bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Polyadenylation Signals in Human DNA Sequences using	Nucleotide Frequencies
Authors: Ahmed Firoz , Kumar Manish , Raghava Gajendra P.S.
Published: December 2019

The polyadenylation signal plays a key role in determining the site for addition of a polyadenylated tail to nascent mRNA and its mutation(s) are reported in many diseases. Thus, identifying poly(A) sites is important for understanding the regulation and stability of mRNA. In this study, Support Vector Machine (SVM) models have been developed for predicting poly(A) signals in a DNA sequence using 100 nucleotides, each upstream and downstream of this signal. Here, we introduced a novel split nucleotide frequency technique, and the models thus developed achieved maximum Matthews correlation coefficients (MCC) of 0.58, 0.69, 0.70 and 0.69 using mononucleotide, dinucleotide, trinucleotide, and tetranucleotide frequencies, respectively. Finally, a hybrid model developed using a combination of dinucleotide, 2nd order dinucleotide and tetranucleotide frequencies, achieved a maximum MCC of 0.72. Moreover, for independent datasets this model achieved a precision ranging from 75.8–95.7% with a sensitivity of 57%, which is better than any other known methods.
An Emergent Self-Organizing Map Based Analysis Pipeline for	Comparative Metabolome Studies
Authors: Haddad Isam , Hiller Karsten , Frimmersdorf Eliane , Benkert Beatrice , Schomburg Dietmar , Jahn Dieter
Published: December 2019

Modern high-throughput techniques allow for the identification and quantification of hundreds of metabolites of a biological system which cover central parts of the metabolome. Due to the amount and complexity of obtained data there is an increasing need for the development of appropriate computational interpretation methods.

A novel data analysis pipeline designed for high-throughput determined metabolomic data is presented. The combination of principal component analysis (PCA) with emergent self-organizing maps (ESOM) and hierarchical cluster analysis (HCA) algorithms is used to unravel the structure underlying metabolomic data sets, including the detection of outliers. Observed differences between various analyzed metabolomes are automatically mapped and visualized using KEGG metabolic pathway maps. This way typical metabolic biomarker for data sets from various analyzed growth conditions and genetic backgrounds become visible. In order to validate the described methods we analyzed time resolved metabolomic datasets obtained for Corynebacterium glutamicum cells grown on various carbon sources consisting of 126 different metabolic patterns.

The analysis pipeline was implemented in the user-friendly Java software eSOMet. The software was successfully used for the clustering of the metabolome data mentioned above. Metabolic biomarkers typical for the utilized carbon sources and analyzed growth phases were identified.
Evolutionary Analysis for the Functional Divergence of the Spo0A	Protein: The Key Sporulation Control Element
Authors: Escobar Andrés Julián Gutiérrez , Casta�o Dolly Montoya
Published: December 2019

Sporulation involves inducing scores of genes in a temporally and spatially coordinated cell development programme. Its initiation is controlled by an expanded two-component signal transduction system, termed a phosphorelay. The Spo0A response regulator is the master control element in the decision to sporulate, consisting of a receiver or phosphoacceptor domain and an effector or transcription activation domain having a high degree of sequence conservation. This study examined long-term Spo0A protein evolution for determining whether concerted evolution or purifying selection was the major factor in its evolution. The proportion of synonymous (pS) and non-synonymous nucleotide (pN) differences between Spo0A genes from 28 bacterial species was analysed. DIVERGE software was used for evaluating site-specific amino acids before phylogenetic divergence between Bacillus and Clostridium for detecting site-selective constrains operating on the Spo0A protein. Evolutionary Trace software was used for tracing the phylogenetic markers for this protein.
A Concept for ab initio Prediction of cis-regulatory Modules
Authors: Ecker K. , Welch L.
Published: December 2019

An important concern in the attempt of understanding the functional code of eukaryotic genes is to elucidate the control structures for regulating gene activation and suppression. One objective in the attempt to understand mechanisms of gene regulation is the elucidation of the regulatory network structure. A preliminary step of a detailed network analysis is identifying the transcription factor binding sites of a regulatory network. Known as cis-regulatory module (CRM), it is understood as part of the genome that comprises a set of short length binding sites.

