bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypercholesterolemia-Induced Erectile Dysfunction: Endothelial Nitric Oxide Synthase (eNOS) Uncoupling in the Mouse Penis by NAD(P)H Oxidase
Authors: Musicki Biljana , Liu Tongyun , Lagoda Gwen A. , Strong Travis D. , Sezen Sena F. , Johnson Justin M. , Burnett Arthur L.
Published: July 2010

Introduction

Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood.

Aims

We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED.

Methods

Low-density-lipoprotein receptor (LDLR)–null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67phox, p47phox, and gp91phox), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes.

Main Outcome Measures

The main outcome measures are the molecular mechanisms of ROS generation and endothelial dysfunction in hypercholesterolemia-induced ED.

Results

Erectile response was significantly (P <0.05) reduced in hypercholesterolemic LDLR-null mice compared with WT mice. Relative to WT mice, hypercholesterolemia increased (P <0.05) protein expressions of NAD(P)H oxidase subunits p67phox, p47phox and gp91phox, eNOS uncoupling, and 4-HNE-modified proteins, and reduced (P <0.05) P-VASP-Ser-239 expression in the penis. Apocynin treatment of LDLR-null mice preserved (P <0.05) maximal intracavernosal pressure, and reversed (P <0.05) the abnormalities in protein expressions of gp67phox and gp47phox, 4-HNE, P-VASP-Ser-239, and eNOS uncoupling in the penis. Apocynin treatment of WT mice did not affect any of these parameters. Protein expressions of P-eNOS-Ser-1177 and total eNOS were unaffected by hypercholesterolemia.

Conclusion

Activated NAD(P)H oxidase in the penis is an initial source of oxidative stress resulting in eNOS uncoupling, thus providing a mechanism of eNOS uncoupling and endothelial dysfunction in hypercholesterolemia-induced ED.
Genital Manifestation of Graft-vs.-Host Disease: A Series of Case Reports
Authors: Da Silva Lara Lúcia Alves , De Andrade Jurandyr Moreira , Mauad Lenira Maria Queiroz , Ferrarese Sany Rose , Marana Heitor Ricardo Cosiski , Tiezzi Daniel Guimarães , De Sá Rosa e Silva Ana Carolina Japur
Published: July 2010

Introduction

After hematopoietic stem cell transplantation (HSCT), many patients present genital graft-vs.-host disease (GVHD) that can culminate with sexual problems, which are poorly dimensioned.

Aim

We hope to draw attention to the need to perform genital biopsy to diagnose genital GVHD, and thus to call attention to the need to incorporate careful attention to sexual health in the treatment of these patients.

Methods

Five allogeneic stem cell transplant recipients complaining of coital pain after HSCT were clinically diagnosed for genital GVHD. Genital biopsies were given for histological analysis, and microphotographs of the corresponding marked field in the slide were taken. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the histological findings. A literature search was performed in PubMed/MEDLINE (1966–2009) for cross-sectional and cohort studies or trials related to genital GVHD. Expert opinions peer reviews and case reports were also considered.

Main Outcome Measures

HSCT, genital GVHD, genital biopsy.

Results

The biopsy showed evidence of dilated apoptotic cells in the basal layer and detachment of the epithelial lining of the mucosa, hyalinization and thickening of collagen fibers, capillary ectasia, and mononuclear inflammatory infiltrate of the submucosa. Three patients presented vulval lesion such as leucoplasia and ulcer on the large lip. Histological analyses showed evidence of epithelial hyperplasia and influx of inflammatory cells to the epithelial surface, intercellular edema and spongiosis, apoptotic bodies on the basal layer of the epithelium, spongiosis, and nuclear vacuolization. A common treatment based on corticotherapy resulted in complete remission of coetaneous or mucous genital lesions in all five patients.

Conclusion

Genital biopsy is important to differentially diagnose GVHD and secondary symptoms due to hypoestrogenism. Prevention is the most important step in controlling the evolution GVHD in the vagina to prevent vaginal obstruction and sexual dysfunction.
The Determination of Total Testosterone and Free Testosterone (RIA) are not Applicable to the Evaluation of Gonadal Function in HIV-Infected Males
Authors: Moreno-Pérez Oscar , Escoín Corina , Serna-Candel Carmen , Portilla Joaquín , Boix Vicente , Alfayate Rocio , González-Sánchez Victor , Mauri Montserrat , Sánchez-Payá José , Picó Antonio
Published: July 2010

Introduction

Hypogonadism is common in human immunodeficiency virus (HIV)-infected men; the high concentration of sex hormone binding globulin (SHBG) in this population, induces a “false increase” in total testosterone (TT) values.

Aims

To validate the determination of TT and measured free testosterone (FT [radioimmunoassay {RIA} ] ) for hypogonadism diagnosis in an HIV-infected population using calculated free testosterone (CFT) as reference method; and also to determine the prevalence and identify the risks factors of hypogonadism.

