Miracle-dz/UniFAR-FTUs huggingface dataset:
A 3D cell culture system: Separation distance between INS‐1 cell and endothelial cell monolayers co‐cultured in fibrin influences INS‐1 cells insulin secretion

The aim of this study was to develop an in vitro cell culture system allowing studying the effect of separation distance between monolayers of rat insulinoma cells (INS‐1) and human umbilical vein endothelial cells (HUVEC) co‐cultured in fibrin over INS‐1 cell insulin secretion. For this purpose, a three‐dimensional (3D) cell culture chamber was designed, built using micro‐fabrication techniques and validated. The co‐culture was successfully carried out and the effect on INS‐1 cell insulin secretion was investigated. After 48 and 72 h, INS‐1 cells co‐cultured with HUVEC separated by a distance of 100 µm revealed enhanced insulin secretion compared to INS‐1 cells cultured alone or co‐cultured with HUVEC monolayers separated by a distance of 200 µm. These results illustrate the importance of the separation distance between two cell niches for cell culture design and the possibility to further enhance the endocrine function of beta cells when this factor is considered. Biotechnol. Bioeng. 2013; 110: 619–627. © 2012 Wiley Periodicals, Inc.
Regularization Matters: Generalization and Optimization of Neural Nets v.s. their Induced Kernel

Recent works have shown that on sufficiently over-parametrized neural nets, gradient descent with relatively large initialization optimizes a prediction function in the RKHS of the Neural Tangent Kernel (NTK). This analysis leads to global convergence results but does not work when there is a standard $\ell_2$ regularizer, which is useful to have in practice. We show that sample efficiency can indeed depend on the presence of the regularizer: we construct a simple distribution in d dimensions which the optimal regularized neural net learns with $O(d)$ samples but the NTK requires $\Omega(d^2)$ samples to learn. To prove this, we establish two analysis tools: i) for multi-layer feedforward ReLU nets, we show that the global minimizer of a weakly-regularized cross-entropy loss is the max normalized margin solution among all neural nets, which generalizes well; ii) we develop a new technique for proving lower bounds for kernel methods, which relies on showing that the kernel cannot focus on informative features. Motivated by our generalization results, we study whether the regularized global optimum is attainable. We prove that for infinite-width two-layer nets, noisy gradient descent optimizes the regularized neural net loss to a global minimum in polynomial iterations.
Aspects of Motivation : Goal Engagement and Goal Disengagement Many theorists assume that individuals help shape their own development

A successful entry into work is one of the key developmental tasks in young adulthood. The present 4-wave longitudinal study examined the interplay between occupational motivation (i.e., goal engagement and goal disengagement) and well-being (i.e., satisfaction with life, satisfaction with work, satisfaction with partnership, positive affect, depressive symptoms, autonomy, purpose in life, positive relations with others) during the transition from university to work. The sample consisted of 498 university graduates from 4 majors with favorable or unfavorable employment opportunities. Data were analyzed using latent growth curve modeling. The results showed that increases in goal engagement were associated with increases in numerous aspects of well-being. Increases in goal disengagement were associated with decreases in numerous aspects of well-being. However, this dynamic was not without exception. Goal engagement at graduation was associated with a decrease in autonomy and, for individuals with unfavorable employment opportunities, an increase in depressive symptoms. Goal disengagement at graduation was associated with an increase in satisfaction with work. These findings elucidate why some individuals may opt for overall maladaptive motivational strategies during the transition into the workforce: They provide selective well-being benefits. In sum, how young adults deal with their occupational goals is closely linked to changes in their well-being.
Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming

Chemical reprogramming of astrocytes into neurons represents a promising approach to regenerate new neurons for brain repair, but the underlying mechanisms driving this trans-differentiation process are not well understood. We have recently identified four small molecules – CHIR99021, DAPT, LDN193189, and SB431542 – that can efficiently reprogram cultured human fetal astrocytes into functional neurons. Here we employ the next generation of RNA-sequencing technology to investigate the transcriptome changes during the astrocyte-to-neuron (AtN) conversion process. We found that the four small molecules can rapidly activate the hedgehog signaling pathway while downregulating many glial genes such as FN1 and MYL9 within 24 h of treatment. Chemical reprogramming is mediated by several waves of differential gene expression, including upregulation of hedgehog, Wnt/β-catenin, and Notch signaling pathways, together with downregulation of TGF-β and JAK/STAT signaling pathways. Our gene network analyses reveal many well-connected hub genes such as repulsive guidance molecule A (RGMA), neuronatin (NNAT), neurogenin 2 (NEUROG2), NPTX2, MOXD1, JAG1, and GAP43, which may coordinate the chemical reprogramming process. Together, these findings provide critical insights into the molecular cascades triggered by a combination of small molecules that eventually leads to chemical conversion of astrocytes into neurons.
Systematic Review of Literature on Single-Nucleotide Polymorphisms Within the Oxytocin and Vasopressin Receptor Genes in the Development of Social Cognition Dysfunctions in Individuals Suffering From Autism Spectrum Disorder

