bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental programs interact with abscisic acid to coordinate root suberization in Arabidopsis
Authors: Wang Chunhua , Wang Hong , Li Pengxue , Li Haiyang , Xu Chunmiao , Cohen Hagai , Aharoni Asaph , Wu Shuang
Published: July 2020

Suberin lamellae, which provide a hydrophobic protective barrier against biotic and abiotic stresses, are widely deposited in various cell types during plant development and in response to stress. However, it remains unclear how developmental programs interact with stress responses to direct the precise spatiotemporal pattern of suberin deposition. In this study, we found that SHORT‐ROOT (SHR), together with its downstream factor MYB36, guided suberization specifically in the root endodermis. Despite a partial dependence on abscisic acid (ABA), the suberization mediated by SHR and MYB36 appeared to derive from a slow readout of developmental programs, which was in contrast to the rapid but transient suberization induced by ABA. Furthermore, we found the MYB39 transcription factor functioned as a common downstream hub of the SHR/MYB36 pathway and the ABA‐triggered response. MYB39 could directly bind to the FAR5 (alcohol‐forming fatty acyl‐coenzyme A reductase) promoter to activate its expression. In addition, overexpression of MYB39 dramatically increased the amount of suberization in Arabidopsis roots. Our results provide important insights into the interaction between developmental programs and environmental stimuli in root suberization in Arabidopsis.
Effect of High Pressures on the Formation of Nitric Oxide in Lean, Premixed Flames
Authors: Versailles Philippe , Durocher Antoine , Bourque Gilles , Bergthorson Jeffrey M.
Published: July 2020

Increasingly stringent regulations are imposed on nitrogen oxides emissions due to their numerous negative impacts on human health and the environment. Accurate, experimentally validated thermochemical models are required for the development of the next generation of combustors. This paper presents a series of experiments performed in lean, premixed, laminar, jet-wall stagnation flames at pressures of 2, 4, 8, and 16 atm. To target postflame temperatures relevant to gas turbine engines, the stoichiometry of the nonpreheated methane–air mixture is adjusted to an equivalence ratio of 0.7. One-dimensional (1D) profiles of temperature and NO mole fraction are measured via laser-induced fluorescence (LIF) thermometry and NO-LIF, respectively, to complement previously published flame speed data (Versailles et al., 2018, “Measurements of the Reactivity of Premixed, Stagnation, Methane-Air Flames at Gas Turbine Relevant Pressures,” ASME. J. Eng. Gas Turbines Power, 141(1), p. 011027). The results reveal that, as the pressure increases, the maximum postflame temperature stays relatively stable, and the concentration of NO produced through the flame front remains constant within uncertainty. Seven thermochemical models, selected for their widespread usage or recent date of publication, are validated against the experimental data. While all mechanisms accurately predict the postflame temperature, thanks to consistent thermodynamic parameters, important disagreements are observed in the NO concentration profiles, which highlights the need to carefully select the models used as design tools. The lack of pressure dependence of NO formation that many models fail to capture is numerically investigated via sensitivity and reaction path analyses applied to the solution of flame simulations. The termolecular reaction H+O2(+M)↔HO2(+M) is shown to hinder the production of atomic oxygen and to consume hydrogen radicals at higher pressures, which inhibits the formation of nitric oxide through the N2O pathway.
Model-Based Design and Optimization for Large Bore Engines: Some Industrial Case Studies
Authors: Srinivasan Prashant , Bhat Sanketh , Sivasubramaniam Manthram , Methekar Ravi , Devarakonda Maruthi , Kumar Chandan
Published: July 2020

Large bore reciprocating internal combustion (IC) engines are used in a wide variety of applications such as power generation, transportation, gas compression, mechanical drives, and mining. Each application has its own unique requirements that influence the engine design and control strategy. The system architecture and control strategy play a key role in meeting the requirements. Traditionally, control design has come in at a later stage of the development process, when the system design is almost frozen. Furthermore, transient performance requirements have not always been considered adequately at early design stages for large engines, thus limiting achievable controller performance. With rapid advances in engine modeling capability, it has now become possible to accurately simulate engine behavior in steady-states and transients. In this paper, we propose an integrated model-based approach to system design and control of reciprocating engines and outline ideas, processes, and real-world case studies for the same. Key benefits of this approach include optimized engine performance in terms of efficiency, transient response, emissions, system and cost optimization, and tools to evaluate various concepts before engine build thus leading to significant reduction in development time and cost.
Exercising your mind
Authors: Ansere Victor A. , Freeman Willard M.
Published: July 2020

A circulating factor induced by exercise contributes to keeping the brain young in mice
Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy
Authors: Chaillon Antoine , Nakazawa Masato , Rawlings Stephen A. , Curtin Genevieve , Caballero Gemma , Scott Brianna , Anderson Christy , Gianella Sara
Published: July 2020

