bluuebunny/crossref_metadata_2025_split huggingface dataset:
Logical relations for fine-grained concurrency
Authors: Turon Aaron J. , Thamsborg Jacob , Ahmed Amal , Birkedal Lars , Dreyer Derek 
Published: November 2016

Fine-grained concurrent data structures (or FCDs) reduce the granularity of critical sections in both time and space, thus making it possible for clients to access different parts of a mutable data structure in parallel. However, the tradeoff is that the implementations of FCDs are very subtle and tricky to reason about directly. Consequently, they are carefully designed to be contextual refinements of their coarse-grained counterparts, meaning that their clients can reason about them as if all access to them were sequentialized.
In this paper, we propose a new semantic model, based on Kripke logical relations, that supports direct proofs of contextual refinement in the setting of a type-safe high-level language. The key idea behind our model is to provide a simple way of expressing the "local life stories" of individual pieces of an FCD's hidden state by means of protocols that the threads concurrently accessing that state must follow. By endowing these protocols with a simple yet powerful transition structure, as well as the ability to assert invariants on both heap states and specification code, we are able to support clean and intuitive refinement proofs for the most sophisticated types of FCDs, such as conditional compare-and-set (CCAS).
Linear dependent types for differential privacy
Authors: Gaboardi Marco , Haeberlen Andreas , Hsu Justin , Narayan Arjun , Pierce Benjamin C. 
Published: November 2016

Differential privacy offers a way to answer queries about sensitive information while providing strong, provable privacy guarantees, ensuring that the presence or absence of a single individual in the database has a negligible statistical effect on the query's result. Proving that a given query has this property involves establishing a bound on the query's sensitivity---how much its result can change when a single record is added or removed.
A variety of tools have been developed for certifying that a given query differentially private. In one approach, Reed and Pierce [34] proposed a functional programming language, Fuzz, for writing differentially private queries. Fuzz uses linear types to track sensitivity and a probability monad to express randomized computation; it guarantees that any program with a certain type is differentially private. Fuzz can successfully verify many useful queries. However, it fails when the sensitivity analysis depends on values that are not known statically.
We present DFuzz, an extension of Fuzz with a combination of linear indexed types and lightweight dependent types. This combination allows a richer sensitivity analysis that is able to certify a larger class of queries as differentially private, including ones whose sensitivity depends on runtime information. As in Fuzz, the differential privacy guarantee follows directly from the soundness theorem of the type system. We demonstrate the enhanced expressivity of DFuzz by certifying differential privacy for a broad class of iterative algorithms that could not be typed previously.
Hyperstream processing systems
Authors: Suenaga Kohei , Sekine Hiroyoshi , Hasuo Ichiro 
Published: November 2016

We exploit the apparent similarity between (discrete-time) stream processing and (continuous-time) signal processing and transfer a deductive verification framework from the former to the latter. Our development is based on rigorous semantics that relies on nonstandard analysis (NSA).
Specifically, we start with a discrete framework consisting of a Lustre-like stream processing language, its Kahn-style fixed point semantics, and a program logic (in the form of a type system) for partial correctness guarantees. This stream framework is transferred as it is to one for hyperstreams---streams of streams, that typically arise from sampling (continuous-time) signals with progressively smaller intervals---via the logical infrastructure of NSA. Under a certain continuity assumption we identify hyperstreams with signals; our final outcome thus obtained is a deductive verification framework of signals. In it one verifies properties of signals using the (conventionally discrete) proof principles, like fixed point induction.
Principled parsing for indentation-sensitive languages
Authors: Adams Michael D. 
Published: November 2016

