bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modifications of commercial pressurized solvent extraction (PSE) systems for the analysis of polychlorinated biphenyls in avian whole blood and serum
Authors: Haskins Stacey D. , Harrison Christina M. , Kelly David G. , Weir Ron D. 
Published: January 2011

The present study considers simple and cost-effective modifications to commercial pressurised solvent extraction cells to extract polychlorinated biphenyls (PCBs) from avian blood and serum. Blood and serum samples of mass 0.2 g were examined. Such masses are consistent with those which may be obtained from many avian species without sacrificing individuals or compromising breeding and (or) migratory success. Extraction vessels are modified by the use of Teflon inserts, which are readily fabricated at low cost. These inserts reduce internal cell volume and surface area. Thus, background contamination is reduced whilst extraction and rinse solvent is used more effectively to afford a small extract volume. Packing of the cell void with sodium sulfate and florisil achieves in situ sample dehydration and lipid removal. When combined with extraction concentration and large volume injection gas chromatography – ion-trap mass spectrometry (LVI-GC–ITMS), the extraction method is capable of polychlorinated biphenyl analysis without post-extraction clean-up. Validation was accomplished using commercial chicken whole blood and serum, and PCB congeners 28, 77, 105, 126, 153, 167, 170, 180, 183, and 194. Surrogate corrected recoveries in the range of 75% to120% for whole blood and 80% to115% for serum were obtained. Detection limits were in the range of 0.01 to 0.22 ng g–1 for whole blood and 0.03 to 0.45 ng g–1 for serum. The relative standard deviations for all congeners investigated were better than 15%.
Synchronous dataflow scenarios
Authors: Geilen Marc 
Published: January 2011

The Synchronous Dataflow (SDF) model of computation by Lee and Messerschmitt has become popular for modeling concurrent applications on a multiprocessor platform. It is used to obtain a guaranteed, predictable performance. The model, on the other hand, is quite restrictive in its expressivity, making it less applicable to many modern, more dynamic applications. A common technique to deal with dynamic behavior is to consider different scenarios in separation. This analysis is, however, currently limited mainly to sequential applications.
In this article, we present a new analysis approach that allows analysis of synchronous dataflow models across different scenarios of operation. The dataflow graphs corresponding to the different scenarios can be completely different. Execution times, consumption and production rates and the structure of the SDF may change. Our technique allows to derive or prove worst-case performance guarantees of the resulting model and as such extends the model-driven approach to designing predictable systems to significantly more dynamic applications and platforms. The approach is illustrated with three MP3 and MPEG-4 related case studies.
Tightening the bounds on feasible preemptions
Authors: Ramaprasad Harini , Mueller Frank 
Published: January 2011

Data caches are an increasingly important architectural feature in most modern computer systems. They help bridge the gap between processor speeds and memory access times. One inherent difficulty of using data caches in a real-time system is the unpredictability of memory accesses, which makes it difficult to calculate worst-case execution times (WCETs) of real-time tasks.
While cache analysis for single real-time tasks has been the focus of much research in the past, bounding the preemption delay in a multitask preemptive environment is a challenging problem, particularly for data caches.
This article makes multiple contributions in the context of independent, periodic tasks with deadlines less than or equal to their periods executing on a single processor.
1) For every task, we derive data cache reference patterns for all scalar and nonscalar references. These patterns are used to derive an upper bound on the WCET of real-time tasks.
2) We show that, when considering cache preemption effects, the critical instant does not occur upon simultaneous release of all tasks. We provide results for task sets with phase differences to prove our claim.

3) We develop a method to calculate tight upper bounds on the maximum number of possible preemptions for
each job
of a task and, considering the worst-case placement of these preemption points, derive a much tighter bound on its WCET. We provide results using both static-and dynamic-priority schemes.

Our results show significant improvements in the bounds derived. We achieve up to an order of magnitude improvement over two prior methods and up to half an order of magnitude over a third prior method for the
number of preemptions
, the
WCET
and the
response time
of a task. Consideration of the best-case and worst-case execution times of higher-priority jobs enables these improvements.
Phase I Study of E7820, an Oral Inhibitor of Integrin α-2 Expression with Antiangiogenic Properties, in Patients with Advanced Malignancies
Authors: Mita Monica , Kelly Kevin R. , Mita Alain , Ricart Alejandro D. , Romero Ofelia , Tolcher Anthony , Hook Laurel , Okereke Chukwuemeka , Krivelevich Ilya , Rossignol Daniel P. , Giles Francis J. , Rowinsky Eric K. , Takimoto Chris 
Published: January 2011

