Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin dysfunction and Tau pathology

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.
Modeling of inter-digitated transducer for high-order contour mode resonators

LiNbO3 contour-mode resonators (CMR) have the potential to fulfill the requirement of multi-frequency wide-bandpass filters. For CMRs, the position of the inter-digitated transducer (IDT) fingers can significantly affect their performance [1], as the reflection of acoustic waves at the sharply defined mechanical boundaries cause strong interferences of these waves. In this paper, we present a model that analytically & intuitively explains the behavior of CMRs with IDT at the mechanical anti-nodes (AN) of the targeted mechanical mode vs. with IDT at the nodes (N). The model is then verified with experimental results.
Using Microworlds to Introduce Programming to Novices

Introduction to programming is a traditional and compulsory course for first year Computer Science students. However, research in the field of computer science education has highlighted that many students lack on problem solving and computational thinking skills. These issues provoke questions in the academic community as to whether the learning methodology of introductory to programming courses is appropriate. As regards the pedagogical procedure in general, the teacher-centered model was amended with the introduction of Interactive Learning Environments, which promote distributed learning. In this paper, we examine the fundamental skills needed for introductory to programming courses. Additionally, we focus on some of the most popular micro worlds and evaluate them in terms of educational suitability.
CONSISTENCY OF RENDERED IMAGES AND THEIR TEXTUAL LABELS

We present algorithms and their implementation in the ZOOM ILLUSTRATOR which enable textual labels to “float”around rendered images to which they refer. The labeling remains consistent, even when the image is rotated or scaled. Furthermore, the level of detail of the labeling adjusts to the screen space available. This is accomplished using fisheye techniques on the labels. We describe a prototypical implementation using the Open Inventorand C++ on Silicon Graphics Workstations.
Efficient Dissemination Algorithm for Scale-Free Topologies

This paper presents an efficient dissemination algorithm suitable for scale-free random topologies which model some complex real world networks. In these topologies, some sites, denoted hubs, have many more connections than the others. By exploiting then the dissemination power of hubs, we propose a new gossip algorithm where sites directly connected to hubs do not forward received messages. Our algorithm offers a very high reliability and does not require any input parameter value that informs each site if it is a hub or not. Such an information is deduced by every site during the algorithm execution. Compared to well-known probabilistic gossip algorithms, performance simulation results show that our algorithm presents good performance in terms of message complexity and latency.
Thymic Alterations in GM2 Gangliosidoses Model Mice

Background Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb −/− mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. Methodology/Principal Findings In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb −/− mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4+/CD8+ T cells and a significantly increased number of CD4+/CD8− T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb −/− mice. Conclusions/Significance These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13.
An introduction to economic geography: globalization, uneven development and place

EconomyEconomic GeographyAn Introduction to Geographical and Urban EconomicsEconomic and Social GeographyInterplacesThe New Oxford Handbook of Economic GeographyThe Changing Economic Geography of GlobalizationAn Introduction to Economic GeographyEvolutionary Economic GeographyIntroduction to Economic GeographyApplied Evolutionary Economics and Economic GeographyThe Economic Geography of InnovationEconomic Geography and the Unequal Development of RegionsIntroduction to Economic GeographyEconomic GeographyGeography and Economy in South Africa and its NeighboursEconomic geographyAn Economic Geography of Oil (Routledge Revivals)Introduction to Economic GeographyDevelopment, Geography, and Economic TheoryApproaches to Economic GeographyEconomic GeographyEconomic GeographyEconomic Geography and Public PolicyEconomic GeographyThe Geography of the World EconomyAn Introduction to Economic GeographyEconomic GeographyAn Introduction to Economic GeographyKey Concepts in Economic GeographyThe Wiley-Blackwell Companion to Economic GeographyEconomic GeographyAn Introduction to Economic GeographyThe Geography of the World EconomyAn Introduction to Economic GeographyIntroduction to Economic GeographyReading Economic GeographyAn Introduction to Economic GeographyAn Introduction to Geographical EconomicsPolitics and Practice in Economic Geography
Gradient Model Versus Mosaic Model of the Sinoatrial Node

