bluuebunny/crossref_metadata_2025 huggingface dataset:
Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model
Authors: Nutt D. , Mandel F. , Baldinetti F.
Published: July 2008

To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = −2.47; P = 0.014) and alprazolam (t = −2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = −0.50) on Spearman’s analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3—4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3—4 h post-first dose.
Novel Linkage of Individual and Geographic Data to Study Firearm Violence
Authors: Branas Charles C. , Culhane Dennis , Richmond Therese S. , Wiebe Douglas J.
Published: July 2008

Firearm violence is the end result of a causative web of individual-level and geographic risk factors. Few, if any, studies of firearm violence have been able to simultaneously determine the population-based relative risks that individuals experience as a result of what they were doing at a specific point in time and where they were, geographically, at a specific point in time. This paper describes the linkage of individual and geographic data that was undertaken as part of a population-based case-control study of firearm violence in Philadelphia. New methods and applications of these linked data relevant to researchers and policymakers interested in firearm violence are also discussed.
A Comparison of Law Enforcement and Medical Examiner Reports in a Violent-Death Surveillance System
Authors: Gabor Lee Anne , Genovesi Andrea , Larsen Gitte Y. , Fullerton-Gleason Lynne , Davis Anna , Olson Lenora M.
Published: July 2008

This study compared information gathered from medical examiner reports to information gathered from law enforcement reports in characterizing incidents of homicide and homicide followed by suicide that were abstracted for a public health violent-death surveillance system. The authors found that law enforcement reports contribute substantively to the surveillance system and often augment or provide additional information to the medical examiner reports. The utility of law enforcement data, particularly the narrative information, must be balanced with the time needed to gather the law enforcement reports and funding limitations. As violent-death surveillance needs grow, linking police and other law enforcement data with medical examiner and other public health data sources will provide a clearer picture of the circumstances relating to homicide and other violent deaths at the state and national level.
Combined functional and molecular analysis of tumor cell signaling defines 2 distinct myeloma subgroups: Akt-dependent and Akt-independent multiple myeloma
Authors: Zöllinger Angela , Stühmer Thorsten , Chatterjee Manik , Gattenlöhner Stefan , Haralambieva Eugenia , Müller-Hermelink Hans-Konrad , Andrulis Mindaugas , Greiner Axel , Wesemeier Carmen , Rath Jörg C. , Einsele Hermann , Bargou Ralf C.
Published: July 2008

Although the phosphatidylinositide 3-kinase (PI3K)/Akt pathway has been reported to contribute to the malignant growth of multiple myeloma (MM), the true relevance of Akt kinases for this disease is still unclear. In particular, functional analyses in primary tumor cells and genetic target validation experiments are missing. Here, we used combined functional and molecular analyses to determine the importance of Akt activity in a large panel of primary MM samples and in MM cell lines. Akt down-regulation with isoform-specific siRNA constructs or with an Akt1/2-specific pharmacologic inhibitor strongly induced apoptosis in approximately half of the primary MM samples analyzed. Sensitivity to Akt inhibition strongly correlated with the activation status of Akt as determined by immunohistochemistry, phospho-Akt–specific flow cytometry, and Western analysis. Additional blockade of the MAPK and the IL-6R/STAT3 pathways was often not sufficient to decrease the viability of MM cells resilient to Akt inhibition. Taken together, these experiments led to the identification of 2 myeloma subgroups: Akt-dependent and Akt-independent MM.
Brain Derived Neurotrophic Factor (BDNF) Contributes to the Pain Hypersensitivity Following Surgical Incision in the Rats
Authors: Li Chang-Qi , Xu Jun-Mei , Liu Dan , Zhang Jian-Yi , Dai Ru-Ping
Published: July 2008

Background:

The pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity.

Methods:

A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various postoperative times (1–72 h). Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal BDNF or peripheral BDNF after incision.

Results:

After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect.

Conclusion:

The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.
Viscoelastic true-amplitude prestack reverse-time depth migration
Authors: Deng Feng , McMechan George A.
Published: July 2008

A new true-amplitude prestack elastic depth-migration algorithm includes compensation for transmission and anelastic attenuation losses in an isotropic medium. Geometric spreading and its compensation are incorporated by extrapolating up- and downgoing waves using a full two-way wave equation. Intrinsic attenuation is simulated and compensated for using composite memory variables derived from standard linear solid relaxation mechanisms. Zoeppritz equations and their approximations are used to compute and analyze the angle-dependent reflection/transmission coefficients; converted energy is included at each interface. Transmission losses for compressional waves are compensated, based on estimation of angle-dependent elastic reflectivity using a two-pass recursive procedure. The image condition is the ratio of the compressional receiver/source wavefield amplitudes. Application to synthetic data from a dipping-layer model and a salt model accurately extracts P-velocity, S-velocity, density, and P-wave impedance beneath the target reflector, even under a salt overhang. Factors not explicitly considered include building of the smooth background velocity and attenuation models, estimates of the source time function, directivity and coupling, multipathing arrivals, and effects of attenuation and anisotropy on the reflection/transmission coefficients.
Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism
Authors: Chen Hui , Simar David , Lambert Karen , Mercier Jacques , Morris Margaret J.
Published: July 2008

Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact.
Molecular Cloning, Characterization, and Evolutionary Analysis of Estrogen Receptors from Phylogenetically Ancient Fish
Authors: Katsu Yoshinao , Kohno Satomi , Hyodo Susumu , Ijiri Shigeho , Adachi Shinji , Hara Akihiko , Guillette Louis J. , Iguchi Taisen
Published: July 2008

Estrogens are necessary for ovarian differentiation during a critical developmental stage in many vertebrates, and they promote the growth and differentiation of the adult female reproductive system. To understand the evolution of vertebrate estrogen receptors (ESRs) and to evaluate estrogen receptor-ligand interactions in phylogenetically ancient fish, we used PCR techniques to isolate the cDNA encoding ESRs from lungfish, sturgeon, and gar. Sequence analyses indicate that these fishes have two ESRs, ESR1 (ERα) and ESR2 (ERβ), as previously reported for other vertebrate species, but a second type of ESR2 (ERβ2) was not found as has been reported in a number of teleost fishes. Phylogenetic analysis of the ESR sequences indicated that the lungfish ESRs are classified to the tetrapod ESR group, not with the teleost fish ESRs as are the ESRs from gar and sturgeon. Using transient transfection assays of mammalian cells, ESR proteins from these three ancient fishes displayed estrogen-dependent activation of transcription from an estrogen-responsive-element containing promoter. We also examined the estrogenic potential of o,p′-dichloro-diphenyl-trichloroethane (o,p′-DDT) and p,p′-DDT as well as one of its common metabolites, p,p′-dichloro-diphenyl-ethylene (p,p′-DDE) on the ESRs from these fishes. Lungfish ESR1 was less sensitive to DDT/DDE than the ESR1 from the other two fishes. The response of lungfish ESR1 to these pesticides is similar to the pattern obtained from salamander ESR1. These data provide a basic tool allowing future studies examining the receptor-ligand interactions and endocrine-disrupting mechanisms in three species of phylogenetically ancient fish and also expands our knowledge of ESR evolution.
HPLC with UV or Mass Spectrometric Detection for Quantifying Endogenous Uracil and Dihydrouracil in Human Plasma
Authors: Švobaitė Rūta , Solassol Isabelle , Pinguet Frederic , Ivanauskas Liudas , Brès Janine , Bressolle Françoise M M
Published: July 2008

Background: We developed and compared 2 different methods for quantifying uracil (U) and dihydrouracil (UH2) in BSA and human plasma. Special attention was paid to the selectivity/specificity and the absence of a matrix effect. The UH2/U ratio is intended as a biomarker to identify patients with deficiency in 5-fluorouracil metabolism.

Methods: We quantified U and UH2 with 2 liquid chromatography methods after solid-phase extraction, one with UV detection (LC-UV) and the other with mass spectrometric detection (LC-MS). We selected 2 internal standards to prevent the risk of interferences. Separation was achieved with a Waters Atlantis dC18 column (LC-MS) or a Waters SymmetryShield RP18 column connected with an Atlantis dC18 (LC-UV). Mass spectrometric data were acquired in single-ion monitoring mode.

Results: Assay imprecision in BSA solution was <15% (LC-UV) and <12% (LC-MS); in plasma, assay imprecision was <9.5% and <9.0%, respectively. Recoveries were 88.2%–110% (LC-UV) and 94.8%–107% (LC-MS). Extraction efficiencies were ≥89.0%. In BSA, the lower limits of quantification for U and UH2 were 2.5 μg/L and 6.25 μg/L, respectively, for the LC-UV method and 2.5 μg/L and 3.1 μg/L for LC-MS. The corresponding values in plasma were 11.6 μg/L and 21.5 μg/L, and 4.1 μg/L and 12.1 μg/L.

