bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis
Authors: Bellomo Gaia , Rainer Carolyn , Quaranta Valeria , Astuti Yuliana , Raymant Meirion , Boyd Elzbieta , Stafferton Ruth , Campbell Fiona , Ghaneh Paula , Halloran Christopher M , Hammond Dean E , Morton Jennifer P , Palmer Daniel , Vimalachandran Dale , Jones Robert , Mielgo Ainhoa , Schmid Michael C
Published: January 2022

Objective

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease and cytotoxic chemotherapy is the standard of care treatment for patients with advanced disease. Here, we investigate how the microenvironment in PDAC liver metastases reacts to chemotherapy and its role in metastatic disease progression post-treatment, an area which is poorly understood.

Design

The impact of chemotherapy on metastatic disease progression and immune cell infiltrates was characterised using flow and mass cytometry combined with transcriptional and histopathological analysis in experimental PDAC liver metastases mouse models. Findings were validated in patient derived liver metastases and in an autochthonous PDAC mouse model. Human and murine primary cell cocultures and ex vivo patient-derived liver explants were deployed to gain mechanistical insights on whether and how chemotherapy affects the metastatic tumour microenvironment.

Results

We show that in vivo, chemotherapy induces an initial infiltration of proinflammatory macrophages into the liver and activates cytotoxic T cells, leading only to a temporary restraining of metastatic disease progression. However, after stopping treatment, neutrophils are recruited to the metastatic liver via CXCL1 and 2 secretion by metastatic tumour cells. These neutrophils express growth arrest specific 6 (Gas6) which leads to AXL receptor activation on tumour cells enabling their regrowth. Disruption of neutrophil infiltration or inhibition of the Gas6/AXL signalling axis in combination with chemotherapy inhibits metastatic growth. Chemotherapy increases Gas6 expression in circulating neutrophils from patients with metastatic pancreatic cancer and recombinant Gas6 is sufficient to promote tumour cell proliferation ex vivo, in patient-derived metastatic liver explants.

Conclusion

Combining chemotherapy with Gas6/AXL or neutrophil targeted therapy could provide a therapeutic benefit for patients with metastatic pancreatic cancer.
Efficacy ofHelicobacter pylorieradication therapy for functional dyspepsia: updated systematic review and meta-analysis
Authors: Ford Alexander C , Tsipotis Evangelos , Yuan Yuhong , Leontiadis Grigorios I , Moayyedi Paul
Published: January 2022

Objective

Functional dyspepsia (FD) is a chronic disorder that is difficult to treat.Helicobacter pylorimay contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication ofH. pylori.

Design

We searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy inH. pylori-positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT).

Results

Twenty-nine RCTs recruited 6781H.pylori-positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=−0.23, p=0.907), but the effect was larger in patients with successful eradication ofH. pylorithan with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy.

Conclusion

There is high quality evidence to suggest thatH. pylorieradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.
Selective arterial temporary flow arrest with balloons during transvenous embolization for the treatment of brain arteriovenous malformations: a feasibility study with MRI-monitored adverse events
Authors: Iosif Christina , Almeida Filho Jose Alberto , Gilbert Clara Esther , Nazemi Rafie Ali , Saleme Suzana , Rouchaud Aymeric , Mounayer Charbel
Published: January 2022

Background

The technique of endovascular transvenous embolization for brain arteriovenous malformations (AVMs) has emerged in the last 8 years as a very promising therapeutic alternative for otherwise incurable cases. Selective temporary flow arrest during transvenous endovascular embolization (TFATVE) is a novel adaptation of our previously described transvenous approach, which employs hyper-compliant balloons intra-arterially for the selective occlusion of arterial feeders during ethylene vinyl copolymer (EVOH) injection, in order to reduce intra-nidal pressure and increase nidi occlusion rates.

Methods

We performed a feasibility study of the TFATVE technique between January 2016 and April 2020. Consecutive patients were included. All patients had at least one axial brain MRI or CT in the first 48 hours following intervention, and at least one brain MRI scan within the first postoperative month, in order to detect both silent and clinically evident adverse events. Patients’ demographics, angio-architectural characteristics, total injection and procedure times, angiographic and clinical outcomes were analyzed.

Results

22 patients underwent TFATVE during transvenous endovascular treatment of brain AVMs. Among them, 86.4% were high Spetzler-Martin’s grade. Good clinical outcome (modified Rankin Scale <2) was achieved in 95.5% of the cases, with 0% of procedure-related mortality and 4.5% of clinically significant, procedure-related morbidity. Total occlusion of the nidus was achieved in >90% of the cases at the end of the procedure and angiographic stability was achieved in all cases; 100% of the cases had angiographic cure at follow-up.