Several popular languages, such as Haskell, Python, and F#, use the indentation and layout of code as part of their syntax. Because context-free grammars cannot express the rules of indentation, parsers for these languages currently use ad hoc techniques to handle layout. These techniques tend to be low-level and operational in nature and forgo the advantages of more declarative specifications like context-free grammars. For example, they are often coded by hand instead of being generated by a parser generator.
This paper presents a simple extension to context-free grammars that can express these layout rules, and derives GLR and LR(k) algorithms for parsing these grammars. These grammars are easy to write and can be parsed efficiently. Examples for several languages are presented, as are benchmarks showing the practical efficiency of these algorithms.
Content-Adaptive Display Power Saving for Internet Video Applications on Mobile Devices
Authors: Liu Yao , Xiao Mengbai , Zhang Ming , Li Xin , Dong Mian , Ma Zhan , Li Zhenhua , Guo Lei , Chen Songqing 
Published: November 2016

Backlight scaling is a technique proposed to reduce the display panel power consumption by strategically dimming the backlight. However, for mobile video applications, a computationally intensive luminance compensation step must be performed in combination with backlight scaling to maintain the perceived appearance of video frames. This step, if done by the Central Processing Unit (CPU), could easily offset the power savings via backlight dimming. Furthermore, computing the backlight scaling values requires per-frame luminance information, which is typically too energy intensive to compute on mobile devices.
In this article, we propose Content-Adaptive Display (CAD) for two typical Internet mobile video applications: video streaming and real-time video communication. CAD uses the mobile device’s Graphics Processing Unit (GPU) rather than the CPU to perform luminance compensation at reduced power consumption. For video streaming where video frames are available in advance, we compute the backlight scaling schedule using a more efficient dynamic programming algorithm than existing work. For real-time video communication where video frames are generated on the fly, we propose a greedy algorithm to determine the backlight scaling at runtime. We implement CAD in one video streaming application and one real-time video call application on the Android platform and use a Monsoon power meter to measure the real power consumption. Experiment results show that CAD can save more than 10% overall power consumption for up to 55.7% videos during video streaming and up to 31.0% overall power consumption in real-time video calls.
Visual abstraction in an interactive programming environment
Authors: Powell Michael L. , Linton Mark A. 
Published: November 2016

We are designing a software development system that implements “what you see is what you get” for programming. The system, called OMEGA, allows software to be displayed, processed, and modified, using pictorial representations to convey the structure and levels of abstraction of the program.
OMEGA takes advantage of the interactive user interface to provide syntax-free input, user selectable display format, and incremental semantic analysis. By distinguishing input specification from output display, and exploiting interaction in semantic analysis, we are able to unify the different abstraction mechanisms present in traditional programming environments.
miRNA-487a Promotes Proliferation and Metastasis in Hepatocellular Carcinoma
Authors: Chang Rui-Min , Xiao Shuai , Lei Xiong , Yang Hao , Fang Feng , Yang Lian-Yue 
Published: November 2016

Abstract
Purpose: Hepatocellular carcinoma (HCC) harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. However, the mechanisms for metastasis and recurrence remain incompletely clear. This study aimed to investigate the role of hsa-miR-487a (miR-487a) in promoting the proliferation and metastasis of HCC and to elucidate the underlying molecular mechanisms.
Experimental Design: 198 HCC samples were analyzed for association between miR-487a expression and patient clinicopathological features and prognosis. The roles of miR-487a in proliferation and metastasis were validated both in vivo and in vitro. The upstream regulator and downstream targets of miR-487a were determined using a dual luciferase reporter assay, chromatin immunoprecipitation and immunohistochemistry.
Results: Our results demonstrate that upregulated miR-487a correlates with a poor prognosis for HCC patients. miR-487a enhances proliferation and metastasis of HCC cells by directly binding to sprouty-related EVH1 domain containing 2 (SPRED2) or phosphoinositide-3-Kinase regulatory subunit 1 (PIK3R1). Interestingly, miR-487a mainly promotes metastasis via SPRED2 induced mitogen activated protein kinase signaling and promotes proliferation via PIK3R1 mediated AKT signaling. Transcription of miR-487a was found to be activated by up-regulated heat shock factor 1, which we previously demonstrated to be an important metastasis-associated transcription factor in a previous study. Phosphorodiamidate morpholino oligomers effectively silenced miR-487a and inhibited HCC tumor progression in mouse models.
Conclusions: Our findings show that miR-487a, mediated by heat shock factor 1, promotes proliferation and metastasis of HCC by PIK3R1 and SPRED2 binding, respectively. Our study provides a rationale for developing miR-487a as a potential prognostic marker or a potential therapeutic target against HCC. Clin Cancer Res; 23(10); 2593–604. ©2016 AACR.
BRM Promoter Polymorphisms and Survival of Advanced Non–Small Cell Lung Cancer Patients in the Princess Margaret Cohort and CCTG BR.24 Trial
Authors: Liu Geoffrey , Cuffe Sinead , Liang Shermi , Azad Abul Kalam , Cheng Lu , Brhane Yonathan , Qiu Xin , Cescon David W. , Bruce Jeffrey , Chen Zhuo , Cheng Dangxiao , Patel Devalben , Tse Brandon C. , Laurie Scott A. , Goss Glenwood , Leighl Natasha B. , Hung Rayjean , Bradbury Penelope A. , Seymour Lesley , Shepherd Frances A. , Tsao Ming Sound , Chen Bingshu E. , Xu Wei , Reisman David N. 
Published: November 2016

