bluuebunny/crossref_metadata_2025 huggingface dataset:
The IL‐21‐TET2‐AIM2‐c‐MAF pathway drives the T follicular helper cell response in lupus‐like disease
Authors: Wu Haijing , Deng Yaxiong , Long Di , Yang Ming , Li Qianwen , Feng Yu , Chen Yongjian , Qiu Hong , Huang Xin , He Zhenghao , Hu Longyuan , Yin Heng , Li Guangdi , Guo Yunkai , Du Wenhan , Zhao Ming , Lu Liwei , Lu Qianjin
Published: March 2022

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves T follicular helper (TFH) cell‐mediated humoral immune responses. Absent in melanoma 2 (human AIM2 and murine Aim2) is a well‐known component of the inflammasome in the innate immune system. Surprisingly, we observed that in SLE patients, upregulated levels of AIM2 expression were found in peripheral blood and skin lesions, with the highest levels detected in TFH‐like cells. In the CD4creAim2fl/fl conditional knockout mice, a markedly reduced TFH cell response was observed, with significantly lower levels of serum autoantibodies and proteinuria, as well as profoundly reduced renal IgG deposition in pristane‐induced lupus mice. Mechanistically, IL‐21 was found to recruit hydroxymethyltransferase ten‐eleven translocation 2 (TET2) to the AIM2 promoter, resulting in DNA demethylation and increased transcription of AIM2. In addition, AIM2 could regulate c‐MAF expression to enhance IL‐21 production, which consequently promoted TFH cell differentiation. Our results have identified a role of AIM2 in promoting the TFH cell response and further revealed that the IL‐21‐TET2‐AIM2‐c‐MAF signalling pathway is dysregulated in lupus pathogenesis, which provides a potential therapeutic target for SLE.
Functional diversity regulates the effects of habitat degradation on biocrust phylogenetic and taxonomic diversities
Authors: Concostrina‐Zubiri Laura , Prieto María , Hurtado Pilar , Escudero Adrián , Martínez Isabel
Published: March 2022

Biocrusts are major contributors to dryland diversity, functioning, and services. However, little is known about how habitat degradation will impact multiple facets of biocrust diversity and measurable functional traits. We evaluated changes in taxonomic, functional, and phylogenetic diversity of biocrust‐forming lichens along a habitat degradation gradient related to the presence of linear infrastructure (i.e., a road) and a profound agricultural driven transformation. To do so, we selected 50 remnants of a Mediterranean shrubland. We considered several surrogates of habitat quality and causal disturbance on the various diversity facets of biocrusts by using structural equation modeling, hypothesizing that habitat degradation primarily affects functional diversity, which in turn regulates changes in taxonomic and phylogenetic diversities, and also that taxonomic and phylogenetic diversities are coupled. Fragment connectivity, distance to linear infrastructure (i.e., a road) and, particularly, soil fertility (i.e., soil P concentration), had mostly negative effects on biocrust functional diversity, which in turn affected both taxonomic and phylogenetic diversities. However, we found no direct effects of habitat degradation variables on the taxonomic and phylogenetic diversities. We also found that increases in phylogenetic diversity had a positive effect on taxonomic diversity along the habitat degradation gradient. Our results indicate that functional diversity of biocrusts is strongly affected by habitat degradation, which may profoundly alter their contribution to ecosystem functioning and services. Furthermore, functional diversity regulates the response of biocrust taxonomic and phylogenetic diversity to habitat degradation. These findings indicate that habitat degradation alters and simplifies the diversity of functional traits of biocrust‐forming lichens, leading to biodiversity loss, with important consequences for the conservation of global drylands biodiversity.
Suspicion, screening, and diagnosis of wild‐type transthyretin amyloid cardiomyopathy: a systematic literature review
Authors: Bay Katrine , Gustafsson Finn , Maiborg Michael , Bagger‐Bahnsen Anne , Strand Anne Mette , Pilgaard Trine , Poulsen Steen Hvitfeldt
Published: March 2022

Wild‐type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non‐invasive diagnosis by bone scintigraphy, and the development of disease‐modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at‐risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light‐chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at‐risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high‐quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at‐risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
Detecting spontaneous deception in the brain
Authors: Feng Yen‐Ju , Hung Shao‐Min , Hsieh Po‐Jang
Published: March 2022

Deception detection can be of great value during the juristic investigation. Although the neural signatures of deception have been widely documented, most prior studies were biased by difficulty levels. That is, deceptive behavior typically required more effort, making deception detection possibly effort detection. Furthermore, no study has examined the generalizability across instructed and spontaneous responses and across participants. To explore these issues, we used a dual‐task paradigm, where the difficulty level was balanced between truth‐telling and lying, and the instructed and spontaneous truth‐telling and lying were collected independently. Using Multivoxel pattern analysis, we were able to decode truth‐telling versus lying with a balanced difficulty level. Results showed that the angular gyrus (AG), inferior frontal gyrus (IFG), and postcentral gyrus could differentiate lying from truth‐telling. Critically, linear classifiers trained to distinguish instructed truthful and deceptive responses could correctly differentiate spontaneous truthful and deceptive responses in AG and IFG with above‐chance accuracy. In addition, with a leave‐one‐participant‐out analysis, multivoxel neural patterns from AG could classify if the left‐out participant was lying or not in a trial. These results indicate the commonality of neural responses subserved instructed and spontaneous deceptive behavior as well as the feasibility of cross‐participant deception validation.
Testing a digitally distributed method to recruit a network of community organizations to fight the consequences of the drug epidemic: A study in 13 American states
Authors: Jung Haesung , Sunderrajan Aashna , Durantini Marta , Sanchez Edgardo , Windsor Liliane , Chan Man‐Pui Sally , O'Brien Thomas , Fayaz Farkhad Bita , Karan Alex , Lee Carol A. , Kwon Soonhyung , Albarracín Dolores
Published: March 2022

