Miracle-dz/UniFAR-FTUs huggingface dataset:
Why is it important to analyze the cardiac sarcomere subproteome?

Diseases of the heart are epidemic and there is an urgent need for better diagnosis, prevention and treatment of these disorders. We focus here on proteomic analysis of cardiac sarcomeres, which house the molecular machines and major energy consumers for cardiac contraction. Established and emerging evidence [1] on the significance of an altered sarcomere subproteome in acquired and genetic disorders of the heart forms a significant rationale for our focus on the sarcomeric subproteome. Moreover, the relatively large abundance of sarcomeric proteins in heart muscle cells makes them excellent candidates for developing and refining analytical methods for the detection of important modifications in less abundant subproteomes. Cardiac sarcomeres represent a highly ordered and multifunctional protein network, significant not only as the molecular machines responsible for ejection of blood, but also as critical elements in signal reception and transduction [2]. Moreover, proteins of the Z-disk and M-band, which communicate with each other through the giant protein, titin, and with the cytoskeletal network form a powerful cellular tool for mechano-signaling. A major signal is cellular Ca, which binds to the sarcomere receptor troponin C and triggers systole by setting into motion a complex set of protein–protein interactions, promoting the reaction of myosin cross-bridges (the molecular motors) with actin [3]. Membrane channels, exchangers, and transporters control release and reuptake of cellular Ca sensed by the sarcomeres [4], but there is strong evidence that systole is maintained by mechanisms intrinsic to the sarcomeres involving co operative processes which spread activation along the thin filaments independently of bound Ca [3]. Thus, in conjunction with the activity of these membrane proteins, sarcomeric proteins play a major role in the control of cardiac dynamics and in tuning the heartbeat to the prevailing heart rate.
Compensatory Mutations in E1, p7, NS2, and NS3 Enhance Yields of Cell Culture-Infectious Intergenotypic Chimeric Hepatitis C Virus

ABSTRACT There is little understanding of mechanisms underlying the assembly and release of infectious hepatitis C virus (HCV) from cultured cells. Cells transfected with synthetic genomic RNA from a unique genotype 2a virus (JFH1) produce high titers of virus, while virus yields are much lower with a prototype genotype 1a RNA containing multiple cell culture-adaptive mutations (H77S). To characterize the basis for this difference in infectious particle production, we constructed chimeric genomes encoding the structural proteins of H77S within the background of JFH1. RNAs encoding polyproteins fused at the NS2/NS3 junction (“H-NS2/NS3-J”) and at a site of natural, intergenotypic recombination within NS2 [“H-(NS2)-J”] produced infectious virus. In contrast, no virus was produced by a chimera fused at the p7-NS2 junction. Chimera H-NS2/NS3-J virus (vH-NS2/NS3-J) recovered from transfected cultures contained compensatory mutations in E1 and NS3 that were essential for the production of infectious virus, while yields of infectious vH-(NS2)-J were enhanced by mutations within p7 and NS2. These compensatory mutations were chimera specific and did not enhance viral RNA replication or polyprotein processing; thus, they likely compensate for incompatibilities between proteins of different genotypes at sites of interactions essential for virus assembly and/or release. Mutations in p7 and NS2 acted additively and increased the specific infectivity of vH-(NS2)-J particles, while having less impact on the numbers of particles released. We conclude that interactions between NS2 and E1 and p7 as well as between NS2 and NS3 are essential for virus assembly and/or release and that each of these viral proteins plays an important role in this process.
Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy

Multiphoton microscopy (MPM) has become increasingly popular and widely used in both basic and clinical liver studies over the past few years. This technology provides insights into deep live tissues with less photobleaching and phototoxicity, which helps us to better understand the cellular morphology, microenvironment, immune responses and spatiotemporal dynamics of drugs and therapeutic cells in the healthy and diseased liver. This review summarizes the principles, opportunities, applications and limitations of MPM in hepatology. A key emphasis is on the use of fluorescence lifetime imaging (FLIM) to add additional quantification and specificity to the detection of endogenous fluorescent species in the liver as well as exogenous molecules and nanoparticles that are applied to the liver in vivo. We anticipate that in the near future MPM‐FLIM will advance our understanding of the cellular and molecular mechanisms of liver diseases, and will be evaluated from bench to bedside, leading to real‐time histology of human liver diseases.
Design and management of networks with low power consumption. (Conception et gestion de réseaux efficaces en énergie)

