Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering enhanced protein disaggregases for neurodegenerative disease

Abstract Protein misfolding and aggregation underpin several fatal neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). There are no treatments that directly antagonize the protein-misfolding events that cause these disorders. Agents that reverse protein misfolding and restore proteins to native form and function could simultaneously eliminate any deleterious loss-of-function or toxic gain-of-function caused by misfolded conformers. Moreover, a disruptive technology of this nature would eliminate self-templating conformers that spread pathology and catalyze formation of toxic, soluble oligomers. Here, we highlight our efforts to engineer Hsp104, a protein disaggregase from yeast, to more effectively disaggregate misfolded proteins connected with PD, ALS, and FTD. Remarkably subtle modifications of Hsp104 primary sequence yielded large gains in protective activity against deleterious α-synuclein, TDP-43, FUS, and TAF15 misfolding. Unusually, in many cases loss of amino acid identity at select positions in Hsp104 rather than specific mutation conferred a robust therapeutic gain-of-function. Nevertheless, the misfolding and toxicity of EWSR1, an RNA-binding protein with a prion-like domain linked to ALS and FTD, could not be buffered by potentiated Hsp104 variants, indicating that further amelioration of disaggregase activity or sharpening of substrate specificity is warranted. We suggest that neuroprotection is achievable for diverse neurodegenerative conditions via surprisingly subtle structural modifications of existing chaperones.
Provenance and trust as new factors for self-organization in a wireless sensor network

Trust can be an important component of wireless sensor networks for believability of the produced data and trust history is a crucial asset in deciding trust of the data. In our previous work, we developed an architecture called ProTru and we showed how provenance can be used for registering previous trust records and other information such as node type, data type, node location, average of historical data. We designed a distributed trust enhancing architecture using only local provenance during sensor fusion with a low communication overhead. Our network is cognitive in the sense that our system reacts automatically upon detecting low trust and restructures itself. In this work, we are extending our previous architecture by storing dataflow provenance graphs. This feature will enhance the cognitive abilities of our system by giving the network the capability of remembering past network snapshots.
The influence of gravitational lensing on the spectra of lensed QSOs

We consider the influence of (milli/micro)lensing on the spectra of lensed QSOs. We propose a method for the observational detection of microlensing in the spectra of lensed QSOs and apply it to the spectra of the three lensed QSOs (PG 1115+080, QSO 1413+117 and QSO 0957+561) observed with Hubble Space Telescope (HST). We find that the flux ratio between images A1 and A2 of PG 1115+080 is wavelengthdependent and shows differential magnification between the emission lines and the continuum. We interpret this magnification as arising from millilensing. We also find that the temporal variations in the continuum of image C of QSO 1413+117 may be caused by microlensing, while the temporal variation observed in QSO 0957+561 was probably an intrinsic one.
Réseau social et capital social : une distinction conceptuelle nécessaire illustrée à l’aide d’une enquête sur l’insertion professionnelle de jeunes Québécois

Dans cet article, nous proposons une operationnalisation de la definition du « capital social » selon Pierre Bourdieu, dans sa relation avec celle du « reseau social ». Dans un premier temps, apres une mise en contexte, le cadre conceptuel presente les differentes acceptions du « capital social » et explicite la definition retenue. Dans un deuxieme temps, nous appliquons ce cadre conceptuel a une analyse de donnees tirees d’une recherche menee au Quebec. Les resultats de l’analyse montrent qu’en depassant la simple notion de reseau de contacts, nous avons pu illustrer la difference entre l’interconnaissance et l’interreconnaissance. Il s’agit certes de nuances, mais qui prennent leur importance dans la comprehension du phenomene. En somme, il s’avere necessaire de distinguer le concept de reseau social de celui de capital social pour en arriver a une meilleure comprehension du processus d’insertion professionnelle des jeunes.
Tackling Structures of Long Noncoding RNAs

RNAs are important catalytic machines and regulators at every level of gene expression. A new class of RNAs has emerged called long non-coding RNAs, providing new insights into evolution, development and disease. Long non-coding RNAs (lncRNAs) predominantly found in higher eukaryotes, have been implicated in the regulation of transcription factors, chromatin-remodeling, hormone receptors and many other processes. The structural versatility of RNA allows it to perform various functions, ranging from precise protein recognition to catalysis and metabolite sensing. While major housekeeping RNA molecules have long been the focus of structural studies, lncRNAs remain the least characterized class, both structurally and functionally. Here, we review common methodologies used to tackle RNA structure, emphasizing their potential application to lncRNAs. When considering the complexity of lncRNAs and lack of knowledge of their structure, chemical probing appears to be an indispensable tool, with few restrictions in terms of size, quantity and heterogeneity of the RNA molecule. Probing is not constrained to in vitro analysis and can be adapted to high-throughput sequencing platforms. Significant efforts have been applied to develop new in vivo chemical probing reagents, new library construction protocols for sequencing platforms and improved RNA prediction software based on the experimental evidence.
Musical perceptual similarity estimation using interactive genetic algorithm

