bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Elastic Constants of Nanohoneycomb Structures
Authors: Ji Hoon Jeon  , Hwang Woonbong , Lee Kun-Hong
Published: May 2009

Five engineering constants of transversely isotropic nanohoneycomb material are obtained, using one tensile test, two bending tests, and two indentation tests. The advantage is that all these tests can be carried out using only simple beam shape specimens. In all but the tensile test, a desired material constant is to be extracted from mixed materials constants. A disadvantage is that the deviation of the desired material constants are increased by the deviation of other related material constants. This is the first attempt to measure mechanical properties of microscopic specimens of brittle transversely isotropic material. It is intended to lay the foundation for easy and simple measurement of complex material constants of microscopic specimens.
Inverse Micromechanical Models for Compressive Strength of Unidirectional Composites
Authors: Mishra Ashish , Naik N.K.
Published: May 2009

Compressive strength of composites is an important engineering requirement. Experimental determination of compressive strength of composites is very much time consuming and error prone. At present, there are some micromechanical models available in the literature to predict the compressive strength of unidirectional composites. But these models require fiber and resin mechanical properties as input. Resin mechanical properties can be obtained experimentally. But there are no standard test techniques for the evaluation of mechanical properties of fibers. In this study, an analytical method is presented for the evaluation of elastic properties of transversely isotropic fibers. Starting with experimentally obtained compressive strengths of typical unidirectional composites and inverse micromechanical models, elastic properties of the transversely isotropic fiber are obtained. This approach gives current elastic properties of the fibers, and not the virgin properties. Further, starting with the current fiber and resin elastic properties, compressive strength of unidirectional composite is determined using micromechanical models for different fiber volume fractions.
Effect of Temperature on Mode I Interlaminar Fracture of IM7/PETI-5 and IM7/977-2 Laminates
Authors: Oliver Mark S. , Johnson W. Steven
Published: May 2009

The mode I critical strain energy release rates, GIC, of two polymer matrix composites were experimentally measured at temperatures ranging from -196°C to 160°C. The two composite materials investigated in this study were IM7/PETI-5 and IM7/977-2. Double cantilever beam specimens were manufactured with a °[0°7/ ± 3°/0°7] lay-up. The experimental results showed that GI had a strong dependence on temperature above 25°C and minimal dependence on temperature below 25°C. In addition, it was found that IM7/PETI-5 was significantly tougher than IM7/977-2 at all the temperatures investigated. These materials can be considered suitable, in the future, for manufacturing cryogenic fuel tanks in space applications; therefore, understanding critical composite properties such as the interlaminar toughness at such temperatures is very important.
Arenas, Arena Architecture and the Impact on Location Desirability: The Case of `Olympic Arenas' in Prenzlauer Berg, Berlin
Authors: Ahlfeldt Gabriel , Maennig Wolfgang
Published: May 2009

This paper investigates impacts of three multifunctional sports arenas situated in Berlin-Prenzlauer Berg, Germany, employing highly disaggregated data on land values. The three arenas, their architecture and location within the city were explicitly designed to contribute to revitalisation of their economically deprived neighbourhoods. A difference-in-differences approach is employed to check for structural breaks in development of land values within areas of potential impact. The results suggest that arenas emanate positive externalities that improve location desirability in their neighbourhoods. However, evidence also supports concerns that the negative external effects of arenas may adversely affect neighbourhoods, when not addressed appropriately during planning.
Economic Migration from the EU 'A8' Accession Countries and the Impact on Low-demand Housing Areas: Opportunity or Threat for Housing Market Renewal Pathfinder Programmes in England?
Authors: Pemberton Simon
Published: May 2009

Since EU enlargement in 2004, there has been a substantial influx of economic migrants to the UK from the `A8' accession countries. A significant number have moved into Housing Market Renewal Pathfinder areas, which are focused on reshaping failing housing markets. Through case study analysis, the degree to which such movement is beneficial—through stabilising areas of low demand and improving community cohesion—or problematic, given the increased demands on local services, is discussed. The research indicates that migrants are positively impacting upon such areas by increasing demand for private rented and owner-occupied housing, as well as having skills and qualifications that are supportive of achieving regional employment targets. However, the nature of such movements suggests that a review of HMR policy may be necessary, particularly in terms of how initiatives can respond to the needs and housing aspirations of those residents at most risk of social exclusion.
Sprawl or Reagglomeration? The Dynamics of Employment Deconcentration and Industrial Transformation in Greater Paris
Authors: Gilli Frederic
Published: May 2009

