bluuebunny/crossref_metadata_2025 huggingface dataset:
Depletion of ESCRT ameliorates APP‐induced AD‐like symptoms in Drosophila
Authors: Zhuang Luming , Li Chenglin , Peng Fei , Xue Elleen , Li Wenzhe , Sun Xinyue , Chen Ping , Zhou Qian , Xue Lei
Published: May 2023

The amyloid‐β (Aβ) peptide, produced from amyloid precursor protein (APP) by β and γ‐secretases, has been implicated in the etiology of Alzheimer's disease (AD). However, the precise intracellular trafficking pathway of APP and its subcellular locations to produce Aβ have remained unclear. To address these issues, we established fly AD models that recapitulated multiple AD‐like symptoms by expressing human APP in the Drosophila nerve system. The ESCRT (endosomal sorting complexes required for transport) machinery regulates the sorting and trafficking of endocytosed proteins, yet its role in AD pathogenesis has not been explored in vivo. We found that knockdown of distinct ESCRT components ameliorated APP‐induced morphological and behavioral defects, including impaired wing expansion, eye degeneration, dopamine neuron loss, locomotor disability, lifespan shortening, and cognitive deficits. Mechanistically, we showed that impaired ESCRT impeded APP's intracellular transportation from early endosomes to late endosomes, resulting in reduced Aβ production and amyloid deposit load. These data suggest that APP undergoes ESCRT‐mediated endocytic trafficking, and Aβ is generated mainly in late endosomes. Our data provide the first in vivo evidence to support a physiological role of ESCRT in AD pathogenesis, suggesting that interfering with ESCRT machinery might be an alternative therapeutic strategy for AD.
Is superstitious responding a matter of detectability? A replication of Killeen (1978)
Authors: Gomes‐Ng Stephanie , Cowie Sarah , Elliffe Douglas
Published: May 2023

Organisms may sometimes behave as if a contingency exists between behavior and consequences, even if this is not actually the case. Killeen (1978) suggested that such superstition occurs because of factors that bias subjects to behave “superstitiously” rather than because of failures of discrimination. We systematically replicated Killeen's experiment and compared contingency discrimination between different consequences. Six pigeons responded in a matching‐to‐sample procedure in which a response‐independent or response‐dependent stimulus change, food delivery, or blackout occurred. The pigeons reported whether the consequence was response dependent or response independent by choosing between two side keys. Discrimination was strongest after stimulus changes, weaker after blackouts, and weakest after food deliveries. These differences persisted even after additional training, suggesting asymmetries that may reflect differences in the disruptive effects of different consequences on remembering and/or behavioral mnemonics. Importantly, the pigeons were not biased to report response‐dependent consequences unless that response was consistent with locational biases; that is, they behaved “superstitiously” when there was a reason to be biased to do so. These findings corroborate Killeen's and demonstrate that behavior may deviate from contingencies not necessarily because subjects cannot discriminate those contingencies but because they are biased to behave otherwise.
Parent perspectives on disclosing a pediatric neurofibromatosis type 1 diagnosis
Authors: Franchi Madeleine , Radtke Heather B. , Lewis Andrea M. , Moss Irene , Cofield Stacey S. , Cannon Ashley
Published: May 2023

Neurofibromatosis 1 (NF1) is a common genetic disorder typically diagnosed in childhood and characterized by cutaneous findings, nerve sheath tumors, skeletal abnormalities, malignancies, and developmental differences. Due to its variability, NF1 is an unpredictable condition that parents have concerns about discussing with their children. While there are publications addressing the disclosure of genetic conditions in general, no NF1‐specific disclosure literature exists. To fill this gap, this mixed methods study sought to evaluate the concerns, barriers, failures, or successes parents or guardians have experienced when they have or have not chosen to tell their child(ren) about an NF1 diagnosis. Parents of children between ages 0 and 17 with a diagnosis of NF1 completed a survey and some parents were selected for an interview invitation. A total of 258 surveys were completed, and 20 parents were interviewed. Interview transcripts were categorized into disclosure and non‐disclosure groups. Themes were organized into five categories based on interview questions: disclosure concerns, factors affecting disclosure/non‐disclosure, approaches to disclosure, desired resources, and recommendations for disclosure. Sentiment analysis was performed on responses about the disclosure discussion itself. Results indicated that most parents (70.5%) disclosed the NF1 diagnosis to their child and overall felt it was a positive experience. Almost one‐third of parents (29.5%) had not disclosed the diagnosis. A strong significance was identified between disclosure and severe presentation of NF1 (p = 0.0008). Parents in both groups shared similar concerns about discussing the diagnosis and multiple factors influenced the disclosure decision. Most parents approached disclosure as a process and emphasized the need to be honest and supportive of their child. Parents highlighted the need for more educational resources for children and guidance on how to disclose. These findings indicate that additional resources and support for parents would facilitate disclosure and the involvement of genetic counselors in the process would be beneficial.
Projections of suitable cultivation area for major fruit trees and climate‐type in South Korea under representative concentration pathway scenarios using the ensemble of high‐resolution regional climate models
Authors: Kim Eung‐Sup , Ahn Joong‐Bae , Shim Kyo‐Moon , Hur Jina , Jo Sera , Suh Myoung‐Seok , Cha Dong‐Hyun , Min Seung‐Ki , Kang Hyun‐Suk
Published: May 2023

