bluuebunny/crossref_metadata_2025 huggingface dataset:
CCNB1IP1 prevents ubiquitination‐mediated destabilization of MYCN and potentiates tumourigenesis of MYCN‐amplificated neuroblastoma
Authors: Zhou Yang , Yan Hui , Zhou Qiang , Wang Penggao , Yang Fang , Yuan Ziqiao , Du Qianming , Zhai Bo
Published: July 2023

Background

MYCN amplification as a common genetic alteration that correlates with a poor prognosis for neuroblastoma (NB) patients. However, given the challenge of directly targeting MYCN, indirect strategies to modulate MYCN by interfering with its cofactors are attractive in NB treatment. Although cyclin B1 interacting protein 1 (CCNB1IP1) has been found to be upregulated in MYCN‐driven mouse NB tissues, its regulation with MYCN and collaboration in driving the biological behaviour of NB remains unknown.

Methods

To evaluate the expression and clinical significance of CCNB1IP1 in NB patients, public datasets, clinical NB samples and cell lines were explored. MTT, EdU incorporation, colony and tumour sphere formation assays, and a mouse xenograft tumour model were utilized to examine the biological function of CCNB1IP1. The reciprocal manipulation of CCNB1IP1 and MYCN and the underlying mechanisms involved were investigated by gain‐ and loss‐of‐function approaches, dual‐luciferase assay, chromatin immunoprecipitation (CHIP) and co‐immunoprecipitation (Co‐IP) experiments.

Results

CCNB1IP1 was upregulated in MYCN‐amplified (MYCN‐AM) NB cell lines and patients‐derived tumour tissues, which was associated with poor prognosis. Phenotypic studies revealed that CCNB1IP1 facilitated the proliferation and tumourigenicity of NB cells in cooperation with MYCN in vitro and in vivo. Mechanistically, MYCN directly mediates the transcription of CCNB1IP1, which in turn attenuated the ubiquitination and degradation of MYCN protein, thus enhancing CCNB1IP1‐MYCN cooperativity. Moreover, CCNB1IP1 competed with F box/WD‐40 domain protein 7 (FBXW7) for MYCN binding and enabled MYCN‐mediated tumourigenesis in a C‐terminal domain‐dependent manner.

Conclusions

Our study revealed a previously uncharacterized mechanism of CCNB1IP1‐mediated MYCN protein stability and will provide new prospects for precise treatment of MYCN‐AM NB based on MYCN‐CCNB1IP1 interaction.
Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery
Authors: Sun Lejia , Ke Xindi , Guan Ai , Jin Bao , Qu Jiangming , Wang Yinhan , Xu Xiang , Li Changcan , Sun Hang , Xu Hengyi , Xu Gang , Sang Xinting , Feng Yifei , Sun Yueming , Yang Huayu , Mao Yilei
Published: July 2023

Background

The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME.

Methods

We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes.

Results

This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC.

Conclusions

Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.
Haemodynamic forces predicting remodelling and outcome in patients with heart failure treated with sacubitril/valsartan
Authors: Fabiani Iacopo , Pugliese Nicola Riccardo , Pedrizzetti Gianni , Tonti Giovanni , Castiglione Vincenzo , Chubuchny Vladislav , Taddei Claudia , Gimelli Alessia , Del Punta Lavinia , Balletti Alessio , Del Franco Annamaria , Masi Stefano , Lombardi Carlo Mario , Cameli Matteo , Emdin Michele , Giannoni Alberto
Published: July 2023

Aims

A novel tool for the evaluation of left ventricular (LV) systo‐diastolic function through echo‐derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events.

Methods and results

Eighty‐nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N‐terminal pro‐B‐type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF‐related hospitalisation, atrial fibrillation and cardiovascular death. Forty‐five (51%) patients were responders. Among baseline variables, only HDF‐derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10–1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23–41) median follow‐up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time‐dependent ROC analysis (optimal cut‐off: ≥0.5%; AUC = 0.811), stratified prognosis (log‐rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61–0.95; p < 0.01), after adjusting for clinical and instrumental variables.