From 1975 to 1999, employment in the Paris metropolitan area became more and more decentralised. The losses from central areas were divided equally between sprawl and peripheral clusters. Parallel to the deconcentration of jobs, the growth of a services-oriented economy has led to an increase in sectoral concentration. However, there is no clear evidence of a vertical spatial disintegration, because at the same time the economy of all places has tended to diversify. One explanation might be that sprawl relies both on endogenous job creation and on job relocation: relocations tend to increase the specialisation of the clusters while endogenous growth is more diverse thanks to the importance of domestic activities.
Immigrant Settlement Structures in Germany: General Patterns and Urban Levels of Concentration of Major Groups
Authors: Schönwälder Karen , Söhn Janina
Published: May 2009

This article investigates the settlement structures of foreigners and, specifically, of Turks, ex-Yugoslavs, Italians, Greeks and ex-Soviets in Germany. The main data source is the as yet unexploited dataset of the Inner-city Spatial Observatory, complemented by data from the 2005 sample census and city statistics. Immigrant settlement is shown to be widely dispersed across west German cities. Within cities, ethnic neighbourhoods are rare. Immigrants typically live in multi-ethnic environments. Although differences exist between national groups, the level of ethnic residential concentration is relatively low in Germany. Hypotheses on the reasons for these findings are developed, focusing on the historical circumstances of migration, the structure of the German housing market, immigrant-specific state intervention as well as ethnic group differences regarding financial resources, discrimination and ethnic preferences.
Development Configurations and Planning Negotiations: A Case of Fringe Development in Sydney, Australia
Authors: Ruming Kristian James
Published: May 2009

This paper explores how formal and informal institutional arrangements are mobilised in unique ways to secure development approval on Sydney's fringe. The institutional configuration mobilised to secure approval rests on the identity and history of the developer and their project managers and their relations with state and development actors. This paper explores the differential enrolment of formal and informal institutions by those who principally operate within the area (local) and by those who have moved into the area from other regions (foreign). It becomes clear that local development actors are more likely to mobilise informal arrangements to secure approval, while foreign actors are more likely to use formal arrangements. However, this picture is complicated given that some foreign actors pursue local consultants in an effort to utilise existing development relations for their own purpose, while some local consultants avoid certain foreign developers for fear that existing relations will be damaged.
Displacement and the New Spaces for Informal Trade in the Latin American City Centre
Authors: Bromley Rosemary D.F. , Mackie Peter K.
Published: May 2009

Using evidence from Cusco, Peru, the paper examines the effects of the planned displacement of informal traders from city-centre streets. Although more than 3500 traders were relocated to new off-centre markets, the research identifies the emergence of `unplanned' alternative city-centre locations for informal trade, especially the new courtyard markets. The municipal-led changes, influenced strongly by concerns to enhance tourism, reveal a process which displays many of the hallmarks of gentrification. Lower-class traders were displaced from city-centre streets for the benefit of middle-class tourists and local people. There was also gentrification of the trading activity itself: by manipulating stall allocation and pricing structures to exclude the poorest traders from the new higher-quality municipal markets. The changing pattern of informal trading can be viewed as an unconventional `barometer' of the progress of policy-led gentrification, applicable to other cities in the developing world.
Making Diabetes Education Accessible for People With Visual Impairment
Authors: Williams Ann S.
Published: May 2009

Purpose

The purpose of this study was to identify changes needed to make the diabetes education materials and programs of the Diabetes Association of Greater Cleveland (DAGC) accessible for people who have visual impairment and diabetes (PVID).

Methods

Using the principles and techniques of participatory action research (PAR), 5 PVID and 4 staff members of a local diabetes association met once a month for a year to plan, implement, and evaluate progress toward full accessibility of all diabetes education materials and programs. The researcher served as facilitator.

Results

Four “transformational moments” are presented through which the PAR process enabled PVID and diabetes professionals to learn to understand and trust each other. Changes made to increase accessibility included production of 2 recordings for providing access to print information about diabetes; planning public education program publicity and locations for access; development of guidelines to help speakers make their diabetes education presentations accessible for people who cannot see slides and gestures; and presentation of an inservice for the entire staff of the diabetes association, including information about how they live with visual impairment, and common courtesies that make communication with PVID more effective.

