bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Dynamic Vehicle Allocation for Carsharing Systems
Authors: Fan Wei (David)
Published: October 2013

Carsharing offers innovative mobility solutions and has been gaining popularity around the world as an environmentally sustainable, socially responsible, and economically feasible form of mobility. Carsharing allows members to benefit from private vehicle use without the costs and responsibilities of ownership and provides individuals with access to a fleet of shared-use vehicles in a network of locations on a short-term, as-needed basis. This paper seeks to develop a stochastic optimization framework to address the dynamic vehicle allocation problem for carsharing systems, in which the service operator needs to manage and determine the optimal vehicle allocation in both time and space to maximize profits. A multistage stochastic linear programming model with recourse, which can account for system uncertainties such as car-sharing demand variation, is formulated and solved. Numerical results are discussed and computational insights are presented on the basis of a seven-stage experimental network pilot study.
Unraveling the Travel Behavior of Carsharing Members from Global Positioning System Traces
Authors: Leclerc Benoit , Trépanier Martin , Morency Catherine
Published: October 2013

As carsharing becomes increasingly popular throughout the world, it would be of interest to understand better the underlying characteristics of the trips made by members when they use the cars. To date, few studies have reported carsharing trip details. This paper presents a methodology to analyze three components of a station-based carsharing member's journey: the locations of the stops, the attributes of the trips, and the characteristics of the trip chains. The method is based on the processing of Global Positioning System traces collected onboard car-sharing vehicles; a 5-min stop criterion is used to divide the trip chains into separate trips. The case study involves the Communauto system in the Greater Montreal area, Quebec, Canada. The study shows that carsharing members make more trips within their trip chains than typical car owners do. However, those trips are shorter and are often made for purposes other than work (shopping or visiting, for example). Members tend to maximize the use of the cars during the rental period (the members are on the move up to 50% of the time for short trip chains and 30% of the time for longer trips).
An in vitro biomechanical investigation of an interlocking nail system developed for buffalo tibia
Authors: Bhat S. A. , Kinjavdekar P. , Zama M. M. S. , Gope P. C. , Pawde A. M. , Ahmad R. A. , Gugjoo M. B. , Aithal H. P.
Published: October 2013

Objectives: The objectives of the study were to determine the mechanical properties of a customized buffalo interlocking nail (BIN), intact buffalo tibia, and ostectomized tibia stabilized with BIN in different configurations, as well as to assess the convenience of interlocking nailing in buffalo tibia.

Methods: The BIN (316L stainless steel, 12 mm diameter, 250 mm long, nine-hole solid nails with 10° proximal bend) alone was loaded in compression and three-point bending (n = 4 each); intact tibiae and ostectomized tibiae (of buffaloes aged 5–8 years, weighing 300–350 kg) stabilized with BIN using 4.9 mm standard or modified locking bolts (4 or 8) in different configurations were subjected to axial compression, cranio-caudal three-point bending and torsion (n = 4 each) using a universal testing machine. Mechanical parameters were determined from load-displacement curves and compared using Kruskal-Wallis test (p <0.05).

Results: Intact tibiae were significantly stronger than BIN and bone-BIN constructs in all testing modes. The strength of fixation constructs with eight locking bolts was significantly more than with four bolts. Overall strength of fixation with modified locking bolts was better than standard bolts. Based on technical ease and biomechanical properties, cranio-caudal insertion of bolts into the bone was found better than medio-lateral insertion.

Clinical significance: The eight bolt BINbone constructs could be useful to treat tibial fractures in large ruminants, especially buffaloes.
Recurrent Nasopharyngeal Carcinoma: A Clinical Dilemma and Challenge
Authors: Xu Tao , Tang J. , Gu M. , Liu L. , Wei W. , Yang H.
Published: October 2013

Recurrent nasopharyngeal carcinoma, which represents a small proportion of head-and-neck cancers, has a unique set of patho-clinical characteristics. The management of recurrent nasopharyngeal carcinoma remains a challenging clinical problem. Traditional treatments offer limited local control and survival benefits; more seriously, they frequently induce severe late complications. Recently, novel treatment techniques and strategies—including precision radiotherapy, endoscopic surgery or transoral robotic resection, third-generation chemotherapy regimens, and targeted therapies and immunotherapy—have provided new hope for patients with recurrent nasopharyngeal carcinoma. Some of these patients can potentially be cured with modern treatments. However, a lack of adequate evidence makes it difficult for clinicians to apply these powerful techniques and strategies. Individualized management guidelines, full evaluation of quality of life in these patients, and a further understanding of the mechanisms underlying recurrence are future directions for research into recurrent nasopharyngeal carcinoma.
The Road to Critical Thinking and Intelligence Analysis
Authors: Rudnianski Michel , Kravcik Milos
Published: October 2013