Conclusions

TFATVE seems a safe and effective technique when conducted in carefully selected patients in highly specialized centers.
Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry
Authors: Sun Dapeng , Jia Baixue , Tong Xu , Kan Peter , Huo Xiaochuan , Wang Anxin , Raynald  , Ma Gaoting , Ma Ning , Gao Feng , Mo Dapeng , Song Ligang , Sun Xuan , Liu Lian , Deng Yiming , Li Xiaoqing , Wang Bo , Luo Gang , Wang Yongjun , Ren Zeguang , Miao Zhongrong
Published: January 2022

Background

Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT).

Objective

To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO).

Methods

Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score.

Results

Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12–36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001).

Conclusions

In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting.

Trial registration number

NCT03370939.
Applied genomics for identification of virulent biothreats and for disease outbreak surveillance
Authors: Nwadiugwu Martin C , Monteiro Nelson
Published: January 2022

Fortifying our preparedness to cope with biological threats by identifying and targeting virulence factors may be a preventative strategy for curtailing infectious disease outbreak. Virulence factors evoke successful pathogenic invasion, and the science and technology of genomics offers a way of identifying them, their agents and evolutionary ancestor. Genomics offers the possibility of deciphering if the release of a pathogen was intentional or natural by observing sequence and annotated data of the causative agent, and evidence of genetic engineering such as cloned vectors at restriction sites. However, to leverage and maximise the application of genomics to strengthen global interception system for real-time biothreat diagnostics, a complete genomic library of pathogenic and non-pathogenic agents will create a robust reference assembly that can be used to screen, characterise, track and trace new and existing strains. Encouraging ethical research sequencing pathogens found in animals and the environment, as well as creating a global space for collaboration will lead to effective global regulation and biosurveillance.
Neuromuscular recovery from severe- and extreme-intensity exercise in men and women
Authors: Alexander Andrew M. , Hammer Shane M. , Didier Kaylin D. , Huckaby Lillie M. , Barstow Thomas J.
Published: January 2022

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90 s following extreme-intensity exercise. However, methodological limitations mask important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120 s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed 2 severe-intensity (40, 50% MVC) and 2 extreme-intensity (70, 80% MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150 s of recovery. Each intensity significantly reduced MVC and Qpot compared with baseline. MVC was greater at Tlim (p < 0.01) and at 150 s of recovery (p = 0.004) following exercise at 80% MVC compared with severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150 s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150 s of recovery following exercise at 80% MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly.

Novelty: Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.
Stability and load-displacement behaviour of axially cyclic loaded displacement piles in sands
Authors: Rimoy Siya , Silva I. Matias , Jardine Richard J.
Published: January 2022

Uncertainties regarding the axial cyclic behaviour of piles driven into sands led to an extended programme of calibration chamber instrumented pile experiments. Broad trends are identified and interpreted with reference to normalised cyclic loading parameters Qcyclic/QT, Qmean/QT, and N. Cyclic damage is shown to be related to changes in the radial effective stress regime close to the shaft. While stable loading leads to little or no change as cycling continues in the sand masses’ effective stress regime, high-level cyclic loading can affect stresses far out into the sand mass. The ratio of the chamber diameter to pile diameter of the test system has a significant impact on outcomes. Piles installed in loose, fine sand are far more susceptible to cyclic loading than those installed in denser, coarser sand. Little or no change in pile stiffness was seen in tests that remained within the stable cyclic region, even over 10 000 or more cycles. Unstable tests lost their stiffness rapidly and metastable cases showed intermediate behaviours. The permanent deflections developed under cycling depend on the combined influence of Qcyclic/QT, Qmean/QT, and N. While model tests provide many valuable insights into the behaviour of piles driven into sand, they are unable to capture some key features observed in the field.
Compressibility and permeability of sand–silt tailings mixtures
Authors: Fan Jiying , Rowe R. Kerry , Brachman Richard W.I.
Published: January 2022

