Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel KCNJ2 Nonsense Mutation, S369X, Impedes Trafficking and Causes a Limited Form of Andersen-Tawil Syndrome

Background— Mutations in KCNJ2, a gene encoding the inward rectifier K+ channel Kir2.1, are associated with Andersen-Tawil syndrome (ATS), which is characterized by (1) ventricular tachyarrhythmias associated with QT (QU)-interval prolongation, (2) periodic paralysis, and (3) dysmorphic features. Methods and Results— We identified a novel KCNJ2 mutation, S369X, in a 13-year-old boy with prominent QU-interval prolongation and mild periodic paralysis. The mutation results in the truncation at the middle of the cytoplasmic C-terminal domain that eliminates the endoplasmic reticulum (ER)-to-Golgi export signal. Current recordings from Chinese hamster ovary cells transfected with KCNJ2-S369X exhibited significantly smaller K+ currents compared with KCNJ2 wild type (WT) (1 &mgr;g each) (−84±14 versus −542±46 picoamperes per picofarad [pA/pF]; −140 mV; P<0.0001). Coexpression of the WT and S369X subunits did not show a dominant-negative suppression effect but yielded larger currents than those of WT+S369X (−724±98 pA/pF>−[84+542] pA/pF; 1 &mgr;g each; −140 mV). Confocal microscopy analysis showed that the fluorescent protein-tagged S369X subunits were predominantly retained in the ER when expressed alone; however, the expression of S369X subunits to the plasma membrane was partially restored when coexpressed with WT. Fluorescence resonance energy transfer analysis demonstrated direct protein-protein interactions between WT and S369X subunits in the intracellular compartment. Conclusions— The S369X mutation causes a loss of the ER export motif. However, the trafficking deficiency can be partially rescued by directly assembling with the WT protein, resulting in a limited restoration of plasma membrane localization and channel function. This alleviation may explain why our patient presented with a relatively mild ATS phenotype.
Molecular Sciences Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male Sterile Lines Genotypes under Cold Stress

Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei'ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the OPEN ACCESS Int. 11399 Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress.
Perceptually-Driven Simplification for Interactive Rendering

We present a framework for accelerating interactive rendering, grounded in psychophysical models of visual perception. This framework is applicable to multiresolution rendering techniques that use a hierarchy of local simplification operations. Our method drives those local operations directly by perceptual metrics; the effect of each simplification on the final image is considered in terms of the contrast the operation will induce in the image and the spatial frequency of the resulting change. A simple and conservative perceptual model determines under what conditions the simplification operation will be perceptible, enabling imperceptible simplification in which operations are performed only when judged imperceptible. Alternatively, simplifications may be ordered according to their perceptibility, providing a principled approach to best-effort rendering. We demonstrate this framework applied to view-dependent polygonal simplification. Our approach addresses many interesting topics in the acceleration of interactive rendering, including imperceptible simplification, silhouette preservation, and gaze-directed rendering.
Evaluation of Germline BMP4 Mutation as a Cause of Colorectal Cancer

Transforming growth factor‐â (TGF‐â) signalling plays a key role in colorectal cancer (CRC). Bone morphogenetic protein‐4 (BMP4) is a member of the TGF‐â family of signal transduction molecules. To examine if germline mutation in BMP4 causes CRC we analysed 504 genetically enriched CRC cases (by virtue of early‐onset disease, family history of CRC) for mutations in the coding sequence of BMP4. We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N‐terminal of the TGF‐â1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function. Segregation of p.C373S with adenoma and hyperplastic polyp in first‐degree relatives of the case suggests germline mutations may confer a juvenile polyposis‐type phenotype. These findings suggest mutation of BMP4is a cause of CRC and the value of protein‐based modelling in the elucidation of rare disease‐causing variants. © 2010 Wiley‐Liss, Inc.
Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the “old” second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and β-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.
Optimal image alignment with random measurements

We consider the problem of image alignment using random measurements. More specifically, this paper is concerned with estimating a transformation that aligns a given reference image with a query image, assuming that not the images themselves but only random measurements are available. According to the theory behind compressed sensing, random projections of signal manifolds nearly preserve pairwise Euclidean distances when the reduced space is sufficiently large. This suggests that image alignment can be performed effectively based on a sufficient number of random measurements. We build on our previous work in order to show that the corresponding objective function can be decomposed as the difference of two convex functions (DC). Thus, the optimization problem becomes equivalent to a DC program that can be solved by an outer-approximation cutting plane method, which always converges to the globally optimal solution.
Delving into internet streaming media delivery: a quality and resource utilization perspective

