bluuebunny/crossref_metadata_2025 huggingface dataset:
Exascale computing: What future architectures will mean for the user community
Authors: Gara Alan  , Nair Ravi
Published: February 2025

Exascale computing platforms will soon emerge over the horizon. Architectures for such platforms are already on drawing boards. This paper will focus on some of the key drivers of the technology that will be needed on exascale platforms along with the impact that these new technology drivers will have on system architecture. The important implications for users of such exascale systems will also be discussed.
Using Multi-Core Architectures to Execute High Performance-Oriented Real-Time Applications
Authors: Aussagues C.  , Ohayon E.  , Brifault K.  , Dinh Q.
Published: February 2025

This paper presents a method and the associated tools to design and implement embedded real-time systems that execute high-performance-oriented applications on multi-core architectures. After presenting the OASIS design, compilation and execution framework, the paper focuses on the principles of the modifications performed on the safety-oriented real-time kernel to execute transparently and consistently multitasking applications on multi-cores. It then gives the first results of benchmarking performed on a Dassault Aviation's HPC application called “2D-tracking algorithm”. It concludes on the future works towards the introduction of data-parallelism in the OASIS parallel time-triggered programming and underlying execution models.
Public Key Cryptosystem Based on Finite Automata for Multilateral Antiterrorist Activity Support
Authors: Margarov Gevorg  , Chopuryan Siranush
Published: February 2025

The public key cryptosystem based on finite automata has been represented in this article, which can be used to support of multilateral antiterrorist activity. The public key cryptosystem based on finite automata possesses high stability against information warfare, which allows protecting the secret information more effectively on the Internet from eavesdroppers. Such cryptosystem also possess high level of performance, which is defined by use fast logic operation at data encryption and decryption.
Characterization of Magnetoelastic Properties at Nanoscale Using Atomic Force Microscopy
Authors: Nalladega Vijay  , Sathish Shamachary  , Gigliotti Michael  , Subramanian P.R.  , Iorio Luana
Published: February 2025

Magnetostriction is an important property of magnetic materials that have many technical applications. It is well known that nanocrystalline magnetic alloys can exhibit excellent soft magnetic properties including small effective saturation magnetostriction. Many research studies have focused on the crystallization kinetics, hardness and coercivity of these magnetic nanocrystalline materials. However, to the knowledge of the authors, no study has been reported so far on the magnetostriction properties of the amorphous and nanocrystalline magnetic alloys at nanoscale resolution. In this paper, we report an atomic force microscopy (AFM) based technique to investigate magnetoelastic properties of amorphous and nanocrystalline magnetic alloys. In a conventional magnetic force microscopy, the magnetic field from the sample can cause random, partial remagnetization of the magnetic tip during the scanning. This may cause problems when imaging soft magnetic materials. Hence, in this study, an attempt has been made to image magnetoelastic properties using nonmagnetic tips. In our experimental set-up, the traditional AFM has been externally modified to detect and measure the magnetoelastic interactions between the tip and the sample. The sample was placed in low frequency external electromagnetic field. The AFM tip was used to detect the surface oscillations of the magnetic sample in the external field. Amorphous and nanocrystalline magnetic materials of the FeSiBNbCu composition class were studied. Magnetostrictive images of both samples were obtained and compared. The differences in the images are explained based on the magnetostriction behavior of both materials.
Remote Field ECT for Evaluation of Local Wall Thinning using Pancake Coils
Authors: Yamamoto Toshihiro  , Takagi Toshiyuki  , Uchimoto Tetsuya
Published: February 2025

The remote field eddy current testing (RFECT) is usually used for inspection of ferromagnetic small tubes with bobbin coils. As a new aspect of RFECT, YuShi Sun introduced RFECT for flat plates using pancake coils. However, a principle of RFECT using pancake coils is still unclear, and a few studies on this kind of RFECT have been reported so far. The aim of this study is to evaluate detection and sizing capabilities of RFECT using pancake coils especially for applying this technique to evaluation of local wall thinning in large diameter pipes from the outside. The present paper shows relationships between detection signals and defect shapes obtained by numerical simulations, and also compares one of the numerical results with a corresponding actual experimental result. The results indicate the possibility of estimating a defect shape from detection signals and the possibility of detecting a defect with a relatively large lift-off height or on the bottom side of double plates.
Micro-magnetic Evaluation of Micro Residual Stresses of the 2nd and 3rd Order
Authors: Rabung M.  , Altpeter I.  , Dobmann G.  , Szielasko K.
Published: February 2025

Micro residual stresses (MRS) of the 2nd and 3rd order play an important role in the fracture mechanical analysis of thermally-cycled materials and thus in lifetime analysis of such components. In multi-phase materials there can exist two kinds of MRS: Thermally-induced MRS of the 2nd order and coherent MRS of 3rd order. The first appear when individual material phases exhibit different thermal expansion coefficients and the second occur when the lattice parameters of the second phase particles which are embedded coherently in the matrix and the lattice parameter of the matrix are different. The main emphasis of the presented research work is the development of a micro-magnetic non-destructive technique for quantitative characterization and separation of MRS of 2nd and 3rd order in iron-based materials.
A Framework for Ecosystem Services Planning
Authors: Staes Jan  , Vrebos Dirk  , Meire Patrick
Published: February 2025