Microstructure showing the involvement of the fine and coarse grains in the soil skeleton is evaluated. Incremental loading tests using a stress-dependent permeameter are conducted on the mixtures of poorly graded sand and nonplastic fines originating from tailings. The results are compared with the published data of various tailings. It is shown that increasing the fines content from 0% to 100%, the involvement of the fine and coarse components of soil skeleton can be classified into four categories: no fines involvement (<10% fines), fines partially involved (10%−35% fines), increasing cushioning effect surrounding the coarse (35%−40% fines), and constant cushioning effect (>40% fines). At the same consolidation stress, the void ratio, e, rapidly decreases for fines less than 30%, then almost remains constant between 30% and 50% fines, and gradually increases for fines exceeding 50%. The hydraulic conductivity, k, decreases more than 20-fold as the fines content increases from 12% to 50%, then remains constant. k is proportional to [e3/(1 + e)]A and inversely proportional to S2, where A is a factor describing the effect of particle angularity and S is the specific surface. Finally, the influence of fines content on the seepage-induced internal stability is discussed.
Inuit youth and environmental research: exploring engagement barriers, strategies, and impacts
Authors: Sadowsky Hilary , Brunet Nicolas D. , Anaviapik Alex , Kublu Abraham , Killiktee Cara , Henri Dominique A.
Published: January 2022

Community leadership in Arctic environmental research is increasingly recognized as one of many pathways to Indigenous self-determination in Nunavut, Canada. While experienced Inuit hunters, trappers, and other recognized environmental knowledge experts are commonly included in research, similar opportunities for Inuit youth to meaningfully engage in environmental research remain limited. Finding ways to increase scientific literacy, particularly among Inuit youth, has been identified as an important step in the continuation of high-quality Arctic environmental research. This paper examines community perspectives on the roles and contributions of Inuit youth in environmental research in Nunavut, barriers that Inuit youth face in becoming meaningfully engaged in field-based environmental research, and strategies for enhancing Inuit youth engagement. Our study was conducted in Pond Inlet, Nunavut, and used interviews, workshops, and observation to gather stories and knowledge from community members about field- and land-based experiential learning pathways. This study found that a complex set of barriers, including a lack of credentials and support systems, among others, may inhibit meaningful Inuit youth engagement in environmental research. Key findings from the study support the view that collaborative land-based research activities can be an effective and meaningful method of enhancing scientific literacy among Inuit youth.
Dynamical robustness of collective neuronal activity upon targeted damage in interdependent networks
Authors: Faci-Lázaro Sergio , Lor Tatiana , Ródenas Guillermo , Mazo Juan J. , Soriano Jordi , Gómez-Gardeñes Jesús
Published: January 2022

In the last decades, the availability of data about the structure of social, technological and biological systems has provided important insights on the mechanisms governing their correct functioning and robustness. These mechanisms are grounded on the complex backbone of interactions among the constituents of the system, which include both topological and dynamical aspects. Here, we analyze interdependent networks composed of two layers of interacting neuronal units and explore their robustness when these synthetic cultures are subjected to damage in the form of either targeted attack or failure. Our results show that the functionality of these networks does not decrease monotonically with damage but, on the contrary, they are able to increase their level of activity when the experienced damage is sufficiently strong.
Recent Advances in 3D Human Pose Estimation: From Optimization to Implementation and Beyond
Authors: Yan Jielu , Zhou Mingliang , Pan Jinli , Yin Meng , Fang Bin
Published: January 2022

3D human pose estimation describes estimating 3D articulation structure of a person from an image or a video. The technology has massive potential because it can enable tracking people and analyzing motion in real time. Recently, much research has been conducted to optimize human pose estimation, but few works have focused on reviewing 3D human pose estimation. In this paper, we offer a comprehensive survey of the state-of-the-art methods for 3D human pose estimation, referred to as pose estimation solutions, implementations on images or videos that contain different numbers of people and advanced 3D human pose estimation techniques. Furthermore, different kinds of algorithms are further subdivided into sub-categories and compared in light of different methodologies. To the best of our knowledge, this is the first such comprehensive survey of the recent progress of 3D human pose estimation and will hopefully facilitate the completion, refinement and applications of 3D human pose estimation.
Realization of the quantum Toffoli gate based on a six-level atomic system
Authors: Chouikh A. , Said T. , Hammani M. , Bennai M.
Published: January 2022

In this paper, we propose a scheme for implementing a Toffoli gate in a system with an atom that has six levels in a lambda configuration, interacting with a high-Q cavity containing four modes. Here, we reduce a six-level system into an effective three-level behavior by applying the adiabatic elimination method. Next, we calculate the probabilities of the states of the interest as well as the fidelity. We also study the effects of photonic and atomic decay rates on the evolution of the system which is reasonably less sensitive to decoherence.
Level -1/2 Realization of Quantum N-Toroidal Algebra in Type Cn
Authors: Jing Naihuan , Wang Qianbao , Zhang Honglian
Published: January 2022

