bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between Language and Music
Authors: BESSON MIREILLE , SCHÖN DANIELE
Published: July 2010

Abstract:Similarities and differences between language and music processing are examined from an evolutionary and a cognitive perspective. Language and music cannot be considered single entities; they need to be decomposed into different component operations or levels of processing. The central question concerns one of the most important claims of the generative grammar theory, that is, the specificity of language processing: do the computations performed to process language rely on specific linguistic processes or do they rely on general cognitive principles? Evidence from brain imaging results is reviewed, noting that this field is currently in need of metanalysis of the available results to precisely evaluate this claim. A series of experiments, mainly using the event‐related brain potentials method, were conducted to compare different levels of processing in language and music. Overall, results favor language specificity when certain aspects of semantic processing in language are compared with certain aspects of melodic and harmonic processing in music. By contrast, results support the view that general cognitive principles are involved when aspects of syntactic processing in language are compared with aspects of harmonic processing in music. Moreover, analysis of the temporal structure led to similar effects in language and music. These tentative conclusions must be supported by other brain imaging results to shed further light on the spatiotemporal dynamics of the brain structure‐function relationship.
Medical Mimics
Authors: PEARL PHILLIP L. , WEISS ROY E. , STEIN MARK A.
Published: July 2010

Abstract: The medical and neurological conditions that simulate ADHD are reviewed, as well as those disorders frequently presenting as comorbidities with ADHD. The localization of ADHD has invoked multiple areas, including frontal lobes, nondominant parietal lobe, and basal ganglia, and the neural network theory of cortical‐subcortical‐cortical loops has been implicated in the pathogenesis of ADHD. The medical evaluation of patients presenting with ADHD should be comprehensive, with an emphasis on demonstrating chronic and permeating symptoms since early childhood without a better medical explanation. Associated thyroid disorders are reviewed, including the syndrome of resistance to thyroid hormone. Suggested laboratory studies are provided, depending on the clinical circumstances.
Recognizing and Responding to a Suicide Crisis
Authors: Hendin Herbert , Maltsberger John T. , Lipschitz Alan , Haas Ann Pollinger , Kyle Jennifer
Published: July 2010

Abstract: Data from therapists who were treating 26 patients when they committed suicide were utilized to identify signs that warned of a suicide crisis. Three factors were identified as markers of the suicide crisis: a precipitating event; one or more intense affective states other than depression; and at least one of three behavioral patterns: speech or actions suggesting suicide, deterioration in social or occupational functioning, and increased substance abuse. Problems in communication between patient and therapist, often originating in therapeutic anxiety over the patient's possible suicide, were identified as factors interfering with crisis recognition. Evaluation of the identified affects and behaviors may help therapists recognize a suicide crisis.
Suicide and the Media
Authors: Gould Madelyn S.
Published: July 2010

Abstract:Evidence continues to amass on the significant impact of media coverage on suicide. The research literature on the impact of news reports of nonfictional suicides as well as fictional suicide stories is reviewed in order to determine the nature and scope of the influence of the mass media on suicide. The current review, building upon earlier reviews, is limited to English language publications or English translations of articles and/or abstracts. The interactive factors that may moderate the impact of media stories are also reviewed. Such interactive factors include characteristics of the stories (agent), individuals' attributes (host), and social context of the stories (environment). Recommendations are presented for the reporting of suicide stories, which may minimize the risk of imitative suicides. The media's positive role in educating the public about risks for suicide and shaping attitudes about suicide is emphasized. In summary, the existence of suicide contagion no longer needs to be questioned. We should refocus our research efforts on identifying which particular story components promote contagion under which circumstances and which components are useful for preventive programming.
Controlled Exposures to Volatile Organic Compounds in Sensitive Groups
Authors: Fiedler Nancy , Kipen Howard M.
Published: July 2010

Abstract: Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low‐level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen's 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self‐reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE‐sensitive). All studies include comparison of age‐ and sex‐matched healthy controls. Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose‐response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE‐sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end‐tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals. For example, Gulf War veterans with CFS/CS experienced reduced end‐tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psycho‐physiologic changes in MTBE‐sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de‐adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.
The Iowa Follow‐up of Chemically Sensitive Persons
Authors: Black Donald W. , Okiishi Christopher , Schlosser Steven
Published: July 2010

