Miracle-dz/UniFAR-FTUs huggingface dataset:
Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases.
Entity Resolution and Federated Learning get a Federated Resolution

Consider two data providers, each maintaining records of different feature sets about common entities. They aim to learn a linear model over the whole set of features. This problem of federated learning over vertically partitioned data includes a crucial upstream issue: entity resolution, i.e. finding the correspondence between the rows of the datasets. It is well known that entity resolution, just like learning, is mistake-prone in the real world. Despite the importance of the problem, there has been no formal assessment of how errors in entity resolution impact learning. In this paper, we provide a thorough answer to this question, answering how optimal classifiers, empirical losses, margins and generalisation abilities are affected. While our answer spans a wide set of losses --- going beyond proper, convex, or classification calibrated ---, it brings simple practical arguments to upgrade entity resolution as a preprocessing step to learning. One of these suggests that entity resolution should be aimed at controlling or minimizing the number of matching errors between examples of distinct classes. In our experiments, we modify a simple token-based entity resolution algorithm so that it indeed aims at avoiding matching rows belonging to different classes, and perform experiments in the setting where entity resolution relies on noisy data, which is very relevant to real world domains. Notably, our approach covers the case where one peer \textit{does not} have classes, or a noisy record of classes. Experiments display that using the class information during entity resolution can buy significant uplift for learning at little expense from the complexity standpoint.
The Lasso Segment Is Required for Functional Dimerization of the Plasmodium Formin 1 FH2 Domain

Apicomplexan parasites, such as the malaria-causing Plasmodium species, utilize a unique way of locomotion and host cell invasion. This substrate-dependent gliding motility requires rapid cycling of actin between the monomeric state and very short, unbranched filaments. Despite the crucial role of actin polymerization for the survival of the malaria parasite, the majority of Plasmodium cellular actin is present in the monomeric form. Plasmodium lacks most of the canonical actin nucleators, and formins are essentially the only candidates for this function in all Apicomplexa. The malaria parasite has two formins, containing conserved formin homology (FH) 2 and rudimentary FH1 domains. Here, we show that Plasmodium falciparum formin 1 associates with and nucleates both mammalian and Plasmodium actin filaments. Although Plasmodium profilin alone sequesters actin monomers, thus inhibiting polymerization, its monomer-sequestering activity does not compete with the nucleating activity of formin 1 at an equimolar profilin-actin ratio. We have determined solution structures of P. falciparum formin 1 FH2 domain both in the presence and absence of the lasso segment and the FH1 domain, and show that the lasso is required for the assembly of functional dimers.
Two Different High Throughput Sequencing Approaches Identify Thousands of De Novo Genomic Markers for the Genetically Depleted Bornean Elephant

High throughput sequencing technologies are being applied to an increasing number of model species with a high-quality reference genome. The application and analyses of whole-genome sequence data in non-model species with no prior genomic information are currently under way. Recent sequencing technologies provide new opportunities for gathering genomic data in natural populations, laying the empirical foundation for future research in the field of conservation and population genomics. Here we present the case study of the Bornean elephant, which is the most endangered subspecies of Asian elephant and exhibits very low genetic diversity. We used two different sequencing platforms, the Roche 454 FLX (shotgun) and Illumina, GAIIx (Restriction site associated DNA, RAD) to evaluate the feasibility of the two methodologies for the discovery of de novo markers (single nucleotide polymorphism, SNPs and microsatellites) using low coverage data. Approximately, 6,683 (shotgun) and 14,724 (RAD) SNPs were detected within our elephant sequence dataset. Genotyping of a representative sample of 194 SNPs resulted in a SNP validation rate of ∼ 83 to 94% and 17% of the loci were polymorphic with a low diversity (H o = 0.057). Different numbers of microsatellites were identified through shotgun (27,226) and RAD (868) techniques. Out of all di-, tri-, and tetra-microsatellite loci, 1,706 loci had sufficient flanking regions (shotgun) while only 7 were found with RAD. All microsatellites were monomorphic in the Bornean but polymorphic in another elephant subspecies. Despite using different sample sizes, and the well known differences in the two platforms used regarding sequence length and throughput, the two approaches showed high validation rate. The approaches used here for marker development in a threatened species demonstrate the utility of high throughput sequencing technologies as a starting point for the development of genomic tools in a non-model species and in particular for a species with low genetic diversity.
Integrating wireless sensor networks and the internet: a security analysis

