bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Behavior of Ductile Quasi-homogeneous Solids
Authors: Murzewski Janusz W.
Published: December 2005

First M.T. Huber in 1904, and later Mises and Hencky suggested equivalent yield criteria for elastic-perfectly plastic solids in three-dimensional stress states. The H-M-H criterion is commonly used in structural design. But, the Huber-Hencky distortion energy formula and the Huber-Mises reduced stress formula do not give unique yielding measures for elastic-nonlinearly plastic solids. The yielding probability κ, which has been introduced by the author in 1954, serves the purpose for ductile elastic-nonlinearly plastic solids. This idea has been a part of a more general probability-based theory such that the yielding ratio κ and a cracking tensor λ are the damage measures for quasi-homogeneous continuous media. Structural concrete has been analyzed in earlier studies. In this study, nominally ductile materials are taken into consideration such as structural steel and aluminum alloys in normal temperatures. The log-normal probability distributions of plastic microstrength and microstress are accepted. Constitutive equations are derived with the yielding ratio κ as the coordinate of state. The Ramberg-Osgood σ-ε curve is taken as the empirical basis for evaluation of the probability distribution parameters. Two points of the curve are taken into account: the conventional yield strength fy and the ultimate strength fu. A numerical example indicates that both elastic and plastic compressible phases of the quasi-homogeneous solid is a likely model of behavior. A shear stress-strain curve is analytically derived. The conventional 0.2% permanent strain for the characteristic plastic strength fy in a simple tension test applies approximately also to shear cases for the same yielding ratio κy at the characteristic strength level. The ultimate strength fu will occur when the effective stress σeff (κ) attains its maximum level for a critical yielding ratio κcr; however, it is not the maximum point σeff(ε) of the monotone Ramberg-Osgood curve. The characteristic κy and critical κcr values are verified in the case of shear.
Synthesis, Evaluation, and Selection of Parts Design Scheme in Supplier Involved Product Development
Authors: Tang Jiafu , Zhang Yan-e , Tu Yiliu , Chen Yizeng , Dong Ying
Published: December 2005

Taking into account the supplier involvement in the new product development (NPD), this article focuses on the synthesis evaluation, and selection of the part design scheme in part deployment process. The concepts of performance indicator (PI) and integrated performance indicators (IPI) are introduced to measure the performance of the part design scheme and product design scheme respectively. A two-layer fuzzy synthesis evaluation method is applied to assess the part design scheme in a supplier-involved new product development process. Combining the information of House of Quality (HoQ) and evaluation results of the part design scheme and taking into account the design budget, a 0–1 integer programming model is developed for selection of the parts combinatorial scheme in supplier-involved part deployment processes. A case study with a type of liquid crystal display (LCD) design in an Electronic Appliance Manufacturing Enterprise is also illustrated in the article.
Distributed Design Process Coordination based on a Service Event Notification Model
Authors: Cao Jian , Zhang Shensheng , Li Minglu , Wang Jie
Published: December 2005

Due to the complexity and uncertainties, the distributed design process requires dynamic collaborations among the heterogeneous systems and human interactions. In order to coordinate different system applications and humans, an event notification model is required. In this article, we propose a service event notification model based on grid service. The model takes advantage of the grid infrastructure and reduces the need for ad hoc development of middleware for supporting process coordination. In this model, an event notification server composed of a group of grid services can capture events from other grid services and generate process events. When an event occurs, event notification server decides to whom it should send the event according to an awareness model that keeps the states of the underlying coordination policies and business rules. The awareness model and the methodology for building an event notification system, together with the infrastructure of the notification server are presented in the article. An example in applying the model to a vehicle design project coordination scenario is presented to illustrate the potential application of the event notification model.
Technology Solutions for Collaborative Product Lifecycle Management – Status Review and Future Trend
Authors: Ming X. G. , Yan J. Q. , Lu W. F. , Ma D. Z.
Published: December 2005

In the modern global economy, companies are facing ever-increasing challenges for short time-to-market to enter into the market early, for reduced time-to-volume to occupy the market quickly, and for decreased time-to-profit to get return from market shortly. Product lifecycle management (PLM) is recognized as one of the key leading technologies to facilitate companies to overcome these challenges, which will offer companies a new way to rapidly plan, organize, manage, measure, and deliver new products or services much faster, better, and cheaper in an integrated way. Following this trend, this study proposes a full scenario of technology solutions for PLM based on the complete analysis of business drivers, industry requirements, limit of current solution, and recent state-of-the-art review in the domain related to PLM. Potential industrial impact of the developed PLM technology solutions is analyzed. It is hoped that the proposed PLM technology solutions will form the frontier basis for further research, development, and application of PLM systems to quickly adapt to the dynamic changing market for industry companies to pursue the most advanced competitiveness.
Integrating Aircraft Cost Modeling into Conceptual Design
Authors: Curran R. , Price M. , Raghunathan S. , Benard E. , Crosby S. , Castagne S. , Mawhinney P.
Published: December 2005