Conclusions

Diabetes education programs should include planning for full accessibility for PVID. Diabetes organizations should publish teaching materials in accessible format.
The Effect of Abduction and Rotation on Footprint Contact for Single-Row, Double-Row, and Modified Double-Row Rotator Cuff Repair Techniques
Authors: Park Maxwell C. , Pirolo Joseph M. , Park Chong J. , Tibone James E. , McGarry Michelle H. , Lee Thay Q.
Published: May 2009

Background

An abduction pillow and abduction and rotation exercises are commonly used after rotator cuff repair. The effect of glenohumeral abduction and rotation on footprint contact has not been elucidated.

Hypothesis

Abduction will decrease tendon-to-bone contact for all repairs. A modified double-row repair will maintain footprint contact more effectively at each position of humeral abduction and rotation than double- or single-row repairs.

Study Design

Controlled laboratory study.

Methods

In 6 fresh-frozen human shoulders, a modified double-row supraspinatus tendon repair was performed; a suture limb from each of 2 medial anchors was bridged over the tendon and fixed laterally. Double- and single-row repairs were performed sequentially; a total of 3 repairs were tested. For all repairs, a Tekscan pressure sensor was fixed at the tendon-footprint interface. The tendon was loaded with 30 N. The shoulders were tested at 0°, 30°, and 60° of abduction with 0° of rotation. For both dual-row repairs, 5 rotation positions were tested.

Results

The greatest contact areas at neutral rotation were achieved at 0° of abduction for the modified double-row, double-row, and single-row repairs (151.3 ± 10.7 mm2, 80.7 ± 30.0 mm2, and 61.3 ± 26.1 mm2, respectively), with values decreasing as abduction increased. Each repair was significantly different from one another at each abduction angle (P <. 05), except between single-and double-row repairs at 0° of abduction. Mean interface pressure exerted over the footprint was greater for the modified double-row technique than for the other techniques at each abduction angle (P <. 05). With respect to rotation, the modified double-row repair had significantly more footprint contact than did the double-row repair at each position tested (P <. 05).

Conclusion

For a given repair, increasing abduction at neutral rotation reduced footprint contact. Internal rotation to 60° provided among the highest contact measurements. The modified double-row technique provided the most contact.

Clinical Relevance

Results are consistent with the practice of immobilizing the shoulder with 30° or less of abduction and up to 60° of internal rotation to optimize footprint contact. A dual-row repair may maximize contact when initiating rehabilitation that involves abduction and rotation.
Tendon Disorders of the Foot and Ankle, Part 2
Authors: Heckman Daniel S. , Gluck George S. , Parekh Selene G.
Published: May 2009

Disorders of the Achilles tendon include both acute and chronic ruptures as well as a spectrum of chronic overuse injuries involving inflammatory and degenerative changes within the tendon and surrounding tissues. These injuries are relatively common in athletes as well as among the general population. There is no consensus on the optimal treatment of Achilles tendon disorders. The goals of this review are to develop a current understanding of the anatomy and diagnostic evaluation of the Achilles tendon, and to present current treatment options and the authors’ preferred surgical techniques for operative management of Achilles tendon disorders.
Development and Application of Smoke Leakage Test Apparatus
Authors: Chuang Ying-Ji , Luan Chung-Pi , Lin Ching-Yuan , Chen Po-Hung
Published: May 2009

The purpose of this study is to establish a CNS 15038 conforming apparatus for smoke leakage testing. The maximum test size accommodated by its test chamber is 3 m(H) × 3 m(W). The test apparatus is capable of controlling temperature and pressure. The test chamber wall, fan, and air duct are enclosed by sandwich construction (steel plate + rock wool + steel plate) and filled with heat resistant materials, which reduces the leakage rate of the apparatus to 1 m3/h. Three circular openings with different areas are used in this study for the basic volumetric airflow rate test. The apparatus proves to be capable of accurately measuring the volumetric airflow rate for a range of opening areas. The measurement is also made for wooden doors. The results of the study show that the volumetric airflow rate decreases gradually when the temperature increases, but as the temperature reaches 150°C, the volumetric airflow rate for wooden doors starts to increase. The test apparatus can be used for measuring the volumetric airflow rate for various gaps or openings. The design of this apparatus also provides an example for establishing other leakage test apparatus in the future.
Thermal Decomposition Behavior of the Flame Retardant Melamine in Slabstock Flexible Polyurethane Foams
Authors: König A. , Fehrenbacher U. , Kroke E. , Hirth T.
Published: May 2009

