bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in LINC00963 attenuates the progression of pulmonary arterial hypertension via microRNA‐328‐3p/profilin 1 axis
Authors: Yang Chengpeng , Rong Rong , Li Yuze , Cheng Mingxun , Luo Yanzhuo
Published: March 2022

Background

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by vascular hyperplasia and remodeling. Long noncoding RNA LINC00963 can regulate cell proliferation and metastasis in nonsmall cell lung cancer. However, the function of LINC00963 on PAH progression is rarely reported.

Methods

Quantitative real‐time PCR was used to determine the expression levels of LINC00963, microRNA (miRNA)‐328‐3p, and profilin 1 (PFN1), as well as vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF‐2), and hypoxia‐inducible factor (HIF)‐α. The protein level of PFN1 was measured by western blotting. The viability and migration of hypoxia‐induced pulmonary arterial smooth muscle cells (PASMCs) were assessed by 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐h‐tetrazolium bromide, and transwell assays, respectively. The target relationships between miR‐328‐3p and LINC00963/PFN1 were confirmed by dual‐luciferase reporter assay. A PAH mouse model was conducted to explore the effects of hypoxia on cardiopulmonary functions.

Results

In hypoxia‐induced PASMCs and PAH mouse model, high expression levels of LINC00963 and PFN1, and low expression of miR‐328‐3p, were determined. The viability, migration of hypoxia‐induced PASMCs, the expression of VEGF, FGF‐2, and HIF‐α were significantly repressed by transfection of si‐LINC00963 or miR‐328‐3p mimics. The inhibitory effects of LINC00963 silencing on cell viability, migration, and the levels of VEGF, FGF‐2, and HIF‐α were partly eliminated by miR‐328‐3p inhibitor or increasing the expression of PFN1. Hypoxia treatment increased the levels of RVSP, mPAP, and RV/(LV+S), as well as the thickness of pulmonary artery wall.

Conclusions

Silencing of LINC00963 ameliorates PAH via modulating miR‐328‐3p/PFN1.
Identification of benzothiazole‐rhodanine derivatives as α‐amylase and α‐glucosidase inhibitors: Design, synthesis, in silico, and in vitro analysis
Authors: Srinivasa Mahendra Gowdru , Aggarwal Natasha Naval , Gatpoh Banylla Felicity Dkhar , Shankar Madan Kumar , Byadarahalli Ravindranath Kannika , Gurubasavaraj Veeranna Pujar , Dixit Sheshagiri , Mandal Subhankar P. , Bommenahally Ravanappa Prashantha Kumar , Khanal Pukar , Bistuvalli Chandrashekarappa Revanasiddappa
Published: March 2022

A novel series of benzothiazole‐rhodanine derivatives (A1‐A10) were designed and synthesized, with the aim of developing possible antidiabetic agents and the spectral characterization of these compounds was done using infrared spectroscopy (IR), proton‐nuclear magnetic resonance (1H‐NMR), carbon‐nuclear magnetic resonance (C13‐NMR), and high resolution mass spectroscopy (HR‐MS) techniques. In vitro hypoglycemic potential of the compounds was evaluated by performing α‐amylase and α‐glucosidase enzyme inhibitory assays. In addition, these compounds were subjected to in silico analysis. Based on the results, compounds A5, A6, and A9 displayed good activity in comparison with the standard acarbose. Based on Lineweaver‐Burk plots, it was concluded that compounds A5 and A9 displayed competitive type of enzyme inhibition. Molecular dynamic simulations were conducted to evaluate the stability of the ligand‐protein complex by the calculation of the root mean square deviation, root means square fluctuation, and solvent accessible surface area.
Clinicopathological correlates of out‐of‐hospital cardiac arrests
Authors: Li Tony , Yap Jonathan , Chng Wei Qiang , Tay Julian Cheong Kiat , Shahidah Nur , Yeo Colin , Gan Han Nee , Tong Khim Leng , Ng Yih Yng , Wu Jia Hao , Wang Marian , Ong Marcus Eng Hock , Ching Chi Keong
Published: March 2022

Background

Sudden cardiac arrest with or without sudden cardiac death (SCD) represents a heterogeneous spectrum of underlying etiology but is often a catastrophic event. Despite improvements in pre‐hospital response and post‐resuscitation care, outcomes remain grim. Thus, we aim to evaluate the predictors of survival in out‐of‐hospital cardiac arrests (OHCAs) and describe autopsy findings of those with the uncertain cause of death (COD).

Methods

This is a subgroup analysis of the Singapore cohort from the Pan Asian Resuscitation Outcome Study which studied 933 OHCAs admitted to two Singapore tertiary hospitals from April 2010 to May 2012.

Results

Of the patients analysed, 30.2% (n = 282) had an initial return of spontaneous circulation (ROSC) at the emergency department, 18.0% (n = 168) had sustained ROSC with subsequent admission and 3.4% (n = 32) had survival to discharge. On multivariate analysis, an initial shockable rhythm, a witnessed event, prehospital defibrillation, and shorter time to hospital predicted ROSC as well as survival to discharge. A total of 163 (17.5%) autopsies were performed of which a cardiac etiology of SCD was noted in 92.1% (n = 151). Ischemic heart disease accounted for 54.3% (n = 89) of the autopsy cohort, with acute myocardial infarction (26.9%, n = 44) and myocarditis (3.7%, n = 6) rounding out the top three causes of demise.

