Miracle-dz/UniFAR-FTUs huggingface dataset:
AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.

Hemophilia B is an X-linked coagulopathy caused by absence of functional coagulation factor IX (F.IX). Previously, we established an experimental basis for gene transfer as a method of treating the disease in mice and hemophilic dogs through intramuscular injection of a recombinant adeno-associated viral (rAAV) vector expressing F.IX. In this study we investigated the safety of this approach in patients with hemophilia B. In an open-label dose-escalation study, adult men with severe hemophilia B (F.IX < 1%) due to a missense mutation were injected at multiple intramuscular sites with an rAAV vector. At doses ranging from 2 x 10(11) vector genomes (vg)/kg to 1.8 x 10(12) vg/kg, there was no evidence of local or systemic toxicity up to 40 months after injection. Muscle biopsies of injection sites performed 2 to 10 months after vector administration confirmed gene transfer as evidenced by Southern blot and transgene expression as evidenced by immunohistochemical staining. Pre-existing high-titer antibodies to AAV did not prevent gene transfer or expression. Despite strong evidence for gene transfer and expression, circulating levels of F.IX were in all cases less than 2% and most were less than 1%. Although more extensive transduction of muscle fibers will be required to develop a therapy that reliably raises circulating levels to more than 1% in all subjects, these results of the first parenteral administration of rAAV demonstrate that administration of AAV vector by the intramuscular route is safe at the doses tested and effects gene transfer and expression in humans in a manner similar to that seen in animals.
Extracting All the Randomness from a Weakly Random Source

In this paper, we give two explicit constructions of extractors, both of which work for a source of any min-entropy on strings of length n. The first extracts any constant fraction of the min-entropy using O(log^2 n) additional random bits. The second extracts all the min-entropy using O(log^3 n) additional random bits Both constructions use fewer truly random bits than any previous construction which works for all min-entropies and extracts a constant fraction of the min-entropy. The extractors are obtained by observing that a weaker notion of "combinatorial design" suffices for the Nisan--Wigderson pseudorandom generator, which underlies the recent extractor of Trevisan. We give near-optimal constructions of such "weak designs which achieve much better parameters than possible with the notion of designs used by Nisan--Wigderson and Trevisan.
Ras and TGFβ cooperatively regulate epithelial cell plasticity and metastasis

Multistep carcinogenesis involves more than six discrete events also important in normal development and cell behavior. Of these, local invasion and metastasis cause most cancer deaths but are the least well understood molecularly. We employed a combined in vitro/in vivo carcinogenesis model, that is, polarized Ha-Ras–transformed mammary epithelial cells (EpRas), to dissect the role of Ras downstream signaling pathways in epithelial cell plasticity, tumorigenesis, and metastasis. Ha-Ras cooperates with transforming growth factor β (TGFβ) to cause epithelial mesenchymal transition (EMT) characterized by spindle-like cell morphology, loss of epithelial markers, and induction of mesenchymal markers. EMT requires continuous TGFβ receptor (TGFβ-R) and oncogenic Ras signaling and is stabilized by autocrine TGFβ production. In contrast, fibroblast growth factors, hepatocyte growth factor/scatter factor, or TGFβ alone induce scattering, a spindle-like cell phenotype fully reversible after factor withdrawal, which does not involve sustained marker changes. Using specific inhibitors and effector-specific Ras mutants, we show that a hyperactive Raf/mitogen-activated protein kinase (MAPK) is required for EMT, whereas activation of phosphatidylinositol 3-kinase (PI3K) causes scattering and protects from TGFβ-induced apoptosis. Hyperactivation of the PI3K pathway or the Raf/MAPK pathway are sufficient for tumorigenesis, whereas EMT in vivo and metastasis required a hyperactive Raf/MAPK pathway. Thus, EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFβ-R and Raf/MAPK signaling.
Rotary-code: Efficient MDS array codes for RAID-6 disk arrays

Low encoding/decoding complexity is essential for practical RAID-6 storage systems. In this paper, we describe a new coding scheme, which we call Rotary-code, for RAID-6 disk arrays. We construct Rotary-code based on a bit matrix-vector product similar to the Reed-Solomon coding, and provide the geometry encoding method and detailed non-recursive decoding algorithms. The capability of two-disk fault-tolerance and the property of Maximum Distance Separable (MDS) are proved in Rotary-code. The key novelty in Rotary-code is that the Rotary-code has optimal encoding complexity and optimal decoding complexity comparing with existing RAID-6 codes.
Understanding the Roles of Appraisal and Coping in the Presence of Cumulative Risk: Test of Mediating and Moderating Effects

