Miracle-dz/UniFAR-FTUs huggingface dataset:
Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense RNF213 Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review

Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in RNF213 (Mysterin) represents the major susceptibility factor. Rare variants in RNF213 have also been found in European MMA patients with incomplete penetrance and are today a recognized susceptibility factor for other cardiovascular disorders, from extracerebral artery stenosis to hypertension. By whole exome sequencing, we identified three rare and previously unreported missense variants of RNF213 in three children with early onset of bilateral MMA, and subsequently extended clinical and radiological investigations to their carrier relatives. Substitutions all involved highly conserved residues clustered in the C-terminal region of RNF213, mainly in the E3 ligase domain. Probands showed a de novo occurring variant, p.Phe4120Leu (family A), a maternally inherited heterozygous variant, p.Ser4118Cys (family B), and a novel heterozygous variant, p.Glu4867Lys, inherited from the mother, in whom it occurred de novo (family C). Patients from families A and C experienced transient hypertransaminasemia and stenosis of extracerebral arteries. Bilateral MMA was present in the proband’s carrier grandfather from family B. The proband from family C and her carrier mother both exhibited annular figurate erythema. Our data confirm that rare heterozygous variants in RNF213 cause MMA in Europeans as well as in East Asian populations, suggesting that substitutions close to positions 4118–4122 and 4867 of RNF213 could lead to a syndromic form of MMA showing elevated aminotransferases and extracerebral vascular involvement, with the possible association of peculiar skin manifestations.
A Comprehensive Approach to Dynamic Project Risk Management

Abstract A large percentage of projects suffer performance, cost, and/or schedule problems. There are many reasons why projects fail, including an inadequate approach to risk management. Inadequate approaches result when a comprehensive identification of risks is not performed at project commencement, when risk assessment fails to consider important aspects, when no subsequent follow-up is carried out for mitigation strategies adopted, when no further identification of risks during project execution is completed, or a combination of these occurs. A number of publications have dealt with different facets of risk management, but not in a comprehensive way. This article compiles the approaches applied and observed by the author based on 25 years of industry experience; these observations were synthesized and result in a procedure for dynamic risk management successfully applied to a number of projects. The use of a broad array of techniques is suggested to identify risks, which are then thoroughly analyzed. The assessment was performed using a comprehensive array of criteria. The complete set of criteria included essential ones such as aggregability factor, triggering factor, early warning, immediacy, and recoverability. The thorough assessment was done dynamically. The initial assessment enables the adoption of the most adequate mitigation strategies, which later on are dynamically validated. New risks are also detected and dealt with dynamically throughout project execution. The main contribution of this work is the synthesis of state-of-the-art knowledge into a state-of-the-practice procedure, which can be applied by engineering managers in all sectors and in all phases of project execution.
Unconditionally convergent time domain adaptive and time-frequency techniques for epicyclic gearbox vibration

_________________________________________________________________________________________ i Abstract Condition monitoring of epicyclic gearboxes through vibration signature analysis, with particular focus on time domain methods and the use of adaptive filtering techniques for the purpose of signal enhancement, is the central theme of this work. Time domain filtering methods for the purpose of removal of random noise components from periodic, but not necessarily stationary or cyclostationary, signals are developed. Damage identification is accomplished through vibration signature analysis by nonstationary timefrequency methods, belonging to Cohen’s general class of time-frequency distributions, strictly based in the time domain. Although a powerful and commonly used noise reduction technique, synchronous averaging requires alternate sensors in addition to the vibration pickup. For this reason the use of time domain techniques that employ only the vibration data is investigated. Adaptive filters may be used to remove random noise from the nonstationary signals considered. The well-known Least Mean Squares algorithm is employed in an adaptive line enhancer configuration. To counter the much discussed convergence difficulties that are often experienced when the least mean squares algorithm is applied, a new unconditionally convergent algorithm based on the spherical quadratic steepest descent method is presented. The spherical quadratic steepest descent method has been shown to be unconditionally convergent when applied to a quadratic objective function. Time-frequency methods are succinctly employed to analyse the vibration signals simultaneously in the time and frequency domains. Transients covering a wide frequency range are a clear and definite indication of impacting events as gear teeth mate, and observation of such events on a timefrequency distribution are used to indicate damage to the transmission. The pseudo Wigner-Ville distribution and the Spectrogram, both belonging to Cohen’s general class of time-frequency distributions are comparatively used to the end of damage identification. It is shown that an unconditionally convergent adaptive filtering technique used in conjunction with time-frequency methods can indicate a damaged condition in an epicyclic gearbox, where the non-adaptively filtered data did not present clear indications of damage. Acknowledgements __________________________________________________________________________________________
Role of matrix metalloproteinase 9 gene polymorphism as genetic risk factor for lung cancer