As part of this study, we evaluated the molecular characteristics of the HIV DNA reservoir over time during antiretroviral treatment (ART) in relation to those of other chronic viral infections (i.e., cytomegalovirus [CMV] and Epstein-Barr virus [EBV]). We demonstrated that the presence of CMV and high-level EBV DNA in peripheral blood cells was associated with changes in HIV DNA molecular diversity. Specifically, HIV DNA molecular diversity increased over time among participants with detectable CMV and high-level EBV DNA, while it significantly declined among participants with no/low viral shedding. Although the current study design does not allow causality to be inferred, it does support the theory that persistent CMV and EBV shedding could contribute to the dynamics of the HIV DNA reservoir during suppressive ART, even when ART is initiated during the earliest phases of HIV infection.
Radical change in osteosarcoma surgical plan due to COVID-19 pandemic
Authors: Gaston Czar Louie Lopez , Pag-ong Johann Proceso , Dacanay Emilleo , Quintos Albert Jerome
Published: July 2020

A 17-year-old man with osteosarcoma of the proximal humerus was planned for possible limb salvage surgery after standard neoadjuvant chemotherapy. However, during the surgical phase of treatment, the COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) outbreak occurred changing the healthcare landscape due to uncertainty regarding the virus, risk of COVID-19 infection and complications, and implementation of an enhanced community quarantine restricting movement of people within cities. Instead of limb salvage surgery, the patient underwent a forequarter amputation. Exposure to the virus in a high-risk hospital setting was minimised with patient discharge after a short hospital stay and home convalescence monitored by video conferencing. Multidisciplinary sarcoma team meetings with family members and a sarcoma navigator nurse were crucial in managing expectations and deciding on appropriate treatment in the setting of a novel infectious disease causing a pandemic.
How can consultant-led childbirth care at time of delivery be maximised? A modelling study
Authors: Allen Michael , Villeneuve Emma , Pitt Martin , Thornton Steve
Published: July 2020

Objective

The Royal College of Obstetricians and Gynaecologists has advised that consolidation of birth centres, where reasonable, into birth centres of at least 6000 admissions per year should allow constant consultant presence. Currently, only 17% of mothers attend such birth centres. The objective of this work was to examine the feasibility of consolidation of birth centres, from the perspectives of birth centre size and travel times for mothers.

Design

Computer-based optimisation.

Setting

Hospital-based births.

Population or sample

1.91 million admissions in 2014–2016.

Methods

A multiple-objective genetic algorithm.

Main outcome measures

Travel time for mothers and size of birth centres.

Results

Currently, with 161 birth centres, 17% of women attend a birth centre with at least 6000 admissions per year. We estimate that 95% of women have a travel time of 30 min or less. An example scenario, with 100 birth centres, could provide 75% of care in birth centres with at least 6000 admissions per year, with 95% of women travelling 35 min or less to their closest birth centre. Planning at local level leads to reduced ability to meet admission and travel time targets.

Conclusions

While it seems unrealistic to have all births in birth centres with at least 6000 admissions per year, it appears realistic to increase the percentage of mothers attending this type of birth centre from 17% to about 75% while maintaining reasonable travel times. Planning at a local level leads to suboptimal solutions.
Cardiac arrest as a reportable condition: a cohort study of the first 6 years of the Norwegian out-of-hospital cardiac arrest registry
Authors: Tjelmeland Ingvild Beathe Myrhaugen , Alm-Kruse Kristin , Andersson Lars-Jøran , Bratland Ståle , Hafstad Arne-Ketil , Haug Bjørn , Langørgen Jørund , Larsen Alf Inge , Lindner Thomas Werner , Nilsen Jan Erik , Olasveengen Theresa M , Soreide Eldar , Skogvoll Eirik , Kramer-Johansen Jo
Published: July 2020

Objectives

The Norwegian Cardiac Arrest Registry (NorCAR) was established in 2013 when cardiac arrest became a mandatory reportable condition. The aim of this cohort study is to describe how the world’s first mandatory, population-based cardiac arrest registry evolved during its first 6 years.

Setting

Norway has a total population of 5.3 million inhabitants with a population density that varies considerably. All residents are assigned a unique identifier number, giving nationally approved registries access to information about all births and deaths in the country. Data in the registry are entered by data processors; public employees with close links to the emergency medical services. All data processors undergo a standardised training and meet for yearly retraining and updates.

Participants

All events of cardiac arrest where bystanders or healthcare professionals have started cardiopulmonary resuscitation or performed defibrillation are included into the NorCAR.

Primary and secondary outcome measures

Since the establishment of the registry, the number of reporting health trusts, the number of reported events and the corresponding population at risk were followed year by year. Outcome is measured as changes in inclusion rate, incidence per 100 000 inhabitants and survival to 30 days after cardiac arrest.

