Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining the Chemokine Basis for Leukocyte Recruitment during Viral Encephalitis

ABSTRACT The encephalitic response to viral infection requires local chemokine production and the ensuing recruitment of immune and inflammatory leukocytes. Accordingly, chemokine receptors present themselves as plausible therapeutic targets for drugs aimed at limiting encephalitic responses. However, it remains unclear which chemokines are central to this process and whether leukocyte recruitment is important for limiting viral proliferation and survival in the brain or whether it is predominantly a driver of coincident inflammatory pathogenesis. Here we examine chemokine expression and leukocyte recruitment in the context of avirulent and virulent Semliki Forest virus (SFV) as well as West Nile virus infection and demonstrate rapid and robust expression of a variety of inflammatory CC and CXC chemokines in all models. On this basis, we define a chemokine axis involved in leukocyte recruitment to the encephalitic brain during SFV infection. CXCR3 is the most active; CCR2 is also active but less so, and CCR5 plays only a modest role in leukocyte recruitment. Importantly, inhibition of each of these receptors individually and the resulting suppression of leukocyte recruitment to the infected brain have no effect on viral titer or survival following infection with a virulent SFV strain. In contrast, simultaneous blockade of CXCR3 and CCR2 results in significantly reduced mortality in response to virulent SFV infection. In summary, therefore, our data provide an unprecedented level of insight into chemokine orchestration of leukocyte recruitment in viral encephalitis. Our data also highlight CXCR3 and CCR2 as possible therapeutic targets for limiting inflammatory damage in response to viral infection of the brain. IMPORTANCE Brain inflammation (encephalitis) in response to viral infection can lead to severe illness and even death. This therefore represents an important clinical problem and one that requires the development of new therapeutic approaches. Central to the pathogenesis of encephalitis is the recruitment of inflammatory leukocytes to the infected brain, a process driven by members of the chemokine family. Here we provide an in-depth analysis of the chemokines involved in leukocyte recruitment to the virally infected brain and demonstrate that simultaneous blockade of two of these receptors, namely, CXCR3 and CCR2, does not alter viral titers within the brain but markedly reduces inflammatory leukocyte recruitment and enhances survival in a murine model of lethal viral encephalitis. Our results therefore highlight chemokine receptors as plausible therapeutic targets in treating viral encephalitis.
Tolerability of NGX-4010, a capsaicin 8% patch for peripheral neuropathic pain

Background/purpose NGX-4010 (QUTENZA™; NeurogesX Inc, San Mateo, CA), a capsaicin 8% dermal patch, is licensed in the European Union for the treatment of peripheral neuropathic pain (PNP) in nondiabetic adults and in the United States for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN). While NGX-4010 treatment is associated with a low risk of systemic adverse events, patch application-related pain is common and may be managed with local cooling and/or oral analgesics. This article characterizes the tolerability of NGX-4010 and will help to guide any pain management. Methods This integrated analysis of tolerability data collected from the NGX-4010 clinical study program included 1696 patients with PNP. Patch application-related pain on the treatment day was captured as Numeric Pain Rating Scale (NPRS) “pain now” scores while “average pain for the past 24 hours” NPRS scores were analyzed for 7 days following treatment. Other tolerability assessments included the percentage of patients completing ≥90% of the intended treatment duration and patients using medication for patch application-related pain. Results The mean maximum change in “pain now” NPRS scores from pretreatment levels during and after patch application was 2.6 for all patients. This pain was transient and resolved following patch removal. Mean “average pain for the past 24 hours” NPRS scores returned to baseline by the evening of the treatment day for patients with PHN, and the evening of day 2 for patients with human immunodeficiency virus-associated distal sensory polyneuropathy or painful diabetic neuropathy. Repeated NGX-4010 applications did not affect the intensity of patch application-related pain. Almost all patients (≥98%) completed ≥90% of the full treatment duration, regardless of the number of treatments received. Conclusion Transient patch application-related pain with NGX-4010 can be managed with local cooling and/or oral analgesics in nearly all cases. Patient adherence to the full intended treatment duration indicated that patch application-related pain was not a barrier to NGX-4010 use.
Cellular Differentiation Regulator BLIMP1 Induces Epstein-Barr Virus Lytic Reactivation in Epithelial and B Cells by Activating Transcription from both the R and Z Promoters

