bluuebunny/crossref_metadata_2025 huggingface dataset:
Promising in vitro antioxidant, anti‐acetylcholinesterase and neuroactive effects of essential oil from two non‐psychotropic Cannabis sativa L. biotypes
Authors: Smeriglio Antonella , Trombetta Domenico , Alloisio Susanna , Cornara Laura , Denaro Marcella , Garbati Patrizia , Grassi Gianpaolo , Circosta Clara
Published: April 2020

The aim of this study was to compare the micro‐morphological features of two different non‐drug Cannabis sativa L. biotypes (Chinese accession G‐309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro‐morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC–FID and GC–MS analyses. Antioxidant and anti‐acetylcholinesterase properties were investigated by several in vitro cell‐free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell‐derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti‐acetylcholinesterase activities (IC50 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively). Furthermore, they showed a concentration‐dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC50 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.
Fruits ofTerminalia chebulaRetz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities
Authors: Nigam Manisha , Mishra Abhay P. , Adhikari‐Devkota Anjana , Dirar Amina Ibrahim , Hassan Md. Mahadi , Adhikari Achyut , Belwal Tarun , Devkota Hari Prasad
Published: April 2020

Fruits ofTerminalia chebulaRetz. (Combretaceae) are widely used as crude drugs in various traditional medicine systems. The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities ofT. chebula. Numerous researches conducted onT. chebulahave confirmed the presence of wide range of the phytochemicals such as flavonoids, tannins, phenolic acids and other bioactive compounds.T. chebulais also widely studied regarding its pharmacological activities such as antioxidant, hepatoprotective, neuroprotective, cytotoxic, antidiabetic, anti‐inflammatory activities among others. However, more in vivo and clinical studies for mechanism‐based pharmacological evaluation should be conducted in future to provide stronger scientific evidences for their traditional uses.
The π‐hole tetrel bond betweenX2TOandCO2: Substituent effects and its potential adsorptivity forCO2
Authors: Hou Mingchang , Liu Zhenbo , Li Qingzhong
Published: April 2020

Quantum chemical calculations are applied to study the complexes between X2TO (X = H, F, Cl, Br, CH3; T = C, Si, Ge, Sn) and CO2. The carbon atom of CO2as a Lewis acid participates in the C···O carbon bond, whereas its oxygen atom as a base engages in the O···T tetrel bond with X2TO. Most of complexes are stabilized by a combination of both C···O and O···T interactions. The interaction energy increases in the T = C < Ge < Sn < Si sequence for most complexes. Both the electron‐withdrawing halogen group and the electron‐donating methyl group increase the interaction energy, up to 51 kJ/mol in F2SiO···CO2. One F2SiO molecule can bind with different numbers of CO2molecules (1–4); as the number of CO2molecules increases, the average interaction energy for each CO2decreases and each CO2molecule can contribute with at least 27 kJ/mol. Therefore, silicon‐containing molecules are good absorbents for CO2.
Optimal conditions for tandem mass spectrometric sequencing of information‐containing nitrogen‐substituted polyurethanes
Authors: Charles Laurence , Mondal Tathagata , Greff Vincent , Razzini Mattia , Monnier Valérie , Burel Alexandre , Carapito Christine , Lutz Jean‐François
Published: April 2020

Rationale

To prevent solubility issues faced with sequence‐defined polyurethanes, a new family of digital polyurethanes was conceived with the alkyl coding chain held by the carbamate nitrogen (N) atom and CH3 instead of OH as the ϖ termination. This led to different dissociation mechanisms that were explored prior to optimizing tandem mass spectrometric (MS/MS) sequencing.

Methods

N‐Substituted polyurethanes (N–R PUs) were dissolved in methanol and subjected to collision‐induced dissociation (CID) as deprotonated chains in the negative ion mode, and as ammonium and sodium adducts in the positive ion mode, using electrospray ionization (ESI) as the ionization technique. Their dissociation behavior was thoroughly investigated using a quadrupole time‐of‐flight (QTOF) instrument in order to provide accurate mass measurements to support proposed fragmentation mechanisms.

Results

While O–(CO) bonds were broken in N–H PUs, the CH2–O linkage between repeating units was cleaved upon CID of N–R PUs. This main process occurred either from deprotonated molecules or from cationized chains but was followed by different rearrangements, producing up to four product ion series. Yet, MS/MS spectra could be drastically simplified for precursor ions having their acidic α group methylated, as was found to spontaneously occur upon storage in methanol.

