bluuebunny/crossref_metadata_2025 huggingface dataset:
Schizophrenia; from structure to function with special focus on the mediodorsal thalamic prefrontal loop
Authors: Pakkenberg B. , Scheel‐Krüger J. , Kristiansen L. V.
Published: October 2009

Objective:  To describe structural and biochemical evidence from postmortem brains that implicates the reciprocal connections between the mediodorsal thalamic nucleus and the prefrontal cortex in cognitive symptoms of schizophrenia.

Method:  The estimation of the regional volumes and cell numbers was obtained using stereological methods. The biochemical analyses of molecular expression in postmortem brain involve quantitative measurement of transcripts and proteins by in‐situ (RNA) or Western blot/autoradiography in brains from patients with schizophrenia and comparison subjects.

Results:  Stereological studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative molecular postmortem studies have found large inter‐subject and between‐study variance at both the transcript and protein levels for receptors and their interacting molecules of several neurotransmitter systems in these interconnected anatomical regions. Combined, large variation in stereological and molecular studies indicates a complex and heterogeneous involvement of the MD thalamic‐prefrontal loop in schizophrenia.

Conclusion:  Based on a considerable heterogeneity in patients suffering from schizophrenia, large variation in postmortem studies, including stereological and molecular postmortem studies of the MD thalamus and frontal cortex, might be expected and may in fact partly help to explain the variable endophenotypic traits associated with this severe psychiatric illness.
‘Salience syndrome’ replaces ‘schizophrenia’ in DSM‐V and ICD‐11: psychiatry’s evidence‐based entry into the 21st century?
Authors: Van Os J.
Published: October 2009

Objective:  Japan was the first country to abandon the 19th century term of ‘mind‐splitting disease’ (schizophrenia). Revisions of DSM and ICD are forthcoming. Should the rest of the world follow Japan’s example?

Method:  A comprehensive literature search was carried out in order to review the scientific evidence for the validity, usefulness and acceptability of current concepts of psychotic disorder.

Results:  The discussion about re‐classifying and renaming schizophrenia and other psychotic disorders is clouded by conceptual confusion. First, it is often misunderstood as a misguided attempt to change societal stigma instead of an attempt to change iatrogenic stigma occasioned by the use of misleading and mystifying terminology. Second, the debate is misunderstood as purely semantic, whereas in actual fact it is about the core concepts underlying psychiatric nosology. Third, it has been suggested that the debate is political. However, solid scientific evidence pointing to the absence of nosological validity of diagnostic categories lies at the heart of the argument. Fourth, there is confusion about what constitutes a syndrome (a group of symptom dimensions that cluster in different combinations in different people and for which one or more underlying diseases may or may not be found) and a disease (a nosologically valid entity with specific causes, symptoms, treatment and course).

Conclusion:  Scientific evidence favours a syndromal system of classification combining categorical and dimensional representations of psychosis. The concept of ‘salience’ has the potential to make the public recognize psychosis as relating to an aspect of human mentation and experience that is universal. It is proposed to introduce, analogous to the functional‐descriptive term ‘Metabolic syndrome’, the diagnosis of ‘Salience syndrome’ to replace all current diagnostic categories of psychotic disorders. Within Salience syndrome, three subcategories may be identified, based on scientific evidence of relatively valid and specific contrasts, named Salience syndrome with affective expression, Salience syndrome with developmental expression and Salience syndrome not otherwise specified.
Ecological niches and their evolution among Neotropical manakins (Aves: Pipridae)
Authors: Anciães Marina , Townsend Peterson A.
Published: October 2009

Study of the evolution of ecological characteristics using phylogenetic information is only beginning, but several new tools and approaches open fascinating possibilities. The Pipridae is a diverse and well‐known family of frugivorous birds that are easily sampled and that are broadly distributed across many Neotropical environments, and as such are appropriate for studies of ecological niche evolution. Using known occurrences and climate and topography data sets, we modeled ecological niches for each species in the family, and carried out analyses aimed at describing ecological niches of manakins and understanding historical patterns of ecological change in the family. Most species’ ecological niches were characterized by warm and relatively humid conditions, reflecting the great diversification of the family in lowland and montane forests of western South America. Ecological niche evolution was in general conservative, with most sister species pairs being closely similar ecologically, indicating that isolation rather than adaptation to new ecological conditions has dominated the diversification in this family. Exceptions to this pattern represent interesting foci for future research, whereas studies of ecological niches focusing on past distributions of manakins will allow further biogeographic inferences.
Patterns of bone loss around teeth restored with endodontic posts
Authors: Katsamakis Sokratis , Timmerman Mark , Van der Velden Ubele , De Cleen Michiel , Van der Weijden Fridus
Published: October 2009

Objectives: This retrospective study described the pattern of bone loss around teeth with endodontic posts in periodontitis patients, and compared it with contra‐lateral teeth without posts.