The article presents cost modeling results from the application of the Genetic-Causal cost modeling principle. Industrial results from redesign are also presented to verify the opportunity for early concept cost optimization by using Genetic-Causal cost drivers to guide the conceptual design process for structural assemblies. The acquisition cost is considered through the modeling of the recurring unit cost and non-recurring design cost. The operational cost is modeled relative to acquisition cost and fuel burn for predominately metal or composites designs. The main contribution of this study is the application of the Genetic-Causal principle to the modeling of cost, helping to understand how conceptual design parameters impact on cost, and linking that to customer requirements and life cycle cost.
Review: Determination of Vitamin D in Dairy Products by High Performance Liquid Chromatography
Authors: Perales S. , Alegría A. , Barberá R. , Farré R.
Published: December 2005

This work reviews the methods used for the determination of vitamin D in some dairy products (milk and infant formulas) by high performance liquid chromatography (HPLC). The low vitamin D contents and the presence of interfering compounds require sample treatment and purification of the extract. The advantages and drawbacks of hot and cold saponification, direct extraction and different types of extract purification are also discussed, taking into account the lack of vitamin D stability by heating, exposure to light and oxidation. With respect to chromatographic determination, the mode (normal or reverse phase), type of column (microcolumn or conventional) and detection system (UV, electrochemical and mass spectrometry) are overviewed, considering the vitamers to be determined.
Effect of Enzyme Amounts Used in Gastrointestinal Digestion Upon Solubility and Caco-2 Cell Uptake Assays of Minerals from Infant Formulas
Authors: Laparra J. M. , Barberá R. , Farré R.
Published: December 2005

The effect of enzyme amounts used in gastrointestinal in vitro digestion upon the solubility and Caco-2 cell uptake of calcium, iron and zinc from infant formulas (IFs) was studied. Different amounts of enzymes (g enzyme/g IF), pepsin (0.002 and 0.048), pancreatin (0.0005, 0.002 and 0.01) and bile extract (0.003, 0.125 and 0.0625) were assayed. Mineral soluble contents and mineral uptakes by Caco-2 cells were affected by the enzyme amounts used in digestion. Although the highest mineral solubility (Ca 98.6 vs 46.2%; Fe 98.1 vs 83.9%; Zn 98.4 vs 83%) was obtained when the lowest enzyme (pepsin 0.002 vs 0.048; pancreatin 0.0005 vs 0.01g/g IF) and bile extract (0.003 vs 0.0625g/g IF) amounts were used, under these conditions uptake decreased with respect to that obtained when the highest amounts were used (Ca 0.4 vs 1.8%; Fe 0.3 vs 4.8%; Zn 1.7 vs 37%), that indicated a lack of relationship between solubility and absorption. Interactions among different products resulting from the proteolytic activity of digestive enzymes and minerals can modify the physicochemical forms in which minerals are available for absorption after gastrointestinal digestion.
Effect of Vital Gluten and Gum Arabic on the Textural Properties of Pasta Made from Pre-gelatinised Broken Rice Flour
Authors: Raina C. S. , Singh Sukhcharn , Bawa A. S. , Saxena D. C.
Published: December 2005

Broken rice flours of three indigenous rice cultivars were utilised for the formulation of tube type pasta (Ziti-cut) using four levels of vital gluten (14-20%, flour weight basis) and gum Arabic (0.5-2.0%, flour weight basis). The textural qualities of pasta were analysed using a texture analyser (TAXT-2i) and by descriptive sensory analysis. The pasta made from native broken rice flour and pre-gelatinised broken rice flour supplementing with vital gluten to obtain 14% protein content were compared for their instrumental texture qualities (hardness and shear strength of raw pasta as well as stickiness and adhesiveness of cooked pasta) and sensory texture analysis (colour, hardness, chewiness, smoothness and grittiness). The pre-gelatinised broken rice flour was found suitable for pasta preparation based on its firmer, larger shear strength and less stickiness and adhesiveness than its native broken rice flour. Among the three varieties, the pre-gelatinised broken rice flour of variety PR-114 with 14% protein content (supplemented by vital gluten) and 1.5% gum Arabic has been found most suitable for the pasta preparation with desirable quality attributes on the basis of instrumental and sensory textural characteristics.
Note. Caffeine Content and Dynamical Bitterness of Yerba Mate Ilex paraguariensis Infusions
Authors: Calviño A. M. , Tamasi O. P. , Ciappini M. C.
Published: December 2005

The infusion of yerba mate (YM) Ilex paraguariensis, with its typical bitterness, is traditionally consumed in South America as a mild stimulant beverage. Two types of YM, with sticks (YM-S) and without sticks (YM-L) and three brands for each type were evaluated for caffeine content and the time course of bitterness. The chemical analysis of the six YM infusions at 5% w/v made by high performance liquid chromatography (HPLC) showed that caffeine levels were higher for YM-L brands. The kinetic study of YM bitterness assessed by time-intensity (TI) curves revealed that the presence of sticks lowered maximum intensity, total duration and area under the curve of bitter perception.
Optimisation of Bleaching Conditions for Soybean Oil Using Response Surface Methodology
Authors: Ortega-García J. , Medina-Juárez L. A. , Gámez-Meza N. , Noriega-Rodriguez J. A.
Published: December 2005