Methods

Cross-sectional, observational study. Ninety HIV-infected males (42 ± 8.2 years), not HCV coinfected, antiretroviral therapy (ART)-naive (14 patients), on current ART with enhanced protease inhibitor (PI) (39 patients), or patients on PI-naive ART (NN) (37 patients).

Main Outcome Measures

CFT was calculated by determining TT, SHBG, and albumin (Vermeulen’s formula); hypogonadism was defined as CFT <0.22 nmol/L (reference range for young healthy males in our laboratory); sensitivity of TT and FT (RIA) for hypogonadism diagnosis was calculated.

Results

Twelve patients (13.3%, 95% confidence interval [CI] 7.8–21.9) by CFT presented hypogonadism. TT and FT (RIA) presented a sensitivity of less than 30% in the diagnosis of hypogonadism. Logistic regression multivariate analysis confirmed an independent association between hypogonadism, the patient’s age per decade, odds ratio (OR) 6.9 (CI 1.9–24.8; P = 0.003), and longer duration of HIV infection per decade, OR 13.1 (CI 1.3–130.6; P = 0.02). Hypogonadism was associated with erectile dysfunction.

Conclusions

TT and FT (RIA) are not useful in the differential diagnosis of hypogonadism in HIV-infected males. There is a significant prevalence of hypogonadism in HIV-infected males, with the patient’s age and duration of the disease being the only identifiable risk factors.
Efficacy and Safety of Oral Mirodenafil in the Treatment of Erectile Dysfunction in Diabetic Men in Korea: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Park Hyun Jun , Choi Hyung Ki , Ahn Tai Young , Park Jong Kwan , Chung Woo Sik , Lee Sung Won , Kim Sae Woong , Hyun Jae Seog , Park Nam Cheol
Published: July 2010

Introduction

Mirodenafil is a newly developed selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED).

Aim

To evaluate the efficacy, safety and tolerability of mirodenafil in the treatment of ED in Korean men with diabetes.

Methods

A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 112 subjects who were randomized to either placebo or mirodenafil 100 mg on demand for 12 weeks.

Main Outcome Measures

Primary efficacy variable was the erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables included change in the scores of IIEF question 3 and 4 (IIEF Q3 and Q4) from baseline, change in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ) and the Life Satisfaction Checklist (LSC).

Results

After 12 weeks of treatment, mirodenafil group showed significantly greater change in the IIEF-EF domain score from baseline compared with the placebo group (9.3 vs. 1.4, P <0.0001). The changes from baseline in the mirodenafil group in IIEF Q3 (1.7 vs. 0.4, P <0.0001) and Q4 (1.7 vs. 0.3, P <0.0001) were higher compared with the placebo group. Differences between the mirodenafil and placebo groups were significant in the SEP2 (82.0% vs. 55.2%, P = 0.0003), SEP3 (68.9% vs. 22.3%, P <0.0001). Difference in GAQ “YES” responses was also significant (76.9% vs. 19.1%, P <0.0001). Normal EF domain scores (≥26) at study end were achieved by 32.7% and 9.4% in the mirodeniafl and placebo groups, respectively (P = 0.0031). As for the LSC scores, the mirodenafil group showed significantly greater improvements in sexual life and partner relationship than the placebo group. Most treatment-associated AEs were mild that resolved spontaneously.

Conclusions

Mirodenafil is an effective and well-tolerated agent for the treatment of diabetic patients with ED in Korea.
Validation of a Chinese Version of the Short Form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire
Authors: Su Tsung-Hsien , Lau Hui-Hsuan
Published: July 2010

Introduction

Sexual dysfunction is prevalent in women with pelvic organ prolapse and/or urinary incontinence. An instrument is needed to assess sexual function in urogynecologic patients who speak Chinese.

Aim

To evaluate the reliability and validity of a Chinese translation of the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) in urogynecologic patients in Taiwan.

Methods

After a pilot study showing good test–retest reliability and internal consistency of the Chinese PISQ-12, 120 urogynecological patients and 63 normal women were recruited. All participants underwent the Pelvic Organ Prolapse Quantification (POP-Q) system and urodynamic assessment. They each completed the Chinese PISQ-12 and the short form of Incontinence Impact Questionnaire (IIQ-7).

Main Outcome Measures

PISQ-12, POP-Q system and IIQ-7 scores were compared between the urogynecologic patients and normal controls.

Results

The test–retest reliability and internal consistency of the Chinese PISQ-12 total score (Pearson correlation coefficient r = 0.939, Cronbach’s alpha=0.892, respectively) and of each of its three domains were excellent. The mean total PISQ-12 score and mean scores in each domain indicated significantly worse sexual dysfunction in the urogynecologic group as compared with the control group were correlated with the severity of prolapse and distress caused by incontinence.