This paper proposes a new approach to estimate the emotional perceptual similarity of music using interactive genetic algorithm. Different combinations of measure function and feature weights construct the searching space, and users' subjective similarity evaluations of musical pieces are used as the fitness. The approach tries to search for the optimal combination of measure function and feature weights to better reflect human's perception. A comparative emotion detection experiment is designed to explore the effectiveness of our approach in our MIDI database. The one is the simple K-Nearest Neighbor (KNN) and the other is the modified KNN using the optimal combination obtained. Experimental results show that our method outperforms the simple KNN classifier, which confirms its usefulness of better reflecting human's perception.
Tools and Products

Department editor Dave Kasik highlights some of the new computer graphics tools and products on the market. In this issue the featured tools and products are a wireless mini trackball keyboard from Adesso, a distribution amplifier from Gefen, a super fast DVD burner from Samsung, an upgrade for photoshop connections from Strata, and a software line for video on-the-go from Pinnacle.
Samuelsonian Economics and the Twenty‐First Century

This volume illuminates and critically assesses Paul A. Samuelson's voluminous and groundbreaking contributions to the field of economics. The volume includes contributions from eminent scholars, including 6 Nobel Laureates, covering the extraordinary depth and breadth of Samuelson's contributions. Samuelson, the first American economist to win the Nobel prize in 1970, was the foremost voice in economics in the latter half of the 20th century. He single-handedly transformed the discipline by creating a new way of presenting economics, making it possible for it to be cast all in mathematical terms. Samuelson developed broad frameworks, such as the neoclassical synthesis, a mixed economy, and the surrogate production function, which provided practitioners with a vision for research. Samuelson's contributions to economics are rich, complex, consequential, and relevant to the ordinary economics of life. The quality of Samuelson's output and methods leave no doubt that his contributions continue to be timely and relevant even in the 21st century. Ideal as a reference or an introduction to Samuelson's work, this is a must-have for students and academics alike. Contributors to this volume - James B. Cooper, Johannes Kepler University, Austria Rod Cross, University of Strathclyde, UK Paul Davidson, University of Tennessee Peter Diamond, MIT Avinash Dixit, Princeton University Franklin Fisher, MIT Milton Friedman, Stanford University Geoff Harcourt, Cambridge University Lawrence R. Klein, University of Pennsylvania Laurence J. Kotlikoff, Boston University Rachel McCulloh, Brandeis University Harry M. Marowitz, University of California, San Diego Robert C. Merton, Harvard University Paul Milgrom, Stanford University William D. Nordhaus, Yale University Luigi Pasinetti, Universita Cattolica del Sacro Cuore, Milano Robert A. Pollak, Washington University Lall Ramrattan, University of California, Berkeley Kenneth Rogoff, Harvard University Thomas Russell, Santa Clara University Robert M. Solow, MIT Joseph E. Stiglitz, Columbia University Michael Szenberg, Pace University Hal R. Varian, University of California, Berkeley
Failure to Downregulate the Epithelial Sodium Channel Causes Salt Sensitivity in Hsd11b2 Heterozygote Mice

In vivo, the enzyme 11&bgr;-hydroxysteroid dehydrogenase type 2 influences ligand access to the mineralocorticoid receptor. Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess. Studies in humans and experimental animals have linked reduced 11&bgr;-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity of blood pressure. In the present study, renal mechanisms underpinning salt sensitivity were investigated in Hsd11b2 +/− mice fed low-, standard-, and high-sodium diets. In wild-type mice, there was a strong correlation between dietary sodium content and fractional sodium excretion but not blood pressure. High sodium feeding abolished amiloride-sensitive sodium reabsorption, consistent with downregulation of the epithelial sodium channel. In Hsd11b2 +/− mice, the natriuretic response to increased dietary sodium content was blunted, and epithelial sodium channel activity persisted. High-sodium diet also reduced renal blood flow and increased blood pressure in Hsd11b2 +/− mice. Aldosterone was modulated by dietary sodium in both genotypes, and salt sensitivity in Hsd11b2 +/− mice was associated with increased plasma corticosterone levels. Chronic administration of an epithelial sodium channel blocker or a glucocorticoid receptor antagonist prevented salt sensitivity in Hsd11b2 +/− mice, whereas mineralocorticoid receptor blockade with spironolactone did not. This study shows that reduced 11&bgr;-hydroxysteroid dehydrogenase type 2 causes salt sensitivity of blood pressure because of impaired renal natriuretic capacity. This reflects deregulation of epithelial sodium channels and increased renal vascular resistance. The phenotype is not caused by illicit activation of mineralocorticoid receptors by glucocorticoids but by direct activation of glucocorticoid receptors.
Empirical assessment of WDP tool: A tool to support web usability inspections