This study projected the future changes in the climate‐type distribution in South Korea according to the Köppen–Trewartha climate classification (KTCC) under the representative concentration pathway (RCP) 4.5/8.5 scenarios and the future change of cultivation area of apple (Malus domestica Borkh.) and mandarin (Citrus unshiu Marc.), which are major fruit crops in South Korea, using five regional climate models with a 12.5 km horizontal resolution. According to KTCC, type temperate (D)s is dominant in most of South Korea during the reference period (1981–2005). On the other hand, it is projected that the area of Type D and Type subtropical (C) will decrease and increase, respectively, towards higher latitudes and elevations in the future under RCP4.5/8.5 scenarios. Accordingly, the cultivation areas of major fruit crops in South Korea are projected to change significantly. The cultivation area of apple (mandarin), which is a major current fruit crop in Type D (C), is projected to be reduced (expanded) as it moves towards higher latitudes and elevations in the future. Apples grown throughout South Korea in the present climate (reference period) are not expected to be cultivated in the late‐21C due to climate change. On the other hand, the cultivation area of mandarins is projected to increase steadily in the future. At present, mandarins are cultivated only in Jeju Island, which is located in the south of the South Korea. However, the cultivation area is expected to increase by 1323% in late‐21C under the RCP8.5 scenario compared to the reference period. Moreover, mandarin cultivation is projected to be possible anywhere in South Korea. Nevertheless, in late‐21C, excessive increases in temperature that exceeds the appropriate temperature for mandarin in Jeju Island and the southern part of South Korea will eventually decrease the cultivation area of mandarins.
Soil salinity estimation in Shule River Basin using support vector regression model
Authors: Tang Yingfu , Wang Zhongjing , Zhang Teng
Published: May 2023

Soil salinization is a progressive degradation process that spreads globally and leads to a decline in soil fertility. Assessing the scale of salinization is crucial for sustainable agricultural development and saline‐land rehabilitation. In this study, we proposed a support vector regression spatial (SVR‐S) model that utilizes spatial dependence information to predict soil salinity over the irrigation area of the Shule River Basin in northwestern China. To investigate the performance of the SVR‐S model, 50 soil samples were collected in the field. Semivariograms of soil salinity (measured as total salt content and ion concentrations) were constructed to measure spatial dependence. The SVR‐S model was compared with the original SVR model and the geographically weighted regression (GWR) model regarding the salinity prediction ability. The soil salinity in the experimental area demonstrated a strong spatial dependence pattern. The SVR‐S model delivered a better performance than the SVR‐O and GWR. SVR‐S showed a correlation coefficient R of 0.87 and a root mean square error (RMSE) of 1.83%, while the performance of SVR‐O (R = 0.75, RMSE = 3.32%) and GWR (R = 0.73, RMSE = 3.47%) was comparatively poor. Topographic indices integrating spatial information contributed the most to the estimation of salinity in the study area. This study provides a new approach to integrating spatial information for accurate soil salinity mapping.
Alternating projection‐based iterative learning control for discrete‐time systems with non‐uniform trial lengths
Authors: Zhuang Zhihe , Tao Hongfeng , Chen Yiyang , Rogers Eric , Oomen Tom , Paszke Wojciech
Published: May 2023

This article develops a novel framework for iterative learning control (ILC) design of discrete‐time systems with non‐uniform trial lengths by using the method of alternating projections. In contrast to existing results for the non‐uniform trial length problem, this article uses the Hilbert space setting and hence the linear discrete‐time system dynamics with non‐uniform trial lengths can be represented by multiple affine subspaces (or linear varieties). Motivated by the successive projection design between two closed convex sets, the considered ILC problem can be transformed into alternating projections between multiple sets, then the Hilbert space setting is used to establish key systems theoretic properties. Moreover, an optimal ILC design is developed for systems with non‐uniform trial lengths, which is also extended to the case of input constraints. A numerical case study is given to illustrate the applicability of the new design.
Optimizing the Electronic Structure of Atomically Dispersed Ru Sites with CoP for Highly Efficient Hydrogen Evolution in both Alkaline and Acidic Media
Authors: Wang Zhuoping , Chi Kai , Yang Shengxiong , Xiao Junwu , Xiao Fei , Zhao Xiaoxu , Wang Shuai
Published: May 2023

