bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verified decision procedures for MSO on words based on derivatives of regular expressions
Authors: Traytel Dmitriy , Nipkow Tobias 
Published: November 2013

Monadic second-order logic on finite words (MSO) is a decidable yet expressive logic into which many decision problems can be encoded. Since MSO formulas correspond to regular languages, equivalence of MSO formulas can be reduced to the equivalence of some regular structures (e.g. automata). This paper presents a verified functional decision procedure for MSO formulas that is not based on automata but on regular expressions. Functional languages are ideally suited for this task: regular expressions are data types and functions on them are defined by pattern matching and recursion and are verified by structural induction.
Decision procedures for regular expression equivalence have been formalized before, usually based on Brzozowski derivatives. Yet, for a straightforward embedding of MSO formulas into regular expressions an extension of regular expressions with a projection operation is required. We prove total correctness and completeness of an equivalence checker for regular expressions extended in that way. We also define a language-preserving translation of formulas into regular expressions with respect to two different semantics of MSO. Our results have been formalized and verified in the theorem prover Isabelle. Using Isabelle's code generation facility, this yields purely functional, formally verified programs that decide equivalence of MSO formulas.
Multi-core composability in the face of memory-bus contention
Authors: Behnam Moris , Inam Rafia , Nolte Thomas , Sjödin Mikael 
Published: November 2013

In this paper we describe the problem of achieving composability of independently developed real-time subsystems to be executed on a multi-core platform, and we provide a solution to tackle it. We evaluate existing work for achieving real-time predictability on multi-cores and illustrate their lack with respect to composability.
To address composability we present a multi-resource server-based scheduling technique to provide predictable performance when composing multiple subsystems on a shared multi-core platform. To achieve composability on multi-core platforms, we propose to add memory bandwidth as an additional server resource. Tasks within our multi-resource servers are guaranteed both CPU- and memory bandwidth; thus the performance of a server will become independent of resource usage by tasks in other servers. We are currently implementing multi-resource servers for the Enea OSE operating system for a Freescale P4080 8-core processor, to be tested with software for a 3G-basestation.
Dual Targeting of EWS-FLI1 Activity and the Associated DNA Damage Response with Trabectedin and SN38 Synergistically Inhibits Ewing Sarcoma Cell Growth
Authors: Grohar Patrick J. , Segars Laure E. , Yeung Choh , Pommier Yves , D'Incalci Maurizio , Mendoza Arnulfo , Helman Lee J. 
Published: November 2013

AbstractPurpose: The goal of this study is to optimize the activity of trabectedin for Ewing sarcoma by developing a molecularly targeted combination therapy.Experimental Design: We have recently shown that trabectedin interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. In this report, we build on this work to develop a trabectedin-based combination therapy with improved EWS-FLI1 suppression that also targets the drug-associated DNA damage to Ewing sarcoma cells.Results: We demonstrate by siRNA experiments that EWS-FLI1 drives the expression of the Werner syndrome protein (WRN) in Ewing sarcoma cells. Because WRN-deficient cells are known to be hypersensitive to camptothecins, we utilize trabectedin to block EWS-FLI1 activity, suppress WRN expression, and selectively sensitize Ewing sarcoma cells to the DNA-damaging effects of SN38. We show that trabectedin and SN38 are synergistic, demonstrate an increase in DNA double-strand breaks, an accumulation of cells in S-phase and a low picomolar IC50. In addition, SN38 cooperates with trabectedin to augment the suppression of EWS-FLI1 downstream targets, leading to an improved therapeutic index in vivo. These effects translate into the marked regression of two Ewing sarcoma xenografts at a fraction of the dose of camptothecin used in other xenograft studies.Conclusions: These results provide the basis and rationale for translating this drug combination to the clinic. In addition, the study highlights an approach that utilizes a targeted agent to interfere with an oncogenic transcription factor and then exploits the resulting changes in gene expression to develop a molecularly targeted combination therapy. Clin Cancer Res; 20(5); 1190–203. ©2013 AACR.
Importance of 5α-Reductase Gene Polymorphisms on Circulating and Intraprostatic Androgens in Prostate Cancer
Authors: Lévesque Éric , Laverdière Isabelle , Lacombe Louis , Caron Patrick , Rouleau Mélanie , Turcotte Véronique , Têtu Bernard , Fradet Yves , Guillemette Chantal 
Published: November 2013

Abstract
Purpose: Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer.
Experimental Design: To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer.
Results: We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids.
Conclusions: Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. Clin Cancer Res; 20(3); 576–84. ©2013 AACR.
Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia
Authors: Kreitman Robert J. , Wilson Wyndham , Calvo Katherine R. , Arons Evgeny , Roth Laura , Sapolsky Jeffrey , Zhou Hong , Raffeld Mark , Stetler-Stevenson Maryalice 
Published: November 2013

