bluuebunny/crossref_metadata_2025 huggingface dataset:
Serializing the Past in and out of the Leisure Hour: Historical Culture and the Negotiation of Media Boundaries1
Authors: Lechner Doris
Published: September 2013

This article explores the media transfer between books and periodicals by example of historical narratives serialized within the Religious Tract Society’s family magazineLeisure Hour(1852-1905). A look at the travelling of texts and ideas between these two media shows that the RTS not only negotiated media boundaries but operated at the intersection of other categories, such as class and gender, linked to the reputation of the different media as well as modes of representation and approaches to history. In a combination of book history and periodical studies under a historical culture perspective, the article focuses on three case studies: (1) the transition from book into periodical serial and the (re)appropriation of history for a working-class audience; (2) the collection of a periodical series into book form and the author’s boundary-work under the regulation of the RTS; (3) the transfer of material features in the creation of monthly parts and shift in historical genre.
Travelling in New Formes: Reissued and Reprinted Travel Literature in the Long Eighteenth Century
Authors: Day Matthew
Published: September 2013

Despite increased recognition of the importance of the material nature of the book to our understanding of the creation of meanings, there has been relatively little focus on the travel literature of the eighteenth century. The market was enormous and a significant part of it comprised reissued and reprinted works. This article looks at the way books that returned to the market were given new contexts and created new meanings without changing the language of the main body of the text. By careful consideration of paratextual features such as title-pages, dedicatory epistles, marginalia and running titles and by considering such issues as the gathering of texts into collections, this article demonstrates the financial, political and ideological motives behind the reissue and reprinting of books. It shows how, through them, texts were 'reformed' in many different ways and suggests that reissues and reprints created, in effect, new books.
Textual Dissidence: The Occasions of Wilde’s ‘The Soul of Man under Socialism’
Authors: Mackie Gregory
Published: September 2013

“The Soul of Man under Socialism” is unique among Oscar Wilde’s essays because it was published as a book during his lifetime. As The Soul of Man, it appeared five days after his sentencing to two years’ imprisonment. Issued by family friend Arthur Humphreys, The Soul of Man was published in a modest, privately printed edition limited to fifty copies. Wilde’s essay provided Humphreys with an opportunity to combat injustice with idealism. Humphreys’ edition went further, intensifying Wilde’s denunciation of a punitive society by emending the essay’s text, specifically by deleting the word “occasional” from Wilde’s critique of crime and punishment. Indeed, the essay’s strident indignation derives from a sense of solidarity with identities considered deviant by public opinion, which, I argue, was precisely Humphreys’ purpose when he pointedly published The Soul of Man in 1895.
Processus de médiation littéraire : les enjeux éditoriaux. Tractations et concurrences éditoriales autour de Francis Ponge
Authors: Doga Marie
Published: September 2013

Cet article, tiré d’un travail de thèse, se propose d’analyser l’histoire des collaborations de Francis Ponge avec Philippe Sollers à partir des contextes de l’édition d’une monographie consacrée au poète, dans la collection « Poètes d’Aujourd’hui » aux Éditions Seghers en 1963, et desEntretiens de Francis Ponge avec Philippe Sollersparus chez Gallimard/Seuil en 1970. L’étude soulève ainsi les enjeux de collaboration entre écrivains, entre générations d’écrivains et entre éditeurs. Elle définit le réseau complexe de relations qui façonne durablement la médiation littéraire de l’oeuvre, notamment l’influence incontestable des rapports concurrentiels entre maisons d’édition sur les conditions de la production et de la médiation littéraires elles-mêmes. Plus largement, ce travail permet d’éclairer l’histoire du livre et du milieu de l’édition littéraire dans le contexte d’effervescence des sciences humaines et sociales des années 60. Cette contribution s’appuie sur une recherche archivistique minutieuse de données publiques et privées familiales (correspondances, corpus d’articles critiques et d’interviews).
Le territoire de l’histoire : une étude de cas dans le Bas-Saint-Laurent
Authors: Flamand-Hubert Maude
Published: September 2013

Dans cet article, nous nous intéresserons à la question des régions québécoises périphériques à partir de l’étude du cas de Louis Bertrand, un notable qui a marqué le développement de L’Isle-Verte au XIXe siècle. Dans le cadre de cette recherche, nous nous sommes arrêtés aux différentes dimensions du contexte territorial dans lequel se sont déroulés les événements. Trois questions se sont posées quant à la définition du territoire : la question de la périphérie, la question historiographique de la seigneurie et celle de la région au Bas-Canada. Ce type de recherche soulève les difficultés que représentent l’utilisation de notions contemporaines et leur articulation avec des phénomènes territoriaux appartenant au passé. Cette réflexion offre la possibilité d’enrichir et de repenser les études en histoire régionale. De nouvelles méthodes doivent être proposées et mises à l’essai pour que nous puissions saisir les tensions et la complexité qui participent à la construction historique des territorialités.
Un Plan Nord comme outil géopolitique en RDP lao : le cas du développement des terres et des ressources naturelles de Luang Namtha
Authors: Mottet Éric
Published: September 2013