Conclusions

Using experimental conditions aimed at avoiding any reactive proton in precursor ions (no acidic end‐groups and alkali adduction), full coverage sequence of N–R PUs was successfully achieved with the single ion series observed in MS/MS, opening a promising perspective for reading large amounts of information stored in these dyad‐encoded polymers.
Laboratory testing of SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 (2019‐nCoV): Current status, challenges, and countermeasures
Authors: Yan Ying , Chang Le , Wang Lunan
Published: April 2020

Emerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS‐CoV‐2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS‐CoV‐2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS‐CoV‐2 are basically similar to SARS‐CoV and MERS‐CoV, the other two beta‐CoVs of medical importance. During the SARS‐CoV and MERS‐CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS‐CoV‐2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, several suggestions are put forward to improve the laboratory testing of SARS‐CoV‐2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high‐quality results; simultaneously amplifying human RNase P gene to avoid false‐negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.
Falco: Fast likelihood‐based collision avoidance with extension to human‐guided navigation
Authors: Zhang Ji , Hu Chen , Chadha Rushat Gupta , Singh Sanjiv
Published: April 2020

We propose a planning method to enable fast autonomous flight in cluttered environments. Typically, autonomous navigation through a complex environment requires a continuous search on a graph generated by a k‐connected grid or a probabilistic scheme. As the vehicle travels, updating the graph with data from onboard sensors is expensive as is the search on the graph especially if the paths must be kinodynamically feasible. We propose to avoid the online search to reduce the computational complexity. Our method models the environment differently in two separate regions. Obstacles are considered to be deterministically known within the sensor range and probabilistically known beyond the sensor range. Instead of searching for the path with the lowest cost (typically the shortest path), the method maximizes the likelihood to reach the goal in determining the immediate next step for navigation. With such a problem formulation, the online method realized by a trajectory library can determine a path within 0.2–0.3 ms using a single central processing unit thread on a modem embedded computer. The method supports two configurations working with and without a prior map. Both configurations can be used to plan toward a goal point. Further, the later can allow human guidance for the navigation through a directional input. In experiments, it enables a lightweight unmanned aerial vehicle to fly at 10 m/s in a cluttered forest environment (see Figure 1 as an example).
Study of zinc pollution in river water: Average mass balance based on irrigation schedule
Authors: Andarani Pertiwi , Yokota Kuriko , Saga Makoto , Inoue Takanobu , Matsumoto Yoshitaka
Published: April 2020

Aichi Prefecture, which has a dense industrial area, is one of the sites in Japan where the levels of zinc are elevated. However, currently, there is no clear evidence of the source of zinc in this prefecture. This study aims to assess zinc concentration and load in a river and identify the main sources of zinc pollution. We conducted a 20‐month survey to identify the temporal and spatial variation of zinc in river water, particularly in the Aizumame River. Using Flame Atomic Absorption Spectrometry, the total fraction of zinc concentrations was determined for nine sampling stations (five points in the mainstream and four points in the tributaries). The results show that the average of zinc concentration was lower during the irrigation period than in the non‐irrigation period. However, the load during the irrigation period was higher. During irrigation, the river discharges were higher resulting in a lower concentration. The highest zinc concentration was 0.139 mg/L in June 2017. Based on this study, the main zinc source was identified from industrial areas which on average contributed about 3,400 g/day into the mainstream. These results became more evident during the non‐irrigation period when only industrial discharges contributed zinc load into the mainstream.
Knot selection in sparse Gaussian processes with a variational objective function
Authors: Garton Nathaniel , Niemi Jarad , Carriquiry Alicia
Published: April 2020

Sparse, knot‐based Gaussian processes have enjoyed considerable success as scalable approximations of full Gaussian processes. Certain sparse models can be derived through specific variational approximations to the true posterior, and knots can be selected to minimize the Kullback‐Leibler divergence between the approximate and true posterior. While this has been a successful approach, simultaneous optimization of knots can be slow due to the number of parameters being optimized. Furthermore, there have been few proposed methods for selecting the number of knots, and no experimental results exist in the literature. We propose using a one‐at‐a‐time knot selection algorithm based on Bayesian optimization to select the number and locations of knots. We showcase the competitive performance of this method relative to optimization of knots simultaneously on three benchmark datasets, but at a fraction of the computational
cost.
Morphology Control of Doped Spiro‐MeOTAD Films for Air Stable Perovskite Solar Cells
Authors: Wang Sisi , Wei Qi , Wang Kaiyang , Zhang Zhipeng , Zhao Dandan , Liang Chao , Liu Tanghao , Guo Jia , Su Chenliang , Li Ying , Xing Guichuan
Published: April 2020

Doped 2,2′,7,7′‐tetrakis(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene (spiro‐MeOTAD), which acts as a hole‐transporting layer (HTL), endows perovskite solar cells (PSCs) with excellent performance. However, the intrinsically hygroscopic nature of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) dopants also aggravates the moisture instability of PSCs. In this work, the origins of the moisture instability of spiro‐MeOTAD HTLs are explored and strategies to enhance moisture resistance are proposed. After 780 h of aging in air, 52% of the initial power conversion efficiency (PCE) can be sustained by prolonging the mixing time of the precursor solution of spiro‐MeOTAD to reduce accumulated LiTFSI. In contrast, only 7% of the initial PCE remains if the precursor solution is mixed briefly. By thermally annealing an HTL to evaporate residual tBP in spiro‐MeOTAD, pinholes are completely eliminated and 65% of the initial PCE remains after the same aging time. In this study, the significance of the initial morphology of spiro‐MeOTAD HTLs on device stability is analyzed and strategies based on physical morphology for controlling PSC moisture instability induced by HTL dopants are developed.
A Single Molecule Drug Targeting Photosensitizer for Enhanced Breast Cancer Photothermal Therapy
Authors: Zou Yang , Li Mingle , Xiong Tao , Zhao Xueze , Du Jianjun , Fan Jiangli , Peng Xiaojun
Published: April 2020

