Miracle-dz/UniFAR-FTUs huggingface dataset:
Adult-Onset Deletion of ATP13A2 in Mice Induces Progressive Nigrostriatal Pathway Dopaminergic Degeneration and Lysosomal Abnormalities

Although most cases of Parkinson’s disease (PD) are sporadic, mutations in over 20 genes are known to cause heritable forms of PD. A surprising number of familial PD-linked genes and PD risk genes are involved in intracellular trafficking and protein degradation. Recessive loss-of-function mutations in ATP13A2, a lysosomal transmembrane P5B-type ATPase and polyamine exporter, can cause early-onset familial PD. Familial ATP13A2 mutations are also linked to related neurodegenerative diseases, including Kufor-Rakeb syndrome (KRS), hereditary spastic paraplegias (HSPs), neuronal ceroid lipofuscinosis, and amyotrophic lateral sclerosis (ALS). Given the severe effects of ATP13A2 mutations in humans, it is surprising that ATP13A2 knockout (KO) mice fail to exhibit neurodegeneration even at advanced ages. This discrepancy between human subjects and rodents makes it challenging to study the neuropathological effects of ATP13A2 loss in vivo. Germline deletion of ATP13A2 in rodents may trigger the upregulation of compensatory pathways during embryonic development that mask the full neurotoxic effects of ATP13A2 loss in the brain. To explore this idea, we selectively deleted ATP13A2 in the adult mouse brain by the unilateral delivery of an AAV-Cre vector into the substantia nigra of young adult mice carrying conditional loxP-flanked ATP13A2 KO alleles. We observe a progressive loss of striatal dopaminergic nerve terminals at 3 and 10 months after AAV-Cre delivery. Cre-injected mice also exhibit robust dopaminergic neuronal degeneration in the substantia nigra at 10 months. Adult-onset ATP13A2 KO also recreates many of the phenotypes observed in aged germline ATP13A2 KO mice, including lysosomal abnormalities, p62-positive inclusions, and neuroinflammation. Our study demonstrates that the adult-onset homozygous deletion of ATP13A2 in the nigrostriatal pathway produces robust and progressive dopaminergic neurodegeneration that serves as a useful in vivo model of ATP13A2-related neurodegenerative diseases.
Dynamic noise estimation: A generalized method for modeling noise fluctuations in decision-making

Computational cognitive modeling is an important tool for understanding the processes supporting human and animal decision-making. Choice data in decision-making tasks are inherently noisy, and separating noise from signal can improve the quality of computational modeling. Common approaches to model decision noise often assume constant levels of noise or exploration throughout learning (e.g., the ϵ-softmax policy). However, this assumption is not guaranteed to hold – for example, a subject might disengage and lapse into an inattentive phase for a series of trials in the middle of otherwise low-noise performance. Here, we introduce a new, computationally inexpensive method to dynamically infer the levels of noise in choice behavior, under a model assumption that agents can transition between two discrete latent states (e.g., fully engaged and random). Using simulations, we show that modeling noise levels dynamically instead of statically can substantially improve model fit and parameter estimation, especially in the presence of long periods of noisy behavior, such as prolonged attentional lapses. We further demonstrate the empirical benefits of dynamic noise estimation at the individual and group levels by validating it on four published datasets featuring diverse populations, tasks, and models. Based on the theoretical and empirical evaluation of the method reported in the current work, we expect that dynamic noise estimation will improve modeling in many decision-making paradigms over the static noise estimation method currently used in the modeling literature, while keeping additional model complexity and assumptions minimal.
Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females

This study aimed to investigate the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hind paws and dorsal root ganglia (DRG). Bulk RNA-seq was used to investigate the gene expression changes in the paw and DRG collected at 1, 16, and 31 days post-PTX. At these time points, differentially expressed DEGs were predominantly related to reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis. These processes were accompanied by regulation of DEGs related to cytoskeleton, extracellular matrix organization and cellular energy production. This gene plasticity during persistent painful neuropathy progression likely represents biological processes linked to tissue regeneration and degeneration. Unlike regeneration/degeneration, gene plasticity related to immune processes was minimal at 1–31 days post-PTX. It was also noted that despite similarities in biological processes and pain chronicity in males and females, specific DEGs showed dramatic sex-dependency. The main conclusions of this study are that gene expression plasticity in paws and DRG during PTX neuropathy progression relates to tissue regeneration and degeneration, minimally affects the immune system processes, and is heavily sex-dependent at the individual gene level.
Food web structure mediate positive and negative effects of diversity on ecosystem functioning in a large floodplain river