Results

In total, 14 849 cases were registered over 6 years, between 2013 and 2018. The number of health trusts reporting rose steadily from 2013. Within 3 years, all trusts reported to the registry with an increasing number of events reported; going from 1101 to 3400 per year. The prevalence of bystander cardiopulmonary resuscitation increased slightly, but the population incidence of survival did not change.

Conclusion

Declaring cardiac arrest as a reportable condition and close follow-up of all reporting areas is essential when building a national registry.
Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial
Authors: Rahmel Tim , Hübner Max , Koos Björn , Wolf Alexander , Willemsen Katrin-Maria , Strauß Gabriele , Effinger David , Adamzik Michael , Kreth Simone
Published: July 2020

Introduction

Sepsis is defined as detrimental immune response to an infection. This overwhelming reaction often abolishes a normal reconstitution of the immune cell homeostasis that in turn increases the risk for further complications. Recent studies revealed a favourable impact of ketone bodies on resolution of inflammation. Thus, a ketogenic diet may provide an easy-to-apply and cost-effective treatment option potentially alleviating sepsis-evoked harm. This study is designed to assess the feasibility, efficiency and safety of a ketogenic diet in septic patients.

Methods and analysis

This monocentric study is a randomised, controlled and open-label trial, which is conducted on an intensive care unit of a German university hospital. As intervention enteral nutrition with reduced amount of carbohydrates (ketogenic) or standard enteral nutrition (control) is applied. The primary endpoint is the detection of ketone bodies in patients’ blood and urine samples. As secondary endpoints, the impact on important safety-relevant issues (eg, glucose metabolism, lactate serum concentration, incidence of metabolic acidosis, thyroid function and 30-day mortality) and the effect on the immune system are analysed.

Ethics and dissemination

The study has received the following approvals: Ethics Committee of the Medical Faculty of Ruhr-University Bochum (No. 18-6557-BR). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers by publication in a peer-reviewed journal.

Trial registration numbers

German Clinical Trial Register (DRKS00017710); Universal Trial Number (U1111-1237-2493).
Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial
Authors: Liu Fang , Zhu Yuan , Zhang Jing , Li Yiming , Peng Zhiyong
Published: July 2020

Introduction

The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19.

Methods and analysis

The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.

Trial registration number

NCT04264533.
Patient deaths and medical residents: an Asian perspective
Authors: Tan Teresa , Koh Pei Lin , Levetown Marcia , Wong Lisa , Lee Joanne , Yong Woon Chai , Yap Eng Soo
Published: July 2020

Objectives

Death is a significant event that affects healthcare providers emotionally. We aimed to determine internal medicine (IM) and paediatric (PD) residents’ responses and the impact on the residents following patient deaths, and to compare any differences between IM and PD residents. We also aimed to determine whether sufficient resources and measures were in place to support residents through their grief process.

Methods

This is a single-centre, cross-sectional study involving residents from IM and PD programmes from an academic tertiary hospital in Singapore. The residents completed a questionnaire regarding their responses and emotions after experiencing patient deaths.

Results

A total of 122 residents (85 IM and 37 PD, equally distributed between year 1 to year 4 of residency training) participated, with 100% response rate. Only half (57%) felt they would be comfortable treating a dying patient and 66.4% reported feeling sad following their patient’s death. Most (79.5%) were not aware of support resources that were available and 82% agreed that formal bereavement training should be included in the residency curriculum. PD residents had more negative symptoms than IM residents, with poor concentration (PD 35.1% vs IM 16.5%, p=0.02) and lethargy (PD 35.1% vs IM 9.4%, p<0.01) being the most common.

Conclusion

In our Asian context, residents are negatively affected by patient deaths, especially the PD residents. There is a need to incorporate relevant bereavement training for all residents.
Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis
Authors: Derakhshan Mohammad H , Dean Linda , Jones Gareth T , Siebert Stefan , Gaffney Karl
Published: July 2020

Objectives

Extra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.

Methods

Clinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.

Results

AAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.

