Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in the Development of Cancer Therapeutics Directed against the RAS-Mitogen-Activated Protein Kinase Pathway

Among mammalian mitogen-activated protein kinase (MAPK) signaling cascades, the extracellular signal-related kinase (ERK) pathway has received the most attention in the oncology drug discovery arena. By virtue of its central role in promoting proliferation, survival, and metastasis, this pathway directly affects both the formation and progression of human tumors. The identification of non–ATP-competitive inhibitors of the MAPK kinase MAPK/ERK kinase (MEK) resulted in the first demonstration that the ERK pathway could be effectively shut down in a highly selective fashion. Subsequent discovery of the oncogenic nature of B-raf kinase led to the escalation of drug discovery efforts revolving around MEK and RAF. The emergence of multiple drug candidates targeting these downstream kinases provides us with the means for validating the importance of the RAS-RAF-MEK-ERK signaling cascade in human tumors. This article highlights the lessons learned in the clinical evaluation of MAPK pathway inhibitors as anticancer agents and the complexities surrounding optimization of their therapeutic potential in light of the challenges posed by genetic heterogeneity within patient populations.
My Voter, My Party, and Me: American and German Parliamentarians on Facebook

ABSTRACT This study compares the political communication of American and German politicians on Facebook by referring to the framework of political communication systems. We analyzed the Facebook profiles and communication of all the members of the 17th German Bundestag and the 112th U.S. Congress. Our results reveal differences between American and German politicians in reference to their general use of Facebook, their voter relationship management on Facebook, and the personalization of their presentation. Because these differences can be interpreted against the background of the countries’ political communication systems, we conclude that structural differences influence how new communication technologies are adopted.
Identification and characterization of vaccinia virus genes encoding proteins that are highly antigenic in animals and are immunodominant in vaccinated humans

Vaccinia virus (VV) is a potent immunogen, but the nature of VV proteins involved in the activation of the immune response of the host is not yet known. By screening a lambda gt11 expression library of rabbitpox virus DNA with serum from humans vaccinated against smallpox or with serum from VV-immunized animals, we identified several VV genes that encode highly antigenic viral proteins with molecular masses of 62, 39, 32, 25, 21, and 14 kDa. It was found that VV proteins of 62, 39, 25, and 21 kDa are part of the virus core, while proteins of 32 and 14 kDa are part of the virus envelope. All of these proteins were synthesized at late times postinfection. Proteins of 62 and 25 kDa were produced by cleavage of larger precursors of 95 kDa (p4a) and 28 kDa, respectively. The 21-kDa protein was the result of a cleavage of p4a, presumably at amino acid Gly-697. DNA sequence analysis, in comparison with the known nucleotide sequence of VV, provided identification of the corresponding open reading frames. Expression of the viral genes in Escherichia coli was used to monitor which of the viral antigens elicit immunodominant responses and the location of antigenic domains. Three viral antigens of 62, 39, and 32 kDa exhibited immunodominant characteristics. The most antigenic sites of 62 and 39 kDa were identified at the N terminus (amino acids 132 to 295) and C terminus (last 103 amino acids), respectively. Immunization of mice with the 62-, 39-, or 14-kDa antigenic proteins conferred different degrees of protection from VV challenge. Proteins of 32 and 14 kDa induced cellular proliferative responses in VV-infected mice. Our findings demonstrate the nature of VV proteins involved in the activation of host immune responses after vaccination, provide identification of the viral gene locus, and define structural and immunological properties of these antigenic VV proteins.
Towards a musical stylistics: Movement in Kate Bush’s ‘Running Up That Hill’

A very recent trend in stylistics proposes the extension of its field of enquiry to accommodate various forms of multimodal art. Reflecting as it does the growing semiotic complexity of contemporary aesthetics, ‘multimodal stylistics’ is a welcome development. So far, however, its proponents have concentrated on genres in which texts are complemented by, or realized through, the visual medium – films, stage plays, television series and illustrated books. In this article, a multimodal stylistic analysis is attempted on a genre which has attracted little critical attention in linguistics – modern pop-rock music. A 1985 song by singer-songwriter Kate Bush, ‘Running Up That Hill’, is studied linguistically and musically. Employing a blend of stylistic and musicological techniques, and some of the insights provided by newborn multimodal stylistics, the author explores the complex ways in which meaning is created in a pop-rock song.
Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma

Background The purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG). Methods A total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan® single nucleotide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene. Results Homocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05). Conclusion Our results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort.
Exploiting Single-Threaded Model in Multi-Core In-Memory Systems

The widely adopted single-threaded OLTP model assigns a single thread to each static partition of the database for processing transactions in a partition. This simplifies concurrency control while retaining parallelism. However, it suffers performance loss arising from skewed workloads as well as transactions that span multiple partitions. In this paper, we present a dynamic single-threaded in-memory OLTP system, called LADS, that extends the simplicity of the single-threaded model. The key innovation in LADS is the separation of dependency resolution and execution into two non-overlapping phases for batches of transactions. After the first phase of dependency resolution, the record actions of the transactions are partitioned and ordered. Each independent partition is then executed sequentially by a single thread, avoiding the need for locking. By careful mapping of the tasks to be performed to threads, LADS is able to achieve a high degree of balanced parallelism. We evaluate LADS against H-Store, a partition-based database; DORA, a data-oriented transaction processing system; and SILO, a multi-core in-memory OLTP engine. The experimental study shows that LADS achieves up to 20x higher throughput than existing systems and exhibits better robustness with various workloads.
Fourier transform based methods for height from gradients

This paper presents a class of Fourier transform based approaches for height from gradients (HFG) problem, which is to reconstruct the 3D surface height of an object from its gradients. The HFG problem results from quite a few research areas in computer vision such as shape from shading, photometric stereo, shape from texture, shape from contours and so on. The proposed methods have some distinct advantages. Firstly, the derivation process of the algorithms has generality, and can be used for more functional dealing with additional constraints. Secondly, they are noniterative so that boundary conditions are not needed. In addition, their robustness to noisy gradient estimates can be improved by choosing associated weighting parameters. Experimental results using synthetic and real images are also presented.
Light Transmission Properties and Shannon Index in One-Dimensional Photonic Media With Disorder Introduced by Permuting the Refractive Index Layers

In this paper, we have studied, with a numerical method, how introducing disorder affects the light transmission properties of 1-D photonic structures over a wide range of wavelengths. A new type of disorder is introduced by permuting the refractive index layers in the optical medium. We compared the light transmission properties of ideal photonic crystals and of disordered media with the same kind and number of scattering elements for different sample lengths. We have calculated the transmission properties, by the transfer matrix method, of thousands of different disordered structures in order to perform a statistical analysis. We found that, below a certain sample length, disorder induces less average light reflection than ordered structures, whereas above the threshold length, disordered structures show more average reflection. Moreover, we have quantified the disorder of the structures with the Shannon index. We have found a decrease in the average light transmission as a function of the Shannon index. Furthermore, the sample length affects the trend of the average transmission as a function of the Shannon index.
Model Predictive Prior Reinforcement Learning for a Heat Pump Thermostat

We combine results from model predictive control, reinforcement learning, and set-back temperature control to develop an algorithm for adaptive control of a heat-pump thermostat. The algorithm borrows from model predictive control the concept of optimizing a controller based on a model of environment dynamics, but then updates the model using online reinforcement learning. An adaptive set-back heuristic further improves energy savings while maintaining target temperature goals. We evaluate the framework in simulation, demonstrating its advantages over standard model predictive control and reinforcement learning alone.
Task Specialization in Social Production Communities: The Case of Geographic Volunteer Work

In social production communities, users' individual and collective efforts lead to the creation of valuable resources — cf. Wikipedia, Open Street Map, and Reddit. Contributors to such communities often specialize in the tasks they choose to do. We found evidence for specialization by work type in Cyclopath, a geographic wiki for bicyclists -- most users edit a single type of map feature, such as points of interest or roads and trails. We also saw a user lifecycle effect: as users gain experience, they specialize in editing roads and trails. Our findings suggest more effective ways to organize social production interfaces, compose units of work, and match them to users who want to help.
Performance analysis of tracking scheme for passive linear array SONARs using split-beam correlation and Kalman filtering

Conventional tracking methods use the split beam correlation technique by forming two half beams and then correlating between them to detect the path delay between the two beams and then estimate the final bearing. This scheme does not offer good performance at low signal to noise ratios. Especially for the case of linear arrays the performance is better along broadside direction and deteriorates as we move towards endfire. These problems may be addressed by employing Kalman filtering to refine the track. The output obtained after split beam correlation is fed to a Kalman filter. The performance evaluation of this system at various SNRs and various look angles are simulated and the results are presented.
A functional channel is necessary for growth suppression by Cx37