Research programs on Biodiversity-Ecosystem Functioning (BEF) and Food Web Structure (FWS) have contributed to understanding the impact of biodiversity on the functioning and architecture of ecosystems, but the interconnectedness between these components was seldom attended until recently. Several theoretical hypotheses predict an interconnection between BEF and FWS but were poorly and independently evaluated. We estimated 63 sink food webs of predatory fish in the Paraná River, covering a large gradient of community richness. We evaluated available hypotheses and their interrelationship through path analyses. A well-supported causal structure was identified, supporting that species richness directly increased standing biomass, modularity, and intermodular connection, whereas decreased interaction strength, connectance, and nestedness. A direct positive effect of modularity and connectance on biomass indicates that FWS can determine the BEF. Richness promotes biomass directly and through the increase in modularity but can also decrease biomass due to the decay in connectance, with similar positive and negative effects of richness on biomass. In this sense, the relationship between diversity and ecosystem functioning cannot be blind to FWS. Environmental homogenization and reduction in functional diversity may undermine the conditions for modular food webs, switching positive BEF to negative ones with potential cascading effects in the whole ecosystem.
Hippocampal reactive neural stem cells are able to phagocytose and have an immunological molecular signature

Hippocampal neural stem cells (NSCs) are the drivers of neurogenesis in the dentate gyrus (DG) of most mammals including humans. During neuronal hyperactivity NSCs become reactive NSCs (react-NSCs), characterized by their activation, morphological changes, and symmetric division, abandoning their neurogenic programme and transforming into reactive astrocytes. Here, using different pathological models that induce react-NSCs in the DG, we looked for novel features of react-NSCs both histologically and by total RNA sequencing. We report that in two pathological models were react-NSCs emerge (mesial temporal lobe epilepsy (MTLE) and traumatic brain injury (TBI)) react-NSCs are capable of phagocytosis of dead cells, a typical immunological function carried out mainly by microglia in the brain. Importantly, MTLE-induced react-NSCs show phagocytic function in tissue and a predominantly immunological molecular signature, with a broad upregulation of phagocytosis-related gene expression. Our results describe a new function of react-NSCs as phagocytic and immunologically active cells in the hippocampal neurogenic niche.
Microalgal biofilm induces larval settlement in the model marine worm Platynereis dumerilii

A free-swimming larval stage features in many marine invertebrate life cycles. To transition to a seafloor-dwelling juvenile stage, larvae need to settle out of the plankton, guided by specific environmental cues that lead them to an ideal habitat for their future life on the seafloor. Although the marine annelid Platynereis dumerilii has been cultured in research labs since the 1950s and has a free-swimming larval stage, specific environmental cues that induce settlement in this nereid worm are yet to be identified. Here we demonstrate that microalgal biofilm is a key settlement cue for P. dumerilii larvae, inducing earlier onset of settlement, and enhancing subsequent juvenile growth as a primary food source. We tested the settlement response of P. dumerilii to 40 different strains of microalgae, predominantly diatom species, finding that P. dumerilii have species-specific preferences in their choice of settlement substrate. The most effective diatom species for inducing P. dumerilii larval settlement were benthic pennate species including Grammatophora marina, Achnanthes brevipes, and Nitzschia ovalis. The identification of specific environmental cues for P. dumerilii settlement enables a link between its ecology and the sensory and nervous system signalling that regulate larval behaviour and development. Incorporation of diatoms into P. dumerilii culture practices will improve the husbandry of this marine invertebrate model.
Development of a Method for Generating Material Input Flow for Transport Conveyor Using Experimental Data

This work is devoted to the development of a method for generating values of the input material flow of a transport conveyor based on experimental data. The experimental data are represented by a single realization of the material flow for a sufficiently large observation time interval. The statistical characteristics of the implementation of the input material flow are studied. To determine the values of the correlation function, the numerical integration method was used. To analyze statistical characteristics, dimensionless parameters are introduced that can be used to construct similarity criteria for input material flows. When constructing the generator of the input material flow, the canonical expansion of the random process in orthogonal functions is used. This decomposition allows transformations to be carried out over a stochastic input flow of material. It is assumed that the implementation of the input material flow is formed for the steady state of material extraction. As a zero approximation when constructing generators of the input material flow values, it is stipulated that random measurements in the canonical expansion have a normal distribution law. Orthogonal functions are represented by a normalized Fourier series. It is shown that centered random variables of the canonical expansion have dispersion values that are defined as expansion coefficients of the correlation function in a Fourier series. Analysis of the generated material flow realization shows that its values have a distribution close to the normal distribution. An example of realization using a random value generator for the input material flow is presented. The accuracy of the realization is determined by the number of terms in the Fourier series expansion and the accuracy of the numerical integration method
Transforming Software Products for Intelligent Automation Services