Abstract: Clinical symptoms and self‐reported health status in persons reporting multiple chemical sensitivities (MCS) are presented from a 9‐year follow‐up study. Eighteen (69%) subjects from a sample of 26 persons originally interviewed in 1988 were followed up in 1997 and given structured interviews and self‐report questionnaires. In terms of psychiatric diagnosis, 15 (83%) met DSM‐IV criteria for a lifetime mood disorder, 10 (56%) for a lifetime anxiety disorder, and 10 (56%) for a lifetime somatoform disorder. Seven (39%) of subjects met criteria for a personality disorder using the Personality Diagnostic Questionnaire‐IV. Self‐report data from the Illness Behavior Questionnaire and Symptom Checklist‐90‐Revised show little change from 1988. The 10 most frequent complaints attributed to MCS were headache, memory loss, forgetfulness, sore throat, joint aches, trouble thinking, shortness of breath, back pain, muscle aches, and nausea. Global assessment showed that 2 (11%) had “remitted”, 8 (45%) were “much” or “very much” improved, 6 (33%) were “improved”, and 2 (11%) were “unchanged/worse”. Mean scores on the SF‐36 health survey showed that, compared to U.S. population means, subjects reported worse physical functioning, more bodily pain, worse general health, worse social functioning, and more emotional‐role impairment; self‐reported mental health was better than the U.S. population mean. All subjects maintained a belief that they had MCS; 16 (89%) acknowledged that the diagnosis was controversial. It is concluded that the subjects remain strongly committed to their diagnosis of MCS. Most have improved since their original interview, but many remain symptomatic and continue to report ongoing lifestyle changes.
Does the Kindling Model of Epilepsy Contribute to Our Understanding of Multiple Chemical Sensitivity?
Authors: Gilbert M. E.
Published: July 2010

Abstract: Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report an increased sensitivity to low levels of chemicals in the environment. Kindling is a model of synaptic plasticity whereby repeated low‐level electrical stimulation to a number of brain sites leads to permanent increases in seizure susceptibility. Stimulation that is initially subthreshold for subclinical seizure provocation comes, over time, to elicit full‐blown motor seizures. Kindling can also be induced by chemical stimulation, and repeated exposures to some pesticides have been shown to induce signs of behavioral seizure, facilitate subsequent electrical kindling, and induce subclinical electrographic signs of hyperexcitability in the amygdala. Many of the symptoms of MCS suggest that CNS limbic pathways involved in anxiety are altered in individuals reporting MCS. Limbic structures are among the most susceptible to kindling‐induced seizures, and persistent cognitive and emotional sequelae have been associated with temporal lobe epilepsy (TLE) in humans and kindling in animals. Thus, a number of parallels exist between kindling and MCS phenomena, leading to initial speculations that MCS may occur via a kindling‐like mechanism. However, kindling requires the activation of electrographic seizure discharge and has thus been primarily examined as a model for TLE. Events leading to the initial evocation of a subclinical electrographic seizure have been much less well studied. It is perhaps these events that may serve as a more appropriate model for the enhanced chemical responsiveness characteristic of MCS. Alternatively, kindling may be useful as a tool to selectively increase sensitivity in subcomponents of the neural fear circuit to address questions relating the role of anxiety in the development and expression of MCS.
Episodic Exposures to Chemicals
Authors: MacPhail R. C.
Published: July 2010

Abstract: Episodic exposures refer to intermittent acute exposures to chemicals that ordinarily have a rapid onset and short duration of effect. There has been a long tradition in preclinical behavioral pharmacology of using episodic‐exposure paradigms in order to establish dose‐response functions in individual organisms. In these experiments, stable baselines of behavior are first established and then followed by administering varying doses of a drug intermittently, for example, once or twice a week. The power of this approach is well established; the within‐subjects design reduces error variance, allows exploration of the entire range of effective doses, and can be used to identify individual differences in drug sensitivity. Of course, the approach is only applicable to reversibly acting compounds, and checks need to be included to insure effects of one dose are not influenced by prior exposure to another dose. We have used baseline approaches to evaluate the effects of pesticides and solvents on the behavior of adult male rats and mice. Moreover, a novel probabilistic dose‐tolerance analysis applied to the data suggests substantial individual differences in chemical sensitivity, often spanning orders of magnitude. These results suggest that individual differences in chemical sensitivity may be much greater than previously acknowledged.
Spinal Cord Neuroplasticity following Repeated Opioid Exposure and Its Relation to Pathological Pain
Authors: Mao Jianren , Mayer David J.
Published: July 2010

