene was excised as early as postnatal day 6; Purkinje cells started to degenerate after approximately 8 weeks, and the animals showed an ataxic gait from around 10 months. Initially, however, the Purkinje cells showed axonal swelling around its terminals from as early as 4 weeks after birth. An electron microscopic analysis revealed the accumulation of autophagosome-like double-membrane structures in the swollen regions, together with numerous membranous organelles, such as tubular or sheet-like smooth endoplasmic reticulum and vesicles. These results suggest that Atg5 plays important roles in the maintenance of axon morphology and membrane structures, and its loss of function leads to the swelling of axons, followed by progressive neurodegeneration in mammalian neurons.
Regularization of Body Core Temperature Prediction during Physical Activity

This paper deals with the prediction of body core temperature during physical activity in different environmental conditions using first-principles models and data-driven models. We argue that prediction of physiological variables through other correlated physiological variables using data-driven techniques is an ill-posed problem. To make predictions produced by data-driven models accurate and stable they need to be regularized. We demonstrate on data collected during laboratory study that data-driven models, if regularized properly, can outperform first-principles models in terms of accuracy of core temperature predictions. We also show that data-driven models can be made "portable" from one subject to another, thus, making them a valuable, practical tool when data from only one subject is available to "train" the model
A Common Haplotype on Methylenetetrahydrofolate Reductase Gene Modifies the Effect of Angiotensin-Converting Enzyme Inhibitor on Blood Pressure in Essential Hypertension Patients—A Family-Based Association Study

Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (ΔDBP and ΔSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of ΔDBP or ΔSBP. For residual of ΔDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of ΔSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.
Hybrid cache architecture replacing SRAM cache with future memory technology

Recently, hybrid cache architecture has become illuminated. As heterogeneous memory dies are stacked, it improves the performance of microprocessor enhanced in terms of power consumption and processing speed. This paper analyzed the hybrid cache architecture using different programs and memory types. SRAM is fixed for L1 cache memory, whereas DRAM, MRAM, and PRAM are the candidates for L2 cache memory. Each memory structure has the area satisfying the least Average Memory Access Time (AMAT) under a given area condition. Architecture composed of SRAM and MRAM shows 16.9% reduction in average memory access time and 15.2% of power reduction compared with that composed of homogeneous SRAM. Structure of SRAM and DRAM represents 33.0% reduction in power consumption, and that of SRAM and PRAM shows a potential to reduce area and power consumption due to their high density.
Two-dimensional bit-stuffing schemes with multiple transformers

We present bit-stuffing schemes which encode arbitrary data sequences into two-dimensional (2-D) constrained arrays. We consider the class of 2-D runlength-limited (RLL) (d, infin) constraints as well as the 'no isolated bits' (n.i.b.) constraint, both defined on the square lattice. The bit stuffing technique was previously introduced and applied to the class of 2-D (d, infin) constraints. Analytical lower bounds on the rate of these encoders were derived. For d = 1, a more general scheme was analyzed and shown to obtain improved performance. We extend the (1, infin)-construction to (d, infin) constraints where d ges 2. We then suggest a bit-stuffing scheme for the n.i. b. constraint, based on a capacity-achieving scheme for a one-dimensional RLL (0,3) constraint. Simulation results demonstrate the performance of the proposed schemes
Responder Feelings in a Three-Player Three-Option Ultimatum Game: Affective Determinants of Rejection Behavior

This paper addresses the role of affect and emotions in shaping the behavior of responders in the ultimatum game. A huge amount of research shows that players do not behave in an economically rational way in the ultimatum game, and emotional mechanisms have been proposed as a possible explanation. In particular, feelings of fairness, anger and envy are likely candidates as affective determinants. We introduce a three-player ultimatum game with three-options, which permits the responder to either penalize the proposer or to penalize a third party by rejecting offers. This allows for partially distinguishing rejections due to a retaliation motive driven by anger towards the proposer from rejections due to inequity aversion driven by feelings of envy towards a third party. Results from two experiments suggest that responders experience feelings of dissatisfaction and unfairness if their share is small in comparison to the proposer’s share; anger, then, may trigger rejections towards the proposer. Responders also experience dissatisfaction and envy when third party shares exceed their own shares; however, in contrast to anger, envy does not trigger rejections and is dissociated from the decision to accept or reject an offer. We conclude that acting upon anger is socially acceptable, whereas envy is not acceptable as a reason for action. Furthermore, we find that responders generally feel better after rejections, suggesting that rejections serve to regulate one’s affective state.
The Growth of Cognitive Modeling in Human-Computer Interaction Since GOMS

The purpose of this article is to review where we stand with regard to modeling the kind of cognition involved in human-computer interaction. Card, Moran, and Newell's pioneering work on cognitive engineering models and explicit analyses of the knowledge people need to perform a procedure was a significant advance from the kind of modeling cognitive psychology offered at the time. Since then, coordinated bodies of research have both confirmed the basic set of parameters and advanced the number of parameters that account for the time of certain component activities. Formal modeling in grammars and production systems has provided an account for error production in some cases, as well as a basis for calculating how long a system will take to learn and how much savings there is from previous learning. Recently, we were given a new tool for modeling nonsequential component processes, adapting the "critical path analysis" from engineering to the specification of interacting processes and their consequent durations. Though these advances have helped, there are still significant gaps in our understanding of the whole process of interacting with computers. The cumulative nature of this empirical body and its associated modeling framework has further highlighted important issues central to research in cognitive psychology: how people move smoothly between skilled performance and problem solving, how people learn, how to design for consistent user interfaces, how people produce and manage errors, how we interpret visual displays for meaning, and what processes run concurrently and which depend on the completion of prior processes. In the bigger picture, cognitive modeling is a method that is useful in both initial design (it can narrow the design space and provide early analyses of design alternatives), evaluation, and training. But it does not extend to broader aspects of the context in which people use computers, partly because there are significant gaps in contemporary cognitive theory to inform the modeling and partly because it is the wrong form of model for certain kinds of more global questions in human-computer interaction. Notably, it fails to capture the user's fatigue, individual differences, or mental workload. And it is not the type of model that will aid the designer in designating the set of functions the software ought to contain, to assess the user's judgment of the acceptability of the software, or the change that could be expected in work life and the organization in which this work and person fits. Clearly, these kinds of considerations require modeling and tools of a different granularity and form.