Modern Internet streaming services have utilized various techniques to improve the quality of streaming media delivery. Despite the characterization of media access patterns and user behaviors in many measurement studies, few studies have focused on the streaming techniques themselves, particularly on the quality of streaming experiences they offer end users and on the resources of the media systems that they consume. In order to gain insights into current streaming services techniques and thus provide guidance on designing resource-efficient and high quality streaming media systems, we have collected a large streaming media workload from thousands of broadband home users and business users hosted by a major ISP, and analyzed the most commonly used streaming techniques such as automatic protocol switch, Fast Streaming, MBR encoding and rate adaptation. Our measurement and analysis results show that with these techniques, current streaming systems these techniques tend to over-utilize CPU and bandwidth resources to provide better services to end users, which may not be a desirable and effective is not necessary the best way to improve the quality of streaming media delivery. Motivated by these results, we propose and evaluate a coordination mechanism that effectively takes advantage of both Fast Streaming and rate adaptation to better utilize the server and Internet resources for streaming quality improvement.
METAHEURISTIC APPROACH FOR THE MULTI-DEPOT VEHICLE ROUTING PROBLEM

Distribution logistics comprises all activities related to the provision of finished products and merchandise to a customer. The focal point of distribution logistics is the shipment of goods from the manufacturer to the consumer. The products can be delivered to a customer directly either from the production facility or from the trader's stock located close to the production site or, probably, via additional regional distribution warehouses. These kinds of distribution logistics are mathematically represented as a vehicle routing problem (VRP), a well-known nondeterministic polynomial time (NP)-hard problem of operations research. VRP is more suited for applications having one warehouse. In reality, however, many companies and industries possess more than one distribution warehouse. These kinds of problems can be solved with an extension of VRP called multi-depot VRP (MDVRP). MDVRP is an NP-hard and combinatorial optimization problem. MDVRP is an important and challenging problem in logistics management. It can be solved using a search algorithm or metaheuristic and can be viewed as searching for the best element in a set of discrete items. In this article, cluster first and route second methodology is adapted and metaheuristics genetic algorithms (GA) and particle swarm optimization (PSO) are used to solve MDVRP. A hybrid particle swarm optimization (HPSO) for solving MDVRP is also proposed. In HPSO, the initial particles are generated based on the k-means clustering and nearest neighbor heuristic (NNH). The particles are decoded into clusters and multiple routes are generated within the clusters. The 2-opt local search heuristic is used for optimizing the routes obtained; then the results are compared with GA and PSO for randomly generated problem instances. The home delivery pharmacy program and waste-collection problem are considered as case studies in this paper. The algorithm is implemented using MATLAB 7.0. 1.
Evaluating machine learning algorithms for automated network application identification

The identification of network applications that create traffic flows is vital to the areas of network management and surveillance. Current popular methods such as port number and payload-based identification are inadequate and exhibit a number of shortfalls. A potential solution is the use of machine learning techniques to identify network applications based on payload independent statistical features. In this paper we evaluate and compare the efficiency and performance of different feature selection and machine learning techniques based on flow data obtained from a number of public traffic traces. We also provide insights into which flow features are the most useful. Furthermore, we investigate the influence of other factors such as flow timeout and size of the training data set. We find significant performance differences between different algorithms and identify several algorithms that provide accurate (up to 99% accuracy) and fast classification. Keywords—Traffic Classification, Machine Learning, Statistical Features I. INTRODUCTION There is a growing need for accurate and timely classification of network traffic flows for purposes such as trend analyses (estimating capacity demand trends for network planning), adaptive, network-based QoS marking of traffic, dynamic access control (adaptive firewalls that detect forbidden applications or attacks) or lawful interception. 'Classification' refers to the identification of an application or group of applications responsible for a traffic flow. Port-based classification is still widely practiced despite being only moderately accurate at best. It is expected to become less effective in the near future due to an ever-increasing number of network applications, extensive use of network address translation (NAT), dynamic port allocation and end-users deliberately choosing non-default ports. For example a large amount of peer-to-peer (p2p) file sharing traffic is found on non- default ports (1). Alternative solutions such as payload- based classification rely on specific application data (protocol decoding or signatures), making it difficult to
Guiding Revision of Regulatory Models with Expression Data

BioLingua is a computational system designed to support biologists' efforts to construct models, make predictions, and interpret data. In this paper, we focus on the specific task of revising an initial model of gene regulation based on expression levels from gene microarrays. We describe BioLingua's formalism for representing process models, its method for predicting qualitative correlations from such models, and its use of data to constrain search through the space of revised models. We also report experimental results on revising a model of photosynthetic regulation in Cyanobacteria to better fit expression data for both wild and mutant strains, along with model mutilation studies designed to test our method's robustness. In closing, we discuss related work on representing, discovering, and revising biological models, after which we propose some directions for future research.
Sensor modeling and demonstration of a multi-object spectrometer for performance-driven sensing

A novel multi-object spectrometer (MOS) is being explored for use as an adaptive performance-driven sensor that tracks moving targets. Developed originally for astronomical applications, the instrument utilizes an array of micromirrors to reflect light to a panchromatic imaging array. When an object of interest is detected the individual micromirrors imaging the object are tilted to reflect the light to a spectrometer to collect a full spectrum. This paper will present example sensor performance from empirical data collected in laboratory experiments, as well as our approach in designing optical and radiometric models of the MOS channels and the micromirror array. Simulation of moving vehicles in a highfidelity, hyperspectral scene is used to generate a dynamic video input for the adaptive sensor. Performance-driven algorithms for feature-aided target tracking and modality selection exploit multiple electromagnetic observables to track moving vehicle targets.
Does that look heavy to you? Perceived weight judgment in lifting actions in younger and older adults

