Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced Metabolizing Activity of Human ES Cell-Derived Hepatocytes Using a 3D Culture System with Repeated Exposures to Xenobiotics.

Highly homogeneous and functional stem cell-derived hepatocyte-like cells (HLCs) are considered a promising option in the cell-based therapy of liver disease and the development of effective in vitro toxicity screening tools. However, the purity of cells and expression and/or activity of drug metabolizing enzymes in stem cell-derived HLCs are usually too low to be useful for clinical or in vitro applications. Here, we describe a highly optimized hepatic differentiation protocol, which produces >90% (BGO1 and CHA15) albumin-positive HLCs with no purification process from human embryonic stem cell lines. In addition, we show that hepatic enzyme gene expressions and activities were significantly improved by generating 3D spheroidal aggregate of HLCs, compared with 2D HLCs. The 3D differentiation method increased expression of nuclear receptors (NRs) that regulate the proper expression of key hepatic enzymes. Furthermore, significantly increased hepatic functions such as albumin and urea secretion were observed in 3D hepatic spheroids, compared with 2D HLCs. HLCs in the spheroid exhibited morphological and ultrastructural features of normal hepatocytes. Importantly, we show that repeated exposures to xenobiotics facilitated further functional maturation of HLC, as confirmed by increased expression of genes for drug metabolizing enzymes and transcription factors. In conclusion, the 3D culture system with repeated exposures to xenobiotics may be a new strategy for enhancing hepatic metabolizing ability of stem cell-derived HLCs as a cell source for in vitro high-throughput hepatotoxicity models.
The influence of trust on collaborative relationships in supply chains

In this paper we theoretically discuss and empirically examine the influence of trust on collaborative behavior in supply chain relationships. These concepts are very important in today’s inter- organizational business world, and therefore in supply chains. In theoretical part of this article we presume that establishment and development of relationships in supply chain depends on development of trust. Trust is defined as a willingness to rely on a partner in a supply chain in whom one has confidence. The stress is on expectation that another partner can be relied on to fulfill obligations and at the same time previous experience with partners in exchange relationships are taken in the consideration. Collaborative behavior is defined as a concept where two or more organizations, which work together in a supply chains, can through complementary characteristics gain shared means and goals that could not be achieved individually. Logistics managers, purchase and sales managers, project managers and employees in logistics department were included in our survey made on primary, secondary and tertiary sector of Slovene economy. We included companies of all sizes, both local and foreign companies present in Slovenia. 118 questionnaires were completed and involved in our research. According to the demographic data, our sample is comparable to population in terms of economy branch and size of companies. The Pearson correlation coefficient and linear regression analysis demonstrate statistically significant strong correlation between trust, shared values and communication and strong negative correlation between trust and opportunistic behavior. At the end we can confirm that there is a statistically significant influence of trust on collaborative behavior in supply chains. The results clearly indicate that all factors included in research are very important for today’s supply chain management.
Turbulence, perturbance, and educational change

While scholarship on educational change has long accepted that disruptions to the status quo are an essential part of the change process, disruption has never been more central to planned change than it is in the current political context in the USA, where legislation has mandated school closure, reconstitution, and turnaround as required remedies for schools failing to produce annual student achievement gains required by government. We are also unfortunately hampered by the imprecise language that surrounds complexity- based theories of educational change. Words such as perturbance, turbulence, and disruption all have gained currency lately, but meanings are unclear and overlapping. This essay seeks to lend some clarity to the debate by defining turbulence as the perception of forces in an organizational environment with the potential to disrupt current modes of operation. This is distinguished from perturbance which is defined as the social process of actors coming together to adjust organizational practice to fit with the changing environmental context. The case is argued that sensible reformers ought to be fostering perturbance while minimizing the harmful consequences of excessive turbulence.
Restoration of caveolin‐1 expression suppresses growth, membrane‐type‐4 metalloproteinase expression and metastasis‐associated activities in colon cancer cells