Abstract:Convincing evidence has accumulated that indicates neuroplastic changes within the spinal cord in response to repeated exposure to opioids. Such neuroplastic changes occur at both cellular and intracellular levels. It has been generally acknowledged that the activation ofN‐methyl‐d‐aspartate (NMDA) receptors plays a pivotal role in the development of neuroplastic changes following repeated opioid exposure. Intracellular cascades can also be activated subsequent to NMDA receptor activation. In particular, protein kinase C has been shown to be a key intracellular element that contributes to the behavioral manifestation of neuroplastic changes. Moreover, interactions between NMDA and opioid receptors can lead to potentially irreversible degenerative neuronal changes in the spinal cord in association with the development of opioid tolerance. Interestingly, similar cellular and intracellular changes occur in the spinal cord following peripheral nerve injury. These findings indicate that interactions exist in the spinal cord neural structures between two seemingly unrelated conditions—chronic opioid exposure and a pathological pain state. These observations may help understand mechanisms of chemical intolerance and multiple chemical sensitivity as well as have significant clinical implications in pain management with opioid analgesics.
Role of Gaseous Neurotransmitters in the Hypothalamic‐Pituitary‐Adrenal Axis
Authors: Rivier Catherine
Published: July 2010

Abstract: Nitric oxide (NO) is an unstable gas that plays important roles in the brain in general and in neuroendocrine functions in particular. We have shown that NO exerts opposite effects within the median eminence‐pituitary axis, where it inhibits ACTH responses to blood‐borne signals [such as the systemic injection of proinflammatory cytokines or vasopressin (VP)], and structures protected by the blood‐brain barrier, where it stimulates the synthesis of the hypothalamic peptides, corticotropin‐releasing factor (CRF) and VP. As a result, when an animal is exposed to stimuli that acutely activate the paraventricular nucleus of the hypothalamus as well as the release of peptides from nerve terminals (such as mild inescapable foot shocks), the net influence of NO on the ACTH response will represent the balance between these two effects. Based on experiments conducted with rats, we propose that, in shocks of low intensity, ACTH release primarily depends, at least in the initial phase, on the interaction between NO and VP (and consequently is augmented by reagents that block NO formation); in shocks of higher intensity, the interaction between NO and the hypothalamus predominates (i.e., it is inhibited by reagents that block NO formation).
A Review of Turbine Blade Tip Heat Transfer
Authors: BUNKER RONALD S.
Published: July 2010

Abstract: This paper presents a review of the publicly available knowledge base concerning turbine blade tip heat transfer, from the early fundamental research which laid the foundations of our knowledge, to current experimental and numerical studies utilizing engine‐scaled blade cascades and turbine rigs. Focus is placed on high‐pressure, high‐temperature axial‐turbine blade tips, which are prevalent in the majority of today's aircraft engines and power generating turbines. The state of our current understanding of turbine blade tip heat transfer is in the transitional phase between fundamentals supported by engine‐based experience, and the ability to a priori correctly predict and efficiently design blade tips for engine service.
Jet‐Impingement Heat Transfer in Gas Turbine Systems
Authors: HAN B. , GOLDSTEIN R. J.
Published: July 2010

Abstract: A review of jet‐impingement heat transfer in gas turbine systems is presented. Characteristics of the different flow regions for submerged jets ‐ free jet, stagnation flow, and wall jet ‐ are reviewed. Heat transfer characteristics of both single and multiple jets are discussed with consideration of the effects of important parameters relevant to gas turbine systems including curvature of surfaces, crossflow, angle of impact, and rotation.
Effect of Reynolds Number, Turbulence Level and Periodic Wake Flow on Heat Transfer on Low Pressure Turbine Blades.
Authors: SUSLOV DMITRY , SCHULZ ACHMED , WITTIG SIGMAR
Published: July 2010

Abstract: The development of effective cooling methods is of major importance for the design of new gas turbines blades. The conception of optimal cooling schemes requires a detailed knowledge of the heat transfer processes on the blade's surfaces. The thermal load of turbine blades is predominantly determined by convective heat transfer which is described by the local heat transfer coefficient.

Heat transfer is closely related to the boundary layer development along the blade surface and hence depends on various flow conditions and geometrical parameters. Particularly Reynolds number, pressures gradient and turbulence level have great impact on the boundary layer development and the according heat transfer. Therefore, in the present study, the influence of Reynolds number, turbulence intensity, and periodic unsteady inflow on the local heat transfer of a typical low pressure turbine airfoil is experimentally examined in a plane cascade.
Effects of Bulk Flow Pulsations on Film Cooling with Shaped Holes
Authors: LEE HONG‐WOOK , LEE JOON SIK
Published: July 2010

Abstract: Experimental results are presented which describe the effects of bulk flow pulsations on injectant behavior and film cooling performance around shaped holes with compound angle orientations. The shaped holes have a 15° forward expansion with an inclination angle of 35°. The orientation angles considered are 0°, 30°, and 60°. The pulsation frequency is fixed at 32 Hz, but changes in the time‐averaged blowing ratios of 0.5, 1.0, and 2.0 produce three different coolant Strouhal numbers. Flow visualization shows that bulk flow pulsations cause significant periodic variations of the injectant flow rate, and produce severe crossflow ingestion at a high coolant Strouhal number. Although shaped holes show improved film coverage compared to round holes under steady condition, shaped holes are so sensitive to flow pulsations that a drastic reduction in the film cooling performance is observed at a high coolant Strouhal number.
Characteristics of Various Film Cooling Jets Injected in a Conduit
Authors: TAKAHASHI HIRONORI , NUNTADUSIT CHAYUT , KIMOTO HIDEO , ISHIDA HIDESHI , UKAI TAKEOMI , TAKEISHI KENICHIRO
Published: July 2010

