Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloramphenicol and tetracycline decrease motility and increase invasion and attachment gene expression in specific isolates of multidrug-resistant Salmonella enterica serovar Typhimurium

Salmonella enterica serovar Typhimurium is one of the most common serovars isolated from humans and livestock, and over 35% of these isolates are resistant to three or more antibiotics. Multidrug-resistant (MDR) Salmonella is a public health concern as it is associated with increased morbidity in patients compared to antibiotic sensitive strains, though it is unknown how the antibiotic resistant isolates lead to a more severe infection. Cellular invasion is temporally regulated in Salmonella and normally occurs during late-log and stationary growth. However, our previous work determined that a 30 min exposure to a sub-inhibitory concentration of tetracycline can induce the full invasion phenotype during early-log growth in certain MDR S. Typhimurium isolates. The current study examined whether sub-inhibitory concentrations of other antibiotics could also induce the invasiveness in the same set of isolates. Ampicillin and streptomycin had no effect on invasion, but certain concentrations of chloramphenicol were found to induce invasion in a subset of isolates. Two of the isolates induced by chloramphenicol were also inducible by tetracycline. RNA-seq analyses demonstrated that chloramphenicol and tetracycline both down-regulated motility gene expression, while up-regulating genes associated with attachment, invasion, and intracellular survival. Eleven fimbrial operons were up-regulated, which is notable as only three fimbrial operons were thought to be inducible in culture; six of these up-regulated operons have been reported to play a role in Salmonella persistence in mice. Overall, these data show that the normal progression of the genetic pathways that regulate invasion can be expedited to occur within 30 min due to antibiotic exposure. This altered invasion process due to antibiotics may play a role in the increased intensity and duration of infection observed in patients with MDR Salmonella.
miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression

Although it is well established that embryonic stem (ES) cells have the potential to differentiate into dopamine neurons, the molecular basis of this process, particularly the role of microRNAs (miRNAs), remains largely unknown. Here we report that miR-132 plays a key role in the differentiation of dopamine neurons by directly regulating the expression of Nurr1 (also known as nuclear receptor subfamily 4 group A member 2; Nr4a2). We constructed a mouse ES cell line CGR8, which stably expresses GFP under the tyrosine hydroxylase (TH) promoter, so the TH-positive neurons could be easily sorted using fluorescence-activated cell sorting (FACS). Then, we performed a miRNA array analysis on the purified TH-positive neurons and found that 45 of 585 miRNAs had more than a fivefold change in expression level during dopamine neuron differentiation. Among the 45 miRNAs, we were particularly interested in miR-132 because this miRNA has been reported to be highly expressed in neurons and to have a potential role in neurodegenerative diseases. We found that the direct downregulation of endogenous miR-132 induced by miR-132 antisense oligonucleotide (miR-132-ASO) promoted the differentiation of TH-positive neurons, whereas ectopic expression of miR-132 in ES cells reduced the number of differentiated TH-positive neurons but did not change the total number of differentiated neurons. Furthermore, we identified that miR-132-ASO could substantially reverse the miR-132-mediated suppression of TH-positive neuron differentiation. Moreover, through a bioinformatics assay we identified the Nurr1 gene as a potential molecular target of miR-132. Using a luciferase-reporter assay and western blot analysis, we demonstrated that miR-132 could directly regulate the expression of Nurr1. Collectively, our data provide the first evidence that miR-132 is an important molecule regulating ES cell differentiation into dopamine neurons by directly targeting Nurr1 gene expression.
Children out of parental care in Russia:what we can learn from the statistics

Svetlana Biryukova – Kandidat nauk (PhD) in Economics, Leading Researcher, Centre for Comprehensive Social Policy Studies at ISP NRU HSE, Moscow, Russia. Email: sbiryukova@hse.ru Oxana Sinyavskaya – Kandidat nauk (PhD) in Economics, Director of Centre for Comprehensive Social Policy Studies at ISP NRU HSE, Moscow, Russia. Email: osinyavskaya@hse.ru The paper presents a detailed analysis of the Russian official statistics for orphans and children placed out of parental care. Employing a wide range of data sources, the authors show that in Russia, the primary risk of orphanhood remains high. Although it has declined over the last fifteen years, in 2015, the share of children taken out of parental care exceeded two percent of the total number of children under eighteen. At the same time, statistical data confirms the ongoing deinstitualisation of the Russian care system, a trend that has continued since the mid‑2000s. Thus, 11.5 % of children out of parental care were institutionalised in 2014, whereas in 2000 this share amounted to as much as 27 %. However, the authors argue that the current childcare system reproduces a number of serious systemic problems. Firstly, despite the fact that over 80 % of children entering the Russian care system per year have living parents, reuniting the children with the birth family is not yet recognised as a primary objective of the policy; according to the official statistics, only one out of ten children goes back home after being taken out of parental care. Secondly, for particular groups of children it is often hard to arrange family placements. Until now, the higher risks of long-term institutionalisation are noticeable in children placed out of parental care at the age of three years or older. This problem is particularly serious for teenagers, as well as for children with physical or mental disabilities. Thirdly, the prevalence and dynamics in children returning to institutions from foster placements highlight the importance of professional training for foster parents and the need for consistent guidance for foster families, aspects that are still underdeveloped in Russia. In the last section of the paper, authors discuss one possible outcome of this analysis with reference to policies aimed at children left out of parental care.
Help seeking in the New Zealand Defence Force using the Theory of Planned Behaviour : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Science in Psychology at Massey University, Albany, New Zealand