When interpreting other people's movements or actions, observers may not only rely on the visual cues available in the observed movement, but they may also be able to “put themselves in the other person's shoes” by engaging brain systems involved in both “mentalizing” and motor simulation. The ageing process brings changes in both perceptual and motor abilities, yet little is known about how these changes may affect the ability to accurately interpret other people's actions. Here we investigated the effect of ageing on the ability to discriminate the weight of objects based on the movements of actors lifting these objects. Stimuli consisted of videos of an actor lifting a small box weighing 0.05–0.9 kg or a large box weighting 3–18 kg. In a four-alternative forced-choice task, younger and older participants reported the perceived weight of the box in each video. Overall, older participants were less sensitive than younger participants in discriminating the perceived weight of lifted boxes, an effect that was especially pronounced in the small box condition. Weight discrimination performance was better for the large box compared to the small box in both groups, due to greater saliency of the visual cues in this condition. These results suggest that older adults may require more salient visual cues to interpret the actions of others accurately. We discuss the potential contribution of age-related changes in visual and motor function on the observed effects and suggest that older adults' decline in the sensitivity to subtle visual cues may lead to greater reliance on visual analysis of the observed scene and its semantic context.
Microscope Projection Photolithography for Rapid Prototyping of Masters with Micron-Scale Features for Use in Soft Lithography

This paper demonstrates the application of projection photolithography, using a standard commercial microscope, for the generation of masters for soft lithography. The procedure is rapid and convenient and produces features smaller in size (as small as 0.6 μm) than those available from other methods of rapid prototyping, albeit over a limited area (∼4 × 104 μm2 per exposure). A transparency photomask (prepared using high-resolution printing) is inserted into the light path of the microscope and projected through the microscope objective onto a photoresist-coated substrate. Features on the order of 1 μm can be produced routinely over the area of sharp focus (a circle of radius r ≅ 100 μm with a 100× objective) by this method without modification or precise calibration of the microscope. The microscope platform also provides two other useful functions, both characteristic of commercial steppers: step-and-repeat exposures and pattern alignment. The developed photoresist is used as a master for the fabricati.
Dynamic Organization of SecA and SecY Secretion Complexes in the B. subtilis Membrane

In prokaryotes, about one third of cellular proteins are translocated across the plasma membrane or inserted into it by concerted action of the cytoplasmic ATPase SecA and the universally conserved SecYEG heterotrimeric polypeptide-translocating pore. Secretion complexes have been reported to localize in specific subcellular sites in Bacillus subtilis. In this work, we used a combination of total internal reflection microscopy, scanning fluorescence correlation spectroscopy, and pair correlation function to study the localization and dynamics of SecA and SecY in growing Bacillus subtilis cells. Both SecA and SecY localized in transient and dynamic foci in the cytoplasmic membrane, which displayed no higher-level organization in helices. Foci of SecA and SecY were in constant flux with freely diffusing SecA and SecY molecules. Scanning FCS confirmed the existence of populations of cellular SecA and SecY molecules with a wide range of diffusion coefficients. Diffusion of SecY as an uncomplexed molecular species was short-lived and only local while SecY complexed with its protein partners traversed distances of over half a micrometer in the cell.
Decoding of four movement directions using hybrid NIRS-EEG brain-computer interface

The hybrid brain-computer interface (BCI)'s multimodal technology enables precision brain-signal classification that can be used in the formulation of control commands. In the present study, an experimental hybrid near-infrared spectroscopy-electroencephalography (NIRS-EEG) technique was used to extract and decode four different types of brain signals. The NIRS setup was positioned over the prefrontal brain region, and the EEG over the left and right motor cortex regions. Twelve subjects participating in the experiment were shown four direction symbols, namely, “forward,” “backward,” “left,” and “right. ” The control commands for forward and backward movement were estimated by performing arithmetic mental tasks related to oxy-hemoglobin (HbO) changes. The left and right directions commands were associated with right and left hand tapping, respectively. The high classification accuracies achieved showed that the four different control signals can be accurately estimated using the hybrid NIRS-EEG technology.
Why is stromatactis so rare in Mesozoic carbonate mud mounds?

The sedimentary–diagenetic structure stromatactis is widespread in Palaeozoic spiculitic carbonate mud mounds, but occurs only sporadically in Mesozoic sponge carbonate mud mounds. Comparative analysis of Palaeozoic and Mesozoic stromatactis limestones suggests that this variation results from the degree of siliceous sponge skeletal rigidity and the amount of internal sediment accumulation in the original cavity network. Partial to entire filling by internal sediment resulted in a continuum, from a small amount of internal sediment and large amount of cement (stromatactis, common in the Palaeozoic), to only internal sediments (aborted stromatactis, common in the Mesozoic). These observations match independent lines of evidence concerning the siliceous sponge evolution and sediment recycling (e.g. bioerosion) across the Palaeozoic to Mesozoic biotic revolution.