In an environment characterized by an ever-increasing flow of data and resulting complexity, the development of intelligence analysis is of core importance. After a brief analysis of three core competences (data processing, empathy, critical thinking), decision making issues are addressed through considering on the one hand cognitive and psychological biases, and on the other hand methodologies based on instrumental rationality. Core factors for the development of critical thinking are then discussed before a specific tool of Game Theory, called Games of Deterrence, is introduced based on bounded rationality. An example of Games of Deterrence’s application to critical thinking is given through using these games to model argumentation. Finally, on the basis of the method adopted, a framework is proposed for building a serious game devoted to critical thinking and intelligence analysis.
Information Retrieval from Deep Web Based on Visual Query Interpretation
Authors: Boughammoura Radhouane , Omri Mohamed Nazih , Hlaoua Lobna
Published: October 2013

Deep Web is growing rapidly. More than 90% of relevant information in web comes from deep Web. Users are usually interested by products which satisfy their needs at the best prices and quality of service .Hence, user’s needs concerns not only one service but many competitive services at the same time. However, for commercial reasons, there is no way to compare all web services products. Each web service is a black box which accepts queries through its own query interface and returns results. As consequence, users ask separately different web services and spend a lot of time comparing products in order to find the best one. This is a burden for novice users. In this paper, the authors propose a new approach which integrates query interfaces of many web services into one universal web service. The new interface describes visually the universal query and is used to ask many web services at the same time. The authors have evaluated their approach on standard datasets and have proved good performances.
Technoethics and Public Reason
Authors: Valkenburg Govert
Published: October 2013

Public reason specifies the rules under which a political community collectively conducts ethical reasoning. Technoethics needs to incorporate an account of how the technologies it aspires to govern bear on these rules. As the case of biobanks shows, technologies have the capacity to change the exact meanings of concepts that play central roles in ethical reasoning. By consequence, a revision of the rules to which this ethical reasoning about the very same biobanks is subject, becomes inevitable. Thus, reasoning in technoethics becomes essentially reflexive, as it is to discuss its own rules at the same level at which it discusses its primary object, namely new technologies. Technoethics is thus not only about how human values are to be incorporated into technology design, but also about what kind of political world is constructed through technology.
Differential T Cell Responses to Residual Viral Antigen Prolong CD4+ T Cell Contraction following the Resolution of Infection
Authors: Misumi Ichiro , Alirezaei Mehrdad , Eam Boreth , Su Maureen A. , Whitton J. Lindsay , Whitmire Jason K.
Published: October 2013

The contraction phase of the T cell response is a poorly understood period after the resolution of infection when virus-specific effector cells decline in number and memory cells emerge with increased frequencies. CD8+ T cells plummet in number and quickly reach stable levels of memory following acute lymphocytic choriomeningitis virus infection in mice. In contrast, virus-specific CD4+ T cells gradually decrease in number and reach homeostatic levels only after many weeks. In this study, we provide evidence that MHCII-restricted viral Ag persists during the contraction phase following this prototypical acute virus infection. We evaluated whether the residual Ag affected the cell division and number of virus-specific naive and memory CD4+ T cells and CD8+ T cells. We found that naive CD4+ T cells underwent cell division and accumulated in response to residual viral Ag for >2 mo after the eradication of infectious virus. Surprisingly, memory CD4+ T cells did not undergo cell division in response to the lingering Ag, despite their heightened capacity to recognize Ag and make cytokine. In contrast to CD4+ T cells, CD8+ T cells did not undergo cell division in response to the residual Ag. Thus, CD8+ T cells ceased division within days after the infection was resolved, indicating that CD8+ T cell responses are tightly linked to endogenous processing of de novo synthesized virus protein. Our data suggest that residual viral Ag delays the contraction of CD4+ T cell responses by recruiting new populations of CD4+ T cells.
HILDA: A Discourse Parser Using Support Vector Machine Classification
Authors: Hernault Hugo , Prendinger Helmut , Verle David A. du , Ishizuka Mitsuru
Published: October 2013

Discourse structures have a central role in several computational tasks, such as question-answering or dialogue generation. In particular, the framework of the Rhetorical Structure Theory (RST) offers a sound formalism for hierarchical text organization. In this article, we present HILDA, an implemented discourse parser based on RST and Support Vector Machine (SVM) classification. SVM classifiers are trained and applied to discourse segmentation and relation labeling. By combining labeling with a greedy bottom-up tree building approach, we are able to create accurate discourse trees in linear time complexity. Importantly, our parser can parse entire texts, whereas the publicly available parser SPADE (Soricut and Marcu 2003) is limited to sentence level analysis. HILDA outperforms other discourse parsers for tree structure construction and discourse relation labeling. For the discourse parsing task, our system reaches 78.3% of the performance level of human annotators. Compared to a state-of-the-art rule-based discourse parser, our system achieves a performance increase of 11.6%.
On the use of Web-based-GIS for managing and disseminating hazard and risk spatial information in volcanic areas
Authors: Le Cozannet G. , Bagni M. , Thierry P. , Aragno C. , Kouokam E.
Published: October 2013