Conclusions: To estimate endogenous U and UH2 concentrations and their ratio, we recommend the use of a drug-free human plasma pool in which baseline U and UH2 concentrations have previously been measured with the standard-addition method. Our LC-MS method, which has the better test performance and is useful for measuring UH2/U ratios in cancer patients, is preferred when this equipment is available.
Extracellular Sensing and Signalling Pheromones Switch-on Thermotolerance and Other Stress Responses in Escherichia Coli
Authors: Rowbury Robin J. , Goodson Margaret
Published: July 2008

The findings reviewed here overturn a major tenet of bacterial physiology, namely that stimuli which switch-on inducible responses are always detected by intracellular sensors, with all other components and stages in induction also being intracellular. Such an induction mechanism even applies to quorum-sensed responses, and some others which involve functioning of extracellular components, and had previously been believed to occur in all cases. In contrast, for the stress responses reviewed here, triggering is by a quite distinct process, pairs of extracellular components being involved, with the stress sensing component (the extracellular sensing component, ESC) and the signalling component, which derives from it and induces the stress (the extracellular induction component, EIC), being extracellular and the stimulus detection occurring in the growth medium. The ESCs and EICs can also be referred to as extracellular sensing and signalling pheromones, since they are not only needed for induction in the stressed culture, but can act as pheromones in the same region activating other organisms which fail to produce the extracellular component (EC) pair. They can also diffuse to other regions and there act as pheromones influencing unstressed organisms or those which fail to produce such ECs. The cross-talk occurring due to such interactions, can then switch-on stress responses in such unstressed organisms and in those which cannot form the ESC/EIC pair. Accordingly, the ESC/EIC pairs can bring about a form of intercellular communication between organisms. If the unstressed organisms, which are induced to stress tolerance by such extracellular components, are facing impending stress challenge, then the pheromonal activities of the ECs provide an early warning system against stress. The specific ESC/EIC pairs switch-on numerous responses; often these pairs are proteins, but non-protein ECs also occur and for a few systems, full induction needs two ESC/EIC pairs. Most of the above ECs needed for response induction are highly resistant to irreversible inactivation by lethal agents and conditions and, accordingly, many killed cultures still contain ESCs or EICs. If these killed cultures come into contact with unstressed living organisms, the ECs again act pheromonally, altering the tolerance to stress of the living organisms. It has been claimed that bacteria sense increased temperature using ribosomes or the DnaK gene product. The work reviewed here shows that, for thermal triggering of thermotolerance and acid tolerance in E. coli, it is ESCs which act as thermometers.
Fast Trains, Slow Boats, and the Ancestry of the Polynesian Islanders
Authors: Oppenheimer Stephen , Richards Martin
Published: July 2008

The question of the origins of the Polynesians has, for over 200 years, been the subject of adventure science. Since Captain Cook's first speculations on these isolated Pacific islanders, their language affiliations have been seen as an essential clue to the solution. The geographic and numeric centre of gravity of the Austronesian language family is in island Southeast Asia, which was therefore originally seen as their dispersal homeland. However, another view has held sway for 15 years, the ‘out of Taiwan’ model, popularly known as the ‘express train to Polynesia’. This model, based on the combined evidence of archaeology and linguistics, proposes a common origin for all Austronesian-speaking populations, in an expansion of rice agriculturalists from south China/Taiwan beginning around 6,000 years ago. However, it is becoming clear that there is, in fact, little supporting evidence in favour of this view. Alternative models suggest that the ancestors of the Polynesians achieved their maritime skills and horticultural Neolithic somewhere between island Southeast Asia and Melanesia, at an earlier date. Recent advances in human genetics now allow for an independent test of these models, lending support to the latter view rather than the former. Although local gene flow occurring between the bio-geographic regions may have been the means for the dramatic cultural spread out to the Pacific, the immediate genetic substrate for the Polynesian expansion came not from Taiwan, but from east of the Wallace line, probably in Wallacea itself.
The Serpins: Nature's Molecular Mousetraps
Authors: Huntington James A. , Carrell Robin W.
Published: July 2008

A special family of inhibitors, known as the serpins, has evolved an extraordinary mechanism to enable the control of the proteolytic pathways essential to life. The serpins undergo a profound change in conformation to entrap their target protease in an irreversible complex. The solving of the structure of this complex now completes a video depiction of the changes involved. The serpin, just like a mousetrap, is seen to change with a springlike movement from an initial metastable state to a final hyperstable form. The structure shows how this conformational shift not only inhibits the protease but also destroys it. A bonus from these structural insights is the realisation that a number of diseases, as diverse as thrombosis, cirrhosis and dementia, all share a common mechanism arising from similar mutations of different serpins.
The Origin of Life II: How Did it Begin?
Authors: Davies Paul
Published: July 2008

