bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies in Rheoencephalography (REG)
Authors: Bodo Michael 
Published: July 2015

Abstract
This article presents an overview of rheoencephalography (REG) – electrical impedance measurements of the brain – and summarizes past and ongoing research to develop medical applications of REG for neuro-critical care and for primary prevention of stroke and cardiovascular disease. The availability of advanced electronics and computation has opened up the potential for use of REG technology as a noninvasive, continuous and inexpensive brain monitor for military and civilian applications. The clinical background information presented here introduces physiological and clinical environments where REG has potential for use in research and clinical settings.
REG studies over the past three decades have involved in vitro and in vivo groups (animal and human), including more than 1500 measurements and related electronic and computational results and practical applications. In vitro studies helped researchers understand the flow/volume relationship between Doppler ultrasound and electrical impedance signals and supported development of REG data processing methods. In animal studies, REG was used to monitor the lower limit of cerebral blood flow (CBF) autoregulation (AR) using a newly developed algorithm. These animal studies also confirmed correlations between REG and measurements of carotid flow (CF) and intracranial pressure (ICP). Human studies confirmed the applicability of REG for detecting cerebrovascular alteration, demonstrating the usefulness of REG in the field of stroke/cardio-vascular disease prevention. In these studies, REG was compared to known stroke risk factors and to results obtained using carotid ultrasound measurements. An intelligent REG system (Cerberus) has been developed for primary stroke prevention. In these studies, the biologically relevant variables of the REG signal were pulse amplitude (minimum – maximum distance) and duration of the anacrotic (rising) portion of the REG pulse wave.
The principal limitation of REG for clinical application is the lack of pathological and physiological correlations. The studies presented here have initiated such inquiries, but many clinical questions about the pathophysiological background of REG remain unanswered.
These results demonstrate that REG development is a multidisciplinary subject with relevance for medicine (vascular neurology and neurosurgery intensive care); electronic engineering; mathematics, and computer science (data processing). It is hoped that information presented in this article will provide assistance to those involved in REG research, particularly in development and clinical applications.
Testing miniaturized electrodes for impedance measurements within the β-dispersion – a practical approach
Authors: Pliquett Uwe , Frense Dieter , Schönfeldt Markus , Frätzer Christian , Zhang Yong , Cahill Brian , Metzen Michael , Barthel Andreas , Nacke Thomas , Beckmann Dieter 
Published: July 2015

Abstract
Miniaturized electrodes are introduced in life sciences in a great number and variety. They are often designed for a special purpose without the need of quantitative analysis, such as for detecting cells or water droplets in a fluid channel. Other developments aim in monitoring a single quantity in a process where all other factors held constant.
To use miniaturized electrodes for quantitative measurements, their behavior should be known in detail and stable over time in order to allow a mathematical correction of the data measured.
Here we show test procedures for evaluating macroscopic but also microscopic electrodes. The most important quality parameters for electrode systems used in life science are the electrode impedance, its stability, the useful frequency range as well as the limits for applied stimulus without driving the electrode system into a non-linear region of the current/voltage relation. Proper electrode design allows a bandwidth from 100 Hz up to some MHz for impedances ranging over decades from 50 Ω up to several MΩ.
Direct localised measurement of electrical resistivity profile in rat and embryonic chick retinas using a microprobe
Authors: Kasi Harsha , Meissner Robert , Babalian Alexandre , Lintel Harald van , Bertsch Arnaud , Renaud Philippe 
Published: July 2015

Abstract
We report an alternative technique to perform a direct and local measurement of electrical resistivities in a layered retinal tissue. Information on resistivity changes along the depth in a retina is important for modelling retinal stimulation by retinal prostheses. Existing techniques for resistivity-depth profiling have the drawbacks of a complicated experimental setup, a less localised resistivity probing and/or lower stability for measurements. We employed a flexible microprobe to measure local resistivity with bipolar impedance spectroscopy at various depths in isolated rat and chick embryo retinas for the first time. Small electrode spacing permitted high resolution measurements and the probe flexibility contributed to stable resistivity profiling. The resistivity was directly calculated based on the resistive part of the impedance measured with the Peak Resistance Frequency (PRF) methodology. The resistivity-depth profiles for both rat and chick embryo models are in accordance with previous mammalian and avian studies in literature. We demonstrate that the measured resistivity at each depth has its own PRF signature. Resistivity profiles obtained with our setup provide the basis for the construction of an electric model of the retina. This model can be used to predict variations in parameters related to retinal stimulation and especially in the design and optimisation of efficient retinal implants.
Eduction, extension, and exhumation of ultrahigh‐pressure rocks in metamorphic core complexes due to subduction initiation
Authors: Petersen Kenni Dinesen , Buck W. Roger 
Published: July 2015