Conclusion

OHCA remains a clinical presentation that portends a poor prognosis. Of those with uncertain COD, cardiac etiology appears to predominate from autopsy study. Identification of prognostic factors will play an important role in improving individual‐level and systemic‐level variables to further optimize outcomes.
Approximation by a class of neural network operators on scattered data
Authors: Yu Dansheng , Cao Feilong
Published: March 2022

Scattered data are a class of common data in the real world. Naturally, how to efficiently process scattered data is important. This paper uses a class of feedforward neural networks with four layers as tool to fit scattered data and establishes the estimates of the approximation error. In particular, an inverse theorem of the approximation is established. Concretely, we first extend an existed result on
to the case of arbitrary bounded convex set
in
. Secondly, we introduce a modified feedforward neural network with four layers, which is a class of quasi‐interpolation operators and can keep the smoothness of the objective function. By establishing two Bernstein‐type inequalities for the operators, we establish both the direct and converse results of the approximation by the operator, which follows the equivalence characterization theorem of the approximation.
Predictors of prolonged admission after outpatient female pelvic reconstructive surgery
Authors: Simi Andrea M. , Chapman Graham C. , Zillioux Jacqueline , Martin Sarah , Slopnick Emily A.
Published: March 2022

Objectives

This study aimed to determine factors associated with prolonged hospital admission following outpatient female pelvic reconstructive surgery (FPRS) and associated adverse clinical outcomes.

Methods

Using the National Surgical Quality Improvement Program database, we identified outpatient FPRS performed 2011–2016. Isolated hysterectomy without concurrent prolapse repair was excluded. Surgeries were classified as major or minor for analysis. The primary outcome was prolonged length of stay (LOS), defined as admission of ≥2 days. Secondary outcomes included complications, readmission and reoperation associated with prolonged LOS. We abstracted data on covariates, and following univariable analysis, performed backward stepwise regression analysis.

Results

A total of 29645 women were included: 12311 (41.5%) major and 17334 (58.5%) minor procedures. A total of 6.9% (2033) had a prolonged LOS. On full cohort multivariable regression analysis, patient characteristics associated with prolonged LOS were older age (odds ratio [OR]: 1.1 per 10 years, confidence interval [CI]: 1.06–1.1, p < 0.001), frailty (OR: 1.8, 95% CI: 1.3–2.6, p = 0.001), and Caucasian race (OR: 1.2, CI: 1.02–1.3, p = 0.024). Associated surgical factors included having a major surgical procedure (OR: 1.3, CI: 1.2–1.4, p < 0.001), use of general anesthesia (OR: 2.0, CI: 1.5–2.6, p < 0.001) and longer operative time (OR: 2.0, CI: 1.8–2.2, p < 0.001). The occurrence of any complication (10.3% vs. 4.7%, p < 0.001), hospital readmission (4.3% vs. 1.7%, p < 0.001), and reoperation (2.7% vs. 1.0%, p < 0.001) were more likely with prolonged LOS.

Conclusions

After outpatient FPRS, 6.9% of patients experience an admission of ≥2 days. Prolonged LOS is more common in patients who are older, frail and Caucasian, and in those who have major surgery with long operative time and general anesthesia.
Post‐yielding fracture mechanics of 3D printed polymer‐based orthopedic cortical screws
Authors: Agarwal Raj , Mehtani Hitesh Kumar , Singh Jaskaran , Gupta Vishal
Published: March 2022

The internal fixation of a fractured bone is generally achieved with bone screws during most orthopedic surgeries. Biodegradable screws have not received as much attention as they deserve. Biodegradable screws reduce the stress‐shielding effect, screw failure, complex, painful revision surgery for screw extraction. The vital focus of the present research is to fabricate cortical bone screws using polylactic acid (PLA) by fused deposition modeling technology. The PLA cortical screws were manufactured with different infill patterns (triangular, honeycomb, grid, and concentric), keeping other parameters constant using three‐dimensional printing. The mechanical behavior and fracture mechanism of different patterned cortical screws were observed based on compression testing and tensile testing of screws. Scanning electron microscopy (SEM) observed the surface topographical features, fracture behavior, and microstructure characterization of different patterned polymeric cortical screws were observed using SEM. Based on the SEM micrographs, mechanical characterization of compression and tensile testing shows the stress, fractures and fatigue cracks propagation at the bone screw interfaces by fractures copy. Moreover, it was observed that the fracture mechanism of ductile to brittle fracture was observed with variation in the infill pattern of the bone screw. The outcomes revealed that the cortical screw with honeycomb infill pattern has the highest compressive and tensile strength than other infill patterns. Honeycomb structured cortical screws have approximately 17% higher compressive strength and 30% higher tensile strength than the triangular patterned cortical screw due to higher bonding surface area at the intercalated layers.
Ring‐opening polymerization of 1,4‐oxathian‐2‐one and its copolymerization with δ‐valerolactone
Authors: Wang Qi‐Yuan , Cao Meng‐Xue , Kan Xiao‐Wei , Lv An , Du Fu‐Sheng , Li Zi‐Chen
Published: March 2022