Mental health is of utmost importance in military settings due to the demanding and often dangerous nature of the work involved. However, military personnel are disproportionately deterred from seeking mental health help when the need arises. Perceived stigma and structural barriers to help seeking have been widely researched in military settings, however, results are often mixed. The current study examined the traditional stigma and structural barriers help seeking model alongside an alternative model of the Theory of Planned Behaviour to explain help seeking behaviour. A cross-sectional study design surveying 2633 enlisted New Zealand Defence Force Personnel was carried out. Within the two models, attitudes, subjective norms, perceived behavioural control, stigma, and structural barriers were assessed as predictors of intentions to seek professional help for mental health problems. The Theory of Planned Behaviour model accounted for 26% of total variance in help seeking intentions, while the traditional model only accounted for 7%. Additionally, the Theory of Planned Behaviour model showed potential for its capacity to include stigma and structural barriers as antecedents to its core predictors, with stigma being partially mediated by attitudes, and structural barriers being fully mediated by perceived behavioural control. Additional group level measures were also considered in relation to help seeking intentions which highlighted at risk groups. A common theme arose across these groups of less chances for both formal and informal learning opportunities about mental health help seeking in the defence force. Using these group level differences, recommendations for how the Theory of Planned Behaviour can be utilized to increase mental health learning experiences for the New Zealand Defence Force personnel are made. Specifically, the potential efficacy of incorporating the sharing of highly ranked personnel’s positive experiences of help seeking early on in new recruits training.
MicroRNA-497 Induces Apoptosis and Suppresses Proliferation via the Bcl-2/Bax-Caspase9-Caspase3 Pathway and Cyclin D2 Protein in HUVECs

Introduction MicroRNAs play crucial roles in various types of diseases. However, to date, no information about the role of miR-497 in the development of atherosclerosis has been reported. This study investigated the possible role of miR-497 in vascular endothelial cell injury during the early stage of atherosclerosis. Materials and Methods The expression level of miR-497 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL was detected using qRT-PCR. To perform gain of function and loss of function analyses, miR-497 mimics were transfected into HUVECs, and miR-497 inhibitors were transfected into HUVECs stimulated with ox-LDL. Flow cytometry was used to analyze cell cycle progression and apoptosis. EdU and CCK-8 assays were employed to detect DNA synthesis and cell proliferation, respectively. After bioinformatics prediction, a dual Luciferase Reporter assay was used to analyze the direct target genes of miR-497. The mRNA and protein levels of the target genes were detected using qRT-PCR and western blot analyses, respectively. Caspase-9/3 activity was analyzed to determine the mechanism of endothelial dysfunction. Results We showed that miR-497 was significantly upregulated in HUVECs stimulated with ox-LDL. Ectopic expression of miR-497 suppressed cell proliferation, induced apoptosis and increased the activity of caspase-9/3. After verification, Bcl2 and CCND2 were shown to be direct target genes of miR-497 in HUVECs. MiR-497 significantly suppressed cell proliferation by arresting the cell cycle through the CCND2 protein and induced apoptosis through the Bcl2/Bax-caspase9-caspase3 pathway. Conclusion Overall, our study shows that miR-497 might play a role in the development of atherosclerosis by inducing apoptosis and suppressing the proliferation of vascular endothelial cells. Therefore, miR-497 could be a potential therapeutic target for the treatment of atherosclerosis.
The Critical Velocity Effect as a Cause for the Hα Emission from the Magellanic Stream

Observations show significant Hα emissions in the Galactic halo near the edges of cold gas clouds of the Magellanic Stream. The source of the ionization of the cold gas is still a wide-open question. In our paper we discuss the critical velocity effect as a possible explanation for the observed Hα emission. The critical velocity effect can yield a fast ionization of cold gas if this neutral gas passes through a magnetized plasma under suitable conditions. We show that for parameters that are typical for the Magellanic Stream, the critical velocity effect has to be considered as a possible ionization source of high relevance.
An Integrated Cognitive Theory of Comprehension