Usability is one of the most important software qualities regarding its acceptability by end users. It is even more important in the context of Web applications. One way of evaluating applications usability is through inspections. The WDP (Web Design Perspectives-based Usability Evaluation) is a usability inspection technique presenting evidence of industrial use feasibility; however the need for some computerized support was suggested by its users. Therefore, the WDP Tool was built aiming to provide automated support to the application of the WDP technique, reducing the effort involved in usability inspections with WDP. This paper presents two observational studies regarding the use of the WDP Tool, which aimed to analyze the cost-effectiveness of its application and its appropriateness to the industrial environment through the Technology Acceptance Model (TAM). The results provide feasibility indication of using the WDP Tool to support usability inspections in real software development projects in industry.
Elicitation, an Effective Strategy for the Biotechnological Production of Bioactive High-Added Value Compounds in Plant Cell Factories

Plant in vitro cultures represent an attractive and cost-effective alternative to classical approaches to plant secondary metabolite (PSM) production (the “Plant Cell Factory” concept). Among other advantages, they constitute the only sustainable and eco-friendly system to obtain complex chemical structures biosynthesized by rare or endangered plant species that resist domestication. For successful results, the biotechnological production of PSM requires an optimized system, for which elicitation has proved one of the most effective strategies. In plant cell cultures, an elicitor can be defined as a compound introduced in small concentrations to a living system to promote the biosynthesis of the target metabolite. Traditionally, elicitors have been classified in two types, abiotic or biotic, according to their chemical nature and exogenous or endogenous origin, and notably include yeast extract, methyl jasmonate, salicylic acid, vanadyl sulphate and chitosan. In this review, we summarize the enhancing effects of elicitors on the production of high-added value plant compounds such as taxanes, ginsenosides, aryltetralin lignans and other types of polyphenols, focusing particularly on the use of a new generation of elicitors such as coronatine and cyclodextrins.
Genetic Convergence in the Adaptation of Dogs and Humans to the High-Altitude Environment of the Tibetan Plateau

The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau.
Analysis and design of a 3-DOF flexure-based zero-torsion parallel manipulator for nano-alignment applications

A flexure-based parallel manipulator (FPM) is a closed-loop compliant mechanism in which the moving platform is connected to the base through a number of flexural legs. Utilizing parallel-kinematics configurations and flexure joints, the FPMs can achieve extremely high motion resolution and accuracy. In this work, we focus on the analysis and design of a 3-DOF (θx -θy -Z) zero-torsion FPM for nano-alignment applications. Among various possible zero-torsion parallel-kinematics configurations, it is identified that the 3-legged Prismatic-Prismatic-Spherical (3PPS) is a suitable candidate. Based on the concept of instantaneous rotation, the critical kinematic design issues, such as displacement and workspace analyses, are addressed. With these analysis algorithms, the major kinematic parameters are readily determined to meet the task requirements. To achieve a large workspace, beam-based flexure joints are employed in the FPM design. As the beam-based Universal (U) flexure joints are able to accommodate the required passive prismatic and spherical motions, each flexure PPS leg can be replaced by a simple flexure PU leg. A research prototype of the 3-DOF 3PU FPM has been developed, which achieves position and orientation resolutions of 20 nm and 0.05 arcsecond throughout a workspace of 5° × 5° × 5 mm, respectively.
What's New in Trauma in the Past 10 Years

The management of patients following injury has undergone a substantial evolution over the past 10 years. Our understanding of the physiology of injury and blood loss continues to be refined. This has allowed us to dispelseveral myths that were long-held dogmas in the area of resuscitation. Improved technology has provided us with more discriminating diagnostic modalities, allowing us to streamline the evaluation process and making important diagnoses earlier. Noninvasive or minimally invasive technology has also evolved, bringing exciting new methods of hemostasis. In addition, we are beginning to understand the physiologic and economic consequences of nontherapeutic exploratory surgery and have become much more selective in our management. As our understanding has increased, so has our ability to cull out special patients, such as older patients, and tailor management strategies specifically for them. Injury management continues to develop quickly and profoundly. Perhaps the most important lesson we have learned over the last 10 years is that we must expand our horizons and reinvestigate those unproven beliefs that have governed many of our treatment decisions. In this chapter, we will describe some of the most important advances made in the field of trauma management over the last 10 years.
Holistic Living in Globalized World: An Indian Perspective