Monomer 1,4‐oxathian‐2‐one (OX) was synthesized by a one pot two‐step method, and it was oxidized to the sulfone ester monomer, 1,4‐oxathian‐2‐one‐4,4‐dioxide (OX‐SO2). Three organic catalysts, 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), and diphenyl phosphate (DPP) were screened for the ring‐opening polymerization (ROP) of OX in dichloromethane at 30°C. It was found that OX has a high polymerizability, the TBD‐catalyzed ROP is very fast but with serious side reactions, the DBU‐catalyzed ROP is moderately controlled, and the DPP‐catalyzed ROP is well controlled until the polymerization reach equilibrium. Bulk ROP of OX‐SO2 was achieved with stannous octoate ((Sn[Oct]2) at 130°C. Poly(OX) is a semicrystalline polyester (Tm = 40‐60°C, Tg = −39.6°C), while Poly(OX‐SO2) is a highly crystalline polyester(Tg = 55°C, Tm = 211°C with decomposition). Kinetics experiments of OX and δ‐valerolactone (VL) revealed that VL polymerized faster than OX with DPP as the catalyst. Thermodynamic parameters of the ROP of OX and VL under identical conditions were measured; the ROP of OX is thermodynamically more favorable than that of VL. A series of random copolymers of OX and VL was prepared using TBD as the catalyst and confirmed that the in‐chain heteroatom greatly affected the crystallization of the copolymers.
Intuitive master device for endoscopic robots with visual‐motor correspondence
Authors: Cheon Byungsik , Baek Hyunwoo , Kim Chang‐Kyun , Ahn Jeongdo , Kwon Dong‐Soo
Published: March 2022

Background

Master devices exclusively used for endoscopes with position control are being developed as an isomorphic form of endoscopes. These master devices are difficult to intuitively operate because the movement direction of the endoscopic image and control handle do not match.

Methods

To solve this problem, a master device was developed. Its movement direction is compatible with that of the endoscopic image. It analyzes image movements according to flexible endoscopic ureteroscope movements for each degree of freedom. A driving testbed experiment was conducted that modelled the internal structure of a kidney.

Results

The time taken in the experiment was shorter when using the proposed master device than the existing isomorphic master device. The proposed device yielded fewer mistakes.

Conclusions

It was confirmed the proposed device is effective in exclusive use for endoscopes because of its feasibility of position control and movement direction's coinciding with that of the endoscopic image.
Effectiveness of rapid antigen testing for screening of asymptomatic individuals to limit the transmission of SARS‐CoV‐2: A rapid review
Authors: Walsh Kieran A. , Broderick Natasha , Ahern Susan , Fawsitt Christopher G. , O’Brien Katie M. , Carrigan Marie , Harrington Patricia , O’Neill Michelle , Smith Susan M. , Spillane Susan , Teljeur Conor , Ryan Máirín
Published: March 2022

Rapid antigen detection tests (RADTs) offer advantages over gold‐standard reverse transcription polymerase chain reaction (RT‐PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS‐CoV‐2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS‐CoV‐2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population‐level screening, four for pre‐event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS‐CoV‐2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real‐world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.
Understanding the Surface Reconstruction on Ternary WxCoBx for Water Oxidation and Zinc–Air Battery Applications
Authors: Saad Ali , Gao Yang , Ramiere Aymeric , Chu Tianzhi , Yasin Ghulam , Wu Yanyan , Ibraheem Shumaila , Wang Miao , Guo Haichuan , Tsiakaras Panagiotis , Cai Xingke
Published: March 2022

Here, the synthesis of a series of pure phase metal borides is reported, including WB, CoB, WCoB, and W2CoB2, and their surface reconstruction is studied under the electrochemical activation in alkaline solution. A cyclic voltammetric activation is found to enhance the activity of the CoB and W2CoB2 precatalysts due to the transformation of their surfaces into the amorphous CoOOH layer with a thickness of 3–4 nm. However, such surface transformation does not happen on the WB and WCoB due to their superior structure stability under the applied voltage, highlighting the importance of metal components for the surface reconstruction process. It is found that, compared with CoB, the W2CoB2 surface shows a quicker reconstruction with a larger active surface area due to the selective leaching of the W from its surface. In the meantime, the metallic W2CoB2 core underneath the CoOOH layer shows a better promotion of its oxygen evolution reaction (OER) performance than CoB. Therefore, the ternary W2CoB2 shows better OER performance than the CoB, as well as the WB and WCoB. It is also found that the mixture of W2CoB2 with Pt/C as the catalysts in air electrode for rechargeable Zn–air battery (ZAB), shows better performance than the IrO2–Pt/C couple‐based ZAB.
Bilateral trigeminal neuropathy associated with multicentric lymphoma in two dogs: Clinical presentation, MRI findings and flow cytometry characteristics
Authors: Zajc Alenka Lavra , Warwick Harry , Rosa Chantal , Grant Jessica , Marrington Mary
Published: March 2022

