bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensor network localization using sensor perturbation
Authors: Zhu Yuanchen , Gortler Steven J. , Thurston Dylan 
Published: March 2011

Sensor network localization is an instance of the NP-Hard graph realization problem. Thus, methods used in practice are not guaranteed to find the correct localization, even if it is uniquely determined by the input distances.
In this article, we show the following: if the sensors are allowed to wiggle, giving us perturbed distance data, we can apply a novel algorithm to realize arbitrary Generically Globally Rigid graphs (GGR), or certain vertex subsets in non-GGR graphs whose relative positions are fixed (which include vertex sets of GGR subgraphs). And this strategy works in any dimension.
In the language of structural rigidity theory, our approach corresponds to calculating the approximate kernel of a generic stress matrix for the given graph and distance data. To make our algorithm suitable for real-world applications, we also present: (i) various techniques for improving the robustness of the algorithm in the presence of measurement noise; (ii) an algorithm for detecting certain subsets of graph vertices whose relative positions are fixed in any generic realization of the graph and robustly localizing these subsets of vertices, (iii) a strategy for reducing the number of measurements needed by the algorithm.
We provide simulation results of our algorithm.
Mathematical Modeling Predicts Synergistic Antitumor Effects of Combining a Macrophage-Based, Hypoxia-Targeted Gene Therapy with Chemotherapy
Authors: Owen Markus R. , Stamper I. Johanna , Muthana Munitta , Richardson Giles W. , Dobson Jon , Lewis Claire E. , Byrne Helen M. 
Published: March 2011

Abstract
Tumor hypoxia is associated with low rates of cell proliferation and poor drug delivery, limiting the efficacy of many conventional therapies such as chemotherapy. Because many macrophages accumulate in hypoxic regions of tumors, one way to target tumor cells in these regions could be to use genetically engineered macrophages that express therapeutic genes when exposed to hypoxia. Systemic delivery of such therapeutic macrophages may also be enhanced by preloading them with nanomagnets and applying a magnetic field to the tumor site. Here, we use a new mathematical model to compare the effects of conventional cyclophosphamide therapy with those induced when macrophages are used to deliver hypoxia-inducible cytochrome P450 to locally activate cyclophosphamide. Our mathematical model describes the spatiotemporal dynamics of vascular tumor growth and treats cells as distinct entities. Model simulations predict that combining conventional and macrophage-based therapies would be synergistic, producing greater antitumor effects than the additive effects of each form of therapy. We find that timing is crucial in this combined approach with efficacy being greatest when the macrophage-based, hypoxia-targeted therapy is administered shortly before or concurrently with chemotherapy. Last, we show that therapy with genetically engineered macrophages is markedly enhanced by using the magnetic approach described above, and that this enhancement depends mainly on the strength of the applied field, rather than its direction. This insight may be important in the treatment of nonsuperficial tumors, where generating a specific orientation of a magnetic field may prove difficult. In conclusion, we demonstrate that mathematical modeling can be used to design and maximize the efficacy of combined therapeutic approaches in cancer. Cancer Res; 71(8); 2826–37. ©2011 AACR.
Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer
Authors: Morgan Richard , Boxall Angela , Bhatt Aagna , Bailey Michael , Hindley Richard , Langley Stephen , Whitaker Hayley C. , Neal David E. , Ismail Mohammed , Whitaker Hamish , Annels Nicola , Michael Agnieszka , Pandha Hardev 
Published: March 2011

Abstract
Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men.
Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102).
Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center.
Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified. Clin Cancer Res; 17(5); 1090–8. ©2011 AACR.
Changes in 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer Treated with Erlotinib
Authors: Mileshkin Linda , Hicks Rodney J. , Hughes Brett G.M. , Mitchell Paul L.R. , Charu Veena , Gitlitz Barbara J. , Macfarlane David , Solomon Benjamin , Amler Lukas C. , Yu Wei , Pirzkall Andrea , Fine Bernard M. 
Published: March 2011

