bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Disparity in Formal Social Control
Authors: Ousey Graham C. , Lee Matthew R.
Published: June 2008

Prior research on racial disparities in arrest rates has been limited by an almost exclusive focus on two explanatory models, an inattention to the mediating processes identified in leading theories, and a relative neglect of nonindex crimes, for which police discretion is greater. This analysis contributes to research on race differences in social control by more comprehensively evaluating mediating factors in the racial threat and benign neglect models and by testing explanatory frameworks that link racial disparities to opportunities for bias that result from residential segregation and variations in police discretionary authority across crime types. Analyses of data from 136 cities reveal two key findings. First, an uneven distribution of Blacks and Whites is associated with higher arrest disparities for drug and weapons arrests, but not with violent or property crime arrest disparities. Second, there is little evidence in support of the venerable racial threat or benign neglect explanatory frameworks.
On Never Reaching the Coast of Utopia
Authors: Elshtain Jean Bethke
Published: June 2008

Elshtain argues that the realist—idealist divide serves no useful heuristic or even polemical purpose. Beginning with Tom Stoppard's acclaimed trilogy, The Coast of Utopia, Elshtain unpacks utopian arguments of recent vintage, showing their distinctive features. She goes on to display the utopistic/idealist `moments' in the work of self-described `realist' E. H. Carr as part of a critical re-examination of Carr's work. The article continues with an appreciative assessment of Martin Wight, concluding that his `idealism' is far more `realistic' than are the arguments of many `realists'. The article's concluding section makes the case for Augustinian realism.
Multinational Military Cooperation and its Challenges: The Case of European Naval Operations in the Wider Mediterranean Area
Authors: Germond Basil
Published: June 2008

In order to cope with current security challenges, such as regional conflicts, humanitarian disasters or terrorist threats, European states in the post-Cold War era make important use of naval forces within a complex multilateral framework. However, the issues relating to European navies have rarely been tackled in the literature on multilateral military cooperation. Therefore this article aims to fill the gap by studying the nature of the European post-Cold War multilateral naval framework, and taking it as a case study to illustrate the current issues facing multinational military cooperation. To do so, the article focuses on the wider Mediterranean region, since most of the security challenges identified by the Europeans are now localized in this area.
PhRMA White Paper on ADME Pharmacogenomics
Authors: Williams J. Andrew , Andersson Tommy , Andersson Tommy B. , Blanchard Rebecca , Behm Martin Otto , Cohen Nadine , Edeki Timi , Franc Monique , Hillgren Kathleen M. , Johnson Keith J. , Katz David A. , Milton Mark N. , Murray Bernard P. , Polli Joseph W. , Ricci Deb , Shipley Lisa A. , Vangala Subrahmanyam , Wrighton Steven A.
Published: June 2008

Pharmacogenomic (PGx) research on the absorption, distribution, metabolism, and excretion (ADME) properties of drugs has begun to have impact for both drug development and utilization. To provide a cross‐industry perspective on the utility of ADME PGx, the Pharmaceutical Research and Manufacturers of America (PhRMA) conducted a survey of major pharmaceutical companies on their PGx practices and applications during 2003–2005. This white paper summarizes and interprets the results of the survey, highlights the contributions and applications of PGx by industrial scientists as reflected by original research publications, and discusses changes in drug labels that improve drug utilization by inclusion of PGx information. In addition, the paper includes a brief review on the clinically relevant genetic variants of drug‐metabolizing enzymes and transporters most relevant to the pharmaceutical industry.
The Effects of Social and Cultural Capital on Student Persistence
Authors: Wells Ryan
Published: June 2008

This study examines the influences of social and cultural capital on persistence from 1st to 2nd year and how these effects differ between community colleges and 4-year institutions. Results show that social and cultural capital have a positive association with student persistence overall but matter less when students begin at a community college.
A simulator for perfusion training
Authors: Turkmen A , Rosinski D , Noyes N
Published: June 2008

In this study, a patient simulator was designed and fabricated to train students to respond to various clinical situations associated with heart-lung bypass machine operation and to respond to changes in patient clinical parameters. The students will use the simulator to gain pre-clinical experience. The training system will initially simulate normal heart-lung bypass conditions. During a training session, the instructor will be able to simulate problems that may happen during a real procedure. Some of these problems are stopping of rotation of one of the roller pump heads, abnormal changes in the vital parameters, such as oxygenation level or biochemical values, high blood pressure, and occlusion in arterial or venous lines. The simulator will train students to respond properly to these situations, hence, allowing them to gain clinical experience without impacting patient safety and the outcome of real life procedures. The simulator can also be used for assessment of the students’ competency levels.
Frequent sampling allows detection of short and rapid surges of exhaled ethane during cardiac surgery
Authors: Stenseth R , Nilsen T , Haaverstad R , Vitale N , Dale O
Published: June 2008