Gene regulatory systems are known to be quite stable during evolution, as compared to relatively frequent replication processes of genes and mutations of the coding sequences. This conservation property of regulatory code can advantageously be used for identifying cis-regulatory modules of potentially co-regulated genes. As the degree of similarity is expected to depend on the phylogenetic distance of homologs or orthologs, we favor an approach that is based on a comparison paradigm. The paper introduces a novel concept for measuring the similarity of cis-regulatory modules which can then be used in an algorithm for comparing regulatory regions. The proposed algorithm searches for pairs of similar modules, and a prototype implementation is applied to human and mouse liver sequences. The results are compared to that of random sequences, and it is shown that a clear decision about co-regulation is possible at this level.
Analysis of Saccharomyces cerevisiae Genome	for the Distributions of Stress-Response Elements Potentially Affecting Gene	Expression by Transcriptional Interference
Authors: Liu Yunkai , Ye Sujuan , Erkine Alexandre M.
Published: December 2019

Cellular stress responses are characterized by coordinated transcriptional induction of genes encoding a group of conserved proteins known as molecular chaperones, most of which are also known as heat shock proteins (HSPs). In S. cerevisiae, transcriptional responses to stress are mediated via two trans-regulatory activators: heat shock transcription factors (HSFs) that bind to heat shock elements (HSEs), and the Msn2 and Msn4 transcription factors that bind to stress response elements (STREs). Recent studies in S. cerevisiae demonstrated that a significant portion of the non-coding region in the genome is transcribed and this intergenic transcription could regulate the transcription of adjacent genes by transcription interference. The goal of this study was to analyze the genomic distribution of HSF and Msn2/4 binding sites and to study the potential for transcription interference regulated by stress response systems. Our genome-wide analysis revealed that 297 genes have STREs in their promoter region, whereas 310 genes contained HSEs. Twenty-five genes had both HSEs and STREs in their promoters. The first set of genes is potentially regulated by the Msn2/Msn4/STRE interaction. For the second set of genes, regulation by heat shock could be mediated through HSF/HSE regulatory mechanisms. The overlap between these groups suggests a co-regulation by the two pathways. Our study yielded 239 candidate genes, whose regulation could potentially be affected by heat-shock via transcription interference directed both from upstream and downstream areas relative to the native promoters. In addition we have categorized 924 genes containing HSE and/or STRE elements within the Open Reading Frames (ORFs), which may also affect normal transcription. Our study revealed a widespread possibility for the regulation of genes via transcriptional interference initiated by stress response. We provided a categorization of genes potentially affected at the transcriptional level by known stress-response systems.
Challenges in the Use of in silico Tools for	Predicting Peptides Binding to HLA-Class II Molecules of HCV E1, E2, and P7
Authors: Dormer Anton , Pauleus Cathelina V. , Syverin Mondy N. , Dacil Clarissa , Smile Peta-Gaye
Published: December 2019

The application of in silico tools for the development of T-cell vaccines is crucial. Yet, due to myriad of polymorphisms of human T-lymphocytic antigen challenges, such therapeutic opportunities present unique roadblocks. There is an obvious advantage in using immunoinformatics (i.e., significantly decreasing cost related to laboratory expenses). A previous publication looked at random binding and nonbinding peptides in order to test the practicality of using such in silico tools to obtain possible immunogenic peptides. The present in silico study applied the same basic approaches to an applicable problem that was to identify promiscuous peptide vaccine candidates for hepatitis C virus (HCV) infection. The data sets used, included the proteins HCV E1, E2 and P7 as the binders (non-self antigens) and the GAD65 and ICA69, which have an association with diabetes, as non-binders (self-antigens). The in silico tools utilized were ProPred, MHC2PRED, and RANKPEP. The resulting differences were identifiable in each of the statistical parameters examined. Variations in the outcomes were evident by the dissimilarities found among the major indices of evaluation Sensitivity, Specificity, Accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Matthews's correlation coefficient (MCC) of the percentages of the predicted promiscuous peptides to HLA-DRB1*0101, *0301, and *0401. The conclusion from this study indicates that more work needs to be done in order to enhance the predictability of programs for the identification of peptide vaccine candidates for HCV. Such programs should not be solely relied upon without in vitro assay verification.
A Computational Approach for Identification of Epitopes in Dengue	Virus Envelope Protein: A Step Towards Designing a Universal Dengue Vaccine	Targeting Endemic Regions
Authors: Chakraborty Sajib , Chakravorty Rajib , Ahmed Musaddeque , Rahman Atiqur , Waise TM Zaved , Hassan Faizule , Rahman Mustafizur , Shamsuzzaman Sohel
Published: December 2019

A major problem in designing vaccine for the dengue virus has been the high antigenic variability in the envelope protein of different virus strains. In this study, a computational approach was adopted to identify a multi-epitope vaccine candidate against dengue virus that may be suitable for large populations in the dengue-endemic regions. Different bioinformatics tools were exploited that helped the identification of a conserved immunological hot-spot in the dengue envelope protein. The tools also rendered the prediction of immunogenicity and population coverage to the proposed 'in silico' vaccine candidate against dengue. A peptide region, spanning 19 amino acids, was identified in the envelope protein which found to be conserved in all four types of dengue viruses. Ten proteasomal cleavage sites were identified within the 19-mer conserved peptide sequence and a total of 8 overlapping putative cytotoxic T cell (CTL) epitopes were identified. The immunogenicity of these epitopes was evaluated in terms of their binding affinities to and dissociation half-time from respective human leukocyte antigen (HLA) molecules. The HLA allele frequencies were studied among populations in the dengue endemic regions and compared with respect to HLA restriction patterns of the overlapping epitopes. The cumulative population coverage for these epitopes as vaccine candidates was high ranging from approximately 80% to 92%. Structural analysis suggested that a 9-mer epitope fitted well into the peptide-binding groove of HLA-A*0201. In conclusion, the 19-mer epitope cluster was shown to have the potential for use as a vaccine candidate against dengue.
Models for Cannabinoid-1 Receptor Antagonistic Activity of	Substituted 2-(3-Pyrazolyl)-1,3,4-Oxadiazoles
Authors: Dutt R. , Madan A.K.
Published: December 2019

