bluuebunny/crossref_metadata_2025 huggingface dataset:
Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation
Authors: Franz Marcus , Wolheim Anke , Richter Petra , Umbreit Claudia , Dahse Regine , Driemel Oliver , Hyckel Peter , Virtanen Ismo , Kosmehl Hartwig , Berndt Alexander
Published: November 2009

J Oral Pathol Med (2010) 39: 290–298

Background:  The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains α2, α3, α4, α5 and γ2 in the stromal compartment/vascular structures in OSCC was analysed.

Methods:  Frozen tissue of OSCC (9× G1, 24× G2, 8× G3) and normal (2×)/hyperplastic (11×) oral mucosa was subjected to laminin chain and α‐smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31.

Results:  Stromal laminin α2 chain significantly decreases and α3, α4, α5 and γ2 chains and also ASMA significantly increase with rising grade. The amount of stromal α3, α4 and γ2 chains significantly increased with rising ASMA positivity. There is a significant decrease in α3 chain positive vessels with neoplastic transformation.

Conclusions:  Mediated by myofibroblasts, OSCC development is associated with a stromal up‐regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning α3 and γ2 chain laminins during tumour angioneogenesis is suggested.
Early postnatal behavioral changes in the Mecp2‐308 truncation mouse model of Rett syndrome
Authors: De Filippis B. , Ricceri L. , Laviola G.
Published: November 2009

In a mouse model of Rett syndrome (RTT) which expresses a truncated form of methyl‐CpG‐binding protein 2 (Mecp2) gene (Mecp2‐308), we performed a neurobehavioral evaluation across the life span, starting from soon after birth till adulthood. A focus was made on those developmental phases and behavioral domains which have not been previously investigated. The results evidenced subtle anomalies on postnatal days (pnds) 3 to 9 (so‐called presymptomatic phase) in spontaneous movements by hemizygous neonatal male mice. Specifically as early as pnd 3, mutant pups exhibited more intense curling and more side responses and on pnd 9 more pivoting and head rising behaviors than wild type (wt) littermates. A significant decrease in ultrasonic vocalization rate, also emerged in Mecp2‐308 pups. The same mice were also characterized by increased anxiety‐like behaviors (open‐field and zero‐maze tests) during the early symptomatic phase, in the absence of changes in cognitive passive‐avoidance task and rotarod performances. Upon the clearly symptomatic stage, 5‐month‐old Mecp2‐308 mice were also associated with reduced spontaneous home‐cage motor activity, motor coordination impairments (rotarod and dowel tests), and a more marked profile of d‐amphetamine (10 mg/kg) released stereotyped behavioral syndrome than wt mice. Present results provide an interesting timeline of the progression of symptoms in the Mecp2‐308 model and emphasize the need for increased attention to the presymptomatic phase which may be especially informative in mouse models of human neurodevelopmental disorders. This analysis has provided evidence of precocious behavioral markers of RTT and has identified an early developmental window of opportunities on which potential therapies could be investigated.
Changes in the professional domain of Dutch dental hygienists
Authors: Jerkovic K , Van Offenbeek MAG , Slot DE , Van Der Schans CP
Published: November 2009

To cite this article:
 
Int J Dent Hygiene 8, 2010; 301–307 DOI: 10.1111/j.1601‐5037.2009.00418.x Jerkovic K, van Offenbeek MAG, Slot DE, Van der Schans CP. Changes in the professional domain of Dutch dental hygienists.

Abstract:  Objective:  This study’s purpose was to compare the scope of practice of Dutch dental hygienists educated through a two‐ or three‐year curriculum (‘old curriculum dental hygienists’ [OCDHs]) with that of hygienists educated through a new extended four‐year curriculum leading to a bachelor’s degree (‘new curriculum dental hygienists’ [NCDHs]).

Methods:  In 2005 and 2007, we obtained surveys from 320 OCDHs and the first 67 NCDHs, respectively, in which respondents were asked to complete a questionnaire and score how often they performed certain dental tasks. By means of factor analysis, these tasks were grouped into nine activity groups and 5 remaining single activities. T‐tests and Mann‐Whitney U‐tests were used to compare the scope of practice between OCDHs and NCDHs.

Results:  NCDHs worked more often in dental offices (instead of being self‐employed) and generally worked more hours per week than OCDHs. They performed more often tasks dealing with caries diagnosis and treatment and less often tasks dealing with prevention and periodontology. These differences were statistically significant. However, in dental offices the differences between OCDHs en NCDHs were far less pronounced. In those practices OCDHs performed dental sealants, small corrections of dentures and/or restoration and caries diagnosis during dental check‐up no less frequently than NCDHs.