Material and Methods: From full‐mouth radiographic surveys of 146 periodontitis patients (35 years), 194 roots with endodontic posts and contra‐laterals without posts were selected. Upper molars, pre‐molars with two posts and roots of lower molars with two posts were excluded. Technical parameters of the post space preparation, endodontic and restorative status were evaluated. The level of alveolar bone measured in millimetre from the cemento‐enamel junction (CEJ)/restoration margin and the pattern of bone loss (angular/horizontal) were evaluated on both mesial and distal aspects of roots with posts and contra‐laterals, but not on the furcal areas of lower molars.

Results: The distance from the bone level to the CEJ/restoration margin was similar for teeth with posts and contra‐laterals. However, teeth with posts had more angular defects mesially (18.8%versus 7.3%) as compared with their contra‐laterals without posts. The defects around teeth with posts appeared to be typical in the sense that their apical level approximated the tip of the endodontic post.

Conclusion: In periodontitis patients, teeth restored by an endodontic post had angular bony defects on the mesial aspect more frequently in comparison with their contra‐laterals.
Histopathology and immunohistochemistry of depigmented lesions in lupus erythematosus
Authors: França Andrea Fernandes Eloy da Costa , De Souza Elemir Macedo
Published: October 2009

Background: Depigmented lesions (DL) have been described in areas previously damaged by inflammation in lupus erythematosus (LE). In the absence of typical lesions, distinction with other achromic diseases might be challenging. We studied the histological features and the behavior of melanocytes in these lesions.

Methods: Tissue sections of 12 patients with lupus and DL were stained with hematoxylin‐eosin, periodic acid‐Schiff and Fontana‐Masson. Melanocytes were counted by immunohistochemistry methods using Melan A and HMB‐45. Ten biopsies of normal skin were used as controls.

Results: The most common histological findings were: cellular infiltration (75%); hyperkeratosis (66.7%); thickening of basement membrane (66.7%); thinning and flattening of the epidermis (58.3%) and degenerative changes in collagen fibers (50%). Epidermal melanin and melanocytes were found in 41.7%. The melanocyte counts by HMB‐45 and Melan A were significantly lower than in normal skin.

Conclusions: The DL still fulfill histological criteria for lupus. In the absence of a precise histological diagnosis, thickening of basement membrane, hyperkeratosis, cellular infiltration, epidermal atrophy and elastosis are the most common features. Loss of melanocytes and the dermal fibrosis suggests that DL in cutaneous LE behave as post‐inflammatory scars.

França AFEC, de Souza EM. Histopathology and immunohistochemistry of depigmented lesions in lupus erythematosus.
The Kinesin Motor Protein Cut7 Regulates Biogenesis and Function of Ago1‐Complexes
Authors: Stoica Cezar , Park Jungsook , Pare Justin M. , Willows Steven , Hobman Tom C.
Published: October 2009

Argonaute proteins are the effectors of small RNA‐dependent gene‐silencing pathways. In the cytoplasm, they are incorporated into large mobile ribonucleoprotein (RNP) complexes that travel along microtubules. We used a genetic screen to identify the microtubule‐associated motor that interacts with Ago1‐containing RNPs. Here, we report that activity of the kinesin family member Cut7 is important for biogenesis and/or stability of Ago1‐containing RNPs in the cytoplasm. Results from pulldown and coimmunoprecipitation assays indicate that Cut7 interacts with Ago1 as well as its two cognate binding proteins, Dcr1 and Rdp1. Loss of Cut7 activity was associated with increased levels of reverse centromeric transcripts, presumably because of a defect in post‐transcriptional gene silencing. Overexpression of the Ago1‐binding region of Cut7 resulted in loss of microscopic Ago1‐containing RNPs. Together, these results suggest that microtubule motor proteins function in the biogenesis and function of gene‐silencing machinery in the cytoplasm.
The Textual Criticism of Middle English Manuscript Traditions: A Survey of Critical Issues in the Interpretation of Textual Data
Authors: Cole Gavin
Published: October 2009

This essay is intended to survey two broad issues which determine the use of textual data. The first is the underlying orientation towards the use of textual data and how this relates to critical evaluations of agency, authority and materiality. This essay surveys two broad orientations: (i) an essentially retrospective genetic orientation and, (ii) an orientation which focuses on the phenomenon of change. Both approaches are dependent on the ability to distinguish original readings from scribal readings, identify genetic relationships and account for acts of horizontal transmission. With this in mind, the second issue with which this essay is concerned is the importance of critical interpretation in the categorisation of textual data. This essay argues that textual criticism is a practical demonstration of the difficulties of interpretation and that no textual data ‘has any real evidential value until it has been interpreted’ (Patterson 90).
The Relationship Between Self-Reported Sexual Satisfaction and General Well-Being in Women
Authors: Davison Sonia Louise , Bell Robin Jean , LaChina Maria , Holden Samantha Lee , Davis Susan Ruth
Published: October 2009

Introduction

The extent to which low sexual function or sexual dissatisfaction in women impacts on well-being remains uncertain, yet this is a critical issue in the controversy as to the benefits of pharmacotherapy for women seeking treatment for female sexual dysfunction.

