bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Relationship Power as a Mediator Between Dating Violence and Sexually Transmitted Infections Among College Women
Authors: Buelna Christina , Ulloa Emilio C. , Ulibarri Monica D.
Published: August 2008

This study examined relationship power as a possible mediator of the relationship between dating violence and sexually transmitted infections (STIs). The proposed mediation model was based on the theory of gender and power as well as previous research on intimate partner violence and STI risk. Survey results from a sample of 290 single, undergraduate women indicated that 85% experienced at least one form of dating violence victimization in the past year, 5.9% tested positive for an STI, and 5.2% received treatment for an STI. Results revealed that women with lower levels of sexual relationship power had higher rates of dating violence victimization and STIs; also, sexual relationship power partially mediated the relationship between dating violence victimization and STIs. Future dating violence and STI-prevention interventions targeting young women may want to use an empowerment approach to decrease their likelihood of dating violence victimization and STI risk.
Meta-Analysis of Math Interventions for Students With Emotional and Behavioral Disorders
Authors: Tran Nguyen Templeton  , Neel Richard S. , Blood Erika
Published: August 2008

Students with emotional and behavioral disorders (EBD) struggle in the area of academics as well as behavior, and these academic difficulties manifest a great deal in mathematics. The number of children with EBD served in general education settings is increasing, and mathematics curriculum is expanding to include additional content areas and more complex mathematical processes. The convergence of these trends creates an enormous instructional challenge: an increasing number of children with EBD, with limited mathematics abilities, dealing with ever more complex subjects. This meta-analysis of mathematics interventions for students with EBD examines math performance outcomes as a function of study and sample characteristics, treatment effects of elements of math instruction, maintenance and generalization effects of these math interventions, and levels of mathematics investigated. Fifteen studies spanning nearly 20 years are included. Results emphasize the need for development of interventions for higher level mathematics and additional research to help guide instruction.
Methodological Challenges of Collecting Evaluation Data From Traumatized Clients/Consumers
Authors: Campbell Rebecca , Adams Adrienne E. , Patterson Debra
Published: August 2008

This project integrates elements of responsive evaluation and participatory evaluation to compare three evaluation data collection methods for use with a hard-to-find (HTF), traumatized, vulnerable population: rape victims seeking postassault medical forensic care. The first method involves on-site, in-person data collection, immediately postservices; the second, telephone follow-up assessments, 1 week postservices; and the third, private, self-administered surveys completed immediately postservices. There are significant differences in response rates across methods: 88% in-person, 17% telephone, and 41% self-administered. Across all phases, clients gave positive feedback about the services they received and about all three methods of data collection. Follow-up analyses suggested that nonresponders did not differ with respect to client characteristics, assault characteristics, or nursing care provided. These findings suggest that evaluations with HTF service clients may need to be integrated into on-site services because other methods may not yield sufficient response rates.
Rasta Gyal Workin' (in) the Culture
Authors: Cadogan Kabira
Published: August 2008

This short creative ethnography experiments with the interrelationships between ethnographic form and function in embodied practice. Gender, sexual, and racial dilemmas play up close and personal as the author hones in closely on just one night, one episode in a series of what makes up 3½ years of ethnographic fieldwork. The author finds that the rhythm of the dancehall cannot be separated from the rhythm of the writing, if she were to attempt to bring the scene to life by being as faithful to her lived experience as possible. Unfettered by theoretical abstractions in this particular writing form, she attempts to transport the reader into a felt understanding of the performative site-a site rich with fodder for the function of shared personal understanding and scholarly exploration.
Politics, Performativity, Autopoiesis: Toward a Discourse Systems Theory of Political Culture
Authors: Kidwell Kirk S.
Published: August 2008

As a field of critical inquiry, cultural studies has engaged with the political primarily at the level of cultural politics—the politics of culture—and has all too often neglected political culture—the culture of politics. Although the emergence of cultural policy studies since the late 1980s has remedied this deficiency to some degree, cultural studies approaches politics and governmental policy primarily insofar as they impinge on a cultural domain bounded by the aesthetic and the intellectual. This essay addresses this lacuna in the cultural studies gaze by elaborating a discourse systems theory of political culture based on Michel Foucault's theory of discourse in The Archaeology of Knowledge, speech act theory, and autopoietic systems theory. The essay argues that political culture is an autopoietic, performative discourse system that regulates the production of political knowledge and the performance of political action.
FcγR-stimulated activation of the NADPH oxidase: phosphoinositide-binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome
Authors: Tian Wei , Li Xing Jun , Stull Natalie D. , Ming Wenyu , Suh Chang-Il , Bissonnette Sarah A. , Yaffe Michael B. , Grinstein Sergio , Atkinson Simon J. , Dinauer Mary C.
Published: August 2008