Lung cancer (LC) is one of the most incident malignancies worldwide. This study investigated the potential role of matrix metalloproteinase9 gene (MMP9) single nucleotide polymorphisms (SNPs) in Lung cancer patients. The study population was included 75 Iraqi patients with confirmed Lung cancer and 25 healthy people as controls. In this study, the -1562 C/T polymorphism in MMP9 gene was detected by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. The genotype distribution results of the -1562 C/T SNP of MMP9 gene have shown no significant differences (p>0.05) between controls (CC: n= 15, 60%; CT: n=9, 36%; TT: n=1, 4%) and Lung cancer patients (CC: n= 44, 58.66%; CT: n=30, 40%; TT: n=1, 1.34%). Results of the association analysis between genotype distribution of the -1562 C/T SNP of MMP9 gene and clinicopathological criteria of cases such as histological grading, TNM staging and lymph node metastasis, had shown no significant association (p>0.05). While analysis of the association between genotype distribution of the -1562 C/T SNP of MMP9 gene and smoking status among patients were statically significant (p<0.05). These results suggested that the SNP in MMP9 gene was involved in lung cancer progression, tissue invasion and metastasis involvement.
Ponatinib after failure of second‐generation tyrosine kinase inhibitor in resistant chronic‐phase chronic myeloid leukemia

Ponatinib, the only third‐generation pan‐BCR::ABL1 inhibitor with activity against all known BCR::ABL1 mutations including T315I, has demonstrated deep and durable responses in patients with chronic‐phase chronic myeloid leukemia (CP‐CML) resistant to prior second‐generation (2G) TKI treatment. We present efficacy and safety outcomes from the Ponatinib Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and CML Evaluation (PACE) and Optimizing Ponatinib Treatment in CP‐CML (OPTIC) trials for this patient population. PACE (NCT01207440) evaluated ponatinib 45 mg/day in CML patients with resistance to prior TKI or T315I. In OPTIC (NCT02467270), patients with CP‐CML and resistance to ≥2 prior TKIs or T315I receiving 45 or 30 mg/day reduced their doses to 15 mg/day upon achieving ≤1% BCR::ABL1IS or received 15 mg/day continuously. Efficacy and safety outcomes from patients with CP‐CML treated with ≥1 2G TKI (PACE, n = 257) and OPTIC (n = 93), 45‐mg starting dose cohort, were analyzed for BCR::ABL1IS response rates, overall survival (OS), progression‐free survival (PFS), and safety. By 24 months, the percentages of patients with ≤1% BCR::ABL1IS response, PFS, and OS were 46%, 68%, and 85%, respectively, in PACE and 57%, 80%, and 91%, respectively, in OPTIC. Serious treatment‐emergent adverse events and serious treatment‐emergent arterial occlusive event rates were 63% and 18% in PACE and 34% and 4% in OPTIC. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response‐based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE.
Observation of splintered Josephson vortices at grain boundaries in YBa2Cu3O7-d

We have directly observed well-separated Josephson vortex splinters with unquantized magnetic flux at asymmetric 45° grain boundaries in YBa2Cu3O7-? films by imaging magnetic flux with scanning SQUID microscopy. The existence of these splinter vortices has been predicted and is well described by a model based on dx2-y2 pairing symmetry and facetting of the grain boundary on a length scale shorter than the Josephson penetration depth.
Spectral flow of exterior Landau-Robin hamiltonians

We study the spectral flow of Landau-Robin hamiltonians in the exterior of a compact domain with smooth boundary. This provides a method to study the spectrum of the exterior Landau-Robin hamiltonian's dependence on the choice of Robin data, even explaining the heuristics of how the spectrum of the Robin problem asymptotically tends to the spectrum of the Dirichlet problem. The main technical result concerns the continuous dependence of Landau-Robin hamiltonians on the Robin data in the gap topology. The problem can be localized to the compact boundary where the asymptotic behavior of the spectral flow in some special cases can be described.
Comparative evaluation of in vitro antioxidant potential of Punica granatum L. leaves extracts

