bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Scalable, Correct Time-Stamped Stack
Authors: Dodds Mike , Haas Andreas , Kirsch Christoph M. 
Published: May 2015

Concurrent data-structures, such as stacks, queues, and deques, often implicitly enforce a total order over elements in their underlying memory layout. However, much of this order is unnecessary: linearizability only requires that elements are ordered if the insert methods ran in sequence. We propose a new approach which uses timestamping to avoid unnecessary ordering. Pairs of elements can be left unordered if their associated insert operations ran concurrently, and order imposed as necessary at the eventual removal.
We realise our approach in a new non-blocking data-structure, the TS (timestamped) stack. Using the same approach, we can define corresponding queue and deque data-structures. In experiments on x86, the TS stack outperforms and outscales all its competitors -- for example, it outperforms the elimination-backoff stack by factor of two. In our approach, more concurrency translates into less ordering, giving less-contended removal and thus higher performance and scalability. Despite this, the TS stack is linearizable with respect to stack semantics.
The weak internal ordering in the TS stack presents a challenge when establishing linearizability: standard techniques such as linearization points work well when there exists a total internal order. We present a new stack theorem, mechanised in Isabelle, which characterises the orderings sufficient to establish stack semantics. By applying our stack theorem, we show that the TS stack is indeed linearizable. Our theorem constitutes a new, generic proof technique for concurrent stacks, and it paves the way for future weakly ordered data-structure designs.
Equations, Contractions, and Unique Solutions
Authors: Sangiorgi Davide 
Published: May 2015

One of the most studied behavioural equivalences is bisimilarity. Its success is much due to the associated bisimulation proof method, which can be further enhanced by means of "up-to bisimulation" techniques such as "up-to context".
A different proof method is discussed, based on unique solution of special forms of inequations called contractions, and inspired by Milner's theorem on unique solution of equations. The method is as powerful as the bisimulation proof method and its "up-to context" enhancements. The definition of contraction can be transferred onto other behavioural equivalences, possibly contextual and noncoinductive.
This enables a coinductive reasoning style on such equivalences, either by applying the method based on unique solution of contractions, or by injecting appropriate contraction preorders into the bisimulation game. The techniques are illustrated on CCS-like languages; an example dealing with higher-order languages is also shown.
Quantitative Interprocedural Analysis
Authors: Chatterjee Krishnendu , Pavlogiannis Andreas , Velner Yaron 
Published: May 2015

We consider the quantitative analysis problem for interprocedural control-flow graphs (ICFGs). The input consists of an ICFG, a positive weight function that assigns every transition a positive integer-valued number, and a labelling of the transitions (events) as good, bad, and neutral events. The weight function assigns to each transition a numerical value that represents a measure of how good or bad an event is. The quantitative analysis problem asks whether there is a run of the ICFG where the ratio of the sum of the numerical weights of good events versus the sum of weights of bad events in the long-run is at least a given threshold (or equivalently, to compute the maximal ratio among all valid paths in the ICFG). The quantitative analysis problem for ICFGs can be solved in polynomial time, and we present an efficient and practical algorithm for the problem.
We show that several problems relevant for static program analysis, such as estimating the worst-case execution time of a program or the average energy consumption of a mobile application, can be modeled in our framework. We have implemented our algorithm as a tool in the Java Soot framework. We demonstrate the effectiveness of our approach with two case studies. First, we show that our framework provides a sound approach (no false positives) for the analysis of inefficiently-used containers. Second, we show that our approach can also be used for static profiling of programs which reasons about methods that are frequently invoked. Our experimental results show that our tool scales to relatively large benchmarks, and discovers relevant and useful information that can be used to optimize performance of the programs.
Deep Specifications and Certified Abstraction Layers
Authors: Gu Ronghui , Koenig Jérémie , Ramananandro Tahina , Shao Zhong , Wu Xiongnan (Newman) , Weng Shu-Chun , Zhang Haozhong , Guo Yu 
Published: May 2015

Modern computer systems consist of a multitude of abstraction layers (e.g., OS kernels, hypervisors, device drivers, network protocols), each of which defines an interface that hides the implementation details of a particular set of functionality. Client programs built on top of each layer can be understood solely based on the interface, independent of the layer implementation. Despite their obvious importance, abstraction layers have mostly been treated as a system concept; they have almost never been formally specified or verified. This makes it difficult to establish strong correctness properties, and to scale program verification across multiple layers.
In this paper, we present a novel language-based account of abstraction layers and show that they correspond to a strong form of abstraction over a particularly rich class of specifications which we call deep specifications. Just as data abstraction in typed functional languages leads to the important representation independence property, abstraction over deep specification is characterized by an important implementation independence property: any two implementations of the same deep specification must have contextually equivalent behaviors. We present a new layer calculus showing how to formally specify, program, verify, and compose abstraction layers. We show how to instantiate the layer calculus in realistic programming languages such as C and assembly, and how to adapt the CompCert verified compiler to compile certified C layers such that they can be linked with assembly layers. Using these new languages and tools, we have successfully developed multiple certified OS kernels in the Coq proof assistant, the most realistic of which consists of 37 abstraction layers, took less than one person year to develop, and can boot a version of Linux as a guest.
Higher Inductive Types as Homotopy-Initial Algebras
Authors: Sojakova Kristina 
Published: May 2015