Dans un contexte d’ouverture et d’intégration régionale, la province de Luang Namtha cristallise l’ensemble des défis auxquels le Laos doit faire face aujourd’hui. En effet, cette région connaît depuis une dizaine d’années des changements importants liés à la construction du corridor nord-sud reliant la Chine à la Thaïlande. Ce Plan Nord, piloté par la Banque asiatique de développement et la Chine, constitue la colonne vertébrale du quadrangle économique, espace transfrontalier de croissance. Pour le gouvernement lao, l’objectif est, d’une part, de transformer ces marges montagneuses en vaste espace de libre-échange et, d’autre part, de consolider l’existence de l’État-nation moderne, à travers le transfert des populations montagnardes vers les plaines afin de mieux contrôler le territoire et ses ressources. En réalité, ce corridor économique constitue un nouvel axe de pénétration pour les investissements laotiens et étrangers privilégiant la mise en exploitation des terres, l’extraction des ressources minières et la production d’hydroélectricité. Le territoire de la province de Luang Namtha et les populations qui y vivent, contraintes de s’adapter aux changements radicaux provoqués par la nouvelle stratégie du pouvoir central, subissent des transformations en profondeur mettant en relief des conflits autour d’enjeux sociaux et environnementaux.
Characterization of Discounting Words as Powerful Factors in Determining the Quality of Cooperation Within a Working Team
Authors: Andonovic Beti , Petkovski Stanislav
Published: September 2013

Abstract: Optimal team communication and long-term cooperation depend on several various categories of factors. One of the factors that may point to efficiency decline within the cooperation is the presence of abusive words (labelling) which are named as discounting words by authors. They represent verbal aggression and are type of condensed metaphors that reflect people’s view of the world around them. Since any communication units that disrupt the good teamwork are of a high interest to any quality manager, there is characterization of the discounting words given. There is a certain correlation between the one who gives the discounting words and the one who receives them. There is also a chart of some of the discounting words given and conclusions included.
Optimization of the Process of Production of Ceramics From Waste Coal Ash Case Study: The Influence of the Mechanical Activation
Authors: Angjusheva Biljana , Jovanov Vojo , Lisichkov Kiril , Fidanchevska Emilija
Published: September 2013

Abstract: Fly ash, a waste by-product obtained in a thermal power plant has been a generated problem of the disposal all over the world. Morphological characteristics, physicochemical properties and pozzolanic activity make this waste potential material for production of ceramics. In this study high density ceramics compacts were produced by using fly ash from the power plant REK Bitola, Republic of Macedonia. In order to increase geometrical factor of activity, the mechanical activation of the fly ash was applied. The process of optimization of the main process parameters is conducted, such as time of mechanical activation, sintering temperature and heating rate and their interactions on the properties of obtained dense ceramic porosity and bending strength as a response function. The optimization was performed through application of 3D surface method and the obtained results are presented in the graphical and analytical form using “Statgraphics Centurion” software package.
Process of Cooperation - The European Union and Western Balkans
Authors: Djuric Manja
Published: September 2013

Abstract: The most important achievement of cooperation between the European Union and the countries of the Western Balkans is a viable and sustained political dialogue. The institutionalization of the dialogue with the European Union called for better communication between the countries in the region, candidate and potential candidate countries for membership of the disadvantaged in the process of integration. The processes of cooperation facilitated the development of the region through enhanced cross-border regional cooperation and contributed greatly to attracting international support by mediating between those who need help and those who are willing to provide help. Regional initiatives are addition to the European integration process and not a substitute for the inclusion of the Western Balkans into the European Union.
The WHISK (Women's Health: Increasing the Awareness of Science and Knowledge) Pilot Project: Recognizing Sex and Gender Differences in Women's Health and Wellness
Authors: Edwards Lorece V. , Dennis Sabriya , Weaks Francesca
Published: September 2013

Women's health encompasses a continuum of biological, psychological, and social challenges that differ considerably from those of men. Despite the remarkable advances in science, women's health and sex differences research is slowly gaining recognition and acceptance. It is important that women's health gain attention as women are usually the gatekeepers of care for the family. Women's health and health outcomes are strongly influenced by sex and gender differences as well as geography. Around the world, the interplay of biology and culture brings about differences in men's and women's health, which have been largely overlooked. The Women's Health: Increasing the Awareness of Science and Knowledge (WHISK) Pilot Project was a multidisciplinary project aimed to increase the awareness of sex and gender differences in women's health and research among healthcare professionals. Theater expression and creative art were used to translate knowledge, enhance understanding, and increase the awareness of sex differences. Findings from this project clearly showed an apparent increase in knowledge and cultivation of new insights.
We Can Do Better than Last Place: Improving the Health of US Women
Authors: Perkins Rebecca B. , Sherman Bonnie J. , Silliman Rebecca A. , Battaglia Tracy A.
Published: September 2013

