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At least 973 records · Page 54Linked to original sources
PubMed2002

Hypermethylation of gene promoters in hematological neoplasia.

Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation-associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents.

Animals↗
PubMedDate not supplied

What kind of healthcare 'internal market'? A cross-Europe view of the options.

Many governments are trying to invent new types of 'internal' healthcare market that will expose health services to competitive pressures to innovate, contain costs, raise service quality, and respond better to consumer demands; but not expose them to 'market failures' which prejudice universal access to 'basic' health services. Policy debates in this area are muddled and constricted by a failure to differentiate the variants of internal market that are available. This article outlines a taxonomy of the main types of internal market: primary doctor purchasing; managed competition; competitive bidding; social insurance; and compulsory private insurance. It notes their main structural characteristics and differences. Although internal market reforms have been intended to support the commercialization of healthcare, the idea of designing new types of economic structure to avoid market failure in healthcare has wider and more radical implications than most policy-makers intend.

Competitive Bidding↗
PubMed2004

Microarrays in biology and medicine.

The remarkable speed with which biotechnology has become critical to the practice of life sciences owes much to a series of technological revolutions. Microarray is the latest invention in this ongoing technological revolution. This technology holds the promise to revolutionize the future of biology and medicine unlike any other technology that preceded it. Development of microarray technology has significantly changed the way questions about diseases and/or biological phenomena are addressed. This is because microarrays facilitate monitoring the expression of thousands of genes or proteins in a single experiment. This enormous power of microarrays has enabled scientists to monitor thousands of genes and their products in a given living organism in one experiment, and to understand how these genes function in an orchestrated manner. Obtaining such a global view of life at the molecular level was impossible using conventional molecular biological techniques. However, despite all the progress made in developing this technology, microarray is yet to reach a point where all data are obtained, analyzed, and shared in a standardized fashion. The present article is a brief overview of microarray technologies and their applications with an emphasis on DNA microarray.

Animals↗
PubMed2003

Adolescent psychotherapy: an introduction.

Adolescent psychotherapy has only recently taken hold as distinct from either child or adult psychotherapy. This new recognition was born of necessity as practitioners saw that theories and techniques developed for treating children and adults were far less effective for treating adolescents. As necessity is often the mother of invention, new models for treating adolescents have emerged. While these models differ in many respects, they share three characteristics: the unique features of adolescents, psychotherapists requiring specialized knowledge and skills, and the need for adolescent psychotherapy to involve the broader systemic context of the adolescent's life. The articles in this issue of In Session: Journal of Clinical Psychology insist that practitioners recognize and challenge their assumptions about how psychotherapy with adolescents should be conducted. The articles highlight the need for specialized training, the scarcity of evidenced-based research, and the ethical dilemmas that frequently occur when working with this population.

Adolescent↗
PubMed2004

Antecedents of two-photon excitation laser scanning microscopy.

In 1931, Maria Göppert-Mayer published her doctoral dissertation on the theory of two-photon quantum transitions (two-photon absorption and emission) in atoms. This report describes and analyzes the theoretical and experimental work on nonlinear optics, in particular two-photon excitation processes, that occurred between 1931 and the experimental implementation of two-photon excitation microscopy by the group of Webb in 1990. In addition to Maria Göppert-Mayer's theoretical work, the invention of the laser has a key role in the development of two-photon microscopy. Nonlinear effects were previously observed in different frequency domains (low-frequency electric and magnetic fields and magnetization), but the high electric field strength afforded by lasers was necessary to demonstrate many nonlinear effects in the optical frequency range. In 1978, the first high-resolution nonlinear microscope with depth resolution was described by the Oxford group. Sheppard and Kompfner published a study in Applied Optics describing microscopic imaging based on second-harmonic generation. In their report, they further proposed that other nonlinear optical effects, such as two-photon fluorescence, could also be applied. However, the developments in the field of nonlinear optical stalled due to a lack of a suitable laser source. This obstacle was removed with the advent of femtosecond lasers in the 1980s. In 1990, the seminal study of Denk, Strickler, and Webb on two-photon laser scanning fluorescence microscopy was published in Science. Their paper clearly demonstrated the capability of two-photon excitation microscopy for biology, and it served to convince a wide audience of scientists of the potential capability of the technique.