The phagocyte NADPH oxidase generates superoxide for microbial killing, and includes a membrane-bound flavocytochrome b558 and cytosolic p67phox, p47phox, and p40phox subunits that undergo membrane translocation upon cellular activation. The function of p40phox, which binds p67phox in resting cells, is incompletely understood. Recent studies showed that phagocytosis-induced superoxide production is stimulated by p40phox and its binding to phosphatidylinositol-3-phosphate (PI3P), a phosphoinositide enriched in membranes of internalized phagosomes. To better define the role of p40phox in FcγR-induced oxidase activation, we used immunofluorescence and real-time imaging of FcγR-induced phagocytosis. YFP-tagged p67phox and p40phox translocated to granulocyte phagosomes before phagosome internalization and accumulation of a probe for PI3P. p67phox and p47phox accumulation on nascent and internalized phagosomes did not require p40phox or PI3 kinase activity, although superoxide production before and after phagosome sealing was decreased by mutation of the p40phox PI3P-binding domain or wortmannin. Translocation of p40phox to nascent phagosomes required binding to p67phox but not PI3P, although the loss of PI3P binding reduced p40phox retention after phagosome internalization. We conclude that p40phox functions primarily to regulate FcγR-induced NADPH oxidase activity rather than assembly, and stimulates superoxide production via a PI3P signal that increases after phagosome internalization.
Overexpression of TOSO in CLL is triggered by B-cell receptor signaling and associated with progressive disease
Authors: Pallasch Christian Philipp , Schulz Alexandra , Kutsch Nadine , Schwamb Janine , Hagist Susanne , Kashkar Hamid , Ultsch Alfred , Wickenhauser Claudia , Hallek Michael , Wendtner Clemens-Martin
Published: August 2008

Resistance toward apoptotic stimuli mediated by overexpression of antiapoptotic factors or extracellular survival signals is considered to be responsible for accumulation of malignant B cells in chronic lymphocytic leukemia (CLL). TOSO was identified as overexpressed candidate gene in CLL, applying unit-transformation assays of publicly available microarray datasets. Based on CLL samples from 106 patients, TOSO was identified to exhibit elevated relative expression (RE) of 6.8 compared with healthy donor B cells using quantitative real-time polymerase chain reaction (PCR; P = .004). High levels of TOSO expression in CLL correlated with high leukocyte count, advanced Binet stage, previous need for chemotherapy, and unmutated IgVH status. CD38+ CLL subsets harboring proliferative activity showed enhanced TOSO expression. We evaluated functional mechanisms of aberrant TOSO expression and identified TOSO expression significantly induced by B-cell receptor (BCR) stimulation compared with control cells (RE; 8.25 vs 4.86; P = .01). In contrast, CD40L signaling significantly reduced TOSO expression (RE, 2.60; P = .01). In summary, we show that the antiapoptotic factor TOSO is associated with progressive disease and enhanced in the proliferative CD38+ CLL subset. Both association with unmutated IgVH and the specific induction of TOSO via the BCR suggest autoreactive BCR signaling as a key mediator of apoptosis resistance in CLL.
A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma
Authors: Lan Qing , Lim Unhee , Liu Chin-San , Weinstein Stephanie J. , Chanock Stephen , Bonner Matthew R. , Virtamo Jarmo , Albanes Demetrius , Rothman Nathaniel
Published: August 2008

Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus–transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood cell DNA from healthy subjects would be associated with future risk of non-Hodgkin lymphoma (NHL). We analyzed mtDNA copy number in 104 incident male NHL cases and 104 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention cohort. There was a dose-response relationship between tertiles of mtDNA copy number and risk of NHL (odds ratio [OR], 95% confidence interval [CI]: 1.0; 1.4 [0.7-2.8]; and 2.4 [1.0-5.5], respectively; Ptrend = .046). The effect was most pronounced for the CLL/small lymphocytic lymphoma (SLL) subtype (OR: 1.0; 3.2 [0.7-15.7]; 14.1 [1.9-103.2]; Ptrend = .009). These results suggest that mtDNA copy number could be associated with the risk of NHL, particularly CLL/SLL.
TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSBmutations in predicting diabetes
Authors: Mahurkar Swapna , Bhaskar Seema , Reddy D Nageshwar , Prakash Swami , Rao G Venkat , Singh Shivaram Prasad , Thomas Varghese , Chandak Giriraj Ratan
Published: August 2008

Background

Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the TCF7L2 gene using a case-control approach, under the hypothesis that TCF7L2 variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the TCF7L2 variants and N34S SPINK1 and L26V CTSB mutations, since they are strong predictors of risk for TCP.

Methods

Two polymorphisms rs7903146 and rs12255372 in the TCF7L2 gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S SPINK1 and L26V CTSB mutations and further subdivided them into TCP and FCPD patients and compared the distribution of TCF7L2 variants between them.

Results

The allelic and genotypic frequencies for both TCF7L2 polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S SPINK1 and L26V CTSB mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S SPINK1 variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while, TCF7L2variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11–2.56, P = 0.013).