Targeting is one of the most important strategies for enhancing the efficacy of cancer photothermal therapy (PTT) and reducing damage to surrounding normal tissues. Compared with the traditional targeting approaches, the active targeting of breast cancer cells in PTT using chemotherapeutic drugs, such as tamoxifen (TAM), in combination with single‐molecule photothermal photosensitizers has superior selectivity and therapeutic effects. However, single‐molecule drug‐targeting photosensitizers for improved PTT efficacy are not widely reported. Accordingly, herein, a near‐infrared induced small‐molecule photothermal photosensitizer (CyT) is developed that actively targets the estrogen receptors (ERs) of breast cancer cells as well as targets mitochondria by structure‐inherent targeting. Cell uptake and cytotoxicity studies using different types of cells show that CyT enhances the efficiency of TAM‐based PTT by targeting ER‐overexpressing breast cancer cells and selectively killing them. In vivo experiments demonstrate that CyT can be used as a photothermal agent for fluorescence imaging‐guided PTT. More importantly, the intravenous injection of CyT results in better targeting and efficiency of tumor inhibition compared with that achieved with the TAM‐free control molecule Cy. Thus, the study presents an excellent small‐molecule photothermal agent for breast cancer therapy with potential clinical application prospects.
Target‐Triggered Assembly of Nanogap Antennas to Enhance the Fluorescence of Single Molecules and Their Application in MicroRNA Detection
Authors: Peng Manshu , Sun Feifei , Na Na , Ouyang Jin
Published: April 2020

Nanogap antennas are plasmonic nanostructures with a strong electromagnetic field generated at the gap region of two neighboring particles owing to the coupling of the collective surface plasmon resonance. They have great potential for improving the optical properties of fluorophores. Herein, nanogap antennas are constructed using an aqueous solution‐based method to overcome the defects of weak fluorescence and photobleaching associated with traditional organic dyes, and a highly sensitive nanogap antenna‐based sensing strategy is presented for the detection of low‐abundance nucleic acid biomarkers via a target‐triggered strand displacement amplification (SDA) reaction between two DNA hairpins that are tagged to the tips of gold nanorods (Au NRs). In the presence of targets, end‐to‐end Au NR dimers gradually form, and the fluorophores quenched by the Au NRs exhibit a dramatic fluorescence enhancement due to the plasmon‐enhanced fluorescence effect of nanogap antennas. Meanwhile, the SDA reaction results in secondary amplification of fluorescence signals. Combined with single‐molecule counting, this method applied in miRNA‐21 detection can achieve a low detection limit of 97.2 × 10−18 m. Moreover, accurate discrimination between different cells through miRNA‐21 imaging demonstrates the potential of this method in monitoring the expression level of low‐abundance nucleic acid biomarkers.
Lanthanide‐Doped Core@Multishell Nanoarchitectures: Multimodal Excitable Upconverting/Downshifting Luminescence and High‐Level Anti‐Counterfeiting
Authors: Huang Hai , Chen Jiangkun , Liu Yutong , Lin Jidong , Wang Shaoxiong , Huang Feng , Chen Daqin
Published: April 2020

The development of luminescent materials with concurrent multimodal emissions is a great challenge to improve security and data storage density. Lanthanide‐doped nanocrystals are particularly appropriate for such applications for their abundant intermediate energy states and distinguishable spectroscopic profiles. However, traditional lanthanide luminescent nanoparticles have a limited capacity for information storage or complexity to shield against counterfeiting. Herein, it is demonstrated that the combination of upconverting and downshifting emissions in a particulate designed lanthanide‐doped core@multishell nanoarchitecture allows the generation of multicolor dual‐modal luminescence over a wide spectral range for complex information storage. Precise control of lanthanide dopants distribution in the core and distinct shells enables simultaneous excitation of 980/808 nm focusing/defocusing laser and 254 nm light and produces complex upconverting emissions from Er, Tm, Eu, and Tb via multiphoton energy transfer processes and downshifting emissions from Eu and Tb via efficient energy transfer from Ce to Eu/Tb in Gd‐assisted lattices. It is experimentally proven that multiple visualized anti‐counterfeit and information encryption with facile decryption and authentication using screen‐printing inks containing the present core@multishell nanocrystals are practically applicable by selecting different excitation modes.
A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2‐73) Phase 2a clinical study
Authors: Hampel Harald , Williams Coralie , Etcheto Adrien , Goodsaid Federico , Parmentier Frédéric , Sallantin Jean , Kaufmann Walter E. , Missling Christopher U. , Afshar Mohammad
Published: April 2020

