Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling distributed RC lines for the transient analysis of complex networks

The development of an approximately equivalent representation of uniformly distributed RClines is described for the transient analysis of complex networks on digital Computers. The representation is a two-port network consisting of an R1C1,‘L’ section in cascade with an R2C2 ‘L’ section. The frequency range for which the model is applicable, and the characteristic of error between the actual response and the response of the approximate representation are examined. The error is found to be within 3.21% of the step input.
Attachment and compassion-threat: Influence of a secure attachment-prime.

OBJECTIVES The present paper proposed and tested a methodology for reducing individual's threat response to compassion-imagery, by increasing their levels of state attachment-security. DESIGN A total of 68 University students (63% female, mean age = 25) completed an experimental study, where they were randomly assigned to either a 10-min attachment-prime (to enhance attachment-security) or an interpersonal skills module (control condition). METHODS Participants completed a compassion-focused imagery exercise before and after the manipulation, to determine the effects of the attachment-prime. To measure the effects of the manipulation on individual's threat response, heart rate variability data were collected at baseline and during both compassion exercises. RESULTS As predicted, individuals who reported higher levels of anxious and avoidant attachment styles were more likely to display a threat response (decreases in heart rate variability), to the first compassion-focused imagery. After receiving an attachment-prime, heart rate variability increased suggesting that individual's experienced greater self-soothing responses and decreased threat responses to the second compassion-focused imagery. CONCLUSIONS The present findings suggest that individuals with insecure attachments are likely to require additional support increasing their attachment-security, before they can successfully engage in compassion-based exercises or therapies. PRACTITIONER POINTS Compassion-based exercises may result in fear and consequently avoidance in some populations of individuals. Threat responses to compassion can be reduced by using attachment-based techniques. Research findings will help inform and broaden the clinical applicability of compassion-based therapies.
Coverage-Ensured Reliable Links with Accurate Timing in Mobile Ad Hoc Network

In practical Mobile Ad-Hoc NETworks (MANETs), the network topology changes while the nodes move quickly. Each node cannot ensure the broadcasting coverage to all other nodes because it cannot update its information on the network topology instantly. This is because the self-pruning based broadcasting can not calculate a valid connected dominating set promptly in the quickly moving environment. For ensuring the broadcasting coverage in MANETs, the period of validity for routing links is taken into account. It is supposed that each node in the network has different transmission ranges, different “Hello” intervals, and moves in different directions and at different velocities. The period of validity of connection can be determined according to the relative speed and the transmission ranges of the nodes. The accurate timing in each node for counting the period of validity of the connection is used to provide the correct and instant information about the network topology. This method is called the Reliable Links with Accurate Timing (RELAT). RELAT guarantees the conditions of connectivity of the virtual network and the availability of the physical links, and in the most cases the consistency of the local view so that it ensures the broadcasting coverage in the network. Simulation results show that this algorithm is sufficient to ensure the broadcasting coverage in MANET and it also has high probabilities of coverage in the case of high node density even the conditions for the algorithm are not fully satisfied.
Fluctuating Regional Brainstem Diffusion Imaging Measures of Microstructure across the Migraine Cycle

Abstract The neural mechanisms responsible for the initiation and expression of migraines remain unknown. Although there is growing evidence of changes in brainstem anatomy and function between attacks, very little is known about brainstem function and structure in the period immediately prior to a migraine. The aim of this investigation is to use brainstem-specific analyses of diffusion weighted images to determine whether the brainstem pain processing regions display altered structure in individuals with migraine across the migraine cycle, and in particular immediately prior to a migraine. Diffusion tensor images (29 controls, 36 migraineurs) were used to assess brainstem anatomy in migraineurs compared with controls. We found that during the interictal phase, migraineurs displayed greater mean diffusivity (MD) in the region of the spinal trigeminal nucleus (SpV), dorsomedial pons (dmPons)/dorsolateral pons (dlPons), and midbrain periaqueductal gray matter (PAG)/cuneiform nucleus (CNF). Remarkably, the MD returned to controls levels during the 24-h period immediately prior to a migraine, only to increase again within the three following days. Additionally, fractional anisotropy (FA) was significantly elevated in the region of the medial lemniscus/ventral trigeminal thalamic tract in migraineurs compared with controls over the entire migraine cycle. These data show that regional brainstem anatomy changes over the migraine cycle, with specific anatomical changes occurring in the 24-h period prior to onset. These changes may contribute to the activation of the ascending trigeminal pathway by either an increase in basal traffic or by sensitizing the trigeminal nuclei to external triggers, with activation ultimately resulting in perception of head pain during a migraine attack.
Innovative therapies for neovascular age-related macular degeneration