Aim

To explore the relationship between well-being and self-perceived satisfaction with sexual function in women and to determine if there is an independent effect of menopausal status or age.

Design

A community-based cross-sectional study.

Patients

A total of 421 women, aged 18 to 65 years were recruited from the community. Women were required to self-identify at study outset as being either satisfied or dissatisfied with their sexual life and be premenopausal or postmenopausal.

Main Outcome Measures

Scores from the Psychological General Well-Being Index (PGWB), the Beck Depression Index (BDI) and a daily diary of sexual function.

Results

A group of 349 women were included in the analysis. Total PGWB and domain scores of positive well-being and vitality were lower in dissatisfied women compared to satisfied women. PGWB total and domain scores of depressed mood, positive well-being and vitality were higher in older women. Menopause did not have an independent effect on well-being.

Conclusions

Women who self-identify as having sexual dissatisfaction have lower psychological general well-being. These findings reinforce the importance of addressing sexual health and well-being in women as an essential component of their health care.
Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse Attempt
Authors: Loran Oleg B. , Ströberg Peter , Lee Sung Won , Park Nam Cheol , Kim Soo-Woong , Tseng Li-Jung , Collins Suzanne , Stecher Vera J.
Published: October 2009

Introduction

Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy.

Aim

Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED.

Methods

Men with ED (score ≤25 on the Erectile Function domain of the International Index of Erectile Function) who had received ≤6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg).

Main Outcome Measures

Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg.

Results

Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose.

Conclusions

Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.
Insulin Therapy and Type 2 Diabetes: Management of Weight Gain
Authors: McFarlane Samy I.
Published: October 2009

The potential for insulin‐related weight gain in patients with type 2 diabetes presents a therapeutic dilemma and frequently leads to delays in the initiation of insulin therapy. It also poses considerable challenges when treatment is intensified. Addressing insulin‐related weight gain is highly relevant to the prevention of metabolic and cardiovascular consequences in this high‐risk population with type 2 diabetes. In addition to lifestyle changes (eg, diet and exercise) and available medical interventions to minimize the risk of weight gain with insulin treatment, familiarity with the weight gain patterns of different insulins may help deal with this problem. The use of basal insulin analogs may offer advantages over conventional human insulin preparations in terms of more physiologic time‐action profiles, reduced risk of hypoglycemia, and reduced weight gain.
Creating an Ontology‐Based Human Phenotyping System: The Rockefeller University Bleeding History Experience
Authors: Mauer Andreas C. , Barbour Edward M. , Khazanov Nickolay A. , Levenkova Natasha , Mollah Shamim A. , Coller Barry S.
Published: October 2009

The lack of standardized methods for human phenotyping is a major obstacle in translational science. We have developed a bleeding history phenotyping system comprising an ontology, a questionnaire, a Web‐based phenotype recording instrument (PRI), and a database. The ontology facilitates transparency, collaboration, aggregation of data, and data analysis. The integrated system allows investigators worldwide to use the PRI, add their de‐identified data to the database, and query the aggregated data. Thus, this system can increase the power to detect genotype–phenotype–environment relationships and help new investigators begin their studies. We anticipate that this approach may be applicable to other disorders.
Neutrophil Elastase Increases Airway Epithelial Nonheme Iron Levels
Authors: Fischer Bernard M. , Domowicz Denise A. Lopez , Zheng Shuo , Carter Jamie L. , McElvaney N. Gerry , Taggart Clifford , Lehmann James R. , Voynow Judith A. , Ghio Andrew J.
Published: October 2009

Alpha‐1‐antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung nonheme iron. To test this hypothesis, we measured bronchoalveolar lavage (BAL) iron and ferritin levels, using inductively coupled plasma (ICP) optical emission spectroscopy and an ELISA, respectively, in A1AT‐deficient patients and healthy subjects. To confirm the role of NE in regulating lung iron homeostasis, we administered intratracheally NE or control buffer to rats and measured BAL and lung iron and ferritin. Our results demonstrated that A1AT‐deficient patients and rats postelastase exposure have elevated levels of iron and ferritin in the BAL. To investigate the mechanism of NE‐induced increased iron levels, we exposed normal human airway epithelial cells to either NE or control vehicle in the presence or absence of ferritin, and quantified intracellular iron uptake using calcein fluorescence and ICP mass spectroscopy. We also tested whether NE degraded ferritin in vitro using ELISA and western analysis. We demonstrated in vitro that NE increased intracellular nonheme iron levels and degraded ferritin. Our results suggest that NE digests ferritin increasing the extracellular iron pool available for cellular uptake.
Implications of Eurocentrism for Social Work Education: Trivialization vis‐à‐vis Skin Color
Authors: Hall Ronald E.
Published: October 2009