During cardiopulmonary bypass (CPB), hypoperfusion and reperfusion may cause oxidative stress and lipid peroxidation that generates ethane. The aim of this pilot study was to assess the feasibility of frequent sampling of exhaled ethane during cardiac surgery. After approval of the Research Ethics Committee, 10 patients undergoing combined aortic valve and coronary artery bypass surgery were enrolled. Breath samples were drawn in the perioperative period and analyzed by a rapid, sensitive and validated gas-chromatographic method. Increased exhaled ethane was regularly seen following sternotomy, after the start of CPB and after aortic clamp removal, whereas no change was seen after termination of bypass. In one patient, the maximum increase in exhaled ethane was 30-fold. Peak durations lasted only 2–4 min. This study demonstrates that frequent sampling of breath ethane is feasible in a clinical setting, allowing detection of rapid ethane surges of short duration.
The use of the retinal nerve fiber layer thickness measurement in determining the effects of cardiopulmonary bypass procedures on the optic nerve
Authors: Buyukates M , Kargi S , Kandemir O , Aktunc E , Turan SA , Atalay A
Published: June 2008

Background: Our aim was to determine the effects of cardiopulmonary bypass procedures on the optic nerve by retinal nerve fiber layer thickness measurements. Methods: Retinal nerve fiber layer thickness was measured using the GDx Nerve Fiber Analyser, 1 day before the surgery and on postoperative days 1, 5 and 30 in 20 patients undergoing coronary artery bypass grafting surgery. Results: Postoperative mean values for retinal nerve fiber layer thickness, except symmetry on the first day and except symmetry and superior nasal ratio on the fifth day, were statsitically decreased. Only the value for the inferior ratio was significantly lower at the end of the first month. Conclusions: Cardiopulmonary bypass procedures cause a temporary decrease in retinal nerve fiber layer thickness.
Post-cardiotomy circulatory support with the Terumo Baby – Rx tm oxygenator in a newborn
Authors: Picarelli D , Kreutzer CH , Barboza M , Antunez S , Pose G , Touyá G , Liguera L , Abdala D , Echegaray G
Published: June 2008

Some patients with severe post-cardiotomy ventricular dysfunction are unable to be separated from cardiopulmonary bypass (CPB). In this setting, extracorporeal circulatory support (ECS) should be instituted to obtain eventual myocardial recovery. We present a newborn in whom an ECS was established with the oxygenator used for the surgical correction.
Effect of Clay Dispersion on Mechanical, Thermal and Vibration Properties of Glass Fiber-Reinforced Vinyl Ester Composites
Authors: Chandradass J. , Ramesh Kumar M. , Velmurugan R.
Published: June 2008

Glass fiber reinforced vinyl ester polymer composites filled with clay particles were synthesized by a hand lay-up technique with the addition of methy ethyl ketone peroxide (MEKP), cobalt napthalate and benzoyl peroxide. Mechanical and thermal properties of vinyl ester-glass fiber composite and clay particles dispersed vinyl-glass fiber hybrids were investigated in the present work. The hybridization effect of nanoclay dispersion in vinyl ester-fiber composite was discussed. Enhanced mechanical, thermal and vibration properties were observed in nanoclay dispersed composites over vinyl ester-glass fiber composite.
The Effects of CFRP Strips for Improving Shear Capacity of RC Beams
Authors: Tanarslan H. Murat , Ertutar Yildirim , Altin Sinan
Published: June 2008

The method of strengthening concrete structures with carbon fiber-reinforced polymer (CFRP) composites has encountered rapid growth in recent years. The most common way to strengthen structures is in bending. However, there is also a need for strengthening in shear. Therefore, an experimental program was conducted to investigate the effects of CFRP on behavior and ultimate strength of shear deficient (without stirrups) reinforced concrete (RC) beams. Seven identical beams were fabricated and tested in the experimental program. One of the beams was tested in its virgin condition to serve as a reference, while the remaining beams were tested after strengthened by using L-shaped, U-jacketed, side-bonded, and ⊔-jacketed CFRP strips. The type and arrangement of CFRP strips and the anchorage used to fasten the strips to the concrete were the variables of this experimental work. The purpose was to obtain ductile behavior from the shear deficient reinforced concrete beams by using CFRP strips. The test result confirmed that all CFRP arrangements improved the strength and stiffness of the specimens at different levels. Afterwards, experimental results were compared with the analytical approaches to demonstrate the validity of them.
Probabilistic Finite Element Analysis of ASTM D6641 Compression Test for Marine Grade Polymer Matrix Composites
Authors: Nader Jacques W. , Dagher Habib J. , El Chiti Fadi , Lopez-Anido Roberto
Published: June 2008

