bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual timeline: a formal abstraction for verifying preemptive schedulers with temporal isolation
Authors: Liu Mengqi , Rieg Lionel , Shao Zhong , Gu Ronghui , Costanzo David , Kim Jung-Eun , Yoon Man-Ki
Published: December 2019

The reliability and security of safety-critical real-time systems are of utmost importance because the failure of these systems could incur severe consequences (e.g., loss of lives or failure of a mission). Such properties require strong isolation between components and they rely on enforcement mechanisms provided by the underlying operating system (OS) kernel. In addition to spatial isolation which is commonly provided by OS kernels to various extents, it also requires temporal isolation, that is, properties on the schedule of one component (e.g., schedulability) are independent of behaviors of other components. The strict isolation between components relies critically on algorithmic properties of the
concrete implementation
of the scheduler, such as timely provision of time slots, obliviousness to preemption, etc. However, existing work either only reasons about an abstract model of the scheduler, or proves properties of the scheduler implementation that are not rich enough to establish the isolation between different components.

In this paper, we present a novel compositional framework for reasoning about algorithmic properties of the concrete implementation of preemptive schedulers. In particular, we use
virtual timeline
, a variant of the supply bound function used in real-time scheduling analysis, to specify and reason about the scheduling of each component in isolation. We show that the properties proved on this abstraction carry down to the generated assembly code of the OS kernel. Using this framework, we successfully verify a real-time OS kernel, which extends mCertiKOS, a single-processor non-preemptive kernel, with user-level preemption, a verified timer interrupt handler, and a verified real-time scheduler. We prove that in the absence of microarchitectural-level timing channels, this new kernel enjoys temporal and spatial isolation on top of the functional correctness guarantee. All the proofs are implemented in the Coq proof assistant.
Parameterized verification under TSO is PSPACE-complete
Authors: Abdulla Parosh Aziz , Atig Mohamed Faouzi , Rezvan Rojin
Published: December 2019

We consider parameterized verification of concurrent programs under the Total Store Order (TSO) semantics. A program consists of a set of processes that share a set of variables on which they can perform read and write operations. We show that the reachability problem for a system consisting of an arbitrary number of identical processes is PSPACE-complete. We prove that the complexity is reduced to polynomial time if the processes are not allowed to read the initial values of the variables in the memory. When the processes are allowed to perform atomic read-modify-write operations, the reachability problem has a non-primitive recursive complexity.
The high-level benefits of low-level sandboxing
Authors: Sammler Michael , Garg Deepak , Dreyer Derek , Litak Tadeusz
Published: December 2019

Sandboxing is a common technique that allows low-level, untrusted components to safely interact with trusted code. However, previous work has only investigated the low-level memory isolation guarantees of sandboxing, leaving open the question of the end-to-end guarantees that sandboxing affords programmers. In this paper, we fill this gap by showing that sandboxing enables reasoning about the known concept of
robust safety
,
i.e.
, safety of the trusted code even in the presence of arbitrary untrusted code. To do this, we first present an idealized operational semantics for a language that combines trusted code with untrusted code. Sandboxing is built into our semantics. Then, we prove that safety properties of the trusted code (as enforced through a rich type system) are upheld in the presence of arbitrary untrusted code, so long as all interactions with untrusted code occur at the “any” type (a type inhabited by all values). Finally, to alleviate the burden of having to interact with untrusted code at only the “any” type, we formalize and prove safe several
wrappers
, which automatically convert values between the “any” type and much richer types. All our results are mechanized in the Coq proof assistant.
Optimal approximate sampling from discrete probability distributions
Authors: Saad Feras A. , Freer Cameron E. , Rinard Martin C. , Mansinghka Vikash K.
Published: December 2019

This paper addresses a fundamental problem in random variate generation: given access to a random source that emits a stream of independent fair bits, what is the most accurate and entropy-efficient algorithm for sampling from a discrete probability distribution (
p
1
, …,
p

n

), where the probabilities of the output distribution (
p̂
1
, …,
p̂

n

) of the sampling algorithm must be specified using at most
k
bits of precision? We present a theoretical framework for formulating this problem and provide new techniques for finding sampling algorithms that are optimal both statistically (in the sense of sampling accuracy) and information-theoretically (in the sense of entropy consumption). We leverage these results to build a system that, for a broad family of measures of statistical accuracy, delivers a sampling algorithm whose expected entropy usage is minimal among those that induce the same distribution (i.e., is “entropy-optimal”) and whose output distribution (
p̂
1
, …,
p̂

n

) is a closest approximation to the target distribution (
p
1
, …,
p

n

) among all entropy-optimal sampling algorithms that operate within the specified
k
-bit precision. This optimal approximate sampler is also a closer approximation than any (possibly entropy-suboptimal) sampler that consumes a bounded amount of entropy with the specified precision, a class which includes floating-point implementations of inversion sampling and related methods found in many software libraries. We evaluate the accuracy, entropy consumption, precision requirements, and wall-clock runtime of our optimal approximate sampling algorithms on a broad set of distributions, demonstrating the ways that they are superior to existing approximate samplers and establishing that they often consume significantly fewer resources than are needed by exact samplers.
Binders by day, labels by night: effect instances via lexically scoped handlers
Authors: Biernacki Dariusz , Piróg Maciej , Polesiuk Piotr , Sieczkowski Filip
Published: December 2019

