bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Laser Printing for Organic Electronics
Authors: Makrygianni Marina , Papazoglou Symeon , Zergioti Ioanna
Published: June 2015

This article reviews the latest developments as well as the background and the evolution of direct laser printing of various materials for organic electronics applications. Current technological trends require the precise deposition of highly resolved features, which preserve their structural and electronic properties upon transfer, while increasing the number of components that can be integrated in a single device. Direct laser printing techniques meet these requirements and examples of selected applications, including chemical sensors and biosensors, organic thin‐film transistors, organic light‐emitting diodes, and power generating devices, are presented highlighting the potential incorporation of lasers into the direct printing of entire devices and components. In particular, the successful laser printing of polymers, metals, semiconducting inks, and viable biological materials such as DNA, proteins, and enzymes with high spatial resolution offers unique advantages compared to traditional inkjet and thin‐film techniques. Moreover, the mechanisms of liquid‐ and solid‐phase laser printing are investigated through time‐resolved studies, while postprinting processes such as laser sintering, a process used for the formation of conductive features on laser‐printed metallic nanoparticle patterns, are also discussed in this article.
Flexible Displays
Authors: Fujikake Hideo
Published: June 2015

As the most promised next‐generation of displays, lightweight, thin, and flexible displays that can be bent freely are expected in the information‐oriented lifestyle and society. This article focuses on flexible material and device strategy for electronic information displays. Flexible plastic substrates, device fabrication methods, display operation (e.g., organic light‐emitting diode display, liquid crystal display, and electrophoretic display), and driving technology are presented. In addition, new practical applications of flexible displays are also discussed.
Feature Selection for 2Dand 3DFace Recognition
Authors: Bennamoun Mohammed , Guo Yulan , Sohel Ferdous
Published: June 2015

Face recognition is a popular research topic with a number of applications in several industrial sectors including security, surveillance, entertainment, virtual reality, and human–machine interaction. Both 2D images and 3D data can now be easily acquired and used for face recognition. For any 2D/3D face recognition system, feature extraction and selection play a significant role. Currently, both holistic and local features have been intensively investigated in the literature. In this article, fundamental background knowledge of face recognition, including 2D/3D data acquisition, data preprocessing, feature extraction, classification, and performance evaluation, is presented. The state‐of‐the‐art feature extraction algorithms, including 2D holistic feature, 2D local feature, 3D holistic feature, and 3D local feature extraction algorithms, are then described in detail. Finally, feature selection and fusion techniques are presented. The article covers the complete related aspects of feature selection for 2D and 3D face recognition.
Electronic Nose Sensors
Authors: Dini Francesca , Di Natale Corrado
Published: June 2015

The aggregation of gas sensors into arrays was introduced to overcome the limited selectivity of solid‐state gas sensors. Indeed, when complemented by a multivariate data analysis technique, such as those used in chemometrics, sensor arrays might allow for the quantification and identification of compounds with a performance well beyond that of a single device. Such arrays have a very close similitude with the properties of the olfactory receptor neurons. Indeed, similarly to sensors, the selectivity of olfactory receptor neurons is also limited, so that a single olfactory receptor neuron senses many compounds and more than one olfactory receptor neuron sense the same compound. The recognition of a specific compound or a specific blend of compounds is then achieved by the collective response of the olfactory receptor neurons. Due to this parallel between olfaction and gas sensor arrays, the latter ones are now currently nicknamed as “electronic noses.”

In this article, an overview of the sensor technology mostly used for electronic noses is presented together with a discussion about the data analysis methods that enable the recognition of odors from the electronic nose signals. Finally, a short overview of the application of electronic noses to practical cases is provided.
Graphical Symbol Recognition
Authors: Santosh K.C. , Wendling Laurent
Published: June 2015

This article focuses on graphical symbol recognition, one of the key issues in document image processing. Graphical symbol recognition is a sub‐field of a larger research domain: pattern recognition. The domain covers several approaches (such as statistical, structural and syntactic) and specially designed symbol recognition techniques inspired by real‐world industrial problems. The article overviews research problems, state‐of‐the‐art methods that convey basic steps as well as prominent concepts, techniques, and research directions that are associated with graphical symbol recognition.
Gait Recognition: Databases, Representations, and Applications
Authors: Makihara Yasushi , Matovski Darko S. , Nixon Mark S. , Carter John N. , Yagi Yasushi
Published: June 2015

There has been a considerable progress in automatic recognition of people by the way they walk since its inception almost 20 years ago: There is now a plethora of techniques and data that continue to show that a person's gait is indeed unique. Gait recognition is a behavioral biometric that is available even at a distance from a camera when other biometrics may be occluded, obscured, or suffering from insufficient image resolution (e.g., a blurred face image or a face image occluded by mask). Since gait recognition does not require subject cooperation due to its noninvasive capturing process, it is expected to be applied for criminal investigation from CCTV footages in public and private places. This article introduces current progress, a research background, and basic approaches for gait recognition in the first three sections, and two important aspects of gait recognition, the gait databases and gait feature representations, are described in the following sections.