Conclusion

Type 2 diabetes associated TCF7L2 variants are not associated with diabetes in TCP. Since, TCF7L2 is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of TCF7L2 variants and the SPINK1 and CTSB mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.
Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients
Authors: Tian Mei , Cui Ya-Zhou , Song Guan-Hua , Zong Mei-Juan , Zhou Xiao-Yan , Chen Yu , Han Jin-Xiang
Published: August 2008

Background

There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells.

Methods

To identify novel potential biomarkers for PDAC from pancreatic juice, we carried out difference gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the identified differently expressed proteins, three up-regulated proteins in pancreatic cancer juice, matrix metalloproteinase-9 (MMP-9), oncogene DJ1 (DJ-1) and alpha-1B-glycoprotein precursor (A1BG), were selected for validation by Western blot and immunohistochemistry. Serum MMP-9 levels were also detected by enzyme linked immunosorbent assay (ELISA).

Results

Fourteen proteins were up-regulated and ten proteins were down-regulated in cancerous pancreatic juice compared with cancer-free controls. Increased MMP-9, DJ-1 and A1BG expression in cancerous pancreatic juice were confirmed by Western blot. Immunohistochemical study showed MMP-9, DJ-1 and A1BG positively expressed in 82.4%, 72.5% and 86.3% of pancreatic cancer tissues, significantly higher than that in normal pancreas tissues. Up-regulation of DJ-1 was associated with better differentiation (p < 0.05). Serum MMP-9 levels were significantly higher in PDAC (255.14 ng/ml) than those in chronic pancreatitis (210.22 ng/ml, p = 0.009) and healthy control (203.77 ng/ml, p = 0.027).

Conclusion

The present proteome analysis revealed MMP-9, DJ-1 and A1BG proteins as elevated in pancreatic juice from PDAC, which suggest their further utility in PDAC diagnosis and screening. This is the first time A1BG was identified as a potential biomarker in pancreatic cancer associated samples. The measurement of serum MMP-9 might be clinically useful for PDAC diagnosis.
Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model
Authors: Jiang Qi-qi , Fan Lin-yu , Yang Guang-li , Guo Wen-Hao , Hou Wen-li , Chen Li-juan , Wei Yu-quan
Published: August 2008

Background

Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon.

Methods

human A549 lung cancer-bearing nude mice were treated with liposomal honokiol, liposomal honokiol plus DDP or with control groups. Apoptotic cells and vessels were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31 respectively.

Results

The present study showed that liposomal honokiol alone resulted in effective suppression of the tumor growth, and that the combined treatment with honokiol plus DDP had the enhanced inhibition of the tumor growth and resulted in a significant increase in life span. The more apparent apoptotic cells in the tumors treated with honokiol plus DDP was found in fluorescent in situ TUNEL assay, compared with the treatment with control groups. In addition, the combination of honokiol and DDP apparently reduced the number of vessels by immunolabeling of CD31 in the tissue sections, compared with control groups.

Conclusion

In summary, our data suggest that honokiol alone had the antitumor activity against human lung cancer in A549 lung cancer xenograft model, and that the combination of honokiol with DDP can enhance the antitumor activity, and that the enhanced antitumor efficacy in vivo may in part result from the increased induction of the apoptosis and the enhanced inhibition of angiogenesis in the combined treatment. The present findings may be of importance to the further exploration of the potential application of the honokiol alone or the combined approach in the treatment of lung carcinoma.
Zoledronic Acid Prevents Bone Loss in Premenopausal Women Undergoing Adjuvant Chemotherapy for Early-Stage Breast Cancer
Authors: Hershman Dawn L. , McMahon Donald J. , Crew Katherine D. , Cremers Serge , Irani Dinaz , Cucchiara Gina , Brafman Lois , Shane Elizabeth
Published: August 2008

Purpose

Adjuvant chemotherapy for breast cancer (BC) may be associated with increased rates of bone loss and decreased bone mineral density (BMD) and may lead to premature osteoporosis and increased fracture risk. We examined whether zoledronic acid (ZA) prevents bone loss in premenopausal women receiving chemotherapy for early-stage BC.

Patients and Methods

This study is a randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg intravenously every 3 months) versus placebo for 1 year. Premenopausal women underwent serial BMD measurements before initiating chemotherapy and at 6 and 12 months. The primary outcome was percent change in lumbar spine (LS) BMD at 6 months. Secondary outcomes were percent change at any BMD site and markers of bone turnover at 12 months. Linear mixed model analysis for repeated measures was performed.

Results

Of 101 women who were randomly assigned and completed baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12-month evaluation. Baseline characteristics were comparable between the groups. Mean age was 42 years. Placebo was associated with significant decline in LS BMD at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8% at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA patients (P < .0001 compared with placebo).

