bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computing Shortest Paths among Curved Obstacles in the Plane
Authors: Chen Danny Z. , Wang Haitao 
Published: April 2015

A fundamental problem in computational geometry is to compute an obstacle-avoiding Euclidean shortest path between two points in the plane. The case of this problem on polygonal obstacles is well studied. In this article, we consider the problem version on curved obstacles, which are commonly modeled as
splinegons
. A splinegon can be viewed as replacing each edge of a polygon by a convex curved edge (polygons are special splinegons), and the combinatorial complexity of each curved edge is assumed to be
O
(1). Given in the plane two points
s
and
t
and a set
s
of
h
pairwise disjoint splinegons with a total of
n
vertices, after a
bounded degree decomposition
of
S
is obtained, we compute a shortest
s
-to-
t
path avoiding the splinegons in
O
(
n
+
h
log
h
+
k
) time, where
k
is a parameter sensitive to the geometric structures of the input and is upper bounded by
O
(
h
2
). The bounded degree decomposition of
S
, which is similar to the triangulation of the polygonal domains, can be computed in
O
(
n
log
n
) time or
O
(
n
+
h
log
1 + ϵ
h
) time for any ϵ > 0. In particular, when all splinegons are convex, the decomposition can be computed in
O
(
n
+
h
log
h
) time and
k
is linear to the number of common tangents in the free space (called “free common tangents”) among the splinegons. Our techniques also improve several previous results:

(1) For the polygon case (i.e., when all splinegons are polygons), the shortest path problem was previously solved in
O
(
n
log
n
) time, or in
O
(
n
+
h
2
log
n
) time. Thus, our algorithm improves the
O
(
n
+
h
2
log
n
) time result, and is faster than the
O
(
n
log
n
) time solution for sufficiently small
h
, for example,
h
=
o
(√
n
,log
n
.

(2) Our techniques produce an optimal output-sensitive algorithm for a basic visibility problem of computing all free common tangents among
h
pairwise disjoint convex splinegons with a total of
n
vertices. Our algorithm runs in
O
(
n
+
h
log
h
+
k
) time and
O
(
n
) working space, where
k
is the number of all free common tangents. Note that
k
=
O
(
h
2
). Even for the special case where all splinegons are convex
polygons
, the previously best algorithm for this visibility problem takes
O
(
n
+
h
2
log
n
) time.

(3) We improve the previous work for computing the shortest path between two points among convex pseudodisks of
O
(1) complexity each.

In addition, a by-product of our techniques is an optimal
O
(
n
+
h
log
h
) time and
O
(
n
) space algorithm for computing the Voronoi diagram of a set of
h
pairwise disjoint convex splinegons with a total of
n
vertices.
A Bounded Budget Network Creation Game
Authors: Ehsani Shayan , Fadaee Saber Shokat , Fazli Mohammadamin , Mehrabian Abbas , Sadeghabad Sina Sadeghian , Safari Mohammadali , Saghafian Morteza 
Published: April 2015

We introduce a network creation game in which each player (vertex) has a fixed budget to establish links to other players. In this model, each link has a unit price, and each agent tries to minimize its cost, which is either its eccentricity or its total distance to other players in the underlying (undirected) graph of the created network. Two versions of the game are studied: In the MAX version, the cost incurred to a vertex is the maximum distance between the vertex and other vertices, and, in the SUM version, the cost incurred to a vertex is the sum of distances between the vertex and other vertices. We prove that in both versions pure Nash equilibria exist, but the problem of finding the best response of a vertex is NP-hard. We take the social cost of the created network to be its diameter, and next we study the maximum possible diameter of an equilibrium graph with
n
vertices in various cases. When the sum of players’ budgets is
n
− 1, the equilibrium graphs are always trees, and we prove that their maximum diameter is Θ(
n
) and Θ(log
n
) in MAX and SUM versions, respectively. When each vertex has a unit budget (i.e., can establish a link to just one vertex), the diameter of any equilibrium graph in either version is Θ(1). We give examples of equilibrium graphs in the MAX version, such that all vertices have positive budgets and yet the diameter is Ω(√log
n
). This interesting (and perhaps counterintuitive) result shows that increasing the budgets may increase the diameter of equilibrium graphs and hence deteriorate the network structure. Then we prove that every equilibrium graph in the SUM version has diameter 2