Caveolin‐1 (cav‐1) and flotillin‐1 are two major structural proteins associated with lipid rafts in mammalian cells. The membrane‐type matrix metalloproteinases (MT‐MMPs) are expressed at the cell surface, hydrolyze extracellular matrix, and play an important role in cancer cell migration and metastasis. Expression of cav‐1, flotillin‐1, and MT4‐MMP in lysates and lipid rafts of LS174T and HM‐7 colon cancer cells was determined. The impact of restoration of cav‐1 expression on proliferation, adhesion, motility in vitro, and growth of implanted tumors in vivo was characterized. Cav‐1 is not expressed in lipid rafts of the highly metastatic colon cancer cell line (HM‐7), but expressed in cytosolic fractions of the parental lower metastatic cell line (LS174T). In contrast, MT4‐MMP was expressed in lipid rafts of HM‐7 cells but not in LS174T cells. Overexpression of cav‐1 in HM‐7 cells down‐regulate proliferation, viability, wound closure, adhesion to laminin, invasion, and development of filopodial and lamellipodial structures in a dose‐dependent manner. Cav‐1 positive HM‐7 clones ceased to express MT4‐MMP in their lipid rafts. Comparative proteomic analyses of lipid rafts from cav‐1 positive and cav‐1 negative cells demonstrated de novo expression of flotillin‐1 only on the cells expressing cav‐1. Xenografting control cells devoid of cav‐1 in nude mice induced development of bigger tumors expressing higher levels of proliferating cell nuclear antigen as compared to mice injected with cells expressing the highest cav‐1 levels. We conclude that cav‐1 orchestrates and reorganize several proteins in lipid rafts, activities directly associated with reduced tumorigenic and metastatic ability of colon cancer cells. © 2012 Wiley Periodicals, Inc.
Inactivation of Glycogen Synthase Kinase-3 by Epidermal Growth Factor Is Mediated by Mitogen-activated Protein Kinase/p90 Ribosomal Protein S6 Kinase Signaling Pathway in NIH/3T3 Cells (*)

The role of the p90 ribosomal protein S6 kinase/mitogen-activated protein kinase (RSK/MAPK) signaling pathway in regulating glycogen synthase kinase-3 (GSK-3) activity was investigated. In vitro studies showed that GSK-3 was inactivated by 50% upon incubation with RSK purified from epidermal growth factor (EGF)-stimulated NIH/3T3 cells. Subsequently, the effect of EGF on GSK-3 activity was measured in NIH/3T3 cells that stably overexpressed mutated forms of MAPK kinase (MAPKK). The activation of RSK by EGF was markedly decreased in cell lines expressing the dominant negative MAPKK mutants S222A and K97A and was increased in cells expressing the S222E mutant as compared with control cell lines. EGF induced a rapid decrease in GSK-3β activity (50%) in control and S222E cells; however, only 25 and 10% inhibition in GSK-3β activity was observed in cell lines expressing the dominant negative mutants K97A and S222A, respectively, suggesting that inhibition of GSK-3 was partially blocked in these cells. Taken together, these results suggest that the action of EGF on GSK-3 inactivation is mediated by the RSK/MAPK signaling pathway in NIH/3T3 cells and provide evidence for a mechanism regulating GSK-3 activity in intact cells.
“What’s in it for me?” - an investigation into the motivations, challenges and benefits of peer leadership in a School of Education.