History, 20th Century↗
PubMed2004

The terminal nerve and its relation with extrabulbar "olfactory" projections: lessons from lampreys and lungfishes.

The definition of the terminal nerve has led to considerable confusion and controversy. This review analyzes the current state of knowledge as well as diverging opinions about the existence, components, and definition of terminal nerves or their components, with emphasis on lampreys and lungfishes. I will argue that the historical terminology regarding this cranial nerve embraces a definition of a terminal nerve that is compatible with its existence in all vertebrate species. This review further summarizes classical and more recent anatomical, developmental, neurochemical, and molecular evidence suggesting that a multitude of terminalis cell types, not only those expressing gonadotropin-releasing hormone, migrate various distances into the forebrain. This results in numerous morphological and neurochemically distinct phenotypes of neurons, with a continuum spanning from olfactory receptor-like neurons in the olfactory epithelium to typical large ganglion cells that accompany the classical olfactory projections. These cell bodies may lose their peripheral connections with the olfactory epithelium, and their central projections or cell bodies may enter the forebrain at several locations. Since "olfactory" marker proteins can be expressed in bona fide nervus terminalis cells, so-called extrabulbar "olfactory" projections may be a collection of disguised nervus terminalis components. If we do not allow this pleiomorphic collection of nerves to be considered within a terminal nerve framework, then the only alternative is to invent a highly species- and stage-specific, and, ultimately, thoroughly confusing nomenclature for neurons and nerve fibers that associate with the olfactory nerve and forebrain.

Animals↗
PubMed2001

Current problems with the zootype and the early evolution of Hox genes.

"Hox cluster type" genes have sparked intriguing attempts to unite all metazoan animals by a shared pattern of expression and genomic organization of a specific set of regulatory genes. The basic idea, the zootype concept, claims the conservation of a specific set of "Hox cluster type genes" in all metazoan animals, i.e., in the basal diploblasts as well as in the derived triploblastic animals. Depending on the data used and the type of analysis performed, different opposing views have been taken on this idea. We review here the sum of data currently available in a total evidence analysis, which includes morphological and the most recent molecular data. This analysis highlights several problems with the idea of a simple "Hox cluster type" synapomorphy between the diploblastic and triploblastic animals and suggests that the "zootype differentiation" of the Hox cluster most likely is an invention of the triploblasts. The view presented is compatible with the idea that early Hox gene evolution started with a single proto-Hox (possibly a paraHox) gene. J. Exp. Zool. (Mol. Dev. Evol.) 291:169-174, 2001.

Animals↗
PubMed2004

Mental tests and fossils.

This article investigates the origins of the intelligence test item known as the Ball and Field in Lewis M. Terman's Stanford Revision of the Binet-Simon Intelligence Scale. The question was initially raised by the resemblance of paleontological ocean bed floor tracings left by ancient creatures to the responses produced by children given the Ball and Field Test. A version of the Ball and Field Test was invented by Clifton F. Hodge, one of Terman's graduate school instructors who devised it as a result of his observations about how birds and other animals navigated and found their way. He then tested how humans and children located hidden objects and found that, in many ways, animals and humans used similar strategies for getting home or finding objects.

Adult↗
PubMed2006

Walter Miles, Pop Warner, B. C. Graves, and the psychology of football.

In 1926-1927, a graduate student, B. C. Graves, working with Stanford University psychologist Walter Miles and legendary football coach Pop Warner, conducted an investigation of variations in signal calling as they affected the charging times of football players. The study was one of two that involved Miles and the ingenious multiple chronograph that he had invented to time the reactions of seven players simultaneously. These studies represented a brief digression in the career of Miles, who certainly was no sport psychologist. They tell of an interesting collaboration between scientist and coaches that produced one of the richest studies in sport psychology in the first half of the twentieth century.