Conclusions

HDF analysis predicts sacubitril/valsartan response and might optimise decision‐making in HFrEF patients.
A probabilistic cross‐impact methodology for explorative scenario analysis
Authors: Roponen Juho , Salo Ahti
Published: July 2023

As one of the approaches to scenario analysis, cross‐impact methods provide a structured approach to building scenarios as combinations of outcomes for selected uncertainty factors. Although they vary in their details, cross‐impact methods are similar in that they synthesize expert judgments about probabilistic or causal dependencies between pairs of uncertainty factors and seek to focus attention on scenarios that can be deemed consistent. Still, most cross‐impact methods do not associate probabilities with scenarios, which limits the possibilities of integrating them in risk and decision analysis. Motivated by this recognition, we develop a cross‐impact method that derives a joint probability distribution over all possible scenarios from probabilistically interpreted cross‐impact statements. More specifically, our method (i) admits a broad range of probabilistic statements about the realizations of uncertainty factors, (ii) supports the process of eliciting such statements, (iii) synthesizes these judgments by solving a series of optimization models from which the corresponding scenario probabilities are derived. The resulting scenario probabilities can be used to construct Bayesian networks, which expands the range of analyses that can be carried out. We illustrate our method with a real case study on the impacts of three‐dimensional (3D)‐printing on the Finnish Defense Forces. The scenarios, their probabilities, and the associated Bayesian network resulting from this case study helped explore alternative futures and gave insights into how the Defence Forces could benefit from 3D‐printing.
Establishing Quality Metrics for Systems Engineering Process
Authors: Powell Rusty , Jandreau Tyler
Published: July 2023

Software engineering companies such as Motorola have clearly defined, robust processes to ensure overall process and system quality. Using Motorola's approach as a baseline, the authors established a process to determine system complexity to support the Systems Engineering & Integration (SE&I) lifecycle. To quantify complexity, the authors established a process including structural complexity (focused on system form), dynamic complexity (focused on system function), and social complexity (focused on identified stakeholders), the sum of which define complexity points. The authors further expanded the process by defining key metrics and parameters to support evaluation throughout the SE&I phases from concept to operationalization. This process, which utilizes fundamentals of Agile Software Development, allows systems engineers (SEs) and program managers (PMs) to quantitatively compare SE&I phases, systems, or projects of different sizes and dollar values to categorize, assess, forecast lifecycle costs, and performance to improve performance with customer satisfaction in mind. Through a satellite system example, the authors present the metrics to support associated analysis through the SE&I lifecycle.
Crafting an Experience‐Based Master's Program in Systems Engineering
Authors: Bronston Marshall , Berenbach Brian , Angel Joe , Doerr Jeremy
Published: July 2023

The Professional Masters in Applied Systems Engineering (PMASE) program provides students with practical and academic material in a setting like a typical work environment. This paper describes the first course in the two‐year program from the perspective of how a “high touch” course provides learning depth. It describes the approach used to provide students with a realistic environment giving academic and practical experience balancing work and studies in an intensive program which culminates in a capstone project. The paper should be of interest to companies and universities interested in a holistic, condensed systems engineering training program.
Configuration Management for Model Based Systems Engineering ‐ An example from the Aerospace Industry
Authors: D'Souza Adriana , Thota Phanikrishna
Published: July 2023

Model Based Systems Engineering approach is increasingly used to manage the complexity of modern systems and to reduce costs of their development. In the Aerospace industry, modelling and simulation is not only a cost effective verification and validation strategy where test rigs and flight tests are far more expensive but also is increasingly used in the certification process. Nevertheless, as with any digital artefact, if the models aren't configured and traceability isn't assured, then the models are not of much use. Configuration Management comes into play as a key discipline to enable the use and maintenance of the models. This paper explores the use of Configuration Management for modelling and simulation in an aerospace setting, with a specific example involving landing gear and its surrounding systems.
A generic hierarchical System of Systems Engineering (SOS) Approach for Model based System Engineering (MBSE) Projects
Authors: Pandey Mohinder
Published: July 2023

Model based systems engineering (MBSE) has been accepted worldwide by many industries, including the automotive industry, for several years. Hundreds of projects have already been developed and deployed using MBSE approaches. MBSE is gaining importance because it provides systems advantageous life cycle processes, such as returns of investments and meeting the demands of global marketplaces, as they become increasingly complex. Consequently, the number and pace of deployment using MBSE approaches will increase in the future.

Our current work objective is to define a generic MBSE methodology compatible with Systems Engineering Body of Knowledge (SEBOK) functional decomposition principles, ‘Automotive open systems architecture’ (AUTOSAR) developments and compliant to ‘Automotive software performance improvement and capability determination’ (ASPICE) processes using the ‘systems modelling language’ (SysML). We have proposed a generic SysML process framework, a hierarchical system of systems (SOS) engineering approach and automation solutions. We have shown that the proposed solution helps meet the defined objectives. The work is targeted and relevant for automotive industry MBSE practitioners. In general, the research, apart from transportation and mobility industries, can also be used in other industries.
Market discipline and the risk‐taking behaviour of banks in India
Authors: Bhat Dilawar Ahmad , Chanda Udayan , Bhat Anil K.
Published: July 2023