Background —A radical reinterpretation (mosaic model) of the makeup of the sinoatrial (SA) node has been proposed to explain the characteristic regional differences in electrical activity between the periphery and center of the SA node. According to the mosaic model, the differences result from a change in the mix of atrial cells and uniform SA node cells from periphery to center, whereas according to the alternative gradient model, there are no atrial cells within the functional SA node, and the differences result from a change in the intrinsic properties of SA node cells from periphery to center. Methods and Results —A mosaic model of peripheral and central tissue has been constructed computationally by use of a coupled ordinary differential equation network (CODE) in a 2D lattice (20×20), with each node of the lattice designated randomly as an atrial cell or SA node cell (in correct proportions for periphery and center). The mosaic model fails to predict the characteristic differences in action potential rate and shape between the periphery and center, whereas the existing gradient model can do so. Conclusions —The mosaic model of the SA node is untenable, and the SA node is adequately described by the gradient model.
Topaz: Mining high-level safety properties from logic simulation traces

Formal specifications are hard to formulate and maintain for evolving complex digital hardware designs. Specification mining offers a (partially) automated route to discovering specifications from large simulation traces. In this paper, we embark on a novel and rigorous mining methodology (data preparation, mining algorithms, selection criteria, etc.) for finite-state automata checkers using an iterative and interactive mining tool, called Topaz. Topaz is evaluated using an open-source 32-bit RISC CPU design as a case study to demonstrate extraction of complex temporal properties cross-cutting through all CPU pipeline stages, guided by the CPU instruction set specification.
Temporal Correlation of Interference and Outage in Mobile Networks With Correlated Mobility in Finite Regions

In practice, wireless networks are deployed over finite domains, the level of mobility is different at different locations, and user mobility is correlated over time. All these features have an impact on the temporal properties of interference which is often neglected. In this paper, we show how to incorporate correlated user mobility into the interference and outage correlation models. We use the Random Waypoint Mobility Model as an example model inducing correlation, and we calculate its displacement law at different locations. Based on that, we illustrate that the temporal correlations of interference and outage are indeed location-dependent, being lower close to the centre of the domain, where the level of mobility is higher than near the boundaries. Close to the boundaries, more time is also needed to see uncorrelated interference at the receiver. Our findings suggest that an accurate description of the mobility pattern is important, because it leads to more accurate understanding/modeling of interference and receiver performance.
Cognitive processes in adults with ADHD

This study aimed to examine four domains of executive functioning in adults with ADHD, namely interference control, concept shifting, verbal fluency, and verbal working memory. Four groups of participants were included: (i) adults diagnosed with ADHD (n = 20) [ADHD]; (ii) adults diagnosed with both ADHD and one or more comorbid disorder(s) (n = 22) [ADHD+]; (iii) adults referred for ADHD due to ADHD symptomatology but not diagnosed as such (n = 34) [non-ADHD]; and (iv) healthy controls (n = 136). ADHD-related deficits (independent of comorbidity) were revealed for concept shifting and verbal working memory. In addition, the ADHD+ and non-ADHD groups displayed deficits in terms of general processing speed. Given that these deficits were not found in the ADHDgroup, we contend that these deficits are likely attributable to comorbidity rather than ADHD itself. Contrary to our expectations, these findings do not correspond with the cognitive subtype hypothesis. Executive functioning in adults with ADHD | 29
Real-time seizure monitoring and spectral analysis microsystem

We present a neural recording and spectral analysis integrated microsystem. It is the instrumentational and computational core of an envisioned miniature implantable brain implant for automated epileptic seizure therapy. The microsystem combines two functional blocks: the neural recording interface and the spectral analysis processor. The neural interface contains 256 signal acquisition channels recording neural field potentials from an array of 16 times 16 electrodes simultaneously, in a distributed fashion. The spectral analysis processor computes a wavelet-based time-frequency map (spectrogram) of the neural recording. We demonstrate the functionality of the integrated microsystem in real-time epileptic seizure monitoring and spectral analysis, as necessary for subsequent automated seizure prediction and prevention
Transcriptional Activators of Human Genes with Programmable DNA-Specificity

TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in a contiguous DNA sequence and a pair of adjacent hypervariable amino acid residues per repeat specifies which base is bound. Rearranging the repeats allows the design of novel TAL proteins with predictable DNA-recognition specificities. TAL protein-based transcriptional activation in plant cells is mediated by a C-terminal activation domain (AD). Here, we created synthetic TAL proteins with designed repeat compositions using a novel modular cloning strategy termed “Golden TAL Technology”. Newly programmed TAL proteins were not only functional in plant cells, but also in human cells and activated targeted expression of exogenous as well as endogenous genes. Transcriptional activation in different human cell lines was markedly improved by replacing the TAL-AD with the VP16-AD of herpes simplex virus. The creation of TAL proteins with potentially any desired DNA-recognition specificity allows their versatile use in biotechnology.
A Combination Forecasting Method Based on GEP

A combination forecasting method based on gene expression programming (GEP) is introduced in this paper. The main idea of this method is that the nonlinear combination forecasting function can be simulated by gene expression programming. Not only the difficulty of constructing the nonlinear combination forecasting function is decreased, but also the prediction precision is improved by the combination forecasting method based GEP.
Why do women bloggers use social media? Recreation and information motivations outweigh engagement motivations

Analyses of survey results from a random sample of women bloggers (N = 298) show three motivations drive women to use social media – information, engagement, and recreation. The recreation motivation outweighs the other two motivations in predicting frequency of social media use. However, when differences between Facebook, Twitter, and other social media were considered, results show women bloggers turn to social media in general for recreation, but to Facebook for engagement and to Twitter for information. Findings also show that psychological needs for affiliation and self-disclosure are related to the engagement motivation, and self-disclosure is associated with the information motivation. The results are discussed in relation to need theory.
Circular Economy

The ongoing discourse of zero-waste and the circular economy in recent time have been underscored by key players, such as the European Commission, NGOs, INGOs, academia, and multinational companies. The discourse revolves around the fact that capitalist form of development has pushed the environment to the brink of destruction. The need of the hour is sustainable growth through the model of the circular economy. Thus, the idea of growth is being de-politicized by a post-growth narrative. This chapter wants to delve into the critical aspect of circular economy which propounds itself as a solution to capitalism driven growth. The first theme it addresses the actual materialization of circular economy whether it is actually a possible phenomenon or not. The second theme it deals with the concept of social sustainability and fulfillment of human wants. The last theme revolves around ideological dimension of post-growth, how the circular growth in the garb of post-growth ideology propels and legitimizes a more growth -driven society.
A full training framework of cross-stream dependence modelling for HMM-based singing voice synthesis

A cross-stream dependence modelling (CSDM) method has been proposed to model the dependence of spectral distributions on F0 observations for hidden Markov model (HMM) based speech synthesis. However, this method incorporates CSDM only for the embedded training of HMM estimation while ignoring CSDM in the clustering of context-dependent HMMs. This paper applies CSDM to HMM-based singing voice synthesis and presents a decision-tree-based model clustering method with explicit CSDM. This method, in conjunction with the previous CSDM method, forms a full CSDM training framework. Experimental results demonstrate that this full CSDM training framework achieves better performance than the previous CSDM method and the baseline without CSDM in a singing voice synthesis task.
Situated open world reference resolution for human-robot dialogue

A robot participating in natural dialogue with a human interlocutor may need to discuss, reason about, or initiate actions concerning dialogue-referenced entities. To do so, the robot must first identify or create new representations for those entities, a capability known as reference resolution. We previously presented algorithms for resolving references occurring in definite noun phrases. In this paper we present GH-POWER: an algorithm for resolving references occurring in a wider array of linguistic forms, by making novel extensions to the Givenness Hierarchy, and evaluate GH-POWER on natural task-based human-human and human-robot dialogues.
Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells

Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine. However, the cellular biology of these cells is not fully understood. The present study characterizes the cyclic ADP‐ribose (cADPR)‐mediated Ca2+ signals in human MSCs and finds that externally applied cADPR can increase the frequency of spontaneous intracellular Ca2+ (Ca2+i) oscillations. The increase was abrogated by a specific cADPR antagonist or an inositol trisphosphate receptor (IP3R) inhibitor, but not by ryanodine. In addition, the cADPR‐induced increase of Ca2+i oscillation frequency was prevented by inhibitors of nucleoside transporter or by inhibitors of the transient receptor potential cation melastatin‐2 (TRPM2) channel. RT‐PCR revealed mRNAs for the nucleoside transporters, concentrative nucleoside transporters 1/2 and equilibrative nucleoside transporters 1/3, IP3R1/2/3 and the TRPM2 channel, but not those for ryanodine receptors and CD38 in human MSCs. Knockdown of the TRPM2 channel by specific short interference RNA abolished the effect of cADPR on the Ca2+i oscillation frequency, and prevented the stimulation of proliferation by cADPR. Moreover, cADPR remarkably increased phosphorylated extracellular‐signal‐regulated kinases 1/2 (ERK1/2), but not Akt or p38 mitogen‐activated protein kinase (MAPK). However, cADPR had no effect on adipogenesis or osteogenesis in human MSCs. Our results indicate that cADPR is a novel regulator of Ca2+i oscillations in human MSCs. It permeates the cell membrane through the nucleoside transporters and increases Ca2+ oscillation via activation of the TRPM2 channel, resulting in enhanced phosphorylation of ERK1/2 and, thereby, stimulation of human MSC proliferation. This study delineates an alternate signalling pathway of cADPR that is distinct from its well‐established role of serving as a Ca2+ messenger for mobilizing the internal Ca2+ stores. Whether cADPR can be used clinically for stimulating marrow function in patients with marrow disorders remains to be further studied.
Variants of Courcelle's Theorem for complexity classes inside P

It is well known that monadic-second order logic (MSO) expresses many natural NP-complete problems. However, a famous theorem of Courcelle states that every problem expressible in MSO can be solved in linear time for input graphs whose tree width is bounded by a fixed constant [Courcelle 1990]. Courcelle's Theorem is the prototypical example of an algorithmic "meta theorem", which states an algorithmic upper bound for a whole family of problems. This column reviews a series of meta theorems several of which refine Courcelle's Theorem by more precisely classifying the complexity of natural families of problems.
Concept-Oriented Programming

Object-oriented programming (OOP) is aimed at describing the structure and behaviour of objects by hiding the mechanism of their representation and access in primitive references. In this article we describe an approach, called concept-oriented programming (COP), which focuses on modelling references assuming that they also possess application-specific structure and behaviour accounting for a great deal or even most of the overall program complexity. References in COP are completely legalized and get the same status as objects while the functions are distributed among both objects and references. In order to support this design we introduce a new programming construct, called concept, which generalizes conventional classes and concept inclusion relation generalizing class inheritance. The main advantage of COP is that it allows programmers to describe two sides of any program: explicitly used functions of objects and intermediate functionality of references having cross-cutting nature and executed implicitly behind the scenes during object access.
ON THE PORTFOLIO STRATEGY WITH THE MEIXNER-EXPONENTIAL DISTRIBUTIONAL RELATIONSHIP

The Meixner process as a special type of the Levy process is related to the Meixner-Pollaczek polynomial by a Martingale relation. Since discovered, the Meixner process has been applied to financial data to show that the Normal distribution is a very poor model to fit log-returns of financial assets like stocks and indices. In this paper, we derived a distribution which is related to Meixner and Exponential distribution. We call this distributional relationship ‘the Meixner-Exponential distribution’ and fit it to financial data to show how good it fits. Furthermore, we apply the distribution to determine the expected value (wealth) of an investor whose initial wealth is and whose returns is Rτ.
Working Paper Series Settlement Risk under Gross and Net Settlement

Previous comparative analyses of gross and net settlement have focused on the credit risk of the central counterparty in net settlement arrangements and on the incentives for participants to alter the risk of the portfolio under net settlement. By modeling the trading economy that generates the demand for payment services, we are able to show some largely unexplored advantages of net settlement. We find that net settlement can prevent certain gridlock situations, which may arise in gross settlement in the absence of delivery versus payment requirements. In addition, we show that net settlement can economize on collateral requirements and avoid trading delays. JEL classification: E58, G21, G28