The variability of compressive mechanical properties of a polymer matrix composite material with woven fabric reinforcement is studied using both experimental work and numerical simulations. Four E-glass/vinyl ester composite plates were fabricated using the vacuum-assisted resin transfer molding (VARTM) by a US Navy contractor. The materials and process selected are representative of marine grade composites typically used by the US Navy. Standard ASTM D6641 coupons were obtained from the plates and the laboratory results were compared with those of a 3D probabilistic finite element analysis (FEA). In the probabilistic FEA model, elastic properties, strength parameters and geometric properties of the woven fabric E-glass/vinyl ester coupons were considered as random fields, and generated using Monte Carlo simulations. The study evaluates the effects of spatial correlation, finite element size, probability distribution functions (PDF) types and failure criteria on statistical strength properties of the [0/90]2sf compression coupons. Comparisons of experimental and probabilistic FEA results provide useful information on how to assign mean, Coefficient of variance (COV) and PDF of material properties to individual finite elements within a mesh. The results are relevant in selecting proper test methods and developing design properties for these composites.
Wood Filler-recycled Polypropylene (WF-RPP) Composite Pallet: Study of Fastening Method
Authors: Khoo T.S. , Ratnam M.M. , Shahnaz S.A.B. , Abdul Khalil H.P.S.
Published: June 2008

Materials handling pallets were developed using wood filler-recycled polypropylene (WF-RPP) composite in our previous work. An important stage in the development of the full-size pallet is the assembly of the various components that make up the pallet. The objective of this work is to find a suitable fastening method, fastener type, and size to assemble the stringer-class pallet made from the composite. The following investigations were carried out: (i) comparative study on the ease of fastening screws with and without pre-drilling, (ii) determination of minimum depth to which pilot holes need to be drilled to enable screws of various sizes (#3 to #10) to penetrate into the composite, (iii) comparison on the ease of fastening the components using different screw types, (iv) determination of the minimum distance between screws and minimum distance of screw from the edge required to assemble the components without cracking, and (v) comparative study on the ease of fastening of composites having different filler loading. The results of the study showed that it is not possible to use wood screws or tapping screws to fasten the various parts of the pallet without pre-drilling. A pilot hole of diameter 2.5 mm and depth more than 6.0 mm was found to be suitable for screws with nominal sizes ranging from gauge #3 (2.515mm) to gauge #8 (4.166mm) to penetrate into the composite without difficulty.
Impact Properties of Kapok Based Unsaturated Polyester Hybrid Composites
Authors: Venkata Reddy G. , Venkata Naidu S. , Shobha Rani T.
Published: June 2008

Natural fabric-based thermoset composites are generally lower in strength performance compared to hybrid composites. However, they have the advantages of design flexibility, cost effectiveness, lack of health-hazard problems and recycling possibilities. Hybridization with some amounts of synthetic fibers makes these natural fabric composites more suitable for technical applications such as automotive interior parts. Kapok fabric is one of the important lignocellulosic plant fabrics and has been used as a reinforcement for hybridizing with glass and sisal fabrics in polyester matrix. This study focused on the performance of impact properties of kapok/ glass and kapok/sisal fabrics reinforced polyester hybrid composites. Results show that hybridization with glass fabric enhanced the performance properties. Similarly, addition of kapok fabric to sisal/ polyester composites enhanced the properties. The effect of alkali treatment of fabrics on impact strength of these composites was studied. Notched Izod impact strength of the hybrid composites exhibited great enhancement (34%). Analysis of fabric distribution in the composite and fracture surface was performed to study the breakage and fracture mechanism of the fabric. Also, we studied the thermal properties of kapok/glass and kapok/sisal fabric reinforced polyester composites.
Effect of Particle Size, Fiber Content and Compatibilizer on the Long-term Water Absorption and Thickness Swelling Behavior of Reed Flour/Polypropylene Composites
Authors: Tajvidi Mehdi , Azad Fattaneh
Published: June 2008

Reed (Phalaris sp.) flour was used to produce natural fiber polypropylene composites and effects of particle size, compatibilizer, and fiber content on the physical properties of the produced composites were evaluated. The particle sizes ranged from 40 mesh to smaller than 100 mesh sizes and fiber contents were 60% and 70% by weight. Composites were made through the extrusion process. Particle size proved to have very significant effects on both water absorption and thickness swelling of the composite formulations. The lowest water absorption and thickness swelling values were obtained at the lower fiber content and smallest particle size. Water diffusion coefficients were also smaller for smaller particle sizes and at lower fiber contents. The effect of compatibilzer was positive in terms of enhancing the dimensional stability of the composites. Composites containing the smallest particle size exhibited different water absorption and thickness swelling behaviors as seen in their considerably longer time required to reach maximum values.
Normative Family Interactions
Authors: Lamborn Susie D. , Moua MyLou
Published: June 2008

Hmong American adolescents' perceptions of their parents were examined using the parenting styles and family ecologies models. Individual interviews of forty 11- to 18-year-old Hmong American teenagers resulted in open-ended and fixed-choice responses. In the open-ended responses, adolescents emphasized themes of parental involvement and depending on the family for support. The theme of depending on the family was more commonly used to describe mothers, whereas respectful relationships was used more frequently to describe fathers. Two emergent themes were the adolescents' views of fathers as hard-working but absent and the adolescents' understanding that parents were preparing them for “the good life.” Using fixed-choice warmth and behavioral control scores, 40% of mothers and 27.5% of fathers were identified as authoritative. The remaining parents showed authoritarian, permissive, or neglectful parenting styles. The older adolescents described relationships with parents that were less close than the descriptions provided by younger adolescents.
Design of Trajectories with Physical Constraints for very Lightweight Single Link Flexible Arms
Authors: Ramos Francisco , Feliu Vicente , Payo Ismael
Published: June 2008