Abstract
Purpose: This phase I study was conducted to characterize the safety profile, pharmacokinetics, pharmacodynamics, dose-limiting toxicity (DLT), and the maximum-tolerated dose of E7820, a novel oral sulfonamide derivative with antiangiogenic properties, when administered to patients with advanced solid malignancies.
Patients and Methods: Patients received single daily doses of E7820 orally for 28 days in cycle 1, followed by a 7-day no-treatment period, after which time-uninterrupted daily dosing ensued. The starting dose of E7820 was 10 mg/d, which was increased to 20, 40, 70, 100, and 200 mg/d in cohorts of new patients.
Results: Thirty-seven patients [21 male; median age 65 (40–82] were enrolled. At 100 mg/d, 1 patient experienced a DLT consisting of grade 3 neutropenia, thrombocytopenia, and elevated liver enzymes. At the 200-mg dose level, 2 patients experienced grade 4 thrombocytopenia and neutropenia. No partial or complete responses were observed; 8 patients had stable disease (≥4 months), including 5 patients with protracted stable disease exceeding 6 months. Mean time to maximum plasma concentration values ranged from 1 to 12 hours, whereas mean terminal half-life values ranged from 5.6 to 8.6 hours. Flow cytometric analysis of platelet integrin α-2 expression showed a sustained greater than 50% decrease beyond day 28 in 3 of 4 patients at 200 mg, whereas moderate (&lt;30%) decreases were observed at 70- and 100-mg dose levels.
Conclusions: The recommended phase II dose of E7820 is 100 mg/d, based on a fasting schedule. E7820 downregulates integrin α-2 expression in surrogate tissues (platelets) and is associated with stable disease in a wide variety of heavily pretreated malignancies. Clin Cancer Res; 17(1); 193–200. ©2011 AACR.
Frequent hSNF5/INI1 Germline Mutations in Patients with Rhabdoid Tumor
Authors: Bourdeaut Franck , Lequin Delphine , Brugières Laurence , Reynaud Stéphanie , Dufour Christelle , Doz François , André Nicolas , Stephan Jean-Louis , Pérel Yves , Oberlin Odile , Orbach Daniel , Bergeron Christophe , Rialland Xavier , Fréneaux Paul , Ranchere Dominique , Figarella-Branger Dominique , Audry Georges , Puget Stéphanie , Evans D. Gareth , Pinas Joan Carles Ferreres , Capra Valeria , Mosseri Véronique , Coupier Isabelle , Gauthier-Villars Marion , Pierron Gaëlle , Delattre Olivier 
Published: January 2011

Abstract
Purpose: Germline hSNF5/INI1 mutations are responsible for hereditary cases of rhabdoid tumors (RT) that constitute the rhabdoid predisposition syndrome (RPS). Our study provides the first precise overview of the prevalence of RPS within a large cohort of RT.
Experimental Design: hSNF5/INI1 coding exons were investigated by sequencing and by multiplex ligation-dependent probe amplification.
Results: Seventy-four constitutional DNAs from 115 apparently sporadic RT were analyzed from 1999 to 2009. Germline mutations were found in 26 patients (35%). Data from 9 individuals from 5 RPS families (siblings) were also studied. The median age at diagnosis was much lower (6 months) in patients with germline mutation (P &lt; 0.01) than in patients without (18 months). Nevertheless, 7 of 35 patients with germline mutation (20%) developed the disease after 2 years of age. The mutation could be detected in only 1 parent whereas germline blood DNA was wild type in the 20 other parent pairs, therefore indicating the very high proportion of germ-cell mosaicism or of de novo mutations in RPS. The former hypothesis could be clearly documented in 1 case in which prenatal diagnosis was positive in a new pregnancy. Finally, the 2 years' overall survival was 7% in mutated and 29% in wild-type patients, mainly due to the worse outcome of RT in younger patients.
Conclusions: Our results show a high proportion of germline mutations in patients with RT that can be found at any age and up to 60% in the youngest patients. Genetic counseling is recommended given the low but actual risk of familial recurrence. Clin Cancer Res; 17(1); 31–8. ©2011 AACR.
Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition
Authors: Castelo-Branco Pedro , Zhang Cindy , Lipman Tatiana , Fujitani Mayumi , Hansford Loen , Clarke Ian , Harley Calvin B. , Tressler Robert , Malkin David , Walker Erin , Kaplan David R. , Dirks Peter , Tabori Uri 
Published: January 2011