The Peer Assisted Study Sessions (PASS) scheme is a student-owned, student-led mentoring scheme involving trained undergraduate student volunteers from levels five and six (second and third year) facilitating weekly study sessions for level four (first year) students. PASS has been running for two years in the School of Education at the University of Brighton. Other enquiries we have made have highlighted positive impacts of PASS on the first year experience. This investigation has concentrated on the experiences of the leaders. Through the voices of two staff supervisors and seven student leaders, this case study explores the key benefits and challenges experienced by the PASS leaders. The findings illustrate the leaders’ awareness of their growing confidence, communication and employability skills development, particularly pertinent for leaders in the School of Education in relation to their future career paths.
In Vivo Cardiac, Acoustic-Radiation-Force-Driven, Shear Wave Velocimetry

Shear wave elasticity imaging (SWEI) was employed to track acoustic radiation force impulse (ARFI)-induced shear waves in the mid-myocardium of the left ventricular free wall (LVFW) of a beating canine heart. Shear waves were generated and tracked with a linear ultrasound transducer that was placed directly on the exposed epicardium. Acquisition was ECG-gated and coincided with the mid-diastolic portion of the cardiac cycle. Axial displacement profiles consistent with shear wave propagation were clearly evident in all SWEI acquisitions (i.e., those including an ARFI excitation); displacement data from control cases (i.e., sequences lacking an ARFI excitation) offered no evidence of shear wave propagation and yielded a peak absolute mean displacement below 0.31 μm after motion filtering. Shear wave velocity estimates ranged from 0.82 to 2.65 m/s and were stable across multiple heartbeats for the same interrogation region, with coefficients of variation less than 19% for all matched acquisitions. Variations in velocity estimates suggest a spatial dependence of shear wave velocity through the mid-myocardium of the LVFW, with velocity estimates changing, in limited cases, through depth and lateral position.
Do women borrowers augment financial performance of MFIs?

ABSTRACT There is some consensus that depth of outreach and financial performance of Microfinance Institutions (MFI) are positively correlated. A majority of microcredit borrowers are women and since the prevalence of female borrowers is even greater among the very poor, there should be a positive correlation between female borrowers and financial performance. Most of the MFIs target women as preferred borrowers. However, no study to date has investigated the relationship between targeting women and MFI’s sustainability with respect to profitability and yield. Utilizing a panel of 892 MFIs over a period of 10 years, this study shows that increased proportion of women borrowers has a statistically significant positive impact on yield and financial performance of MFIs. Consequently, this article also analyses the implication as to whether female borrowers have better repayment rate than male borrowers.
Marked decrease in suicide among men and women in the former USSR during perestroika

At the same time as substantial and rapid socio‐political and socio‐economic changes took place during the period of perestroika, suicide rates in the former USSR decreased by approximately 32% for men and 19% for women. The decreases in the suicide rates of men in the former USSR were unlike the suicide rate decreases taking place in 22 other European countries, where rates decreased by approximately 8% for men and 17% for women during this time period. Declines in suicide rates from 1984 to 1986–1988 occurred in all republics, with the largest decreases in Russia and Belarus, at 42% for men and 20% for women. The decrease in suicide rates of men in the former USSR was most pronounced until 1986–1988, after which time an increasing trend was observed. Suicide rates for men in the former USSR decreased 3.8‐fold more than they did for men in other parts of Europe, while decreases in the suicide rates for women in the former USSR were on the same level as in Europe.
"Motherese" of Mr. Rogers: a description of the dialogue of educational television programs.

Dialogue from 30-min samples each from Sesame Street and Mr. Rogers' Neighborhood was described. Three aspects of language were measured: grammar, content, and discourse. The findings indicate that the dialogue of these programs is well suited to young viewers, with adjustments similar to those evident in adults' speech to young children. The mean length of utterance is comparable to that of adults in interactions with children, the ratio of different words to total words is the same as that of young children's language, sentence structure is simplified, and there is a heavy emphasis on the here and now (a majority of present tense verbs, a high proportion of utterances about immediately visible topics or referents, and a preponderance of narrative about shared immediate events). There are repeated instances of linguistic emphasis, with frequent repetition of key terms. Both programs avoid complex word forms. Overall, the dialogue of educational children's programs follows the constraints and adjustments evident in adults' child-directed language.
Optical Brain Monitoring of the Cerebrovascular Effects Induced by Acute Cocaine Exposure in Neonatal Pigs.