Introduction

The search for drugs to treat Alzheimer's disease (AD) has failed to yield effective therapies. Here we report the first genome‐wide search for biomarkers associated with therapeutic response in AD. Blarcamesine (ANAVEX2‐73), a selective sigma‐1 receptor (SIGMAR1) agonist, was studied in a 57‐week Phase 2a trial (NCT02244541). The study was extended for a further 208 weeks (NCT02756858) after meeting its primary safety endpoint.

Methods

Safety, clinical features, pharmacokinetic, and efficacy, measured by changes in the Mini‐Mental State Examination (MMSE) and the Alzheimer's Disease Cooperative Study‐Activities of Daily Living scale (ADCS‐ADL), were recorded. Whole exome and transcriptome sequences were obtained for 21 patients. The relationship between all available patient data and efficacy outcome measures was analyzed with unsupervised formal concept analysis (FCA), integrated in the Knowledge Extraction and Management (KEM) environment.

Results

Biomarkers with a significant impact on clinical outcomes were identified at week 57: mean plasma concentration of blarcamesine (slope MMSE:P < .041), genomic variants SIGMAR1 p.Gln2Pro (ΔMMSE:P < .039; ΔADCS‐ADL:P < .063) and COMT p.Leu146fs (ΔMMSE:P < .039; ΔADCS‐ADL:P < .063), and baseline MMSE score (slope MMSE:P < .015). Their combined impact on drug response was confirmed at week 148 with linear mixed effect models.

Discussion

Confirmatory Phase 2b/3 clinical studies of these patient selection markers are ongoing. This FCA/KEM analysis is a template for the identification of patient selection markers in early therapeutic development for neurologic disorders.
An enhanced analytical model for airfoil‐based shrouded wind turbines
Authors: Werle Michael J.
Published: April 2020

This paper provides a simple yet accurate lower order model for predicting the performance of shrouded wind turbines for a range of shroud airfoil shapes varying in length, camber, and thickness. The model employs classic thin airfoil aerodynamic principals and is an enhancement of a previous related model developed for shrouded propellers. The new method's accuracy is assessed using inviscid and viscous computational studies employing an actuator‐disc representation for the turbine rotor. Detailed comparisons are made for three shrouds over a full range of rotor loadings. For the range of configurations assessed, it was found that the algebraic solutions from the new method provided very good engineering approximations at all operating conditions considered, thereby enabling rapid preliminary design of shrouded power systems. Additionally, the new model is used to establish a Betz‐like power performance limit for airfoil‐based shrouded turbines.
Role of thermal decomposition process in the photocatalytic or photoluminescence properties of BiPO4 polymorphs
Authors: Bouddouch Abdessalam , Amaterz Elhassan , Bakiz Bahcine , Taoufyq Aziz , Guinneton Frédéric , Villain Sylvie , Gavarri Jean‐Raymond , Ezahri Mohmad , Valmalette Jean‐Christophe , Benlhachemi Abdeljalil
Published: April 2020

Thermal decomposition process was used to obtain modified photocatalytic and/or photoluminescence properties of bismuth phosphate polymorphs. The precursor BiPO4, 0.7H2O was synthesized by a coprecipitation route. The observed polymorphs were the hexagonal P3121 hydrate phase BiPO4, 0.7H2O at 25°C, a mix system of hexagonal and monoclinic P21/n phases at 200°C and 400°C, a mix system of monoclinic phases P21/n and P21/m at 600°C, and a unique monoclinic phase P21/m at 900°C. The X‐ray diffraction analyses allowed evidencing lattice deformations due to structural defects. The photocatalytic activities in the presence of rhodamine B in aqueous solution were determined using UV light irradiation. The best photocatalytic efficiencies were observed with the mix systems resulting from thermal decomposition at 400 and 600°C. Photoluminescence experiments performed under UV‐laser light irradiation revealed unexpected emissions in the green‐orange range, with optimal intensities for the mix systems observed at 400°C. The role of structural defects resulting from decomposition process is discussed.