Conclusion

Premenopausal women receiving chemotherapy for BC sustained significant bone loss at the LS and hip, whereas BMD remained stable in women who received ZA. Administration of ZA during the first year of chemotherapy is an effective and well-tolerated strategy for preventing bone loss.
Global-optimization-based methods for use in boundary layer transition control
Authors: Veres G V , Tutty O R , Rogers E , Nelson P A
Published: August 2008

Turbulent flow has a significantly higher drag than the corresponding laminar flow at the same flow conditions, and therefore incurs a significant penalty of increased fuel consumption due to the extra thrust required. One possible way of decreasing the drag is to apply surface suction to delay the transition from laminar to turbulent flow. In this paper an aerofoil with three non-overlapping panels covering up to 20 per cent of chord for boundary layer transition control is considered. The problem is complicated by the fact that panels can change both their positions and lengths. The complexity of the optimization problem is such that it is not practical to perform the investigation using a single processor. A constrained global parallel algorithm based on a combination of deformed configuration methods and a controlled random search method is developed. It is shown that for the problem considered, good solutions can be found efficiently.
Modelling and robust control of fluidic thrust vectoring and circulation control for unmanned air vehicles
Authors: Gu D-W , Natesan K , Postlethwaite I
Published: August 2008

This paper presents actuator models for fluidic thrust vectoring and circulation control and they are used in the design of a robust controller for an unmanned air vehicle. The pitching and rolling moments for the aircraft are produced through the use of a co-flow fluidic thrust vectoring arrangement at the wing trailing edges. Experimental results for the co-flow actuators are used to derive mathematical models and their performance is compared with conventional control surfaces. For the controller design, nonlinear dynamic models are approximated by a simplified linear parameter varying (LPV) model. The polytopic nature of the controller is exploited to reformulate the LPV controller design problem into a μ-synthesis problem. The LPV controllers exhibit superior stability properties over the entire operating region, when compared to conventional gain-scheduling schemes.
Extensions of adaptive slope-seeking for active flow control
Authors: Henning L , Becker R , Feuerbach G , Muminovic R , King R , Brunn A , Nitsche W
Published: August 2008

To speed up gradient estimation in a slope-seeking controller two different modifications are proposed in this study. In a first approach, the gradient estimation is based on a locally identified black-box model. A further improvement is obtained by applying an extended Kalman filter to estimate the local gradient of an input—output map. Moreover, a simple method is outlined to adapt the search radius in the classical extremum- and slope-seeking approach to reduce the perturbations near the optimal state. To show the versatility of the slope-seeking controller for flow control applications two different wind tunnel experiments are considered, namely with a two-dimensional bluff body and a generic three-dimensional car model (Ahmed body).
Minimizing transient energy growth in plane Poiseuille flow
Authors: Whidborne J F , McKernan J , Papadakis G
Published: August 2008

The feedback control of laminar plane Poiseuille flow is considered. In common with many flows, the dynamics of plane Poiseuille flow is very non-normal. Consequently, small perturbations grow rapidly with a large transient that may trigger non-linearities and lead to turbulence, even though such perturbations would, in a linear flow, eventually decay. This sensitivity can be measured using the maximum transient energy growth. The linearized flow equations are discretized using spectral methods and then considered at one wave-number pair in order to obtain a model of the flow dynamics in a form suitable for advanced control design. State feedback controllers that minimize an upper bound on the maximum transient energy growth are obtained by the repeated solution of a set of linear matrix inequalities. The controllers are tested using a full Navier—Stokes solver, and the transient energy response magnitudes are significantly reduced compared with the uncontrolled case.
Jet flow induced by a surface plasma actuator
Authors: Jukes T N , Choi K-S , Segawa T , Yoshida H
Published: August 2008

The induced flow field in the vicinity of a single, symmetric, AC plasma actuator has been studied in initially static air at atmospheric pressure. Hot-wire and cold-wire anemometry, together with flow visualization, were used to observe the temporal and spatial structure of the induced flow. The plasma discharge is pulsed on a millisecond scale and the flow forms a series of pulsed wall jets, which can be maintained indefinitely, similar to a synthetic jet. It was observed that the plasma actuator initiates a pair of vortices at the instant of plasma creation, moving at 25° to the surface. After an initiation period, the plasma develops into a laminar wall jet. Thermal imagery has been used to estimate the surface temperature of the dielectric sheet during plasma operation.
Detached eddy simulation of a synthetic jet for flow control
Authors: Qin N , Xia H
Published: August 2008

Synthetic jets have been proposed for efficient flow control due to their unique zero-net-mass-flux feature and the conceptual simplicity of the system. However, the effectiveness of the control is heavily dependent upon the complicated flow interaction of the jets with the flow stream on which the jet is applied. To understand the flow control mechanism better, a numerical simulation method is investigated in this paper. Using a computational fluid dynamics technique, the detached eddy simulation for an isolated synthetic jet for flow control is presented. A cubic-root filter is introduced with continuous eddy viscosity variation at the switching point between the Reynolds-averaged Navier—Stokes solution region and the large eddy simulation region. The intention is to explore the effects of unstructured grids for such a filtering strategy. A dissipation-controlled Roe scheme is applied and a dynamic grid technique is employed to implement the periodically moving diaphragm. The results obtained are compared with the experimental data and a previous study using structured grids.
Pulsed microjet control of supersonic impinging jets via low-frequency excitation
Authors: Annaswamy A M , Choi J J , Alvi F S
Published: August 2008