Developing efficient and stable electrocatalysts for hydrogen evolution reaction (HER) over a wide pH range and industrial large‐scale hydrogen production is critical and challenging. Here, a tailoring strategy is developed to fabricate an outstanding HER catalyst in both acidic and alkaline electrolytes containing high‐density atomically dispersed Ru sites anchored in the CoP nanoparticles supported on carbon spheres (NC@RuSA‐CoP). The obtained NC@RuSA‐CoP catalyst exhibits excellent HER performance with overpotentials of only 15 and 13 mV at 10 mA cm−2 in 1 m KOH and 0.5 m H2SO4, respectively. The experimental results and theoretical calculations indicate that the strong interaction between the Ru site and the CoP can effectively optimize the electronic structure of Ru sites to reduce the hydrogen binding energy and the water dissociation energy barrier. The constructed alkaline anion exchange membrane water electrolyze (AAEMWE) demonstrates remarkable durability and an industrial‐level current density of 1560 mA cm−2 at 1.8 V. This strategy provides a new perspective on the design of Ru‐based electrocatalysts with suitable intermediate adsorption strengths and paves the way for the development of highly active electrocatalysts for industrial‐scale hydrogen production.
Strain‐Engineering of Mesoporous Cs3Bi2Br9/BiVO4 S‐Scheme Heterojunction for Efficient CO2 Photoreduction
Authors: Zhou Biao , Xu Shuang , Wu Liqin , Li Mingjie , Chong Yanan , Qiu Yongcai , Chen Guangxu , Zhao Yun , Feng Chunhua , Ye Daiqi , Yan Keyou
Published: May 2023

Slow charge kinetics and unfavorable CO2 adsorption/activation strongly inhibit CO2 photoreduction. In this study, a strain‐engineered Cs3Bi2Br9/hierarchically porous BiVO4 (s‐CBB/HP‐BVO) heterojunction with improved charge separation and tailored CO2 adsorption/activation capability is developed. Density functional theory calculations suggest that the presence of tensile strain in Cs3Bi2Br9 can significantly downshift the p‐band center of the active Bi atoms, which enhances the adsorption/activation of inert CO2. Meanwhile, in situ irradiation X‐ray photoelectron spectroscopy and electron spin resonance confirm that efficient charge transfer occurs in s‐CBB/HP‐BVO following an S‐scheme with built‐in electric field acceleration. Therefore, the well‐designed s‐CBB/HP‐BVO heterojunction exhibits a boosted photocatalytic activity, with a total electron consumption rate of 70.63 µmol g−1 h−1, and 79.66% selectivity of CO production. Additionally, in situ diffuse reflectance infrared Fourier transform spectroscopy reveals that CO2 photoreduction undergoes a formaldehyde‐mediated reaction process. This work provides insight into strain engineering to improve the photocatalytic performance of halide perovskite.
Molecular Dynamics of Drying‐Induced Structural Transformations in a Single Nanocellulose
Authors: Fujisawa Shuji , Daicho Kazuho , Yurtsever Ayhan , Fukuma Takeshi , Saito Tsuguyuki
Published: May 2023

Nanocellulose is attracting attention in the field of materials science as a sustainable building block. Nanocellulose‐based materials, such as films, membranes, and foams, are fabricated by drying colloidal dispersions. However, little is known about how the structure of a single nanocellulose changes during the complex drying process. Here, all‐atom molecular dynamics simulations and atomic force microscopy is used to investigate the structural dynamics of single nanocellulose during drying. It is found that the twist morphology of the nanocellulose became localized along the fibril axis during the final stage of the drying process. Moreover, it is shown that conformational changes at C6 hydroxymethyl groups and glycoside bond is accompanied by the twist localization, indicating that the increase in the crystallinity occurred in the process. It is expected that the results will provide molecular insights into nanocellulose structures in material processing, which is helpful for the design of materials with advanced functionalities.
Top‐Emitting Quantum Dot Light‐Emitting Diodes: Theory, Optimization, and Application
Authors: Lee Taesoo , Lee Minhyung , Seo Hansol , Kim Minjun , Chun Beomsoo , Kwak Jeonghun
Published: May 2023

The superior optical properties of colloidal quantum dots (QDs) have garnered significant broad interest from academia and industry owing to their successful application in self‐emitting QD‐based light‐emitting diodes (QLEDs). In particular, active research is being conducted on QLEDs with top‐emission device architectures (TQLEDs) owing to their advantages such as easy integration with conventional backplanes, high color purity, and excellent light extraction. However, due to the complicated optical phenomena and their highly sensitive optoelectrical properties to experimental variations, TQLEDs cannot be optimized easily for practical use. This review summarizes previous studies that have investigated top‐emitting device structures and discusses ways to advance the performance of TQLEDs. First, theories relevant to the optoelectrical properties of TQLEDs are introduced. Second, advancements in device optimization are presented, where the underlying theories for each are considered. Finally, multilateral strategies for TQLEDs to enable their wider application to advanced industries are discussed. This work believes that this review can provide valuable insights for realizing commercial TQLEDs applicable to a broad range of applications.
Key Challenges to Urban Water Management in ASEAN
Authors: Ong Corinne , Tortajada Cecilia , Arora Ojasvee
Published: May 2023

The ASEAN region experiences several socio-economic and environmental challenges brought on by rapid urbanisation, rising living standards, population growth, and climate change. Such challenges are severely impacting the region’s water access and long-term security. As a response to these challenges, governments have identified urban water demand management (WDM) as one of the measures of strategic importance. WDM aims to provide water users with efficient, cost-effective, and sustainable water supplies through various mechanisms.
The DeepHypergraph Library
Authors: Dai Qionghai , Gao Yue
Published: May 2023

