Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing the Native Tropism of Adenovirus Vectors Requires Removal of both CAR and Integrin Interactions

ABSTRACT The development of tissue-selective virus-based vectors requires a better understanding of the role of receptors in gene transfer in vivo, both to rid the vectors of their native tropism and to introduce new specificity. CAR and αv integrins have been identified as the primary cell surface components that interact with adenovirus type 5 (Ad5)-based vectors during in vitro transduction. We have constructed a set of four vectors, which individually retain the wild-type cell interactions, lack CAR binding, lack αv integrin binding, or lack both CAR and αv integrin binding. These vectors have been used to examine the roles of CAR and αv integrin in determining the tropism of Ad vectors in a mouse model following intrajugular or intramuscular injection. CAR was found to play a significant role in liver transduction. The absence of CAR binding alone, however, had little effect on the low level of expression from Ad in other tissues. Binding of αv integrins appeared to have more influence than did binding of CAR in promoting the expression in these tissues and was also found to be important in liver transduction by Ad vectors. An effect of the penton base modification was a reduction in the number of vector genomes that could be detected in several tissues. In the liver, where CAR binding is important, combining defects in CAR and αv integrin binding was essential to effectively reduce the high level of expression from Ad vectors. While there may be differences in Ad vector tropism among species, our results indicate that both CAR and αv integrins can impact vector distribution in vivo. Disruption of both CAR and αv integrin interactions may be critical for effectively reducing native tropism and enhancing the efficacy of specific targeting ligands in redirecting Ad vectors to target tissues.
Type 1 fimbriae deliver an LPS‐ and TLR4‐dependent activation signal to CD14‐negative cells

Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae‐dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll‐like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS‐ and TLR4‐dependent signal to the CD14‐negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS‐dependent response in those cells. A similar LPS‐ and fimbriae‐dependent response was observed in the urinary tract of TLR4‐proficient mice, but not in TLR4‐defective mice. The moderate inflammatory response in the TLR4‐defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14‐negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host ‘sees’ LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells.
Antibodies to beta2-glycoprotein-I: relation of anticardiolipin antibodies with clinical and laboratory parameters in patients with systemic lupus erythematosus.

OBJECTIVES There are controversial reports on the frequency of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). Thus, we aimed to determine the frequency and clinical importance of aPL isotypes in Turkish patients with SLE. DESIGN AND METHODS Fifty-nine patients with SLE and 41 healthy controls were included. Serum aPL levels were measured both in patients and healthy subjects by ELISA. RESULTS Fifteen of the patients with SLE had the antiphospholipid syndrome (APS) (25.4%). The percentage of anticardiolipin antibody (aCL)-positive SLE patients among all patients was 56%. At least one isotype of anti-beta(2)-glycoprotein I (beta(2)-GPI) antibody was positive in 83% of patients. The positivity rates of aCL and anti-beta(2)-GPI antibodies in patients with or without APS were higher than the healthy controls. There were positive correlations between isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI and manifestations of APS. CONCLUSION It seems that the isotypes of IgM aCL, IgG and IgM anti-beta(2)-GPI are correlated with manifestations of APS. They may play a role in pathogenesis and may be helpful in establishing the diagnosis.
Enhancement mode strained (1.3%) germanium quantum well FinFET (WFin=20nm) with high mobility (μHole=700 cm2/Vs), low EOT (∼0.7nm) on bulk silicon substrate

Compressively strained Ge (s-Ge) quantum well (QW) FinFETs with Si<sub>0.3</sub>Ge<sub>0.7</sub> buffer are fabricated on 300mm bulk Si substrate with 20nm W<sub>Fin</sub> and 80nm fin pitch using sidewall image transfer (SIT) patterning process. We demonstrate (a) in-situ process flow for a tri-layer high-κ dielectric HfO<sub>2</sub>/Al<sub>2</sub>O<sub>3</sub>/GeO<sub>x</sub> gate stack achieving ultrathin EOT of 0.7nm with low D<sub>IT</sub> and low gate leakage; (b) 1.3% s-Ge FinFETs with Phosphorus doped Si<sub>0.3</sub>Ge<sub>0.7</sub> buffer on bulk Si substrate exhibiting peak μ<sub>h</sub>=700 cm<sup>2</sup>/V<sub>s</sub>, μ<sub>h</sub>=220 cm<sup>2</sup>/Vs at 10<sup>13</sup> /cm<sup>2</sup> hole density. The s-Ge FinFETs achieve the highest μ*C<sub>max</sub> of 3.1×10<sup>-4</sup> F/Vs resulting in 5x higher I<sub>ON</sub> over unstrained Ge FinFETs.
Modularized buck-boost + Cuk converter for high voltage series connected battery cells

