Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncogenic BRAF Regulates Melanoma Proliferation through the Lineage Specific Factor MITF

The Microphthalmia-associated transcription factor (MITF) is an important regulator of cell-type specific functions in melanocytic cells. MITF is essential for the survival of pigmented cells, but whereas high levels of MITF drive melanocyte differentiation, lower levels are required to permit proliferation and survival of melanoma cells. MITF is phosphorylated by ERK, and this stimulates its activation, but also targets it for degradation through the ubiquitin-proteosome pathway, coupling MITF degradation to its activation. We have previously shown that because ERK is hyper-activated in melanoma cells in which BRAF is mutated, the MITF protein is constitutively down-regulated. Here we describe another intriguing aspect of MITF regulation by oncogenic BRAF in melanoma cells. We show oncogenic BRAF up-regulates MITF transcription through ERK and the transcription factor BRN2 (N-Oct3). In contrast, we show that in melanocytes this pathway does not exist because BRN2 is not expressed, demonstrating that MITF regulation is a newly acquired function of oncogenic BRAF that is not performed by the wild-type protein. Critically, in melanoma cells MITF is required downstream of oncogenic BRAF because it regulates expression of key cell cycle regulatory proteins such as CDK2 and CDK4. Wild-type BRAF does not regulate this pathway in melanocytes. Thus, we show that oncogenic BRAF exerts exquisite control over MITF on two levels. It downregulates the protein by stimulating its degradation, but then counteracts this by increasing transcription through BRN2. Our data suggest that oncogenic BRAF plays a critical role in regulating MITF expression to ensure that its protein levels are compatible with proliferation and survival of melanoma cells. We propose that its ability to appropriate the regulation of this critical factor explains in part why BRAF is such a potent oncogene in melanoma.
Diversity in Skylines

Given an integer k, a diverse skyline contains the k skyline points that best describe the tradeoffs (among different dimensions) offered by the full skyline. This paper gives an overview of the latest results on this topic. Specifically, we first describe the state-of-the-art formulation of diverse skylines. Then, we explain several algorithms for finding a diverse skyline, where the objective is to save cost by avoiding the computation of the entire skyline. In particular, we will discuss a polynomial-time algorithm in 2D space that returns the exact result, the NP-hardness of the problem in dimensionality at least 3, and an approximate solution with good quality guarantees.
Current trends in initial management of hypopharyngeal cancer: The declining use of open surgery

Squamous cell carcinoma of the hypopharynx represents a distinct clinical entity. Most patients present with significant comorbidities and advanced‐stage disease. The overall survival is relatively poor because of high rates of regional and distant metastasis at presentation or early in the course of the disease. A multidisciplinary approach is crucial in the overall management of these patients to achieve the best results and maintain or improve functional results. Traditionally, operable hypopharyngeal cancer has been treated by total (occasionally partial) laryngectomy and partial or circumferential pharyngectomy, followed by reconstruction and postoperative radiotherapy in most cases.
Composite events for network event correlation

With the increasing complexity of enterprise networks and the Internet, event correlation is playing an increasingly important role in network as well as integrated system management systems. Even though the timing of events often reveals important diagnostic information about event relationships and should therefore be represented in event correlation rules or models, most extant approaches lack a formal mechanism to define complex temporal relationships among correlated events. In this paper, we discuss the formal use of composite events for event correlation and present a composite event specification approach that can precisely express complex timing constraints among correlated event instances, for which efficient compilation and detection algorithms have been developed in Mok et al., (1997). A Java implementation of this approach, called Java Event Correlator (JECTOR), is described, and some preliminary experimental results of using JECTOR in an experimental network management environment are also discussed in the paper.
Hardware evolution : on the nature of artificially evolved electronic circuits

Much of the work presented in this thesis has been previously published as listed below. Although some of these papers have co-authors, the work appearing in this thesis is entirely my own, with the exception of parts of chapter 3, which presents work jointly carried out by myself and Adrian Thompson. The respective contributions to this work will be explicitly stated at the beginning of the chapter.
Hybrid simulation studies and Hybrid Simulation systems: Definitions, challenges, and benefits