In recent academic and commercial literature, the extensive transformations of software products have been a focal topic. However, the discourse has insufficiently addressed the emergence and role of low-code technologies, including robotic process automation (RPA). With the growing significance of RPA and low-code solutions, a salient transition has been observed from conventional On-Premise to Software-As-A-Service (SaaS) paradigms, signifying a critical juncture in its developmental trajectory. Our research, placed at the context of intelligent automation (IA) offerings, explored the product transformation practices conducted by ECIT Veny AS, a renowned Nordic provider of process automation services. In this context, our study discovered a novel observation: notwithstanding the rapid commoditization of RPA technology across diverse business infrastructures, there is a transition for automation service providers to shift their focus from mere technological prowess to holistically addressing client-centric challenges and demands. It has triggered the conceptualization and deployment of a novel product named Robot as a Service - Process Automation (‘RaaS - P’) , characterized by an innovative approach to service level agreement (SLA). This approach placed emphasis on facets such as system availability, operational stability, expedited recovery mechanisms, and transaction quality, all underpinned by the principles of simplicity and predictability.
Schubert cells and quadratic public keys of Multivariate Cryptography

Studies of linear codes in terms of finite projective geometries form traditional direction in Coding Theory. Some applications of projective geometries are known. We introduce new public keys of Multivariate Cryptography given by quadratic public rules generated via walks on incidence substructures of projective geometry with vertexes from two largest Schubert cells. It differs from the known algorithms of Code Based Cryptography and can be considered as the first attempt to combine ideas of this area with the approach of Multivariate Cryptography.
Research on Hate Speech. A Proposal of bibliometric analysis in Spain and LATAM during 2021 and 2022

This research is based on bibliometric analysis to ﬁnd out if Hate Speech in Spain and Latin America has consolidated as a mature research ﬁeld in recent years (2021 and 2022). Through the consultation of the Web of Science (WoS) database and by searching speciﬁc terms, we obtained a universe of 153 articles that allowed us to address our objective. The results revealed that the analysis of hate speech in Spain and LATAM is mature, characterized by consistent publication trends and inﬂuential authors while productive researchers tend to be highly cited. Conceptual trends include Hate Speech, social media, Twitter
How to Support ML End-User Programmers through a Conversational Agent

Machine Learning (ML) has become an indispensable part of several End-User Programmers’ (EUPs) daily work, which increasingly includes software engineering tasks. Machine Learning End-User Programmers (ML-EUPs) without the right background face a steep learning curve and an increased risk of errors and bugs in their ML models. In this work, we designed a conversational agent named “Newton” that can act as a 24/7 expert to support ML-EUPs. The design of Newton was informed by reviewing the existing literature and identifying six challenges that ML-EUPs face and five strategies to help them. We evaluated Newton’s design by conducting a Wizard of Oz within-subjects study with 12 ML-EUPs. We found that Newton proved to help support the ML-EUPs, irrespective of whether participants finished their tasks or not. Still, Newton’s de-sign, which featured the identified strategies, effectively mitigated the challenges from the literature. Based on participants’ interactions with Newton, we proposed six design guidelines for future conversational agents in this domain.
Factors affecting on the duration of Ventilation among Mechanically Ventilated Patients

Background : Mechanical ventilation is a therapeutic modality which is commonly used to support patients with life-threatening illnesses. Weaning from mechanical ventilation is an essential element in the care of mechanical ventilated patient. Repeated ventilator weaning failure can cause prolonged mechanical ventilation period which may increase morbidity and mortality of patients. Aim of the study: This study aimed to assess factors affecting on the duration of Ventilation among Mechanically Ventilated Patients. Research design: A descriptive exploratory design was used. Setting: Study was conducted at General intensive care units and cardiopulmonary intensive care unit of Damanhur Medical Institute . Methods: A purposive sample of 60 adult patients undergoing Co-ordinated Spontaneous Awakening and Breathing Trials from previously mentioned setting. Tools : Three tools were used included: First tool spontaneous Awakening Trial Safety Screen, Second tool spontaneous Breathing Trial Safety Screen, Third tool mechanical ventilation duration measurement record. Results: The main factors affecting on the duration of mechanical ventilation were SAT, and SBT co-ordinated protocol before weaning. Conclusion: It can be concluded that the factors affecting on the duration of ventilation for mechanical ventilated patients were Co-ordinated Spontaneous Awakening and Breathing Trials. Recommendations: Apply Co-ordinated Spontaneous Awakening and Breathing Trials for mechanical ventilated patients help to decrease duration of mechanical ventilation.
Primary Arthroplasty Why Do Medial Unicompartmental Knee Arthroplasties Fail Today?