Conclusion

This Chinese translation of the PISQ-12 is a reliable, consistent and valid instrument to evaluate sexual function in Taiwanese women with pelvic organ prolapse and/or urinary incontinence.
Androgen Deprivation Therapy for Prostate Cancer: Recommendations to Improve Patient and Partner Quality of Life
Authors: Elliott Stacy , Latini David M. , Walker Lauren M. , Wassersug Richard , Robinson John W. , ADT Survivorship Working Group
Published: July 2010

Introduction

Because of improved prostate cancer detection, more patients begin androgen deprivation therapy (ADT) earlier and remain on it longer than before. Patients now may be androgen deprived for over a decade, even when they are otherwise free of cancer symptoms.

Aim

An ADT Survivorship Working Group was formed to develop and evaluate interventions to limit the physiological and emotional trauma patients and their partners experience from this treatment.

Methods

The multidisciplinary Working Group met for 2 days to define the challenges couples face when patients commence ADT. A writing sub-group was formed. It compiled the meeting’s proceedings, reviewed the literature and, in consultation with the other members of the working group, wrote the manuscript.

Main Outcome Measures

Expert opinion of the side effects of ADT that affect the quality of life (QOL) of patients and their partners and the recommendations for managing ADT to optimize QOL were based on the best available literature, clinical experience, and widespread internal discussions among Working Group members.

Results

Side effects identified as particularly challenging include: (i) body feminization; (ii) changes in sexual performance; (iii) relationship changes; (iv) cognitive and affective symptoms; and (v) fatigue, sleep disturbance, and depression. Recommendations for managing ADT include providing information about ADT side effects before administration of ADT, and, where appropriate, providing referrals for psychosocial support. Sexual rehabilitation principles for persons with chronic illness may prove useful. Psychological interventions for sexual sequelae need to be offered and individualized to patients, regardless of their age or partnership. Support should also be offered to partners.

Conclusions

Our hope is that this plan will serve as a guide for optimizing how ADT is carried out and improve the lives of androgen-deprived men and their intimate partners.
Association between Attributes of a Cyclist and Bicycle Seat Pressure
Authors: Bressel Eadric , Nash Dustin , Dolny Dennis
Published: July 2010

Introduction

Bicycle seat pressure is thought to be the principal risk factor for bicycle seat injuries such as erectile dysfunction; however there is a lack of understanding regarding the characteristics of a cyclist that predict bicycle seat pressure.

Aim

The purpose of this study was to determine if select attributes of a cyclist are associated with seat pressure during stationary bicycling. A secondary purpose was to determine which of the associated attributes were the best predictors of seat pressure and if they were consistent between two different seats.

Methods

There were two data collection phases to this correlational study in which 40 males between the ages 20 and 50 years volunteered. For the first phase, select attributes of the cyclist (age, weight, flexibility, experience level, and ischial tuberosity width) were measured. The second phase required participants to ride a stationary cycle ergometer while pelvic tilt angles and seat pressures were measured on two different traditional seats.

Main Outcome Measure

The main outcome is the mean and peak bicycle seat interface pressure over the anterior and total seat.

Results

Body weight explained up to 50% of the variance in mean total seat pressure (P = 0.001). Regarding peak total pressure, pelvic tilt angle and flexibility explained 43% and 17% of the variance, respectively, for the two seats tested (P = 0.01).

Conclusion

These results indicate that predictors of mean seat pressure are not the same for peak pressure. Body weight alone accounted for the most variance in mean pressure whereas pelvic tilt and flexibility accounted for the most variance in peak pressure. These variables related to seat pressure may give some guidance to cyclists and clinicians who intend to prevent or alleviate the symptoms associated with bicycle seat injuries that include erectile dysfunction.
Severe Depressive Symptoms and Cardiovascular Risk in Subjects with Erectile Dysfunction
Authors: Bandini Elisa , Fisher Alessandra D. , Corona Giovanni , Ricca Valdo , Monami Matteo , Boddi Valentina , Balzi Daniela , Melani Cecilia , Forti Gianni , Mannucci Edoardo , Maggi Mario
Published: July 2010

Introduction

Erectile dysfunction (ED) and mood depression are often associated and both are correlated with an increased risk of cardiovascular morbidity and mortality.

Aim

The aim of the present study is to explore biological and clinical correlates of depressive symptomatology in a sample of men consulting for sexual dysfunction and to verify possible associations between depressive symptoms and incidence of major cardiovascular events (MACE).

Methods

A consecutive series of 2,303 male patients attending the Outpatient Clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N=1,687) was enrolled in a longitudinal study. All patients were investigated using a Structured Interview on Erectile Dysfunction (SIEDY), composed of 3 scales which explore organic, relational and intra-psychic components of ED. MHQ-D scoring from Middlesex Hospital Questionnaire (MHQ) was used as a putative marker of depressive symptoms.

Main Outcome Measures

Information on MACE was obtained through the City of Florence Registry Office.

