bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System
Authors: Hidano Shinya , Randall Louise M. , Dawson Lucas , Dietrich Hans K. , Konradt Christoph , Klover Peter J. , John Beena , Harris Tajie H. , Fang Qun , Turek Bradley , Kobayashi Takashi , Hennighausen Lothar , Beiting Daniel P. , Koshy Anita A. , Hunter Christopher A. 
Published: November 2016

ABSTRACTThe local production of gamma interferon (IFN-γ) is important to controlToxoplasma gondiiin the brain, but the basis for these protective effects is not fully understood. The studies presented here reveal that the ability of IFN-γ to inhibit parasite replication in astrocytesin vitrois dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of antimicrobial pathways and increased cyst formation in astrocytes. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen.IMPORTANCEAstrocytes are the most numerous cell type in the brain, and they are activated in response to many types of neuroinflammation, but their function in the control of CNS-specific infection is unclear. The parasiteToxoplasma gondiiis one of the few clinically relevant microorganisms that naturally infects astrocytes, and the studies presented here establish that the ability of astrocytes to inhibit parasite replication is essential for the local control of this opportunistic pathogen. Together, these studies establish a key role for astrocytes as effector cells and in the coordination of many aspects of the protective immune response that operates in the brain.
Mercury enrichments in lower Aptian sediments support the link between Ontong Java large igneous province activity and oceanic anoxic episode 1a
Authors: Charbonnier Guillaume , Föllmi Karl B. 
Published: November 2016

Abstract
The early Aptian recorded one of the most significant episodes of environmental change during the Mesozoic—the Selli oceanic anoxic episode (OAE 1a). It has often been suggested that magmatic activity related to the emplacement of the Greater Ontong Java large igneous province (LIP) triggered OAE 1a. A major challenge, however, resides in the establishment of precise temporal relationships between the environmental perturbations associated with OAE 1a and the phases of volcanic activity. In this study we evaluate the potential of mercury (Hg) as a proxy of volcanic activity and investigate lower Aptian sediments with different total organic carbon (TOC) contents, which are exposed at Roter Sattel (Briançonnais, Swiss Alps), Glaise (Vocontian Basin, southeast France), and La Bédoule (South Provencal Basin, southeast France). The intervals equivalent to OAE 1a are marked by significant increases in Hg contents, which are only partially dependent on TOC contents. This is shown by the Hg anomalies in the TOC-poor sediments of La Bédoule, the only moderate correlation of Hg and TOC contents in the TOC-enriched sediments of Roter Sattel (R2 = 0.48), and the persistence of the anomaly in Hg/TOC ratios in all sediments except for the TOC-enriched ones. These results suggest that the Hg anomaly not only is related to primary productivity, redox conditions, and organic-matter preservation, but has deeper roots. Volcanic outgassing related to Greater Ontong Java LIP activity is taken here as the main source of the Hg enrichment recorded in the western Tethyan sediments. Our Hg data indicate that magmatic pulses at the onset and during the OAE 1a triggered the early Aptian environmental perturbations.
Climate-controlled shifts in sediment provenance inferred from detrital zircon ages, western Peruvian Andes
Authors: Litty Camille , Lanari Pierre , Burn Marco , Schlunegger Fritz 
Published: November 2016

Abstract
Provenance analysis of Pleistocene terrace deposits, together with modern sediments from the same streams, from four catchments draining the western margin of the Andes in Peru is used to infer changes in erosion patterns between the past and the present period by matching detrital zircon ages with crystallization ages of source rocks. Age populations suggest major changes in sediment provenance through the past 100 k.y. At present, sediment sources are mainly located along the steep middle reaches of the rivers, whereas during the Pleistocene, sources were additionally located in the low-relief headwaters of these catchments. These shifts in the loci of erosion are interpreted to reflect changes in precipitation patterns, where periods of stronger precipitation on the Altiplano allowed the entrainment of material from the low-relief plateau in the past. In contrast, modern precipitation patterns result in negligible erosion rates on the Altiplano, and the site of material entrainment shifts to the knickzone reaches where steeper slopes and higher stream power promote erosion. In that sense, this work illustrates that terrace aggradation is associated with major shifts in provenance sources.
Delayed maximum northern European summer temperatures during the Last Interglacial as a result of Greenland Ice Sheet melt
Authors: Jones R.T. , Turney C.S.M. , Lang B. , Brooks S.J. , Rundgren M. , Hammarlund D. , Björck S. , Fogwill C.J. 
Published: November 2016