Introduction: Autism spectrum disorder (ASD) is found in virtually all population groups regardless of ethnic or socioeconomic backgrounds. Among others, dominant symptoms of autism persistent throughout its course of development include, inter alia, qualitative disorders of social communication and social interactions. Numerous studies have been performed on animal models as well as groups of healthy individuals to assess the potential role of oxytocinergic and vasopresynergic systems in normal social functioning. These studies have also discussed their potential participation in the development of social cognition dysfunctions in the course of ASD. This literature review aimed to identify studies examining single-nucleotide polymorphisms of the oxytocin (OXT) and arginine vasopressin (AVP) receptor genes and their differential effects on social cognitive dysfunction in the development of ASD. Methods: A systematic review of literature published within the last 10 years and accessible in PubMed, Google Scholar, Cochrane Library, and APA PsycNET databases was conducted by each author separately. Inclusion criteria required that articles should 1) be published between January 2008 and August 2018; 2) be published in English or Polish; 3) be located in periodical publications; 4) focus on the role of polymorphisms within oxytocin and vasopressin receptor genes in autistic population; 5) provide a clear presentation of the applied methodology; and 6) apply proper methodology. Results: From the 491 studies qualified to the initial abstract analysis, 15 met the six inclusion criteria and were included in the full-text review. Conclusions: The analysis of available literature seems to indicate that there is an association between social cognition dysfunctions in the course of autism and selected alleles of polymorphisms within the OXT receptor AVP 1A receptor genes. However, previous studies neither specify the nature of this association in an unequivocal way nor select genotypes that are the basis for this association.
Inhibition and Production of Anger Cost More: Evidence From an ERP Study on the Production and Switch of Voluntary Facial Emotional Expression

Humans need to flexibly produce or switch different facial emotional expressions to meet social communication need. However, little is known about the control of voluntary facial emotional expression. We investigated the production and switch of facial expressions of happiness and anger in a response-priming task of 23 Chinese female university students and recorded electroencephalographic (EEG) signals. Results revealed that a frontal-central P2 component demonstrated greater positivity in the invalidly cued condition compared with the validly cued condition. Comparing the two facial emotional expressions, data from the contingent negative variation (CNV) component revealed that happiness and anger did not differ in the motor preparation phase. While data from N2 and P3 showed that switching from anger to happiness elicited larger N2 amplitudes than switching from happiness to anger and switching from happiness to anger elicited larger P3 than switching from anger to happiness. The results revealed that in invalidly cued condition, the inhibition (N2) and reprogramming (P3) cost of anger was greater than that of happiness. The findings indicated that during the switching process, both the inhibition and the reprogramming of anger cost more processing resources than those of happiness.
Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder

Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified. Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined. Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex. Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.
Effect of autologous and allogenic platelet-rich plasma on human gingival fibroblast function.

OBJECTIVE Platelet-rich plasma (PRP) has been proposed as a method of delivering growth factors to enhance regeneration. The aim of this study was to investigate the use of autogenous and allogenic PRP and platelet-poor plasma (PPP) on migration and proliferation of human gingival fibroblasts in vitro. METHODS Various concentrations of PRP, as well as PPP, were prepared from autologous and allogenic sources and applied to primary gingival fibroblasts. Migration was determined by assessing the fibroblast response to a concentration gradient. (3)H-thymidine incorporation and crystal violet colorimetric assays were utilized to assess DNA synthesis and proliferation. RESULTS Platelet-rich plasma provides a significant migratory stimulus to gingival fibroblasts. Furthermore, the various concentrations of PRP (50%, 20% and 10%) do not promote DNA synthesis in the short term (24 h), but over the longer term (5 days) they stimulate an increase in cell proliferation. Compared with PPP, PRP was superior in terms of encouraging migration, but was inferior in terms of promoting DNA synthesis and cell proliferation. No difference was noted between the autologous and allogenic PRP preparations on cell function. CONCLUSION Both PPP and PRP promote gingival fibroblast migration and proliferation in vitro, without differences between preparations obtained from autologous and allogenic sources.
Learning Semantics-aware Distance Map with Semantics Layering Network for Amodal Instance Segmentation