Life expectancy for US women lags behind that for women in other countries. Factors contributing to inequitable health for women are complex and include policy, community, healthcare access, and the interaction between the patient and her healthcare provider working within the healthcare system. We propose a societal pyramid of health accounting for the effects of these different factors and their impact on prevention, screening, diagnosis, and management of disease using the examples of smoking and obesity, two of the most important yet modifiable risk factors for chronic disease and death among US women.
Reproductive Health Disparities: A Focus on Family Planning and Prevention among Minority Women and Adolescents
Authors: Haider Sadia , Stoffel Cynthia , Donenberg Geri , Geller Stacie
Published: September 2013

Minority women and adolescent females of all races and ethnicities are disproportionately affected by unintended pregnancy in the United States. Adolescents also experience an additional proportion of the burden compared to other age groups, as 82% of pregnancies among women 19 years old and younger are unintended. Moreover, minority and adolescent mothers are at increased risk for having preterm deliveries, low birth weight infants, and other complications. Unintended pregnancy continues to be an important public health problem in the United States, and prevention through family planning is urgently needed. This review presents an overview of the US demographics for unintended pregnancy among both minority and adolescent women and identifies current and past efforts to reduce unintended pregnancy, specifically among minority and adolescent females, through contraception and family-planning programs.
Modeling and Characterization of On‐Chip Interconnects
Authors: Yin Wen‐Yan , Zhao Wen‐Sheng
Published: September 2013

In this article, one distributed circuit model for the on‐chip single interconnect will be introduced at first, where all the lumped elements are frequency independent and can be directly obtained from its geometrical and physical parameters. This ensures proper scalability of the model parameters because no optimization tuning or fitting for them is involved. Some popular and low‐cost techniques, such as patterned ground shield (PGS) structures for suppressing the substrate loss of silicon substrate at high frequencies and differential signal transmission, are also addressed here. Then, electromagnetic modeling of on‐chip coupled (a)symmetrical interconnects will be performed, including all distributed parameters. The average power handling capability (APHC) of on‐chip interconnects and even thin‐film microstrip lines (TFML) are also addressed here. Finally, the electrothermal analysis of multilevel interconnects under electrostatic discharge (ESD) stress will be reported using the time‐domain finite‐element method (FEM).
Defected Microstrip Structure
Authors: Xiao Jian‐Kang
Published: September 2013

Defected microstrip structure (DMS) is made by etching certain slot patterns in the microstrip line, and it exhibits the properties of slow‐wave, rejecting microwaves in certain frequencies that are similar to the defected ground structure (DGS) but without any manipulation of the ground plane. DMS is more easily integrated with other microwave circuits, and it has an effectively reduced circuit size compared with DGS. DMS increases the electric length of the microstrip line and makes the effective capacitance and inductance increase. The defection in the microstrip line creates resonances, and many novel, compact microwave components and antennas can be realized by using the advantages and characteristics of DMS.
Flip‐Chip Underfills
Authors: Lu Daniel , Sun Yangyang , Wong C. P.
Published: September 2013

Electronic materials play an important role in advancing the semiconductor and microelectronic packaging technologies. This chapter will give an overview of major electronic packaging materials–flip‐chip underfills. Fundamental knowledge about underfill, including history, process, types, compositions, and properties, was described. Underfill filler technology for fine pitch application was explained in terms of surface treatment mechanisms and underfill material properties. Advanced underfill technologies for mobile device application, wafer‐level application, and through silicon via (TSV) three‐dimensional (3D)‐IC were also introduced.
Archaeal Cells
Authors: Klingl Andreas , Flechsler Jennifer , Heimerl Thomas , Rachel Reinhard
Published: September 2013

At a first glance, Archaea are structurally seen quite similar to Bacteria, and for a long time they were named ‘Archaebacteria’. They can form cocci, rods, spirals or irregular shaped cells and are equally sized as Bacteria. Together they are referred to as ‘Prokaryotes’ because neither Archaea nor Bacteria have a nucleus. Although this term indeed might be helpful in habitual language use, it does not refer to a phylogenetic group. In fact, transcription and translation machineries of Archaea have much more in common with eukaryotic cells than with Bacteria. In addition, there are many features that remain characteristic for Archaea, given by the fact that many representatives live and thrive under extreme environmental conditions. In the review, the authors give a comprehensive overview about the stunning diversity of structural features in archaeal cell envelopes, membranes and cell appendages.