Abstract
Here we report a new quantitative mean July temperature reconstruction using non-biting midges (chironomids) from the Danish Last Interglacial (LIG) site Hollerup (spanning 127–116 ka). We find that peak mean July temperatures of 17.5 °C, similar to those of the present day (1961–1990 CE), were reached shortly before the onset of the regional Carpinus pollen zone. Through comparison to terrestrial and marine sequences we demonstrate that peak summer warmth took place some three millennia after the onset of LIG warming in Europe, a marked delay in line with records from the North Atlantic. Crucially, the warmest northern European summer temperatures appear to follow maximum Greenland Ice Sheet mass loss, implying that meltwater substantially reduced Atlantic Meridional Overturning Circulation and depressed European temperatures during the early part of the interglacial.
Preparticipation predictors for championship injury and illness: cohort study at the Beijing 2015 International Association of Athletics Federations World Championships
Authors: Timpka Toomas , Jacobsson Jenny , Bargoria Victor , Périard Julien D , Racinais Sébastien , Ronsen Ola , Halje Karin , Andersson Christer , Dahlström Örjan , Spreco Armin , Edouard Pascal , Alonso Juan-Manuel 
Published: November 2016

ObjectivesTo determine preparticipation predictors of injury and illness at a major Athletics championship.MethodsA cohort study design was used. Before the 2015 International Association of Athletics Federations World Championships in Athletics, all 207 registered national teams were approached about partaking in a study of preparticipation health; 50 teams accepted. The athletes (n=957) in the participating teams were invited to complete a preparticipation health questionnaire (PHQ). New injuries and illnesses that occurred at the championships were prospectively recorded. Logistic regression analyses were performed with simple and multiple models using any in-championship injury and in-championship illness as outcomes.ResultsThe PHQ was completed by 307 (32.1%) of the invited athletes; 116 athletes (38.3%) reported an injury symptom during the month before the championships, while 40 athletes (13%) reported an illness symptom. 20 (6.5%) of the participating athletes sustained a health problem during the championships. Endurance athletes were almost 10-fold more likely to sustain an in-championship illness than speed/power athletes (OR, 9.88; 95% CI 1.20 to 81.31; p=0.033). Participants reporting a preparticipation gradual-onset injury symptom were three times more likely (OR, 3.09; 95% CI 1.08 to 8.79; p=0.035) and those reporting an illness symptom causing anxiety were fivefold more likely (OR, 5.56; 95% CI 1.34 to 23.15; p=0.018) to sustain an in-championship injury.Summary and conclusionsAnalyses of preparticipation predictors of injury and illness at a major Athletics championship suggest that endurance athletes require particular clinical attention. Preparticipation symptoms causing anxiety are interesting predictors for in-championship health problems.
Use of combination therapy in the treatment of primary osteoporosis: protocol for a network meta-analysis of randomised trials
Authors: Lou Shenghan , Lv Houchen , Chen Yuxiang , Zhang Licheng , Tang Peifu 
Published: November 2016

