Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralization of Gating Charges in Domain II of the Sodium Channel α Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin

β-Scorpion toxins shift the voltage dependence of activation of sodium channels to more negative membrane potentials, but only after a strong depolarizing prepulse to fully activate the channels. Their receptor site includes the S3–S4 loop at the extracellular end of the S4 voltage sensor in domain II of the α subunit. Here, we probe the role of gating charges in the IIS4 segment in β-scorpion toxin action by mutagenesis and functional analysis of the resulting mutant sodium channels. Neutralization of the positively charged amino acid residues in the IIS4 segment by mutation to glutamine shifts the voltage dependence of channel activation to more positive membrane potentials and reduces the steepness of voltage-dependent gating, which is consistent with the presumed role of these residues as gating charges. Surprisingly, neutralization of the gating charges at the outer end of the IIS4 segment by the mutations R850Q, R850C, R853Q, and R853C markedly enhances β-scorpion toxin action, whereas mutations R856Q, K859Q, and K862Q have no effect. In contrast to wild-type, the β-scorpion toxin Css IV causes a negative shift of the voltage dependence of activation of mutants R853Q and R853C without a depolarizing prepulse at holding potentials from −80 to −140 mV. Reaction of mutant R853C with 2-aminoethyl methanethiosulfonate causes a positive shift of the voltage dependence of activation and restores the requirement for a depolarizing prepulse for Css IV action. Enhancement of sodium channel activation by Css IV causes large tail currents upon repolarization, indicating slowed deactivation of the IIS4 voltage sensor by the bound toxin. Our results are consistent with a voltage-sensor–trapping model in which the β-scorpion toxin traps the IIS4 voltage sensor in its activated position as it moves outward in response to depolarization and holds it there, slowing its inward movement on deactivation and enhancing subsequent channel activation. Evidently, neutralization of R850 and R853 removes kinetic barriers to binding of the IIS4 segment by Css IV, and thereby enhances toxin-induced channel activation.
SeamlessDesign: a face-to-face collaborative virtual/augmented environment for rapid prototyping of geometrically constrained 3-D objects

We propose SeamlessDesign, a novel collaborative workspace for rapid creation of reactive 3-D objects. SeamlessDesign has two significant characteristics in terms of seamless. First, SeamlessDesign supports a wide range of designing processes seamlessly. Users of SeamlessDesign can design from rough drafts to highly detailed 3-D objects in a unified and intuitive manner including not only their geometric appearances but also their behavioral design. Second, SeamlessDesign utilizes both virtual and augmented setups seamlessly for supporting two-user face-to-face collaboration. In a see-through mode, using see-through head mounted displays, users of SeamlessDesign see their partners as they are, and in a blind mode, the real scene gets invisible and they see realistic avatars in the case of navigation or scaling of the workspaces. Owing to these characteristics, users of SeamlessDesign can create complicated, reactive 3-D objects in a short time.
[Episodes of depression with attempted suicide after taking valsartan with hydrochlorothiazide].

HISTORY AND CLINICAL FINDINGS A 43-year-old woman was admitted after a suicide attempt with 1.5 g atenolol. Physical and neurological examination showed no abnormality, but psychiatric examination revealed symptoms of a major depression. Four weeks prior to admission a valsartan-hydrochlorothiazide combination had been added to the antihypertensive medication. INVESTIGATIONS Laboratory tests, electrocardiography, chest-x-ray, electroencephalography and cranial computerised tomography showed no abnormality. DIAGNOSIS AND COURSE The depressive disorder resolved within ten days after discontinuation of valsartan and hydrochlorothiazide without specific treatment. Blood pressure was normal under treatment with metoprolol. CONCLUSION Depressive drug reactions can produce a substantial morbidity. This case of a drug induced affective disorder should heighten the awareness of unusual reactions to valsartan-hydrochlorothiazide therapy.
Characterisation of residual stress in dielectric films studied by automated wafer mapping

SU-8 is a negative epoxy based photoresist, which is widely used as a structural and dielectric layer in the fabrication of MEMS devices. However this material normally develops high levels of stress during processing. This paper reports detailed quantitative data following previous work, where Parylene-C has been proposed as a possible replacement for SU-8. In particular, this paper details the characterisation of residual stress in (i) SU-8 films as a function of processing temperatures and (ii) post-processing thermal treatment of Parylene-C. This characterisation includes wafer mapping strain using rotating pointer arm test structures, and deriving the stress from independent measurements of strain and Young's modulus.
Back-Office Web Traffic on The Internet