Dans cette these, nous etudions plusieurs modeles de routage efficaces en energie. Pour chaque modele, nous presentons une formulation en programmation lineaire mixte permettant de trouver une solution exacte. En outre, comme il s’agit de problemes NP-Difficiles, nous proposons des heuristiques efficaces pour des reseaux de grande taille. Dans la premiere partie de cette these, nous etudions une solution de routage efficace en energie dans laquelle nous ajoutons la possibilite d’eliminer des redondances dans les paquets transmis sur le reseau. Nous montrons premierement que l’ajout de l’elimination des redondances permet d’ameliorer l’efficacite energetique des reseaux en eteignant plus de liens. Ensuite, nous etendons le modele afin qu’il prenne en compte un certain niveau d’incertitudes dans le volume de trafic et le taux de redondances. La deuxieme partie de cette these est consacree aux problemes qui se posent lors du deploiement de tels protocoles dans les reseaux. Plus particulierement, nous proposons de minimiser les changements entre deux configurations reseaux consecutives lorsque plusieurs matrices de trafic sont considerees. Le routage des demandes etant alors assure avec le protocole de routage OSPF (Open Shortest Path First). Ensuite, nous abordons le probleme de la limitation du nombre de regles de routage dans les routeurs en utilisant une technologie de type SDN (Software Defined Networks). Enfin, nous presentons en annexe des travaux complementaires realises au cours de cette these concernant le routage multicast et le controle de congestion TCP.
Study of design-dependent electroluminescence linewidth of quantum cascade lasers

Electroluminescence linewidth is an important characteristic of quantum cascade lasers (QCLs) because the gain and the emission spectra of QCLs significantly depend on electroluminescence linewidth. Electroluminescence linewidth depends on the different intra-subband and inter-subband electron scattering mechanisms. Since the electron scattering rates due to different mechanisms vary when the applied electric field, temperature, and the quantum mechanical design vary, so does the electroluminescence linewidth of QCLs. In this work, we have studied the change in electroluminescence linewidth of QCLs when the quantum mechanical design and the material composition vary. We find that the linewidth of QCLs with diagonal lasing transition is greater than the linewidth of QCLs with vertical lasing transition; the linewidth of QCLs with strain-compensated material system is greater than the linewidth of QCLs with lattice-matched material system; and the linewidth of QCLs built on InGaAs/InAlAs material system is greater than the linewidth of QCLs built on GaAs/AlGaAs material system.
From 1.0 to 2.0: Swedish municipalities online

ABSTRACT The current study examines the social media use of Swedish municipalities, detailing the potential relationship between traditional forms of e-government initiatives and social media engagement of municipal bodies. By bringing these two forms of digital politics together, a more valid measurement of the supply of online democratic tools for citizen engagement is suggested. Moreover, the potential variation in determinants influencing these two concepts is examined as well. The main results indicate that municipalities’ adoption of social media is related to the procuration of more traditional services through their Web sites. Hence, a tendency of a “rich-get-richer” effect is indicated. In this respect, drivers of the different types of government use of digital services are to some extent similar. According to previous research, population size has a positive effect on the studied phenomena. Somewhat surprisingly, however, other explanatory factors differ. For example, although socioeconomic factors appear to have a positive influence on more traditional forms of online services, previous ambitions of e-government development appear as important for social media adoption by municipalities.
A note on comparison of scientific impact expressed by number of citations in different fields of science

Citation distributions for 1992, 1994, 1996, 1997, 1999, and 2001, which were published in the 2004 report of the National Science Foundation, USA, are analyzed. It is shown that the ratio of the total number of citations of any two broad fields of science remains close to constant over the analyzed years. Basing on this observation, normalization of total numbers of citations with respect to the number of citations in mathematics is suggested as a tool for comparing scientific impact expressed by the number of citations in different fields of science.
Retrieval of trade mark images by shape feature

Many different approaches have been taken, some focusing on highly specific topics such as improved pattern-matching algorithms, others taking a much broader view, and attempting to study the issues involved by developing and evaluating prototype systems. Work on image retrieval at Northumbria University falls mainly into this second category. Our long-term aim is to investigate the principles on which workable shape retrieval systems can be constructed. Our approach has been essentially pragmatic to develop a series of steadily more sophisticated prototypes capable of handling an increasingly broad range of image types and retrieval paradigms. Our first project, the development and evaluation of SAFARI (Shape Analysis For Automatic Retrieval of Images), a prototype shape retrieval system for two dimensional engineering drawings of simple machined parts, demonstrated that we could achieve excellent retrieval performance within a restricted class of images. The aim of our current ARTISAN (Automatic Retrieval of Trademark Images by Shape ANalysis) project is twofold: to develop and evaluate a prototype shape retrieval system for trade mark images consisting of abstract geometric designs, and to assess the feasibility of generalizing the image retrieval approach developed in our earlier SAFARI system to a wider range of image types. It is hoped that the prototype system developed will provide a basis from which the Patent Office Trade Marks Registry can develop an improved image retrieval system for their own use.
An Andersen-Tawil Syndrome Mutation in Kir2.1 (V302M) Alters the G-loop Cytoplasmic K+ Conduction Pathway*