Equipment Design↗
PubMed2006

The lost direction in binocular vision: the neglected signs posted by Wells, Towne, and LeConte.

Studies of vision have informed theories first in philosophy and then in psychology. Over the centuries, an increasing number of phenomena have been enlisted to refute or reinforce particular theories. Nowhere has this been more evident than in binocular vision. How we see a single world with two eyes is one of the oldest and most consistently studied topics in vision research. It has been discussed at least since the time of Aristotle and it has been examined experimentally since the second century, when Ptolemy defined lines of visual correspondence for the two eyes. Prior to Wheatstone's invention of the stereoscope in the 1830s, binocular vision had been studied in terms of visual directions. The stereoscope established distance (or depth) as well as direction as dimensions of binocular vision. Subsequently, depth rather than direction has been the principal concern of students of vision, and texts in English devoted to analyses of direction rather than depth have been neglected. We examine the experiments on binocular visual direction conducted by Wells before Wheatstone, and by Towne and LeConte after him, and discuss the reasons for their neglect.

History, 17th Century↗
PubMed2002

Ontogenetic and phylogenetic transformations of the ear ossicles in marsupial mammals.

This study is based on the examination of histological sections of specimens of different ages and of adult ossicles from macerated skulls representing a wide range of taxa and aims at addressing several issues concerning the evolution of the ear ossicles in marsupials. Three-dimensional reconstructions of the ear ossicles based on histological series were done for one or more stages of Monodelphis domestica, Caluromys philander, Sminthopsis virginiae, Trichosurus vulpecula, and Macropus rufogriseus. Several common trends were found. Portions of the ossicles that are phylogenetically older develop earlier than portions representing more recent evolutionary inventions (manubrium of the malleus, crus longum of the incus). The onset of endochondral ossification in the taxa in which this was examined followed the sequence; first malleus, then incus, and finally stapes. In M. domestica and C. philander at birth the yet precartilaginous ossicles form a supportive strut between the lower jaw and the braincase. The cartilage of Paauw develops relatively late in comparison with the ear ossicles and in close association to the tendon of the stapedial muscle. A feeble artery traverses the stapedial foramen of the stapes in the youngest stages of M. domestica, C. philander, and Sminthopsis virginiae examined. Presence of a large stapedial foramen is reconstructed in the groundplan of the Didelphidae and of Marsupialia. The stapedial foramen is absent in all adult caenolestids, dasyurids, Myrmecobius, Notoryctes, peramelids, vombatids, and phascolarctids. Pouch young of Perameles sp. and Dasyurus viverrinus show a bicrurate stapes with a sizeable stapedial foramen. Some didelphids examined to date show a double insertion of the Tensor tympani muscle. Some differences exist between M. domestica and C. philander in adult ossicle form, including the relative length of the incudal crus breve and of the stapes. Several differences exist between the malleus of didelphids and that of some phalangeriforms, the latter showing a short neck, absence of the lamina, and a ventrally directed manubrium. Hearing starts in M. domestica at an age in which the external auditory meatus has not yet fully developed, the ossicles are not fully ossified, and the middle ear space is partially filled with loose mesenchyme. The ontogenetic changes in hearing abilities in M. domestica between postnatal days 30 and 40 may be at least partially related to changes in middle ear structures.

Animals↗
PubMed2004

Solid-phase microextraction: a powerful sample preparation tool prior to mass spectrometric analysis.