This paper proposes a new bidirectional dc-dc converter - buck-boost + Cuk converter - for series connected battery cells. Traditionally, in order to balance n battery cells in a string, (2n-1) switches are required by either the buck-boost converter or the Cuk converter. However, by nicely combine the buck-boost converter and the Cuk converter together, the proposed buck-boost + Cuk converter only requires n switches. It achieves almost half of the switch count reduction, without losing the advantage of modularization or sacrificing the device voltage stress, unlike many other existing one-switch-per-cell topologies. Meanwhile, it still maintains the buck-boost battery charge equalizer's best characteristic - simple pulse width modulation (PWM) - 50% duty cycle. Moreover, it offers a solution to bypass the open-circuit faulty cells, and prolong the life time of the whole battery string. Simulation and experimental results are given to demonstrate the functionality of the proposed buck-boost + Cuk converter.
Bringing generations together: Social network adapted for elders

Using modern social media solutions requires skills and technical knowledge that elders usually do not possess. In this paper we present social network adapted for elders in order to reconnect them with friends and family. Main features of this social network are platform independent video communication, simple user interface and intuitive navigation. In addition, we integrated e-health service to expand usability of developed social network by providing elders with a content they might find interesting.
Regulation of early Xenopus development by the PIAS genes

Originally identified as cytokine inhibitors, protein inhibitors of activated STAT (PIAS) are shown to regulate activities of a plethora of proteins and influence diverse processes such as immune response, cancer formation, and cell cycle progression. However, the roles of PIAS during vertebrate embryogenesis are less understood. In this study, we report isolation and initial characterization of all four PIAS genes from Xenopus laevis. The Xenopus PIAS genes are expressed throughout early development and have overlapping and distinct expression patterns, with, for example, high levels of PIAS2 in the notochord and strong expression of PIAS4 in the neural and neural crest derivatives. Overexpression of PIAS disrupts mesoderm induction and impairs body axis formation. PIAS proteins have differential ability to regulate signals from the growth factors activin, bone morphogenetic protein 4 (BMP4), and Wnt8. Our data suggest that Xenopus PIAS play important roles in mesodermal induction and patterning during early frog development. Developmental Dynamics 240:2120–2126, 2011. © 2011 Wiley‐Liss, Inc.
Cas9–crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria

Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide adaptive immunity against viruses and plasmids in bacteria and archaea. The silencing of invading nucleic acids is executed by ribonucleoprotein complexes preloaded with small, interfering CRISPR RNAs (crRNAs) that act as guides for targeting and degradation of foreign nucleic acid. Here, we demonstrate that the Cas9–crRNA complex of the Streptococcus thermophilus CRISPR3/Cas system introduces in vitro a double-strand break at a specific site in DNA containing a sequence complementary to crRNA. DNA cleavage is executed by Cas9, which uses two distinct active sites, RuvC and HNH, to generate site-specific nicks on opposite DNA strands. Results demonstrate that the Cas9–crRNA complex functions as an RNA-guided endonuclease with RNA-directed target sequence recognition and protein-mediated DNA cleavage. These findings pave the way for engineering of universal programmable RNA-guided DNA endonucleases.
SSM: Secure Service Manager for the Internet of Things

Internet of Things (IoT) has attracted attention in various fields where small devices such as sensors and actuators are intended to be connected with each other by using TCP/IP protocols. To build value-added services in such fields, security is one of the most important considerations. The IETF standard group has proposed to use the DTLS protocol to provide security services with constrained devices in lossy networks. However, the protocol cannot cover all constrained devices because of heterogeneous properties. Under the respect, we propose a secure IoT architecture and design a secure service manager (SSM) that is motivated by traditional web service architecture.
A social analytics platform for smarter commerce solutions