ABSTRACT Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept – a fusion protein of the VEGF receptor domains, KSI-301 – an anti-VEGF antibody biopolymer conjugate, and OPT-302 – an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.
Self-acidity induced effervescence and manual shaking-assisted microextraction of neonicotinoid insecticides in orange juice.

A novel dispersive liquid-liquid microextraction that combines self-induced acid-base effervescent reaction and manual shaking, coupled with ultra-performance liquid chromatography-tandem mass spectrometry was developed for simultaneous determination of 10 neonicotinoid insecticides and metabolites in orange juice. An innovative aspect of this method was the utilization of the acidity of the juice for a self-reaction between acidic components contained in the juice sample and added sodium carbonate which generated carbon dioxide bubbles in situ, accelerating the analytes transfer to the extractant of 1-undecanol. The total acid content of juice sample was measured to produce the maximum amount of bubbles with minimum usage of carbonate. Manual shaking subsequently adopted was proven to enhance the extraction efficiency. The factors affecting the performance, including the type and the amount of the carbon dioxide source and extractant, and ionic strength were optimized. Compared with the conventional methods, this approach exhibited low limits of detection (0.001-0.1 μg/L), good recoveries (86.2-103.6%), high enrichment factors (25-50), and negligible matrix effects (-12.3-13.7%). The proposed method was demonstrated to provide a rapid, practical and environmentally friendly procedure due to no acid reagent, toxic solvent or external energy required, giving rise to potential application on other high acid-content matrices. This article is protected by copyright. All rights reserved.
Cardiomyocyte orientation modulated by the Numb family proteins–N-cadherin axis is essential for ventricular wall morphogenesis

Significance The formation of ridge-like trabeculae from the myocardium is central to heart formation, as it allows for the increase in muscle mass before the formation of coronary circulation. We found that cardiomyocytes display spatiotemporal orientation during trabecular formation. Cardiomyocytes in the Numb and Numblike double knockout display abnormal cellular orientation. The knockout hearts display reduced membrane localized N-cadherin due to attenuated N-cadherin recycling to the membrane. When chick N-cadherin is overexpressed in the knockouts via a mosaic model, the defects of cellular orientation and trabeculation were at least partially rescued, suggesting that Numb and Numblike regulate cellular orientation and trabeculation via N-cadherin. Cellular orientation might modulate the directionality of cellular migration, mitotic spindle orientation, and cellular organization during heart morphogenesis. The roles of cellular orientation during trabecular and ventricular wall morphogenesis are unknown, and so are the underlying mechanisms that regulate cellular orientation. Myocardial-specific Numb and Numblike double-knockout (MDKO) hearts display a variety of defects, including in cellular orientation, patterns of mitotic spindle orientation, trabeculation, and ventricular compaction. Furthermore, Numb- and Numblike-null cardiomyocytes exhibit cellular behaviors distinct from those of control cells during trabecular morphogenesis based on single-cell lineage tracing. We investigated how Numb regulates cellular orientation and behaviors and determined that N-cadherin levels and membrane localization are reduced in MDKO hearts. To determine how Numb regulates N-cadherin membrane localization, we generated an mCherry:Numb knockin line and found that Numb localized to diverse endocytic organelles but mainly to the recycling endosome. Consistent with this localization, cardiomyocytes in MDKO did not display defects in N-cadherin internalization but rather in postendocytic recycling to the plasma membrane. Furthermore, N-cadherin overexpression via a mosaic model partially rescued the defects in cellular orientation and trabeculation of MDKO hearts. Our study unravels a phenomenon that cardiomyocytes display spatiotemporal cellular orientation during ventricular wall morphogenesis, and its disruption leads to abnormal trabecular and ventricular wall morphogenesis. Furthermore, we established a mechanism by which Numb modulates cellular orientation and consequently trabecular and ventricular wall morphogenesis by regulating N-cadherin recycling to the plasma membrane.
Development and Cell Biology of the Blood-Brain Barrier.