Key Concepts:

By application of recently developed PCR techniques, Archaea can be found in almost every habitat and sometimes are even more abundant than bacteria.

Archaea show special adaptations to their sometimes extreme environments, like caldarchaeols, which are more stable at high temperatures.

Like Bacteria, Archaea are also surrounded by a lipid bilayer, but in the latter case the lipid moiety consists of C5‐isoprenoid units that are coupled to glycerol via ether bonds at (sn)‐2,3 positions of the glycerol.

Cell walls can be as simple as a proteinaceous surface layer or as complicated as in some methanogens with multiple layers, additional sheats enclosing several cells and even more complex cell wall compounds.

Archaea exhibit a broad variety in cell appendages that are different to bacterial ones in fine structure, composition, biosynthesis and anchorage in the cell.
Visual System Development in Vertebrates
Authors: Herrera Eloisa , Erskine Lynda
Published: September 2013

The development of a functional visual system involves a complex series of inductive and signalling interactions essential for the formation of the eye and its central connections with the brain. Outpouchings from the forebrain, together with the overlying surface ectoderm and neural crest cells give rise to the major structures of the eye (neural retina, pigmented epithelium, lens and cornea). Central connections between the eye and brain regions that receive direct connections from the eye (visual targets) are formed by the axons of retinal ganglion cells. Attractive and repulsive cues in the extracellular environment guide the retinal axon along specific pathways in the brain. Gradients of signalling molecules, together with spontaneous neural activity, drive a point‐to‐point mapping of retinal axons in visual targets, ensuring accurate reconstruction of the visual image. The cellular, molecular and inductive mechanisms that sculpt each of these key developmental processes essential for normal visual system development are beginning to be understood.

Key Concepts:

The eye primordia (optic cups) develop as outgrowths from the forebrain.

Contact of the optic cup with the overlying surface ectoderm induces formation of the lens.

Signals from the lens induce the formation of the cornea.

Retinal cells differentiate into overlapping central–peripheral waves to form three layers of cell bodies separated by two plexiform (synaptic) layers.

Inhibitory signalling and local adhesive interactions control synaptic specificity in the retina.

Attractive and repulsive signals in the extracellular environment direct growth of retinal axons to target regions in the brain.

Retinal axons map topographically in target regions of the brain.

Map formation is controlled through the graded action of repulsive signalling molecules and spontaneous retinal activity.

Activity‐dependent mechanisms drive the formation of eye‐specific layering of synaptic inputs in visual targets.
Interleukins
Authors: Meager Anthony , Wadhwa Meenu
Published: September 2013

The interleukins are a major class of biologically active protein mediators, known as cytokines, that following release from activated cells bind to specific cell surface receptors to induce growth and differentiating functions in target cells. Extensive studies into their genes, structures, receptors, signal transduction pathways and activities in experimental cell cultures have provided considerable knowledge leading to their molecular and biological characterisation. Fundamental findings are that they are mostly pleiotropic mediators, that is, act on more than one cell type or at different stages of cellular development, and stimulate multiple activities, especially where acting in combinations of two or more interleukins. Their production as essentially pure recombinant proteins has enabled studies in experimental model systems to determine whether their activities could be of clinical benefit, or harmful. Subsequently, several interleukins and their antagonists have been evaluated for clinical efficacy and safety in clinical studies, and have yielded promising, though not fully effective, therapeutic treatments for patients with cancer and autoinflammatory diseases. In this article, the molecular characteristics of interleukins, their cognate receptors and intracellular signalling pathways, their biological activities and their potential clinical uses are briefly described.

Key Concepts:

Interleukins are a broad class of biologically active proteins with hormone‐like actions that regulate the development, differentiation and functions of cells of the immune and haematopoietic systems.

The activities of interleukins are mediated via cell surface receptors.

Binding of interleukins to receptors triggers gene induction via the activation of intracellular signal transduction pathways.

Interleukins exhibit complex biological interactions, both among themselves and with other molecular mediators,in vivo.

The proinflammatory and immune‐stimulatory activities of interleukins are essential for host defence against pathogens.

Interleukins can be ‘two‐edged swords’, being largely beneficial to the host at low concentrations but deleterious and toxic at high concentrations.

The biological properties of interleukins have suggested their potential for development as therapeutic drugs (biopharmaceuticals) against infections and chronic diseases, such as cancer, but so far only a few have proved clinically useful.

Antibody and receptor antagonists of interleukins are showing promise for the treatment of autoinflammatory and autoimmune diseases, such as irritable bowel disorders and RA.
Kidney Development
Authors: Davies Jamie
Published: September 2013

Mammals produce three pairs of kidneys: the pronephros and mesonephros are discarded during fetal life whereas the metanephros remains as the permanent excretory organ. It forms when two progenitor tissues – ureteric bud and metanephrogenic mesenchyme – meet and exchange signals. These signals cause the bud to branch repeatedly to form the urinary collecting duct system and cause the mesenchyme to create a stem cell population, and elements of that population to differentiate into excretory nephrons and supporting cells. Further exchanges of signals control endothelial invasion to make the blood system, and the process of innervation. They act by linking to cellular morphogenetic effectors. Many important questions about renal development remain unanswered; some are listed in this article.