Conclusion

The higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.
ENABLING THE UTILIZATION OF POTENTIALLY DISRUPTIVE DIGITAL INNOVATIONS BY INCUMBENTS: THE IMPACT OF CONTEXTUAL, ORGANISATIONAL, AND INDIVIDUAL FACTORS IN REGULATED CONTEXTS
Authors: STEINHAUSER STEFANIE
Published: July 2020

Incumbents’ inertia in the face of disruptive innovations has been emphasised in prior literature. The relevance of inertia is particularly topical in the context of digital transformation. However, incumbents may be able to invest in disruptive digital innovations appropriately if they possess the motivation and ability to do so. In this paper, I use three streams of research in order to investigate contextual, organisational, and individual antecedents of incumbents’ motivation and ability to adopt and use potentially disruptive digital innovations in health care: institutional theory, the resource-based view, and technology acceptance literature. I employ factor analyses and logistic regressions to test the impact on the adoption and usage of telemedicine applications using a dataset of 9,196 European general practitioners. I examine B2B as well as B2C applications in order to determine the effect of the antecedents on different business models. My findings suggest that only isomorphic pressure, complementary assets, and perceived output quality significantly influence both adoption and usage as well as B2B and B2C business models in the same way. Formal institutions and individual factors yield ambiguous results. These findings provide important implications for the understanding of incumbents’ response to potentially disruptive digital innovations in regulated contexts.
Comprehension and Evolution of Combinatorial Models and Test Plans
Authors: Tzoref Rachel
Published: July 2020

Combinatorial test design (CTD) [1] is an effective test design technique, considered to be a testing best practice. CTD provides automatic test plan generation, but it requires a manual definition of the test space in the form of a combinatorial model, consisting of parameters, their respective values, and constraints on the value combinations. A valid test in the test space is defined to be an assignment of one value to each parameter that satisfies the constraints. A CTD algorithm automatically constructs a subset of the set of valid tests, termed a test plan, which covers all valid value combinations of every t parameters, where t is usually a user input. Such a test plan is said to achieve 100% t-way interaction coverage. A significant combinatorial reduction is achieved in the size of the resulting test plan (compared to manually designed test plans for example) because the tests generated by the CTD algorithm are very different from one another, maximizing their added value -- each of them covers as many unique t-way value tuples as possible. Note that tests produced by the algorithm are parameter-value assignments. Generating executable tests from them is often a separate, manual effort.
Summary of the 2nd Workshop on Gender Equality in Software Engineering (GE 2019)
Authors: Crnkovic Ivica , Kohl Silveira Karina , Sprenkle Sara
Published: July 2020

The 2nd Workshop on Gender Equality in Software Engineering was a continuation of the first workshop with a goal to increase awareness of gender-related challenges in Software Engineering community. Further the workshop's goals were to illuminate the problem in a variety of contexts, evaluate proposed solutions, discuss approaches to move towards gender equality, and to develop a community to support meaningful change in gender equality in software engineering. In its second year, the workshop featured a keynote from ACM-W president Jodi Tims, ten papers, two posters on work-in-progress, and a fivemember panel. Jodi Tims presented principles and best practices of work to improve the gender balance. Paper topics focused on gender in computer science in a variety of domains, including in education, parenting, and industry, and on creating inclusive environments, including in open source. The panel discussed particularly difficult challenges-including the potential bias of data that is used by artificial intelligence to make decisions-and how aggressive institutions can be to make meaningful change. Thirty-eight people from seventeen countries participated in the workshop, and even more people were reached via Twitter.
Delay-Optimal Policies in Partial Fork-Join Systems with Redundancy and Random Slowdowns
Authors: Zubeldia Martin
Published: July 2020

We consider a large distributed service system consisting of n homogeneous servers with infinite capacity FIFO queues. Jobs arrive as a Poisson process of rate λn/kn (for some positive constant kn and integer kn). Each incoming job consists of ???? identical tasks that can be executed in parallel, and that can be encoded into at least ???? ?replicas" of the same size (by introducing redundancy) so that the job is considered to be completed when any kn replicas associated with it finish their service. Moreover, we assume that servers can experience random slowdowns in their processing rate so that the service time of a replica is the product of its size and a random slowdown.

First, we assume that the server slowdowns are shifted exponential and independent of the replica sizes. In this setting we show that the delay of a typical job is asymptotically minimized (as n - ∞) when the number of replicas per task is a constant that only depends on the arrival rate λ, and on the expected slowdown of servers.

Second, we introduce a new model for the server slowdowns in which larger tasks experience less variable slowdowns than smaller tasks. In this setting we show that, under the class of policies where all replicas start their service at the same time, the delay of a typical job is asymptotically minimized (as n - ∞) when the number of replicas per task is made to depend on the actual size of the tasks being replicated, with smaller tasks being replicated more than larger tasks.
Achieving Efficient Routing in Reconfigurable DCNs
Authors: Yang Zhenjie , Cui Yong , Xiao Shihan , Wang Xin , Li Minming , Li Chuming , Liu Yadong
Published: July 2020