Understanding the Roles of Appraisal and Coping in the Presence of Cumulative Risk: Tests of Mediating and Moderating Effects Stephanie F. Thompson Chair of Supervisory Committee: Professor Liliana J. Lengua Department of Psychology Concurrent and longitudinal relations among appraisal, coping, cumulative risk, and adjustment were examined using a community sample (N=316) of children in preadolescence (8-12 years old) representing the full range of income. Path analyses were used to test direct effects of appraisal and coping on adjustment and mediating and moderating effects of appraisal and coping of the relation of cumulative risk to adjustment. Threat appraisal and avoidant coping were hypothesized to mediate the effects of cumulative risk on child adjustment, whereas positive appraisal and active coping were hypothesized to moderate the relation of cumulative risk with adjustment. Rank order changes in appraisal and coping predicted rank order changes in adjustment. Concurrent cumulative risk was related to higher threat appraisal and avoidant coping at each time point. Threat appraisal and avoidant coping mediated the relations of cumulative risk to adjustment. There was little support for moderation. The development of appraisal and coping and their significance to children’s adjustment within the context of cumulative risk are discussed.
Intestinal permeability and systemic infections in critically ill patients: Effect of glutamine*

Objective:This article provides a critical review of the evidence indicating that an increase in intestinal permeability is associated with the installation of bacteremia, sepsis, and the multiple organ failure syndrome and that glutamine in pharmacologic doses reduces the acute increase of intestinal permeability and the infection frequency in critically ill patients. Data Source:All studies published until December 2004 about intestinal permeability, bacterial translocation, and glutamine were located by search of PubMed and Web of Science. The reference lists of review articles and primary publications were also examined to identify references not detected in the computer search. Study Selection:Clinical and experimental studies investigating the correlation between intestinal permeability, bacterial translocation, and frequency of infections, associated or not with the effect of glutamine administration. Data Extraction:Information regarding patient population, experimental design, glutamine doses and routes of administration, nutritional therapy prescribed, methods used to assess intestinal permeability, metabolic variables, and the frequency of infections were obtained from the primary literature. Data Synthesis:Intestinal permeability is increased in critically ill patients. The results have not always been consistent, but the studies whose results support the association between intestinal permeability and systemic infections have had better design and more appropriate controls. The administration of glutamine by the intravenous or oral route and at the doses recommended before or immediately after surgery, burns, or the administration of parenteral nutrition has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine reduces the frequency of systemic infections and may also reduce the translocation of intestinal bacteria and toxins, but this has not been demonstrated. Conclusions:Glutamine administration improves the prognosis of critically ill patients presumably by maintaining the physiologic intestinal barrier and by reducing the frequency of infections.
Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation

Abstract: We have recently demonstrated that nitric oxide (NO) donors can trigger either apoptosis or necrosis of neurons as a function of the intensity of the exposure. Here, we show that the apoptosis induced by the NO donors S‐nitrosocysteine (SNOC) or S‐nitroso‐N‐acetylpenicillamine (SNAP) in cultured cerebellar granule cells (CGCs) depends on NMDA receptor (NMDA‐R) activation leading to intracellular Ca2+ overload. Early dissolution of actin filaments followed by breakdown of microtubules and nuclear lamins preceded the appearance of typical apoptotic features. NO donors induced tyrosine nitration in neurons, in a small population of contaminating astrocytes, and in cultures of cerebellar astroglial cells. However, astrocytes neither displayed cytoskeletal alterations nor underwent apoptosis. Competitive and uncompetitive NMDA receptor antagonists, such as d‐aminophosphonovaleric acid and MK‐801, did not influence tyrosine nitration but prevented the accumulation of intracellular Ca2+, cytoskeletal breakdown, and apoptosis induced by either SNOC or SNAP in CGCs. Taken together, these data strongly suggest that Ca2+ influx through NMDA‐R‐gated ion channels is a critical event in CGC apoptosis induced by NO donors.
5 and 7 bit/symbol 4D Modulation Formats Based on 2A8PSK

We propose 5 and 7 bit/symbol 4D modulation formats based on 2A8PSK, which outperform previously known modulation formats for each spectral eﬃciency. Combined with the recently reported 6 bit/symbol 2A8PSK, the 2A8PSK family covers 5-7 bits without signiﬁcant hardware modiﬁcations
A decoding procedure for compress-and-forward and quantize-and-forward relaying

In this paper, a decoding procedure is developed for both the compress-and-forward (CF) and the short message quantize-and-forward (QF-SM) relaying schemes. This procedure is based on exploiting a common feature of the mapping used by both schemes to determine the relay output from the estimate of its input. Using this decoding procedure, it is shown that the CF scheme achieves higher rates than both the conventional CF and the QF-SM schemes. The advantage of the proposed procedure is demonstrated in a Gaussian multicast one-message two-destination relay network and a multicast two-message three-destination network.
Opening up the Window into “Chemobrain”: A Neuroimaging Review

