Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of C/EBPα as a novel target of the HPV8 E6 protein regulating miR-203 in human keratinocytes

Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions. We provide evidence that CCAAT/enhancer-binding protein α (C/EBPα), a differentiation-regulating transcription factor and suppressor of UV-induced skin carcinogenesis, directly binds the miR-203 gene within its hairpin region and thereby induces miR-203 transcription. Our data further demonstrate that the HPV8 E6 protein significantly suppresses this novel C/EBPα/mir-203-pathway. As a consequence, the miR-203 target ΔNp63α, a proliferation-inducing transcription factor, is up-regulated, while the differentiation factor involucrin is suppressed. HPV8 E6 specifically down-regulates C/EBPα but not C/EBPβ expression at the transcriptional level. As shown in knock-down experiments, C/EBPα is regulated by the acetyltransferase p300, a well-described target of cutaneous E6 proteins. Notably, p300 bound significantly less to the C/EBPα regulatory region in HPV8 E6 expressing keratinocytes than in control cells as demonstrated by chromatin immunoprecipitation. In situ analysis confirmed congruent suprabasal expression patterns of C/EBPα and miR-203 in non-lesional skin of EV-patients. In HPV8-positive EV-lesions both factors are potently down-regulated in vivo further supporting our in vitro data. In conclusion our study has unraveled a novel p300/C/EBPα/mir-203-dependent mechanism, by which the cutaneous HPV8 E6 protein may expand p63-positive cells in the epidermis of EV-patients and disturbs fundamental keratinocyte functions. This may drive HPV-mediated pathogenesis and may potentially also pave the way for skin carcinogenesis in EV-patients.
Computational fluid dynamics based iterative learning control of peak loads in wind turbines

Improving the aerodynamic effectiveness and hence energy production of wind turbines is of critical importance and there is currently research into to the inclusion of smart devices in rotor blades in conjunction with collective and individual pitch control. The main objective is to reduce fatigue loads which have periodic and non-periodic components. This paper gives results on the use of iterative learning control in this application area based on first constructing a simple but realistic computational fluid dynamics model to represent flow past an airfoil. As a first investigation into the control of wind turbines using such a model, the design of control laws with a simple structure is investigated.
Predictive models for autism spectrum disorder based on multiple cortical features

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide phenotypic range, often affecting personality and communication. Previous surface-based morphometry (SBM) work only used cortical thickness to generate classification model between ASD and normal control. The goals of this study were twofold: 1) to construct predictive models for ASD, based on combination any of these five cortical measurements (cortical thicknesses (T), mean curvature (MC), Gaussian curvature (GC), folding index (FI), and curvature index(CI)) extracted from SBM, 2) and to compare these models. Our study included 22 subjects with ASD (mean age 9.2±2.1 years) and 16 volunteer controls (mean age 10.0±1.9 years). Using SBM, we obtained T, MC, GC, FI and CI for 66 brain structures for each subject. Then, we combined any of these five cortical measurements and obtained 31 combinations as classification inputs. To generate predictive models, we employed three machine-learning techniques: support vector machines (SVMs), functional trees (FTs), and logistic model trees (LMTs). We found that “thickness + mean curvature”-based classification model was modest superior to that based on thickness-based features when LMT employed, and curvature only provide limited information to thickness in ASD predictive model. Our result suggested that ASD may be cortical thickness abnormal disorder rather than cortical curvature abnormal disorder.
Inferring relevant cell types for complex traits using single-cell gene expression

Previous studies have prioritized trait-relevant cell types by looking for an enrichment of GWAS signal within functional regions. However, these studies are limited in cell resolution by the lack of functional annotations from difficult-to-characterize or rare cell populations. Measurement of single-cell gene expression has become a popular method for characterizing novel cell types, and yet, hardly any work exists linking single-cell RNA-seq to phenotypes of interest. To address this deficiency, we present RolyPoly, a regression-based polygenic model that can prioritize trait-relevant cell types and genes from GWAS summary statistics and single-cell RNA-seq. We demonstrate RolyPoly’s accuracy through simulation and validate previously known tissue-trait associations. We discover a significant association between microglia and late-onset Alzheimer’s disease, and an association between oligodendrocytes and replicating fetal cortical cells with schizophrenia. Additionally, RolyPoly computes a trait-relevance score for each gene which reflects the importance of expression specific to a cell type. We found that differentially expressed genes in the prefrontal cortex of Alzheimer’s patients were significantly enriched for highly ranked genes by RolyPoly gene scores. Overall, our method represents a powerful framework for understanding the effect of common variants on cell types contributing to complex traits.
Data-driven inversion of GPR surface reflection data for lossless layered media