AbstractThe controversy over the exhumation of ultrahigh‐pressure (UHP) rocks centers on whether it involves rising of pieces of crust detached from subducted continental lithosphere or an entire subducted plate that undergoes “eduction,” i.e., reverse subduction. We present a new thermomechanical model of continental subduction showing that these apparently contrasting mechanisms can occur together: crust subducted deep enough is heated and weakened, causing limited diapiric rise, while crust subducted to shallower depths retains strength and is exhumed only by eduction. The model also shows for the first time how eduction followed by seafloor spreading can occur in a zone of regional convergence. This occurs spontaneously when subduction of buoyant crust causes a subduction zone to “lock up” in one place causing a new subduction zone to form in another. The model is consistent with many features of the youngest region of UHP rock exhumation on earth: the D'Entrecasteaux Islands. UHP exhumation and the amount of regional extension, as well as the seismic structure around the islands, can be explained by eduction. Ductile flow fabrics, seen on the islands, would result from exhumation of the most deeply subducted crust heated enough to undergo partial melting. Reversal of motion on the north‐dipping continental subduction zone, required by this model, was likely triggered by initiation of the New Britain Trench, as suggested previously. Our model implies that the crust of Goodenough Basin, south of the islands, was exhumed by eduction in the last 5 Ma and this hypothesis can be tested by drilling.
Borsäure und Tetraborate [BAT Value Documentation in German language, 2015]
Authors: Bolt H.M. , Golka K. 
Published: July 2015

Abstract

Veröffentlicht in der Reihe
Biologische Arbeitsstoff‐Toleranz‐Werte (BAT‐Werte), Expositionsäquivalente für krebserzeugende Arbeitsstoffe (EKA) und Biologische Leitwerte (BLW)
, 22. Lieferung, Ausgabe 2015

Der Artikel enthält folgende Kapitel:

Metabolismus und Toxikokinetik

Kritische Toxizität

Belastung und Beanspruchung

Auswahl der Indikatoren

Untersuchungsmethoden

Hintergrundbelastung

Evaluierung

Interpretation
Addendum zu Benzol [BAT Value Documentation in German language, 2015]
Authors: Weistenhöfer W. , Drexler H. 
Published: July 2015

Abstract

Veröffentlicht in der Reihe
Biologische Arbeitsstoff‐Toleranz‐Werte (BAT‐Werte), Expositionsäquivalente für krebserzeugende Arbeitsstoffe (EKA) und Biologische Leitwerte (BLW)
, 22. Lieferung, Ausgabe 2015
Tubulin and Microtubules
Authors: Amos Linda A 
Published: July 2015