Sample preparation is an essential step in analysis, greatly influencing the reliability and accuracy of resulted the time and cost of analysis. Solid-Phase Microextraction (SPME) is a very simple and efficient, solventless sample preparation method, invented by Pawliszyn in 1989. SPME has been widely used in different fields of analytical chemistry since its first applications to environmental and food analysis and is ideally suited for coupling with mass spectrometry (MS). All steps of the conventional liquid-liquid extraction (LLE) such as extraction, concentration, (derivatization) and transfer to the chromatograph are integrated into one step and one device, considerably simplifying the sample preparation procedure. It uses a fused-silica fibre that is coated on the outside with an appropriate stationary phase. The analytes in the sample are directly extracted to the fibre coating. The SPME technique can be routinely used in combination with gas chromatography, high-performance liquid chromatography and capillary electrophoresis and places no restriction on MS. SPME reduces the time necessary for sample preparation, decreases purchase and disposal costs of solvents and can improve detection limits. The SPME technique is ideally suited for MS applications, combining a simple and efficient sample preparation with versatile and sensitive detection. This review summarizes analytical characteristics and variants of the SPME technique and its applications in combination with MS.

Animals↗
PubMed2005

The Orbitrap: a new mass spectrometer.

Research areas such as proteomics and metabolomics are driving the demand for mass spectrometers that have high performance but modest power requirements, size, and cost. This paper describes such an instrument, the Orbitrap, based on a new type of mass analyzer invented by Makarov. The Orbitrap operates by radially trapping ions about a central spindle electrode. An outer barrel-like electrode is coaxial with the inner spindlelike electrode and mass/charge values are measured from the frequency of harmonic ion oscillations, along the axis of the electric field, undergone by the orbitally trapped ions. This axial frequency is independent of the energy and spatial spread of the ions. Ion frequencies are measured non-destructively by acquisition of time-domain image current transients, with subsequent fast Fourier transforms (FFTs) being used to obtain the mass spectra. In addition to describing the Orbitrap mass analyzer, this paper also describes a complete Orbitrap-based mass spectrometer, equipped with an electrospray ionization source (ESI). Ions are transferred from the ESI source through three stages of differential pumping using RF guide quadrupoles. The third quadrupole, pressurized to less than 10(-3) Torr with collision gas, acts as an ion accumulator; ion/neutral collisions slow the ions and cause them to pool in an axial potential well at the end of the quadrupole. Ion bunches are injected from this pool into the Orbitrap analyzer for mass analysis. The ion injection process is described in a simplified way, including a description of electrodynamic squeezing, field compensation for the effects of the ion injection slit, and criteria for orbital stability. Features of the Orbitrap at its present stage of development include high mass resolution (up to 150,000), large space charge capacity, high mass accuracy (2-5 ppm), a mass/charge range of at least 6000, and dynamic range greater than 10(3). Applications based on electrospray ionization are described, including characterization of transition-metal complexes, oligosaccharides, peptides, and proteins. Use is also made of the high-resolution capabilities of the Orbitrap to confirm the presence of metaclusters of serine octamers in ESI mass spectra and to perform H/D exchange experiments on these ions in the storage quadrupole.

Alcohol Dehydrogenase↗
PubMed2004

New perspectives for visual characterization of pharmaceutical solids.

The utilization of descriptive image information in pharmaceutical powder technology is rather limited. Consequently, the development of this discipline is a challenge within physical characterization of pharmaceutical solids. The aim of this study was to develop and evaluate an inventive visual characterization approach for monitoring the granule growth in a fluidized-bed granulation process and to use the generated image information in the prediction of tabletting behavior of granules. Surface images of samples from 34 granulations were continuously captured during the spraying and drying phases of the process and particle size distributions were determined. The gray scale difference matrix (GSDM) was derived from two surface images taken in controlled illumination conditions. The particle size calculation from the surface images was based on a multivariate Partial Least Square (PLS) model between the GSDM and sieve analysis measurements. The image information of the end-point samples was also evaluated with respect to tabletting behavior of the granules produced. Principal component analysis (PCA) was used for data visualization. The introduced approach was suitable in particle size measurements of granules during all process phases and in the monitoring of different kinds of granule growth behavior. The visual inspection of the granule samples was powerful, enabling representational batch-to-batch comparisons. The tabletting behavior of the granules could be predicted directly from particle size information generated from the surface images. PCA as a projection method was efficient in data visualization. Development of process analytical technologies (PAT) aims at improving the efficiency of processes. The presented visual characterization approach can be an effective process analytical tool in particle size analysis also enabling the evaluation of the further product quality in the end of the granulation process. The idea of characterization of bulk surface images opens new perspectives for characterization of pharmaceutical solids.