Loss-of-function mutations in the inward rectifier potassium channel, Kir2.1, cause Andersen-Tawil syndrome (ATS-1), an inherited disorder of periodic paralysis and ventricular arrhythmias. Here, we explore the mechanism by which a specific ATS-1 mutation (V302M) alters channel function. Val-302 is located in the G-loop, a structure that is believed to form a flexible barrier for potassium permeation at the apex of the cytoplasmic pore. Consistent with a role in stabilizing the G-loop in an open conformation, we found the V302M mutation specifically renders the channel unable to conduct potassium without altering subunit assembly or attenuating cell surface expression. As predicted by the position of the Val-302 side chain in the crystal structure, amino acid substitution analysis revealed that channel activity and phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity are profoundly sensitive to alterations in the size, shape, and hydrophobicity of side chains at the Val-302 position. The observations establish that the Val-302 side chain is a critical determinant of potassium conduction through the G-loop. Based on our functional studies and the cytoplasmic domain crystal structure, we suggest that Val-302 may influence PIP2 gating indirectly by translating PIP2 binding to conformational changes in the G-loop pore.
Do #ifdef-based Variation Points Realize Feature Model Constraints?

Two mechanisms widely used in the Software Product Lines (SPL) Engineering are the feature model and the conditional compilation. The former models the variability in the problem space and the latter realizes it in the solution space. Even though the research community know that the feature model imposes a number of constraints to the product line implementation, there is a lack of support to co-evolve problem space and solution space. In this paper, we present an exploratory study whether problem space constraints are considered at source code level of #ifdef-based SPL implementations. In order to accomplish our goal, we developed a preliminary approach to check problem and solution spaces in a prototype tool (fclcheck). The results show a lack of realization of feature model constraints while implementing variation points with that mechanism. We also evaluated the scalability of the approach and the recoverability of the tool.
Phorbol ester‐induced change in astrocyte morphology: Correlation with protein kinase C activation and protein phosphorylation

Treatment with 300 nM phorbol 12‐myristate 13‐acetate (PMA) transforms polygonal‐shaped cultured astrocytes into process‐bearing cells and produces a shift in protein kinase C (PK‐C) from the cytosol to the membrane. Exposure to PMA also produces increases in the phosphorylation of several proteins including vimentin, glial fibrillary acidic protein (GFAP), an acidic 80,000 molecular weight protein, and two 30,000 molecular weight proteins (pI5.5 and 5.7). The effects of PMA on the translocation of PK‐C and on protein phosphorylation precede the PMA‐induced changes in astrocyte morphology, and a close correlation exists between the concentration of PMA necessary to elicit half‐maximal and maximal effects on the shift of PK‐C to the membrane and on protein phosphorylation. In addition, the PMA‐induced alterations in cell morphology are not permanent, and within 24 hr after PMA treatment the cells have reverted almost to their original morphology. A second exposure to PMA at this time fails to elicit further change in cell shape and is also incapable of producing increases in the phosphorylation of proteins. It was determined that there is little, if any, PK‐C present in these PMA‐pretreated cells. The morphological responsiveness to PMA gradually returns in 5 to 8 days after the initial treatment with PMA, and this is accompanied by the recovery of PK‐C activity and the phosphorylation response. Therefore, these studies suggest that the effect of PMA on astrocyte morphology is mediated by the activation of PK‐C and subsequent protein phosphorylation.
Generalized traveling-wave-based waveform approximation technique for the efficient signal integrity verification of multicoupled transmission line system

As very large scale integration (VLSI) circuit speed rapidly increases, the inductive effects of interconnect lines strongly impact the signal integrity of a circuit. Since these inductive effects make the signal integrity problems much more serious as well as intricate, they become one of the critical issues in today's high-speed/high-density VLSI circuit design. In this paper, a generalized traveling-wave-based waveform approximation (TWA) technique is presented which can be accurately as well as efficiently employed for the signal integrity verification of the inductively dominated (moderate Q) multicoupled RLC transmission line system. The technique is composed of three steps. First, the signals in the multicoupled (n-coupled) transmission line system are decoupled into n-isolated eigen-modes (i.e., basis vectors). Next, the slow-transient low-frequency characteristics of the system response are determined, approximately, in the frequency-domain by using the dominant poles of the basis vectors. Finally, the fast-transient high-frequency characteristics of the system response are calculated in the time domain by using the traveling wave characteristics of the basis vectors. It is shown that the time-domain responses of the multicoupled RLC transmission line system can be accurately as well as efficiently modeled with the generalized TWA technique. Then, in inductance-dominant multicoupled interconnect networks, switching-dependent signal integrity, i.e., signal delay, crosstalk, ringing, and glitches are investigated extensively with the proposed technique.
Toward Secure Services from Untrusted Developers