After the financial crisis, the Indian banking system has accumulated a mountain of bad loans which has crippled the banking sector and halted the credit flow to the industry. Several immediate causes for the bad loan crisis have been pointed out. However, poor market discipline, the ultimate root cause of the bad loan crisis, has not been paid adequate attention. This study seeks to investigate how effectively the market disciplinary forces, captured through information disclosure, interbank deposits, concentration and ownership structure, incentivise the Indian banks to adopt prudential risk management by enhancing their risk‐weighted capital ratio. The findings of the study show that information disclosure and interbank deposits do not induce prudential risk behaviour among banks in India. However, with increasing concentration in the banking sector, a higher level of information disclosure effectively induces banks to maintain higher capital ratios, but inter‐bank deposits do not have any significant effect on bank capital. We also observe that government banks maintain lower capital ratios as compared to private banks indicating government banks' higher expectation of government bailout.
Exceptional designs in some extended quadratic residue codes
Authors: Ishikawa Reina
Published: July 2023

In the present paper, we give proofs of the existence of a 3‐design in the extended ternary quadratic residue code of length 14 and the extended quaternary quadratic residue code of length 18.
Incidence of blast phase in myelofibrosis according to anemia severity
Authors: Mora Barbara , Maffioli Margherita , Rumi Elisa , Guglielmelli Paola , Caramella Marianna , Kuykendall Andrew , Palandri Francesca , Iurlo Alessandra , De Stefano Valerio , Kiladjian Jean‐Jacques , Elli Elena M. , Polverelli Nicola , Gotlib Jason , Albano Francesco , Silver Richard T. , Benevolo Giulia , Ross David M. , Devos Timothy , Borsani Oscar , Barbui Tiziano , Porta Matteo G. Della , Bertù Lorenza , Komrokji Rami , Vannucchi Alessandro M. , Passamonti Francesco
Published: July 2023

Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%–20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and ‐in primary MF‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF.

Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.
A low‐spur harmonic‐cancelation digital predistortion based on neural network for frequency‐hopping HF transmitters
Authors: Chen Long , Chen Wenhua , Chen Xiaofan , Liu Youjang , Chu Jiaming , Ghannouchi Fadhel M. , Feng Zhenghe
Published: July 2023

High frequency (HF) transmitter implemented with the multioctave broadband power amplifier (PA) is always faced with the problem of interfering harmonics because of the nonlinearity of the PA. With the harmonic‐cancelation digital predistortion (HC‐DPD) scheme, the harmonics at lower frequencies can be canceled by the injected components and the harmonics at higher frequencies can be filtered out using a low‐pass filter (LPF). However, the HC‐DPD scheme brings the problem of unwanted spurs while lowering the requirements for sampling rate. In this article, a time‐delay neural network (TDNN) model is used to replace the conventional memory polynomial (MP) model in the forward modeling. Theoretical derivation and simulation results validate the effectiveness of the TDNN model in harmonic cancelation and spur suppression. Further, a frequency‐agile neural network (FANN) model is proposed based on the TDNN model. By adding the carrier frequency to the inputs of the network, the trained model can apply to all the trained carrier frequencies and is more friendly to the frequency‐hopping scenarios. Experiments were carried out on a 2–30 MHz HF transmitter testbench. Measurement results show that the harmonic‐to‐fundamental power ratio, the adjacent channel power ratio (ACPR), and the error vector magnitude (EVM) performances were all improved by more than 20 dB. Compared with the MP model, the unwanted spurs can be suppressed by up to 22 dB. In addition, the number of total model coefficients of the proposed FANN model is only 22% of that of the TDNN model under the frequency‐hopping scenario.
A review of the mechanisms of blood–brain barrier disruption during COVID‐19 infection
Authors: Jamil Al‐Obaidi Mazen M. , Desa Mohd Nasir Mohd
Published: July 2023