A 6‐year‐old, female, neutered crossbreed and a 6.5‐year‐old, male, neutered Labrador retriever presented with oral dysphagia. Both dogs underwent investigations, including magnetic resonance imaging of the head, cytology and immunophenotyping. A diagnosis of stage Vb multicentric B‐cell lymphoma with plasmacytoid differentiation, likely Waldenstrom's macroglobulinemia with bilateral trigeminal neuropathy, Horner's syndrome and paraneoplastic hypercalcaemia was obtained in the first case. In the second case, a diagnosis of stage Vb multicentric high‐grade T‐cell lymphoma with bilateral trigeminal neuropathy and suspected paraneoplastic polycythaemia was obtained. There was no evidence of central nervous system involvement in either case. There are very few previous reports of non‐idiopathic bilateral trigeminal neuropathy secondary to multicentric lymphoma, and to the best of the authors’ knowledge, this is the first report describing the phenotypic and magnetic resonance imaging characteristics.
Introduction
Authors: Bremer Anne , Strand Roger
Published: March 2022

This introductory chapter gives an overview of the context in which the book was written, and goes through the central themes being addressed. The book is a result of long-held collaborations between oncologists, clinicians, philosophers, STSers, anthropologists, economists, ethicists, and media studies scholars, who, for the most part, are affiliated to the Centre for Cancer Biomarker (CCBIO), in Bergen, Norway. In addressing the issues at stake and matters of concern around precision oncology and cancer biomarker research, the authors come to see precision oncology as a sociotechnical imaginary, around which a high degree of confusion between hope and reality is observed, and where debates around the feasibility and desirability of precision medicine are altogether political, social, ethical, scientific and medical. The contributions to this book variously approach the culture of biomarker research, powered to a significant extent by a sociotechnical imaginary of precision oncology, with a focus on the following overarching themes: (i) the uncomfortable knowledge that comes to undermine the legitimacy of precision oncology by point at its shortfalls, and the lack of ambivalence in the discourses and practices around precision oncology; (ii) the dynamics of framing and overflowing, when trying to control biological, social and ethical complexity; and (iii) the role of the economy of hope in legitimising and sustaining the imaginary of precision oncology, and the starch dichotomy between illness and disease it leads to.
Cancer Currencies: Making and Marketing Resources in a First-in-Human Drug Trial in Denmark
Authors: Hillersdal Line , Svendsen Mette N.
Published: March 2022

Welfare state service delivery is increasingly driven by public-private collaborations and strategies aimed at turning the provision of core welfare services into a profitable business at an international scale. Particularly within cancer treatment development, the cost of medical research is increasing, and many policymakers see partnerships between private and public partners as mandatory to sustain public welfare services. But how do welfare state practices and values intersect with commercial interests as cancer research becomes increasingly entangled with big pharma interests? We explore this question by investigating the collaboration between a public hospital in Denmark and a multi-national pharmaceutical company and the practical work involved in setting up and running early cancer drug trials for personalised medicine. Based on ethnographic research we analyse how competition, investment and exchange practices shape how welfare resources for personalised medicine are defined, produced, and offered. We argue that qualities facilitated by the welfare state – i.e., fast-tracking trial procedures, high-quality data and high compliance of research subjects – become currencies transactable on the global market for drug development.
HER2 Revisited: Reflections on the Future of Cancer Biomarker Research
Authors: Bremer Anne , Wik Elisabeth , Akslen Lars A.
Published: March 2022

In this chapter, we revisit the successful story of the HER2 biomarker for breast cancer, to reflect on the conditions of its inception, some of the reasons for its success, and the challenges met along the way. HER2 is a standard in the field of cancer biomarker research, against which all biomarkers are measured. It is also one of the central arguments used for illustrating the feasibility and desirability of precision oncology. But critically revisiting the story of HER2 shows us that it too faced a winding road from its discovery in the lab to its use in the clinic, and that it currently operates in a context of high levels of biological complexity and persistent uncertainties, in particular with regard to cancer heterogeneity and its implications. By drawing a parallel between the story of HER2 and a ‘scientific bandwagon’, we examine some of the legal, social, and economic challenges and dilemmas that HER2 faces, and conclude with some reflections on the future of cancer biomarker research. Notably, we highlight the need for a greater focus on ‘good enough’ biomarkers, particularly in the setting of precision oncology driven by hyper-precision and the wish for molecular certainty. We emphasise the importance of being open about the low success rate of 1% of published biomarkers which reach clinical practice when justifying the risks and opportunity costs of precision oncology.
Crossing the Styx: If Precision Medicine Were to Become Exact Science
Authors: Strand Roger , Chu Dominique
Published: March 2022