The significance of skin color among people of color and its relative absence in social work literature is arguably attributed to Eurocentrism. Eurocentrism defines human reality via Eurocentric norms, ideas, values and perspectives. Evidence of Eurocentrism in social work is contained in its literature priorities, skin color litigation, brown racism and skin bleaching. Demonstration of the aforementioned social pathologies involving skin color pertaining to people of color is a critical, existential phenomenon. If social work is to remain viable and be sustained in the future, it must conform to the dictates of changes in the population. That will require a commensurate adjustment and a willingness of its intelligentsia to accommodate skin color and other alternative views relative to education and practice.
Optimal Pricing and Production Planning for Subscription‐Based Products
Authors: Huh Woonghee Tim , Kachani Soulaymane , Sadighian Ali
Published: October 2009

In this paper, we address the problem of a magazine publishing firm facing stochastic demand over multiple periods. We model the dynamics of customer subscription and retention/attrition. We identify the key decision variables to enhance magazine profitability: production quantity, subscription price, and newsstand price. First, we provide a dynamic programming formulation of the firm's problem and then propose a single‐stage reduction that admits a classical newsvendor characterization. For both the finite and infinite horizon cases, we characterize the optimal policy of the firm where the decision variables are one, two, or all three of the aforementioned variables. Next, we consider the duopolistic setting, where firms benefit from the overflow of the competitor's unmet demand, and we provide analytic solutions in the case of uniform demand distributions. Finally, we report on computational experiments in both monopolistic and duopolistic settings and provide managerial insights.
Network Game and Capacity Investment Under Market Uncertainty
Authors: Hu Qiaohai (Joice)
Published: October 2009

This paper investigates the impacts of competition and market uncertainty on airlines' network structures and capacity investment. The airlines choose their network structures and construct capacities while demands are unknown. After uncertainty is resolved, they determine the total number of seats to offer in each leg constrained by their capacities built earlier. We conclude that market uncertainty is the driving force of hub‐and‐spoke networks, whereas the market mean is the driving force of point‐to‐point networks. Which of the two countervailing forces dominates determines the equilibrium network structures. Moreover, we find that the airlines' total expected profits in the mixed equilibrium in which the airlines employ different networks are larger than in the pure hub‐and‐spoke network equilibrium in which each airline employs the hub‐and‐spoke network. However, the mixed equilibrium does not necessarily yield larger profits than the pure point‐to‐point equilibrium in which each airline employs the point‐to‐point network.
Influence of endogenous angiotensin II on control of sympathetic nerve activity in human dehydration
Authors: Rabbitts J. A. , Strom N. A. , Sawyer J. R. , Curry T. B. , Dietz N. M. , Roberts S. K. , Kingsley‐Berg S. M. , Charkoudian N.
Published: October 2009

Arterial blood pressure can often fall too low during dehydration, leading to an increased incidence of orthostatic hypotension and syncope. Systemic sympathoexcitation and increases in volume regulatory hormones such as angiotensin II (AngII) may help to maintain arterial pressure in the face of decreased plasma volume. Our goals in the present study were to quantify muscle sympathetic nerve activity (MSNA) during dehydration (DEH), and to test the hypothesis that endogenous increases in AngII in DEH have a mechanistic role in DEH‐associated sympathoexcitation. We studied 17 subjects on two separate study days: DEH induced by 24 h fluid restriction and a euhydrated (EUH) control day. MSNA was measured by microneurography at the peroneal nerve, and arterial blood pressure, electrocardiogram, and central venous pressure were also recorded continuously. Sequential nitroprusside and phenylephrine (modified Oxford test) were used to evaluate baroreflex control of MSNA. Losartan (angiotensin type 1 receptor (AT1) antagonist) was then administered and measurements were repeated. MSNA was elevated during DEH (42 ± 5 vs. EUH: 32 ± 4 bursts per 100 heartbeats, P= 0.02). Blockade of AT1 receptors partially reversed this change in MSNA during DEH while having no effect in the control EUH condition. The sensitivity of baroreflex control of MSNA was unchanged during DEH compared to EUH. We conclude that endogenous increases in AngII during DEH contribute to DEH‐associated sympathoexcitation.
Impact of transcranial direct current stimulation on spinal network excitability in humans
Authors: Roche N. , Lackmy A. , Achache V. , Bussel B. , Katz R.
Published: October 2009