To mitigate the opioid epidemic, a concerted effort to educate, prevent, diagnose, treat, and engage residents is required. In this study, a digitally distributed method to form a large network of organizations was tested with 99 counties in regions with high vulnerability to hepatitis C virus (HCV). The method involved a cascade of contacts going from email to phone calls, to videoconferencing and measuring the number of contacts required, amount of time taken, and the proportion of success at recruiting at least one community organization per county. A recruitment period of 5 months and 2118 contact attempts led to the recruitment of organizations from 73 out of our 99 target counties. Organizations belonging to health departments required more attempts and time to recruit but ultimately enrolled at higher rates than did other organizations such as coalitions and agencies. Organizations from counties more (vs. less) vulnerable to HCV outbreaks required more attempts to recruit and, using multiple recruitment methods (e.g., emails, phone calls, and Zoom meetings), improved enrollment success. Overall, this method proved to be successful at remotely engaging a large‐scale network of communities with different levels of risk within a large geographic region.
The influence of reinforcement schedule on experience‐dependent changes in motivation
Authors: Johnson Amy R. , Christensen Brooke A. , Kelly Shannon J. , Calipari Erin S.
Published: March 2022

The progressive ratio procedure is used across fields to assess motivation for different reinforcers, define the effects of experimental interventions on motivation, and determine experience‐dependent changes in motivation. However, less is known about how operant training schedules affect performance on this widely utilized task. Here we designed an experiment to examine the effect of variable ratio versus fixed ratio training schedules of reinforcement on progressive ratio performance while holding other performance variables constant between groups. We found a robust increase in maximum ratio completed between the pretest and posttraining test highlighting a robust training effect on progressive ratio performance. However, it did not matter if the training was under a fixed or variable ratio schedule. Additionally, we show that neither individual rates during training nor extinction responding correlated with maximum ratio achieved during the sessions. Finally, we show that rates during the training sessions do correlate with extinction performance, suggesting that these variables measure a different aspect of performance that does not predict motivation.
A synthesis of [14C]formamidine acetate
Authors: Filer Crist N. , Ullas Giliyar V.
Published: March 2022

The one‐step synthesis of [14C]formamidine acetate from [14C]barium cyanamide is described with product characterization by TLC and proton NMR.
Tough and Fatigue Resistant Cellulose Nanocrystal Stitched Ti3C2Tx MXene Films
Authors: Usman Ken Aldren S. , Bacal Christine Jurene O. , Zhang Jizhen , Qin Si , Lynch Peter A. , Mota‐Santiago Pablo , Naebe Minoo , Henderson Luke C. , Hegh Dylan Y. , Razal Joselito M.
Published: March 2022

Ti3C2Tx MXene (or “MXene” for simplicity) has gained noteworthy attention for its metal‐like electrical conductivity and high electrochemical capacitance—a unique blend of properties attractive toward a wide range of applications such as energy storage, healthcare monitoring, and electromagnetic interference shielding. However, processing MXene architectures using conventional methods often deals with the presence of defects, voids, and isotropic flake arrangements, resulting in a trade‐off in properties. Here, a sequential bridging (SB) strategy is reported to fabricate dense, freestanding MXene films of interconnected flakes with minimal defects, significantly enhancing its mechanical properties, specifically tensile strength (≈285 MPa) and breaking energy (≈16.1 MJ m–3), while retaining substantial values of electrical conductivity (≈3050 S cm–1) and electrochemical capacitance (≈920 F cm–3). This SB method first involves forming a cellulose nanocrystal‐stitched MXene framework, followed by infiltration with structure‐densifying calcium cations (Ca2+), resulting in tough and fatigue resistant films with anisotropic, evenly spaced, and strongly interconnected flakes — properties essential for developing high‐performance energy‐storage devices. It is anticipated that the knowledge gained in this work will be extended toward improving the robustness and retaining the electronic properties of 2D nanomaterial‐based macroarchitectures.
Thumbs up for electrodiagnosis in neonatal brachial plexopathy
Authors: Karakis Ioannis
Published: March 2022

See article on pages 24–30 in this issue.
Mining and Competing Sovereignties in New Caledonia
Authors: Le Meur Pierre‐Yves , Levacher Claire
Published: March 2022