Due to their low density, high surface-to-mass ratio, high air permeability and open cell structure, slabstock polyurethane foams ignite easily and have a high burning velocity. In this study, the decomposition behavior of melamine in both an inert and an oxygen atmosphere has been investigated. TGA/DSC and EGA-IR experiments revealed the decomposition steps and products in inert and oxygen atmospheres, respectively. Cone calorimeter, NIR-flame characterization and small-scale burner test results showed that the excellent working mechanism of melamine as a flame retardant mainly depends on the formation of an effective closed char layer, which may involve condensation of melamine to form melam, melem, and related products as well as reactions of the amino and isocyanato groups forming urea derivatives, and the sublimation of melamine at the exact temperature at which TDI release occurs.
Studies of the Action of Silicone at the Interphase on the Flame Retardant System of EBA Copolymer-chalk
Authors: Nianhua Huang  , Jianqi Wang
Published: May 2009

Mechanistic study on the system has been performed with the aid of XPS in combination with other appraisal techniques, like TGA/LOI/CONE. It follows that remarkable enhancement of silicon-containing species at the surface region in the course of the combustion appear to play the crucial role for the protective barrier.
Flow Structure Downstream of a Confined Buoyant Round Jet in Cross Flow with Relevance to Tunnel Fires
Authors: Michaux Ghislain , Vauquelin Olivier
Published: May 2009

The flow structure downstream of a confined buoyant round jet in cross flow discharging into a channel is investigated. Experimental visualizations in the rectangular channel cross-section revealed that the interface between the upper layer of light gas and the lower clean air layer is distorted, appearing in the form of `hollows' and `bulges.' Numerical simulations show that these flow features are due to vorticity transfers from the upper to the lower part of the channel. Applied to the tunnel fire issue, this study contributes to the understanding of the impact of a longitudinal ventilation on a fire plume in a tunnel that can affect the smoke natural stratification.
“If We're Proud of Freud . . .”
Authors: Shore Marci
Published: May 2009

This essay examines the vexed question of the relationship between Jews and communism. Drawing largely on archival material, I examine the experiences of several Polish-Jewish communists before, during and after the Second World War. I argue that “Judeo-Bolshevism” is perhaps best understood neither as a antisemitic stereotype or as a sociologically (over)determined proclivity but rather as biography, as epic human drama. A Freudian motif—in particular Oedipal rebellion—frames the essay, which begins and ends with the children and grandchildren of “Judeo-Bolshevism.”
Contested Constitutions
Authors: de Raadt Jasper
Published: May 2009

What were the effects of constitution-making procedures on the acceptance of the new “rules of the political game” in postcommunist Central Europe? This article sets out to scrutinise the increasingly popular claim among politicians and scholars of democratisation that inclusiveness and popular involvement in constitution-making processes enhance a constitution's legitimacy. The concept of constitutional conflict, referring to political contestation over the interpretation and application of constitutional relations among state institutions, is introduced as a way to assess constitutional acceptance among politicians. The investigation concentrates on constitutional conflict patterns during the five years following constitution-making in seven Central European countries: Bulgaria, the Czech Republic, Estonia, Hungary, Poland, Romania, and Slovakia. Constitution-making procedures varied substantially among the cases, as did the intensity and timing of constitutional conflict. The article finds that differences in constitution-making procedures do not necessarily determine the legitimacy of constitutions among political elites. Instead, ambiguity on the allocation of formal competencies among political actors and increasing political tensions between pro-reform and anti-reform parties during the early 1990s proved to be more important triggers of constitutional conflict. Accordingly, studies on constitution-making and democratisation should focus less on procedural aspects and take into account the fuzziness of important constitutional provisions and the extent to which constitutions can survive periods of intense political polarisation.
A Comparison of Artificial Neural Networks and Multiple Regression in the Context of Research on Personality and Work Performance
Authors: Minbashian Amirali , Bright Jim E. H. , Bird Kevin D.
Published: May 2009

The current study provides an exposition of artificial neural network (ANN) methodology in the context of research on personality and work performance. We demonstrate some of the benefits and limitations of this methodology relative to multiple regression (MR) for conducting exploratory research. Using three data sets that each contained personality scores and measures of work performance, we compared the predictive accuracy of ANNs to both simple and complex MR equations. Across the three data sets, the neural networks performed as well or better than the MR equations on a relational measure of predictive accuracy but performed no better than the simplest regression equations on an absolute measure of predictive accuracy. Furthermore, through a combination of sensitivity analysis and graphical representations, we were able to identify the specific configural and nonlinear relationships that accounted for the superior performance of the neural networks with respect to the relational measure. The implications of the findings for researchers interested in applying ANNs to study organizational behavior are discussed.
Investigation of microstructure, surface and subsurface characteristics in titanium alloy friction stir welds of varied thicknesses
Authors: Edwards P. D. , Ramulu M.
Published: May 2009