Several fluid flow problems related to propulsion and power generation exhibit strong acoustic resonances. Produced due to interactions of the acoustics with other underlying unsteady mechanisms such as unsteady heat release or shear flow instability, these resonances manifest as large and sustained pressure oscillations. Active control of such resonances has been shown to be highly effective, resulting in a dramatic reduction in the acoustic resonances using a very small fraction of the system energy. In this paper, a specific fluid flow problem is discussed, that of supersonic impinging jets, and the control of the acoustic resonances that are produced by these jets, via detailed experimental investigations. The actuator used for active control consists of a pulsed microjet, by which it is shown that in a scaled supersonic experimental facility acoustic resonances can be reduced, utilizing a fraction of the mass flowrate needed with a steady microjet. Several parameters related to pulsed injection are varied to evaluate their impact on the resonances, and it is found that duty cycle and pulsing frequency have the most dominant effect on the jet noise as well as on the overall flow field. System identification based models of the uncontrolled and controlled jet are derived to explain the results obtained. The effect of low-frequency pulsing on resonance suppression is explained via the introduction of a controller in the closed-loop whose parameters vary non-linearly with the pulsing parameters.
An evaluation of the mass and power scaling of synthetic jet actuator flow control technology for civil transport aircraft applications
Authors: Crowther W J , Gomes L T
Published: August 2008

This paper aims to develop understanding of the systems costs associated with the application of flow control systems to civil transport aircraft based on the use of electrically powered synthetic jet actuators (SJAs). The study is based on the development of a low-order mass model using estimated power specific masses of generation, management, distribution, and conversion subsystems; application of existing empirical rules for application of pneumatic boundary layer mixing flow control devices to determine the required fluid power for an A320 case study application; and characterization and optimization of lab-based SJA technology to establish realistic estimates for power conversion efficiency and actuator maximum authority. The peak velocity obtained from a velocity-optimized synthetic jet actuator was 130 m/s, at a corresponding power efficiency of 7 per cent. The highest power efficiency obtained was 14 per cent, corresponding to a peak velocity of 70 m/s. The power specific mass for the overall flow control system considered for the A320 application is estimated to be around 1 kg of system mass per kW of electrical power required, of which around 50 per cent is due to power generation and 30 per cent is due to power conversion (actuation).
Active flow control of jet mixing using steady and pulsed fluid tabs
Authors: Behrouzi P , Feng T , McGuirk J J
Published: August 2008

Flow control techniques for increasing the rate of jet mixing in axisymmetric nozzle flows have been investigated. A combination of water tunnel and high-speed airflow facilities is used to assess the near-field jet behaviour. Solid tabs, steady fluid tabs (i.e. discrete radially discharged control jets located close to the core jet exit), and pulsed fluid tabs are compared. The effect of fluid tab velocity amplitude, pulse rate, and pulse phase are studied using open-loop control. The measurements indicate that fluid tabs generate a similar streamwise vortex formation process (and hence display increased mixing) as previously observed in solid-tabbed nozzle flows. In incompressible testing the mixing effectiveness with a pair of pulsed fluid tabs 180° out-of-phase was as good as a twin solid tab nozzle for a control jet flowrate of only 0.5 per cent of the primary (core) jet flow. In preliminary high-speed testing similar benefits of fluid tabs over solid tabs were observed. Further study of pulsed fluid tabs is recommended; they have the attractive performance benefit that they can be easily switched off when not needed and offer increased flexibility as the basis of an optimized active control jet mixing device.
Testosterone and the breast
Authors: Shufelt Chrisandra L , Braunstein Glenn D
Published: August 2008

Although women have been treated with testosterone (T) for female sexual dysfunction since the 1950s, the role of T in normal female physiology is not yet fully defined. One of the major safety concerns of androgen therapy is whether androgens have a stimulatory effect on the breast that could lead to breast carcinomas. The proposed mechanisms for such stimulation include local estrogen production from the aromatase enzyme complex present in the breast tissue or by the direct stimulation of the androgen receptor. Predominant data from in vitro studies have shown that androgens actually have apoptotic and antiproliferative effects and not stimulatory effects. Animal models have shown similar results to in vitro studies, finding that androgens inhibit breast cancer growth. Prospective and retrospective epidemiological analyses have shown mixed outcomes, with no clear consensus regarding androgen use and breast cancer risk. Hyperandrogenism in patients with polycystic ovarian syndrome with elevated levels of endogenous T is not associated with an increased risk of breast cancer and may, in fact, be protective. Another human model with excess of T is female-to-male transgenderism, in which genotypic women are treated with large doses of exogenous T with no increased risk. High-dose androgen therapy also has been effective in treating patients with advanced breast cancer. Thus, the preponderance of data suggests that T use in females is not associated with an increased risk of breast carcinoma.
Prophylactic oophorectomy in premenopausal women and long-term health
Authors: Shuster Lynne T , Gostout Bobbie S , Grossardt Brandon R , Rocca Walter A
Published: August 2008

Objective

To review the data on long-term outcomes in women who underwent prophylactic bilateral oophorectomy, a common surgical procedure that has more than doubled in frequency since the 1960s.