Abstract
Introduction: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non–small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression.
Experimental Design: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms. Associations of BRM variants with survival were assessed using log-rank tests, the method of Kaplan and Meier, and Cox proportional hazards models. Promoter swap, luciferase assays, and chromatin immunoprecipitation (ChIP) experiments evaluated polymorphism function. In silico analysis of publicly available gene expression datasets with outcome were performed.
Results: Carrying the homozygous variants of both polymorphisms (“double homozygotes”, DH) when compared with those carrying the double wild-type was associated with worse overall survival, with an adjusted hazard ratios (aHR) of 2.74 (95% CI, 1.9–4.0). This was confirmed in the BR.24 trial (aHR, 8.97; 95% CI, 3.3–18.5). Lower BRM gene expression (by RNA-Seq or microarray) was associated with worse outcome (P &lt; 0.04). ChIP and promoter swap experiments confirmed binding of MEF2D and HDAC9 only to homozygotes of each polymorphism, associated with reduced promoter activity in the DH.
Conclusions: Epigenetic regulatory molecules bind to two BRM promoter sequence variants but not to their wild-type sequences. These variants are associated with adverse overall and progression-free survival. Decreased BRM gene expression, seen with these variants, is also associated with worse overall survival. Clin Cancer Res; 23(10); 2460–70. ©2016 AACR.
The Effect of Preservative and Temperature on the Analysis of Circulating Tumor DNA
Authors: Parpart-Li Sonya , Bartlett Bjarne , Popoli Maria , Adleff Vilmos , Tucker Laura , Steinberg Rebecca , Georgiadis Andrew , Phallen Jill , Brahmer Julie , Azad Nilo , Browner Ilene , Laheru Daniel , Velculescu Victor E. , Sausen Mark , Diaz Luis A. 
Published: November 2016