Mining, especially nickel mining, has a long history in New Caledonia and cannot be separated from the trajectory of this territory as a settler colony. However, the construction of mining as a political stake and resource in the New Caledonian public arenas has come surprisingly late, only emerging explicitly in the 1990s as pro‐independence parties pushed the issue to the fore in their negotiations with the French state and anti‐independence parties. Nickel mining and processing became part of the claim for sovereignty in the form of a ‘resource nationalism’ discourse. This paper discusses the multi‐layered nature of sovereignty through the theoretical propositions of Richard Joyce on ‘competing sovereignties’ (2013) to illustrate both the complexities of a decolonization situation that has lasted for 20 years and the challenges posed to sovereignty by mining.
Social adaptation can reduce the strength of social–ecological feedbacks from ecosystem degradation
Authors: Bartelet Henry A. , Barnes Michele L. , Zoeller Kim C. , Cumming Graeme S.
Published: March 2022

Feedbacks between people and ecosystems are central to the study of social–ecological systems (SES) but remain poorly understood. It is commonly assumed that changes in ecosystems leading to a reduction in ecosystem services will trigger human responses that seek to restore service provision. Other responses are possible, however, but remain less studied.

We evaluated the effect of environmental change, specifically the degradation of coral reefs, on the supply of and demand for a cultural ecosystem service (CES); that is, recreation. We found that declines in coral cover reduced demand for recreational ecosystem services but had no apparent effect on the benefits received from recreation.

While this finding seems counter‐intuitive given previous experimental data that suggest ecosystem quality affects people's satisfaction, our analysis suggests that social adaptation could have mediated the anticipated negative impact of environmental change on CES benefits. We propose four mechanisms that may explain this effect and that require further research: spatial diversification; (service) substitution; shifting baselines; and time‐delayed effects.

Our findings emphasize the importance of human culture and perception as influences on human responses to environmental change, and the relevance of the more subjective elements of social systems for understanding social–ecological feedbacks.

Read the free Plain Language Summary for this article on the Journal blog.
Artificial intelligence to identify genetic alterations in conventional histopathology
Authors: Cifci Didem , Foersch Sebastian , Kather Jakob Nikolas
Published: March 2022

Precision oncology relies on the identification of targetable molecular alterations in tumor tissues. In many tumor types, a limited set of molecular tests is currently part of standard diagnostic workflows. However, universal testing for all targetable alterations, especially rare ones, is limited by the cost and availability of molecular assays. From 2017 to 2021, multiple studies have shown that artificial intelligence (AI) methods can predict the probability of specific genetic alterations directly from conventional hematoxylin and eosin (H&E) tissue slides. Although these methods are currently less accurate than gold standard testing (e.g. immunohistochemistry, polymerase chain reaction or next‐generation sequencing), they could be used as pre‐screening tools to reduce the workload of genetic analyses. In this systematic literature review, we summarize the state of the art in predicting molecular alterations from H&E using AI. We found that AI methods perform reasonably well across multiple tumor types, although few algorithms have been broadly validated. In addition, we found that genetic alterations inFGFR,IDH,PIK3CA,BRAF,TP53, and DNA repair pathways are predictable from H&E in multiple tumor types, while many other genetic alterations have rarely been investigated or were only poorly predictable. Finally, we discuss the next steps for the implementation of AI‐based surrogate tests in diagnostic workflows. © 2022 The Authors.The Journal of Pathologypublished by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Noninvasive prenatal testing of hereditary colorectal cancer syndromes using cell‐free DNA in maternal plasma
Authors: Wang Yao , Li Suqing , Wu Di , Yan Hongli
Published: March 2022

Objective

This study aimed to establish a practical protocol for early noninvasive prenatal testing (NIPT) for fetuses at risk of Peutz‐Jeghers syndrome or familial adenomatous polyposis, two classical types of hereditary colorectal cancer syndromes, for risk evaluation and whole‐life monitoring.

Method

Target enrichment was performed using hybridization probes coordinating the serine‐threonine kinase 11 gene region and APC gene region, with 1458 highly heterozygous Single Nucleotide Polymorphisms included. Semitarget amplification random sequencing was used for large fragment deletion detection. For relative haplotype dosage (RHDO) analysis, haplotype construction was performed by segmented haplotype estimation and imputation tool software, the circular binary segmentation algorithm was used for recombination event calculation, and Bayes factor was used for the determination of whether the fetus was affected.

Results

Haplotypes were successfully constructed in the nine recruited families with different pedigree characteristics, and the results for the RHDO analysis were consistent with the amniocentesis sampling detection results. The cell‐free fetal DNA fraction can be detected as low as 2% in maternal plasma.

Conclusion

This is the first NIPT assay on hereditary colorectal cancer syndromes based upon RHDO analysis.
Contribution of pharmaceutical drugs of dependence to the incidence of neonatal abstinence syndrome in Western Australia between 2003 and 2018
Authors: Kelty Erin A. , Cumming Craig N. , Preen David B.
Published: March 2022

Study objective

The aim of this study was to examine the incidence of neonatal abstinence syndrome (NAS) in Western Australia (WA) and estimate the contribution of pharmaceutical drugs of dependence (PDD) to NAS.

Design

A population‐based birth cohort study.

Data source

Neonates were identified through the Midwives Notification Scheme. Linked medication dispensing and hospital records were used to identify exposure to PDD and NAS diagnosis.