This article proposes an integrated cognitive theory of reading and listening that draws on a maximalist account of comprehension and emphasizes the role of bottom-up and top-down processing. The theoretical framework draws on the findings of previous research and integrates them into a coherent and plausible narrative to explain and predict the comprehension of written and auditory inputs. The theory is accompanied by a model that schematically represents the fundamental components of the theory and the comprehension mechanisms described. The theory further highlights the role of perception and word recognition (underresearched in reading research), situation models (missing in listening research), mental imagery (missing in both streams), and inferencing. The robustness of the theory is discussed in light of the principles of scientific theories adopted from Popper (1959).
CPI-0004Na, a new extracellularly tumor-activated prodrug of doxorubicin: in vivo toxicity, activity, and tissue distribution confirm tumor cell selectivity.

The search for cancer therapies that are more selective for tumor cells and spare normal sensitive cells has been very active for at least 20 years. The extracellularly tumor-activated peptidic prodrug of doxorubicin (Dox) CPI-0004Na (N-succinyl-beta-alanyl-L-leucyl-L-alanyl-L-leucyl-Dox) is potentially such a treatment. Here, we report the results of lethality studies performed with this compound in the mouse, showing that it is up to 4.6 times less toxic than Dox.HCl by the i.v. route and up to 16.2 times after i.p. administration. Pharmacokinetics and tissue distribution data indicate that this reduced toxicity is attributable to a lower uptake of Dox in normal tissues after treatment with CPI-0004Na than after the administration of an equimolar dose of Dox.HCl. For example, heart exposure to Dox is reduced >10-fold. Because of this reduced toxicity, higher doses of CPI-0004Na than of the parent drug could be used to treat nude mice bearing s.c. human breast (MCF-7/6) and colon (LS-174-T and CXF-280/10) tumors. In all three models, the prodrug showed a much improved efficacy as compared with Dox.HCl. Particularly, LS-174-T tumors that do not respond to Dox were inhibited by 68% after treatment with CPI-0004Na. Tissue distribution studies performed with MCF-7/6 tumor-bearing nude mice and comparing CPI-0004Na and Dox.HCl confirmed that the improved activity of the prodrug is actually the result of selective generation and uptake of Dox at the tumor site. Dox levels in tumor tissue were 2-fold higher after treatment with CPI-0004Na than after treatment with an equimolar dose of Dox.HCl, whereas normal tissue levels were reduced 1.4-29-fold.
Quasi-projections in Teichmüller space.

where d(x, C) = inf d(x, C). (Provided Xis proper, i.e. /? -balls are compact, nc(x) is never yeC empty. ) Suppose now that X is a simply-connected Riemannian manifold with non-positive sectional curvatures, and that C is a geodesic segment, ray or line. In this case nc(x) always consists of a single point. If the sectional curvatures are bounded above by a negative constant, then \\dnc\\ -> 0 äs d(x, C) goes to oo (where dnc is the differential of nc). In other words, is contracting at large distances.
Multi-dimensional simple waves in fully relativistic fluids

Multi-dimensional simple waves built on the basis of the Boillat condition are employed for fully relativistic fluid and plasma flows. Three essential modes, namely the vortex, the entropy and sound modes, are derived where each of them is different from its non-relativistic analogue. The vortex and entropy modes are formally solved in both the laboratory and wave frame (co-moving with the wavefront) to yield a few classical solutions. It is shown that by making a suitable transformation to the wave frame, it will be possible to exactly solve the sound mode at ultra-relativistic temperatures. In addition, the surface which is the boundary between the permitted and forbidden regions of the solutions is introduced and determined. Finally, a symmetry analysis is performed for the vortex mode equation up to both point and contact transformations. The derived symmetry properties and their corresponding fundamental invariants are shown to create a wide variety of classical solutions; some of them may have physical interest.
Are oxygen and neon enriched in PNe and is the current solar Ne/O abundance ratio underestimated?

A thorough critical literature survey has been carried out for reliable measurements of oxygen and neon abundances of planetary nebulae (PNe) and H ii regions. By contrasting the results of PNe and of H ii regions, we aim to address the issues of the evolution of oxygen and neon in the interstellar medium (ISM) and in the late evolutionary phases of low- and intermediate-mass stars (LIMS), as well as the currently hotly disputed solar Ne/O abundance ratio. Through the comparisons, we find that neon abundance and Ne/O ratio increase with increasing oxygen abundance in both types of nebulae, with positive correlation coefficients larger than 0.75. The correlations suggest different enrichment mechanisms for oxygen and neon in the ISM, in the sense that the growth of neon is delayed compared to oxygen. The differences of abundances between PNe and H ii regions are mainly attributed to the results of nucleosynthesis and dredge-up processes that occurred in the progenitor stars of PNe. We find that both these α-elements are significantly enriched at low metallicity (initial oxygen abundance ≲8.0) but not at metallicity higher than the Small Magellanic Cloud (SMC). The fact that Ne/O ratios measured in PNe are almost the same as those in H ii regions, regardless of the metallicity, suggest a very similar production mechanism of neon and oxygen in intermediate-mass stars (IMS) of low initial metallicities and in more massive stars, a conjecture that requires verification by further theoretical studies. This result also strongly suggests that both the solar neon abundance and the Ne/O ratio should be revised upwards by ∼0.22 dex from the Asplund, Grevesse & Sauval values or by ∼0.14 dex from the Grevesse & Sauval values.
Lifelong learning in Singapore: where are we?