This chapter introduces the DeepHypergraph library, which bridges the hypergraph theory and hypergraph applications. This library provides the generation of multiple low-order structures (such as graph and directed graph), high-order structures (such as hypergraph and directed hypergraph), datasets, operations, learning methods, visualizations, etc. We first introduce the design motivation and the overall architecture of the library. Then, we introduce the “correlation structure” and “function library” of the Deephypergraph library, respectively.
Mathematical Foundations of Hypergraph
Authors: Dai Qionghai , Gao Yue
Published: May 2023

In this chapter, we introduce the mathematical foundations of hypergraph and present the mathematical notations that are used to facilitate deep understanding and analysis of hypergraph structure. A hypergraph is composed of a set of vertices and hyperedges, and it is a generalization of a graph, where a weighted hypergraph quantifies the relative importance of hyperedges or vertices. Hypergraph can also be divided into two main categories, i.e., the undirected hypergraph representation and the directed hypergraph representation. The latter one further divides the vertices in one hyperedge into the source vertex set and the target vertex set to model more complex correlations. Additionally, we discuss the relationship between hypergraph and graph from the perspective of structural transformation and expressive ability. The most intuitive difference between a simple graph and a hypergraph can be observed in the size of order and expression of adjacency. A hypergraph can be converted into a simple graph using clique expansion, star expansion, and line expansion. Moreover, the proof based on random walks and Markov chains establishes the relationship between hypergraphs with edge-independent vertex weights and weighted graphs.
Hypergraph Modeling
Authors: Dai Qionghai , Gao Yue
Published: May 2023

Hypergraph modeling is the fundamental task in hypergraph computation, which targets on establishing a high-quality hypergraph structure to accurately formulate the high-order correlation among data. In this section, we introduce different hypergraph modeling methods to show how to build hypergraphs using various pieces of information, such as features, attributes, and/or graphs. These methods are organized into two broad categories, depending on whether these correlations are explicit or implicit, to distinguish the similarities and differences. We then further discuss different hypergraph structure optimization and generation methods, such as adaptive hypergraph modeling, generative hypergraph modeling, and knowledge hypergraph generation.
Hyers-Ulam stability of a general linear partial differential equation
Authors: Ciplea Sorina Anamaria , Lungu Nicolaie , Marian Daniela , Rassias Themistocles M.
Published: May 2023

In this paper we will study Hyers-Ulam stability for a general linear partial differential equation of first order in a Banach space.
Geometric T-Duality: Buscher Rules in General Topology
Authors: Waldorf Konrad
Published: May 2023

The classical Buscher rules d escribe T-duality for metrics and B-fields in a topologically trivial setting. On the other hand, topological T-duality addresses aspects of non-trivial topology while neglecting metrics and B-fields. In this article, we develop a new unifying framework for both aspects.
Characterization of CTBT-Relevant Radioxenon Detections at IMS Stations Using Isotopic Activity Ratio Analysis
Authors: Liu Boxue , Kalinowski Martin , Sun Yunwei , Carrigan Charles R. , Saragiotis Christos , Wang Jun , Ertl Martin , Kijima Yuichi , Schoemaker Robin , Kuśmierczyk-Michulec Jolanta , Tipka Anne , Antoun Tarabay
Published: May 2023

Radioxenon isotopes measured at radionuclide stations of the Comprehensive Nuclear-Test-Ban Treaty’s (CTBT) International Monitoring System (IMS) may indicate releases from underground nuclear explosions (UNEs) but are often caused by emissions from nuclear facilities. Characterization of CTBT-relevant nuclear events may use the evolution of isotopic activity ratios over time, which goes from the release of an assumed UNE, through atmospheric transport, to sample collections and measurements. A mathematical approach is presented to discuss the characterization of the spatial and temporal relationships between a nuclear explosion and radioxenon measurements. On the one hand, activity concentrations at an IMS station are estimated by using the assumed release scenario regarding a UNE and atmospheric transport modelling. On the other hand, the activities collected in the samples are determined by spectral analysis first and the activity concentrations in the air passing over the IMS station are estimated under an assumption of constant concentration during sampling. The isotopic ratios of activities released from the UNE are related to the isotopic ratios of activity concentrations in the plume of air crossing the IMS station, resulting in a function of the isotopic activity ratio over the time from detonation to sample measurement. The latter is used for discrimination of a nuclear test and estimation of the time of detonation, such as a four radioxenon plot of the activity ratio relationship of 135Xe/133Xe versus 133mXe/131mXe.
Extended hydrodynamical models for plasmas
Authors: Alì Giuseppe , Mascali Giovanni , Pezzi Oreste , Valentini Francesco
Published: May 2023

We propose an extended hydrodynamical model for plasmas, based on the moments of the electron distribution function which satisfies the Fokker–Planck–Landau (FPL) transport equation. The equations for the moments can be obtained by multiplying the FPL equation by the corresponding weight functions and integrating over the velocity space. The moments are decomposed in their convective and non–convective parts and closure relations for the fluxes and production terms can be obtained by using the maximum entropy distribution function, which depends on Lagrangian multipliers. These latter can be expressed in terms of the state variables by imposing the constraints that the maximum entropy distribution function reproduces the moments chosen as state variables. In particular, we will concentrate on the 13-moment system. As a first application, we treat the case of the relaxation towards equilibrium of a homogeneous plasma with a temperature anisotropy, showing that the results are in good agreement with those obtained by means of the Kogan solution of the kinetic equation.
Tolerance analysis by static analogy on 2D assemblies with fits and fasteners
Authors: Armillotta Antonio
Published: May 2023