ABSTRACT Epstein-Barr virus (EBV) maintains a lifelong latent infection within a subset of its host's memory B cells, while lytic EBV replication takes place in plasma cells and differentiated epithelial cells. Therefore, cellular transcription factors, such as BLIMP1, that are key mediators of differentiation likely contribute to the EBV latent-to-lytic switch. Previous reports showed that ectopic BLIMP1 expression induces reactivation in some EBV-positive (EBV+) B-cell lines and transcription from Zp, with all Z+ cells in oral hairy leukoplakia being BLIMP1+. Here, we examined BLIMP1's role in inducing EBV lytic gene expression in numerous EBV+ epithelial and B-cell lines and activating transcription from Rp. BLIMP1 addition was sufficient to induce reactivation in latently infected epithelial cells derived from gastric cancers, nasopharyngeal carcinomas, and normal oral keratinocytes (NOK) as well as some, but not all B-cell lines. BLIMP1 strongly induced transcription from Rp as well as Zp, with there being three or more synergistically acting BLIMP1-responsive elements (BRE) within Rp. BLIMP1's DNA-binding domain was required for reactivation, but BLIMP1 did not directly bind the nucleotide (nt) −660 Rp BRE. siRNA knockdown of BLIMP1 inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced lytic reactivation in NOK-Akata cells, cells that can be reactivated by R, but not Z. Thus, we conclude that BLIMP1 expression is both necessary and sufficient to induce EBV lytic replication in many (possibly all) EBV+ epithelial-cell types, but in only a subset of EBV+ B-cell types; it does so, at least in part, by strongly activating expression of both EBV immediately early genes, BZLF1 and BRLF1. IMPORTANCE This study is the first one to show that the cellular transcription factor BLIMP1, a key player in both epithelial and B-cell differentiation, induces reactivation of the oncogenic herpesvirus Epstein-Barr virus (EBV) out of latency into lytic replication in a variety of cancerous epithelial cell types as well as in some, but not all, B-cell types that contain this virus in a dormant state. The mechanism by which BLIMP1 does so involves strongly turning on expression of both of the immediate early genes of the virus, probably by directly acting upon the promoters as part of protein complexes or indirectly by altering the expression or activities of some cellular transcription factors and signaling pathways. The fact that EBV+ cancers usually contain mostly undifferentiated cells may be due in part to these cells dying from lytic EBV infection when they differentiate and express wild-type BLIMP1.
Transcript versus transcription?: The regulation of X-inactivation by antisense Tsix expression

Numerous sense-antisense gene pairs have been discovered in various organisms. Antisense genes play important roles in establishing parentally imprinted gene expression patterns in mammals. Typically, protein-coding sense genes are reciprocally regulated by their non-coding antisense partners. One example for antisense regulation is the Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation. Xist works as a functional RNA molecule that recruits repressive chromatin factors towards one of the female Xs for inactivation. Antisense Tsix transcription negatively regulates Xist and protects one X-chromosome in cis from inactivation by Xist. Albeit, the precise molecular mechanism is still obscure it has been shown that Tsix transcription regulates the chromatin structure by altering histone tail modifications and DNA methylation at the Xist promoter. In addition, Xist and Tsix RNA form an RNA duplexes in vivo and are processed to small RNAs, which have a potential regulatory function. Here we review the latest findings and based on ample experimental data consider models for antisense-mediated gene regulation in X-inactivation.
An Efficient Face Detection Method Using Adaboost and Facial Parts