Purpose – This paper aims to analyze the security issues that arise when integrating wireless sensor networks (WSN) and the internet. Also, it seeks to review whether existing technology mechanisms are suitable and can be applied in this context.Design/methodology/approach – The paper considers the possible approaches that can be used to connect a WSN with the internet, and analyzes the security of their interactions.Findings – By providing the services of the network through a front‐end proxy, a sensor network and the internet can interact securely. There are other challenges to be solved if the sensor nodes are integrated into the internet infrastructure, although there exists interesting advances on his matter.Research limitations/implications – The complete integration of sensor networks and the internet still remains as an open issue.Practical implications – With the current state of the art, it is possible to develop a secure sensor network that can provide its services to internet hosts with certai.
Institutional computed tomography diagnostic reference levels based on water-equivalent diameter and size-specific dose estimates

Size-specific institutional diagnostic reference levels (DRLs) were generated for chest and abdominopelvic computed tomography (CT) based on size-specific dose estimates (SSDEs) and depending on patients’ water-equivalent diameter (Dw). 1690 CT examinations were included in the IRB-approved retrospective study. SSDEs based on the mean water-equivalent diameter of the entire scan volume were calculated automatically. SSDEs were analyzed for different patient sizes and institutional DRLs (iDRLS; 75% percentiles) based on Dw and SSDEs were generated. iDRLs were compared to the national DRLs. Mean volumetric computed tomography dose index (CTDIvol), Dw and SSDEs for all 1690 CT examinations were 7.2 ± 4.0 mGy (0.84–47.9 mGy), 29.0 ± 3.4 cm and 8.5 ± 3.8 mGy (1.2–37.7 mGy), respectively. Overall, the mean SSDEs of all CT examinations were higher than the CTDIvol in chest CT, abdominopelvic CT and upper abdominal CT, respectively (p < 0.001 for all). There was a strong linear correlation between Dw and SSDEs in chest (R2 = 0.66), abdominopelvic (R2 = 0.98) and upper abdominal CT (R2 = 0.96) allowing for the implementation of size-specific institutional DRLs based on SSDEs and patients’ Dw. We generated size-specific, Dw-dependent institutional DRLs based on SSDEs, which allow for easier and more comprehensive analyses of CT radiation exposure. Our results indicate that implementation of SSDEs into national DRLs may be beneficial.
High input impedance voltage‐mode first‐order all‐pass sections

This paper proposes six new first‐order voltage‐mode all‐pass sections (VM‐APSs) based on three general topologies. Each circuit uses two differential voltage current conveyors and three grounded passive components. All the circuits possess high input impedance and easy control of pole frequency either by a simple matching of resistors (two equal‐valued resistors) for the three canonical circuits or by a single resistor for three non‐canonical circuits. PSPICE simulation results using real device 0. 5µ CMOS parameters are given to validate the proposed circuits. Copyright © 2007 John Wiley & Sons, Ltd.
Comparison of CNN and MLP classifiers for algae detection in underwater pipelines

Artificial neural networks, such as the multilayer perceptron (MLP), have been increasingly employed in various applications. Recently, deep neural networks, specially convolutional neural networks (CNN), have received considerable attention due to their ability to extract and represent high-level abstractions in data sets. This article describes a vision inspection system based on deep learning and computer vision algorithms for detection of algae in underwater pipelines. The proposed algorithm comprises a CNN or a MLP network, followed by a post-processing stage operating in spatial and temporal domains, employing clustering of neighboring detection positions and a region interception framebuffer. The performances of MLP, employing different descriptors, and CNN classifiers are compared in real-world scenarios. It is shown that the post-processing stage considerably decreases the number of false positives, resulting in an accuracy rate of 99.39%.
Targeting postprandial glycaemia in children with diabetes: Opportunities and challenges

Postprandial glycaemia makes a substantial contribution to overall glycaemic control in diabetes, particularly in patients whose preprandial glycaemia is relatively well controlled and glycated haemoglobin (HbA1c) only modestly elevated. Our review addresses the determinants of postprandial glycaemia and how it may be targeted therapeutically in children with diabetes. Postprandial glycaemia is influenced by preprandial glycaemia, macronutrients and their absorption, insulin delivery and sensitivity, the action of the enteroendocrine system, and the rate of gastric emptying. Contemporary continuous glucose monitoring systems reveal patterns of post prandial glycaemia and allow management to be guided more precisely. Delays in blood glucose determination, insulin delivery and its absorption remain challenges in the rapidly evolving closed loop continuous subcutaneous insulin and glucagon delivery systems developed for children with type 1 diabetes. Augmentation of the incretin system through nutritional preloads or incretin mimetics targets postprandial glycaemia by slowing gastric emptying as well as insulinotropic and glucagonostatic effects. These treatments are of particular relevance to children with type 2 diabetes. Following the development of targeted therapies in adults, postprandial blood glucose control will now be increasingly targeted in the treatment of diabetes in children.
Humanin enhances the cellular response to stress by activation of chaperone-mediated autophagy