Abstract: In the present study, film cooling characteristics by the jets through various easy‐to‐make straight holes and slots have been investigated. In this experiment, seven kinds of injection geometries were used. They were circular, rectangular, elliptic and oval holes and slots, respectively.
Finite Element Analysis of Flowfield in the Single Hole Film Cooling Technique
Authors: BAZDIDI‐TEHRANI F. , MAHMOODI A. A.
Published: July 2010

Abstract: Film cooling is currently used in gas turbine hot sections, such as the combustor wall and the turbine blades, to prevent those sections from failing at elevated temperatures. In the single hole film cooling method, coolant air is injected from a hole into the mainstream and thus the flow is naturally three dimensional. In this paper, the Navier‐Stokes and the energy equations are solved on a flat plate by the Finite Element Method (FEM) using brick elements. Algebraic equations are obtained by use of the Petrov‐Galerkin method. The pressure term is removed from the momentum equations, by employing the Penalty method. The governing equations are transient and the flow is incompressible and turbulent. The model of turbulence in the near wall region is the wall function method, and in the fully turbulent region is the k‐ε model. The system of the algebraic equations are solved by the Frontal method. The coolant injection angle and the blowing rate are among the parameters which are studied. In order to examine the present computer code, the results are compared with the Blasius (exact) solution and also with the empirical 1/7th power‐law and good agreement is shown. Also, the optimum cooling performance is shown to be at 35 degree angle of coolant injection and the optimum blowing rate is 0.5. The film cooling effectiveness data, at the optimum conditions, is directly compared with the experimental results of Goldstein et al.16 and good agreement is demonstrated.
Mach Number Effect On Jet Impingement Heat Transfer
Authors: BREVET P. , DORIGNAC E. , VULLIERME J.J.
Published: July 2010

Abstract: An experimental investigation of heat transfer from a single round free jet, impinging normally on a flat plate is described. Flow at the exit plane of the jet is fully developed and the total temperature of the jet is equal to the ambient temperature. Infrared measurements lead to the characterization of the local and averaged heat transfer coefficients and Nusselt numbers over the impingement plate. The adiabatic wall temperature is introduced as the reference temperature for heat transfer coefficient calculation. Various nozzle diameters from 3 mm to 15 mm are used to make the injection Mach number M vary whereas the Reynolds number Re is kept constant. Thus the Mach number influence on jet impingement heat transfer can be directly evaluated. Experiments have been carried out for 4 nozzle diameters, for 3 different nozzle‐to‐target distances, with Reynolds number ranging from 7200 to 71500 and Mach number from 0.02 to 0.69. A correlation is obtained from the data for the average Nusselt number.
Development of Non‐destructive Inspection Method for the Performance of Thermal Barrier Coating
Authors: MORINAGA M. , TAKAHASHI T.
Published: July 2010

Abstract: This paper shows that our proprietary non‐destructive inspection method can be used to effectively measure the thermal barrier performance of the thermal barrier coating used to coat gas turbine hot parts by the results of numerical analysis and laboratory experiments.
Pharmacological Interventions against Aging through the Cell Plasma Membrane
Authors: ZS.‐NAGY IMRE
Published: July 2010

As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928:187‐199, 2001), oxyradicals cannot be considered only as harmful by‐products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site‐specific, radical‐induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH•free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane‐related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE‐001 is also reported.
Coenzyme Q10 Protects the Aging Heart against Stress
Authors: ROSENFELDT FRANKLIN L. , PEPE SALVATORE , LINNANE ANTHONY , NAGLEY PHILIP , ROWLAND MICHAEL , OU RUCHONG , MARASCO SILVANA , LYON WILLIAM , ESMORE DONALD
Published: July 2010

With aging of the population, increasing numbers of elderly patients are presenting for cardiac surgery. However, the results in the elderly are inferior to those in the young. A likely contributing factor is an age‐related reduction in cellular energy production in the myocardium during surgery, which is known to induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to improve energy production in mitochondria by bypassing defective components in the respiratory chain as well as by reducing the effects of oxidative stress. We hypothesized that CoQ10 pretreatment prior to stress could improve the recovery of the myocardium after stress.
Mitochondrial Damage in Aging and Apoptosis
Authors: SASTRE JUAN , BORRÁS CONSUELO , GARCÍA‐SALA DAVID , LLORET ANA , PALLARDÓ FEDERICO V. , VIÑA JOSÉ
Published: July 2010

