bluuebunny/crossref_metadata_2025 huggingface dataset:
Unfractionated heparin and enoxaparin reduce high-stretch ventilation augmented lung injury: a prospective, controlled animal experiment
Authors: Li Li-Fu , Huang Chung-Chi , Lin Horng-Chyuan , Tsai Ying-Huang , Quinn Deborah A , Liao Shuen-Kuei
Published: July 2009

Introduction

Dysregulation of coagulation and local fibrinolysis found in patients with acute lung injury often results in the need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and suppression of fibrinolytic activity, but the mechanisms are unclear. We hypothesized that subcutaneous injections of unfractionated heparin and enoxaparin would decrease neutrophil infiltration, lung edema, and plasminogen-activator inhibitor-1 (PAI-1) production in mice exposed to high-tidal-volume ventilation.

Methods

Male C57BL/6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume (30 ml/kg) or low-tidal-volume (6 ml/kg) mechanical ventilation with room air for 1 to 5 hours after 200 IU/kg or 400 IU/kg unfractionated heparin and 4 mg/kg or 8 mg/kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet- to dry-weight ratio, histopathologic grading of epithelium, myeloperoxidase, and gene expression of PAI-1 were measured. The expression of PAI-1 was studied by immunohistochemistry.

Results

High-tidal-volume ventilation induced increased microvascular permeability, neutrophil influx, PAI-1 mRNA expression, production of PAI-1 protein, and positive staining of PAI-1 in epithelium in a dose-dependent manner. Lung injury induced by high-tidal-volume ventilation was attenuated with PAI-1-deficient mice and pharmacologic inhibition of PAI-1 activity by low-dose unfractionated heparin and enoxaparin.

Conclusions

We conclude that high-tidal-volume mechanical ventilation increased microvascular permeability, neutrophil influx, lung PAI-1 mRNA expression, production of active PAI-1. The deleterious effects were attenuated by low-dose unfractionated heparin or enoxaparin treatment. Understanding the protective mechanism of unfractionated heparin and enoxaparin related to the reduction of PAI-1 may afford further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury.
Myeloablative Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: Analysis of Graft Sources and Long-Term Outcome
Authors: Tomblyn Michael B. , Arora Mukta , Baker K. Scott , Blazar Bruce R. , Brunstein Claudio G. , Burns Linda J. , DeFor Todd E. , Dusenbery Kathryn E. , Kaufman Dan S. , Kersey John H. , MacMillan Margaret L. , McGlave Philip B. , Miller Jeffrey S. , Orchard Paul J. , Slungaard Arne , Tomblyn Marcie R. , Vercellotti Gregory M. , Verneris Michael R. , Wagner John E. , Weisdorf Daniel J.
Published: July 2009

Purpose

Analysis of hematopoietic cell transplantation (HCT) for high-risk or recurrent acute lymphoblastic leukemia (ALL) using different donor sources is confounded by variable conditioning and supportive care.

Patients and Methods

We studied 623 consecutive ALL myeloablative HCT (1980 to 2005). Donors were autologous (n = 209), related (RD; n = 245), unrelated (URD; n = 100), and umbilical cord blood (UCB; n = 69).

Results

After median of 8.3 years of follow-up, 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 29% (95% CI, 26% to 32%), 26% (95% CI, 23% to 29%), and 43% (95% CI, 39% to 47%), respectively. Treatment-related mortality (TRM) at 2 years was 28% (95% CI, 25% to 31%). Mismatched URD sources yielded higher TRM (relative risk [RR], 2.2; P < .01) and lower OS (RR, 1.5; P = .05) than RD or UCB HCT. Autografting yielded significantly more relapse (68%; 95% CI, 59% to 77%; P < .01) and poorer LFS (14%; 95% CI, 10% to 18%; P = .01). HCT in first complete remission (CR1) yielded significantly better outcomes than later HCT. In a 1990 to 2005 allogeneic CR1/second complete response cohort, 5-year OS, LFS, and relapse rates were 41% (95% CI, 35% to 47%), 38% (95% CI, 32% to 44%), and 25% (95% CI, 19% to 31%), respectively; 2-year TRM was 34% (95% CI, 28% to 40%). With RD, well-matched URD and UCB sources, 5-year LFS was 40% (95% CI, 31% to 49%), 42% (95% CI, 14% to 70%), and 49% (95% CI, 34% to 64%), respectively, while relapse was 31% (95% CI, 22% to 40%), 17% (95% CI, 0% to 37%), and 27% (95% CI, 13% to 41%). Acute graft-versus-host disease was associated with fewer relapses. Since 1995, we noted progressive improvements in OS, LFS, and TRM.

Conclusion

Allogeneic, but not autologous, HCT for ALL results in durable LFS. Importantly, HCT using UCB led to similar outcomes as either RD or well-matched URD. HCT in early remission can best exploit the potent antileukemic efficacy of allografting from UCB, RD, or URD sources.
Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Authors: Hess Georg , Herbrecht Raoul , Romaguera Jorge , Verhoef Gregor , Crump Michael , Gisselbrecht Christian , Laurell Anna , Offner Fritz , Strahs Andrew , Berkenblit Anna , Hanushevsky Orysia , Clancy Jill , Hewes Becker , Moore Laurence , Coiffier Bertrand
Published: July 2009

Purpose

Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease.