Handlers of algebraic effects aspire to be a practical and robust programming construct that allows one to define, use, and combine different computational effects. Interestingly, a critical problem that still bars the way to their popular adoption is how to combine different uses of
the same
effect in a program, particularly in a language with a static type-and-effect system. For example, it is rudimentary to define the “mutable memory cell” effect as a pair of operations,
put
and
get
, together with a handler, but it is far from obvious how to use this effect a number of times to operate a number of memory cells in a single context. In this paper, we propose a solution based on lexically scoped effects in which each use (an “instance”) of an effect can be singled out by name, bound by an enclosing handler and tracked in the type of the expression. Such a setting proves to be delicate with respect to the choice of semantics, as it depends on the explosive mixture of effects, polymorphism, and reduction under binders. Hence, we devise a novel approach to Kripke-style logical relations that can deal with open terms, which allows us to prove the desired properties of our calculus. We formalise our core results in Coq, and introduce an experimental surface-level programming language to show that our approach is applicable in practice.
Visualization by example
Authors: Wang Chenglong , Feng Yu , Bodik Rastislav , Cheung Alvin , Dillig Isil
Published: December 2019

While visualizations play a crucial role in gaining insights from data, generating useful visualizations from a complex dataset is far from an easy task. In particular, besides understanding the functionality provided by existing visualization libraries, generating the desired visualization also requires reshaping and aggregating the underlying data as well as composing different visual elements to achieve the intended visual narrative. This paper aims to simplify visualization tasks by automatically synthesizing the required program from simple visual sketches provided by the user. Specifically, given an input data set and a visual sketch that demonstrates how to visualize a very small subset of this data, our technique automatically generates a program that can be used to visualize the entire data set.

From a program synthesis perspective, automating visualization tasks poses several challenges that are not addressed by prior techniques. First, because many visualization tasks require data wrangling in addition to generating plots from a given table, we need to decompose the end-to-end synthesis task into two separate sub-problems. Second, because the intermediate specification that results from the decomposition is necessarily imprecise, this makes the data wrangling task particularly challenging in our context. In this paper, we address these problems by developing a new compositional visualization-by-example technique that (a) decomposes the end-to-end task into two different synthesis problems over different DSLs and (b) leverages bi-directional program analysis to deal with the complexity that arises from having an imprecise intermediate specification.

We have implemented our visualization-by-example approach in a tool called Viser and evaluate it on over 80 visualization tasks collected from on-line forums and tutorials. Viser can solve 84 of these benchmarks within a 600 second time limit, and, for those tasks that can be solved, the desired visualization is among the top-5 generated by Viser in 70% of the cases.
Kind inference for datatypes
Authors: Xie Ningning , Eisenberg Richard A. , Oliveira Bruno C. d. S.
Published: December 2019

In recent years, languages like Haskell have seen a dramatic surge of new features that significantly extends the expressive power of their type systems. With these features, the challenge of kind inference for datatype declarations has presented itself and become a worthy research problem on its own. This paper studies kind inference for datatypes. Inspired by previous research on type-inference, we offer declarative specifications for what datatype declarations should be accepted, both for Haskell98 and for a more advanced system we call PolyKinds, based on the extensions in modern Haskell, including a limited form of dependent types. We believe these formulations to be novel and without precedent, even for Haskell98. These specifications are complemented with implementable algorithmic versions. We study soundness, completeness and the existence of principal kinds in these systems, proving the properties where they hold. This work can serve as a guide both to language designers who wish to formalize their datatype declarations and also to implementors keen to have principled inference of principal types.
Backpropagation in the simply typed lambda-calculus with linear negation
Authors: Brunel Aloïs , Mazza Damiano , Pagani Michele
Published: December 2019