Patients

All live born neonates born in WA between 2003 and 2018.

Measurements

The incidence of NAS and percentage of NAS diagnoses associated with exposure to PDD.

Main results

During the study period, the incidence of NAS did not significantly change (annual percentage change (APC): 0.6, 95%CI: −1.3, 2.6), with 3.8 neonates per 1,000 live births diagnosed with NAS. PDD were dispensed to 41.4% of mothers of neonates with NAS, with PDD used to treat opioid use disorders the most commonly prescribed (35.2% of neonates with NAS), while opioid PDD used in the treatment of pain contributed to 5.2% of NAS cases. Non‐opioid PDD contributed to 1.7% of cases of NAS. The incidence of NAS associated with the use of opioids used to treat opioid use disorders (OUD) decreased over the study period (APC: −6.5, 95%CI: −9.5, −3.4), while NAS associated with opioids used to treat pain remained stable (APC: −2.7, 95%CI: −7.1, 1.9).

Conclusion

The incidence of neonatal abstinence syndrome in WA remained stable from 2003 to 2018. Medications used to treat opioid use disorders were a substantial driver of NAS, although NAS associated with these medications has declined over time.
Robot joint friction compensation learning enhanced by 6D virtual sensor
Authors: Roveda Loris , Bussolan Andrea , Braghin Francesco , Piga Dario
Published: March 2022

High‐performance robot control is one of the most investigated topics in both research and industry. Being able to compensate for robot dynamics is indeed one major challenge. Joint friction is commonly the main issue, especially in sensorless (i.e., no availability of torque/force sensors) compliance‐controlled robots for interaction application purposes. The presented paper aims to propose a methodology for sensorless Cartesian impedance controlled robots to learn local friction compensation controllers. Exploiting a 6D virtual sensor to quantify the joint friction effects, a Bayesian optimization (BO)‐based algorithm is proposed to minimize the estimated external interaction in free‐motion tasks (related to friction effects). The BO algorithm enhances the impedance control performance by tuning the model‐based friction compensator parameters. To validate the proposed approach, experimental tests have been executed on a Franka EMIKA panda robot, highlighting the suitability of the proposed 6D virtual sensor and BO‐based algorithm to minimize the estimated external interaction for joint friction compensation purposes.
Finite‐time tracking for state‐constrained strict‐feedback systems without feasibility conditions
Authors: Li Zeqiang , Wang Yujuan
Published: March 2022

This paper investigates the finite‐time tracking control problem for a class of nonlinear strict‐feedback systems subject to asymmetric and time‐varying full‐state constraints. The proposed method is able to achieve practical finite‐time tracking stability without the feasibility conditions, that is, the tracking error converges to a small region around zero in a finite time that can be explicitly expressed and adjusted, which is different from most existing results on strict‐feedback systems subject to constraints where only ultimately uniformly bounded results are obtained and the feasibility conditions are normally required. Three major design steps are utilized. Firstly, by introducing a novel barrier function, the technical obstacle associated with the feasibility conditions is removed; Secondly, to circumvent the technical difficulty in finite‐time stability analysis, a time‐varying index is introduced and incorporated into the adaptive law; And thirdly, both a linear feedback term and a fractional feedback term are included into the virtual filter of the dynamic surface control‐based method. It is the combination of these design skills that allows the practical finite‐time tracking results to be established. The effectiveness of the proposed scheme is verified by the numerical simulation.
PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State
Authors: Green Brenda J. , Marazzini Margherita , Hershey Ben , Fardin Amir , Li Qingsen , Wang Zongjie , Giangreco Giovanni , Pisati Federica , Marchesi Stefano , Disanza Andrea , Frittoli Emanuela , Martini Emanuele , Magni Serena , Beznoussenko Galina V. , Vernieri Claudio , Lobefaro Riccardo , Parazzoli Dario , Maiuri Paolo , Havas Kristina , Labib Mahmoud , Sigismund Sara , Fiore Pier Paolo Di , Gunby Rosalind H. , Kelley Shana O. , Scita Giorgio
Published: March 2022

Circulating tumor cell (CTC) clusters are associated with increased metastatic potential and worse patient prognosis, but are rare, difficult to count, and poorly characterized biophysically. The PillarX device described here is a bimodular microfluidic device (Pillar‐device and an X‐magnetic device) to profile single CTCs and clusters from whole blood based on their size, deformability, and epithelial marker expression. Larger, less deformable clusters and large single cells are captured in the Pillar‐device and sorted according to pillar gap sizes. Smaller, deformable clusters and single cells are subsequently captured in the X‐device and separated based on epithelial marker expression using functionalized magnetic nanoparticles. Clusters of established and primary breast cancer cells with variable degrees of cohesion driven by different cell‐cell adhesion protein expression are profiled in the device. Cohesive clusters exhibit a lower deformability as they travel through the pillar array, relative to less cohesive clusters, and have greater collective invasive behavior. The ability of the PillarX device to capture clusters is validated in mouse models and patients of metastatic breast cancer. Thus, this device effectively enumerates and profiles CTC clusters based on their unique geometrical, physical, and biochemical properties, and could form the basis of a novel prognostic clinical tool.
Artificial Nanoplatelets Depend on Size for Precisely Inducing Thrombosis in Tumor Vessels
Authors: Zong Xiaoqing , Liu Lamei , Yang Haiyuan , Wu Jinpei , Yuan Pengfei , Chen Xinjie , Yang Caiqi , Li Xiaodi , Li Yuchao , Ji Xin , Shi Changzheng , Xue Wei , Dai Jian
Published: March 2022

