bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropilins in Tumor Biology
Authors: Bagri Anil , Tessier-Lavigne Marc , Watts Ryan J.
Published: February 2009

The neuropilin receptors were first discovered as regulators of nervous system development, acting as semaphorin coreceptors with plexins. Subsequently, the neuropilins were identified as receptors for vascular endothelial growth factor. Since those seminal discoveries, additional ligands that bind neuropilins have been described, and many studies have implicated neuropilins in playing key roles in tumor biology. Recent evidence has shown that manipulating neuropilin function can regulate tumor growth and metastasis through effects on vascular biology in the case of neuropilin-1 and lymphatic biology in the case of neuropilin-2. A direct role for neuropilins within in tumor cells has also been postulated. As data continue to accumulate pointing to a role for neuropilins in cancer, the promise for targeting this pathway is beginning to unfold.
Triptolide Inhibits Bcr-Abl Transcription and Induces Apoptosis in STI571-resistant Chronic Myelogenous Leukemia Cells Harboring T315I Mutation
Authors: Shi Xianping , Jin Yanli , Cheng Chao , Zhang Hui , Zou Waiyi , Zheng Qin , Lu Zhongzheng , Chen Qi , Lai Yingrong , Pan Jingxuan
Published: February 2009

Purpose: Resistance to STI571 is an emerging problem for patients with chronic myelogenous leukemia (CML). Mutation in the kinase domain of Bcr-Abl is the predominant mechanism of the acquired resistance to STI571. In the present study, we investigated the effect of triptolide on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl.

Experimental Design: CML cell lines (KBM5 versus KBM5-T315I, BaF3-Bcr-Abl versus BaF3-Bcr-Abl-T315I) and primary cells from CML patients with clinical resistance to STI571 were treated with triptolide, and analyzed in terms of growth, apoptosis, and signal transduction. Nude mouse xenograft model was also used to evaluate the antitumor activity.

Results: Triptolide potently down-regulated the mRNA and protein levels of Bcr-Abl independently of the caspase or proteosome activation in CML cells. It induced mitochondrial-dependent apoptosis in Bcr-Abl-T315I CML cells and primary cells from CML patients with clinical resistance to STI571. Additionally, triptolide inhibited the growth of STI571-sensitive KBM5 and STI571-resistant KBM5-T315I CML cells in nude mouse xenografts. Triptolide also down-regulated the expression of survivin, Mcl-1, and Akt in CML cells, which suggests that it may have multiple targets.

Conclusions: These findings suggest that triptolide is a promising agent to overcome STI571-resistant CML cells, and warrant a clinical trial of triptolide derivatives for CML with Bcr-Abl-T315I mutation.
Bcl-2 Blocks Cisplatin-Induced Apoptosis and Predicts Poor Outcome Following Chemoradiation Treatment in Advanced Oropharyngeal Squamous Cell Carcinoma
Authors: Michaud William A. , Nichols Anthony C. , Mroz Edmund A. , Faquin William C. , Clark John R. , Begum Shahnaz , Westra William H. , Wada Hiroshi , Busse Paul M. , Ellisen Leif W. , Rocco James W.
Published: February 2009

Purpose: This study aimed to test the hypothesis that elevated expression of antiapoptotic Bcl-2 family proteins predicts a poor therapeutic response of oropharyngeal squamous cell carcinoma (OPSCC) to concurrent platinum-based chemoradiation therapy.

Experimental Design: Levels of Bcl-2, Bcl-XL, and Bcl-w were determined and correlated with resistance to cisplatin in a large panel of cell lines derived from squamous cell carcinoma of the head and neck (HNSCC). Univariate and multivariate analyses were used to evaluate the relationship between Bcl-2 and Bcl-XL expression and disease-free survival following chemoradiation therapy in a uniformly treated cohort of patients with OPSCC.

Results: In HNSCC cell lines, high endogenous Bcl-2 expression was associated with increased cisplatin resistance, and experimental overexpression of Bcl-2 promoted cisplatin resistance. In patients, tumors positive for Bcl-2 before treatment had greater risk of treatment failure (hazard ratio, 5.99; 95% confidence interval, 1.73–20.8; P = 0.0014). In contrast, endogenous Bcl-XL showed no correlation either with cisplatin sensitivity in the cell line panel in vitro, or with risk of recurrence in vivo (hazard ratio, 1.28; 95% confidence interval, 0.39–4.19; P = 0.68). Associations between Bcl-2 expression and other clinical characteristics did not account for the predictive value of Bcl-2.