Coronaviruses are prevalent in mammals and birds, including humans and bats, and they often spread through airborne droplets. In humans, these droplets then interact with angiotensin‐converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which are the main receptors for the SARS‐CoV‐2 virus. It can infect several organs, including the brain. The blood–brain barrier (BBB) is designed to maintain the homeostatic neural microenvironment of the brain, which is necessary for healthy neuronal activity, function, and stability. It prevents viruses from entering the brain parenchyma and does not easily allow chemicals to pass into the brain while assisting numerous compounds in exiting the brain. The purpose of this review was to examine how COVID‐19 influences the BBB along with the mechanisms that indicate the BBB's deterioration. In addition, the cellular mechanism through which SARS‐CoV‐2 causes BBB destruction by binding to ACE2 was evaluated and addressed. The mechanisms of the immunological reaction that occurs during COVID‐19 infection that may contribute to the breakdown of the BBB were also reviewed. It was discovered that the integrity of the tight junction (TJs), basement membrane, and adhesion molecules was damaged during COVID‐19 infection, which led to the breakdown of the BBB. Therefore, understanding how the BBB is disrupted by COVID‐19 infection will provide an indication of how the SARS‐CoV‐2 virus is able to reach the central nervous system (CNS). The findings of this research may help in the identification of treatment options for COVID‐19 that can control and manage the infection.
Nano‐enabled stress‐smart agriculture: Can nanotechnology deliver drought and salinity‐smart crops?
Authors: Raza Ali , Charagh Sidra , Salehi Hajar , Abbas Saghir , Saeed Faisal , Poinern Gérrard E. J. , Siddique Kadambot H. M. , Varshney Rajeev K.
Published: July 2023

Salinity and drought stress substantially decrease crop yield and superiority, directly threatening the food supply needed to meet the rising food needs of the growing total population. Nanotechnology is a step towards improving agricultural output and stress tolerance by improving the efficacy of inputs in agriculture via targeted delivery, controlled release, and enhanced solubility and adhesion while also reducing significant damage. The direct application of nanoparticles (NPs)/nanomaterials can boost the performance and effectiveness of physio‐biochemical and molecular mechanisms in plants under stress conditions, leading to advanced stress tolerance. Therefore, we presented the effects and plant responses to stress conditions, and also explored the potential of nanomaterials for improving agricultural systems, and discussed the advantages of applying NPs at various developmental stages to alleviate the negative effects of salinity and drought stress. Moreover, we feature the recent innovations in state‐of‐the‐art nanobiotechnology, specifically NP‐mediated genome editing via CRISPR/Cas system, to develop stress‐smart crops. However, further investigations are needed to unravel the role of nanobiotechnology in addressing climate change challenges in modern agricultural systems. We propose that combining nanobiotechnology, genome editing and speed breeding techniques could enable the designing of climate‐smart cultivars (particularly bred or genetically modified plant varieties) to meet the food security needs of the rising world population.
Improving Photoluminescence Emissions and Photostability of Dye/MgAl‐Layered Double Hydroxide Nanohybrids
Authors: Rezvani Zolfaghar , Jafari Foruzin Leila , Nejati Kamellia
Published: July 2023

The purpose of this study was the preparation of layered double hydroxide (LDH) ‐based nanohybrids with improved photoluminescence emission and high photostability. The anion exchange‐based microwave method was applied for the intercalation of mordant orange 1 into MgAl‐LDH. The prepared organic‐inorganic nanohybrid was confirmed by X‐ray diffraction, thermal gravimetric analysis (TGA), inductively coupled plasma spectrometry (ICP), and infrared spectra (FT‐IR). Also, the morphology of the obtained sample was investigated using the field emission‐scanning electron microscopy (FE‐SEM) method. In the MgAl‐LDH interlayer space, a tilted orientation and bilayer arrangement were predicted for the mordant orange 1 anions. Compared with the pure mordant orange 1, the MgAl‐LDH/mordant orange 1‐MA (prepared using the microwave‐based anion exchange method) has improved photoluminescence emission with high Photostability. These findings supply a new approach for designing photoluminescence materials that potentially apply to optical devices with high Photostability.
The Invisibles: Religious and Political Values Among Different Social Classes
Authors: Bréchon Pierre
Published: July 2023

Poverty and social exclusion can be defined as an accumulation of impediments: lack of work and income, bad housing, low education, maltreatment, disempowerment, loss of dignity. Types of poverty are indeed diverse, with the poor including both those who have inherited poverty and those who are newly poor in the age of globalisation. The first group is probably less visible than the second, more claiming. The poor present specificities of values. At the religious level, they are rather more believing – particularly in relation to paradise, and they practise their religion more. The discrepancies between social groups are greater when it comes to political matters. The invisibles are more individualistic and less individualised. They are less politicised but nevertheless more dissatisfied with those in power, and they mobilise less strongly in public action (voting and political protest). They do not easily trust others or institutions. They are less attached to democratic values, and they demonstrate greater xenophobia and nationalism. They therefore share many features of populism. These specificities of political values essentially correspond to perennial trends in poor classes. Differences in religious and political values between countries and geographical areas are also very large. But in each part of Europe, we observe value differences between social groups.
Symmetries of κ-Minkowski space-time: a possibility of exotic momentum space geometry?
Authors: Nandi Partha , Chakraborty Anwesha , Pal Sayan Kumar , Chakraborty Biswajit , Scholtz Frederik G.
Published: July 2023

