bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controllable conformal maps for shape deformation and interpolation
Authors: Weber Ofir , Gotsman Craig 
Published: July 2010

Conformal maps are considered very desirable for planar deformation applications, since they allow only local rotations and scale, avoiding shear and other visually disturbing distortions of local detail. Conformal maps are also orientation-preserving C
∞
diffeomorphisms, meaning they are extremely smooth and prevent unacceptable "foldovers" in the plane. Unfortunately, these maps are also notoriously difficult to control, so working with them in an interactive animation scenario to achieve specific effects is a significant challenge, sometimes even impossible.

We describe a novel 2D shape deformation system which generates conformal maps, yet provides the user a large degree of control over the result. For example, it allows discontinuities at user-specified boundary points, so true "bends" can be introduced into the deformation. It also allows the prescription of angular constraints at corners of the target image. Combining these provides for a very effective user experience. At the heart of our method is a very natural differential shape representation for conformal maps, using so-called "conformal factors" and "angular factors", which allow more intuitive control compared to representation in the usual spatial domain. Beyond deforming a given shape into a new one at each key frame, our method also provides the ability to interpolate between shapes in a very natural way, such that also the intermediate deformations are conformal.
Our method is extremely efficient: it requires only the solution of a small dense linear system at preprocess time and a matrix-vector multiplication during runtime (which can be implemented on a modern GPU), thus the deformations, even on extremely large images, may be performed in real-time.
The Epidermal Growth Factor Receptor Antibody Cetuximab Induces Autophagy in Cancer Cells by Downregulating HIF-1α and Bcl-2 and Activating the Beclin 1/hVps34 Complex
Authors: Li Xinqun , Fan Zhen 
Published: July 2010

Abstract
Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here, we report that autophagy is induced by cetuximab, a therapeutic antibody that blocks epidermal growth factor receptor function. Cancer cell treatment with cetuximab triggered autophagosome formation, conversion of microtubule-associated protein 1 light chain 3 from its cytoplasmic to membrane-associated form, and increased acidic vesicular organelle formation. Autophagy occurred when cetuximab inhibited the class I phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway, but not when it inhibited only the mitogen-activated protein/extracellular signal-regulated kinase kinase/Erk pathway, and it was accompanied by decreased levels of hypoxia inducible factor-1 α (HIF-1α) and Bcl-2. Stable overexpression of a HIF-1α mutant prevented cetuximab-induced autophagy and decrease in Bcl-2 levels. Knockdown of autophagy regulator beclin 1 or cell treatment with autophagy inhibitor 3-methyladenine, a class III PI3K (hVps34) inhibitor, also inhibited cetuximab-induced autophagy. Furthermore, knockdown of beclin 1 or Atg7 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cetuximab-induced apoptosis. Mechanistic analysis argued that cetuximab acted by promoting an association between beclin 1 and hVps34, which was inhibited by overexpression of Bcl-2. Our findings suggest that the autophagy protects cancer cells from the proapoptotic effects of cetuximab. Cancer Res; 70(14); 5942–52. ©2010 AACR.
Transplanting Normal Vascular Proangiogenic Cells to Tumor-Bearing Mice Triggers Vascular Remodeling and Reduces Hypoxia in Tumors
Authors: Sasajima Junpei , Mizukami Yusuke , Sugiyama Yoshiaki , Nakamura Kazumasa , Kawamoto Toru , Koizumi Kazuya , Fujii Rie , Motomura Wataru , Sato Kazuya , Suzuki Yasuaki , Tanno Satoshi , Fujiya Mikihiro , Sasaki Katsunori , Shimizu Norihiko , Karasaki Hidenori , Kono Toru , Kawabe Jun-ichi , Ii Masaaki , Yoshiara Hiroki , Kamiyama Naohisa , Ashida Toshifumi , Bardeesy Nabeel , Chung Daniel C. , Kohgo Yutaka 
Published: July 2010