Backpropagation is a classic automatic differentiation algorithm computing the gradient of functions specified by a certain class of simple, first-order programs, called computational graphs. It is a fundamental tool in several fields, most notably machine learning, where it is the key for efficiently training (deep) neural networks. Recent years have witnessed the quick growth of a research field called differentiable programming, the aim of which is to express computational graphs more synthetically and modularly by resorting to actual programming languages endowed with control flow operators and higher-order combinators, such as map and fold. In this paper, we extend the backpropagation algorithm to a paradigmatic example of such a programming language: we define a compositional program transformation from the simply-typed lambda-calculus to itself augmented with a notion of linear negation, and prove that this computes the gradient of the source program with the same efficiency as first-order backpropagation. The transformation is completely effect-free and thus provides a purely logical understanding of the dynamics of backpropagation.
'Platformizing' a bad business does not make it a good business
Authors: Cusumano Michael A.
Published: December 2019

Transaction platforms link third-party applications and services providers with users.
Application of Stochastic Gradient Boosting Approach to Early Prediction of Safety Accidents at Construction Site
Authors: Shin Yoonseok
Published: December 2019

The construction industry is one of the deadliest industries in the United States and Korea. The number of accidents at a construction site has been recently increasing despite institutional supports and managerial efforts. A proactive prediction of safety accidents is the best way to prevent them, but a dynamic change in particular conditions of a construction project makes the prediction very tricky and complicated. Moreover, preventive work for any safety accident at a construction site mainly depends on the intuitive and subjective opinions of practitioners with limited experience. The stochastic gradient boosting (SGB) approach may be an attractive alternative to conventional methods for predicting safety accidents because of its superior predictive performance. Therefore, SGB is applied to an early prediction of safety accidents at a construction site in order to examine its applicability to the construction safety domain. The prediction result of the proposed model is compared to an artificial neural network model and a decision tree model. The proposed model shows a slightly better result compared to the ANN and DT models. Moreover, the result of the proposed model also demonstrates the advantages of a simple parameter set in constructing a model and a comprehensible decision‐making procedure for safety management.
Recent Trends in the Clinicopathological Features of Thyroid Nodules in Pediatric Patients: A Single Tertiary Center Experience over 25 Years
Authors: Rah Cheong-Sil , Kim Won Woong , Lee Yu-mi , Kim Won Gu , Song Dong Eun , Chung Ki-Wook , Kim Seong Chul , Hong Suck Joon , Sung Tae-Yon
Published: December 2019

Background. The trends in pediatric patients having thyroid nodules have not been well evaluated. Here, we analyzed the clinicopathological features of the children who have presented with thyroid nodules at our center over several decades in order to determine a change of trend. Materials and Methods. We analyzed 215 pediatric patients who had undergone a thyroidectomy between 1990 and 2014 at our single tertiary center. The clinicopathological features were analyzed according to age, sex, and the year of diagnosis. Results. The most common reason for hospital admission was a palpable anterior neck mass (76.7%). The males in the patient cohort were younger than the females (13 vs. 15 years old, p<0.05). The female patients increased from 50.0% to 83.0% with age (p<0.05). The rate of malignancy did not increase with age (p<0.05). However, the malignancy rate was higher in the more recently seen patients (23.8% during the early study period and 86.8% in the late study period; p<0.05). Conclusion. Following a thyroidectomy in children with thyroid nodules, there was no change in the rate of detection of thyroid cancer over time with age, although the detected frequency of malignancy has increased in more recent patients. Therefore, early thyroid nodule detection for malignant screening is likely to be required for pediatric patients in the near future.
Innate Lymphoid Cells: Regulators of Gut Barrier Function and Immune Homeostasis
Authors: Fan Hui , Wang Aiyun , Wang Yuan , Sun Ye , Han Jing , Chen Wenxing , Wang Shijun , Wu Yuanyuan , Lu Yin
Published: December 2019

Innate lymphoid cells (ILCs), identified in the early years of this century as a new class of leukocyte family unlike the B or T lymphocytes, play a unique role bridging the innate and adaptive immune responses in mucosal immunity. Their origin, differentiation, and activation process and functions have caught global interest. Recently, accumulating evidence supports that ILCs are vital regulators for gastrointestinal mucosal homeostasis through interactions with other structural and stromal cells in gut epithelial barriers. This review will explore the functions of ILCs and other cells in maintaining gut homeostasis and feature the crosstalk between ILCs with other cells and potential pharmacotherapy targeting ILCs applicable in intestinal innate immunity.
Image Encryption Algorithm Based on Adaptive Wavelet Chaos
Authors: An Feng-Ping , Liu Jun-e
Published: December 2019