Abstract
Purpose: In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab.
Experimental Design: Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m2 beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry.
Results: By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P &lt; 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections.
Conclusion: Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer. Clin Cancer Res; 19(24); 6873–81. ©2013 AACR.
Activity of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Small Cell Lung Cancer
Authors: Polański Radosław , Hodgkinson Cassandra L. , Fusi Alberto , Nonaka Daisuke , Priest Lynsey , Kelly Paul , Trapani Francesca , Bishop Paul W. , White Anne , Critchlow Susan E. , Smith Paul D. , Blackhall Fiona , Dive Caroline , Morrow Christopher J. 
Published: November 2013

Abstract
Purpose: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use.
Experimental Design: AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC.
Results: AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors.
Conclusions: This study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond. Clin Cancer Res; 20(4); 926–37. ©2013 AACR.
Pulmonary Embolism in Ischemic Stroke: Clinical Presentation, Risk Factors, and Outcome
Authors: Pongmoragot Jitphapa , Rabinstein Alejandro A. , Nilanont Yongchai , Swartz Richard H. , Zhou Limei , Saposnik Gustavo ,   The Investigators of the Registry of the Canadian Stroke Network (RCSN) and University of Toronto Stroke Program for the Stroke Outcomes Research Canada (SORCan [www.sorcan.ca]) Working Group
Published: November 2013

Background

Limited information is available on the frequency of pulmonary embolism (
PE
) in patients with an acute ischemic stroke (
AIS
). We evaluated clinical characteristics, predisposing factors, and outcomes in
AIS
patients with
PE
.

Methods and Results

We included all
AIS
patients admitted to participating institutions in the
R
egistry of the
C
anadian
S
troke
N
etwork. Clinically
PE
was documented by a physician and confirmed by computed tomography pulmonary angiography within 30 days of the stroke case index. The primary outcome was death or disability at discharge. Secondary outcomes included disposition, length of hospital stay, mortality at 3 months and 1 year. Among 11 287 patients with
AIS
,
PE
was found in 89 (0.78%) patients. History of cancer, deep vein thrombosis (
DVT
)/
PE
, and
DVT
during the hospitalization were associated with
PE
.
PE
was associated with higher risk of death at 30 days (25.8% versus 13.6%;
P
<0.001), at 1 year (47.2% versus 24.6%;
P
<0.001), and disability at discharge (85.4% versus 63.6%;
P
<0.001). Mean length of stay was longer in stroke patients with
PE
(36 versus 16 days;
P
=0.001). After adjusting for age, sex, and stroke severity,
PE
remained associated with lower survival at 30 days and 1 year, and death or disability at discharge (
OR
3.02; 95%
CI
1.56 to 5.83).

Conclusions

In this large cohort study,
PE
occurred in nearly 1% of
AIS
patients.
PE
was more common in patients with severe stroke, history of cancer, previous
DVT
/
PE
or acute
DVT
and associated with lower short‐ and long‐term survival, greater disability, and longer length of stay.
Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation
Authors: Steinberg Benjamin A. , Holmes DaJuanicia N. , Piccini Jonathan P. , Ansell Jack , Chang Paul , Fonarow Gregg C. , Gersh Bernard , Mahaffey Kenneth W. , Kowey Peter R. , Ezekowitz Michael D. , Singer Daniel E. , Thomas Laine , Peterson Eric D. , Hylek Elaine M. ,   The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Investigators and Patients
Published: November 2013

Background
Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown.

Methods and Results

We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974
atrial fibrillation
patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years,
P
<0.0001), more likely to be white (92% versus 89%,
P
=0.005), more likely to have private insurance (33% versus 25%,
P
<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%,
P
<0.0001). They had more new‐onset
atrial fibrillation
(8.8% versus 4.1%,
P
<0.0001), lower
CHADS
2
scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3,
P
<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8,
P
<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73,
P
=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4,
P
<0.0001).

Conclusions
Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted.

Clinical Trial Registration

URL
: Clinicaltrials.gov. Unique identifier:
NCT
01165710.
The determinants of dominance relationships among subordinate females in the cooperatively breeding meerkat
Authors: Thavarajah N.K. , Fenkes M. , Clutton-Brock T.H. 
Published: November 2013

In cooperatively breeding species with high reproductive skew, a single breeding female is dominant to all other group members, but it is not yet known if there are consistent dominance relationships among subordinates. In this study on meerkats (Suricata suricatta), we used naturally observed dominance assertions and submissive interactions within dyads of subordinate females to investigate: (i) whether or not a dominance structure exists among them and what factors influence dominance relationships; and (ii) how dominance may influence the future reproductive success of subordinate females. Our study indicates that superiority in age and weight provide a competitive advantage during conflicts among subordinate females and that females who consistently dominate in these contests are subsequently more likely to attain a dominant breeding position. This provides a starting point for further investigations into dominance structure among subordinates in meerkat societies and other cooperative breeders.
Nematodes from galls on Myrtaceae. V. Fergusobia from large multilocular shoot bud galls from Angophora and Eucalyptus in Australia, with descriptions of six new species
Authors: Davies KERRIE A. , Giblin-Davis ROBIN M. , YE WEIMIN , LISNAWITA LISNAWITA , TAYLOR GARY S. , W. THOMAS KELLEY 
Published: November 2013