Abstract : We present a secure service prototype built from untrusted, contributed code. The service manages private data for a variety of different users, and user programs frequently require access to other users' private data. However, aside from covert timing channels, no part of the service can corrupt private data or leak it between users or outside the system without permission from the data's owners. Instead, owners may choose to reveal their data in a controlled manner. This application model is demonstrated by Muenster, a job search website that protects both the integrity and secrecy of each user's data. In spite of running untrusted code, Muenster and other services can prevent overt leaks because the untrusted modules are constrained by the operating system to follow pre-specified security policies, which are nevertheless flexible enough for programmers to do useful work. We build Muenster atop Asbestos, a recently described operating system based on a form of decentralized information flow control [5].
A systematic review of the efficacy and safety outcomes of anti-VEGF agents used for treating neovascular age-related macular degeneration: comparison of ranibizumab and bevacizumab

Abstract Objective: To systematically review ocular and systemic events in treatment of wet age-related macular degeneration (AMD) with anti-vascular endothelial growth factor antibodies, ranibizumab and bevacizumab, and to provide a detailed perspective of their differences on clinical use, efficacy and safety. Research design and methods: This review was based on a 2010 PubMed literature search performed using two separate terms: ‘lucentis’ OR ‘ranibizumab’ AND ‘age-related macular degeneration’ OR ‘AMD’ or ‘avastin’ OR ‘bevacizumab’ AND ‘age-related macular degeneration’ OR ‘AMD’. A clinical diagnosis of wet AMD was defined by the authors of the trial reports. Clinical studies that met Level I or Level II evidence criteria were considered for review. Findings: Eight large, randomized, controlled trials of ranibizumab (Level I) included 1485 patients (range 162–716) and four open-label studies of ranibizumab (Level II) included 4484 patients (range 32–4300). Six studies (one Level I, five Level II) of bevacizumab included 424 patients (range 28–165). All demonstrated improvements in visual acuity. Only one study (Level II) compared the efficacy of ranibizumab and bevacizumab. Adverse ocular and systemic safety events occurring during the study were prospectively recorded for ranibizumab, irrespective of their suspected relationship to study treatments. Only three of six bevacizumab studies reported details of adverse ocular or systemic events. There was extensive Level I and Level II evidence to support both the efficacy and safety of ranibizumab in wet AMD. Data suggest that bevacizumab provides efficacy in wet AMD, but the safety profile of intravitreal bevacizumab remains to be established. Conclusion: In contrast to ranibizumab, current safety data for bevacizumab are incomplete and not yet robust. If the medical community remains committed to using intravitreal bevacizumab, it is critical to establish that it has an acceptable safety profile, supported by evidence-based medicine. Considerable further research is warranted to achieve this.
From Design to Code: An Educational Approach

Model Driven Engineering (MDE), despite having many advantages, is often overlooked by programmers due to lack of proper understanding and training in the matter. This paper investigates the advantages and disadvantages of MDE and looks at research results showing the adoption rates of design models. In light of the findings, an educational tool, namely Lorini, was developed to provide automated code generation from the design models. The implemented tool consists in a plug-in for the Astah framework aimed at teaching Java programming to students through UML diagrams. It features instantaneous code generation from three types of UML diagrams, code-diagram matching, a feedback panel for error displays and on-the-fly compilation and execution of the resulting program. Evaluation of the tool indicated it to be successful with unique educational features and intuitive to use.
Expert and Corpus-Based Evaluation of a 3-Space Model of Conceptual Blending

This paper presents the 3-space model of conceptual blending that estimates the figurative similarity between Input spaces 1 and 2 using both their analogical similarity and the interconnecting Generic Space. We describe how our Dr Inventor model is being evaluated as a model of lexically based figurative similarity. We describe distinct but related evaluation tasks focused on 1) identifying novel and quality analogies between computer graphics publications 2) evaluation of machine generated translations of text documents 3) evaluation of documents in a plagiarism corpus. Our results show that Dr Inventor is capable of generating novel comparisons between publications but also appears to be a useful tool for evaluating machine translation systems and for detecting and assessing the level of plagiarism between documents. We also outline another more recent evaluation, using a corpus of patent applications.
Can metrics help to bridge the gap between the improvement of OO design quality and its automation?

During the evolution of object-oriented (OO) systems, the preservation of a correct design should be a permanent quest. However, for systems involving a large number of classes and that are subject to frequent modifications, the detection and correction of design flaws may be a complex and resource-consuming task. The use of automatic detection and correction tools can be helpful for this task. Various works have proposed transformations that improve the quality of an OO system while preserving its behavior. In this paper, we investigate whether some OO metrics can be used as indicators for automatically detecting situations where a particular transformation can be applied to improve the quality of a system. The detection process is based on analyzing the impact of various transformations on these OO metrics using quality estimation models.