Abstract

The quest for a quantum gravity phenomenology has inspired a quantum notion of space-time, which motivates us to study the fate of the relativistic symmetries of a particular model of quantum space-time, as well as its intimate connection with the plausible emergent curved “physical momentum space”. We here focus on the problem of Poincare symmetry of κ-Minkowski type non-commutative (quantum) space-time, where the Poincare algebra, on its own, remains undeformed, but in order to preserve the structure of the space-time non-commutative (NC) algebra, the actions of the algebra generators on the operator-valued space-time manifold must be enveloping algebra valued that lives in entire phase space i.e. the cotangent bundle on the space-time manifold (at classical level). Further, we constructed a model for a spin-less relativistic massive particle enjoying the deformed Poincare symmetry, using the first order form of geometric Lagrangian, that satisfies a new deformed dispersion relation and explored a feasible regime of a future Quantum Gravity theory in which the momentum space becomes curved. In this scenario there is only a mass scale (Planck mass mp), but no length scale. Finally, we relate the deformed mass shell to the geodesic distance in this curved momentum space, where the mass of the particle gets renormalized as a result of noncommutativity. We show, that under some circumstances, the Planck mass provides an upper bound for the observed renormalized mass.
FIMP dark matter from flavon portals
Authors: Babu K. S. , Chakdar Shreyashi , Das Nandini , Ghosh Dilip Kumar , Ghosh Purusottam
Published: July 2023

Abstract

We investigate the phenomenology of a non-thermal dark matter (DM) candidate in the context of flavor models that explain the hierarchy in the masses and mixings of quarks and leptons via the Froggatt-Nielsen (FN) mechanism. A flavor-dependent U(1)FN symmetry explains the fermion mass and mixing hierarchy, and also provides a mechanism for suppressed interactions of the DM, assumed to be a Majorana fermion, with the Standard Model (SM) particles, resulting in its FIMP (feebly interacting massive particle) character. Such feeble interactions are mediated by a flavon field through higher dimensional operators governed by the U(1)FN charges. We point out a natural stabilizing mechanism for the DM within this framework with the choice of half-integer U(1)FN charge n for the DM fermion, along with integer charges for the SM fermions and the flavon field. In this flavon portal scenario, the DM is non-thermally produced from the decay of the flavon in the early universe which becomes a relic through the freeze-in mechanism. We explore the allowed parameter space for this DM candidate from relic abundance by solving the relevant Boltzmann equations. We find that reproducing the correct relic density requires the DM mass to be in the range (100 − 300) keV for n = 7.5 and (3 − 10) MeV for n = 8.5 where n is the U(1)FN charge of the DM fermion.
A complex subsistence regime revealed for Cucuteni–Trypillia sites in Chalcolithic eastern Europe based on new and old macrobotanical data
Authors: Kirleis Wiebke , Corso Marta Dal , Pashkevych Galyna , Schlütz Frank , Hofmann Robert , Terna Andreea , Dreibrodt Stefan , Rud Vitalii , Videiko Mykhailo Y. , Müller Johannes
Published: July 2023

We present a comprehensive data-based characterization of the subsistence economy of Chalcolithic Cucuteni–Trypillia societies (CTS) on the Moldovian and Suceava plateaus and the Podolian and the Dnieper uplands. This study is based on a quantitative evaluation of archaeobotanical samples from 34 settlement sites, with a focus on Trypillia mega-sites and on stable isotopic analysis of ancient crop residues. The isotopic analysis allows us to identify specific cultivation strategies, which show a close relationship with animal husbandry for manure. We describe the economy of the Trypillia mega-sites as having been based on an elaborate agricultural system, in which the inhabitants knew how to grow crops that could withstand the ecological constraints of growth, especially along the forest steppe ecotone. We also argue that the agglomeration of greater population densities at these mega-sites contributed to landscape change from woodland and forest to open grassland and steppe. Following on from this, we suggest that cultivation practices of the CTS were important in the establishment of the present-day cultural steppe in this region.
Telomere dynamics in the Pacific crown-of-thorns seastar (Acanthaster cf. solaris): effect of age, diet, and tissue type
Authors: Kwong Sarah Lok Ting , Villacorta-Rath Cecilia , Pratchett Morgan , Uthicke Sven
Published: July 2023