With the fast growth of cloud services and network scales, the heavy and highly dynamic traffic demands pose great challenges to the efficient traffic engineering in today's data center networks (DCNs) [21]. The DCN flows can be broadly classified into two main categories: delay-sensitive small flows (e.g., queries or realtime small messages) and throughput-sensitive large flows (e.g., the backup traffic). In general, more than 80% flows in data centers are small flows, while the majority of the traffic volume is contributed by the top 10% large flows [3, 7]. To handle the mixed traffic, today's data centers [1, 14] generally follow the tree-based topologies (e.g., fat-tree) and take the load-agnostic routing strategies based on random path selection (e.g., ECMP1) [14, 19]. Although it is applicable for routing small flows which are highly random, these strategies are likely to route several large flows through the same output link and lead to long-lived congestions [2, 8]. With the limited switch buffer occupied by large flows for a long time, small flows are reported to experience one order of magnitude larger delay, which compromises the performance of DCNs and makes the users suffer [3].
I Know What You Did Last Summer
Authors: Ivkin Nikita , Ben Basat Ran , Liu Zaoxing , Einziger Gil , Friedman Roy , Braverman Vladimir
Published: July 2020

Modern telemetry systems require advanced analytic capabilities such as drill down queries. These queries can be used to detect the beginning and end of a network anomaly by efficiently refining the search space. We present the first integral solution that (i) enables multiple measurement tasks inside the same data structure, (ii) supports specifying the time frame of interest as part of its queries, and (iii) is sketch-based and thus space efficient. Namely, our approach allows the user to define both the measurement task (e.g., heavy hitters, entropy estimation, cardinality estimation) and the time frame of relevance (e.g., 5PM-6PM) at query time. Our approach provides accuracy guarantees and is the only space-efficient solution that offers such capabilities. Finally, we demonstrate how the algorithm can be used to accurately pinpoint the beginning of a realistic DDoS attack.
Latency Imbalance Among Internet Load-Balanced Paths
Authors: Pi Yibo , Jamin Sugih , Danzig Peter , Qian Feng
Published: July 2020

Load balancers choose among load-balanced paths to distribute traffic as if it makes no difference using one path or another. This work shows that the latency difference between load-balanced paths (called latency imbalance), previously deemed insignificant, is now prevalent from the perspective of the cloud and affects various latency-sensitive applications. In this work, we present the first large-scale measurement study of latency imbalance from a cloudcentric view. Using public cloud around the globe, we measure latency imbalance both between data centers (DCs) in the cloud and from the cloud to the public Internet. Our key findings include that 1) Amazon's and Alibaba's clouds together have latency difference between load-balanced paths larger than 20ms to 21% of public IPv4 addresses; 2) Google's secret in having lower latency imbalance than other clouds is to use its own well-balanced private WANs to transit traffic close to the destinations and that 3) latency imbalance is also prevalent between DCs in the cloud, where 8 pairs of DCs are found to have load-balanced paths with latency difference larger than 40ms. We further evaluate the impact of latency imbalance on three applications (i.e., NTP, delay-based geolocation and VoIP) and propose potential solutions to improve application performance. Our experiments show that all three applications can benefit from considering latency imbalance, where the accuracy of delay-based geolocation can be greatly improved by simply changing how ping measures the minimum path latency.
Characterizing Transnational Internet Performance and the Great Bottleneck of China
Authors: Zhu Pengxiong , Man Keyu , Wang Zhongjie , Qian Zhiyun , Ensafi Roya , Halderman J. Alex , Duan Haixin
Published: July 2020

Transnational Internet performance is an important indication of a country's level of infrastructure investment, globalization, and openness. We conduct a large-scale measurement study of transnational Internet performance in and out of 29 countries and regions, and find six countries that have surprisingly low performance. Five of them are African countries and the last is mainland China, a significant outlier with major discrepancies between downstream and upstream performance. We then conduct a comprehensive investigation of the unusual transnational Internet performance of mainland China, which we refer to as the "Great Bottleneck of China". Our results show that this bottleneck is widespread, affecting 79% of the receiver-sender pairs we measured. More than 70% of the pairs suffer from extremely slow speed (less than 1 Mbps) for more than 5 hours every day. In most tests the bottleneck appeared to be located deep inside China, suggesting poor network infrastructure to handle transnational traffic. The phenomenon has far-reaching implications for Chinese users' browsing habits as well as for the ability of foreign Internet services to reach Chinese customers.
Stability and Scalability of Blockchain Systems
Authors: Gopalan Aditya , Sankararaman Abishek , Walid Anwar , Vishwanath Sriram
Published: July 2020

The blockchain paradigm, introduced in the Bitcoin whitepaper [10], enables distributed consensus over a peer-to-peer network. Each peer constantly mines new information called blocks. Thus, blocks in the network are created over time. Each peer that creates (mines) a block also creates references to one or more previously created blocks. Peers also communicate blocks in order to synchronize their information sets; i.e., the sets of blocks and references the peers are aware of.
Optimal Data Placement for Heterogeneous Cache, Memory, and Storage Systems
Authors: Zhang Lei , Karimi Reza , Ahmad Irfan , Vigfusson Ymir
Published: July 2020

New memory technologies are blurring the previously distinctive performance characteristics of adjacent layers in the memory hierarchy. No longer are such layers orders of magnitude different in request latency or capacity. Beyond the traditional single-layer view of caching, we now must re-cast the problem as a data placement challenge: which data should be cached in faster memory if it could instead be served directly from slower memory?