The term “precision medicine” is used to denote existing practices as well as how medical research and practice are imagined to become in the future. One important element of the imaginaries of precision medicine is the development of systems biology and computational models with the promise of numerical precision and conceptual rigour. If precision medicine were to become an exact science that relies on computational models, it might increase precision in diagnosis and treatment, specifying the right drug to the right patient at the right time. It should be noted, though, that computational models require explicit specification of the properties and boundaries of the system to be modelled, whereas cells, tissues and patients are predominantly open systems in their natural state. Accordingly, such models risk being precisely wrong instead of approximately right. Right and wrong, however, are value judgements that depend upon the aims and scope of the scientific and medical enterprise. In order for medicine to become an exact science, cells, tissues and patients would have to be reconceived and/or reconfigured as relatively closed systems with relatively deterministic behaviour. The realization of precision medicine as an exact science may thus be accompanied by a transition from a world of complex natural life to a world of reduced life or a simple delay of death; a transition to be likened with the crossing of the Styx.
A Max-SMT Superoptimizer for EVM handling Memory and Storage
Authors: Albert Elvira , Gordillo Pablo , Hernández-Cerezo Alejandro , Rubio Albert
Published: March 2022

Superoptimization is a compilation technique that searches for the optimal sequence of instructions semantically equivalent to a given (loop-free) initial sequence. With the advent of SMT solvers, it has been successfully applied to LLVM code (to reduce the number of instructions) and to Ethereum EVM bytecode (to reduce its gas consumption). Both applications, when proven practical, have left out memory operations and thus missed important optimization opportunities. A main challenge to superoptimization today is handling memory operations while remaining scalable. We present $$\textsf {GASOL}^{v2}$$

GASOL

v
2

, a gas and bytes-size superoptimization tool for Ethereum smart contracts, that leverages a previous Max-SMT approach for only stack optimization to optimize also wrt. memory and storage. $$\textsf {GASOL}^{v2}$$

GASOL

v
2

can be used to optimize the size in bytes, aligned with the optimization criterion used by the Solidity compiler , and it can also be used to optimize gas consumption. Our experiments on 12,378 blocks from 30 randomly selected real contracts achieve gains of 16.42% in gas wrt. the previous version of the optimizer without memory handling, and gains of 3.28% in bytes-size over code already optimized by .
Inferring Interval-Valued Floating-Point Preconditions
Authors: Krämer Jonas , Blatter Lionel , Darulova Eva , Ulbrich Mattias
Published: March 2022

Aggregated roundoff errors caused by floating-point arithmetic can make numerical code highly unreliable. Verified postconditions for floating-point functions can guarantee the accuracy of their results under specific preconditions on the function inputs, but how to systematically find an adequate precondition for a desired error bound has not been explored so far. We present two novel techniques for automatically synthesizing preconditions for floating-point functions that guarantee that user-provided accuracy requirements are satisfied. Our evaluation on a standard benchmark set shows that our approaches are complementary and able to find accurate preconditions in reasonable time.
Automated Translation of Natural Language Requirements to Runtime Monitors
Authors: Perez Ivan , Mavridou Anastasia , Pressburger Tom , Goodloe Alwyn , Giannakopoulou Dimitra
Published: March 2022

Runtime verification (RV) enables monitoring systems at runtime, to detect property violations early and limit their potential consequences. This paper presents an end-to-end framework to capture requirements in structured natural language and generate monitors that capture their semantics faithfully. We leverage NASA’s Formal Requirement Elicitation Tool (fret), and the RV systemCopilot. We extendfretwith mechanisms to capture additional information needed to generate monitors, and introduceOgma, a new tool to bridge the gap betweenfretandCopilot. With this framework, users can write requirements in an intuitive format and obtain real-time C monitors suitable for use in embedded systems. Our toolchain is available as open source.
MaskD: A Tool for Measuring Masking Fault-Tolerance
Authors: Putruele Luciano , Demasi Ramiro , Castro Pablo F. , D’Argenio Pedro R.
Published: March 2022

We present , an automated tool designed to measure the level of fault-tolerance provided by software components. The tool focuses on measuring masking fault-tolerance, that is, the kind of fault-tolerance that allows systems to mask faults in such a way that they cannot be observed by the users. The tool takes as input a nominal model (which serves as a specification) and its fault-tolerant implementation, described by means of a guarded-command language, and automatically computes the masking distance between them. This value can be understood as the level of fault-tolerance provided by the implementation. The tool is based on a sound and complete framework we have introduced in previous work. We present the ideas behind the tool by means of a simple example and report experiments realized on more complex case studies.
A Sorted Datalog Hammer for Supervisor Verification Conditions Modulo Simple Linear Arithmetic
Authors: Bromberger Martin , Dragoste Irina , Faqeh Rasha , Fetzer Christof , González Larry , Krötzsch Markus , Marx Maximilian , Murali Harish K , Weidenbach Christoph
Published: March 2022

In a previous paper, we have shown that clause sets belonging to the Horn Bernays-Schönfinkel fragment over simple linear real arithmetic (HBS(SLR)) can be translated into HBS clause sets over a finite set of first-order constants. The translation preserves validity and satisfiability and it is still applicable if we extend our input with positive universally or existentially quantified verification conditions (conjectures). We call this translation a Datalog hammer. The combination of its implementation in SPASS-SPL with the Datalog reasoner VLog establishes an effective way of deciding verification conditions in the Horn fragment. We verify supervisor code for two examples: a lane change assistant in a car and an electronic control unit of a supercharged combustion engine.