Connexin 37 (Cx37) profoundly suppresses the proliferation of rat insulinoma (Rin) cells by unknown mechanisms. To determine whether a functional pore domain is necessary for Cx37-mediated growth suppression, we introduced a mutation that converted threonine 154 into alanine (T154A). Like other connexins mutated at the homologous site, Cx37-T154A localized to appositional membrane but failed to form functional channels and exerted a dominant-negative effect on coexpressed wild-type Cx37 or Cx43. Unlike the wild-type protein, Cx37-T154A did not suppress the proliferation of Rin cells and did not, with serum deprivation, result in cell cycle arrest. Furthermore, progression through the cell cycle was unaffected by expression of Cx37-T154A. These results indicate that a pore-forming domain that is able to form functional channels is essential for the anti-proliferative, cell-cycle arrest and serum-sensitivity effects of Cx37, and furthermore that the normally localized C-terminal domain is not sufficient for these effects of Cx37.
Line Outage Detection Using Phasor Angle Measurements

Although phasor measurement units (PMUs) have become increasingly widespread throughout power networks, the buses monitored by PMUs still constitute a very small percentage of the total number of system buses. Our research explores methods to derive useful information from PMU data in spite of this limited coverage. In particular, we have developed an algorithm which uses known system topology information, together with PMU phasor angle measurements, to detect system line outages. In addition to determining the outaged line, the algorithm also provides an estimate of the pre-outage flow on the outaged line. To demonstrate the effectiveness of our approach, the algorithm is demonstrated using simulated and real PMU data from two systems - a 37-bus study case and the TVA control area.
P 2 P Overlay , Internet Underlay and Their Mutual Impact

2 Studying the Internet Topology (Underlay) 6 2.1 AS-level Topology of the Internet . 6 2.1. 1 Data Sources for AS-level Topology . 7 2.1. 2 Characterization Methods for AS-level Topology . 10 2.1. 3 Modeling the AS-level Topology . 13 2.2 Router-level Topology of the Internet . 15 2.2.1 Data Sources for Router-level Topology . 15 2.2.2 Characterization Methods for Router-level Topology . 18 2.2. 3 Modeling the Router-level Topology . 19
Modeling energy and performance of Phoenix++ based parallel programs

In order to provide more processing power, computer systems manufacturers are trying to increase the performance of their products. Nowadays, multi-core processors are being used as a solution to reach more performance via thread level parallelism. MapReduce are considered as one of the most appropriate models of programming for data parallelism. Different frameworks have been developed based on this model. Phoenix++ is one of these frameworks that has been implemented for shared memory systems. Since computing is becoming more and more important in people's life, more and more energy spent computation. Energy is also becoming as big challenge in human life. Therefore doing energy efficient computation is becoming very important. For a long time, performance was considered as the most important metric for computing systems. However energy consumption has become as important as performance these days. We offer models in this paper to determine a system configuration for parallel programs based on Phoenix++ framework in way to minimize energy delay product (EDP) by selecting proper number of active cores, the number of threads, and working frequency level. The model accuracy is evaluated by running experiments on a real system.
Expression of the eRF1 translation termination factor is controlled by an autoregulatory circuit involving readthrough and nonsense-mediated decay in plants

Abstract When a ribosome reaches a stop codon, the eukaryotic Release Factor 1 (eRF1) binds to the A site of the ribosome and terminates translation. In yeasts and plants, both over- and underexpression of eRF1 lead to altered phenotype indicating that eRF1 expression should be strictly controlled. However, regulation of eRF1 level is still poorly understood. Here we show that expression of plant eRF1 is controlled by a complex negative autoregulatory circuit, which is based on the unique features of the 3΄untranslated region (3΄UTR) of the eRF1-1 transcript. The stop codon of the eRF1-1 mRNA is in a translational readthrough promoting context, while its 3΄UTR induces nonsense-mediated decay (NMD), a translation termination coupled mRNA degradation mechanism. We demonstrate that readthrough partially protects the eRF1-1 mRNA from its 3΄UTR induced NMD, and that elevated eRF1 levels inhibit readthrough and stimulate NMD. Thus, high eRF1 level leads to reduced eRF1-1 expression, as weakened readthrough fails to protect the eRF1-1 mRNA from the more intense NMD. This eRF1 autoregulatory circuit might serve to finely balance general translation termination efficiency.
Lighting Networks - A New Approach for Designing Lighting Algorithms