Hybrid Simulation (HS) is not new. However there is contention in academic discourse as to what qualifies as HS? Is there a distinction between multi-method, multi-paradigm and HS? How do we integrate methods from disciplines like OR and computer science that contribute to the success of a M&S study? How do we validate a hybrid model when the whole (the combined model) is greater than the sum of its parts (the individual models)? Most dynamic simulations have a notion of time, how do we realize a unified representation of simulation time across methodologies, techniques and packages, and how do we prevent causality during inter-model message exchange? These are but some of the questions which we found to be asking ourselves frequently, and this panel paper provided a good opportunity to stimulate a discussion along these lines and to open it up to the M&S community.
Safe Runtime Reconfiguration in Component-Based Software Systems

Long life and critical software systems require high availability. Therefore, their reconfiguration should be achieved dynamically during their running time. This type of updating is not safe as static update because it lacks test phase in order to validate the modifications. This paper discusses different sources of risk with runtime reconfiguring, it presents Message-based Interaction in Component-based System (MICS) framework that facilitates updating the system online, and ensures system safety during and after system modification.
Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling

The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre‐treatment of DSS significantly improved cell survival and protected against I/R‐induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy‐ and apoptosis‐related proteins (including p62, LC3‐II, Beclin‐1, Bax, and Caspase‐3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre‐treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation.
Complete Solving of Linear Diophantine Equational and Inequational Systems without Adding Variables

In this report, we present an algorithm for solving {\em directly} linear Diophantine systems of both equations and inequations. Here directly means without adding slack variables for encoding inequalities as equalities. This algorithm is an extension of the algorithm due to Contejean and Devie \cite{contejean94ic} for solving linear Diophantine systems of equa­tions, which is itself a generalization of the algorithm of Fortenbacher \cite{clausen89} for solving a single linear Diophantine equation. All the nice properties of the algorithm of Contejean and Devie are still satisfied by the new algorithm: it is complete, {\em i.e.} provides a (finite) description of the set of solutions, it can be implemented with a {\em bounded} stack, and it admits an incremental version. All of these characteristics enable its easy integration in the CLP paradigm.
Extracting Concrete Thermal Characteristics from Temperature Time History of RC Column Exposed to Standard Fire

A numerical method to identify thermal conductivity from time history of one-dimensional temperature variations in thermal unsteady-state is proposed. The numerical method considers the change of specific heat and thermal conductivity with respect to temperature. Fire test of reinforced concrete (RC) columns was conducted using a standard fire to obtain time history of temperature variations in the column section. A thermal equilibrium model in unsteady-state condition was developed. The thermal conductivity of concrete was then determined by optimizing the numerical solution of the model to meet the observed time history of temperature variations. The determined thermal conductivity with respect to temperature was then verified against standard thermal conductivity measurements of concrete bricks. It is concluded that the proposed method can be used to conservatively estimate thermal conductivity of concrete for design purpose. Finally, the thermal radiation properties of concrete for the RC column were estimated from the thermal equilibrium at the surface of the column. The radiant heat transfer ratio of concrete representing absorptivity to emissivity ratio of concrete during fire was evaluated and is suggested as a concrete criterion that can be used in fire safety assessment.
On optimizing replica migration in distributed cloud storage systems

With the wide adoption of large-scale Internet services and big data, the cloud has become the ideal environment to satisfy the ever-growing storage demand, thanks to its seemingly limitless capacity, high availability and faster access time. In this context, data replication has been touted as the ultimate solution to improve data availability and reduce access time. However, replica placement systems usually need to migrate and create a large number of data replicas over time between and within data centers, incurring a large overhead in terms of network load and availability. In this paper, we propose CRANE, an effiCient Replica migrAtion scheme for distributed cloud Storage systEms. CRANE complements any replica placement algorithm by efficiently managing replica creation in geo-distributed infrastructures by (1) minimizing the time needed to copy the data to the new replica location, (2) avoiding network congestion, and (3) ensuring a minimal availability of the data. Our results show that, compared to swift (the OpenStack project for managing data storage), CRANE is able to minimize up to 30% of the replica creation time and 25% of inter-data center network traffic, while ensuring the minimum required availability of the data.
Hubs and Homogeneity: Improving Content-Based Music Modeling