Abstract
Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally in adult tissues to repair “injured” blood vessels, leading us to hypothesize that bone marrow mononuclear cells (BMMNC) may be able to restore appropriate vessel function in the tumor vasculature. Culturing BMMNCs in endothelial growth medium resulted in the early outgrowth of spindle-shaped attached cells expressing CD11b/Flt1/Tie2/c-Kit/CXCR4 with proangiogenic activity. Intravenous administration of these cultured vascular proangiogenic cells (VPC) into nude mice bearing pancreatic cancer xenografts and Pdx1-Cre;LSL-KrasG12D;p53lox/+ genetically engineered mice that develop pancreatic ductal adenocarcinoma significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Increases in vascularized areas within VPC-injected xenografts were visualized with an ultrasound diagnostic system during injection of a microbubble-based contrast agent (Sonazoid), indicating a functional “normalization” of the tumor vasculature. In addition, gene expression profiles in the VPC-transplanted xenografts revealed a marked reduction in major factors involved in drug resistance and “stemness” of cancer cells. Together, our findings identify a novel alternate approach to regulate abnormal tumor vessels, offering the potential to improve the delivery and efficacy of anticancer drugs to hypoxic tumors. Cancer Res; 70(15); 6283–92. ©2010 AACR.
Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung
Authors: Yan Hannah H. , Pickup Michael , Pang Yanli , Gorska Agnieszka E. , Li Zhaoyang , Chytil Anna , Geng Yipeng , Gray Jerome W. , Moses Harold L. , Yang Li 
Published: July 2010

Abstract
The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-γ production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis. Cancer Res; 70(15); 6139–49. ©2010 AACR.
Magnetic Resonance Imaging Delineates the Ischemic Area at Risk and Myocardial Salvage in Patients With Acute Myocardial Infarction
Authors: Berry Colin , Kellman Peter , Mancini Christine , Chen Marcus Y. , Bandettini W. Patricia , Lowrey Tracy , Hsu Li-Yueh , Aletras Anthony H. , Arai Andrew E. 
Published: July 2010

Background—
The area at risk (AAR) is a key determinant of myocardial infarction (MI) size. We investigated whether magnetic resonance imaging (MRI) measurement of AAR would be correlated with an angiographic AAR risk score in patients with acute MI.

Methods and Results—

Bright-blood, T2-prepared, steady-state, free-precession MRI was used to depict the AAR in 50 consecutive acute MI patients, whereas infarct size was measured on gadolinium late-contrast-enhancement images. AAR was also estimated by the APPROACH and DUKE angiographic jeopardy scores and ST-segment elevation score. Myocardial salvage was calculated as AAR minus infarct size. Results are mean±SD unless specified otherwise. Patients were 61±12 years of age, 76% had an ST-segment elevation MI, and 20% had a prior MI. All underwent MRI 4±2 days after initial presentation. The relation between MRI and the APPROACH angiographic estimates of AAR was similar (overall size relative to left ventricular mass was 32±12% vs 30±12%, respectively,
P
=0.33), correlated well (
r
=0.78,
P
<0.0001), and had a 2.5% bias on Bland-Altman analysis. The DUKE jeopardy score underestimated AAR relative to infarct size and was correlated less well with MRI (
r
=0.39,
P
=0.0055). ST-segment elevation score underestimated infarct size in 19 subjects (50%) and was not correlated with MRI (
r
=0.27,
P
=0.06). Myocardial salvage varied according to Thrombolysis in Myocardial Infarction flow grade at the end of angiography/percutaneous coronary intervention (
P
=0.04), and Thrombolysis in Myocardial Infarction flow grade was a univariable predictor of myocardial salvage (
P
=0.011). In multivariable analyses, infarct size was predicted by T2-prepared, steady-state, free-precession MRI (
P
<0.0001).