Patients and Methods

In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1:1:1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (PFS) by independent assessment.

Results

Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus 175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients treated with temsirolimus 175/75-mg had significantly longer PFS than those treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44); those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P = .0618; hazard ratio = 0.65). Objective response rate was significantly higher in the 175/75-mg group (22%) compared with the investigator's choice group (2%; P = .0019). Median overall survival for the temsirolimus 175/75-mg group and the investigator's choice group was 12.8 months and 9.7 months, respectively (P = .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups were thrombocytopenia, anemia, neutropenia, and asthenia.

Conclusion

Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL.
Patients With Merkel Cell Carcinoma Tumors ≤ 1.0 cm in Diameter Are Unlikely to Harbor Regional Lymph Node Metastasis
Authors: Stokes Jayme B. , Graw Katherine S. , Dengel Lynn T. , Swenson Brian R. , Bauer Todd W. , Slingluff Craig L. , Ledesma Elihu J.
Published: July 2009

Purpose

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous malignancy. Current recommendations include offering regional lymph node evaluation by either sentinel lymph node biopsy (SLNB) or complete lymph node dissection (CLND) to all patients with MCC; however, we hypothesized a cohort of low-risk patients may exist for whom regional nodal metastasis would be unlikely.

Methods

A retrospective review of the Department of Veterans Affairs national health care database was performed. Patients undergoing resection of primary MCC were identified; and demographic, medical, and social history; tumor characteristics; nodal status; and recurrence events were recorded.

Results

Between 1995 and 2006, 346 patients were diagnosed with MCC. Of these, 213 underwent resection of the primary lesion and evaluation of the draining lymph node basin. Fifty-four patients (25%) had tumors ≤ 1.0 cm in diameter. Average tumor diameter was 0.7 cm, and 63% were located on the head or neck. Only two patients (4%) with tumors ≤ 1.0 cm had regional lymph node metastasis, compared with 51 (24%) of 213 patients with tumors more than 1.0 cm (P < .0001). Both patients had clinically evident nodal disease at presentation and underwent CLND. Both have remained recurrence-free for 40 months. Thirteen (25%) of 51 patients with nodal metastasis and tumors more than 1 cm had occult nodal metastasis.

Conclusion

In this series, patients with MCC ≤ 1.0 cm were unlikely to have regional lymph node metastasis, suggesting that regional nodal evaluation may reasonably be avoided in these patients. However, these data support SLNB for MCC more than 1 cm in diameter.
An in Vivo Study on Adjudin and Blood-Testis Barrier Dynamics
Authors: Kopera Ilona A. , Su Linlin , Bilińska Barbara , Cheng C. Yan , Mruk Dolores D.
Published: July 2009

Adjudin is known to specifically affect Sertoli-germ cell adhesion, resulting in germ cell loss from the seminiferous epithelium and transient infertility. The apical ectoplasmic specialization (ES) was shown to be the primary target of adjudin because adhesion was unaffected in organs that lack this structure. Herein we expand previous findings by treating rat pups with adjudin, and we aimed to address two questions. First, can adjudin perturb germ cell adhesion in the seminiferous epithelium of testes in which the apical ES is not yet present? Second, can adjudin affect assembly of the blood-testis barrier (BTB) at 15–18 d of age? Interesting changes were noted when aged-matched testes from control and adjudin-treated rats were examined, including a delay in the appearance of developing germ cells as well as a delay in the formation of the tubule lumen. Immunoblotting using antibodies against BTB-constituent proteins indicated that formation of the BTB was affected in rat pups gavaged with adjudin. These results were corroborated by immunofluorescence microscopy, which showed profound changes in the cellular distribution of tight junction and basal ES proteins. Moreover, the BTB was shown to be compromised in 30-d-old rats when its integrity was assessed by a functional in vivo assay. By 45 d of age, however, the seminiferous epithelium of treated rats was indistinguishable from that of control rats. Collectively these results demonstrate that adjudin targets the apical ES as well as the basal ES and tight junction, which in turn delays assembly of the BTB.
Minireview: Epigenetic Changes in Ovarian Cancer
Authors: Balch Curt , Fang Fang , Matei Daniela E. , Huang Tim H.-M. , Nephew Kenneth P.
Published: July 2009

Epigenetic aberrations, including DNA methylation, histone modifications, and micro-RNA dysregulation, are now well established in the development and progression of ovarian cancer, and their gradual accumulation is associated with advancing disease stage and grade. Epigenetic aberrations are relatively stable, associated with distinct disease subtypes, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic modifications are potentially reversible by epigenetic therapies, including inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic monotherapies have not shown activity against solid tumors, including ovarian cancer, preclinical studies suggest they will be effective when used in combination with one another or with conventional chemotherapeutics, and combinatorial epigenetic therapy regiments are being examined in cancer clinical trials. A greater understanding of the role of epigenetics in ovarian neoplasia will provide for improved interventions against this devastating malignancy.
Gonadotropin-Releasing Hormone-Mediated Phosphorylation of Estrogen Receptor-α Contributes to fosB Expression in Mouse Gonadotrophs
Authors: Chen Junling , An Beum-Soo , Cheng Linan , Hammond Geoffrey L. , Leung Peter C. K.
Published: July 2009