Background: Failure rates are higher in medial unicompartmental knee arthroplasty (UKA) than total knee arthroplasty. To improve these failure rates, it is important to understand why medial UKA fail. Because individual studies lack power to show failure modes, a systematic review was performed to assess medial UKA failure modes. Furthermore, we compared cohort studies with registry-based studies, early with midterm and late failures and ﬁ xed-bearing with mobile-bearing implants. Methods: Databases of PubMed, EMBASE, and Cochrane and annual registries were searched for medial UKA failures. Studies were included when they reported > 25 failures or when they reported early ( < 5 years), midterm (5-10 years), or late failures ( > 10 years). Results: Thirty-seven cohort studies (4 level II studies and 33 level III studies) and 2 registry-based studies were included. A total of 3967 overall failures, 388 time-dependent failures, and 1305 implant design failures were identi ﬁ ed. Aseptic loosening (36%) and osteoarthritis (OA) progression (20%) were the most common failure modes. Aseptic loosening (26%) was most common early failure mode, whereas OA progression was more commonly seen in midterm and late failures (38% and 40%, respectively). Polyethylene wear (12%) and instability (12%) were more common in ﬁ xed-bearing implants, whereas pain (14%) and bearing dislocation (11%) were more common in mobile-bearing implants. Conclusion: This level III systematic review identi ﬁ ed aseptic loosening and OA progression as the major failure modes. Aseptic loosening was the main failure mode in early years and mobile-bearing implants, whereas OA progression caused most failures in late years and ﬁ xed-bearing implants. © 2016 Elsevier
Indacenodithiophene-benzothiadiazole organic field-effect transistors with gravure-printed semiconductor and dielectric on plastic

We demonstrate the gravure printing of a high-performance indacenodithiophene (IDT) copolymer, indacenodithiophene—benzothiadiazole (C_16IDT-BT), onto self-aligned organic field-effect transistor architectures on flexible plastic substrates. We observed that the combination of a gravure-printed dielectric with gravure-printed semiconductor yielded devices with higher mean-effective mobility than devices manufactured using photolithographically patterned dielectric. Peak mobilities of μ = 0.1 cm^2 V^−1 s^−1 were measured, and exceed previous reports for non-printed C_16IDT-BT on non-flexible silicon substrates.
Demographic Profile of Self-Help Group Members Effects the Women’s Entrepreneurship Empowerment

The financial development of an organization generally relies upon Human Resources, women comprise around half of the complete total population of world. All around the world ladies are assuming a crucial part in the business local area. In India, but women have made a similarly late passage into the business situation principally due to the universal and customary culture, however they are partaking in a specialization in the public. Today a woman is more freed and driven a glad and tranquil existence with the help of spouse and relatives. Micro credit programmes, has substantially improved the respondent's economic condition, social condition and living standards [2,5,7]. The demographic characteristic of members of Self-Help Groups (SHGs) effects the empowerment of entrepreneurship among the women.
Data-Driven Evidence-Based Syntactic Sugar Design

Programming languages are essential tools for developers, and their evolution plays a crucial role in supporting the activities of developers. One instance of programming language evolution is the introduction of syntactic sugars, which are additional syntax elements that provide alternative, more readable code constructs. However, the process of designing and evolving a programming language has traditionally been guided by anecdotal experiences and intuition. Recent advances in tools and methodologies for mining open-source repositories have enabled developers to make data-driven software engineering decisions. In light of this, this paper proposes an approach for motivating data-driven programming evolution by applying frequent subgraph mining techniques to a large dataset of 166,827,154 open-source Java methods. The dataset is mined by generalizing Java control-flow graphs to capture broad programming language usages and instances of duplication. Frequent subgraphs are then extracted to identify potentially impactful opportunities for new syntactic sugars. Our diverse results demonstrate the benefits of the proposed technique by identifying new syntactic sugars involving a variety of programming constructs that could be implemented in Java, thus simplifying frequent code idioms. This approach can potentially provide valuable insights for Java language designers, and serve as a proof-of-concept for data-driven programming language design and evolution.
in Relation to Formant Frequencies Evaluated by Automatic Speech Recognition

Recent studies measured signiﬁcant diﬀerences in formant values in the production of short and long high vowel pairs in the Czech language. Perceptional impacts of such ﬁndings were conﬁrmed employing listening tests proving that a perceived vowel length is inﬂuenced by formant values related to a tongue position. Non-native speakers of Czech may experience diﬃculties in communication when they interchange the vowel length in words, which may lead to a completely diﬀerent meaning of the message. This paper analyses perception of two-syllable words with manipulated duration and formant frequencies of high vowels i/i: or u/u: in the ﬁrst syllable using automatic speech recognition (ASR) system. Such a procedure makes it possible to set a ﬁne resolution in the range of examined factors. Our study conﬁrms the formant values have a substantial impact on the perception of high vowels’ length by ASR, comparable to mean values obtained from listening tests performed on a group of human participants.