AbstractMicrotubules are found in almost all types of eukaryotic cell. Their principal constituents are the highly conserved proteins of the tubulin family, in the form of longitudinal protofilaments of tubulin heterodimers. The conserved lateral interactions produce a characteristic 2D lattice. Tubulin structure and conformational changes are now known to atomic resolution. Its GTP‐dependent dynamic self‐assembly and disassembly is modulated by a host of other proteins. This dynamic activity and a more passive role as tracks for interaction with motor proteins, kinesin and dynein, allow microtubules to perform vital roles in various forms of cell motility. They are an essential component of cell division, provide oriented tracks for the transport of cellular organelles and vesicles and are responsible for the relative positioning of cellular compartments. Thus, they are important targets in the control of cancer cells, as their essential activity is severely affected by a variety of drugs.Key ConceptsTubulin heterodimers, consisting of highly homologous α‐ and β‐tubulin monomers, self‐assemble into a unique lattice with polar longitudinal ‘protofilaments’The assembled sheet has a slightly variable curvature, producing microtubules, with around 13 protofilaments but not strictly defined unless they are grown from a γ‐tubulin template or given a curvature appropriate to exactly 13 protofilaments by accessory proteinsThe structure of microtubules has been solved to near‐atomic level both with GTP homologues bound to β‐tubulin and with GDP bound; also a depolymerised protofilament structure in a longitudinally curved conformation is knownHydrolysis of bound GTP enables microtubules to assemble with ‘dynamic instability’, behaviour that depends on stochastic disassembly when the GTP ‘cap’ is lost from a growing endMicrotubule behaviour is modified by many different accessory proteins that may act just at the tips or everywhere on the lattice wallTo play different roles according to their positions in cells, the properties of microtubules may vary owing to different tubulin isotypes and be modified by a wide range of associated proteinsChanges can also vary with time (‘ageing’) as a result of post‐translational modification of tubulin and of some accessory proteinsMicrotubules are employed in axonemes of cilia and flagella, where the motor protein dynein interacts with them to produce beating while other linking components help control the wave‐formCytoplasmic microtubules provide tracks for vesicles and other cargoes driven by kinesins and cytoplasmic dyneinMitotic and meiotic spindles are assembled from microtubules, which interact with kinetochores and with multiple motor proteinsMicrotubules are susceptible to many small molecules that depolymerise or hyperstabilise them and thus serve as anti‐cancer drugs.
Immunogenicity
Authors: Galson Jacob D , O'Connor Daniel 
Published: July 2015

Abstract

An antigen refers to a molecule that is able to bind to the cells of the immune system. If an antigen can also stimulate an immune response, it is termed an immunogen. Immunogenicity is a measure of this ability to activate the immune response: that is, the B and T cells underlying humoral and cell‐mediated immunity. Understanding the concept of immunogenicity is therefore vital in understanding the field of immunology as a whole. The determinants of immunogenicity are complex, but much research has been conducted in this area in the context of vaccination and protein therapeutics, where understanding immunogenicity is of key clinical significance. While obtaining accurate measures of immunogenicity is difficult, a range of techniques to both predict the immunogenicity of a substance and to measure immunogenicity based on B and T cell activation have been developed.

Key Concepts

Immunogenicity is defined as the ability of a substance to elicit an adaptive immune response.

The immunogenicity of a substance depends on multiple factors relating to the properties of the substance itself, the biological system, and how the substance is delivered to the biological system.

Immunogenicity is necessary for our body to respond to and destroy pathogens, as well as to remove tumourogenic and dying cells.

Understanding immunogenicity is important for pharmaceutical development, where it is sometimes necessary to either increase (vaccination) or decrease (protein therapeutics) the immunogenicity of a product.

Experimental model systems, and more recently, computational tools, are being developed to predict immunogenicity.

Immunogenicity can be measured empirically by assessing the numbers of activated T or B cells, or antibody levels during a response to the substance.
Antibody Synthesis
In Vitro
Authors: Iborra Antoni , Martínez Paz , Palacio José Ramón 
Published: July 2015

Abstract

Antibodies are specific proteins that recognise nearly any chemical structure. During
in vivo
immunisation B cells are activated by antigen. Antigen‐specific cells proliferate and some differentiate into antibody‐secreting plasma cells. Monoclonal antibody technology was first reported by Köhler and Milstein in 1975. Briefly, B cells with specificity for a known antigen were fused with myeloma to make them immortal. Hybridomas grow in culture indefinitely and secrete monoclonal antibodies (mAbs) of a desired specificity. Hybridoma technology and antibody engineering have contributed in Biomedicine to the diagnosis of malignancies, tissue typing, identification of individual cell types, detection of cytokines, growth factors and hormones. The mAbs have become important in human immunotherapy and diagnosis. Murine mAbs have limited potential in human therapeutic applications due to human immune response to the murine antibodies. Several strategies for human mAbs production for immunotherapy are described in this article. Monoclonal antibodies have also a wide range of applications in Health and Food Sciences, Environmental Sciences, Technology and Experimental Sciences among others.