The problem of how a mixture of chemicals can spontaneously transform themselves into even a simple living organism remains one of the great outstanding challenges to science. Various primordial soup theories have been proposed in which chemical self-organization brings about the required level of complexity. Major conceptual obstacles remain, however, such as the emergence of the genetic code, and the “chicken-and-egg” problem concerning which came first: nucleic acids or proteins. Currently fashionable is the so-called RNA world theory, which casts RNA in the role of both chicken and egg. Other theories assume that protein chemistry and even clay crystal life came before nucleic acids. To be fully successful, a theory of biogenesis has to explain not merely the emergence of molecular replication and chemical complexity, but the crucial information content and information processing capabilities of the living cell.
On the Physics of Ferroelectrics
Authors: Webb J. F.
Published: July 2008

The main physical properties of ferroelectric crystals are described, and the macroscopic and microscopic viewpoints are discussed along with some applications, such as in capacitors and nonlinear optics. The emphasis is on physical understanding, while the mathematical level is kept to a minimum or supplemented by graphical representations to make the article more accessible.
The determinants of Lifespan in the Nematode Caenorhabditis Elegans: A Short Primer
Authors: Geanacopoulos Mark
Published: July 2008

Transparent, easily-maintained, amenable to genetic manipulation, and living for only a few weeks, the nematode Caenorhabditis elegans is a leading animal model for the study of the determinants of lifespan. The original genetic screen for increased longevity identified a mutant, age-1, with a defect in one component of a signal transduction pathway. This pathway functioned as a genetic switch and governed the decision whether to enter a specialized larval form, dauer, that enables the worm to withstand the scarcity of food or other stressful conditions. These age-1 worms had an increased tendency to become dauers, but if they did not adopt the dauer developmental pathway, they lived longer than wild type worms. age-1 and other longevity mutants with dauer phenotypes are vigorous, indicating that they do not suffer from a significant energy deficit, and stress resistant. Mutation of genes encoding mitochondrial components was found to be another means of extending the lifespan of the worm, although the associated phenotypes suggest a deficiency of available energy. While there are now many documented genetic manipulations which can extend the worm's lifespan, it has been difficult to come to definite conclusions as to the mechanism (s) by which lifespan is extended. The most carefully studied mutant strains have complex changes in gene expression and metabolism making it difficult to ascertain what changes are critical.

The free radical theory of aging is the dominant biochemical theory of aging, and the phenotypes of the well-characterized longevity mutants worm can be accommodated to it. However discrete interventions to lower reactive oxygen species, or mitigate their effects, have not produced consistent easily-interpretable results in terms of lifespan extension. It has become clear that the insulin-dependent signalling mechanism that regulates lifespan in the worm functions in the context of a complex endocrine system and the hormonal control of aging is an emerging focus of research in worms and higher organisms.
Bacterial Sensitivity to Bacteriophage in the Aquatic Environment
Authors: Day Martin
Published: July 2008

There are several unusual features about phage when you first encounter them as a biologist. They are small, but conform to one of a few morphological types. Next their genomes can be composed of DNA or RNA and be single or double stranded. Finally they are numerically more abundant than prokaryotes and a significant proportion of them form an association in their microbial host populations termed lysogeny. The latter findings indicate that they are numerically significant in microbial populations. Since bacterial and phage abundance or lack of it is related in environments, this implies that the phage populations ‘titrate’ their hosts, and more probably the host's physiological status. Microbial populations wax and wane with nutritional inputs and there is a dynamic relationship between phage population sizes and host numbers and physiology. Overlay this with the different phage life cycle strategies, exemplified at the extremes by phage lambda (temperate) and phage T4 (virulent), then it becomes apparent that phage are a component in nutrient cycling in ecology. But their contribution does not stop there. Many are capable of transduction, moving DNA from one cell into another. So they can also aid the evolutionary progress of microbial populations by allowing them to share genes, just as gene exchange via plasmids and transformation does. Our perception of bacteria has been derived from pure culture studies and we are just being able to appreciate how subtle their ecological interactions are. This is no less true of the studies on bacteriophage, which are almost all based on laboratory experimentation, where the hosts are physiologically stressed by growing in ‘high nutritional and optimum conditions’. The natural environment is naturally discontinuous and life evolved in this. Thus our perceptions of bacteriophage and their life cycle patterns derived from laboratory experimentation may be a little off the mark when we come to understand how they and their hosts interact in the niches available to them. It is worth just considering this as you read the article, as I suspect phage behaviours are more intimately involved in, and moderated by the physiological stresses in the life cycle of bacteria than we currently believe.
Endophytes — the Chemical Synthesizers inside Plants
Authors: Owen Noel L. , Hundley Nicholas
Published: July 2008