Although traffic between Web servers and Web browsers is readily apparent to many knowledgeable end users, fewer are aware of the extent of server-to-server Web traffic carried over the public Internet. We refer to the former class of traffic as front-office Internet Web traffic and the latter as back-office Internet Web traffic (or just front-office and back-office traffic, for short). Back-office traffic, which may or may not be triggered by end-user activity, is essential for today's Web as it supports a number of popular but complex Web services including large-scale content delivery, social networking, indexing, searching, advertising, and proxy services. This paper takes a first look at back-office traffic, measuring it from various vantage points, including from within ISPs, IXPs, and CDNs. We describe techniques for identifying back-office traffic based on the roles that this traffic plays in the Web ecosystem. Our measurements show that back-office traffic accounts for a significant fraction not only of core Internet traffic, but also of Web transactions in the terms of requests and responses. Finally, we discuss the implications and opportunities that the presence of back-office traffic presents for the evolution of the Internet ecosystem.
Enforcing Correct Behavior without Trust in Cloud Key-Value Databases

Traditional computation outsourcing and modern cloud computing are affected by a common risk of distrust between service requestor and service provider. We propose a novel protocol, named Probus, that offers guarantees of correct behavior to both parts without assuming any trust relationship between them in the context of cloud-based key-value databases. Probus allows a service requestor to have evidence of cloud provider misbehavior on its data, and a cloud provider to defend itself from false accusations by demonstrating the correctness of its operations. Accusation and defense proofs are based on cryptographic mechanisms that can be verified by a third party. Probus improves the state-of-the-art by introducing novel solutions that allow for efficient verification of data security properties and by limiting the overhead required to provide its security guarantees. Thanks to Probus it is possible to check the correctness of all the results generated by a cloud service, thus improving weaker integrity assurance based on probabilistic verifications that are adopted by related work.
UvA-DARE ( Digital Academic Repository ) Systems biology tools for toxicology

An important goal of toxicology is to understand and predict the adverse effects of drugs and other xenobiotics. For pharmaceuticals, such effects often emerge unexpectedly in man even when absent from trials in vitro and in animals. Although drugs and xenobiotics act on molecules, it is their perturbation of intracellular networks that matters. The tremendous complexity of these networks makes it difficult to understand the effects of xenobiotics on their ability to function. Because systems biology integrates data concerning molecules and their interactions into an understanding of network behaviour, it should be able to assist toxicology in this respect. This review identifies how in silico systems biology tools, such as kinetic modelling, and metabolic control, robustness and flux analyse, may indeed help understanding network-mediated toxicity. It also shows how these approaches function by implementing them vis-à-vis the glutathione network, which is important for the detoxification of reactive drug metabolites. The tools enable the appreciation of the steady state concept for the detoxification network and make it possible to simulate and then understand effects of perturbations of the macromolecules in the pathway that are counterintuitive. We review how a glutathione model has been used to explain the impact of perturbation of the pathway at various molecular sites, as would be the effect of single-nucleotide polymorphisms. We focus on how the mutations impact the levels of glutathione and of two candidate biomarkers of hepatic glutathione status. We conclude this review by sketching how the various systems biology tools may help in the various phases of drug development in the pharmaceutical industry.
Radiation hormesis.

"Radiation hormesis" is the name given to the putative stimulatory effects of low level ionizing radiation (generally in the range of 1-50 cGy of low-LET radiation). Based on historical and pharmacologic principles reminiscent of some of the major tenets of homeopathy, most of these effects are now generally ascribed to protective feedback systems that, upon exposure to low concentrations of toxins, proceed to stimulate metabolic detoxification and repair networks. The activation of these networks may then result in net beneficial effects on the cell, organism or species. Discussions of possible stimulatory effects of low levels of ionizing radiation have recently become entangled with the separate but related question of whether a threshold dose level exists on the radiotoxicologic dose-response curve. This review summarizes some of the relevant historical and scientific data bearing on the question of radiation hormesis. We find the data in support of most of the hormesis postulates intriguing but inconclusive.
On the Speedup of Recovery in Large-Scale Erasure-Coded Storage Systems

Modern storage systems stripe redundant data across multiple nodes to provide availability guarantees against node failures. One form of data redundancy is based on XOR-based erasure codes, which use only XOR operations for encoding and decoding. In addition to tolerating failures, a storage system must also provide fast failure recovery to reduce the window of vulnerability. This work addresses the problem of speeding up the recovery of a single-node failure for general XOR-based erasure codes. We propose a replace recovery algorithm, which uses a hill-climbing technique to search for a fast recovery solution, such that the solution search can be completed within a short time period. We further extend the algorithm to adapt to the scenario where nodes have heterogeneous capabilities (e.g., processing power and transmission bandwidth). We implement our replace recovery algorithm atop a parallelized architecture to demonstrate its feasibility. We conduct experiments on a networked storage system testbed, and show that our replace recovery algorithm uses less recovery time than the conventional recovery approach.
Effects of cognitive-behavioural therapy on anxiety for children with high-functioning autistic spectrum disorders.