The refining process applied to soybean oil (SBO) in order to obtain the desirable purity characteristics as edible oil, produces chemical changes by partially removing desirable components such as tocopherols. In this study, the effect of temperature (76.4-143.6°C), contact time (6.4-73.6min) and clay amount (0.16-1.84% w/w) on tocopherol content and quality of SBO were evaluated. Neutralised soybean oil was subjected to bleaching using different clay amounts (Tonsil Optimum 320 FF), stirring (250rpm), and partial vacuum (60mmHg). A response surface methodology (RSM) was used to find the parameters that produce bleached oil with minimum peroxide value (PV), maximum tocopherol retention (TOCR) and light colour. The optimal bleaching conditions for SBO were: temperature, 96°C; time, 23min; clay amount, 1.4% w/w oil. Under these conditions, a bleached soybean oil with 0.1meq/kg of PV, 91.74% of TOCR, and colour 1.53 Lovibond red value units was obtained.
Open Sun Drying of Tinospora cordifolia, Curcuma longa L. and Zingiber officinale. Thermal Analysis
Authors: Prasad J. , Vijay V. K.
Published: December 2005

Open sun drying is a common method of drying of agricultural products in developing countries. Despite having several disadvantages, it is widely practised because it is a very simple way of drying. Tinospora cordifolia (a type of herb), Curcuma longa L. and Zingiber officinale (spices) were dried in the open sun and determined thermal parameters like product temperature, temperature around the product surface and rate of moisture transfer. The drying time for Tinospora cordifolia, Curcuma longa L. and Zingiber officinale were 41, 43 and 45 sunshine hours respectively with average solar radiation of 10.8MJ/m2. Convective heat transfer coefficient ( hc) for Tinospora cordifolia, Curcuma longa L. and Zingiber officinale were 1.57-3.85W/m2°C, 2.32-3.42W/m2°C and 1.62-3.34W/m2°C respectively, and increased by raising the difference in temperature between the product and the temperature around the product surface (T) from 0.3°C to 8.1°C. A fair agreement was observed between fitted and experimental results with coefficient of correlation ranging from 0.9984-0.9921, 0.9960-0.9856 and 0.9983-0.9898 for product temperature, temperature around the product surface and moisture content during drying.
Damage Characteristics of Composite Honeycomb Sandwich Panels in Bending under Quasi-static Loading
Authors: Zhou G. , Hill M. , Loughlan J. , Hookham N.
Published: December 2005

Damage characteristics of composite-skinned honeycomb sandwich panels in bending are investigated with both hemispherical (HS) and flat-ended (FE) indenters. The thickness of the cross-ply skins varies from 8 to 16 plies, whereas the density of the 12.7-mm thick aluminum honeycomb core varies from 50 to 70 kg/m3. Clamped panels with a 100-mm testing area are loaded quasi-statically either in bending or on a rigid base. The effects of varying these parameters on damage mechanisms are examined through response curves as well as cross sections of selected specimens. Special emphasis is placed on their potential change induced by the variation of skin thickness and core density with a specific indenter. Damage mechanisms are identified as core crush, top-skin delamination, and fracture or shear-out. The threshold and ultimate loads as well as the initial slope increase significantly either on increase of skin thickness or change of the nose shape of indenter from a hemisphere to a flat-end. The increase in the post-initial-damage slope is small and can be attributed to membrane stretching of the damaged top skin. Increasing the core density affects substantially not only the threshold load, but also the initial slope associated with the FE indenter. Changing the nose shape of the indenter has an overriding effect on the nature of damage mechanisms. In particular, top-skin delaminations occur after core crush. The panel deflection contributes to 20-53% sandwich deformation. The bottom skin in all the tests remains intact.
Design and Characterization of Polymeric Stents
Authors: Irsale Swagat , Adanur Sabit
Published: December 2005

The study focuses on prototype manufacturing of polymeric stents. The prototype is an integrated braided and tubular narrow woven fabric assembly. The braided structure manufactured with polyester monofilaments, acts as the reinforcing component and the tubular narrow woven fabric tightly covering it, acts as the sealing component. Prototypes of bifurcated braided stent for abdominal aortic aneurysm applications are also manufactured with braiding of polyester monofilaments. Three-way ANOVA results show statistically significant effects of braid angle, braid diameter, and heatset time on the compression force of the reinforcing component of polymeric stents. All components of the polymeric stents are manufactured with the available textile machinery.
Mechanical Performance of Biofiber/Glass-reinforced Epoxy Hybrid Composites
Authors: Priya S. Padma , Rai S. K.
Published: December 2005

The degree of mechanical reinforcement that can be obtained by the introduction of glass fibers in biofiber (silk fabric)-reinforced epoxy composites has been assessed experimentally. The addition of a relatively small amount of glass fabric to the silk fabric reinforced epoxy matrix enhances the mechanical properties of the resulting hybrid composites. It has also been observed that the properties increase with the increase in the weight fraction of reinforcement content to the maximum extent. The water uptakes of hybrid composites are observed to be less than that of unhybridized composites.
Critical role for the Ets transcription factor ELF-1 in the development of tumor angiogenesis
Authors: Huang Xuling , Brown Courtney , Ni Weihua , Maynard Elizabeth , Rigby Alan C. , Oettgen Peter
Published: December 2005