We construct a level -1/2 vertex representation of the quantum [Formula: see text]-toroidal algebra of type [Formula: see text], which is a natural generalization of the usual quantum toroidal algebra. The construction also provides a vertex representation of the quantum toroidal algebra for type [Formula: see text] as a by-product.
G-Algebra Structure on the Higher Order Hochschild Cohomology HS2∗(A,A)
Authors: Carolus Samuel , Staic Mihai D.
Published: January 2022

We present a deformation theory associated to the higher Hochschild cohomology [Formula: see text]. We also study a [Formula: see text]-algebra structure associated to this deformation theory.
On Existence of Primitive Normal Elements of Cubic Form over Finite Fields
Authors: Hazarika Himangshu , Basnet Dhiren Kumar
Published: January 2022

For a prime [Formula: see text]and a positive integer[Formula: see text], let [Formula: see text] and [Formula: see text] be the extension field of [Formula: see text]. We derive a sufficient condition for the existence of a primitive element [Formula: see text] in[Formula: see text] such that [Formula: see text] is also a primitive element of [Formula: see text], a sufficient condition for the existence of a primitive normal element [Formula: see text] in [Formula: see text] over [Formula: see text] such that [Formula: see text] is a primitive element of [Formula: see text], and a sufficient condition for the existence of a primitive normal element [Formula: see text] in [Formula: see text] over [Formula: see text] such that [Formula: see text] is also a primitive normal element of [Formula: see text] over [Formula: see text].
Quantum information effects
Authors: Heunen Chris , Kaarsgaard Robin
Published: January 2022

We study the two dual quantum information effects to manipulate the amount of information in quantum computation: hiding and allocation. The resulting type-and-effect system is fully expressive for irreversible quantum computing, including measurement. We provide universal categorical constructions that semantically interpret this arrow metalanguage with choice, starting with any rig groupoid interpreting the reversible base language. Several properties of quantum measurement follow in general, and we translate (noniterative) quantum flow charts into our language. The semantic constructions turn the category of unitaries between Hilbert spaces into the category of completely positive trace-preserving maps, and they turn the category of bijections between finite sets into the category of functions with chosen garbage. Thus they capture the fundamental theorems of classical and quantum reversible computing of Toffoli and Stinespring.
On type-cases, union elimination, and occurrence typing
Authors: Castagna Giuseppe , Laurent Mickaël , Nguyễn Kim , Lutze Matthew
Published: January 2022

We extend classic union and intersection type systems with a type-case construction and show that the combination of the union elimination rule of the former and the typing rules for type-cases of our extension encompasses
occurrence typing
. To apply this system in practice, we define a canonical form for the expressions of our extension, called MSC-form. We show that an expression of the extension is typable if and only if its MSC-form is, and reduce the problem of typing the latter to the one of reconstructing annotations for that term. We provide a sound algorithm that performs this reconstruction and a proof-of-concept implementation.
Reasoning about “reasoning about reasoning”: semantics and contextual equivalence for probabilistic programs with nested queries and recursion
Authors: Zhang Yizhou , Amin Nada
Published: January 2022

Metareasoning can be achieved in probabilistic programming languages (PPLs) using agent models that
recursively nest
inference queries inside inference queries. However, the semantics of this powerful, reflection-like language feature has defied an operational treatment, much less reasoning principles for contextual equivalence. We give formal semantics to a core PPL with continuous distributions, scoring, general recursion, and nested queries. Unlike prior work, the presence of nested queries and general recursion makes it impossible to stratify the definition of a sampling-based operational semantics and that of a measure-theoretic semantics—the two semantics must be defined mutually recursively. A key yet challenging property we establish is that probabilistic programs have well-defined meanings: limits exist for the step-indexed measures they induce. Beyond a semantics, we offer relational reasoning principles for probabilistic programs making nested queries. We construct a step-indexed, biorthogonal logical-relations model. A soundness theorem establishes that logical relatedness implies contextual equivalence. We demonstrate the usefulness of the reasoning principles by proving novel equivalences of practical relevance—in particular, game-playing and decisionmaking agents. We mechanize our technical developments leading to the soundness proof using the Coq proof assistant. Nested queries are an important yet theoretically underdeveloped linguistic feature in PPLs; we are first to give them semantics in the presence of general recursion and to provide them with sound reasoning principles for contextual equivalence.
Certifying derivation of state machines from coroutines
Authors: Ikebuchi Mirai , Erbsen Andres , Chlipala Adam
Published: January 2022