Two wavefields can be retrieved from the measured reflection response at the surface. One is the Green's function at a chosen virtual receiver depth level in a layered model generated by a source at the surface. The other wavefield consists of the upgoing and downgoing parts of a wavefield that focuses at the virtual receiver depth level. From the upgoing part of the focusing wavefield an image can be computed at one-way vertical travel time and with correct amplitudes of the local reflection coefficients as a function of incidence angle. These reflection coefficient values can be used to invert for electric permittivity and magnetic permeability. From these values and the known image times the layer thickness values can be obtained for each layer. This method renders the full waveform inversion problem for horizontally layered media a linear problem.
A Simple Random Access Scheme With Multilevel Power Allocation

This letter proposes a decentralized power allocation approach for random access with capabilities of multi-packet reception (MPR) and successive interference cancellation (SIC). Considering specific features of SIC, a bottom-up per-level algorithm is proposed to obtain discrete transmission power levels and the corresponding probabilities. Comparing with the conventional power allocation scheme with MPR and SIC, our approach significantly improves the system sum rate; this is confirmed by computer simulations.
[Mutation analysis of KLF6 gene in human nasopharyngeal carcinomas].

BACKGROUND & OBJECTIVE Nasopharyngeal carcinoma (NPC) is one of the most common cancers in South China and Southeast Asia. The etiological factor is believed to be the interaction between genetic susceptibility, EBV infection and environmental factors, involved in the multi-step process of carcinogenesis and development of NPC. However, the molecular pathology of NPC is unclear yet. Kruppel-like factor 6(KLF6) is a ubiquitously expressed nuclear transcription factor, which is deleted and/or mutated with high frequency in a subset of prostate cancer. This study was designed to investigate KLF6 mutation in NPC tumors and NPC cell lines. METHODS Genomic DNAs from 19 NPC tumor biospies and 3 NPC cell lines were used in mutation detection of KLF6 coding region and splice sites by PCR-sequencing. 100 chromosomes from 50 random healthy individuals were used as control. RESULTS In 3 of 19 NPC tissues, 3 different mutations (Glu75Val, Ser136Arg, Arg243 Lys) in KLF6 gene were found by PCR-sequencing. None of the 3 mutations were detected in the 50 random healthy individuals. CONCLUSION KLF6 gene may be involved in carcinogenesis of sporadic NPC.
Identification of new therapeutic targets for prevention of CNS inflammation

Multiple sclerosis (MS) is a disease of complex pathologies, which involves infiltration by CD4+ and CD8+ T cells of and response within the central nervous system. Expression in the CNS of cytokines, reactive nitrogen species and costimulator molecules have all been described in MS. Notably, the cytokines IFN-γ and TNF are strongly expressed. Microglial cells in the CNS express costimulator molecules and it is assumed that they play a role in directing or inducing the T cell response. Transgenic experiments have tested the effects of overexpression of these molecules in mice and have shown that TNF has multiple effects in the CNS. These range from pro-inflammatory effects of soluble TNF signalling through one of its receptors TNF-RI, to protective/regenerative effects of membrane-associated TNF signalling through the other receptor, TNF-RII. Although IFN-γ induces nitric oxide production via the enzyme inducible nitric oxide synthase, which is immunosuppressive, IFN-γ is predominantly pro-inflammatory. In CNS disease in mice that involves CD8+ T cells, IFN-γ blockade is protective. Finally, microglial expression of the costimulator ligand B7.2 induces demyelinating pathology. Animal experiments therefore point to IFN-γ and costimulatory microglia as logical targets of therapy for MS. IFN-γ represents a more accessible target and should therefore be pursued at the earliest opportunity.
Green Infrastructure and the Hidden Politics of Urban Stormwater Governance in a Postindustrial City