Abstract
Purpose: Analysis of genomic alterations in cell-free DNA (cfDNA) is evolving as an approach to detect, monitor, and genotype malignancies. Methods to separate the liquid from the cellular fraction of whole blood for circulating tumor DNA (ctDNA) analyses have been largely unstudied, although these may be a critical consideration for assay performance.
Experimental Design: To evaluate the influence of blood processing on cfDNA and ctDNA quality and yield, we compared the cfDNA levels in serum with those in plasma. Given the limitations of serum for ctDNA analyses, we evaluated the effects of two plasma processing approaches, K2EDTA and Cell-Free DNA BCT (BCT) tubes, on cfDNA and ctDNA recovery. A total of 45 samples from nine patients with cancer were collected in both tube types. Once collected, blood was processed into plasma immediately or kept at room temperature and processed into plasma at 1, 3, 5, or 7 days.
Results: As early as 24 hours after collection, plasma isolated from blood collected in K2EDTA tubes contained an elevated level of cfDNA that increased over time compared with BCT tubes where no significant increase in cfDNA levels was observed. When samples from an additional six patients with cancer, collected in the same manner, were stored at 4°C in K2EDTA tubes over the course of 3 days, total cfDNA and ctDNA levels were comparable between samples collected in BCT tubes. At day 3, there was a trend toward a decrease in ctDNA levels in both tubes that was more pronounced when measuring the mutant allele fraction for cases stored at 4°C in K2EDTA tubes.
Conclusions: In summary, methods of blood processing have a strong influence on cfDNA and ctDNA levels and should be a consideration when evaluating ctDNA in peripheral circulation. Clin Cancer Res; 23(10); 2471–7. ©2016 AACR.
Isolation of T-Cell Receptors Specifically Reactive with Mutated Tumor-Associated Antigens from Tumor-Infiltrating Lymphocytes Based on CD137 Expression
Authors: Parkhurst Maria , Gros Alena , Pasetto Anna , Prickett Todd , Crystal Jessica S. , Robbins Paul , Rosenberg Steven A. 
Published: November 2016

Abstract
Purpose: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T-cell receptors (TCR) can mediate tumor regression. Some tumor-infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TILs target tumor-specific neoantigens. Here we attempted to isolate neoantigen-reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs.
Experimental Design: Mutations expressed by tumors were identified using whole-exome and RNA sequencing. Tandem minigene (TMG) constructs encoding 12–24 mutated gene products were synthesized, each encoding the mutated amino acid flanked by 12 amino acids of the normal protein sequence. TILs were cultured with autologous dendritic cells (DC) transfected with in vitro transcribed (IVT) mRNAs encoding TMGs and were evaluated for IFNγ secretion and CD137 expression. Neoantigen-reactive T cells were enriched from TILs by sorting for CD137+ CD8+ T cells and expanded in vitro. Dominant TCR α and β chains were identified in the enriched populations using a combination of 5′ rapid amplification of cDNA ends, deep sequencing of genomic DNA, PairSeq analysis, and single-cell RT-PCR analysis. Human PBL retrovirally transduced to express the TCRs were evaluated for recognition of relevant neoantigens.
Results: We identified 27 TCRs from 6 patients that recognized 14 neoantigens expressed by autologous tumor cells.
Conclusions: This strategy provides the means to generate T cells expressing neoantigen-reactive TCRs for use in future adoptive cell transfer immunotherapy trials for patients with cancer. Clin Cancer Res; 23(10); 2491–505. ©2016 AACR.
Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction
Authors: Savarese Gianluigi , Hage Camilla , Orsini Nicola , Dahlström Ulf , Perrone-Filardi Pasquale , Rosano Giuseppe M.C. , Lund Lars H. 
Published: November 2016

Background—
In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.

Methods and Results—
In the Swedish Heart Failure Registry, HFmrEF (EF=40%–49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36–0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29–0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34–0.62). These findings were replicated in HFmrEF and HFpEF separately.

Conclusions—
In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.
Angiogenic Imbalance and Residual Myocardial Injury in Recovered Peripartum Cardiomyopathy Patients
Authors: Goland Sorel , Weinstein Jean Marc , Zalik Adi , Kuperstein Rafael , Zilberman Liaz , Shimoni Sara , Arad Michael , Ben Gal Tuvia , George Jacob 
Published: November 2016

Background—
Recent studies suggest that angiogenic imbalance during pregnancy may lead to acute peripartum cardiomyopathy (PPCM). We propose that angiogenic imbalance and residual cardiac dysfunction may exist even after recovery from PPCM.

