bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin
Authors: Belyanskaya Larisa L , Marti Thomas M , Hopkins-Donaldson Sally , Kurtz Stefanie , Felley-Bosco Emanuela , Stahel Rolf A 
Published: October 2007

AbstractBackgroundThe incidence of malignant pleural mesothelioma (MPM) is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1) or TRAIL-R2 has been thought to be a promising cancer therapy.ResultsWe have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab) and TRAIL-R2 (Lexatumumab) and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine.ConclusionOur results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.
The contribution of peroxynitrite generation in HIV replication in human primary macrophages
Authors: Aquaro Stefano , Muscoli Carolina , Ranazzi Alessandro , Pollicita Michela , Granato Teresa , Masuelli Laura , Modesti Andrea , Perno Carlo-Federico , Mollace Vincenzo 
Published: October 2007

AbstractBackgroundMonocytes/Macrophages (M/M) play a pivotal role as a source of virus during the whole course of HIV-1 infection. Enhanced oxidative stress is involved in the pathogenesis of HIV-1 infection. HIV-1 regulatory proteins induce a reduction of the expression and the activity of MnSOD, the mitochondrial isoform leading to a sustained generation of superoxide anions and peroxynitrite that represent important mediators of HIV-1 replication in M/M. MnTBAP (Mn(III)tetrakis(4-benzoic acid)porphrin chloride), a synthetic peroxynitrite decomposition catalyst, reduced oxidative stress subsequent to peroxynitrite generation.ResultsVirus production was assessed by p24 ELISA, western blot, and electron microscopy during treatment with MnTBAP. MnTBAP treatment showed a reduction of HIV-1 replication in both acutely and chronically infected M/M: 99% and 90% inhibition of p24 released in supernatants compared to controls, respectively. Maturation of p55 and p24 was strongly inhibited by MnTBAP in both acutely and chronically infected M/M. EC50and EC90are 3.7 (± 0.05) μM and 19.5 (± 0.5) μM, in acutely infected M/M; 6.3 (± 0.003) μM and 30 (± 0.6) μM, in chronically infected M/M. In acutely infected peripheral blood limphocytes (PBL), EC50and EC90are 7.4 (± 0.06) μM and of 21.3 (± 0.6) μM, respectively. Treatment of acutely-infected M/M with MnTBAP inhibited the elevated levels of malonildialdehyde (MDA) together with the nitrotyrosine staining observed during HIV-1 replication. MnTBAP strongly reduced HIV-1 particles in infected M/M, as shown by electron microscopy. Moreover, in presence of MnTBAP, HIV-1 infectivity was reduced of about 1 log compared to control.ConclusionResults support the role of superoxide anions in HIV-1 replication in M/M and suggest that MnTBAP may counteract HIV-1 replication in combination with other antiretroviral treatments.
Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status
Authors: Fehm Tanja , Becker Sven , Duerr-Stoerzer Silke , Sotlar Karl , Mueller Volkmar , Wallwiener Diethelm , Lane Nancy , Solomayer Erich , Uhr Jonathan 
Published: October 2007

Abstract
Introduction
At the time when metastatic disease is identified, assessment of human epidermal growth factor receptor (HER)2 status might help to optimize treatment decisions if HER2 status was not determined at first diagnosis and if HER2 positivity has been acquired during disease progression. Within this context, determination of serum HER2 or evaluation of HER2 status in circulating tumor cells (CTCs) may be of clinical relevance because metastatic tissue may be difficult to obtain for analysis as a result of its localization. The aim of this study was therefore to determine the HER2 status in serum and corresponding CTCs in patients with metastatic breast cancer whose primary tumors were HER2 negative or of unknown HER2 status.

Methods
Blood samples were obtained from 77 metastatic breast cancer patients with negative (n = 44) or unknown (n = 33) HER2 status. Serum HER2 was determined using a commercial HER2/neu ELISA kit. CTCs were detected by slide-based assay using immunomagnetic enrichment and characterized by phenotyping and genotyping. Alternatively, a commercial kit, based on RT-PCR, was used to detect and characterize CTCs.

Results
Twenty out of 77 patients with metastatic disease had elevated serum levels of HER2. Blood samples could be analyzed for the presence of CTCs in 67 patients. Eight out of 21 patients with detectable CTCs exhibited HER2 amplification. Twenty-three out of 77 patients were HER2 positive using at least one method. Concordance between HER2 status of CTCs and serum HER2 was observed in 15 of 21 patients (71%). In six patients conflicting results were obtained. Three patients with elevated serum HER2 status had HER2-negative CTCs, whereas three patients with HER2-positive CTCs had normal serum HER2 levels.