Homotopy Type Theory is a new field of mathematics based on the recently-discovered correspondence between Martin-Löf's constructive type theory and abstract homotopy theory. We have a powerful interplay between these disciplines - we can use geometric intuition to formulate new concepts in type theory and, conversely, use type-theoretic machinery to verify and often simplify existing mathematical proofs.
Higher inductive types form a crucial part of this new system since they allow us to represent mathematical objects, such as spheres, tori, pushouts, and quotients, in the type theory. We investigate a class of higher inductive types called W-suspensions which generalize Martin-Löf's well-founded trees. We show that a propositional variant of W-suspensions, whose computational behavior is determined up to a higher path, is characterized by the universal property of being a homotopy-initial algebra. As a corollary we get that W-suspensions in the strict form are homotopy-initial.
Polymorphic Functions with Set-Theoretic Types
Authors: Castagna Giuseppe , Nguyen Kim , Xu Zhiwu , Abate Pietro 
Published: May 2015

This article is the second part of a two articles series about the definition of higher order polymorphic functions in a type system with recursive types and set-theoretic type connectives (unions, intersections, and negations).
In the first part, presented in a companion paper, we defined and studied the syntax, semantics, and evaluation of the explicitly-typed version of a calculus, in which type instantiation is driven by explicit instantiation annotations. In this second part we present a local type inference system that allows the programmer to omit explicit instantiation annotations for function applications, and a type reconstruction system that allows the programmer to omit explicit type annotations for function definitions.
The work presented in the two articles provides the theoretical foundations and technical machinery needed to design and implement higher-order polymorphic functional languages with union and intersection types and/or for semi-structured data processing.
Higher-Order Approximate Relational Refinement Types for Mechanism Design and Differential Privacy
Authors: Barthe Gilles , Gaboardi Marco , Gallego Arias Emilio Jesús , Hsu Justin , Roth Aaron , Strub Pierre-Yves 
Published: May 2015

Mechanism design is the study of algorithm design where the inputs to the algorithm are controlled by strategic agents, who must be incentivized to faithfully report them. Unlike typical programmatic properties, it is not sufficient for algorithms to merely satisfy the property, incentive properties are only useful if the strategic agents also believe this fact.
Verification is an attractive way to convince agents that the incentive properties actually hold, but mechanism design poses several unique challenges: interesting properties can be sophisticated relational properties of probabilistic computations involving expected values, and mechanisms may rely on other probabilistic properties, like differential privacy, to achieve their goals.
We introduce a relational refinement type system, called HOARe2, for verifying mechanism design and differential privacy. We show that HOARe2 is sound w.r.t. a denotational semantics, and correctly models (epsilon,delta)-differential privacy; moreover, we show that it subsumes DFuzz, an existing linear dependent type system for differential privacy. Finally, we develop an SMT-based implementation of HOARe2 and use it to verify challenging examples of mechanism design, including auctions and aggregative games, and new proposed examples from differential privacy.
Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium
Authors: Kane Eleanor , Skibola Christine F. , Bracci Paige M. , Cerhan James R. , Costas Laura , Smedby Karin Ekström , Holly Elizabeth A. , Maynadié Marc , Novak Anne J. , Lightfoot Tracy J. , Ansell Stephen M. , Smith Alex G. , Liebow Mark , Melbye Mads , Morton Lindsay , de Sanjosé Silvia , Slager Susan L. , Wang Sophia S. , Zhang Yawei , Zheng Tongzhang , Roman Eve 
Published: May 2015

Abstract
Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.
Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).
Results: Obesity (BMI ≥ 30 kg/m2) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02–1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27–2.94), with a RERI of 0.41 (95% CI, −0.05–0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.
Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.
Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G&gt;A in the pathogenesis of lymphoma. Cancer Epidemiol Biomarkers Prev; 24(7); 1061–70. ©2015 AACR.
Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after Endocrine Therapy
Authors: Khan Sofia , Fagerholm Rainer , Rafiq Sajjad , Tapper William , Aittomäki Kristiina , Liu Jianjun , Blomqvist Carl , Eccles Diana , Nevanlinna Heli 
Published: May 2015

