bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelagosite revisited: The origin and significance of a laminated aragonitic encrustation of Mediterranean supralittoral rocks
Authors: Montanari Alessandro , Bice David M. , Jull A.J. Timothy , Kudryavtsev Anatoliy B. , Macalady Jennifer L. , Schaperdoth Irene , Sharp Warren D. , Shimabukuro David , Schopf William J. , Vucetić Visnja
Published: October 2019

In this paper, we review ~140 yr of investigations about pelagosite, a usually black aragonitic encrustation with a vitreous luster that forms in the splash zone of Mediterranean rocky coasts. Prior to the mid-1920s, the geologic community considered pelagosite to be a separate mineral of uncertain composition, but then in 1926, Italian mineralogist Ettore Onorato determined that pelagosite has the same structure as aragonite (orthorhombic CaCO3), and also that it contained cells of blue-green algae (i.e., cyanobacteria). Once pelagosite was declassed from the status of a mineral, and its name was eliminated from catalogues and textbooks, Onorato’s documentation of the cyanobacterial cells contained in this encrustation seems to have fallen into almost total oblivion during the rest of the twentieth century. We revisited pelagosite in its original type locality, the remote southern Adriatic island of Pelagosa (today’s Croatian island of Palagruža), as well as in the Dalmatian island of Hvar. Using modern analytical methods and techniques, we redefined the mineralogical and geochemical composition of pelagosite, the nature and significance of its microbial content, and the origin of its pisolitic “tree-ring” internal structure, which probably reflects cyclic climate changes.
Nutcracker syndrome complicated with intestinal malrotation
Authors: Nishio Yosuke , Kawano Yoshihiko , Hara Shinya
Published: October 2019

Nutcracker syndrome (NCS) is a pathological condition in which the left renal vein (LRV) is compressed between the superior mesenteric artery (SMA) and aorta. NCS can predispose patients to the onset of chronic kidney disease because of persistent increase in LRV pressure. Although NCS in children is often idiopathic, it can also be caused by underlying pathologies such as retroperitoneal tumours. To the best of our knowledge, there have been no reports regarding paediatric cases of NCS complicated with intestinal malrotation. Here, we report the case of a 12-year-old girl with intestinal malrotation complicated with NCS whose haematuria resolved after surgical intervention for intestinal malrotation. The present case findings indicate that intestinal malrotation with concomitant weight loss is a potential underlying aetiology in NCS. Thus, when NCS is especially diagnosed with gastrointestinal symptoms, intestinal malrotation should be considered as an underlying aetiology.
Towards universal health coverage: advancing the development and use of traditional medicines in Africa
Authors: Kasilo Ossy Muganga Julius , Wambebe Charles , Nikiema Jean-Baptiste , Nabyonga-Orem Juliet
Published: October 2019

African traditional medicine (ATM) and traditional health practitioners (THPs) could make significant contributions to the attainment of universal health coverage (UHC). Consequently, the WHO provided technical tools to assist African countries to develop ATM as a significant component of healthcare. Many African countries adopted the WHO tools after appropriate modifications to advance research and development (R&D) of ATM. An analysis of the extent of this development was undertaken through a survey of 47 countries in the WHO African region. Results show impressive advances in R&D of ATM, the collaboration between THP and conventional health practitioners, quality assurance as well as regulation, registration and THP integration into the national health systems. We highlight the various ways investment in the R&D of ATM can impact on policy, practice and the three themes of UHC. We underscore the need for frameworks for fair and equitable sharing of all benefits arising from the R&D of ATM products involving all the stakeholders. We argue for further investment in ATM as a complement to conventional medicine to promote attainment of the objectives of UHC.
Safety and quality of endovascular therapy under general anesthesia and conscious sedation are comparable: results from the GOLIATH trial
Authors: Sørensen Leif H , Speiser Lasse , Karabegovic Sanja , Yoo Albert J , Rasmussen Mads , Sørensen Kristina E , Simonsen Claus Z
Published: October 2019

Background

The “General or Local Anesthesia in Intra-Arterial Therapy” (GOLIATH) trial compared infarct growth and outcome in patients undergoing endovascular therapy (EVT) under either general anesthesia (GA) or conscious sedation (CS). The results were the same for the primary outcome (infarct growth) but successful reperfusion was higher in the GA arm.

Objective

To further examine differences in the quality and safety of EVT with the two anesthetic regimens in a post hoc analysis of GOLIATH.

Methods

In GOLIATH, 128 subjects with anterior circulation large vessel occlusion stroke within 6 hours of onset were randomized to either GA or CS (1:1 allocation). We compared the quality of reperfusion, treatment delay, use of catheters, and contrast and radiation dosage between the trial arms.