Mitochondria are essential to cellular aging, and free radical production by mitochondria is increased with aging. The rate of oxidant production by mitochondria correlates inversely with maximal life span of species. In many species, females live longer than males. We report that mitochondrial oxidant production by females is significantly lower than that of males. However, mitochondria from ovariectomized females have a similar oxidant production as those of males. Thus, gender difference in life span can be explained, at least in part, by different oxidant generation by mitochondria. Administration of antioxidants, such as vitamins C and E, or a Ginkgo biloba extract, protects against age‐associated oxidative damage to mitochondrial DNA, oxidation of glutathione, and other signs of oxidative damage to mitochondria.
Theiler's Virus‐Mediated Autoimmunity
Authors: TOMPKINS S. MARK , FULLER KEVIN G. , MILLER STEPHEN D.
Published: July 2010

Abstract: Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a neurotropic picornavirus that induces a chronic, CD4+ T cell‐mediated demyelinating disease with a clinical course and histopathology similar to those of chronic‐progressive multiple sclerosis. Upon infection, TMEV‐specific CD4+ T cells target persistent viral antigens in the CNS and initiate myelin damage. Later in the disease, myelin‐specific CD4+ T cells are primed by epitope spreading, and these autoimmune T cells contribute to the pathogenesis of the chronic‐progressive disease. This review focuses upon aspects of the initiation of a virally induced CD4+ T cell‐mediated autoimmune response. First, the steps involved in the hierarchical activation of non‐cross‐reactive myelin‐specific T cells in the SJL/J mouse after CNS infection with TMEV and the role of these autoreactive T cells in chronic myelin damage are discussed. Second, the process of epitope spreading and the role of CNS antigen presenting cells in the temporal presentation of self‐antigens is considered. Finally, we will discuss aspects of T cell activation and antigen presentation, and how they can impact autoimmune disease.
A View on Beta Cell Transplantation in Diabetes
Authors: PIPELEERS DANIEL , KEYMEULEN BART , CHATENOUD LUCIENNE , HENDRIECKX CHRISTEL , LING ZHIDONG , MATHIEU CHANTAL , ROEP BART , YSEBAERT DIRK
Published: July 2010

Abstract: Organ donors also offer a source of insulin‐producing tissue that might be used for the treatment of diabetes. Clinical protocols for transplantation of this tissue aim for the prevention of chronic diabetes complications without introducing new serious side effects. Pancreas and islet cell transplantation are discussed in this perspective. The future of islet cell implants looks favorable but depends on finding ways to induce immune tolerance to the donor beta cells. Clinical trials can take advantage of relevant progress in animal models. In a limited study, recipient treatment with antilymphocyte antibodies and culture of donor cell preparations appeared useful to induce a state of operational immune tolerance in type 1 diabetic patients, as indirectly judged by graft survival and by analysis of auto‐ and alloreactivities in recipients. Use of cultured beta cell preparations also allows donor cell recruitment from suboptimal donor organs and increases the degree of standardization and quality control of islet cell grafts. The future of these grafts will depend on the development of techniques for the neogenesis of beta cells.
Genetics of Latent Autoimmune Diabetes in Adults
Authors: SANJEEVI C. B. , GAMBELUNGHE G. , FALORNI A. , SHTAUVERE‐BRAMEUS A. , KANUNGO A.
Published: July 2010

Abstract: Slowly progressive insulin‐dependent diabetes mellitus (IDDM), like classical IDDM, is also associated with genetic markers. HLA‐DR3 but not DR4 is associated with latent autoimmune diabetes in adults (LADA). In GAD65 antibody‐positive Finnish LADA patients, DQB1*0302 is positively associated with the disease. Alleles of the MHC class I chain‐related A (MICA) gene located centromeric to the HLA‐B gene is associated with LADA. Allele 5.1 of MICA was associated with both LADA and adult‐onset Italian IDDM patients when compared to controls. This finding was also observed in Indian and Latvian patients with LADA. These findings suggest that certain genetic markers distinguish LADA better.
Relation between Course of Disease in Type 1 Diabetes and Islet Cell Antibodies
Authors: ZAMAKLAR M. , JOTIC A. , LALIC N. , LALIC K. , RAJKOVIC N. , MILICIC T.
Published: July 2010