Conclusions—
T2-prepared, steady-state, free-precession MRI delineates the AAR and enables estimation of myocardial salvage when coupled with a measurement of infarct size.
Dutch perfusion incident survey
Authors: Groenenberg Ingrid , Weerwind Patrick W , Everts Peter AM , Maessen Jos G 
Published: July 2010

Background: Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. Methods: An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. Results: The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. Conclusions: In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended.
High-Field Magnetic Resonance Imaging Assessment of Articular Cartilage before and after Marathon Running
Authors: Luke Anthony C. , Stehling Christoph , Stahl Robert , Li Xiaojuan , Kay Terry , Takamoto Stephen , Ma Benjamin , Majumdar Sharmilla , Link Thomas 
Published: July 2010

Background There is continuing controversy whether long-distance running results in irreversible articular cartilage damage. New quantitative magnetic resonance imaging (MRI) techniques used at 3.0 T have been developed including T1rho (T1ρ) and T2 relaxation time measurements that detect early cartilage proteoglycan and collagen breakdown. Hypothesis Marathon runners will demonstrate T1ρ and T2 changes in articular cartilage on MRI after a marathon, which are not seen in nonrunners. These changes are reversible. Study Design Cohort study; Level of evidence, 2. Methods Ten asymptomatic marathon runners had 3-T knee MRI scans 2 weeks before, within 48 hours after, and 10 to 12 weeks after running a marathon. The T1ρ and T2 MRI sequences in runners were compared with those of 10 age- and gender-matched controls who had MRI performed at baseline and 10 to 12 weeks. Results Runners did not demonstrate any gross morphologic MRI changes after running a marathon. Postmarathon studies, however, revealed significantly higher T2 and T1ρ values in all articular cartilage areas of the knee (P < .01) except the lateral compartment. The T2 values recovered to baseline except in the medial femoral condyle after 3 months. Average T1ρ values increased after the marathon from 37.0 to 38.9 (P < .001) and remained increased at 3 months. Conclusion Runners showed elevated T1ρ and T2 values after a marathon, suggesting biochemical changes in articular cartilage, T1ρ values remain elevated after 3 months of reduced activity. The patellofemoral joint and medial compartment of the knee show the highest signal changes, suggesting they are at higher risk for degeneration.
Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study
Authors: Anderson VM , Fisniku LK , Khaleeli Z. , Summers MM , Penny SA , Altmann DR , Thompson AJ , Ron MA , Miller DH 
Published: July 2010

Background: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy. Objectives: To investigate and compare hippocampal volume loss in patients with relapsing—remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction. Methods: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function. Results: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm3 (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm3 (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS. Conclusion: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.
Sample size calculations for evaluating treatment policies in multi-stage designs
Authors: Dawson Ree , Lavori Philip W 
Published: July 2010

Background Sequential multiple assignment randomized (SMAR) designs are used to evaluate treatment policies, also known as adaptive treatment strategies (ATS). The determination of SMAR sample sizes is challenging because of the sequential and adaptive nature of ATS, and the multi-stage randomized assignment used to evaluate them. Purpose We derive sample size formulae appropriate for the nested structure of successive SMAR randomizations. This nesting gives rise to ATS that have overlapping data, and hence between-strategy covariance. We focus on the case when covariance is substantial enough to reduce sample size through improved inferential efficiency. Methods Our design calculations draw upon two distinct methodologies for SMAR trials, using the equality of the optimal semi-parametric and Bayesian predictive estimators of standard error. This ‘hybrid’ approach produces a generalization of the t-test power calculation that is carried out in terms of effect size and regression quantities familiar to the trialist. Results Simulation studies support the reasonableness of underlying assumptions as well as the adequacy of the approximation to between-strategy covariance when it is substantial. Investigation of the sensitivity of formulae to misspecification shows that the greatest influence is due to changes in effect size, which is an a priori clinical judgment on the part of the trialist. Limitations We have restricted simulation investigation to SMAR studies of two and three stages, although the methods are fully general in that they apply to ‘K-stage’ trials. Conclusions Practical guidance is needed to allow the trialist to size a SMAR design using the derived methods. To this end, we define ATS to be ‘distinct’ when they differ by at least the (minimal) size of effect deemed to be clinically relevant. Simulation results suggest that the number of subjects needed to distinguish distinct strategies will be significantly reduced by adjustment for covariance only when small effects are of interest.
Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells
Authors: Kochenderfer James N. , Yu Zhiya , Frasheri Dorina , Restifo Nicholas P. , Rosenberg Steven A. 
Published: July 2010

AbstractAdoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)–expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19–CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19–CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19–CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19–CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19–CAR-transduced T-cell infusion. Anti-CD19–CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19–CAR-transduced T cells in a clinically relevant murine model.
Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy
Authors: Kantarjian Hagop M. , Giles Francis J. , Greenberg Peter L. , Paquette Ron L. , Wang Eunice S. , Gabrilove Janice L. , Garcia-Manero Guillermo , Hu Kuolung , Franklin Janet L. , Berger Dietmar P. 
Published: July 2010

Abstract
We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs ≥ 50 × 109/L) and randomized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 μg, romiplostim 750 μg, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy. This study was registered at www.clinicaltrials.gov as #NCT00321711.
Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
Authors: Lugli Enrico , Goldman Carolyn K. , Perera Liyanage P. , Smedley Jeremy , Pung Rhonda , Yovandich Jason L. , Creekmore Stephen P. , Waldmann Thomas A. , Roederer Mario 
Published: July 2010

Abstract
Interleukin-15 (IL-15) is a cytokine with potential therapeutic application in individuals with cancer or immunodeficiency to promote natural killer (NK)– and T-cell activation and proliferation or in vaccination protocols to generate long-lived memory T cells. Here we report that 10-50 μg/kg IL-15 administered intravenously daily for 12 days to rhesus macaques has both short- and long-lasting effects on T-cell homeostasis. Peripheral blood lymphopenia preceded a dramatic expansion of NK cells and memory CD8 T cells in the circulation, particularly a 4-fold expansion of central memory CD8 T cells and a 6-fold expansion of effector memory CD8 T cells. This expansion is a consequence of their activation in multiple tissues. A concomitant inverted CD4/CD8 T-cell ratio was observed throughout the body at day 13, a result of preferential CD8 expansion. Expanded T- and NK-cell populations declined in the blood soon after IL-15 was stopped, suggesting migration to extralymphoid sites. By day 48, homeostasis appears restored throughout the body, with the exception of the maintenance of an inverted CD4/CD8 ratio in lymph nodes. Thus, IL-15 generates a dramatic expansion of short-lived memory CD8 T cells and NK cells in immunocompetent macaques and has long-term effects on the balance of CD4+ and CD8+ T cells.
Graph-based clustering and characterization of repetitive sequences in next-generation sequencing data
Authors: Novák Petr , Neumann Pavel , Macas Jiří 
Published: July 2010

Abstract

Background
The investigation of plant genome structure and evolution requires comprehensive characterization of repetitive sequences that make up the majority of higher plant nuclear DNA. Since genome-wide characterization of repetitive elements is complicated by their high abundance and diversity, novel approaches based on massively-parallel sequencing are being adapted to facilitate the analysis. It has recently been demonstrated that the low-pass genome sequencing provided by a single 454 sequencing reaction is sufficient to capture information about all major repeat families, thus providing the opportunity for efficient repeat investigation in a wide range of species. However, the development of appropriate data mining tools is required in order to fully utilize this sequencing data for repeat characterization.

Results
We adapted a graph-based approach for similarity-based partitioning of whole genome 454 sequence reads in order to build clusters made of the reads derived from individual repeat families. The information about cluster sizes was utilized for assessing the proportion and composition of repeats in the genomes of two model species, Pisum sativum and Glycine max, differing in genome size and 454 sequencing coverage. Moreover, statistical analysis and visual inspection of the topology of the cluster graphs using a newly developed program tool, SeqGrapheR, were shown to be helpful in distinguishing basic types of repeats and investigating sequence variability within repeat families.

Conclusions
Repetitive regions of plant genomes can be efficiently characterized by the presented graph-based analysis and the graph representation of repeats can be further used to assess the variability and evolutionary divergence of repeat families, discover and characterize novel elements, and aid in subsequent assembly of their consensus sequences.