Study design

Literature review of the published data on the consequences of prophylactic bilateral oophorectomy. Special emphasis was given to the Mayo Clinic Cohort Study of Oophorectomy and Aging.

Main outcome measures

Overall mortality, cardiovascular disease, cognitive impairment and dementia, parkinsonism, osteoporosis, psychological wellbeing and sexual function.

Results

There is a growing body of evidence suggesting that the premature loss of ovarian function caused by bilateral oophorectomy performed before natural menopause is associated with several negative outcomes. In particular, studies have revealed an increased risk of premature death, cardiovascular disease, cognitive impairment or dementia, parkinsonism, osteoporosis and bone fractures, decline in psychological wellbeing and decline in sexual function. The effects involve different organs (e.g. heart, bone, or brain), and different functions within organs (e.g. cognitive, motor, or emotional brain functions). Estrogen treatment may prevent some but not all of these negative outcomes.

Conclusion

The potential adverse effects of prophylactic bilateral oophorectomy on heart health, neurological health, bone health and quality of life should be carefully weighed against its potential benefits for cancer risk reduction in women at average risk of ovarian cancer.
Urogenital atrophy
Authors: Pitkin Joan , Rees Margaret
Published: August 2008

The British Menopause Society Council aims to aid health professionals to inform and advise women about postreproductive health. This guidance refers to the long-term condition of urogenital atrophy. Treatment choice should be based on up to date information and targeted to individual women's needs. Non-estrogen and estrogen-based treatments are discussed.
An Approximate Dynamic Programming Algorithm for Large-Scale Fleet Management: A Case Application
Authors: Simão Hugo P. , Day Jeff , George Abraham P. , Gifford Ted , Nienow John , Powell Warren B.
Published: August 2008

We addressed the problem of developing a model to simulate at a high level of detail the movements of over 6,000 drivers for Schneider National, the largest truckload motor carrier in the United States. The goal of the model was not to obtain a better solution but rather to closely match a number of operational statistics. In addition to the need to capture a wide range of operational issues, the model had to match the performance of a highly skilled group of dispatchers while also returning the marginal value of drivers domiciled at different locations. These requirements dictated that it was not enough to optimize at each point in time (something that could be easily handled by a simulation model) but also over time. The project required bringing together years of research in approximate dynamic programming, merging math programming with machine learning, to solve dynamic programs with extremely high-dimensional state variables. The result was a model that closely calibrated against real-world operations and produced accurate estimates of the marginal value of 300 different types of drivers.
Alternative pathways for production of β-amyloid peptides of Alzheimer's disease
Authors: Hook Vivian , Schechter Israel , Demuth Hans-Ulrich , Hook Gregory
Published: August 2008

This highlight article describes three Alzheimer's disease (AD) studies presented at the 5th General Meeting of the International Proteolysis Society that address enzymatic mechanisms for producing neurotoxic β-amyloid (Aβ) peptides. One group described the poor kinetics of BACE 1 for cleaving the wild-type (WT) β-secretase site of APP found in most AD patients. They showed that cathepsin D displays BACE 1-like specificity and cathepsin D is 280-fold more abundant in human brain than BACE 1. Nevertheless, as BACE 1 and cathepsin D show poor activity towards the WT β-secretase site, they suggested continuing the search for additional β-secretase(s). The second group reported cathepsin B as an alternative β-secretase possessing excellent kinetic efficiency and specificity for the WT β-secretase site. Significantly, inhibitors of cathepsin B improved memory, with reduced amyloid plaques and decreased Aβ(40/42) in brains of AD animal models expressing amyloid precursor protein containing the WT β-secretase site. The third group addressed isoaspartate and pyroglutamate (pGlu) posttranslational modifications of Aβ. Results showed that cathepsin B, but not BACE 1, efficiently cleaves the WT β-secretase isoaspartate site. Furthermore, cyclization of N-terminal Glu by glutaminyl cyclase generates highly amyloidogenic pGluAβ(3–40/42). These presentations suggest cathepsin B and glutaminyl cyclase as potential new AD therapeutic targets.
Isoaspartate-containing amyloid precursor protein-derived peptides alter efficacy and specificity of potential β-secretases
Authors: Böhme Livia , Hoffmann Torsten , Manhart Susanne , Wolf Raik , Demuth Hans-Ulrich
Published: August 2008