Six new species of Fergusobia, from large multilocular shoot bud galls on two species of Angophora and four species of Eucalyptus from both subgenera Eucalyptus and Symphyomyrtus, are described. Fergusobia cosmophyllae Davies n. sp. is characterized by the combination of a C-shaped parthenogenetic female with a short arcuate conoid tail, a broad (small a ratio) arcuate infective female with an hemispherical tail tip, and an arcuate to J-shaped male with broad, angular spicules and short bursa. Fergusobia delegatensae Davies n. sp. has an open C-shaped parthenogenetic female with a broadly conoid tail, an infective female of variable shape with an hemispherical tail tip, and a male of open C-shape with a crenate bursa that arises 40–70% along the length of the body from the tail tip and terminates just anterior to the cloaca. Fergusobia diversifoliae Davies n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate, C- or J-shaped male with angular spicule and a long peloderan bursa. Fergusobia floribundae Davies n. sp. has a C-shaped parthenogenetic female with a narrow, arcuate, conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate or J-shaped male with an angular spicule and a short to mid-body length peloderan bursa. Fergusobia minimus Lisnawita n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to open C-shaped male with an angular spicule and a peloderan bursa arising at about 10–30% of body length. Fergusobia pimpamensis Davies n. sp. has an open C to C-shaped parthenogenetic female with a narrow conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to C-shaped male with an arcuate spicule and a long, crenate, peloderan bursa. An inventory of all known Fergusobia/Fergusonina associations from terminal shoot bud galls is presented. The larval shield morphology of the associated mutualistic Fergusonina species is discussed where known. Analyses of DNA sequences of D2/D3 and COI suggested that the six new species are distributed between three clades of Fergusobia.
Nested Large-Eddy Simulations of the Intermittently Turbulent Stable Atmospheric Boundary Layer over Real Terrain
Authors: Zhou Bowen , Chow Fotini Katopodes 
Published: November 2013

AbstractThe nighttime stable atmospheric boundary layer over real terrain is modeled with nested high-resolution large-eddy simulations (LESs). The field site is located near Leon, Kansas, where the 1999 Cooperative Atmosphere–Surface Exchange Study took place. The terrain is mostly flat with an average slope of 0.5°. The main topographic feature is a shallow valley oriented in the east–west direction. The night of 5 October is selected to study intermittent turbulence under prevailing quiescent conditions. Brief turbulent periods triggered by shear-instability waves are modeled with good magnitude and temporal precision with a dynamic reconstruction turbulence closure. In comparison, conventional closures fail to excite turbulent motions and predict a false laminar flow. A plausible new intermittency mechanism, previously unknown owing to limited spatial coverage of field instruments at this site, is unveiled with the LESs. Turbulence can be generated through gravity wave breaking over a stagnant cold-air bubble in the valley upwind of the main tower. The bubble is preceded by the formation of a valley cold-air pool due to down-valley drainage flows during the evening transition. The bubble grows in depth by entraining cold down-valley and downslope flows from below and is eroded by shear-induced wave breaking on the top. The cyclic process of formation and erosion is repeated during the night, leading to sporadic turbulent bursting.
High-Resolution Hurricane Vector Winds from C-Band Dual-Polarization SAR Observations
Authors: Zhang Biao , Perrie William , Zhang Jun A. , Uhlhorn Eric W. , He Yijun 
Published: November 2013

Abstract
This study presents a new approach for retrieving hurricane surface wind vectors utilizing C-band dual-polarization (VV, VH) synthetic aperture radar (SAR) observations. The copolarized geophysical model function [C-band model 5.N (CMOD5.N)] and a new cross-polarized wind speed retrieval model for dual polarization [C-band cross-polarized ocean surface wind retrieval model for dual-polarization SAR (C-2POD)] are employed to construct a cost function. Minimization of the cost function allows optimum estimates for the wind speeds and directions. The wind direction ambiguities are removed using a parametric two-dimensional sea surface inflow angle model. To evaluate the accuracy of the proposed method, two RADARSAT-2 SAR images of Hurricanes Bill and Bertha are analyzed. The retrieved wind speeds and directions are compared with collocated Quick Scatterometer (QuikSCAT) winds, showing good consistency. Results suggest that the proposed method has good potential to retrieve hurricane surface wind vectors from dual-polarization SAR observations.