Miracle-dz/UniFAR-FTUs huggingface dataset:
Baseline differences between vascular cognitive impairment no dementia reverters and non-reverters

Background: The underlying factors of reversion from cognitive impairment to normal cognitive functioning in stroke are not well understood. We compare demographic, cognitive and imaging factors in Vascular Cognitive Impairment, No Dementia (Vascular CIND) patients who revert to normal cognitive functioning to Vascular CIND patients who do not revert. Methods: Thirty-one ischaemic stroke patients, who met classification criteria for Vascular CIND, were >49.5 years old, met NINDS stroke criteria, and were free from additional neurological illness, completed baseline and 1-year examinations. Forty-five per cent of the Vascular CIND participants reverted to no cognitive impairment at 1-year follow-up examination. Results: There was greater cognitive impairment in non-reverters on a summary score spanning several neuropsychological domains and on psychomotor and working memory summary scores. There were no differences on demographic factors or in stroke severity between reverters and non-reverters. Structural MRI analyses revealed no baseline differences in number of strokes, stroke volume or stroke location. However, there was greater frontal white matter hyperintensity load in the non-reverter group. Conclusions: These results suggest that Vascular CIND reversion may be a function of a combination of baseline neuropsychological function and location of cerebrovascular disease.
Correlated random effects models for clustered survival data

Frailty models are frequently used to analyse clustered survival data in medical contexts. The frailties, or random effects, are used to model the association between individual survival times within clusters. Analysis of survival times of related individuals is typically complicated because follow up on an event type of interest is censored by events of secondary interest. Treating such competing events as independent may yield an incorrect analysis when the random effects associated with other event types are dependent of the event type of interest. We study two related inferential procedures for dependent data where the frailties of the type specific hazards may be correlated between competing event types. Routine registers offer possibilities to study covariate effects on survival times for rare diseases, for which large cohorts are required. However, the vast amount of data and the clustering of related individuals pose statistical challenges. In the first paper we adapt maximum likelihood methods for semiparametric transformation regression models to a cohort register subsampling design. This approach drastically reduces the computing times with a minor loss of efficiency, and results in practically useful estimation procedures. In the second paper we propose an estimator of covariate effects based on the observed intensities, where the nonparametric baseline hazards are profiled out. Thereby we reduce the problem to finite dimensions, where e.g. the covariance matrix is more directly estimated. A set of frailty structures for paired competing risks data based on sums of gamma variables is investigated through simulations. We establish the asymptotic properties of the estimators and present consistent covariance estimators. Worked examples are provided for illustration.
Guideline-Based Development of Quality Indicators for Hypertensive Diseases in Pregnancy

Objective. Hypertensive disorders in pregnancy are one of the main causes of maternal morbidity and mortality. Internationally, several organizations have developed clinical guidelines to assist professionals and to supply patients with the best possible care. To improve the care for this group of patients, insight into the application of clinical guidelines in daily practise is needed. Valid quality indicators are necessary to estimate actual guideline adherence. In this study, we developed a set of valid guideline-based quality indicators for hypertensive diseases in pregnancy. Methods. A systematic RAND-modified Delphi method was used to develop a set of quality indicators on the basis of evidence-based guidelines and literature on hypertension and pregnancy. Experts’ opinions were used to select the indicators regarding specific criteria such as efficacy, level of health gain, and potential for care improvement. Results. A representative set of 14 quality indicators was selected from 48 initial guideline recommendations. Indicators concerned both professional performance and organization of care for patients with hypertension in pregnancy. Conclusions. This study describes the systematic, stepwise method used to develop quality indicators that can be used to monitor care for hypertensive diseases in pregnancy.
A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population

Leigh disease is a progressive, infantile‐onset, neurodegenerative disorder characterized by feeding difficulties, failure to thrive, hypotonia, seizures, and central respiratory compromise. Metabolic and neuroimaging investigations typically identify abnormalities consistent with a disorder of mitochondrial energy metabolism. Mutations in more than 35 genes affecting the mitochondrial respiratory chain encoded from both the nuclear and mitochondrial genomes have been associated with Leigh disease. The clinical presentations of five individuals of Hutterite descent with Leigh disease are described herein. An identity‐by‐descent mapping and candidate gene approach was used to identify a novel homozygous c.393dupA frameshift mutation in the NADH dehydrogenase (ubiquinone) Fe‐S protein 4 (NDUFS4) gene. The carrier frequency of this mutation was estimated in >1,300 Hutterite individuals to be 1 in 27. © 2017 Wiley Periodicals, Inc.
Cogging torque analysis based on energy approach in surface-mounted PM machines