O
(√log
n
)

. Finally, we show that if the budget of each player is at least
k
, then every equilibrium graph in the SUM version is
k
-connected or has a diameter smaller than 4.
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models
Authors: Eberlein Catherine A. , Stetson Daniel , Markovets Aleksandra A. , Al-Kadhimi Katherine J. , Lai Zhongwu , Fisher Paul R. , Meador Catherine B. , Spitzler Paula , Ichihara Eiki , Ross Sarah J. , Ahdesmaki Miika J. , Ahmed Ambar , Ratcliffe Laura E. , O'Brien Elizabeth L. Christey , Barnes Claire H. , Brown Henry , Smith Paul D. , Dry Jonathan R. , Beran Garry , Thress Kenneth S. , Dougherty Brian , Pao William , Cross Darren A.E. 
Published: April 2015

Abstract
Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition. Cancer Res; 75(12); 2489–500. ©2015 AACR.
A New B7:CD28 Family Checkpoint Target for Cancer Immunotherapy: HHLA2
Authors: Xiao Yanping , Freeman Gordon J. 
Published: April 2015

Abstract
HHLA2 is a newly identified B7 family member that modulates T-cell functions through interaction with TMIGD2 and possibly a second receptor, with coinhibition in two studies and costimulation in one study. HHLA2 is expressed on a variety of human cancers, and its coinhibitory function makes it a candidate for cancer immunotherapy. Clin Cancer Res; 21(10); 2201–3. ©2015 AACR.
See related article by Janakiram et al., p. 2359
Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to Induce Durable Complete Remissions
Authors: Filatenkov Alexander , Baker Jeanette , Mueller Antonia M.S. , Kenkel Justin , Ahn G-One , Dutt Suparna , Zhang Nigel , Kohrt Holbrook , Jensen Kent , Dejbakhsh-Jones Sussan , Shizuru Judith A. , Negrin Robert N. , Engleman Edgar G. , Strober Samuel 
Published: April 2015

AbstractPurpose: The goals of the study were to elucidate the immune mechanisms that contribute to desirable complete remissions of murine colon tumors treated with single radiation dose of 30 Gy. This dose is at the upper end of the ablative range used clinically to treat advanced or metastatic colorectal, liver, and non–small cell lung tumors.Experimental Design: Changes in the tumor immune microenvironment of single tumor nodules exposed to radiation were studied using 21-day (&gt;1 cm in diameter) CT26 and MC38 colon tumors. These are well-characterized weakly immunogenic tumors.Results: We found that the high-dose radiation transformed the immunosuppressive tumor microenvironment resulting in an intense CD8+ T-cell tumor infiltrate, and a loss of myeloid-derived suppressor cells (MDSC). The change was dependent on antigen cross-presenting CD8+ dendritic cells, secretion of IFNγ, and CD4+T cells expressing CD40L. Antitumor CD8+ T cells entered tumors shortly after radiotherapy, reversed MDSC infiltration, and mediated durable remissions in an IFNγ-dependent manner. Interestingly, extended fractionated radiation regimen did not result in robust CD8+ T-cell infiltration.Conclusions: For immunologically sensitive tumors, these results indicate that remissions induced by a short course of high-dose radiotherapy depend on the development of antitumor immunity that is reflected by the nature and kinetics of changes induced in the tumor cell microenvironment. These results suggest that systematic examination of the tumor immune microenvironment may help in optimizing the radiation regimen used to treat tumors by adding a robust immune response. Clin Cancer Res; 21(16); 3727–39. ©2015 AACR.
The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association
Authors: Kridel Robert , Xerri Luc , Gelas-Dore Bénédicte , Tan King , Feugier Pierre , Vawda Ayesha , Canioni Danielle , Farinha Pedro , Boussetta Sami , Moccia Alden A. , Brice Pauline , Chavez Elizabeth A. , Kyle Alastair H. , Scott David W. , Sanders Ashley D. , Fabiani Bettina , Slack Graham W. , Minchinton Andrew I. , Haioun Corinne , Connors Joseph M. , Sehn Laurie H. , Steidl Christian , Gascoyne Randy D. , Salles Gilles 
Published: April 2015