As more chemotherapy-treated cancer patients are reaching survivorship, side-effects such as cognitive impairment warrant research attention. The advent of neuroimaging has helped uncover a neural basis for these deficits. This paper offers a review of neuroimaging investigations in chemotherapy-treated adult cancer patients, discussing the benefits and limitations of each technique and study design. Additionally, despite the assumption given by the chemobrain label that chemotherapy is the only causative agent of these deficits, other factors will be considered. Suggestions are made on how to more comprehensively study these cognitive changes using imaging techniques, thereby promoting generalizability of the results to clinical applications. Continued investigations may yield better long-term quality of life outcomes by supporting patients' self-reports, and revealing brain regions being affected by chemotherapy.
The Impact of Evasion on the Generalization of Machine Learning Algorithms to Classify VoIP Traffic

We propose a novel approach to generate well generalized signatures to classify Skype VoIP traffic using a machine learning based approach. Results show that the performance of the signatures did not degrade significantly when they were evaluated on traffic that was captured from different locations and at different times as well as employed against evasion attacks. Our results on the evasion of Skype classifier demonstrate that the performance of the signatures are very promising even if the user tries maliciously to alter the characteristics of Skype traffic to evade the classifier.
Plasmodium falciparum msp2 Genotypes and Multiplicity of Infections among Children under Five Years with Uncomplicated Malaria in Kibaha, Tanzania

Genetic diversity of Plasmodium falciparum may pose challenges in malaria treatment and prevention through chemotherapy and vaccination. We assessed Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) of P. falciparum infections and sort relationship of parasitaemia with P. falciparum msp2 genotypes as well as with the number of infecting clones. The study was carried out in Kibaha, Tanzania. Ninety-nine children under five years with uncomplicated malaria were recruited. Genetic diversity was analyzed by genotyping the msp2 gene using PCR-Restriction Fragment Length Polymorphism. Thirty-two different msp2 alleles were obtained. The msp2 3D7 allelic frequency was higher (48.1%) and more prevalent than FC27 (27.3%) (p < 0.05). Twenty-four percent of the infections were mixed alleles. The individuals with FC27 had high parasitemia compared to those with 3D7 alleles (p = 0.038). The mean MOI was low (1.4 clones, 95% CI 1.2–1.5). The P. falciparum population among children at Kibaha is composed of distinct P. falciparum clones, and parasites having 3D7 are more frequent than those with FC27 alleles. Individuals with parasite having FC27 alleles have high parasite densities suggesting that parasites with FC27 alleles may associate with severity of disease in Kibaha. Low MOI at Kibaha suggests low malaria transmission rate.
The relationship between perceived organizational support, perceived coworker support, debriefing and professional quality of life in Florida law enforcement officers

The purpose of this study was to examine the relationships between perceived organizational support, perceived coworker support, and debriefing on the one hand, and compassion satisfaction, burnout, and secondary traumatic stress on the other hand in Florida law enforcement officers. To explore the relationships between these constructs, the research examined the relationships of the work environment of Florida law enforcement personnel by administering surveys gaging perceived organizational support, perceived coworker support, psychological resilience, and debriefing activities that the personnel participate in. The Professional Quality of Life: Compassion Satisfaction and Compassion Fatigue Version 5 was also sent out to establish the self-reported levels of compassion satisfaction, burnout, and secondary traumatic stress. A total of 826 surveys were completed by law enforcement personnel across the state of Florida. The study found that there were relationships between perceived organizational support, perceived coworker support, and debriefing activities and the levels of compassion satisfaction, burnout, and secondary traumatic stress in Florida law enforcement personnel.
Exploring annotation of head gesture forms in spontaneous human interaction.

Face-to-face interaction is characterised by head gestures that vary greatly in form and function. We present on-going exploratory work in characterising the form of these gestures. In particular, we define a kinematic annotation scheme and compute various agreement measures among two trained annotators. Gesture type mismatches among annotators are compared against kinematic characteristics of head gesture classes derived from motion capture data.
The Open University ’ s repository of research publications and other research outputs Supporting user tasks and context : challenges for Semantic Web research Conference Item

Whilst the tasks users perform online are often complex and wideranging, the tools currently available may not adequately support them. Attempts to classify user behaviors online have tended to focus on the medium of the web, where searching and browsing are seen as the primary modes of interaction. This paper introduces a comprehensive user-oriented classification of online tasks that emphasizes the user’s goals without assuming the use of particular internet tools or technologies. Taking greater account of a user’s context is also discussed as an essential component in better supporting performance of tasks online. Finally we consider how Semantic Web technologies can support the development of task-focused context-aware tools.
A New Digital Image Watermarking Algorithm Resilient to Desynchronization Attacks