Globalization is a multidimensional phenomenon. The process is irreversible and we have to live through it. It does have several advantages, but at the same time it impacts individual's personal life, social relationships and world's ecosystem adversely. These challenges can be met through adopting tenets of holistic life prescribed in traditional Indian culture. In contrast to Western linear world view, the relational worldview in Indian culture sees life through harmonious relationships where healthy living is achieved by maintaining balance between the many interrelating factors in one's circle of life. The relational worldview model for holistic living can best be represented through three major factors that together must come into balance. These factors represent mind-body-spirit and their positive relationship with society and nature. Besides internal harmony in mind-bodyspirit, ancient literature verbalizes of relational harmony with the ecology and society. It emphasizes on an understanding of the intrinsic interdependence of all beings. Social harmony in accordance with the percepts of dharma and karma are considered essential for a healthy and peaceful life journey towards self-realization. Every individual is considered as a biologically, psychologically and spiritually part of nature's nonpolluting, intelligent ways. The nature itself is a living system, and the psyche and body exists within this larger system. The paper presents Indian tradition of holistic living that has time tested concepts for the all round development of an individual with proper balance of the importance of self, the society and the nature. The concepts have survived since the vedic period because of their sheer practicality. They are still valid and in fact, more relevant in today's complexities of day-to-day life.
Word learning under adverse listening conditions: Context-specific recognition

Previous studies of word learning have presented the items to listeners under ideal conditions. Here we ask how listeners learn new vocabulary items under adverse listening conditions. Would listeners form acoustically-specific representations that incorporated the noise, base their representations on noise-free language knowledge, or both? To address these questions, listeners learned 16 words as labels for unfamiliar shapes presented on a computer display. During the learning phase, word-shape pairings were presented with either clear or white-noise-embedded tokens. For each word (e.g. dabo), another word shared consonants (e.g. dubei) and a third shared vowels (e.g. gapo). Learning was assessed in a 4AFC picture-selection task. The highest accuracy and speed were achieved by listeners who experienced the same noise level at exposure and test (both clear or both noisy), suggesting that listeners' representations of noisy words were faithful to the spectral context experienced during the learning phase. Implications for word learning and recognition across a variety of listening conditions are discussed.
Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models.

Article de synthese sur l'adaptation cellulaire (assimilation du glucose) et moleculaire (flux d'oxygene; enzymes glycolytiques) des muscles squelettiques en reponse a un exercice (aerobique, exercice de resistance). Utilisation de plusieurs modeles animaux (vertebres), de cultures cellulaires et comparaison avec l'activite physique humaine. Synthese sur les adaptations affectant le flux cardiaque, le flux sanguin peripherique et le petabolisme des myocytes cardiaques
Adjusting to new work teams: Testing work experience as a multidimensional resource for newcomers

Summary The successful performance adjustment of team newcomers is an increasingly important consideration given the prevalence of job-changing and the uncertainty associated with starting work in a new team setting. Consequently, using sensemaking and uncertainty reduction theories as a conceptual basis, the present study tested work experience as a potential resource for newcomer performance adjustment in teams. Specifically, we tested work experience as a multidimensional predictor of both initial newcomer performance and the rate of performance change after team entry. We tested hypotheses using longitudinal newcomer performance data in the context of professional basketball teams. Although the traditional quantitative indicators of the length and amount of work experience were not meaningfully associated with newcomer performance adjustment, their interaction was. In addition, the qualitative indicator of newcomers' past transition experience revealed a significant, positive association with the rate of newcomer performance improvement following team entry. These results suggest that work experience is a meaningful facilitator of newcomer adjustment in teams and emphasize the dual consideration of both quantitative and qualitative work experiences. The theoretical and practical implications of these findings are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Low power design without compromise (panel)

It is mid 1998. The Speedy Microsystems design team is discussing a memo they have just received from Marketing about their next generation machine due to tape out in 2000, a 1.5V, lGHz, 100 watt, 40 million transistor superscalar microprocessor with multimedia extensions to be fabricated in O.lSum CMOS. Only one problem. Marketing has just announced a major push into Network Computers, and all of a sudden the power budget has dropped to 4 watts. Including the multimedia extensions and an onchip radio. Worse yet, a major customer has just invented a 50mW color display and is threatening to cancel its $1 billion order unless Speedy can deliver a 1OOmW processor in 18 months. Not only that, Marketing wants to continue pushing forward at the high end because these has been explosive growth in the serves market.