This article deals with feedforward control of very lightweight, flexible robotic arms. In particular, we develop a new, objective method of designing a trajectory that can be used as a modified input, to cancel tip vibrations during robot manoeuvres. This method takes into account the constraints found in real actuators (DC-motors), such as the maximum torque the motor can supply, and also those due to the mechanical limits of the link, like the maximum deflection before reaching the elastic limit of the link. The parameters of the internal control of the actuators are also derived from the design process, achieving the fastest performance possible without saturating the motor. Lastly, we show some experimental results which clearly demonstrate the benefits of the new trajectories by comparing them to a ramp one.
Aeroservoelasticity Analysis Method Based on an Error Analytical Form Applied on a Business Aircraft
Authors: Biskri D.E. , Botez R.M. , Stathopoulos N. , Thérien S. , Dickinson M. , Rathe A.
Published: June 2008

Aeroservoelasticity is a multidisciplinary study that combines the following disciplines: aerodynamics, aeroelasticity and servo-controls. For aeroelasticity studies, the Doublet Lattice Method (DLM) is used to calculate the aerodynamic unsteady forces for a set of reduced frequencies k and Mach numbers M on a business aircraft in the subsonic flight regime. There are three classical methods in the aeroservoelasticity used to approximate these forces Q (k, M) by rational functions in the Laplace domain Q(s): Least Square (LS), Matrix Padé (MP) and Minimum State (MS). A new method called Corrected Least Square (CLS) is presented. This new method uses an analytical form of the error as a function of Laplace variable similar to the analytical form of the aerodynamic forces calculated by use of the LS method. The new CLS method does not take additional time to the computation of the unsteady aerodynamic forces when compared to the LS method, and the aerodynamic forces calculated with the CLS method are closer to the aerodynamic forces data in the frequency domain than the aerodynamic forces calculated by the standard LS method. The new CLS method applied on a business aircraft gives better results (flutter speeds and frequencies) and faster (as it uses smaller number of lag terms) than the LS method.
Application of Fuzzy PID Control to Cluster Control of Viaduct Road Vibrations
Authors: Ömürlü Vasfi Emre , Engin Şeref Naci , Yüksek İsmail
Published: June 2008

Distributed parameter systems have infinite-degrees of freedom. Algorithms for vibration control of these systems have provided satisfactory results for low-frequency ranges but these approaches may cause spillover and undesired conditions at high-frequency ranges resulting in unsatisfactory control performance. In this study, the application of cluster control on viaduct roads composed of flat parts is introduced. Cluster control consists of three stages: sensing, actuation and control of desired mode groups using a control method. Sensing and actuation of mode groups are introduced separately. The grouping and sensing of mode groups are realized by using Finite Element Analysis. Various control architectures, of which the most popular ones are classical PID controllers, have been suggested to apply cluster control for vibrating structures. In this study, a Mamdani-type fuzzy PID controller with two input and two output is suggested and the system responses, whose dynamics are gathered from a scaled size of a viaduct road, are collected for proposed fuzzy-PID and sliding mode controllers. Analysis of the performance of cluster control along with the individual effects of the controller parameters on system frequency response is discussed and presented.
Suppression of Vehicle-induced Bridge Vibration Using Tuned Mass Damper
Authors: Xiaomin Shi  , Cai C.S.
Published: June 2008

This paper focused on a numerical model for vehicle-induced bridge vibrations controlled with a tuned mass damper (TMD) system, taking road surface conditions into account. A computer program was developed to study the possible effectiveness of the TMD for suppressing the vibration of bridges under vehicle loads. Then, a comprehensive investigation was conducted on different bridges under two vehicle load patterns, i.e. two trucks moving side by side or several trucks passing over the bridge in a traffic flow. It was found that the additional damping provided by the TMD results in a reduction of the maximum dynamic displacement for both free and forced vibrations. On the other hand, for all the bridges investigated in this study, the reduction of acceleration is also significant. More generally speaking, it can be concluded that for the same TMD installed on the same bridge, it is more effective for cases with trucks passing over the bridge in traffic flow than for cases with only one truck. Such a study is helpful in evaluating the control performance before the real control devices are designed in practice.
Empowerment and Physical Violence Throughout Women's Reproductive Life In Mexico
Authors: Castro Roberto , Casique Irene , Brindis Claire D.
Published: June 2008