Practitioner points

Thermal decomposition is used to introduce structural defects in BiPO4 polymorphs

The BiPO4 intermediate systems are used to photodegrade rhodamine B

Active species trapping experiments are performed

Photoluminescence experiments highlight green‐orange emissions

Structural defects are at the origin of this photoluminescence
Naturally occurring modified ribonucleosides
Authors: McCown Phillip J. , Ruszkowska Agnieszka , Kunkler Charlotte N. , Breger Kurtis , Hulewicz Jacob P. , Wang Matthew C. , Springer Noah A. , Brown Jessica A.
Published: April 2020

The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as the “fifth” ribonucleotide in 1951. Since then, the ever‐increasing number and complexity of modified ribonucleosides have been found in viruses and throughout all three domains of life. Such modifications can be as simple as methylations, hydroxylations, or thiolations, complex as ring closures, glycosylations, acylations, or aminoacylations, or unusual as the incorporation of selenium. While initially found in transfer and ribosomal RNAs, modifications also exist in messenger RNAs and noncoding RNAs. Modifications have profound cellular outcomes at various levels, such as altering RNA structure or being essential for cell survival or organism viability. The aberrant presence or absence of RNA modifications can lead to human disease, ranging from cancer to various metabolic and developmental illnesses such as Hoyeraal–Hreidarsson syndrome, Bowen–Conradi syndrome, or Williams–Beuren syndrome. In this review article, we summarize the characterization of all 143 currently known modified ribonucleosides by describing their taxonomic distributions, the enzymes that generate the modifications, and any implications in cellular processes, RNA structure, and disease. We also highlight areas of active research, such as specific RNAs that contain a particular type of modification as well as methodologies used to identify novel RNA modifications.

This article is categorized under:

RNA Processing > RNA Editing and Modification
Molecular networks in Network Medicine: Development and applications
Authors: Silverman Edwin K. , Schmidt Harald H. H. W. , Anastasiadou Eleni , Altucci Lucia , Angelini Marco , Badimon Lina , Balligand Jean‐Luc , Benincasa Giuditta , Capasso Giovambattista , Conte Federica , Di Costanzo Antonella , Farina Lorenzo , Fiscon Giulia , Gatto Laurent , Gentili Michele , Loscalzo Joseph , Marchese Cinzia , Napoli Claudio , Paci Paola , Petti Manuela , Quackenbush John , Tieri Paolo , Viggiano Davide , Vilahur Gemma , Glass Kimberly , Baumbach Jan
Published: April 2020

Network Medicine applies network science approaches to investigate disease pathogenesis. Many different analytical methods have been used to infer relevant molecular networks, including protein–protein interaction networks, correlation‐based networks, gene regulatory networks, and Bayesian networks. Network Medicine applies these integrated approaches to Omics Big Data (including genetics, epigenetics, transcriptomics, metabolomics, and proteomics) using computational biology tools and, thereby, has the potential to provide improvements in the diagnosis, prognosis, and treatment of complex diseases. We discuss briefly the types of molecular data that are used in molecular network analyses, survey the analytical methods for inferring molecular networks, and review efforts to validate and visualize molecular networks. Successful applications of molecular network analysis have been reported in pulmonary arterial hypertension, coronary heart disease, diabetes mellitus, chronic lung diseases, and drug development. Important knowledge gaps in Network Medicine include incompleteness of the molecular interactome, challenges in identifying key genes within genetic association regions, and limited applications to human diseases.

This article is categorized under:

Models of Systems Properties and Processes > Mechanistic Models

Translational, Genomic, and Systems Medicine > Translational Medicine

Analytical and Computational Methods > Analytical Methods

Analytical and Computational Methods > Computational Methods
Modular Inference of Linear Types for Multiplicity-Annotated Arrows
Authors: Matsuda Kazutaka
Published: April 2020

Bernardy et al. [2018] proposed a linear type system $$\lambda ^q_\rightarrow $$

λ
→
q

as a core type system of Linear Haskell. In the system, linearity is represented by annotated arrow types $$A \rightarrow _m B$$

A

→
m

B

, where m denotes the multiplicity of the argument. Thanks to this representation, existing non-linear code typechecks as it is, and newly written linear code can be used with existing non-linear code in many cases. However, little is known about the type inference of $$\lambda ^q_\rightarrow $$

λ
→
q

. Although the Linear Haskell implementation is equipped with type inference, its algorithm has not been formalized, and the implementation often fails to infer principal types, especially for higher-order functions. In this paper, based on OutsideIn(X) [Vytiniotis et al., 2011], we propose an inference system for a rank 1 qualified-typed variant of $$\lambda ^q_\rightarrow $$

λ
→
q

, which infers principal types. A technical challenge in this new setting is to deal with ambiguous types inferred by naive qualified typing. We address this ambiguity issue through quantifier elimination and demonstrate the effectiveness of the approach with examples.
Proving the Safety of Highly-Available Distributed Objects
Authors: Nair Sreeja S. , Petri Gustavo , Shapiro Marc
Published: April 2020

To provide high availability in distributed systems, object replicas allow concurrent updates. Although replicas eventually converge, they may diverge temporarily, for instance when the network fails. This makes it difficult for the developer to reason about the object’s properties, and in particular, to prove invariants over its state. For the subclass of state-based distributed systems, we propose a proof methodology for establishing that a given object maintains a given invariant, taking into account any concurrency control. Our approach allows reasoning about individual operations separately. We demonstrate that our rules are sound, and we illustrate their use with some representative examples. We automate the rule using Boogie, an SMT-based tool.
Graded Algebraic Theories
Authors: Kura Satoshi
Published: April 2020