In tolerance analysis, the effect of clearance fits is especially difficult to estimate because the mating parts are not necessarily in actual contact and can take an infinite number of relative positions. The treatment of these situations is allowed in most of the available methods, possibly introducing additional elements in the dimension chains with appropriate statistical assumptions. The paper provides a similar extension for the static analogy, a previously proposed method that converts the tolerance analysis problem into an equivalent problem of force analysis. The procedure represents each fit, possibly between patterns of features (e.g., fasteners and holes), with a proper constraint in the equivalent static model. The ability of the constraint to transmit forces and torques is determined according to the types and directions of misalignments allowed by the joint clearance. With simple rules, this avoids complications in the static model, which must include only the constraint between parts rather than the geometric details of the mating features. The extended method, currently limited to 2D dimension chains, is demonstrated on examples involving both dimensional and geometric tolerances. The comparison with existing methods shows the correctness of the proposed procedure. The simplicity of the workflow confirms the possibility, already demonstrated for the static analogy, of avoiding numerical simulations or even the use of computer-based tools.
The Existence of a Weak Solution to Volume Preserving Mean Curvature Flow in Higher Dimensions
Authors: Takasao Keisuke
Published: May 2023

In this paper, we construct a family of integral varifolds, which is a global weak solution to the volume preserving mean curvature flow in the sense of$$L^2$$L2-flow. This flow is also a distributional BV-solution for a short time, when the perimeter of the initial data is sufficiently close to that of a ball with the same volume. To construct the flow, we use the Allen–Cahn equation with a non-local term motivated by studies of Mugnai, Seis, and Spadaro, and Kim and Kwon. We prove the convergence of the solution for the Allen–Cahn equation to the family of integral varifolds with only natural assumptions for the initial data.
Volterra-type operators mapping weighted Dirichlet space into $$H^\infty $$
Authors: Peláez José Ángel , Rättyä Jouni , Wu Fanglei
Published: May 2023

The problem of describing the analytic functions g on the unit disc such that the integral operator $$T_g(f)(z)=\int _0^zf(\zeta )g'(\zeta )\,d\zeta $$

T
g

(
f
)

(
z
)

=

∫
0
z

f

(
ζ
)

g
′

(
ζ
)

d
ζ

is bounded (or compact) from a Banach space (or complete metric space) X of analytic functions to the Hardy space $$H^\infty $$

H
∞

is a tough problem, and remains unsettled in many cases. For analytic functions g with non-negative Maclaurin coefficients, we describe the boundedness and compactness of $$T_g$$

T
g

acting from a weighted Dirichlet space $$D^p_\omega $$

D
ω
p

, induced by an upper doubling weight $$\omega $$
ω
, to $$H^\infty $$

H
∞

. We also characterize, in terms of neat conditions on $$\omega $$
ω
, the upper doubling weights for which $$T_g: D^p_\omega \rightarrow H^\infty $$

T
g

:

D
ω
p

→

H
∞

is bounded (or compact) only if g is constant.
Chord skill: learning optimized hand postures and bimanual coordination
Authors: Verwey Willem B.
Published: May 2023

This reaction time study tested the hypothesis that in the case of finger movements skilled motor control involves the execution of learned hand postures. After delineating hypothetical control mechanisms and their predictions an experiment is described involving 32 participants who practiced 6 chord responses. These responses involved the simultaneous depression of one, two or three keys with either four right-hand fingers or two fingers of both hands. After practicing each of these responses for 240 trials, the participants performed the practiced and also novel chords with the familiar and with the unfamiliar hand configuration of the other practice group. The results suggest that participants learned hand postures rather than spatial or explicit chord representations. Participants practicing with both hands also developed a bimanual coordination skill. Chord execution was most likely slowed by interference between adjacent fingers. This interference seemed eliminated with practice for some chords but not for others. Hence, the results support the notion that skilled control of finger movements is based on learned hand postures that even after practice may be slowed by interference between adjacent fingers.
Polynomial-Time Axioms of Choice and Polynomial-Time Cardinality
Authors: Grochow Joshua A.
Published: May 2023