We present Chopt, an offline algorithm for data placement across multiple tiers of memory with asymmetric read and write costs. We show that Chopt is optimal and can therefore serve as the upper bound of performance gain for any data placement algorithm. We also demonstrate an approximation of Chopt which makes its execution time for long traces practical using spatial sampling of requests incurring a small 0.2% average error on representative workloads at a sampling ratio of 1%. Our evaluation of Chopt on more than 30 production traces and benchmarks shows that optimal data placement decisions could improve average request latency by 8.2%-44.8% when compared with the long-established gold standard: Belady and Mattson's offline, evict-farthest-in-the-future optimal algorithms. Our results identify substantial improvement opportunities for future online memory management research.
Logarithmic Communication for Distributed Optimization in Multi-Agent Systems
Authors: London Palma , Vardi Shai , Wierman Adam
Published: July 2020

Classically, the design of multi-agent systems is approached using techniques from distributed optimization such as dual descent and consensus algorithms. Such algorithms depend on convergence to global consensus before any individual agent can determine its local action. This leads to challenges with respect to communication overhead and robustness, and improving algorithms with respect to these measures has been a focus of the community for decades.

This paper presents a new approach for multi-agent system design based on ideas from the emerging field of local computation algorithms. The frameworkwe develop, LOcal Convex Optimization (LOCO), is the first local computation algorithm for convex optimization problems and can be applied in a wide-variety of settings. We demonstrate the generality of the framework via applications to Network Utility Maximization (NUM) and the distributed training of Support Vector Machines (SVMs), providing numerical results illustrating the improvement compared to classical distributed optimization approaches in each case.
Unimodal Bandits with Continuous Arms
Authors: Combes Richard , Proutiere Alexandre , Fauquette Alexandre
Published: July 2020

We consider stochastic bandit problems with a continuous set of arms and where the expected reward is a continuous and unimodal function of the arm. For these problems, we propose the Stochastic Polychotomy (SP) algorithms, and derive finite-time upper bounds on their regret and optimization error. We show that, for a class of reward functions, the SP algorithm achieves a regret and an optimization error with optimal scalings, i.e., O( √ T ) and O(1/ √ T ) (up to a logarithmic factor), respectively.
The Genetic Control of Stoichiometry Underlying Autism
Authors: Darnell Robert B.
Published: July 2020

Autism is a common and complex neurologic disorder whose scientific underpinnings have begun to be established in the past decade. The essence of this breakthrough has been a focus on families, where genetic analyses are strongest, versus large-scale, case-control studies. Autism genetics has progressed in parallel with technology, from analyses of copy number variation to whole-exome sequencing (WES) and whole-genome sequencing (WGS). Gene mutations causing complete loss of function account for perhaps one-third of cases, largely detected through WES. This limitation has increased interest in understanding the regulatory variants of genes that contribute in more subtle ways to the disorder. Strategies combining biochemical analysis of gene regulation, WGS analysis of the noncoding genome, and machine learning have begun to succeed. The emerging picture is that careful control of the amounts of transcription, mRNA, and proteins made by key brain genes—stoichiometry—plays a critical role in defining the clinical features of autism.
Association of Central Precocious Puberty with a Rare Presentation of Schimmelpenning–Feuerstein–Mims Syndrome in a Peruvian Girl
Authors: De los Santos-La Torre Miguel Angel , Del Águila-Villar Carlos Manuel , Lu-de Lama Luis Rómulo , Nuñez-Almache Oswaldo , Chávez-Tejada Eliana Manuela , Espinoza-Robles Oscar Antonio , Pinto-Ibárcena Paola Marianella , Calagua-Quispe Martha Rosario
Published: July 2020