Images, as one of the important carriers for information exchange, play an important role in work and daily life. Image encryption technology has received a lot of attention, and varieties of encryption technologies for images have emerged. Early image encryption technologies have shortcomings such as simple algorithm structure, small key space, and poor resistance to plaintext attacks. These algorithms have been unable to meet the needs of information security at this stage. Based on the wavelet algorithm, chaos algorithm, and cyclic encryption algorithm, combined with frequency domain encryption and spatial domain encryption, a digital image encryption algorithm based on adaptive wavelet is proposed in this paper. In terms of frequency, this paper enhances the adaptive ability of the wavelet algorithm by convex optimization-particle swarm optimization (PSO). At the same time, the chaotic algorithm is used to scramble the low-frequency coefficients. In the aspect of airspace, this paper uses the block-encryption adaptive encryption algorithm to rescramble the wavelet-reconstructed image. And the SHA-1 algorithm is introduced into the plaintext image generation key sequence as a cyclic index value for cyclic encryption. The key composition of the encryption algorithm proposed in this paper is complex, and the idea of a one-time pad is used, which makes the improved algorithm increase the key space and improve the ability to resist the choice of plaintext attack. In each cyclic encryption of the airspace, mutual encryption is performed by image subblocks, and the algorithm adaptability is improved. Through the experimental test of statistical characteristics, key space, and key sensitivity, the encryption performance of the algorithm is verified, and it has strong antiattack and interference ability. It is a relatively secure encryption algorithm.
Biofilm Formation and Detection of Fluoroquinolone- and Carbapenem-Resistant Genes in Multidrug-ResistantAcinetobacter baumannii
Authors: Avila-Novoa María-Guadalupe , Solís-Velázquez Oscar-Alberto , Rangel-López Daniel-Eduardo , González-Gómez Jean-Pierre , Guerrero-Medina Pedro-Javier , Gutiérrez-Lomelí Melesio
Published: December 2019

Acinetobacter baumanniiis an important opportunistic pathogen that shows resistance to cephalosporins, penicillins, carbapenems, fluoroquinolones, and aminoglycosides, the multiresistance being associated with its ability to form biofilms in clinical environments. The aim of this study was to determine biofilm formation and its potential association with genes involved in antibiotic resistance mechanisms ofA. baumanniiisolates of different clinical specimens. We demonstrated 100% of theA. baumanniiisolates examined to be multidrug resistant (MDR), presenting a 73.3% susceptibility to cefepime and a 53.3% susceptibility to ciprofloxacin. AllA. baumanniiisolates were positive forblaOXA-51, 33.3% being positive forblaOXA-23and ISAba1, and 73.3% being positive forgyrA. We found 86.6% ofA. baumanniistrains to be low-grade biofilm formers and 13.3% to be biofilm negative; culturing on Congo red agar (CRA) plates revealed that 73.3% of theA. baumanniiisolates to be biofilm producers, while 26.6% were not. These properties, combined with the role ofA. baumanniias a nosocomial pathogen, increase the probability ofA. baumanniicausing nosocomial infections and outbreaks as a complication during therapeutic treatments and emphasize the need to controlA. baumanniibiofilms in hospital environments.
Study on the Stability of Unpackaged CdS/CdTe Solar Cells with Different Structures
Authors: Zeng Guanggen , Liu Xiaolan , Zhao Yubo , Shi Yuanmao , Li Bing , Zhang Jingquan , Feng Lianghuan , Wang Qionghua
Published: December 2019

In this work, the stability of unpackaged CdTe solar cells with different configurations was investigated according to the International Electrotechnical Commission IEC 61215-2016. The measurements of thermal cycling from -40°C to +85°C and 24-hour temperature cycling from -40°C to +85°C withstanding the effects of 20-hour penetration of 85°C were carried out in CdS/CdTe solar cells with structures of FTO/CdS/CdTe/Au, FTO/CdS/CdTe/back contact/Au, and FTO/MZO/CdS/CdTe/back contact/Au, respectively. The performances of these cells before and after the thermal aging experiments were investigated by using light and dark I‐V together with C‐V. The results reveal varied performance degradation before and after thermal aging in the cells with different structures. Among these, the most deteriorated device is the one without back contact (BC), whose efficiency decreased by 25.12% after thermal cycling accompanying an obvious roll-over phenomenon when forward bias was greater than open circuit voltage. On the contrary, the reduction in the efficiency was about 16.80% in the case cells with BC, and the roll-over phenomenon was not so significant. Furthermore, for the devices with optimized front contact of FTO/MZO, the thermal stability was improved obviously. Interestingly, short-circuit current density associated with the carrier concentration of cells remained relatively small variations compared with the change of Voc and fill factor. All the results indicated that an efficient back contact layer and an optimized front electrode were the indispensable structural elements to attain high stabilization in the CdS/CdTe solar cells.
Diet Alters Serum Metabolomic Profiling in the Mouse Model of Chronic Chagas Cardiomyopathy
Authors: Lizardo Kezia , Ayyappan Janeesh Plakkal , Ganapathi Usha , Dutra Walderez O. , Qiu Yunping , Weiss Louis M. , Nagajyothi Jyothi F.
Published: December 2019

Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary. Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi-infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease.
Outcome of a Low-Cost Glaucoma Implant versus the Baerveldt Glaucoma Implant for Paediatric Glaucoma in a Tertiary Hospital in Egypt
Authors: Rateb Mahmoud F. , Abdel Motaal Hazem , Shehata Mohamed , Anwar Mohamed , Tohamy Dalia , Saleh Mohamed G. A.
Published: December 2019

Purpose. To compare safety and efficacy between a low-cost glaucoma drainage device (GDD), the Aurolab aqueous drainage implant (AADI), and the Baerveldt glaucoma implant (BGI) in refractory childhood glaucoma in Egypt. Methods. This is a retrospective study of patients who received either an AADI or BGI at a tertiary care postgraduate teaching institute. Children aged <16 years with uncontrolled intraocular pressure (IOP) with or without prior failed trabeculectomy who completed a minimum 6-month follow-up were included. The outcome measures were IOP reduction from preoperative values and postoperative complications. Results. Charts of 57 children (younger than 16 years old) diagnosed with refractory childhood glaucoma were included. Of these, 27 eyes received AADI implants (group A), while 30 received BGI implants (group B). The mean preoperative baseline IOP was 34 ± 5 mmHg in group A versus 29 ± 2 mmHg in group B (

p
=
0.78

) in patients on maximum allowed glaucoma medications. In group A versus group B, the mean IOP decreased to 13.25 ± 8.74 mmHg (

p
=
0.6

), 12.8 ± 5.4 mmHg (

p
=
0.7

), and 12.6 ± 5.6 mmHg (

p
=
0.9

) after 1 week, 3 months, and 6 months, respectively. However, in group A, an anterior chamber reaction appeared around the tube in 14 cases starting from the first month and resolved with treatment in only 4 cases. In the other 10 cases, the reaction became more severe and required surgical intervention. This complication was not observed in any eye in group B. Conclusion. AADI, a low-cost glaucoma implant, is effective in lowering IOP in patients with recalcitrant paediatric glaucoma. However, an intense inflammatory reaction with serious consequences developed in some of our patients; we believe these events are related to the valve material. We therefore strongly recommend against its use in children.
Dose-Dependent Behavioral and Antioxidant Effects of Quercetin and Methanolic and Acetonic Extracts fromHeterotheca inuloideson Several Rat Tissues following Kainic Acid-InducedStatus Epilepticus
Authors: Carmona-Aparicio Liliana , Cárdenas-Rodríguez Noemí , Delgado-Lamas Guillermo , Pedraza-Chaverri José , Montesinos-Correa Hortencia , Rivera-Espinosa Liliana , Torres-Espíndola Luz María , Hernández Maria Eugenia , López-Aceves Teresita , Pérez-Lozano Diana Leticia , Hernández-Velasco Natalia , Narváez-Delgado Omar , Gutiérrez-Alejandre Ana Paulina , Fuentes-Mejía Monserrat , Bello-Robles Edith , Martínez-Ponce Karina , Sánchez-Valle Vicente , Sampieri Aristides , Granados-Rojas Leticia , Coballase-Urrutia Elvia
Published: December 2019

Kainic acid (KA) has been used to study the neurotoxicity induced afterstatus epilepticus(SE) due to activation of excitatory amino acids with neuronal damage. Medicinal plants can protect against damage caused by KA-induced SE; in particular, organic extracts ofHeterotheca inuloidesand its metabolite quercetin display antioxidant activity and act as hepatoprotective agents. However, it is unknown whether these properties can protect against the hyperexcitability underlying the damage caused by KA-induced SE. Our aim was to study the protective effects (with regard to behavior and antioxidant activity) of administration of natural products methanolic (ME) and acetonic (AE) extracts and quercetin (Q) fromH. inuloidesat doses of 30 mg/kg (ME30, AE30, and Q30 groups), 100 mg/kg (ME100, AE100, and Q100 groups), and 300 mg/kg (ME300, AE300, and Q300 groups) against damage in brain regions of male Wistar rats treated with KA. We found dose-dependent effects on behavioral and biochemical studies in the all-natural product groupsvs.the control group, with decreases in seizure severity (Racine’s scale) and increases in seizure latency (p<0.05in the ME100, AE100, Q100, and Q300 groups andp<0.01in the AE300 and ME300 groups); on lipid peroxidation and carbonylated proteins in all brain tissues (p<0.0001); and on GPx, GR, CAT, and SOD activities with all the treatments vs. KA (p≤0.001). In addition, there were strong negative correlations between carbonyl levels and latency in the group treated with KA and in the group treated with methanolic extract in the presence of KA (r=‐0.9919,p=0.0084). This evidence suggests that organic extracts and quercetin fromH. inuloidesexert anticonvulsant effects via direct scavenging of reactive oxygen species (ROS) and modulation of antioxidant enzyme activity.
Comparison of Diagnostic Yield and Safety between Semirigid Pleuroscopic Cryobiopsy and Forceps Biopsy for Undiagnosed Pleural Effusion
Authors: Lee Chung-Shu , Li Shih-Hong , Chang Chih-Hao , Chung Fu-Tsai , Chiu Li-Chung , Chou Chun-Liang , Wang Chih-Wei , Lin Shu-Min
Published: December 2019