Conclusions: Immunohistochemical assessment of Bcl-2 in pretreatment biopsy specimens can predict response of advanced OPSCC to concurrent platinum-based chemoradiation. As treatments targeting Bcl-2 and its family members become available, this immunohistochemical assessment could help personalize therapy by identifying a subpopulation of patients with a poor prognosis who might benefit from such treatments.
Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins
Authors: Sassano Antonella , Lo Iacono Marco , Antico Giovanni , Jordan Alison , Uddin Shahab , Calogero Raffaele A. , Platanias Leonidas C.
Published: February 2009

There is emerging evidence that, beyond their cholesterol-lowering properties, statins exhibit important antileukemic effects in vitro and in vivo, but the precise mechanisms by which they generate such responses remain to be determined. We have previously shown that statins promote differentiation of acute promyelocytic leukemia cells and enhance generation of all-trans retinoic acid (ATRA)–dependent antileukemic responses. We now provide evidence that statin-dependent leukemic cell differentiation requires engagement and activation of the c-Jun NH2-terminal kinase kinase pathway. In addition, in experiments, to define the molecular targets and mediators of statin-induced differentiation, we found a remarkable effect of statins on ATRA-dependent gene transcription, evidenced by the selective induction of over 400 genes by the combination of atorvastatin and ATRA. Altogether, our studies identify novel statin molecular targets linked to differentiation, establish that statins modulate ATRA-dependent transcription, and suggest that combined use of statins with retinoids may provide a novel approach to enhance antileukemic responses in acute promyelocytic leukemia and possibly other leukemias. [Mol Cancer Ther 2009;8(3):615–25]
Large-Scale Production and Characterization of Novel CD4+ Cytotoxic T Cells with Broad Tumor Specificity for Immunotherapy
Authors: Jursik Claudia , Prchal Michaela , Grillari-Voglauer Regina , Drbal Karel , Fuertbauer Elke , Jungfer Herbert , Albert Winfried H. , Steinhuber Eva , Hemetsberger Thomas , Grillari Johannes , Stockinger Hannes , Katinger Hermann
Published: February 2009

Immune-cell–based approaches using cytotoxic and dendritic cells are under constant scrutiny to design novel therapies for the treatment of tumors. These strategies are hampered by the lack of efficient and economical large-scale production methods for effector cells. Here we describe the propagation of large amounts of a unique population of CD4+ cytotoxic T cells, which we termed tumor killer T cells (TKTC), because of their potent and broad antitumor cell activity. With this cultivation strategy, TKTCs from peripheral blood mononuclear cells are generated within a short period of time using a pulse with a stimulating cell line followed by continuous growth in serum-free medium supplemented with a mixture of interleukin-2 and cyclosporin A. Expression and functional profiling did not allow a classification of TKTCs to any thus far defined subtype of T cells. Cytotoxic assays showed that TKTCs kill a panel of tumor targets of diverse tissue origin while leaving normal cells unaffected. Blocking experiments revealed that TKTC killing was, to a significant extent, mediated by tumor necrosis factor-related apoptosis-inducing ligand and was independent of MHC restriction. These results suggest that TKTCs have a high potential as a novel tool in the adoptive immunotherapy of cancer. (Mol Cancer Res 2009;7(3):339–53)
Age in High-Functioning Healthy Men Is Associated with Nonlinear Decline in Some ‘Executive’ Functions in Late Middle Age
Authors: Silver Henry , Goodman Craig , Bilker Warren
Published: February 2009

Background/Aim: Age-related cognitive decline might involve selective deterioration of specific brain systems. We studied the relationship between age and cognition by comparing cognitive function of older and younger high functioning men. Methods: A cross-sectional study comparing neuropsychological test battery performance of younger (18–60 years) and older (61–85 years) men. Results: Older men showed impaired psychomotor speed, working memory, attention, declarative verbal memory and executive functions. Impairment in executive function was prominent and not explained by psychomotor slowing, impaired working memory or attention. Regression models showed a non-linear relationship between age and executive function with a change of slopes in the mid-50s. The relationship of age with verbal memory was linear. Conclusions: The nonlinear change in late middle age is consistent with the hypothesis that an age-related selective diatheses impacts selectively on executive function.
“Berlin … Your Dance Partner Is Death”
Authors: Elswit Kate
Published: February 2009

Dance and death combined in post-WWI Germany to complicate the material authority they were seen to share. Using nascent modern dance techniques to exploit the expressive capacities of the dancing body, choreographers turned to dances of death to portray the increasingly difficult conditions of humanity. The logistics of performing these spectacles of the real are investigated through three choreographer/performers of the Weimar Republic: Kurt Jooss, Valeska Gert, and Anita Berber.
Effects of Pressure on Collision, Coalescence, and Breakup of Raindrops. Part I: Experiments at 50 kPa
Authors: List Roland , Fung C. , Nissen R.
Published: February 2009

Previous breakup experiments have been carried out at laboratory pressures (∼100 kPa). However, raindrop interactions mainly take place higher up in the atmosphere, even in the supercooled part of a cloud where drops can be initiated by shedding from hailstones. Thus, 50 kPa, corresponding to a height of ∼5.5 km in the atmosphere at a temperature of ∼−20°C, was selected to bracket the region of interest for rain. Six drop pairs were studied at 50 kPa and laboratory temperature (∼20°C), one of them with reduced surface tension.