Key Concepts:

Development of the permanent mammalian kidney (metanephros) occurs almost autonomously, so that even a kidney rudiment in culture, isolated from the rest of the embryo, will develop most of the anatomical features of a normal fetal kidney (but not vascularisation or innervation). The ability to build a kidney is therefore largely a property of the 2–3 cell types present in the rudiment.

The precise anatomy of the kidney, like many other organs, is flexible and responsive to environmental influences (mechanical, chemical and hormonal): its general layout may be specified genetically but its microarchitecture is not.

Elements of the kidney develop in a specific order: in any given part of the kidney, the collecting duct system, which defines the renal architecture, begins to develop first. Nephrons develop next, with the blood and nervous systems following so that they connect to the nephrons already present. Development continues centrifugally, so that the outer part of the kidney is (until development ceases near birth) still undergoing ‘early’ events, for example, nephron induction, while the central core is much more mature.

Kidney development depends on, and is coordinated by, the exchange of signals between cells that regulate motility, proliferation, survival and differentiation.

Genetic defects in signalling pathways or in the effector systems that they should trigger result in a significant fraction of common human congenital abnormalities. Mechanical defects in the rest of the embryo can also cause congenital renal defects.

The kidney does contain stem cells even after the development has completed, but its capacity for regeneration is limited.

There is a major, freely accessible database for urogenital development –http://www.gudmap.org
T
Lymphocytes: Helpers
Authors: Kawachi Izumi , Kondo Takayuki
Published: September 2013

Helper T lymphocytes (T
H
) are major histocompatibility complex (MHC) class II restricted CD4
+
T cells that can be divided into several subsets depending on their cytokine releasing patterns: T‐helper 1 (T
H
1), T
H
2, T
H
17, T‐follicular helper (T
FH
), forkhead box P3
+
regulatory T (Treg) cells and the recently described T
H
9 and T
H
22 cells and others. T
H
1 cells activate infected macrophages for the destruction of intracellular pathogens. T
H
2 and T
FH
cells provide help to B cells for antibody production. T
H
17 cells enhance neutrophil response for extracellular pathogens. Treg cells actively suppress immune reactions and help prevent the development of autoimmunity during immune response. It was initially thought that each T
H
subset retained a stable phenotype with a distinct lineage and played a distinct role in host defense and autoimmunity. Considerable overlap and flexibility of cytokine production by CD4
+
T cells is challenging earlier concepts.

Key Concepts:

Helper T lymphocytes (T
H
) are MHC class II restricted CD4
+
T cells that can be divided into several subsets of cytokine releasing patterns: T‐helper 1 (T
H
1), T‐helper 2 (T
H
2), T‐helper 17 (T
H
17), regulatory T (Treg), T‐follicular helper (T
FH
) and others.

T
H
cell subsets express a distinct set of genes that encode hallmark cytokines and unique transcription factors.

IFN‐γ, IL‐4, IL‐17, IL‐10/TGF‐β and IL‐21 are the representative cytokines of T
H
1, T
H
2, T
H
17, Treg and T
FH
cells, respectively, and are often used as subtype markers.

T
H
1 cells play an important role in cellular immune functions such as delayed‐type hypersensitivity or defense against intracellular organisms.

T
H
2 cells enhance antibody production by B cells.

T
H
17 cells are potent inducers of tissue inflammation in autoimmune diseases and confer protection against extracellular bacterial and fungal pathogens.

Treg cells consist of a heterogeneous class of cells that suppress T‐cell activity and help prevent the development of autoimmunity during immune response.

T
FH
cells regulate the step‐wise development of antigen‐specific B cell immunity in B cell follicles of lymphoid tissues.
Molecular Evolution: Patterns and Rates
Authors: Bromham Lindell
Published: September 2013

The rates and patterns of evolution of
deoxyribonucleic acid (DNA)
sequences vary among species, across the genome and between sites in a gene. These patterns can be considered in the light of the rate and type of mutations, and the forces that determine which of these mutations become substituted in the population. Mutations can rise in frequency if the individuals carrying those mutations leave proportionally more offspring. If a mutation increases in frequency until it replaces all other alternatives in the population, it becomes a substitution, carried by all members of that population. Substitution is driven by selection and chance, and the relative power of each of these processes is affected by population dynamics. The complexity of patterns and rates of DNA sequence evolution create a rich record in the genome of evolutionary mechanisms and history.

Key Concepts:

Mutations are heritable changes to the DNA sequence, created by damage to DNA or by errors made when DNA is copied.