The Ets transcription factors regulate a wide variety of biologic processes. Several members have been shown to play a role in regulating angiogenesis and vascular development. For example, the Ets factor ELF-1 is enriched in the developing vasculature of the embryo, where it regulates the expression of the Tie2 gene. We have determined that ELF-1 and Tie2 expression is also enriched in tumor blood vessels, and have identified a short peptide, 34 amino acids in length, corresponding to the terminal portion of the highly conserved ETS domain that potently blocks the function of ELF-1. A tailored ELF-1 blocking peptide, containing a 12–amino acid HIV-1 TAT protein, readily crosses the cell membrane and enters into the nucleus of endothelial cells, leading to a marked reduction in the expression of ELF-1 gene targets including Tie2 and endothelial nitric oxide synthase. Furthermore, the ELF-1 blocking peptide potently inhibits angiopoietin-1–mediated endothelial cell migration. Systemic administration of this peptide markedly attenuates B16 melanoma tumor growth and tumor-associated angiogenesis in nude mice. These results support the function of ELF-1 in the regulation of Tie2 gene expression during the development of tumor angiogenesis.
Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha
Authors: Jones Amy V. , Silver Richard T. , Waghorn Katherine , Curtis Claire , Kreil Sebastian , Zoi Katerina , Hochhaus Andreas , Oscier David , Metzgeroth Georgia , Lengfelder Eva , Reiter Andreas , Chase Andrew J. , Cross Nicholas C. P.
Published: December 2005

Imatinib and recombinant interferon alpha (rIFNα) can induce remission in polycythemia vera (PV) patients, but gauging the depth of responses has not been possible due to lack of a specific disease marker. We found that patients undergoing imatinib (n = 14) or rIFNα (n = 7) therapy remained strongly positive for V617F JAK2, although there was a significant reduction in the median percentage of mutant alleles that correlated with hematologic response (P = .001). Furthermore, individuals who achieved complete hematologic remission had lower levels of V617F than those who did not (P = .001). Of 9 imatinib-treated cases for whom pretreatment samples were available, 7 with no or partial hematologic responses showed a marginal increase (median, 1.2-fold; range, 1.0-1.5) in the percentage of V617F alleles on treatment, whereas the 2 patients who achieved complete hematologic remission showed a 2- to 3-fold reduction. Our data indicate that, although PV patients may benefit from imatinib or rIFNα, molecular responses are relatively modest.
A microarray data-based semi-kinetic method for predicting quantitative dynamics of genetic networks
Authors: Yugi Katsuyuki , Nakayama Yoichi , Kojima Shigen , Kitayama Tomoya , Tomita Masaru
Published: December 2005

Background

Elucidating the dynamic behaviour of genetic regulatory networks is one of the most significant challenges in systems biology. However, conventional quantitative predictions have been limited to small networks because publicly available transcriptome data has not been extensively applied to dynamic simulation.

Results

We present a microarray data-based semi-kinetic (MASK) method which facilitates the prediction of regulatory dynamics of genetic networks composed of recurrently appearing network motifs with reasonable accuracy. The MASK method allows the determination of model parameters representing the contribution of regulators to transcription rate from time-series microarray data. Using a virtual regulatory network and a Saccharomyces cerevisiae ribosomal protein gene module, we confirmed that a MASK model can predict expression profiles for various conditions as accurately as a conventional kinetic model.

Conclusion

We have demonstrated the MASK method for the construction of dynamic simulation models of genetic networks from time-series microarray data, initial mRNA copy number and first-order degradation constants of mRNA. The quantitative accuracy of the MASK models has been confirmed, and the results indicated that this method enables the prediction of quantitative dynamics in genetic networks composed of commonly used network motifs, which cover considerable fraction of the whole network.
Gene capture prediction and overlap estimation in EST sequencing from one or multiple libraries
Authors: Wang Ji-Ping Z , Lindsay Bruce G , Cui Liying , Wall P Kerr , Marion Josh , Zhang Jiaxuan , dePamphilis Claude W
Published: December 2005

Background

In expressed sequence tag (EST) sequencing, we are often interested in how many genes we can capture in an EST sample of a targeted size. This information provides insights to sequencing efficiency in experimental design, as well as clues to the diversity of expressed genes in the tissue from which the library was constructed.

Results

We propose a compound Poisson process model that can accurately predict the gene capture in a future EST sample based on an initial EST sample. It also allows estimation of the number of expressed genes in one cDNA library or co-expressed in two cDNA libraries. The superior performance of the new prediction method over an existing approach is established by a simulation study. Our analysis of four Arabidopsis thaliana EST sets suggests that the number of expressed genes present in four different cDNA libraries of Arabidopsis thaliana varies from 9155 (root) to 12005 (silique). An observed fraction of co-expressed genes in two different EST sets as low as 25% can correspond to an actual overlap fraction greater than 65%.