Abstract
Purpose: Although most patients with estrogen receptor (ER)–positive breast cancer benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies.
Experimental Design: We performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer Study, 805 patients, with 240 receiving endocrine therapy and Prospective study of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155 endocrine therapy patients, evaluating 486,478 single-nucleotide polymorphisms (SNP). The top four associations from the endocrine treatment subgroup were further investigated in two independent datasets totaling 5,011 patients, with 3,485 receiving endocrine therapy.
Results: A meta-analysis identified a common SNP rs8113308, mapped to 19q13.41, associating with reduced survival among endocrine-treated patients [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.37–2.07; P = 6.34 × 10−7] and improved survival among ER-negative patients, with a similar trend in ER-positive cases not receiving endocrine therapy. In a multivariate analysis adjusted for conventional prognostic factors, we found a significant interaction between the rs8113308 and endocrine treatment, indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast cancer survival, with the per-allele HR for interaction 2.16 (95% CI, 1.30–3.60; Pinteraction = 0.003) and HR = 7.77 (95% CI, 0.93–64.71) for the homozygous genotype carriers. A biologic rationale is suggested by in silico functional analyses.
Conclusions: Our findings suggest carrying the rs8113308 rare allele may identify patients who will not benefit from adjuvant endocrine treatment. Clin Cancer Res; 21(18); 4086–96. ©2015 AACR.
Dissecting the Dual Role of AMPK in Cancer: From Experimental to Human Studies
Authors: Zadra Giorgia , Batista Julie L. , Loda Massimo 
Published: May 2015

Abstract
The precise role of 5′AMP-activated kinase (AMPK) in cancer and its potential as a therapeutic target is controversial. Although it is well established that activation of this energy sensor inhibits the main anabolic processes that sustain cancer cell proliferation and growth, AMPK activation can confer on cancer cells the plasticity to survive under metabolic stress such as hypoxia and glucose deprivation, which are commonly observed in fast growing tumors. Thus, AMPK is referred to as both a “conditional” tumor suppressor and “contextual” oncogene. To add a further layer of complexity, AMPK activation in human cancer tissues and its correlation with tumor aggressiveness and progression appears to vary in different contexts. The current review discusses the different faces of this metabolic regulator, the therapeutic implications of its modulation, and provides an overview of the most relevant data available on AMPK activation and AMPK-activating drugs in human studies. Mol Cancer Res; 13(7); 1059–72. ©2015 AACR.
Pharmacologically Increasing Mdm2 Inhibits DNA Repair and Cooperates with Genotoxic Agents to Kill p53-Inactivated Ovarian Cancer Cells
Authors: Carrillo Alexia M. , Hicks Mellissa , Khabele Dineo , Eischen Christine M. 
Published: May 2015

Abstract
The Mdm2 oncogene is a negative regulator of the p53 tumor suppressor and recently identified inhibitor of DNA break repair. Nutlin-3 is a small-molecule inhibitor of Mdm2–p53 interaction that can induce apoptosis in cancer cells through activation of p53. Although this is a promising therapy for those cancers with wild-type p53, half of all human cancers have inactivated p53. Here, we reveal that a previously unappreciated effect of Nutlin is inhibition of DNA break repair, stemming from its ability to increase Mdm2 protein levels. The Nutlin-induced increase in Mdm2 inhibited DNA double-strand break repair and prolonged DNA damage response signaling independent of p53. Mechanistically, this effect of Nutlin required Mdm2 and acted through Nbs1 of the Mre11–Rad50–Nbs1 DNA repair complex. In ovarian cancer cells, where &gt;90% have inactivated p53, Nutlin combined with the genotoxic agents, cisplatin or etoposide, had a cooperative lethal effect resulting in increased DNA damage and apoptosis. Therefore, these data demonstrate an unexpected consequence of pharmacologically increasing Mdm2 levels that when used in combination with genotoxic agents induces synthetic lethality in ovarian cancer cells, and likely other malignant cell types, that have inactivated p53.
Implications: Data reveal a therapeutically beneficial effect of pharmacologically increasing Mdm2 levels combined with chemotherapeutic agents for malignancies that have lost functional p53. Mol Cancer Res; 13(8); 1197–205. ©2015 AACR.
PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial CD8 T Cells in Human Ovarian Cancer
Authors: Webb John R. , Milne Katy , Nelson Brad H. 
Published: May 2015