We explore the origins of hubs in timbre-based song modeling in the context of content-based music recommendation and propose several remedies. Specifically, we find that a process of model homogenization, in which certain components of a mixture model are systematically removed, improves performance as measured against several groundtruth similarity metrics. Extending the work of Aucouturier, we introduce several new methods of homogenization. On a subset of the uspop data set, model homogenization improves artist R-precision by a maximum of 3.5% and agreement to user collection co-occurrence data by 7.4%. We also explore differences in the effectiveness of the various homogenization methods for hub reduction. Further, we extend the modeling of frame-based MFCC features by using a kernel density estimation approach to non-parametric modeling. We find that such an approach significantly reduces the number of hubs (by 2.6% of the dataset) while improving agreement to ground-truth by 5% and slightly improving artist R-precision as compared with the standard parametric model.
Bcl-XL specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum

Bcl-2 family members Bak and Bax constitute a mitochondrial gateway for multiple death pathways. Both proteins are also present in the endoplasmic reticulum where they control apoptosis through the regulation of calcium levels. We show here that reticular Bak has the additional capacity of modulating the structure of this organelle. Coexpression of Bak and Bcl-XL provokes extensive swelling and vacuolization of reticular cisternae. A Bak version lacking the BH3 domain suffices to induce this phenotype, and reticular targeting of this mutant retains the activity. Expression of upstream BH3-only activators in similar conditions recapitulates ER swelling and vacuolization if ryanodine receptor calcium channel activity is inhibited. Experiments with Bak and Bax-deficient mouse embryonic fibroblasts show that endogenous Bak mediates the effect, whereas Bax is mainly irrelevant. These results reveal a previously unidentified role of Bak in regulating reticular conformation. Because this activity is absent in Bax, it constitutes one of the first examples of functional divergence between the two multidomain homologues.
Control engineering of autonomous cognitive vehicles-a practical tutorial

An introduction is provided to artificial agent methodologies applicable to control engineering of autonomous vehicles and robots. The fundamentals that make a machine autonomous are considered: decision making that involves cognitive modelling the environment and forming data abstractions for symbolic processing and logic based reasoning. Capabilities such as navigation, path planning, tracking control and communications are treated as basic skills of cognitive agents. The ANSI standard of intelligent systems is used followed by the fundamental types of possible agent architectures for autonomous vehicles are presented, starting from reactive, through layered, to advanced architectures in terms of beliefs, goals and intentions. Cognitive capabilities of agents can fill in missing links between computer science results on discrete agents and engineering results of continuous world sensing, actuation and path planning. Design tools for “abstractions programming” are identified as needed to fill in the gap between logic based reasoning and sensing.
A quantitative analysis of reconfigurable coprocessors for multimedia applications

Recently, computer architectures that combine a reconfigurable (or retargetable) coprocessor with a general-purpose microprocessor have been proposed. These architectures are designed to exploit large amounts of fine grain parallelism in applications. In this paper, we study the performance of the reconfigurable coprocessors on multimedia applications. We compare a Field Programmable Gate Array (FPGA) based reconfigurable coprocessor with the array processor called REMARC (Reconfigurable Multimedia Array Coprocessor). REMARC uses a 16-bit simple processor that is much larger than a Configurable Logic Block (CLB) of an FPGA. We have developed a simulator, a programming environment, and multimedia application programs to evaluate the performance of the two coprocessor architectures. The simulation results show that REMARC achieves speedups ranging from a factor of 2.3 to 7.3 on these applications. The FPGA coprocessor achieves similar performance improvements. However, the FPGA coprocessor needs more hardware area to achieve the same performance improvement as REMARC.
Authentication techniques for e-commerce applications: A review

E-commerce applications are nowadays facilitating users to access resources spread at different places. It has increased the reach of people and has shortened the horizon. There can be many threats and attacks scenarios possible in the completion of an e-commerce application. So security must be intact at every step in this process. User authentication is very challenging aspect of e-commerce application. Which is secured and being backed up by remote user authentication technique. There are many schemes presently available for remote user authentication like smart card based, password based, dynamic id based and cookie based authentication. This paper analyses the various authentication techniques of remote user authentication used in e-commerce applications these days.
How does research evaluation impact educational research? Exploring intended and unintended consequences of research assessment in the United Kingdom, 1986–2014