Publicly available gait databases are essential for benchmarking individual approaches, and such databases should contain a sufficient number of subjects as well as covariate factors to realize statistically reliable performance evaluation and also robust gait recognition. Gait recognition researchers have therefore built such useful gait databases that incorporate subject diversities and/or rich covariate factors.

Gait feature representation is also an important aspect for effective and efficient gait recognition. We describe the two main approaches to representation: model‐free (appearance‐based) approaches and model‐based approaches. In particular, silhouette‐based model‐free approaches predominate in recent studies and many have been proposed and are described in detail.

Performance evaluation results of such recent gait feature representations on two of the publicly available gait databases are reported: USF Human ID with rich covariate factors such as views, surface, bag, shoes, and time elapse and OU‐ISIR LP with more than 4000 subjects. Since gait recognition is suitable for criminal investigation, applications of the gait recognition to forensics are addressed with real criminal cases in the application section. Finally, several open problems of the gait recognition are discussed to show future research avenues of the gait recognition.
Evolutionary Algorithms: Principles and Applications
Authors: Zelinka Ivan
Published: June 2015

Evolutionary algorithms (EAs) are search methods that can be used for solving optimization problems. They mimic principles of natural evolution by employing a population‐based approach (or swarm‐like), associating each individual of the population with the so‐called fitness and including elements of randomness, although the random is directed through a selection process. This article presents the basic principles of evolutionary algorithms and discusses their dynamics, structure, and applications. In doing so, it is particularly shown how the fundamental understanding of natural evolution processes has cleared the ground for the origin of evolutionary algorithms. Major implementation variants and their structural as well as functional elements are discussed here with attention on examples from electrical engineering.
Vocabularies for Video Event Detection
Authors: Habibian Amirhossein , Snoek Cees G. M.
Published: June 2015

In general, event detection systems can be characterized by two main components: video vocabulary and event modeling. The video vocabulary converts the raw video data into a feature vector, which contains the multimodal information considered useful for detecting the event of interest. The event modeling component learns a model for each event detection. This article discusses both low‐ and high‐level vocabularies for video event detection. In addition, representative benchmarks for evaluating event detection are also presented.
Smart Grid
Authors: Güngör Vehbi Cagri , Tuna Gurkan , Potirakis Stelios M. , Vokas Georgios A.
Published: June 2015

Smart grid (SG) is a modern electrical energy infrastructure with a robust two‐way communications capability using distributed computing technologies and advanced sensors to improve the efficiency, safety, and reliability of power delivery and use. Since the SG can be described as the integration of the existing power grid with a sophisticated communication infrastructure, a flexible, secure, and interoperable two‐way communication backbone is a must to deal with the communication requirements of each SG component, given that these pose communication requirements with varying degrees of QoS, reliability, and security. In this chapter, the SG concept is explained. In addition, the requirements for SG applications and communications technologies are discussed in detail.
Self‐Immolative Polymers
Authors: Fan Bo , Gillies Elizabeth R.
Published: June 2015

Self‐immolative linear polymers are a recently developed class of materials that typically undergo head‐to‐tail depolymerization in response to the cleavage of stimuli‐responsive end‐caps from their termini. These polymers have been inspired by self‐immolative dendrimers and oligomers that undergo cascades of cyclization and/or elimination reactions in response to the activation or cleavage of a trigger moiety. During the past decade, several backbones have been introduced including polycarbamates, polycarbonates, polythiocarbamates, polythiocarbonates, polyacetals, and poly(benzyl ether)s. These backbones have been tuned to control the depolymerization rate, and end‐caps responsive to stimuli including enzymes, light, heat, acid, and small molecules such as fluoride ions have been incorporated. They have been explored for the development of sensing devices, microcapsules, and nanoscale assemblies such as micelles and vesicles. In these applications, their depolymerization in response to end‐cap cleavage affords effective amplification of these stimuli, resulting in enhanced sensitivity. Their depolymerization kinetics has also been studied in detail. This article will review the development and current status of both the chemistry and application of linear self‐immolative polymers.
Uncertainty in training image‐based inversion of hydraulic head data constrained to ERT data: Workflow and case study
Authors: Hermans Thomas , Nguyen Frédéric , Caers Jef
Published: June 2015