Antagonism of cannabinoid receptor-1 has emerged as a most promising therapeutic target for the development of anti-obesity drugs. In the present study, an in silico approach using decision tree, random forest and moving average analysis has been applied to a data set comprising of 76 analogues of substituted 2-(3-pyrazolyl)-1,3,4-oxadiazoles for development of models for prediction of antagonistic activity of cannabinoid receptor-1. A total of 46 2D and 3D molecular descriptors of diverse nature were employed for decision tree and random forest analysis. The values of majority of these descriptors for each analogue involved in the dataset were computed using E-Dragon software (version 1.0). Random forest correctly classified the analogues into active and inactive with an accuracy of 95%. A decision tree was also utilized for determining the importance of molecular descriptors. The decision tree learned the information from the input data with an accuracy of 99% and correctly predicted the cross-validated (10 fold) data with an accuracy up to 90%. Finally, three molecular descriptors of diverse nature (including best descriptor identified by decision tree analysis) were subsequently used to build suitable models using moving average analysis. These models resulted in the prediction of cannabinoid receptor-1 antagonistic activity with an accuracy of 95–96%. High predictability of proposed models offer vast potential for providing lead structures for the development of potent cannabinoid receptor-1 antagonists for the treatment of obesity.
Overlapping Genes May Control Reprogramming of Mouse Somatic	Cells into Induced Pluripotent Stem Cells (iPSCs) and Breast Cancer Stem Cells
Authors: Mosca Ettore , Cocola Cinzia , Sabour Davood , Pelucchi Paride , Bertalot Giovanni , Palumbo Orazio , Carella Massimo , Götte Martin , Schöler Hans R. , Reinbold Rolland , Zucchi Ileana , Milanesi Luciano
Published: December 2019

Recent findings suggest the possibility that tumors originate from cancer cells with stem cell properties. The cancer stem cell (CSC) hypothesis provides an explanation for why existing cancer therapies often fail in eradicating highly malignant tumors and end with tumor recurrence. Although normal stem cells and CSCs both share the capacity for self-renewal and multi-lineage differentiation, suggesting that CSC may be derived from normal SCs, the cellular origin of transformation of CSCs is debatable. Research suggests that the tightly controlled balance of self-renewal and differentiation that characterizes normal stem cell function is dis-regulated in cancer. Additionally, recent evidence has linked an embryonic stem cell (ESC)-like gene signature with poorly differentiated high-grade tumors, suggesting that regulatory pathways controlling pluripotency may in part contribute to the somatic CSC phenotype. Here, we introduce expression profile bioinformatic analyses of mouse breast cells with CSC properties, mouse embryonic stem (mES) and induced pluripotent stem (iPS) cells with an emphasis on how study of pluripotent stem cells may contribute to the identification of genes and pathways that facilitate events associated with oncogenesis. Global gene expression analysis from CSCs and induced pluripotent stem cell lines represent an ideal model to study cancer initiation and progression and provide insight into the origin cancer stem cells. Additionally, insight into the genetic and epigenomic mechanisms regulating the balance between self-renewal and differentiation of somatic stem cells and cancer may help to determine whether different strategies used to generate iPSCs are potentially safe for therapeutic use.
Multimodal literacies and academic publishing: The eTalks
Authors: Clivaz Claire , Pache Cécile , Rivoal Marion , Sankar Martial
Published: December 2019

Academic publications and pedagogy have been deeply reconfigured by the emergence of a new kind of knowledge produced by multimodal literacies (text, image and sound together). Academic publishing needs a digital multimedia editing platform, that can be carefully edited and quoted in details, in the same way that printed sources are. Consequently, the Swiss Institute of Bioinformatics (Vital-IT, Lausanne, CH) is developing such a platform with the “eTalks”. The eTalks application is implemented via an easy-to-use editor interface, designed for the use of researchers themselves, to create and edit original eTalks. This permits the linking together of images, sounds and textual materials with hyperlinks, enriching it with relevant information. The final release of eTalks allows complete ‘citability’ of its contents: each and every portion of the researchers’ talks can be precisely referred to and thus cited with a specific identifier, just like any traditional, paper-based academic publication but with all the potential for plural literacies. It is openly accessible and the code is open source, including guidelines to install the eTalks. It is notably developed in collaboration with the Erasmus+ project #dariahTeach. The DRM (Digital Right Management) is a key issue in such an open access editing platform.
Agent-Community-based P2P semantic MyPortal information retrieval system architecture
Authors: Yu Haibo , Mine Tsunenori , Amamiya Makoto
Published: December 2019