Population irruptions of crown-of-thorns seastar (CoTS,Acanthasterspp.) represent a perennial threat to Indo-Pacific coral reefs. Age determination of CoTS is challenging, thereby hindering understanding and management of this nuisance species. Telomeres, which are protective DNA structure found at the ends of eukaryotic chromosomes that shorten at each cell division, have been used to estimate age in wild animals. To investigate the use of telomeres in CoTS, we optimized a quantitative PCR protocol to measure relative telomere length (rTL) in CoTS for the first time. Comparing rTL among four age groups (4, 7, 16, > 24 months post-settlement), we found that adult CoTS generally exhibit shorter rTL than juveniles, which is the first evidence of age-related telomere attrition in CoTS. However, there was large within-age class variation, and no significant relationships were found between adult CoTS rTL and potential age-indicating external features. Furthermore, we found accelerated telomere attrition under sub-optimal diet, where individuals that were fed crustose coralline algae for 16 months exhibited shorter rTL than their counterparts fed on coral. A positive correlation was found between rTL of tube feet and pyloric caeca, suggesting synchronization of telomere dynamics across somatic tissues in CoTS. Overall, our results suggest that rTL could be used to classify CoTS into broad age groups, though individual variation constrains the ability to resolve specific cohorts. The present study contributes to the understanding of telomere dynamics in marine invertebrates, while laying the groundwork for future research into rTL as biomarker for age and potentially stress for CoTS.
Control of nutrient metal availability during host-microbe interactions: beyond nutritional immunity
Authors: Djoko Karrera Y.
Published: July 2023

The control of nutrient availability is an essential ecological function of the host organism in host-microbe systems. Although often overshadowed by macronutrients such as carbohydrates, micronutrient metals are known as key drivers of host-microbe interactions. The ways in which host organisms control nutrient metal availability are dictated by principles in bioinorganic chemistry. Here I ponder about the actions of metal-binding molecules from the host organism in controlling nutrient metal availability to the host microbiota. I hope that these musings will encourage new explorations into the fundamental roles of metals in the ecology of diverse host-microbe systems.
Ein–Lazarsfeld–Mustopa conjecture for the blow-up of a projective space
Authors: Miró-Roig Rosa M. , Salat-Moltó Marti
Published: July 2023

We solve the Ein–Lazarsfeld–Mustopa conjecture for the blow up of a projective space along a linear subspace. More precisely, let X be the blow up of $${\mathbb {P}}^n$$

P

n

at a linear subspace and let L be any ample line bundle on X. We show that the syzygy bundle $$M_{L}$$

M
L

defined as the kernel of the evalution map $$H^{0}(X,L)\otimes {\mathcal {O}}_{X}\rightarrow L$$

H
0

(
X
,
L
)

⊗

O
X

→
L

is L-stable. In the last part of this note we focus on the rigidness of $$M_{L}$$

M
L

to study the local shape of the moduli space around the point $$[M_{L}]$$

[

M
L

]

.
The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT)
Authors: Pharaoh Gavin , Kamat Varun , Kannan Sricharan , Stuppard Rudolph S. , Whitson Jeremy , Martín-Pérez Miguel , Qian Wei-Jun , MacCoss Michael J. , Villén Judit , Rabinovitch Peter , Campbell Matthew D. , Sweet Ian R. , Marcinek David J.
Published: July 2023

Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and mitochondrial function in aging and binds directly to the mitochondrial ADP transporter ANT. We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT. Mitochondrial ADP sensitivity is rapidly modifiable. This research supports the hypothesis that ELAM improves ANT function in aging and links mitochondrial ADP sensitivity to physiological function.

Graphical abstract

ELAM binds directly to ANT and ATP synthase and ELAM treatment improves ADP sensitivity, increases ATP production, and improves physiological function in old muscles. ADP (adenosine diphosphate), ATP (adenosine triphosphate), VDAC (voltage-dependent anion channel), ANT (adenine nucleotide translocator), H+ (proton), ROS (reactive oxygen species), NADH (nicotinamide adenine dinucleotide), FADH2 (flavin adenine dinucleotide), O2 (oxygen), ELAM (elamipretide), –SH (free thiol), –SSG (glutathionylated protein)
Operationalizing the Nature Futures Framework for ecological infrastructure
Authors: Mayer Paula , Rabe Sven-Erik , Grêt-Regamey Adrienne
Published: July 2023