Mutations occur in individual genomes, and are inherited in copies made from those genomes.

A beneficial mutation that increases the chances of its carrier successfully reproducing will tend to increase in frequency over generations (positive selection).

A deleterious mutation that decreases the chances of its carrier successfully reproducing will tend to decrease in frequency over generations (negative selection).

A neutral mutation that has no effect on fitness can increase in frequency through random sampling, and may become fixed in the population by chance (drift).

In small populations, drift can overwhelm selection for mutations with a small impact on fitness, so the rate of fixation of slightly deleterious mutations should be greatest in small populations.

The interaction between selection and drift creates complex patterns of molecular evolution across the genome, over time and between species.
Macrophage Function Disorders
Authors: Lee Keith M , Yin Charles , Verschoor Chris P , Bowdish Dawn ME
Published: September 2013

Macrophages are sentinel cells of the innate immune response. Macrophages recognise pathogen‐associated molecular patterns (e.g. microbial products) and endogenous ligands (e.g. apoptotic cells) through a broad and adaptable range of pattern‐recognition receptors. The consequence of this recognition is generally effective clearance via phagocytosis; however, when this is not effective, macrophages may become inappropriately activated and initiate an inappropriate inflammatory response. Because macrophages are extremely variable in phenotype and function and share a common ancestry with monocytes and dendritic cells, there are very few genes that are expressed exclusively in macrophages. Consequently, macrophage‐specific immunodeficiencies are rare. There are, however, a number of genetic immunodeficiencies that affect macrophage function. In addition, as macrophages are exquisitely attuned to their microenvironment, their function appears to be adversely affected by and contributes to chronic inflammatory conditions such as cancer, atherosclerosis and obesity. Thus, genetic deficiencies, in addition to microenvironmental dysregulation, can contribute to macrophage function disorders.

Key Concepts:

Macrophages functions include sensing of modified host proteins, microbes and microbial components. Macrophages respond to these ligands primarily through phagocytic and inflammatory receptors.

Macrophage function is exquisitely attuned to the microenvironment and when chronic inflammatory conditions alter the microenvironment, macrophage function can become impaired.

Primary immunodeficiencies have been identified that impair macrophage phagocytosis and inflammatory responses and leave the patient susceptible to infectious disease and other chronic conditions.

Macrophages are able to sense a wide and diverse variety of endogenous and exogenous ligands, including modified host proteins, microbes, and microbial components.

Chronic inflammatory conditions such as cancer and atherosclerosis alter the microenvironment, which can impair the ability of macrophages to maintain homeostasis.
Protein Denaturation and the Denatured State
Authors: Hammarström Per , Jonsson Bengt‐Harald
Published: September 2013

Protein denaturation experiments are routinely used to determine protein stability and to elucidate structural and dynamic effects of mutations, cofactors and ligands. Denatured states of proteins have gained wide interest in recent years owing to their fundamental importance in a wide variety of phenomena such as deciphering the protein folding problem and the molecular understanding of many diseases. Because the integrity of the folded protein structure is strongly affected by environmental factors denaturation is often studied by monitoring the effects of increasing temperature, changing pH or addition of chaotropic agents such as urea and guanidinium chloride. The structural and dynamical effects of denaturation are most efficiently characterised by using a combination of spectroscopic methods most notably circular dichroism, fluorescence and nuclear magnetic resonance. Amide hydrogen–deuterium exchange experiments can efficiently characterise partly unfolded protein structures.

Key Concepts:

There are many spectroscopic methods to study protein denaturation and denatured states.

Transitions between folded and denatured conformations of proteins are often highly cooperative.

Denatured states of proteins are ensembles of rapidly converting conformations on the nanosecond timescale.

Denatured states of proteins possess residual structures which often reside within hydrophobic cores.

Denatured states of proteins can be informative of the protein folding pathway.
Architecture of Membrane Proteins
Authors: Shlykov Maksim A , Yee Daniel C , Saier Milton H
Published: September 2013

Biological membranes are exquisite multifunctional structures that border all living cells and intracellular organelles in virtually all types of organisms from bacteria to man. In addition to the fundamental phospholipid unit, present in most bacteria and eukaryotes, and the dominant ether lipids present in many archaea, other lipids, proteins, carbohydrates and sterols contribute to the lipid bilayer. Most important, from a functional perspective, are the specialised membrane proteins of diverse functions that are embedded in or associated with membranes. Membrane architectural features and the methods used to gain relevant information are presented. Integral, peripheral and lipid‐anchored membrane proteins as well as the inhomogeneity of membranes are considered from structural, functional and evolutionary standpoints. Transport proteins that provide avenues of communication and material exchange, and toxins that target membranes and kill cells by creating transmembrane pores, are discussed in some detail, especially from mechanistic points of view.