Particle Size↗
PubMed2004

Investigating the history of prehistoric glues by gas chromatography-mass spectrometry.

Although organic materials are very sensitive to biochemical alteration processes, they may be preserved for millennia in various archaeological contexts. Remains of adhesives made during prehistory were discovered at different sites, in the form of residues adhering to flint tools and ceramic vessels or as free lumps in sediment. To characterise the natural substances exploited for adhesive production during late prehistory, we undertook GC and GC/MS analysis of 90 samples from 8 sites dating from the Neolithic to Iron Age periods. This paper discusses our approach to the study of organic adhesives preserved in archaeological contexts, with a particular focus on the presentation of the various categories of organic adhesives that we analysed and the choice of chromatographic conditions adapted to the specificity of such samples. The results obtained show that birch bark tar, a triterpenoid adhesive made by destructive distillation of white birch bark, was predominantly used during the neolithic period even though other materials such as various barks or organic fossil substance were also used. During the Bronze and Iron ages, which follow the Neolithic period, adhesive production is evolving through the expansion of the range of the natural substances used (identification of diterpenoid pine resin) and the addition of beeswax as a plasticiser to birch bark tar. By combining chromatographic analysis and archaeological data, it was thus possible to follow the evolution of adhesive making at the end of prehistory, testifying to the inventiveness of the craftsmen whatever the period considered.

Journal Article↗
PubMed2004

The evolution of comprehensive two-dimensional gas chromatography (GC x GC).

For a technology little over a decade old, comprehensive two-dimensional gas chromatography (GC x GC) has quickly reached the status of one of the most powerful analytical tools for volatile organic compounds. At the heart of any GC x GC system is an interface, which physically connects the primary and the secondary columns and acts to preserve the separation obtained in the first dimension (first column) while allowing additional separation in the second dimension. The paper presents a review of the technology, including fundamental principles of the technique, data processing and interpretation and a timeline of inventive contributions to interface design. In addition, applications of the technique are presented, with a more detailed discussion of selected examples.

Journal Article↗
PubMed2004

Applications of silica-based monolithic HPLC columns.

The recent invention and successive commercial introduction of monolithic silica columns has motivated many scientists from both academia and industry to study their use in HPLC. The first paper on monolithic silica columns appeared in 1996. Currently about 200 papers have been published relating to applications and characterization of monolithic silica columns, including monolithic capillaries. This review attempts to give an overview covering various aspects of this new column type in the field of high throughput analysis of drugs and metabolites, chiral separations, analysis of pollutants and food-relevant compounds, as well as in bioanalytical separations such as in proteomics. Some of the applications are described in greater detail. The numerous publications dealing with the physicochemical and chromatographic characterization of monolithic silica columns are briefly summarized.

Adsorption↗
PubMed1994

Clinical applications of lasers in otolaryngology--head and neck surgery.

The use of lasers in otolaryngology--head and neck surgery is described from the invention of the laser in 1960, through the current uses of the laser, and concludes with a summary for the future directions of laser surgery. The various lasers, including the argon, the KTP, and the carbon dioxide lasers used in otolaryngology, are briefly described. The applications of lasers in the larynx, sinuses, and the ear are separately covered, as well as pediatric otolaryngology. In addition to a brief description of the procedure, the complications and limitations are given. Anesthetic considerations are also covered.

Head and Neck Neoplasms↗