IntroductionThe existing medications approved for treatment of primary osteoporosis can be divided into antiresorptive drugs and anabolic drugs. According to the mechanisms of action, the combined therapy may produce a synergistic effect on bone mineral density (BMD) compared with monotherapy, and thus improves the efficacy of fracture resistance. This network meta-analysis aims to compare the efficacies of different combined methods for the treatment of primary osteoporosis.Methods and analysisMEDLINE, EMBASE and Cochrane databases will be searched to identify all randomised controlled trials (RCTs) and quasi-RCTs that evaluate the effectiveness of combined therapy versus monotherapy for primary osteoporosis. The primary outcome will be the BMD changes at the lumbar spine and total hip, and the secondary outcome will be the risks of vertebral fracture and non-vertebral fracture. The efficacies of different combined methods will be compared via traditional pairwise meta-analysis, trial sequential analysis and Bayesian network meta-analysis. Risk of bias will be assessed using the Cochrane tool and the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation for network meta-analysis.Ethics and disseminationEthical approval is not required because this is a protocol for a systematic review without including confidential personal data or data on interventions on patients. Our results will be published in a peer-review journal.Trial registration numberPROSPERO CRD42016038569.
Evidence of the deformation of dykes from the Central Deccan Volcanic Province, Aurangabad, Maharashtra, India
Authors: Babar M. D. , Kaplay Ramakant D. , Mukherjee Soumyajit , Kulkarni P. S. 
Published: November 2016

Abstract

The Deccan Volcanic Province (DVP) covers an area of more than 500 000 km
2
. There are three major dyke swarms in this province, viz. the Narmada-Tapi, the Western Coast and the Pune-Nasik. In addition, the Nandurbar-Dhule and Pachmari dykes have also been studied. However, the Central Deccan Volcanic Province (CDVP), including parts of Aurangabad (Maharashtra, India), has received less attention than the SW, northern and NE parts of the Deccan Trap. We report on deformed/offset dykes in and around Aurangabad, in the CDVP. These dykes intrude the stratified host basaltic lava flows composed of weathered porphyritic and amygdaloidal basalt. This rheological contrast locally affected the emplacement of dykes, producing offset, the formation of sills, the curvature of dyke walls and finger-like intrusions. The offset of dykes is presumably caused by variations in local stress. The dyke swarm from the CDVP is reported for the first time. The range in the length and width of the dykes is 2.4–26.2 and 1–27 m, respectively. The dykes trend NE, which matches that of the Narmada-Tapi dyke swarm. The present study indicates that the feeder dyke(s) may have fed the basaltic lava flows of the Aurangabad region. The bent pipe vesicles indicate that the lava flowed towards the SE.
Measuring the ‘Great Unconformity’ on the North China Craton using new detrital zircon age data
Authors: He Tianchen , Zhou Ying , Vermeesch Pieter , Rittner Martin , Miao Lanyun , Zhu Maoyan , Carter Andrew , Pogge von Strandmann Philip A. E. , Shields Graham A. 
Published: November 2016

Abstract

New detrital zircon ages confirm that the Neoproterozoic strata of the southeastern North China Craton (NCC) are mostly of early Tonian age, but that the Gouhou Formation, previously assigned to the Tonian, is Cambrian in age. A discordant hiatus of >150–300 myr occurs across the NCC, spanning most of the late Tonian, Cryogenian, Ediacaran and early Cambrian periods. This widespread unconformable surface is akin to the Great Unconformity seen elsewhere in the world and highlights a major shift in depositional style from largely erosional, marked by low rates of net deposition, during the mid- to late Neoproterozoic to high rates of transgressive deposition during the mid- to late Cambrian. The age spectra for the southeastern NCC and northern India are consistent with a provenance affinity linking the NCC and East Gondwana by
c.
510 Ma.