Conclusion

The proposed method provides a convenient tool for gene capture prediction and cDNA library property diagnosis in EST sequencing.
Simplified screening for the detection of soluble fusion constructs expressed in E. coli using a modular set of vectors
Authors: Dümmler Annett , Lawrence Ann-Marie , de Marco Ario
Published: December 2005

Background

The solubility of recombinant proteins expressed in bacteria is often disappointingly low. Several strategies have been developed to improve the yield and one of the most common strategies is the fusion of the target protein with a suitable partner. Despite several reports on the successful use of each of these carriers to increase the solubility of some recombinant proteins, none of them was always successful and a combinatorial approach seems more efficient to identify the optimal combination for a specific protein. Therefore, the efficiency of an expression system critically depends on the speed in the identification of the optimal combination for the suitable fusion candidate in a screening process. This paper describes a set of expression vectors (pETM) designed for rapid subcloning, expression and subsequent purification using immobilized metal affinity chromatography (IMAC).

Results

A single PCR product of two Yellow Fluorescent Proteins (EYFPs) was cloned into 18 vectors comprising identical restriction sites and varying fusion partners as well as differing protease recognition sites. After a small-scale expression, the yields of the different constructs were compared using a Coomassie stained SDS-polyacrylamide gel and the results of this preliminary screening were then confirmed by large-scale purification. The yields were calculated and the stability of the different constructs determined using three independent conditions. The results indicated a significant correlation between the length and composition of non-native amino acid tails and stability. Furthermore, the buffer specificity of TEV and 3C proteases was tested using fusion proteins differing only in their protease recognition sequence, and a His-GST-EYFP construct was employed to compare the efficiency of the two alternative affinity purification methods.

Conclusion

The experiments showed that the set of pETM vectors could be used for the rapid production of a large array of different constructs with specific yield, stability, and cleavage features. Their comparison allowed the identification of the optimal constructs to use for the large-scale expression. We expect that the approach outlined in this paper, i.e. the possibility to obtain in parallel fusion products of the target protein with different partners for a preliminary evaluation, would be highly beneficial for all them who are interested in the rapid identification of the optimal conditions for protein expression.
Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds
Authors: Hargrove James L
Published: December 2005

Hummingbirds and other nectar-feeding, migratory birds possess unusual adaptive traits that offer important lessons concerning obesity, diabetes and the metabolic syndrome. Hummingbirds consume a high sugar diet and have fasting glucose levels that would be severely hyperglycemic in humans, yet these nectar-fed birds recover most glucose that is filtered into the urine. Hummingbirds accumulate over 40% body fat shortly before migrations in the spring and autumn. Despite hyperglycemia and seasonally elevated body fat, the birds are not known to become diabetic in the sense of developing polyuria (glucosuria), polydipsia and polyphagia. The tiny (3–4 g) Ruby-throated hummingbird has among the highest mass-specific metabolic rates known, and loses most of its stored fat in 20 h by flying up to 600 miles across the Gulf of Mexico. During the breeding season, it becomes lean and maintains an extremely accurate energy balance. In addition, hummingbirds can quickly enter torpor and reduce resting metabolic rates by 10-fold. Thus, hummingbirds are wonderful examples of the adaptive nature of fat tissue, and may offer lessons concerning prevention of metabolic syndrome in humans.
p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells
Authors: Ciccarelli Carmela , Marampon Francesco , Scoglio Arianna , Mauro Annunziata , Giacinti Cristina , De Cesaris Paola , Zani Bianca M
Published: December 2005

Background

p21WAF1, implicated in the cell cycle control of both normal and malignant cells, can be induced by p53-dependent and independent mechanisms. In some cells, MEKs/ERKs regulate p21WAF1transcriptionally, while in others they also affect the post-transcriptional processes. In myogenic differentiation, p21WAF1expression is also controlled by the myogenic transcription factor MyoD. We have previously demonstrated that the embryonal rhabdomyosarcoma cell line undergoes growth arrest and myogenic differentiation following treatments with TPA and the MEK inhibitor U0126, which respectively activate and inhibit the ERK pathway.

In this paper we attempt to clarify the mechanism of ERK-mediated and ERK-independent growth arrest and myogenic differentiation of embryonal and alveolar rhabdomyosarcoma cell lines, particularly as regards the expression of the cell cycle inhibitor p21WAF1.

Results

p21WAF1expression and growth arrest are induced in both embryonal (RD) and alveolar (RH30) rhabdomyosarcoma cell lines following TPA or MEK/ERK inhibitor (U0126) treatments, whereas myogenic differentiation is induced in RD cells alone. Furthermore, the TPA-mediated post-transcriptional mechanism of p21WAF1-enhanced expression in RD cells is due to activation of the MEK/ERK pathway, as shown by transfections with constitutively active MEK1 or MEK2, which induces p21WAF1expression, and with ERK1 and ERK2 siRNA, which prevents p21WAF1expression. By contrast, U0126-mediated p21WAF1expression is controlled transcriptionally by the p38 pathway. Similarly, myogenin and MyoD expression is induced both by U0126 and TPA and is prevented by p38 inhibition. Although MyoD and myogenin depletion by siRNA prevents U0126-mediated p21WAF1expression, the over-expression of these two transcription factors is insufficient to induce p21WAF1. These data suggest that the transcriptional mechanism of p21WAF1expression in RD cells is rescued when MEK/ERK inhibition relieves the functions of myogenic transcription factors. Notably, the forced expression of p21WAF1in RD cells causes growth arrest and the reversion of anchorage-independent growth.