In many regions in Western Europe the rural matrix is under high pressure because of land use fragmentation and environmental degradation. New frameworks and approaches are needed to revalue the rural matrix and stop its degradation. The Flemish Region of Belgium has a severely degraded environmental and ecological quality. Increasing environmental degradation in Flanders is mainly remediated by technical measures and infrastructure. Due to institutional fragmentation of competences in environmental management, there is a lack of integrated measures that improve environmental quality on multiple aspects, which often leads to inefficient or adverse policy initiatives. The ecosystem services (ES) approach can be a unifying concept, bringing together different environmental, social, and economic aspects. The potential of landscape management and planning for ecosystem service generation needs to be recognized as a true option to reach both environmental and societal policy objectives at different scales [1]. We use the “ecosystem service approach” as an umbrella concept to advocate for the creation or restoration of functional ecosystems as a cost-efficient and multipurpose strategy to improve environmental quality. The identification and quantification of hidden demands for ecosystem services is confronted with potential ecosystem services creation, based on hydro-geomorphologic suitability. The aim of this methodological framework is to develop an adequate scientific basis to contribute to a policy-relevant strategy for ecosystem services research in Belgium as part of the overall policy of sustainable development. A framework is presented that aims to (a) overcome the policy-science gap by presenting the ecosystem approach as an alternative for the increasing cost and failure of traditional environmental management; (b) identify and map potential ES; (c) quantify the potential delivery of ES by use of conceptual models that account for the spatial and temporal variability within a landscape context as ecosystems generate and receive fluxes from surrounding land-use; and (d) develop a policy support tool that allows optimal geographical implementation of ES generation. The proposed methodological framework will be further elaborated and implemented through a Strategic Basic Research project, funded by the Flemish Institute for Science and Technology.
Lightning Electromagnetic Fields Radiation Computation by Hybrid Method: Influence of Lightning Return Stroke Current Parameters
Authors: M'ziou Nassima  , Mokhnache Leila  , Boubakeur Ahmed  , Kattan Rafic
Published: February 2025

The aim of this paper is the computation of electromagnetic fields radiated by lightning witch is necessary in order to protect effectively the electrical and electronic systems against disturbances caused by this kind of discharges. In this paper we propose a hybrid method to evaluate the electromagnetic field associated to lightning return stroke current. This method is the combination of the images method and finite difference time-domain (FDTD) method. We calculate first, the magnetic field with images method (using the Simpson integration numerical method), and, secondly, the electric field based partially on the FDTD method. The lightning return stroke current is modeled by the engineering models. In this study we compare five lightning return stroke current models, namely the Transmission Line (TL) model, the Modified Transmission Line with exponential decay (MTLE) model, the Modified Transmission Line with linear decay (MTLL) model, Traveling current Source (TCS) model, and Bruce and Gold model (BG) model by assuming a common current wave shape at the channel base. In this work we have presented the influence of the variable speed of the return stroke current and the variable factor λ of the MTLE model on the computation of lightning electromagnetic field.
High Frequency Oscillation Modes in a Transformer Winding Disc
Authors: Tavakoli Hanif  , Bormann Dierk  , Engdahl Göran
Published: February 2025

The high frequency resonant behavior of a winding disc is studied by measurements on a test setup, and by computer simulation of lumped-element circuit models. It is shown that in order to achieve satisfactory agreement between both, every turn must be described by several segments in the model. The reason is that the high frequency end of the spectrum is dominated by “azimuthal” resonance modes which are not present in models with lower resolution. The intermediate frequency range is characterized by “radial” resonances, present even in lower resolution models. The different physical character and properties of these modes are discussed. Our findings provide new insight into the interpretation of frequency response measurements on power transformers.
Permanent Magnet Generator for Hybrid Electric Vehicle
Authors: Valtonen Mikko  , Parviainen Asko
Published: February 2025

Hybrid electric vehicle (HEV) may include a combustion engine which operates associated with an electric generator. The electric generator converts the mechanical energy produced by the combustion engine into electric energy, which is converted with AC – DC transducer to DC voltage and stored in the batteries or super capacitors or used directly in driving motors of HEV. For such applications, a compact, high performance electric machine is required. This paper proposes axial-flux permanent magnet machines for such applications. As a prototype, a 120 kW permanent magnet generator is constructed. The generator type is a double sided axial-flux permanent magnet generator (AFPMG) with the internal PM disk rotor.
Steady State Simplified Mathematical Model of a Particular Permanent Magnet Transverse Flux Motor
Authors: Viorel Ioan-Adrian  , Strete Larisa  , Viorel Alina-Cristina
Published: February 2025