The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A unique feature of the central nervous system (CNS) vasculature is the blood-brain barrier (BBB). The BBB regulates substance influx and efflux to maintain a homeostatic environment for proper brain function. Here, we review the development and cell biology of the BBB, focusing on the cellular and molecular regulation of barrier formation and the maintenance of the BBB through adulthood. We summarize unique features of CNS endothelial cells and highlight recent progress in and general principles of barrier regulation. Finally, we illustrate why a mechanistic understanding of the development and maintenance of the BBB could provide novel therapeutic opportunities for CNS drug delivery. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Metabolic and behavioral parameters of mice with reduced expression of Syndecan-1

Energy balance is essential for all species. Ligand-receptor interactions mediate processes that regulate body activities like reproduction and metabolism based on the energy status. Such receptors are the heparan sulfate proteoglycans and specifically the family of syndecans. Therefore we investigated the differences of metabolic parameters of heterozygous Syndecan 1 mice (Sdc1+/-) with reduced expression of Sdc1 and the corresponding wild type mice. Sdc1+/- mice have a reduced body weight although they show increased leptin and decreased corticosterone levels. Furthermore, their food and water intake is increased. This is accompanied with less adipose tissue, smaller adipocytes and thus an increased density of adipocytes. For the detailed analysis of the metabolism the automated PhenoMaster system has been used, which allowed continuous and undisturbed recording of food and water intake, energy expenditure and movement. The reason for the lower body weight was the higher energy expenditure of these animals compared to controls. Additionally, female Sdc1+/- mice showed an increased locomotor activity. Referring to organs, the intestine in Sdc1+/- mice was heavier and longer, but no differences at the cellular level could be observed. These findings were independent of normal mating or vice versa embryo transfers of Sdc1+/- and wild type embryos in recipient females of the other genotype. Herein we showed that the reduced expression of Sdc1 led to an altered metabolism on fetal as well as on maternal side, which may play a role in the growth restriction observed in human pregnancy pathologies and in mice lacking Sdc1.
Emerging roles for high‐density lipoproteins in neurodegenerative disorders

Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid‐related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high‐density lipoproteins (HDLs) and their major protein component, apoA‐I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL‐related neurological disorders.
Dairy Products and Cancer Risk in a Northern Sweden Population

Abstract The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5–Q1), 1.11; 95% CI, 0.97–1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5–Q1, 0.95; 95% CI, 0.88–1.04; Ptrend = 0.039), smoking-related (HR Q5–Q1, 0.84; 95% CI, 0.72–0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5–Q1, 0.82; 95% CI, 0.63–1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5–Q1, 0.91; 95% CI, 0.81–1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.
Can TQM improve the sustainability of family owned business

TQM or total quality management is a management philosophy that aims to improve the performance of firms. For a family owned business, a better firm performance is widely acknowledged to be the path to pass down the wealth and business from generation to generation. Thus the sustainability objective is the main agenda for business continuity of a family owned firm. The paper discuss the possible contribution of TQM to the performance and sustainability to family owned business by adopting and learning from a TQM model as well as from Stafford et al.'s (1999) sustainable family business model.
Is Grade Inflation Related to Faculty Status?