Neuritic plaques of Alzheimer patients are composed of multiple protein components. Among them, the amyloid β-peptides (Aβ) 1–40/42 and further N- and C-terminally modified fragments of Aβ are highly abundant. Most prominent are the isoaspartate (isoAsp)-Aβ peptides and pyroglutamyl (pGlu)-Aβ. While pGlu-Aβ can only be formed from an N-terminal glutamate by glutaminyl cyclase, spontaneous isoAsp-isomerization cannot occur at an N-terminal aspartate of peptides. This means that isoAsp-Aβ formation must precede proteolysis of the amyloid precursor protein (APP). Aβ generation from APP by β- and γ-secretases initiates the amyloid peptide aggregation and deposition process. Two aspartate proteases have been identified as secretases: BACE-1 (β-site amyloid precursor protein cleaving enzyme) and the intramembrane γ-secretase multiprotein complex. However, recent evidence supports more than one β-secretase initiating this cascade. Formation of Aβ1–40/42 was predominantly studied by expression of mutated human APP sequences in cell culture and transgenic animals, generating Aβ fragments that did not contain such multiple posttranslational modifications as in Alzheimer's disease. This prompted us to investigate the catalytic turnover of Asp- or isoAsp-containing APP-derived peptide sequences by BACE-1 and cathepsin B, another potential β-secretase. While cathepsin B is more effective than BACE-1 in processing the Asp-containing peptide derivatives, only cathepsin B can cleave the isoAsp-containing peptides, which occurs with high catalytic efficiency.
Angiotensin-converting enzyme limits inflammation elicited byTrypanosoma cruzicysteine proteases: a peripheral mechanism regulating adaptive immunity via the innate kinin pathway
Authors: Scharfstein Julio , Monteiro Ana Carolina , Schmitz Veronica , Svensjö Erik
Published: August 2008

Tissue injury by pathogens induces a stereotyped inflammatory response that alerts the innate immune system of the potential threat to host integrity. Here, we review knowledge emerging from investigations of the role of the kinin system in the mechanisms that link innate to the adaptive phase of immunity. Progress in this field started with results demonstrating that bradykinin is an endogenous danger signal that induces dendritic cell (DC) maturation via G protein-coupled bradykinin B2receptors (B2R). The immunostimulatory role of kinins was recently confirmed in two different mouse models ofTrypanosoma cruziinfection, a parasitic protozoan equipped with kinin-releasing cysteine proteases (cruzipain). Infection by the intraperitoneal route showed that DCs from B2R-/-mice (susceptible phenotype) failed to sense kinin ‘danger’ signals proteolytically released by parasites, explaining why these mutant mice display lower frequencies of interferon-γ-producing effector T-cells. Studies of the dynamics of inflammation in the subcutaneous model of infection revealed that the balance between cruzipain and angiotensin-converting enzyme, respectively acting as kinin-generating and degrading enzymes, governs extent of DC maturation and TH1 development via the B2R-dependent innate pathway. Studies of the kinin role in immunity may shed light on the relationship between proteolytic networks and the cytokine circuits that guide T-cell development.
Some assembly required: dedicated chaperones in eukaryotic proteasome biogenesis
Authors: Kusmierczyk Andrew R. , Hochstrasser Mark
Published: August 2008

The 26S proteasome is the key eukaryotic protease responsible for the degradation of intracellular proteins. Protein degradation by the 26S proteasome plays important roles in numerous cellular processes, including the cell cycle, differentiation, apoptosis, and the removal of damaged or misfolded proteins. How this 2.5-MDa complex, composed of at least 32 different polypeptides, is assembled in the first place is not well understood. However, it has become evident that this complicated task is facilitated by a framework of protein factors that chaperone the nascent proteasome through its various stages of assembly. We review here the known proteasome-specific assembly factors, most only recently discovered, and describe their potential roles in proteasome assembly, with an emphasis on the many remaining unanswered questions about this intricate process of assisted self-assembly.
A common binding motif for various bacteria of the bacteria-binding peptide SRCRP2 of DMBT1/gp-340/salivary agglutinin
Authors: Leito Jelani T.D. , Ligtenberg Antoon J.M. , Nazmi Kamran , de Blieck-Hogervorst Jolanda M.A. , Veerman Enno C.I. , Nieuw Amerongen Arie V.
Published: August 2008

Salivary agglutinin (DMBT1SAG) is identical to lung glycoprotein-340 and encoded by the deleted in malignant brain tumors-1 gene. It is a member of the scavenger receptor cysteine-rich (SRCR) superfamily, proteins that have one or more SRCR domains. Salivary agglutinin plays a role in oral innate immunity by the binding and agglutination of oral streptococci. Streptococcus mutans has been shown to bind to a 16-mer peptide (QGRVEVLYRGSWGTVC) located within the SRCR domains. Within this peptide, designated SRCR peptide 2, residues VEVL and W are critical for binding. The aim of this study was to investigate binding of DMBT1SAG to other bacteria. Therefore, interaction between a series of bacteria and DMBT1SAG, SRCR peptide 2 and its alanine substitution variants was investigated in adhesion and agglutination assays. For different bacteria there was a highly significant correlation between adhesion to DMBT1SAG and adhesion to SRCR peptide 2, suggesting that SRCR peptide 2 is the major bacteria-binding site. An alanine substitution scan showed that eight amino acids are involved in binding (xRVEVLYxxSWxxxx). The binding motifs varied for different species, but the residues VxVxY and W are always present. In conclusion, a common binding motif (RVEVLYxxxSW) within the SRCR domains is responsible for the broad bacteria-binding spectrum of DMBT1SAG.
Putative identification of an amphipathic α-helical sequence in hemolysin of Escherichia coli (HlyA) involved in transmembrane pore formation
Authors: Valeva Angela , Siegel Isabel , Wylenzek Mark , Wassenaar Trudy M. , Weis Silvia , Heinz Natalia , Schmitt Robert , Fischer Christina , Reinartz Ricarda , Bhakdi Sucharit , Walev Iwan
Published: August 2008