For undiagnosed pleural effusion, diagnostic yields and safety were similar between pleuroscopic cryobiopsy and forceps biopsy, but cryobiopsy obtained a larger pleural tissue sample than forceps biopsy.
Multicriteria Decision Making Based on Archimedean Bonferroni Mean Operators of Hesitant Fermatean 2‐Tuple Linguistic Terms
Authors: Wang Huijuan , Wang Xin , Wang Lidong
Published: December 2019

The study is concerned with the representation and aggregation of complex uncertainty information. First, the concept of hesitant Fermatean 2‐tuple linguistic sets (HF2TLSs) is introduced for characterizing an individual’s imprecision preferences and assessing information by combining 2‐tuple linguistic terms and Fermatean fuzzy sets. The advantage of hesitant Fermatean 2‐tuple linguistic information is that it can handle higher levels of uncertainty and express the decision‐makers’ hesitancy. Second, we extend Bonferroni mean (BM) operators under the background of HF2TLSs for the sake of their application in information fusion and decision making. The Archimedean t‐norm and s‐norm‐ (ATS‐) based hesitant Fermatean 2‐tuple linguistic weighted Bonferroni mean (A‐HF2TLWBM) operator and the ATS‐based hesitant Fermatean 2‐tuple linguistic weighted geometric Bonferroni mean (A‐HF2TLWGBM) operator are developed by considering the interrelationship between any two variables. The main benefit of the proposed operators is that these operators deliver more complete and flexible results compared to existing methods. Moreover, some fundamental properties and special cases are examined by adjusting parameter values. Finally, an approach is designed as a support for handling decision making problems, and an example regarding investment selection is provided to demonstrate the practicality of the designed method with a detailed discussion of parameter influence and comparisons with the existing methods.
Role of Inflammation in Classification of Diabetic Macular Edema by Optical Coherence Tomography
Authors: Chung Yoo-Ri , Kim Young Ho , Ha Seong Jung , Byeon Hye-Eun , Cho Chung-Hyun , Kim Jeong Hun , Lee Kihwang
Published: December 2019

Diabetic macular edema (DME) is the abnormal accumulation of fluid in the subretinal or intraretinal spaces in the macula in patients with diabetic retinopathy and leads to severely impaired central vision. Technical developments in retinal imaging systems have led to many advances in the study of DME. In particular, optical coherence tomography (OCT) can provide longitudinal and microstructural analysis of the macula. A comprehensive review was provided regarding the role of inflammation using OCT-based classification of DME and current and ongoing therapeutic approaches. In this review, we first describe the pathogenesis of DME, then discuss the classification of DME based on OCT findings and the association of different types of DME with inflammation, and finally describe current and ongoing therapeutic approaches using OCT-based classification of DME. Inflammation has an important role in the pathogenesis of DME, but its role appears to differ among the DME phenotypes, as determined by OCT. It is important to determine how the different DME subtypes respond to intravitreal injections of steroids, antivascular endothelial growth factor agents, and other drugs to improve prognosis and responsiveness to treatment.
Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging
Authors: Bales Brian C. , Grimmond Brian , Johnson Bruce F. , Luttrell M. Todd , Meyer Dan E. , Polyanskaya Tatyana , Rishel Michael J. , Roberts Jeannette
Published: December 2019

Contrast-enhanced magnetic resonance imaging is an essential tool for disease diagnosis and management; all marketed clinical magnetic resonance imaging (MRI) contrast agents (CAs) are gadolinium (Gd) chelates and most are extracellular fluid (ECF) agents. After intravenous injection, these agents rapidly distribute to the extracellular space and are also characterized by low serum protein binding and predominant renal clearance. Gd is an abiotic element with no biological recycling processes; low levels of Gd have been detected in the central nervous system and bone long after administration. These observations have prompted interest in the development of new MRI contrast agents based on biotic elements such as iron (Fe); Fe-HBED (HBED = N,N′-bis(2-hydroxyphenyl)ethylenediamine-N,N′-diacetic acid), a coordinatively saturated iron chelate, is an attractive MRI CA platform suitable for modification to adjust relaxivity and biodistribution. Compared to the parent Fe-HBED, the Fe-HBED analogs reported here have lower serum protein binding and higher relaxivity as well as lower relative liver enhancement in mice, comparable to that of a representative gadolinium-based contrast agent (GBCA). Fe-HBED analogs are therefore a promising class of non-Gd ECF MRI CA.
Use of Pluronic P103 Triblock Copolymer as Structural Agent during Synthesis of Hybrid Silver Nanoparticles
Authors: Tepale Nancy , Fernández-Escamilla Víctor V. A. , Flores-Aquino Eric , Sánchez-Cantú Manuel , Luna-Flores Adan , González-Coronel Valeria J.
Published: December 2019