Results

We found a positive relationship between MHQ-D score and a progressive impairment in obtaining an erection hard enough for penetration, even after adjusting for confounding factors. Moreover, we observed positive relationships between MHQ-D score and the three pathogenetic domains underlying ED. When the longitudinal subset was evaluated, during a mean follow-up of 4.3 ± 2.6 years, 139 MACE, 15 of which were fatal, were observed. Unadjusted incidence of MACE was significantly associated with baseline depressive symptoms. When the presence of severe depressive symptoms were introduced in a Cox regression model, along with the arteriogenic ED and partner’s hypoactive sexual desire, after adjusting for age, Chronic Diseases Score, and ΣMHQ (a broader index of psychopathology), severe depressive symptomatology was independently associated with a higher incidence of MACE.

Conclusion

Depressive symptomatology constitutes an independent risk factor for cardiac morbidity and mortality in men with ED.
Behavior, metamorphosis, and muscular organization of the predatory rotifer Acyclus inquietus (Rotifera, Monogononta)
Authors: Hochberg Rick , O'Brien Stephen , Puleo Alaina
Published: July 2010

Abstract. The atrochid rotifer, Acyclus inquietus, is a sedentary predator that lives within the colonies of its prey, the rotifer Sinantherina socialis. After larvae infiltrate and become associated with the colony, they secrete a permanent gelatinous tube and undergo metamorphosis to the adult stage. We followed settlement and metamorphosis using bright‐field microscopy to document specific larval behaviors after eclosion, and used epifluorescence and confocal microscopy of phalloidin‐labeled specimens to visualize some of the morphological changes that occur during metamorphosis. Upon eclosion, larvae possess paired eyespots and a ciliated corona that functions strictly in locomotion. After leaving the parent's gelatinous tube, larvae eventually settle on unoccupied colonies of S. socialis or on other substrates if colonies are unavailable. Settlement involves a period of gliding among colony members before attachment with the foot and the secretion of a gelatinous tube. After settlement, there is a drastic reconfiguration of the corona that involves loss of the eyespots, loss of the coronal cilia, and the formation of the cup‐shaped infundibulum, a deep depression in the anterior of the head that leads to the mouth. The development of the infundibulum involves the expansion of tissues around the mouth and is accompanied by a reorientation of the underlying musculature that supplies the infundibulum and allows its use in prey capture. The arrangement of the muscles in the trunk and foot regions, which contain outer circular (complete and incomplete) and inner longitudinal bands, remains unchanged between ontogenetic stages, and reflects the condition characteristic of other rotifers.
The PC12 cell as model for neurosecretion
Authors: Westerink R. H. S. , Ewing A. G.
Published: July 2010

This review attempts to touch on the history and application of amperometry at PC12 cells for fundamental investigation into the exocytosis process. PC12 cells have been widely used as a model for neural differentiation and as such they have been used to examine the effects of differentiation on exocytotic release and specifically release at varicosities. In addition, dexamethasone‐differentiated cells have been shown to have an increased number of releasable vesicles with increased quantal size, thereby allowing for an even broader range of applications including neuropharmacological and neurotoxicological studies. PC12 cells exhibiting large numbers of events have two distinct pools of vesicles, one about twice the quantal size of the other and each about half the total releasable vesicles. As will be outlined in this review, these cells have served as an extremely useful model of exocytosis in the study of the latency of stimulation‐release coupling, the role of exocytotic proteins in regulation of release, effect of drugs on quantal size, autoreceptors, fusion pore biophysics, environmental factors, health and disease. As PC12 cells have some advantages over other models for neurosecretion, including chromaffin cells, it is more than likely that in the following decade PC12 cells will continue to serve as a model to study exocytosis.
Noteworthy Discrepancies in China's GDP Accounting
Authors: He Xinhua
Published: July 2010

Consistency is essential in statistical data processing. This paper reports some notable discrepancies in China's GDP accounting, which are unexpectedly found after testing the consistency of GDP accounting and its components. Although these discrepancies are mainly attributed to the revision methodology adopted after the 2004 economic census, the intention to harmonize GDP accounting data, in terms of production and expenditure, also contributes to the discrepancies. Our finding highlights the need for careful checking of consistency and for testing before formal release of any official statistics.
Business Cycle Asymmetry in China: Evidence from Friedman's Plucking Model
Authors: Zheng Tingguo , Teng Yujuan , Song Tao
Published: July 2010

Friedman's plucking model of business fluctuations suggests that output cannot exceed an upper limit, but it is occasionally “plucked” downward below trends as a result of economic recessions. This paper investigates China's business fluctuations using quarterly real GDP data for the period 1978–2009. Our results show some evidence supporting Friedman's plucking model. We find that a ceiling effect of real output exists, and that negative asymmetric shocks significantly affect the transitory component, which captures the plucking downward behavior during the recession. The results also suggest that the basic asymmetric unobserved component model is not appropriate for directly modeling China's real output because the business cycle is inaccurately measured, but it works quite well when considering a structural break in the second quarter of 1992. The results reveal that although China's economy strengthened in the second quarter of 2009, it is essential for China's government to take further positive and effective measures to maintain sustainable development of the economy.
From Molecules to Mind
Authors: McEwen Bruce S.
Published: July 2010