When providing customers with a personalized shopping experience, there is tremendous value in understanding and applying social data shared by those consumers. Understanding this data and how best to generate business value from it is the core challenge of many businesses today. Friends, family, and experts alike influence consumers in their shopping preferences and purchase decisions. Yet, the ability of a business to analyze data on such influence, and recommend products and services that best respond to its customers' needs or aspirations, is typically limited by fragmented capabilities; a business relies heavily on the use of spreadsheets, manual market analysis, isolated software, or reactive messaging. This paper offers a solution to this fragmentary approach by introducing a social analytics platform for smarter commerce. This platform provides a holistic understanding of the customer by making use of social and enterprise data to present recommendations and related opinions, and to isolate influencers so as to ultimately provide customers with a personalized shopping experience. The functionality described in this paper is in the context of the retail industry but can be applied to other industries. The paper describes the architecture of the social analytics platform and the various analytics components currently implemented as part of the platform.
Designing for Digital Reading

Reading is a complex human activity that has evolved, and co-evolved, with technology over thousands of years. Mass printing in the fifteenth century firmly established what we know as the modern book, with its physical format of covers and paper pages, and now-standard features such as page numbers, footnotes, and diagrams. Today, electronic documents are enabling paperless reading supported by eReading technologies such as Kindles and Nooks, yet a high proportion of users still opt to print on paper before reading. This persistent habit of "printing to read" is one sign of the shortcomings of digital documents -- although the popularity of eReaders is one sign of the shortcomings of paper. How do we get the best of both worlds? The physical properties of paper (for example, it is light, thin, and flexible) contribute to the ease with which physical documents are manipulated; but these properties have a completely different set of affordances to their digital equivalents. Paper can be folded, ripped, or scribbled on almost subconsciously -- activities that require significant cognitive attention in their digital form, if they are even possible. The nearly subliminal interaction that comes from years of learned behavior with paper has been described as lightweight interaction, which is achieved when a person actively reads an article in a way that is so easy and unselfconscious that they are not apt to remember their actions later. Reading is now in a period of rapid change, and digital text is fast becoming the predominant mode of reading. As a society, we are merely at the start of the journey of designing truly effective tools for handling digital text. This book investigates the advantages of paper, how the affordances of paper can be realized in digital form, and what forms best support lightweight interaction for active reading. To understand how to design for the future, we review the ways reading technology and reader behavior have both changed and remained constant over hundreds of years. We explore the reasoning behind reader behavior and introduce and evaluate several user interface designs that implement these lightweight properties familiar from our everyday use of paper. We start by looking back, reviewing the development of reading technology and the progress of research on reading over many years. Drawing key concepts from this review, we move forward to develop and test methods for creating new and more effective interactions for supporting digital reading. Finally, we lay down a set of lightweight attributes which can be used as evidence-based guidelines to improve the usability of future digital reading technologies. By the end of this book, then, we hope you will be equipped to critique the present state of digital reading, and to better design and evaluate new interaction styles and technologies.
Forgoing Medically Provided Nutrition and Hydration in Pediatric Patients

Discussion of the ethics of forgoing medically provided nutrition and hydration tends to focus on adults rather than infants and children. Many appellate court decisions address the legal propriety of forgoing medically provided nutritional support of adults, but only a few have ruled on pediatric cases that pose the same issue. The cessation of nutritional support is implemented most commonly for patients in a permanent vegetative state (often referred to as persistent vegetative state (hereinafter “PVS”)). An estimated 4,000 to 10,000 American children are in the permanent vegetative state, compared to 10,000 to 25,000 adults. Yet the dearth of literature, case reports, and court decisions suggests that physicians and families of pediatric patients stop medically provided nutrition or seek court orders much less frequently.
Fuzzy behavior fusion for reactive control of an autonomous mobile robot: MARGE

A distributed heterogeneous network of fuzzy control agents has been developed for reactive behavior-based control of an autonomous mobile robot This methodology allows the authors' vehicle, MARGE, to perform realistic tasks in unstructured environments. Control actions for the robot are generated by a colony of independent agents that compete and cooperate to determine the emergent motion of the vehicle. Fuzzy rules are used to implement a diverse array of real-time functions within one simple development environment. The authors' multi-layer approach differs from other methods that perform the fuzzy inference mapping in one step. Real-time control without special hardware is possible by using a singleton centroid calculation and by breaking complex behaviors down into simple modules. <<ETX>>
Atypical inflammation in the central nervous system in prion disease