In this paper, we propose a conceptual architecture for a personal semantic Web information retrieval system. It incorporates semantic Web, Web service, P2P and multi-agent technologies to enable not only precise location of Web resources but also the automatic or semi-automatic integration of Web resources delivered through Web contents and Web services. In this architecture, the semantic issues concerning the whole lifecycle of information retrieval were considered consistently and the integration of Web contents and Web services is enabled seamlessly. The architecture consists of three main components: consumer, provider and mediator. All providers and consumers are constructed as semantic “MyPortal” which provides a gateway to all the information relevant to a user. Each provider describes its capabilities in what we call a WSCD (Web site capability description), and each consumer will submit relevant queries based on user requirements when a Web search is necessary. The mediator is composed of agents assigned to the consumer and providers using an Agent-Community-based P2P information retrieval (ACP2P) method to fullfill the information sharing among semantic MyPortals. Some preliminary experimental results are presented to show the efficiency of the ACP2P method and the usefulness of two query/response histories for looking up new information sources and for reducing communication loads.
FPGA-based ROM-free network intrusion detection using shift-OR circuit
Authors: Hwang Wen-Jyi , Roan Huang-Chun , Shih Ying-Nan , Lo Chia-Tien Dan , Ou Chien-Min
Published: December 2019

This paper introduces a novel FPGA-based signature match co-processor that can serve as the core of a hardware-based network intrusion detection system (NIDS). The co-processor is based on simple shift registers and bitmap encoders for the efficient signature match in hardware. As compared with related work, experimental results show that the proposed work achieves higher throughput and less hardware resource in the FPGA implementations of NIDS systems.
A system-level design methodology for application-specific networks-on-chip
Authors: Bartzas Alexandros , Papadopoulos Lazaros , Soudris Dimitrios
Published: December 2019

Modern embedded consumer devices execute complex network and multimedia applications that require high performance and low energy consumption. For implementing complex applications on Network-on-Chips (NoCs), a design methodology is needed for performing exploration at NoC system-level, in order to select the optimal application-specific NoC architecture, serving the application requirements in the best way. The design methodology we present in this paper is based on the exploration of different NoC characteristics and is supported by a flexible NoC simulator which provides the essential evaluation metrics in order to select the optimal communication parameters of the NoC architectures. We illustrated that it is possible with the evaluation metrics provided by the simulator we present, to perform exploration of several NoC aspects and select the optimal communication characteristics for NoC platforms having network and multimedia applications as the target domains. With our methodology we can achieve a gain of 57% in the Energy × Delay Product on average.
Embedded software energy characterization: Using non-intrusive measures for application source code annotation
Authors: Fournel Nicolas , Fraboulet Antoine , Feautrier Paul
Published: December 2019

In this paper we propose a complete system energy model based on non-intrusive measurements. This model aims at being integrated in fast cycle accurate simulation tools to give energy consumption feedback for embedded systems software programming. Estimations take into account the whole system consumption including peripherals. Experiments on a complex ARM9 platform show that our model estimates are in error by less than 10% from real system consumption, which is precise enough for source code application design, while simulation speed remains fast.
Clock-tree synthesis for low-EMI design
Authors: Pandini Davide , Repetto Guido A. , Sinisi Vincenzo
Published: December 2019

In modern digital ICs, the increasing demand for performance and throughput requires higher operating frequencies of hundreds of megahertz, and in several cases exceeding the gigahertz range. Following the technology scaling trends, this request will continue to rise, thus increasing the electromagnetic interference (EMI) generated by electronic systems. The enforcement of strict governmental regulations and international standards, mainly (but not only) in the automotive domain, are driving new efforts towards design solutions for electromagnetic compatibility (EMC). Hence, EMC/EMI is rapidly becoming a major concern for high-speed circuit and package designers. The on-chip clock signals with fast rise/fall times are among the most detrimental sources of electromagnetic (EM) noise, since not only they generate radiated emissions, but they also have a large impact con the conducted emissions, as the power rail noise localized in close proximity of the toggling clock edges propagates to the board through the power and ground I/O pads. In this work, we analyze the impact of different clock distribution solutions on the spectral content of typical on-chip waveforms, in order to develop an effective methodology for EMC-aware clock-tree synthesis, which globally reduces the EM emissions. Our approach can be seamlessly integrated into a typical design flow, and its effectiveness is demonstrated with experimental results obtained from the clock distribution network of an industrial digital design.
Power profile estimation and compiler-based software optimization for mobile devices
Authors: Grumer Matthias , Wendt Manuel , Steger Christian , Weiss Reinhold , Neffe Ulrich , Muehlberger Andreas
Published: December 2019