Due to the heterogeneity of a tumor, the tumor vascular interruption‐based therapy has become an ideal treatment strategy. Herein, artificial nanoplatelets are reported to induce selective thrombosis in tumor vessels, which can achieve rapid and large‐scale necrosis of tumor cells. For one, the nanoplatelets are exploited to specially release thrombin into target regions without affecting the established coagulation factors system. For another, the thrombin elicits vascular infarction to provide tumor‐ablation effects. More importantly, the size‐dependent effect of nanoplatelets (with diameters of 200, 400, and 800 nm) in vivo on blocking the tumor vessels is evaluated. The results show that the nanoplatelets from nanometer to submicron have achieved different biodistribution and therapeutic effects through the vascular transport. Notably, 400 nm scale nanoplatelets can induce thrombosis in tumor vessels and achieve 83% of the tumor elimination rate, thus manifesting the effectiveness of anti‐tumor strategy compared with the other two scales of nanoplatelets (200 and 800 nm). These findings highlight the need of concern about nanoparticle size, providing a promising strategy for the future design of advanced vascular targeting reagents and the clinical translation of tumor vascular interruption‐based therapy.
A first-order logic characterisation of safety and co-safety languages
Authors: Cimatti Alessandro , Geatti Luca , Gigante Nicola , Montanari Angelo , Tonetta Stefano
Published: March 2022

Linear Temporal Logic ($$\mathsf {LTL}$$
LTL
) is one of the most popular temporal logics, that comes into play in a variety of branches of computer science. Its widespread use is also due to its strong foundational properties. One of them is Kamp’s theorem, showing that $$\mathsf {LTL}$$
LTL
and the first-order theory of one successor ($$\mathsf {S1S}[\mathsf {FO}]$$

S
1
S

[
FO
]

) are expressively equivalent. Safety and co-safety languages, where a finite prefix suffices to establish whether a word does not or does belong to the language, respectively, play a crucial role in lowering the complexity of problems like model checking and reactive synthesis for $$\mathsf {LTL}$$
LTL
. $$\mathsf {Safety\text {-} \mathsf {LTL}}$$

Safety
-
LTL

(resp., $$\mathsf {coSafety\text {-} \mathsf {LTL}}$$

coSafety
-
LTL

) is a fragment of $$\mathsf {LTL}$$
LTL
where only universal (resp., existential) temporal modalities are allowed, that recognises safety (resp., co-safety) languages only. In this paper, we introduce a fragment of $$\mathsf {S1S}[\mathsf {FO}]$$

S
1
S

[
FO
]

, called $$\mathsf {Safety\text {-} FO}$$

Safety
-
FO

, and its dual $$\mathsf {coSafety\text {-} FO}$$

coSafety
-
FO

, which are expressively complete with regards to the $$\mathsf {LTL}$$
LTL
-definable safety languages. In particular, we prove that they respectively characterise exactly $$\mathsf {Safety\text {-} \mathsf {LTL}}$$

Safety
-
LTL

and $$\mathsf {coSafety\text {-} \mathsf {LTL}}$$

coSafety
-
LTL

, a result that joins Kamp’s theorem, and provides a clearer view of the charactisations of (fragments of) $$\mathsf {LTL}$$
LTL
in terms of first-order languages. In addition, it gives a direct, compact, and self-contained proof that any safety language definable in $$\mathsf {LTL}$$
LTL
is definable in $$\mathsf {Safety\text {-} \mathsf {LTL}}$$

Safety
-
LTL

as well. As a by-product, we obtain some interesting results on the expressive power of the weak tomorrow operator of $$\mathsf {Safety\text {-} \mathsf {LTL}}$$

Safety
-
LTL

interpreted over finite and infinite traces.
Modal Logics and Local Quantifiers: A Zoo in the Elementary Hierarchy
Authors: Fervari Raul , Mansutti Alessio
Published: March 2022

We study a family of modal logics interpreted on tree-like structures, and featuring local quantifiers $$\exists ^{k}p$$

∃
k

p

that bind the proposition p to worlds that are accessible from the current one in at most k steps. We consider a first-order and a second-order semantics for the quantifiers, which enables us to relate several well-known formalisms, such as hybrid logics, $$\textsf {S5Q}$$

S
5
Q

and graded modal logic. To better stress these connections, we explore fragments of our logics, called herein round-bounded fragments. Depending on whether first or second-order semantics is considered, these fragments populate the hierarchy $${2\textsc {NExp} \subset 3\textsc {NExp} \subset \cdots }$$

2
NE

X
P

⊂
3
NE

X
P

⊂
⋯

or the hierarchy $${2\textsc {AExp}_{pol} \subset 3\textsc {AExp}_{pol} \subset \cdots }$$