Transcranial direct current stimulation (tDCS) when applied over the motor cortex, modulates excitability dependent on the current polarity. The impact of this cortical modulation on spinal cord network excitability has rarely been studied. In this series of experiments, performed in healthy subjects, we show that anodal tDCS increases disynaptic inhibition directed from extensor carpi radialis (ECR) to flexor carpi radialis (FCR) with no modification of presynaptic inhibition of FCR Ia terminals and FCR H‐reflex recruitment curves. We also show that cathodal tDCS does not modify spinal network excitability. Our results suggest that the increase of disynaptic inhibition observed during anodal tDCS relies on an increase of disynaptic interneuron excitability and that tDCS over the motor cortex in human subjects induces effects on spinal network excitability. Our results highlight the fact that the effects of tDCS should be considered in regard to spinal motor circuits and not only to cortical circuits.
Influence of ageing on carotid baroreflex peak response latency in humans
Authors: Fisher James P. , Kim Areum , Young Colin N. , Ogoh Shigehiko , Raven Peter B. , Secher Niels H. , Fadel Paul J.
Published: October 2009

The stability of a physiological control system, such as the arterial baroreflex, depends critically upon both the magnitude (i.e. gain or sensitivity) and timing (i.e. latency) of the effector response. Although studies have examined resting arterial baroreflex sensitivity in older subjects, little attention has been given to the influence of ageing on the latency of peak baroreflex responses. First, we compared the temporal pattern of heart rate (HR) and mean arterial blood pressure (BP) responses to selective carotid baroreceptor (CBR) unloading and loading in 14 young (22 ± 1 years) and older (61 ± 1 years) subjects, using 5 s pulses of neck pressure (NP, +35 Torr) and neck suction (NS, −80 Torr). Second, CBR latency was assessed following pharmacological blockade of cardiac parasympathetic nerve activity in eight young subjects, to better understand how known age‐related reductions in parasympathetic nerve activity influence CBR response latency. In response to NP, the time to the peak increase in HR and mean BP were similar in young and older groups. In contrast, in response to NS the time to peak decrease in HR (2.1 ± 0.2 vs. 3.8 ± 0.2 s) and mean BP (6.7 ± 0.4 vs. 8.3 ± 0.2 s) were delayed in older individuals (young vs. older, P < 0.05). The time to peak HR and mean BP were delayed in young subjects following cardiac parasympathetic blockade (glycopyrrolate). Collectively, these data suggest that ageing is associated with delayed peak cardiovascular responses to acute carotid baroreceptor loading that may be, in part, due to age‐related reductions in cardiac parasympathetic tone.
Cell–cell and intracellular lactate shuttles
Authors: Brooks George A.
Published: October 2009

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. ‘Cell–cell’ and ‘intracellular lactate shuttle’ concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell–cell shuttles include lactate exchanges between between white‐glycolytic and red‐oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down‐regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G‐protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.
Extracellular ATP inhibits chloride channels in mature mammalian skeletal muscle by activating P2Y1 receptors
Authors: Voss Andrew A.
Published: October 2009

ATP is released from skeletal muscle during exercise, a discovery dating back to 1969. Surprisingly, few studies have examined the effects of extracellular ATP on mature mammalian skeletal muscle. This electrophysiological study examined the effects of extracellular ATP on fully innervated rat levator auris longus using two intracellular microelectrodes. The effects of ATP were determined by measuring the relative changes of miniature endplate potentials (mEPPs) and voltage responses to step current pulses in individual muscle fibres. Exposure to ATP (20 μ
m) prolonged the mEPP falling phase by 31 ± 7.5% (values ±s.d., n= 3 fibres). Concurrently, the input resistance increased by 31 ± 2.0% and the time course of the voltage responses increased by 59 ± 3.0%. Analogous effects were observed using 2 and 5 μmATP, and on regions distal from the neuromuscular junction, indicating that physiologically relevant levels of ATP enhanced electrical signalling over the entire muscle fibre. The effects of extracellular ATP were blocked by 200 μmanthracene‐9‐carboxylic acid, a chloride channel inhibitor, and reduced concentrations of extracellular chloride, indicating that ATP inhibited chloride channels. A high affinity agonist for P2Y receptors, 2‐methylthioadenosine‐5′‐O‐diphosphate (2MeSADP), induced similar effects to ATP with an EC50 of 160 ± 30 nm. The effects of 250 nm2MeSADP were blocked by 500 nmMRS2179, a specific P2Y1 receptor inhibitor, suggesting that ATP acts on P2Y1 receptors to inhibit chloride channels. The inhibition of chloride channels by extracellular ATP has implications for muscle excitability and fatigue, and the pathophysiology of myotonias.
PKC‐permitted elevation of sarcolemmal KATP concentration may explain female‐specific resistance to myocardial infarction
Authors: Edwards Andrew G. , Rees Meredith L. , Gioscia Rachel A. , Zachman Derek K. , Lynch Joshua M. , Browder Jason C. , Chicco Adam J. , Moore Russell L.
Published: October 2009