Infrastructure tells a material story of ongoing challenges in cities, reflecting the diverse, normative desires of different communities. In this article we examine the introduction of green infrastructure technologies into urban infrastructure systems to think critically about these challenges and desires. Green infrastructure is an intentionally designed, multifunctional technology that directly uses or mimics the ecological processes of soils and plants (e.g., green rooftops, rain gardens, and bioswales). Facing budget shortfalls as well as demands to mitigate hazards and green the city, urban leaders are looking at green infrastructure as a facility that can provide diverse cobenefits along with traditional services. A focus on stormwater-based metrics, however—effectively reframing green infrastructure as green stormwater infrastructure—discursively tamps down alternative politics and desires for the city. Through a case study of Pittsburgh’s stormwater governance, we argue that the work to (re)technologize green infrastructure as green stormwater infrastructure is an act of depoliticization that hinders needed conversations about just infrastructure outcomes. We draw on themes from qualitative interviews with community members engaged in urban water governance to suggest that these moments of transition provide an opportunity to illuminate previously obscured infrastructure politics and challenge the forms of knowledge that bind us to conventional routines of urban environmental governance. We see an opportunity to reframe the conversation in a way that opens up opportunities for historically disenfranchised communities to voice their needs beyond the technocratic problem of stormwater management.
Is energy subsidy reform in an oil-exporting small economy beneficial to trade?

Fossil fuel subsidies have been widely accepted by economists as being both distortionary and a generally inefficient and costly means of resource allocation – they lead to wasteful consumption and distort international trade and local markets. Such impacts have motivated international organizations such as the G7, the G20, and the Asia–Pacific Economic Cooperation (APEC) to draw commitments from various member countries to reduce fossil fuel subsidies. The Centre for Trade and Sustainable Development (ICTSD) and the World Trade Organization (WTO) have also targeted effectuating subsidy reform, through the use of trade rules.
Changing patterns of household decision-making and the education of rural migrant children: comparing Shenzhen and Mumbai

In both China and India, migrant families face difficult decisions about education and livelihoods. In China, migrant children have limited access to urban schools, because of high documentary barriers to enrolment. In India, administrative barriers are fewer, but other structural factors, including households’ need for child labour, restrict opportunities. Although much research globally has explored household negotiations leading to migration, we know little about livelihoods decision-making processes after initial migration. How is decision-making affected by changes in household dynamics as a result of moving to the city? Drawing on over 300 interviews with migrants in Shenzhen and Mumbai from 2007 to 2016, this article compares the ways that Chinese and Indian rural-migrant households negotiate their children’s limited access to education, and demonstrates significant shifts within families after the initial rural–urban movement in both countries. Mothers in particular gain greater roles in developing household strategies, and more attention is paid to the voices of (some, mostly male) children. However, contrary to existing literature on non-migrant populations, increased maternal and child autonomy within the migrant household does not necessarily result in educational gains. Instead, the exercise of agency outside the household remains highly constrained by structural factors including poverty and marginalisation, education policies, and gendered social relations.
Threats of school violence in Pennsylvania after media coverage of the Columbine High School massacre: examining the role of imitation.

BACKGROUND Following the April 20, 1999, massacre at Columbine High School, Littleton, Colo, school administrators, law enforcement officials, and the media reported a rash of successive bomb threats and threats of school violence that were attributed to imitation. OBJECTIVE To establish that the clustering of threats of school violence following the Columbine massacre was initiated by imitation. DESIGN A database of threats of school violence reported to the Pennsylvania Emergency Management Agency, Harrisburg, during the 50 days following the Columbine incident was examined to determine the daily frequency of threats. To determine factors that predict the occurrence of these threats, counties and school districts in which threats occurred were noted. RESULTS Pennsylvania school districts reported 354 threats of school violence during the 50 days after the Columbine massacre, far exceeding the 1 or 2 threats per year estimated by school administrators before 1999. The frequency of these threats over time demonstrated a crescendo-decrescendo pattern. Fifty-six percent of the threats were made on or before day 10 after the incident, and more than one third occurred on days 8, 9, and 10. Factors that predicted the likelihood of a school's receiving a threat after the massacre included a greater proportion of white students and larger school enrollment. CONCLUSIONS Successive threats of violence follow a publicized act of school violence. The media should recognize that imitation threats can occur and craft their stories accordingly.
Equity Risk Factors and the Intertemporal CAPM

Recent prominent equity factor models are to a large degree compatible with the Merton's (1973) Intertemporal CAPM (ICAPM). Factors associated with (alternative) profitability measures forecast the equity premium in a way that is consistent with the ICAPM. Several factors (in particular those based on asset growth) forecast a significant decline in stock volatility, being consistent with their prices of risk. Investment-based factors are also strong predictors of an improvement in future economic activity. These predictive abilities are not subsumed by traditional ICAPM state variables. Our results largely legitimate the ICAPM as a common theoretical background for the new multifactor models.
Investigation Into Time Response of Polymer Fiber Bragg Grating Based Humidity Sensors