One of the biggest implementation challenges in security-critical network protocols is nested state machines. In practice today, state machines are either implemented manually at a low level, risking bugs easily missed in audits; or are written using higher-level abstractions like threads, depending on runtime systems that may sacrifice performance or compatibility with the ABIs of important platforms (e.g., resource-constrained IoT systems). We present a compiler-based technique allowing the best of both worlds, coding protocols in a natural high-level form, using freer monads to represent nested
coroutines
, which are then compiled automatically to lower-level code with explicit state. In fact, our compiler is implemented as a tactic in the Coq proof assistant, structuring compilation as search for an equivalence proof for source and target programs. As such, it is straightforwardly (and soundly) extensible with new hints, for instance regarding new data structures that may be used for efficient lookup of coroutines. As a case study, we implemented a core of TLS sufficient for use with popular Web browsers, and our experiments show that the extracted Haskell code achieves reasonable performance.
Verified compilation of C programs with a nominal memory model
Authors: Wang Yuting , Zhang Ling , Shao Zhong , Koenig Jérémie
Published: January 2022

Memory models play an important role in verified compilation of imperative programming languages. A representative one is the block-based memory model of CompCert---the state-of-the-art verified C compiler. Despite its success, the abstraction over memory space provided by CompCert's memory model is still primitive and inflexible. In essence, it uses a fixed representation for identifying memory blocks in a global memory space and uses a globally shared state for distinguishing between used and unused blocks. Therefore, any reasoning about memory must work uniformly for the global memory; it is impossible to individually reason about different sub-regions of memory (i.e., the stack and global definitions). This not only incurs unnecessary complexity in compiler verification, but also poses significant difficulty for supporting verified compilation of open or concurrent programs which need to work with contextual memory, as manifested in many previous extensions of CompCert.

To remove the above limitations, we propose an enhancement to the block-based memory model based on nominal techniques; we call it the nominal memory model. By adopting the key concepts of nominal techniques such as atomic names and supports to model the memory space, we are able to 1) generalize the representation of memory blocks to any types satisfying the properties of atomic names and 2) remove the global constraints for managing memory blocks, enabling flexible memory structures for open and concurrent programs.

To demonstrate the effectiveness of the nominal memory model, we develop a series of extensions of CompCert based on it. These extensions show that the nominal memory model 1) supports a general framework for verified compilation of C programs, 2) enables intuitive reasoning of compiler transformations on partial memory; and 3) enables modular reasoning about programs working with contextual memory. We also demonstrate that these extensions require limited changes to the original CompCert, making the verification techniques based on the nominal memory model easy to adopt.
On incorrectness logic and Kleene algebra with top and tests
Authors: Zhang Cheng , de Amorim Arthur Azevedo , Gaboardi Marco
Published: January 2022

Kleene algebra with tests (KAT) is a foundational equational framework for reasoning about programs, which has found applications in program transformations, networking and compiler optimizations, among many other areas. In his seminal work, Kozen proved that KAT subsumes propositional Hoare logic, showing that one can reason about the (partial) correctness of while programs by means of the equational theory of KAT.

In this work, we investigate the support that KAT provides for reasoning about incorrectness, instead, as embodied by O'Hearn's recently proposed incorrectness logic. We show that KAT cannot directly express incorrectness logic. The main reason for this limitation can be traced to the fact that KAT cannot express explicitly the notion of codomain, which is essential to express incorrectness triples. To address this issue, we study Kleene Algebra with Top and Tests (TopKAT), an extension of KAT with a top element. We show that TopKAT is powerful enough to express a codomain operation, to express incorrectness triples, and to prove all the rules of incorrectness logic sound. This shows that one can reason about the incorrectness of while-like programs by means of the equational theory of TopKAT.
Relational e-matching
Authors: Zhang Yihong , Wang Yisu Remy , Willsey Max , Tatlock Zachary
Published: January 2022

We present a new approach to e-matching based on relational join; in particular, we apply recent database query execution techniques to guarantee worst-case optimal run time. Compared to the conventional backtracking approach that always searches the e-graph "top down", our new relational e-matching approach can better exploit pattern structure by searching the e-graph according to an optimized query plan. We also establish the first data complexity result for e-matching, bounding run time as a function of the e-graph size and output size. We prototyped and evaluated our technique in the state-of-the-art egg e-graph framework. Compared to a conventional baseline, relational e-matching is simpler to implement and orders of magnitude faster in practice.
A Quantum interpretation of separating conjunction for local reasoning of Quantum programs based on separation logic
Authors: Le Xuan-Bach , Lin Shang-Wei , Sun Jun , Sanan David
Published: January 2022