In this paper, we improve our Datalog hammer in several ways: we generalize it to mixed real-integer arithmetic and finite first-order sorts; we extend the class of acceptable inequalities beyond variable bounds and positively grounded inequalities; and we significantly reduce the size of the hammer output by a soft typing discipline. We call the result the sorted Datalog hammer. It not only allows us to handle more complex supervisor code and to model already considered supervisor code more concisely, but it also improves our performance on real world benchmark examples. Finally, we replace the before file-based interface between SPASS-SPL and VLog by a close coupling resulting in a single executable binary.
Comparative Verification of the Digital Library of Mathematical Functions and Computer Algebra Systems
Authors: Greiner-Petter André , Cohl Howard S. , Youssef Abdou , Schubotz Moritz , Trost Avi , Dey Rajen , Aizawa Akiko , Gipp Bela
Published: March 2022

Digital mathematical libraries assemble the knowledge of years of mathematical research. Numerous disciplines (e.g., physics, engineering, pure and applied mathematics) rely heavily on compendia gathered findings. Likewise, modern research applications rely more and more on computational solutions, which are often calculated and verified by computer algebra systems. Hence, the correctness, accuracy, and reliability of both digital mathematical libraries and computer algebra systems is a crucial attribute for modern research. In this paper, we present a novel approach to verify a digital mathematical library and two computer algebra systems with one another by converting mathematical expressions from one system to the other. We use our previously developed conversion tool (referred to as

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) to translate formulae from the NIST Digital Library of Mathematical Functions to the computer algebra systems and . The contributions of our presented work are as follows: (1) we present the most comprehensive verification of computer algebra systems and digital mathematical libraries with one another; (2) we significantly enhance the performance of the underlying translator in terms of coverage and accuracy; and (3) we provide open access to translations for and of the formulae in the NIST Digital Library of Mathematical Functions.
Verifying Fortran Programs with CIVL
Authors: Wu Wenhao , Hückelheim Jan , Hovland Paul D. , Siegel Stephen F.
Published: March 2022

Fortran is widely used in computational science, engineering, and high performance computing. This paper presents an extension to the CIVL verification framework to check correctness properties of Fortran programs. Unlike previous work that translates Fortran to C, LLVM IR, or other intermediate formats before verification, our work allows CIVL to directly consume Fortran source files. We extended the parsing, translation, and analysis phases to support Fortran-specific features such as array slicing and reshaping, and to find program violations that are specific to Fortran, such as argument aliasing rule violations, invalid use of variable and function attributes, or defects due to Fortran’s unspecified expression evaluation order. We demonstrate the usefulness of our tool on a verification benchmark suite and kernels extracted from a real world application.
NORMA: a tool for the analysis of Relay-based Railway Interlocking Systems
Authors: Amendola Arturo , Becchi Anna , Cavada Roberto , Cimatti Alessandro , Ferrando Andrea , Pilati Lorenzo , Scaglione Giuseppe , Tacchella Alberto , Zamboni Marco
Published: March 2022

We present Norma, a tool for the modeling and analysis of Relay-based Railways Interlocking Systems (RRIS). Norma is the result of a research project funded by the Italian Railway Network, to support the reverse engineering and migration to computer-based technology of legacy RRIS. The frontend fully supports the graphical modeling of Italian RRIS, with a palette of over two hundred basic components, stubs to abstract RRIS subcircuits, and requirements in terms of formal properties. The internal component based representation is translated into highly optimized Timed nuXmv models, and supports various syntactic and semantic checks based on formal verification, simulation and test case generation. Norma is experimentally evaluated, demonstrating the practical support for the modelers, and the effectiveness of the underlying optimizations.
From Bounded Checking to Verification of Equivalence via Symbolic Up-to Techniques
Authors: Koutavas Vasileios , Lin Yu-Yang , Tzevelekos Nikos
Published: March 2022

We present a bounded equivalence verification technique for higher-order programs with local state. This technique combines fully abstract symbolic environmental bisimulations similar to symbolic game semantics, novel up-to techniques, and lightweight state invariant annotations. This yields an equivalence verification technique with no false positives or negatives. The technique is bounded-complete, in that all inequivalences are automatically detected given large enough bounds. Moreover, several hard equivalences are proved automatically or after being annotated with state invariants. We realise the technique in a tool prototype called Hobbit and benchmark it with an extensive set of new and existing examples. Hobbit can prove many classical equivalences including all Meyer and Sieber examples.
A Theoretical Analysis of Random Regression Test Prioritization
Authors: Yi Pu , Wang Hao , Xie Tao , Marinov Darko , Lam Wing
Published: March 2022