Endophytes are microbial entities that live within living tissues of plants. In most cases their relationship with the host plant is symbiotic and probably mutualistic. Many are capable of synthesizing bio-active compounds that can be used by the plant for defense against pathogenic fungi and bacteria. Some of these compounds have proven useful for novel drug discovery. By encouraging the endophytes to grow outside the plant in nutrient rich media, it is possible to harvest the bio-active compounds that they produce. However, much needs to be discovered and understood about the host/endophyte relationship before we can fully utilize endophytes in the discovery of medicinally important compounds.
Superconductivity
Authors: Grosche F. M.
Published: July 2008

Electrons in metals can self-organise. The complex interplay between lattice dynamics, electrostatic interaction and band structure brings forth numerous types of electronic order. Because of its spectacular phenomenology, superconductivity has enjoyed a central place among these, since its discovery nearly 100 years ago. This short introduction into one of the largest fields of condensed matter research focuses on the most fundamental experimental signatures of superconductivity – perfect conductivity and perfect diamagnetism – and their explanation. A conventional broken symmetry argument is presented, which introduces a superconducting order parameter in analogy to the case of superfluid 4He, and discusses its microscopic origin in the framework of the BCS model of superconductivity. New materials have brought to light novel forms of superconductivity. Many cases are now known which fall outside the orthodox BCS model, ranging from the high temperature superconductors, to various organic and d- and f- metal compounds. The article presents key concepts from this intense area of research and touches on the equally puzzling behaviour of many of these materials above their superconducting transition temperature.
Compatible and Counteracting Solutes: Protecting Cells from the Dead Sea to the Deep Sea
Authors: Yancey Paul H.
Published: July 2008

Cells of many organisms accumulate certain small organic molecules -called compatible and counteracting solutes, compensatory solutes, or chemical chaperones – in response to certain physical stresses. These solutes include certain carbohydrates, amino acids, methylamine and methylsulphonium zwitterions, and urea. In osmotic dehydrating stress, these solutes serve as cellular osmolytes. Unlike common salt ions and urea (which inhibit proteins), some organic osmolytes are compatible; i.e., they do not perturb macromolecules such as proteins. In addition, some may protect cells through metabolic processes such as antioxidation reactions and sulphide detoxification. Other osmolytes, and identical or similar solutes accumulated in anhydrobiotic, heat and pressure stresses, are termed counteracting solutes or chemical chaperones because they stabilise proteins and counteract protein-destabilising factors such as urea, temperature, salt, and hydrostatic pressure. Stabilisation of proteins, not necessarily beneficial in the absence of a perturbant, may result indirectly from effects on water structure. Osmotic shrinkage of cells activates genes for chaperone proteins and osmolytes by mechanisms still being elucidated. These solutes have applications in agriculture, medicine and biotechnology.
Intracellular and Extracellular Components as Bacterial Thermometers, and Early Warning against Thermal Stress
Authors: Rowbury Robin J.
Published: July 2008

Responses induced by cold or heat are triggered following detection of temperature changes by specific sensing molecules, complexes or structures. Low temperature responses are often induced following sensing of cold-induced falls in membrane fluidity, such changes turning-on or -off enzymic activities in membrane proteins, although ribosomes and DNA may also function in cold perception. Many thermal sensors are components of structures damaged by the heat, with sensing involving changes to ribosomes, DNA, intracellular proteins and, less commonly, membrane fluidity. Additionally, secreted proteins (extracellular sensing components, ESCs) detect temperature increases i.e. act as thermometers, with ESC activation in the medium, by the stimulus, converting such sensors to extracellular signalling molecules, the extracellular induction components (EICs), which induce thermal responses. Several ESC/EIC pairs trigger thermal responses, and have the unique property of giving early warning of the stress by diffusing to regions (and organisms) not yet exposed to elevated temperatures.
Making sense of Lanthanide Luminescence
Authors: Werts Martinus H.V.
Published: July 2008

The luminescence of trivalent lanthanide ions has found applications in lighting, lasers, optical telecommunications, medical diagnostics, and various other fields. This introductory review presents the basics of organic and inorganic luminescent materials containing lanthanide ions, their applications, and some recent developments. After a brief history of the discovery, purification and early spectroscopic studies of the lanthanides, the radiative and nonradiative transitions of the 4f electrons in lanthanide ions are discussed. Lanthanide-doped phosphors, glasses and crystals as well as luminescent lanthanide complexes with organic ligands receive attention with respect to their preparation and their applications. Finally, two recent developments in the field of luminescent materials are addressed: near-infrared luminescent lanthanide complexes and lanthanide-doped nanoparticles.
Molecular engineering of Surfaces Using Self-Assembled Monolayers
Authors: Whitesides George M. , Kriebel Jennah K. , Love J. Christopher
Published: July 2008