There is no single canonical polynomial-time version of the Axiom of Choice (AC); several statements of AC that are equivalent in Zermelo-Fraenkel (ZF) set theory are already inequivalent from a constructive point of view, and are similarly inequivalent from a complexity-theoretic point of view. In this paper we show that many classical formulations of AC, when restricted to polynomial time in natural ways, are equivalent to standard complexity-theoretic hypotheses, including several that were of interest to Selman. This provides a unified view of these hypotheses, and we hope provides additional motivation for studying some of the lesser-known hypotheses that appear here. Additionally, because several classical forms of AC are formulated in terms of cardinals, we develop a theory of polynomial-time cardinality. Nerode & Remmel (Contemp. Math.106, 1990 and Springer Lec. Notes Math. 1432, 1990) developed a related theory, but restricted to unary sets. Downey (Math. Reviews MR1071525) suggested that such a theory over larger alphabets could have interesting connections to more standard complexity questions, and we illustrate some of those connections here. The connections between AC, cardinality, and complexity questions also allow us to highlight some of Selman’s work. We hope this paper is more of a beginning than an end, introducing new concepts and raising many new questions, ripe for further research.
The relationship between tumour dosimetry, response, and overall survival in patients with unresectable Neuroendocrine Neoplasms (NEN) treated with 177Lu DOTATATE (LuTate)
Authors: Alipour R. , Jackson P. , Bressel M. , Hogg A. , Callahan J. , Hicks R. J. , Kong G.
Published: May 2023

Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess the predictive and prognostic implications of tumour dosimetry with respect to response by 68 Ga DOTATATE (GaTate) PET/CT molecular imaging tumour volume of SSR (MITVSSR) change and RECIST 1.1, and overall survival (OS).

Methods

Patients with gastro-entero-pancreatic (GEP) NEN who received LuTate followed by quantitative SPECT/CT (Q-SPECT/CT) the next day (Jul 2010 to Jan 2019) were retrospectively reviewed. Single time-point (STP) lesional dosimetry was performed for each cycle using population-based pharmacokinetic modelling. MITVSSR and RECIST 1.1 were measured at 3-months post PRRT.

Results

Median of 4 PRRT cycles were administered to 90 patients (range 2–5 cycles; mean 27.4 GBq cumulative activity; mean 7.6 GBq per cycle). 68% received at least one cycle with radiosensitising chemotherapy (RSC). RECIST 1.1 partial response was 24%, with 70% stable and 7% progressive disease. Cycle 1 radiation dose in measurable lesions was associated with local response (odds ratio 1.5 per 50 Gy [95% CI: 1.1–2.0], p = 0.002) when adjusted by tumour grade and RSC. Median change in MITVSSR was -63% (interquartile range -84 to -29), with no correlation with radiation dose to the most avid lesion on univariable or multivariant analyses (5.6 per 10 Gy [95% CI: -1.6, 12.8], p = 0.133). OS at 5-years was 68% (95% CI: 56–78%). Neither baseline MITVSSR (hazard ratio 1.1 [95% CI: 1.0, 1.2], p = 0.128) nor change in baseline MITVSSR (hazard ratio 1.0 [95% CI: 1.0, 1.1], p = 0.223) were associated with OS when adjusted by tumour grade and RSC but RSC was (95% CI: 0.2, 0.8, p = 0.012).

Conclusion

Radiation dose to tumour during PRRT was predictive of radiologic response but not survival. Survival outcomes may relate to other biological factors. There was no evidence that MITVSSR change was associated with OS, but a larger study is needed.
Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology
Authors: Panni Usman Y. , Chen Michael Y. , Zhang Felicia , Cullinan Darren R. , Li Lijin , James C. Alston , Zhang Xiuli , Rogers S. , Alarcon A. , Baer John M. , Zhang Daoxiang , Gao Feng , Miller Christopher A. , Gong Qingqing , Lim Kian-Huat , DeNardo David G. , Goedegebuure S. Peter , Gillanders William E. , Hawkins William G.
Published: May 2023

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.
Methoden zur Erfassung der Krankheitsaktivität der Polymyalgia rheumatica
Authors: Reisch Myriam , Dejaco Christian
Published: May 2023

Die Polymyalgia rheumatica (rPMR) ist die zweithäufigste entzündlich rheumatische Erkrankung im höheren Lebensalter. In klinischen Studien werden häufig die Remission und das Rezidiv als Endpunkte festgesetzt, jedoch existieren für diese Zustände noch keine einheitlichen Definitionen, was die Vergleichbarkeit von Studien erschwert. Der PMR-AS (PMR-Aktivitätsscore) ist derzeit der einzige für die PMR entwickelte Composite Score, durch den neben der Remission auch eine niedrige, mittlere und hohe Krankheitsaktivität definiert werden. In neueren Studien wird der PMR-AS häufig verwendet und die niedrige Krankheitsaktivität als Endpunkt festgelegt. Eine Limitation des PMR-AS ist die mögliche Beeinflussung der einzelnen Variablen durch Komorbiditäten. Beim Einsatz von Medikamenten, welche die Interleukin-6-Achse beeinflussen, sind das C‑reaktive Protein (CRP) und die Blutsenkungsgeschwindigkeit (BSG) für die Beurteilung der Krankheitsaktivität der PMR nur eingeschränkt verwertbar. Vielversprechende alternative Biomarker sind Calprotectin und Osteopontin, die bereits bei der rheumatoiden Arthritis die Erkrankungsaktivität unabhängig vom CRP widerspiegeln konnten. Darüber hinaus könnten bildgebende Verfahren wie die Sonographie, Magnetresonanztomographie und FDG(Fluordesoxyglucose)-Positronenemissionstomographie zum Monitoring der Krankheitsaktivität eingesetzt werden, wobei diese erst in weiteren Studien validiert werden müssen. Die PMR-IS (PMR-Impact Scale) ist ein Composite Score zur Erfassung der Auswirkungen von PMR auf die Patient:innen. Sie wurde allerdings bisher noch nicht in klinischen Studien angewendet. Die Entwicklung von weiteren PROs („patient reported outcomes“) für die PMR und die Definition von einheitlichen Kriterien zur Erfassung der Remission und des Rezidivs sind für die PMR wichtige zukünftige Forschungsfragen.
Morphokinetic analysis of early human embryonic development and its relationship to endometriosis resection: a retrospective time-lapse study using the KIDScore™ D3 and D5 implantation data algorithm
Authors: Herbert Saskia-Laureen , Staib Claudia , Wallner Theresa , Löb Sanja , Curtaz Carolin , Schwab Michael , Wöckel Achim , Häusler Sebastian
Published: May 2023