Schimmelpenning–Feuerstein–Mims syndrome (SFM), an epidermal nevus syndrome characterized by skin lesions, has an estimated incidence of 1 per 10 000 live births. Nevus sebaceous, the most common cutaneous lesion, and verrucous nevus, the less frequent lesion, are coupled with a wide range of extracutaneous manifestations. As part of these manifestations, rarely, central precocious puberty can arise. We report the case of a 1-year-5-month-old girl who presented to the Endocrinology and Metabolism Department with breast enlargement that began at one year of age, growth of pubic and axillary hair three months later, and vaginal bleeding that occurred five months later. During clinical examination, melanocytic nevi, with a diameter ranging from 3 to 5 mm, were noted on the face. Verrucous nevi of variable size with a tendency for coalescence following the lines of Blaschko and melanocytic nevi with a diameter ranging from 3 to 6 mm were observed on the right hemibody and on the left hemibody, respectively. Right asymmetry of the lower extremities was observed. Laboratory findings showed a significant increase in the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after the gonadotropin-releasing hormone (GnRH) stimulation test; additionally, imaging demonstrated advanced bone age and pubertal changes in the internal genitals. Analyses of the H-RAS, K-RAS, and N-RAS genes in the blood and in the skin were performed, and a missense mutation in exon 2 of the gene, H-RAS c37G > C (p.G13R), was detected in the latter. Treatment with triptorelin, a GnRH analog, was initiated, and it gave good clinical response. Epidermal nevus syndrome has a wide and variable systemic involvement. Thus, it is important to consider the development of precocious puberty for a prompt diagnosis and to strategize a multidisciplinary approach from the beginning.
Gelatin Encapsulated Curcumin Nanoparticles Moderate Behavior of Human Primary Gingival Fibroblasts In Vitro
Authors: Nguyen Mai Thi-Hoang , Ly Khanh Loan , Kieu Thoai Quoc , Nguyen Hiep Thi , Huynh Nam Cong-Nhat
Published: July 2020

Objective.Currently, there is no study evaluating the effect of nano-curcumin on human oral cells in vitro. In this study, we developed gelatin encapsulated curcumin nanoparticles (GelCur) and cultured the primary human gingival fibroblasts (hGFs) to verify the effect of GelCur on the cellular events related to oral wound healing capacities, such as cell migration and proliferation of gingival fibroblasts.Materials and Methods.GelCur was produced by the sonoprecipitation method. Particle size, zeta potential, SEM morphological observation, entrapment efficiency, and drug loading were used to characterize new GelCur. Primary hGFs were cultured from the attached gingival tissue of healthy third molar teeth. The effect of different concentrations of GelCur on hGFs was investigated by cell toxicity assay (MTT), cell proliferation assay, and cell migration assays by scratch test and transwell migration assay.Results.The average particle size of GelCur was around 356 nm with a moderate zeta potential of 26.5 mV. The mean PdI value of GelCur was 0.2, while the entrapment efficiency and drug loading of curcumin in this study were around 57% and 2.4%, respectively. IC30of GelCur on hGFs was 3.96 mg/ml, while IC50was 12,37 mg/ml. More than 70% of cells were viable after 24 hours incubated with 1, 2, and 3 mg/ml GelCur. At the concentration of 2 mg/ml GelCur virtually limited cell proliferation and migration.Conclusions.GelCur remained physically stable and did not alter cell proliferation and migration. The concentration of GelCur <3.96 mg/ml did not cause hGF cytotoxicity. Our study showed that within appropriate doses, GelCur can be used safely for hGFs.
Effect of Exercise on Quality of Life in Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Chen Kui , Tan Yan , Lu You , Wu Jiayan , Liu Xueyuan , Zhao Yanxin
Published: July 2020

Background. Exercise has an integral impact on the physical and mental wellbeing of patients with Parkinson’s disease (PD), yet no comprehensive and quantitative analysis has been conducted on the effect of exercise on quality of life (QoL) in these patients. This study aimed to evaluate the effect of exercise on overall QoL and different domains of QoL in people with PD, as well as investigating the influence of factors such as the exercise type and intervention period. Methods. Databases, such as PubMed, Embase, and Cochrane Central Register of Controlled Trials, were searched since inception to August 14, 2018 to identify randomized controlled trials that compare the effect of exercise versus no intervention on QoL in PD patients. Following the subgroup analysis, heterogeneity was further explored. The quality of eligible studies was assessed according to PRISMA guidelines. Results. 20 studies were included with 1,143 participants in total. A meta-analysis showed a significant improvement in QoL after exercise intervention in PD patients (SMD = −0.24, 95% CI = −0.36 to −0.12, P<0.001). A subgroup analysis of exercise types revealed significant QoL improvement with aerobic exercise, martial arts, and dance, but not anaerobic exercise and combined exercise. Interventions lasting 12 weeks or longer improved QoL significantly. Conclusions. Exercise interventions, especially aerobic exercise, dance, and Tai Chi, significantly improve QoL in PD patients. At least 12 weeks of exercise is needed to bring about significant benefits.
A Qualitative Study of Patients’ Beliefs and Perception on Medicinal Properties of Natural Hot Spring Bath for Musculoskeletal Problems
Authors: Vaidya Binit , Nakarmi Shweta
Published: July 2020