2
AE

X
P

pol

⊂
3
AE

X
P

pol

⊂
⋯

, respectively. For formulae up-to modal depth k, the complexity improves by one exponential.
The Different Shades of Infinite Session Types
Authors: Gay Simon J. , Poças Diogo , Vasconcelos Vasco T.
Published: March 2022

Many type systems include infinite types. In session type systems, infinite types are important because they specify communication protocols that are unbounded in time. Usually infinite session types are introduced as simple finite-state expressions "Equation missing" or by non-parametric equational definitions "Equation missing". Alternatively, some systems of label- or value-dependent session types go beyond simple recursive types. However, leaving dependent types aside, there is a much richer world of infinite session types, ranging through various forms of parametric equational definitions, to arbitrary infinite types in a coinductively defined space. We study infinite session types across a spectrum of shades of grey on the way to the bright light of general infinite types. We identify four points on the spectrum, characterised by different styles of equational definitions, and show that they form a strict hierarchy by establishing bidirectional correspondences with classes of automata: finite-state, 1-counter, pushdown and 2-counter. This allows us to establish decidability and undecidability results for type formation, type equivalence and duality in each class of types. We also consider previous work on context-free session types (and extend it to higher-order) and nested session types, and locate them on our spectrum of infinite types.
Complete and tractable machine-independent characterizations of second-order polytime
Authors: Hainry Emmanuel , Kapron Bruce M. , Marion Jean-Yves , Péchoux Romain
Published: March 2022

The class of Basic Feasible Functionals $$\mathtt{BFF}$$
BFF
is the second-order counterpart of the class of first-order functions computable in polynomial time. We present several implicit characterizations of $$\mathtt{BFF}$$
BFF
based on a typed programming language of terms. These terms may perform calls to imperative procedures, which are not recursive. The type discipline has two layers: the terms follow a standard simply-typed discipline and the procedures follow a standard tier-based type discipline. $$\mathtt{BFF}$$
BFF
consists exactly of the second-order functionals that are computed by typable and terminating programs. The completeness of this characterization surprisingly still holds in the absence of lambda-abstraction. Moreover, the termination requirement can be specified as a completeness-preserving instance, which can be decided in time quadratic in the size of the program. As typing is decidable in polynomial time, we obtain the first tractable (i.e., decidable in polynomial time), sound, complete, and implicit characterization of $$\mathtt{BFF}$$
BFF
, thus solving a problem opened for more than 20 years.
Variable binding and substitution for (nameless) dummies
Authors: Hirschowitz André , Hirschowitz Tom , Lafont Ambroise , Maggesi Marco
Published: March 2022

By abstracting over well-known properties of De Bruijn’s representation with nameless dummies, we design a new theory of syntax with variable binding and capture-avoiding substitution. We propose it as a simpler alternative to Fiore, Plotkin, and Turi’s approach, with which we establish a strong formal link. We also show that our theory easily incorporates simple types and equations between terms.
On the Translation of Automata to Linear Temporal Logic
Authors: Boker Udi , Lehtinen Karoliina , Sickert Salomon
Published: March 2022

While the complexity of translating future linear temporal logic (LTL) into automata on infinite words is well-understood, the size increase involved in turning automata back to LTL is not. In particular, there is no known elementary bound on the complexity of translating deterministic$$\omega $$ω-regular automata to LTL.

Our first contribution consists of tight bounds for LTL over a unary alphabet: alternating, nondeterministic and deterministic automata can be exactly exponentially, quadratically and linearly more succinct, respectively, than any equivalent LTL formula. Our main contribution consists of a translation of general counter-free deterministic$$\omega $$ω-regular automata into LTL formulas of double exponential temporal-nesting depth and triple exponential length, using an intermediate Krohn-Rhodes cascade decomposition of the automaton. To our knowledge, this is the first elementary bound on this translation. Furthermore, our translation preserves the acceptance condition of the automaton in the sense that it turns a looping, weak, Büchi, coBüchi or Muller automaton into a formula that belongs to the matching class of the syntactic future hierarchy. In particular, it can be used to translate an LTL formula recognising a safety language to a formula belonging to the safety fragment of LTL (over both finite and infinite words).
Categorical composable cryptography
Authors: Broadbent Anne , Karvonen Martti
Published: March 2022

We formalize the simulation paradigm of cryptography in terms of category theory and show that protocols secure against abstract attacks form a symmetric monoidal category, thus giving an abstract model of composable security definitions in cryptography. Our model is able to incorporate computational security, set-up assumptions and various attack models such as colluding or independently acting subsets of adversaries in a modular, flexible fashion. We conclude by using string diagrams to rederive the security of the one-time pad and no-go results concerning the limits of bipartite and tripartite cryptography, ruling out e.g., composable commitments and broadcasting.
Comparing the expressiveness of the $$\pi $$-calculus and CCS
Authors: van Glabbeek Rob
Published: March 2022

This paper shows that the $$\pi $$
π
-calculus with implicit matching is no more expressive than $$\mathrm {CCS}_{\gamma }$$

CCS
γ

, a variant of CCS in which the result of a synchronisation of two actions is itself an action subject to relabelling or restriction, rather than the silent action $$\tau $$
τ
. This is done by exhibiting a compositional translation from the $$\pi $$
π
-calculus with implicit matching to $$\mathrm {CCS}_{\gamma }$$

CCS
γ

that is valid up to strong barbed bisimilarity.