In the past, new global illumination algorithms have usually been designed as a single module that was responsible for the simulation of all aspects of illumination in a scene. A recently developed alternative is the design of small and specialized algorithms (lighting operators) together with an infrastructure for creating more complex algorithms by connecting these building blocks – the Lighting Network. In this paper, we discuss the benefits of the Lighting Network approach for designing new and improved global illumination algorithms. Lighting Networks not only provide a flexible infrastructure for new algorithms, they also support a better theoretic understanding of the lighting simulation process. We show that a small number of global light propagation operators already provides the basis for creating many of todays illumination algorithms. Their illumination results are converted into more suitable representations by purely local conversion operators that are specific to an illumination algorithm. Varying the composition of these operators and introducing new elements allows us to create and explore the benefits of new simulation algorithms. We demonstrate the potential of Lighting Networks with several examples, implementing a diverse set of algorithms, such as density estimation, irradiance gradients, and a composite lighting simulation.
Does Pivotality Convey Information to Voters: Some Experimental Results

In case of voting with common interests, a voter’s decision should in principle take account of the information implicitly revealed by the event that she is 'pivotal'. Question is: in reality to what extent members of small groups incorporate or ignore the information implicit in being pivotal before choosing an alternative? It is impossible to answer this question with happenstance data. In a game-theoretic set up two aspects of voters’ strategy selection refer to correctly inferring the strategies of other group members and conditioning her actions on the event of being pivotal. We have abstracted away from the group considerations in voters’ strategy selection and constructed an experimental model based on decision problem. We found evidence for strategic voting in our sample. However strategic behavior was not robust when the posterior probability of a state given a signal increased. A significant proportion of the discrepancy between predicted and observed behavior at the individual level was attributable to differential cognitive abilities of the subjects.
Attribute-Based Partial Geo-Replication System

Existing partial geo-replication systems do not always provide optimal cost or latency, because their replication decisions are based on statically established data access popularity metrics, regardless of the application types. We demonstrate that additional reduction in cost and latency can be achieved by (1) using the right object attributes for making replication decisions for each type of application, (2) using multi-attribute-based replications, and (3) combining the popularity-based but reactive approach with the more random but proactive approach to data replication. Toward this end, we propose Acorn, an Attribute-based COntinuous partial geo-ReplicatioN system, and its prototype implementation based on Apache Cassandra. Experiments with two types of global-scale, data-sharing applications demonstrate up to 54% and 90% cost overhead reduction over existing systems or 38% and 91% latency overhead reduction.
Crowdsourced context-modeling as key to future smart spaces

Managing smart spaces with software requires the acquisition and processing of context information about a space. To be usable for exchanging information, a context representation has to be structured with a context model. Existing context-modeling techniques usually require experts and lack support for collaborative distributed creation, which prevents a crowdsourced development in a distributed collaborative way by non-experts. To facilitate context modeling, this paper presents a hybrid meta model that combines features from key-value, markup, object oriented, and ontology based context-modeling approaches. An architecture is introduced that allows the dynamic collaborative extension and crowdsourced convergence of context models.
Access to innovative oncology medicines in Europe

The incidence of cancer will increase within the next 5 years up to 15 million patients per year worldwide with a further increasing tendency. Therefore, there is a requirement for more emphasis on cancer prevention, research and effective anticancer drugs including a rapid licensing and market availability for the patients. In the EU, the centralized procedure (CP) of the European Medicine Agency (EMA) is mandatory for marketing authorization for anticancer drugs. A CP will result in one marketing authorization for all Member States granted by the European Commission. At variance, numerous independent healthcare sys-tems are in operation across the EU, and each Health Technology Assessment (HTA) body follows its own methodologies and scientific value judgements in the assessment of the ad-ditional clinical benefit of a new anticancer drug. Payer organisations in the various member states consider these assessments to a varying degree as input in their pricing and reim-bursement negotiations. At the same time international reference pricing and parallel trade have an inherent tendency to establish rather uniform price levels across member states. Consequently, drug access for patients differs considerably within the EU. Initiatives to im-prove the interface between the different stakeholders are currently on the way, but are unlikely sufficient to overcome these fundamental problems.