AbstractPurpose: Cancer recurrence is one of the major setbacks in oncology. Maintaining telomeres is essential for sustaining the limitless replicative potential of such cancers. Because telomerase is thought to be active in all tumor cells and normal stem cells, telomerase inhibition may be nonspecific and have detrimental effects on tissue maintenance and development by affecting normal stem cell self-renewal.Methods: We examined telomerase activity, telomere maintenance, and stem cell maturation in tumor subpopulations from freshly resected gliomas, long-term, primary, neural tumor-initiating cells (TIC) and corresponding normal stem cell lines. We then tested the efficacy of the telomerase inhibitor Imetelstat on propagation and self-renewal capacity of TIC and normal stem cells in vitro and in vivo.Results: Telomerase was undetectable in the majority of tumor cells and specific to the TIC subpopulation that possessed critically short telomeres. In contrast, normal tissue stem cells had longer telomeres and undetectable telomerase activity and were insensitive to telomerase inhibition, which results in proliferation arrest, cell maturation, and DNA damage in neural TIC. Significant survival benefit and late tumor growth arrest of neuroblastoma TIC were observed in a xenograft model (P = 0.02). Furthermore, neural TIC exhibited irreversible loss of self-renewal and stem cell capabilities even after cessation of treatment in vitro and in vivo.Conclusions: TIC exhaustion with telomerase inhibition and lack of telomerase dependency in normal stem cells add new dimensions to the telomere hypothesis and suggest that targeting TIC with telomerase inhibitors may represent a specific and safe therapeutic approach for tumors of neural origin. Clin Cancer Res; 17(1); 111–21. ©2011 AACR.
EphA2 Induces Metastatic Growth Regulating Amoeboid Motility and Clonogenic Potential in Prostate Carcinoma Cells
Authors: Taddei Maria Letizia , Parri Matteo , Angelucci Adriano , Bianchini Francesca , Marconi Chiara , Giannoni Elisa , Raugei Giovanni , Bologna Mauro , Calorini Lido , Chiarugi Paola 
Published: January 2011

Abstract
EphA2 kinase regulates cell shape, adhesion, and motility and is frequently overexpressed in several cancers, including melanoma, prostate, breast, and colon cancers and lung carcinoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 in tumor progression is still debated. In melanoma, EphA2 has been reported to affect cell migration and invasiveness allowing cells to move by a proteolysis-independent strategy, commonly referred as amoeboid motility. With the aim to understand the role of EphA2 in prostate cancer metastatic spreading, we stably silenced EphA2 expression in a model of aggressive metastatic prostate carcinoma. Our results show that EphA2 drives the metastatic program of prostate carcinoma, although its involvement greatly differs among metastatic steps. Indeed, EphA2 expression (i) greatly affects prostate carcinoma cell motility style, guiding an amoeboid movement based on Rho-mediated cell rounding and independent from metalloprotases, (ii) is ineffective on transendothelial migration, adhesion onto extracellular matrix proteins, and on resistance to anoikis, (iii) regulates clonogenic potential of prostate carcinoma, thereby increasing anchorage-independent growth and self-renewal, prostasphere formation, tumor onset, dissemination to bone, and growth of metastatic colonies. Our finding indicate that EphA2-overexpressing prostate carcinoma cells gain an invasive benefit from their amoeboid motility style to escape from primary tumors and then, enhancing their clonogenic potential successfully target bone and grow metastases, thereby acknowledging EphA2 as a target for antimetastatic therapy of aggressive prostate cancers. Mol Cancer Res; 9(2); 149–60. ©2011 AACR.
The Homologous Recombination Protein RAD51D Mediates the Processing of 6-Thioguanine Lesions Downstream of Mismatch Repair
Authors: Rajesh Preeti , Litvinchuk Alexandra V. , Pittman Douglas L. , Wyatt Michael D. 
Published: January 2011