Key Concepts:

Architecture of membranes and membrane proteins.

Functions of transmembrane proteins.

Membrane microcompartmentalisation.

Protein pore‐forming toxins.

Lipid rafts and caveolae.
Phylogenetic Likelihood
Authors: de Oliveira Martins Leonardo , Mallo Diego , Posada David
Published: September 2013

The input data for any phylogenetic analysis is a set of characters belonging to different individuals or loci, and assumed to have a common ancestor. Given a set of aligned
deoxyribonucleic acid (DNA)
or protein sequences, the likelihood of a phylogenetic tree depicting their ancestry relationships will be proportional to the probability of the alignment having been generated along this tree. The likelihood can be used not only as an objective criterion to find the optimal phylogenetic tree, but also to compare trees and evolutionary models, always in a probabilistic framework. The likelihood is the central ingredient of any statistical phylogenetic analysis, as it makes the connection between the data (the alignment) and the model, including the tree, branch lengths and other evolutionary assumptions.

Key Concepts:

The phylogenetic likelihood is the probability of the DNA sequence alignment X given a model of nucleotide substitution with parameters θ and phylogenetic tree τ (topology plus branch lengths).

The phylogenetic likelihood can be similarly calculated for amino acid or coding sequences, and they are all based on the instantaneous probability of a change of state.

The phylogenetic likelihood is the basis for any probabilistic phylogenetic inference, for both classical and Bayesian analyses.

There are many substitution models available, and the likelihood allows us to compare them and to find the best model, as well as the best phylogenetic tree.

In maximum likelihood phylogenetic estimation, the objective is to find the set of parameter values, particularly tree topology and branch lengths, that maximize the likelihood function.

In a Bayesian setting, the posterior probability of a particular set of phylogenetic parameter values (e.g. topology and branch lengths) is proportional to their likelihood multiplied by the prior probability of these values. The objective is then to describe these values with their associated posterior probabilities.
Genomic
DNA
: Purification
Authors: Tümmler Burkhard , Stanke Frauke
Published: September 2013

Genomic
deoxyribonucleic acid (DNA)
can be prepared from any source by three steps: cell lysis, deproteinisation, and recovery of DNA. The basic protocol needs to be adapted to the demands of the application, the number of samples to be processed, the requested yield, purity and molecular weight of the DNA, and the amount and history of the source. Traditional protocols based on the lysis with sodium dodecyl sulfate/proteinase K, extraction with phenol/chloroform/isoamyl alcohol, purification with ethanol and storage in Tris/ethylenediamine tetraacetic acid buffer are recommended for the purification of long‐term stable high‐molecular weight genomic DNA from freshly obtained specimens. Intact chromosomal DNA is recovered from agarose‐embedded cells. Automated extraction methods are preferred for forensic applications and high‐throughput processing for biobanking. The technically challenging recovery of ancient DNA needs to be optimised on a case‐to‐case basis, because ancient DNA is damaged and chemically modified and contains large amounts of polymerase chain reaction inhibitors.

Key Concepts:

The analysis of complex genomes requires the preparation of pure genomic deoxyribonucleic acid (DNA) of high molecular weight.

Genomic DNA can be prepared from any source by three steps: cell lysis, deproteinisation and recovery of DNA.

Intact chromosomal megabase‐sized DNA is purified in solid agarose to protect the DNA during preparation.

DNA extraction for biobanking relies on automated systems and robotics.

Automated systems have been increasingly utilised for DNA extraction by forensic laboratories to handle the growing numbers of forensic casework samples while minimising the risk of human errors and assuring high reproducibility.

The recovery of ancient DNA from palaeontological specimens is a demanding task, because ancient DNA is damaged and chemically modified and contains large amounts of PCR inhibitors that interfere with DNA amplification that are copurified with the DNA.
Stomatal Patterning
Authors: Bringmann Martin , Bergmann Dominique C
Published: September 2013

Stomatal development is a model for understanding the integration of multiple inputs into a simple cell fate choice. Intense research during the past decade has revealed mechanisms that govern stomatal development including inter‐ and intracellular signalling, transcriptional regulation, cell polarisation and asymmetric cell divisions. Recent discoveries in
Arabidopsis
include conserved families of transcription factors that drive differentiation and morphogenesis in the stomatal lineage. Specific proteins and pathways that mediate the transduction of signals, and thereby contribute to fate decisions such as secreted protein ligands, receptor kinases, mitogen activated protein kinase kinases and light and hormones have also recently been described. Studies in
Arabidopsis
and maize revealed novel proteins polarised within dividing stomatal lineage precursors. Together, these discoveries set the foundation to untangle mechanisms that lead to pattern and cell fate acquisition in plant systems.

Key Concepts:

Stomata are cellular pores that regulate gas exchange in plant leaves.