Conclusion

Our data provide evidence of the key role played by the MEK/ERK pathway in the growth arrest of Rhabdomyosarcoma cells. The results of this study suggest that the targeting of MEK/ERKs to rescue p21WAF1expression and myogenic transcription factor functions leads to the reversal of the Rhabdomyosarcoma phenotype.
Socio economic crisis and mortality. Epidemiological testimony of the financial collapse of Argentina
Authors: Gurfinkel Enrique P , Bozovich Gerardo E , Dabbous Omar , Mautner Branco , Anderson Frederick
Published: December 2005

Background

Natural disasters, war, and terrorist attacks, have been linked to cardiac mortality. We sought to investigate whether a major financial crisis may impact on the medical management and outcomes of acute coronary syndromes.

Methods

We analyzed the Argentine cohort of the international multicenter Global Registry of Acute Coronary Events (GRACE). The primary objective was to estimate if there was an association between the financial crisis period (April 1999 to December 2002) and in- hospital cardiovascular mortality, with the post-crisis period (January 2003 to September 2004) as the referent. Each period was defined according to the evolution of the Gross Domestic Product. We investigated the demographic characteristics, diagnostic and therapeutic procedures, morbidity and mortality.

Results

We analyzed data from 3220 patients, 2246 (69.8%) patients in the crisis period and 974 (30.2%) in the post-crisis frame. The distribution of demographic and clinical baseline characteristics were not significantly different between both periods. During the crisis period the incidence of in-hospital myocardial infarction was higher (6.9% Vs 2.9%; p value < 0.0001), as well as congestive heart failure (16% Vs 11%; p value < 0.0001). Time to intervention with angioplasty was longer during the crisis, especially among public sites (median 190 min Vs 27 min). The incidence proportion of mortality during hospitalization was 6.2% Vs 5.1% after crisis. The crude OR for mortality was 1.2 (95% C.I. 0.87, 1.7). The odds for mortality were higher among private institutions {1.9 (95% C.I. 0.9, 3.8)} than for public centers {1.2 (95% C.I. 0.83, 1.79)}. We did not observe a significant interaction between type of hospital and crisis.

Conclusion

Our findings suggest that the financial crisis may have had a negative impact on cardiovascular mortality during hospitalization, and higher incidence of medical complications.
JC virus meningitis in a patient with systemic lupus erythematosus
Authors: Viallard J-F , Ellie E , Lazaro E , Lafon M-E , Pellegrin J-L
Published: December 2005

The human neurotropic JC virus (JCV) is most commonly acquired during childhood, and, because no clinical illness has been associated with primary infection, is presumed to be asymptomatic. In the immunocompromised host, JCV is responsible for progressive multifocal leukoencephalopathy (PML). We describe a patient with longstanding systemic lupus erythematosus who presented with acute meningitis without encephalitis or PML. JCV was the only pathogen found in the cerebrospinal fluid suggesting a primary infection or symptomatic reactivation. Our observation demonstrates the expanding clinical importance of JCV in autoimmune diseases, and diagnostic tests for JCV should be included in the investigative work-up for meningitis or encephalitis in these patients.
Streynsham Master's office: accounting for collectivity, order and authority in 17th-century India
Authors: Ogborn Miles
Published: December 2005

This paper examines the uses of writing in early modern global trade in order to argue for the constitutive role of inscription practices in the making of the social and spatial relations of mercantile capitalism. At the heart of this is a detailed study of the reform of the accounting and bookkeeping practices of the English East India Company at Fort St George carried out by Streynsham Master (1640–1724) in the late 17th century. This is used to show that the collective decision-making, social and moral order, and relationships of respect upon which the Company relied were constructed in and through the factory's consultation books, accountancy ledgers and the letters sent between England and India. This paperwork was part of the making of institutional structures and spaces which worked through a series of divisions between ‘public’ and ‘private’, and which made the ‘logic’ of mercantile capital evident to the Company's servants.
From beyond: H. P. Lovecraft and the place of horror
Authors: Kneale James
Published: December 2005

The work of the American horror writer H. P. Lovecraft offers a valuable opportunity to study the representation of space in literature, but while Lovecraft's biography provides a useful way of making sense of his horror fictions, it also risks obscuring the importance of his represented spaces. Many of these impossible spaces mark a threshold between the known and unknown, and the paper argues that an attention to narrative demonstrates that these thresholds constitute the fulcrum about which his plots move. The work of Mikhail Bakhtin also suggests that Lovecraft's belief that ‘change is the enemy of everything really worth cherishing’ explains why these thresholds are represented as threats rather than progressive engagements with social space.
‘You cannot shake that shimmie here’: producing mobility on the dance floor
Authors: Cresswell Tim
Published: December 2005