A simplified mathematical model of a particular permanent magnet transverse flux motor (PMTFM) is introduced in the paper. Based on magnetic equivalent circuits which allow calculating the main no-load, armature reaction and leakage fluxes, the model is simple and quite accurate as proved by the comparison made with the 3D-FEM results calculated for a sample motor.
Frequency Response Performance Analysis of p-i-n Photodiodes
Authors: Pereira Jorge Manuel Torres
Published: February 2025

This paper investigates the effects due to the absorption region width, bias voltage, temperature and wavelength of the incident light on the transit time limited frequency response of p-i-n photodiodes. The implemented numerical model is very general and enables us to obtain the frequency response of p-i-n photodiodes with an arbitrary electric field profile and non-uniform illumination. The bandwidth is seen to decrease when the absorption region width, bias voltage and temperature increase. For light incident on the p side, the bandwidth decreases when the wavelength of the incident light increases.
Reconstruction of Conductivity Distribution in Low Conductive Materials Using Magnetic Induction Tomography and Adjoint Model
Authors: Baniukiewicz Piotr
Published: February 2025

In this paper, an iterative algorithm applied for MIT image reconstruction is considered. Commonly applied algorithms based on sensitivity method are very computationally intensive and only the low resolution images can be reconstructed within practical time limits. The author proposes a modification of standard differential algorithms relying on the application of the adjoint method. Moreover, the MIT image is reconstructed in four steps in order to stabilize the solution.
The South Ossetian Conflict and Post-Conflict Prospects for Georgia
Authors: Japaridze Tedo
Published: February 2025

In this paper, Tedo Japaridze analyses the post-war situation in Georgia and South Ossetia following the 2008 conflict with Russia. He appeals to the country's western friends to help resolve a problem that he argues is theirs too. Japaridze has served as Georgian Foreign Minister, as Chair of Georgia's National Security Council, and as Georgian Ambassador to the United States, Canada and Mexico. He has also served as Secretary-General of the Organization for Black Sea Economic Cooperation (BSEC).
Online Social Networks for the Elderly – Acceptable Interfaces for People with Serious Impairments
Authors: Zejda David
Published: February 2025

Today's Web 2.0 is a place, where people express themselves, interact share their lives, socialize. Thousands of elderly people join various social networking sites or use the Net to keep in touch with their families. But, as we show in the paper, today's social software does not target their needs sufficiently. While there are usable solutions, usability itself does not imply acceptability. Acceptable interfaces should reflect user's habits, follow understandable metaphors, and above all, target their deep needs as precisely as possible. Further, the elderly can not be taken as a homogeneous group characterized by the impairments, but rather as a set of individual human beings, with specific wishes, desires, habits, and with some disabilities, of course. In the paper we formulated qualities which should social software meet to be widely perceived as beneficial and in result accepted by the elderly and by people with serious impairments.
Gene Mutations Frequency in Tradescantia Cells as a Bioindicator of the Environment at Risk
Authors: Cebulska-Wasilewska Antonina
Published: February 2025

Any accidentally contaminated complex mixtures like ambient air, water or soil pose the environmental risk and can lead to a potential danger to living organisms and create the human health hazard. It is important that the limited resources available are focused on first discerning major harmful or genetic and/or carcinogenic hazards. It is important to search for the correlation between evidence of the induced genotoxic damage in exposed living organisms and human with the accurate measures of exposures. Bio-monitoring techniques associated with simple methods like plant systems are an essential component of a cost-effective attempt to improve the situation. Tradescantia stamen hair (Trad-SH) assay is based on one of the most radiosensitive plant known. Extremely high radiosensitivity of the heterozygous clones of Tradescantia is followed by very high sensitivity to chemical mutagens as well. A good correlation between genotoxicity data obtained in the studies in vitro with Trad-SH assay and cytogenetic damage (CA, SCE) induced in human lymphocytes after exposures to the same genotoxic agents (radiation or chemicals) has been reported. Existing correlations between physical measurements of genotoxic agents and various biological end-points detected in somatic cells of Tradescantia stamen, combined with indicated similarity of the Trad-SH cells with human cells responses to the physical and chemical mutagens, establish this system as one of the most acknowledged bioindicators suitable for monitoring a quality of the environment and indicating the emergency situation or potential genetoxic risk to human health.
Crossing the Border: Exploring Complexity Methods in Establishing International Borders and Other Evidence-Based Policy Decisions
Authors: Johnston Erik W.  , Quigley Paul  , Kim Yushim
Published: February 2025