Estrogen receptors (ERs) are activated by their ligands as well as signaling pathways that alter ER phosphorylation in response to peptide hormones and growth factors. In pituitary gonadotrophs, GnRHs act via the type I GnRH receptor (GnRHR). Both GnRH subtypes (GnRH-I and -II) activate an estrogen response element (ERE)-driven luciferase reporter gene in LβT2 mouse pituitary cells, and GnRH-I is most potent in this regard. Moreover, antide (a GnRH antagonist) and a GnRHR small interfering RNA (siRNA) abrogate this effect, whereas an ERα antagonist (ICI 182,780) does not. The ERα in LβT2 cells is phosphorylated at Ser118 in the nucleus and at Ser167 in both nucleus and cytoplasm after GnRH treatments and coincided with increased ERα binding to its coactivator, the p300/cAMP response element-binding protein-associated factor (PCAF). Moreover, siRNA-mediated knockdown of PCAF levels attenuated GnRH-induced ERE-luciferase transactivation in these cells. Most importantly, both GnRH subtypes robustly up-regulated expression of the immediate early response gene, fosB, whereas cotreatment with ERα siRNA or PCAF siRNA attenuated this effect. This appears to occur at the transcriptional level because corecruitment of ERα and PCAF to an ERE within the endogenous fosB promoter was increased by GnRH treatments, as shown by chromatin immunoprecipitation assays. These data demonstrate that GnRH-mediated phosphorylation of ERα in mouse LβT2 pituitary cells results in its rapid association with PCAF and the transcriptional activation of fosB, and we demonstrate that this in turn likely activates other genes in pituitary cells including the FSH β-subunit gene.
Computerized gear cutting simulation using a psuedo-planar method
Authors: Chiang C-J , Fong Z-H , Chang K-L
Published: July 2009

The gear cutting process is generally simulated by solving the simultaneous system equations derived from the theory of gearing. However, in the presence of undercutting or secondary enveloping, the solution to these equations is numerically unstable. Hence, this paper proposes a simplified pseudo-planar gear cutting simulation method using ObjectARX in an AutoCAD environment. In this method, execution of a script file generated by Visual C++ allows simulation of the gear cutting process and calculation of the gear tooth profile without the need to solve simultaneous system equations. The generated thread—s tooth profile is obtained by subtracting the cutter locus from the workpiece—s transverse section. Since the entire process occurs in the transverse plane, it is more rapid than three-dimensional computer-aided design software calculations. Additionally, as illustrated by the numerical examples of cylindrical gear form grinding and hypoid gear face milling processes, respectively, the proposed method is applicable to cylindrical gear and bevel gear cutting simulation. It can also be applied in the case of undercutting or secondary enveloping.
Theoretical and experimental studies on the steady-state performance of low-speed high-torque hydrostatic drives. Part 2: Experimental investigation
Authors: Mandal S K , Dasgupta K , Pan S , Chattopadhyay A
Published: July 2009

The performance investigations of an open-circuit and a closed-circuit low-speed high-torque hydrostatic drive are presented. The modelling of both drives and determination of their loss coefficients are presented in Part 1 of this article (pg. 2663 of this issue). This study determines and analyses the overall efficiency and slip characteristics of the hydrostatic drives using the expressions describing the characteristics of their loss coefficients. The effects of critical control parameters of the pumps and the motor are investigated on the basis of their steady-state performance. This investigation is based on the performance of the hydrostatic transmission drives at different torque levels.
Unsteady behaviour of the tip clearance vortex in a rotor equivalent compressor cascade
Authors: Schrapp H , Stark U , Saathoff H
Published: July 2009

From earlier experimental investigations in a single-stage axial-flow pump and different numerical calculations of the flow in single-stage axial-flow compressors, it is known that vortex breakdown of the tip clearance vortex can take place in turbomachines, although an experimental proof for subsonic compressors is lacking.

Vortex breakdown, if existent, is a source of high instability in the sensitive tip region of axial-flow pumps and compressors and will also play an important role in the stall inception process. Therefore, the flow in a linear compressor cascade with a 3 per cent tip clearance to one side has been investigated at different flow angles from the design point up to the stability limit of the cascade. The cascade resembles the tip section of a single-stage, axial-flow, low-speed compressor that is also in use at the Technical University of Braunschweig.

The measuring techniques used were (a) a commercial particle image velocimetry (PIV) system and (b) a pressure measuring system with several flush mounted high-response pressure transducers at selected locations where the vortex was expected. As the cascade approaches its stall limit, the analysis of the pressure signals in the frequency domain revealed a bump of increased amplitude at a certain non-dimensional frequency for some of the measuring positions. The measuring positions that exhibited the bump correlated very well with a paraboloid-shaped region of high standard deviation enveloping an area of very low momentum fluid. It is shown that the frequency of the striking bump corresponds to the rotational frequency of the vortex calculated from the PIV measurements.
Numerical investigation of the interaction between jet and bucket in a Pelton turbine
Authors: Santolin A , Cavazzini G , Ardizzon G , Pavesi G
Published: July 2009

This article presents the numerical investigation of the interaction between the jet and the bucket in a Pelton turbine. Unsteady numerical analyses were carried out on a single jet Pelton turbine installed in the north of Italy. A two-phase inhomogeneous model was used.