Supplementary material:
Sample descriptions, sampling GPS locations and a compiled dataset of detrital zircon U–Pb LA-ICP-MS dating results are available at
https://doi.org/10.6084/m9.figshare.c.3571119
Speculative linearizability
Authors: Guerraoui Rachid , Kuncak Viktor , Losa Giuliano 
Published: November 2016

Linearizability is a key design methodology for reasoning about implementations of concurrent abstract data types in both shared memory and message passing systems. It provides the illusion that operations execute sequentially and fault-free, despite the asynchrony and faults inherent to a concurrent system, especially a distributed one. A key property of linearizability is inter-object composability: a system composed of linearizable objects is itself linearizable. However, devising linearizable objects is very difficult, requiring complex algorithms to work correctly under general circumstances, and often resulting in bad average-case behavior. Concurrent algorithm designers therefore resort to speculation: optimizing algorithms to handle common scenarios more efficiently. The outcome are even more complex protocols, for which it is no longer tractable to prove their correctness.

To simplify the design of efficient yet robust linearizable protocols, we propose a new notion:
speculative linearizability
. This property is as general as linearizability, yet it allows intra-object composability: the correctness of independent protocol phases implies the correctness of their composition. In particular, it allows the designer to focus solely on the proof of an optimization and derive the correctness of the overall protocol from the correctness of the existing, non-optimized one.

Our notion of protocol phases allows processes to independently switch from one phase to another, without requiring them to reach agreement to determine the change of a phase. To illustrate the applicability of our methodology, we show how examples of speculative algorithms for shared memory and asynchronous message passing naturally fit into our framework.
We rigorously define speculative linearizability and prove our intra-object composition theorem in a trace-based as well as an automaton-based model. To obtain a further degree of confidence, we also formalize and mechanically check the theorem in the automaton-based model, using the I/O automata framework within the Isabelle interactive proof assistant. We expect our framework to enable, for the first time, scalable specifications and mechanical proofs of speculative implementations of linearizable objects.
JANUS
Authors: Tripp Omer , Manevich Roman , Field John , Sagiv Mooly 
Published: November 2016

This paper addresses the problem of reducing unnecessary conflicts in optimistic synchronization. Optimistic synchronization must ensure that any two concurrently executing transactions that commit are properly synchronized. Conflict detection is an approximate check for this condition. For efficiency, the traditional approach to conflict detection conservatively checks that the memory locations mutually accessed by two concurrent transactions are accessed only for reading.
We present JANUS, a parallelization system that performs conflict detection by considering sequences of operations and their composite effect on the system's state. This is done efficiently, such that the runtime overhead due to conflict detection is on a par with that of write-conflict-based detection. In certain common scenarios, this mode of refinement dramatically improves the precision of conflict detection, thereby reducing the number of false conflicts.
Our empirical evaluation of JANUS shows that this precision gain reduces the abort rate by an order of magnitude (22x on average), and achieves a speedup of up to 2.5x, on a suite of real-world benchmarks where no parallelism is exploited by the standard approach.
Engage
Authors: Fischer Jeffrey , Majumdar Rupak , Esmaeilsabzali Shahram 
Published: November 2016

Many modern applications are built by combining independently developed packages and services that are distributed over many machines with complex inter-dependencies. The assembly, installation, and management of such applications is hard, and usually performed either manually or by writing customized scripts. We present Engage, a system for configuring, installing, and managing complex application stacks. Engage consists of three components: a domain-specific model to describe component metadata and inter-component dependencies; a constraint-based algorithm that takes a partial installation specification and computes a full installation plan; and a runtime system that co-ordinates the deployment of the application across multiple machines and manages the deployed system. By explicitly modeling configuration metadata and inter-component dependencies, Engage enables static checking of application configurations and automated, constraint-driven, generation of installation plans across multiple machines. This reduces the tedious manual process of application configuration, installation, and management.
We have implemented Engage and we have used it to successfully host a number of applications. We describe our experiences in using Engage to manage a generic platform that hosts Django applications in the cloud or on premises.
The power of parameterization in coinductive proof
Authors: Hur Chung-Kil , Neis Georg , Dreyer Derek , Vafeiadis Viktor 
Published: November 2016