The self-assembly of molecules into structurally organized monolayers (SAMs) uses the flexibility of organic chemistry and coordination chemistry to generate well-defined, synthetic surfaces with known molecular and macroscopic properties. The process of designing monolayers with a specified structure gives a high level of control over the molecular-level composition in the direction perpendicular to a surface; soft lithographic technique gives useful (if lower) resolution in the plane of the surface. Alkanethiolates adsorbed on gold, silver, mercury, palladium and platinum are currently the best-defined systems of SAMs. They provide substrates for a number of applications-from studies of wetting and electron transport to patterns for growing mammalian cells. SAMs have made organic surfaces a central part of surface science. Understanding the principles by which they form, and connecting molecular-level structure with macroscopic properties, opens a wide range of areas to study and exploitation.
Patho-Biotechnology; Using Bad Bugs to Make Good Bugs Better
Authors: Sleator Royd , Hill Colin
Published: July 2008

Given the increasing commercial and clinical relevance of probiotic cultures, improving their stress tolerance profile and ability to overcome the physio-chemical defences of the host is an important biological goal. Pathogenic bacteria have evolved sophisticated strategies to overcome host defences, interact with the immune system and interfere with essential host systems. We coin the term ‘patho-biotechnology’ to describe the exploitation of these valuable traits in biotechnology and biomedicine. This approach shows promise for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications as well as the development of novel vaccine and drug delivery platforms.
Efficient TiO2 Photocatalysts from Surface Hybridization of TiO2 Particles with Graphite‐like Carbon
Authors: Zhang Li‐Wu , Fu Hong‐Bo , Zhu Yong‐Fa
Published: July 2008

Surface hybridization of TiO2 with graphite‐like carbon layers of a few molecular layers thickness yields efficient photocatalysts. Photoelectrochemical measurements confirm an electronic interaction between TiO2 and the graphite‐like carbon. A TiO2 photocatalyst with a carbon shell of three molecular layers thickness (∼1 nm) shows the highest photocatalytic activity which is about two times higher than that of Degussa P25 TiO2 under UV light irradiation. The mechanism of the enhanced photocatalytic activity under UV irradiation is based on the high migration efficiency of photoinduced electrons at the graphite‐like carbon/TiO2 interface, which is due to the electronic interaction between both materials. In addition, a high activity under visible light irradiation is observed after graphite‐like carbon hybridization. TiO2's response is extended into the visible range of the solar spectrum due to the electronic coupling of π states of the graphite‐like carbon and conduction band states of TiO2.
Templateless Synthesis of Polygonal Gold Nanoparticles: An Unsupported and Reusable Catalyst with Superior Activity
Authors: Rashid Md. Harunar , Mandal Tarun K.
Published: July 2008

We report the synthesis of polygonal gold nanoparticles (GNPs) by an in situ reduction technique using ferric ammonium citrate as reducing agent in absence of any surfactant or polymeric template. Transmission electron microscopic analysis and selected area electron diffraction patterns confirmed the formation of well‐crystalline polygonal GNPs grown preferentially along the (111) direction, which is consistent with the results of X‐ray diffractometry analysis. The results of control experiments of HAuCl4 with tri‐ammonium citrate in presence of different externally added metal ions like Fe3+, Ni2+, Cu2+, Zn2+, and Al3+ suggested the ion‐induced growth mechanism in the formation of polygonal GNPs. The purified polygonal GNPs were then successfully used as catalyst in the borohydride reduction of three isomeric nitrophenols and also in the aerobic oxidation of different D‐hexoses (e.g., D‐glucose, D‐mannose, D‐fructose). The catalytic activity of these polygonal GNPs is higher by a factor of 300–1000, depending on the GNP's sample type, in nitrophenol reduction compared to that of spherical GNPs. Similar activity enhancement was also observed in the aerobic oxidation of different D‐hexoses. These polygonal GNPs catalyst are very stable and could be reused several times in the borohydride reduction of nitrophenols without much losing in their virgin catalytic activity.
Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder
Authors: Campbell Daniel B. , Li Chun , Sutcliffe James S. , Persico Antonio M. , Levitt Pat
Published: July 2008

