Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells

Biallelic inactivation of cancer susceptibility gene BRCA1 leads to breast and ovarian carcinogenesis. Paradoxically, BRCA1 deficiency in mice results in early embryonic lethality, and similarly, lack of BRCA1 in human cells is thought to result in cellular lethality in view of BRCA1's essential function. To survive homozygous BRCA1 inactivation during tumorigenesis, precancerous cells must accumulate additional genetic alterations, such as p53 mutations, but this requirement for an extra genetic “hit” contradicts the two-hit theory for the accelerated carcinogenesis associated with familial cancer syndromes. Here, we show that heterozygous BRCA1 inactivation results in genomic instability in nontumorigenic human breast epithelial cells in vitro and in vivo. Using somatic cell gene targeting, we demonstrated that a heterozygous BRCA1 185delAG mutation confers impaired homology-mediated DNA repair and hypersensitivity to genotoxic stress. Heterozygous mutant BRCA1 cell clones also showed a higher degree of gene copy number loss and loss of heterozygosity in SNP array analyses. In BRCA1 heterozygous clones and nontumorigenic breast epithelial tissues from BRCA mutation carriers, FISH revealed elevated genomic instability when compared with their respective controls. Thus, BRCA1 haploinsufficiency may accelerate hereditary breast carcinogenesis by facilitating additional genetic alterations.
Fracture Behavior of Minimally Invasive, Posterior, and Fixed Dental Prostheses Manufactured from Monolithic Zirconia.

OBJECTIVES To compare ultimate fracture load (Fu ), load at first damage (F1d ), and fracture pattern for posterior fixed dental prostheses (FDPs) manufactured from translucent, yttria-stabilized zirconia polycrystal. METHODS Premolar-size FDPs in 4 test groups (n = 16/group) were constructed as veneered complete crown-retained (group 1), monolithic complete crown-retained (group 2), monolithic partial veneer crown-retained (group 3), or monolithic resin-bonded (group 4) prostheses with minimum zirconia wall thickness (0.5 mm). Adhesively cemented to metal abutments, half of the prostheses were artificially aged by use of 10,000 thermocycles (6.5°C/60°C) and 1,200,000 chewing cycles (F = 108 N), before fracture loading. Statistics included two-way non-parametric ANOVA and Dunn-Bonferroni post-hoc tests (α = 0.05). RESULTS None of the restorations failed during artificial aging. Fu was affected by test group (p < 0.001); F1d was also affected by the factor combination of test group and aging (p = 0.001 for test group; p = 0.049 for test group*aging). Mean Fu for all groups exceeded 1000 N; it was comparable for group 1 and group 2 and statistically significantly higher for group 2 and group 3 than for group 4 (p < 0.01). Fracture usually occurred through the retainer wall. F1d = 200 N was determined for individual samples in group 1 (chipping) and group 3 (local debonding). CONCLUSIONS Fu of all the restorations was adequate for clinical use. Complications might, however, be expected at forces below 500 N for veneered prostheses (chipping) as well as for monolithic partial veneer crown-retained prostheses (local debonding). CLINICAL SIGNIFICANCE With regard to fracture behavior, all-ceramic complete crown-retained fixed dental prostheses (FDP) manufactured from monolithic zirconia, with a retainer wall thickness of 0.5 mm, might be suitable for use as a conservative alternative to their veneered counterparts in the rehabilitation of posterior tooth loss. Monolithic zirconia resin-bonded FDP might, moreover, be a viable alternative to resin-bonded FDPs with metal adhesive retainers in posterior arches, with improved esthetics and biocompatibility. The performance of both should, however, be verified in clinical trials. (J Esthet Restor Dent 28:367-381, 2016).
Transmission of the rare HRAS mutation (c. 173C > T; p.T58I) further illustrates its attenuated phenotype