The complexity of mobile devices is continuously growing due to the increasing requirements on performance. In portable systems such as smart cards, not only performance is an important attribute, but also the power and energy consumed by a given application. It is mandatory to accomplish software power optimizations based on accurate power consumption models characterized for the processor. Both the optimization and the characterization are carried out mostly manually and are thus very time consuming processes. This paper presents an environment for automated instruction set characterization, based on physical power measurements. Further, an optimization system is presented that allows an automated reduction of power peaks based on a compiler optimization.
Direct memory access usage optimization in network applications for reduced memory latency and energy consumption
Authors: Bartzas Alexandros , Peon-Quiros Miguel , Mamagkakis Stylianos , Catthoor Francky , Soudris Dimitrios , Mendias Jose M.
Published: December 2019

Today, wireless networks are becoming increasingly ubiquitous. Usually several complex multi-threaded applications are mapped on a single embedded system and each of them is triggered by a different input stream (in accordance with the run-time behaviours of the user and the environment). This dynamicity renders the task of fully analyzing at design-time these systems very complex, if not impossible. Therefore, run-time information has to be used in order to produce an efficient design. This introduces new challenges, especially for embedded system designers using a Direct Memory Access (DMA) module, who have to know in advance the memory transfer behaviour of the whole system, in order to design and program their DMA efficiently. This is especially important in embedded systems with DRAM memories as the concurrent accesses from different processing elements can adversely affect the page-based architecture of these memory elements. Even more, the increasingly common usage of dynamic data types further complicates the problem because the exact location of data instances in the memory is unknown at design-time. In this paper we propose a system-level optimization methodology to adapt the DMA usage parameters automatically at run-time, according to online information. With our proposed optimization approach we manage to reduce the mean latency of the memory transfers by more than 18%, thus reducing the average number of cycles that processing elements or DMAs have to waste waiting for data from the main memory, while optimizing energy consumption and system responsiveness. We evaluate our approach using a set of real-life applications and real wireless dynamic streams.
Investigation of bearing capacity factor of T-bar penetrometer at shallow depths in clayey soils
Authors: Almeida Márcio S.S. , Oliveira José Renato M.S. , Rammah Khader I. , Trejo Pablo C.
Published: December 2019

The T-bar penetrometer is normally used in both in-situ and on the centrifuge to establish profiles of the undrained shear strength of fine-grain soils. However, adequate measurement of the undrained shear strength at shallow depths requires understanding the failure mechanism at these depths. For onshore and offshore structures such as pipelines, the assessment of soil parameters, in particular the undrained shear strength at shallow depth can be very critical to achieve both efficient and economic design. However, this requires the evaluation of the value of T-bar bearing factor (Nb) corresponding to both shallow and very shallow depths. This paper describes a series of geotechnical centrifuge tests undertaken using three different sizes of the T-bar penetrometer on two types of clayery soil. The results of the undrained strength obtained from each T-bar were compared with the results obtained from the bigger T-bars. The curves that describes the variation of the T-bar factor (Nb) versus the penetration depth were established from the comparison of all results obtained from the three different sizes of the T-bar. The results of (Nb) obtained in this study were compared with results obtained from both numerical and analytic solutions proposed in the literature. Generally, the experimental data obtained in this study presented Nb values higher than those predicted by others authors for all H/D ratios. However, the comparison indicates that the Nb values obtained in this study showed relatively reasonable agreement with those values obtained from the literature by adopting a non-homogenous strength profile.
On the response of fluidized piles from laboratory model tests in granular soils
Authors: Schnaid F. , Passini L. , Stracke F. , Mezzomo S.
Published: December 2019

Design guidelines of foundation anchors and piles embedded in fluidized sand comprises understanding of installation processes, defining constitutive parameters and establishing analysis techniques. These fundamental aspects have been investigated by a series of laboratory model tests designed to evaluate the mechanism taking place during pile installation through the influence of downwardly-directed vertical water jets in the geometry of fluidized cavities in saturated sands. Measurements indicate fluidization geometry to be controlled by combined effects of jet velocity and the ratio of particle and jet diameters which can be conveniently expressed by the Froude number of particles. Characteristics of the fluidized zone geometry prior and after fluidization indicate considerable reduction of relative density of fluidized samples. Limit equilibrium analysis using geotechnical parameters approaching critical state provided indicative horizontal stress levels to estimate the uplift skin friction of model steel piles.
Right Ventricular Dysfunction in the R6/2 Transgenic Mouse Model of Huntington's Disease is Unmasked by Dobutamine
Authors: Buonincontri Guido , Wood Nigel I. , Puttick Simon G. , Ward Alex O. , Carpenter T. Adrian , Sawiak Stephen J. , Morton A. Jennifer
Published: December 2019