Key Concepts

Antigen is a molecule that binds specifically to B cell receptor (BCR) or soluble antibodies. T cell receptor (TCR) recognise processed antigen presented by MHC (major histocompatibility complex).

Epitope or antigenic determinant is part of an antigen that is recognised specifically by TCR‐MHC or by BCR or by soluble antibodies.

Immunogen is an antigen that generates a cellular and humoral immune response.

Antibody is an immunoglobulin that recognises specifically a particular antigenic epitope.

Antibody affinity is the strength of binding between a single binding site of an antibody and a single antigenic determinant or epitope.

Plasma B cells are differentiated B cells that, after binding to an antigen, secrete soluble antibodies.

Hybridoma is a hybrid cell line obtained by cell fusion of an immortalised lymphocyte tumor line, or myeloma, and B lymphocytes with defined antigen specificities.

Monoclonal antibody is an immunoglobulin with specificity for one antigenic determinant or epitope, derived from a single B‐clone.

Antibody immunotherapy is applied in immunopathology and in cancer. The main therapeutic agents are human or humanised monoclonal antibodies.
Antibody Engineering
Authors: Paul Sudhir , Planque Stephanie , Massey Richard 
Published: July 2015

AbstractAntibodies contain sites in the heavy and light chain variable domains (V domains) with antigen‐binding activity largely independent of their constant domains (C domains). Recombinant antibodies that bind with pathological proteins are used widely as drugs. In addition, antibodies containing V domain nucleophilic sites that bind protein targets irreversibly or catalyse target breakdown. Target‐specific therapeutic antibodies can be obtained by inducing adaptive B cell development in transgenic animal or by test‐tube affinity maturation of cloned antibody V domain repertoires. The V domains are recloned as full‐length antibodies to improve their pharmacokinetic behaviour, restore the C domain‐dependent catalytic activity and incorporate effector functions residing in the C domains. Assembly of the V domains into multivalent constructs improves the binding avidity. Linkage to enzymes, toxins or delivery proteins imparts novel functions to the constructs. Uptake of antibodies by internalisation of membrane‐bound antigen forms can render intracellular antigens sensitive to antibody targeting.Key ConceptsAntibodies are highly adaptive structures. They are encoded by germline genes that have diversified over evolutionary time and then undergo further antigen‐driven adaptive development over the life time of an individual organism.The antigen combining site is composed of the antibody light and heavy chain subunit variable domains. The constant domain contributes effector functions such as complement activation and Fc receptor binding.Monoclonal IgG antibodies that bind protein target reversibly have emerged as a major class of biological drugs for various diseases. The efficacy and safety of antibody drugs depend on their antigen recognition affinity, specificity andin vivopharmacokinetics.Understanding the natural process underlying adaptive sequence diversification has permitted isolation of monoclonal antibodies, meeting the criteria for therapeutic applications. Antibody display and cloning methods have enabled identification of individual antibodies with defined antigenic specificities from vast repertoires.Improvement of IgG antibody functions can be attained in the test tube by rational or random mutagenesis coupled with directed selection of the mutants.The new electrophilic immunisation approach has enabled on‐demand production of next‐generation monoclonal IgGs with superior protein target neutralisation capacity made possible by irreversible target binding.Combined innate and adaptive immunity algorithms have been applied to produce monoclonal IgM, IgA and V domains that rapidly and specifically catalyse the degradation of disease‐associated protein targets, making feasible the development of more efficacious and safer therapeutic antibodies.
Anaemia: Overview
Authors: Houston Brett L , Houston Donald S , Zarychanski Ryan 
Published: July 2015

Abstract

Anaemia, a decrease in erythrocyte mass that is reflected in a reduction in the haemoglobin concentration in the peripheral blood, is the most common haematologic condition for which medical attention is sought. Erythrocytes are critical to tissue oxygenation and carbon dioxide removal, and severe anaemia may lead to tissue hypoxia and organ dysfunction. Erythropoiesis is a highly regulated process controlled by erythropoietin. Adaptive mechanisms permit moderate anaemia to be well tolerated, and the clinical importance of mild to moderate anaemia is its representation of an underlying disease. Mild to moderate anaemia may be one of the first clues of an underlying disease. Although many of the signs and symptoms of anaemia are nonspecific, a pragmatic classification of anaemia based on integration of kinetic and morphologic characteristics of erythrocytes allows efficient investigation of the underlying aetiology.