Abstract. In volcanic areas exposed to multiple geological hazards, the efficient interpretation of the increasing amount of geographical data is a challenging issue. Within the European MIAVITA project, we investigated to which extent WebGIS can facilitate this interpretation through the visualization of such complex hazard and risk database. This analysis was structured around (1) the development of a Web-based Geographical Information System (WebGIS) and of an application for managing the geographical database, and (2) interactions with a group of hazard and risk analysts and managers, civil security officers, GIS analysts and system developers. We tested the system in the Mount Cameroon volcano, taking advantage of a complex hazard and risk geographical database collected previously. Key requirements here related to the need for a structured and flexible GIS-database and to manage user's privileges differently according to their profile and the status of the volcano. In addition, this study showed that it is important for such systems to manage different status for data, from data than can only be interpreted by experts (e.g. some complex remote sensing products) to data that can be disseminated to any potential user (e.g. a regulatory hazard map). While the developed tool is able to provide users with enough flexibility to respond to the users' requirements, it is still necessary to own expertise in WebGIS to manage such tools in the long term in local volcano observatory. Nevertheless, this study shows that WebGIS-based systems can relatively easily integrate some most important working procedures of hazard and risk management in volcanic areas.
Analyzing Copy Number Variation Using SNP Array Data: Protocols for Calling CNV and Association Tests
Authors: Lin Chiao‐Feng , Naj Adam C. , Wang Li‐San
Published: October 2013

High‐density SNP genotyping technology provides a low‐cost, effective tool for conducting Genome Wide Association (GWA) studies. The wide adoption of GWA studies has indeed led to discoveries of disease‐ or trait‐associated SNPs, some of which were subsequently shown to be causal. However, the nearly universal shortcoming of many GWA studies—missing heritability—has prompted great interest in searching for other types of genetic variation, such as copy number variation (CNV). Certain CNVs have been reported to alter disease susceptibility. Algorithms and tools have been developed to identify CNVs using SNP array hybridization intensity data. Such an approach provides an additional source of data with almost no extra cost. In this unit, we demonstrate the steps for calling CNVs from Illumina SNP array data using PennCNV and performing association analysis using R and PLINK. Curr. Protoc. Hum. Genet. 79:1.27.1‐1.27.15. © 2013 by John Wiley & Sons, Inc.
Genome‐Scale Sequencing to Identify Genes Involved in Mendelian Disorders
Authors: Markello Thomas C. , Adams David R.
Published: October 2013

The analysis of genome‐scale sequence data can be defined as the interrogation of a complete set of genetic instructions in a search for individual loci that produce or contribute to a pathological state. Bioinformatic analysis of sequence data requires sufficient discriminant power to find this needle in a haystack. Current approaches make choices about selectivity and specificity thresholds, and the quality, quantity, and completeness of the data in these analyses. There are many software tools available for individual, analytic component‐tasks, including commercial and open‐source options. Three major types of techniques have been included in most published exome projects to date: frequency/population genetic analysis, inheritance state consistency, and predictions of deleteriousness. The required infrastructure and use of each technique during analysis of genomic sequence data for clinical and research applications are discussed. Future developments will alter the strategies and sequence of using these tools and are also discussed.Curr. Protoc. Hum. Genet. 79:6.13.1‐6.13.19. © 2013 by John Wiley & Sons, Inc.
Analysis and Annotation of Whole‐Genome or Whole‐Exome Sequencing–Derived Variants for Clinical Diagnosis
Authors: Worthey Elizabeth A.
Published: October 2013

Over the last several years, next‐generation sequencing (NGS) has transformed genomic research through substantial advances in technology and reduction in the cost of sequencing, and also in the systems required for analysis of these large volumes of data. This technology is now being used as a standard molecular diagnostic test under particular circumstances in some clinical settings. The advances in sequencing have come so rapidly that the major bottleneck in identification of causal variants is no longer the sequencing but rather the analysis and interpretation. Interpretation of genetic findings in a clinical setting is scarcely a new challenge, but the task is increasingly complex in clinical genome‐wide sequencing given the dramatic increase in dataset size and complexity. This increase requires the development of novel or repositioned analysis tools, methodologies, and processes. This unit provides an overview of these items. Specific challenges related to implementation in a clinical setting are discussed. Curr. Protoc. Hum. Genet. 79:9.24.1‐9.24.24. © 2013 by John Wiley & Sons, Inc.
Lengths of Schwabe cycles in the seventh and eighth centuries indicated by precise measurement of carbon‐14 content in tree rings
Authors: Miyake Fusa , Masuda Kimiaki , Nakamura Toshio
Published: October 2013