The female myocardium, relative to that of the male, exhibits sustained resistance to ischaemic tissue injury, a phenomenon termed sex‐specific cardioprotection (SSC). SSC is dependent upon the sarcolemmal KATP channel (sarcKATP), and protein kinase C (PKC). Here we investigate whether PKC‐mediated regulation of sarcKATP concentration can explain this endogenous form of protection. Hearts from male (M) and female (F) rats were Langendorff‐perfused for 30 min prior to either regional ischaemia–reperfusion (I/R), or global ischaemia (GISC). For both protocols, pre‐ischaemic blockade of PKC was achieved by chelerythrine (Chel) in male (M + C) and female (F + C) hearts. Additional female hearts underwent sarcKATP antagonism during I/R by HMR‐1098 (HMR), either alone or in combination with Chel (HMR + Chel). GISC hearts were fractionated to assess cellular distribution of PKCɛ and sarcKATP. Sex‐specific infarct resistance was apparent under control I/R (F, 23 ± 3%vs. M, 36 ± 4%, P < 0.05) and abolished by Chel (F + C, 36 ± 3%). Female infarct resistance was susceptible to sarcKATP blockade (Control, 16 ± 2%vs. HMR, 27 ± 3%), and PKC blockade had no additional effect (HMR + Chel, 26 ± 2%). The prevalence of Kir6.2 and SUR2 was higher in the sarcolemmal fractions of females (Kir6.2: F, 1.24 ± 0.07 vs. M, 1.02 ± 0.06; SUR2: F, 3.16 ± 0.22 vs. M, 2.45 ± 0.09; ratio units), but normalized by Chel (Kir6.2: F, 1.06 ± 0.07 vs. M, 0.99 ± 0.06; SUR2: F, 2.99 ± 0.09 vs. M, 2.82 ± 0.22, M; ratio units). Phosphorylation of sarcolemmal PKCɛ was reduced by Chel (p‐PKCɛ/PKCɛ: control, 0.43 ± 0.02; Chel, 0.29 ± 0.01; P < 0.01). We conclude that PKC‐mediated regulation of sarcKATP may account for the physiologically sustainable dependence of SSC upon both PKC and sarcKATP, and that this regulation involves PKC‐permitted enrichment of the female sarcolemma with sarcKATP. As such, the PKC‐sarcKATP axis may represent a target for sustainable prophylactic induction of cardioprotection.
Evaluation of Formability in Bending/Hemming of Aluminum Alloys Using Plane-Strain Tensile Tests
Authors: Lin Guosong , Hu S. Jack , Cai Wayne
Published: October 2009

This paper presents a fundamental study for the characterization of formability in bending/hemming, or “bendability/hemmability,” of automotive aluminum alloys. Based on the strain/stress nature of the hemline (bent corner) surfaces, maximum surface strain was proposed as the hemming fracture criterion, and it is believed that bendability/hemmability of aluminum alloys can be directly approximated by the fracture strains from plane-strain tensile tests. The criterion was verified by comparing hemming and plane-strain tensile experiments on AA6111-T4 and AAx611-T4 with fracture strains measured, respectively, via a modified angled line method and thickness reductions. After a verification of material hardening laws, the identified failure criterion was implemented into 2D and 3D finite element hemming simulations for fracture predictions. The findings provide the basis for the design of aluminum hems under formality constraints, and it is expected that the fundamental theory and established methodology are applicable to bendability/hemmability evaluations for general sheet materials.
Pore Formation in Laser-Assisted Powder Deposition Process
Authors: Wang L. , Pratt P. , Felicelli S. D. , El Kadiri H. , Berry J. T. , Wang P. T. , Horstemeyer M. F.
Published: October 2009

Pore formation remains a concern in the area of rapid manufacturing by the laser engineered net shaping process. Results usually conflict on the origin of these pores; whether it should stem from an effect due to the physical/mechanical properties of the material or from an effect purely related to the processing parameters. We investigated this problem spanning a range of process parameters for deposition and using three different material powders, namely, an AISI 410 grade stainless steel, AISI 316L grade stainless steel, and AISI 4140 grade medium-carbon low alloy steel. The volume fraction, number density, and size distribution of pores were quantified using X-ray computed tomography and optical microscopy. Pores formed both at the interface between the adjacent layers and within the bulk of the layer. They were systematically sensitive to both the powder material composition and the process parameters.
Extended Geometric Filter for Reconstruction as a Basis for Computational Inspection
Authors: Miropolsky Alexander , Fischer Anath
Published: October 2009

The inspection of machined objects is one of the most important quality control tasks in the manufacturing industry. Contemporary scanning technologies have provided the impetus for the development of computational inspection methods, where the computer model of the manufactured object is reconstructed from the scan data, and then verified against its digital design model. Scan data, however, are typically very large scale (i.e., many points), unorganized, noisy, and incomplete. Therefore, reconstruction is problematic. To overcome the above problems the reconstruction methods may exploit diverse feature data, that is, diverse information about the properties of the scanned object. Based on this concept, the paper proposes a new method for denoising and reduction in scan data by extended geometric filter. The proposed method is applied directly on the scanned points and is automatic, fast, and straightforward to implement. The paper demonstrates the integration of the proposed method into the framework of the computational inspection process.
Crack Propagation in Glass by Laser Irradiation Along Laser Scribed Line
Authors: Yamamoto Koji , Hasaka Noboru , Morita Hideki , Ohmura Etsuji
Published: October 2009