Two different jet configurations were analysed and compared. In the first configuration, the interaction between the runner and an axial-symmetric jet characterized by a given velocity jet profile was investigated, whereas in the second configuration the runner was coupled with the needle nozzle and the final part of the penstock and the interaction between the jet and the bucket was analysed.

A detailed analysis of the torque highlighted the influence of the shape of the water jet on the turbine losses and the influence of the stator on the efficiency of this type of hydraulic machines was shown. The numerical results were compared with the experimental data derived from the installation test of the turbine in order to validate the numerical analysis.
Development of an improved urea-selective catalytic reduction—diesel particulate filter system for heavy-duty commercial vehicles
Authors: Hirata K , Masaki N , Yano M , Akagawa H , Takada K , Kusaka J , Mori T
Published: July 2009

Many heavy-duty commercial vehicles are now equipped with urea-selective catalytic reduction (SCR) systems, which can reduce NO x emissions sufficiently to meet the requirements of legislation such as Japan's New Long-term Diesel Emissions Regulations. However, in order to meet even stricter exhaust emissions regulations (and fuel consumption standards) due to be imposed in many parts of the world in the near future, urea-SCR systems with greater catalytic efficiency combined with diesel particulate filters (DPFs) will be needed. Therefore, in the study presented here the scope for enhancing the efficiency of a urea-SCR system was explored by optimizing the urea dosing system and injection strategies, and the gas flow in the exhaust pipe. However, since improving the catalysis parameters could have the greatest overall effect on conversion efficiency, work focused on modifying the catalyst materials to increase their adsorption capacity for the NH3 reducing agent, and thus increase the collision frequency between NO x and NH3 absorbed on the surface of the catalyst. In addition, the oxidation parameters of the oxidation catalyst were optimized, which enhanced the NO x conversion efficiency of the system, not only in a steady cycle but also in a transient cycle. Following these adjustments, a DPF-plus-SCR system with the new catalytic material delivered 90 per cent conversions of NO x and particulate matter to N2 and CO2 respectively, in the JE05 test cycle.

In addition, a new concept, a miniaturized ‘urea-SCR with DPF function system’ was proposed and tested, which delivered 90 per cent NO x conversion rates and 90 per cent reductions in particulate matter emissions in the JE05 test cycle.
A Dynamic Model for Posttraumatic Stress Disorder Among U.S. Troops in Operation Iraqi Freedom
Authors: Atkinson Michael P. , Guetz Adam , Wein Lawrence M.
Published: July 2009

We develop a dynamic model in which Operation Iraqi Freedom (OIF) servicemembers incur a random amount of combat stress during each month of deployment, develop posttraumatic stress disorder (PTSD) if their cumulative stress exceeds a servicemember-specific threshold, and then develop symptoms of PTSD after an additional time lag. Using Department of Defense deployment data and Mental Health Advisory Team PTSD survey data to calibrate the model, we predict that—because of the long time lags and the fact that some surveyed servicemembers experience additional combat after being surveyed—the fraction of Army soldiers and Marines who eventually suffer from PTSD will be approximately twice as large as in the raw survey data. We cannot put a confidence interval around this estimate, but there is considerable uncertainty (perhaps ±30%). The estimated PTSD rate translates into ≈300,000 PTSD cases among all Army soldiers and Marines in OIF, with ≈20,000 new cases each year the war is prolonged. The heterogeneity of threshold levels among servicemembers suggests that although multiple deployments raise an individual's risk of PTSD, in aggregate, multiple deployments lower the total number of PTSD cases by ≈30% relative to a hypothetical case in which the war was fought with many more servicemembers (i.e., a draft) deploying only once. The time lag dynamics suggest that, in aggregate, reserve servicemembers show symptoms ≈1–2 years before active servicemembers and predict that >75% of OIF servicemembers who self-reported symptoms during their second deployment were exposed to the PTSD-generating stress during their first deployment.
Organization of Hyaluronan and Versican in the Extracellular Matrix of Human Fibroblasts Treated With the Viral Mimetic Poly I:C
Authors: Evanko Stephen P. , Potter-Perigo Susan , Johnson Pamela Y. , Wight Thomas N.
Published: July 2009