The problem of cogging torques produced in permanent magnet (PM) machines is crucial. Motor and generator applications require the machines to produce a smooth torque with very low cogging torque components. This paper presents a simplified energy approach for a model of the machine with PM located on the rotor surface. Briefly, analytical co-energy formulas are applied in order to determine the cogging torque harmonics and show methods of their reduction. Additionally, the analysis of cogging torque for machines with the poles composed of segmented PM are presented.
Dopamine D2‐like receptors selectively block N‐type Ca2+ channels to reduce GABA release onto rat striatal cholinergic interneurones

The modulatory roles of dopamine (DA) in inhibitory transmission onto striatal large cholinergic interneurones were investigated in rat brain slices using patch‐clamp recording. Pharmacologically isolated GABAA receptor‐mediated IPSCs were recorded by focal stimulation within the striatum. Bath application of DA reversibly suppressed the amplitude of evoked IPSCs in a concentration‐dependent manner (IC50, 10.0 μm). A D2‐like receptor agonist, quinpirole (3–30 μm), also suppressed the IPSCs, whereas a D1‐like receptor agonist, SKF 81297, did not affect IPSCs. Sulpiride, a D2‐like receptor antagonist, blocked the DA‐induced suppression of IPSCs (apparent dissociation constant (KB), 0.36 μm), while a D1‐like receptor antagonist, SCH 23390 (10 μm), had no effect. DA (30 μm) reduced the frequency of spontaneous miniature IPSCs (mIPSCs) without changing their amplitude distribution, suggesting that GABA release was inhibited, whereas the sensitivity of postsynaptic GABAA receptors was not affected. The effect of DA on the frequency of mIPSCs was diminished when extracellular Ca2+ was replaced by Mg2+ (5 mm), indicating that DA affected the Ca2+ entry into the presynaptic terminal. An N‐type Ca2+ channel selective blocker, ω‐conotoxin GVIA (ω‐CgTX, 3 μm), suppressed IPSCs by 65.4%, whereas a P/Q‐type Ca2+ channel selective blocker, ω‐agatoxin IVA (ω‐Aga‐IVA, 200 nm), suppressed IPSCs by 78.4%. Simultaneous application of both blockers suppressed IPSCs by 95.9%. Assuming a 3rd power relationship between Ca2+ concentration and transmitter release, the contribution of N‐, P/Q‐ and other types of Ca2+ channels to presynaptic Ca2+ entry is estimated to be, respectively, 29.8, 40.0 and 34.5% at this synapse. After the application of ω‐CgTX, DA (30 μm) no longer affected IPSCs. In contrast, ω‐Aga‐IVA did not alter the level of suppression by DA, suggesting that the action of DA was selective for N‐type Ca2+ channels. A G protein alkylating agent, N‐ethylmaleimide (NEM), significantly reduced the DA‐induced suppression of IPSCs. These results suggest that presynaptic D2‐like receptors are present on the terminals of GABAergic afferents to striatal cholinergic interneurones, and down‐regulate GABA release by selectively blocking N‐type Ca2+ channels through NEM‐sensitive G proteins.
Investigation of High-Frequency Noise Characteristics in Tensile-Strained nMOSFETs

For the first time, the high-frequency noise behavior of tensile-strained n-channel metal-oxide-semiconductor field effect transistors, including their temperature dependency, is experimentally examined. Our experimental results show that with similar saturation voltages, the strained device is found to have larger channel noise than the control device at the same bias point. For given direct-current power consumption, however, due to enhanced transconductance, the strained device has better small signal behaviors (higher ft and fmax) and noise characteristics (smaller NFmin and Rn) than the control device.
Factors Affecting E-Commerce Stages of Growth in Small Chinese Firms in New Zealand: An Analysis of Adoption Motivators and Inhibitors

We investigate an e-commerce stages of growth model in a cross-cultural business context for small Chinese firms in New Zealand. Research findings from 14 case studies show that the Chinese owners/managers of these small firms have a high power distance, and their attitude toward e-commerce technology directly influences their firmsâ€™ e-commerce growth process. It was found that the higher the stage of e-commerce adoption, the greater the need for owners having a more positive attitude toward e-commerce, more innovativeness and enthusiasm, and more technology literacy. The higher the tolerance for ambiguity and the higher the risk-taking propensity, the higher the stage of e-commerce adoption achieved. In addition, firms at lower growth stages of e-commerce adoption are highly rated on individualism, while those firms at higher growth stages of commerce adoption are highly rated on collectivism. The research has implications for small business managers operating in a cross-cultural business context as they move through the different stage of e-commerce adoption.
Rapid Decrease in KRT14 and TP53 mRNA Expression in the Buccal Mucosa of Patients Receiving Total-Body Irradiation for Allogeneic Stem Cell Transplantation