AbstractThiopurines are extensively used as immunosuppressants and in the treatment of childhood cancers, even though there is concern about therapy-induced leukemias and myelodysplastic syndromes resulting from thiopurine use. Following metabolic activation, thiopurines are incorporated into DNA and invoke mismatch repair (MMR). Recognition of 6-thioguanine (6-thioG) in DNA by key MMR proteins results in cell death rather than repair. There are suggestions that homologous recombination (HR) is involved downstream of MMR following thiopurine treatment, but the precise role of HR is poorly understood. In this study, we demonstrate that cells deficient in RAD51D (a RAD51 paralogue) are extremely sensitive to 6-thioG. This sensitivity is almost completely rescued by the deletion of Mlh1, which suggests that HR is involved in the repair of the 6-thioG–induced recombinogenic lesions generated by MMR. Furthermore, 6-thioG induces chromosome aberrations in the Rad51d-deficient cells. Interestingly, Rad51d-deficient cells show a striking increase in the frequency of triradial and quadriradial chromosomes in response to 6-thioG therapy. The presence of these chromatid exchange–type aberrations indicates that the deficiency in RAD51D-dependent HR results in profound chromosomal damage precipitated by the processing of 6-thioG by MMR. The radials are notable as an important source of chromosomal translocations, which are the most common class of mutations found in hematologic malignancies. This study thus suggests that HR insufficiency could be a potential risk factor for the development of secondary cancers that result from long-term use of thiopurines in patients. Mol Cancer Res; 9(2); 206–14. ©2011 AACR.
Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb Ischemia
Authors: Walter Dirk H. , Krankenberg Hans , Balzer Jörn O. , Kalka Christoph , Baumgartner Iris , Schlüter Michael , Tonn Torsten , Seeger Florian , Dimmeler Stefanie , Lindhoff-Last Edelgard , Zeiher Andreas M. ,   for the PROVASA Investigators
Published: January 2011

Background—
Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking.

Methods and Results—

Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm
2
to 1.89±3.5 cm
2
[
P
=0.014] versus placebo, 2.92±3.5 cm
2
to 2.89±4.1 cm
2
[
P
=0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [
P
=0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [
P
=0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups.

Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (
r
=0.8;
P
<0.001).

Conclusions—
Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00282646.
Simple or Complex Stenting for Bifurcation Coronary Lesions
Authors: Behan Miles W. , Holm Niels R. , Curzen Nicholas P. , Erglis Andrejs , Stables Rodney H. , de Belder Adam J. , Niemelä Matti , Cooter Nina , Chew Derek P. , Steigen Terje K. , Oldroyd Keith G. , Jensen Jan S. , Lassen Jens Flensted , Thuesen Leif , Hildick-Smith David 
Published: January 2011

Background—
Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE).

Methods and Results—

Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66],
P
=0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3%; hazard ratio 1.90 [95% confidence interval 1.22 to 2.94],
P
=0.004), wide-angled bifurcations >60 to 70° (n=217, simple 9.6% versus complex 15.7%; hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62],
P
=0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7%; hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80],
P
=0.011), longer length (>5 mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1%; hazard ratio 1.71 [95% confidence interval 1.05 to 2.77],
P
=0.029), or equivalent sized vessels (side branch <0.25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5%; hazard ratio 1.35 [95% confidence interval 0.48 to 3.70],
P
=0.57).

Conclusions—
For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT 00376571 and NCT 00351260.
Impact of Drug-Eluting Stents and Diabetes Mellitus in Patients With Coronary Bifurcation Lesions: A Survey From the Italian Society of Invasive Cardiology
Authors: Capodanno Davide , Tamburino Corrado , Sangiorgi Giuseppe M. , Romagnoli Enrico , Colombo Antonio , Burzotta Francesco , Gasparini Gabriele L. , Bolognese Leonardo , Paloscia Leonardo , Rubino Paolo , Sardella Gennaro , Briguori Carlo , Ettori Federica , Franco Gianfranco , Di Girolamo Domenico , Sheiban Imad , Piatti Luigi , Greco Cesare , Petronio Anna Sonia , Loi Bruno , Lyoi Ernesto , Benassi Alberto , Patti Aldo , Gaspardone Achille , De Servi Stefano ,   for the I-BIGIS Study Group
Published: January 2011

Background—
We investigated the long-term impact of different stent types and diabetes mellitus (DM) in patients undergoing percutaneous coronary intervention (PCI) of bifurcation lesions, based on a large multicenter survey endorsed by the Italian Society of Invasive Cardiology.

Methods and Results—

Relative benefits of drug eluting stent (DES) over bare metal stent (BMS) in patients with (n=1049) and without (n=3020) DM were analyzed with extensive multivariable adjustment. At 3 years, stenting with DES was associated with lower adjusted risk of major adverse cardiac events (MACE, adjusted hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.15 to 0.49,
P
<0.001), cardiac death, and target lesion revascularization in DM patients but failed to demonstrate any significant benefit in patients without DM.

Conclusions—
In a large observational registry with admitted potential for selection bias and residual confounding, DES in DM patients with coronary bifurcation lesions were associated with improved outcomes in terms of MACE, cardiac death, and repeat revascularization at long-term follow up. These figures were not replicated in non-DM subjects.