Synchronization is crucial to design a robust image watermarking scheme. In this paper, a novel feature-based image watermarking scheme against desynchronization attacks is proposed. The robust feature points, which can survive various signal-processing and affine transformation, are extracted by using the Harris-Laplace detector. A local characteristic region (LCR) construction method based on the scale-space representation of an image is considered for watermarking. At each LCR, the digital watermark is repeatedly embedded by modulating the magnitudes of discrete Fourier transform coefficients. In watermark detection, the digital watermark can be recovered by maximum membership criterion. Simulation results show that the proposed scheme is invisible and robust against common signal processing, such as median filtering, sharpening, noise adding, JPEG compression, etc., and desynchronization attacks, such as rotation, scaling, translation, row or column removal, cropping, and random bend attack, etc.
Design of 18-bit decimator for sigma-delta analog to digital converter with variable oversampling rate for audio application

An 18-bit decimator design for sigma-delta analog to digital converter with variable oversampling rate for audio application was successfully implemented in TSMC 0.13 um Logic CMOS Technology. Behavioral model of this project is implemented using MATLAB and actual implementation using RTL Code with the aid of Verilog Compiler Simulator. The oversampling rates used in this decimator design are 32, 64, 128 and 256. Also, this decimator uses 1 sinc filter and 2 halfband filters as the main blocks for the whole system. The result of the design actually minimized the delay of the signal as compared to the behavioral simulation obtained. The total cell area is reduced reaching the desirable signal-to-noise ratio.
Very Large Scale Optimization

The purpose of this research under the NASA Small Business Innovative Research program was to develop algorithms and associated software to solve very large nonlinear, constrained optimization tasks. Key issues included efficiency, reliability, memory, and gradient calculation requirements. This report describes the general optimization problem, ten candidate methods, and detailed evaluations of four candidates. The algorithm chosen for final development is a modern recreation of a 1960s external penalty function method that uses very limited computer memory and computational time. Although of lower efficiency, the new method can solve problems orders of magnitude larger than current methods. The resulting BIGDOT software has been demonstrated on problems with 50,000 variables and about 50,000 active constraints. For unconstrained optimization, it has solved a problem in excess of 135,000 variables. The method includes a technique for solving discrete variable problems that finds a "good" design, although a theoretical optimum cannot be guaranteed. It is very scalable in that the number of function and gradient evaluations does not change significantly with increased problem size. Test cases are provided to demonstrate the efficiency and reliability of the methods and software.
The Open University ’ s repository of research publications and other research outputs Signaling strategic commitment for organizational transition : how to manage potential M & As through voluntary disclosures Conference Item

(2012). Signaling strategic commitment for organizational transition: how to manage potential M&As through voluntary disclosures. Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online's data policy on reuse of materials please consult the policies page.
Modeling The Formation of Language

Motivated by attempts to understand the origins and evolution of language, various researchers have been investigating during the past decade how a communication system with similar properties as human natural languages can form through self-organisation in a population of 'agents'. This approach rests on the assumption that the origins of language was a cultural event (44), in other words that anatomically modern humans used their available cognitive resources to invent complex communication systems similar to the way they invented and propagated tools, agriculture, or societal organisations, and that these communication systems have since propagated in a cultural fashion from one generation to the next (33), (35). This assumption contrasts with the alternative hypothesis that the origins of language has a biological origin, i.e. that there was a genetic mutation or series of mutations which has given rise to a highly specialised area in the brain, a language organ, and that the genes laying down this language organ then propagated by the well known processes of genetic transmission and natural selection ((3), (22), (8)). There are of course intermediary hypotheses possible. Specifically, some researchers have argued for Baldwinian genetic assimilation of the neuronal structures that support language (5), (43). However this would require that language or precursors of language arise through cultural evolution in the first place, suggesting a tight interaction between cultural evolution and genetic evolution (13). Note that the cultural approach does not argue that language appears out of nothing. Communicating individuals must have a 'language-ready' brain (1) with a broad range of cognitive skills, embedded in a sufficiently complex body whose control is very non-trivial. In order to make sophisticated rapid symbolic communication beneficial, they must be confronted with an environment of high ecological complexity and live in social groups that must cooperate in order to survive. These two aspects are both preconditions for the origins of language, just like pre-biotic chemistry is a precondition for the origins of life and complex ecologies are preconditions for pushing life towards greater complexity. Research to understand the formation of language has a secondary motivation. Current interfaces and language technologies invariably start from the idea that a communication system is static once it has been established, either by design or by machine learning. However analysis of natural dialogue clearly shows that humans constantly adapt to their partners at