Conclusion
A subgroup of patients with initially negative or unknown HER2 status can have elevated serum HER2 levels and/or HER2-positive CTCs at the time of development of metastatic disease. Although only a small number of patients were studied, our observations are of clinical relevance because, currently, these patients do not have access to HER2-targeted therapy.
Assessment of thermal comfort in a car cabin with sky-roof
Authors: Cascetta F , Musto M 
Published: October 2007

The need to address the problem of thermal comfort inside a car cabin is becoming more significant for the automobile industry especially as recent developments in vehicle styling entail an increase in the glazed surfaces of the car, in particular for sky-roof models. The extended glazed surfaces produce an increase in radiative thermal loads on the area involved and so greater attention is being given to the enhancement and upgrading of the heating, ventilation, and air-conditioning system capacity, and efforts are being made to find solutions to the problem of thermal comfort inside the cabin. This paper is a first experimental study which focuses on assessing the performance of four different types of special laminated sky-roof (with a low-emissivity internal surface). A performance comparison between special and traditional sky-roofs has been carried out in a field test (on the road) in summer conditions. The main results show that the special sky-roofs allow the temperature inside the car cabin to be reduced.
Some aspects concerning the combination of downsizing with turbocharging, variable compression ratio, and variable intake valve lift
Authors: Clenci A C , Descombes G , Podevin P , Hara V 
Published: October 2007

The inefficient running of the spark ignition engine at part loads due to the load control method but, mostly, their major weighting in the vehicle's operation time justifies the interest in the technical solutions, which act in this particular operating range. These drawbacks encountered at low part loads are even more amplified when considering larger engines. For instance, it is well known that, at the same engine load, a larger engine is more throttled than a smaller engine; therefore the concerns are the higher pumping work, the lower real compression ratio, and the overall mechanical efficiency, which is also lower. One solution is a reduction in the displacement without affecting the power output. This is what is now commonly known as the downsizing technique. The combination of downsizing and uploading an engine has been known for a long time. However, the conversion, in an acceptable way, of this potential to actual practice is very challenging. On the one hand, the degree of the downsizing is related to the boost pressure. In order to cope with the knocking phenomenon, the downsized high-pressure turbocharged gasoline engine requires a lower volumetric compression ratio that limits the efficiency on part loads. Therefore, the degree of the downsizing has been limited and, thus, the possible fuel consumption reduction has not yet been fully achieved. On the other hand, other problems are encountered when considering a downsized turbocharged gasoline engine: insufficient low-end torque, poor starting performance, and turbo lag. In order to solve these problems an effective combination of the downsized turbocharged gasoline engine with additional technologies is needed. Thus, the paper will present a so-called adaptive thermal engine, which has at the same time a variable compression ratio and a variable intake valve lift. It will then be demonstrated that it is highly suitable for turbocharging, thus resulting in a high downsizing factor.
The deformity index as a predictor of final radiological outcome in Perthes’ disease
Authors: Nelson D. , Zenios M. , Ward K. , Ramachandran M. , Little D. G. 
Published: October 2007

The deformity index is a new radiological measurement of the degree of deformity of the femoral head in unilateral Perthes’ disease. Its values represent a continuous outcome measure of deformity incorporating changes in femoral epiphyseal height and width compared with the unaffected side. The sphericity of the femoral head in 30 radiographs (ten normal and 20 from patients with Perthes’ disease) were rated blindly as normal, mild, moderate or severe by three observers. Further blinded measurements of the deformity index were made on two further occasions with intervals of one month. There was good agreement between the deformity index score and the subjective grading of deformity. Intra- and interobserver agreement for the deformity index was high. The intraobserver intraclass correlation coefficient for each observer was 0.98, 0.99 and 0.97, respectively, while the interobserver intraclass correlation coefficient was 0.98 for the first and 0.97 for the second set of calculations. We also reviewed retrospectively 96 radiographs of children with Perthes’ disease, who were part of a multicentre trial which followed them to skeletal maturity. We found that the deformity index at two years correlated well with the Stulberg grading at skeletal maturity. A deformity index value above 0.3 was associated with the development of an aspherical femoral head. Using a deformity index value of 0.3 to divide groups for risk gives a sensitivity of 80% and specificity of 81% for predicting a Stulberg grade of III or IV. We conclude that the deformity index at two years is a valid and reliable radiological outcome measure in unilateral Perthes’ disease.
Aneurysmal bone cysts of the distal fibula in children
Authors: Lampasi M. , Magnani M. , Donzelli O. 
Published: October 2007