Background: Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 mouse model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence. Objective: To investigate RV function in the R6/2 mouse model of Huntington's disease (HD). Methods: Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. Results: There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent. Conclusions: This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.
Experimental Mutagenesis of Huntingtin to Map Cleavage Sites: Different Outcomes in Cell and Mouse Models
Authors: Tebbenkamp Andrew T.N. , Xu Guilian , Siemienski Zoe B. , Janus Christopher , Fromholt Susan E. , Brown Hilda H. , Swing Debbie , Tessarollo Lino , Borchelt David R.
Published: December 2019

Background: N-terminal cleavage products of mutant huntingtin (htt) generate pathologic neuronal inclusion bodies. The precise length of the htt fragment, termed Cp-A/1, that produces HD pathologic inclusions is unknown. Objective: We sought to elucidate the protein sequence elements within the N-terminus of htt that mediate its proteolysis based on a model in which engineered htt fragments terminating at residue 171 are cleaved to produce Cp-A/1 fragments. Methods: We expressed htt N171 cDNAs harboring a series of experimental mutations in the presumptive cleavage site that generates Cp-A/1 in cells to identify cleavage resistant mutants of htt N171. One of these constructs was expressed in mice, followed by analysis using immunoblots of brain extracts and immunohistochemistry of transgenic mouse brain tissues. Results: Using the HEK293 cell model, mutagenesis studies mapped the cleavage site in htt N171 to sequences between residues 105–114. Mutation of 8 positively charged residues (H, K, R) located between residues 88 and 114 to alanine to neutralize the charge also blocked the generation of Cp-A/1 like fragments. Transgenic mice expressing this latter construct, termed N171-82Q-N8, developed phenotypes similar to previously characterized N171-82Q transgenic mice, including rotarod deficiency, intranuclear inclusions, and premature death. Surprisingly, the N171-82Q-N8 protein was efficiently cleaved in vivo to produce Cp-A/1 fragments that accumulated as insoluble inclusions. Conclusion: Mutagenesis of htt to identify critical amino acids that direct its cleavage predicted a role for charged residues in the sequence flanking the presumptive cleavage site. However, the role for these residues could not be confirmed in vivo. The basis for the discrepancy between predicted outcomes in HEK293 cells and the mouse models remain unresolved, but the data provide another validation of the hypothesis that Cp-A/1 fragments of mutant htt can induce HD-like phenotypes.
Does Interval Between Screening and Baseline Matter in HD Cognitive Clinical Trials?
Authors: Beglinger Leigh J. , Adams William H. , Langbehn Douglas , Fiedorowicz Jess G. , Caviness John , Biglan Kevin , Olson Blair , Paulsen Jane S.
Published: December 2019

Background: “Practice effects” (PE), or performance improvements due to prior exposure to testing, are known to confound cognitive test results, particularly when short intervals occur between two test sessions. Objective: We examined two subsamples with short or long re-test intervals from a recent clinical trial. Methods: Thirty-four non-depressed adults with mild Huntington Disease (HD) participated. Three cognitive tests were administered at screening and again at baseline, before active treatment randomization. Half the sample had a 24-hour retest interval while the other half was >6-days. Results: The two groups differed on demographic/clinical factors (age, Total Motor Score and Total Functional Capacity). After controlling for age and motor score, PE differences were found on three of the five UHDRS cognitive tests: the longer interval group showed larger PE on Symbol-Digit Modalities and Stroop color, while the rapid interval group had larger PE on Stroop interference. Controlling for screening cognitive performance yielded similar results. Conclusions: Length of interval between screening and baseline visits and level of disease severity may influence stability of UHDRS cognitive test results in clinical trials in HD.
Adaptive hybrid optical switching: Performance and energy efficiency
Authors: Aleksic Slavisa , Fiorani Matteo , Casoni Maurizio
Published: December 2019

Hybrid optical switching (HOS) has the potential to provide highly efficient operation through combining various switching paradigms and different implementation options within the same network. The flexibility of choosing between circuit, packet or burst switching and electronic or optical implementation results in an improvement of both energy and data transport efficiency because the most appropriate method and less power consuming elements can be selected and used for transmission of data through the network while temporarily inactive elements are switched off or put in a low-power mode. In this paper, we introduce a novel network concept that we refer to as adaptive hybrid optical switching (AHOS) and present and investigate several architectures and realization options for AHOS nodes. The corresponding control plane comprises two layers, of which one implements routing, signalling and link management functions as defined in the GMPLS standard while the other is responsible for managing already established circuits and scheduling the transmission of packets and bursts. We present results on both performance and energy consumption for different AHOS node realizations, network configurations and traffic patterns, which prove the potential for a high improvement in energy efficiency with respect to conventional electronic packet-switched networks.
A distributed framework for energy-efficient lightpaths in computational grids
Authors: Tafani Daniele , Kantarci Burak , Mouftah Hussein T. , McArdle Conor , Barry Liam P.
Published: December 2019