Abstract: The social and physical environments in which we live have an enormous impact on our physiology and behavior and influence the process of adaptation, or “allostasis.” Genes, early development, adult experiences, life style, and stressful life experiences all contribute to the way the body adapts to a changing environment; and these factors all help to determine the cost to the body, or “allostatic load.” Studies of these processes involve the disciplines of biology and psychology, but they are incomplete without the input from other fields, such as cultural anthropology, economics, epidemiology, political science, and sociology. These fields provide a description and analysis of the social and cultural institutions and economic forces that affect individual human health. Specific examples of shared concepts and terminology are given to illustrate progress towards consilience in the study of socioeconomic determinants of health.
Original Article: A primary school outbreak of pandemic 2009 influenza A (H1N1) in China
Authors: Huai Yang , Lin Jinyan , Varma Jay K. , Peng Zhibin , He Jianfeng , Cheng Chen , Zhong Haojie , Chen Yuansheng , Zheng Yingdong , Luo Yuan , Liang Wenjia , Wu Xiaoling , Huang Zhenyu , McFarland Jeffrey , Feng Zijian , Uyeki Timothy M. , Yu Hongjie
Published: July 2010

Please cite this paper as: Huai et al. (2010) A primary school outbreak of pandemic 2009 influenza A (H1N1) in China. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00150.x.

Background  We investigated the first known outbreak of pandemic 2009 influenza A (H1N1) at a primary school in China.

Objectives  To describe epidemiologic findings, identify risk factors associated with 2009 H1N1 illness, and inform national policy including school outbreak control and surveillance strategies.

Methods  We conducted retrospective case finding by reviewing the school’s absentee log and retrieving medical records. Enhanced surveillance was implemented by requiring physicians to report any influenza‐like illness (ILI) cases to public health authorities. A case–control study was conducted to detect potential risk factors for 2009 H1N1 illness. A questionnaire was administered to 50 confirmed cases and 197 age‐, gender‐, and location‐matched controls randomly selected from student and population registries.

Results  The attack rate was 4% (50/1314), and children from all grades were affected. When compared with controls, confirmed cases were more likely to have been exposed to persons with respiratory illness either in the home or classroom within 7 days of symptom onset (OR, 4·5, 95% CI: 1·9–10·7). No cases reported travel or contact with persons who had traveled outside of the country.

Conclusions  Findings in this outbreak investigation, including risk of illness associated with contacting persons with respiratory illness, are consistent with those reported by others for seasonal influenza and 2009 H1N1 outbreaks in school. The outbreak confirmed that community‐level transmission of 2009 H1N1 virus was occurring in China and helped lead to changes in the national pandemic policy from containment to mitigation.
REVIEW: γ‐Secretase Inhibitors for the Treatment of Alzheimer's Disease: The Current State
Authors: Panza Francesco , Frisardi Vincenza , Imbimbo Bruno P. , Capurso Cristiano , Logroscino Giancarlo , Sancarlo Daniele , Seripa Davide , Vendemiale Gianluigi , Pilotto Alberto , Solfrizzi Vincenzo
Published: July 2010

Aims: Drugs currently used for the treatment of Alzheimer's disease (AD) partially stabilize patients’ symptoms without modifying disease progression. Brain accumulation of oligomeric species of β‐amyloid (Aβ) peptides, the principal components of senile plaques, is believed to play a crucial role in the development of AD. Based on this hypothesis, huge efforts are being spent to identify drugs able to interfere with proteases regulating Aβ formation from amyloid precursor protein (APP). This article briefly reviews the profile of γ‐secretase inhibitors, compounds that inhibit γ‐secretase, the pivotal enzyme that generates Aβ, and that have reached the clinic. Discussion: Several classes of potent γ‐secretase inhibitors have been designed and synthesized. Preclinical studies have indicated that these compounds are able to lower brain Aβ concentrations and, in some cases, reduce Aβ plaque deposition in transgenic mouse models of AD. The most developmentally advanced of these compounds is semagacestat, presently in Phase III clinical trials. In animals, semagacestat reduced Aβ levels in the plasma, cerebrospinal fluid (CSF), and the brain. However, studies have not reported on its cognitive effects. Studies in both healthy volunteers and patients with AD have demonstrated a dose‐dependent inhibition of plasma Aβ levels, and a recent study in healthy subjects demonstrated a robust, dose‐dependent inhibition of newly generated Aβ in the CSF after single oral doses. Conclusions: Unfortunately, γ‐secretase inhibitors may cause intestinal goblet cell hyperplasia, thymus atrophy, decrease in lymphocytes, and alterations in hair color, effects associated with the inhibition of the cleavage of Notch, a protein involved in cell development and differentiation. Nevertheless, at least other two promising γ‐secretase inhibitors are being tested clinically. This class of drugs represents a major hope to slow the rate of decline of AD.
Preserving Domesticity: Reading Tupperware in Women's Changing Domestic, Social and Economic Roles*
Authors: VINCENT SUSAN
Published: July 2010

L'image représentée par Tupperware est essentiellement féminine. Cet article analyse la littérature entourant Tupperware pour y retrouver cette image de la fémininité de classe moyenne, euronord‐américaine et domestique. L'analyse de cette littérature se fait en tenant compte des changements et continuités, au cours des 50 dernières années, des rôles domestiques, économiques et sociaux des femmes nord‐américaines. Ces rôles domestiques et économiques se sont entrelacés, ce qui a permis à L'entreprise de mieux les exploiter. La réussite de Tupperware en s'associant à cette image très précise peut servir comme baromètre pour révéler comment les femmes négocient les pressions combinées de la maison et du travail.