Abstract
Purpose: We aimed to assess the prognostic significance of follicular lymphoma–associated macrophages in the era of rituximab treatment and maintenance.
Experimental Design: We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets.
Results: An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).
Conclusions: CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received. Clin Cancer Res; 21(15); 3428–35. ©2015 AACR.
Characteristics of Ventricular Tachycardia Ablation in Patients With Continuous Flow Left Ventricular Assist Devices
Authors: Sacher Frederic , Reichlin Tobias , Zado Erica S. , Field Michael E. , Viles-Gonzalez Juan F. , Peichl Petr , Ellenbogen Kenneth A. , Maury Philippe , Dukkipati Srinivas R. , Picard Francois , Kautzner Josef , Barandon Laurent , Koneru Jayanthi N. , Ritter Philippe , Mahida Saagar , Calderon Joachim , Derval Nicolas , Denis Arnaud , Cochet Hubert , Shepard Richard K. , Corre Jerome , Coffey James O. , Garcia Fermin , Hocini Meleze , Tedrow Usha , Haissaguerre Michel , d’Avila Andre , Stevenson William G. , Marchlinski Francis E. , Jais Pierre 
Published: April 2015

Background—
Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device.

Methods and Results—
All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230–740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT.

Conclusions—
Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.
Task-Specific, Age Related Effects in the Cross-Modal Identification and Localisation of Objects
Authors: Barrett Maeve M. , Newell Fiona N. 
Published: April 2015

We investigated age-related effects in cross-modal interactions using tasks assessing spatial perception and object perception. Specifically, an audio-visual object identification task and an audio-visual object localisation task were used to assess putatively distinct perceptual functions in four age groups: children (8–11 years), adolescents (12–14 years), young and older adults. Participants were required to either identify or locate target objects. Targets were specified as unisensory (visual/auditory) or multisensory (audio-visual congruent/audio-visual incongruent) stimuli. We found age-related effects in performance across both tasks. Both children and older adults were less accurate at locating objects than adolescents or young adults. Children were also less accurate at identifying objects relative to young adults, but the performance between young adults, adolescents and older adults did not differ. A greater cost in accuracy for audio-visual incongruent relative to audio-visual congruent targets was found for older adults, children and adolescents relative to young adults. However, we failed to find a benefit in performance for any age group in either the identification or localisation task for audio-visual congruent targets relative to visual-only targets. Our findings suggest that visual information dominated when identifying or localising audio-visual stimuli. Furthermore, on the basis of our results, object identification and object localisation abilities seem to mature late in development and that spatial abilities may be more prone to decline as we age relative to object identification abilities. In addition, the results suggest that multisensory facilitation may require more sensitive measures to reveal differences in cross-modal interactions across higher-level perceptual tasks.
Applicability of the Bulk-Transfer Approach to Estimate Evapotranspiration from Boreal Peatlands
Authors: Isabelle Pierre-Erik , Nadeau Daniel F. , Rousseau Alain N. , Coursolle Carole , Margolis Hank A. 
Published: April 2015