This article analyzes intimate partner violence (IPV) against women aged 15 to 21, 30 to 34, and 45 to 49, based on the 2003 National Survey on the Dynamics of Household Relationships (in Spanish, ENDIREH) in Mexico. The authors examined the degree of women's empowerment and autonomy in relation to their partners. Logit regression analyses showed that variables significantly associated with physical violence varied between the three age groups, suggesting that women followed specific trajectories throughout their reproductive lives. Some dimensions of empowerment reduced the risk of violence (women's ability to decide whether to work, when to have sexual relations, and the extent of their partners' participation in household chores). Other dimensions (women's decision making regarding reproductive matters) increased such risk. Thus, access to resources meant to empower women did not automatically decrease the risk of violence. The authors recommend specific interventions tailored to each age group, aimed at breaking the cycle of violence.
The use and effectiveness of granulocyte colony-stimulating factor in primary prophylaxis for febrile neutropenia in the outpatient setting
Authors: Tuffaha Haitham W , Treish Imad M , Zaru Luna
Published: June 2008

Objectives. To conduct a drug utilization review (DUR) on the use of granulocyte colony-stimulating factor (G-CSF) and to study the effectiveness of this agent in preventing the incidence of febrile neutropenia (FN).

Methods. Outpatients to whom G-CSF was dispensed were identified and their actual medical records were reviewed to verify patients who received G-CSF for primary prophylaxis. Literature was reviewed to determine the expected incidence and risk of FN for chemotherapy regimens used, and the compliance of prescribers with the institutional guidelines was evaluated. After that, the proportion of patients who developed FN was identified and compared to the expected incidence from literature. Data analysis was performed on the outcome of patient-cycle.

Results. Of the 99 patient-cycles, 53 (53%) were compliant with guidelines whereas 46 (47%) were not. FN developed in 12 (12.1%, 95% CI = 5.7, 18.5) while the expected average incidence of FN was 32.7%. Eleven (21%, 95% CI = 10.1, 32.2) of the 53 patient-cycles that were compliant with guidelines developed FN, whereas one patient among the non-compliant group developed FN (2%, 95% CI = 0.0, 6.2). The expected incidence of FN was 42.9 and 21.5%, in the compliant group, and noncompliant group, respectively. Based on expected FN rates, the respective reduction in the incidence of FN was 51, and 90%.

Conclusions. Lack of adherence to institutional guidelines was noticed in G-CSF prescribing. Reasons behind poor compliance with the guidelines must be verified and resolved. Prophylactic G-CSF is effective in reducing the incidence of FN; however, further research in a larger population is warranted to confirm these findings. J Oncol Pharm Practice (2008) 14: 131—138.
Up-regulation of WRN and DNA ligase IIIα in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks
Authors: Sallmyr Annahita , Tomkinson Alan E. , Rassool Feyruz V.
Published: June 2008

Expression of oncogenic BCR-ABL in chronic myeloid leukemia (CML) results in increased reactive oxygen species (ROS) that in turn cause increased DNA damage, including DNA double-strand breaks (DSBs). We have previously shown increased error-prone repair of DSBs by nonhomologous end-joining (NHEJ) in CML cells. Recent reports have identified alternative NHEJ pathways that are highly error prone, prompting us to examine the role of the alternative NHEJ pathways in BCR-ABL–positive CML. Importantly, we show that key proteins in the major NHEJ pathway, Artemis and DNA ligase IV, are down-regulated, whereas DNA ligase IIIα, and the protein deleted in Werner syndrome, WRN, are up-regulated. DNA ligase IIIα and WRN form a complex that is recruited to DSBs in CML cells. Furthermore, “knockdown” of either DNA ligase IIIα or WRN leads to increased accumulation of unrepaired DSBs, demonstrating that they contribute to the repair of DSBs. These results indicate that altered DSB repair in CML cells is caused by the increased activity of an alternative NHEJ repair pathway, involving DNA ligase IIIα and WRN. We suggest that, although the repair of ROS-induced DSBs by this pathway contributes to the survival of CML cells, the resultant genomic instability drives disease progression.
Validation of PDGFRβ and c-Src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: preclinical efficacy of the novel, orally available inhibitor dasatinib
Authors: Coluccia Addolorata Maria Luce , Cirulli Teresa , Neri Paola , Mangieri Domenica , Colanardi Maria Cristina , Gnoni Antonio , Di Renzo Nicola , Dammacco Franco , Tassone Pierfrancesco , Ribatti Domenico , Gambacorti-Passerini Carlo , Vacca Angelo
Published: June 2008