In inverse problems, investigating uncertainty in the posterior distribution of model parameters is as important as matching data. In recent years, most efforts have focused on techniques to sample the posterior distribution with reasonable computational costs. Within a Bayesian context, this posterior depends on the prior distribution. However, most of the studies ignore modeling the prior with realistic geological uncertainty. In this paper, we propose a workflow inspired by a Popper‐Bayes philosophy that data should first be used to falsify models, then only be considered for matching. We propose a workflow consisting of three steps: (1) in defining the prior, we interpret multiple alternative geological scenarios from literature (architecture of facies) and site‐specific data (proportions of facies). Prior spatial uncertainty is modeled using multiple‐point geostatistics, where each scenario is defined using a training image. (2) We validate these prior geological scenarios by simulating electrical resistivity tomography (ERT) data on realizations of each scenario and comparing them to field ERT in a lower dimensional space. In this second step, the idea is to probabilistically falsify scenarios with ERT, meaning that scenarios which are incompatible receive an updated probability of zero while compatible scenarios receive a nonzero updated belief. (3) We constrain the hydrogeological model with hydraulic head and ERT using a stochastic search method. The workflow is applied to a synthetic and a field case studies in an alluvial aquifer. This study highlights the importance of considering and estimating prior uncertainty (without data) through a process of probabilistic falsification.
Replicating the 1970s' Weddell Polynya using a coupled ocean‐sea ice model with reanalysis surface flux fields
Authors: Cheon Woo Geun , Lee Sang‐Ki , Gordon Arnold L. , Liu Yanyun , Cho Chang‐Bong , Park Jong Jin
Published: June 2015

The 1970s' Weddell Polynya is simulated in the framework of a coupled ocean‐sea ice model forced by reanalysis surface flux fields. A rapid emergence of strongly negative wind stress curl over the Weddell Sea intensifies the cyclonic Weddell gyre and thus causes the relatively warm and salty Weddell Deep Water (WDW) to upwell, generating an open‐ocean polynya by melting sea ice or hindering its formation. Once the polynya occurs in the austral winter, the underlying water column is destabilized due to the combined effect of the high‐salinity WDW, a massive cooling at the air‐sea interface, and the ensuing brine rejection from newly forming ice, thus inducing open‐ocean deep convection. Further analysis shows that the buildup of a large heat reservoir at depth by the mid‐1970s was a necessary condition to establish the Weddell Polynya of the 1970s.
Use of a forest sapwood area index to explain long‐term variability in mean annual evapotranspiration and streamflow in moist eucalypt forests
Authors: Benyon Richard G. , Lane Patrick N. J. , Jaskierniak Dominik , Kuczera George , Haydon Shane R.
Published: June 2015

Mean sapwood thickness, measured in fifteen 73 year old Eucalyptus regnans and E. delegatensis stands, correlated strongly with forest overstorey stocking density (R2 0.72). This curvilinear relationship was used with routine forest stocking density and basal area measurements to estimate sapwood area of the forest overstorey at various times in 15 research catchments in undisturbed and disturbed forests located in the Great Dividing Range, Victoria, Australia. Up to 45 years of annual precipitation and streamflow data available from the 15 catchments were used to examine relationships between mean annual loss (evapotranspiration estimated as mean annual precipitation minus mean annual streamflow), and sapwood area. Catchment mean sapwood area correlated strongly (R2 0.88) with catchment mean annual loss. Variation in sapwood area accounted for 68% more variation in mean annual streamflow than precipitation alone (R2 0.90 compared with R2 0.22). Changes in sapwood area accounted for 96% of the changes in mean annual loss observed after forest thinning or clear‐cutting and regeneration. We conclude that forest inventory data can be used reliably to predict spatial and temporal variation in catchment annual losses and streamflow in response to natural and imposed disturbances in even‐aged forests. Consequently, recent advances in mapping of sapwood area using airborne light detection and ranging will enable high resolution spatial and temporal mapping of mean annual loss and mean annual streamflow over large areas of forested catchment. This will be particularly beneficial in management of water resources from forested catchments subject to disturbance but lacking reliable long‐term (years to decades) streamflow records.
Language
Authors: Osterhout Lee
Published: June 2015

Unlike the communicative systems of other species, human language allows us to transmit an essentially unlimited set of meanings to other people. Spoken language is an evolved skill and is acquired at an early age by all normally developing humans. Written language is a human invention that must be intentionally learned. The unique expressive power of language derives from the human ability to combine smaller units of language into larger ones, at multiple levels. Sounds can be combined to form words, morphemes can be combined to form complex words and words can be combined to form phrases, clauses and sentences. These combinations are governed by complex grammatical rules. Language production and comprehension are ‘real‐time’ processes that rely on specific cognitive abilities and neural circuitry. Information about the neurobiology of language comes from studying the consequences of brain lesions and from electrophysiological and brain imaging studies of healthy individuals.

Key Concepts

Human language is an evolved system for transmitting an enormous array of specific meanings.

The lexicon is a store of symbols for concepts, and syntax is a body of rules for combining them.

The speech planning process is revealed by a careful study of speech errors.

Our ability to perceive distinctive speech sounds depends on
categorical perception
.

We compute separate representations of sentence meaning and grammatical form.

The brain region most closely linked to language is the cortex surrounding the sylvian fissure in the left hemisphere.