Evidence-based approaches to international policy-making may improve the quality of policy decisions compared to traditional decision making principles. For example, decision makers traditionally rely on existing administrative boundaries when establishing new international borders following the dissolution of a state or the secession of part of that state. An evidence-based alternative could involve consideration of numerous other factors and goals in establishing a border. Policy informatics, encompassing new knowledge, tools, and approaches should become increasingly useful for informing policy decisions, especially where decision makers are faced with a constant influx of information, conflicting values and political pressures. Specifically, a complexity approach has shown utility in effectively extracting useful patterns from complex landscapes in various science areas. However, its applications to public policy problems have been limited due to some unique obstacles and barriers inherent to these problems. Through the example of border resolutions, we examine the evolution of using scientific reasoning to make policy choices and how we might be able to include a complexity approach more regularly in evidence-based policy debates.
Societal Dynamics around Nanothreats: Myths Complex and the Reality (or Experimental Facts)
Authors: Kharlamov Oleksii  , Skripnichenko Alla  , Kharlamova Ganna  , Fomenko Veneamin
Published: February 2025

The appearance of a new threat to humanity – nanothreat – is connected to the epoch of discoveries in the field of physics and chemistry at the end of the last century: 1) By the creation of electronic microscopes capable to identify individual molecules and nanodimensional objects such as nanoparticles (nanophases) and nanostructures; 2) By detection of a new state of substance, the properties of which radically differ from all previously known. These substances are extremely chemically active and their influence on living organisms is largely not known yet. Nanoparticles from the environment, food and clothes can easily penetrate human organism by all accessible routes (nose, mouth and skin) and weaken (or injure) various organs. Therefore the nanoecological threat is practically uncontrollable. 3) By the appearance of an opportunity to manipulate separate molecules, by atoms and nanoparticles, and to create nanorobots, various optical and electronic nanosystems (which can be capable of self-reproduction). However, the process of self-reproduction of “smart” nanosystems potentially resulting with “grey goo” can be uncontrollable. Nanotechnological threat is connected to the creation of nanoweapons as well as nanosystems for the replacement of natural organs, potentially transforming Homo sapiens into nanopeople. Nanoprogress is created (as a rule) simultaneously with the development and deepening of democracy, therefore personal nanosensors of residence, intelligence and feelings will present the main threats at the nanodemocracy epoch.
Complexity and the Role of Interactions
Authors: Martinás Katalin
Published: February 2025

Our civilization is a complex system of individuals interacting with the environment. Societal dynamics develops via human actions, which are governed by decisions. The action of individuals is always a choice among the possibilities recognized as allowed by the circumstances. The choice always implies a decision. The theory of human decisions will be discussed with an emphasis on the difference between simple system and complex system approaches. The basic criterion for decisions is that the best is selected, but which is the best one? Founders and best proponents of utilitarianism, Jeremy Bentham (1748-1832) and John Stuart Mill (1806-1873) started with the postulate known as the “greatest happiness principle”. It can be viewed as the governing law of human actions. In the first part we summarize the way in which the greatest happiness principle did appear in the history. In the second part we outline a new approach to axiomatic economics, with the greatest happiness principle as the basic axiom. The result is a new dynamic microeconomics where the maximization rule of rational-choice decisions is replaced by a force law. The resulting theory is consistent with both physics and economics, especially the resource and environmental branches.
Democratization and Civil Society in the Post-Soviet South Caucasus
Authors: Ergun Ayça
Published: February 2025

The post-Soviet period in the South Caucasus is shaped by the processes of nation and state-building and attempts to democratization as elsewhere in the former Soviet Union. The aim of this article is to highlight the peculiarities of the post-Soviet transition in the region while focusing on the nature of political transformation, democratization and civil society development. The analysis of the post-independence politics in the South Caucasus shows that the entire process of transition is dominated by the co-existence of continuity and change. The patterns of continuity inherited from the Soviet past are predominantly represented and reproduced by the ruling elite with varying degrees whereas the patterns of change associated with liberalization and democratization are mainly internalized and propagated by the societal actors. Yet, it is quite clear that unless the ruling elite's initiatives and policies towards democratic change are secured, the transformative power of societal actors remains insufficient.
Arabic Family in Transition: The Case of Palestinians Living in Israel
Authors: Veronese Guido  , Castiglioni Marco  , Said Mahmoud
Published: February 2025

Arab culture views the family as the symbolic fortress of social cohesion. The family holds the traditional narratives and passes them on, ensuring their continued value; conversations within the home and between neighboring families feed into accounts of identity which in turn serve to maintain the great Arab “cultural” narrative. this chapter will explore some characteristics of the Palestinian family in Israel. The next two sections provide some historical background and a description of the distinctive features of Palestinian families in the State of Israel and the Occupied Territories respectively. A further section briefly outlines a qualitative field study examining some of these aspects. Finally, the key findings of the research are discussed in the light of the existing literature.
Solid-state NMR on membrane proteins: Methods and applications
Authors: Ader Christian  , Nand Deepak  , Renault Marie  , Cukkemane Abhishek A.  , Baldus Marc
Published: February 2025

