bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating nonrigid motion from inconsistent intensity with robust shape features
Authors: Liu Wenyang , Ruan Dan 
Published: November 2013

Purpose:To develop a nonrigid motion estimation method that is robust to heterogeneous intensity inconsistencies amongst the image pairs or image sequence.Methods:Intensity and contrast variations, as in dynamic contrast enhanced magnetic resonance imaging, present a considerable challenge to registration methods based on general discrepancy metrics. In this study, the authors propose and validate a novel method that is robust to such variations by utilizing shape features. The geometry of interest (GOI) is represented with a flexible zero level set, segmented via well‐behaved regularized optimization. The optimization energy drives the zero level set to high image gradient regions, and regularizes it with area and curvature priors. The resulting shape exhibits high consistency even in the presence of intensity or contrast variations. Subsequently, a multiscale nonrigid registration is performed to seek a regular deformation field that minimizes shape discrepancy in the vicinity of GOIs.Results:To establish the working principle, realistic 2D and 3D images were subject to simulated nonrigid motion and synthetic intensity variations, so as to enable quantitative evaluation of registration performance. The proposed method was benchmarked against three alternative registration approaches, specifically, optical flow, B‐spline based mutual information, and multimodality demons. When intensity consistency was satisfied, all methods had comparable registration accuracy for the GOIs. When intensities among registration pairs were inconsistent, however, the proposed method yielded pronounced improvement in registration accuracy, with an approximate fivefold reduction in mean absolute error (MAE = 2.25 mm, SD = 0.98 mm), compared to optical flow (MAE = 9.23 mm, SD = 5.36 mm), B‐spline based mutual information (MAE = 9.57 mm, SD = 8.74 mm) and mutimodality demons (MAE = 10.07 mm, SD = 4.03 mm). Applying the proposed method on a real MR image sequence also provided qualitatively appealing results, demonstrating good feasibility and applicability of the proposed method.Conclusions:The authors have developed a novel method to estimate the nonrigid motion of GOIs in the presence of spatial intensity and contrast variations, taking advantage of robust shape features. Quantitative analysis and qualitative evaluation demonstrated good promise of the proposed method. Further clinical assessment and validation is being performed.
Complete Genome Sequence of Channel Catfish Gastrointestinal Septicemia Isolate Edwardsiella tarda C07-087
Authors: Tekedar Hasan C. , Karsi Attila , Williams Michele L. , Vamenta Stefanie , Banes Michelle M. , Duke Mary , Scheffler Brian E. , Lawrence Mark L. 
Published: November 2013

ABSTRACT

Edwardsiella tarda
is a Gram-negative facultative anaerobe causing disease in animals and humans. Here, we announce the complete genome sequence of the channel catfish isolate
E. tarda
strain C07-87, which was isolated from an outbreak of gastrointestinal septicemia on a commercial catfish farm.
Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73
T
Authors: Lin Zhe , Liu Zhaoshan , Yang Rentao , Zou Yuanqiang , Wan Daiwei , Chen Jing , Guo Min , Zhao Jiao , Fang Chengxiang , Yang Ruifu , Liu Feng 
Published: November 2013

ABSTRACT

Lactobacillus shenzhenensis
strain LY-73
T
is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of
Lactobacillus shenzhenensis
LY-73
T
.
Folded Variscan thrusts in the Herrera Unit of the Iberian Range (NE Spain)
Authors: Calvín-Ballester Pablo , Casas Antonio 
Published: November 2013