Specific language disorders can occur with restricted damage to particular brain structures or regions.
Orbiviruses and Bluetongue Virus
Authors: Mertens Peter , Mohd Jaafar Fauziah , Attoui Houssam
Published: June 2015

Bluetongue virus
(BTV) is the type species of the genus
Orbivirus
within the family
Reoviridae
(the largest double‐stranded ribonucleic acid (dsRNA) virus family). BTV is an arthropod‐borne pathogen that is transmitted by the bites of its vector, the
Culicoides
biting midges, which transmit the virus between its ruminant hosts. The virus can infect most species of domestic and wild ruminants. BT clinical signs are most common in sheep and some species of deer. In recent years, the distribution of BTV has changed considerably, particularly in Europe. New outbreaks have occurred each year from 1998 in southern and central Europe, involving several strains from 10 different serotypes. In 2006, BTV serotype 8 caused an outbreak approximately 5° further north in Europe than ever before, infecting ruminants in a wide area across northern Europe. A new virus (
Toggenburg virus
) has been identified in goats from Switzerland in 2008 and designated as the twenty‐fifth serotype of BTV and another one isolated from goats in Corsica in France more recently and was designated as serotype 27. Additional serotypes have been detected/isolated, bringing now the number of serotypes to 29.

Key Concepts

Genus
Orbivirus
is the most diverse genus of family
Reoviridae
containing 32 virus species.

Bluetongue disease affects mainly sheep causing severe clinical signs and high mortality.

Bluetongue virus
is transmitted by competent species of
Culicoides
midges.

Phylogenetic analysis identifies two major groups of orbiviruses, those with their subcore shell protein (T2 protein) being the VP2 and those with the T2 being VP3. Orbiviruses are nonturreted members of family
Reoviridae
, and the atomic structure of BTV core has been determined.
Pathogenic Viruses: Clinical Detection
Authors: Zuckerman Mark
Published: June 2015

The clinical and laboratory diagnosis of the viral aetiology of an individual's illness involves understanding their clinical symptoms and signs, how the host's immune system responds to a viral infection as well as which diagnostic tests are the most sensitive and specific to detect that virus or the host's immune response. Once the choice of test is made, the correct specimen must be collected and the results of these tests interpreted in the context of the clinical picture. Detection of viral RNA and DNA has revolutionised clinical virology and has resulted in being able to detect emerging virus infections and measure the amount of the virus, known as viral load, in different samples. These tests are critical in monitoring viral infections as well as the response to antiviral therapy. In addition, automated nucleotide sequence analysis has helped in the investigation of outbreaks of infection.

Key Concepts

Viral infections cause a broad range of illness which depends on viral virulence, susceptibility of the host and in particular whether the host is immunocompetent or immunocompromised. The host immune response may also be critical in the pathogenesis of the infection.

The relative importance of virus‐induced or immune‐mediated pathogenesis differs for each virus, and the symptoms that occur during a viral infection may be due to either mechanism or both.

The symptoms with which the patient presents to the doctor and the signs that the doctor notes during a physical examination are important guides to make a differential diagnosis.

Specific symptoms or symptom complexes may suggest a specific viral infection.

An understanding of the central and/or peripheral target sites where viral replication occurs, as well as the assays available for detection of virus, viral antigen or viral nucleic acid, helps decide which type of specimen to collect.

Staff safety, care in specimen separation to avoid errors and maintaining virus viability are important issues for proper handling of specimens for viral diagnosis.

Laboratory diagnostic methods are divided into viral antigen or nucleic acid detection and serological techniques.

Automated nucleic acid extraction, sample handling and real‐time PCR platforms have revolutionised nucleic acid detection and quantification, making these methods part of routine laboratory service provision.

Automated nucleotide sequence analysis can be used to determine antiviral resistance mutations and subtype or genotype of the virus and investigate outbreaks of infection.
Amyloidosis
Authors: Benson Merrill D
Published: June 2015

The amyloidoses are a group of β‐structure protein deposition diseases that may be systemic or localised, sporadic, hereditary or associated with chronic inflammation. Many serum proteins are capable of forming β‐structure and participate in the formation of 10 nm fibrils which are the hallmark of amyloid deposits. These proteins include immunoglobulin light chains, several proteins synthesised mainly by the liver (serum amyloid A, fibrinogen, apolipoproteins AI and AII, leukocyte chemotaxin factor‐2) plus lysozyme, cystatin‐C, gelsolin and probably others not yet identified. Pathology is the result of displacement of normal tissue structures. The systemic forms of amyloidosis may cause the nephrotic syndrome and renal failure, cardiac arrhythmias and heart failure, hepatic failure and bowel dysfunction in varying combinations and degrees of severity.

Key Concepts

Amyloidosis is a generic term to designate any biologic condition where protein fibrils measure 8–12 nm and aggregate to form deposits in extracellular space of most body organs.

Many proteins have the potential to form amyloid fibrils. Some have extensive β‐structure, a prerequisite for fibril formation, while others may acquire β‐structure during catabolism (metabolic processes).

Some normal proteins have properties to form amyloid fibrils. Alzheimer β‐protein and transthyretin have this capacity.

Mutation either inherited or acquired in some proteins can accelerate the path to amyloid fibril formation.