We describe recent progress in using Magic-Angle-Spinning based solid-state NMR to study structural aspects of membrane-embedded proteins. Experimental aspects such as protein production and reconstitution are reviewed. Moreover, we discuss solid-state NMR methods leading to a comprehensive description of the conformational landscape of membrane proteins and review applications to retinal proteins and a chimeric ion channel.
Advances in cell-free protein synthesis for NMR sample preparation
Authors: Kralicek Andrew V.  , Ozawa Kiyoshi
Published: February 2025

Cell-based expression strategies exist for the2H,13C and15N stable-isotope enrichment of target proteins for NMR studies. However, there are no guarantees that the protein will express to a reasonable level or be folded correctly. In addition, the economic cost of producing an isotope-labeled protein may be prohibitive because of the scale of production required or the cost of isotope-labeling sources. Many of these problems may be alleviated by the use of cell-free protein synthesis systems. The open nature of these systems allows the addition of molecules that can aid the folding and stabilization of the protein being produced. Same-day mg/ml production of isotope-enriched proteins can be achieved cheaply by using isotope-labeled amino acids sparingly in the reaction mix. Cell-free systems based on Escherichia coli and wheat germ extracts have been adapted for the isotope enrichment of proteins. The best expression conditions and construct design for target protein production can be screened on the microlitre scale prior to preparative production on the millilitre scale. Selective and uniform isotope enrichment is achieved by simply replacing the amino acids in the reaction mix with their equivalent labeled versions. Combinatorial selective labeling strategies have been developed to enable residue-specific and sequence-specific assignment of NMR spectra. The study of large proteins and complexes can be facilitated by cell-free deuteration of the target protein(s), or by the stereo-array isotope labeling (SAIL) approach. The open nature of the cell-free system means that subunits of a complex can be exclusively labeled by expressing them in the presence of their unlabeled binding partners. In this way, normally insoluble subunits can be rescued into soluble complexes. A number of strategies also exist for the site-specific incorporation of non-natural amino acids. In the future, these methods will enable the incorporation of novel amino acids that can aid NMR assignment or investigations of functional activity by NMR.
Isotope labeling of larger DNAs for NMR structural studies
Authors: Wijmenga Sybren S.  , Nelissen Frank H.T.  , Heus Hans A.  , Tessari Marco
Published: February 2025

Isotope labeling has contributed markedly to the success of multi-dimensional hetero-nuclear NMR spectroscopy in structure and dynamics investigations of proteins, RNAs, DNAs and their complexes. For proteins and RNAs, isotope labeling has become standard practice. In sharp contrast, isotope labeling of larger ds/ssDNAs remains a significant challenge, largely due to a lack of comparably simple, flexible and cost-efficient methods for their synthesis. Here we review isotope labeling of DNA and RNA for NMR structural studies and highlight recent progress made in the field of isotope labeling of larger ssDNA and related RNA labeling. The progress includes labeling schemes with selective deuteration as well as segmental labeling approaches.
Hyphenated NMR techniques
Authors: Kesting Julie R.  , Johansen Kenneth T.  , Jaroszewski Jerzy W.
Published: February 2025

This chapter describes principles and applications of on-line coupling (hyphenation) of NMR spectroscopy with liquid-chromatographic and other separation methods as well as with other forms of spectroscopy. This results in highly integrated and automated systems for structure determination of components of complex mixtures at microgram and nanogram levels. Hyphenated NMR techniques provide accelerated and detailed insight into components of complex mixtures of biological origin without initial separation of the constituents.
NMR and SAXS: A Perfect Marriage and New Approach for RNA Structure Determination
Authors: Zuo Xiaobing  , Wang Jinbu  , Wang Yun-Xing
Published: February 2025

RNAs are versatile molecules and play important roles in various biological processes. Their functions are embedded in their structures and dynamics, yet there is little propensity correlation between a primary sequence of an RNA and its three-dimensional structure except in the case of simple RNA hairpins and the special case of tRNAs. Despite more than a decade of significant progress in both X-ray crystallography and NMR spectroscopy, structure determination and elucidation of large RNAs with complex folds, using either experimental, computational or combined approaches, remains a major interest as well as a challenge to the research community in contemporary biology. In this chapter we outline a new strategy for solution structure determination of RNA using restraints that are derived from experimental NMR measurements and small-angle X-ray scattering data. In addition, we present practical details on how to prepare RNA sample solutions for successful SAXS experiments.
Requirements Models for Critical Systems
Authors: Heitmeyer Constance
Published: February 2025

This chapter describes a formal approach to the modeling, specification, validation, and verification of the requirements, i.e., the required externally visible behavior, of a software system. The focus is on a special class of systems called critical systems, systems which require compelling evidence that the system delivers essential services and satisfies critical properties, such as safety and security properties. The objective of a formal approach to requirements is to produce a complete, consistent, and correct model of the requirements. The approach described relies on a formal specification of the requirements model in the SCR tabular notation, which allows several kinds of tool-based analyses of the model.
Discrete Convexity and Its Applications
Authors: Koshevoy G.A.
Published: February 2025