Research question

Does complete resection of endometriosis improve embryo quality as assessed by morphokinetic parameters using time-lapse microscopy?

Design

For this retrospective study we analysed 237 fertilised, cultured and transferred embryos from 128 fresh IVF and/ or ICSI transfer cycles. Endometriosis was confirmed or excluded by laparoscopy. Patients were stimulated with recombinant FSH using GnRH agonist and antagonist protocols. After fertilisation, a time-lapse incubation system was used for observation. Embryo quality was assessed using the KIDScore™ D3 and D5 implantation data algorithm.

Results

The analysis showed a median KIDScore™ D5 of 2.6 (on a scale of 1 to 9.9) for embryos from patients with endometriosis without complete resection. The control group without endometriosis achieved a score of 6.8 (p = 0.003). The median score for embryos from endometriosis patients with complete resection was 7.2, which was a significant increase compared to embryos from patients without complete resection (p = 0.002). We observed an effect size of r = 0.4 for complete resection versus no resection of endometriosis using the KIDScore™ D5. There were no differences in KIDScore™ D3 between the three patient groups. Pregnancy and miscarriage rates showed the same clinical trends. In three of our four case series of patients who underwent IVF/ ICSI cycles before and after complete resection, we found a marked improvement in embryo quality after complete resection.

Conclusions

Complete resection of endometriosis could significantly improve the otherwise poor embryo quality of patients undergoing IVF-procedures. The data, therefore, strongly support recommending surgery to patients with endometriosis prior to assisted reproduction.
Self-organizing maps on “what-where” codes towards fully unsupervised classification
Authors: Sa-Couto Luis , Wichert Andreas
Published: May 2023

Interest in unsupervised learning architectures has been rising. Besides being biologically unnatural, it is costly to depend on large labeled data sets to get a well-performing classification system. Therefore, both the deep learning community and the more biologically-inspired models community have focused on proposing unsupervised techniques that can produce adequate hidden representations which can then be fed to a simpler supervised classifier. Despite great success with this approach, an ultimate dependence on a supervised model remains, which forces the number of classes to be known beforehand, and makes the system depend on labels to extract concepts. To overcome this limitation, recent work has been proposed that shows how a self-organizing map (SOM) can be used as a completely unsupervised classifier. However, to achieve success it required deep learning techniques to generate high quality embeddings. The purpose of this work is to show that we can use our previously proposed What-Where encoder in tandem with the SOM to get an end-to-end unsupervised system that is Hebbian. Such system, requires no labels to train nor does it require knowledge of which classes exist beforehand. It can be trained online and adapt to new classes that may emerge. As in the original work, we use the MNIST data set to run an experimental analysis and verify that the system achieves similar accuracies to the best ones reported thus far. Furthermore, we extend the analysis to the more difficult Fashion-MNIST problem and conclude that the system still performs.
Genotype–phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder
Authors: D’Onofrio Gianluca , Accogli Andrea , Severino Mariasavina , Caliskan Haluk , Kokotović Tomislav , Blazekovic Antonela , Jercic Kristina Gotovac , Markovic Silvana , Zigman Tamara , Goran Krnjak , Barišić Nina , Duranovic Vlasta , Ban Ana , Borovecki Fran , Ramadža Danijela Petković , Barić Ivo , Fazeli Walid , Herkenrath Peter , Marini Carla , Vittorini Roberta , Gowda Vykuntaraju , Bouman Arjan , Rocca Clarissa , Alkhawaja Issam Azmi , Murtaza Bibi Nazia , Rehman Malik Mujaddad Ur , Al Alam Chadi , Nader Gisele , Mancardi Maria Margherita , Giacomini Thea , Srivastava Siddharth , Alvi Javeria Raza , Tomoum Hoda , Matricardi Sara , Iacomino Michele , Riva Antonella , Scala Marcello , Madia Francesca , Pistorio Angela , Salpietro Vincenzo , Minetti Carlo , Rivière Jean-Baptiste , Srour Myriam , Efthymiou Stephanie , Maroofian Reza , Houlden Henry , Vernes Sonja Catherine , Zara Federico , Striano Pasquale , Nagy Vanja
Published: May 2023

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell–cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with “Pitt-Hopkins-like syndrome-1” (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype–phenotype correlation. Patients (M:F 14:8) were aged between 3 and 19 years and affected by global developmental delay (GDD) (n = 21), moderate to profound intellectual disability (n = 17) and epilepsy (n = 21). Seizures mainly started in the first two years of life (median 22.5 months). Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. Autism spectrum disorder (ASD) and/or other neuropsychiatric comorbidities were present in nine patients (40.9%). Nonspecific midline brain anomalies were noted in most patients while focal signal abnormalities in the temporal lobes were noted in three subjects. Genotype–phenotype correlation was performed by also including 50 previously published patients (15 mono- and 35 bi-allelic variants). Overall, GDD (p < 0.0001), epilepsy (p < 0.0001), hyporeflexia (p = 0.012), ASD (p = 0.009), language impairment (p = 0.020) and severe cognitive impairment (p = 0.031) were significantly associated with the presence of biallelic versus monoallelic variants. We have defined the main features associated with biallelic CNTNAP2 variants, as severe cognitive impairment, epilepsy and behavioral abnormalities. We propose CASPR2-deficiency neurodevelopmental disorder as an exclusively recessive disease while the contribution of heterozygous variants is less likely to follow an autosomal dominant inheritance pattern.
Matrix Whittaker processes
Authors: Arista Jonas , Bisi Elia , O’Connell Neil
Published: May 2023

We study a discrete-time Markov process on triangular arrays of matrices of size$$d\ge 1$$d≥1, driven by inverse Wishart random matrices. The components of the right edge evolve as multiplicative random walks on positive definite matrices with one-sided interactions and can be viewed as ad-dimensional generalisation of log-gamma polymer partition functions. We establish intertwining relations to prove that, for suitable initial configurations of the triangular process, the bottom edge has an autonomous Markovian evolution with an explicit transition kernel. We then show that, for a special singular initial configuration, the fixed-time law of the bottom edge is a matrix Whittaker measure, which we define. To achieve this, we perform a Laplace approximation that requires solving a constrained minimisation problem for certain energy functions of matrix arguments on directed graphs.
Near-optimal distributed dominating set in bounded arboricity graphs
Authors: Dory Michal , Ghaffari Mohsen , Ilchi Saeed
Published: May 2023

We describe a simple deterministic $$O( \varepsilon ^{-1} \log \Delta )$$

O
(

ε

-
1

log
Δ
)

round distributed algorithm for $$(2\alpha +1)(1 + \varepsilon )$$

(
2
α
+
1
)
(
1
+
ε
)

approximation of minimum weighted dominating set on graphs with arboricity at most $$\alpha $$
α
. Here $$\Delta $$
Δ
denotes the maximum degree. We also show a lower bound proving that this round complexity is nearly optimal even for the unweighted case, via a reduction from the celebrated KMW lower bound on distributed vertex cover approximation (Kuhn et al. in JACM 63:116, 2016). Our algorithm improves on all the previous results (that work only for unweighted graphs) including a randomized $$O(\alpha ^2)$$

O
(

α
2

)

approximation in $$O(\log n)$$

O
(
log
n
)

rounds (Lenzen et al. in International symposium on distributed computing, Springer, 2010), a deterministic $$O(\alpha \log \Delta )$$

O
(
α
log
Δ
)

approximation in $$O(\log \Delta )$$

O
(
log
Δ
)

rounds (Lenzen et al. in international symposium on distributed computing, Springer, 2010), a deterministic $$O(\alpha )$$

O
(
α
)

approximation in $$O(\log ^2 \Delta )$$

O
(

log
2

Δ
)

rounds (implicit in Bansal et al. in Inform Process Lett 122:21–24, 2017; Proceeding 17th symposium on discrete algorithms (SODA), 2006), and a randomized $$O(\alpha )$$

O
(
α
)

approximation in $$O(\alpha \log n)$$

O
(
α
log
n
)

rounds (Morgan et al. in 35th International symposiumon distributed computing, 2021). We also provide a randomized $$O(\alpha \log \Delta )$$

O
(
α
log
Δ
)

round distributed algorithm that sharpens the approximation factor to $$\alpha (1+o(1))$$

α
(
1
+
o
(
1
)
)

. If each node is restricted to do polynomial-time computations, our approximation factor is tight in the first order as it is NP-hard to achieve $$\alpha - 1 - \varepsilon $$

α
-
1
-
ε

approximation (Bansal et al. in Inform Process Lett 122:21-24, 2017).
Nonlinear nonlocal Douglas identity
Authors: Bogdan Krzysztof , Grzywny Tomasz , Pietruska-Pałuba Katarzyna , Rutkowski Artur
Published: May 2023

We give Hardy–Stein and Douglas identities for nonlinear nonlocal Sobolev–Bregman integral forms with unimodal Lévy measures. We prove that the corresponding Poisson integral defines an extension operator for the Sobolev–Bregman spaces. As an application, we obtain the boundedness of the Dirichlet-to-Neumann operator on weighted $$L^p$$

L
p

spaces. We also show that the Poisson integrals are quasiminimizers of the Sobolev–Bregman forms.