We provide graded extensions of algebraic theories and Lawvere theories that correspond to graded monads. We prove that graded algebraic theories, graded Lawvere theories, and finitary graded monads are equivalent via equivalence of categories, which extends the equivalence for monads. We also give sums and tensor products of graded algebraic theories to combine computational effects as an example of importing techniques based on algebraic theories to graded monads.
Polynomial Identification of $$\omega $$-Automata
Authors: Angluin Dana , Fisman Dana , Shoval Yaara
Published: April 2020

We study identification in the limit using polynomial time and data for models of $$\omega $$-automata. On the negative side we show that non-deterministic $$\omega $$-automata (of types Büchi, coBüchi, Parity or Muller) can not be polynomially learned in the limit. On the positive side we show that the $$\omega $$-language classes $$\mathbb {IB}$$, $$\mathbb {IC}$$, $$\mathbb {IP}$$, and $$\mathbb {IM}$$ that are defined by deterministic Büchi, coBüchi, parity, and Muller acceptors that are isomorphic to their right-congruence automata (that is, the right congruences of languages in these classes are fully informative) are identifiable in the limit using polynomial time and data. We further show that for these classes a characteristic sample can be constructed in polynomial time.
VeriAbs : Verification by Abstraction and Test Generation (Competition Contribution)
Authors: Afzal Mohammad , Chakraborty Supratik , Chauhan Avriti , Chimdyalwar Bharti , Darke Priyanka , Gupta Ashutosh , Kumar Shrawan , Babu M Charles , Unadkat Divyesh , Venkatesh R
Published: April 2020

VeriAbs is a strategy selection based reachability verifier for C code. It analyzes the structure of loops, and intervals of inputs to choose one of the four verification strategies implemented in VeriAbs. In this paper, we present VeriAbs version 1.4 with updates in three strategies. We add an array verification technique called full-program induction, and enhance the existing techniques of loop pruning, k-path interval analysis, and disjunctive loop summarization. These changes have improved the verification of programs with arrays, and unstructured loops and unstructured control flows.
Java Ranger at SV-COMP 2020 (Competition Contribution)
Authors: Sharma Vaibhav , Hussein Soha , Whalen Michael W. , McCamant Stephen , Visser Willem
Published: April 2020

Path-merging is a known technique for accelerating symbolic execution. One technique, named “veritesting” by Avgerinos et al. uses summaries of bounded control-flow regions and has been shown to accelerate symbolic execution of binary code. But, when applied to symbolic execution of Java code, veritesting needs to be extended to summarize dynamically dispatched methods and exceptional control-flow. Such an extension of veritesting has been implemented in Java Ranger by implementing as an extension of Symbolic PathFinder, a symbolic executor for Java bytecode. In this paper, we briefly describe the architecture of Java Ranger and describe its setup for SV-COMP 2020.
CPU Energy Meter: A Tool for Energy-Aware Algorithms Engineering
Authors: Beyer Dirk , Wendler Philipp
Published: April 2020

Verification algorithms are among the most resource-intensive computation tasks. Saving energy is important for our living environment and to save cost in data centers. Yet, researchers compare the efficiency of algorithms still in terms of consumption of CPU time (or even wall time). Perhaps one reason for this is that measuring energy consumption of computational processes is not as convenient as measuring the consumed time and there is no sufficient tool support. To close this gap, we contribute CPU Energy Meter, a small tool that takes care of reading the energy values that Intel CPUs track inside the chip. In order to make energy measurements as easy as possible, we integrated CPU Energy Meter into BenchExec, a benchmarking tool that is already used by many researchers and competitions in the domain of formal methods. As evidence for usefulness, we explored the energy consumption of some state-of-the-art verifiers and report some interesting insights, for example, that energy consumption is not necessarily correlated with CPU time.
Stress-mediated generation of deleterious ROS in healthy individuals - role of cytochrome c oxidase
Authors: Ramzan Rabia , Vogt Sebastian , Kadenbach Bernhard
Published: April 2020

Psychosocial stress is known to cause an increased incidence of coronary heart disease. In addition, multiple other diseases like cancer and diabetes mellitus have been related to stress and are mainly based on excessive formation of reactive oxygen species (ROS) in mitochondria. The molecular interactions between stress and ROS, however, are still unknown. Here we describe the missing molecular link between stress and an increased cellular ROS, based on the regulation of cytochrome c oxidase (COX). In normal healthy cells, the “allosteric ATP inhibition of COX” decreases the oxygen uptake of mitochondria at high ATP/ADP ratios and keeps the mitochondrial membrane potential (ΔΨm) low. Above ΔΨm values of 140 mV, the production of ROS in mitochondria increases exponentially. Stress signals like hypoxia, stress hormones, and high glutamate or glucose in neurons increase the cytosolic Ca2+ concentration which activates a mitochondrial phosphatase that dephosphorylates COX. This dephosphorylated COX exhibits no allosteric ATP inhibition; consequently, an increase of ΔΨm and ROS formation takes place. The excess production of mitochondrial ROS causes apoptosis or multiple diseases.
Evolution of microbial dynamics with the introduction of real seawater portions in a low-strength feeding anammox process
Authors: Ji Xiaoming , Wang Yongli , Lee Po-Heng
Published: April 2020