We explain what subsets of the lattice \mathbb{Z}nand what functions on the lattice \mathbb{Z}ncould be called convex. The basis of the theory is the following three main postulates of classical convex analysis: concave functions are closed under sums; they are also closed under convolutions; and the superdifferential of a concave function is nonempty at each point of the domain. Interesting (and even dual) classes of discrete concave functions arise if we require either the existence of superdifferentials and closeness under convolutions or the existence of superdifferentials and closeness under sums. The corresponding classes of convex sets are obtained as the affinity domains of such discretely concave functions. The classes of the first type are closed under (Minkowski) sums, and the classes of the second type are closed under intersections. In both classes, the separation theorem holds true. Unimodular sets play an important role in the classification of such classes. The so-called polymatroidal discretely concave functions, most interesting for applications, are related to the unimodular system An:= {±ei, ei− ej}. We demonstrate that such functions naturally appear in mathematical economics, in combinatorics, play an important role for solution of the Horn problem, for describing submodule invariants over discrete valuation rings, etc.
Activation of Cell Cycle Proteins in Transgenic Mice in Response to Neuronal Loss But Not Aß and Tau Pathology
Authors: Lopes Joao P.  , Blurton-Jones Mathew  , Yamasaki Tritia R.  , Agostinho Paula  , LaFerla Frank M.
Published: February 2025

Cell cycle proteins are elevated in the brain of patients and in transgenic models of Alzheimer's disease (AD), suggesting that aberrant cell cycle re-entry plays a key role in this disorder. However, the precise relationship between cell cycle reactivation and the AD hallmarks, amyloid-beta (Aβ) plaques and tau-laden neurofibrillary tangles, remains unclear. We sought to determine whether cell cycle reactivation initiates in direct response to Aβ and tau accumulation or whether it occurs as a downstream consequence of neuronal death pathways. Therefore, we used a triple transgenic mouse model of AD (3xTg-AD) that develops plaques and tangles, but does not exhibit extensive neuronal loss, whereas to model hippocampal neuronal death a tetracycline-regulatable transgenic model of neuronal ablation (CaM/Tet-DTAmice) was used. Cell-cycle proteins activation was determined in these two models of neurodegeneration, using biochemical and histological approaches. Our findings indicate that Cdk4, PCNA and phospho-Rb are significantly elevated in CaM/Tet-DTAmice following neuronal death. In contrast, no significant activation of cell-cycle proteins occurs in 3xTg-AD mice versus non-transgenic controls. Taken together, our data indicate that neuronal cell cycle reactivation is not a prominent feature induced by Aß or tau pathology, but rather appears to be triggered by acute neuronal loss.
Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-alcoholic Steatohepatitis
Authors: de la Monte Suzanne M.  , Lyn-Cook Jr. Lascelles E.  , Lawton Margot  , Tong Ming  , Silbermann Elizabeth  , Longato Lisa  , Jiao Ping  , Mark Princess  , Xu Haiyan  , Wands Jack R.
Published: February 2025

Background: Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can lead to cognitive impairment and neurodegeneration. Experimental high fat diet (HFD) induced obesity with T2DM causes neurodegeneration with brain insulin resistance. Objective: Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated their potential role in neurodegeneration. Methods: C57BL/6 mice were pair-fed HFD or control diets for 4-20 weeks. Pro-ceramide genes and biochemical indices of neurodegeneration were measured. In vitro experiments directly examined neurodegenerative effects of ceramides. Results: Chronic HFD feeding gradually increased body weight, but after 16 weeks, liver weight surged (P<0.001) due to triglyceride accumulation (P<0.001), and brain weight declined (P<0.0001). HFD increased pro-ceramide gene expression in liver (P<0.05-P<0.001), but not brain. Temporal lobes of HFD fed mice had increased ubiquitin (P<0.001) and 4-hydroxynonenal (P<0.05 or P<0.01), and decreased tau, β-actin, and choline acetyltransferase levels (P<0.05-P<0.001) with development of NASH. Ceramide treatment of neuronal cultures caused cell death, oxidative stress, mitochondrial dysfunction, and insulin resistance. Conclusions: In obesity, T2DM, or NASH, excess hepatic production of neurotoxic ceramides that readily cross the blood-brain barrier causes cognitive impairment with brain insulin resistance via a liver-brain axis of neurodegeneration.
Animal Model of Insulin-Resistant Brain State: Intracerebroventricular Streptozotocin Injection Deteriorates Alzheimer-Like Changes in Tg2576 APP-Overexpressing Mice
Authors: Plaschke Konstanze  , Kopitz Jürgen  , Siegelin Markus  , Schliebs Reinhard  , Salkovic-Petrisic Melita  , Riederer Peter  , Hoyer Siegfried
Published: February 2025