Friction stir welding of titanium alloy (Ti–6Al–4V) was demonstrated on 3, 6, 9 and 12 mm thickness square groove butt joints. Complete microstructural and microhardness evaluations were conducted in addition to surface and subsurface examinations for each case. The 3 mm welds exhibited an extremely fine grained microstructure with evidence of processing temperatures below the beta transus temperature of the alloy. The 6, 9 and 12 mm samples possessed larger grains formed by a slower cooling rate from above the beta transus temperatures. The thick section weld exhibited a nearly uniform microhardness, while the thinner welds showed a slight, 6%, increase in hardness compared with the parent material.
Influence of welding parameters on distribution of wire feeding elements in CO2 laser GMA hybrid welding
Authors: Zhao L. , Sugino T. , Arakane G. , Tsukamoto S.
Published: May 2009

The effect of welding parameters on the distribution of wire feeding elements has been investigated during CO2 laser and pulsed gas metal arc hybrid welding process. The molten metal flow on the pool surface and inside of the samples was observed by a high speed video camera and an in situ X-ray transmission imaging system respectively. The results indicate that the fluid flow towards the inside of keyhole, namely inward flow, improves the homogeneity of weld metal. The distribution of alloying elements is more homogeneous in leading laser compared with leading arc, since both of the drag force of the plasma jet and momentum of droplet promote the inward flow in leading laser. Almost homogeneous distribution of alloying elements can be attained if the oxygen content in the shielding gas is more than 2%, since the Marangoni flow direction changes from outward to inward with increasing the oxygen content.
Noninvasive in vivo imaging of CD4 cells in simian-human immunodeficiency virus (SHIV)–infected nonhuman primates
Authors: Di Mascio Michele , Paik Chang H. , Carrasquillo Jorge A. , Maeng Jin-Soo , Jang Beom-Su , Shin In Soo , Srinivasula Sharat , Byrum Russ , Neria Achilles , Kopp William , Catalfamo Marta , Nishimura Yoshiaki , Reimann Keith , Martin Malcolm , Lane H. Clifford
Published: May 2009

Since the earliest days of the HIV epidemic, the number of CD4+ T cells per unit volume of blood has been recognized as a major prognostic factor for the development of AIDS in persons with HIV infection. It has also been generally accepted that approximately 2% of total body lymphocytes circulate in the blood. In the present study, we have used a nondepleting humanized anti-CD4 monoclonal antibody labeled with the gamma emitter indium-111 to visualize the CD4+ T-cell pool in vivo in nonhuman primates with simian HIV infection. A strong correlation was noted between radiotracer uptake in spleen, tonsil, axillary lymph nodes, and peripheral blood CD4 T-cell counts (ρ = 0.75, 0.93, and 0.85, respectively, P < .005). The relationship between radiotracer retention in lymphoid tissues and CD4+ T-cell counts in the circulation was governed by an exponential law. These data provide an estimate for the total number of lymphocytes in the body as being between 1.9 and 2.9 × 1012 and suggest that the partition between peripheral blood and lymphoid tissue is between 0.3% and 0.5%.
EBV Zta protein induces the expression of interleukin-13, promoting the proliferation of EBV-infected B cells and lymphoblastoid cell lines
Authors: Tsai Shu-Chun , Lin Sue-Jane , Chen Po-Wen , Luo Wen-Yi , Yeh Te-Huei , Wang Hsei-Wei , Chen Chi-Ju , Tsai Ching-Hwa
Published: May 2009