Inhibition of multiple myeloma (MM) plasma cells in their permissive bone marrow microenvironment represents an attractive strategy for blocking the tumor/vessel growth associated with the disease progression. However, target specificity is an essential aim of this approach. Here, we identified platelet-derived growth factor (PDGF)–receptor beta (PDGFRβ) and pp60c-Src as shared constitutively activated tyrosine-kinases (TKs) in plasma cells and endothelial cells (ECs) isolated from MM patients (MMECs). Our cellular and molecular dissection showed that the PDGF-BB/PDGFRβ kinase axis promoted MM tumor growth and vessel sprouting by activating ERK1/2, AKT, and the transcription of MMEC-released proangiogenic factors, such as vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). Interestingly, pp60c-Src TK-activity was selectively induced by VEGF in MM tumor and ECs, and the use of small-interfering (si)RNAs validated pp60c-Src as a key signaling effector of VEGF loop required for MMEC survival, migration, and angiogenesis. We also assessed the antitumor/vessel activity of dasatinib, a novel orally bioactive PDGFRβ/Src TK-inhibitor that significantly delayed MM tumor growth and angiogenesis in vivo, showing a synergistic cytotoxicity with conventional and novel antimyeloma drugs (ie, melphalan, prednisone, bor-tezomib, and thalidomide). Overall data highlight the biologic and therapeutic relevance of the combined targeting of PDGFRβ/c-Src TKs in MM, providing a framework for future clinical trials.
Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2
Authors: Fang Jing , Menon Madhu , Zhang Diya , Torbett Bruce , Oxburgh Leif , Tschan Mario , Houde Estelle , Wojchowski Don M.
Published: June 2008

The adult erythron is maintained via dynamic modulation of erythroblast survival potentials. Toward identifying novel regulators of this process, murine splenic erythroblasts at 3 developmental stages were prepared, purified and profiled. Stage-to-stage modulated genes were then functionally categorized, with a focus on apoptotic factors. In parallel with BCL-X and NIX, death-associated protein kinase-2 (DAPK2) was substantially up-modulated during late erythropoiesis. Among hematopoietic lineages, DAPK2 was expressed predominantly in erythroid cells. In a Gata1-IE3.9int-DAPK2 transgenic mouse model, effects on steady-state reticulocyte and red blood cell (RBC) levels were limited. During hemolytic anemia, however, erythropoiesis was markedly deficient. Ex vivo ana-lyses revealed heightened apoptosis due to DAPK2 at a Kit−CD71highTer119− stage, together with a subsequent multifold defect in late-stage Kit−CD71highTer119+ cell formation. In UT7epo cells, siRNA knock-down of DAPK2 enhanced survival due to cytokine withdrawal, and DAPK2's phosphorylation and kinase activity also were erythropoietin (EPO)-modulated. DAPK2 therefore comprises a new candidate attenuator of stress erythropoiesis.
Phylogenetic studies of the genus Cebus(Cebidae-Primates) using chromosome painting and G-banding
Authors: Amaral PJS , Finotelo LFM , De Oliveira EHC , Pissinatti A , Nagamachi CY , Pieczarka JC
Published: June 2008

Background

Chromosomal painting, using whole chromosome probes from humans and Saguinus oedipus, was used to establish karyotypic divergence among species of the genus Cebus, including C. olivaceus, C. albifrons, C. apella robustus and C. apella paraguayanus. Cytogenetic studies suggested that the species of this genus have conservative karyotypes, with diploid numbers ranging from 2n = 52 to 2n = 54.

Results

Banding studies revealed morphological divergence among some chromosomes, owing to variations in the size of heterochromatic blocks. This analysis demonstrated that Cebus species have five conserved human associations (i.e., 5/7, 2/16, 10/16, 14/15, 8/18 and 3/21) when compared with the putative ancestral Platyrrhini karyotype.

Conclusion

The autapomorphies 8/15/8 in C. albifrons and 12/15 in C. olivaceus explain the changes in chromosome number from 54 to 52. The association 5/16/7, which has not previously been reported in Platyrrhini, was also found in C. olivaceus. These data corroborate previous FISH results, suggesting that the genus Cebus has a very similar karyotype to the putative ancestral Platyrrhini.
Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials
Authors: Meyer-Lucht Yvonne , Otten Celine , Püttker Thomas , Sommer Simone
Published: June 2008

Background

Research on the genetic architecture and diversity of the MHC has focused mainly on eutherian mammals, birds and fish. So far, studies on model marsupials used in laboratory investigations indicated very little or even no variation in MHC class II genes. However, natural levels of diversity and selection are unknown in marsupials as studies on wild populations are virtually absent. We used two endemic South American mouse opossums, Gracilinanus microtarsus and Marmosops incanus, to investigate characteristic features of MHC selection. This study is the first investigation of MHC selection in free-ranging Neotropical marsupials. In addition, the evolutionary history of MHC lineages within the group of marsupials was examined.

Results

G. microtarsus showed extensive levels of MHC diversity within and among individuals as 47 MHC-DAB alleles and high levels of sequence divergence were detected at a minimum of four loci. Positively selected codon sites were identified, of which most were congruent with human antigen binding sites. The diversity in M. incanus was rather low with only eight observed alleles at presumably two loci. However, these alleles also revealed high sequence divergence. Again, positive selection was identified on specific codon sites, all congruent with human ABS and with positively selected sites observed in G. microtarsus. In a phylogenetic comparison alleles of M. incanus interspersed widely within alleles of G. microtarsus with four alleles being present in both species.