INTRODUCTION Children with autistic spectrum disorders (ASD) often exhibit one or more comorbid disorders, including anxiety, disruptive behaviour, mental retardation, and depression. Various studies have documented the effectiveness of cognitive-behavioural therapy (CBT) in treating children with anxiety. Although studies have indicated a high prevalence of anxiety in individuals with ASD, there is a lack of systematic studies substantiating the effectiveness of cognitive-behavioural interventions among children with high-functioning autism. METHODS This pilot study investigated the effects of a 16-session CBT programme on six high-functioning children diagnosed with ASD (mean age 11.50 years, standard deviation 0.84 years). These children were diagnosed with ASD or Asperger's syndrome by the DSM-IV criteria. Measures on levels of child's anxiety, parental and teacher stress were administered at pre- and post-treatment. RESULTS Children showed lower levels of anxiety at post-treatment. Parents and teachers also reported lower levels of stress following the CBT programme. CONCLUSION Findings from the present study provided some evidence of the effects of CBT for high-functioning autistic children in reducing anxiety, parental and teacher stress. Interpretation of the findings, recommendations for future research and implications of the present study are presented.
Sensorless magnetic model and pm flux identification of synchronous drives at standstill

This paper proposes a sensorless self-commissioning technique for PM-assisted synchronous reluctance motors. The identification of the machine's flux maps is performed at standstill without any position transducer and with no need of rotor locking. The machine is first excited with alternated high voltage pulses, injected in the estimated d and q directions of the rotor to determine its saturation curves. Then, direct current values are applied in a fixed stator direction so that the rotor aligns in specific positions giving information on the PM flux linkage. Experimental results are provided on a PM-assisted synchronous reluctance motor prototype, confirming the validity of the proposed method. The key original feature of the proposed work is the estimation of magnet flux linkage at standstill. For the motor under test, the magnet flux linkage was sensorless estimated at standstill with an error lower than 3%.
Impact of injected water salinity on CO2 storage efficiency in homogenous reservoirs

Water alternating gas (WAG) injection significantly improves enhanced oil recovery efficiency by improving the sweep efficiency. However, the impact of injected water salinity during WAG injection on CO2 storage efficiency has not been previously demonstrated. Thus, a 3D reservoir model has been developed for simulating CO2 injection and storage processes in homogeneous reservoirs with different water injection scenarios (i.e. low salinity water injection (1000 ppm NaCl), high salinity water injection (250 000 ppm NaCl) and no water injection), and the associated reservoir-scale CO2 plume dynamics and CO2 dissolution have been predicted. Furthermore, in this work, we have investigated the efficiency of dissolution trapping with and without WAG injection. For all water injection scenarios, 5000 kton of CO2 were injected during a 10-year CO2 injection period. For high and low salinity water injection scenarios, 5 cycles of CO2 injection (each cycle is one year) at a rate of 1000 kton/year were carried out, and each CO2 cycle was followed by a one year water injection at a rate of 0.015 pore volume per year. This injection period was followed by a 500-year post injection (storage) period. Our results clearly indicate that injected water salinity has a significant impact on the quantity of dissolved CO2 and on the CO2 plume dynamics. The low salinity water injection resulted in the maximum CO2 dissolution and minimum vertical migration of CO2. Also, our results show that WAG injection enhances dissolution trapping and reduces CO2 leakage risk for both injected water salinities. Thus, we conclude that the low salinity water injection improves CO2 storage efficiency.
A STRATEGIC METAGAME PLAYER FOR GENERAL CHESS‐LIKE GAMES

This paper introduces METAGAMER, the first program designed within the paradigm of Metagame‐playing (Metagame). This program plays games in the class of symmetric chess‐like games, which includes chess, Chinese chess, checkers, draughts, and Shogi. METAGAMER takes as input the rules of a specific game and analyzes those rules to construct an efficient representation and an evaluation function for that game; they are used by a generic search engine. The strategic analysis performed by METAGAMER relates a set of general knowledge sources to the details of the particular game. Among other properties, this analysis determines the relative value of the different pieces in a given game. Although METAGAMER does not learn from experience, the values resulting from its analysis are qualitatively similar to values used by experts on known games and are sufficient to produce competitive performance the first time METAGAMER plays a new game. Besides being the first Metagame‐playing program, this is the first program to have derived useful piece values directly from analysis of the rules of different games. This paper describes the knowledge implemented in METAGAMER, illustrates the piece values METAGAMER derives for chess and checkers, and discusses experiments with METAGAMER on both existing and newly generated games.
SRAD-CNN for adaptive synthetic aperture radar image classification