We have examined structural details of hyaluronan- and versican-rich peri-cellular matrices in human lung fibroblasts, as well as fixation effects after treatment with the viral mimetic, poly I:C. Lateral aggregation of hyaluronan chains was promoted by acid-ethanol-formalin fixation compared with a network appearance with formalin alone. However, hyaluronidase-sensitive cable structures were seen in live cells, suggesting that they are not a fixation artifact. With all fixatives, versican and hyaluronan probes bound alternately along strands extending from the plasma membrane. However, a yellow colocalization signal required aggregation/overlap of several hyaluronan/versican strands and was more pronounced after acid-ethanol-formalin fixation. In addition to the main cell surface, hyaluronan and versican were also associated with fine actin-positive membrane protrusions, retraction fibers, and surface blebs. After wounding plus treatment with poly I:C, cells displayed larger hyaluronan coats and cable-like structures, as well as more membrane protrusions. However, treated cells did not migrate and had increased stress fibers compared with control wounded cells. Deposition of hyaluronan into cable-like structures in response to poly I:C was diminished but still apparent following actin filament disruption with cytochalasin D, suggesting that the protrusions only partially facilitate cable formation. As seen by scanning electron microscopy, the membrane protrusions may participate in poly I:C-induced binding of monocytes to hyaluronan- and versican-rich matrices. These results suggest that poly I:C-induced hyaluronan- and versican-rich cable structures are not deposited during migration, and that cellular protrusions partially contribute to hyaluronan cable formation. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Cellular Inflammatory Response to Flaviviruses in the Central Nervous System of a Primate Host
Authors: Maximova Olga A. , Faucette Lawrence J. , Ward Jerrold M. , Murphy Brian R. , Pletnev Alexander G.
Published: July 2009

Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus, and St. Louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. Flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. Development of safe and effective live-virus vaccines against neurotropic flavivirus infections demands a detailed knowledge of their neuropathogenesis in a primate host that is evolutionarily close to humans. Here, we used computerized morphometric analysis to quantitatively assess the cellular inflammatory responses in the central nervous system (CNS) of rhesus monkeys infected with three antigenically divergent attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of microglial activation, trafficking of T and B cells, and changes in T cell subsets within the CNS define unique phenotypic signatures for each of the three viruses. Our results provide a benchmark for investigation of cellular inflammatory responses induced by attenuated flaviviruses in the CNS of primate hosts and provide insight into the neuropathogenesis of flavivirus encephalitis that might guide the development of safe and effective live-virus vaccines.
Rational maps in real algebraic geometry
Authors: Kucharz Wojciech
Published: July 2009

The paper deals with rational maps between real algebraic sets. We are interested in the rational maps which extend to continuous maps defined on the entire source space. In particular, we prove that every continuous map between unit spheres is homotopic to a rational map of such a type. We also establish connections with algebraic cycles and vector bundles.
Fatigue to Fracture: An Informative, Fast, and Reliable Approach for Assessing Medical Implant Durability
Authors: Gong X.-Y. , Chwirut D. J. , Mitchell M. R. , Choules B. D.
Published: July 2009

This paper compares the differences between the “test to success” and “test to fracture” paradigms for medical implant durability assessment. It recognizes that test to success can be one of the tests within test to fracture, in addition to a series of shorter cycle, higher force/deformation tests. In addition, by “testing to fracture,” one can validate the fatigue analysis capability, learn the consequences of in vitro fractures, and provide information that can either be used for product improvement or for clinicians to make life-saving decisions.
A New Technology of Recycling 100 % Reclaimed Asphalt Pavements
Authors: Do Huh Jung , Park Joo Young
Published: July 2009

Recycling of 100 % reclaimed asphalt pavement (RAP) without adding any virgin materials is a challenging task. Most of the present RAP-recycling technology is limited to use the 20 %–30 % RAP as a maximum content for wearing courses of asphalt pavements. The main goal of the existing recycling technology is focused to restore original properties of the straight asphalt pavement mixtures by using rejuvenators. Here, a new technology is introduced to use 100 % RAP-recycling by adding a specially developed polymer-modifier. The hot mix asphalt design is used to figure out the content of the modifier. Quality of the new recycled mixtures is excellent such that their properties are superior over the virgin straight asphalt mixtures. Excellent quality, maximum use of RAP, simple process, and competitive price will make this technology very attractive.
Study on Low-Temperature Cracking Performance of Asphalt Mortar Modified by an Aluminate Coupling Agent
Authors: Liu Shu-tang , Hou Feng , Cao Wei-dong , Liu Ying
Published: July 2009

The low-temperature performance properties of asphalt mortar modified by an aluminate coupling agent (ACA) were investigated and are reported in this paper. An orthogonal experiment design method was used, and the creep stiffness and m-value were adopted as the indicators to investigate the modifier effects of the filler-asphalt ratio, ACA, and stearic acid on the low-temperature performance of asphalt mortar. The influence of other factors on the high-temperature, anti-rutting performance and intermediate-temperature fatigue performance of asphalt mortar was also evaluated. Analysis indicated that ACA could improve significantly the low-temperature performance and intermediate-temperature fatigue performance of asphalt mortar but reduced the high-temperature performance. Asphalt mortar modified by a moderate filler-asphalt ratio, a significant amount of ACA, and stearic acid showed better low-temperature performance properties.
Prediction of In-Service Fatigue Life of Flexible Pavements Based on Accelerated Pavement Testing
Authors: Guo Runhua , Prozzi Jorge A.
Published: July 2009