Abstract

The Variscan structure of the Herrera unit (Iberian Chain, NE Spain) is characterized by a system of NNW–SSE-striking, east-verging, foreland-dipping thrusts, generated in a thin-skinned context, whose formation was favoured by the presence of two main detachment levels (Precambrian and Silurian shales). During the formation of the thrust system (first phase of deformation, D
1
), the thrust sheets were deformed internally, mainly by asymmetrical folds with axial surface cleavage and east-verging thrusts; the normal evolution of the thrust system and the emplacement of an underlying thrust sheet resulted in progressive tilting and stacking, thus generating a foreland-dipping thrust system. These structures were folded and tilted by the emplacement of the Datos thrust (second phase of deformation, D
2
), generating an associated deformation characterized by subvertical folds with axial surface cleavage, with slight east vergence. These structures can obliterate the previous D
1
structures in the sector near the Datos thrust. D
1
and D
2
structures have not been observed in the same outcrops, but the relationship between bedding and cleavage as well as cleavage relationship with other structures allows discrimination between the two cleavage sets. Based on the features of Palaeozoic rocks of the Iberian Range and the Iberian Massif, we support the idea that the Herrera unit belongs to the Cantabrian Zone.
What a Tangled Web We Weave: Emerging Resistance Mechanisms to Inhibition of the Phosphoinositide 3-Kinase Pathway
Authors: Klempner Samuel J. , Myers Andrea P. , Cantley Lewis C. 
Published: November 2013

Abstract
The phosphoinositide 3-kinase (PI3K) pathway is one of the most frequently mutated pathways in cancer, and is actively being pursued as a therapeutic target. Despite the importance of the PI3K pathway in cancer, durable responses to PI3K pathway-targeted therapies are uncommon with monotherapy. Several in vitro and xenograft models have elucidated compensatory signaling and genomic changes which may limit the therapeutic effectiveness of PI3K inhibitors in the clinic. Future clinical trials with prospective evaluation of tumor signaling and genomic changes are likely to identify novel resistance mechanisms as well as subsets of patients who may derive maximal benefit from PI3K pathway inhibitors.
Significance: There are multiple ongoing clinical trials targeting the PI3K pathway members in several malignancies. This review summarizes the known mechanisms of resistance to targeting the PI3K pathway. Understanding of resistance mechanisms will help to inform more rational clinical trial design to optimize the clinical impact of targeting the PI3K pathway in cancer. Cancer Discov; 3(12); 1345–54. ©2013 AACR.
The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma
Authors: Van Allen Eliezer M. , Wagle Nikhil , Sucker Antje , Treacy Daniel J. , Johannessen Cory M. , Goetz Eva M. , Place Chelsea S. , Taylor-Weiner Amaro , Whittaker Steven , Kryukov Gregory V. , Hodis Eran , Rosenberg Mara , McKenna Aaron , Cibulskis Kristian , Farlow Deborah , Zimmer Lisa , Hillen Uwe , Gutzmer Ralf , Goldinger Simone M. , Ugurel Selma , Gogas Helen J. , Egberts Friederike , Berking Carola , Trefzer Uwe , Loquai Carmen , Weide Benjamin , Hassel Jessica C. , Gabriel Stacey B. , Carter Scott L. , Getz Gad , Garraway Levi A. , Schadendorf Dirk 
Published: November 2013

Abstract
Most patients with BRAFV600-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAFV600-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a “long tail” of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance. In three cases, multiple resistance gene alterations were observed within the same tumor biopsy. Overall, RAF inhibitor therapy leads to diverse clinical genetic resistance mechanisms, mostly involving MAPK pathway reactivation. Novel therapeutic combinations may be needed to achieve durable clinical control of BRAFV600-mutant melanoma. Integrating clinical genomics with preclinical screens may model subsequent resistance studies.
Significance: The use of RAF inhibitors for BRAFV600-mutant metastatic melanoma improves patient outcomes, but most patients demonstrate early or acquired resistance to this targeted therapy. We reveal the genetic landscape of clinical resistance mechanisms to RAF inhibitors from patients using whole-exome sequencing, and experimentally assess new observed mechanisms to define potential subsequent treatment strategies. Cancer Discov; 4(1); 94–109. ©2013 AACR.
See related commentary by Solit and Rosen, p. 27
This article is highlighted in the In This Issue feature, p. 1
Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy
Authors: Shi Hubing , Hugo Willy , Kong Xiangju , Hong Aayoung , Koya Richard C. , Moriceau Gatien , Chodon Thinle , Guo Rongqing , Johnson Douglas B. , Dahlman Kimberly B. , Kelley Mark C. , Kefford Richard F. , Chmielowski Bartosz , Glaspy John A. , Sosman Jeffrey A. , van Baren Nicolas , Long Georgina V. , Ribas Antoni , Lo Roger S. 
Published: November 2013