The authors performed a statistical analysis to investigate whether grade inflation existed in the business school at a small private college in the northeast region of the United States. The results showed that grade inflation existed and exhibited a linear trend over a 20-year period. The authors found that grade inflation was related to faculty status with significant differences seen between mean grade point averages of students being taught by tenured and adjunct faculty and between those students taught by nontenured and adjunct faculty. They also found that average grades given by adjunct faculty were higher than those of either tenured or nontenured faculty. Thus, the results indicate the increased use of adjunct faculty exacerbates grade inflation in higher education.
Blood‐based biomarkers in the maternal circulation associated with fetal growth restriction

Fetal growth restriction (FGR) is associated with threefold to fourfold increased risk of stillbirth. Identifying FGR, through its commonly used surrogate—the small‐for‐gestational‐age (SGA, estimated fetal weight and/or abdominal circumference <10th centile) fetus—and instituting fetal surveillance and timely delivery decrease stillbirth risk. Methods available to clinicians for antenatal identification of SGA fetuses have surprisingly poor sensitivity. About 80% of cases remain undetected. Measuring the symphysis‐fundal height detects only 20% of SGA fetuses, and even universal third trimester ultrasound detects, at best, 57% of those born SGA. There is an urgent need to find better ways to identify this at‐risk cohort. This review summarises efforts to identify molecular biomarkers (proteins, metabolites, or ribonucleic acids) that could be used to better predict FGR. Most studies examining potential biomarkers to date have utilised case‐control study designs without proceeding to validation in independent cohorts. To develop a robust test for FGR, large prospective studies are required with a priori validation plans and cohorts. Given that current clinical care detects 20% of SGA fetuses, even a screening test with ≥60% sensitivity at 90% specificity could be clinically useful, if developed. This may be an achievable aspiration. If discovered, such a test may decrease stillbirth.
Whole-Cell Models and Simulations in Molecular Detail.

Comprehensive data about the composition and structure of cellular components have enabled the construction of quantitative whole-cell models. While kinetic network-type models have been established, it is also becoming possible to build physical, molecular-level models of cellular environments. This review outlines challenges in constructing and simulating such models and discusses near- and long-term opportunities for developing physical whole-cell models that can connect molecular structure with biological function. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Development of the Intrahepatic and Extrahepatic Biliary Tract: A Framework for Understanding Congenital Diseases.

The involvement of the biliary tract in the pathophysiology of liver diseases and the increased attention paid to bile ducts in the bioconstruction of liver tissue for regenerative therapy have fueled intense research into the fundamental mechanisms of biliary development. Here, I review the molecular, cellular and tissular mechanisms driving differentiation and morphogenesis of the intrahepatic and extrahepatic bile ducts. This review focuses on the dynamics of the transcriptional and signaling modules that promote biliary development in human and mouse liver and discusses studies in which the use of zebrafish uncovered unexplored processes in mammalian biliary development. The review concludes by providing a framework for interpreting the mechanisms that may help understand the origin of congenital biliary diseases. Expected final online publication date for the Annual Review of Pathology: Mechanisims of Disease Volume 15 is January 24, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
A multiplex platform to identify mechanisms and modulators of proteotoxicity in neurodegeneration

Neurodegenerative disorders are a family of diseases that remain poorly treated despite their growing global health burden. A shared feature of many neurodegenerative disorders is the accumulation of toxic misfolded proteins. To gain insight into the mechanisms and modulators of protein misfolding, we developed a multiplex reverse genetics platform. Using this novel platform 29 cell-based models expressing proteins that undergo misfolding in neurodegeneration were probed against more than a thousand genetic modifiers. The resulting data provide insight into the nature of modifiers that act on multiple misfolded proteins as compared to those that show activity on only one. To illustrate the utility of this platform, we extensively characterized a potent hit from our screens, the human chaperone DNAJB6. We show that DNAJB6 is a general modifier of the toxicity and solubility of multiple amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD)-linked RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1. Biophysical examination of DNAJB6 demonstrated that it co-phase separates with, and alters the behavior of FUS containing condensates by locking them into a loose gel-like state which prevents their fibrilization. Domain mapping and a deep mutational scan of DNAJB6 support the critical importance for DNAJB6 phase separation in its effects on multiple RNA-binding proteins. Crucially, these studies also suggest that this property can be further tuned to generate novel variants with enhanced activity that might illuminate potential avenues for clinical translation.