Epstein-Barr virus (EBV) infection can modify the cytokine expression profiles of host cells and determine the fate of those cells. Of note, expression of interleukin-13 (IL-13) may be detected in EBV-associated Hodgkin lymphoma and the natural killer (NK) cells of chronic active EBV-infected patients, but its biologic role and regulatory mechanisms are not understood. Using cytokine antibody arrays, we found that IL-13 production is induced in B cells early during EBV infection. Furthermore, the EBV lytic protein, Zta (also known as the BZLF-1 product), which is a transcriptional activator, was found to induce IL-13 expression following transfection. Mechanistically, induction of IL-13 expression by Zta is mediated directly through its binding to the IL-13 promoter, via a consensus AP-1 binding site. Blockade of IL-13 by antibody neutralization showed that IL-13 is required at an early stage of EBV-induced proliferation and for long-term maintenance of the growth of EBV immortalized lymphoblastoid cell lines (LCLs). Thus, Zta-induced IL-13 production facilitates B-cell proliferation and may contribute to the pathogenesis of EBV-associated lymphoproliferative disorders, such as posttransplantation lymphoproliferative disease (PTLD) and Hodgkin lymphoma.
Increased frequency (12%) of circulating chronic lymphocytic leukemia–like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach
Authors: Nieto Wendy G. , Almeida Julia , Romero Alfonso , Teodosio Cristina , López Antonio , Henriques Ana F. , Sánchez Maria Luz , Jara-Acevedo María , Rasillo Ana , González Marcos , Fernández-Navarro Paulino , Vega Tomás , Orfao Alberto ,   the Primary Health Care Group of Salamanca for the Study of MBL
Published: May 2009

Monoclonal B-cell lymphocytosis (MBL) indicates the presence of less than 5 × 109/L circulating monoclonal B cells in otherwise healthy subjects. Recently, it has been reported that circulating chronic lymphocytic leukemia (CLL)–like B cells can be detected using 4- or 5-multicolor flow cytometry in 5% to 7% of adults with normal lymphocyte counts. We investigated the frequency of circulating monoclonal B cells in 608 healthy subjects older than 40 years with normal blood counts, using a highly sensitive 8-color flow cytometry approach and systematic screening for total PB leukocyte count higher than 5 × 106. We show that the frequency of PB monoclonal B cells is markedly higher than previously reported (12% for CLL-like B cells, found at frequencies of 0.17 ± 0.13 × 109 cells/L), the incidence progressively increasing with age. Most cases (62%) showed clonal B-cell levels below the maximum sensitivity of the techniques described by others (< 0.01%), supporting the notion that detection of MBL may largely depend on the sensitivity of the flow cytometry approach used.
PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model
Authors: Zhang Long , Gajewski Thomas F. , Kline Justin
Published: May 2009

Negative regulatory mechanisms within the solid tumor microenvironment inhibit antitumor T-cell function, leading to evasion from immune attack. One inhibitory mechanism is up-regulation of programmed death-ligand 1 (PD-L1) expressed on tumor or stromal cells which binds to programmed death-1 (PD-1) on activated T cells. PD-1/PD-L1 engagement results in diminished antitumor T-cell responses and correlates with poor outcome in murine and human solid cancers. In contrast to available data in solid tumors, little is known regarding involvement of the PD-1/PD-L1 pathway in immune escape by hematopoietic cancers, such as acute myeloid leukemia (AML). To investigate this hypothesis, we used the murine leukemia, C1498. When transferred intravenously, C1498 cells grew progressively and apparently evaded immune destruction. Low levels of PD-L1 expression were found on C1498 cells grown in vitro. However, PD-L1 expression was up-regulated on C1498 cells when grown in vivo. PD-1−/− mice challenged with C1498 cells generated augmented antitumor T-cell responses, showed decreased AML burden in the blood and other organs, and survived significantly longer than did wild-type mice. Similar results were obtained with a PD-L1 blocking antibody. These data suggest the importance of the PD-1/PD-L1 pathway in immune evasion by a hematologic malignancy, providing a rationale for clinical trials targeting this pathway in leukemia patients.
Adult onset lung disease following transient disruption of fetal stretch-induced differentiation
Authors: Hudak Joseph J , Killeen Erin , Chandran Ashok , Cohen J Craig , Larson Janet E
Published: May 2009

One of the mechanisms by which adult disease can arise from a fetal origin is by in utero disruption of organogenesis. These studies were designed to examine respiratory function changes in aging rats following transient disruption of lung growth at 16 days gestation. Fetuses were treated in utero with a replication deficient adenovirus containing the cystic fibrosis conductance transmembrane regulator (CFTR) gene fragment cloned in the anti-sense direction. The in utero-treated rats demonstrated abnormal lung function beginning as early as 30 days of age and the pathology progressed as the animals aged. The pulmonary function abnormalities included decreased static compliance as well as increased conducting airway resistance, tissue damping, and elastance. Pressure volume (PV) curves demonstrated a slower early rise to volume and air trapping at end-expiration. The alterations of pulmonary function correlated with lung structural changes determined by morphometric analysis. These studies demonstrate how transient disruption of lung organogensis by single gene interference can result in progressive change in lung function and structure. They illustrate how an adult onset disease can arise from subtle changes in gene expression during fetal development.
TGF-beta signaling proteins and the Protein Ontology
Authors: Arighi Cecilia N , Liu Hongfang , Natale Darren A , Barker Winona C , Drabkin Harold , Blake Judith A , Smith Barry , Wu Cathy H
Published: May 2009

Background

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or post-translational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO.