A mechanical breaking process after laser scribing is indispensable to complete the separation of glass substrate since the crack depth induced by the laser scribing is limited. Laser irradiation along the laser scribed line is introduced in this paper as a crack propagation method in depth direction after the laser scribing of a relatively thick glass in order to make the mechanical breaking easier. Since the separating load decreases by propagating the scribed crack deeply, it contributes to the inhibition of glass particle generation. The target of this research is to clarify the mechanism of crack propagation by the laser irradiation along the laser scribed line. Two-dimensional thermal elasticity analysis was conducted by a finite element method based on the experimental results in order to theoretically estimate the laser irradiation condition, which propagates crack. The following results were obtained. Compressive stress is generated on the glass surface and tensile stress is generated inside the glass by the laser irradiation along the laser scribed line. The tensile stress concentrates at the crack tip induced by the laser scribing, and the crack propagates into the depth direction. The condition of crack propagation can be estimated from the maximum surface temperature and the maximum tensile stress of the crack tip in practical processing velocity (200 mm/s or more mm/s).
The Effect of Heat Treatment on the Room Temperature and Elevated Temperature Fracture Toughness Response of Alloy 718
Authors: Mills W. J.
Published: October 2009

The effect of heat treatment on the JIC fracture toughness behavior of Alloy 718 was characterized at room temperature, 427°C and 538°C. Two different heat treatments were used: the conventional (ASTM A637) treatment, and a modified heat treatment designed to improve the toughness of Alloy 718 base metal and weldments. The elastic-plastic JIC fracture toughness response of the modified Alloy 718 was found to be superior to the JIC behavior exhibited by the conventional material over the entire test temperature range. Metallographic and fractographic examinations of Alloy 718 fracture surfaces revealed that the inferior fracture resistance of the conventional superalloy was attributed to the presence of coarse δ precipitates throughout the conventional matrix. The increased fracture toughness response of the modified Alloy 718 was related to the dissolution of coarse δ precipitates during the high temperature solution anneal employed in the modified treatment.
Problems in Damage Analysis Under Nonproportional Cycling
Authors: Leis B. N. , Laflen J. H.
Published: October 2009

This paper uses examples to illustrate problems in damage analysis under nonproportional cycling. Nonproportional histories examined include multiaxial loading with either fixed or rotating principal directions. Currently popular concepts advanced for use in damage analysis of nonproportional cycling are reviewed and examined in terms of their potential ability to assess damage for example histories. It is shown that while such damage measures may be valid for mildly nonproportional histories, their successful application to general nonproportional cycling is unlikely. The paper closes with a commentary on the issues considered.
High-Cycle Fatigue Behavior of Solution-Annealed and Thermally-Aged Type 304 Stainless Steel
Authors: Soo P. , Chow J. G. Y.
Published: October 2009

High-cycle, load-controlled fatigue data have been obtained for solution-annealed and thermally-aged Type 304 stainless steel, for temperatures between 22 and 593°C (72-1100°F) at a cycling rate of 40 Hz. Although these data are principally used to assess fatigue failure in components subjected to rapid stress cycling, it has been shown that they may be correlated with available low-cycle data if cyclic stress-strain curves are used for converting the high-cycle stresses to effective strains. Differences in initial stress-strain history and cycling rates for the high- and low-cycle data evaluated are found to be unimportant. For the thermally-aged material there is an initial enhancement of the high-cycle-fatigue strength but, after long aging times, the strength decreases to a value close to that for unaged material. The carbide precipitates formed during aging appear to influence fatigue life through changes they impart in the cyclic work-hardening rates.
Fatigue Life Estimates for Bluntly Notched Members
Authors: Socie D. F.
Published: October 2009

Methods for estimating the total fatigue lives of bluntly notched members are presented. Analytical estimates are compared to experimental data generated in the Society of Automotive Engineers Cumulative Fatigue Damage Test Program. The crack initiation lives were predicted using strain life concepts and fracture mechanics methods were employed to predict the fatigue crack growth stages. The methods used highlighted the proportions of the total fatigue life spent in crack initiation and propagation. These were found to depend on load amplitude and level of mean load. For the bluntly notched member investigated the initiation and early stages of crack formation formed the major part of the total life, when the loading was predominantly tensile. Conversely for a loading history where most of the cycles were compressive the majority of the fatigue life was expended in crack growth away from the notch.
Structural Integrity in Merchant Ships
Authors: Rolfe S. T.
Published: October 2009