The apparatus consists of drop-producing nozzles, acceleration systems, deflectors, a timing and selection control, a pressure regulator, and a photographic unit, mostly set up in a low-pressure chamber. After acceleration to terminal speed, a smaller drop is blown into the path of the larger one while an electronic timing system selects suitable drop pairs that may collide, thereby triggering eight subsequent flashes with a frequency of up to 100 kHz. The results are displayed in terms of a normalized fragment probability per size bin, ready for parameterization in the Part II of this paper.

Five drop pairs were studied in 772 individual events. Overall, 51% resulted in filament breakup, 22% in sheet breakup, 7% in disk breakup, and 20% ended in coalescence. No bag breakups were observed. When compared to the 100-kPa results, the fragment numbers increased at large collision kinetic energies (CKEs) by factors of between 2.64 and 4.37 with pressure decreasing from 100 to 50 kPa, and they remained unchanged at low CKE. Detailed diagrams and tables show the results for the different drop pairs and collision categories. Increasing the sensitivity of the optical measurements from 0.05 to 0.01 cm increased the number of recognized fragments by factors up to 4.4, but only for the two higher-CKE cases. The higher resolution did not increase the fragment numbers detected in the lower-CKE range.
Characteristics of the Raindrop Size Distribution and Drop Shape Relation in Typhoon Systems in the Western Pacific from the 2D Video Disdrometer and NCU C-Band Polarimetric Radar
Authors: Chang Wei-Yu , Wang Tai-Chi Chen , Lin Pay-Liam
Published: February 2009

The drop size distribution (DSD) and drop shape relation (DSR) characteristics that were observed by a ground-based 2D video disdrometer and retrieved from a C-band polarimetric radar in the typhoon systems during landfall in the western Pacific, near northern Taiwan, were analyzed. The evolution of the DSD and its relation with the vertical development of the reflectivity of two rainband cases are fully illustrated. Three different types of precipitation systems were classified—weak stratiform, stratiform, and convective—according to characteristics of the mass-weighted diameter Dm, the maximum diameter, and the vertical structure of reflectivity. Further study of the relationship between the height H of the 15-dBZ contour of the vertical reflectivity profile, surface reflectivity Z, and the mass-weighted diameter Dm showed that Dm increased with a corresponding increase in the system depth H and reflectivity Z.

An analysis of DSDs retrieved from the National Central University (NCU) C-band polarimetric radar and disdrometer in typhoon cases indicates that the DSDs from the typhoon systems on the ocean were mainly a maritime convective type. However, the DSDs collected over land tended to uniquely locate in between the continental and maritime clusters. The average mass-weighted diameter Dm was about 2 mm and the average logarithmic normalized intercept Nw was about 3.8 log10 mm−1 m−3 in typhoon cases. The unique terrain-influenced deep convective systems embedded in typhoons in northern Taiwan might be the reason for these characteristics.

The “effective DSR” of typhoon systems had an axis ratio similar to that found by E. A. Brandes et al. when the raindrops were less than 1.5 mm. Nevertheless, the axis ratio tended to be more spherical with drops greater than 1.5 mm and under higher horizontal winds (maximum wind speed less than 8 m s−1). A fourth-order fitting DSR was derived for typhoon systems and the value was also very close to the estimated DSR from the polarimetric measurements in Typhoon Saomai (2006).
Statistics and Dynamics of Aircraft Encounters of Turbulence over Greenland
Authors: Lane Todd P. , Doyle James D. , Sharman Robert D. , Shapiro Melvyn A. , Watson Campbell D.
Published: February 2009

Historical records of aviation turbulence encounters above Greenland are examined for the period from 2000 to 2006. These data identify an important flow regime that contributes to the occurrence of aircraft turbulence encounters, associated with the passage of surface cyclones that direct easterly or southeasterly flow over Greenland’s imposing terrain. The result of this incident flow is the generation of mountain waves that may become unstable through interactions with the background directional wind shear. It is shown that this regime accounted for approximately 40% of the significant turbulent events identified in the 7-yr database. In addition, two specific cases from the database are examined in more detail using a high-resolution mesoscale model. The model simulations highlight the important role of three-dimensional gravity wave–critical level interactions and demonstrate the utility of high-resolution forecasts in the prediction of such events.
A New Approach to Forecasting Typhoon Frequency over the Western North Pacific
Authors: Fan Ke , Wang Huijun
Published: February 2009