AbstractαE(CD103)β7 is a TGFβ-regulated integrin that mediates retention of lymphocytes in peripheral tissues by binding to E-cadherin expressed on epithelial cells. We recently reported that αE(CD103)β7 specifically demarcates intraepithelial CD8+ tumor-infiltrating lymphocytes (CD8 TIL) in ovarian cancer and that CD103+ TIL have a surface profile consistent with an active effector phenotype (HLA-DR+, Ki67+, and CD127lo). These findings led us to hypothesize that, over time, CD103-mediated retention of CD8 TIL within the tumor epithelium might result in chronic stimulation by tumor antigen, which in turn might lead to an exhausted phenotype. To investigate this possibility, we evaluated PD-1 expression in a large cohort of ovarian tumors (N = 489) with known CD103+ TIL content. PD-1+ cells were present in 38.5% of high-grade serous carcinomas (HGSC), but were less prevalent in other histologic subtypes. PD-1+ TIL were strongly associated with increased disease-specific survival in HGSC (HR, 0.4864; P = 0.0007). Multicolor immunohistochemistry and flow cytometry revealed a high degree of PD-1 and CD103 coexpression, specifically within the CD8 TIL compartment. PD-1+CD103+ CD8 TIL were quiescent when assessed directly ex vivo yet were capable of robust cytokine production after pharmacologic stimulation. Moreover, they showed negligible expression of additional exhaustion-associated markers, including TIM-3, CTLA-4, and LAG-3. Thus, as hypothesized, CD103+ CD8 TIL express PD-1 and appear quiescent in the tumor microenvironment. However, these cells retain functional competence and demonstrate strong prognostic significance. We speculate that, after standard treatment, PD-1+CD103+ CD8 TIL might regain functional antitumor activity, an effect that potentially could be augmented by immune modulation. Cancer Immunol Res; 3(8); 926–35. ©2015 AACR.
Hypertension Suppression, Not a Cumulative Thrust of Quantitative Trait Loci, Predisposes Blood Pressure Homeostasis to Normotension
Authors: Crespo Kimberley , Ménard Annie , Deng Alan Y. 
Published: May 2015

Background—
Genetics of high blood pressure (BP) has revealed causes of hypertension. The cause of normotension, however, is poorly understood. Inbred Lewis rats sustain normotension despite a genetic push in altering BP. It was unknown whether this rigid resistance to BP changes is because of an insufficient hypertensive impact from limited alleles of quantitative trait loci (QTLs) or because of an existence of a master control superseding the combined strength of hypertensive QTL alleles.

Methods and Results—
Currently, BP-elevating QTL alleles from hypertensive Dahl salt-sensitive rats (DSS) replaced those of Lewis on chromosomes 7, 8, 10, and 17 on the Lewis background. These hypertensive QTL alleles were then merged to systematically achieve multiple combinations. Results showed that there was no quantitative correlation between BP variations and the number of hypertensive QTL alleles, and that BP was only slightly elevated from a combined force of normotensive alleles from 7 QTLs. Thus, a genetic factor aside from the known QTLs seemed to be at play in preserving normotension and act as a hypertension suppressor. A follow-up study using consecutive backcrosses from Dahl salt-sensitive rats and Lewis identified a chromosome segment where a hypertension suppressor might reside.

Conclusions—
Our results provide the first evidence that normotension is not enacted via a numeric advantage of BP-lowering QTL alleles, and instead can be achieved by a particular genetic component actively suppressing hypertensive QTL alleles. The identification of this hypertension suppressor could result in formulating unique diagnostic and therapeutic targets, and above all, preventive measures against essential hypertension.
Dynamic Linkage between Cold Air Outbreaks and Intensity Variations of the Meridional Mass Circulation
Authors: Yu Yueyue , Ren Rongcai , Cai Ming 
Published: May 2015

Abstract
This study investigates the dynamical linkage between the meridional mass circulation and cold air outbreaks using the ERA-Interim data covering the period 1979–2011. It is found that the onset date of continental-scale cold air outbreaks coincides well with the peak time of stronger meridional mass circulation events, when the net mass transport across 60°N in the warm or cold air branch exceeds ~88 × 109 kg s−1. During weaker mass circulation events when the net mass transport across 60°N is below ~71.6 × 109 kg s−1, most areas of the midlatitudes are generally in mild conditions except the northern part of western Europe. Composite patterns of circulation anomalies during stronger mass circulation events greatly resemble that of the winter mean, with the two main routes of anomalous cold air outbreaks being along the climatological routes of polar cold air: namely, via East Asia and North America. The Siberian high shifts westward during stronger mass circulation events, opening up a third route of cold air outbreaks through eastern Europe, where lies the poleward warm air route in the winter-mean condition. The strengthening of the Icelandic low and Azores high during stronger mass circulation events acts to close off the climatological-mean cold air route via western Europe; this is responsible for the comparatively normal temperature there. The composite pattern for weaker mass circulation events is generally reversed, where the weakening of the Icelandic low and Azores high, corresponding to the negative phase of the North Atlantic Oscillation (NAO), leads to the reopening and strengthening of the equatorward cold air route through western Europe, which is responsible for the cold anomalies there.