Results

Sixty-five subjects were randomized to GA. Baseline demographic and clinical variables were similar between the treatment arms. We found no difference in procedure time, contrast dose, or radiation dose between the two arms. Tandem occlusions were associated with a longer procedure time, but there was no difference between the two arms. There was no difference in reperfusion rates between the direct aspiration technique and a stent retriever (86% vs 79%, respectively, p=0.54), but aspiration was associated with a shorter procedure time (28 min vs 42 min for a stent retriever), p=0.03.

Conclusion

Safety and quality of EVT under either GA and CS are comparable.

Trial registration

Unique identifier:NCT02317237;Post-results.
Progress and prospects of marine microplastic research in China
Authors: Li Daoji , Peng Guyu , Zhu Lixin
Published: October 2019

Research on microplastics in China is progressing rapidly. Within recent years, more than 30 research institutes have conducted research on marine microplastic in estuaries, coasts, open sea, and Polar regions. Microplastics have been detected in freshwater systems (lakes, rivers, and wastewater treatment plants) and coastal and marine environments. This paper reviews the research progress of microplastics in China, providing information on topics including the methodology, quantification of microplastics in various habitats, eco-toxicological effect, biodegradation, management, and control of plastic waste and microplastics. This paper discusses the sampling and analysis of microplastic in different media, followed by spatial and temporal distribution of microplastics in marginal seas and coastal and freshwater systems. After summarizing the recent advances on toxicology research and risk assessment of microplastics, this paper provides suggestions for future study to provide baseline information for better risk assessment and improved understanding of the lifecycle of microplastics in the environment.
Salvianolic acid B exerts a protective effect in acute liver injury by regulating the Nrf2/HO-1 signaling pathway
Authors: Jin Yong-mei , Tao Xiang-ming , Shi Yi-ning , Lu Youjin , Mei Jin-yu
Published: October 2019

Salvianolic acid B (Sal B) exerts strong antioxidant activity and eliminates the free radical effect. However, how it affects the antioxidant pathway is not very clear. The objective of this study was to investigate the underlying mechanism of Sal B in CCl4-induced acute liver injury, especially its effect on the Nrf2/HO-1 signaling pathway. For the in vivo experiment, an acute liver injury model was induced using CCl4 and treated with Sal B. For the in vitro experiment, an oxidative damage model was established followed by Sal B treatment. Serum biochemical indicators and reactive oxygen species activity were detected using corresponding kits. Oxidant/antioxidant status was determined based on the levels of malondialdehyde, glutathione, and superoxide dismutase. Nrf2 and HO-1 levels were analyzed by Western blotting and immunohistochemical staining. Sal B treatment improved liver histology, decreased the aminotransferase levels, and attenuated oxidative stress in the acute liver injury model. Nrf2 and HO-1 levels were increased both in vivo and in vitro. Sal B suppresses acute liver injury and Nrf2/HO-1 signaling plays a key role in this process.
Aberrant Connectivity During Pilocarpine-Induced Status Epilepticus
Authors: Cui Yan , Liu Jie , Luo Yan , He Shan , Xia Yang , Zhang Yangsong , Yao Dezhong , Guo Daqing
Published: October 2019

Status epilepticus (SE) is a common, life-threatening neurological disorder that may lead to permanent brain damage. In rodent models, SE is an acute phase of seizures that could be reproduced by injecting with pilocarpine and then induce chronic temporal lobe epilepsy (TLE) seizures. However, how SE disrupts brain activity, especially communications among brain regions, is still unclear. In this study, we aimed to identify the characteristic abnormalities of network connections among the frontal cortex, hippocampus and thalamus during the SE episodes in a pilocarpine model with functional and effective connectivity measurements. We showed that the coherence connectivity among these regions increased significantly during the SE episodes in almost all frequency bands (except the alpha band) and that the frequency band with enhanced connections was specific to different stages of SE episodes. Moreover, with the effective analysis, we revealed a closed neural circuit of bidirectional effective interactions between the frontal regions and the hippocampus and thalamus in both ictal and post-ictal stages, implying aberrant enhancement of communication across these brain regions during the SE episodes. Furthermore, an effective connection from the hippocampus to the thalamus was detected in the delta band during the pre-ictal stage, which shifted in an inverse direction during the ictal stage in the theta band and in the theta, alpha, beta and low-gamma bands during the post-ictal stage. This specificity of the effective connection between the hippocampus and thalamus illustrated that the hippocampal structure is critical for the initiation of SE discharges, while the thalamus is important for the propagation of SE discharges. Overall, our results demonstrated enhanced interaction among the frontal cortex, hippocampus and thalamus during the SE episodes and suggested the modes of information flow across these structures for the initiation and propagation of SE discharges. These findings may reveal an underlying mechanism of aberrant network communication during pilocarpine-induced SE discharges and deepen our knowledge of TLE seizures.
Klein’s paradox in the presence of a scalar potential
Authors: Ainouz B. , Haouat S.
Published: October 2019

In this paper, we have studied the Klein’s paradox in the presence of both scalar and vector potential barriers. From the corresponding Dirac equation, we have calculated the transmission and reflection coefficients. It is shown that the presence of a scalar barrier the scalar potential widens the gap between positive and negative energies and so the forbidden region. Accordingly, the Klein’s paradox disappears when the scalar barrier exceeds a critical value. Considering the problem within the framework of quantum field theory, we have calculated the related pair creation probability, the mean number of created particles and the probability of a vacuum to remain a vacuum. Then it is shown that the scalar potential cuts down the Klein range and minimizes the creation of particles; the particle creation decreases as the scalar potential increases and ceases definitely when the scalar potential reaches the critical value.
Analysis of fusion cross-sections of 6He, 8He and 11Li halo nuclei by using temperature-independent and temperature-dependent potentials
Authors: Aygun M.
Published: October 2019

Analysis of the fusion reactions of halo nuclei is one of the important subjects of nuclear physics. In addition, temperature-dependent analysis of fusion cross-sections of these nuclei is a deficient topic in the literature. In order to overcome this deficiency, the fusion cross-sections of 6He, 8He and [Formula: see text]Li which are the most important halo nuclei are analyzed by using both temperature-independent potential and temperature-dependent potential. All the theoretical results are compared with each other as well as the experimental data. It is seen that the results of temperature-independent potential are in good agreement with the data while the temperature-dependent potential has a significant impact on the fusion cross-sections. Finally, the changes with the temperature of both real and nuclear potentials of all the reactions are investigated.
Truth-Preservation under Fuzzy pp-Formulas
Authors: Dellunde Pilar , Vidal Amanda
Published: October 2019

How can non-classical logic contribute to the analysis of complexity in computer science? In this paper, we give a step towards this question, taking a logical model-theoretic approach to the analysis of complexity in fuzzy constraint satisfaction. We study fuzzy positive-primitive sentences, and we present an algebraic characterization of classes axiomatized by this kind of sentences in terms of homomorphisms and direct products. The ultimate goal is to study the expressiveness and reasoning mechanisms of non-classical languages, with respect to constraint satisfaction problems and, in general, in modelling decision scenarios.
EFFECT OF FAR-FIELD FLOW ON THE GROWTH OF COLUMNAR CRYSTAL IN TERNARY UNDERCOOLED MELT
Authors: FAN HAILONG , CHEN MINGWEN , SHAN YANYAN
Published: October 2019

The asymptotic method has been used to investigate the columnar crystals growth subjected to far-field flow in ternary undercooled melt under non-isothermal conditions, and approximate analytical expression of radius and interface growth rate of columnar crystals growth have been given. It is found that the flow causes columnar crystal to grow faster in the upstream direction and slower in the downstream direction, and the growth of columnar crystals in flowing ternary melt is also affected by impurity content, that is, the higher the impurity content, the faster the columnar crystal grows in the upstream direction and the slower the growth in the downstream direction. The growth problem of columnar crystals from multi-component melt under flow is more complicated than that of a pure melt because it involves both the heat transport process and mass transport in the solute. The results show that the deflection angle of columnar crystals is a result of interaction of flow and impurity content.
EXPERIMENTAL STUDY ON STEADY DYNAMIC FRICTION OF MWCNTs MIXED LUBRICANTS
Authors: GONDANE SHRADDHA , SINGH ARUN K. , SINHA NITISH , VIJAYAKUMAR R. P.
Published: October 2019

This paper investigates the steady sliding behavior of multiwalled carbon nanotubes (MWCNTs) mixed lubricants at the metal–metal interface in direct shear tests. Slide-free-slide (SFS) experiments were performed to understand dynamic frictional stress of the sliding surfaces above the critical velocity. The experimental observations show that the dynamic stress decreases with increase in sliding velocity, but the same increases with normal stress. Further, in the case of change in concentration of the MWCNTs in the lubricant, the dynamic stress increases initially and then decreases to a minimum value and then further increases with addition of more nanoparticles in the lubricant. Dynamic stress and corresponding critical velocity are found to be minimum about 1.6% (wt./vol.) of MWCNTs concentration. Magnitude of cohesion as well as the coefficient of friction were also determined experimentally with the Coulomb friction law. The friction results are discussed in terms of the scaling laws in three regimes, namely viscous, rolling and sliding. These laws are justified on the basis of the mixed lubrication regime of Stribeck curve. Surface morphology of the test specimens before and after the experiment was also examined using SEM and EDS tests. No evidence of surface damage owing to motion of the nanoparticles was observed.
ANNEALING EFFECT ON STRUCTURAL AND OPTICAL PROPERTIES OF COPPER-DOPED BISMUTH TRIOXIDE Cu:Bi2O3 THIN FILMS
Authors: BOUCHAREB FATIMA ZOHRA , HAMDADOU NASR-EDDINE
Published: October 2019

In this work, we have examined the effect of annealing temperature on Cu-doped Bi2O3 thin films at 1%, 3% and 5% doping rate successfully prepared by spray pyrolysis technique onto glass substrates. The obtained films were subsequently annealed at different temperature for 4[Formula: see text]h. GIXRD analysis reveals the polycrystalline nature of deposited films and shows the formation of mixed [Formula: see text]- and [Formula: see text]-Bi2O3 phases. With the increase of doping rate, [Formula: see text]-phase of Bi2O3 was identified at medium temperature. The average grain size of thin films at different doping rate of Cu decreases with the increase of annealing temperature. The optical characterization shows that the optical transmittance of the films decreases with the increase of annealing temperature in the range (70–50%) and (40–10%) for 1% and 5% doping rate of Cu, respectively. The evaluation of the optical bandgap energy reveals that the indirect transition is controlling the optical response of the films. The optimum annealing temperature to reduce Bi2O3 energy bandgap to be 3.09[Formula: see text]eV, is 450∘C and 550∘C for 3% and 5% doping rate of Cu.
Pooling Risk Games
Authors: Alon Tzvi , Haviv Moshe
Published: October 2019

There are numerous situations in which variability reduction is desirable. We examine cases where such reductions can be achieved by cooperating agents who share similar interests. Our goal is to quantify the contribution of each of the agents toward this reduction. We model this situation as a cooperative game in which the cost is defined as the minimal standard deviation the cooperating agents can achieve. We show that this game is subadditive and has a nonempty core. We derive special presentations for the Shapley and Banzhaf values.
Bound on the diameter of metacyclic groups
Authors: Rajeevsarathy Kashyap , Sarkar Siddhartha
Published: October 2019

Let [Formula: see text] be the split metacyclic group, where [Formula: see text] is a unit modulo [Formula: see text]. We derive an upper bound for the diameter of [Formula: see text] using an arithmetic parameter called the weight, which depends on [Formula: see text], [Formula: see text], and the order of [Formula: see text]. As an application, we show how this would determine a bound on the diameter of an arbitrary metacyclic group.
A stochastic operational matrix method for numerical solutions of mixed stochastic Volterra–Fredholm integral equations
Authors: Singh S. , Saha Ray S.
Published: October 2019

In this paper, we have studied space-time Brownian motion and its applications to mixed type stochastic integral equations. Approximate solutions of mixed stochastic integral equations have been obtained by using two-dimensional (2D) second kind Chebyshev wavelets (CWs). Furthermore, some examples have been presented to justify the efficiency of 2D second kind CWs.
Strong vb-dominating and vb-independent sets of a graph
Authors: Udupa Sayinath , Bhat R. S.
Published: October 2019

Let [Formula: see text] be a graph. A vertex [Formula: see text] strongly (weakly) b-dominates block [Formula: see text] if [Formula: see text] ([Formula: see text]) for every vertex [Formula: see text] in the block [Formula: see text]. A set [Formula: see text] is said to be strong (weak) vb-dominating set (SVBD-set) (WVBD-set) if every block in [Formula: see text] is strongly (weakly) b-dominated by some vertex in [Formula: see text]. The strong (weak) vb-domination number [Formula: see text] ([Formula: see text]) is the order of a minimum SVBD (WVBD) set of [Formula: see text]. A set [Formula: see text] is said to be strong (weak) vertex block independent set (SVBI-set (WVBI-set)) if [Formula: see text] is a vertex block independent set and for every vertex [Formula: see text] and every block [Formula: see text] incident on [Formula: see text], there exists a vertex [Formula: see text] in the block [Formula: see text] such that [Formula: see text] ([Formula: see text]). The strong (weak) vb-independence number [Formula: see text] ([Formula: see text]) is the cardinality of a maximum strong (weak) vertex block independent set (SVBI-set) (WVBI-set) of [Formula: see text]. In this paper, we investigate some relationships between these four parameters. Several upper and lower bounds are established. In addition, we characterize the graphs attaining some of the bounds.
Response Time Analysis for Tasks with Fixed Preemption Points under Global Scheduling
Authors: Zhou Quan , Li Guohui , Li Jianjun , Deng Chenggang , Yuan Ling
Published: October 2019

As an effective method for detecting the schedulability of real-time tasks on multiprocessor platforms, Response time analysis (RTA) has been deeply researched in recent decades. Most of the existing RTA methods are designed for tasks that can be preempted at any time. However, in some real-time systems, a task may have some fixed preemption points (FPPs) that divide its execution into a series of non-preemptive regions (NPRs). In such environments, the task can only be preempted at its FPPs, which makes existing RTA methods for arbitrary preemption tasks not applicable. In this article, we study the schedulability analysis on tasks with FPPs under both global fixed-priority (G-FP) scheduling and global earliest deadline first (G-EDF) scheduling. First, based on the idea of limiting the time interval between two consecutive executions of an NPR, a novel RTA method for tasks with FPPs under G-FP scheduling is proposed. Second, we propose an effective RTA method for tasks with FPPs under G-EDF scheduling. Finally, extensive simulations are conducted and the results validate the effectiveness of the proposed methods.
TLA+ model checking made symbolic
Authors: Konnov Igor , Kukovec Jure , Tran Thanh-Hai
Published: October 2019

TLA+ is a language for formal specification of all kinds of computer systems. System designers use this language to specify concurrent, distributed, and fault-tolerant protocols, which are traditionally presented in pseudo-code. TLA+ is extremely concise yet expressive: The language primitives include Booleans, integers, functions, tuples, records, sequences, and sets thereof, which can be also nested. This is probably why the only model checker for TLA+ (called TLC) relies on explicit enumeration of values and states.

In this paper, we present APALACHE -- a first symbolic model checker for TLA+. Like TLC, it assumes that all specification parameters are fixed and all states are finite structures. Unlike TLC, APALACHE translates the underlying transition relation into quantifier-free SMT constraints, which allows us to exploit the power of SMT solvers. Designing this translation is the central challenge that we address in this paper. Our experiments show that APALACHE outperforms TLC on examples with large state spaces.
Value-centric dynamic partial order reduction
Authors: Chatterjee Krishnendu , Pavlogiannis Andreas , Toman Viktor
Published: October 2019

The verification of concurrent programs remains an open challenge, as thread interaction has to be accounted for, which leads to state-space explosion. Stateless model checking battles this problem by exploring traces rather than states of the program. As there are exponentially many traces, dynamic partial-order reduction (DPOR) techniques are used to partition the trace space into equivalence classes, and explore a few representatives from each class. The standard equivalence that underlies most DPOR techniques is the
happens-before
equivalence, however recent works have spawned a vivid interest towards coarser equivalences. The efficiency of such approaches is a product of two parameters: (i) the size of the partitioning induced by the equivalence, and (ii) the time spent by the exploration algorithm in each class of the partitioning.

In this work, we present a new equivalence, called
value-happens-before
and show that it has two appealing features. First, value-happens-before is always at least
as coarse as
the happens-before equivalence, and can be even exponentially coarser. Second, the value-happens-before partitioning is efficiently explorable when the number of threads is bounded. We present an algorithm called
value-centric
DPOR (
VCDPOR
), which explores the underlying partitioning using polynomial time per class. Finally, we perform an experimental evaluation of
VCDPOR
on various benchmarks, and compare it against other state-of-the-art approaches. Our results show that value-happens-before typically induces a significant reduction in the size of the underlying partitioning, which leads to a considerable reduction in the running time for exploring the whole partitioning.
A path to DOT: formalizing fully path-dependent types
Authors: Rapoport Marianna , Lhoták Ondřej
Published: October 2019

The Dependent Object Types (DOT) calculus aims to formalize the Scala programming language with a focus on
path-dependent types
 — types such as
x
.
a
1
…
a

n

.
T
that depend on the runtime value of a
path
x
.
a
1
…
a

n

to an object. Unfortunately, existing formulations of DOT can model only types of the form
x
.
A
which depend on
variables
rather than general paths. This restriction makes it impossible to model nested module dependencies. Nesting small components inside larger ones is a necessary ingredient of a modular, scalable language. DOT’s variable restriction thus undermines its ability to fully formalize a variety of programming-language features including Scala’s module system, family polymorphism, and covariant specialization.

This paper presents the pDOT calculus, which generalizes DOT to support types that depend on paths of arbitrary length, as well as singleton types to track path equality. We show that naive approaches to add paths to DOT make it inherently unsound, and present necessary conditions for such a calculus to be sound. We discuss the key changes necessary to adapt the techniques of the DOT soundness proofs so that they can be applied to pDOT. Our paper comes with a Coq-mechanized type-safety proof of pDOT. With support for paths of arbitrary length, pDOT can realize DOT’s full potential for formalizing Scala-like calculi.
Reliable and fast DWARF-based stack unwinding
Authors: Bastian Théophile , Kell Stephen , Zappa Nardelli Francesco
Published: October 2019

Debug information, usually encoded in the DWARF format, is a hidden and obscure component of our computing infrastructure. Debug information is obviously used by debuggers, but it also plays a key role in program analysis tools, and, most surprisingly, it can be relied upon by the runtime of high-level programming languages. For instance the C++ runtime leverages DWARF stack unwind tables to implement exceptions! Alas, generating debug information adds significant burden to compiler implementations, and the debug information itself can be pervaded by subtle bugs, making the whole infrastructure unreliable. Additionally, interpreting the debug tables is a time-consuming task and, for some applications as sampling profilers, it turns out to be a performance bottleneck.

In this paper we focus on the DWARF .eh_frame table, that enables stack unwinding in absence of frame-pointers. We will describe two techniques to perform validation and synthesis of the DWARF stack unwinding tables, and their implementation for the x86_64 architecture. The validation tool has proven effective for compiler and inline assembly testing, while the synthesis tool can generate DWARF unwind tables for arbitrary binaries lacking debug information. Additionally, we report on a technique to precompile unwind tables into native x86_64 code, which we have implemented and integrated into libunwind, resulting in 11x-25x DWARF-based unwind speedups.
DProf: distributed profiler with strong guarantees
Authors: Benavides Zachary , Vora Keval , Gupta Rajiv
Published: October 2019

Performance analysis of a distributed system is typically achieved by collecting profiles whose underlying events are timestamped with unsynchronized clocks of multiple machines in the system. To allow comparison of timestamps taken at different machines, several timestamp synchronization algorithms have been developed. However, the inaccuracies associated with these algorithms can lead to inaccuracies in the final results of performance analysis. To address this problem, in this paper, we develop a system for constructing distributed performance profiles called DProf. At the core of DProf is a new timestamp synchronization algorithm, FreeZer, that tightly bounds the inaccuracy in a converted timestamp to a time interval. This not only allows timestamps from different machines to be compared, it also enables maintaining strong guarantees throughout the comparison which can be carefully transformed into guarantees for analysis results. To demonstrate the utility of DProf, we use it to implement dCSP and dCOZ that are accuracy bounded distributed versions of Context Sensitive Profiles and Causal Profiles developed for shared memory systems. While dCSP enables user to ascertain existence of a performance bottleneck, dCOZ estimates the expected performance benefit from eliminating that bottleneck. Experiments with three distributed applications on a cluster of heterogeneous machines validate that inferences via dCSP and dCOZ are highly accurate. Moreover, if FreeZer is replaced by two existing timestamp algorithms (linear regression & convex hull), the inferences provided by dCSP and dCOZ are severely degraded.
Duet: an expressive higher-order language and linear type system for statically enforcing differential privacy
Authors: Near Joseph P. , Darais David , Abuah Chike , Stevens Tim , Gaddamadugu Pranav , Wang Lun , Somani Neel , Zhang Mu , Sharma Nikhil , Shan Alex , Song Dawn
Published: October 2019

During the past decade, differential privacy has become the gold standard for protecting the privacy of individuals. However, verifying that a particular program provides differential privacy often remains a manual task to be completed by an expert in the field. Language-based techniques have been proposed for fully automating proofs of differential privacy via type system design, however these results have lagged behind advances in differentially-private algorithms, leaving a noticeable gap in programs which can be automatically verified while also providing state-of-the-art bounds on privacy.

We propose Duet, an expressive higher-order language, linear type system and tool for automatically verifying differential privacy of general-purpose higher-order programs. In addition to general purpose programming, Duet supports encoding machine learning algorithms such as stochastic gradient descent, as well as common auxiliary data analysis tasks such as clipping, normalization and hyperparameter tuning - each of which are particularly challenging to encode in a statically verified differential privacy framework.

We present a core design of the Duet language and linear type system, and complete key proofs about privacy for well-typed programs. We then show how to extend Duet to support realistic machine learning applications and recent variants of differential privacy which result in improved accuracy for many practical differentially private algorithms. Finally, we implement several differentially private machine learning algorithms in Duet which have never before been automatically verified by a language-based tool, and we present experimental results which demonstrate the benefits of Duet's language design in terms of accuracy of trained machine learning models.
Dependence-aware, unbounded sound predictive race detection
Authors: Genç Kaan , Roemer Jake , Xu Yufan , Bond Michael D.
Published: October 2019

Data races are a real problem for parallel software, yet hard to detect. Sound predictive analysis observes a program execution and detects data races that exist in some other, unobserved execution. However, existing predictive analyses miss races because they do not scale to full program executions or do not precisely incorporate data and control dependence.

This paper introduces two novel, sound predictive approaches that incorporate data and control dependence and handle full program executions. An evaluation using real, large Java programs shows that these approaches detect more data races than the closest related approaches, thus advancing the state of the art in sound predictive race detection.
I/O dependent idempotence bugs in intermittent systems
Authors: Surbatovich Milijana , Jia Limin , Lucia Brandon
Published: October 2019

Intermittently-powered, energy-harvesting devices operate on energy collected from their environment and must operate intermittently as energy is available.

Runtime systems for such devices often rely on checkpoints or redo-logs to save execution state between power cycles, causing arbitrary code regions to re-execute on reboot. Any
non-idempotent
program behavior—behavior that can change on each execution—can lead to incorrect results.

This work investigates non-idempotent behavior caused by repeating I/O operations, not addressed by prior work. If such operations affect a control statement or address of a memory update, they can cause programs to take different paths or write to different memory locations on re-executions, resulting in inconsistent memory states. We provide the first characterization of input-dependent idempotence bugs and develop IBIS-S, a program analysis tool for detecting such bugs at compile time, and IBIS-D, a dynamic information flow tracker to detect bugs at runtime.

These tools use taint propagation to determine the reach of input. IBIS-S searches for code patterns leading to inconsistent memory updates, while IBIS-D detects concrete memory inconsistencies. We evaluate IBIS on embedded system drivers and applications. IBIS can detect I/O-dependent idempotence bugs, giving few (IBIS-S) or no (IBIS-D) false positives and providing actionable bug reports. These bugs are common in sensor-driven applications and are not fixed by existing intermittent systems.
Initialize once, start fast: application initialization at build time
Authors: Wimmer Christian , Stancu Codrut , Hofer Peter , Jovanovic Vojin , Wögerer Paul , Kessler Peter B. , Pliss Oleg , Würthinger Thomas
Published: October 2019

Arbitrary program extension at run time in language-based VMs, e.g., Java's dynamic class loading, comes at a startup cost: high memory footprint and slow warmup. Cloud computing amplifies the startup overhead. Microservices and serverless cloud functions lead to small, self-contained applications that are started often. Slow startup and high memory footprint directly affect the cloud hosting costs, and slow startup can also break service-level agreements. Many applications are limited to a prescribed set of pre-tested classes, i.e., use a closed-world assumption at deployment time. For such Java applications, GraalVM Native Image offers fast startup and stable performance.

GraalVM Native Image uses a novel iterative application of points-to analysis and heap snapshotting, followed by ahead-of-time compilation with an optimizing compiler. Initialization code can run at build time, i.e., executables can be tailored to a particular application configuration. Execution at run time starts with a pre-populated heap, leveraging copy-on-write memory sharing. We show that this approach improves the startup performance by up to two orders of magnitude compared to the Java HotSpot VM, while preserving peak performance. This allows Java applications to have a better startup performance than Go applications and the V8 JavaScript VM.
Intermittent restraint-induced sympathetic activation attenuates hepatic steatosis and inflammation in a high-fat diet-fed mouse model
Authors: Lee Sung Bae , Kim Hyeong Geug , Lee Jin Seok , Kim Won Yong , Lee Myong Min , Kim Yun Hee , Lee Jung Ok , Kim Hyeon Soo , Son Chang Gue
Published: October 2019

Nonalcoholic fatty liver disease (NAFLD) is very prevalent worldwide and is associated with insulin resistance and metabolic syndrome. Stress is a physiological and biological response to maintain homeostasis of the body against stressors while severe stress response is an important contributor to various illnesses, including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a high-fat diet (HFD)-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 wk, with or without intermittent restraint stress (3 h) conducted three times a week. HFD administration increased fat accumulation in liver tissues. Unlike the stressed standard diet group, the levels of hepatic total cholesterol and triglycerides were significantly ameliorated in the HFD with stress group compared with the HFD alone group. These beneficial results were in accordance with serum levels of liver enzymes (aspartate transaminase, alanine transaminase) and hepatic levels of TNF-α and oxidative stress parameters (reactive oxygen species, nitric oxide, and malondialdehyde). The intermittent restraint stress significantly attenuated the HFD-derived alterations in serum insulin levels, hepatic protein kinase B activity, and gene expression, especially related to lipogenesis. This intermittent restraint stress also elevated the serum epinephrine concentration and activated the adrenergic receptor β2 or β3 in livers or white adipose tissue (WAT). Activation of energy expenditure markers (uncoupling protein 1, peroxisome proliferator-activated receptor-γ coactivator-1α) in brown adipose tissue and the browning of WAT were also observed in the HFD with stress group. Taken together, our findings showed the beneficial effects of sympathetic activation by intermittent restraint stress on HFD-induced hepatic steatosis and partial inflammation.

NEW & NOTEWORTHY In modern society, stress is a part of daily life, and a certain level of stress is inevitable to most of the general population. Uncontrolled severe stress is obviously harmful; however, certain kind/level of stress could be beneficial on lipid metabolism via sympathetic activation. Our data suggest that a sympathetic activation by intermittent restraint stress could play a positive role in maintaining the balance of hepatic lipid metabolism, especially under high-fat diet conditions.
Cell-specific regulatory effects of CXCR2 on cholestatic liver injury
Authors: Konishi Takanori , Schuster Rebecca M. , Goetzman Holly S. , Caldwell Charles C. , Lentsch Alex B.
Published: October 2019

The CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2−/− mice were subjected BDL. CXCR2 chimeric mice were created to assess the cell-specific role of CXCR2 on liver injury after BDL. SB225002, a selective CXCR2 antagonist, was administrated intraperitoneally after BDL to investigate the potential of pharmacological inhibition. CXCR2−/− mice had significantly less liver injury than wild-type mice at 3 and 14 days after BDL. There was no difference in biliary fibrosis among groups. The chemokines CXCL1 and CXCL2 were induced around areas of necrosis and biliary structures, respectively, both areas where neutrophils accumulated after BDL. CXCR2−/− mice showed significantly less neutrophil accumulation in those injured areas. CXCR2Liver+/Myeloid+ and CXCR2Liver−/Myeloid− mice recapitulated the wild-type and CXCR2-knockout phenotypes, respectively. CXCR2Liver+/Myeloid+ mice suffered higher liver injury than CXCR2Liver+/Myeloid− and CXCR2Liver−/Myeloid+; however, only those chimeras with knockout of myeloid CXCR2 (CXCR2Liver+/Myeloid− and CXCR2Liver−/Myeloid−) showed reduction of neutrophil accumulation around areas of necrosis. Daily administration of SB225002 starting after 3 days of BDL reduced established liver injury at 6 days. In conclusion, neutrophil CXCR2 guides the cell to the site of injury, while CXCR2 on liver cells affects liver damage independent of neutrophil accumulation. CXCR2 appears to be a viable therapeutic target for cholestatic liver injury.