Treatment of amyloidosis may target reduction of the amount of precursor protein available for fibril formation or alteration of metabolic processes intrinsic to the generation of amyloid fibrils.
Mixed T‐ and B‐Lymphocyte Deficiency Disorders
Authors: Vihinen Mauno
Published: June 2015

Mixed immunodeficiency diseases are intrinsic defects of the immune system affecting both B and T cells and thus the adaptive immune system. Mixed or combined immune deficiencies may also be associated with or secondary to other diseases. Patients have severe symptoms and the condition can be fatal unless properly treated. Early and reliable diagnosis is in many instances crucial for the efficient treatment of these diseases as delayed diagnosis and management can cause severe and irreversible complications, even the death of the patient. Combined immunodeficiencies, which are a heterogeneous disease group, appear throughout the immune system and affect several crucial genes and proteins. The symptoms and signs vary significantly between the different forms of combined immunodeficiencies. Despite variations in single factors, both B‐ and T‐cell responses are affected in these diseases.

Key Concepts

Combined immunodeficiency affects both B and T cells.

Lymphocytes are white blood cells including B and T cells.

Haematopoietic stem cell transplantation, the intravenous infusion of autologous or allogeneic stem cells collected from bone marrow, peripheral blood or umbilical cord blood, re‐establishes haematopoietic function in patients.

V(D)J recombination is genetic recombination which randomly selects and assembles segments of genes encoding specific proteins in the immune system.
Jean‐Baptiste Lamarck
Authors: Corsi Pietro
Published: June 2015

More quoted than read, hailed as a prophet or vilified as a confused mind, Lamarck remains an enigmatic figure in the history of evolution theories. A reading of his entire corpus reveals a naturalist who considered himself as a physicist and a natural philosopher, rivalling the great materialistic synthesis of the Enlightenment. Properties of an eternal matter and eternally active physical laws could explain the indefinite cycles of the Earth as well as the working of the nervous fluids, capable of producing all our emotional and intellectual life. Even religious ideas resulted from the operations of our brain. His reference to the giraffe stretching its neck to reach leaves occurs only three times in thousands of pages. What he was really concerned with was the explanation of the taxonomic tree in terms of non‐linear modifications gradually brought forth by extremely slow changes in the geo‐climatic environment. To him, Nature was a blind, patient and constantly active set of laws deprived of all intention or goal.
Liquid Chromatography
Authors: Mansoor Mohammad Azam
Published: June 2015

Liquid chromatography, with various modes, is a technique, which deals with the separation of molecules in samples by using specific solvents or buffers. Liquid chromatography or high‐pressure liquid (HPLC) is a popular quantitative analytical technique applied in many areas of chemical, biomedical and pharmaceutical sciences. HPLC is used for separation, detection and measurement of amino acids, proteins, lipids, carbohydrates, vitamins, trace elements and ions in various types of samples. It is also used for the analysis of polymorphisms in genes coding for specific proteins or enzymes. HPLC is widely used in diagnostic and research purposes in industry, hospitals, educational and research institutions. Liquid chromatography currently accounts for about 60% of separation technology applied in life sciences worldwide. HPLC analytical methods have high assay precision, specificity and accuracy.

Key Concepts

HPLC is an important analytical technology used worldwide.

HPLC is used for the analysis of micro‐ and macromolecules in human body fluids, water and food items for research and diagnostic purposes.

HPLC is also used for the analysis of polymorphisms in genes coding for the enzymes.
Two‐Dimensional Crystallisation of Membrane Proteins and Structural Assessment
Authors: Fotiadis Dimitrios , Engel Andreas
Published: June 2015

Two‐dimensional (2D) crystallisation of membrane proteins reconstitutes them into their native environment, the lipid bilayer. Electron crystallography allows the structural analysis of these regular protein–lipid arrays up to atomic resolution. The crystal quality depends on the protein purity, its stability and on the crystallisation conditions. The basics of 2D crystallisation and different recent advances are reviewed and electron crystallography approaches summarised. Progress in 2D crystallisation, sample preparation, image detectors and automation of the data acquisition and processing pipeline makes 2D electron crystallography particularly attractive for the structural analysis of membrane proteins that are too small for single‐particle analyses and too unstable to form three‐dimensional (3D) crystals.

Key Concepts

Structural integrity and full biological activity require membrane proteins to be embedded in the bilayer. However, structural assessment at atomic resolution can be achieved only if milligram‐amounts of purified membrane protein are available. Therefore, their solubilisation by detergent cannot be avoided. The advantages of 2D crystallisation concern the reconstitution of the membrane protein in the bilayer and the possibility to study the structure of small and large membrane proteins by electron crystallography.
Laboratory of Molecular Biology (LMB)
Authors: de Chadarevian Soraya
Published: June 2015

The Medical Research Council Laboratory of Molecular Biology, founded in 1962, gathered several research groups working on the structure and function of nucleic acids and proteins under one roof. The laboratory played a key role in the formation of the new science of molecular biology. Between 1962 and 2013, LMB researchers collected 10 Nobel Prizes for research performed in the laboratory, making it one of the most successful research institutions. The laboratory attracted many young researchers from around the world who spent their formative years at the LMB before moving on to set up their own laboratories, often exporting part of the LMB research culture. The LMB pursues fundamental research, but since the 1980s, it has also played an important role in technology transfer and in the creation of biotech start‐ups in the Cambridge area.