Full-scale accelerated pavement testing (APT) is a supplement to typical laboratory procedures. As such, it leads to significant advances in practice and economic savings for the evaluation of new pavement configurations, stress level related factors, new materials, and design improvements. This type of testing closely simulates field conditions; however, it does not capture actual pavement performance because of the limited ability to address long-term phenomena. Therefore, to fully utilize the benefits of APT, there is a need for a methodology to predict the long-term performance of in-service pavement structures based on the generated test results in order to account for such differences. The bias correction factor (BCF) or bias correction functions should account for the quantifiable differences between the fatigue life of the pavement site under APT and the in-service conditions. The BCF represents an improvement of the currently used “shift factors” since they are more general and are based on laboratory testing or computer simulations. By applying the proposed methodology, APT performance results from a structure similar to an in-service structure can be used to perform four-point bending beam tests and structural analysis to obtain an accurate estimate of the necessary BCF to estimate in-service performance.
Buchbesprechungen
Authors: Voß Christian
Published: July 2009

Fremdes Europa? Selbstbilder und Europa-Vorstellungen in Bulgarien (18501945). Hrsg. von Petǎr PETROV, Katerina GEHL und Klaus ROTH. Berlin: LIT Verlag 2007, 366 S. ( Kulturgeschichtliche Perspektiven, 6) ISBN 978-3-8258-0793-1
curledEncodes the Drosophila Homolog of the Vertebrate Circadian Deadenylase Nocturnin
Authors: Grönke Sebastian , Bickmeyer Iris , Wunderlich Roman , Jäckle Herbert , Kühnlein Ronald P
Published: July 2009

Drosophila melanogaster curled, one of the first fly mutants described by T. H. Morgan >90 years ago, is the founding member of a series of curled wing phenotype mutants widely used as markers in fruit fly genetics. The expressivity of the wing phenotype is environmentally modulated, suggesting that the mutation affects the metabolic status of cells rather than a developmental control gene. However, the molecular identity of any of the curled wing marker mutant genes is still unknown. In a screen for starvation-responsive genes, we previously identified the single fly homolog of the vertebrate nocturnin genes, which encode cytoplasmic deadenylases that act in the post-transcriptional control of genes by poly(A) tail removal of target mRNAs prior to their degradation. Here we show that curled encodes Drosophila Nocturnin and that the gene is required at pupal stage for proper wing morphogenesis after eclosion of the fly. Despite the complex ontogenetic expression pattern of the gene, curled is not expressed in the developing wing, and wing-specific curled knockdown mediated by RNAi does not result in the curled wing phenotype, indicating a tissue-nonautonomous, systemic mode of curled gene function. Our study not only presents an entry point into the functional analysis of invertebrate nocturnins but also paves the way for the identification of the still elusive Nocturnin target mRNAs by genetic suppressor screens on the curled wing phenotype.
Quantitative Analysis of CPR Quality During In-Hospital Resuscitation of Older Children and Adolescents
Authors: Sutton Robert M. , Niles Dana , Nysaether Jon , Abella Benjamin S. , Arbogast Kristy B. , Nishisaki Akira , Maltese Matthew R. , Donoghue Aaron , Bishnoi Ram , Helfaer Mark A. , Myklebust Helge , Nadkarni Vinay
Published: July 2009

OBJECTIVE: Few data exist on pediatric cardiopulmonary resuscitation (CPR) quality. This study is the first to evaluate actual in-hospital pediatric CPR. We hypothesized that with bedside CPR training and corrective feedback, CPR quality can approach American Heart Association (AHA) targets.

PATIENTS AND METHODS: Using CPR recording/feedback defibrillators, quality of CPR was assessed for patients ≥8 years of age who suffered a cardiac arrest in the PICU or emergency department (ED). Before and during the study, a bedside CPR training program was initiated.

RESULTS: Between October 2006 and February 2008, twenty events in 18 patients met inclusion criteria and resulted in 36749 evaluable chest compressions (CCs) during 392.3 minutes of arrest. CCs were shallow (<38 mm or <1.5 in) in 27.2% (9998 of 36749), with excessive residual leaning force (≥2500 g) in 23.4% (8611 of 36749). Segmental analysis of the first 5 minutes of the events demonstrated that shallow CCs and excessive residual leaning force were less prevalent during the first 5 minutes. AHA targets were not achieved for CC rate in 62 (43.1%) of 144 segments, CC depth in 52 (36.1%) of 144 segments, and residual leaning force in 53 (36.8%) of 144 segments.

CONCLUSIONS: This prospective, observational study demonstrates feasibility of monitoring in-hospital pediatric CPR. Even with bedside CPR retraining and corrective audiovisual feedback, CPR quality frequently did not meet AHA targets. Importantly, no flow fraction target of 10% was achieved. Future studies should investigate novel educational methods and targeted feedback technologies.
13C-Sucrose Breath Test: Novel Use of a Noninvasive Biomarker of Environmental Gut Health
Authors: Ritchie Brett K. , Brewster David R. , Davidson Geoffrey P. , Tran Cuong D. , McNeil Yvette , Hawkes Joanna S. , Butler Ross N.
Published: July 2009

OBJECTIVE: Environmental enteropathy syndrome may compromise growth and predispose to infectious diseases in children in the developing world, including Australian Aboriginal children from remote communities of the Northern Territory. In this study, we described the use of a biomarker 13C-sucrose breath test (SBT) to measure enterocyte sucrase activity as a marker of small intestinal villus integrity and function.