Dilute aqueous solutions of triblock copolymer Pluronic P103 were used to synthesize silver nanoparticles (Ag-NPs) by chemical reduction of silver nitrate (AgNO3) with sodium borohydride (NaBH4). This copolymer was used as a structural agent since monomers act as a stabilizer and micelles act as nanoreactors for nucleation and growth of Ag-NPs. The growth of the nanoparticles (NPs) was monitored by UV-visible spectroscopy on the basis of measuring surface plasmon resonance absorption over a temperature range of 25 to 70°C. Shape and size of hybrid silver/P103 nanomaterials were tuned by varying the micellar structure of Pluronic P103 using a simple synthesis procedure. Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) were used to study the size and shape of the hybrid nanomaterials. It was observed that Ag-NPs synthesized without Pluronic P103 at 25°C exhibited a great variety of sizes. However, when Pluronic P103 was used below its critical micellar concentration (CMC), spherical-shaped Ag-NPs with uniform size were formed, suggesting that the copolymer had a stabilizing effect. On the other hand, when Ag-NPs were prepared with Pluronic P103 above the CMC, NPs with similar sizes as the micelles were detected, suggesting that the copolymer functioned as a nanoreactor. Furthermore, as temperature reached 35°C, oval-shaped micelles were formed and small NPs were incorporated into the crown of the micelles. Independent Ag-NPs were not observed since they used the surface of the micelles as a soft template. Therefore, it was possible to obtain tiny Ag-NPs with homogeneous size.
Existence of Solutions for Anti-Periodic Fractional Differential Inclusions with ψ-Caupto Fractional Derivative
Authors: Yang Dandan , Bai Chuanzhi
Published: December 2019

In this paper, we investigate the existence of solutions for a class of fractional boundary value problems with anti-periodic boundary value conditions with ψ-Caupto fractional derivative. By means of some standard fixed point theorems, sufficient conditions for the existence of solutions for the fractional differential inclusions with ψ-Caputo derivatives are presented. Our result generalizes the known special case if ψx=x and single known results to the multi-valued ones.
Downregulation of miR-223 Expression Is an Early Event during Mammary Transformation and Confers Resistance to CDK4/6 Inhibitors in Luminal Breast Cancer
Authors: Citron Francesca , Segatto Ilenia , Vinciguerra Gian Luca Rampioni , Musco Lorena , Russo Francesca , Mungo Giorgia , D'Andrea Sara , Mattevi Maria Chiara , Perin Tiziana , Schiappacassi Monica , Massarut Samuele , Marchini Cristina , Amici Augusto , Vecchione Andrea , Baldassarre Gustavo , Belletti Barbara
Published: December 2019

miR-223 is an anti-inflammatory miRNA that in cancer acts either as an oncosuppressor or oncopromoter, in a context-dependent manner. In breast cancer, we demonstrated that it dampens the activation of the EGF pathway. However, little is known on the role of miR-223 during breast cancer onset and progression. miR-223 expression was decreased in breast cancer of luminal and HER2 subtypes and inversely correlated with patients' prognosis. In normal luminal mammary epithelial cells, miR-223 acted cell autonomously in the control of their growth and morphology in three-dimensional context. In the MMTV-Δ16HER2 transgenic mouse model, oncogene transformation resulted in a timely abrogation of miR-223 expression, likely due to activation of E2F1, a known repressor of miR-223 transcription. Accordingly, treatment with CDK4/6 inhibitors, which eventually results in restraining E2F1 activity, restored miR-223 expression and miR-223 ablation induced luminal breast cancer resistance to CDK4/6 inhibition, both in vitro and in vivo. Notably, miR-223 expression was lost in microdissected ductal carcinoma in situ (DCIS) from patients with luminal and HER2-positive breast cancer. Altogether, these results identify downmodulation of miR-223 as an early step in luminal breast cancer onset and suggest that it could be used to identify aggressive DCIS and predict the response to targeted therapy.