Natural therapy modalities such as thermal therapy and balneotherapy are commonly being practiced for the management of chronic aches and pain all over the world. Nepal has many such natural hot water springs among which few are famous for therapeutic purposes. Thousands of people with some musculoskeletal problem visit those places in the hope of getting rid of their problems. This study aimed to understand their belief in such therapies, expectations, and satisfaction after treatment along with their knowledge of the safety of hot spring water bath. Among 126 participants interviewed, 31% had inflammatory arthritis, followed by degenerative disorders in 29.4% and soft-tissue rheumatism in 12.7%. Around three-quarters believed that hot spring water has natural healing power and thus can improve their pain. Many even believed that water in natural springs is devoid of any chemicals. So, it is a safe treatment option. Regarding the expectation of cure, they had mixed opinions. Naïve participants hoped they might find a permanent cure in thermal baths. However, repeated visitors said that the effect usually lasted for a few months and they have to visit there regularly. Almost two-thirds of people thought that such natural treatment does not have any side effects. Few stated that they had faced certain problems after the treatment. The water tested from the study site showed that it contained a higher amount of chlorine and sulfate in comparison to other hot water springs in Nepal. The minerals present in water might be a cause of temporary relief of pain. Also, outbreaks of infection from common spring baths have to be considered as such cases have been reported in the past. In conclusion, the medicinal benefits of such natural hot water springs have to be studied further and awareness regarding safety should be given to the people seeking treatment.
Huoxin Pill Attenuates Cardiac Inflammation by Suppression of TLR4/NF‐κB in Acute Myocardial Ischemia Injury Rats
Authors: Chu Jianfeng , Zhou Xueling , Peng Meizhong , Lu Yan , Farman Ali , Peng Lianli , Gao Huajian , Li Qi , Chen Xintong , Xie Lingling , Chen Youqin , Shen Aling , Peng Jun
Published: July 2020

Huoxin Pill (HXP), a traditional Chinese medicine, has been prescribed widely in the treatment of coronary heart disease, angina pectoris, and other diseases. However, the possible protective mechanisms of HXP on myocardial ischemia remain unclear. In the current study, we investigated the effects and potential mechanism of HXP on myocardial ischemia and cardiac inflammation and the activation of TLR4/NF‐κB pathway. Determination of electrocardiogram, echocardiography, and heart weight index (HWI) indicated that HXP treatment obviously attenuated the elevation of ST‐segment, end‐diastolic volume, and HWI in the AMI rat model. Enzyme‐linked immunosorbent assay (ELISA) demonstrated that Huoxin Pill treatment significantly decreased the levels of CTnT, CK‐MB, MDA, IL‐6, and TNF‐α, while it increased SOD content in serum of the AMI rat model. Moreover, hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining revealed that HXP treatment alleviated pathological change, infiltration of inflammatory cells, levels of IL‐6 and TNF‐α, and expression of TLR4 and p‐NF‐κB in cardiac tissues of the AMI rat model. In conclusion, HXP treatment significantly improves cardiac function and attenuates cardiac inflammation by suppressing the activation of TLR4/NF‐κB pathway in the ISO‐induced AMI rat model. This study provides insights into the potential of HXP on prevention and treatment of AMI.
Proximal Tubular Transcription Factors in Acute Kidney Injury: Recent Advances
Authors: Piret Sian E. , Mallipattu Sandeep K.
Published: July 2020

The proximal tubule (PT) is a major target in acute kidney injury (AKI), leading to profound changes in PT cell biology. Amongst the genes with early and robust changes in expression are many transcription factors (TFs), which themselves account for other transcriptomic changes. Potentially important TFs are being revealed in large sequencing datasets; however, to understand whether these TFs account for adaptive or maladaptive changes requires further mechanistic studies, which may reveal novel therapeutic targets. This mini review will highlight the identification and biology of 3 novel TFs in AKI: Sox9, Foxm1, and Foxo3.
Soluções detalhadas para 20 problemas da Olimpíada Internacional de Matemática
Authors:   Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Linares Juan López
Published: July 2020

A Olimpíada Internacional de Matemática é uma competição para estudantes do Ensino Médio em que o número de participantes cresceu de forma sistemática ao longo do tempo. Os objetivos das olimpíadas são descobrir, estimular e desafiar estudantes talentosos em Matemática. A delegação do Brasil realizou sua primeira participação em 1979 e vem apresentando continuamente uma melhora de desempenho. Neste livro são apresentados e discutidos, de forma detalhada, vinte problemas de Álgebra propostos para alguma das versões - o intuito é poderem ser usados não somente no treinamento de estudantes que se preparam para olimpíadas nacionais e internacionais, mas também por professores e estudantes do Ensino Universitário. Os problemas aparecem organizados em quatro capítulos, e cada problema lança mão de conhecimentos ligados a mais de uma área da Matemática. Em várias seções, é apresentada uma introdução aos conhecimentos chaves para a resolução do problema.