Key Concepts

The LMB was the first institution to carry the term ‘molecular biology’ in its name. It played a key role in the formation of the new science.

For a long time in Britain, the LMB was regarded as synonymous with molecular biology.

The LMB is independent from the University of Cambridge. It is funded by the Medical Research Council.

Many of the important achievements of the LMB lay in the development of innovative approaches for molecular structure determination, including X‐ray crystallography, electron microscopy, computational methods and sequencing techniques.

The Sanger Institute in Hinxton, funded by the Wellcome Trust, started out as s a spin‐off of the LMB, dedicated to the sequencing of model organisms and the human genome.

The LMB pursues fundamental research, but since the 1980s, it has also played an important role in technology transfer and in the creation of biotech start‐ups in the Cambridge area.
Somitogenesis in Vertebrate Development
Authors: Bailey Charlotte , Dale Kim
Published: June 2015

A segmented body plan is a conserved feature of all vertebrate species and is established early in embryonic development by the formation of somites, the precursors to the skeleton, musculature and dermis. These epithelialised structures are formed with a species‐specific periodicity during the process of somitogenesis. Gathering evidence suggests that somitogenesis is regulated by a molecular oscillator mechanism that, together with a morphogenic gradient, stipulates when and where somites form. Mutations in key molecular players in this mechanism have been closely linked to developmental disorders and segmental malformations. It is therefore of great medical interest to elucidate the regulatory mechanisms which govern this key developmental process, much of which is still not yet fully understood.

Key Concepts

A segmented body plan is a conserved feature of all vertebrate species.

Somitogenesis describes the periodic formation of somites, which is the first overt sign of segmentation to appear in the embryonic vertebrate body plan.

The temporal periodicity of somitogenesis is thought to be regulated by a molecular oscillator mechanism termed the segmentation clock.

There is emerging evidence to suggest a significant degree of conservation of the regulatory mechanisms governing somitogenesis in different vertebrate species.

Some particular disease states characterised by segmentation defects have been shown to result from mutation in key Notch‐regulated components of somitogenesis.

Many of the mechanisms thought to regulate somitogenesis and somite boundary formation appear to be highly reliant on the Notch signalling pathway.

There is a large degree of crosstalk between the Notch, Wnt and FGF signalling pathways that orchestrate somitogenesis.

Future advances in our understanding of the regulatory mechanisms governing somitogenesis rely on developing mathematical models and interdisciplinary approaches to direct and cooperate with biological investigation.
HoxGenes: Embryonic Development
Authors: Montavon Thomas
Published: June 2015

Hoxgenes encode a family of transcription factors responsible for the establishment of the animal body plan. Their organisation in genomic clusters is conserved during evolution and is instrumental in defining the domain of activity of each gene in the embryo: the place and time ofHoxgene expression is dictated by the position of each gene within the cluster. A unique set ofHoxgenes is active at each axial level along the embryonic anterior to posterior axis. These diverse complements of Hox proteins determine morphological identities by controlling the transcription of specific target genes. Changes inHoxgenes number, expression and function likely participated in morphological diversification during animal evolution.

Key Concepts

Hoxgenes determine the identity of structures along the anterior–posterior embryonic axis.

Hoxgenes are widely conserved among animal species and are organised in genomic clusters.

Colinearity is the correspondence between the order ofHoxgenes within the cluster and their time and place of expression along the embryonic axis.

Loss or gain of function ofHoxgenes lead to homeosis, the morphological transformation of a body structure into another one.

Hox proteins regulate specific sets of target genes by interacting with dedicated cofactors.

Hoxgene regulation integrates multiple inputs via complex sets of local and long‐range cis‐acting regulatory elements.

Chromatin modifiers of the Polycomb and Trithorax families are critical in controlling the onset and maintenance ofHoxgene transcription.

Changes inHoxgene expression and function accompanied major morphological transitions during animal evolution.
Pathogen Resistance Signalling in Plants
Authors: Corrion Alex , Day Brad
Published: June 2015

Within natural ecosystems, most plants are resistant to most pathogens. At a fundamental level, this seemingly simply truth may hold the key to our understanding of how plants have evolved to survive under a myriad of environmental conditions and their associated stresses. Indeed, in defining how plants evolve, adapt and maintain broad spectrum resistance to most pathogens – typically referred to as non‐host resistance – we may not only reveal the mechanisms that underpin plant resistance signalling but also the precise manner in which plants regulate these processes under various environmental conditions. Herein lies the greatest challenge and unanswered question in the field of agriculture today:
How do we feed 9 billion people by the year 2050?
To address this, one of the first hurdles that must be overcome is a full understanding of the processes that regulate stress (i.e. abiotic and biotic) signalling in plants, as well as the processes that define pathogen and host specificity, including the performance of these processes under rapidly changing environmental conditions. In the case of pathogen infection, plants utilise a broad suite of innate and inducible mechanisms to resist invasion. In large part, these processes are governed by the activity of resistance (R) proteins, which are evolutionarily conserved and highly evolved proteins that function not only in pathogen recognition but also in the activation of the cellular processes necessary to defend against proliferation and the elicitation of disease. Furthermore, recent data supports the hypothesis that numerous processes, such as the balance between growth and defence, also contribute to the host resistance and pathogen virulence.