We report the results of the treatment of nine children with an aneurysmal bone cyst of the distal fibula (seven cysts were juxtaphyseal, and two metaphyseal). The mean age of the children was 10 years and 3 months (7 years and 4 months to 12 years and 9 months). All had open physes. All cysts were active and in seven cases substituted and expanded the entire width of the bone (type-2 lesions). The mean longitudinal extension was 5.7 cm (3 to 10). The presenting symptoms were pain, swelling and pathological fracture. Moderate fibular shortening was evident in one patient. In six patients curettage was performed, using phenol as adjuvant in three. Three with juxtaphyseal lesions underwent resection. A graft from the contralateral fibula (one case) and allografts (two cases) were positioned at the edge of the physis for reconstruction. The mean follow-up was 11.6 years (3.1 to 27.5). There was no recurrence. At the final follow-up there was no significant difference in the American Orthopaedic Foot and Ankle Society scores (excellent/good in all cases) and in growth disturbance, alignment, stability and bone reconstitution, but in the resection group the number of operations, including removal of hardware, complications (two minor) and time of immobilisation/orthosis, were increased. Movement of the ankle was restricted in one patient. The potential risks in the management of these lesions include recurrence, physeal injury, instability of the ankle and hardware and graft complications. Although resection is effective it should be reserved for aggressive or recurrent juxtaphyseal lesions.
Are occult fractures of the hip and pelvic ring mutually exclusive?
Authors: Lakshmanan P. , Sharma A. , Lyons K. , Peehal J. P. 
Published: October 2007

We have evaluated retrospectively the relationship of bony injuries seen on 106 consecutive MR scans in elderly patients of a mean age of 81.4 years (67 to 101) who were unable to bear weight after a low-energy injury. There were no visible fractures on plain radiographs of the hip but eight patients (7.5%) had fractures of the pubic ramus. In 43 patients (40.5%) MRI revealed a fracture of the femoral neck and in 26 (24.5%) there was a fracture of a pubic ramus. In 17 patients (16%) MRI showed an occult sacral fracture and all of these had a fracture of the pubic ramus. No patient with a fracture of the femoral neck had an associated fracture of the pelvic ring or vice versa. Occult fracture of the hip and of the pelvic ring appear to be mutually exclusive and if an acute fracture of the pubic ramus is diagnosed radiologically further investigations are not needed to rule out an occult fracture of the hip.
Osteoarthritis of the costovertebral joints
Authors: Sales J. R. , Beals R. K. , Hart R. A. 
Published: October 2007

Thoracic back pain caused by osteoarthritis of a single costovertebral joint is a poorly recognised condition. We report a series of five patients who were successfully treated by resection arthroplasty of this joint. Each had received a preliminary image-guided injection of local anaesthetic and steroid into the joint to confirm it as the source of pain. The surgical technique is described. There were no complications. The pain improved from a mean of 7.0 (6 to 8) on a visual analogue scale to 2.0 (0 to 4) post-operatively. The final post-operative Oswestry disability index was a mean of 19.4 (9 to 38). Isolated osteoarthritis of a costovertebral joint is a rare but treatable cause of thoracic back pain. It is possible to obtain excellent short- and intermediate-term relief from pain with resection arthroplasty in appropriately selected patients.
Enantioselective synthesis via sparteine-induced asymmetric deprotonation
Authors: Hoppe D. , Hintze F. , Tebben P. , Paetow M. , Ahrens H. , Schwerdtfeger J. , Sommerfeld P. , Haller J. , Guarnieri W. , Kolczewski S. , Hense T. , Hoppe I. 
Published: October 2007

Abstract
Biphasic Effect of Prostaglandin E2 on Osteoclast Formation in Spleen Cell Cultures: Role of the EP2 Receptor
Authors: Ono Katsuhiro , Kaneko Hironori , Choudhary Shilpa , Pilbeam Carol C , Lorenzo Joseph A , Akatsu Takuhiko , Kugai Nobuo , Raisz Lawrence G 
Published: October 2007