In this work, we demonstrate yet another approach to tackle the amodal segmentation problem. Specifically, we first introduce a new representation, namely a semantics-aware distance map (sem-dist map), to serve as our target for amodal segmentation instead of the commonly used masks and heatmaps. The sem-dist map is a kind of level-set representation, of which the different regions of an object are placed into different levels on the map according to their visibility. It is a natural extension of masks and heatmaps, where modal, amodal segmentation, as well as depth order information, are all well-described. Then we also introduce a novel convolutional neural network (CNN) architecture, which we refer to as semantic layering network, to estimate sem-dist maps layer by layer, from the global-level to the instance-level, for all objects in an image. Extensive experiments on the COCOA and D2SA datasets have demonstrated that our framework can predict amodal segmentation, occlusion, and depth order with state-of-the-art performance.
Effect of antiserum to rat prolactin on milk yield and food intake in the rat.

Anti-ovine prolactin injected into the duct of a rabbit mammary gland inhibits the local lactogenic response of prolactin in the same duct (Saji & Crighton, 1968), and inhibits the proliferative effect of concurrently-injected prolactin in the pigeon crop-sac assay (Hayashida, 1962). Anti-ovine prolactin also decreases the weights of the prostate and seminal vesicle of male rabbits (Asano, Kanzaki, Sekiguchi & Tasaka, 1971). Anti-mouse prolactin has been reported to suppress the growth of mammary tumours in mice (Sinha, Lewis & Vanderlaan, 1974) and to inhibit the biological activity of mouse prolactin as measured by the pigeon crop-sac test (Kosugiyama, Mori & Nagasawa, 1970). Anti-rat prolactin injected into lactating rats lowered the progesterone secretion rate (Yoshinaga, 1973), while anti-human placental lactogen injected to pregnant rats during Days 1 to 5 of gestation reduced the weight of the young and increased their mortality (El Tomi, Boots & Stevens, 1971). Sinha et al. (1971) injected anti-mouse prolactin to 4-day-old rats; 39% died within a few days of the injections, and there was poor growth of the surviving young. In a further experiment, Sinha et al. (1972) reported suppression of the growth of young rats after injecting anti-mouse prolactin into the mothers, and regarded this as suggesting involvement of prolactin in milk synthesis. The present study involved the injection of anti-rat prolactin into lactating rats and, by subsequent measurement of their food and water intake in addition to the growth and survival of their young, determination of the effect on milk yield of neutralizing the endogenous prolactin. Anti-serum to rat prolactin was prepared by a modification of the method described by Vaitukaitis, Robbins, Nieschlag & Ross (1971) by intradermal injections into multiple sites in the necks of 2to 3-month-old rabbits. The rat prolactin was dissolved in a minimal quantity of 1/10 sodium hydroxide solution, made up to a final dilution of 0-1 mg/ml with phosphate buffer, and emulsified with twice the volume of Freund's complete adjuvant. Dried tuber¬ culosis bacilli were then added by vigorous mixing to give a final concentration of 2-5 mg bacilli/1 ml emulsion, and the mixture was injected at a dose of 0-1 mg/rabbit. A booster injection was prepared by dissolving prolactin in sodium hydroxide solution and made up with phosphate buffer, pH 7-6, to a final concentration of 0-25 mg/ml. The booster solution was injected intramuscularly into the paws, and the rabbits were bled 14 days later and the sera were assayed for anti-prolactin by the double-antibody system using NIAMD rat prolactin
Elevated Sensitivity to Tactile Stimuli in Stereotypic Horses

Although stereotypic behaviors are a common problem in captive animals, why certain individuals are more prone to develop them remains elusive. In horses, individuals show considerable differences in how they perceive and react to external events, suggesting that this may partially account for the emergence of stereotypies in this species. In this study, we focused on crib-biting, the most common stereotypy displayed by horses. We compared how established crib-biters (“CB” = 19) and normal controls (“C” = 18) differed in response to a standard “personality” assessment test battery, i.e., reactivity to humans, tactile sensitivity, social reactivity, locomotor activity, and curiosity vs. fearfulness (both in novel and suddenness situations). Our analyses showed that crib-biters only differed from control horses in their tactile sensitivity, suggesting an elevated sensitivity to tactile stimuli. We suggest that this higher tactile sensitivity could be due to altered dopamine or endogenous opioid physiology, resulting from chronic stress exposition. We discuss these findings in relation to the hypothesis that there may be a genetic predisposition for stereotypic behavior in horses, and in relation to current animal husbandry and management practices.
The Cognitive Neuroscience of Stable and Flexible Semantic Typicality