METHODS: This was a hospital-based prospective case-control study of Aboriginal and non-Aboriginal children with and without acute diarrheal disease. Using the SBT, we compared 36 Aboriginal case subjects admitted to a hospital (18 diarrheal and 18 nondiarrheal disease), with 7 healthy non-Aboriginal control subjects. Intestinal permeability using the lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test was performed simultaneously with the SBT. The SBT results are expressed as a cumulative percentage of the dose recovered at 90 minutes.

RESULTS: Aboriginal children with acute diarrheal disease have a significantly decreased absorptive capacity, as determined by the SBT, with a mean of 1.9% compared with either Aboriginal children without diarrhea (4.1%) or non-Aboriginal (6.1%) control subjects. The mean L/R ratio in the diarrhea group was 31.8 compared with 11.4 in Aboriginal children without diarrhea. There was a significant inverse correlation between the SBT and the L/R ratio.

CONCLUSIONS: The SBT was able to discriminate among Aboriginal children with diarrhea, asymptomatic Aboriginal children with an underlying environmental enteropathy, and healthy non-Aboriginal controls. This test provides a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine and could be a valuable tool in evaluating the efficacy of interventions aimed at improving gut health.
Attending Physician Work Hours: Ethical Considerations and the Last Doctor Standing
Authors: Mercurio Mark R. , Peterec Steven M.
Published: July 2009

Based at least in part on concerns for patient safety and evidence that long shifts are associated with an increased risk of physician error, residents' and fellows' work hours have been strictly limited for the past several years. Little attention has been paid, however, to excessive attending physician shift duration, although there seems to be no reason to assume that this common practice poses any less risk to patients. Potential justifications for allowing attending physicians to work without hourly limits include physician autonomy, workforce shortages in certain communities or subspecialties, continuity of care, and financial considerations. None of these clearly justify the apparent increased risk to patients, with the exception in some settings of workforce shortage. In many hospital settings, the practice of allowing attending physicians to work with no limit on shift duration could pose an unnecessary risk to patients.
Nonlinear predictive control of an industrial slurry reactor
Authors: Fontes C. H. , Mendes M. J.
Published: July 2009

A nonlinear model predictive control (NMPC) is applied to a slurry polymerization stirred tank reactor for the production of high-density polyethylene. Its performance is examined to reach the required mean molecular weight and comonomer composition, together with the temperature setpoint. A complete phenomenological model including the microscale, the mesoscale and the macroscale levels was developed to represent the plant. The control algorithm comprises a neural dynamic model that uses a neural network structure with a feedforward topology. The algorithm implementation considers the optimization problem, the manipulated and controlled variables adopted and presents results for the regulatory and servo problems, including the possibility of dead time and multi-rate sampling in the controlled variables. The simulation results show the high performance of the NMPC algorithm based in a model for one-step ahead prediction only, and, at the same time, attests the strong difficulty to control polymer properties with dead time in their measurements.
Controle de sistemas lineares com comutação
Authors: Deaecto Grace S. , Geromel José C.
Published: July 2009

Este trabalho tem como objetivo o estudo de estabilidade de sistemas lineares com comutação sujeitos à perturbações impulsivas tendo em vista o projeto de controle via realimentação de estado com comutação. As condições obtidas são baseadas nas desigualdades de Lyapunov-Metzler, que asseguram a estabilidade mesmo quando o sistema evoluir sobre um modo deslizante. Estas desigualdades permitem levar em conta um custo garantido de desempenho. De forma a analisar a qualidade do resultado, um limitante inferior para o custo verdadeiro é determinado. A teoria desenvolvida é aplicada em um problema de controle H2 multiobjetivo com critérios possivelmente conflitantes. É mostrado que, neste contexto, o uso de controle com comutação fornece resultados melhores quando comparados com outros métodos encontrados na literatura. Exemplos acadêmicos são usados para ilustração.
Método da histerese por auto-ajuste para minimização de esforço de controle no separador submarino VASPS
Authors: Melo André V. de , Serapião Adriane B. S. , Mendes José R. P.
Published: July 2009

Neste trabalho apresenta-se o estudo do desenvolvimento de um controlador não-tradicional baseado em um mecanismo de histerese com auto-ajuste para o controle de nível de líquido de um sistema de separação e bombeio submarino conhecido como VASPS. O controlador desenvolvido gera sinais enviados para a bomba centrífuga submersa para controlar o nível de líquido no tanque do separador, evitando que ele atinja valores muito baixos que poderiam danificar a bomba ou valores muito altos que reduziriam a eficiência da separação líquido/gás. Os sinais de controle gerados pelo controlador visam solicitar a bomba o mínimo possível de modo a evitar o seu desgaste e falhas prematuras. Nas simulações, o controlador desenvolvido foi testado sob grandes variações nas condições de operação, tais como golfadas, produzindo resultados bastante satisfatórios e promissores.
Security constrained optimal active power flow via network model and interior point method
Authors: Azevedo Anibal T. de , Castro Carlos A. , Oliveira Aurelio R.L. , Soares Secundino
Published: July 2009