Sporadic Alzheimer's disease has been proposed to start with an insulin-resistant brain state (IRBS). We investigated the effect of IRBS induced by intracerebroventricularly (icv) administered streptozotocin (STZ) on behavior, glycogen synthase kinase-3 (GSK)alpha/beta content, and the formation of AD-like morphological hallmarks Abeta-amyloid and tau protein in amyloid precursor protein (APP) tg2576 mice. Nine-month-old tg mice were investigated 6 months after a single icv injection of STZ or placebo. Spatial cognition was analyzed using the Morris water maze test. Soluble and aggregated Abeta40/42 fragments, total and phosphorylated tau protein, and GSK-3alpha/beta were determined by ELISA. Cerebral (immuno)histological analyses were performed. In tg mice, STZ treatment increased mortality, reduced spatial cognition, and increased cerebral aggregated Abeta fragments, total tau protein, and congophilic amyloid deposits. These changes were associated with decreased GSK-3alpha/beta ratio (phosphorylated/total). A linear negative correlation was detected between Abeta42 and cognition, and between GSK-3alpha/beta ratio and aggregated Abeta40+42. No marked necrotic and apoptotic changes were observed. In conclusion, IRBS may aggravate AD-like changes such as behavioral and increase the formation of pathomorphological AD hallmarks via GSK-3alpha/beta pathway in APP-overexpressing mice.
Developing Immunotherapies for Alzheimer's Disease Using a Cholesterol-Fed Rabbit Model in the Context of Th Cell Differentiation
Authors: Coico Richard  , Woodruff-Pak Diana
Published: February 2025

The success of strategies that therapeutically exploit immune responses to self antigens such as those expressed on melanoma cells to treat patients suffering from melanoma is well established. In transgenic Alzheimer's disease (AD) animal models, elimination of β-amyloid (Aβ) pathology using Aβ immunization galvanized the AD research community a decade ago. Using an animal model of AD with closer parallels to human AD, the cholesterolemic rabbit model, we tested immunotherapeutic strategies that could maximize humoral immune responses while minimizing proinflammatory responses. The finding that some patients with AD enrolled in a clinical trial to inoculate against A experienced a misdirected polarization of Th cells reminds us that our knowledge of T cell biology, immune regulation, and the precise functional properties of adjuvants is incomplete. In this article, we review this knowledge and consider the advantages of the rabbit for immunological studies. The langomorph species is proximate to primates on the phylogenetic scale, its amino acid sequence of A is identical to the human A sequence, and the rabbit model system is extensively characterized on a form of associative learning with parallels in normal aging in rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits treated with Aβ immunotherapy generate high titer anti-Aβ responses. The cholesterol-fed rabbit model of AD with its close parallels to human genetics and physiology, along with its validity from molecular to cognitive levels as a model of human AD, provides a promising vehicle for development of immunotherapies.
Anti-Amyloid-β Immunotherapy in Alzheimer's Disease: Relevance of Transgenic Mouse Studies to Clinical Trials
Authors: Wilcock Donna M.  , Colton Carol A.
Published: February 2025

Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the amyloid-β peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the other pathologies of Alzheimer's disease. One such therapy that has attracted significant attention is anti-amyloid-β immunotherapy. First described in 1999, immunotherapy uses anti-amyloid-β antibodies to lower brain amyloid levels. Active and passive immunization were shown to lower brain amyloid levels and improve cognition in multiple transgenic mouse models. Mechanisms of action were studied in these mice and revealed a complex set of mechanisms that depended on the type of antibody used. When active immunization advanced to clinical trials a subset of patients developed meningoencephalitis, an event not predicted in mouse studies. It was suspected that a T-cell response due to the type of adjuvant used was the cause. Passive immunization has also advanced to Phase III clinical trials on the basis of successful transgenic mouse studies. Reports from the active immunization clinical trial indicated that, similarly to effects observed in mouse studies, amyloid levels in brain were reduced.
Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-Type Neuropathology and Cognitive Deterioration
Authors: Ho Lap  , Chen Ling Hong  , Wang Jun  , Zhao Wei  , Talcott Stephen T.  , Ono Kenjiro  , Teplow David  , Humala Nelson  , Cheng Alice  , Percival Susan S.  , Ferruzzi Mario  , Janle Elsa  , Dickstein Dara L.  , Pasinetti Giulio Maria
Published: February 2025

We recently found that moderate consumption of two un-related red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type beta-amyloid (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms.
Delivery of NGF to the Brain: Intranasal Versus Ocular Administration in Anti-NGF Transgenic Mice
Authors: Capsoni Simona  , Covaceuszach Sonia  , Ugolini Gabriele  , Spirito Francesca  , Vignone Domenico  , Stefanini Barbara  , Amato Gianluca  , Cattaneo Antonino
Published: February 2025

Nerve Growth Factor (NGF) has a great potential for the treatment of Alzheimer's disease. However, the therapeutic administration of NGF represents a significant challenge, due to the difficulty to deliver relevant doses to the brain, in a safe and non-invasive way.
Cognitive Performances of Cholinergically Depleted Rats Following Chronic Donepezil Administration
Authors: Cutuli Debora  , Foti Francesca  , Mandolesi Laura  , De Bartolo Paola  , Gelfo Francesca  , Laricchiuta Daniela  , Petrosini Laura
Published: February 2025