A comparative evaluation of tannins, flavonoid, phenol quantification and antioxidant potential of aqueous, methanol, n-hexane, acetone and chloroform extracts of Punica granatum leaves were determined. Quantification of phenolic was carried out by the technique of Folin-Ciocalteau, using rutin as standard flavonoids were evaluated through the technique of colorimetry, tannin was measured by the difference of total phenolics and free phenolics assay procedure. Antioxidant activities were evaluated by four standards antioxidant techniques including Superoxide dismutase (SOD)-like activity, Hydrogen Peroxide (H2O2) scavenging activity,1, 1’-diphynyl- 2-picrylhydrazyl (DPPH) activity and Nitric oxide (NO) scavenging activity method using ascorbic acid as standard. The antioxidant activities showed that methanol extract at 500μg/mL calculated maximum DPPH inhibition activity was 78±1%, H2O2 scavenging activity was 90±0%, SOD-like activity was 88±0% and NO scavenging activity was 90±0%. The outcomes indicated the major antioxidant actions were carried out by the extract of methanol; the entire potential was increased in the directive of methanol> chloroform> acetone>aqueous>n-hexane extracts. The results indicate that Punica granatum leaves extracts to have potent antioxidant activities that would have beneficial effects on human health and methanol extracts are superior with better antioxidant potential. The leaves extracts of Punica granatum could be of enormousattention in the enhancement of top value-added secondary products and the appliance of functional and green substitutes in thecosmetics, food and pharma industries.
Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response

Pediatric cancer treatment has evolved significantly in recent decades. The implementation of risk stratification strategies and the selection of evidence-based chemotherapy combinations have improved survival outcomes. However, there is large interindividual variability in terms of chemotherapy-related toxicities and, sometimes, the response among this population. This variability is partly attributed to the functional variability of drug-metabolizing enzymes (DME) and drug transporters (DTS) involved in the process of absorption, distribution, metabolism and excretion (ADME). The DTS, being ubiquitous, affects drug disposition across membranes and has relevance in determining chemotherapy response in pediatric cancer patients. Among the factors affecting DTS function, ontogeny or maturation is important in the pediatric population. In this narrative review, we describe the role of drug uptake/efflux transporters in defining pediatric chemotherapy-treatment-related toxicities and responses. Developmental differences in DTS and the consequent implications are also briefly discussed for the most commonly used chemotherapeutic drugs in the pediatric population.
Some aspects of change-point analysis

Change-points divide statistical models into homogeneous segments. Inference about change-points is discussed here in the context of testing the hypothesis of 'no change', point and interval estimation of a change-point, changes in nonparametric models, changes in regression, and detection of change in distribution of sequentially observed data. 1? Introduction. Suppose that in a linear array of independent observations Y\,. ,Yn, the distribution is subject to change after Yr for some 1 < t < ? - 1. Detection and estimation of change-points which in this way divide statistical models into homogeneous segments is a fast-developing area of research in statistical theory and methods. We shall present here a brief account of some of the areas of change-point analysis. The most basic problems are those of testing the hypothesis of uno change," and of estimating a change-point by a point estimator or a confidence set when the presence of one is suspected. In Sections 2-4, we shall discuss these problems and some nonparametric methods will be presented in Section 5. Change-point problems also occur in the context of regression when the nature of dependence of one variate on another may be different in two segments of the data, and in situations where the observations are obtained sequentially with the possibility of a change in distribution at any stage. Methods in these two areas will be discussed in Sections 6 and 7.
To be or not to be in the EU: the international economic effects of Brexit uncertainty

This paper evaluates the impact of Brexit-related uncertainty on the economies of the UK, EU, and the US. We propose a measure of Brexit uncertainty that has not been employed before in the literature. We first construct a binary variable by selecting Brexit-related events. We subsequently employ the Qual VAR model of Dueker [2005. “Dynamic Forecasts of Qualitative Variables: A Qual VAR Model of US Recessions. ” Journal of Business & Economic Statistics 23: 96–104] to transform this variable to a continuous latent variable that captures uncertainty on important economic and financial variables. Next, this latent variable enters a structural Factor-Augmented Vector AutoRegression model combined with 452 macro and financial variables for the sample countries. Overall, our results indicate that the prolonged period of uncertainty, had a positive effect on the economies of major EU countries and negative effects for the UK economy. Additionally, the UK is the most important net sender of uncertainty spillovers in the EU, while Germany and France are among the most important net receivers of uncertainty shocks.
Parameter estimation for chaotic system based on particle swarm optimization

It's of vital importance to estimate the unknown parameters of chaos systems in chaos control and synchronization. We firstly improve the newly developed particle swarm optimization (PSO) in view of the population initialization and objective function treatment. Then we use the improved algorithms for parameter estimation and on-line estimation of chaotic system for its global searching ability. Experiments show that the improved method has better adaptability, reliability and high precision is robust to noise. It is proved to be a successful approach in parameter estimation for chaotic systems.
Takagi-Seguno Fuzzy Systems Based Nonlinear Adaptive Control

This paper develops a fuzzy model reference adaptive control of continuous-time nonlinear systems described by Takagi-Seguno (TS) fuzzy model. The tracking performance is assured using a direct TS fuzzy controller. Both full state information and observer-based control schemes are investigated. It is proved, using Lyapunov stability tools, that this adaptive scheme is asymptotically stable and the tracking and observation errors converge to zero. Simulation results illustrate the performance of the proposed approach.
Young Creative Entrepreneur Pathways: COVID-19 and the Creative Industry Sectors