Results

PRO is manually curated on the basis of PrePRO, an automatically generated file with content derived from standard protein data sources. Manual curation ensures that the treatment of the protein classes and the internal and external relationships conform to the PRO framework. The current release of PRO is based upon experimental data from mouse and human proteins wherein equivalent protein forms are represented by single terms. In addition to the PRO ontology, the annotation of PRO terms is released as a separate PRO association file, which contains, for each given PRO term, an annotation from the experimentally characterized sub-types as well as the corresponding database identifiers and sequence coordinates. The annotations are added in the form of relationship to other ontologies. Whenever possible, equivalent forms in other species are listed to facilitate cross-species comparison. Splice and allelic variants, gene fusion products and modified protein forms are all represented as entities in the ontology. Therefore, PRO provides for the representation of protein entities and a resource for describing the associated data. This makes PRO useful both for proteomics studies where isoforms and modified forms must be differentiated, and for studies of biological pathways, where representations need to take account of the different ways in which the cascade of events may depend on specific protein modifications.

Conclusion

PRO provides a framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses.
Testis-expressed profilins 3 and 4 show distinct functional characteristics and localize in the acroplaxome-manchette complex in spermatids
Authors: Behnen Martina , Murk Kai , Kursula Petri , Cappallo-Obermann Heike , Rothkegel Martin , Kierszenbaum Abraham L , Kirchhoff Christiane
Published: May 2009

Background

Multiple profilin isoforms exist in mammals; at least four are expressed in the mammalian testis. The testis-specific isoforms profilin-3 (PFN3) and profilin-4 (PFN4) may have specialized roles in spermatogenic cells which are distinct from known functions fulfilled by the "somatic" profilins, profilin-1 (PFN1) and profilin-2 (PFN2).

Results

Ligand interactions and spatial distributions of PFN3 and PFN4 were compared by biochemical, molecular and immunological methods; PFN1 and PFN2 were employed as controls. β-actin, phosphoinositides, poly-L-proline and mDia3, but not VASP, were confirmed as in vitro interaction partners of PFN3. In parallel experiments, PFN4 bound to selected phosphoinositides but not to poly-L-proline, proline-rich proteins, or actin. Immunofluorescence microscopy of PFN3 and PFN4 revealed distinct subcellular locations in differentiating spermatids. Both were associated first with the acroplaxome and later with the transient manchette. Predicted 3D structures indicated that PFN3 has the actin-binding site conserved, but retains only approximately half of the common poly-L-proline binding site. PFN4, in comparison, has lost both, polyproline and actin binding sites completely, which is well in line with the experimental data.

Conclusion

The testis-specific isoform PFN3 showed major hallmarks of the well characterized "somatic" profilin isoforms, albeit with distinct binding affinities. PFN4, on the other hand, did not interact with actin or polyproline in vitro. Rather, it seemed to be specialized for phospholipid binding, possibly providing cellular functions which are distinct from actin dynamics regulation.
Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats
Authors: van Ampting Marleen TJ , Schonewille Arjan J , Vink Carolien , Brummer Robert Jan , Meer Roelof vander , Bovee-Oudenhoven Ingeborg MJ
Published: May 2009

Background

Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation.

Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion) or cystine (glutathione maintenance). Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella
enteritidis (or saline for non-infected controls), Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea.

Results

Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1β. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation.

Conclusion

Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione.
Improving consensus contact prediction via server correlation reduction
Authors: Gao Xin , Bu Dongbo , Xu Jinbo , Li Ming
Published: May 2009

Background

Protein inter-residue contacts play a crucial role in the determination and prediction of protein structures. Previous studies on contact prediction indicate that although template-based consensus methods outperform sequence-based methods on targets with typical templates, such consensus methods perform poorly on new fold targets. However, we find out that even for new fold targets, the models generated by threading programs can contain many true contacts. The challenge is how to identify them.