Abstract
BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAFV600-mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that mitogen-activated protein kinase reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification, and alternative splicing being most common. We also detected PI3K–PTEN–AKT–upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions in both core drug escape pathways were commonly detected concurrently in the same tumor or among multiple tumors from the same patient. Beyond harboring extensively heterogeneous resistance mechanisms, melanoma regrowth emerging from BRAF inhibitor selection displayed branched evolution marked by altered mutational spectra/signatures and increased fitness. Thus, melanoma genomic heterogeneity contributes significantly to BRAF inhibitor treatment failure, implying upfront, cotargeting of two core pathways as an essential strategy for durable responses.
Significance: This study provides critical insights into how human BRAF-mutant melanoma, a malignancy with marked mutational burden, escapes from BRAF inhibitors. Understanding the core resistance pathways as well as tumor heterogeneity, fitness, and mutational patterns, which emerge under drug selection, lays a foundation to rationalize clinical studies and investigate mechanisms of disease progression. Cancer Discov; 4(1); 80–93. ©2013 AACR.
See related commentary by Solit and Rosen, p. 27
This article is highlighted in the In This Issue feature, p. 1
Ex Vivo Assays of Dendritic Cell Activation and Cytokine Profiles as Predictors of In Vivo Effects in an Anti-Human CD40 Monoclonal Antibody ChiLob 7/4 Phase I Trial
Authors: Chowdhury F. , Johnson P.W. , Glennie M.J. , Williams A.P. 
Published: November 2013

Abstract
Immunostimulatory antibodies entering the clinic create challenge in terms of not only pharmacodynamics for monitoring anticipated mechanisms but also predetermining cytotoxicity. We show the use of ex vivo whole-blood samples to predict the activation requirements, cytokine signature, and adverse events of an anti-human-CD40 chimeric IgG1 antibody, ChiLob 7/4. Assessments were initially undertaken on human myeloid (mDC1) and plasmacytoid (pDC) dendritic cells, in which an absolute need for cross-linking was shown through the upregulation of activation markers CD83 and CCR7. Subsequent cytokine secretion evaluations of ex vivo whole blood showed the cross-linked antibody-induced increases in MIP1β, interleukin (IL)-8, IL-12, TNFα, and IL-6. This cytokine signature compared favorably with the Toll-like receptor (TLR) ligand lipopolysaccharide (LPS), in which levels of TNFα and IL-6 were significantly higher, suggesting a less intense proinflammatory response and possible modified cytokine release syndrome when used in human trials. Following first-in-human use of this agent within a dose escalation study, in vivo evaluations of dendritic cell activation and secreted cytokines closely matched the predetermined immunomonitoring endpoints. Patients showed a comparable pattern of MIP1β, IL-8, and IL-12 secretion, but no TNFα and IL-6 were identified. Mild symptoms relating to a cytokine release syndrome were seen at an equivalent dosage to that observed for dendritic cell activation and cytokine release. In summary, ChiLob 7/4 induces a distinctive pattern of dendritic cell activation and cytokine secretion in ex vivo assays that can be predictive of in vivo responses. Such preclinical approaches to monoclonal antibody evaluation may inform both the starting dosages and the anticipated cytokine release events that could occur, providing a valuable adjunct for future first-in-human assessments of immunostimulatory antibodies. Cancer Immunol Res; 2(3); 229–40. ©2013 AACR.
C-Reactive Protein Predicts Hematoma Growth in Intracerebral Hemorrhage
Authors: Di Napoli Mario , Parry-Jones Adrian R. , Smith Craig J. , Hopkins Stephen J. , Slevin Mark , Masotti Luca , Campi Veronica , Singh Puneetpal , Papa Francesca , Popa-Wagner Aurel , Tudorica Valerica , Godoy Daniel Agustin 
Published: November 2013

Background and Purpose—
Early hematoma growth (EHG) occurs in about one third of patients with spontaneous intracerebral hemorrhage. The main aim of this study was to investigate the potential of plasma C-reactive protein (CRP) for predicting EHG after acute spontaneous intracerebral hemorrhage.