It is well-known that quantum programs are not only complicated to design but also challenging to verify because the quantum states can have exponential size and require sophisticated mathematics to encode and manipulate. To tackle the state-space explosion problem for quantum reasoning, we propose a Hoare-style inference framework that supports local reasoning for quantum programs. By providing a quantum interpretation of the separating conjunction, we are able to infuse separation logic into our framework and apply local reasoning using a quantum frame rule that is similar to the classical frame rule. For evaluation, we apply our framework to verify various quantum programs including Deutsch–Jozsa’s algorithm and Grover's algorithm.
Static prediction of parallel computation graphs
Authors: Muller Stefan K.
Published: January 2022

Many algorithms for analyzing parallel programs, for example to detect deadlocks or data races or to calculate the execution cost, are based on a model variously known as a cost graph, computation graph or dependency graph, which captures the parallel structure of threads in a program. In modern parallel programs, computation graphs are highly dynamic and depend greatly on the program inputs and execution details. As such, most analyses that use these graphs are either dynamic analyses or are specialized static analyses that gather a subset of dependency information for a specific purpose.

This paper introduces graph types, which compactly represent all of the graphs that could arise from program execution. Graph types are inferred from a parallel program using a graph type system and inference algorithm, which we present drawing on ideas from Hindley-Milner type inference, affine logic and region type systems. We have implemented the inference algorithm over a subset of OCaml, extended with parallelism primitives, and we demonstrate how graph types can be used to accelerate the development of new graph-based static analyses by presenting proof-of-concept analyses for deadlock detection and cost analysis.
A dual number abstraction for static analysis of Clarke Jacobians
Authors: Laurel Jacob , Yang Rem , Singh Gagandeep , Misailovic Sasa
Published: January 2022

We present a novel abstraction for bounding the Clarke Jacobian of a Lipschitz continuous, but not necessarily differentiable function over a local input region. To do so, we leverage a novel abstract domain built upon dual numbers, adapted to soundly over-approximate all first derivatives needed to compute the Clarke Jacobian. We formally prove that our novel forward-mode dual interval evaluation produces a sound, interval domain-based over-approximation of the true Clarke Jacobian for a given input region.

Due to the generality of our formalism, we can compute and analyze interval Clarke Jacobians for a broader class of functions than previous works supported – specifically, arbitrary compositions of neural networks with Lipschitz, but non-differentiable perturbations. We implement our technique in a tool called DeepJ and evaluate it on multiple deep neural networks and non-differentiable input perturbations to showcase both the generality and scalability of our analysis. Concretely, we can obtain interval Clarke Jacobians to analyze Lipschitz robustness and local optimization landscapes of both fully-connected and convolutional neural networks for rotational, contrast variation, and haze perturbations, as well as their compositions.
Staging with class: a specification for typed template Haskell
Authors: Xie Ningning , Pickering Matthew , Löh Andres , Wu Nicolas , Yallop Jeremy , Wang Meng
Published: January 2022

Multi-stage programming using typed code quotation is an established technique for writing optimizing code generators with strong type-safety guarantees. Unfortunately, quotation in Haskell interacts poorly with type classes, making it difficult to write robust multi-stage programs.

We study this unsound interaction and propose a resolution, staged type class constraints, which we formalize in a source calculus λ
⇒
that elaborates into an explicit core calculus
F
. We show type soundness of both calculi, establishing that well-typed, well-staged source programs always elaborate to well-typed, well-staged core programs, and prove beta and eta rules for code quotations.

Our design allows programmers to incorporate type classes into multi-stage programs with confidence. Although motivated by Haskell, it is also suitable as a foundation for other languages that support both overloading and quotation.
Efficient algorithms for dynamic bidirected Dyck-reachability
Authors: Li Yuanbo , Satya Kris , Zhang Qirun
Published: January 2022

Dyck-reachability is a fundamental formulation for program analysis, which has been widely used to capture properly-matched-parenthesis program properties such as function calls/returns and field writes/reads. Bidirected Dyck-reachability is a relaxation of Dyck-reachability on
bidirected graphs
where each edge
u
→

(

i

v
labeled by an open parenthesis “(

i

” is accompanied with an inverse edge
v
→

)

i

u
labeled by the corresponding close parenthesis “)

i

”, and vice versa. In practice, many client analyses such as alias analysis adopt the bidirected Dyck-reachability formulation. Bidirected Dyck-reachability admits an optimal reachability algorithm. Specifically, given a graph with
n
nodes and
m
edges, the optimal bidirected Dyck-reachability algorithm computes
all-pairs
reachability information in
O
(
m
) time.