&NA; The inflammatory response in prion diseases is dominated by microglial activation. Contrary to their profile in vitro none of the pro‐inflammatory cytokines interleukin‐1&bgr;, interleukin‐6, or tumour necrosis factor‐&agr; are significantly upregulated in the ME7 model of prion disease. However, two major inflammatory mediators are elevated: transforming growth factor‐&bgr;1 and prostaglandin E2. This cytokine profile is the same as that reported for macrophages during phagocytosis of apoptotic cells and indeed transforming growth factor‐&bgr;1 and prostaglandin E2 are responsible for the downregulated phenotype of these macrophages. Transforming growth fact‐or‐&bgr;1 may also have roles in extracellular matrix deposition and in amyloidogenesis and may play a direct role in disease pathogenesis. There is also now evidence to suggest that a peripheral infection, and its consequent systemic cytokine expression, may drive central nervous system cytokine expression and perhaps exacerbate disease.
Light‐scattering study of DNA condensation: Competition between collapse and aggregation

Light‐scattering studies were done to investigate the DNA collapse transition, a large and discontinuous reduction in the radius of gyration. Of particular concern was differentiating the compaction of a single DNA molecule from aggregation. Solutions of RK2 plasmid DNA (Mr = 37 × 106) or bacteriophage T7 DNA (Mr = 25 × 106) were titrated with the condensing reagents spermidine in aqueous solvent or magnesium ion in ethanol–water solvent. The transition was followed by the change in scattering at a single angle or by the change in the angular dependence of scattering. At concentrations below 1 μg/mL, only aggregation could be detected by observation at a single angle; therefore, to study the collapse transition, it was necessary to measure the angular dependence of scattering. The intensities measured between the angles 30° and 60° were fit to known scattering functions. At low concentrations of the condensing reagent, the data were consistent with the scattering function of a random coil. On the other hand, during the transition at higher reagent concentrations, the curve that fit the data required two components—the scattering function for a random coil with a large radius of gyration, plus that for a sphere with a radius about one‐fifth of that of the coil. The fractional concentration of the sphere increased with increasing condensing‐reagent concentration. This two‐component behavior is in apparent contrast to the situation with a more flexible polymer such as polystyrene, in accord with theoretical predictions. At still higher reagent concentrations, aggregation was apparent. Condensation to a collapsed state was reversible without hysteresis, while dissolution of the aggregated state nearly always occurred with hysteresis. Qualitative agreement between the observed DNA collapse transition and the theoretical phase diagram presented in the preceding paper was found, although the light‐scattering results did not show quantitative agreement with the simple theoretical model.
Attention Deficit Hyperactivity Disorder: Current Progress and Controversies

Objective: Attention deficit hyperactivity disorder (ADHD) is a common chronic and disabling condition in children. This paper reviews the taxonomic issues and the major comorbid conditions, neurobiological correlates, treatment and public health issues associated with ADHD. Method: Pertinent recent papers are reviewed from the psychological and psychiatric literature. Results: The two major taxonomies now define a similar group of children with ADHD of a combined type/hyperkinetic disorder. Advances in the understanding and treatment of ADHD demonstrate the complex multidimensional links between neurobiology, psychology and behaviour. Careful assessment of individual factors in treatment planning and ongoing monitoring of psychostimulant medication treatment in the longer term are recommended. Conclusions: There is much still to learn about ADHD, and increased levels of clinical research and treatment resources are required.
An Improved Method of Measuring the Quality of Web Search Results

Disclaimers • This talk presents the opinions of the authors. It does not necessarily reflect the views of Yahoo! Inc. • This talk does not imply that these metrics are used by Yahoo! , or should they be used, they may not be used in the way described in this talk. • The examples are just that – examples. Please do not generalize them to the level of comparing search engines. • To learn about user satisfaction metrics • To learn about how to interpret metrics results • To get the relevant bibliography • To learn about the open problems 5
Structure--side-effect sorting of drugs. II. Skin sensitization.

A computerized sorting program was used to sort out 120 drugs that have been reported to cause skin sensitization from a data bank of 540 clinically useful drugs. Based on an analysis of functional groups, a number of unique common denominators were found for skin sensitization due to covalent bond formation with body proteins. These include potential epoxide-forming groups such as an electron-deficient benzene ring, a vinyl group, hydroxylamine and N-oxide precursors, drugs capable of forming a benzylic radical, β-lactam derivatives, and α,β-unsaturated ketones. By using multiple-regression analysis, the quantitative structure–activity relationship for skin-sensitizing properties of 3-alkyl catechols and 2,4-dinitrobenzene derivatives are also reported.