Methods and Results—

Twenty-nine women at least 12 months after presentation with PPCM, who exhibited recovery of left ventricular (LV) ejection fraction (≥50%), were included in the study (mean age 35±6 years, LV ejection fraction 61.0±3.9%). The number of circulating endothelial progenitor cells (EPCs) and plasma levels of proangiogenic vascular endothelial growth factor and of soluble vascular endothelial growth factor receptor Flt1 (sFlt1) were measured. All patients underwent comprehensive cardiac function assessment, including tissue Doppler imaging and 2-dimensional (2D) strain echocardiography. All measurements were compared with healthy controls. Patients with a history of PPCM have significantly higher sFlt1 concentrations (median [25th–75th percentile]; 149.57, [63.14–177.89] versus 20.29, [15.00–53.89] pg/mL,
P
<0.001) and significantly decreased vascular endothelial growth factor/sFlt1 ratio (
P
=0.012) compared with controls, with a trend toward lower concentration of circulating CD34
+
/KDR
+
levels. In addition, patients with PPCM had lower early velocities E′ septal (9.9±2.1 versus 11.0±1.5 cm/s,
P
=0.02), with a significantly lower systolic velocity S′ septal (7.6±1.2 versus 8.5±1.2 cm/s,
P
=0.003) by tissue Doppler imaging. Significantly lower LV global longitudinal (−19.1±3.3 versus −22.7±2.2%,
P
<0.001) and apical circumferential 2D strain (−16.6±4.9 versus −21.2±7.9,
P
=0.02) were present in patients with PPCM compared with controls.

Conclusions—
Higher concentration of sFlt1 with concomitant decreased circulating endothelial progenitor cell levels along with inappropriate attenuated vascular endothelial growth factor levels may imply an angiogenic imbalance that exists even after recovery and may thus predispose to PPCM. In addition, tissue Doppler imaging and 2D strain were able to identify residual myocardial injury in post-PPCM women with apparent recovery of LV systolic function. Both angiogenic imbalance and residual myocardial injury may play an important role in the recurrence of LV dysfunction during subsequent pregnancies.
Incidence and Determinants of Complications in Rotational Atherectomy
Authors: Sakakura Kenichi , Inohara Taku , Kohsaka Shun , Amano Tetsuya , Uemura Shiro , Ishii Hideki , Kadota Kazushige , Nakamura Masato , Funayama Hiroshi , Fujita Hideo , Momomura Shin-ichi 
Published: November 2016

Background—
The usage of rotational atherectomy (RA) is growing in the current percutaneous coronary intervention (PCI) because of the expansion of PCI indication to more complex lesions. However, the complications after RA have been linked to procedure-related morbidity and mortality. The purpose of this study was to investigate the incidence and determinants of complications in RA using a large nationwide registration system in Japan (J-PCI).

Methods and Results—
The primary composite outcome of this study was defined as the occurrence of in-hospital death, cardiac tamponade, and emergent surgery after RA. A total of 13 335 RA cases (3.2% of registered PCI cases) were analyzed. The composite outcome was observed in 175 cases (1.31%) and included 80 in-hospital deaths (0.60%), 86 tamponades (0.64%), and 24 emergent surgeries (0.18%). The clinical variables associated with occurrence of the composite outcome were age (odds ratio [OR] 1.03 per unit increment, 95% confidence interval [CI] 1.02–1.05), impaired kidney function (OR 1.59, 95% CI 1.15–2.19), previous myocardial infarction (OR 1.69, 95% CI 1.21–2.35), emergent PCI (OR 4.02, 95% CI 1.66–8.27), and triple-vessel disease (versus single-vessel disease: OR 2.17, 95% CI 1.43–3.28). Notably, institutional volume of RA cases was inversely associated with the composite outcomes (high- versus low-volume institution: OR 0.56, 95% CI 0.36–0.89).

Conclusions—
The reported incidence of important procedure-related complication rate was 1.3%, with each component ranging between 0.2% and 0.6% in J-PCI. Its determinants were both patient related (age, impaired kidney function, and previous myocardial infarction) and procedure related (emergent procedures, number of diseased vessels, and institutional volume of RA).