Regression testing is an important activity to check software changes by running the tests in a test suite to inform the developers whether the changes lead to test failures. Regression test prioritization (RTP) aims to inform the developers faster by ordering the test suite so that tests likely to fail are run earlier. Many RTP techniques have been proposed and are often compared with the random RTP baseline by sampling some of the n! different test-suite orders for a test suite with n tests. However, there is no theoretical analysis of random RTP. We present such an analysis, deriving probability mass functions and expected values for metrics and scenarios commonly used in RTP research. Using our analysis, we revisit some of the most highly cited RTP papers and find that some presented results may be due to insufficient sampling. Future RTP research can leverage our analysis and need not use random sampling but can use our simple formulas or algorithms to more precisely compare with random RTP.
Efficient Analysis of Cyclic Redundancy Architectures via Boolean Fault Propagation
Authors: Bozzano Marco , Cimatti Alessandro , Griggio Alberto , Jonáš Martin
Published: March 2022

Many safety critical systems guarantee fault-tolerance by using several redundant copies of their components. When designing such redundancy architectures, it is crucial to analyze their fault trees, which describe combinations of faults of individual components that may cause malfunction of the system. State-of-the-art techniques for fault tree computation use first-order formulas with uninterpreted functions to model the transformations of signals performed by the redundancy system and an AllSMT query for computation of the fault tree from this encoding. Scalability of the analysis can be further improved by techniques such as predicate abstraction, which reduces the problem to Boolean case.

In this paper, we show that as far as fault trees of redundancy architectures are concerned, signal transformation can be equivalently viewed in a purely Boolean way as fault propagation. This alternative view has important practical consequences. First, it applies also to general redundancy architectures with cyclic dependencies among components, to which the current state-of-the-art methods based on AllSMT are not applicable, and which currently require expensive sequential reasoning. Second, it allows for a simpler encoding of the problem and usage of efficient algorithms for analysis of fault propagation, which can significantly improve the runtime of the analyses. A thorough experimental evaluation demonstrates the superiority of the proposed techniques.
BRICK: Path Enumeration Based Bounded Reachability Checking of C Program (Competition Contribution)
Authors: Bu Lei , Xie Zhunyi , Lyu Lecheng , Li Yichao , Guo Xiao , Zhao Jianhua , Li Xuandong
Published: March 2022

BRICK is a bounded reachability checker for embedded C programs. BRICK conducts a path-oriented style checking of the bounded state space of the program, that enumerates and checks all the possible paths of the program in the threshold one by one. To alleviate the path explosion problem, BRICK locates and records unsatisfiable core path segments during the checking of each path and uses them to prune the search space. Furthermore, derivative free optimization based falsification and loop induction are introduced to handle complex program features like nonlinear path conditions and loops efficiently.
Deagle: An SMT-based Verifier for Multi-threaded Programs (Competition Contribution)
Authors: He Fei , Sun Zhihang , Fan Hongyu
Published: March 2022

is an SMT-based multi-threaded program verification tool. It is built on top of (front-end) and (back-end). The basic idea of is to integrate into the SMT solver an ordering consistency theory that handles ordering relations over the shared variable accesses in the program. The front-end encodes the input program into an extended propositional formula that contains ordering constraints. The back-end is reinforced with a solver for the ordering consistency theory. This paper presents the basic idea, architecture, installation, and usage of .
The Static Analyzer Frama-C in SV-COMP (Competition Contribution)
Authors: Beyer Dirk , Spiessl Martin
Published: March 2022

Frama-C is a well-known platform for source-code analysis of programs written in C. It can be extended via its plug-in architecture by various analysis backends and features an extensive annotation language called ACSL. So far it was hard to compare Frama-C to other software verifiers. Our competition participation contributes an adapter named Frama-C-SV, which makes it possible to evaluate Frama-C against other software verifiers. The adapter transforms standard verification tasks (from the well-known SV-Benchmarks collection) in a way that can be understood by Frama-C and produces a verification witness as output. While Frama-C provides many different analyses, we focus on the Evolved Value Analysis (EVA), which uses a combination of different domains to over-approximate the behavior of the analyzed program.
Graves-CPA: A Graph-Attention Verifier Selector (Competition Contribution)
Authors: Leeson Will , Dwyer Matthew B.
Published: March 2022

Graves-CPA is a verification tool which uses algorithm selection to decide an ordering of underlying verifiers to most effectively verify a given program. Graves-CPA represents programs using an amalgam of traditional program graph representations and uses state-of-the-art graph neural network techniques to dynamically decide how to run a set of verification techniques. The Graves technique is implementation agnostic, but it’s competition submission, Graves-CPA, is built using several CPAchecker configurations as its underlying verifiers.
The Static Analyzer Infer in SV-COMP (Competition Contribution)
Authors: Kettl Matthias , Lemberger Thomas
Published: March 2022

We present Infer-sv, a wrapper that adapts Infer for SV-COMP. Infer is a static-analysis tool for C and other languages, developed by Facebook and used by multiple large companies. It is strongly aimed at industry and the internal use at Facebook. Despite its popularity, there are no reported numbers on its precision and efficiency. With Infer-sv, we take a first step towards an objective comparison of Infer with other SV-COMP participants from academia and industry.
Ultimate GemCutter and the Axes of Generalization
Authors: Klumpp Dominik , Dietsch Daniel , Heizmann Matthias , Schüssele Frank , Ebbinghaus Marcel , Farzan Azadeh , Podelski Andreas
Published: March 2022