This paper presents a new approach for forecasting the typhoon frequency of the western North Pacific (WNP). The year-to-year increase or decrease in typhoon frequency is first forecasted to yield a net typhoon frequency prediction. Five key predictors for the year-to-year increment in the number of typhoons in the WNP have been identified, and a forecast model is established using a multilinear regression method based on data taken from 1965 to 2001. Using the forecast model, a hindcast of the typhoon frequency of the WNP during 2002–07 is made. The model exhibited a reasonably close fit for the period 1965–2007, including the larger anomalies in 1997 and 1998. It also accounted for the smaller variability of the typhoon frequency of the WNP during the validation period 2002–07 with an average root-mean-square error (RMSE) of 1.3 (2.85) during 2002–07 (1965–2001). The cross-validation test of the prediction model shows that the new approach and the prediction model demonstrate better prediction skill when compared to the models established based on typhoon frequency rather than the typhoon frequency increment. Thus, this new approach has the potential to improve the operational forecasting skill for typhoon frequency in the WNP.
Hypertrophic and Hypertensive Hypertrophic Cardiomyopathy—A True Association?
Authors: Papadopoulos Dimitris P. , Papademetriou Vasilios
Published: February 2009

The cardiomyopathies were previously defined as ‘‘heart muscle diseases of unknown cause’’ and were differentiated from specific heart muscle disease with known cause. With increasing understanding of etiology and pathogenesis, the difference between cardiomyopathy and specific heart muscle disease has become indistinct. The term specific cardiomyopathies are used to describe heart diseases that are associated with specific cardiac or systemic disorders. These were previously defined as specific heart muscle diseases. They included ischemic cardiomyopathy, valvular cardiomyopathy, hypertensive cardiomyopathy, inflammatory cardiomyopathy, metabolic cardiomyopathy, general system disease, muscular dystrophies, sensitivity and toxic reactions, and peripartal cardiomyopathy. The cardiomyopathies are therefore classified by the dominant pathophysiology or, if possible, by etiological/pathogenetic factors. Topol in 1985 described a syndrome called hypertensive hypertrophic cardiomyopathy that included severe concentric cardiac hypertrophy, a small left ventricular cavity, and supernormal indexes of systolic function without concurrent medical illness or ischemic heart disease. The aim of this review was to highlighted this syndrome from pathophysiological, clinical, diagnostical view and clear all the possible correlations with genetic, inflammatory, and other markers.
Buying Peace? Oil Wealth, Corruption and Civil War, 1985—99
Authors: Fjelde Hanne
Published: February 2009

This article argues that, contrary to received wisdom, political corruption is not necessarily associated with a higher risk of civil war in oil-rich states. Political corruption can be used to accommodate opposition and placate restive groups by offering private privilege in exchange for political loyalty. Since oil wealth is associated with large rents accruing in state treasuries, it provides an economic foundation for such clientelist rule. This article thus argues that oil-rich governments can use political corruption to buy support from key segments of society, effectively outspending other entrepreneurs of violence. Based on a logit analysis of civil war onsets, 1985—99, the article finds support for this `co-optation argument'. A negative and statistically significant interaction term between oil production and political corruption is consistent across different models and robust to a number of specifications. While both variables per se increase the risk of conflict overall, higher levels of corruption seem to weaken the harmful impact of oil on the risk of civil war. This finding suggests the need for a more nuanced understanding of the relationship between natural resource wealth, governance and armed conflict. Political corruption has prolonged poverty and bred economic and political inequality in many oil-rich states, but it has also helped cement powerful alliances with a stake in the continuation of the corrupt regimes.
Nephrotic Syndrome Induced by Dibasic Sodium Phosphate Injections for Twenty-eight Days in Rats
Authors: Tsuchiya Noriko , Torii Mikinori , Narama Isao , Matsui Takane
Published: February 2009

Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman’s capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.
Community managed offenders' access to healthcare services: Report of a pilot study
Authors: Brooker C. , Syson-Nibbs L. , Barrett Paul , Fox C.
Published: February 2009