Key Concepts

Most plants are resistant to most pathogens.

Modern agriculture practices positively impact crop yield and durability. These practices can also have a negative impact on the unintended selection and enrichment of virulent pathogens.

Plants defend against pathogen invasion using a suite of highly conserved resistance (
R
) genes.

Pathogens have evolved to recognise and respond to the activity of plant R proteins through the deployment of secreted virulence factors.

Immune signalling in plants utilises various pre‐formed and inducible processes to defend against pathogen infection.

Many basic physiological processes, including response to light, temperature and water availability, are associated with, and required for, immune signalling.

The development of advanced genome sequencing technologies has increased the speed at which the development and selection of elite breeding lines are deployed into cropping systems.

Current plant breeding approaches utilise a hybrid of molecular genomics and classical breeding techniques to identify and introduce desirable traits into crops to enhance plant performance (e.g. resistance) and yield.
Retroviral Pseudotypes – From Scientific Tools to Clinical Utility
Authors: Temperton Nigel J , Wright Edward , Scott Simon D
Published: June 2015

Retroviral pseudotypes are important research and diagnostic tools for basic and clinical virology studies, facilitating the detailed investigation of individual genes, cellular receptors, antibody responses, serosurveillance and antiviral therapies. Importantly, pseudotypes enable the study of highly pathogenic viruses, without the need for high containment. Their use as gene therapy vectors is widely documented, but other uses, once less well known, are becoming more prominent. The substitution of envelope proteins expressed on the virion surface enables pseudotypes to be employed as surrogates for wildtype viruses in antibody neutralisation or antiviral screening assays and for the study of cell–virus receptor interactions. In addition, they are increasingly being utilised as vaccine immunogens, expressing the antigen either on the particle surface or as a transfer gene for cellular expression. These studies demonstrate the potential for using pseudotypes for both scientific and clinical applications.

Key Concepts

Students will learn:

What are retroviral pseudotypes.

How they are constructed and titrated.

The common elements that comprise a retroviral pseudotype.

How retroviral pseudotypes can be used to deliver genes.

How they can be used as tools for the study of viral attachment, entry and receptor identification.

About using pseudotypes as surrogate viruses in antibody neutralisation assays.

The use of pseudotypes to measure vaccine immunogenicity and screen for antiviral activity and resistance.

How pseudotypes can be used as experimental vaccines.
Coltiviruses and Seadornaviruses
Authors: Mohd Jaafar Fauziah , Attoui Houssam
Published: June 2015

Coltiviruses and seadornaviruses are members of the family
Reoviridae
, which encompasses alongside the genera
Coltivirus
and
Seadornavirus
, 13 other genera of viruses that can infect mammals, birds, aquatic animals, reptiles, insects, plants, fungi and protists. Coltiviruses are transmitted by hard ticks of the family
Ixodidae
, whereas seadornaviruses are mosquito‐borne. These viruses can infect humans, following the bite of adult infected female ticks or mosquitoes, causing febrile illnesses and are occasionally responsible for encephalitis. Coltiviruses are principally endemic in the north‐western parts of the United States and Canada and were also reported in European countries, including France and Germany. Antibodies to coltiviruses have also been identified from patients in the former Czechoslovakia and South Korea. Seadornaviruses are principally endemic in the south‐east Asia, although recent data showed that there has been an expansion of their distribution northwards, reaching the north‐western Chinese borders. Banna virus (
Seadornavirus
) has been isolated from human encephalitis cases.

Key Concepts

Coltiviruses are transmitted by adult female tick (family
Ixodidae
) bite and have animal reservoirs.

Coltiviruses can infect humans causing febrile illnesses and can cause encephalitis in rare cases.

Seadornaviruses are transmitted by mosquitoes and no animal reservoir is known to date.

Seadornaviruses can infect animals and humans causing febrile illnesses and were reported to be responsible for cases of encephalitis.

Coltiviruses show an evolutionary relationship to the turreted mycoreoviruses, aquareoviruses and orthoreoviruses.

Seadornaviruses show an evolutionary relationship to the nonturreted rotaviruses.

Coltiviruses seem to represent a missing link between turreted and nonturreted members of the family
Reoviridae
.

Differential diagnostic serological and molecular assays for coltiviruses and seadornaviruses are available.