Tupperware projects a quintessentially gendered image. This article explores writings by and about Tupperware to discover its representation of middle‐class white domestic femininity. This image is read against changes and continuities in North American women's domestic, economic and social roles over the past fifty years. There has been an ongoing intertwining of women's domestic and paid work roles that Tupperware has been able to exploit. The enduring success of Tupperware as a company associated with a specific image is thus a useful barometer indicating how women are contending with the combined pressures of home and work.
Short-Term Regulation of BOD Upsets in an Estuary
Authors: Jain R. K. , Denn M. M.
Published: July 2010

Local dynamic regulation of BOD upsets in an estuary is considered using optimal control theory. It is concluded that such regulation is not a feasible means of maintaining water quality.
Statistical Modeling of Pharmacokinetic Systems
Authors: Tsokos J. O. , Tsokos C. P.
Published: July 2010

A statistical treatment of a pharmacokinetic compartmental model is described, wherein the initial drug concentration and/or the rate constants governing the distribution of the drug between the appropriate compartments are considered to be random variables. A specific pharmacokinetic model which describes the profile of the antibiotic coumermycin A, following intravenous and oral administration in man, is stochastized and a numerical comparison between the deterministic and the mean of the random solutions as a function of time is presented.
Deterministic and Stochastic Effects in Population Dynamics
Authors: Oster G. F. , Auslander D. M. , Allen T. T.
Published: July 2010

An age-structured model based on an extension of the equations for convective flow is constructed and tested for laboratory populations of sheep blowflies. The model is shown to be capable of reproducing major frequency components in the data not hitherto predicted by deterministic models. Through the introduction of stochastic mortality and fecundity, the effects of individual variation are taken into account, thus extending the model’s validity to very low population levels.
Statistical Weather Forecasting
Authors: Grosjean A. , Kueny J. L.
Published: July 2010

This paper illustrates the use of statistical methods such as multiple correlation analysis, discriminant analysis and principal component analysis for weather forecasting. Two examples are presented: the first is a qualitative local prediction of daily precipitation for the next day, using pressure measures of the present day and of past days, by means of discriminant analysis; the second is an analysis of the 500-mbar geopotential heights over Western Europe by means of principal component analysis, followed by a quantitative synoptic prediction of the evolution of these geopotential heights for the next week to come, by means of multiple correlation analysis. For each of these two prediction problems, good predictors are chosen among a great number of candidate ones by a special stepwise selection procedure.
Price Level Stabilization Experiments Using the Dynamic Phillips Curve Concept
Authors: Healey A. J. , Medina F.
Published: July 2010

This paper deals with the price-level stabilization issue from a monetarist point of view. Government fiscal action is assumed to be ineffective without corresponding monetary actions. The price-level stabilization is studied here using the dynamic econometric model developed by the St. Louis Federal Reserve Bank and, employing a linear parameterised control law, optimized monetary policies are found which drive the economy to specified target inflation rates. The economic response is described in terms of dynamic Phillips curves and the tradeoff between short term unemployment and long term stabilized inflation rates is given. The control solution indicates that optimized monetary policy should be initially contractionary, followed by a mild expansionary phase. There is a short term rise in unemployment which is the price paid for stabilized low inflation rates.
Some Simple Nonlinear Dynamic Models of Interacting Element Cycles in Aquatic Ecosystems
Authors: Quinlan A. V. , Paynter H. M.
Published: July 2010

The underlying mechanism of eutrophication and its environmental impacts can be approached by considering the matter-flow rate mechanisms of each crucial element cycle of the nutrient-enriched ecosystem, together with requisite interactions between these element cycles. The balanced aquarium is taken as a prototype aquatic ecosystem, giving rise to a rudimentary element-cycle model. Such models are then employed to demonstrate how element cycles may interact via functional intercoupling through rate-law dependencies and via physical interconnection through transport processes. The resulting behavior includes free and forced limit cycles, which approach “multivibrator” response in limiting cases. These features and other system properties are analyzed and discussed in some detail.
Optimal Control of a National Economic System With Full Employment
Authors: Yeo L. T. , Teo K. L.
Published: July 2010