In order to build a fully automated system that analyzes the information in face image, there is a need for robust and efficient face detection algorithms. One of the fastest and most successful approaches in this field was presented by Viola. In this paper, Viola approach is used as the basis algorithm in order to propose a new efficient face detection system. Using Haar-like features for facial parts and learning these features by AdaBoost algorithm make proposed approach possible to detect occluded faces and increase the detection rate. Moreover, some preprocessing techniques are also used to limit the candidate places which make final algorithm runs faster. The experimental results represent that, the proposed approach has the capability of achieving a detection rate of 94.7% while false positive rate is just 2% . Furthermore, this system can detect faces in image, averagely four times faster than Viola approach.
The conserved arginine in rho-GTPase-activating protein is essential for efficient catalysis but not for complex formation with Rho.GDP and aluminum fluoride.

The Rho family of small GTP-binding proteins are downregulated by an intrinsic GTPase, which is enhanced by GTPase-activating proteins (GAPs). RhoGAPs contain a single conserved arginine residue that has been proposed to be involved in catalysis. Here, the role of this arginine has been elucidated by mutagenesis followed by determination of catalytic and equilibrium binding constants using single-turnover kinetics, isothermal titration calorimetry, and scintillation proximity assays. The turnover numbers for wild-type, R282A, and R282K RhoGAPs were 5.4, 0.023, and 0.010 s-1, respectively. Thus, the function of this arginine could not be replaced by lysine or alanine. Nevertheless, the R282A mutation had a minimal effect on the binding affinity of RhoGAP for either Rho. GTP or Rho.GMPPNP, which confirms the importance of the arginine residue for catalysis as opposed to formation of the protein-protein complex. The R282A mutant RhoGAP still increased the hydrolysis rate of Rho.GTP by 160-fold, whereas the wild-type enzyme increased it by 38000-fold. We conclude that this arginine contributes half of the total reduction of activation energy of catalysis. In the presence of aluminum fluoride, the R282A mutant RhoGAP binds almost as well as the wild type to Rho.GDP, demonstrating that the conserved arginine is not required for this interaction. The affinity of wild-type RhoGAP for the triphosphate form of Rho is similar to that for Rho.GDP with aluminum fluoride. These last two observations show that this complex is not associated with the free energy changes expected for the transition state, although the Rho.GDP. AlF4-. RhoGAP complex might well be a close structural approximation.
P-recognition: you are already recognized

The user's intention is reflected in not only the actual input action but the ones immediately before it as well. "P-Recognition"" recognizes the preceding actions, and predicts the intention just when the actual action starts. This paper tests P-Recognition in a pen-based map navigation interface as an example, where the map is panned by user's dragging strokes and zoomed by user's enclosure by a circle. The feasibility of the proposal is confirmed in an experiment. We find that dragging and circling actions are distinguishable before the pen touches the screen. Moreover, for some users we can recognize their intention to write text. It is confirmed that the user's intention is present in the preceding actions and so is detectable.
Porous hydrogel biomedical foam scaffolds for tissue repair

Abstract: In the present chapter, the state-of-the-art of porous hydrogel foams will be described and emphasis will be made on their relevance for biomedical applications and, more specifically, tissue repair. The description aims at emphasizing both some novel aspects as well as the versatility of hydrogel foams. In addition, an overview of some general hydrogel aspects will be given. Next, a section will deal with natural polymers commonly used and suitable for hydrogel foam development and their respective tissue regeneration applications, followed by a description on advanced technologies applied to design and characterize novel hydrogel foams.
Timestamp snooping: an approach for extending SMPs