Since acute and chronic administration of the acetylcholinesterase inhibitors (AChE-Is), namely of donepezil, improves cognitive functions in patients afflicted by mild to moderate dementia and reverses memory deficits in experimental models of learning and memory, it seemed interesting to assess the effects of chronic donepezil treatment on cognitive functions in adult rats with forebrain cholinergic depletion. Lesions were performed by means of intracerebroventricular injections of the immunotoxin 192 IgG-saporin. The cognitive functions of lesioned animals treated or not with donepezil were compared with those of intact animals. Cholinergic depletion affected working memory functions, weakened procedural competencies, affected the acquisition of localizing knowledge, and evoked remarkable compulsive and perseverative behaviors. In lesioned animals, chronic donepezil treatment ameliorated localizatory capabilities, performances linked to cognitive flexibility and procedural abilities. Furthermore, it attenuated compulsive deficits. The present data indicate positive effects of chronic donepezil treatment on specific cognitive performances, suggesting that an aimed use of AChE-Is, targeting some symptoms more than others, may be beneficial in the case of cholinergic hypofunction. The animal model used in the present research may provide an efficient method for analyzing cognition-enhancing drugs before clinical trials.
Alzheimer's Disease Selective Vulnerability and Modelling in Transgenic Mice
Authors: Götz Jürgen  , Schonrock Nicole  , Vissel Bryce  , Ittner Lars M.
Published: February 2025

Neurodegenerative diseases are characterized by ‘hot spots’ of degeneration. The regions of primary vulnerability vary between different neurodegenerative diseases. Within these regions, some neurons are lost whereas others that are morphologically indiscriminable survive. The enigma of this selective vulnerability is tightly linked to two fundamental problems in the neurosciences. Firstly, it is not understood how many neuronal cell types make up the mammalian brain; estimates are in the order of more than thousand. Secondly, the mechanisms by which some nerve cells undergo functional impairment followed by degeneration while others do not, remain elusive. Understanding the basis for this selective vulnerability has significant implications for understanding the pathogenesis of disease and for developing treatments. Here, we review what is known about selective vulnerability in Alzheimer's disease, frontotemporal dementia and Parkinson's disease. We suggest, since transgenic animal models of disease reproduce aspects of selective vulnerability, that these models offer a valuable system for future investigations into the physiological basis of selective vulnerability.
Community Initiative for Reducing Flood Risks – a Case Study
Authors: Coldewey Wilhelm G.  , Böcker Christoph  , Schuppelius Jörg
Published: February 2025

During and after flood events the persons affected undertake various actions. The initial focus is on saving life and limb and also personal property. The following case study looks at the activities undertaken by a community initiative to explore the causes of flooding in the affected region, in addition to possibilities for prevention. This is a unique approach in Germany.
Numerical Simulation of Acoustoelastic Effect in Pre-stressed Media
Authors: Pei Cuixiang  , Demachi Kazuyuki
Published: February 2025

In this work, a code of finite element method is developed for numerical simulation of the acoustoelastic effect in pre-stressed media. The possibility of assessing the stress status, by using the EMAT (electromagnetic acoustic transducer) receiver for precise measurement of LCR (refracted longitudinal) wave, is investigated. Besides that, the relationship between the polarization of transient Rayleigh wave and the state of stress is also predicted by simulation.
Flux Leakage Measurements for Defect Characterization Using NDT Adapted GMR Sensors
Authors: Pelkner Matthias  , Neubauer Andreas  , Blome Mark  , Reimund Verena  , Thomas Hans-Martin  , Kreutzbruck Marc
Published: February 2025

High-precision magnetic field sensors are of increasing interest in non destructive testing (NDT). In particular GMR-sensors (giant magneto resistance) are qualified because of their high sensitivity, high signal-to-noise ratio and high spatial resolution. We performed magnetic flux leakage measurements of artificial cracks with a GMR-gradiometer and a 3-axes GMR-magnetometer. Cracks of a depth of 44 μm still could be detected with a sufficient high signal-to-noise ratio. A semi-analytic magnetic dipole model was used for swiftly predicting magnetic stray fields. The reliable reconstruction based on measurements of artificial rectangular-shaped defects is demonstrated.
Giant Magneto-Resistive Sensor based Magnetic Flux Leakage Technique for Inspection of Track Ropes
Authors: Singh W. Sharatchandra  , Rao B.P.C.  , Mahadevan S.  , Jayakumar T.  , Raj Baldev
Published: February 2025

Giant magneto-resistive (GMR) sensor based magnetic flux leakage (MFL) technique is proposed for detection of defects in 64 mm diameter track ropes. Helmholtz coil is used for magnetization and tangential component of leakage flux from defects is measured using a GMR sensor. This technique is able to detect local flaws and loss of metallic cross-sectional area type defects in the track rope.