Increased oxidative stress and loss of proteostasis are characteristics of aging. Failure to remove the oxidative stress-damaged components has been recognized to play critical roles in the pathophysiology of common age-related disorders including neurodegenerative disease such as Parkinson’s disease and Alzheimer’s disease, and cardiovascular diseases such as myocardial infarction and heart failure. Strategies to diminish oxidative stress or effectively eliminate oxidative-damaged intracellular proteins may therefore provide novel therapeutic option for many age-related diseases. Chaperone-mediated autophagy (CMA) allows for selective degradation of soluble proteins in lysosomes, contributing to the cellular quality control and maintenance of cellular energetic balance [1]. CMA substrate proteins are targeted by the chaperone hsc70 to the lysosomal surface where, upon binding to the lysosome-associated membrane protein type 2A (LAMP2A), they are translocated into the lysosomal lumen for degradation. CMA is activated by oxidative stress to facilitate degradation of damaged proteins [2], thereby eliminating the insults of oxidative stress. Given the fact that CMA activity declines with age [3], and oxidative damage in cells increases during aging, CMA activators hold the potential for development as a new generation of treatment option for age-related diseases. In our recent study, we identified that humanin (HN), an antiapoptotic, mitochondria-associated peptide is an endogenous CMA activator [4]. We demonstrated that HN protects multiple cell types including cardiomyoblasts, primary cardiomyocytes and dopaminergic neuronal cells from oxidative stress-induced cell death in a CMAdependent manner. In fact, this protective effect is lost in CMA-incompetent cells (LAMP-2A knockdown). Both exogenously added HN as well as the endogenously generated HN cooperate in CMA activation. Thus, knockdown of endogenous HN decreases CMA activation in response to oxidative stress. Both endogenous and exogenous HN localize at the lysosomal membrane where they cooperate to enhance CMA efficiency. HN acts by stabilizing binding of the chaperone HSP90 to the upcoming substrates at the cytosolic side of lysosomal membrane. Our study provided the first evidence that regulatory Editorial: Autophagy and Cell Death
Embodied cognition

Traditional views in philosophy of mind and cognitive science depict the mind as an information processor, one whose connections with the body and the world are of little theoretical importance. On the contrary, mounting empirical evidence shows that bodily states and modality-speciﬁc systems for perception and action underlie information processing, and that embodiment contributes to various aspects and effects of mental phenomena. This article will brieﬂy review and discuss some of this evidence and what it implies. By challenging mainstream accounts of mind and cognition, embodiment views offer new ways of conceptualizing knowledge and suggest novel perspectives on cognitive variation and mind-body reductionism.
Biogeochemistry of a deep-sea whale fall: sulfate reduction, sulfide efflux and methanogenesis

Deep-sea whale falls create sulfidic habi- tats supporting chemoautotrophic communities, but microbial processes underlying the formation of such habitats remain poorly evaluated. Microbial degrada- tion processes (sulfate reduction, methanogenesis) and biogeochemical gradients were studied in a whale-fall habitat created by a 30 t whale carcass deployed at 1675 m depth for 6 to 7 yr on the California margin. A variety of measurements were conducted including photomosaicking, microsensor measurements, radio- tracer incubations and geochemical analyses. Sedi- ments were studied at different distances (0 to 9 m) from the whale fall. Highest microbial activities and steepest vertical geochemical gradients were found within 0.5 m of the whale fall, revealing ex situ sulfate reduction and in vitro methanogenesis rates of up to 717 and 99 mmol m -2 d -1 , respectively. In sediments containing whale biomass, methanogenesis was equiv- alent to 20 to 30% of sulfate reduction. During in vitro sediment studies, sulfide and methane were produced within days to weeks after addition of whale biomass, indicating that chemosynthesis is promoted at early stages of the whale fall. Total sulfide production from sediments within 0.5 m of the whale fall was 2.1 ± 3 and 1.5 ± 2.1 mol d -1 in Years 6 and 7, respectively, of which ~200 mmol d -1 were available as free sulfide. Sulfate reduction in bones was much lower, account- ing for a total availability of ~10 mmol sulfide d -1 . Over periods of at least 7 yr, whale falls can create sulfidic conditions similar to other chemosynthetic habitats such as cold seeps and hydrothermal vents.
Structure and Molecular Evolution of CDGSH Iron-Sulfur Domains