Abstract: The aim of this study was to estimate the possibility of predicting the course of type 1 diabetes. We analyzed the importance of islet cell antibody levels and residual β cell function in 46 newly diagnosed patients with diabetes. Islet cell antibodies (ICAs; Juvenile Diabetes Foundation [JDF] units) were determined at the time of diagnosis by the indirect immunofluorescent method. β cell function was estimated by C peptide levels (nmol/L) before and after glucagon stimulation at the time of clinical remission. Of the 46 patients, 13 were ICA negative (group A). Among ICA‐positive patients, ICAs were < 20 JDF units (group B) in 15, between 20 and 80 JDF in 9 (group C), and > 80 JDF in 9 (group D). In group A, 9 patients had clinical remission for 7.5 ± 1.7 months. Their basal C peptide level was 0.26 ± 0.05 nmol/L and it increased after stimulation to 44.5 ± 2.5%. Ten patients in group B had remission for 6.2 ± 1.5 months. Their basal C peptide levels (0.28 ± 0.07 nmol/L) were similarly increased after stimulation (47.5 ± 2.5%). In group C, all patients had remission and it was of the longest duration (14.7 ± 1.5 months). They had the highest basal C peptide levels (0.45 ± 0.12 nmol/L) with increases to 57.5 ± 3.5%. Seven patients in group D with ICA levels > 80 JDF had a short remission (3.2 ± 1.2 months) despite good basal C peptide levels (0.42 ± 0.05 nmol/L) and excellent increases after stimulation (92.5%). Our results suggest that moderate levels of ICA are associated with good residual β cell function and longer remission. Very high ICA levels (> 80 JDF) at the time of diagnosis despite better β cell function are associated with short clinical remission. Therefore, high ICA levels could be a marker of strong autoimmune reaction and accelerated depletion of β cell function.
Islet Autoantibodies in Latvian Subjects with Non‐Insulin‐Dependent Diabetes Mellitus
Authors: SHTAUVERE‐BRAMEUS A. , FALORNI A. , RUMBA I. , SANJEEVI C. B.
Published: July 2010

Abstract: In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA‐2) among patients with clinically diagnosed NIDDM identify group of patients with slow‐onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA‐2 autoantibodies as well as 21‐hydroxylase (21‐OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was ≥ 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA‐2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA‐2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21‐OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow‐onset type 1 diabetes but not polyendocrine autoimmunity.
The Lymphocyte as a Cellular Model to Study Insights into the Pathophysiology of Diabetes and Its Complications
Authors: BALASUBRAMANYAM M. , PREMANAND C. , MOHAN V.
Published: July 2010

Abstract: Blood cells from subjects with hypertension and/or diabetes mellitus have been successfully studied in the past to gain insight into pathological alterations of several signal transduction pathways. Diabetes mellitus is also considered to be a disease of abnormal cellular Ca2+ metabolism, as metabolic derangements of Ca2+ transport have been noticed both in the prediabetic state and as a consequence of hyperglycemia and oxidative stress. In this report, we used peripheral blood lymphocytes from type 2 diabetes patients and control subjects to study and delineate different mechanisms of Ca2+ turnover that determine the level of cytosolic calcium (Cai). While demonstrating the specific Ca2+ turnover alterations, we suggest that insights into the pathophysiology of diabetic complications originating from signal transduction defects could be conveniently studied using blood cell types such as lymphocytes and that such studies could lead to the identification of new molecular drug targets.
Prospects for Single‐Molecule Information‐Processing Devices for the Next Paradigm
Authors: WADA YASUO
Published: July 2010

Abstract:Present information technologies use semiconductor devices and magnetic/optical disks; however, they are all foreseen to face fundamental limitations within a decade. Therefore, superseding devices are required for the next paradigm of high‐performance information technologies. The paper first describes architectures suitable for single‐molecule information processing, in which it is claimed that the performance of information processing is higher if speed and element number product is larger in almost all known architectures. Thus, single‐molecule information‐processing devices should be the most appropriate approach for the next paradigm. Then, prospects for single‐molecule devices suitable for future information‐processing technologies are described. Four possible milestones for realizing the Peta/Exa‐floating operations per second (FLOPS) personal molecular supercomputer are proposed. Current status and necessary technologies of the first milestone are described, and necessary technologies for the next three milestones are also discussed.
Molecular Wires, Switches, and Memories
Authors: CHEN J. , WANG W. , KLEMIC J. , REED M. A. , AXELROD B. W. , KASCHAK D. M. , RAWLETT A. M. , PRICE D. W. , DIRK S. M. , TOUR J. M. , GRUBISHA D. S. , BENNETT D. W.
Published: July 2010

Abstract: Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through‐bond electronic transport properties of nanoscale metal‐1,4‐phenylene diisocyanide‐metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide‐Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on‐off peak‐to‐valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox‐center‐containing molecular devices are observed; and a two‐terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.
Semiclassical Theory for Dissipative Tunneling Through a Molecular Wire
Authors: BURIN ALEXANDER L. , BERLIN YURI A. , RATNER MARK A.
Published: July 2010