Over the past decade, the ever-increasing energy demands of IT infrastructures have posed significant challenges for the research community in terms of reducing their total power consumption and minimizing their environmental impact. Optical communication networks are envisioned to be promising candidates to help preventing this problem affecting the Internet backbone, as well as for distributed applications such as computational grids. In this paper, we propose an adaptive and distributed scheme for the establishment of energy-efficient lightpaths in computational grids. The grid is deployed over an optical circuit-switched backbone network, defining an optical grid network. Each node of the backbone network maintains two different dynamic thresholds values and estimates the changes in network performance by evaluating the moving average of the total wavelength channel occupancy on all its input/output links. The nodes have the ability of reducing the energy consumption by entering into an Energy Saving Mode (ESM) on the basis of a comparison between their channel occupancy and the thresholds. Furthermore, we extend our framework by allowing the thresholds to be dynamically adapted depending on the network performance in terms of blocking probability. We show that the proposed method achieves considerable energy savings when compared to a normal energy-unaware operational mode and still allows to maintain an acceptable level of network performance in terms of blocking probability and end-to-end delay. Numerical results are obtained with a Java event-driven simulator of two different optical network topologies.
Improved network survivability using multi-threshold adaptive range clustering (M-TRAC) algorithm for energy balancing in wireless sensor networks
Authors: Shivaprakasha K.S. , Kulkarni Muralidhar , Joshi Nishant
Published: December 2019

Wireless Sensor Networks (WSNs) have become one of the most prominent areas of research in the field of modern communication systems. But unlike IP based routing, WSNs focus on data centric communication. Thus routing is one of the important issues to be considered for a WSN. As sensor networks are generally deployed in hostile environments, batteries cannot be recharged often. Thus energy conservation is one of the important design parameters for WSNs. Many energy aware routing protocols were proposed in the literature. Cluster based algorithms were proved to be better compared to multi-hop routing. In this paper an attempt is made in proposing a novel cluster based energy efficient routing algorithm for WSNs namely the Multi-Threshold Adaptive Range Clustering (M-TRAC) algorithm, which incorporates centralized network management with variable thresholds in order to assure a uniform load distribution amongst nodes, thus improving the network lifetime.
Investigation of TCP and UDP multiple-flow traffic in wireless mobile ad-hoc networks
Authors: Ikeda Makoto , Kulla Elis , Hiyama Masahiro , Barolli Leonard , Takizawa Makoto
Published: December 2019

In this paper, we deal with congestion control for multi-flow traffic in wireless mobile ad-hoc networks (MANET). For simulations, we used NS-3 open source network simulator considering Ad-hoc On-Demand Distance Vector (AODV) and Optimized Link State Routing (OLSR) routing protocols. We present the MANET performance considering random waypoint mobility model for different number of nodes and different area sizes, by sending multiple UDP or TCP flow traffic in the network. We investigate and compare the packet delivery fraction (PDF) and throughput. Simulation results show that the performance of the network is high when the number of nodes is 20 and maximum speed is 6 m/s for multiple flows. We found that coupling congestion control mechanisms between multiple flows have problems in some cases.
A decentralized and self organizing architecture for wide area synchronized monitoring of smart grids
Authors: Formato Giuseppina , Loia Vincenzo , Paciello Vincenzo , Vaccaro Alfredo
Published: December 2019

Synchronized Wide-Area Monitoring Systems (WAMS) involve the use of power system-wide measurements to avoid large disturbances and reduce the probability of catastrophic events. In these systems a large volume of raw data is collected by distributed sensors and sent to central servers for post processing activities.

Many research works conjectured that this hierarchical monitoring paradigm could be not affordable in addressing the increasing network complexity and the massive data exchanging characterizing modern smart grids. Unaffordable complexity, hardware redundancy, network bandwidth and data storage resources are the main barriers imposed by technology and costs.

Moreover, in WAMS the global absolute time reference for sensors synchronization is typically obtained by satellite-based timing signals processing. Since these signals are extremely vulnerable to radiofrequency interference (i.e. cyber-attacks), effective countermeasures aimed at increasing the resilience of synchronized WAMS to external and internal interferences need to be designed.