Abstract
Purpose: Assessing clinical activity of molecularly targeted anticancer agents, especially in the absence of tumor shrinkage, is challenging. To evaluate on-treatment 18F-fluorodeoxyglucose (FDG) and/or 18F-fluorodeoxythymidine (FLT) positron emission tomography (PET) for this purpose, we conducted a prospective multicenter trial assessing PET response rates and associations with progression-free (PFS) and overall survival (OS) in 2nd/3rd-line non–small-cell lung cancer patients treated with erlotinib.
Experimental Design: PET/computed tomography (CT) scans were conducted at baseline, day (d)14 and d56 after the first daily erlotinib dose, with diagnostic CT at baseline and d56 (all scans centrally reviewed). PET partial metabolic response (PMR) was defined as a mean decrease (in ≤5 lesions/patient) of 15% or more maximum standardized uptake value. PFS was investigator-determined.
Results: Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13 of 51 (26%) FDG-evaluable patients had PMR at d14, as did 9 of 50 (18%) FLT-evaluable patients. Four (7.8%) showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET with 3 PMRs by d14 FLT-PET. Three of the 4 patients with CT PR had evaluable archival tumor tissue; all 3 had epidermal growth factor receptor mutations. D14 and d56 PMRs by FDG or FLT were associated with improved PFS; HRs for PET responders versus nonresponders were 0.3 to 0.4. D14 FDG-PET PMR was associated with improved OS (P = 0.03) compared with FDG-PET nonresponders.
Conclusion: Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent Response Evaluation Criteria in Solid Tumors response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects. Clin Cancer Res; 17(10); 3304–15. ©2011 AACR.
A Human Model of Epithelial to Mesenchymal Transition to Monitor Drug Efficacy in Hepatocellular Carcinoma Progression
Authors: van Zijl Franziska , Mall Sabine , Machat Georg , Pirker Christine , Zeillinger Robert , Weinhaeusel Andreas , Bilban Martin , Berger Walter , Mikulits Wolfgang 
Published: March 2011

AbstractThe epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling, and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. We show that liver cancer cell lines exhibited either an epithelial or mesenchymal phenotype of which the latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this EMT model of human HCC allows the identification of molecular mechanisms and the assessment of therapeutic drug efficacy during liver cancer progression in preclinical studies. Mol Cancer Ther; 10(5); 850–60. ©2011 AACR.
hTERT Promotes Imatinib Resistance in Chronic Myeloid Leukemia Cells: Therapeutic Implications
Authors: Deville Laure , Hillion Josette , Pendino Frédéric , Samy Mona , Nguyen Eric , Ségal-Bendirdjian Evelyne 
Published: March 2011

Abstract
Imatinib mesylate has shown remarkable efficacy in the treatment of patients in the chronic phase of chronic myeloid leukemia. However, despite an overall significant hematological and cytogenetic response, imatinib therapy may favor the emergence of drug-resistant clones, ultimately leading to relapse. Some imatinib resistance mechanisms had not been fully elucidated yet. In this study we used sensitive and resistant sublines from a Bcr-Abl positive cell line to investigate the putative involvement of telomerase in the promotion of imatinib resistance. We showed that sensitivity to imatinib can be partly restored in imatinib-resistant cells by targeting telomerase expression, either by the introduction of a dominant-negative form of the catalytic protein subunit of the telomerase (hTERT) or by the treatment with all-trans-retinoic acid, a clinically used drug. Furthermore, we showed that hTERT overexpression favors the development of imatinib resistance through both its antiapoptotic and telomere maintenance functions. Therefore, combining antitelomerase strategies to imatinib treatment at the beginning of the treatment should be promoted to reduce the risk of imatinib resistance development and increase the probability of eradicating the disease. Mol Cancer Ther; 10(5); 711–19. ©2011 AACR.
HIF-1–Dependent Stromal Adaptation to Ischemia Mediates In Vivo Tumor Radiation Resistance
Authors: Schwartz David L. , Bankson James , Bidaut Luc , He Yi , Williams Ryan , Lemos Robert , Thitai Arun Kumar , Oh Junghwan , Volgin Andrei , Soghomonyan Suren , Yeh Hsin-Hsien , Nishii Ryuichi , Mukhopadhay Uday , Alauddin Mian , Mushkudiani Ioseb , Kuno Norihito , Krishnan Sunil , Bornman William , Lai Stephen Y. , Powis Garth , Hazle John , Gelovani Juri 
Published: March 2011

Abstract
Purpose: Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor–stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1–dependent resistance pathways.
Methods: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in nu/nu mice.
Results: In vitro, single-dose irradiation of C6 and HN5 reporter cells modestly impacted HIF-1 signaling in normoxic monolayers and inhibited HIF-1 signaling in maturing spheroids. In contrast, irradiation of C6 or HN5 reporter xenografts with 8 Gy in vivo elicited marked upregulation of HIF-1 signaling and downstream proangiogenic signaling at 48 hours which preceded recovery of tumor growth. In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. High-resolution positron emission tomography and dual-contrast DCE-MRI of immobilized dorsal skin window tumors confirmed postradiotherapy HIF-1 signaling to spatiotemporally coincide with impaired stromal vascular function. Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance.
Conclusions: Our results illustrate that tumor radioresistance is mediated by a capacity to compensate for stromal vascular disruption through HIF-1–dependent proangiogenic signaling and that clinically relevant vascular imaging techniques can spatially define mechanisms associated with tumor irradiation. Mol Cancer Res; 9(3); 259–70. ©2011 AACR.
STAT-3 Activates NF-κB in Chronic Lymphocytic Leukemia Cells
Authors: Liu Zhiming , Hazan-Halevy Inbal , Harris David M. , Li Ping , Ferrajoli Alessandra , Faderl Stefan , Keating Michael J. , Estrov Zeev 
Published: March 2011