Costello syndrome was delineated based on its distinctive phenotype including severe failure‐to‐thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. Heterozygous germline mutations in the proto‐oncogene HRAS cause Costello syndrome, and its inheritance pattern would thus be autosomal dominant. With exception of two instances of parental mosaicism, one presumed gonadal and the other proven somatic mosaicism for the p.G12S change, all published cases resulted from de novo mutations, typically arising in the paternal germline. More than 90% of these mutations affect the glycine residues in position 12 or 13, and result in a gain‐of‐function of the altered protein. A rare heterozygous HRAS alteration (c.173C > T; p.T58I) associated with an attenuated phenotype was previously reported in one patient. We identified two additional individuals with this mutation, father and son. Further studies supported origin of the alteration in the grand‐paternal germline. Transmission of the mutation underscores its attenuated phenotype compatible with reproduction. We reviewed the phenotype in the newly identified individuals (Patient 1, 2) and include updated information on the first previously reported individual with HRAS p.T58I (Patient 3). Macrocephaly was present in all three. Cardiac findings included hypertrophic cardiomyopathy with double‐chambered right ventricle; or mitral valve prolapse in one patient each. While subtle neurologic abnormalities or developmental delay were present in all, only one showed significant cognitive and functional impairment. None developed papillomata or a malignant tumor. Genetic counseling for Costello syndrome needs to take into consideration the particular HRAS mutation. © 2012 Wiley Periodicals, Inc.
Region-Based Association Analysis of Human Quantitative Traits in Related Individuals

Regional-based association analysis instead of individual testing of each SNP was introduced in genome-wide association studies to increase the power of gene mapping, especially for rare genetic variants. For regional association tests, the kernel machine-based regression approach was recently proposed as a more powerful alternative to collapsing-based methods. However, the vast majority of existing algorithms and software for the kernel machine-based regression are applicable only to unrelated samples. In this paper, we present a new method for the kernel machine-based regression association analysis of quantitative traits in samples of related individuals. The method is based on the GRAMMAR+ transformation of phenotypes of related individuals, followed by use of existing kernel machine-based regression software for unrelated samples. We compared the performance of kernel-based association analysis on the material of the Genetic Analysis Workshop 17 family sample and real human data by using our transformation, the original untransformed trait, and environmental residuals. We demonstrated that only the GRAMMAR+ transformation produced type I errors close to the nominal value and that this method had the highest empirical power. The new method can be applied to analysis of related samples by using existing software for kernel-based association analysis developed for unrelated samples.
Socially Motivated Data Caching in Ultra-Dense Small Cell Networks

UDN is considered as a promising technique to boost the network capacity by reducing the path loss between the base station and UE for the upcoming 5G mobile communication, while the backhaul capacity has become the bottleneck in huge data traffic generated by UEs. One effective approach to coping with the bottleneck is caching the content at the edge of UDNs. Taking advantage of D2D communication, not only SBSs but also UE can serve as cache nodes to help others for data access by sharing a channel to directly communicate with each other, thus tackling the bandwidth limitation of backhaul links. However, due to the selfish nature of mobile users in the network, incentive is needed for UEs to cache for others. In this article, the data caching incentive problem in UDNs is studied by exploring caching cost of SBS and social factors among UEs. A social group utility maximization (SGUM) game is exploited to motivate data caching among SBSs and UEs. Based on SGUM, a socially motivated caching approach is proposed. The evaluation of the proposed socially motivated caching approach is provided and compared to baseline caching schemes. The corresponding results and observations support the vision of a socially motivated caching paradigm for the future UDNs.
Low-power signal processing devices for portable ECG detection

An analog front end for diagnosing and monitoring the behavior of the heart is presented. This sensing front end has two low-power processing devices, including a 5th-order Butterworth operational transconductance-C (OTA-C) filter and an 8-bit successive approximation analog-to-digital converter (SAADC). The components fabricated in a 0.18-μm CMOS technology feature with power consumptions of 453 nW (filter) and 940 nW (ADC) at a supply voltage of 1 V, respectively. The system specifications in terms of output noise and linearity associated with the two integrated circuits are described in this paper.
Distribution and levels of alpha‐1‐antitrypsin in the lung and plasma in smokers and chronic obstructive pulmonary disease