This paper focuses on the dynamic version of bidirected Dyck-reachability. In particular, we consider the problem of maintaining all-pairs Dyck-reachability information in bidirected graphs under a sequence of edge insertions and deletions. Dynamic bidirected Dyck-reachability can formulate many program analysis problems in the presence of code changes. Unfortunately, solving dynamic graph reachability problems is challenging. For example, even for maintaining transitive closure, the fastest deterministic dynamic algorithm requires
O
(
n
2
) update time to achieve
O
(1) query time. All-pairs Dyck-reachability is a generalization of transitive closure. Despite extensive research on incremental computation, there is no algorithmic development on dynamic graph algorithms for program analysis with worst-case guarantees.

Our work fills the gap and proposes the first dynamic algorithm for Dyck reachability on bidirected graphs. Our dynamic algorithms can handle each graph update (
i.e.
, edge insertion and deletion) in
O
(
n
·α(
n
)) time and support any all-pairs reachability query in
O
(1) time, where α(
n
) is the inverse Ackermann function. We have implemented and evaluated our dynamic algorithm on an alias analysis and a context-sensitive data-dependence analysis for Java. We compare our dynamic algorithms against a straightforward approach based on the
O
(
m
)-time optimal bidirected Dyck-reachability algorithm and a recent incremental Datalog solver. Experimental results show that our algorithm achieves orders of magnitude speedup over both approaches.
Multimodality in VR: A Survey
Authors: Martin Daniel , Malpica Sandra , Gutierrez Diego , Masia Belen , Serrano Ana
Published: January 2022

Virtual reality (VR) is rapidly growing, with the potential to change the way we create and consume content. In VR, users integrate multimodal sensory information they receive to create a unified perception of the virtual world. In this survey, we review the body of work addressing multimodality in VR and its role and benefits in user experience, together with different applications that leverage multimodality in many disciplines. These works thus encompass several fields of research and demonstrate that multimodality plays a fundamental role in VR, enhancing the experience, improving overall performance, and yielding unprecedented abilities in skill and knowledge transfer.
Approximate greatest common divisor of several polynomials from Hankel matrices
Authors: Belhaj Skander , Alsulami Abdulrahman
Published: January 2022

This paper is devoted to present a new method for computing the approximate Greatest Common Divisor (GCD) of several polynomials (not pairwise) from the generalized Hankel matrix. Our approach based on the calculation of cofactors is tested for several sets of polynomials.
Modified Sawhorse Waveform for the Voltammetric Detection of Oxytocin
Authors: Liu Favian A. , Ardabili Negar , Brown Izaiah , Rafi Harmain , Cook Clarice , Nikopoulou Rodanthi , Lopez Arianna , Zou Shouzhong , Hartings Matthew R. , Zestos Alexander G.
Published: January 2022

Carbon fiber microelectrodes (CFMEs) have been used to detect neurotransmitters and other biomolecules using fast-scan cyclic voltammetry (FSCV) for the past few decades. This technique measures neurotransmitters such as dopamine and, more recently, physiologically relevant neuropeptides. Oxytocin, a pleiotropic peptide hormone, is physiologically important for adaptation, development, reproduction, and social behavior. This neuropeptide functions as a stress-coping molecule, an anti-inflammatory agent, and serves as an antioxidant with protective effects especially during adversity or trauma. Here, we measure tyrosine using the Modified Sawhorse Waveform (MSW), enabling enhanced electrode sensitivity for the amino acid and oxytocin peptide. Applying the MSW, decreased surface fouling and enabled codetection with other monoamines. As oxytocin contains tyrosine, the MSW was also used to detect oxytocin. The sensitivity of oxytocin detection was found to be 3.99 ± 0.49 nA μM−1, (n = 5). Additionally, we demonstrate that applying the MSW on CFMEs allows for real time measurements of exogenously applied oxytocin on rat brain slices. These studies may serve as novel assays for oxytocin detection in a fast, sub-second timescale with possible implications for in vivo measurements and further understanding of the physiological role of oxytocin.
Synthesis and Introducing Au-Cu Alloy Nanoparticles/Porous Silicon as a Novel Modifier of Screen Printed Carbon Electrode in Simultaneous Electrocatalytic Detection of Codeine and Acetaminophen
Authors: Allahnouri Farzad , Farhadi Khalil , Imanzadeh Hamideh , Molaei Rahim , Eskandari Habibollah
Published: January 2022