In this paper, we consider an optimal control problem of a national economic system with full employment in which the “Marginal Propensity to Save” and the “Profit Margin” are treated as control variables. This problem is modelled and modified on the basis of the cyclical growth theory developed by Keynes, Phillips, Bergstrom [2], The well-known Pontryagin Maximum Principle and the transversality condition [6] are then applied to obtain the optimum saving policy and profit margin following the steps of Ahmed and Yeo [1]. For illustration, a numerical example is solved using Davidon, Fletcher, Powell method with Fibonacci search technique in the last section.
Simulation of Market Price Formation as a Game Between Stochastic Automata
Authors: El-Fattah Y. M. , Henriksen R.
Published: July 2010

A seller in a free competitive market attempts to optimize his profit by manipulating the price of his commodity. A seller does not know a priori the market conditions such as the conditional probability of the buyers demand, the criteria or even the number of his seller opponents. Subject to this lack of information, the process of market price formation can be simulated as a game between stochastic automata. As time unfolds each seller-automaton learns the market conditions and changes accordingly its price probabilities in view of maximizing its profit. A simple reinforcement scheme is introduced for the design of such automata. The simulation results demonstrate the expediency of the automata behavior.
Application of Optimal Input Synthesis to Aircraft Parameter Identification
Authors: Gupta N. K. , Mehra R. K. , Hall W. E.
Published: July 2010

This paper considers an application of the Frequency Domain Input Synthesis procedure reference [12] for identifying the stability and control derivatives of an aircraft. In previous studies, the input design has mostly been carried out in the time-domain. However, by using a frequency-domain approach, one can handle criteria that are not easily handled by the time-domain approaches. Numerical results are presented for optimal elevator deflections to estimate the longitudinal stability and control derivatives subject to root-mean square constraints on the input. The applicability of the steady state optimal inputs to finite duration flight testing is investigated. It is shown that the steady state approximation of frequency-domain synthesis is good for data lengths greater than two time cycles for the short period mode of the aircraft longitudinal motions. For data lengths shorter than this, the phase relationships between different frequency components becomes important. The frequency domain inputs are shown to be much better than the conventional doublet inputs.
Distributed System Identification: A Green’s Function Approach
Authors: Spalding G. R.
Published: July 2010

A method is presented for identifying linear distributed parameter systems. Emphasis is placed on identification as a function of spatial coordinates by considering time-transformed, noise-free systems. Measurements of system response are combined with the Green’s function method of analysis to obtain integral equations that can be solved for unknown spatial operators or coefficients. A discrete form of the theory is developed, utilizing Chebyshev polynomials. This allows prior estimates to be used to determine the number and location of spatial measurements. Where estimates are of sufficient order, the modeling process is exact.
Scheduling Delays in Synchronous Transportation Networks
Authors: Kornhauser A. L. , McEvaddy P. J.
Published: July 2010

This paper investigates the performance of proposed network management policies responsible for routing and scheduling vehicles in automated transportation networks Performance is quantified in probabilistic terms of expected delays inherent to the scheduling process. Improved performance resulting from extensions of synchronous management to include considerations of multiple feasible routes and scheduled slot slipping is quantified and compared to quasi-synchronous management. This comparison suggests a bound on the minimum number of feasible routes and slot slipping capability for synchronous management to rival quasi-synchronous. The implications of network management on queue formation in stations and, consequently, on station design and layout are presented. It is found that synchronous-type management policies require parallel or lateral berthing in stations, whereas quasi-synchronous management imposes no such restriction on station design.
On the Stability in the Sense of Liapunov of a Rubber Tire Vehicle
Authors: Sachs H. K. , Chou C. C.
Published: July 2010

A qualitative evaluation of the vehicle stability problem is given for the purpose of establishing a measure of the performance limit of automobiles for the imposed conditions of constant speed and fixed steer control.
Analysis of a Platform for Measuring Moments and Products of Inertia of Large Vehicles
Authors: Orne D. , Schmitz T.
Published: July 2010

A rigid platform symmetrically supported by four sloping cables is proposed for measuring the center-of-gravity coordinates and the moments and products of inertia of large vehicles such as buses, trucks, and trailers. In addition to a torsional degree-of-freedom, the system undergoes pitch and roll motions about axes through the system instantaneous center which lies directly below the center of the platform at the intersection of the cable lines-of-action under quiescent conditions. The natural frequencies and normal modes of the freely vibrating loaded platform are used as inputs to a linearized System Identification Algorithm for computing the inertia properties of the test vehicle. Hypothetical test data generated from the Free Vibration Analysis of a sample test configuration are used to evaluate the sensitivity of the System Identification Algorithm to inaccuracies in test data or to truncation errors in computation.
A Historical Review of Autopilot Development, Research, and Theory in Germany
Authors: Oppelt Winfried
Published: July 2010

German flight-control development began with directional control. Damping gyros, measuring the angular velocity, were already used in the first systems. Servo-loops were formed including feedback devices as well as controllers without feedback, which proved to be satisfactory too. Finally integrating-gyros and electrical servomechanisms were put together for systems with outstanding performance capabilities. Among the many engineers acting in this field only a few distinguished themselves by producing ideas. Their names are documented here.
The Early Development of Control Theory. II
Authors: Fuller A. T.
Published: July 2010