The main purpose of this paper was to propose a strategic conceptual framework using the Theory of Planned Behavior in the context of entrepreneurship intention among young creative entrepreneurs. The dynamic environment of the COVID-19 pandemic has significantly affected the cultural resilience of art and design. The present study identified eight hypotheses for pathways of strategic direction for young creative entrepreneurs within and after the pandemic. The conceptual framework developed examines the influence of entrepreneurship education on attitudes, subjective norms, and perceived behavioral control. Furthermore, this study also outlines guidance for young creative entrepreneurs based on attitudes toward entrepreneurship intention, entrepreneurship self-identity, subjective norms surrounding entrepreneurship intention, perceived behavioral control, and entrepreneurship commitment and enactment. Keywords: entrepreneurship education, Theory of Planned Behavior, entrepreneurship self-identity, entrepreneurship plan enactment, entrepreneurship commitment
Corporate social responsibilities and the well-being of rural dwellers: The Lafarge Cement Company’s example

Using the Lafarge Cement Company’s example, the study examined the impact of corporate social responsibility (CSR) on the well-being of rural dwellers in Nigeria. The design adopted is cross-sectional, where quantitative and qualitative methods were applied in obtaining data from one thousand one hundred and four (1104) respondents from selected communities in the Southern Senatorial District of Cross River State, Nigeria. The research used a multi-stage sampling technique. Data were then analysed using descriptive statistics such as percentages and frequency tables. At the same time, the qualitative data were analysed using content analysis techniques. However, the findings revealed that 62.1% of the respondents reported that they are aware of the existing projects executed by Lafarge Cement Company. While 36.4% of the respondents reported construction and rehabilitation of roads as the projects with the highest attention. The findings of the study further showed that 36.4% of the respondents identified improved income and wealth as the most impacted aspect of their well-being. Beyond investing in infrastructure, the study recommended that more resources be invested in young people’s human capital development in rural areas. This will help in achieving sustainable development in rural areas
Evaluation of the sleep modulating effects of methanolic extracts of Strychnos spinosa and Strychnos innocua fruits in mice

This study aimed to evaluate the sleep modulating properties of Strychnos spinosa and Strychnos innocua fruits in Swiss albino mice. The depressant effect of the extracts on the central nervous system was studied using a diazepam-induced sleep model in mice. The mice were divided into four groups of six mice each. The test groups received Strychnos spinosa and Strychnos innocua fruits extracts at the doses of 250, 500, and 1000 mg/kg body weight intraperitoneally. In contrast, the control group received distilled water at 10 ml/kg. Diazepam (Ranbaxy®, India) was used as a standard drug and administered 30 minutes after the initial treatment. The lethal doses (LD50) of the two extracts were estimated to be >5000 mg/kg. The results obtained from the onset of sleep of rats administered methanol extracts of Strychnos spinosa, and Strychnos innocua fruits showed that the extracts at 250, 500, and 1000 mg/kg, respectively, did not significantly (p >0.05) alter the onset of sleep when compared with the control. The onset of sleep in the groups treated with Strychnos spinosa fruit extracts indicated a dose-dependent decrease pattern. The study also revealed a prolonged duration of sleep in all the experimental groups treated with the two extracts compared to the control group. The treated groups of 250, 500 and 1000 mg/kg significantly (p <0.05) prolonged the duration of diazepam-induced sleep in a dose-dependent manner when compared to the control group. The group treated with 1000 mg/kg of Strychnos innocua fruit extract was significant (p <0.05) compared to the control group. In conclusion, the high LD50 observed in this study suggests that the two extracts are relatively safe and contain promising bioactive ingredients that cause sleep modulation in mice.
Notes on Iron Age copper-smelting technology in the Transvaal

Earlier reports on Iron Age copper metallurgy and copper-smelting techniques in the Transvaal are surveyed, and a descriptionption and tentative classification of the copper furnaces are given. The analyses of furnace slags and sherds of glazed crucibles from archaeological sites of the Transvaal and the neighbouring Orange Free State pro. vide evidence of copper smelting there in Iron Age times. An investigation conducted by the Department of Archaeology of the University ofthe Witwatersrand provided information on the details of furnace construction and smelting processes, on the composition of the materials used and produced, and on the making and handling of tools and accessories, such as bellows and tongs, needed by Iron Age smelters. Three models (the KaondejVenda furnace, the Rooiberg crucible furnace, and the Uitkomst furnace) were constructed and operated as a demonstration of Iron Age copper smelting as it was practised in the Transvaal.