In the present study, a bimetallic nanostructure of gold-copper (Au-CuNPs) was decorated on the surface of porous silicon (PSi) using an easy galvanic replacement reaction between metal ions and PSi in the presence of 0.1 M hydrofluoric acid solution. The morphology and structures of the Au-CuNPs@PSi nanocomposite were characterized using X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) energy-dispersive X-ray spectroscopy (EDX) and cyclic voltammetry (CV) techniques. Then, prepared nanocomposite was used as a modifier in screen-printed carbon electrode (SPCE) for the highly sensitive simultaneous determination of codeine (COD) and acetaminophen (ACE). The combination of PSi and metals nanoparticles provide a porous and high surface area with excellent electrical conductivity which leads to reduce the peak potentials and enhance the oxidation peak currents of COD and ACE at the surface of the Au-CuNPs@PSi/SPCE nanosensor. The dynamic linear ranges were obtained from 0.06 to 0.6 μM for both COD and ACE and the detection limits (3.0 S/N) estimated 0.35 μM for COD and 0.30 μM for ACE, respectively. Moreover, recovery tests were carried out in real samples such as urine, human blood plasma, and tablets.
ECS’s IE&EE
Authors: Savinell Robert F.
Published: January 2022

The name of our division is sometimes confused with an organization representing electrical engineers. As a matter of fact, recently I saw a Call for Papers with reference to sponsorship by the IEEE, but I didn’t recognize the symposium. As it turns out, that symposium was indeed from the dry side of the Society, and it did refer to that other society.
Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5−/− mice
Authors: Foltz Steven , Wu Fang , Ghazal Nasab , Kwong Jennifer Q. , Hartzell H. Criss , Choo Hyojung J.
Published: January 2022

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene ( ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of patients with LGMD-R12 are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5−/− mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5−/− mice were indistinguishable from wild type. Despite these differences, both male and female Ano5−/− mice exhibited exercise intolerance. Although exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5−/− female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease.
Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection
Authors: Wang Ruobing , Hume Adam J. , Beermann Mary Lou , Simone-Roach Chantelle , Lindstrom-Vautrin Jonathan , Le Suer Jake , Huang Jessie , Olejnik Judith , Villacorta-Martin Carlos , Bullitt Esther , Hinds Anne , Ghaedi Mahboobe , Rollins Stuart , Werder Rhiannon B. , Abo Kristine M. , Wilson Andrew A. , Mühlberger Elke , Kotton Darrell N. , Hawkins Finn J.
Published: January 2022

There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors angiotensin-converting enzyme 2 ( ACE2), and transmembrane protease serine 2 ( TMPRSS2). Multiciliated cells are the primary initial target of SARS-CoV-2 infection. On infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses, and treatment with remdesivir or camostat mesylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.
The Construction of University Network Education System Based on Mobile Edge Computing in the Era of Big Data
Authors: Zhu Min
Published: January 2022

This article first established a university network education system model based on physical failure repair behavior at the big data infrastructure layer and then examined in depth the complex common causes of multiple data failures in the big data environment caused by a single physical machine failure, all based on the principle of mobile edge computing. At the application service layer, a performance model based on queuing theory is first established, with the amount of available resources as a conditional parameter. The model examines important events in mobile edge computing, such as queue overflow and timeout failure. The impact of failure repair behavior on the random change of system dynamic energy consumption is thoroughly investigated, and a system energy consumption model is developed as a result. The network education system in colleges and universities includes a user login module, teaching resource management module, student and teacher management module, online teaching management module, student achievement management module, student homework management module, system data management module, and other business functions. Later, the theory of mobile edge computing proposed a set of comprehensive evaluation indicators that characterize the relevance, such as expected performance and expected energy consumption. Based on these evaluation indicators, a new indicator was proposed to quantify the complex constraint relationship. Finally, a functional use case test was conducted, focusing on testing the query function of online education information; a performance test was conducted in the software operating environment, following the development of the test scenario, and the server’s CPU utilization rate was tested while the software was running. The results show that the designed network education platform is relatively stable and can withstand user access pressure. The performance ratio indicator can effectively assist the cloud computing system in selecting a more appropriate option for the migrated traditional service system.