A functional promoter variant of the gene encoding the MET receptor tyrosine kinase alters SP1 and SUB1 transcription factor binding, and is associated with autism spectrum disorder (ASD). Recent analyses of postmortem cerebral cortex from ASD patients revealed altered expression of MET protein and three transcripts encoding proteins that regulate MET signaling, hepatocyte growth factor (HGF), urokinase plasminogen activator receptor (PLAUR) and plasminogen activator inhibitor‐1 (SERPINE1). To address potential risk conferred by multiple genes in the MET signaling pathway, we screened all exons and 5′ promoter regions for variants in the five genes encoding proteins that regulate MET expression and activity. Identified variants were genotyped in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls. Replicating our initial findings, family‐based association test (FBAT) analyses demonstrated that the MET promoter variant rs1858830 C allele was associated with ASD in 101 new families (P=0.033). Two other genes in the MET signaling pathway also may confer risk. A haplotype of the SERPINE1 gene exhibited significant association. In addition, the PLAUR promoter variant rs344781 T allele was associated with ASD by both FBAT (P=0.006) and case–control analyses (P=0.007). The PLAUR promoter rs344781 relative risk was 1.93 (95% confidence interval [CI]: 1.12–3.31) for genotype TT and 2.42 (95% CI: 1.38–4.25) for genotype CT compared to genotype CC. Gene–gene interaction analyses suggested a significant interaction between MET and PLAUR. These data further support our hypothesis that genetic susceptibility impacting multiple components of the MET signaling pathway contributes to ASD risk.
Development of a fatigue and functional impact scale in anemic cancer patients receiving chemotherapy
Authors: Cella David , Viswanathan Hema N. , Hays Ron D. , Mendoza Tito R. , Stein Kevin D. , Pasta David J. , Foreman Aimee J. , Vadhan‐Raj Saroj , Kallich Joel D.
Published: July 2008

BACKGROUND.

This study was conducted to develop a brief measure of fatigue and functional impact in cancer patients with anemia.

METHODS.

Data were obtained from a multisite, phase 2 study of darbepoetin‐α (n = 1558). Eligible patients were ≥18 years with nonmyeloid malignancies and anemia (hemoglobin ≤11 g/dL) who were receiving chemotherapy. Items from the Functional Assessment of Cancer Therapy‐Fatigue (FACT‐F), Brief Fatigue Inventory (BFI), Fatigue Symptom Inventory (FSI), and items adapted from the Medical Outcomes Study SF‐36 physical functioning scale were evaluated for inclusion in the measure. Items were selected by identifying the best predictors of total FACT‐F scores, hemoglobin, and adjusted maximum oxygen uptake (VO2Max) in regression models. Correlations were examined between scale scores and adjusted VO2Max, hemoglobin, performance status, self‐reported energy, and productivity.

RESULTS.

Data from 401 patients with complete data were used to identify 8 items for the Fatigue and Functional Impact Scale (FFIS), which was then evaluated using 1355 of the 1558 patients. The FFIS had an estimated internal consistency reliability of 0.90. The FFIS had significant correlations with the FACT‐F (r = 0.94), FSI (r = 0.80), and BFI (r = 0.86), from which it was derived. The FFIS also correlated substantially with single‐item measures of energy (r = 0.75) and productivity (r = 0.72).

CONCLUSIONS.

The FFIS is a reliable, brief, and practical tool that is potentially suitable for identifying fatigue and functional impact in cancer patients. Cancer 2008. © 2008 American Cancer Society.
Assessment of a high‐order finite difference upwind scheme for the simulation of convection–diffusion problems
Authors: Ferreira V. G. , Kurokawa F. A. , Queiroz R. A. B. , Kaibara M. K. , Oishi C. M. , Cuminato J. A. , Castelo A. , Tomé M. F. , McKee S.
Published: July 2008

This article deals with the study of the development and application of the high‐order upwind ADBQUICKEST scheme, an adaptative bounded version of the QUICKEST for unsteady problems (Commun. Numer. Meth. Engng 2007; 23:419–445), employing both linear and nonlinear convection term discretization. This scheme is applicable to a wide range of computational fluid dynamics problems, where transport phenomena are of special importance. In particular, the performance of the scheme is assessed through an extensive numerical simulation study of advection–diffusion problems. The scheme, implemented in the context of finite difference methodology, combines a good approximation of shocks (or discontinuities) with a good approximation of the smooth parts of the solutions. In order to assess the performance of the scheme, seven problems are solved, namely (a) advection of scalars; (b) non‐linear viscous Burgers equation; (c) Euler equations of gas dynamics; (d) Newtonian flow in a channel; (e) axisymmetric Newtonian jet flow; (f) axisymmetric non‐Newtonian (generalized Newtonian) flow in a pipe; and (g) collapse of a fluid column. The numerical experiments clearly show that the scheme provides more consistent solutions than those found in the literature. From the study, the flexibility and robustness of the ADBQUICKEST scheme is confirmed by demonstrating its capability to solve a variety of linear and nonlinear problems with and without discontinuous solutions. Copyright © 2008 John Wiley & Sons, Ltd.
Pseudoaneurysm of the external carotid artery—Review of literature
Authors: Nadig Shri , Barnwell Stanley , Wax Mark K.
Published: July 2008

Background.