Symmetric multiprocessor (SMP) servers provide superior performance for the commercial workloads that dominate the Internet. Our simulation results show that over one-third of cache misses by these applications result in cache-to-cache transfers, where the data is found in another processor's cache rather than in memory. SMPs are optimized for this case by using snooping protocols that broadcast address transactions to all processors. Conversely, directory-based shared-memory systems must indirectly locate the owner and sharers through a directory, resulting in larger average miss latencies.This paper proposes timestamp snooping, a technique that allows SMPs to i) utilize high-speed switched interconnection networks and ii) exploit physical locality by delivering address transactions to processors and memories without regard to order. Traditional snooping requires physical ordering of transactions. Timestamp snooping works by processing address transactions in a logical order. Logical time is maintained by adding a few bits per address transaction and having network switches perform a handshake to ensure on-time delivery. Processors and memories then reorder transactions based on their timestamps to establish a total order.We evaluate timestamp snooping with commercial workloads on a 16-processor SPARC system using the Simics full-system simulator. We simulate both an indirect (butterfly) and a direct (torus) network design. For OLTP, DSS, web serving, web searching, and one scientific application, timestamp snooping with the butterfly network runs 6-28% faster than directories, at a cost of 13-43% more link traffic. Similarly, with the torus network, timestamp snooping runs 6-29% faster for 17-37% more link traffic. Thus, timestamp snooping is worth considering when buying more interconnect bandwidth is easier than reducing interconnect latency.
Solving “Hard” Satisfiability Problems Using GridSAT

We present the latest instantiation of GridSAT [5], a distributed and complete satisfiability solver that is explicitly designed to aggregate grid resources for application performance. GridSAT was previously shown to outperform the state-of-the-art sequential solvers. In this work, we explore the unprecedented solving power GridSAT enables through algorithmic and implementation innovations. We describe the implementation techniques that allow GridSAT to leverage a variety of high-end batch-scheduled resources, clusters, interactive workstations, and personal computing resources through autonomous scheduling, checkpoint scheduling, and work migration. These innovations have allowed GridSAT to solve a set of “hard” and previously unsolved industrial and community satisfiability problems. In addition to this new solution power, GridSAT also outperforms the otherwise highest performance general solvers on the annual SAT competition performance benchmarks.
An Empirical Evaluation of IP Time To Live Covert Channels

Communication is not necessarily made secure by the use of encryption alone. The mere existence of communication is often enough to raise suspicion and trigger investigative actions. Covert channels aim to side-step this problem by hiding additional information within the 'normal' behaviour of preexisting communication streams. The huge amount of data and vast number of different protocols in the Internet make it ideal as a high-bandwidth vehicle for covert channels. Several researchers have proposed modulation techniques to encode covert information into the IP Time To Live field. In this paper we compare the different encoding techniques and also propose two new improved encoding schemes. We present a software framework developed for evaluating covert channels in network protocols. We use this software to empirically evaluate the transmission rates of the different TTL modulation techniques for real Internet traffic.
DESIGN AND CONTROL OF A ROBOT WITH ONE ARTICULATED LEG FOR LOCOMOTION ON IRREGULAR TERRAIN

In this paper a control algorithm for a hopping robot having one articulated leg is presented and a description of the mechanical design of a prototype, constructed at the Department of Mechanical Engineering of the VUB, is given. The control algorithm enables the robot, whose name is OLIE (One Leg Is Enough), to control simultaneously its forward velocity during flight, its hopping height, the placement of its foot on desired footholds, the orientation of its body and its angular momentum. The model of the hopping robot under study and its control algorithm are given in section 2. Simulation results are presented and remarks are made in section 3. In section 4 a description is given of the design of the experimental prototype of the robot. Finally, in section 5, conclusions are drawn and comments on further research are made.
Viewpoint Sensitivity in Eba and Fba 1 Fmri–adaptation Studies of Viewpoint Tuning in the Extrastriate and Fusiform Body Areas 1 2