The full $$\pi $$
π
-calculus can be similarly expressed in $$\mathrm {CCS}_{\gamma }$$

CCS
γ

enriched with the triggering operation of Meije.

I also show that these results cannot be recreated with CCS in the rôle of $$\mathrm {CCS}_{\gamma }$$

CCS
γ

, not even up to reduction equivalence, and not even for the asynchronous $$\pi $$
π
-calculus without restriction or replication.

Finally I observe that CCS cannot be encoded in the $$\pi $$
π
-calculus.
View-Based Owicki–Gries Reasoning for Persistent x86-TSO
Authors: Bila Eleni Vafeiadi , Dongol Brijesh , Lahav Ori , Raad Azalea , Wickerson John
Published: March 2022

The rise of persistent memory is disrupting computing to its core. Our work aims to help programmers navigate this brave new world by providing a program logic for reasoning about x86 code that uses low-level operations such as memory accesses and fences, as well as persistency primitives such as flushes. Our logic, Pierogi, benefits from a simple underlying operational semantics based on views, is able to handle optimised flush operations, and is mechanised in the Isabelle/HOL proof assistant. We detail the proof rules of Pierogi and prove them sound. We also show how Pierogi can be used to reason about a range of challenging single- and multi-threaded persistent programs.
An Institutional Approach to Communicating UML State Machines
Authors: Rosenberger Tobias , Knapp Alexander , Roggenbach Markus
Published: March 2022

We present a new approach on how to provide institution-based semantics for communicating UML state machines in form of a hybrid modal logic $$\mathcal {M}^{\downarrow }_{\mathcal {D}}$$

M

D
↓

. A theoroidal comorphism maps $$\mathcal {M}^{\downarrow }_{\mathcal {D}}$$

M

D
↓

into the $$\textsc {Casl}$$

C

A
S
L

institution. This allows for symbolic reasoning on communicating UML state machines.
Ensemble updating of categorical state vectors
Authors: Loe Margrethe Kvale , Tjelmeland Håkon
Published: March 2022

An ensemble updating method for categorical state vectors is proposed. The method is based on a Bayesian view of the ensemble Kalman filter (EnKF). In the EnKF, Gaussian approximations to the forecast and filtering distributions are introduced, and the forecast ensemble is updated with a linear shift. Given that the Gaussian approximation to the forecast distribution is correct, the EnKF linear update corresponds to conditional simulation from a Gaussian distribution with mean and covariance such that the posterior samples marginally are distributed according to the Gaussian approximation to the filtering distribution. In the proposed approach for categorical vectors, the Gaussian approximations are replaced with a (possibly higher order) Markov chain model, and the linear update is replaced with simulation based on a class of decomposable graphical models. To make the update robust against errors in the assumed forecast and filtering distributions, an optimality criterion is formulated, for which the resulting optimal updating procedure can be found by solving a linear program. We explore the properties of the proposed updating procedure in a simulation example where each state variable can take three values.
Androgenic properties of the dietary supplement 5α-hydroxy-laxogenin
Authors: Beer Carolin , Keiler Annekathrin M.
Published: March 2022

Dietary supplements sold for anabolic benefits or performance enhancement often contain substances, which are non-approved and might lack quality controls. With regard to athletes, the inclusion of substances or methods in the prohibited list of the World Anti-Doping Agency is based on medical or scientific evidence. 5α-hydroxy-laxogenin is a synthetic spirostane-type steroid, which is contained in dietary supplements and advertised as anabolic agent. To date, evidence is missing on anabolic or androgenic activity of 5α-hydroxy-laxogenin. We investigated its androgenic potential in two in vitro bioassays. While no activity was observed in the yeast androgen screen, 5α-hydroxy-laxogenin was able to trans-activate the androgen receptor in human prostate cells in a dose-dependent manner. Interestingly, a biphasic response was observed with antagonistic properties at lower concentrations and agonistic effects at higher concentrations tested. The demonstrated androgenic properties of the higher concentrations demonstrate that further investigations should focus on the safety as well as on potential anabolic effects of 5α-hydroxy-laxogenin. This is of interest with regard to abuse for doping purposes.
The effect of adolescent social isolation on vulnerability for methamphetamine addiction behaviours in female rats
Authors: Webb Paige I. , Hill Timothy J. , Everett Nicholas A. , Thornton Jade L. , Cornish Jennifer L. , Baracz Sarah J.
Published: March 2022

Rationale

Stress exposure during adolescence contributes to developing a methamphetamine (METH) use disorder. However, most of the studies investigating addiction-related behaviours include only male rodents, despite METH addiction rates being higher in females. Furthermore, animal studies investigating the effects of stress on methamphetamine addiction have used only basic self-administration models which may not be sensitive to the effects of stress.

Objectives

This project explored whether adolescent isolation stress exposure increases the incidence of four key addiction-related behaviours in female rats.