Conclusion

Our investigations revealed extensive MHC class II polymorphism in a natural marsupial population, contrary to previous assumptions. Furthermore, our study confirms for the first time in marsupials the presence of three characteristic features common at MHC loci of eutherian mammals, birds and fish: large allelic sequence divergence, positive selection on specific sites and trans-specific polymorphism.
Transformation of MCF-10A cells by random mutagenesis with frameshift mutagen ICR191: A model for identifying candidate breast-tumor suppressors
Authors: Zientek-Targosz Helena , Kunnev Dimiter , Hawthorn Lesleyann , Venkov Mikhail , Matsui Sei-Ichi , Cheney Richard T , Ionov Yuri
Published: June 2008

Background

Widely accepted somatic mutation theory of carcinogenesis states that mutations in oncogenes and tumor suppressor genes in genomes of somatic cells is the cause of neoplastic transformation. Identifying frequent mutations in cancer cells suggests the involvement of mutant genes in carcinogenesis.

Results

To develop an in vitro model for the analysis of genetic alterations associated with breast carcinogenesis, we used random mutagenesis and selection of human non-tumorigenic immortalized breast epithelial cells MCF-10A in tissue-culture conditions that mimic tumor environment. Random mutations were generated in MCF-10A cells by cultivating them in a tissue-culture medium containing the frameshift-inducing agent ICR191. The first selective condition we used to transform MCF1-10A cells was cultivation in a medium containing mutagen at a concentration that allowed cell replication despite p53 protein accumulation induced by mutagen treatment. The second step of selection was either cell cultivation in a medium with reduced growth-factor supply or in a medium that mimics a hypoxia condition or growing in soft agar. Using mutagenesis and selection, we have generated several independently derived cultures with various degrees of transformation. Gene Identification by Nonsense-mediated mRNA decay Inhibition (GINI) analysis has identified the ICR191-induced frameshift mutations in the TP53, smoothelin, Ras association (RalGDS/AF-6) domain family 6 (RASSF6) and other genes in the transformed MCF-10A cells. The TP53 gene mutations resulting in the loss of protein expression had been found in all independently transformed MCF-10A cultures, which form large progressively growing tumors with sustained angiogenesis in nude mice.

Conclusion

Identifying genes containing bi-allelic ICR191-induced frameshift mutations in the transformed MCF-10A cells generated by random mutagenesis and selection indicates putative breast-tumor suppressors. This can provide a model for studying the role of mutant genes in breast carcinogenesis.
TRPM8 Mechanism of Autonomic Nerve Response to Cold in Respiratory Airway
Authors: Xing Hong , Ling Jennifer X , Chen Meng , Johnson Richard D , Tominaga Makoto , Wang Cong-Yi , Gu Jianguo
Published: June 2008

Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.
Burkitt's lymphoma of the colon and bronchi: three case reports
Authors: Musallam Khaled M , Taher Ali T , Shamseddine Ali I
Published: June 2008

Introduction

Burkitt's lymphoma is a form of non-Hodgkin's B-cell lymphoma with more than one identifiable variant. The sporadic form most commonly presents with abdominal lymph node involvement.

Case reports

We herein report on three patients from our experience that presented with either endobronchial or colonic Burkitt's lymphoma. Their clinical presentation mimicked that of other syndromes. After confirmatory pathological diagnosis, the patients had complete remission through the use of an optimal treatment protocol.

Conclusion

Our review of the cases and comparable reports warrants careful workup of such presentations to ensure early diagnosis and therapeutic planning of this highly aggressive disease.
Iridium-catalyzed Vinylic C–H Borylation of Cyclic Vinyl Ethers by Bis(pinacolato)diboron
Authors: Kikuchi Takao , Takagi Jun , Ishiyama Tatsuo , Miyaura Norio
Published: June 2008

Vinylic C–H borylation of cyclic vinyl ethers by bis(pinacolato)diboron was effectively catalyzed by iridium complexes comprised of 1/2[Ir(OMe)(cod)]2 and 4,4′-di-tert-butyl-2,2′-bipyridine in hexane or octane to give the corresponding vinylboron compounds in good yields. The reaction of 1,4-dioxene occurred even at room temperature, whereas the reactions of dihydropyran and dihydrofuran derivatives required a temperature above 80 °C. Although dihydropyran and dihydrofuran themselves produced regioisomeric mixtures of α- and β-borylated products, similar substrates possessing substituents at the γ-position selectively underwent borylation at the α-position.
Relative Comparison Method of Rolling Contact Fatigue Performance of Silicon Nitrides by Stepwise Loading Balls-on-Flat Test—A Candidate for Standard Practice for Comparison of RCF Performance
Authors: Kanematsu Wataru
Published: June 2008