Conclusions:  Although prevention remains the core domain (or role) of all Dutch dental hygienists surveyed, the scope of practice substantially differed. This, however, depended not only on education, but also on type of practice. The new curriculum answers to and legitimates an already developed practice of task delegation.
A prospective study on the persistence of infant crying, sleeping and feeding problems and preschool behaviour
Authors: Schmid G , Schreier A , Meyer R , Wolke D
Published: November 2009

Aim:  To determine the persistence of regulatory problems (RP), i.e. excessive crying (>3 months of age), feeding and sleeping difficulties from infancy to preschool age, and to evaluate whether RP at 5 months are predictive of preschool adaptive behaviour and social skills.

Method:  A prospective population study of newborns admitted to neonatal care. RP at 5, 20 and 56 months of age were obtained via parent interviews and neurological examination and preschool adaptive behaviour and social skills by parent ratings. Logistic and linear regression analyses were conducted and controlled for psychosocial and neurological factors.

Results:  More than half of the sample had RP at least at one measurement point. In about 8% of infants, RP persisted across the preschool years. Multiple RP and feeding problems increased the odds of eating problems at 20 and 56 months. Persistent RP and feeding problems were predictive of deficits in preschool adaptive behaviour and social skills. In addition, sex differences were found.

Conclusions:  Multiple RP and feeding problems had the highest stability. Persistent RP were predictive of adverse social and adaptive behaviour. Understanding of the aetiology may help to prevent persistent RP
The influence of fig proteases on the inhibition of angiotensin I‐converting and GABA formation in meat
Authors: LI Jinyue , IZUMIMOTO Masatoshi , YONEHARA Makiko , HIROTSU Seiya , KURIKI Takayoshi , NAITO Ichiro , YAMADA Hidenori
Published: November 2009

The purposes of this research were to use fig protease for texture tenderizing, and to inhibit angiotensin I‐converting enzyme (ACE) action and γ‐aminobutyric acid (GABA) formation of meat. Liberated peptides by the enzymatic action of fig protease in processing meat and free amino acids were determined and ACE inhibitory activity was assayed. Meat treated with fig protease became tender as indicated by shear force value (SFV) which was half of those of non‐fig treated meat during storage even at 5°C. Liberated peptides, free amino acids and GABA increased while extremely low levels of Glu were detected after storage. The optimal temperature of fig protease against meat was 80°C. However, the activity of fig protease decreased after pre‐heating more than 40°C. High ACE inhibitory activity of a mixture of fig and meat was found around 80°C, and the value corresponded to the amount of liberated peptide. A lot of liberated peptides were found at 60–80°C and pasterization of meat product becomes convenient to produce peptides. Production of ACE inhibitory peptides and GABA can be expected as the healthy functional meat product such as antihypertensive activity and improve brain function.
Regional specialization of the Ganglion cell density in the retina of the Ostrich (Struthio camelus)
Authors: RAHMAN Mohammad L. , KURODA Kengo , AOYAMA Masato , SUGITA Shoei
Published: November 2009

In this study, retinal whole‐mount specimens were prepared and stained with 0.1% cresyl violet for the ganglion cell study in the Ostrich (Struthio camelus). The total number, distribution, and size of these cells were determined in different retinal regions. The mean total number of ganglion cells (three retinas) was 1 435 052 with an average density of 652 cells/mm2. The temporo – nasal area of the retina with high cell density were identified with the peak of 7525 cells/mm2 in the central area. The size of most ganglion cells ranged from 113–403 µm2, with smaller cells predominating along the temporo‐nasal streak above the optic disc and larger cells comprising more of the peripheral regions. The average thickness of the retina was 196 µm. The central area was the thickest area (268.6 µm), whereas the peripheral area was the thinnest area. Thus, the specialization of ganglion cell densities, their sizes and the thickness of the retina support the notion that the conduction of visual information towards the brain from all regions of the retina is not uniform, and suggests that the temporo – nasal streak is the fine quality area for vision in ostriches.
Early metaphase II oocytes treated with dibutyryl cyclic adenosine monophosphate provide suitable recipient cytoplasm for the production of miniature pig somatic cell nuclear transfer embryos
Authors: SUGIMURA Satoshi , YAMANAKA Ken‐ichi , KAWAHARA Manabu , WAKAI Takuya , YOKOO Masaki , SATO Eimei
Published: November 2009

We investigated the effects of in vitro maturation duration and treatment with dibutyryl cyclic adenosine monophosphate (dbcAMP) on the blind enucleation efficiency and developmental competence of miniature pig somatic cell nuclear transfer (SCNT) embryos. Oocytes were cultured for 22 h in NCSU‐23 medium with or without 1 mM dbcAMP and then additionally cultured in dbcAMP‐free NCSU‐23 for 14, 18, or 22 h. Regardless of dbcAMP treatment, the rate of nuclear maturation reached a plateau at 36 and 40 h. However, mitochondrial distribution, a marker for cytoplasmic maturation, differed between the dbcAMP‐untreated oocytes at 36 h and dbcAMP‐treated oocytes at 40 h. The metaphase II chromosomes were adjacent to the first polar body in 68.8% and 63.5% of the dbcAMP‐untreated oocytes at 36 h and dbcAMP‐treated oocytes at 40 h, respectively. Furthermore, the blind enucleation efficiency by removing a small volume of cytoplasm was significantly higher in the dbcAMP‐untreated oocytes at 36 h (82.9%) and dbcAMP‐treated oocytes at 40 h (89.9%) than other groups. The rate of blastocyst formation was highest in the dbcAMP‐treated oocytes at 40 h. Hence, this study demonstrated that dbcAMP‐treated early metaphase II oocytes are suitable for the production of miniature pig SCNT embryos.
Cyclin T1 stabilizes expression levels of HIV‐1 Tat in cells
Authors: Imai Kenichi , Asamitsu Kaori , Victoriano Ann Florence B. , Cueno Marni E. , Fujinaga Koh , Okamoto Takashi
Published: November 2009

Transcription from HIV‐1 proviral DNA is a rate‐determining step for HIV‐1 replication. Interaction between the cyclin T1 (CycT1) subunit of positive transcription elongation factor b (P‐TEFb) and the Tat transactivator protein of HIV‐1 is crucial for viral transcription. CycT1 also interacts directly with the transactivation‐responsive element (TAR) located on the 5′end of viral mRNA, as well as with Tat through the Tat–TAR recognition motif (TRM). These molecular interactions represent a critical step for stimulation of HIV transcription. Thus, Tat and CycT1 are considered to be feasible targets for the development of novel anti‐HIV therapies. In this study, we demonstrate that CycT1 is positively involved in the Tat protein stability. Selective degradation of CycT1 by small interfering RNA (siRNA) culminated in proteasome‐mediated degradation of Tat and eventual inhibition of HIV‐1 gene expression. We noted that the siRNA‐mediated knockdown of CycT1 could inhibit HIV‐1 transcription without affecting cell viability and Tat mRNA levels. These findings clearly indicate that CycT1 is a feasible therapeutic target, and inactivation or depletion of CycT1 should effectively inhibit HIV replication by destabilizing Tat and suppressing Tat‐mediated HIV transcription.
Role of Adenosine Signaling in Penile Erection and Erectile Disorders
Authors: Phatarpekar Prasad V. , Wen Jiaming , Xia Yang
Published: November 2009

Introduction

Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection.

Aim

To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders.

Main Outcome Measures

Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism.

Methods

The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism.

Results

Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A2B receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism.

Conclusion

Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism.
Labour Market Dynamics in Resource Dependent Regions: an Examination of the Western Australian Goldfields
Authors: TONTS MATTHEW
Published: November 2009

Labour shortages have become an increasingly significant barrier to economic development in regional Australia. Many firms and government agencies are operating below capacity as a result of their inability to fill jobs. In the mineral resources sector, this has been compounded by rapidly rising demand for commodities and the very remote locations of many mine sites. This paper explores the dynamics of labour shortages in the minerals sector of the Western Australian Goldfields. It demonstrates close linkages between commodity price, labour supply and demand, and resource output. Against the background of a state‐wide ‘resources boom’, the paper also points to an increase in intra‐ and inter‐ regional competition for labour.
Indigenous Methodologies: Suggestions for Junior Researchers
Authors: NAKAMURA NAOHIRO
Published: November 2009

Indigenous methodologies in geography have recently been developed to decolonise Western dominated paradigms. It has been argued that research which does not benefit Indigenous communities should not be conducted. However, Indigenous methodologies are not taught in many post‐secondary institutions. Therefore, when they pursue Indigenous topics, many junior researchers are self‐taught in these methodologies. However, these methodologies cannot be defined simply and they are too diverse to be learnt in a short period. In Japan, Indigenous peoples are not widely recognised and research on contemporary Indigenous issues is limited. The concept of Indigenous methodologies is rarely discussed. Because of this, Japanese researchers rarely identify their research as adopting an Indigenous methodology. Indigenous researchers are thereby discouraged from pursuing Indigenous methodologies. Furthermore, a methodology or a thesis statement used by researchers to reflect Indigenous perspectives often gets little support from Indigenous peoples. My master's research on the Ainu mirrored this situation. While Indigenous methodologies remain difficult to learn, junior researchers should not be discouraged from this form of engagement. Practical suggestions are therefore necessary to encourage their use and application. Based on my experience, I suggest that researchers approach Indigenous communities from a learning perspective. This would encourage open‐mindedness and sensitivity. Researchers should also be prepared and willing to refine their research questions and to continue their literature searches after their fieldwork is completed. These strategies could limit misinterpretation and exploitation of Indigenous knowledges and peoples.
Flowpath Independent Monitoring of Reductive Dechlorination Potential in a Fractured Rock Aquifer
Authors: Bradley Paul M. , Lacombe Pierre J. , Imbrigiotta Thomas E. , Chapelle Francis H. , Goode Daniel J.
Published: November 2009

The flowpath dependent approaches that are typically employed to assess biodegradation of chloroethene contaminants in unconsolidated aquifers are problematic in fractured rock settings, due to difficulties defining discrete groundwater flowpaths in such systems. In this study, the variation in the potential for chloroethene biodegradation with depth was evaluated in a fractured rock aquifer using two flowpath independent lines of field evidence: (1) the presence of the three biochemical prerequisites [electron donor(s), chloroethene electron acceptor(s), and chlororespiring microorganism(s)] for efficient chloroethene chlororespiration and (2) the in situ accumulation of chloroethene reductive dechlorination daughter products. The validity of this approach was assessed by comparing field results with the results of [1, 2‐14C] cis‐DCE microcosm experiments. Microcosms were prepared with depth‐specific core material, which was crushed and emplaced in discrete packer intervals for 1 year to allow colonization by the indigenous microbial community. Packer intervals characterized by significant electron donor concentrations, elevated numbers of chlororespiring microorganisms, and high reductive dechlorination product to parent contaminant ratios correlated well with the production of 14C‐labeled reductive dechlorination products in the microcosm experiments. These results indicate that, in the absence of information on discrete groundwater flowpaths, a modified approach emphasizing flowpath independent lines of evidence can provide insight into the temporal and spatial variability of contaminant biodegradation in fractured rock systems.
Paleosols in Central Illinois as Potential Sources of Ammonium in Groundwater
Authors: Glessner Justin J. G. , Roy William R.
Published: November 2009

Glacially buried paleosols of pre‐Holocene age were evaluated as potential sources for anomalously large concentrations of ammonium in groundwater in East Central Illinois. Ammonium has been detected at concentrations that are problematic to water treatment facilities (greater than 2.0 mg/L) in this region. Paleosols characterized for this study were of Quaternary age, specifically Robein Silt samples. Paleosol samples displayed significant capacity to both store and release ammonium through experiments measuring processes of sorption, ion exchange, and weathering. Bacteria and fungi within paleosols may significantly facilitate the leaching of ammonium into groundwater by the processes of assimilation and mineralization. Bacterial genetic material (DNA) was successfully extracted from the Robein Silt, purified, and amplified by polymerase chain reaction to produce 16S rRNA terminal restriction fragment length polymorphism (TRFLP) community analyses. The Robein Silt was found to have established diverse and viable bacterial communities. 16S rRNA TRFLP comparisons to well‐known bacterial species yielded possible matches with facultative chemolithotrophs, cellulose consumers, nitrate reducers, and actinomycetes. It was concluded that the Robein Silt is both a source and reservoir for groundwater ammonium. Therefore, the occurrence of relatively large concentrations of ammonium in groundwater monitoring data may not necessarily be an indication of only anthropogenic contamination. The results of this study, however, need to be placed in a hydrological context to better understand whether paleosols can be a significant source of ammonium to drinking water supplies.
Careful counsel: Management of unintended pregnancy
Authors: O'Reilly Monica
Published: November 2009

Purpose: To provide a guideline for the care of women with unintended pregnancies, highlight the magnitude of unintended pregnancy, identify the demographic population at highest risk, offer assessment and diagnostic information, and describe the importance and practice of comprehensive, nondirective pregnancy options counseling, including information on abortion, adoption, and parenthood.

Data sources: Extensive literature review of government publications, professional clinical, nursing, and medical journals and textbooks.

Conclusions: The practice of counseling women and couples in a nondirective manner and providing comprehensive overview of options is paramount and should be the standard practice for all clinicians, especially within organizations funded by Title X funds.

Implications for practice: As we strive toward diligent patient advocacy, it is essential that NPs implement and endorse the ethical provision of options counseling through promoting values clarification and continuing education.
Optimizing outcomes with incretin‐based therapies: Practical information for nurse practitioners to share with patients
Authors: Fleury‐Milfort Evelyne
Published: November 2009

Purpose: To introduce the role of incretin therapies and suggest strategies for nurse practitioners to implement them in practice.

Data sources: PubMed, Medline, summary of product characteristics/package inserts.

Conclusions: Incretin‐based therapies offer a new alternative to currently available agents. They provide adequate levels of glycemic control and are associated with low incidence of hypoglycemia and weight gain. Dipeptidyl peptidase‐4 inhibitors, for example sitagliptin, have a modest effect on A1c levels (−0.7%) as monotherapy; however, they reduce A1c to a greater extent when combined with metformin (∼2.0%). Typical starting dose of sitagliptin is 100 mg; dose adjustments are required in subjects with renal complications. Glucagon‐like peptide‐1 receptor agonists, exenatide and liraglutide, reduce A1c levels (often in excess of 1.5%) and body weight. Exenatide has a starting dose of 5 μg and is not recommended for patients with hepatic impairment or severe/end‐stage renal disease. Liraglutide has been found to benefit from a stepwise dose escalation (i.e., 0.6 mg weekly increments) until a 1.8‐mg dose is reached. Unlike exenatide, dose adjustments in patients with renal and hepatic complications are not required.

Implications for practice: Incretin‐based therapies may help to overcome some of the drawbacks of current therapies used to treat type 2 diabetes.
Biomarkers in Alzheimer's Disease
Authors: Coley N , Andrieu S , Delrieu J , Voisin T. , Vellas B.
Published: November 2009

Clinical tests are currently used as endpoints in Alzheimer's disease (AD) trials to measure disease progression based on cognitive, functional, or overall decline. These endpoints are not a perfect reflection of the underlying disease pathology and may be insensitive to disease progression, especially in early AD. Furthermore, they are subject to high variability, leading to large sample sizes and long trial durations. A biomarker that could better reflect AD progression and also predict clinical benefits of drug treatments—a surrogate endpoint—would be of great use. Currently, no surrogate endpoints have been validated in AD. Structural imaging seems to be a better candidate than plasma or CSF biomarkers, but is not yet validated as a surrogate endpoint. More prospective clinical trials are needed for the validation process. While AD biomarkers cannot currently be used as formal surrogate markers, they may nonetheless be useful measures in clinical trials alongside clinical outcomes.
Risk Factors for Development of Depression and Psychosis
Authors: Pariante Carmine M.
Published: November 2009

Increased levels of glucocorticoid hormones—the main product of the hypothalamic‐pituitary‐adrenal (HPA) axis—have been considered to be “depressogenic,” but this notion has largely derived from studies in patients with endocrine conditions, such as Cushing's syndrome or exogenous treatment with synthetic glucocorticoids. In these conditions, it is likely that the full impact of the high glucocorticoid levels is felt on the brain, through over‐stimulation of the glucocorticoid receptors (GRs); indeed, normalizing these high levels leads to an improvement of mood in these patients. However, a completely different mechanism may be operating in major depression, where the increased levels of glucocorticoid hormones are conceptualized as driven by an impairment in GR function (glucocorticoid resistance), and therefore as a “compensatory” mechanism. Moreover, clinical and experimental studies have shown that antidepressants increase GR function, thus leading to resolution of glucocorticoid resistance. Interestingly, a number of studies have also demonstrated that manipulating GR function with both agonists and antagonists has an antidepressant effect, and indeed that other drugs targeting the HPA axis and cortisol secretion—even drugs with opposite effects on the HPA axis—have antidepressant effects. These studies do not support the notion that “high levels of glucocorticoids” always have a depressogenic effect, nor that decreasing the effects of these hormones always has an antidepressant effects.
Mechanisms Generating Diversity in Glucocorticoid Receptor Signaling
Authors: Revollo Javier R. , Cidlowski John A.
Published: November 2009

Glucocorticoids regulate diverse biological processes throughout the body via the glucocorticoid receptor (GR). Ligand‐bound GR translocates into the nucleus and can elicit changes in gene expression by direct contact with the DNA or by protein–protein interactions with other transcription factors. The GR can also mediate rapid nongenomic signaling events initiated in the cytoplasm. In this chapter, we review the biological and physiological implications of glucocorticoids, the GR, and many of the signal transduction mechanisms that mediate their action.
Glucocorticoid Signaling in the Cell
Authors: Chrousos George P. , Kino Tomoshige
Published: November 2009

Glucocorticoids contribute to the maintenance of basal and stress‐related homeostasis in all higher organisms, and influence a large proportion of the expressed human genome, and their effects spare almost no organs or tissues. Glucocorticoids regulate many functions of the central nervous system, such as arousal, cognition, mood, sleep, the activity and direction of intermediary metabolism, the maintenance of a proper cardiovascular tone, the activity and quality of the immune and inflammatory reaction, including the manifestations of the sickness syndrome, and growth and reproduction. The numerous actions of glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor (GR) isoforms forming homo‐ or hetero‐dimers. The GRs consist of multifunctional domain proteins operating as ligand‐dependent transcription factors that interact with many other cell signaling systems, including large and small G proteins. The presence of multiple GR monomers and homo‐ or hetero‐dimers expressed in a cell‐specific fashion at different quantities with quantitatively and qualitatively different transcriptional activities suggest that the glucocorticoid signaling system is highly stochastic. Glucocorticoids are heavily involved in human pathophysiology and influence life expectancy. Common behavioral and/or somatic complex disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis with its cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and allergic disorders, all appear to have a glucocorticoid‐regulated component.
Biomarkers in Oncology
Authors: Taube Sheila E.
Published: November 2009

Few apparently promising oncology biomarkers actually make their way into routine clinical use. There are many reasons for this lack of success, and the complexity of cancer biology is only one of  the reasons. Challenges involved in evaluating the analytical and the clinical performance of cancer biomarkers account for the lack of successful translation to the clinic. The lack of clear definition of the clinical need often results in tests that may perform reproducibly but are not used because they do not help with important patient care decisions. The National Cancer Institute Cancer Diagnosis Program launched the Program for the Assessment of Clinical Cancer Tests in an effort to move biomarkers more efficiently and effectively into the clinic. A development pathway is proposed that defines the steps required for evaluation of a biomarker assay's analytical and clinical performance. Several pilot projects are ongoing to test the process, and these are described.
Conference Summary and Conclusions
Authors: Sternberg Esther M. , Judd Lewis L.
Published: November 2009

The discovery of glucocorticoids and their enormous therapeutic benefits led to the use of these compounds as valuable medications for a wide variety of diseases. In 1950 this effort was ushered in by a landmark event—the awarding of the 1950 Nobel Prize in Physiology and Medicine to Drs. Phillip Hench, Edward Kendall, and Tadeus Reichstein. It was Hench who described and researched the successful use of the glucocorticoid, cortisone, and pituitary adrenocorticotrophic hormones to treat rheumatoid arthritis. Significant scientific discovery preceded Hench and colleagues’ efforts, but the revolutionary accumulation of discovery in glucocorticoids since then is one of the unique scientific stories in the history of medicine. The scientific conference upon which this volume is based represents an attempt to convene a state‐of‐the‐science meeting on the current understanding and scientific status of this fascinating, far‐reaching, and fast‐moving field. This last chapter will summarize the exciting presentations of this 2‐day conference.
Epidemiology of Type 2 diabetes mellitus in Aleppo, Syria
Authors: ALBACHE Nizar , AL ALI Radwan , RASTAM Samer , FOUAD Fouad M. , MZAYEK Fawaz , MAZIAK Wasim
Published: November 2009

Background:  Type 2 diabetes mellitus (T2DM) is considerable public health problem, but data on the prevalence and correlates of T2DM in Syria are scarce. The aim of the present study was to establish reliable estimates of the prevalence of T2DM in Syria.

Methods:  A cross‐sectional, population‐based survey was conducted in Aleppo, Syria (population 2.5 million), in 2006. The study was conducted on a random sample of 1168 subjects ≥25 years of age (47.7% men; mean age 44.7 ± 12.7 years). Information regarding a personal history of diabetes and other risk factors was collected, followed by measurement of weight, height, and the waist:hip ratio (WHR). Of the 1168 participants, 806 provided fasting blood samples that were analyzed for fasting plasma glucose (FPG) and HbA1c.

Results:  The prevalence of T2DM based on FPG ≥126 mg/dL and HbA1c ≥6.5% was 15.6% (11.2% self‐reported; 5.0% diagnosed) and 14.8%, respectively. The prevalence of impaired fasting glucose (FPG ≥110 and <126 mg/dL) was 8.6%. There was a significant positive association between T2DM and age, WHR, a family history of T2DM, and body mass index (BMI) and an inverse association between T2DM and physical activity (P < 0.01 for all). Multivariate analysis showed that age, BMI, WHR, and a family history of T2DM were the most important factors associated with T2DM. Only 16.7% of treated cases of T2DM were under control (i.e. HbA1c <7%).

Conclusions:  Based on the results obtained in our sample, T2DM is widespread in Syria. Many of those with T2DM are unaware of their disease and most have unsatisfactory control of their disease.
Endogenous extracellular serotonin modulates the spinal locomotor network of the neonatal mouse
Authors: Dunbar Mary J. , Tran Michelle A , Whelan Patrick J.
Published: November 2009

Serotonin (5‐HT) can potently activate and modulate spinal locomotor circuits in a variety of species. Many of these findings have been obtained by applying serotonin exogenously to the isolated spinal cord ofin vitropreparations, which has the drawback of indiscriminately activating extrasynaptic receptors and neurons. To investigate the role of endogenously released serotonin in modulating locomotor networks, the selective serotonin reuptake inhibitor citalopram was used. Fictive locomotion was elicited by either electrical stimulation of the brainstem or the sacral 4 (S4) dorsal root. The addition of 20 μmof citalopram caudal to thoracic segment 5 (T5) had an overall inhibitory effect on the lumbar central pattern generator (CPG). Left–right and flexor–extensor coupling were significantly decreased, and there was also a phase shift in the flexor–extensor relationship. In addition, there was a significant decrease in burst amplitude. These effects were observed during both afferent and brainstem evoked fictive locomotion. When citalopram was added in the presence of 5‐HT1Aand 5‐HT1Bantagonists, the inhibitory effects were largely reversed. The remaining excitatory effects were mediated by 5‐HT7and 5‐HT2receptors. These results suggest that endogenous 5‐HT release can modulate locomotor‐like activity early in neonatal development.
IHcurrent generates the afterhyperpolarisation following activation of subthreshold cortical synaptic inputs to striatal cholinergic interneurons
Authors: Oswald Manfred J. , Oorschot Dorothy E. , Schulz Jan M. , Lipski Janusz , Reynolds John N. J.
Published: November 2009

Pauses in the tonic firing of striatal cholinergic interneurons emerge during reward‐related learning and are triggered by neutral cues which develop behavioural significance. In a previousin vivostudy we have proposed that these pauses in firing may be due to intrinsically generated afterhyperpolarisations (AHPs) evoked by excitatory synaptic inputs, including those below the threshold for action potential firing. The aim of this study was to investigate the mechanism of the AHPs using a brain slice preparation which preserved both cerebral hemispheres. Augmenting cortically evoked postsynaptic potentials (PSPs) by repetitive stimulation of cortical afferents evoked AHPs that were unaffected by blocking either GABAAreceptors with bicuculline, or GABABreceptors with saclofen or CGP55845. Apamin (a blocker of small conductance Ca2+‐activated K+channels) had minimal effects, while chelation of intracellular Ca2+with BAPTA reduced the AHP by about 30%. In contrast, blocking hyperpolarisation and cyclic nucleotide activated (HCN) cation current (IH) with ZD7288 or Cs+diminished the size of the AHPs by 60% and reduced the proportion of episodes that contained this hyperpolarisation. The reversal potential (−20 mV) and voltage dependence of the AHPs were consistent with the hypothesis that a transient deactivation ofIHcaused most of the AHP at hyperpolarised potentials, while the slow AHP‐type Ca2+‐activated K+channels increasingly contributed at more depolarised membrane potentials. Subthreshold somatic current injections yielded similar AHPs with a median duration of ∼700 ms that were not affected by firing of a single action potential. These results indicate that transient deactivation of HCN channels evokes pauses in tonic firing of cholinergic interneurons, an event likely to be elicited by augmentation of afferent synaptic inputs during learning.
Exercise‐induced histone modifications in human skeletal muscle
Authors: McGee Sean L. , Fairlie Erin , Garnham Andrew P. , Hargreaves Mark
Published: November 2009

Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP‐activated protein kinase (AMPK) and the calcium–calmodulin‐dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation‐dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.
Direct Simulation Based Model-Predictive Control of Flow Maldistribution in Parallel Microchannels
Authors: Martin Mathieu , Patton Chris , Schmitt John , Apte Sourabh V.
Published: November 2009

Flow maldistribution, resulting from bubbles or other particulate matter, can lead to drastic performance degradation in devices that employ parallel microchannels for heat transfer. In this work, direct numerical simulations of fluid flow through a prescribed parallel microchannel geometry are performed and coupled with active control of actuated microvalves to effectively identify and reduce flow maldistribution. Accurate simulation of fluid flow through a set of three parallel microchannels is achieved utilizing a fictitious-domain representation of immersed objects such as microvalves and artificially introduced bubbles. Flow simulations are validated against experimental results obtained for flow through a single high-aspect ratio microchannel, flow around an oscillating cylinder, and flow with a bubble rising in an inclined channel. Results of these simulations compare very well to those obtained experimentally, and validate the use of the solver for the parallel microchannel configuration of this study. System identification techniques are employed on numerical simulations of fluid flow through the geometry to produce a lower dimensional model that captures the essential dynamics of the full nonlinear flow, in terms of a relationship between valve angles and the exit flow rate for each channel. A model-predictive controller is developed, which employs this reduced order model to identify flow maldistribution from exit flow velocities and to prescribe actuation of channel valves to effectively redistribute the flow. Flow simulations with active control are subsequently conducted with artificially introduced bubbles. The model-predictive control methodology is shown to adequately reduce flow maldistribution by quickly varying channel valves to remove bubbles and to equalize flow rates in each channel.
Calculated Dynamic Response of an Articulated Tower in Waves—Comparison With Model Tests
Authors: Schellin T. E. , Koch T.
Published: November 2009

Calculated dynamic response of an articulated tower in waves is compared with model tests. The theory used is based on Morison’s equation and linear wave theory and requires specified hydrodynamic force coefficients. Calculations are done with three different sets of coefficients. Firstly, coefficients are assumed not to vary with wave period. Secondly, they are selected from experimental data of oscillating flow past stationary cylinders. Thirdly, they are based on calculations using diffraction theory. Added mass and inertia coefficients have a predominant effect on calculated response, drag coefficients have almost no effect. Calculated tower top motion and horizontal force at the universal joint correlate well for all three sets of coefficients, indicating that hydrodynamic coefficients for normal flow are reasonably well selected and need not be specified with undue precision. In contrast, hydrodynamic coefficients for axial flow need to be chosen carefully. Calculated vertical force at the joint, using initially specified axial flow coefficients, correlates poorly with measurements. Correlation is greatly improved using reduced coefficients for axial flow. Calculated response is reasonably linear with wave height. Spectral analysis techniques are used to determine statistical measures for three irregular seastates. Agreement with corresponding model test results is satisfactory.
Model Studies of Wave-Seabed Interactions
Authors: Chari T. R. , Dawe C. R. , Barbour S. A.
Published: November 2009

Several factors such as the wave characteristics, the seabed type, the sediment size, and the porosity characteristics influence the transient porewater pressure response below the mudline due to wave-seabed interaction. Experiments were conducted in a soil-wave tank in which the pressure variation profile inside a porous bed of sand was measured for different wave types. The measured pressures were correlated with simple theories based on wave energy dissipation in permeable seabed. Tests were conducted in which the combination of wave and soil conditions caused soil liquefaction and instability. These results were extrapolated to predict the potential conditions that may cause seabed instability in the Hibernia area of the Newfoundland Grand Banks. The experimental assembly, the results and correlations, and the limitations are discussed in this paper.
The Distribution of Ice Pressure Acting on Offshore Pile Structure and the Failure Mechanics of Ice Sheet
Authors: Tanaka S. , Saeki H. , Ono T.
Published: November 2009

The total ice force acting on offshore pile structures, located in cold regions, has already been investigated by many researchers. Few papers, however, have described the distribution of ice pressure on the structures and the failure mechanics of ice sheet. It is necessary to study them in order to design the pile structures, keeping in mind safety and economic factors. The results of our experiments on failure mechanics of an ice sheet are useful for dynamic analysis. For analysis of stress and, especially, local buckling of structures, it is essential to examine the distribution of ice pressure acting on the structures. This paper describes a systematic study of these aspects through field tests with three rectangular piles (20, 40, 60 cm in width) in Saroma Lagoon in Hokkaido, Japan’s northernmost island, to clarify the effect of aspect ratio. It is clear from our experiments on ice pressure that the distribution of ice pressure can be classified into two types according to the strain rate ε˙ (= V/4B, V: penetration velocity of piles, B: pile width) defined by Michel and Toussaint [1] in each aspect ratio, B/h (h: ice thickness). It is our hypothesis that the failure periods of ice sheet are determined by the aforementioned strain rate and the aspect ratio.
Analysis of High-Frequency Vibration of Tension Leg Platforms
Authors: Nordgren R. P.
Published: November 2009

The dynamic response of a tension leg platform is studied using spectral analysis techniques. Equations of motion are derived for the rigid platform and its legs which are idealized as cables with longitudinal inertia. Attention is focused on the high-frequency resonant response of the platform in heave, pitch and roll modes with typical periods of 3 to 5 s. These modes are lightly damped, but the wave excitation at the high natural frequencies is small. Thus the response may turn out to be small. Formulas are derived for expected fatigue damage in the tethers due to high-frequency resonant vibration. The analysis includes linear damping from wave radiation and from energy dissipation in the tethers. By way of example, the results of the analysis are applied to a typical tension leg platform for petroleum production in 640 m (2100 ft) of water. The fatigue life for resonant vibration is found to be adequate.
Determination of Propeller-Ice Milling Loads
Authors: Kotras T. , Humphreys D. , Baird A. , Morris G. , Morley G.
Published: November 2009

In designing ice transiting ships, a major concern is the design of the propeller to provide adequate strength to resist ice loads due to propeller ice milling while still providing good propeller efficiency for open water observations as well as high icebreaking thrust at slow advance speeds. As a result, propeller design is a compromise between strength and efficiency. This is especially true for ice transiting ships that must transit long distances on ice-free routes and then perform difficult ice-breaking operations. The geometric properties of a propeller blade that provide good strength are blade width and thickness. Unfortunately, increasing these properties does not provide the best efficiency. Propeller design for ice transiting ships in general has tended to favor strength and reliability over efficiency in design compromises. The purpose of this paper is to outline a methodology for determining propeller ice milling loads as a function of propeller characteristics, propeller speed, ship speed, ice conditions and depth of ice milling to help in the propeller design process.
Ice Mass Motions Near an Offshore Structure
Authors: Isaacson M.
Published: November 2009

The present paper treats the motions of an ice mass up to the instant of impact with a large fixed offshore structure, and describes a numerical method for predicting these motions taking account of the interaction between the ice mass and structure. In general an ice mass will undergo wave-induced oscillatory motions as well as drift motion. The former are calculated by linear diffraction theory applied to bodies of arbitrary shape so that interaction effects are fully accounted for. The drift motion is calculated by a time-stepping procedure applied to the drift equations of motion which involve zero frequency added masses, drag forces and wave drift forces. As an example of the methods application, results are presented for a typical design situation which illustrate the nature of the hydrodynamic interaction between the ice mass and structure.