Since World War II, periodic changes in the fabrication, design, and material specifications for ship steels have been made to preclude brittle fractures. These various changes are described briefly, along with a history of fracture control for ships to serve as background information for a discussion of the present-day structural integrity program for ships in the marine industry. As additional information related to the structural integrity of ship structures, a review of two recent ship failures (e.g., the Ingram Barge in 1972 and the Chester A. Poling in 1977) is presented to demonstrate some of the factors involved in brittle fractures of ships. In both of these failures there were other factors contributing to the final brittle fractures that were more important than the notch toughness levels. These factors are reviewed as the basis for an observation regarding the overall structural integrity of merchant ships.
Minimizing Fatigue and Fracture in Steel Bridges
Authors: Fisher J. W. , Yen B. T. , Frank K. H.
Published: October 2009

Steel bridges are subjected to live loads which produce variable stress ranges in bridge components. At welded bridge details, the existence of initial defects and residual stresses eliminate the initiation stage of fatigue crack growth, and stress range is found to be the controlling factor for crack propagation. Laboratory tests have resulted in stress range-fatigue life relationships for various bridge details. These data correlate well with fracture mechanics theory and with field data. Limits on live load stresses have been adopted for steel bridges. Coupled with material fracture toughness requirements, the stress range limits minimize the probability of fatigue and fracture in steel bridges.
Systems Approach to Failure Resistant Cast Steel Railroad Carwheel Design
Authors: Haley M. R. , Larson H. R. , Kleeschulte D. G.
Published: October 2009

This paper describes the systems approach used in the design of a more failure-resistant cast steel railroad carwheel. Control of fracture toughness in high carbon steel is discussed and data are presented. Aspects of design geometry which produce lower thermal and mechanical stresses are discussed. The use of finite element computer models and full scale verification, including destructive drag dynamometer tests, are described. Consideration is given to computer solidification models and also to manufacturing constraints.
Fracture Mechanics Consideration of Residual Stresses Introduced by Coldworking Fastener Holes
Authors: Cathey W. H. , Grandt A. F.
Published: October 2009

Aluminum test specimens are prepared with precracked fastener holes, coldworked by means of an oversized mandrel, and then cycled to failure under constant amplitude loading. A simplified fracture mechanics analysis is performed to predict the fatigue crack growth life caused by the coldworking process. As discussed here, the analysis method is capable of obtaining reasonable estimates for the test specimen fatigue life and of determining the maximum crack size which can be “permanently” arrested by the coldworking process.
The Relationship Between Stress Intensity Factor, Crack Opening Displacement and J-Integral in Zr-2.5 Percent Nb
Authors: Simpson L. A.
Published: October 2009

Crack opening displacement (COD) has been determined in Zr-2.5 percent Nb over a wide range of applied stress intensity, K. Prior to initiation of crack extension, COD was determined from measurements of stretch zones in specimens which had undergone hydrogen-induced, sub-critical crack growth. In post initiation measurements (during slow stable crack extension), COD was determined from crack face displacement. Both methods were self consistent and depended on the plastic-zone-corrected K in accordance with the Wells equation. The J-integral was also determined during stable crack extension using the method of Garwood, et al. The results are consistent with the COD measurements based on theoretical relationships between the two crack tip parameters.
On the Use of Side-Grooves in Estimating JIc Fracture Toughness With Charpy-Size Specimens
Authors: Server W. L. , Wullaert R. A. , Ritchie R. O.
Published: October 2009

The problem of obtaining a meaningful value of toughness from small Charpy-size surveillance specimens, tested at temperature corresponding to the upper shelf where ductile fracture predominates, is investigated. Following the procedures of Green and Knott for measurement of crack opening displacements at initiation of ductile fracture, a test procedure is adopted in which small precracked Charpy-size bend specimens are side-grooved to increasing depths and tested to failure under both quasi-static and dynamic loading rates. Values of the J-contour integral at maximum load (Jmax) for specimens side-grooved in excess of 30 percent are found to agree, within acceptable limits, with “valid” initiation JIc fracture toughness values determined independently using multi-specimen resistance-curve techniques. Three nuclear pressure vessel materials (two base metals, SA533B-1 and SA302B, and a submerged arc weld metal) were evaluated at temperatures between 71 and 177° C, which correspond to upper shelf temperatures. The test procedure described offers a simple, inexpensive, small specimen compromise for estimating the fracture toughness at the onset of ductile fracture from a single Charpy-size bend test piece for both quasi-static and dynamic loading rates. This approach could be readily adopted in nuclear surveillance programs for toughness evaluation of unirradiated and neutron irradiated pressure vessel steels.
A Comparison of Cold Rolling Theories Based on the Equilibrium Approach
Authors: Saeed Usamah , Lenard J. G.
Published: October 2009

Roll separating force and roll torque are studied in cold rolling of steel and aluminum strips. In the analysis roll deformation is accounted for by a numerical technique; in the experimental portion force and torque transducers are used to monitor the variables. It is concluded that in spite of using average constant frictional coefficients, the technique of Atreya and Lenard predicts roll force and torque somewhat better than Orowan’s approach.