This article describes how a sample group of community managed offenders engaged with a range of health services. This is based on the findings from a pilot health needs assessment involving a representative sample of 183 offenders within two county-wide probation services. Health information was collected using a specially designed structured health needs assessment tool and complemented by exploratory interviews with probation workers. The results indicated that community offenders were found to have greater physical and mental health needs than the general population. Some problems were identified, particularly in engaging with dental and mental health services. Although many participants did not report any difficulty in accessing services, it would appear that offenders' engagement with health services was incommensurate with their likely level of need. There are clear implications for NHS joint commissioning groups who plan health services for this vulnerable group.
Antidepressants that inhibit neuronal norepinephrine reuptake are not associated with increased spontaneous reporting of cardiomyopathy
Authors: Ratcliffe S. , Younus M. , Hauben M. , Reich L.
Published: February 2009

A recent literature review linked norepinephrinergic stimulation to alterations in cyclic adenosine monophosphate (cAMP)-mediated signaling in cardiac myocytes and suggested that this might contribute to the pathological mechanisms that lead to chamber enlargement and hypocontractility, which are seen in dilated cardiomyopathy. This accompanies a large body of literature linking cardiac sympathetic outflow activation in early heart failure with progressive myocyte deterioration. As the mode of action of a number of antidepressants involves the inhibition of neuronal norepinephrine reuptake to varying degrees, this study was conducted to assess whether such agents might be associated with disproportionate reporting of cardiomyopathy. Limited data exist specifically examining the association between the antidepressant use and the cardiomyopathy. Using a data mining algorithm (DMA), we quantitatively investigated the association between antidepressant agents that predominantly exert their effects through inhibiting neuronal norepinephrine reuptake (rather than serotonin) and cardiomyopathy. We retrospectively applied a Bayesian DMA, the Bayesian Confidence Propagation Neural Network, to the cumulative reports in the Food and Drug Administration Adverse Event Reporting System (through the fourth quarter of 2006) and World Health Organization Vigibase (through the second quarter of 2007) databases. A threshold of the posterior interval 95% lower limit > 0 was used to define a signal of disproportionate reporting with individual or groups of antidepressants and cardiomyopathy-related terms. The analysis suggested that there is no direct relationship between antidepressants with greater norepinephrine reuptake inhibitor activity (affinity for norepinephrine reuptake transporter or selectivity for norepinephrine versus serotonin) and reporting of cardiomyopathy. In contrast, an inverse correlation might exist with a higher number of cases identified with tricyclic antidepressants showing lower norepinephrine reuptake inhibition and the serotonin/norepinephrine reuptake inhibitors as well as with serotonin/ norepinephrine/slight dopamine reuptake inhibitor.
From urban political economy to cultural political economy: rethinking culture and economy in and beyond the urban
Authors: Ribera-Fumaz Ramon
Published: February 2009

Discussions about the culture-economy articulation have occurred largely within the confines of economic geography. In addition, much attention has been diverted into caricaturized discussions over the demise of political economy or the invalidity of culturalist arguments. Moving the argument from inquiry on the `nature' of the economy itself to the transformation of the role of culture and economy in understanding the production of urban form from perspectives based in urban political economy (UPE), this paper focuses on how the challenges posed by the cultural turn have enabled urban political economy to participate constructively in interdisciplinary efforts to reorient political economy in the direction of a critical cultural political economy.
On the prevailing construction waste recycling practices: a South East Queensland study
Authors: Tam Vivian W.Y. , Kotrayothar Duangthidar , Loo Yew-Chaye
Published: February 2009

Waste generated from construction and building demolition work constitutes about 68% of all solid waste generated each year in South East Queensland. Consequently, it has created a serious waste management problem. The State Governments of Victoria and New South Wales have been encouraging the use of recycled materials from construction and related waste; they have also promulgated specifications for their use. In Queensland, however, similar regulations are not anticipated in the near future, which explains the lack of funded research conducted in this important arena. This paper presents an evaluation of the prevailing waste recycling practices in Queensland. Nine sites were visited, including two construction sites, three demolition sites, three recycling plants and one landfill in South East Queensland. The difficulties encountered by the recycling programme operators and their associates at these sites are described and the benefits of recycling construction materials are presented. One of the major barriers is that the local councils disallow the use of recycled materials in new construction work. To help rectify these impediments to recycling, recommendations are given to increase the use of recycled construction waste in South East Queensland.
Incentive regulation and performance measurement of the Portuguese solid waste management services
Authors: Marques Rui Cunha , Simões Pedro
Published: February 2009