Radiocarbon (14C) is produced in the atmosphere by galactic cosmic rays, which are modulated by solar magnetic activity. Its content in tree rings is retained and provides a record of past cosmic ray intensity and solar activity. We have measured, with 2 year resolution, the 14C content in Japanese cedar tree rings for the period A.D. 600 to 760, which includes a small grand solar minimum in the seventh to eighth centuries. Periodicity analysis of the 14C data shows that there is a component in the frequency band of the Schwabe cycle, with a period of 12–13 years continuing throughout the minimum. This is the fourth case in which an increase in the length of the Schwabe cycle has been observed in a grand solar minimum, after the Maunder Minimum, the Spörer Minimum, and the Fourth Century B.C. Minimum.
Observation errors in early historical upper‐air observations
Authors: Wartenburger R. , Brönnimann S. , Stickler A.
Published: October 2013

Upper‐air observations are a fundamental data source for global atmospheric data products, but uncertainties, particularly in the early years, are not well known. Most of the early observations, which have now been digitized, are prone to a large variety of undocumented uncertainties (errors) that need to be quantified, e.g., for their assimilation in reanalysis projects. We apply a novel approach to estimate errors in upper‐air temperature, geopotential height, and wind observations from the Comprehensive Historical Upper‐Air Network for the time period from 1923 to 1966. We distinguish between random errors, biases, and a term that quantifies the representativity of the observations. The method is based on a comparison of neighboring observations and is hence independent of metadata, making it applicable to a wide scope of observational data sets. The estimated mean random errors for all observations within the study period are 1.5 K for air temperature, 1.3 hPa for pressure, 3.0 ms−1for wind speed, and 21.4° for wind direction. The estimates are compared to results of previous studies and analyzed with respect to their spatial and temporal variability.
Ion Channels
Authors: Lipscombe Diane , Toro Cecilia P
Published: October 2013

Ion channels are membrane proteins that create specialised routes for ions to cross cell membrane lipid bilayers selectively, and at relatively high speeds. All cells of all organisms use ion channels of different types to control a range of functions. The majority of electrical membrane signals originate from the flow of select types of ions through ion channels. Cellular control of ion channel activity is critical for single‐cell and multicellular organisms to respond to their environments. Avoiding external threats, seeking nutrients, adapting to normal developmental processes, creating memories and modifying outputs according to previous events all involve ion channel activity. Ion channel dysfunction underlies multiple human disorders and diseases. Developmental disorders, pain syndromes that include extreme pain as well as congenital indifference to pain, certain types of migraines, epilepsies, ataxias, paralyses, cardiac arrhythmias and renal failure can all be due to malfunctioning ion channels. Thus, ion channels are critically important drug targets for the treatment of many illnesses and disorders.

Key Concepts:

Ion channels are found in all living cells.

Ion channels create specialised routes for ions to cross biological cell membranes.

Ion channels support the rapid flow of ions across biological membranes to generate electrical membrane signalling.

Ion channels are gated (opened and closed) by a wide range of biological signals.

Ion channels are selectively permeable to specific ions.

Certain ion channels control the influx of calcium, a critical intracellular second messenger.

A range of extracellular, intracellular and membrane signals alter the activity of ion channels.

Abnormal ion channel function underlies many disorders and diseases.

Ion channels are important targets of drugs and toxins.
Nonsense Mutations and Suppression
Authors: Herrington Muriel B
Published: October 2013

A nonsense mutation occurs when a sense codon, one that codes for an amino acid, is changed to one of the chain‐termination codons, UAG, UAA or UGA. A nonsense suppressor can result from a second mutation affecting the translational apparatus. This mutation enables the cell to insert an amino acid in response to the nonsense codon, resulting in a wild‐type or near wild‐type phenotype. Some suppressor mutations change the anticodon of atransfer ribonucleic acid (tRNA)such that it can pair with the nonsense codon. Other suppressors increase the readthrough of the nonsense mutation. Readthrough occurs at low levels but changes in the ribosome, in tRNA, or in translation factors can increase readthrough by altering the initial selection steps, proofreading or quality control in decoding of themessenger RNA. Manipulation of the accuracy of translation holds promise as a method for the treatment of genetic diseases, many of which result from nonsense mutations.

Key Concepts:

Suppression results when one mutation counteracts the effect of another mutation to give a wild‐type phenotype.

The nonsense codons UAG, UAA and UGA do not code for amino acids, but signal the end of the protein‐coding sequence in the mRNA.

Nonsense suppression competes with chain termination.

Errors occur during translation, and include reading a nonsense codon as sense as well as misreading and frameshifting.

Decoding during elongation involves conformational changes in the ribosome, tRNA and EF‐Tu.