Abstract
NF-κB plays a major role in the pathogenesis of B-cell neoplasms. A broad array of mostly extracellular stimuli has been reported to activate NF-κB, to various degrees, in chronic lymphocytic leukemia (CLL) cells. Because CLL cells harbor high levels of unphosphorylated STAT-3 (USTAT-3) and USTAT-3 was reported to activate NF-κB, we sought to determine whether USTAT-3 activates NF-κB in CLL. Using the electrophoretic mobility shift assay (EMSA), we studied peripheral blood low-density cells from 15 patients with CLL and found that CLL cell nuclear extracts from all the samples bound to an NF-κB DNA probe, suggesting that NF-κB is constitutively activated in CLL. Immunoprecipitation studies showed that STAT-3 bound NF-κB p65, and confocal microscopy studies detected USTAT-3/NF-κB complexes in the nuclei of CLL cells, thereby confirming these findings. Furthermore, infection of CLL cells with retroviral STAT-3-short hairpin RNA attenuated the binding of NF-κB to DNA, as assessed by EMSA, and downregulated mRNA levels of NF-κB–regulated genes, as assessed by quantitative PCR. Taken together, our data suggest that USTAT-3 binds to the NF-κB p50/p65 dimers and that the USTAT-3/NF-κB complexes bind to DNA and activate NF-κB–regulated genes in CLL cells. Mol Cancer Res; 9(4); 507–15. ©2011 AACR.
Paclitaxel-Eluting Stents Compared With Bare Metal Stents in Diabetic Patients With Acute Myocardial Infarction
Authors: Witzenbichler Bernhard , Wöhrle Jochen , Guagliumi Giulio , Peruga Jan Z. , Brodie Bruce R. , Dudek Dariusz , Kornowski Ran , Hartmann Franz , Hood Kristin L. , Parise Helen , Lansky Alexandra J. , Nikolsky Eugenia , Mehran Roxana , Stone Gregg W. 
Published: March 2011

Background—
In the prospective, randomized Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, implantation of paclitaxel-eluting stents (PES) safely reduced the rates of ischemic target lesion revascularization (TLR) compared with bare metal stents (BMS) in patients with ST-segment–elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention. Diabetes mellitus is a known predictor of adverse outcomes after percutaneous intervention in STEMI. We therefore sought to assess the impact of PES in diabetic patients with STEMI from the HORIZONS-AMI trial.

Methods and Results—

A total of 478 patients with diabetes and 2527 without diabetes were randomly assigned to receive PES versus BMS. The 12-month rates of ischemic TLR were significantly reduced by PES compared with BMS in both diabetic (11.2% versus 5.2%; hazard ratio [95% confidence interval]=0.45 [0.21 to 0.93];
P
=0.03) and nondiabetic (6.8% versus 4.3%, hazard ratio [95% confidence interval]=0.63 [0.44 to 0.92];
P
=0.02) patients. In patients with insulin-treated diabetes, PES compared with BMS reduced the 12-month TLR rate from 21.4% to 7.3% (hazard ratio [95% confidence interval]=0.35 [0.12 to 1.03];
P
=0.046). Angiographic late loss and binary restenosis at 13 months were also significantly reduced in PES-treated diabetic patients. There were no significant differences between the BMS and PES groups in the 12-month rates of death, reinfarction, stroke, or stent thrombosis in either diabetic or nondiabetic patients.

Conclusions—
In the large-scale, prospective, randomized HORIZONS-AMI trial, implantation of PES compared with BMS in patients with STEMI and diabetes mellitus resulted in significant reductions in ischemia-driven TLR and angiographic restenosis at 1 year, with comparable safety outcomes, including stent thrombosis. These results suggest that PES can safely be used to reduce restenosis in high-risk diabetic patients presenting with STEMI.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00433966.
Gender Bias in Studies for Food and Drug Administration Premarket Approval of Cardiovascular Devices
Authors: Dhruva Sanket S. , Bero Lisa A. , Redberg Rita F. 
Published: March 2011

Background—
Cardiovascular devices can have different safety and effectiveness profiles in men and women. The type and quality of sex-specific data reviewed by the Food and Drug Administration (FDA) before approval of these devices are unknown.