Measuring the performance of solid waste management services usually uncovers very high potential for gains in efficiency and productivity. This circumstance occurs, naturally, due to the fact that these services are outside the market and because they are subjected to various market failures in their organizational framework. The aim of this study was to examine the Portuguese regulatory model and to measure the performance of the Portuguese solid waste management services in order to identify the major reforms carried out and their outcomes. As a first objective, the sunshine regulatory approach adopted in Portugal, in which performance comparison and its public discussion are the main tools, was investigated. The second objective was to compute the efficiency of the Portuguese solid waste management services by means of the non-parametric technique of data envelopment analysis (DEA), evaluating the Portuguese regulatory model and the existing market structure, as well as the influence of the operational environment on efficiency. The benchmarking frontier technique of DEA is particularly useful in the efficiency measurement of public utilities, in which knowledge of the production function is relatively scarce. Several DEA models were used and they all depicted significant inefficiency. The study also proved that efficiency did not depend on ownership (public or private) and that there was no difference in efficiency between the players, irrespective of whether they were regulated or not.
The Average Distance Between Item Values
Authors: Sturman Edward D. , Cribbie Robert A. , Flett Gordon L.
Published: February 2009

This article presents a method for assessing the internal consistency of scales that works equally well with short and long scales, namely, the average proportional distance. The method provides information on the average distance between item scores for a particular scale. In this article, we sought to demonstrate how this relatively simple statistic could be calculated and present examples that show its advantage over traditional methods. Simulation and empirical tests were conducted to establish standards for the average proportional distance of scores. The implications for test construction are discussed with a particular emphasis on the advantages of developing shorter scales for psychological and educational research.
Pesticide Risk Communication, Risk Perception, and Self-Protective Behaviors Among Farmworkers in California's Salinas Valley
Authors: Cabrera Nolan L. , Leckie James O.
Published: February 2009

Agricultural pesticide use is the highest of any industry, yet there is little research evaluating farmworkers' understandings of the health risks chemical exposure poses. This study examines pesticide education, risk perception, and self-protective behaviors among farmworkers in California's Salinas Valley. Fifty current and former farmworkers were interviewed for this research. Despite several potential barriers to risk communication (e.g., language differences and nonuniform methods of pesticide safety training), the respondents understood many of the potential health consequences of exposure while holding elevated levels of risk perception relative to the general public. They received information on the health effects of pesticide exposure from both grower-based training and personal social networks; however, the respondents continued to participate in unnecessarily risky behaviors.
Developmental Outcome of Children With Enlargement of the Cisterna Magna Identified in Utero
Authors: Dror Raheli , Malinger Gustavo , Ben-Sira Liat , Lev Dorit , Pick Chaim G. , Lerman-Sagie Tally
Published: February 2009

An enlarged cisterna magna can be identified during routine ultrasound screening in the second half of pregnancy. It is important to be able to give an accurate prognosis. We evaluated the developmental outcome of these children. A total of 29 fetuses with a large cisterna magna identified in utero were compared to 35 children with a normal fetal ultrasound. The children were evaluated by the Gesell Developmental Schedules and the Peabody Developmental Motor Scale. The study group showed a significantly worse performance in the Gesell test. However, the overall performance for both groups was within normal limits. Four children in the study group had a borderline developmental quotient. Both groups performed similarly in the Peabody test. Walking age was significantly delayed in the study group. Children with an enlarged cisterna magna may be at risk for mild developmental delay. In cases of nonisolated enlargement of the cisterna magna, the outcome may be guarded.
Kaempferol, a mutagenic flavonol from Helichrysum simillimum
Authors: Elgorashi EE , van Heerden FR , van Staden J
Published: February 2009

Helichrysum simillimum is native to South Africa. It is used for the treatment of coughs, colds, fever, infections, headache, and menstrual pain. Extracts of this species showed mutagenic effects in the Salmonella/microsome assay. The aim of this study was to isolate and determine the mutagenic constituents of H. simillimum. Bioassay-guided fractionation of 90% aqueous methanol extracts, using Salmonella typhimurium TA98, led to the isolation of the flavonol kaempferol.
An Eigenvalue Based Approach for Assessing the Decomposability of Interdependent Design Project Tasks
Authors: Bashir Hamdi A. , AlZebdeh Khalid , Abdo Jamil
Published: February 2009

The Concurrent engineering process is characterized by executing a large number of interdependent project tasks. One effective way of managing such tasks is to decompose them into groups. However, not all tasks are decomposable. Without the need to apply a decomposition method, this paper describes a simple, quantitative approach to test whether an underlying pattern of relationships exists between interdependent project tasks, such that they may be rearranged into groups. In addition, a grouping efficiency index is introduced to predict how good the best possible decomposition is. The proposed approach and the grouping index are applied to simple hypothetical projects and a sample project adapted from the literature. Both the approach and the grouping index are proved to be powerful yet very easy to use.
Collaborative Design and Modeling of Complex Opto-mechanical Systems
Authors: Basdogan Ipek
Published: February 2009