Results

In this paper, we develop an integer linear programming model for consensus contact prediction. In contrast to the simple majority voting method assuming that all the individual servers are equally important and independent, the newly developed method evaluates their correlation by using maximum likelihood estimation and extracts independent latent servers from them by using principal component analysis. An integer linear programming method is then applied to assign a weight to each latent server to maximize the difference between true contacts and false ones. The proposed method is tested on the CASP7 data set. If the top L/5 predicted contacts are evaluated where L is the protein size, the average accuracy is 73%, which is much higher than that of any previously reported study. Moreover, if only the 15 new fold CASP7 targets are considered, our method achieves an average accuracy of 37%, which is much better than that of the majority voting method, SVM-LOMETS, SVM-SEQ, and SAM-T06. These methods demonstrate an average accuracy of 13.0%, 10.8%, 25.8% and 21.2%, respectively.

Conclusion

Reducing server correlation and optimally combining independent latent servers show a significant improvement over the traditional consensus methods. This approach can hopefully provide a powerful tool for protein structure refinement and prediction use.
A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial
Authors: Meng Wenxia , Dong Yi , Liu Jie , Wang Zhi , Zhong Xiaobo , Chen Ruiyang , Zhou Hongmei , Lin Mei , Jiang Lu , Gao Feng , Xu Tao , Chen Qianming , Zeng Xin
Published: May 2009

Background

Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS) in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox.

Methods

We performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU) were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets.

Results

Amlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6) and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6). No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox.

Conclusions

Amlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients.

Trials registration

Nederlands Trial Register NTR1727.
Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575
Authors: Garcia-Alloza Monica , Subramanian Meenakshi , Thyssen Diana , Borrelli Laura A , Fauq Abdul , Das Pritam , Golde Todd E , Hyman Bradley T , Bacskai Brian J
Published: May 2009

The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg) for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology.
High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors
Authors: Haverty Peter M , Hon Lawrence S , Kaminker Joshua S , Chant John , Zhang Zemin
Published: May 2009

Background

DNA copy number alterations are frequently observed in ovarian cancer, but it remains a challenge to identify the most relevant alterations and the specific causal genes in those regions.

Methods

We obtained high-resolution 500K SNP array data for 52 ovarian tumors and identified the most statistically significant minimal genomic regions with the most prevalent and highest-level copy number alterations (recurrent CNAs). Within a region of recurrent CNA, comparison of expression levels in tumors with a given CNA to tumors lacking that CNA and to whole normal ovary samples was used to select genes with CNA-specific expression patterns. A public expression array data set of laser capture micro-dissected (LCM) non-malignant fallopian tube epithelia and LCM ovarian serous adenocarcinoma was used to evaluate the effect of cell-type mixture biases.

Results

Fourteen recurrent deletions were detected on chromosomes 4, 6, 9, 12, 13, 15, 16, 17, 18, 22 and most prevalently on X and 8. Copy number and expression data suggest several apoptosis mediators as candidate drivers of the 8p deletions. Sixteen recurrent gains were identified on chromosomes 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, and 20, with the most prevalent gains localized to 8q and 3q. Within the 8q amplicon,PVT1, but notMYC, was strongly over-expressed relative to tumors lacking this CNA and showed over-expression relative to normal ovary. Likewise, the cell polarity regulatorsPRKCIandECT2were identified as putative drivers of two distinct amplicons on 3q. Co-occurrence analyses suggested potential synergistic or antagonistic relationships between recurrent CNAs. Genes within regions of recurrent CNA showed an enrichment of Cancer Census genes, particularly when filtered for CNA-specific expression.

Conclusion

These analyses provide detailed views of ovarian cancer genomic changes and highlight the benefits of using multiple reference sample types for the evaluation of CNA-specific expression changes.
Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex
Authors: Wu Long-Jun , Kim Susan S , Li Xiangyao , Zhang Fuxing , Zhuo Min
Published: May 2009

Functional human brain imaging studies have indicated the essential role of cortical regions, such as the anterior cingulate cortex (ACC), in romantic love and sex. However, the neurobiological basis of how the ACC neurons are activated and engaged in sexual attraction remains unknown. Using transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent genec-fos, we found that ACC pyramidal neurons are activated by sexual attraction. The presynaptic glutamate release to the activated neurons is increased and pharmacological inhibition of neuronal activities in the ACC reduced the interest of male mice to female mice. Our results present direct evidence of the critical role of the ACC in sexual attraction, and long-term increases in glutamate mediated excitatory transmission may contribute to sexual attraction between male and female mice.