Methods

Thirty-two female rat pups were caged in groups of four or individually during adolescence from postnatal (PND) day 22, with the latter being re-socialised in groups of four on PND 43. In adulthood, rats were tested for addiction-like behaviours in a METH self-administration paradigm modelling motivation to take METH, persistence in drug-seeking behaviour when METH was not available, resistance to extinction, and propensity to reinstate after a period of withdrawal.

Results

Adolescent social isolation resulted in lower METH intake during acquisition; however, the paradigm modelling drug-seeking when the drug was unavailable engendered intermittent METH bingeing in all rats, abolishing the group differences in intake during this phase. Adolescent social isolation also accelerated extinction of non-reinforced lever pressing, and increased stress-primed reinstatement, compared to the group-housed rats.

Conclusions

Adolescent social isolation stress alters various methamphetamine addiction-like behaviours in female rats.
Risk of mortality from suicide in patients with Huntington’s disease is increased compared to the general population in England
Authors: Alothman Danah , Marshall Charles R. , Tyrrell Edward , Lewis Sarah , Card Timothy , Fogarty Andrew
Published: March 2022

Objective

To examine the relative risk of suicide mortality in patients with Huntington’s disease (HD).

Methods

A case–control study design was used. We used linked electronic records from primary care, secondary care and Office for National Statistics from England from 2001 through 2019. Controls were matched to cases by general practice and suicide date. Odds ratios (ORs) were adjusted for gender and age at suicide/index date.

Results

Data were available for 594,674 individuals. Patients with HD who died from suicide were significantly younger at time of death than patients with HD who died from causes other than suicide (p < 0.001). The adjusted OR for HD was 9.2 (95% confidence intervals, CI 4.9–17.4) compared to those without HD. The increase in risk was higher amongst the younger age group who were ≤ 45.8 years at suicide/index date (OR 54.5, 95% CI 10.8–276.1).

Conclusion

The markedly elevated suicide risk in patients with HD suggests that implementation of suicide risk assessment may improve survival in individuals with these diseases, especially in younger patients.
Chemical and mechanical properties of dual-polymerizing core build-up materials
Authors: Kelch Matthias , Stawarczyk Bogna , Mayinger Felicitas
Published: March 2022

Objectives

To investigate the chemical (degree of conversion (DC)) and mechanical properties (Martens hardness (HM), elastic indentation modulus (EIT), and biaxial flexural strength (BFS)) of four dual-polymerizing resin composite core build-up materials after light- and self-polymerization.

Materials and methods

Round specimens with a diameter of 12 mm and a thickness of 1.5 mm were manufactured from CLEARFIL DC CORE PLUS (CLE; Kuraray), core·X flow (COR; Dentsply Sirona), MultiCore Flow (MUL; Ivoclar Vivadent), and Rebilda DC (REB; VOCO) (N = 96, n = 24/material). Half of the specimens were light-polymerized (Elipar DeepCure-S, 3 M), while the other half cured by self-polymerization (n = 12/group). Immediately after fabrication, the DC, HM, EIT, and BFS were determined. Data was analyzed using Kolmogorov–Smirnov, Mann–Whitney U, and Kruskal–Wallis tests, Spearman’s correlation, and Weibull statistics (p < 0.05).

Results

Light-polymerization either led to similar EIT (MUL; p = 0.119) and BFS (MUL and REB; p = 0.094–0.326) values or higher DC, HM, EIT, and BFS results (all other groups; p < 0.001–0.009). When compared with the other materials, COR showed a high DC (p < 0.001) and HM (p < 0.001) after self-polymerization and the highest BFS (p = 0.020) and Weibull modulus after light-polymerization. Positive correlations between all four tested parameters (R = 0.527–0.963, p < 0.001) were found.

Conclusions

For the tested resin composite core build-up materials, light-polymerization led to similar or superior values for the degree of conversion, Martens hardness, elastic indentation modulus, and biaxial flexural strength than observed after self-polymerization. Among the tested materials, COR should represent the resin composite core build-up material of choice due to its high chemical (degree of conversion) and mechanical (Martens hardness, elastic indentation modulus, and biaxial flexural strength) properties and its high reliability after light-polymerization. The examined chemical and mechanical properties showed a positive correlation.

Clinical relevance

The chemical and mechanical performance of dual-polymerizing resin composite core build-up materials is significantly affected by the chosen polymerization mode.
The Cohomological Hall Algebras of a Preprojective Algebra with Symmetrizer
Authors: Yang Yaping , Zhao Gufang
Published: March 2022

This paper aims at a geometric realization of the Yangian of non-simply laced type in terms of quiver with potentials. For every quiver with symmetrizer, there is an extended quiver with superpotential, whose Jacobian algebra is the generalized preprojective algebra of Geiß, Leclerc, and Schröer (Inventiones Mathematicae 209(1), 61–158, 2017). We study the cohomological Hall algebra of Kontsevich and Soibelman associated to this quiver with potential. In particular, we prove a dimensional reduction result, and provide a shuffle formula of this cohomological Hall algebra. In the case when the quiver with symmetrizer comes from a symmetrizable Cartan matrix, we prove that this shuffle algebra satisfies the relations of the Yangian associated to this Cartan matrix.