Key Concepts

Anaemia is the most common haematologic condition encountered in medical practice

Erythrocytes are critical to tissue oxygenation and carbon dioxide removal

Physiologic compensatory mechanisms allow mild to moderate anaemia to be well tolerated; severe anaemia may be associated with tissue hypoxia and organ dysfunction

Erythropoiesis, the production of erythrocytes, is a tightly regulated process controlled predominantly by the synthesis of erythropoietin in response to hypoxia

The clinical significance of mild–moderate anaemia lies in its association with an underlying systemic disease; the finding of anaemia should prompt consideration of additional investigations

Classification of anaemia based on kinetic and morphologic erythrocyte characteristics allows pragmatic segregation into microcytic, macrocytic or normocytic anaemia, further directing the investigation of an underlying disease
Alcohol and Pregnancy and the Foetal Alcohol Syndrome
Authors: Bonthius Daniel J 
Published: July 2015

Abstract

Foetal alcohol syndrome is a specific pattern of birth defects caused by prenatal alcohol exposure. The syndrome's components include somatic growth restrictions, characteristic midface abnormalities and brain dysfunction. ‘Foetal alcohol spectrum disorders’ (FASDs) includes the broad range of offspring effects caused by prenatal alcohol exposure. Alcohol is a teratogenic drug to which the developing brain is particularly vulnerable. Alcohol induces brain injury and dysfunction in the offspring through a variety of mechanisms, one of the most important of which is neuronal death. Alcohol‐induced neurodevelopmental sequelae most often include learning disorders, attention deficits and behaviour problems. These deficits can range from mild to severe, depending on dose and timing of the alcohol exposure, maternal and foetal genetics and other conditions of exposure. Because alcohol use is so prevalent and because the developing brain is so vulnerable, FASD is the most important preventable cause of cognitive deficiency in the western world.

Key Concepts

Foetal alcohol syndrome (FAS) is a constellation of developmental abnormalities that results from maternal alcohol abuse during pregnancy.

Components of FAS include prenatal and postnatal growth restrictions, a characteristic set of midface abnormalities and central nervous system dysfunction.

‘Foetal alcohol spectrum disorders’ (FASD) is an umbrella term that encompasses the full range of adverse effects of alcohol on the offspring.

Many children who were prenatally exposed to alcohol have FASD, which most commonly manifests as neurodevelopmental problems, without having the full FAS syndrome.

The brain is the most vulnerable of the foetal organs to alcohol‐induced damage.

Alcohol damages the developing brain in a variety of ways, one of the most important of which is neuronal death.

The vulnerability of developing neurons to alcohol‐induced injury depends on a variety of factors, including the dose and timing of alcohol exposure.

Not all foetuses are equally vulnerable to alcohol‐induced injury; some possess certain genes that can increase or decrease their susceptibility to alcohol teratogenesis.

The most common neurodevelopmental problems induced by prenatal alcohol exposure are learning disorders, attention deficits and behaviour problems.

People with FASD are often particularly disabled by severe deficits in executive functions, a group of cognitive integrative behaviours that reflect the ability to self‐regulate, effectively plan, organise, keep focused on and carry out goal‐directed activity.
Frosch, Paul
Authors: Berger Silvia 
Published: July 2015

Abstract
Paul Frosch (1860–1928) was a German bacteriologist and a pioneer of animal virology. He worked at the Institute for Infectious Diseases in Berlin as a close co‐worker of Robert Koch, the leading figure of medical bacteriology, and became later appointed professor at the veterinary school in Berlin. On the basis of a study on typhoid, Frosch introduced the term ‘infection carrier’ for infected persons without manifest symptoms, and emphasised the role they played in spreading the epidemic. The concept subsequently became the cornerstone of epidemic control for a variety of infectious diseases in Germany. In 1898, Frosch pioneered virus research when he described the aetiological agent of the foot‐and‐mouth disease together with Friedrich Loeffler, characterising it as an ultravisible, filterable substance.