Abstract: The exact semiclassical wavefunction for a tunneling electron, coupled to the degrees of freedom of the host medium, is constructed. As a specific application, the result is used to calculate the tunneling amplitude for the electron interacting with a single vibrational mode of the medium. In agreement with previous numerical studies, the tunneling rate is enhanced due to the interaction—stimulated decrease of the tunneling barrier. Several tunneling regimes can be distinguished, depending on the relationship of vibrational frequency and tunneling time.
The Amazon Project
Authors: BARBERA ANNA , PROSA LINA
Published: July 2010

Abstract: The Amazon Project combines science, myth, and theater to explore problems linked to cancer and its surgical management in women from a social, political, and cultural point of view. This Project is concerned with change in the hope that one day it will be possible to discuss, along with the Science of Medicine, the Science of Patients as well.
Hepatocellular Carcinoma
Authors: VILLA ERICA , GROTTOLA ANTONELLA , COLANTONI ALESSANDRA , DE MARIA NICOLA , BUTTAFOCO PAOLA , FERRETTI ILVA , MANENTI FEDERICO
Published: July 2010

Abstract: Experimental and clinical evidence indicates that estrogens have a relevant role in the pathogenesis of cancer of hormone‐sensitive organs. Estrogen receptors (ERs) are present in liver cells. Normal liver expresses almost exclusively wild‐type ERs derived from the full‐length transcript of the gene. During progression of liver disease to hepatocellular carcinoma, variant forms of ERs have been demonstrated that greatly influence the course of the disease and the possibility of palliative treatment. Peritumoral cirrhotic tissue of patients with hepatocellular carcinoma, especially males, expresses a variant form of ER (vER) with an exon 5 deletion. In hepatocellular carcinoma, vER largely predominates and sometimes becomes the only form expressed. That the occurrence of vER alone is limited almost exclusively to males suggests that it could be one of the molecular events that eventually lead to the preferential development of hepatocellular carcinoma in males. In addition, the presence of vER appears most frequently in patients infected with the hepatitis B virus. The growth rate of hepatocellular carcinoma in patients with vER is also significantly higher than that in patients with tumors expressing wtER.
Antiestrogenic Regulation of Transforming Growth Factor Beta Receptors I and II in Human Breast Cancer Cells
Authors: BUCK M. , DER FECHT J. VON , KNABBE C.
Published: July 2010

Abstract: To obtain more information about the interactions between antiestrogens and transforming growth factor beta (TGF‐β) signaling, we analyzed the influence of different types of antiestrogens on the expression of TGF‐β receptors I (TβRI) and II (TβRII). Our results show that antiestrogens selectively induce TβRII but not TβRI mRNA.
Human Type 1 Estrogen Sulfotransferase
Authors: FAUCHER FRÉDÉRIC , LACOSTE LUCILLE , VAN LUU‐THE
Published: July 2010

Abstract: Using purified human type 1 estrogen sulfotransferase (hEST1), we show that the best substrate for this enzyme is 2‐hydroxy‐catecholestrogen. The enzyme also catalyzes the transformation of 4‐hydroxy‐estrogens and 16‐hydroxy‐estrogens, but with a lower affinity. We also present evidence to indicate that estrogen sulfotransferase may play a role in processes other than the detoxification and elimination of steroids. Indeed, hEST1 may also be involved in the production of stable precursors for local steroid biosynthesis or in the activation of promutagenic estrogen metabolites into carcinogens.
Effects of Weight Control and Physical Activity in Cancer Prevention
Authors: KAAKS RUDOLF , LUKANOVA ANNEKATRIN
Published: July 2010

Abstract: Excess body weight and/or lack of physical activity are increasingly recognized as major risk factors for cancer of the colon, breast, endometrium, and prostate. This paper reviews the effects of excess body weight and physical inactivity on endogenous hormone metabolism (insulin, the IGF‐I/IGFBP system, and sex steroids) and of endocrine alterations with risk of cancer of the endometrium, breast, prostate, and colon.
Current Understanding of Cross‐Reactivity of Food Allergens and Pollen
Authors: VIETHS STEFAN , SCHEURER STEPHAN , BALLMER‐WEBER BARBARA
Published: July 2010