Coinduction is one of the most basic concepts in computer science. It is therefore surprising that the commonly-known lattice-theoretic accounts of the principles underlying coinductive proofs are lacking in two key respects: they do not support compositional reasoning (i.e. breaking proofs into separate pieces that can be developed in isolation), and they do not support incremental reasoning (i.e. developing proofs interactively by starting from the goal and generalizing the coinduction hypothesis repeatedly as necessary).
In this paper, we show how to support coinductive proofs that are both compositional and incremental, using a dead simple construction we call the parameterized greatest fixed point. The basic idea is to parameterize the greatest fixed point of interest over the accumulated knowledge of "the proof so far". While this idea has been proposed before, by Winskel in 1989 and by Moss in 2001, neither of the previous accounts suggests its general applicability to improving the state of the art in interactive coinductive proof.
In addition to presenting the lattice-theoretic foundations of parameterized coinduction, demonstrating its utility on representative examples, and studying its composition with "up-to" techniques, we also explore its mechanization in proof assistants like Coq and Isabelle. Unlike traditional approaches to mechanizing coinduction (e.g. Coq's cofix), which employ syntactic "guardedness checking", parameterized coinduction offers a semantic account of guardedness. This leads to faster and more robust proof development, as we demonstrate using our new Coq library, Paco.
Library abstraction for C/C++ concurrency
Authors: Batty Mark , Dodds Mike , Gotsman Alexey 
Published: November 2016

When constructing complex concurrent systems, abstraction is vital: programmers should be able to reason about concurrent libraries in terms of abstract specifications that hide the implementation details. Relaxed memory models present substantial challenges in this respect, as libraries need not provide sequentially consistent abstractions: to avoid unnecessary synchronisation, they may allow clients to observe relaxed memory effects, and library specifications must capture these.
In this paper, we propose a criterion for sound library abstraction in the new C11 and C++11 memory model, generalising the standard sequentially consistent notion of linearizability. We prove that our criterion soundly captures all client-library interactions, both through call and return values, and through the subtle synchronisation effects arising from the memory model. To illustrate our approach, we verify implementations against specifications for the lock-free Treiber stack and a producer-consumer queue. Ours is the first approach to compositional reasoning for concurrent C11/C++11 programs.
Synthesis of biological models from mutation experiments
Authors: Koksal Ali Sinan , Pu Yewen , Srivastava Saurabh , Bodik Rastislav , Fisher Jasmin , Piterman Nir 
Published: November 2016

Executable biology presents new challenges to formal methods. This paper addresses two problems that cell biologists face when developing formally analyzable models.
First, we show how to automatically synthesize a concurrent in-silico model for cell development given in-vivo experiments of how particular mutations influence the experiment outcome. The problem of synthesis under mutations is unique because mutations may produce non-deterministic outcomes (presumably by introducing races between competing signaling pathways in the cells) and the synthesized model must be able to replay all these outcomes in order to faithfully describe the modeled cellular processes. In contrast, a "regular" concurrent program is correct if it picks any outcome allowed by the non-deterministic specification. We developed synthesis algorithms and synthesized a model of cell fate determination of the earthworm C. elegans. A version of this model previously took systems biologists months to develop.
Second, we address the problem of under-constrained specifications that arise due to incomplete sets of mutation experiments. Under-constrained specifications give rise to distinct models, each explaining the same phenomenon differently. Addressing the ambiguity of specifications corresponds to analyzing the space of plausible models. We develop algorithms for detecting ambiguity in specifications, i.e., whether there exist alternative models that would produce different fates on some unperformed experiment, and for removing redundancy from specifications, i.e., computing minimal non-ambiguous specifications.
Additionally, we develop a modeling language and embed it into Scala. We describe how this language design and embedding allows us to build an efficient synthesizer. For our C. elegans case study, we infer two observationally equivalent models expressing different biological hypotheses through different protein interactions. One of these hypotheses was previously unknown to biologists.