1 fMRI–adaptation studies of viewpoint tuning in the extrastriate and fusiform body areas 1 2 John C. Taylor 3 Alison J. Wiggett 4 Paul E. Downing 5 6 Wales Institute of Cognitive Neuroscience 7 School of Psychology 8 Bangor University 9 United Kingdom 10 11 Running head: Viewpoint sensitivity in EBA and FBA 12 13 John Taylor 14 School of Psychology 15 Bangor University 16 Adeilad Brigantia 17 Penrallt Road 18 Bangor 19 LL57 2AS 20 21 Email: psp223@bangor.ac. uk 22 23 24 25 26 27 28 Articles in PresS. J Neurophysiol (December 23, 2009). doi:10.1152/jn.00637. 2009
Six Sigma Quality Approach to Robust Optimization

In electromagnetic design, uncertainties in design variables are inevitable, thus in addition to pursuing the theoretical optimum of the objective function the evaluation of robustness of the optimum solution is also critical. Several methodologies exist to tackle robust optimization, such as worst case optimization and gradient index; this paper investigates the use of standard deviation and mean value of objective function under uncertainty of variables. A modified Kriging model with the ability of balancing exploration and exploitation is employed to facilitate the objective function prediction. Two TEAM benchmark problems are solved using different methodologies to compare the advantages and disadvantages of different robust optimization approaches.
Smooth Newton method for implicit Lagrangian twin support vector regression

A new smoothing approach for the implicit Lagrangian twin support vector regression is proposed in this paper. Our formulation leads to solving a pair of unconstrained quadratic programming problems of smaller size than in the classical support vector regression and their solutions are obtained using Newton-Armijo algorithm. This approach has the advantage that a system of linear equations is solved in each iteration of the algorithm. Numerical experiments on several synthetic and real-world datasets are performed and, their results and training time are compared with both the support vector regression and twin support vector regression to verify the effectiveness of the proposed method.
Runtime Verification for LTL and TLTL

This article studies runtime verification of properties expressed either in lineartime temporal logic (LTL) or timed lineartime temporal logic (TLTL). It classifies runtime verification in identifying its distinguishing features to model checking and testing, respectively. It introduces a three-valued semantics (with truth values true, false, inconclusive) as an adequate interpretation as to whether a partial observation of a running system meets an LTL or TLTL property. For LTL, a conceptually simple monitor generation procedure is given, which is optimal in two respects: First, the size of the generated deterministic monitor is minimal, and, second, the monitor identifies a continuously monitored trace as either satisfying or falsifying a property as early as possible. The feasibility of the developed methodology is demontrated using a collection of real-world temporal logic specifications. Moreover, the presented approach is related to the properties monitorable in general and is compared to existing concepts in the literature. It is shown that the set of monitorable properties does not only encompass the safety and cosafety properties but is strictly larger. For TLTL, the same road map is followed by first defining a three-valued semantics. The corresponding construction of a timed monitor is more involved, yet, as shown, possible.
A Soil Sampling Method Based on Field Measurements, Remote Sensing Images and Kriging Technique

How to determine a representative and economical soil sampling method that combines soil properties with advanced technologies has been an unsolved issue in soil related studies. This paper proposes a new method for soil sampling based on some measured salinity data and remote sensing images, as well as analysis of spatial distributions of soil properties in Lubotan land reclamation area in Shaanxi, China. The results showed that with the available data sets of 33 points, up to 101 unknown points can be estimated, and further interpolation of 343 points displayed spatial distribution of soil salinity in the study area, the coefficients of determination (R2) for the predicted soil salinity were 0.817, respectively. A further Kriging analysis for top soil salinity distribution in the study area showed that soil salinity has a medium degree of autocorrelation and low variability. The study in this paper may help understand the effect of soil reclamation efforts and local water management practice.
User patience and the Web: a hands-on investigation

We present a study of Web user behavior when network performance decreases causing an increase of page transfer times. Real traffic measurements are analyzed to infer whether worsening network conditions translate into greater impatience by the user, which translates in early interruption of TCP connections. Several parameters are studied in order to gather their impact on the interruption probability on Web transfers: time of day, file size, throughput and time elapsed since the beginning of the download. From the results presented, we try to paint a picture of the complex interactions between user perception of the Web and network-level events.