Abstract: Pollen‐allergic patients frequently present allergic symptoms after ingestion of several kinds of plant‐derived foods. The majority of these reactions is caused by four distinct cross‐reactive structures that are present in birch pollen. Proteins that share common epitopes with Bet v 1, the major birch pollen allergen, occur in pollens of several tree species: apples, stone fruits, celery, carrot, nuts, and soybeans. Approximately 70% of our patients who are allergic to birch pollen may experience symptoms after consumption of foods from these groups. In contrast, two minor allergenic structures—profilins and cross‐reactive carbohydrate determinants (CCD)—that sensitize approximately 10‐20% of all pollen‐allergic patients are also present in grass pollen and weed pollen. Moreover, IgE‐binding proteins related to the birch pollen minor allergen Bet v 6 have been found in many vegetable foods such as apple, peach, orange, lychee fruit, strawberry, persimmon, zucchini, and carrot. Frequently, the occurrence of cross‐reactive IgE antibodies is not correlated with the development of clinical food allergy. In particular, the clinical relevance of sensitization to CCD is doubtful. Generally, pollen‐related allergens tend to be more labile during heating procedures and in the digestive tract compared to allergens from classical allergenic foods such as peanut. However, recent DBPCFC studies have shown that both cooked celery and roasted hazelnuts still pose an allergenic risk for pollen‐sensitized subjects. Since pathogenesis‐related proteins share several common features with allergens and both the Bet v 1 and the Bet v 6‐related food allergens are defense‐related proteins, approaches to introduce such proteins as a measure to protect plants against diseases should be performed with caution as they may increase the allergenicity of these crops.
Sequence Analysis for Assessing Potential Allergenicity
Authors: GENDEL STEVEN M.
Published: July 2010

Abstract: Sequence analysis plays an important role in assessing the potential allergenicity of proteins used in transgenic foods, particularly for proteins that have not previously been part of the food supply. Sequence comparisons are used to indicate potential unexpected cross reactivity to existing allergens and to assess the potential for developing new sensitivities. Although the concept of using sequence analysis is straightforward, implementing a bioinformatic analysis that is accurate and complete can be complex. Several factors need to be considered, including the design and content of the sequence database, the analysis strategy, and the criteria for evaluating the results.
Assessment of Protein Allergenicity
Authors: KNIPPELS LÉON M.J. , PENNINKS ANDRÉ H.
Published: July 2010

Abstract: For the safety evaluation of genetically engineered crops, the potential allergenicity of the newly introduced protein(s) has become an important issue. There is, however, no universal and reliable test system for the evaluation of the allergic sensitizing ability of food proteins. Therefore, there is a growing interest in the development of animal models. This paper summarizes the results of a promising food allergy model developed in Brown Norway (BN) rats. The results demonstrate that BN rats can be sensitized via the relevant oral route of exposure. Daily gavage dosing of the animals with several food proteins, without the use of adjuvants, resulted in significant antigen‐specific IgE responses. In addition, the profile of allergens recognized by the immune system of the BN rat, appeared comparable to the profile of allergens recognized by allergic humans. Besides oral sensitization, local and systemic immune‐mediated effects, such as increased gastrointestinal permeability, decreased breathing frequency, and decreased blood pressure, could also be observed in the sensitized animals after an oral challenge. All together, these observations suggest that this BN rat model might provide a suitable animal model to study the allergenicity of food proteins in humans.
Behavioral Consequences of Methamphetamine‐Induced Neurotoxicity in Mice: Relevance to the Psychopathology of Methamphetamine Addiction
Authors: ITZHAK YOSSEF , ALI SYED F.
Published: July 2010

Abstract:Methamphetamine (METH) is a major drug of abuse in the United States. A high dose of METH given to mice and rats causes long‐lasting depletion of tyrosine hydroxylase activity, dopamine (DA), and DA‐transporter (DAT) binding sites in the striatum. In human METH‐abusers, a marked decrease of the DAT in the caudate putamen was observed. Despite intensive investigations of the mechanism associated with METH‐induced neurotoxicity, the behavioral consequences of this phenomenon are not clear. We used the mouse model of METH‐induced neurotoxicity to investigate the response of the animals to the psychomotor‐stimulating effect of METH and the rewarding effect of the drug. Mice pre‐exposed to a neurotoxic dose of METH developed a marked sensitization to the psychomotor‐stimulating effect of METH, which lasted for more than two months. The rewarding effect of METH was determined by the conditioned place preference (CPP) paradigm. Mice pre‐exposed to the neurotoxic dose of METH showed reduced sensitivity to the rewarding effect of METH compared with control animals. While CPP was maintained for three months in the control group, the conditioned response in the METH pre‐exposed animals lasted only a few days. These findings indicate that METH neurotoxicity is associated with opposing and long‐lasting behavioral outcomes: (a) sensitization to the psychomotor‐stimulating effect of the drug and (b) desensitization to the rewarding properties of the drug. These consequences may be relevant to the psychopathology of METH abuse. Sensitization is pertinent to compulsive drug‐seeking behavior that is accompanied by desensitization to the rewarding effect of METH.