Methods and Results—
We performed a systematic review of the demographics, comments on gender bias, and analysis of results by sex for 78 high-risk cardiovascular devices that received premarket approval by the FDA between 2000 and 2007. FDA summaries of evidence did not report sex of enrollees in 34 (28%) of 123 studies. For studies reporting sex distribution, the study populations were, on average, 67% men. There was no increase in the enrollment of women over time. Explanations for the relatively low percentage of women often stated that the trials reflected either underlying disease distribution or referral rates for similar procedures or that the sex distribution reflected similar or previous trials. Forty-one percent of studies included a gender bias comment or analysis, and 12 (26%) of 47 of these analyses identified some difference in device safety or effectiveness by sex.

Conclusions—
There is a lack of sex-specific safety and effectiveness data for high-risk cardiovascular devices before FDA approval. The justifications for this lack of evidence may perpetuate the status quo. More rigorous FDA requirements for sex-specific data before device approval could present an opportunity to improve cardiovascular outcomes.
Anisotropy of Longwave Radiation Emergent from a Broken Cloud Field and its Effect on Satellite Estimates of Flux
Authors: Duvel J. P. , Kandel R. S. 
Published: March 2011

Abstract
Simple geometric considerations suggest that in the same way as broken cloud cover appears practically total near a ground observer's horizon, the anisotropy of the longwave radiation emitted to space from an area of broken cloud should be substantially enhanced.
Using a simple model consisting of parallel bands of “black” clouds of rectangular cross section, imbedded in an otherwise horizontally homogeneous vertically stratified atmosphere, we evaluate the longwave radiance emergent in different directions, averaged over the cloud pattern, and find this expectation to be confirmed in a wide range of cases. At large zenith angles, the emergent radiance can exhibit considerable dependence on azimuth, relative to the direction of the band structure. Although such azimuthal dependence practically disappears for many 3-dimensional broken cloud fields (e.g., hexagonal cells), the enhanced zenith angle dependence remains. This can be a source of bias in cloud extractions or Earth radiation budget determinations based on geostationary satellite data, since zenith angle is directly related to geographical location of the point under observation.
With our model cloud arrays, and considering radiative transfer in the atmosphere, we have evaluated the bias in the broad-band longwave (3–100 μm) radiant exitance values derived, assuming horizontal homogeneity, from either broad-band or narrow-band (10.5–12.5 μm) radiance data. We find that the bias for near-nadir observations can be as large as 20% (40 W m−2) in extreme cases involving bands of opaque high-level cloud over warm ground. It may remain substantial in situations which are encountered in nature. We examine the dependence of the broken cloud effects on the geometrical parameters of the field.
We discuss how such effects might be detected and how they can influence determinations of Earth radiation budget components and of cloud cover. We note that “brokenness” will be a factor in cloud-radiation feedback.
A Comparison of NMC and GWC Analysis Field Temperatures with Aircraft Measurements
Authors: Jasperson William H. , Nastrom Gregory D. 
Published: March 2011

Abstract
Comparison between in situ aircraft observations of temperature and National Meteorological Center and Global Weather Central analysis fields of temperature is presented for a continental and oceanic flight route. The standard deviations of the temperature differences over several hundred flights are found to be 2.5 and 3.5°C for the continental and oceanic route, respectively. A bias towards warm temperatures of about 0.85°C for the analysis fields was found for the oceanic route. Only small differences are found between the NMC and GWC analysis field temperatures.
Strategies for Assessing Skill and Significance of Screening Regression Models with Emphasis on Monte Carlo Techniques
Authors: Lanzante John R. 
Published: March 2011

Abstract
This paper reviews the considerations in evaluating the skill and significance of screening multiple linear regression (SMLR) models. Formulations and procedures are given along with relevant references to prior studies. Topics discussed include predictor selection, serial correlation, artificial skill, true skill, and Monte Carlo significance testing. New results with wide applicability in the assessment of SMLR model skill and significance are presented in graphical form. However, the results are restricted to situations involving predictors which are independent of one another and are serially uncorrelated. The methodology presented is suggested for use in both model evaluation and experimental design.
On the Nature of the Nonexistence of Ordinal Relationships between Measures of the Accuracy and Value of Probability Forecasts : An Example
Authors: Murphy Allan H. , Thompson Jack C. 
Published: March 2011

Abstractt has been shown previously that ordinal relationships between measures of the accuracy and value ofprobability forecasts do not exist, in general, in N-state (N > 2) situations. Some implications of this resultare illustrated by comparing the accuracy and value of such forecasts in a realistic decision-making situation-a three-action, three-state situation involving the protection of a fruit orchard against frosts and freezes.Geometrical interpretations of the forecasts and measures are described and then used to investigate the existence of ordinal relationships in this so-called fruit-frost situation. The results indicate, as expected, thatan increase in forecast accuracy can lead to a decrease in forecast value. Some generalizations and speculations related to the existence and nonexistence of such ordinal relationships are presented.