Stomatal density and distribution is modulated by the environment and responds to changes in light, CO
2
and humidity.

Stomatal development provides a framework for the understanding of cell fate, cell–cell signalling and cell polarity in plants.

Progression through the stages of stomatal development in
Arabidopsis
requires a balance of fate promoting transcription factors, and fate and division repressing cell–cell signalling.

Based on genetic studies, plants and animals display considerable conservation in the molecules and mechanisms used for developmental fates, but plant‐specific modules are used to generate physically asymmetric cell divisions that characterise early stomatal development.
Evolution of the Human Immune System
Authors: Danilova Nadia
Published: September 2013

Human immune system is an orchestra of various defence mechanisms functioning at different levels, from individual cells to the whole body. Specialised immune mechanisms can be subdivided into innate and adaptive immune systems. Innate immune mechanisms use receptors recognising conserved molecular patterns of pathogens. Adaptive immune system depends on the production of vast repertoires of immune receptors and selective expansion of pathogen‐specific ones. Some basic cellular functions such as ubiquitination and autophagy as well as stress response pathways also contribute to the immune defence. Various immune defence systems work autonomously but in communication with each other. All responses are coordinated at the body level by hormones and other mediators. Layered and redundant structure of the human immune system offers great efficiency in the detection and elimination of pathogens. All immune mechanisms evolve interactively in concordance with human environment and history.

Key Concepts:

Human immune system is a multilayered structure that includes various mechanisms.

Basic cellular mechanisms may contribute to immune defence.

Specialised immune mechanisms are subdivided into innate and adaptive based on the receptors used for antigen recognition.

Immune mechanisms comprise those based on humoral factors and those based on cells.

Most immune defence mechanisms work semiautonomously in interaction with other systems.

Immune mechanisms can be controlled at the body level by hormones and other mediators.

Immune receptors evolve by gene duplication, balancing selection, changes in coding and regulatory sequences, and other mechanisms.

Human immune system continues to evolve.

Individual immune mechanisms evolve in interaction with other mechanisms and basic cellular machinery.
Cancer Stem Cells – Basic Biological Properties and Experimental Approaches
Authors: Hatina Jiří , Fernandes Maria Inès , Hoffmann Michèle J , Zeimet Alain G
Published: September 2013

Cancer stem cells (CSCs) are defined as a self‐renewing and self‐protecting subpopulation of tumour cells that can differentiate into all other tumour cell types found within a tumour. They can be prospectively identified and purified, either on the basis of specific cell surface marker expression, or by virtue of their biological properties; their self‐protection has been harnessed to develop several purification strategies, for example, side population or Aldefluor assays. Other prominent biological properties of CSCs include their exclusive clonogenicity and tumourigenicity. Many of these basic biological characteristics are shared between normal and CSCs, as are multiple signalling pathways regulating self‐renewal and differentiation. Unlike normal stem cells, CSCs often seem to be distinctly less stable, dynamically modulating their stemness and differentiation according to various environmental signals and/or genetic and epigenetic changes accumulated during the carcinogenic process. This plasticity of CSCs might underlie the prominent biological characteristics of malignant tumours, especially their propensity to metastasise.

Key Concepts:

Stem cells are long‐lived and protect their genome.

Existence of long‐lived, undifferentiated and self‐protecting cells could be indirectly inferred in tumours.

Cancer stem cells express specific cell surface markers and are amenable to differential staining procedures.

Cancer stem cells frequently exploit similar signalling pathways as embryonic stem cells and normal adult stem cells.

Hypoxia activates a multifaceted stem cell programme in tumours.

Cancer stem cell phenotype can be unstable, with repeated or even ongoing differentiation and dedifferentiation.
Molecular Genetics of Bipolar Disorder
Authors: Offord James D
Published: September 2013

Bipolar disorder (BPD) is a disease of unknown etiology, which is a major cause of disability. The disease is characterised by oscillation between a manic state and a depressed state, and has a significant genetic component. To try to improve understanding of the disease, linkage studies and association studies have been conducted on bipolar subjects. To date these studies have yielded equivocal results. A very small number of genomic regions and genes have been identified which are associated with the bipolar disease. This small number of genes does not explain the high heritability of the disease. Using the results of these screens as starting points it should prove possible to develop a model for the underlying molecular components of BPD.

Key Concepts:

Bipolar disorder is a highly heritable psychiatric disorder where genetics are proving to be complex.

Psychiatric linkage studies have been less successful than genome wide association studies at showing involvement of genes in psychiatric disease.

Genome wide association studies can provide information about genes that are involved in a disorder.

Not all of the heritability of bipolar disorder has been explained by genetic association studies. The nature of this ‘missing heritability’ remains unclear.

Genetic modifiers are genes that can alter the phenotype caused by a mutation. These genetic modifiers may account for some of the missing heritability seen in bipolar disorder.