The salinity effect on anammox bacteria has been widely reported; however, rare studies describe the microbial dynamics of anammox-based process response to the introduction of real seawater at mainstream conditions. In this study, an anammox process at mainstream conditions without pre-enriching anammox bacteria was shifted to the feeds of a synthetic wastewater with a portion of seawater mixture. It achieved over 0.180 kg-N/(m3 day) of nitrogen removal rate with an additional seawater proportion of 20% in the influent. The bacterial biodiversity was significantly increased with the increase of seawater proportions. High relative abundance of anammox bacteria (34.24–39.92%) related to Ca. Brocadia was enriched and acclimated to the saline environment. However, the introduction of seawater caused the enrichment of nitrite-oxidizing Ca. Nitrospira, which was responsible for the deterioration of nitrogen removal efficiency. Possible adaptation metabolisms in anammox bacteria and other nitrogen transforming bacteria are discussed. These results highlight the importance of microbial diversity for anammox process under the saline environments of 20% and 40% seawater composition.
Evidence gap on antihyperglycemic pharmacotherapy in frail older adults
Authors:   MedQoL-Group (Medication and Quality of Life in frail older persons), Bollig Claudia , Torbahn Gabriel , Bauer Jürgen , Brefka Simone , Dallmeier Dhayana , Denkinger Michael , Eidam Annette , Klöppel Stefan , Zeyfang Andrej , Voigt-Radloff Sebastian
Published: April 2020

Background

Although antihyperglycemic pharmacotherapy in frail older adults with type 2 diabetes mellitus (T2DM) is challenging, recommendations from international guidelines are mainly based on indirect evidence from trials not including frail participants.

Objective

This systematic review investigated the effectiveness and safety of pharmacotherapy in frail older adults with T2DM.

Material and methods

Randomized (RCT) and non-randomized prospective clinical trials (non-RCT) were searched in three electronic databases (Medline, Embase, Central) up to October 2018. Trials in older adults with T2DM who were assessed as significantly or severely impaired by defined cut-off scores of assessment instruments on frailty, activities of daily living or physical functional impairment were included.

Results

Two reviewers independently screened 17,391 references for inclusion and assessed risk of bias with ROBINS‑I. Five non-RCTs and no RCT were identified. Treatment of T2DM without insulin compared to insulin could be associated with increased improvement in cardiac functions in patients with cardiac resynchronization therapy and with decreased falls in frail older women. While better glycemic control with low variability and low HbA1c (hemoglobin A1c) values (<7%) was associated with better maintenance of physical function in community-dwelling older persons, higher HbA1c values (8–8.9%) were associated with a reduction in the composite outcome of death or functional decline in community-dwelling diabetic older adults with need for skilled assistance. Due to serious risk of bias in all studies, results should be considered with caution.

Conclusion

Well-designed, large-scale RCTs including this important group of patients are required to assess the effectiveness and safety of pharmacotherapy and HbA1c targets.
Point-to-line last passage percolation and the invariant measure of a system of reflecting Brownian motions
Authors: FitzGerald Will , Warren Jon
Published: April 2020

This paper proves an equality in law between the invariant measure of a reflected system of Brownian motions and a vector of point-to-line last passage percolation times in a discrete random environment. A consequence describes the distribution of the all-time supremum of Dyson Brownian motion with drift. A finite temperature version relates the point-to-line partition functions of two directed polymers, with an inverse-gamma and a Brownian environment, and generalises Dufresne’s identity. Our proof introduces an interacting system of Brownian motions with an invariant measure given by a field of point-to-line log partition functions for the log-gamma polymer.
Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication
Authors: Vinke Jeroen , Kaper Hans J. , Vissink Arjan , Sharma Prashant K.
Published: April 2020

Objectives

The aims of this study are to assess different saliva substitutes for their efficacy to lubricate the oral cavity, and to relate this oral lubrication to the ability of saliva substitutes to adsorb on and change the structure of the existing salivary conditioning film (SCF).

Materials and methods

Quartz crystal microbalance with dissipation was used to study the capability of saliva substitutes to interact with natural SCF and the ability to change the secondary SCF (S-SCF). A tongue-enamel friction system mimicking xerostomic conditions was used to assess the relief and relief period expected from these substitutes under set circumstances.