Escherichia coli hemolysin is a pore-forming protein belonging to the RTX toxin family. Cysteine scanning mutagenesis was performed to characterize the putative pore-forming domain of the molecule. A single cysteine residue was introduced at 48 positions within the sequence spanning residues 170–400 and labeled with the polarity-sensitive dye badan. Spectrofluorimetric analyses indicated that several amino acids in this domain are inserted into the lipid bilayer during pore formation. An amphipathic α-helix spanning residues 272–298 was identified that may line the aqueous pore. The importance of this sequence was highlighted by the introduction of two prolines at positions 284 and 287. Disruption of the helix structure did not affect binding properties, but totally abolished the hemolytic activity of the molecule.
Cleaved SLPI, a novel biomarker of chymase activity
Authors: Belkowski Stanley M. , Masucci John , Mahan Andrew , Kervinen Jukka , Olson Matthew , de Garavilla Lawrence , D'Andrea Michael R.
Published: August 2008

Secretory leukocyte protease inhibitor (SLPI) is a protease inhibitor of the whey acidic protein-like family inhibiting chymase, chymotrypsin, elastase, proteinase 3, cathepsin G and tryptase. Performing in vitro enzymatic assays using both Western blotting and liquid chromatography/mass spectrometry techniques we showed that, of the proteases known to interact with SLPI, only chymase could uniquely cleave this protein. The peptides of the cleaved SLPI (cSLPI) remain coupled due to the disulfide bonds in the molecule but under reducing conditions the cleavage can be observed as peptide products. Subsequent ex vivo studies confirmed the presence of SLPI in human saliva and its susceptibility to cleavage by chymase. Furthermore, inhibitors of chymase activity are able to inhibit this cleavage. Human saliva from both normal and allergic individuals was analyzed for levels of cSLPI and a correlation between the level of cSLPI and the extent of allergic symptoms was observed, suggesting the application of cSLPI as a biomarker of chymase activity in humans.
Pursuing different ‘TRADDes’: TRADD signaling induced by TNF-receptor 1 and the Epstein-Barr virus oncoprotein LMP1
Authors: Kieser Arnd
Published: August 2008

The pro-apoptotic tumor necrosis factor (TNF)-receptor 1-associated death domain protein (TRADD) was initially identified as the central signaling adapter molecule of TNF-receptor 1 (TNFR1). Upon stimulation with the pro-inflammatory cytokine TNFα, TRADD is recruited to the activated TNFR1 by direct interaction between the death domains of both molecules. TRADD mediates TNFR1 activation of NF-κB and c-Jun N-terminal kinase (JNK), as well as caspase-dependent apoptosis. Surprisingly, TRADD is also recruited by latent membrane protein 1 (LMP1), the major oncoprotein of the human Epstein-Barr tumor virus. By mimicking a constitutively active receptor, LMP1 is essential for B-cell transformation by the virus, activating NF-κB, phosphatidylinositol 3-kinase, JAK/STAT and mitogen-activated protein kinase signaling. In contrast to TNFR1, LMP1's interaction with TRADD is independent of a functional death domain. The unique structure of the LMP1-TRADD complex dictates an unusual type of TRADD-dependent NF-κB signaling and subverts TRADD's potential to induce apoptosis. This article provides an overview of TNFR1 and LMP1 signal transduction with a focus on TRADD's functions in apoptotic and transforming signaling, incorporating recent results from TRADD RNAi and knockout studies.
Influenza viruses and the NF-κB signaling pathway – towards a novel concept of antiviral therapy
Authors: Ludwig Stephan , Planz Oliver
Published: August 2008

Influenza A virus remains a major public health concern, both in its annual toll in death and debilitation and its potential to cause devastating pandemics. Like any other virus, influenza A viruses are strongly dependent on cellular factors for replication. One of the hallmark signaling factors activated by viral pathogens is the transcription factor NF-κB. Activation of NF-κB leads to the up-regulation of a variety of antiviral genes. Thus, the factor is commonly regarded as a major regulator of the innate immune defense to infection. However, several recent studies indicate that influenza viruses have acquired the capability to reprogram this antiviral activity and to exploit the factor for efficient replication. These data provide novel insights into the pathophysiological function of NF-κB in the special environment of a virus-infected cell. Furthermore, the unexpected viral dependency on a cellular signaling factor may pave the path for novel antiviral approaches targeting essential cellular components rather than viral factors.