In this work we experimentally investigate the response time of humidity sensors based on polymer optical fiber Bragg gratings. By the use of etching with acetone we can control the poly (methyl methacrylate) based fiber in order to reduce the diffusion time of water into the polymer and hence speed up the relative wavelength change caused by humidity variations. A much improved response time of 12 minutes for humidity decrease and 7 minutes for humidity increase, has been achieved by using a polymer optical fiber Bragg grating with a reduced diameter of 135 microns.
Interruptions of Men and Women in Selected Debates of Al-Jazeera Arabic Channel: A Pragmatic Analysis of the Opposite Direction

The present study aims to explore the gender patterns during interruptions in the context of political television discussions in the Arab community. Five mixed-sex episodes of the well-known program “The Opposite Direction” presented on Al-Jazeera Channel were examined. Quantitative and qualitative analyses were carried out to determine, which gender did more interruptions than the other. The study has considered each gender to use verbal and non-verbal statements to express that they were doing interruptions or that they were being interrupted. The results showed that women interrupted more than did men. Moreover, it has also been shown that men reacted in a more severe and aggressive way, when they were interrupted by women.
Capturing tumour stage in a cancer information database.

OBJECTIVE 1. To present the steps taken and lessons learned from one cancer centre's efforts to capture tumour stage information in a cancer database. 2. To determine the accuracy of the stage data through a chart audit. 3. To describe the potential uses of stage information in a cancer centre. DESIGN AND SETTING This is a retrospective review of an initiative to capture tumour stage information at a regional cancer centre in Ontario. DATA SOURCES The minutes of the centre's Health Records and Medical Advisory Committees related to staging were reviewed. Data on stage by tumour type was extracted from the centre's Oncology Patient Information System (OPIS). Three hundred and ninety charts were analysed to assess the accuracy of stage information and identify staging errors. Health Information Services workload statistics were reviewed to determine the types and frequency of projects undertaken using stage-related data. RESULTS In January 1994, the Ottawa Regional Cancer Centre introduced policies and procedures to capture stage-related information. Standardized staging forms and a physician reminder system encouraged the centre's physicians to record tumour stage within 3 months of new patient registration. Of all qualifying cases in 1994, 92% were staged. A medical audit in 1998 of 390 charts from the 3 previous years of staging data revealed that 71.5% of the charts reviewed had been staged completely. Of the incompletely staged cases, 19% to 57% had TNM recorded, but the stage grouping was not recorded, or the "stage" was the extent of disease at the time of disease progression rather than at initial diagnosis (35% to 71%). Physician-related staging errors occurred in 2% to 5% of cases; data-entry errors occurred in 3% to 6% of cases. CONCLUSIONS Stage information has enabled the centre to better describe its patient clientele for accreditation purposes and to assist researchers in estimating the number of patients potentially available for prospective and retrospective studies. It is being used to guide targeted educational initiatives to selected populations in the region's catchment area and assists administrators in estimating resource needs. Resistance to the capture of stage information can be overcome with persistence, the development of procedures that facilitate physician compliance, including a reminder system, the development of institutional policies and procedures and by feedback on the uses and availability of stage information.
Neural correlates of switching set as measured in fast, event‐related functional magnetic resonance imaging

Attentional switching has shown to involve several prefrontal and parietal brain regions. Most cognitive paradigms used to measure cognitive switching such as the Wisconsin Card Sorting Task (WCST) involve additional cognitive processes besides switching, in particular working memory (WM). It is, therefore, questionable whether prefrontal brain regions activated in these conditions, especially dorsolateral prefrontal cortex (DLPFC), are involved in cognitive switching per se, or are related to WM components involved in switching tasks. Functional magnetic resonance imaging (fMRI) was used to examine neural correlates of pure switching using a paradigm purposely designed to minimize WM functions. The switching paradigm required subjects to switch unpredictably between two spatial dimensions, clearly indicated throughout the task before each trial. Fast, event‐related fMRI was used to compare neural activation associated with switch trials to that related to repeat trials in 20 healthy, right‐handed, adult males. A large cluster of activation was observed in the right hemisphere, extending from inferior prefrontal and pre‐ and postcentral gyri to superior temporal and inferior parietal cortices. A smaller and more caudal cluster of homologous activation in the left hemisphere was accompanied by activation of left dorsolateral prefrontal cortex (DLPFC). We conclude that left DLPFC activation is involved directly in cognitive switching, in conjunction with parietal and temporal brain regions. Pre‐ and postcentral gyrus activation may be related to motor components of switching set. Hum. Brain Mapp.21:247–256, 2004. © 2004 Wiley‐Liss, Inc.