Scenarios are useful for considering development pathways under different future conditions. To manage a functioning ecological infrastructure (EI) as a network of natural and semi-natural habitats that can promote biodiversity and provide nature’s contributions to people (NCPs), one needs to understand future biophysical and socio-economic influences on its development. However, scenarios often do not incorporate the reciprocity of biophysical and societal changes. This has prompted new proposals from the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) on the importance of creating nature-centered multiscale scenarios that include a normative dimension accounting for diverse human–nature relationships. In this contribution, we operationalize the Nature Futures Framework (NFF), developed under IPBES, into integrated normative and exploratory scenarios framing the development of a functioning EI in Switzerland until 2060. We follow a two-stage participatory approach methodologically aligned with the IPBES development. First, we elaborated positive visions for future EI with stakeholders in four regions of Switzerland. We then collaborated with experts to create integrated normative and exploratory scenarios through a process comprising literature research, workshops and a survey. By positioning status quo and future scenarios within the Nature Futures Framework, we demonstrate the diversity of nature values in a specific context of EI in Switzerland, thus contributing to the global set of Nature Futures scenarios. Integrating both plausible and desirable developments, these scenarios will serve as a valuable tool in the planning of long-term measures to ensure a functioning EI in Switzerland.
Quaternionic Convolutional Neural Networks with Trainable Bessel Activation Functions
Authors: Vieira Nelson
Published: July 2023

Quaternionic convolutional neural networks (QCNN) possess the ability to capture both external dependencies between neighboring features and internal latent dependencies within features of an input vector. In this study, we employ QCNN with activation functions based on Bessel-type functions with trainable parameters, for performing classification tasks. Our experimental results demonstrate that this activation function outperforms the traditionalReLUactivation function. Throughout our simulations, we explore various network architectures. The use of activation functions with trainable parameters offers several advantages, including enhanced flexibility, adaptability, improved learning, customized model behavior, and automatic feature extraction.
Back to Actual Behavior – A Modest Proposal on the Example of Exploratory Behavior in Children on the Autism Spectrum
Authors: Pisula Ewa , Pisula Wojciech
Published: July 2023

Autism spectrum is characterized by difficulties in social communication and interactions and limited, restricted patterns of behavior, interests, and activity. It is diagnosed and described on the basis of behavioral characteristics. Therefore, behavior research plays a critical role in better understanding the functioning of this group of children. Studies on their interests and curiosity take mainly the form of experiments on visual and object exploration. We argue that important aspects of behavior might be neglected within these studies and propose to refine the approach by incorporating the achievements of classic ethology, contemporary measurement and analytical tools, and the theory of integrative levels. We conclude with an outline of the proposed approach in a short list of major methodological postulates.
The Origin and Purpose of Legal Protection for the Integrity of Copyright Metadata
Authors: Cadavid Jhonny Antonio
Published: July 2023

Rights management information is copyright metadata legally protected by copyright law. The origin of such protection was a United States policy for governance of the information superhighway (the internet) and digital networks. The main discussion documents leading up to the WIPO internet treaties reveal that the policy behind protecting the integrity of copyright metadata was aimed at higher objectives of public interest, such as consumer protection, market efficiencies, and authenticity of creative content. Copyright management information was envisaged as one element of digital infrastructures for creating global electronic commerce, but digital copyright was also foreseen as important for the dissemination of cultural heritage. Today these infrastructures have become a reality through legislation on orphan and out-of-commerce works in Europe, and for the licensing and distribution of royalties for musical works and sound recordings in the US. Countries that implement the WIPO treaties or transplant the US law without considering the whole policy behind the protection of copyright metadata are falling into a copyright management gap because, globally, the discovery, visibility, compensation, and monetisation of local content from places without adequate digital rights metadata infrastructures will be more challenging. This article shows that US digital dominance is codifying and writing the DNA of cultural content.
Measuring cognitive flexibility in anorexia nervosa: Wisconsin Card Sorting Test versus cued task-switching
Authors: Dann Kelly M. , Veldre Aaron , Miles Stephanie , Sumner Philip , Hay Phillipa , Touyz Stephen
Published: July 2023

Purpose

The Wisconsin Card Sorting Test (WCST) is the most common measure of cognitive flexibility in anorexia nervosa (AN), but task-switching paradigms are beginning to be utilized. The current study directly compared performance on a cued task-switching measure and the WCST to evaluate their association in participants with a lifetime diagnosis of AN, and to assess which measure is more strongly associated with clinical symptoms.

Methods

Forty-five women with a lifetime diagnosis of AN completed the WCST, cued color-shape task-switching paradigm, Anti-saccade Keyboard Task, Running Memory Span, Eating Disorder Examination Questionnaire, Depression Anxiety Stress Scales short form and Eating Disorder Flexibility Index.

Results

There was no evidence of a significant association between WCST perseverative errors and cued task-switching switch costs. Results suggest lower working memory capacity is a determinant of higher perseverative error rate. When controlling for mood variables, neither cognitive flexibility measure was a significant independent predictor of symptom severity.

Conclusions

Results provide support for previous suggestions that WCST perseverative errors could occur due to difficulties with working memory, sensitivity to feedback, and issues with concept formation. Cued task-switching paradigms may provide a useful measure of cognitive flexibility for future eating disorders research by reducing task-specific confounds.

Level of evidence

Level III Case–control analytic study.
Coal petrology, sedimentology and depositional environment of the Parvadeh coals in the Upper Triassic, Tabas Block of Central-East Iran
Authors: Zamani Ziba , Rahimpour-Bonab Hossain , Littke Ralf
Published: July 2023

Peat forming environment strongly influences the economic value of any coal seam and coal-bearing strata. Hence, palaeoenvironmental studies provide important information for coal resource exploration. In this context, detailed studies on selected coals from the Parvadeh Area, Iran, were conducted using sedimentology, coal petrology, X-ray diffraction (XRD), scanning electron microscopy- energy dispersive X-ray analyzer (SEM-EDX), and proximate analysis. The sedimentary facies above and below the coal seams are mainly marine or marine-influenced facies, supporting that the coal-forming mires in the Parvadeh Area developed in a paralic environment, where the base level must be closely related to sea level. Sulfur contents are moderate to high and mark the influence of brackish/marine water, especially during transgression after peat growth in a lower delta plain environment. The peat-forming mires extended on coastal/delta plain lobes. The lower delta plain/coastal plain coals are characterized by lateral continuity and substantial thickness, whereas few coals possibly representing the upper delta plain are thin and more discontinuous. The detrital nature and composition of the numerous partings and the overall high ash yield in the coal seams indicate an active tectonic area with high rates of creation of accommodation space over peat growth. Coal petrology and coal facies analysis exhibits a permanently high water table within a forest swamp and mostly rheotrophic conditions, sometimes with connection to the seawater. According to paleoenvironmental reconstructions, it seems that coal layers may be thicker, with less sulfur (pyrite), but more clastic minerals and partings toward the western part of the area. Although these coal seams presently have low economic potential for the mining operation, partly due to great depth, this humic, high-volatile to medium-volatile bituminous coal may be suitable for exploration of coal bed methane resources.
Computer aided derivation of vehicle modules and functions from use cases in order to create user orientated vehicle interior concepts
Authors: Riddoch Angus , Twer Arne , Raulf Christian , Roß Tobias , Sieg Christian , Gronau Hendrik , Küçükay Ferit , Vietor Thomas , Mantwill Frank
Published: July 2023

Trends such as autonomous driving, non-driving related activities and digitalisation are contributing to a revolution in vehicle concept design. An aspect of this is the consideration of future use cases in shaping vehicle architectures. Future user scenarios can help identify relevant use cases, from which the user needs and system requirements can be derived. The derived requirements need to be matched to vehicle functions and architectural modules that can fulfil them. However, the optimal combination of functions and modules can be difficult to identify due to the numerous possibilities. The aim of this paper is to apply a matrix-based methodology that enables the systematic matching of requirements to vehicle functions and/or modules, as well as the identification of an ideal module/function combination for all the considered requirements. An example is presented that considers a requirement specification that has been derived from predetermined user needs. The requirements are matched to suitable functions/modules and the best possible combinations are determined using the proposed matrix-based methodology. Two optimal combinations are selected, one for a vehicle in the entry level segment and the other for a premium vehicle. The results indicate it is possible to determine an optimal combination for both vehicle segments considered, as well as the substantial influence the rating parameters have on the end result. Lastly, it is shown how the results can be applied by concept designers in order to draft tailored, user-orientated interior concepts.
Exploring investor behavior in Bitcoin: a study of the disposition effect
Authors: Schatzmann Jürgen E. , Haslhofer Bernhard
Published: July 2023

Investors commonly exhibit the disposition effect—the irrational tendency to sell their winning investments and hold onto their losing ones. While this phenomenon has been observed in many traditional markets, it remains unclear whether it also applies to atypical markets like cryptoassets. This paper investigates the prevalence of the disposition effect in Bitcoin using transactions targeting cryptoasset exchanges as proxies for selling transactions. Our findings suggest that investors in Bitcoin were indeed subject to the disposition effect, with varying intensity. They also show that the disposition effect was not consistently present throughout the observation period. Its prevalence was more evident from the boom and bust year 2017 onwards, as confirmed by various technical indicators. Our study suggests irrational investor behavior is also present in atypical markets like Bitcoin.