Significance:

miR-223 may represent a predictive biomarker of response to CDK4/6 inhibitors and its loss could identify DCIS lesions that are likely to progress into invasive breast cancer.
Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling
Authors: Cui Renzhe , Tian Lianji , Lu Di , Li Huiying , Cui Jun
Published: December 2019

Aims: Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2O2) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress. Methods: Human RPE ARPE-19 cells were treated with H2O2 to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively. Results: H2O2 significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H2O2-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H2O2-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H2O2. Conclusions: EX4 attenuated oxidative damage induced by H2O2 in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD.
Model-based whole-brain effective connectivity to study distributed cognition in health and disease
Authors: Gilson Matthieu , Zamora-López Gorka , Pallarés Vicente , Adhikari Mohit H. , Senden Mario , Campo Adrià Tauste , Mantini Dante , Corbetta Maurizio , Deco Gustavo , Insabato Andrea
Published: December 2019

Neuroimaging techniques are now widely used to study human cognition. The functional associations between brain areas have become a standard proxy to describe how cognitive processes are distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. This goes in line with the many efforts devoted to the assessment of directional interactions between brain areas from the observed neuroimaging activity. This opinion article provides an overview of our model-based whole-brain effective connectivity to analyze fMRI data, while discussing the pros and cons of our approach with respect to other established approaches. Our framework relies on the multivariate Ornstein-Uhlenbeck (MOU) process and is thus referred to as MOU-EC. Once tuned, the model provides a directed connectivity estimate that reflects the dynamical state of BOLD activity, which can be used to explore cognition. We illustrate this approach using two applications on task-evoked fMRI data. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools present some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. Our framework provides a comprehensive set of tools that open exciting perspectives to study distributed cognition, as well as neuropathologies.
Enhanced ENSO Prediction via Augmentation of Multimodel Ensembles with Initial Thermocline Perturbations
Authors: O’Kane Terence J. , Squire Dougal T. , Sandery Paul A. , Kitsios Vassili , Matear Richard J. , Moore Thomas S. , Risbey James S. , Watterson Ian G.
Published: December 2019

Recent studies have shown that regardless of model configuration, skill in predicting El Niño–Southern Oscillation (ENSO), in terms of target month and forecast lead time, remains largely dependent on the temporal characteristics of the boreal spring predictability barrier. Continuing the 2019 study by O’Kane et al., we compare multiyear ensemble ENSO forecasts from the Climate Analysis Forecast Ensemble (CAFE) to ensemble forecasts from state-of-the-art dynamical coupled models in the North American Multimodel Ensemble (NMME) project. The CAFE initial perturbations are targeted such that they are specific to tropical Pacific thermocline variability. With respect to individual NMME forecasts and multimodel ensemble averages, the CAFE forecasts reveal improvements in skill when predicting ENSO at lead times greater than 6 months, in particular when predictability is most strongly limited by the boreal spring barrier. Initial forecast perturbations generated exclusively as disturbances in the equatorial Pacific thermocline are shown to improve the forecast skill at longer lead times in terms of anomaly correlation and the random walk sign test. Our results indicate that augmenting current initialization methods with initial perturbations targeting instabilities specific to the tropical Pacific thermocline may improve long-range ENSO prediction.
Multiyear Hybrid Prediction of Atlantic Tropical Cyclone Activity and the Predictability Sources
Authors: Chang Chuan-Chieh , Wang Zhuo
Published: December 2019

A hybrid statistical–dynamical model is developed to predict multiyear variability of Atlantic tropical cyclone (TC) activity. A Poisson model takes sea surface temperature (SST) averaged over the Atlantic main development region (MDR) and the Atlantic subpolar gyre region (SPG) from the initialized CESM prediction as predictors, and skillfully predicts the basinwide TC frequency, accumulated cyclone energy (ACE), landfalling TC frequency, and hurricane and major hurricane days. Further analysis shows that the SPG SST is a more important source of predictability than the MDR SST for multiyear Atlantic TC activity. The comparison between the uninitialized and initialized CESM predictions suggests that the SPG SST is better predicted by the initialized CESM owing to the better prediction of Atlantic meridional overturning circulation, which contributes to the overall more skillful TC predictions. On the other hand, the skillful prediction of the basinwide TC frequency by the uninitialized CESM suggests the role of external forcing in the variability of Atlantic TC activity. The dependence of the hybrid prediction skills on the dynamic model ensemble size is also explored, and an ensemble size of ~20 is suggested as optimal. Further analysis shows that the SPG SST is associated with the variability of vertical wind shear and precipitable water over the tropical Atlantic even when the influence of the MDR SST is controlled. The spatial patterns of vertical wind shear and precipitable water suggest a strong modulation of ACE and hurricane frequency but a relatively weak influence on the basinwide TC frequency. The physical mechanisms between the SPG SST and Atlantic TC activity are discussed.