Ultimate GemCutter verifies concurrent programs using the CEGAR paradigm, by generalizing from spurious counterexample traces to larger sets of correct traces. We integrate classical CEGAR generalization with orthogonal generalization across interleavings. Thereby, we are able to prove correctness of programs otherwise out-of-reach for interpolation-based verification. The competition results show significant advantages over other concurrency approaches in the Ultimate family.
Wit4Java: A Violation-Witness Validator for Java Verifiers (Competition Contribution)
Authors: Wu Tong , Schrammel Peter , Cordeiro Lucas C.
Published: March 2022

We describe and evaluate a violation-witness validator for Java verifiers called Wit4Java. It takes a Java program with a safety property and the respective violation-witness output by a Java verifier to generate a new Java program whose execution deterministically violates the property. We extract the value of the program variables from the counterexample represented by the violation-witness and feed this information back into the original program. In addition, we have two implementations for instantiating source programs by injecting counterexamples. Experimental results show that Wit4Java can correctly validate the violation-witnesses produced by JBMC and GDart in a few seconds.
A Direct Symbolic Algorithm for Solving Stochastic Rabin Games
Authors: Banerjee Tamajit , Majumdar Rupak , Mallik Kaushik , Schmuck Anne-Kathrin , Soudjani Sadegh
Published: March 2022

We consider turn-based stochastic 2-player games on graphs with$$\omega $$ω-regular winning conditions. We provide a direct symbolic algorithm for solving such games when the winning condition is formulated as a Rabin condition. For a stochastic Rabin game withkpairs over a game graph withnvertices, our algorithm runs in$$O(n^{k+2}k!)$$O(nk+2k!)symbolic steps, which improves the state of the art.

We have implemented our symbolic algorithm, along with performance optimizations including parallellization and acceleration, in a BDD-based synthesis tool called . We demonstrate the superiority of compared to the state of the art on a set of synthetic benchmarks derived from the VLTS benchmark suite and on a control system benchmark from the literature. In our experiments, performed significantly faster with up totwoorders of magnitude improvement in computation time.
Sky Is Not the Limit
Authors: Havlena Vojtěch , Lengál Ondřej , Šmahlíková Barbora
Published: March 2022

We propose several heuristics for mitigating one of the main causes of combinatorial explosion in rank-based complementation of Büchi automata (BAs): unnecessarily high bounds on the ranks of states. First, we identifyelevator automata, which is a large class of BAs (generalizing semi-deterministic BAs), occurring often in practice, where ranks of states are bounded according to the structure of strongly connected components. The bounds for elevator automata also carry over to general BAs that contain elevator automata as a sub-structure. Second, we introduce two techniques for refining bounds on the ranks of BA states using data-flow analysis of the automaton. We implement out techniques as an extension of the toolRankerfor BA complementation and show that they indeed greatly prune the generated state space, obtaining significantly better results and outperforming other state-of-the-art tools on a large set of benchmarks.
Distributed Coalgebraic Partition Refinement
Authors: Birkmann Fabian , Deifel Hans-Peter , Milius Stefan
Published: March 2022

Partition refinement is a method for minimizing automata and transition systems of various types. Recently we have developed a partition refinement algorithm and the tool that is generic in the transition type of the input system and matches the theoretical run time of the best known algorithms for many concrete system types. Genericity is achieved by modelling transition types as functors on sets and systems as coalgebras. Experimentation has shown that memory consumption is a bottleneck for handling systems with a large state space, while running times are fast. We have therefore extended an algorithm due to Blom and Orzan, which is suitable for a distributed implementation to the coalgebraic level of genericity, and implemented it in . Experiments show that this allows to handle much larger state spaces. Running times are low in most experiments, but there is a significant penalty for some.
Revisiting type-II see-saw: present limits and future prospects at LHC
Authors: Ashanujjaman Saiyad , Ghosh Kirtiman
Published: March 2022

Abstract

The type-II see-saw mechanism based on the annexation of the Standard Model by weak gauge triplet scalar field proffers a natural explanation for the very minuteness of neutrino masses. Noting that the phenomenology for the non-degenerate triplet Higgs spectrum is substantially contrasting than that for the degenerate one, we perform a comprehensive study for an extensive model parameter space parametrised by the triplet scalar vacuum expectation value (VEV), the mass-splitting between the triplet-like doubly and singly charged scalars and the mass of the doubly charged scalar. Considering all Drell-Yan production mechanisms for the triplet-like scalars and taking into account the all-encompassing complexity of their decays, we derive the most stringent 95% CL lower limits on the mass of the doubly charged scalar for a vast model parameter space by implementing already existing direct collider searches by CMS and ATLAS. These estimated limits are stronger by approximately 50–230 GeV than those reported by CMS and ATLAS. Strikingly, we also find a specific region of the parameter space that is beyond the reach of the existing LHC search strategies. Then, we forecast future limits by extending an ATLAS search at high-luminosity, and we propose a search strategy that yields improved limits for a part of the parameter space.