ABSTRACT The performance of synthetic aperture radar (SAR) image classification based on a conventional convolutional neural network (CNN) is limited by a trade-off between immunity to speckle noise and the ability to locate boundaries accurately. Difficulties regarding the accurate location of boundaries are a result of the smoothing effect of the pooling layer. To address this issue, we propose a novel framework called SRAD-CNN for SAR image classification. In this framework, we apply a filtering layer constructed according to prior knowledge of the speckle reducing anisotropic diffusion (SRAD) filter. The filtering layer can not only reduce speckle but also enhance the boundaries. The main parameter that controls the degree of filtering can be optimized adaptively by a backpropagation algorithm. Image patches adaptively filtered by the filtering layer are then put into the CNN layers to assign a label. Due to the effect of the filtering layer, for our proposed SRAD-CNN, both the speckle noise immunity and the sensitivity to boundaries are superior to those of conventional CNN.To confirm the performance of the proposed SRAD-CNN, we conducted experiments using both simulated and real SAR images. The experimental results demonstrated that the parameter of the filtering layer could be optimized adaptively for different scenes, different noise levels, and different image resolutions. The SRAD-CNN outperformed the conventional CNN in both overall classification accuracy and maintenance of boundary accuracy on images with different resolutions and noise levels with limited training samples.
ATSR MAPS CORAL BLEACHING ON AUSTRALIA ’ S GREAT BARRIER REEF

The Australian Great Barrier Reef (GBR) experienced its most intensive and extensive coral bleaching event on record in early 1998 [1]. This period also saw extensive damage to other reefs around the globe. There is concern among environmental scientists and GBR-based industries, especially tourism, that widespread death and bleaching of corals caused by extremely high temperatures during 1997-98 may occur more frequently on the GBR if global climate change unfolds as predicted during the coming decades [2]. Currently NOAA/NESDIS are developing "SST Anomaly" maps based on AVHRR data which may be useful in monitoring reefs that are under threat. However, coral bleaching temperature thresholds are highly sensitive depending on species and geographic location, and AVHRR absolute accuracies may not be adequate for this task. The sea surface temperatures provided by ATSR and AVHRR data are compared with in situ measurements from several buoys located on the GBR. Maps of coral-bleached areas are also compared with sea surface temperature maps obtained from the satellite data. Although the ATSR has limited coverage due to its narrow swath, the advantage of accessing high spatial resolution data in reef and coastal areas may give a better means of monitoring the water temperature of reefs at risk of coral bleaching. The potential for ATSR to provide improved temperature maps over sections of the GBR is under investigation and progress and results will be reported in this paper. The potential of core samples taken from coral reefs to provide a long term record of local water temperature will also be reported.
POSTER: Detecting Malicious Web Pages based on Structural Similarity of Redirection Chains

Detecting malicious web pages used in attacks and building blacklists and signatures from them are done to protect users against drive-by download attacks. Gathering the content on web pages by crawling and evaluating it to check if it is malicious can help in detecting malicious web pages. Methods that apply supervised machine learning to this evaluation are proposed for detecting malicious web pages from a massive amount of web pages. However, these methods need manual inspections for preparing training data when classifiers are retrained in accordance with changes in the content on malicious web pages. In this paper, we propose a method that evaluates whether web pages are malicious and needs only the discrimination results of web pages identified by high-interaction honeyclients to prepare training data. This method evaluates maliciousness on the basis of the structural similarity of redirection chains arising from drive-by download attacks. The results of our experiments with two years of data showed that the accuracy of our method was about 20\% higher than that of the previous method.
Regulation of Trabecular Meshwork Cell Contraction and Intraocular Pressure by miR-200c

Lowering intraocular pressure (IOP) delays or prevents the loss of vision in primary open-angle glaucoma (POAG) patients with high IOP and in those with normal tension glaucoma showing progression. Abundant evidence demonstrates that inhibition of contractile machinery of the trabecular meshwork cells is an effective method to lower IOP. However, the mechanisms involved in the regulation of trabecular contraction are not well understood. Although microRNAs have been shown to play important roles in the regulation of multiple cellular functions, little is known about their potential involvement in the regulation of IOP. Here, we showed that miR-200c is a direct postranscriptional inhibitor of genes relevant to the physiologic regulation of TM cell contraction including the validated targets Zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), and formin homology 2 domain containing 1 (FHOD1), as well as three novel targets: lysophosphatidic acid receptor 1 (LPAR1/EDG2), endothelin A receptor (ETAR), and RhoA kinase (RHOA). Consistently, transfection of TM cells with miR-200c resulted in strong inhibition of contraction in collagen populated gels as well as decreased cell traction forces exerted by individual TM cells. Finally, delivery of miR-200c to the anterior chamber of living rat eyes resulted in a significant decrease in IOP, while inhibition of miR-200c using an adenoviral vector expressing a molecular sponge led to a significant increase in IOP. These results demonstrate for the first time the ability of a miRNA to regulate trabecular contraction and modulate IOP in vivo, making miR-200c a worthy candidate for exploring ways to alter trabecular contractility with therapeutic purposes in glaucoma.