Typicality effects are among the most well-studied phenomena in the study of concepts. The classical notion of typicality is that typical concepts share many features with category co-members and few features with members of contrast categories. However, this notion was challenged by evidence that typicality is highly context dependent and not always dependent on central tendency. Dieciuc and Folstein (2019) argued that there is strong evidence for both views and that the two types of typicality effects might depend on different mechanisms. A recent theoretical framework, the controlled semantic cognition framework (Lamdon Ralph et al., 2017) strongly emphasizes the classical view, but includes mechanisms that could potentially account for both kinds of typicality. In contrast, the situated cognition framework (Barsalou, 2009b) articulates the context-dependent view. Here, we review evidence from cognitive neuroscience supporting the two frameworks. We also briefly evaluate the ability of computational models associated with the CSC to account for phenomena supporting SitCog (Rogers and McClelland, 2004). Many predictions of both frameworks are borne out by recent cognitive neuroscience evidence. While the CSC framework can at least potentially account for many of the typicality phenomena reviewed, challenges remain, especially with regard to ad hoc categories.
17β‐Estradiol regulation of protein kinase C activity in chondrocytes is sex‐dependent and involves nongenomic mechanisms

17β‐Estradiol (E2) regulates growth plate chondrocyte differentiation in both a sex‐ and cell maturation–dependent manner, and the sex‐specific effects of E2 appear to be mediated in part by membrane events. In this study, we examined whether E2 regulates protein kinase C (PKC) in a cell‐maturation and sex‐specific manner and whether E2 uses a nongenomic mechanism in regulating this enzyme. In addition, we determined if PKC mediates the E2‐dependent stimulation of alkaline phosphatase activity seen in chondrocytes. Confluent, fourth passage resting zone (RC) and growth zone (GC) chondrocytes from male and female rat costochondral cartilage were treated with 10−10 to 10−7 M E2. E2 caused a dose‐dependent increase in PKC in RC and GC cells from female rats. Peak stimulation was at 90 min. Increased PKC was evident by 3 min in both RC and GC and was still evident in RC cells at 720 min, but in GC cells activity returned to baseline by 270 min. Actinomycin D had no effect at 9, 90, 270, or 720 min, but there was a small decrease in E2‐stimulated PKC in RC treated with cycloheximide at 90 and 270 min and in GC treated for 90 min. E2 increased cytosolic and membrane PKC at 9 min and by 90 min promoted translocation of PKC activity from the cytosol to the membranous compartment of female RC cells. Antibodies specific for the α, β, δ, ε, and ζ isoforms of PKC revealed that PKCα in female GC and RC cells is activated by E2. There was a small, but statistically significant, increase in PKC in male RC cells in response to E2, but it was not dose‐dependent, and no effect of E2 was noted in male GC cells. 17α‐estradiol, an inactive isomer of E2, did not affect PKC specific activity in RC or GC cells from either female or male rats. Chelerythrine, a specific inhibitor of PKC, inhibited E2‐dependent alkaline phosphatase activity, indicating that E2 mediates its rapid effects on alkaline phosphatase via PKC. J. Cell. Physiol. 176:435–444, 1998. © 1998 Wiley‐Liss, Inc.
iVAMS 1.0: Polynomial-Metamodel-Integrated Intelligent Verilog-AMS for Fast, Accurate Mixed-Signal Design Optimization

Electronic circuit behavioral models built with hardware description/modeling languages such as Verilog-AMS for system-level simulations are typically functional models. They do not capture the physical design (layout) information of the target design. Numerous iterations of post-layout design adjustments are usually required to ensure that design specifications are met with the presence of layout parasitics. In this paper a paradigm shift of the current trend is presented that integrates layout-level information in Verilog-AMS through metamodels such that system-level simulation of a mixed-signal circuit/system is realistic and as accurate as true parasitic netlist simulation. The simulations performed with these parasitic-aware models can be used to estimate system performance without layout iterations. We call this new form of Verilog-AMS as iVAMS (i.e. Intelligent Verilog-AMS). We call this iVAMS 1.0 as it is simple polynomial-metamodel integrated Intelligent Verilog-AMS. As a specific case study, a voltage-controlled oscillator (VCO) Verilog-AMS behavioral model and design flow are proposed to assist fast PLL design space exploration. The PLL simulation employing quadratic metamodels achieves approximately 10X speedup compared to that employing the layout extracted, parasitic netlist. The simulations using this behavioral model attain high accuracy. The observed error for the simulated lock time and average power dissipation are 0.7% and 3%, respectively. This behavioral metamodel approach bridges the gap between layout-accurate but fast simulation and design space exploration. The proposed method also allows much shorter design verification and optimization to meet stringent time-to-market requirements. Compared to the optimization using the layout netlist, the runtime using the behavioral model is reduced by 88.9%.