Changes in the ribosome or other components of the translational apparatus can modify changes associated with decoding and thus enhance or reduce readthrough of nonsense codons.
Regeneration of Vertebrate Appendages
Authors: Ferretti Patrizia
Published: October 2013

Some vertebrates can faithfully replace complex parts of their body, a feature that is more commonly observed in invertebrates. They can perform this remarkable task because of their capacity to recruit progenitor cells and activate developmental programmes that largely parallel those used during embryogenesis. Tailed amphibians (urodeles), fish and deer provide the most striking examples of regeneration of appendages in adult animals. Frogs (anurans) can regenerate their limbs only at larval stages and can provide valuable models for studying loss of regenerative capability in the same species. Although birds and mammals cannot regenerate their limbs, digit tips display notable regenerative capability. The most striking example of mammalian appendage replacement is antler regeneration. Information on molecular landmarks of mature cell reprogramming in response to amputation is rapidly building up together with insights into the complex regulatory machinery controlling subsequent proliferation, differentiation and patterning of regenerating appendages.

Key Concepts:

Appendage regeneration can occur in some lower vertebrates, fish and amphibians.

Wound healing modality and appropriate inflammatory responses are crucial for regeneration.

Regeneration of vertebrate appendages occurs via formation of a growth zone, the blastema.

Blastema formation in adult lower vertebrates involves a reversal of the differentiated state.

Resident progenitor cells can contribute to regeneration.

Blastemal cells in regenerating limbs largely maintain their original identity.

The presence of a specialized wound epidermis is essential for regeneration throughout the process.

The presence of the nerve is crucial for the initial stages of limb and fin regeneration and also for mammalian digit tip regeneration.

Limb regeneration becomes nerve dependent after the developing limb is innervated.

Redeployment of certain developmental mechanisms underlies patterning in regenerating appendages.

Although, by and large, the same key signalling pathways are involved in regenerative responses across species, existence of species‐specific molecules may provide some rationale for differences in adult appendage regenerative capability.
Human Populations: Origins and Evolution
Authors: Barbujani Guido , Colonna Vincenza
Published: October 2013

The origins of modern human diversity have long been debated within a framework set by two hypotheses: ‘Out‐of‐Africa’ versus multiregional evolution. Humans are genetically closer to each other than members of all other primate species, most of our genetic diversity is accounted for by individual differences within populations, and only a small fraction of the species' genetic variance represents differences among populations or geographic groups. All these findings are hard to reconcile with the notion of parallel evolution in different continents, implicit in the multiregional model; the alternative hypotheses are now better described as either complete replacement of archaic human populations, or as partial assimilation into anatomically modern populations. Critical information about human demographic history has emerged from analyses of genomic diversity, clearly supporting an African origin of our species, followed by dispersal of rather small groups of people in the other continents. However, ancient
deoxyribonucleic acid
from fossil specimens seems to suggest low, but significant, levels of hybridisation between anatomically archaic and modern humans in the course of the latter's expansion from Africa, although alternative explanations of the data cannot be ruled out.

Key Concepts:

Genetic differences between humans are smaller than in any other primate species.

Genetic differences between human populations account for a minor fraction of the species' diversity.

Most human polymorphic alleles are present in all continents.

Each population contains an ample subset of human allelic variants.

African populations show the highest genome diversity worldwide, and alleles in other continents can largely be regarded as subsets of African diversity.

Differences between populations are structured in the geographical space, showing evidence of repeated founder effects as humans expanded to colonise the whole planet.

Models of genetic replacement, partial or total, of archaic human forms by anatomically modern humans account for current diversity better than any alternative models.

Non‐African people consistently show an excess of DNA similarity with the Neandertal genome, which is often (but not necessarily) interpreted as a consequence of archaic hybridisation between Neandertals and anatomically modern people dispersing from Africa.
Protein Tertiary Structures: Prediction from Amino Acid Sequences
Authors: Tress Michael
Published: October 2013

Proteins have a crucial role in all cellular processes. The function of a protein is intrinsically linked to its structure, so solving protein tertiary structures is the key to understanding the biological functions of proteins. Resolving protein three‐dimensional (3D) structures is complicated and time‐consuming, so despite recent efforts to determine representative structures for each protein family, the number of known protein structures is dwarfed by the number of known protein sequences. Computational methods for the prediction of protein tertiary structures directly from their amino acid sequences have been developed to bridge this gap. These structure prediction algorithms are based on the observation that there are a limited number of protein folds and that most protein sequences will fold into one of these limited globular structures. The field of structure prediction is now quite mature and many stable methods exist for generating alignments between sequences and structures and for building 3D models.

Key Concepts:

Structure can be predicted from sequence because protein folds are relatively stable.

A wide variety of methods exist for the prediction of 3D structure from protein sequence.

The easiest targets are those for which it is possible to detect an evolutionary related template structure that aligns with more than 30% sequence and few gaps.

In these cases, structure prediction is trivial and the emphasis should be placed on all atom refinement measures.

Where template structures are more remotely related, maximum effort should be put into obtaining an alignment between template and target sequences.