This paper examines the regulation of ballroom dancing in England in the first four decades of the 20th century. It demonstrates how various forms of dance considered to be ‘American’, particularly the ‘shimmy’, were labelled as degenerate and threatening, and how the newly formed Imperial Society for Teachers of Dancing and the dance master and band leader Victor Silvester sought to produce a thoroughly regulated and encoded ‘English’ style of ballroom dancing. The paper charts the various strategies of representation and standardization that were used to enact this regulation of corporeal mobility. Theoretically the paper argues for an interpretive approach to bodily movement that considers bodily movement in the context of wider contexts of cultural geographies of mobility. In so doing it contributes to a growing body of work on the politics of mobility in the modern West and, particularly, the cultural politics of dance.
‘A new look at the English landscape’: landscape architecture, movement and the aesthetics of motorways in early postwar Britain
Authors: Merriman Peter
Published: December 2005

In the past decade or so geographers have been arguing for more performative, practice-oriented and non-representational accounts of the ways in which people encounter, move through and inhabit landscapes, spaces and places. In this paper I argue that these theoretical concerns should also prompt geographers to explore the fairly long history of critical commentaries and aesthetic interventions by writers, artists, film-makers and landscape practitioners who have shown a sensibility to movement and embodied practices in the landscape. The paper then examines how landscape architects focused their attention on the movements, speed and visual perspective of vehicle drivers in their arguments for the landscaping and design of motorways in early postwar Britain. During the 1940s the Institute of Landscape Architects pushed for the involvement of their members in the landscaping and planting of all future roads, and prominent landscape architects criticized the tendency of local authorities and organizations such as the Roads Beautifying Association to plant ornamental trees and shrubs which would interrupt the flow of the landscape and distract drivers travelling at speed. Landscape architects such as Brenda Colvin, Sylvia Crowe and Geoffrey Jellicoe argued for a focus on simplicity, flow and the visual perspective of drivers, and the government's Advisory Committee on the Landscape Treatment of Trunk Roads applied similar criticisms to the work of Sir Owen Williams and Partners in designing and landscaping the earliest sections of Britain's first major motorway, the London to Yorkshire Motorway or M1. The paper examines how landscape architects pushed for a functional modernism to be constructed around the movements and speed of motorists, and it concludes by discussing how an admiration for foreign motorways was tempered by calls for a British motorway modernism reworked in regional and local settings.
A geography of big things
Authors: Jacobs Jane M.
Published: December 2005

This paper sketches some conceptual tools by which cultural geographers might advance geographies of architecture. It does so by thinking specifically about one architectural form: the modernist residential highrise, which is the ‘big thing’ of this paper. The paper draws on recent developments in material semiotics in order to interrogate features often uniquely associated with the highrise, such as its global reach, uniformity, and scale. The paper first rethinks how cultural geography has traditionally explained the movement of built forms, explicitly turning from diffusionist accounts to the notion of translation. It then offers a reconsideration of the way geographers might think about scale in relation to a ‘big’ and ‘global’ thing like the modernist highrise, arguing that scale is produced relationally and in specific contexts. Finally, it offers a template for cultural geographical scholarship which takes seriously the technical work entailed in things, like a highrise, materialising or de-materializing. It does so by way of two illustrative stories: one about the productive social science of highrise suicides in Singapore; the other about the destructive role of the inquiry into collapse of Ronan point in the UK.
FGFR-1 signaling is involved in spermiogenesis and sperm capacitation
Authors: Cotton Leanne , Gibbs Gerard M. , Sanchez-Partida L. Gabriel , Morrison John R. , de Kretser David M. , O'Bryan Moira K.
Published: December 2005

Cloning of the fibroblast growth factor receptor (FGFR) adaptor Snt-2 cDNA and the identification of FGFR-1 protein in association with sperm tails, suggested that FGFR-1 signaling was involved in either sperm tail development or function. This hypothesis was tested by the creation of transgenic mice that specifically expressed a dominant-negative variant of FGFR-1 in male haploid germ cells. Mating of transgenic mice showed a significant reduction in pups per litter compared with wild-type littermates. Further analysis demonstrated that this subfertility was driven by a combination of reduced daily sperm output and a severely compromised ability of those sperm that were produced to undergo capacitation prior to fertilization. An analysis of key signal transduction proteins indicated that FGFR-1 is functional on wild-type sperm and probably signals via the phosphatidylinositol 3-kinase pathway. FGFR-1 activation also resulted in the downstream suppression of mitogen activated protein kinase signaling. These data demonstrate the FGFR-1 is required for quantitatively and qualitatively normal spermatogenesis and has a key role in the regulation of the global tyrosine phosphorylation events associated with sperm capacitation.
Cell adhesion regulates Ser/Thr phosphorylation and proteasomal degradation of HEF1
Authors: Zheng Mingzhe , McKeown-Longo Paula J.
Published: December 2005