Abstract Lifelong learning policy came and went in many countries in the last few decades. Much of the lifelong learning policy experience has been either ineffective or drifting in and out of policy discussions unnoticed. Yet, in 2015, Singapore launched a new policy initiative known as SkillsFuture, which brought lifelong learning back into mainstream policy. In this paper, we re-examine the origins of lifelong learning as a concept with a view of providing useful points of reference for policy discussion in Singapore. We employ the Delors Four Pillars of lifelong learning and data from the Organization for Economic Cooperation and Development (OECD) Programme for the International Assessment of Adult Competencies (PIAAC) to make a comparison between Singapore and its international peers. We use this comparison to identify potential policy challenges that lie ahead for Singapore. We argue that the historical focus in Singapore on formal education, both pre-employment and continuing, provides a solid foundation for lifelong learning. Nevertheless, recent policy shifts have begun to bring the humanistic elements of learning – for example, living together and self-actualization – back to the front stage of policy for learning. This is where potential policy gaps may exist in Singapore, as the utilitarian emphasis has dominated for a long time. An understanding of these different elements of lifelong learning and how they are linked in Singapore’s context will be valuable for policymakers and practitioners to prepare for the challenges ahead.
Building and Analyzing a Global Co-Authorship Network Using Google Scholar Data

By publishing papers together, academic authors can form a co-authorship network, modeling the collaboration among them. This paper presents a data-driven study by crawling and analyzing the vast majority of author profiles of Google Scholar. We make the following major contributions: (1) We present a demographic analysis and get an informative overview of the authors from different aspects, such as the distribution of countries, scientific labels, and academic titles. (2) Based on the publication lists of crawled authors, we build a global co-authorship network with 402.39K authors to study the collaboration among authors. With the aid of social network analysis (SNA), we observe several unique features of this network. (3) We explore the relationship between the co-authorship network and citation metrics. We find a strong correlation between PageRank and h-index.
Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways

Purpose. Tumor microenvironment confers drug resistance to kinase inhibitors by increasing RKT ligand levels that result in the activation of cell-survival signaling including PI3K and MAPK signals. We assessed whether HSC-LX2 coculture conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the drug resistance. Experimental Design. The effect of LX2 on sorafenib resistance was determined by coculture system with Huh7 cells. The rescue function of LX2 supernatants was assessed by MTT assay and fluorescence microscopy. The underlying mechanism was tested by administration of pathway inhibitors and manifested by Western blotting. Results. LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK. LX2 secreted HGF into the culture medium that triggered drug resistance, and exogenous HGF could also induce sorafenib resistance. The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture. Increased phosphorylation of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells. The Jak inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3 activation. The combined administration of sorafenib and p-Stat3 inhibitor S3I-201 augmented induced apoptosis even in the presence of sorafenib resistance. Conclusions. HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. A combined administration of sorafenib and S3I-201 was able to augment sorafenib-induced apoptosis even in the presence of LX2 coculture.
Advancing Performance Measurement Theory by Focusing on Subjects: Lessons from the Measurement of Social Value

Performance measurement and management (PMM) researchers have recently called for a closer inspection of social controls – the cultural and behavioural aspects of PMM inside organisations – as a complement to longstanding inquiries into technical controls – the rational and structural processes that enable measurement. We address this call by first reviewing the principal findings obtained in the field of social value measurement (SVM), which focuses on the measurement of how and to what extent individuals and groups perceive and realise subjective changes (i.e., in knowledge, access, health, etc.) from interactions with organisations. Subsequently, we distil the main characteristics of SVM research (i.e., the basic conceptualisations, stated purposes and normative principles). We find that SVM tends to highlight the importance of individual and group wellbeing and welfare, aims to understand how organisational actions influence these conditions, and focuses upon individuals’ lived experiences of measuring or being measured. In comparison, PMM research concentrates on technical controls, mainly relies on notions of systems and structured processes, and assumes people’s behaviours are impacted by measures, but does not fully explore their responses. We argue that to properly acknowledge and integrate social aspects of PMM into research and practice, subjects – with their thoughts, emotions and experiences – should be included more explicitly in future studies and theorisations.