Abstract
We examined the effect of PGE2 on OC formation from spleen cells treated with M-CSF and RANKL. PGE2 decreased OC number at 5–6 days of culture and increased OC number, size, and resorptive activity at 7–8 days. A selective EP2 receptor agonist mimicked these effects. Deletion of the EP2 receptor or depletion of T-cells abrogated the increase in OC number.
Introduction: Prostaglandin E2 (PGE2) has been reported to increase osteoclast (OC) number in spleen cells cultured with RANKL and macrophage-colony-stimulating factor (M-CSF). In this study, we examined the time course of PGE2 effects on spleen cells cultured with RANKL and M-CSF. We then investigated which PGE receptors and cell types were involved in these effects.
Materials and Methods: Spleen cells were cultured from wildtype C57BL/6 mice and EP2 or EP4 receptor-deficient (−/−) and wildtype (+/+) mice on a mixed genetic background. Spleen cells were cultured with M-CSF and RANKL for 5–9 days with or without PGE2 or selective agonists for the four PGE2 receptors (EP1A, EP2A, EP3A, or EP4A). Some cultures were performed using T-cell-depleted spleen cells. OC number and size were quantitated. OC apoptosis and pit formation were measured at 7 or 8 days.
Results: PGE2 decreased the number of OCs formed in the presence of RANKL and M-CSF at 5–6 days of culture and increased OC number at 8–9 days compared with cultures without PGE2. PGE2 also increased OC size at 7 and 8 days, decreased apoptosis of OC at 7 days, and increased pit formation at 8 days. EP1A or EP4A had no effect on OC. EP3A decreased OC number. EP2A mimicked effect of PGE2. EP2−/− spleen cells showed no increase in OC number in response to PGE2, whereas deletion of EP4 had no effect. Depletion of T-cells abrogated the late increase of OC number.
Conclusions: We conclude that PGE2 has an initial inhibitory effect on OC formation in spleen cell cultures, possibly mediated by both EP2 and EP3 receptors, and a later stimulatory effect, mediated by the EP2 receptor, possibly acting on T-cells.
Understanding Low-Sloped Roofs Under Hurricane Charley From Field to Practice
Authors: Baskaran A. , Molleti S. , Roodvoets D. 
Published: October 2007

Abstract
Natural wind hazard damages have been dramatic in recent years, incurring losses of life and property around the world. Wind-induced failure is one of the major contributors to insurance claims, and it is rising. To address these growing concerns, RICOWI (Roofing Industry Committee on Weather Issues) started a Wind Investigation Program (WIP) to investigate the field performance of roofing assemblies after major windstorm events and to factually describe roof assembly performance and modes of damage. As part of this program, Hurricane Charley, which hit Punta Gorda, FL, with winds exceeding 140 mph (63 m/s), was investigated. This paper mainly focuses on the field performance of the low-sloped roofs with three important parameters that were found critical in the failure of the roofing systems, namely, • Effect of corner wind suction, • Effect of parapet, • Effect of internal pressure. For each scenario, first scientific documentation was presented, and then how the field observation reflects the fundamental principles were discussed. Based on this exercise, correlations are developed for roof wind design. In addition, wind design data from the North American codes of practice are also calculated and compared to show the impact of science and field observation on durable roof design. With these illustrations, this paper offers recommendations to advance the roof system design for hurricane-prone regions.
Experimental Study of Phase-Transformation Effects on Relative Permeabilities in Fractures
Authors: Chen Chih-Ying , Li Kewen , Horne Roland N. 
Published: October 2007

Summary
Phase transformation affects multiphase flow in geothermal and gas/condensate reservoirs owing to the same substance occurring in different phases. These effects change the phase behavior and the flow characteristics. The goals of this research were to compare the flow behavior and relative permeability differences between two-phase flow with and without phase-transformation effects in smooth-walled and rough-walled fractures. During this research, an experimental apparatus was built to capture the unstable nature of the two-phase flow in fractures and to display the flow structures in real time. Two-phase-flow experiments with phase-transformation effects (steam/water flow) and without phase-transformation effects (nitrogen/water flow) were conducted. The porous-medium approach was used to calculate two-phase relative permeabilities. From the results in this study, steam/water relative permeabilities are different from nitrogen/water relative permeabilities. The enhanced steam-phase relative permeability is caused by the effects of phase transformation. This shows consistency with some earlier studies in porous media. The nitrogen/water relative permeability is described most appropriately by using the viscous coupling model. However, steam/water flow in the rough-walled fracture, which is coupled with strong phase-transformation effects, seems to be represented better by Brooks-Corey relative permeability functions for fractured media (λ→∞). The results from this study suggest that relative permeabilities accounting for phase-transformation effects must be used in simulations of geothermal and solution-gas reservoirs to represent two-phase interactions adequately.
Simulation of Miscible Flow Including Bypassed Oil and Dispersion Control
Authors: Coats K. H. , Thomas L. K. , Pierson R. G. 
Published: October 2007

Summary
This paper describes methods for the simulation of first-contact miscible (FCM), multicontact miscible, and vaporizing gas drive, which include logic to account for bypassed oil. Dispersion control is included for FCM cases.
First-contact miscibility may be simulated in fully compositional mode with any number of components, Nc, or in two-pseudocomponent equation-of-state (EOS) mode. Pseudoization is performed internally in the model so that hydrocarbon-fluid density and viscosity, as functions of pressure and composition, are the same as calculated in Nc-component mode. Bypassed oil and dispersion control are based on an extension of Koval's (1963) method. This procedure allows the user to adjust the fractional flow of oil during upscaling or history matching to match fine-grid or historical results. This feature can be used to simulate both water-alternating-gas (WAG) and tertiary-recovery projects where solvent injection is preceded by a water-injection period.
Example cases are included to illustrate the techniques presented in this paper. Results are also given on the efficiencies of the algorithms.