Methods—

Plasma CRP was measured within 6 hours of onset (median, 120 minutes) in 399 patients with primary or vitamin K antagonist–associated spontaneous intracerebral hemorrhage and without recent infection. Computed tomography brain scans were performed at baseline and repeated within 24 hours (median, 22 hours). The primary outcome was EHG, defined as absolute growth >12.5 cm
3
or relative growth >33%. Secondary outcomes included early neurological worsening (ENW) using the Glasgow Coma Scale and 30-day mortality. Multivariable regression analyses were used to evaluate associations of CRP concentration and outcomes. Kaplan–Meier analysis was used for survival.

Results—

EHG occurred in 25.8%, ENW in 19.3%, and mortality was 31.8% at 30 days. Thirty-day mortality was significantly higher in patients with ENW (hazard ratio, 3.21; 95% confidence interval, 2.00–5.17;
P
<0.0001) and in patients with EHG (hazard ratio, 2.13; 95% confidence interval, 1.42–3.18;
P
<0.0001, log-rank test). Median CRP was 12 mg/L (interquartile range, 10–17) in the EHG group and 7 mg/L (interquartile range, 4–12.1) in those without EHG (
P
<0.0001). In multivariable analyses, plasma CRP>10 mg/L independently predicted EHG (odds ratio, 4.71; 95% confidence interval, 2.75–8.06;
P
<0.0001) and ENW (odds ratio, 2.70; 95% confidence interval, 1.50–4.84;
P
=0.0009).

Conclusions—
CRP>10 mg/L is independently predictive of EHG and ENW, both of which are associated with increased mortality. Inflammation may be important in contributing to EHG and warrants further investigation.
A Prospective Cohort Study of Patients With Transient Ischemic Attack to Identify High-Risk Clinical Characteristics
Authors: Perry Jeffrey J. , Sharma Mukul , Sivilotti Marco L.A. , Sutherland Jane , Worster Andrew , Émond Marcel , Stotts Grant , Jin Albert Y. , Oczkowski Wieslaw J. , Sahlas Demetrios J. , Murray Heather E. , MacKey Ariane , Verreault Steve , Wells George A. , Stiell Ian G. 
Published: November 2013

Background and Purpose—
The occurrence of a transient ischemic attack (TIA) increases an individual’s risk for subsequent stroke. The objectives of this study were to determine clinical features of patients with TIA associated with impending (≤7 days) stroke and to develop a clinical prediction score for impending stroke.

Methods—
We conducted a prospective cohort study at 8 Canadian emergency departments for 5 years. We enrolled patients with a new TIA. Our outcome was subsequent stroke within 7 days of TIA diagnosis.

Results—
We prospectively enrolled 3906 patients, of which 86 (2.2%) experienced a stroke within 7 days. Clinical features strongly correlated with having an impending stroke included first-ever TIA, language disturbance, longer duration, weakness, gait disturbance, elevated blood pressure, atrial fibrillation on ECG, infarction on computed tomography, and elevated blood glucose. Variables less associated with having an impending stroke included vertigo, lightheadedness, and visual loss. From this cohort, we derived the Canadian TIA Score which identifies the risk of subsequent stroke ≤7 days and consists of 13 variables. This model has good discrimination with a c-statistic of 0.77 (95% confidence interval, 0.73–0.82).

Conclusions—
Patients with TIA with their first TIA, language disturbance, duration of symptoms ≥10 minutes, gait disturbance, atrial fibrillation, infarction on computed tomography, elevated platelets or glucose, unilateral weakness, history of carotid stenosis, and elevated diastolic blood pressure are at higher risk for an impending stroke. Patients with vertigo and no high-risk features are at low risk. The Canadian TIA Score quantifies the impending stroke risk following TIA.
A sperm competition model for the European bitterling (Rhodeus amarus)
Authors: Smith Carl , Reichard Martin 
Published: November 2013