The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis. In this study, we obtained miRNAs and mRNAs from daily buccal swabs collected from patients undergoing allogeneic stem cell transplantation. Unexpectedly, there was no prominent p53-induced mRNA or miRNA response in these samples, despite the fact that the p53 pathway is a well-characterized radiation-inducible response. Instead, the expression of mRNAs encoding p53 and cytokeratin 14 (TP53 and KRT14, respectively) decreased precipitously within hours of the first radiation treatment. These patients went on to develop oral mucositis, however, it is unclear whether TP53 and/or KRT14 expression are predictive of this adverse event. Larger scale analysis of buccal epithelial samples from patients undergoing allogeneic stem cell transplantation appears to be warranted.
Systems-Level Analysis of ErbB4 Signaling in Breast Cancer: A Laboratory to Clinical Perspective

Although expression of the ErbB4 receptor tyrosine kinase in breast cancer is generally regarded as a marker for favorable patient prognosis, controversial exceptions have been reported. Alternative splicing of ErbB4 pre-mRNAs results in the expression of distinct receptor isoforms with differential susceptibility to enzymatic cleavage and different downstream signaling protein recruitment potential that could affect tumor progression in different ways. ErbB4 protein expression from nontransfected cells is generally low compared with ErbB1 in most cell lines, and much of our knowledge of the role of ErbB4 in breast cancer is derived from the ectopic overexpression of the receptor in non–breast-derived cell lines. One of the primary functions of ErbB4 in vivo is in the maturation of mammary glands during pregnancy and lactation induction. Pregnancy and extended lactation durations have been correlated with reduced risk of breast cancer, and the role of ErbB4 in tumor suppression may therefore be linked with its role in lactation. Most reports are consistent with a role for ErbB4 in reversing growth stimuli triggered by other ErbB family members during puberty. In this report, we provide a systems-level examination of several reports highlighting the seemingly opposing roles of ErbB4 in breast cancer and potential explanations for the discrepancies and draw the conclusion that future studies examining the function of ErbB4 in breast cancer should also take into account the pregnancy history, lactation status, and hormone supplementation or ablation history of the patient from whom the tumor or tumor cells are derived. (Mol Cancer Res 2008;6(6):885–91)
Closed-Loop Control of a Flame and its Application in a Dump Combustor

A closed-loop control system was constructed to control the lift-off height of a premixed flame at the lean flammability limit. Control authority was obtained by forcing the initial shear layer of the fuel/air mixture, thus generating small scale vortices which improved the flame stability. The optimal forcing was determined in open-loop control tests, which defined the effective range and relate it to the Kelvin-Helmholtz instability of the shear layer. An amplitude modulation (AM) controller was developed using the open-loop frequency as a carrier signal. Bode and Nyquist analyses showed that the flame is stable only in a limited range due to convective time lag, related to the convection time of the vortices. In spite of the high noise level of this turbulent combustion system, it was possible to use linear control theory to analyze the time-averaged transfer functions. The application of lead and lag compensations was studied to extend the stability margins. The control system response to changes in operating conditions such as set-point and flow rates were compared to the open-loop control operation and found to be superior, leading to a small extension of the lean flammability limit relative to an open-loop controller. The same approaches investigated in the flame experiments are used for active combustion control in the dump combustor. Shear-layer excitation was investigated using acoustic drivers. Various parameters affecting the efficiency of the methods for active combustion control were studied, including frequency, amplitude, and phase information.
Adoption of polymeric micelles to enhance the oral bioavailability of dexibuprofen: formulation, in-vitro evaluation and in-vivo pharmacokinetic study in healthy human volunteers

Abstract This work aimed to incorporate Dexibuprofen (DXI), the pharmacologically active and more potent form of ibuprofen, into polymeric micelles based tablets with enhanced oral bioavailability. Thin film hydration technique was employed to prepare DXI polymeric micelles using Pluronic® F127 and/or P123 solutions in different ratios (ranging from 1:1 up to 1:10). Prepared micelles were characterized regarding particle size, drug loading and entrapment efficiency. Selected formulae were lyophilized in presence of cryoprotectants and subjected to solid-state characterization as well as scanning and transmission electron microscopy. Subsequently, tablets were prepared and evaluated in-vitro regarding physical properties and drug release. An in-vivo pharmacokinetic study was performed in six healthy human volunteers in comparison to the commercially available tablet of DXI. Solid-state characterization proved that DXI was homogenously dispersed in Pluronic micelles’ matrices. Formula TF5 tablets comprising lyophilized micelles (F5; DXI: Pluronic F127 in 1:1 ratio and 0.25% mannitol) showed higher Cmax and earlier tmax values than those of the commercial formula, where the relative bioavailability was calculated to be 160.15%. The experimental evidence in this research leads to the conclusion that polymeric micelles present enabling properties for oral delivery of drugs with low solubility.
Controlled expression of Drosophila homeobox loci using the Hostile takeover system