Structure of the viral particles of Banna virus shows striking similarities to that of the rotaviruses.
Virus‐Induced Human Oncogenesis
Authors: Bedi Manmeet S , Ploubidou Aspasia
Published: June 2015

Infectious agents are estimated to contribute to oncogenesis in
c
. 25% of human cancers worldwide. Approximately half of them are attributed to infection by oncogenic viruses. Viruses are obligatory intracellular pathogens, which disrupt host cell homeostasis during their life cycle. The induction of malignancy is not part of their life cycle, but rather a multistep outcome, that may occur several years after the infection. Oncogenesis is initiated by the disruption of cellular mechanisms (detecting and repairing DNA damage, activating checkpoints and inducing apoptosis or survival) through the activity of viral proteins. Host and environmental factors further contribute to the multistep aetiology of cancer development and progression. This article describes the common molecular mechanisms by which human oncogenic viruses disrupt cell homeostasis and the prophylactic and therapeutic treatment options for virus‐induced malignancies and discusses the identification of emerging oncogenic infectious agents.

Key Concepts

Oncogenic viruses are estimated to contribute to approximately 15% of all human malignancies.

Human oncogenic viruses include both DNA viruses (EBV, HPV, MCV, HBV and KSHV) and RNA viruses (HCV and HTLV‐1).

Induction of malignancy is not part of the viral life cycle and confers no benefit to the virus per se.

Oncogenic viruses disrupt host cellular pathways (DNA repair mechanisms, cellular checkpoints and apoptosis) for efficient viral replication, consequently initiating cancer development.

Viral oncogenesis is a multi‐step process, initiated by the action of viral proteins but requiring additional factors for disease development and progression.

Transmission of oncogenic viruses takes place mainly via human contact including, but not limited to, sexual transmission.

Prophylactic (vaccine) treatment options are limited. Therapeutic treatments include anti‐virals in combination with chemotherapy and surgical removal of the tumours.

Emerging oncogenic viruses comprise a growing group of newly identified viruses with putative oncogenic potential, which have been detected in association with human cancers.
Togaviruses
Authors: Powers Ann M
Published: June 2015

The viruses of the familyTogaviridaeare an extremely diverse group. There are two genera in the family:AlphavirusandRubivirus.Rubiviruscontains a single member (rubella virus) while there are 31 distinct members in the genusAlphavirus. The alphaviruses are typically transmitted by arthropods, primarily mosquitoes, whereas rubella virus is transmitted via respiratory secretions. The togaviruses have a nearly global distribution, cause a wide range of illness in humans and other animals, and have multiple mechanisms of pathogenesis. Interestingly, while the viruses are genetically extremely simple, the disease they cause ranges from mild or asymptomatic illness to severe polyarthralgia to encephalitis. This work summarises the current understanding of togavirus epidemiology, transmission and pathogenesis and describes current and future options for control of these pathogens.

Key Concepts

Togaviruses are an exceptionally diverse group of viruses with global distribution, a wide array of clinical disease, and distinct modes of transmission.

While sharing genome functional elements and general virion structure, viruses of the generaRubivirusandAlphavirushave few other common features.

Alphaviruses are continuing to emerge in new ecological and epidemiological patterns.

Despite a widely available and efficacious vaccine, rubella virus persists as a global health concern.

More investigations are required to understand the pathogenesis of the vast range of alphaviruses.
Bayh‐Dole
Authors: Winickoff David E , Valdivia Walter D
Published: June 2015

Bayh‐Dole is shorthand for the public policy in the United States that allows universities to take title to patents on discoveries made from state‐funded research. The Bayh‐Dole Act, enacted by the US Congress in 1980, has been emulated in many countries around the world for its putative benefits on national rates of innovation and has exerted a profound influence on university patenting practices in the United States and abroad. Bayh‐Dole has contributed to the sharp increase in university patenting activity. Its impact on the innovation system as a whole is harder to measure and has been the subject of scholarly and political controversy. While proponents of this policy argue that it has injected American innovation with new dynamism, other analysts have cast doubt on the economic benefits of Bayh‐Dole. Furthermore, there are concerns that the Act negatively effects academic cooperation and runs against the public mission of universities.

Key Concepts

Technology transfer is the dynamic exchange of knowledge among universities, industry and governmental agencies.

Bayh‐Dole regulates intellectual property aspects of university technology transfer.

The Bayh‐Dole policy of facilitating university ownership of state‐funded discoveries has been emulated in many countries, which has helped increase the rates of university patenting in the United States and abroad.

Increased rates of patenting per se are not indicators of increased rates of new product development and new economic activity.

The actual effects of Bayh‐Dole on the innovation system are hard to measure and the subject of scholarly and political controversy within the United States and elsewhere.

Patenting and licensing constitute just one of many modes of university technology transfer, which also occurs
inter alia
through student training, collaborative research agreements, dissemination of new knowledge through publication and public talks.

Bayh‐Dole has become a lightning rod for debates about the commercialisation of research and higher education reform.