AbstractIn northern landscapes, peatlands are widespread and their hydrological processes are complex. Furthermore, they are typically remote, limiting the amount and accuracy of in situ measurements. This is especially the case for evapotranspiration ET, which strongly influences watershed hydrology. The objective of this paper is to demonstrate the validity of the bulk-transfer approach to estimate ET over boreal peatlands. The simplicity of the model relies on four assumptions: (i) near-neutral atmospheric conditions; (ii) wet surface; (iii) constant momentum roughness length depending on vegetation height; and (iv) constant water vapor roughness length, with the last two assumptions implying a constant water vapor transfer coefficient CE. Using eddy covariance data from three Canadian peatlands—Necopastic (James Bay, Québec), Mer Bleue (Ottawa, Ontario), and Western Peatland (Athabasca, Alberta)—this paper shows that these sites are characterized by frequent occurrences of near-neutral atmospheric conditions, especially the Necopastic site, with nearly 76% of the 30-min data segments occurring under near-neutral stratification. The analysis suggests these near-neutral conditions occur as a result of strong mechanical turbulence and weak buoyancy effects. The bulk-transfer approach gives promising results for 30-min and daily ET in terms of mean error and correlation, with performances similar to the Penman equation, without requiring net radiation data. The accuracy of the approach is likely related to the number of near-neutral periods and the elevated position of the water table, which backs up the wet surface assumption.
EU foreign policy through the lens of practice theory: A different approach to the European External Action Service
Authors: Lequesne Christian 
Published: April 2015

There is a proliferation of works on the new European External Action Service (EEAS). Most of these approach the EEAS through a rationalist framework, assessing how a new institution can solve long-term questions of EU foreign policy-making to ensure consistency and coherence while reducing transaction costs between actors (both supranational and national) in a multilevel governance structure. This paper takes a different direction. Using 30 interviews with officials from the EEAS, the European Commission, and national ministries of foreign affairs, conducted between 2010 and 2013, it shows how the study of practice aids understanding of the nature of the EEAS. As a new institution, the EEAS lends itself particularly well to practice-based study because new institutions must develop new practices. The first section of the article defines the notion of practice and shows the importance of historicizing the struggles around practices in understanding the creation of the EEAS. The second section demonstrates how agents’ practices shape professional cultures within the EEAS. The third section highlights the relationship between practices and rule-making. Going over the EEAS as a case study, the conclusion focuses on the importance of analysing actors’ practices for understanding the current evolution of diplomacy and international relations in general.
Students’ Perception of an Integrated Approach of Teaching Entire Sequence of Medicinal Chemistry, Pharmacology, and Pharmacotherapeutics Courses in PharmD Curriculum
Authors: Islam Mohammed A. , Schweiger Teresa A. 
Published: April 2015

Purpose: To develop an integrated approach of teaching medicinal chemistry, pharmacology, and pharmacotherapeutics and to evaluate students’ perceptions of integration as they progress through the PharmD curriculum. Methods: Instructors from each discipline jointly mapped the course contents and sequenced the course delivery based on organ systems/disease states. Medicinal chemistry and pharmacology contents were integrated and aligned with respective pharmacotherapeutics contents to deliver throughout second and third year of the curriculum. In addition to classroom lectures, active learning strategies such as recitation, case studies, online-discussion boards, open book quizzes, and writing patient progress notes were incorporated to enhance student learning. Student learning was assessed by examination scores, patient progress notes, and writing assignments. The impact of course integration was evaluated by a Web-based survey. Results: One hundred and sixty-nine students completed the survey. Students exhibited positive attitude toward the integrated approach of teaching medicinal chemistry, pharmacology, and therapeutics. The P3 and P4 students better appreciated the benefits of integration compared to P2 students ( P < .05). Conclusion: Students perceived the course integration as an effective way of learning. This study supports course improvement and the viability of expanding the concept of integration to other courses in the curriculum.
Influence of Different β-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy
Authors: Ignjatovic Vladimir , Pavlovic Sinisa , Miloradovic Vladimir , Andjelkovic Nebojsa , Davidovic Goran , Djurdjevic Predrag , Stolic Radojica , Iric-Cupic Violeta , Simic Ivan , Ignjatovic Vesna D. , Petrovic Njegos , Smiljanic Zorica , Zdravkovic Vladimir , Simovic Stefan , Jovanovic Danijela , Nesic Jelena 
Published: April 2015

Introduction: The use of β-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of β-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. Objective: To examine the effect of different β-blockers on platelet aggregation in patients on dual antiplatelet therapy. Methodology: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of β-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. Results: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. Conclusion: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.