Research evaluation systems in many countries aim to improve the quality of higher education. Among the first of such systems, the UK’s Research Assessment Exercise (RAE) dating from 1986 is now the Research Excellence Framework (REF). Highly institutionalised, it transforms research to be more accountable. While numerous studies describe the system’s effects at different levels, this longitudinal analysis examines the gradual institutionalisation and (un)intended consequences of the system from 1986 to 2014. First, we analyse historically RAE/REF’s rationale, formalisation, standardisation, and transparency, framing it as a strong research evaluation system. Second, we locate the multidisciplinary field of education, analysing the submission behaviour (staff, outputs, funding) of departments of education over time to find decreases in the number of academic staff whose research was submitted for peer review assessment; the research article as the preferred publication format; the rise of quantitative analysis; and a high and stable concentration of funding among a small number of departments. Policy instruments invoke varied responses, with such reactivity demonstrated by (1) the increasing submission selectivity in the number of staff whose publications were submitted for peer review as a form of reverse engineering, and (2) the rise of the research article as the preferred output as a self-fulfilling prophecy. The funding concentration demonstrates a largely intended consequence that exacerbates disparities between departments of education. These findings emphasise how research assessment impacts the structural organisation and cognitive development of educational research in the UK.
G2-instantons over twisted connected sums

We introduce a method to construct G2 ‐instantons over compact G2 ‐manifolds arising as the twisted connected sum of a matching pair of building blocks. Our construction is based on gluing G2 ‐instantons obtained from holomorphic vector bundles over the building blocks via the first author’s work. We require natural compatibility and transversality conditions which can be interpreted in terms of certain Lagrangian subspaces of a moduli space of stable bundles on a K3 surface.
Effect of DC link discharge resistor on transient stability of DFIG wind generator

For a Doubly Fed Induction Generator (DFIG) the effect of discharge resistor in series with DC link capacitor is investigated in respect to its transient stability performance. Observations are carried out with different values of resistor for different types of fault and fault location. For the study, 9MW wind farm model in MATLAB simulink module is considered where generators are lumped into a single mass. Time domain analysis is performed for the assessment.
Representing Energy Technologies in Top-down Economic Models Using Bottom-up Information

This paper uses bottom-up engineering information as a basis for modeling new technologies within the MIT Emissions Prediction and Policy Analysis (EPPA) model, a computable general equilibrium model of the world economy. Natural gas combined cycle (NGCC) without carbon capture and sequestration (CCS), natural gas combined cycle with CCS, and integrated coal gasification with CCS power generation technologies are introduced into the EPPA model. These compete in the electricity sector with conventional fossil generation, nuclear, hydro, wind, and biomass power generation. Engineering cost data are used together with EPPA data, including the underlying Social Accounting Matrix (SAM) and supplementary physical energy accounts, to assure that technologies, when simulated within the model, meet thermodynamic efficiency limits, and that they reflect regional differences in the cost structure of the electric sector. Alternative capital vintaging approaches are investigated and an explicit treatment of market penetration of new technologies is developed. Simulations through 2100 show the introduction of the new technologies and their decline as fuel and input prices, and carbon policies, change. A general result is that NGCC plants with or without capture, while currently less costly methods of abating carbon emissions from the electric sector based on engineering data, play only a limited and shortterm role in meeting carbon limits. By 2050 the coal CCS plants, currently the most costly of the three technologies, dominate in the simulated policy scenarios because rising gas prices raise the cost of the gas-based technologies.
A Coordination Model for Distributed Transactions in Digital Business EcoSystems

In this paper we present a model for coordinating distributed long running and multi-service transactions in digital business EcoSystems. The model supports various forms of service composition, which are translated into a tuples-based behavioural description that allows to reason about the required behaviour in terms of ordering, dependencies and alternative execution. The compensation mechanism warranties consistency, including omitted results, without breaking local autonomy. The proposed model is considered at the deployment level of SOA, rather than the realisation level, and is targeted to business transactions between collaborating SMEs as it respects the loose-coupling of the underlying services.