Background: Hostile takeover (Hto) is a Drosophila protein trapping system that allows the investigator to both induce a gene and tag its product. The Hto transposon carries a GAL4‐regulated promoter expressing an exon encoding a FLAG‐mCherry tag. Upon expression, the Hto exon can splice to a downstream genomic exon, generating a fusion transcript and tagged protein. Results: Using rough‐eye phenotypic screens, Hto inserts were recovered at eight homeobox or Pax loci: cut, Drgx/CG34340, Pox neuro, araucan, shaven/D‐Pax2, Zn finger homeodomain 2, Sex combs reduced (Scr), and the abdominal‐A region. The collection yields diverse misexpression phenotypes. Ectopic Drgx was found to alter the cytoskeleton and cell adhesion in ovary follicle cells. Hto expression of cut, araucan, or shaven gives phenotypes similar to those of the corresponding UAS‐cDNA constructs. The cut and Pox neuro phenotypes are suppressed by the corresponding RNAi constructs. The Scr and abdominal‐A inserts do not make fusion proteins, but may act by chromatin‐ or RNA‐based mechanisms. Conclusions: Hto can effectively express tagged homeodomain proteins from their endogenous loci; the Minos vector allows inserts to be obtained even in transposon cold‐spots. Hto screens may recover homeobox genes at high rates because they are particularly sensitive to misexpression. Developmental Dynamics 244:808–825, 2015. © 2015 Wiley Periodicals, Inc.
Avian Visual Pigments: Characteristics, Spectral Tuning, and Evolution

Birds are highly visual animals with complex visual systems. In this article, we discuss the spectral characteristics and genetic mechanisms of the spectral tuning of avian visual pigments. The avian retina contains a single type of rod, four spectrally distinct types of single cone, and a single type of double cone photoreceptor. Only the single cones are thought to be involved in color discrimination; double cones are thought to be involved in achromatic visual tasks, such as movement detection and pattern recognition. Visual pigment opsin protein genes in birds are orthologous to those in other vertebrates and have a common origin early in vertebrate evolution. Mechanisms of spectral tuning in the different classes of avian cone visual pigments show similarities in most instances to those in other vertebrates. The exception is the ultraviolet/violet (SWS1) class of pigments; phylogenetic evidence indicates that the ancestral vertebrate SWS1 pigment was ultraviolet sensitive (UVS), with different molecular mechanisms accounting for the generation of violet‐sensitive (VS) pigments in different vertebrate classes. In birds, however, UVS visual pigments have re‐evolved from an ancestral avian VS pigment by using a novel molecular mechanism not seen in other vertebrate classes. This has occurred independently in four of the 14 avian orders examined to date, although the adaptive significance of this is currently unknown.
Gastric emptying of a non‐digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract Gastric emptying of digestible solids occurs after trituration of food particles. Non‐digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non‐digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r = 0.813; P < 0.01) and correlated moderately with solid‐phase gastric emptying (r = 0.606 with T‐50% and r = 0.565 with T‐90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r = 0.979; P < 0.01). The non‐digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid‐phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non‐digestible solid.
Linear motor tracking control based on adaptive robust control and extended state observer

Trajectory tracking control for linear oscillating motor is critical to improve the performance of linear electro-hydrostatic actuator (LEHA). However, both structured uncertainties (i.e., parametric uncertainties) and unstructured uncertainties (i.e., unmodeled dynamics, external disturbances, nonlinear friction) exist in LEHA may severely deteriorate the control performance of the system. In this paper, a control strategy which integrates adaptive robust control (ARC) and extended state observer (ESO) together is proposed to handle both structured and unstructured uncertainties. The proposed control strategy takes the advantages of ARC and ESO, which nullifies the disadvantages of ARC and ESO as well, guarantees accurate high-frequency trajectory tracking performance. In addition, a second-order system model is established by adapting dipole cancellation method and dominant pole theory before the design procedure of the controller. The simulation results are presented to verify the effectiveness and the achievable excellent performance of the proposed control strategy.