In this article, we propose a concurrent design methodology that employs physics-based high fidelity computational models together with analysis methods to predict the performance of complex opto-mechanical systems. For this purpose, we developed a web-based collaborative design and modeling environment for the simulation of complex opto-mechanical systems (SIMCOMS). The analysis tools and the methodology presented in this article provide a systematic and quantitative way to investigate the end-to-end system performance of such systems, perform sensitivity analysis, and identify the critical components of the system that degrade the performance. The SIMCOMS integrates all the modeling and analysis tools in a common MATLAB computational environment and it can be accessed through standard web browsers. Through the use of structural, optical, and controls modules, SIMCOMS allows modeling and SIMCOMS. The analysis modules of SIMCOMS provide the means for predicting the performance of such systems and diagnosing the problematic components that degrade the performance. The web interface of SIMCOMS provides a flexible and robust environment for designing such complex opto-mechanical systems and keeps an archive of models to compare different design configurations. The design can be conducted concurrently by multidisciplinary teams located physically at different sites, which leads to savings in time and cost. We demonstrated the use of SIMCOMS through a case study which includes the redesign process of a siderostat mirror; one of the main optical components of the SIM PlanetQuest (formerly called Space Interferometry Mission). SIM will determine the positions and distances of stars several hundred times more accurately than any previous program. SIM provides a good example case for testing the functionality of SIMCOMS since the precise tolerance required by the SIM instrument facilitates the investigation of many design options, trades, and methods for minimizing interaction between the actively controlled optics and the structure.
Gender-related Differences in Drug-induced Prolongation of Cardiac Repolarization in Prepubertal Guinea Pigs
Authors: Hreiche Raymond , Morissette Pierre , Zakrzewski-Jakubiak Hubert , Turgeon Jacques
Published: February 2009

Underlying mechanisms of drug-induced long QT syndrome are not fully understood. Our objective was to evaluate gender-related differences for block of the rapid (IKr) or/and the slow (IKs) components of the delayed rectifier potassium current in prepubertal male and female guinea pigs (n = 120) treated with or without verapamil. Indapamide (IKsblocker) prolonged the monophasic action potential duration at 90% repolarisation (MAPD90) in females more than in males (15.1 + 0.5 vs 9.7 + 1.3 msec; P < .05) in verapamil treated animals. In contrast, MAPD90prolongation induced by domperidone or dofetilide (IKrblockers) was not different between genders. Verapamil treatment augmented prolongation of MAPD90caused by dofetilide or domperidone (P < .01). In conclusion, 1) females exhibited greater prolongation of MAPD90when exposed to indapamide, 2) no gender-related differences were observed for IKrblockers, and 3) verapamil treatment did not uncover gender-related differences in IKror IKsblock, although it augmented prolongation of cardiac repolarization by IKrblockers.
The Plasticity of Identity under Anarchy
Authors: Legro Jeffrey W.
Published: February 2009

Why do national identities usually endure but sometimes radically change? Much of the time, identity socializes or constrains leaders to act in patterned ways. Occasionally, however, leaders are able to dramatically alter those self-images. This article offers a general argument for varying identity plasticity. It brings together organizational theory and social theory to demonstrate how ideas about means to goals can in certain circumstances change how states see themselves. I examine the plausibility of this explanation in cases of continuity and change in Japan's identity in the 19th century and the Soviet Union's identity in the 20th century — in both instances challenging the common wisdom that identity was a direct product of international pressures. The argument suggests the importance of synthetic explanations — i.e. concrete generalizable propositions on how ideas and power interact in specific ways to influence the evolution of national identity.
Hot cracking in laser braze joint of high strength stainless steel using gold brazing filler metal – prevention of hot cracking by controlling thermal cycle
Authors: Saida K. , Sakatani T. , Song W. , Nishimoto K.
Published: February 2009