In a previous paper Airy’s contributions to control theory were reviewed, and the developments in control which led up to Airy’s 1840 paper were summarized. The present paper continues the investigation into the history of control theory, and is mainly concerned with Maxwell’s paper of 1868. A preliminary background study deals with the development of integral control during 1837–1868. Then an expanded version is given of Maxwell’s rather terse exposition of stability of speed control systems.
On Multilevel Optimization of a Combined Static and Dynamic Problem
Authors: Nikiforuk P. N. , Gupta M. M. , Tamura K.
Published: July 2010

The solution of a combined static and dynamic optimization problem is considered in this paper. By means of a feasible decomposition procedure this combined problem is first decomposed into a two-level optimization problem. In this new problem the first-level subproblem is found to be one of conventional optimal control and mathematical programming which can be solved using known techniques. For the solution of the second-level problem a computational algorithm is developed using the gradient projection method. The existence of the solution is investigated. To illustrate the applicability of the method, a simplified gantry crane yard design problem is considered and some computational results are given.
Modeling of Enzyme Reaction Kinetics
Authors: Cheruy A.
Published: July 2010

It is shown in this paper how a kinetic analysis of enzymatic reactions with the goal of determining their reaction mechanisms corresponds to the modeling of a certain class of processes. Typical problems of these biosystems are discussed.
Minimax Output Feedback Regulators
Authors: Yahagi T.
Published: July 2010

The linear quadratic regulator problem is considered, and a method for obtaining an optimal output feedback control subject to a minimax performance index is presented. The optimal constant feedback matrix, which denotes the optimal constant feedback gains, is determined by minimizing the effects of the worst value of the initial state on the system performance measure. First, the necessary conditions for a minimax solution are given analytically. However, it is very difficult to determine the minimax solution directly from these necessary conditions. Then, a method for obtaining an optimal numerical solution by using a recursive formula is presented. Two iterative algorithms for the minimax solution are given. These algorithms are based on Theorem 4 and the saddle point assumption is not used. As shown in the illustrative examples the iterative solutions converge to the minimax value rapidly, and this method is useful for obtaining the minimax output feedback solution.
On the Identification of Noise Covariances in Continuous Linear Systems
Authors: Yoshimura T. , Soeda T.
Published: July 2010

This paper is concerned with an approach for identifying the input and observation noise covariances in continuous linear systems. The estimates of noise covariances are evaluated as the mean squares of Brownian motion processes conditioned upon all the available observation data. The suboptimal solutions are obtained in the sense that the differential equations for the evolution of the estimates are derived. Numerical examples for a simple system indicate acceptable performance of the proposed method.
“Optimum Linear Preview Control With Application to Vehicle Suspension”—Revisited
Authors: Tomizuka Masayoshi
Published: July 2010

Preview control of vehicle suspension as proposed by Bender is studied from the viewpoint of discrete optimal control. Improvements of the suspension system similar to those observed by Bender (reduction of acceleration and suspension clearance space) are rediscovered. The structure of the preview controller derived in this paper is clear, and is suited for practical use. The formulation and solution of a class of discrete optimal finite preview problems are given in a general form. Thus they apply not only to the suspension problem but also to other problems in which preview is possible. A comparison of Bender’s solution with the present solution is provided along with acceleration versus clearance space tradeoff information.
Transfer Functions of Hyperbolic Distributed Parameter Systems
Authors: Sen A. K.
Published: July 2010

Concepts and analytical methods of construction of transfer functions of linear hyperbolic distributed systems are developed. In addition to the usual class of problems with boundary inputs, an important new class of problems with internal inputs is discussed.
Dynamic Testing in Nuclear Power Plants for Model Validation
Authors: Kerlin T. W. , Katz E. M. , Chen A. T. , Thakkar J. G. , Chang S. I.
Published: July 2010

Dynamics tests were preformed at the Oconee pressurized water reactor to obtain information for checking a theoretical plant model. Low level, periodic reactivity perturbations were introduced and several system responses (reactor power, temperatures, pressures) were monitored. The data were processed off-line to give frequency responses. A linear state-variable model for the plant was formulated and used to compute theoretical frequency responses. A computerized, model-reference identification procedure was used to identify the fuel temperature coefficient of reactivity and the overall fuel-to-coolant heat transfer coefficient. The study showed that dynamic tests can be performed in operating nuclear power plants with insignificant interference to normal operation. Also, the use of automatic parameter identification procedures was demonstrated.
Bond Graphs for Nonholonomic Dynamic Systems
Authors: Brown F. T.
Published: July 2010

Two very different dynamic systems, one holonomic and the other nonholonomic, can have identical expressions for generalized kinetic energy, generalized potential energy, and transformational constraints between the generalized velocities, and therefore might be confused. Bond graphs for a broad class of nonholonomic systems are shown to differ from their holonomic counterparts simply by the deletion of certain gyrators. Simple examples suggest the engineering significance of nonholonomic systems.