> Objective: The purpose of this study was to assess the direct effects of cocaine on cerebral blood flow and oxygenation in newborn piglets using optical spectroscopy. Optical spectroscopy is capable of monitoring changes in cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin continuously, noninvasively, and in real time. Methods: Five anesthetized and ventilated newborn piglets were injected intravenously with 1 mg/kg cocaine through a central venous catheter over 60 seconds. Cerebral blood flow and oxygenation were assessed by optical spectroscopy and standard physiologic monitoring: mean arterial pressure, carotid blood flow, cerebrovascular resistance, and arterial hemoglobin oxygen saturation (by pulse oximetry). Results: Cocaine induced a profound increase in cerebrovascular resistance, a decrease in carotid blood flow, and a decrease in mean arterial pressure and heart rate. Cerebrovascular changes were detected readily by optical spectroscopy (i.e. a decrease in cerebral oxyhemoglobin was associated with an increase in deoxyhemoglobin). The hypotensive response augmented the cerebral vasoconstriction effect on carotid blood flow. A good correlation existed between the changes in carotid Doppler blood flow and total hemoglobin in each animal and for all animals combined. Peripheral arterial hemoglobin oxygen saturation measured by pulse oximetry remained normal throughout the experiment. Conclusions: The cause for the apparent idiosyncratic hypotensive response to intravenous injections of cocaine is uncertain and requires further investigation. Our study clearly demonstrates that optical spectroscopy might become an extremely useful tool for monitoring cerebral hemodynamics and oxygenation in cocaine-exposed fetuses and infants.
Spin transport in graphene: Fundamental concepts and practical implications

Electronic devices based on spin transport are expected to play a major role in future Information and Communication Technologies (ICT). Those spintronics devices will use the spin degree of freedom to store, transport and process information. Even if magnetic read heads have been the cornerstone of magnetic hard drives since 1996, it is only recently that the full potential of spintronics has been included in the ITRS road map. Spin information processing will require the ability to inject, manipulate and detect spins. To this respect, the seminal spintransistor proposed by Datta and Das [1] is a very simple device based on spin injection and detection using ferromagnetic electrodes and on the manipulation of the spin information through the spin-orbit coupling (Rashba effect). It was, however, soon understood that fundamental constraints on the physics governing spin transport will make this concept very difficult to achieve with conventional semiconductors (GaAs or Si) [2, 3]. Here we will present a set of results on an alternative route where the channel is no longer a conventional semiconductor but graphene. Graphene is expected to be a good candidate for spin information transport as its mobility at room temperature outperforms that of any other material [5] and its spin orbit coupling as well as the hyperfine interaction of 12C are expected to be very small. Using Multilayer graphene grown on SiC wafers we experimentally demonstrate using spin transport experiments in the lateral spin-valve geometry that the spin diffusion length is at least of the order of 100 μm [6].
Nanoscale MOSFET Modeling: Part 2: Using the Inversion Coefficient as the Primary Design Parameter

This article illustrates the use of the inversion coefficient (IC) as the main design parameter to explore the various tradeoffs faced in the design of analog circuits. We start with showing that the same transconductance, gain-bandwidth (GBW) product, or input-referred thermal noise resistance of a common-source (CS) amplifier can be achieved with lower current by shifting the IC toward moderate inversion (MI) at the cost of a slight increase of the transistor aspect ratio and area. In such case the self-loading gate capacitance cannot be ignored, and accounting for it introduces a minimum bias current at an IC that lies in the middle of the MI to achieve a given GBW.
Crude Oil Price Uncertainty and Stock Markets in Gulf Corporation Countries: A Var-Garch Copula Model

The main objectives of this study are twofold. The first objective is to examine the volatility spillover between the GCC stock markets and Oil prices, over the period 2005-2012, in a multivariate setting, using the VAR (1)-GARCH (1,1) model which allows for transmission in returns and volatility. The second is to investigate the dependence structure and to test the degree of the dependence between financial returns using copula functions. Five candidates, the Gaussian, the Studentâ€™s t, the Frank, the Clayton and the Gumbel copulas, are compared. Our empirical results for the first objective suggest that there exist moderate cross market volatility transmission and shocks between the markets, indicating that the past innovation in stock market have great effect on future volatility in oil market and vice versa. 0
T‐loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P‐TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes

P‐TEFb functions to induce the elongation step of RNA polymerase II transcription by phosphorylating the carboxyl‐terminal domain of the largest subunit of RNA polymerase II. Core P‐TEFb is comprised of Cdk9 and a cyclin regulatory subunit, with Cyclin T1 being the predominant Cdk9‐associated cyclin. The kinase activity of P‐TEFb is dependent on phosphorylation of the Thr186 residue located within the T‐loop domain of the Cdk9 subunit. Here, we used immunofluorescence deconvolution microscopy to examine the subcellular distribution of phospho‐Thr186 Cdk9/Cyclin T1 P‐TEFb heterodimers. We found that phospho‐Thr186 Cdk9 displays a punctate distribution throughout the non‐nucleolar nucleoplasm and it co‐localizes with Cyclin T1 almost exclusively within nuclear speckle domains. Phospho‐Thr186 Cdk9 predominantly co‐localized with the hyperphosphorylated forms of RNA polymerase II. Transient expression of kinase‐defective Cdk9 mutants revealed that neither is Thr186 phosphorylation or kinase activity required for Cdk9 speckle localization. Lastly, both the Brd4 and HEXIM1 proteins interact with P‐TEFb at or very near speckle domains and treatment of cells with the Cdk9 inhibitor flavopiridol alters this distribution. These results indicate that the active form of P‐TEFb resides in nuclear speckles and raises the possibility that speckles are sites of P‐TEFb function and exchange between negative and positive P‐TEFb regulatory complexes. J. Cell. Physiol. 224:84–93, 2010 © 2010 Wiley‐Liss, Inc.
Characteristics and response to treatment among Indigenous people receiving injectable diacetylmorphine or hydromorphone in a randomised controlled trial for the treatment of long‐term opioid dependence

INTRODUCTION AND AIMS To determine the effectiveness of injectable hydromorphone and dicaetylmorphine for Indigenous participants in the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) clinical trial. The study additionally aims to explore the prevalence and frequency of crack cocaine use among subgroups of participants (by gender and ethnicity). This secondary analysis is particularly relevant given the current need for expanded medication assisted treatments for opioid dependence across North America. DESIGN AND METHODS Participants self-identifying as First Nations, Métis or Inuit were included in the analysis of Indigenous participants. Six-month treatment outcomes are reported as the difference between diacetylmorphine and hydromorphone treatment arms among Indigenous participants and change from baseline to 6 months in each treatment arm. Differences in outcomes are tested between Indigenous and non-Indigenous participants. Crack cocaine use was explored to determine differences between and within subgroups. RESULTS Approximately one-third of SALOME participants self-identified as Indigenous. Indigenous participants presented to treatment with more structural vulnerabilities (e.g. lower education, higher rates of foster care and separation from biological parents) compared to non-Indigenous participants. After 6 months, Indigenous participants in both treatment arms had a significant reduction in days of street heroin use, opioid use, crack cocaine use and illegal activity. Treatment retention did not differ by treatment arm. DISCUSSION AND CONCLUSIONS Indigenous people that are not engaged by first-line treatments for opioid dependence are in need of effective alternative treatments. Given the political and logistical barriers facing diacetylmorphine, hydromorphone could serve as a more accessible medication to reach and treat this population. [Oviedo-Joekes E, Palis H, Guh D, Marchand K, Brissette S, Lock K, MacDonald S, Harrison S, Anis AH, Krausz M, March DC, Schechter MT. Characteristics and response to treatment among Indigenous people receiving injectable diacetylmorphine or hydromorphone in a randomised controlled trial for the treatment of long-termopioid dependence. Drug Alcohol Rev 2018;37:137-146].