The hot cracking behaviour in the diode laser braze joint of 13Cr–4Ni stainless steel using Au–18Ni, Ag–10Pd and Ag–21Cu–25Pd filler metals has been investigated. The types of joint investigated were the T fillet joint and the L fillet joint which simulated the second braze bead in the T fillet joint. Tandem beam brazing was also carried out in order to prevent the hot cracking by post-heating treatment with a trailing beam. A centreline crack, characterised as a ductility dip crack, occurred in the second braze bead of the T fillet joint using Au–Ni filler metal. On the other hand, no cracks occurred in either the first or the second braze bead in T fillet braze joints using Ag–Pd and Ag–Cu–Pd filler metals. The hot cracking susceptibility of the Au–Ni braze metal was evaluated by the spot Varestraint test. Most of the cracks observed in the spot Varestraint test specimen were also characterised as ductility dip cracks, and the susceptibility to such cracking increased with increasing the augmented strain. The ductility dip temperature range (DTR) was estimated from the crack position and length to be 1000–1250 K at strains over 0·4%. Numerical analyses of the thermal stress and strain revealed that the plastic strain–temperature curve intersected the DTR in the single beam brazing, but did not intersect the DTR with post-heating during the laser brazing. The effect of post-heating on the crack prevention was verified by tandem beam brazing of L fillet joint with a trailing beam. No cracks occurred in the braze bead made with a trailing beam at laser powers of 200–300 W. The authors concluded that hot cracking in the Au–Ni braze metal could be successfully prevented by controlling the thermal cycle during the laser brazing process.
The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis
Authors: Senis Yotis A. , Tomlinson Michael G. , Ellison Stuart , Mazharian Alexandra , Lim Jenson , Zhao Yan , Kornerup Kristin N. , Auger Jocelyn M. , Thomas Steve G. , Dhanjal Tarvinder , Kalia Neena , Zhu Jing W. , Weiss Arthur , Watson Steve P.
Published: February 2009

Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.
Essential role of the disintegrin-like domain in ADAMTS13 function
Authors: de Groot Rens , Bardhan Ajoy , Ramroop Nalisha , Lane David A. , Crawley James T. B.
Published: February 2009

ADAMTS13 is a highly specific multidomain plasma metalloprotease that regulates the multimeric size and function of von Willebrand factor (VWF) through cleavage at a single site in the VWF A2 domain. The precise role that the ADAMTS13 disintegrin-like domain plays in its function remains uncertain. Truncated ADAMTS13 variants suggested the importance of the disintegrin-like domain for both enzyme activity and specificity. Targeted mutagenesis of nonconserved regions (among ADAMTS family members) in the disintegrin-like domain identified 3 of 8 ADAMTS13 mutants (R349A, L350G, V352G) with reduced proteolytic activity. Kinetic analyses revealed a 5- to 20-fold reduction in catalytic efficiency of VWF115 (VWF residues 1554-1668) proteolysis by these mutants. These residues form a predicted exposed exosite on the surface of the disintegrin-like domain that lies approximately 26 Å from the active site. Kinetic analysis of VWF115 carrying the D1614A mutation suggested that Arg349 in the ADAMTS13 disintegrin-like domain interacts directly with Asp1614 in VWF A2. We hypothesize that this interaction assists in positioning the scissile bond within the active site of ADAMTS13 and therefore plays a major role in determining cleavage parameters (Km and kcat), as opposed to binding affinity (Kd) of ADAMTS13 for VWF, the latter being primarily determined by the spacer domain.
A monoclonal gammopathy precedes multiple myeloma in most patients
Authors: Weiss Brendan M. , Abadie Jude , Verma Pramvir , Howard Robin S. , Kuehl W. Michael
Published: February 2009

Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.
Genome-scale identification of Caenorhabditis elegans regulatory elements by tiling-array mapping of DNase I hypersensitive sites
Authors: Shi Baochen , Guo Xiangqian , Wu Tao , Sheng Sitong , Wang Jie , Skogerbø Geir , Zhu Xiaopeng , Chen Runsheng
Published: February 2009

Background

A major goal of post-genomics research is the integrated analysis of genes, regulatory elements and the chromatin architecture on a genome-wide scale. Mapping DNase I hypersensitive sites within the nuclear chromatin is a powerful and well-established method of identifying regulatory element candidates.

Results

Here, we report the first genome-wide analysis of DNase I hypersensitive sites (DHSs) in Caenorhabditis elegans. The data was obtained by hybridizing DNase I-treated and end-captured material from young adult worms to a high-resolution tiling microarray. The data show that C. elegans DHSs were significantly enriched within intergenic regions located 2 kb upstream and downstream of coding genes, and also that a considerable fraction of all DHSs mapped to intergenic positions distant to annotated coding genes. Annotated transcribed loci were generally depleted in DHSs relative to intergenic regions, but DHSs were nonetheless enriched in coding exons and UTRs, whereas introns were significantly depleted in DHSs. Many DHSs appeared to be associated with annotated non-coding RNAs and recently detected transcripts of unknown function. It has been reported that nematode highly conserved non-coding elements were associated with cis-regulatory elements, and we also found that DHSs, particularly distal intergenic DHSs, were significantly enriched in regions that were conserved between the C. elegans and C. briggsae genomes.

Conclusion

We describe the first genome-wide analysis of C. elegans DHSs, and show that the distribution of DHSs is strongly associated with functional elements in the genome.