Structural domains, disorder, secondary structure and important functional residues need to be considered when building a model of a target protein.
Telomerase: Structure and Function
Authors: Shay Jerry W
Published: October 2013

In contrast to normal cells, tumour cells generally have short telomere lengths and show no continuing loss of telomere length with successive cell divisions, suggesting that telomere stability may be required for cells to escape from replicative senescence and proliferate indefinitely. Most, but not necessarily all, malignant tumours are immortal to sustain their growth, thus, the cellular ribonucleoprotein (reverse transcriptase) enzyme complex termed telomerase may be a rate‐limiting step required for the continuing proliferation of advanced cancers. Telomerase, the enzyme that completes
deoxyribonucleic acid (DNA)
replication at the termini of eukaryotic chromosomes, is an important factor in DNA replication, chromosomal stability and tumorigenesis.

In human tumours, telomere length is maintained by a balance between processes that lengthen telomeres (telomerase) and processes that shorten telomeres (lack of complete lagging DNA strand synthesis ‘end replication problem’ and other end processing events). Telomerase stabilises telomere length by adding TTAGGG repeats onto the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres that occurs in its absence. As telomerase is expressed in almost all human cancers, approaches for inhibiting telomerase as a target for cancer therapeutics are currently progressing through clinical trials.

Key Concepts:

Telomeres, the ends of human chromosomes progressively shorten throughout life in all dividing human cells and when critically shortened become ‘uncapped’ leading to a DNA damage signal and then undergo growth arrest termed replicative senescence (cell ageing).

A hallmark of cancer cells is unlimited cell growth.

Advanced cancer cells accomplish immortality almost universally by activating or upregulating the ribonucleoprotein complex termed telomerase.

Telomerase is composed of two essential components, TERT (reverse transcriptase component) and TERC (functional or template RNA that recognises the ends of chromosomes).

Telomerase is expressed during early human development and remains silent in almost all human tissues except transiently amplified stem cells throughout life.

Approximately 90% of all human cancers express telomerase activity.

A small fraction of human tumours do not express telomerase and some of these may engage a DNA recombination mechanism to maintain telomeres termed ALT, alternative lengthening of telomeres.

Introduction of hTERT into normal telomerase silent cells is sufficient to immortalise cells in appropriate culture conditions without the cells becoming cancerous.

As telomerase is almost a universal oncology target, inhibiting telomerase should be a potent anticancer therapeutic target.
Comparing the Human and Sea Urchin Genomes
Authors: Cameron R Andrew
Published: October 2013

To compare the genomes of humans and sea urchins seems, at first glance, awkward. The human body is bilaterally symmetrical with a complex head containing many sensory structures, whereas the sea urchin has radial symmetry and a globose form with no suggestion of a head. However, sea urchins belong to a group of animals (the echinoderms) that lies on the same major branch of the tree of life (the deuterostomes) to which humans belong. As echinoderms diverged very early from the major lineage of the deuterostomes, their genomes reflect the basic qualities of this lineage and inform to a deep reach of time the evolutionary changes leading to the human genome. Even though the sea urchin form differs radically from that of vertebrates, they share many of the same gene families. Indeed, the invention of new genes in this evolutionary path is subordinate to the diverse changes in the abundance of genes in existing families.

Key Concepts:

The relative proximity of sea urchins to humans on the deuterostome branch of the evolutionary tree renders them a good comparison to humans for gene and genome evolution.

The sea urchin genome is one‐quarter the size of the human but has about the same number of genes.

Gene comparisons between these distantly related species show that differences in body plans result from spatial and temporal differences in gene activity rather than the possession of different genes.

The sea urchin HOX gene cluster is modified from the linear arrangement found in humans.

Without an adaptive immune system, the sea urchin appears to use a huge expansion in innate immune genes.
Speciation Genes
Authors: Mensch Julián , Frankel Nicolás , Hasson Esteban
Published: October 2013

Even though there is no universal criterion for species definition, the key event in speciation research is the advent of reproductive isolation or barriers that prevent gene flow between populations. The search for genetic factors underlying isolating barriers is the field of speciation genetics. The development of sophisticated methods of genetic analysis coupled with statistical advances allowed a finer dissection of the genetic factors underlying the origins of species down to the level of the individual loci and even at the
deoxyribonucleic acid (DNA)
‐sequence level. Traditionally, speciation geneticists concentrated, almost exclusively, on genes causing hybrid incompatibilities (especially intrinsic postzygotic barriers). However, barriers to gene flow caused by speciation genes can arise at multiple prezygotic and postzygotic life‐history stages. Thus, a general definition of speciation genes should refer to those genes that contributed to the splitting of two lineages by reducing the amount of gene flow between them.

Key Concepts:

The evolution of barriers to genetic exchange between groups is the crucial event for the origin of new sexually reproducing species.

Barriers to gene flow can be divided in two main categories: (i) prezygotic that preclude the formation of hybrid offspring and (ii) postzygotic that later prevent the success and propagation of hybrid offspring.

The identification and characterisation of genes that contribute to the interruption of gene flow between populations is currently one of the main focuses in the field of speciation.

Speciation genes are the genes that contributed to the splitting of two lineages by reducing the amount of gene flow between them.