Results

Saliva Orthana spray, Biotène spray and Gum Hydral gel had an immediate effect on a SCF, increasing its structural softness. BioXtra gel, Biotène gel, Gum Hydral gel and Glandosane spray changed the S-SCF by increasing salivary protein adsorption, while others showed no sign of interaction. With respect to relief, only 2 out of the 16 saliva substitutes tested (Saliva Orthana spray and Gum Hydral gel) performed better than water. Overall, relief period correlated positively to structural softness change, whereas a positive correlation was seen between relief and mass adsorption.

Conclusions

The majority of saliva substitutes did not adsorb on the SCF, thus did not enhance lubrication. Only saliva substitutes containing carrageenan, carboxymethylcellulose, pig gastric mucin, xanthan gum and carbomer performed better in enhancing oral lubrication.

Clinical relevance

This objective assessment will help clinicians and patients make better choice of saliva substitutes. This study provides a scientific basis for future improvement in saliva substitutes.
Farmers’ landslide risk perceptions and willingness for restoration and conservation of world heritage site of Honghe Hani Rice Terraces, China
Authors: Gao Xuan , Roder Giulia , Jiao Yuanmei , Ding Yinping , Liu Zhilin , Tarolli Paolo
Published: April 2020

The Honghe Hani Rice Terraces (China) is an ancient world heritage agricultural landscape that has been evolved in centuries as a result of farmers’ indigenous practices and knowledge. The area, however, is prone to landslides that can burden the conservation of these landscapes including their social, cultural, economic and aesthetic value. In June 2018, a landslide threatened the villages of Duosha and Mengpin affecting 138 inhabitants and the terraces structure. This event marked the need to understand how farmers coexist with these natural hazards and which are the behaviours people adopt to conserve their environment and safeguard their livelihood. Results from 125 in-person interviews showed that farmers feel threaten by landslide events derived by their personal experience, but their poor perceived preparedness and the inefficient disaster information make them more vulnerable to those events. Nevertheless, they demonstrated a desire to increase their knowledge on terraces restoration and conservation practices. This is an important signal for public authorities and practitioners that need to underpin training activities and create momentum for discussion. The demonstrated high trust in authorities’ decisions is a crucial element to pursue the objective and sustain the conservation of the terraces and the tourism economy.
Pesticide use and risk of Hodgkin lymphoma: results from the North American Pooled Project (NAPP)
Authors: Latifovic Lidija , Freeman Laura E. Beane , Spinelli John J. , Pahwa Manisha , Kachuri Linda , Blair Aaron , Cantor Kenneth P. , Zahm Shelia Hoar , Weisenburger Dennis D. , McLaughlin John R. , Dosman James A. , Pahwa Punam , Koutros Stella , Demers Paul A. , Harris Shelley A.
Published: April 2020

Purpose

The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP).

Methods

Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2–4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient.

Results

In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04–6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02–33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00–3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28–7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34–4.97).

Conclusion

In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.
The role of lipid species in membranes and cancer-related changes
Authors: Skotland Tore , Kavaliauskiene Simona , Sandvig Kirsten
Published: April 2020

Several studies have demonstrated interactions between the two leaflets in membrane bilayers and the importance of specific lipid species for such interaction and membrane function. We here discuss these investigations with a focus on the sphingolipid and cholesterol-rich lipid membrane domains called lipid rafts, including the small flask-shaped invaginations called caveolae, and the importance of such membrane structures in cell biology and cancer. We discuss the possible interactions between the very long-chain sphingolipids in the outer leaflet of the plasma membrane and the phosphatidylserine species PS 18:0/18:1 in the inner leaflet and the importance of cholesterol for such interactions. We challenge the view that lipid rafts contain a large fraction of lipids with two saturated fatty acyl groups and argue that it is important in future studies of membrane models to use asymmetric membrane bilayers with lipid species commonly found in cellular membranes. We also discuss the need for more quantitative lipidomic studies in order to understand membrane function and structure in general, and the importance of lipid rafts in biological systems. Finally, we discuss cancer-related changes in lipid rafts and lipid composition, with a special focus on changes in glycosphingolipids and the possibility of using lipid therapy for cancer treatment.
Competitors in merger control: Shall they be merely heard or also listened to?
Authors: Giebe Thomas , Lee Miyu
Published: April 2020

There are legal grounds to hear competitors in merger control proceedings, and competitor involvement has gained significance. To what extent this is economically sensible is the focus of our game-theoretic analysis. The competition authority applies some welfare standard while the competitor cares about its own profit. In expectation, there is neither a pure conflict nor a complete alignment of interest. We distinguish hard and soft information and ask whether hearing the competitor might convey valuable but non-verifiable information to the authority. We identify a case where, based on the authority’s verifiable information, the authority’s decision is improved by following the competitor’s selfish but non-verifiable communication. We argue that the practical relevance of this constellation is very limited, especially so under a consumer welfare standard. Thus, non-verifiable information should mostly be ignored. Complementary to our analysis, we provide empirical data of competitor involvement in EU merger cases and give an overview of the legal discussion in the EU and US.