This paper presents a new formulation for the security constrained optimal active power flow problem which enables the representation of three basic constraints: branch outage, generator outage and multiple equipment congestion. It consists of a network model with additional linear equality and inequality constraints and quadratic separable objective function, which is efficiently solved by a predictor-corrector interior point method. Sparsity techniques are used to exploit the matricial structure of the problem.Case studies with a 3,535-bus and a 4,238-branch Brazilian power system are presented and discussed, to demonstrate that the proposed model can be efficiently solved by an interior point method, providing security constrained solutions in a reasonable time.
The Role of Src in Solid Tumors
Authors: Wheeler Deric L. , Iida Mari , Dunn Emily F.
Published: July 2009

The proto-oncogene c-Src (Src) encodes a nonreceptor tyrosine kinase whose expression and activity are correlated with advanced malignancy and poor prognosis in a variety of human cancers. Nine additional enzymes with homology to Src have been identified and collectively are referred to as Src family kinases (SFKs). Together, SFKs represent the largest family of nonreceptor tyrosine kinases and interact directly with receptor tyrosine kinases, G-protein-coupled receptors, steroid receptors, signal transducers and activators of transcription, and molecules involved in cell adhesion and migration. These interactions lead to a diverse array of biological functions including proliferation, cell growth, differentiation, cell shape, motility, migration, angiogenesis, and survival. Studies investigating mutational activation of Src in human cancers suggest that this may be a rare event and that wild-type Src is weakly oncogenic. Thus, the role of Src in the development and progression of human cancer remains unclear. Recently, it was suggested that increased SFK protein levels and, more importantly, SFK tyrosine kinase activity are linked to cancer progression and metastatic disease by facilitating the action of other signaling proteins. This accumulating body of evidence indicates that SFKs may represent a promising therapeutic target for the treatment of solid tumors. This review discusses the role of SFKs in solid tumors and the recent therapeutic advances aimed at targeting this family of tyrosine kinases in cancer.
The restoration of parasites, parasitoids, and pathogens to heathland communities
Authors: Henson Kate S. E. , Craze Paul G. , Memmott Jane
Published: July 2009

Higher trophic level species such as parasites, parasitoids, and pathogens are frequently ignored in community studies, despite playing key roles in the structure, function, and stability of ecological communities. Furthermore, such species are typically among the last in a community to reestablish due to their reliance upon lower trophic level resources and a requirement for persistent, stable ecological conditions. Consequently their presence alone can be indicative of healthy ecosystems. Using replicated, quantitative food webs we studied the impacts of a restoration treatment upon the interactions of a tri‐trophic community consisting of plants, their bumble bee pollinators, and the parasites, parasitoids, and pathogens of the bumble bees at heathland sites. We found the lower trophic levels of the community successfully reinstated at restored relative to control sites. However the abundance, load per host, prevalence of parasitism, prevalence of superparasitism, and host range of a key dipteran parasitoid of the family Conopidae were all significantly reduced in restored heathlands. Potential causes for this incomplete reestablishment at restored sites include the lag in floral resources due to differences in floral species composition, and the reduced ability of this parasitoid species in accessing host resources relative to other natural enemy species present in these communities. Moreover the incomplete reinstatement of the natural enemy community was found to significantly reduce levels of network vulnerability (a measure of how vulnerable prey is to being consumed) at restored sites relative to ancient, control networks.
Edaphic quality and plant–pathogen interactions: effects of soil calcium on fungal infection of a serpentine flax
Authors: Springer Yuri P.
Published: July 2009

Spatial variation in the frequency and outcome of interspecific interactions is thought to play a central role in shaping geographic patterns of biodiversity. Previous empirical studies and modeling exercises suggest that negative species interactions should occur with greater frequency and intensity in high‐quality/low‐stress environments. I tested this hypothesis through a four‐year epidemiological study of interactions between the plant Hesperolinon californicum and the pathogenic rust fungus Melampsora lini. By virtue of its association with serpentine soils, H. californicum is exposed to edaphic conditions that are stressful to most plants. Notable among these is the low availability of calcium, an element that plays critically important roles in the immune responses of plants to attacking pathogens. As a serpentine generalist, however, H. californicum grows in soils with a wide range of calcium concentrations, and this should lead to differences in the frequency and/or severity of rust infection among host populations. I investigated geographic variation in disease pressure by conducting annual surveys in 16 populations spanning the host's distribution and representing a range of soil calcium concentrations. Results indicated that plants growing in more stressful low‐calcium soils experienced higher rates of rust infection, suggesting that soil calcium may modulate host susceptibility in a manner opposite to that predicted by the a priori hypothesis. Epidemiological surveys further revealed a latitudinal cline in disease prevalence, with high infection rates in northern host populations decreasing gradually toward the south. Studies of the fitness effects of disease demonstrated that rust infection caused significant reductions in host survival and fecundity, and there was evidence of a demographic feedback between infection prevalence and host density across survey years.