The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs.
Context Ontology-Based Reasoning Service for Multimedia Conferencing Process Intelligence

This paper proposes a Semantic Web-based context ontological reasoning service for multimedia conferencing process management. When the chairman enters the basic conference information, the process will automatically select the appropriate means of notifications based on the conference time and the participant contact details. In this system, all types of multimedia conferencing processes are encapsulated in Web services and deployed on an enterprise service bus. A large multimedia conference ontology is created that contains business rules. In addition, with the objective of improving and management for data redundancy in ontological reasoning service, we propose an extensible breadth-first-search-based graph search algorithm that can successfully eliminate the redundant portion of the ontology, which can ensure validity of context ontology reasoning. Finally, the proposed multimedia conferencing process management can obtain the desired results, and some corresponding experimental analysis are reported.
Malignant progression of a peripheral nerve sheath tumor in the setting of rhabdoid tumor predisposition syndrome

Malignant progression of a benign or low‐grade tumor in individuals with germline alteration of SMARCB1 gene is not well characterized. In a family in which two carrier children had germline SMARCB1 mutations and atypical teratoid rhabdoid tumor, we report malignant progression of a nerve sheath tumor over a 7‐year period in an affected adult family member. Prompt identification of the germline SMARCB1 alteration and the resultant rhabdoid tumor predisposition syndrome can help guide genetic counseling and surveillance in affected family members.
Laboratory Study on Ultraviolet Radiation Aging of Bitumen

The effects of ultraviolet (UV) radiation on degradation of bitumen have received much attention from both academic and industrial points of view. However, quantitative evaluations of bitumen photo-oxidation in pavements have apparently not been determined. In this study, the effects of photo-oxidation of bitumen were investigated by exposing pressed thin films of bitumen. The data for thermal aging only were compared with corresponding data for photo-oxidation from exposure to UV radiation. The levels of aging were evaluated by following increases in the carbonyl functional group, and increases in viscosity. The results indicated that both thermal and UV aging occurred during exposure in the UV radiation oven test for thin bitumen films of both unmodified and SBS-modified bitumen. UV aging had a significant effect on bitumen properties, particularly when the bitumen film thickness was less than 150 μm. Results also showed that the level of UV irradiation intensity had a significant influence on the level of photo-oxidation of the bitumen.
New Role of Nod Proteins in Regulation of Intestinal Goblet Cell Response in the Context of Innate Host Defense in an Enteric Parasite Infection

ABSTRACT Mucins secreted by intestinal goblet cells are considered an important component of innate defense in a number of enteric infections, including many parasitic infections, but also likely provide protection against the gut microbiota. Nod proteins are intracellular receptors that play key roles in innate immune response and inflammation. Here, we investigated the role of Nod proteins in regulation of intestinal goblet cell response in naive mice and mice infected with the enteric parasite Trichuris muris. We observed significantly fewer periodic acid-Schiff (PAS)-stained intestinal goblet cells and less mucin (Muc2) in Nod1 and Nod2 double-knockout (Nod DKO) mice after T. muris infection than in wild-type (WT) mice. Expulsion of parasites from the intestine was significantly delayed in Nod DKO mice. Treatment of naive WT mice with Nod1 and Nod2 agonists simultaneously increased numbers of PAS-stained goblet cells and Muc2-expressing cells, whereas treatment with Nod1 or Nod2 separately had no significant effect. Stimulation of mucin-secreting LS174T cells with Nod1 and Nod2 agonists upregulated core 3 β1,3-N-acetylglucosaminyltransferase (C3GnT; an important enzyme in mucin synthesis) and MUC2. We also observed lower numbers of PAS-stained goblet cells and less Muc2 in germfree mice. Treatment with Nod1 and Nod2 agonists enhanced the production of PAS-stained goblet cells and Muc2 in germfree mice. These data provide novel information on the role of Nod proteins in goblet cell response and Muc2 production in relation to intestinal innate defense.