Pseudoneurysms of the carotid artery are rarely encountered in clinical practice. When encountered they are most likely secondary to acute neck trauma, and involve the internal carotid. External carotid artery involvement is very rare.

Methods.

We report a case of an external carotid aneurysm following a neck dissection review the literature and discuss the investigation and management of these unusual lesions.

Results.

Incidence is 0.07%, but mortality can be as high as 30%. Clinical features include swelling and neurological complications. Diagnosis is with a high index of suspicion and imaging with duplex ultrasonography and CT angiography. Management options include observation, anticoagulation, ligation of the carotid artery with or without a bypass procedure, and arterial reconstruction.

Conclusion.

Early management with appropriate imaging and treatment to prevent significant mortality and morbidity is recommended. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
DNA copy number variation and loss of heterozygosity in relation to recurrence of and survival from head and neck squamous cell carcinoma: A review
Authors: Chen Yu , Chen Chu
Published: July 2008

Genetic aberrations, such as DNA copy number variation (CNV) and loss of heterozygosity (LOH), have been implicated in head and neck squamous cell carcinoma (HNSCC) initiation and progression. This review examines CNV and LOH as predictors of HNSCC recurrence and mortality. We searched PubMed for relevant publications and compared and discussed results from the articles. Certain CNV and LOH events have consistently been associated with HNSCC recurrence and survival. The recent high‐resolution single nucleotide polymorphism (SNP) arrays have the potential to identify many more genetic changes and concurrent genome‐wide CNV, copy‐neutral and/or allelic imbalance LOH in HNSCC that may bear on prognosis. Our review confrms that outcome in HNSCC can be predicted to a considerable extent by the presence of tumor cell genetic aberrations. It points out the limitations of some methodologies that were used in the past and discusses the advantages and challenges of using genome‐wide SNP arrays. © 2008 Wiley Periodicals, Inc. Head Neck 2008
Prognostic value of primary tumor volume after concurrent chemoradiation with daily low‐dose cisplatin for advanced‐stage head and neck carcinoma
Authors: Hoebers Frank J. P. , Pameijer Frank A. , de Bois Josien , Heemsbergen Wilma , Balm Alfons J. M. , Schornagel Jan H. , Rasch Coen R. N.
Published: July 2008

Background.

The purpose of this study was to evaluate the prognostic value of tumor volume in head and neck squamous cell carcinoma treated with chemoradiation.

Methods.

Forty‐six patients were treated with radiotherapy and cisplatin (6 mg/m2 IV x20, daily). Baseline primary tumor volume was recorded from MRI scans. The prognostic impact of tumor volume and other factors for locoregional control, disease‐free survival (DFS), and overall survival (OS) was tested.

Results.

Mean tumor volume was 28 cm3 (median 23 cm3; range, 3–112). The locoregional control rate at 3 years was 81% for patients with tumor volumes <median compared to 48% for tumor volumes ≥ median (p = .036). At multivariate analysis, it appeared that tumor volume remained an independent determinant of locoregional control and survival when adjusted for other factors.

Conclusions.

In advanced‐stage head and neck squamous cell carcinoma treated with concurrent chemoradiation, primary tumor volume is associated with locoregional control and survival. Larger studies are needed to confirm whether incorporation of tumor volume in the staging system improves prediction of treatment outcome and can serve as a tool to guide treatment options. © 2008 Wiley Periodicals, Inc. Head Neck 2008
Molecular signatures of metastasis in head and neck cancer
Authors: Colella Stefano , Richards Kristy L. , Bachinski Linda L. , Baggerly Keith A. , Tsavachidis Spiridon , Lang James C. , Schuller David E. , Krahe Ralf
Published: July 2008

Background.

Metastases are the primary cause of cancer treatment failure and death, yet metastatic mechanisms remain incompletely understood.

Methods.

We studied the molecular basis of head and neck cancer metastasis by transcriptionally profiling 70 samples from 27 patients—matching normal adjacent tissue, primary tumor, and cervical lymph node metastases.

Results.

We identified tumor‐associated expression signatures common to both primary tumors and metastases. Use of matching metastases revealed an additional 46 dysregulated genes associated solely with head and neck cancer metastasis. However, despite being metastasis‐specific in our sample set, these 46 genes are concordant with genes previously discovered in primary tumors that metastasized.

Conclusions.

Although our data and related studies show that most of the metastatic potential appears to be inherent to the primary tumor, they are also consistent with the notion that a limited number of additional clonal changes are necessary to yield the final metastatic cell(s), albeit in a variable temporal order. © 2008 Wiley Periodicals, Inc. Head Neck 2008