We have demonstrated a simple comparison method for rolling contact fatigue (RCF) performance of silicon nitrides using the balls-on-flat RCF test under stepwise loading. The RCF performance was evaluated by the mean effective mechanical input (Min)m which is the product of the mean effective load Pm, calculated from test loads and revolutions during the dwell time for each load, and the number of load cycles. The test materials were six kinds of commercially available silicon nitride, four of bearing-grade silicon nitrides (BG) and two general purpose ones (GP). The minimum test loads were 1 and 0.5 kN for BG and GP, respectively. The load was increased stepwise with each step 107 contact cycles unless failure of the specimen was detected by the acceleration pickup mounted on the loading arm of the testing machine. The balls and test specimen were immersed in mineral oil with kinematic viscosities of 8 mm2/s for BG and 68 mm2/s for GP. A clear distinction in (Min)m was made among the BG, and the GP have lower (Min)m compared to BG, despite small differences in conventional mechanical properties such as Vickers hardness, fracture toughness, and elastic modulus. The results of the balls-on-flat RCF test under constant load for one BG lend support to the hypothesis that the loading history in stepwise loading can be converted to the mean effective load Pm. It is also supported by the fact that classification of failure mechanisms in stepwise loading is similar to that for a constant load of 4 kN, which is close to the mean of Pm of the material. These results imply the viability of a standardized comparison method for RCF performance of bearing-grade silicon nitrides as well as screening for poor performance materials.
On the quantification of the constraint effect along a three-dimensional crack front
Authors: Wang Xin
Published: June 2008

In this paper we examined the characterization of constraint effects for surface cracked plates under uniaxial and biaxial tension loadings. First, three-dimensional (3D) modified boundary layer analyses were conducted using the finite element method to study the constraint effect at a typical 3D crack front. The analyses were carried out using small geometry change formulation and deformation plasticity material model. Elastic-plastic crack front stress fields at a constant J and various T-stress levels were obtained. Three-dimensional elastic-plastic analyses were performed for semi-circular surface cracks in a finite thickness plate, under remote uniaxial and biaxial tension loading conditions. In topological planes perpendicular to the crack fronts, the crack stress fields were obtained. Then, J-Q and J-T two-parameter approaches are used in characterizing the elastic-plastic crack-tip stress fields along the 3D crack front. It is found that the J-Q characterization provides good estimate for the constraint effect for crack-tip stress fields. Reasonable agreements are achieved between the T-stress based Q-factors and the Q-factors obtained from finite element analysis.
A Generalized Method for Calculating Strain for a Circular Cross-Section Specimen Subject to Axial Force and Bending
Authors: Liang Xin Bang , Gao Yi Fei
Published: June 2008

A theoretical analysis was performed with multiple-point measurements of the bending strain distribution along the circumferential cross section of a cylindrical alignment cell. A simple and general equation for representing the maximum bending strain was developed to unify the expression of bending strain. Also, both the general equation for the net bending contributions, due, respectively, to the testing machine and the specimen and the equation for the general orientation angle after separation of the testing machine component and the specimen component are provided.
Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers α-fetoprotein and human chorionic gonadotropin
Authors: Fottner Christian , Sattarova Sabina , Hoffmann Kerstin , Spöttl Gerald , Weber Matthias M
Published: June 2008

Background/aims

Alterations of the IGF system have been described in several different types of cancer. However, no information is available about the role of the IGF system in patients with non-seminomatous germ cell cancer.

Methods

Free IGF-I, IGF-II, acid-labile subunit, and IGF-binding proteins (IGFBPs) 1–4 were analyzed by specific RIAs in 32 patients with untreated non-seminomas and compared with IGFBP levels of 38 healthy controls. Serum IGFBPs were analyzed by western ligand blotting (WLB) and immunoblotting. In 16 patients, IGFBP profiles were measured before, during, and after treatment.

Results

In patients with testicular cancer, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027±48 ng/ml versus 711±30 ng/ml, P<0.0001). IGFBP-2 levels were on average 2.6-fold higher (586±58 ng/ml versus 226±17 ng/ml, P<0.001). During follow-up, a decrease in IGFBP-2 levels was observed in all successfully treated patients, which correlated closely with a decrease in the tumor markers α-fetoprotein and human chorionic gonadotropin. Additionally, in all patients with recurrent disease, a significant further increase in IGFBP-2 levels (from 358±97 to 976±260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared with controls. However, WLB analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy.

Conclusion

Our results demonstrate that markedly elevated IGF-II and IGFBP-2 serum levels in patients with non-seminomatous germ cell cancer, showing a significant decrease after successful therapy and an increase in recurrent disease. Additionally, indirect evidence points to an increased proteolytic activity for IGFBP-3 in untreated testicular cancer patients.
Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile
Authors: Lourenço D M , Toledo R A , Mackowiak I I , Coutinho F L , Cavalcanti M G , Correia-Deur J E M , Montenegro F , Siqueira S A C , Margarido L C , Machado M C , Toledo S P A
Published: June 2008

Objective

Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree, which included 715 at-risk family members.

Design

Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members.

Results

Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T, −2.87±0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients, while marked bone mineral loss in the lumbar spine (T, −1.95±0.39), with most cancellous bone, and femoral neck (mixed composition; T, −1.48±0.27) were also present.

Conclusions

In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore, we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT.