bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias
Authors: Alcolea Daniel , Delaby Constance , Muñoz Laia , Torres Soraya , Estellés Teresa , Zhu Nuole , Barroeta Isabel , Carmona-Iragui María , Illán-Gala Ignacio , Santos-Santos Miguel Ángel , Altuna Miren , Sala Isabel , Sánchez-Saudinós Mª Belén , Videla Laura , Valldeneu Sílvia , Subirana Andrea , Pegueroles Jordi , Hirtz Christophe , Vialaret Jérôme , Lehmann Sylvain , Karikari Thomas K , Ashton Nicholas J , Blennow Kaj , Zetterberg Henrik , Belbin Olivia , Blesa Rafael , Clarimón Jordi , Fortea Juan , Lleó Alberto
Published: June 2021

Objectives

All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer’s disease (AD) through an easy and minimally invasive approach.

Methods

We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination.

Results

The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A–T– participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1–42/Aβ1–40 (Rho=−0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001).

Conclusions

Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach.
Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment
Authors: Zein Ahmad Fariz Malvi Zamzam , Sulistiyana Catur Setiya , Raffaello Wilson Matthew , Wibowo Arief , Pranata Raymond
Published: June 2021

Purpose

This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19.

Methods

We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs).

Results

There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000.

Conclusion

SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery.

Protocol registration

PROSPERO: CRD42021247510.
Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews
Authors: Rodriguez-García Sebastián Cruz , Castellanos-Moreira Raul , Uson Jacqueline , Naredo Esperanza , O'Neill Terence W , Doherty Michael , Boesen Mikael , Pandit Hemant , Möller Parera Ingrid , Vardanyan Valentina , Terslev Lene , Kampen Will Uwe , D'Agostino Maria Antonieta , Berenbaum Francis , Nikiphorou Elena , Pitsillidou Irene , de la Torre-Aboki Jenny , Carmona Loreto
Published: June 2021

Objective

To summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations.

Methods

An overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool.

Results

Of 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences.

Conclusions

This overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found.
GCN5 enables HSP12 induction promoting chromatin remodeling, not histone acetylation
Authors: Antonazzi Francesca , Di Felice Francesca , Camilloni Giorgio
Published: June 2021

Regulation of stress-responsive genes represent one of the best examples of gene induction, and the relevance and involvement of different regulators may change for a given gene depending on the challenging stimulus. The HSP12 gene is induced by very different stimuli; however, the molecular response to stress has been characterized in detail only for heat shock treatments. In this study, we aimed to verify whether the regulation of transcription induced by oxidative stress utilizes the same epigenetic solutions as those employed in the heat shock response. We also monitored HSP12 induction by employing spermidine, a known acetyltransferase inhibitor, and observed an oxidative stress that synergizes with spermidine treatment. Our data show that during transcriptional response to H2O2, histone acetylation and chromatin remodeling occur. However, when the relevance of Gcn5p to these processes was studied, we observed that induction of transcription is GCN5-dependent, and this does not rely on histone acetylation by Gcn5p despite its HAT activity. Chromatin remodeling accompanying gene activation is GCN5 dependent. Thus, GCN5 controls HSP12 transcription after H2O2 treatment by allowing chromatin remodeling, and it is only partially involved in HSP12 histone acetylation regardless of its HAT activity.
Effects of seasonal weathering on dewatering and strength of an oil sands tailings deposit
Authors: Rima Umme Salma , Beier Nicholas A.
Published: June 2021

Considerable research has been conducted over the past decade by oil sands mining companies to improve the dewatering and strength properties of fluid fine tailings deposits in an effort to meet the regulatory and closure requirements. Commercially employed dewatering treatment technologies (inline flocculation, thickening, and centrifugation) may not be sufficient to develop the strength for the creation of trafficable landscape without the use of soft soil capping technologies. These treated tailings are continuously deposited creating soft and saturated deep deposits. Seasonal weathering may be an additional promising technology to further dewater the treated tailings and promote the development of shear strength at the surface. This paper presents the effects of seasonal weathering on dewatering and strength that were investigated by performing multiple cycles of freeze–thaw and alternate drying–wetting cycles on two types of treated tailings deposit. The results indicate that multiple cycles of seasonal weathering significantly increased the dewatering and strength properties. However, different parameters such as freezing gradient, number of seasonal cycles, and pore water chemistry play an influential role in changing the magnitude of the strength. The results also suggest that a minimum threshold strength value is required where the effects of rainfall rewetting had a minimal impact on strength reduction (the strength corresponding to the moisture content approaching the plastic limit).
Semi-synthesis of novel buprenorphine derivatives and their anti-nociceptive properties and dependency potential
Authors: Hasanpour Zahra , Salehi Peyman , Bunch Lennart , Khoramjouy Mona , Bararjanian Morteza , Staerk Dan , Faizi Mehrdad
Published: June 2021

Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared with morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine.
Effect of gravitational wave on shadow of a Schwarzschild black hole
Authors: Wang Mingzhi , Chen Songbai , Jing Jiliang
Published: June 2021

We have studied the shadows of a Schwarzschild black hole under a special polar gravitational perturbation, which is a particular solution of Einstein equations expanded up to first order. It is shown that the black hole shadow changes periodically with time and the change of shadow depends on the Legendre polynomial order parameter l and the frequency $$\sigma $$
σ
of gravitational wave. For the odd order of Legendre polynomial, the center of shadow oscillates along the direction which is vertical to equatorial plane. For even l, the center of shadow does not move, but the shadow alternately stretches and squeezes with time along the vertical direction. Moreover, the presence of the gravitational wave leads to the self-similar fractal structures appearing in the boundary of the black hole shadow. We also find that this special gravitational wave has a greater influence on the vertical direction of black hole shadow.
A multiplicity results for a singular quasilinear elliptic equation
Authors: Hsini Mounir , Saoudi Kamel , Seddik Mouldi
Published: June 2021

The purpose of this work is to study the following singular problem: [Formula: see text] where [Formula: see text], [Formula: see text] be a bounded smooth domain, [Formula: see text] is a positive parameter, [Formula: see text] such that [Formula: see text] and [Formula: see text], [Formula: see text] where [Formula: see text] We employ the Nehari manifold approach and the fibering maps in order to show the existence of [Formula: see text] such that for all [Formula: see text], problem [Formula: see text] has at least two solutions.
Adjusted dynamics of COVID-19 pandemic due to herd immunity in Bangladesh
Authors: Hoque Md. Enamul , Islam Md. Shariful , Das Susanta Kumar , Mitra Dipak Kumar , Amin Mohammad Ruhul
Published: June 2021

Amid growing debate between scientists and policymakers on the trade-off between public safety and reviving economy during the COVID-19 pandemic, the government of Bangladesh decided to relax the countrywide lockdown restrictions from the beginning of June 2020. Instead, the Ministry of Public Affairs officials have declared some parts of the capital city and a few other districts as red zones or high-risk areas based on the number of people infected in the late June 2020. Nonetheless, the COVID-19 infection rate had been increasing in almost every other part of the country. Ironically, rather than ensuring rapid tests and isolation of COVID-19 patients, from the beginning of July 2020, the Directorate General of Health Services restrained the maximum number of tests per laboratory. Thus, the health experts have raised the question of whether the government is heading toward achieving herd immunity instead of containing the COVID-19 pandemic. In this paper, the dynamics of the pandemic due to SARS-CoV-2 in Bangladesh is analyzed with integrated the Unscented Kalman Filter (UKF) in the SIRD model. We demonstrate that the herd immunity threshold can be reduced to 31% than that of 60% by considering age group cluster analysis resulting in a total of 53.0 million susceptible populations. With the data of COVID-19 cases till January, 2021, the time-varying reproduction numbers are used to explain the nature of the pandemic. Based on the estimations of active, severe and critical cases, we discuss a set of policy recommendations to improve the current pandemic control methods in Bangladesh.
Negative energy states in the Reissner–Nordström metric
Authors: Zaslavskii O. B.
Published: June 2021

We consider electrogeodesics on which the energy [Formula: see text] in the Reissner–Nordström metric. It is shown that outside the horizon there is exactly one turning point inside the ergoregion for such particles. This entails that such a particle passes through an infinite chain of black–white hole regions or terminates in the singularity. These properties are relevant for two scenarios of high energy collisions in which the presence of white holes is essential.
A new anomaly-free flipped 341 model
Authors: Djouala M. , Mebarki N. , Aissaoui H.
Published: June 2021

A new flipped [Formula: see text] model without exotic electric charges is proposed. All the quark families are arranged in the same representation while lepton generations are in different representations leading to a tree level FCNC. Moreover, it is shown that the cancellation of the triangle gauge anomalies requires new additional leptons a 10-plet and a quadruplet. All fermion masses have been also discussed. Furthermore, using the most recent experimental data of the branching ratios of [Formula: see text] and [Formula: see text] rare decay modes, stringent bounds on the heavy neutral bosons masses and the muon-electron mixing matrix element are obtained.
Bio-mathematical analysis of electro-osmotically modulated hemodynamic blood flow inside a symmetric and nonsymmetric stenosed artery with joule heating
Authors: Saleem Anber , Akhtar Salman , Nadeem Sohail
Published: June 2021

This is the first paper that explains electro-osmotically modulated hemodynamic inside a stenosed artery, considering both cases of symmetric and nonsymmetric shapes of stenosis. Blood is treated as an aqueous ionic solution. The energy equation incorporates viscous dissipation as well as Joule heating effects. Exact solutions are calculated for governing equations subject to “no slip” boundary conditions. These solutions are further discussed through graphical results. The flow pattern for symmetric and nonsymmetric stenosis is visualized by plotting streamlines for this flow problem.
Diffeomorphism type of symplectic fillings of unit cotangent bundles
Authors: Geiges Hansjörg , Kwon Myeonggi , Zehmisch Kai
Published: June 2021

We prove uniqueness, up to diffeomorphism, of symplectically aspherical fillings of certain unit cotangent bundles, including those of higher-dimensional tori.
Pitaya peel derived carbons with ultra-high specific surface area for solid-state flexible asymmetric supercapacitors
Authors: Yang Wei , Zhu Cailian , Li Li , Wang Weihua , Yang Zheng
Published: June 2021

In this paper, a well-designed process to fabricate bio-mass carbon with ultra-high specific surface area (UHSSA) and hierarchical porous (HP) structure is achieved. The process pre-treating with ethanol and KOH cooperatively is first introduced to optimize the microstructure and porosity. The as-prepared carbons present an UHSSA of ca. 3521 m2 [Formula: see text] g[Formula: see text], with large amounts of micro and mesopores. The assembled asymmetric flexible super-capacitor (SC) holds very high energy density of 49.9 Wh [Formula: see text] kg[Formula: see text] at 90 W [Formula: see text] kg[Formula: see text], and 10.3 Wh [Formula: see text] kg[Formula: see text] at the higher power density of 9 kW [Formula: see text] kg[Formula: see text], demonstrating that the device possesses long cyclic life and well stability. The exciting results reveal that our study provides an effective approach to biomass recycling by pre-treatment of ethanol and KOH producing HP carbons possessing ultra-high SSA for high-energy storage applications.
Bearing capacity of conical footings on Hoek–Brown rock masses using finite element limit analysis
Authors: Keawsawasvong Suraparb
Published: June 2021

New plastic solutions for the bearing capacity factors of conical footings on rock masses obeying the Hoek–Brown yield criterion are presented in the paper by using the lower and upper bound finite element limit analysis. A conical footing has a cone apex angle and is penetrated into a rock mass. The considered dimensionless parameters include the cone apex angle, the yield parameter, and the geological strength index of a rock mass, where the effects of these dimensionless parameters on the bearing capacity factor are compressively investigated. The collapse mechanisms of conical footings on rock masses are examined and discussed in the paper.
Problems and Challenges Related to Advanced Data Analysis in Multi-Site Enterprises
Authors: Dudycz Helena , Stefaniak Paweł , Pyda Paweł
Published: June 2021

The new generation of industry, i.e. Industry 4.0, pertains to the processing of immense amounts of data, resulting, among other things, from the large-scale use of microcontrollers to control machines, an increase in the scale of automation, the use of the Internet of Things technology — e.g. in sensors installed at different stages of the production process, the implementation of the digital twin concept, and many other technologies designed to collect data (e.g. GPS or RFID). These data are collected in the enterprise’s variety of resources and databases. These data can be a valuable source of information and knowledge if the right approach to advanced data analysis is adopted, which depends, among other things, on the enterprise’s existing IT infrastructure. This paper sets out to present conclusions formulated on the basis of research consisting in the analysis of multinational manufacturing companies’ existing IT infrastructures. Three basic model solutions of IT architecture occurring in multi-site enterprises were identified, which made it possible to identify the main problems stemming from the IT architecture in place and concerning the analysis of data for the needs of company management. Additionally, this paper discusses the challenges faced by multi-site manufacturing companies. One such activity is the modification and expansion of the company’s IT infrastructure, including the implementation of Big Data and Master Data Management (MDM) solutions. The contribution provided by this paper consists in the analysis of the IT infrastructure in large, multi-site enterprises, which enabled the identification of problems and challenges related to advanced data analysis in this type of companies.
Expressiveness and Nash Equilibrium in Iterated Boolean Games
Authors: Gutierrez Julian , Harrenstein Paul , Perelli Giuseppe , Wooldridge Michael
Published: June 2021

We define and investigate a novel notion of expressiveness for temporal logics that is based on game theoretic equilibria of multi-agent systems. We use
iterated Boolean games
as our abstract model of multi-agent systems [Gutierrez et al. 2013, 2015a]. In such a game, each agent 

has a goal 

, represented using (a fragment of)

Linear Temporal Logic (

)

. The goal 

captures agent 

’s preferences, in the sense that the models of 

represent system behaviours that would satisfy 

. Each player controls a subset of Boolean variables

, and at each round in the game, player

is at liberty to choose values for variables

in any way that she sees fit. Play continues for an infinite sequence of rounds, and so as players act they collectively trace out a model for

, which for every player will either satisfy or fail to satisfy their goal. Players are assumed to act strategically, taking into account the goals of other players, in an attempt to bring about computations satisfying their goal. In this setting, we apply the standard game-theoretic concept of (pure) Nash equilibria. The (possibly empty) set of Nash equilibria of an iterated Boolean game can be understood as inducing a set of computations, each computation representing one way the system could evolve if players chose strategies that together constitute a Nash equilibrium. Such a set of equilibrium computations expresses a temporal property—which may or may not be expressible within a particular

fragment. The new notion of expressiveness that we formally define and investigate is then as follows:

What temporal properties are characterised by the Nash equilibria of games in which agent goals are expressed in specific fragments of 

? We formally define and investigate this notion of expressiveness for a range of

fragments. For example, a very natural question is the following:

Suppose we have an iterated Boolean game in which every goal is represented using a particular fragment

of

: is it then always the case that the equilibria of the game can be characterised within

?

We show that this is not true in general.
Leveraging Individual and Collective Regularity to Profile and Segment User Locations from Mobile Phone Data
Authors: Leng Yan , Zhao Jinhua , Koutsopoulos Haris
Published: June 2021

The dynamic monitoring of home and workplace distribution is a fundamental building block for improving location-based service systems in fast-developing cities worldwide. Inferring these places is challenging; existing approaches rely on labor-intensive and untimely survey data or ad hoc heuristic assignment rules based on the frequency of appearance at given locations. Motivated by the regularities in human behavior, we propose a novel method to infer the home, workplace, and third place based on an individual’s spatial-temporal patterns inferred from Call Detail Records. To capture the individual regularity, our method develops, for each person-location, the probability distribution that the person will appear in that location at a specific time of day using geo-temporal travel patterns a panel of individuals. To reveal the collective regularity, we apply eigen-decomposition to the matrix of historical geo-temporal data. Unsupervised machine learning techniques are then used to extract commonalities across locations for different groups of travelers, making inferences, such as home and workplace. Testing the methodology on real-world data with known location labels shows that our method identifies home and workplace with significant accuracy, improving upon the best practices in the literature by 79% and 34%, respectively. The methodology proposed is computationally efficient and is highly scalable to other real-world applications with historical tracking data. It provides a basis to improve location-based services, such as mobile commerce, social events recommendations, and urban transit design.
Ranking and Repulsing Supermartingales for Reachability in Randomized Programs
Authors: Takisaka Toru , Oyabu Yuichiro , Urabe Natsuki , Hasuo Ichiro
Published: June 2021

Computing reachability probabilities is a fundamental problem in the analysis of randomized programs. This article aims at a comprehensive and comparative account of various
martingale-based methods
for over- and under-approximating reachability probabilities. Based on the existing works that stretch across different communities (formal verification, control theory, etc.), we offer a unifying account. In particular, we emphasize the role of order-theoretic fixed points—a classic topic in computer science—in the analysis of randomized programs. This leads us to two new martingale-based techniques, too. We also make an experimental comparison using our implementation of template-based synthesis algorithms for those martingales.
PAVER
Authors: Tripathy Devashree , Abdolrashidi Amirali , Bhuyan Laxmi Narayan , Zhou Liang , Wong Daniel
Published: June 2021

The massive parallelism present in GPUs comes at the cost of reduced L1 and L2 cache sizes per thread, leading to serious cache contention problems such as thrashing. Hence, the data access locality of an application should be considered during thread scheduling to improve execution time and energy consumption. Recent works have tried to use the locality behavior of regular and structured applications in thread scheduling, but the difficult case of irregular and unstructured parallel applications remains to be explored.

We present
PAVER
, a
P
riority-
A
ware
V
ertex schedul
ER
, which takes a graph-theoretic approach toward thread scheduling. We analyze the cache locality behavior among
thread blocks
(
TBs
) through a just-in-time compilation, and represent the problem using a graph representing the TBs and the locality among them. This graph is then partitioned to TB groups that display maximum data sharing, which are then assigned to the same streaming multiprocessor by the locality-aware TB scheduler. Through exhaustive simulation in Fermi, Pascal, and Volta architectures using a number of scheduling techniques, we show that PAVER reduces L2 accesses by 43.3%, 48.5%, and 40.21% and increases the average performance benefit by 29%, 49.1%, and 41.2% for the benchmarks with high inter-TB locality.
A Programming Language for Data Privacy with Accuracy Estimations
Authors: Lobo-Vesga Elisabet , Russo Alejandro , Gaboardi Marco
Published: June 2021

Differential privacy offers a formal framework for reasoning about the privacy and accuracy of computations on private data. It also offers a rich set of building blocks for constructing private data analyses. When carefully calibrated, these analyses simultaneously guarantee the privacy of the individuals contributing their data, and the accuracy of the data analysis results, inferring useful properties about the population. The compositional nature of differential privacy has motivated the design and implementation of several programming languages to ease the implementation of differentially private analyses. Even though these programming languages provide support for reasoning about privacy, most of them disregard reasoning about the accuracy of data analyses. To overcome this limitation, we present DPella, a programming framework providing data analysts with support for reasoning about privacy, accuracy, and their trade-offs. The distinguishing feature of DPella is a novel component that statically tracks the accuracy of different data analyses. To provide tight accuracy estimations, this component leverages taint analysis for automatically inferring
statistical independence
of the different noise quantities added for guaranteeing privacy. We evaluate our approach by implementing several classical queries from the literature and showing how data analysts can calibrate the privacy parameters to meet the accuracy requirements, and vice versa.
Fast Key-Value Lookups with Node Tracker
Authors: Cavus Mustafa , Shatnawi Mohammed , Sendag Resit , Uht Augustus K.
Published: June 2021

Lookup operations for in-memory databases are heavily memory bound, because they often rely on pointer-chasing linked data structure traversals. They also have many branches that are hard-to-predict due to random key lookups. In this study, we show that although cache misses are the primary bottleneck for these applications, without a method for eliminating the branch mispredictions only a small fraction of the performance benefit is achieved through prefetching alone. We propose the Node Tracker (NT), a novel programmable prefetcher/pre-execution unit that is highly effective in exploiting inter key-lookup parallelism to improve single-thread performance. We extend NT with branch outcome streaming (BOS) to reduce branch mispredictions and show that this achieves an extra 3× speedup. Finally, we evaluate the NT as a pre-execution unit and demonstrate that we can further improve the performance in both single- and multi-threaded execution modes. Our results show that, on average, NT improves single-thread performance by 4.1× when used as a prefetcher; 11.9× as a prefetcher with BOS; 14.9× as a pre-execution unit and 18.8× as a pre-execution unit with BOS. Finally, with 24 cores of the latter version, we achieve a speedup of 203× and 11× over the single-core and 24-core baselines, respectively.
Twizzler: A
Data-centric
OS for Non-volatile Memory
Authors: Bittman Daniel , Alvaro Peter , Mehra Pankaj , Long Darrell D. E. , Miller Ethan L.
Published: June 2021

Byte-addressable, non-volatile memory (NVM) presents an opportunity to rethink the entire system stack. We present Twizzler, an operating system redesign for this near-future. Twizzler removes the kernel from the I/O path, provides programs with memory-style access to persistent data using small (64 bit), object-relative cross-object pointers, and enables simple and efficient long-term sharing of data both between applications and between runs of an application. Twizzler provides a clean-slate programming model for persistent data, realizing the vision of
Unix
in a world of persistent RAM.

We show that Twizzler is simpler, more extensible, and more secure than existing I/O models and implementations by building software for Twizzler and evaluating it on NVM DIMMs. Most persistent pointer operations in Twizzler impose less than 0.5 ns added latency. Twizzler operations are up to

faster than
Unix
, and SQLite queries are up to

faster than on PMDK. YCSB workloads ran 1.1–

faster on Twizzler than on native and NVM-optimized SQLite backends.
Host-Based Virtual Machine Workload Characterization Using Hypervisor Trace Mining
Authors: Nemati Hani , Azhari Seyed Vahid , Shakeri Mahsa , Dagenais Michel
Published: June 2021

Cloud computing is a fast-growing technology that provides on-demand access to a pool of shared resources. This type of distributed and complex environment requires advanced resource management solutions that could model virtual machine (VM) behavior. Different workload measurements, such as CPU, memory, disk, and network usage, are usually derived from each VM to model resource utilization and group similar VMs. However, these course workload metrics require internal access to each VM with the available performance analysis toolkit, which is not feasible with many cloud environments privacy policies.

In this article, we propose a non-intrusive host-based virtual machine workload characterization using hypervisor tracing. VM blockings duration, along with virtual interrupt injection rates, are derived as features to reveal multiple levels of resource intensiveness. In addition, the VM exit reason is considered, as well as the resource contention rate due to the host and other VMs. Moreover, the processes and threads preemption rates in each VM are extracted using the collected tracing logs. Our proposed approach further improves the selected features by exploiting a page ranking based algorithm to filter non-important processes running on each VM. Once the metric features are defined, a two-stage VM clustering technique is employed to perform both coarse- and fine-grain workload characterization. The inter-cluster and intra-cluster similarity metrics of the silhouette score is used to reveal distinct VM workload groups, as well as the ones with significant overlap. The proposed framework can provide a detailed vision of the underlying behavior of the running VMs. This can assist infrastructure administrators in efficient resource management, as well as root cause analysis.
New Developments in Flavor Evolution of a Dense Neutrino Gas
Authors: Tamborra Irene , Shalgar Shashank
Published: June 2021

Neutrino–neutrino refraction dominates the flavor evolution in core-collapse supernovae, neutron star mergers, and the early Universe. Ordinary neutrino flavor conversions develop on timescales determined by the vacuum oscillation frequency. However, when the neutrino density is large enough, collective flavor conversions may arise because of pairwise neutrino scattering. Pairwise conversions are deemed fast because they are expected to occur on timescales that depend on the neutrino–neutrino interaction energy (i.e., on the neutrino number density) and are regulated by the angular distributions of electron neutrinos and antineutrinos. The enigmatic phenomenon of fast pairwise conversions has been overlooked for a long time. However, because of the fast conversion rate, pairwise conversions could occur in the proximity of the neutrino decoupling region with yet-to-be-understood implications for the hydrodynamics of astrophysical sources and the synthesis of the heavy elements. We review the physics of this fascinating phenomenon and its implications for neutrino-dense sources.
The Capitalization of Agricultural Subsidies into Land Prices
Authors: Ciaian Pavel , Baldoni Edoardo , Kancs d'Artis , Drabik Dušan
Published: June 2021

We review the recent theoretical and empirical literature on the capitalization of agricultural subsidies into land prices. The theoretical literature predicts that agricultural subsidies are capitalized into land prices when land supply is inelastic and land markets function well. The share of capitalized subsidies significantly depends on the implementation of farm subsidies, local land-market institutions, rural market imperfections, and spatial effects. Most empirical studies have shown that agricultural subsidies are only partially capitalized into land prices, estimating that decoupled payments and land-based subsidies exhibit higher capitalization than coupled payments and nonland-based subsidies, respectively. However, estimated capitalization rates vary widely across studies largely because of data availability and identification challenges.
Retina Metabolism and Metabolism in the Pigmented Epithelium: A Busy Intersection
Authors: Hurley James B.
Published: June 2021

The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O2, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions.
Restrain Price Collusion in Trade‐Based Supply Chain Finance
Authors: Wei Qiang , Gou Xinyu , Deng Tianyu , Bai Chunguang
Published: June 2021

Collusion can increase the transaction value among supply chain members to obtain higher loans from supply chain finance (SCF) service provider, which will bring some serious risks for SCF. However, it is difficult to be identified and restrain the SCF service provider due to its stability and hiddenness. Different SCF transaction structures will affect the profits of supply chain members from collusion. This paper develops various game models for collusion and not collusion for different SCF transaction structures and investigates the impact of SCF transaction structures on the boundary conditions of collusion. Through comparative analysis, the findings of models are as follows: (1) in a two‐echelon supply chain, the supplier and retailer are more likely to conduct collusion under the sequential game than under the simultaneous game; (2) collusion in the two‐echelon supply chain can obtain higher loans than that in the three‐echelon supply chain, so it has more serious hidden danger; (3) in the two‐echelon supply chain, collusion is easier to form than in the three‐echelon SCF supply chain that has spontaneous endogenous constraints. We also develop two types of mechanisms to restrain collusion behavior from profit sharing and incomplete information perspectives. Finally, we summarize the theoretical implications and analyze the management implications through a case study.
Insights into Underrail Rubber Pad’s Effect on Vehicle‐Track‐Viaduct System Dynamics
Authors: Liu Linya , Zuo Zhiyuan , Zhou Yunlai , Qin Jialiang , Niu Zhenyu
Published: June 2021

To scientifically characterize the dynamic mechanical characteristics of the rubber pad under the rail of fasteners and its influence on the dynamic response of the vehicle‐rail‐viaduct system, taking the rubber pad under the rail of WJ‐7B high‐speed railway (HSR) with constant resistance as an example, a TFDV model was applied to characterize the viscoelasticity of the rubber pad and the theoretical model in the dynamic coupling of vehicle‐rail‐bridge was also studied. The results show that the energy storage modulus and loss factor of rubber pad under rail show a curved surface relation versus the change of frequency‐temperature. In a certain frequency/temperature range, the energy storage modulus and loss factor of rubber pad under rail increase with the decrease of temperature and the increase of frequency, and the influence of low temperature on dynamic parameters is more significant. With the decrease of temperature, the minimum value of total dynamic flexibility decreases, and the corresponding extreme frequency shifts to high frequency. Viscoelastic dynamic features of rubber pad under rail mainly affect the dynamic response of vehicle subsystem and rail‐bridge subsystem. With the decrease of ambient temperature of rubber pad, the dominant frequency band of power spectrum curve of each structure shifts to high frequency.
Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling
Authors: Jia Yanqiu , Li Zhe , Wang Tianjun , Fan Mingyue , Song Jiaxi , Lv Peiyuan , Jin Wei
Published: June 2021

Shikonin (SK) exerts neuroprotective effects; however, to date, its protective effect against chronic cerebral hypoperfusion- (CCH-) induced vascular dementia (VaD) has not been investigated. Therefore, the current study investigated whether SK could mitigate the cognitive deficits caused by CCH. The effects of SK treatment on the PTEN/Akt/CREB/BDNF signaling pathway and apoptosis in hippocampal neurons were examined in a rat model of VaD established via bilateral common carotid artery occlusion (BCCAO). Fifty-two rats were randomly divided into 4 groups: sham, vehicle, SK-L (10 mg/kg SK per day), and SK-H (25 mg/kg SK per day). SK was regularly administered by gavage for 2 weeks. The results of the water maze test revealed that the escape latency in the vehicle group was significantly longer than that in the sham group, and rats in the vehicle group spent a smaller proportion of time in the target quadrant than those in the sham group. SK treatment reduced the escape latencies and increased the proportion of time spent in the target quadrant. Nissl staining showed morphological damage in the CA1 areas of the hippocampus in the vehicle group. SK treatment alleviated the injuries to hippocampal neurons. Western blot analysis showed higher p-PTEN and lower p-Akt, p-CREB, and BDNF expression in the vehicle group than in the sham group. SK administration reversed the upregulation of p-PTEN and the downregulation of p-Akt, p-CREB, and BDNF. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling- (TUNEL-) positive cells in the hippocampal CA1 region of the vehicle group was significantly increased. Treatment with SK decreased the number of positive cells. Furthermore, as marker proteins of apoptosis, bcl-2 expression was decreased and bax expression was increased; thus, the ratio of bcl-2/bax was decreased in the vehicle group. SK treatment upregulated the expression of bcl-2 and downregulated the expression of bax, thereby elevating the bcl-2/bax ratio. Moreover, the aforementioned effects of SK were dose-dependent. The effect of 25 mg/kg per day was more obvious than that of 10 mg/kg per day. In conclusion, SK inhibited hippocampal neuronal apoptosis to protect against CCH-induced injury by regulating the PTEN/Akt/CREB/BDNF signaling pathway, consequently improving cognitive impairment.
Hydrochemistry and Entropy-Based Groundwater Quality Assessment in the Suining Area, Southwestern China
Authors: Zhang Yunhui , Li Xiao , Luo Ming , Wei Changli , Huang Xun , Xiao Yong , Qin Limao , Pei Qiuming
Published: June 2021

Groundwater is an essential resource for sustainable development, whose quality is significant for human health. In the present study, twenty-eight groundwater samples were collected from domestic tube wells and public water supply wells in the Suining area, southwestern China. The integration of statistical analysis, correlations of ions, geomodelling, and entropy-weighted water quality index (EWQI) was carried out to clarify the hydrochemistry and groundwater quality in the study area. By the statistical analysis, the cations followed the concentration order as Ca2+> Na+> Mg2+> K+, while anions’ concentrations were HCO3− > SO42− > Cl− > NO3− > F−. Piper trilinear diagram showed the hydrochemical type was characterized as Ca-HCO3. Correlations of ions and geomodelling revealed the concentrations of major ions were mainly determined by carbonate dissolution and ion exchange process, and NO3− concentrations were controlled by agriculture activities. EWQI computation demonstrated that most of the groundwater samples possessed EWQI values higher than 100. Therefore, groundwater quality is lower than the permissible limit of the World Health Organization (WHO), suitable for drinking purposes in the Suining area. Our study provides vital knowledge for groundwater management in the Suining and other similar areas.
RIPK3‐Mediated Necroptosis in Diabetic Cardiomyopathy Requires CaMKII Activation
Authors: Chen Yun , Li Xinshuai , Hua Yuyun , Ding Yue , Meng Guoliang , Zhang Wei
Published: June 2021

Activation of Ca2+/calmodulin‐dependent protein kinase (CaMKII) has been proved to play a vital role in cardiovascular diseases. Receptor‐interaction protein kinase 3‐ (RIPK3‐) mediated necroptosis has crucially participated in cardiac dysfunction. The study is aimed at investigating the effect as well as the mechanism of CaMKII activation and necroptosis on diabetic cardiomyopathy (DCM). Wild‐type (WT) and the RIPK3 gene knockout (RIPK3-/-) mice were intraperitoneally injected with 60 mg/kg/d streptozotocin (STZ) for 5 consecutive days. After 12 w of feeding, 100 μL recombinant adenovirus solution carrying inhibitor 1 of protein phosphatase 1 (I1PP1) gene was injected into the caudal vein of mice. Echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK1 expression, mixed lineage kinase domain‐like protein (MLKL) phosphorylation, and mitochondrial ultrastructure were measured. The results showed that cardiac dysfunction, CaMKII activation, and necroptosis were aggravated in streptozotocin‐ (STZ‐) stimulated mice, as well as in (Lepr) KO/KO (db/db) mice. RIPK3 deficiency alleviated cardiac dysfunction, CaMKII activation, and necroptosis in DCM. Furthermore, I1PP1 overexpression reversed cardiac dysfunction, myocardial injury and necroptosis augment, and CaMKII activity enhancement in WT mice with DCM but not in RIPK3-/- mice with DCM. The present study demonstrated that CaMKII activation and necroptosis augment in DCM via a RIPK3‐dependent manner, which may provide therapeutic strategies for DCM.
C‐Reactive Protein Levels and Clinical Prognosis in LAA‐Type Stroke Patients: A Prospective Cohort Study
Authors: Zeng Qingjia , Zeng Yaying , Slevin Mark , Guo Baoqiang , Shen Zhipeng , Deng Binbin , Zhang Wenbo
Published: June 2021

Background and Purpose. There are increasing evidences that show that the prognosis of patients with acute ischemic stroke (AIS) is closely related to the inflammatory response. In the inflammation caused by AIS, plasma C‐reactive protein (CRP) will increase and is associated with prognosis in these patients; few studies have looked at the relationship between CRP and large artery atherosclerosis‐ (LAA‐) type AIS. We aim to investigate the role of CRP in predicting the functional outcome of LAA‐type AIS patients. Methods. We prospectively included 200 patients with LAA‐type AIS and tested their CRP levels on admission. We followed these patients consecutively. The primary outcome was an adverse event, defined as a modified Rankin Scale score of 2‐6 at months 3, 6, and 12 after discharge. A logistic regression model was used to analyze the relationship between CRP and the functional outcome of LAA stroke. Results. We divided 200 patients into 3 groups evenly based on CRP level. After adjustment for gender, age, smoking history, drinking history, history of hyperlipidemia, history of diabetes, lipid levels, and blood glucose levels, logistic regression showed that the incidence of LAA‐type AIS poor outcome was positively associated with CRP level at admission, whether it was 3 months, 6 months, or 12 months after discharge, respectively (OR: 2.574, 95% CI: 1.213‐5.463; OR: 2.806, 95% CI: 1.298‐6.065; OR: 2.492, 95% CI: 1.167‐5.321. In the highest tertile vs. the lowest tertile as a reference), and both were statistically different. Conclusions. High CRP level predicts poor functional outcome in LAA‐type AIS patients, which provides a strong basis for clinicians to make treatment decisions for these patients.