In trying and addressing these challenges, in this paper the role of decentralized consensus protocols for decentralized and synchronized wide area smart grids monitoring is analyzed.
Energy efficient data caching for content dissemination networks
Authors: Imai Satoshi , Leibnitz Kenji , Murata Masayuki
Published: December 2019

As various multimedia services are being provided on networks, broadband traffic is growing as well. Reducing traffic is important because power consumption in networks has been increasing year by year. Meanwhile, in-network caching for CCN (Content-Centric Networking) is expected to achieve an adaptive content delivery in the network and to reduce traffic by storing content data on each router. Therefore, in-network caching is beneficial in view of energy efficiency. However, in order to improve energy efficiency of the network, it is necessary to cache content appropriately in consideration of both power consumption of content caching and transmission of traffic. In this paper, we propose a design method which derives the most energy efficient cache locations of content and a distributed cache mechanism for CCN to search for energy efficient cache locations. Furthermore, we demonstrate the effectiveness of the proposed method.
Navigation-aware association control in vehicular wireless networks
Authors: Liu Chuan-Gang , Liu I-Hsien , Yang Tsung-Ta , Li Jung-Shian
Published: December 2019

Currently, internetworking over Wireless Vehicular Ad Hoc Networks (VANET) is getting more attention and discussion. Mobile devices, including smartphones, laptops and PDAs, associate with nearby access points that are located on the roadside to access Internet in VANETs. Hence, people can use these devices to communicate in VANETs. However, the unbalanced traffic distribution often occurs among the APs in the networks, which leads to unfair bandwidth share for each user. This situation may get worse in VANETs composed of thousands of high mobility vehicles. Hence, this study focuses on association control to achieve load balancing among APs (RSUs), and we propose a novel association control algorithm with an aid of the navigation system. Based on the use of fully-fledged navigation system, our proposed algorithm plans a RSU-association-schedule, which selects a series of appropriate RSUs (roadside units) in advance to reach destination and meanwhile achieves load balancing among RSUs. The simulation results show that our scheme does improve the fairness and overall performance in VANETs.
An optimized design of optical networks using evolutionary algorithms
Authors: Abedifar Vahid , Eshghi Mohammad
Published: December 2019

Optical networks are key enablers of the modern communication services to handle the increasing bandwidth requests. Virtualization is a feasible technology to response to the users' demands. On the other hand, the cloud computing, as a distinguished use case of the virtualized optical networks, has impacted the IT world. In virtualization of the resources, optimum mapping of the virtual optical networks on the physical infrastructure plays an important role. In this paper, a novel optimized scheme for mapping the virtual optical networks on the physical infrastructure is proposed. A new formulation for Routing and Wavelength Assignment, RWA, problem is presented. A novel encoding method for optical networks is proposed based on categorizing the wavelengths into different groups according to data transmission rate. Then, the Genetic Algorithm, GA, and Binary Particle Swarm Optimization, BPSO, as two popular evolutionary algorithms are implemented to find the optimum map of the virtual optical networks on the physical infrastructure using the proposed encoding method. The optimization constraints and two heuristics, proposed to satisfy them, are detailed. Finally, the simulation results for a physical infrastructure and different virtual optical networks are presented. Results show that the GA outperforms the BPSO in terms of providing optimized solutions with less values of the defined cost function. But the run time required to find the optimum map of the virtual optical networks is more than the BPSO.
On DRC-cycle covering in optical networks
Authors: Liang Zhihe , Xie Chunli
Published: December 2019

This paper consider the case when the physical graph G=Ctn (a ring of size tn) and logical graph is λKt(n). We want to minimize the number of cycles ρ(nt,λ) in the DRC covering. For this problem, we obtain the optimal solutions when both n and t are odd.
Fairness in orthogonal frequency-division multiplexing optical networks
Authors: Alyatama Anwar
Published: December 2019

Orthogonal frequency-division multiplexing (OFDM) optical networks allow multiple subcarriers to be allocated so that both subwavelength and superwavelength traffic can be accommodated. The success of OFDM is based on routing and spectrum allocation, and fairness in this allocation is an important factor in guaranteeing customer satisfaction. In a traditional wavelength-division multiplexing network environment, the fairness is limited to individual source–destination pairs, and the blocking probabilities of calls requesting higher bandwidths are exponentially higher than those requesting lower bandwidths. We utilize here the fairness index to measure the fairness in allocating different calls in the network and investigate four fairness methods for resolving the fairness problem in OFDM: limited subcarrier reservation, limited waiting, limited number of alternate routes, and limited state blocking. We present simulation results obtained by assuming static routing and the first-fit frequency assignment. Limited subcarrier reservation and limited state blocking can substantially improve fairness with a minimum loss in the network gain.
Energy saving mechanisms on high communication layers
Authors: Oulmahdi Mohamed , Chassot Christophe , Exposito Ernesto
Published: December 2019

With the large deployment of interconnected objects and systems, energy consumed by computing equipment is becoming more and more important, and saving energy consumption, particularly at the network layer, becomes a very pertinent issue. Energy saving solutions are generally considered at low communication layers; however, higher layers, typically transport and application ones, have not only an important impact on energy consumption, but also can negatively influence the energy saving mechanisms applied at lower MAC and physical levels. In this context, we propose two energy saving mechanisms for the transport and application layers of the Internet stack. The first one consists in an improvement of a classical but not well-known mechanism aimed at maintaining opened transport level connections. The second one is related to the adaptation of the qos offered to multimedia applications in order to minimize energy requirements of underlying layers. NS-3 simulation results show the benefits of each mechanism.