The most solid evidence that a gene causes reproductive isolation combines fine mapping studies with genetic manipulation experiments (such as positional cloning, gene replacement or knockout, gene expression assays and transgenic manipulations).

Alleles underlying hybrid incompatibilities between species may arise by neutral or nearly neutral processes or may be a direct consequence of positive selection or a byproduct of adaptive evolution.
Ras Mutations in Cancer
Authors: Barault Ludovic , Lamba Simona , Di Nicolantonio Federica
Published: October 2013

Mutations affecting the three isoforms of the RAS gene – KRAS, HRAS and NRAS – represent the most common oncogenic event in several cancer types. RAS mutations lead to constitutive activation of the corresponding protein and contribute to different hallmarks of cancers, including increased proliferation and resistance to apoptosis. Activating mutations in
KRAS
are currently used in the clinic to exclude colorectal cancer patients from treatment with ineffective epidermal growth factor receptor targeted‐based therapies. Future studies are needed to fully elucidate the role of all
RAS
oncogenic variants in cancer biology, as well as to assess the potential prognostic and predictive value of individual
RAS
genetic alterations in clinical settings other than colorectal cancer.

Key Concepts:

RAS in human consists in 4 isoforms (KRAS4A, KRAS4B, NRAS, and HRAS) encoded by 3 genes (
KRAS
,
NRAS
, and
HRAS
).

Isoforms of the
RAS
gene (
KRAS
,
NRAS
,
HRAS
) are the major oncogenes mutated in several cancer types.

Mutations in
RAS
family genes lead to constitutive protein activation by inhibition of the catalytic reaction which converts active RAS–GTP to inactive RAS–GDP.

Different types of mutations occur in different cancers.

Mutations in
RAS
family genes may differ in terms of biochemical effectors, biological activities and prognostic or predictive value.
Signalling via Single‐Pass Transmembrane Proteins
Authors: Pahl Matthew C , Askinazi Olga L , Hamilton Catherine , Cheng Irene , Cichewicz Karol , Kuhn Jason , Manohar Sumanth , Deppmann Christopher D
Published: October 2013

Single‐pass transmembrane proteins (TM1) are a diverse group of proteins characterised by a single transmembrane domain. In total, the authors found approximately 1300 TM1 proteins in the human genome, most of which have characterised functions. The extracellular domains of these proteins range up to 22 000 amino acids with an average size being six times larger than intracellular domains. This suggests that these proteins have evolved the capacity to bind a wide array of ligands and substrates. Consequently, these proteins are involved in many processes, such as adhesion, migration, growth and cell death, among others. Although many act as receptors for first messengers (extracellular signalling molecules), they can also serve as ligands, adaptors, proteases and coreceptors. Herein, the authors provide a broad overview of these different roles along with examples of their involvement in pathological and physiological situations.

Key Concepts:

Single‐pass transmembrane proteins participate in signalling in a variety of ways, either as ligands, receptors, enzymes coreceptors and/or adaptors.

TM1 proteins appear to have undergone evolutionary expansion as a function of body plan complexity.

The extracellular domains of TM1 proteins cluster well based on family, whereas the intracellular domains do not.

TM1 proteins are adapted to bind very large substrates/ligands compared with other receptor families (ion channels and GPCRs).

TM1 have roles in every organ system and are particularly important in the immune and nervous systems.
Molecular Genetic Analysis of Ménière's Disease
Authors: Hietikko Elina , Kotimäki Jouko , Männikkö Minna
Published: October 2013

Ménière's disease (MD) is an inner ear disease characterised by tinnitus, vertigo and sensorineural hearing loss. The exact aetiology of MD is unknown but it is generally considered as a multifactorial disease. The role of genetic factors in the development of MD has been well documented. Familial clustering of MD has been observed in several studies and the proportion of familial cases is estimated to be 5–23.5%. Single locus on chromosome 12p12.3 has been reported in Swedish MD families. In addition, several inconclusive candidate‐gene analyses have been performed. At the moment, knowledge of genetic factors associated with MD is modest. Molecular genetic study of MD is complicated by genetic and clinical heterogeneity and diagnostic challenges. However, modern genetics may be useful in discovering new pathways associated with the pathophysiology of MD in the future.

Key Concepts:

The knowledge of genetic factors associated with MD is currently modest.

Genetic and clinical heterogeneity, diagnostic challenges, multifactorial origin and late onset of MD create challenges to the molecular genetic analysis of the disease.

Family‐based studies may assist to reduce genetic and phenotypic heterogeneity to identify molecular mechanisms or pathways involved in the pathogenesis of MD.

Candidate‐gene analysis is an ineffective way to study the genetics of MD and future genetic studies should emphasise the usage of linkage analyses and next‐generation sequencing as well as studying epigenetic pathways.