NEW & NOTEWORTHY This study is the first to reveal cell-specific roles of the chemokine receptor CXCR2 in cholestatic liver injury caused by bile duct ligation. CXCR2 on neutrophils facilitates neutrophil recruitment to the liver, while CXCR2 on liver cells contributes to liver damage independent of neutrophils. CXCR2 may represent a viable therapeutic target for cholestatic liver injury.
Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets
Authors: Spear Estelle T. , Mawe Gary M.
Published: October 2019

Intestinal functions, including motility and secretion, are locally controlled by enteric neural networks housed within the wall of the gut. The fidelity of these functions depends on the precision of intercellular signaling among cellular elements, including enteric neurons, epithelial cells, immune cells, and glia, all of which are vulnerable to disruptive influences during inflammatory events. This review article describes current knowledge regarding inflammation-induced neuroplasticity along key elements of enteric neural circuits, what is known about the causes of these changes, and possible therapeutic targets for protecting and/or repairing the integrity of intrinsic enteric neurotransmission. Changes that have been detected in response to inflammation include increased epithelial serotonin availability, hyperexcitability of intrinsic primary afferent neurons, facilitation of synaptic activity among enteric neurons, and attenuated purinergic neuromuscular transmission. Dysfunctional propulsive motility has been detected in models of colitis, where causes include the changes described above, and in models of multiple sclerosis and other autoimmune conditions, where autoantibodies are thought to mediate dysmotility. Other cells implicated in inflammation-induced neuroplasticity include muscularis macrophages and enteric glia. Targeted treatments that are discussed include 5-hydroxytryptamine receptor 4 agonists, cyclooxygenase inhibitors, antioxidants, B cell depletion therapy, and activation of anti-inflammatory pathways.
Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets
Authors: Jacobson Richard A. , Wienholts Kiedo , Williamson Ashley J. , Gaines Sara , Hyoju Sanjiv , van Goor Harry , Zaborin Alexander , Shogan Benjamin D. , Zaborina Olga , Alverdy John C.
Published: October 2019

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing.

NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.
BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus
Authors: Thorsdottir Daniella , Cruickshank Nicholas C. , Einwag Zachary , Hennig Grant W. , Erdos Benedek
Published: October 2019

Brain-derived neurotrophic factor (BDNF) is upregulated in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli such as stress and hyperosmolality, and BDNF acting in the PVN plays a key role in elevating sympathetic activity and blood pressure. However, downstream mechanisms mediating these effects remain unclear. We tested the hypothesis that BDNF increases blood pressure, in part by diminishing inhibitory hypotensive input from nucleus of the solitary tract (NTS) catecholaminergic neurons projecting to the PVN. Male Sprague-Dawley rats received bilateral PVN injections of viral vectors expressing either green fluorescent protein (GFP) or BDNF and bilateral NTS injections of vehicle or anti-dopamine-β-hydroxylase-conjugated saporin (DSAP), a neurotoxin that selectively lesions noradrenergic and adrenergic neurons. BDNF overexpression in the PVN without NTS lesioning significantly increased mean arterial pressure (MAP) in awake animals by 18.7 ± 1.8 mmHg. DSAP treatment also increased MAP in the GFP group, by 9.8 ± 3.2 mmHg, but failed to affect MAP in the BDNF group, indicating a BDNF-induced loss of NTS catecholaminergic hypotensive effects. In addition, in α-chloralose-urethane-anesthetized rats, hypotensive responses to PVN injections of the β-adrenergic agonist isoprenaline were significantly attenuated by BDNF overexpression, whereas PVN injections of phenylephrine had no effect on blood pressure. BDNF treatment was also found to significantly reduce β1-adrenergic receptor mRNA expression in the PVN, whereas expression of other adrenergic receptors was unaffected. In summary, increased BDNF expression in the PVN elevates blood pressure, in part by downregulating β-receptor signaling and diminishing hypotensive catecholaminergic input from the NTS to the PVN.

NEW & NOTEWORTHY We have shown that BDNF, a key hypothalamic regulator of blood pressure, disrupts catecholaminergic signaling between the NTS and the PVN by reducing the responsiveness of PVN neurons to inhibitory hypotensive β-adrenergic input from the NTS. This may be occurring partly via BDNF-mediated downregulation of β1-adrenergic receptor expression in the PVN and results in an increase in blood pressure.