Sperm competition occurs when the spermatozoa of one male coincide with those of another to fertilise the same eggs. In some taxa males perform multiple ejaculations, which may function in sperm competition or in maintaining a baseline density of spermatozoa in the female reproductive tract to ensure fertilisation, a process that has been termed ‘topping up’. We investigated multiple ejaculations in the European bitterling (Rhodeus amarus), a freshwater fish that oviposits in freshwater mussels. We quantified spermatozoa in the mussel mantle cavity following ejaculation, and measured sperm motility parameters of males adopting different mating tactics. Following ejaculation spermatozoa density in the mussel increased linearly, peaked after 30 s, and then declined exponentially. Spermatozoa motility parameters did not differ between male mating tactics. We parameterised a model of sperm competition forR. amarus, which accurately predicted male fertilisation probability. We discuss these results in the context of multiple ejaculations and male mating tactics.
Female and male adult brush mice (Peromyscus boylii) use ultrasonic vocalizations in the wild
Authors: Petric R. , Kalcounis-Rueppell M.C. 
Published: November 2013

We examined the individual context of ultrasonic vocalizations (USVs) produced by free-living wild male and female adult brush mice (Peromyscus boylii). We tested the hypothesis that USV production is dependent on behavioral context, and is important during both adult male and female interactions. Our methods included a 12-channel microphone array, radio-telemetry and thermal imaging that allowed us to determine: (1) who produced USVs, (2) characteristics of USVs, (3) type of USVs, (4) behavioral context of USVs and (5) the identity of the second mouse if an individual was not alone when a USV was produced. Females vocalized as much as males and produced the same types of USVs as males. There were no differences between spectral characteristics of male and female USVs. Females and males vocalized in the presence of one another. Importantly, when females were together they vocalized more than expected based on the proportion of time they spent together. Our results suggest that, in addition to facilitating courtship and mating, USVs are general territorial calls for neighbors because females vocalized in the presence of their neighbors. Despite a large literature on laboratory mouse (Mus musculus) USVs, studies are heavily biased towards males. Our results on brush mice, a species with a similar breeding system to the lab mouse and other rodents, suggest that female–female communication is an important and underappreciated component of the evolution and maintenance of mouse USVs.
Langmuir Turbulence in Swell
Authors: McWilliams James C. , Huckle Edward , Liang Junhong , Sullivan Peter P. 
Published: November 2013

Abstract
The problem is posed and solved for the oceanic surface boundary layer in the presence of wind stress, stable density stratification, equilibrium wind-waves, and remotely generated swell-waves. The addition of swell causes an amplification of the Lagrangian-mean current and rotation toward the swell-wave direction, a fattening of the Ekman velocity spiral and associated vertical Reynolds stress profile, an amplification of the inertial current response, an enhancement of turbulent variance and buoyancy entrainment rate from the pycnocline, and—for very large swell—an upscaling of the coherent Langmuir circulation patterns. Implications are discussed for the parameterization of Langmuir turbulence influences on the mean current profile and the material entrainment rate in oceanic circulation models. In particular, even though the turbulent kinetic energy monotonically increases with wave amplitude inversely expressed by the turbulent Langmuir number La, the Lagrangian shear eddy viscosity profile κL(z) is a nonmonotonic function of La, first increasing with increasing wave amplitude up to approximately the wind-wave equilibrium level, then decreasing with additional swell-wave amplitude. In contrast, the pycnocline entrainment rate is a monotonic function ~La−2.
Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis
Authors: Wildhagen Karin C. A. A. , García de Frutos Pablo , Reutelingsperger Chris P. , Schrijver Roy , Aresté Cristina , Ortega-Gómez Almudena , Deckers Niko M. , Hemker H. Coenraad , Soehnlein Oliver , Nicolaes Gerry A. F. 
Published: November 2013

Key PointsNonanticoagulant heparin is shown to bind histones and provide cytoprotection in mouse models of sterile inflammation and sepsis.
A new model for segmentation of gray-scale and color images
Authors: Zhang Dazhi , Sun Jiebao , Guo Zhichang , Zhai Yanli 
Published: November 2013

Abstract
In this paper, we propose a new model for segmentation of both gray-scale and color images. This model is inspired by the GAC model, the region-scalable fitting model, the weighted bounded variation model and the active contour model based on the Mumford-Shah model. Compared with other active contour models, our new model cannot only make full use of advantages of both edge-based and region-based models, but also maintain more accurate overall message of segmented objects. Moreover, we establish the existence of the global minimum of the new energy functional and analyze the property of it. Finally, numerical results show the effectiveness of our proposed model.