A strong interdisciplinary research environment is needed to successfully study molecular genetics of MD. Combined efforts of highly skilled otologists, geneticists and statisticians are needed to overcome the difficulties in the molecular genetic analyses of MD. To achieve power for genetic studies, a greater number of subjects are needed. This shortcoming may be corrected by an international cooperation between study groups.
Studying Wound Repair in the Mouse
Authors: Tan Nguan S. , Wahli Walter
Published: October 2013

Animal models of wound healing provide vital insights into the mechanisms and pathophysiology of cutaneous wound repair and are a crucial part of clinical research into the development of new strategies and approaches to rational wound therapy. Although considerable biological variation in the wound healing response exists even among inbred animal strains, consistent surgical procedure and wound analysis can yield significant conclusions. Many different aspects of the healing process can be characterized and quantified in a reproducible, controlled environment. Here, we detail methods for full‐thickness excisional and incisional wounding and for analysis of wound biopsies. Curr. Protoc. Mouse Biol. 3:171‐185 © 2013 by John Wiley & Sons, Inc.
Critical Literacy and Critical Discourse Analysis
Authors: Valdez Paolo Nino
Published: October 2013

Critical discourse analysis is an area of scholarly inquiry that attempts to unravel manifestations of power, ideology, and control embedded within texts. Its socially oriented focus in the analysis of language has established the importance of reflexivity in accounting for the non‐neutrality of language in real‐life contexts. Typical investigations of
CDA
fall under the rubric of political discourses concerning government on issues of difference (race, sex, and age), media discourse's influence in representing individuals and different sectors of society, and influence of other domains in colonizing institutional discourses.

On the other hand, critical literacy (
CL
) is an approach to life and learning. Specifically,
CL
's actualization is the empowerment of the learners as active agents of change through meaningful inquiry and dialogue to achieve true progress. Scholars who espouse
CL
firmly believe that practitioners need to engage in a politics in their work in order to achieve authentic change—one that benefits all members of the community.
The Dictionary as a Tool in Language Learning
Authors: East Martin
Published: October 2013

The dictionary, according to Kirkness, is

an essential source, if not indeed the principal source, of information on language for all members of literate societies who might have questions on any aspect of the form, meaning, and/or use of a word or words in their own or in another language. (p. 54)

Seen from this perspective, dictionaries are vital tools invoked by language users in a range of situations when they are seeking clear and definitive answers on problems they encounter with language in use.
Portfolio Assessment
Authors: Hung Shao‐Ting Alan , Huang Heng‐Tsung Danny
Published: October 2013

Portfolio assessment represents a form of alternative assessment and, as its name reveals, assesses learning performance via evaluating portfolios. As defined by Genesee and Upshur, a portfolio refers to “a purposeful collection of students' work that demonstrates . . . their efforts, progress and achievement in given areas”(p. 99) and might include such artifacts as writing samples, reading logs, drawings, journals, personal reflections, and teacher and student comments on students' progress, among others.

Portfolio assessment came into prominence largely as a response to the need to transcend standardized testing and, more importantly, the need to integrate instruction and assessment. As Hamp‐Lyons and Condon asserted, a portfolio

provides an instrument that incorporates the products of instruction and that can, if the assessment is designed carefully, provide an evaluation that feeds back into the process of instruction . . . Perhaps the greatest theoretical and practical strength of a portfolio, used as an assessment instrument, is the way it reveals and informs teaching and learning (pp. 3–4).
Vocabulary and Listening
Authors: van Zeeland Hilde
Published: October 2013

Second language (
L2
) listening has received relatively little research attention, and this is also the case in the field of vocabulary. Considerably fewer vocabulary studies have been conducted in the context of listening than reading. However, the existing research has emphasized the reciprocal importance of listening and vocabulary: vocabulary knowledge is a prerequisite for listening comprehension, and listening can serve as a useful source for vocabulary acquisition. This entry provides an overview of the existing research by considering both points in turn: (a) the role of vocabulary knowledge in listening (their relationship, the vocabulary requirements for listening, and vocabulary recognition in listening); and (b) the acquisition of vocabulary from listening.
Parameter set selection for dynamic systems under uncertainty via dynamic optimization and hierarchical clustering
Authors: Dai Wei , Bansal Loveleena , Hahn Juergen , Word Daniel
Published: October 2013

It is common that only a subset of the parameters of models can be accurately estimated. One approach for identifying a subset of parameters for estimation is to perform clustering of the parameters into groups based upon their sensitivity vectors. However, this has the drawback that uncertainty cannot be directly incorporated into the procedure as the sensitivity vectors are based upon the nominal values of the parameters. This article addresses this drawback by presenting a parameter set selection technique that can take uncertainty in the parameter space into account. This is achieved by defining sensitivity cones, where a sensitivity cone includes all sensitivity vectors of a parameter for different values, resulting from the uncertainty, in the parameter space. Parameter clustering can then be performed based upon the angles between the sensitivity cones, instead of the angle between sensitivity vectors. The presented technique is applied to two case studies. © 2013 American Institute of Chemical Engineers AIChE J, 60: 181–192, 2014