Human enhancer of filamentation 1 (HEF1), a multifunctional docking protein of the Cas family, participates in integrin and growth factor signaling pathways that regulate global cellular processes including growth, motility and apoptosis. HEF1 consists of two isoforms, p105 and p115, the larger molecular weight form resulting from Ser/Thr phosphorylation of p105HEF1. The molecular mechanisms that regulate the interconversion of the two HEF1 species as well as the function of HEF1 Ser/Thr phosphorylation are unknown. Our study reveals that cell adhesion and detachment regulate the interconversion of the two HEF1 isoforms. Experiments using various inhibitors of cytoskeletal organization indicated that disruption of actin microfilaments but not intermediate filaments or microtubules resulted in a complete conversion of p115HEF1 to p105HEF1. The conversion of p115HEF1 to p105HEF1 was prevented by inhibition of protein phosphatase 2A (PP2A), suggesting that cytoskeletal regulation of PP2A activity controlled the dephosphorylation of p115HEF1. Degradation of endogenous HEF1 was dependent on proteasomes with the p115 species of HEF1 being preferentially targeted for turnover. Dephosphorylation of HEF1 by suspending cells or disrupting actin filaments protected HEF1 from degradation. These results suggest that the adhesion-dependent actin organization regulates proteasomal turnover of HEF1 through the activity of PP2A.
β2-chimaerin provides a diacylglycerol-dependent mechanism for regulation of adhesion and chemotaxis of T cells
Authors: Siliceo María , García-Bernal David , Carrasco Silvia , Díaz-Flores Ernesto , Leskow Federico C. , Teixidó Joaquín , Kazanietz Marcelo G. , Mérida Isabel
Published: December 2005

The small GTPase Rac contributes to regulation of cytoskeletal rearrangement during chemokine-induced lymphocyte adhesion and migration in a multi-step process that is very precisely coordinated. Chimaerins are Rac1-specific GTPase-activating proteins of unknown biological function, which have a canonical diacylglycerol C1-binding domain. Here we demonstrate endogenous expression of β2-chimaerin in T lymphocytes and study the functional role of this protein in phorbol ester and chemokine (CXCL12)-regulated T-cell responses. We used green fluorescent protein-tagged β2-chimaerin and phorbol ester stimulation to investigate changes in protein localization in living lymphocytes. Our results demonstrate that active Rac cooperates with C1-dependent phorbol ester binding to induce sustained GFP-β2-chimaerin localization to the membrane. Subcellular distribution of GFP β2-chimaerin in living cells showed no major changes following CXCL12 stimulation. Nonetheless Rac1-GTP levels were severely inhibited in GFP-β2-chimaerin-expressing cells, which displayed reduced CXCL12-induced integrin-dependent adhesion and spreading. This effect was dependent on chimaerin GTPase-activating protein function and required diacylglycerol generation. Whereas β2-chimaerin overexpression decreased static adhesion, it enhanced CXCL12-dependent migration via receptor-dependent diacylglycerol production. These studies demonstrate that β2-chimaerin provides a novel, diacylglycerol-dependent mechanism for Rac regulation in T cells and suggest a functional role for this protein in Rac-mediated cytoskeletal remodeling.
ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice
Authors: Huang Guojin , Yao Jian , Zeng Weizhong , Mizuno Yusuke , Kamm Kristine E. , Stull James T. , Harding Heather P. , Ron David , Muallem Shmuel
Published: December 2005

Disruption of protein synthesis and folding results in ER stress, which is associated with the pathophysiology of diverse diseases affecting secretory and muscle cells. Cells are protected against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2α to attenuate protein synthesis. PERK-/- cells are unable to modulate ER protein load and experience high levels of ER stress. In addition to its role in protein synthesis, the ER also orchestrates many signaling events essential for cell survival, prominent among which is Ca2+ signaling. It is not known, however, whether there is a relationship between ER stress and the function of the Ca2+-signaling pathway in muscle and non-muscle cells. To directly address this question we characterized Ca2+ signaling in the secretory pancreatic and parotid acinar cells and in urinary bladder smooth muscle (UBSM) cells obtained from PERK-/- and wild-type mice. Deletion of PERK that results in high levels of ER stress, and distention and fragmentation of the ER slowed the rate of agonist-mediated Ca2+ release from the ER and reduced Ca2+-induced Ca2+ release, although IP3 production, localization of the IP3 receptors, IP3-mediated Ca2+ release, Cav1.2 current and RyRs activity remained unaltered. On the other hand, ER stress disrupted the integrity of the Ca2+-signaling complexes in both secretory and UBSM cells, as revealed by markedly reduced co-immunoprecipitation of plasma membrane- and ER-resident Ca2+-signaling proteins. These findings establish a relationship between the unfolding protein response, ER stress and Ca2+ signaling and highlight the importance of communication within the terminal ER-plasma membrane microdomain for propagation of the Ca2+ signal from the plasma membrane into the cell.
Take-off and landing forces in jumping frogs
Authors: Nauwelaerts Sandra , Aerts Peter
Published: December 2005

Anurans use a saltatorial (jumping) mode of locomotion. A jumping cycle can be divided into four subphases: propulsion, flight, landing and recovery. We studied the landing phase during locomotion in Rana esculenta by measuring the ground reaction forces during propulsion and landing over a range of distances. Landing performance affects locomotor ability in jumping frogs. Landing and recovery together take up one third of the locomotor cycle. Peak landing forces are on average almost three times larger than propulsive forces. The forelimbs appear to be fully extended when they make contact with the substrate and absorb the first impact peak. The height of this peak varies depending on arm positioning and jumping distance. Since the stiffness of the arms stays constant over the full jumping range, it is possible that this is a limiting factor in the ability of the forelimbs to work as dampers. A spring-dashpot model is used to model the effect of arm angle at touch down. Damping during landing is performed by placing the forelimbs at an optimal angle to cancel frictional forces effectively.