Our recent non‐biased proteomic screening study revealed elevated SerpinA1 i.e. alpha‐1‐antitrypsin (AAT) levels in induced sputum of smokers with Chronic obstructive pulmonary disease (COPD). This study was designed to further investigate the role of AAT in smokers and subjects with COPD. The expression/distribution of AAT was studied by immunohistochemistry/digital image morphometry in the lung, by Western blot in the lung and sputum, and by ELISA in the plasma at baseline (n = 349) and after a 2‐year follow‐up (n = 58). AAT was localized mainly in airway and alveolar epithelium and endothelium, especially in smokers and in those with COPD. AAT was elevated in smokers and in subjects with COPD in the lung endothelial cells. Total lung AAT immunoreactivity was elevated in subjects with moderate COPD compared with smokers and with non‐smokers. AAT showed elevated tendency in sputum of smokers with COPD compared with ‘healthy’ smokers. Plasma AAT levels were elevated in smokers with/without COPD compared with non‐smokers. In the follow‐up, plasma AAT concentrations decreased significantly after quitting smoking. Chronic smoking/COPD leads to AAT elevation especially in the endothelium of the lung periphery; these changes reflect only modestly to the AAT in sputum, while plasma AAT significantly reflects smoking‐related systemic manifestations, and decreases after smoking cessation.
Knowledge of Good Blood Culture Sampling Practice among Healthcare Staffs in An Emergency Department - Are We Getting It Right?

BACKGROUND Although a vital test, blood culture is often plagued with the problem of contamination and false results, especially in a chaotic emergency department setting. The objectives of this pilot study is to find out the level of understanding among healthcare staffs in emergency department, Hospital Universiti Sains Malaysia (HUSM) regarding good blood culture sampling practice. METHODS All healthcare staffs in emergency department, HUSM who consented to this study were given a set of selfadministered anonymous questionnaire to fill. RESULTS More than half (53.1%) of the 64 participants are emergency medicine residents. Majority of them (75%) have been working in the emergency medicine, HUSM for more than 2 years. More than half of them were able to answer correctly the amount of blood volume needed for culture in adult and pediatric patients. When asked what are the factors required to improve the true yield as well as to reduce the risk of culture contamination, the four commonest answers given were observing proper aseptic technique during blood sampling, donning sterile glove, proper hand scrubbing as well as ensuring the sterility of the equipments. DISCUSSION AND CONCLUSION This study suggests that there is a lack of proper knowledge of good blood culture sampling practice among our healthcare staffs in emergency department.
On the Interaction of Influence and Trust in Social Networks

This paper focuses on finding important nodes in a social network based on their behaviour as well as the structure of the network; a problem of considerable interest in social recommender systems. This paper views the propagation of information in a social network as a process of infection. Furthermore, a proposal regarding infection and trust is made. The paper proposes an algorithm called the Probability Propagation Method for measuring the probability of infection of all the nodes in a network starting from a given node in the network. Assuming independence in activation of network nodes, a method is proposed for ranking nodes according to their capabilities in infecting a larger number of nodes in a network. These methods are validated using simulation software in which a non-deterministic information diffusion model is simulated on several classes of network.
Tracking the Migraine Cycle Using Visual Tasks

There are a number of reports that perceptual, electrophysiological and imaging measures can track migraine periodicity. As the electrophysiological and imaging research requires specialist equipment, it has few practical applications. This study sought to track changes in performance on four visual tasks over the migraine cycle. Coherence thresholds were measured for two motion and two orientation tasks. The first part of the study confirmed that the data obtained from an online study produced comparable results to those obtained under controlled laboratory conditions. Thirteen migraine with aura, 12 without aura, and 12 healthy controls participated. The second part of the study showed that thresholds for discriminating vertical coherent motion varied with the migraine cycle for a majority of the participants who tested themselves multiple times (four with aura, seven without). Performance improved two days prior to a migraine attack and remained improved for two days afterwards. This outcome is as expected from an extrapolation of earlier electrophysiological research. This research points to the possibility of developing sensitive visual tests that patients can use at home to predict an impending migraine attack and so take steps to try to abort it or, if it is inevitable, to plan their lives around it.
5-HT1A and 5-HT2A receptor control of a panic-like defensive response in the rat dorsomedial hypothalamic nucleus

The dorsomedial nucleus of the hypothalamus (DMH) has long been implicated in the genesis/regulation of escape, a panic-related defensive behavior. In the dorsal periaqueductal gray matter (dPAG), another key panic-associated area, serotonin, through the activation of 5-HT1A and 5-HT2A receptors, exerts an inhibitory role on escape expression. This panicolytic-like effect is facilitated by chronic treatment with clinically effective antipanic drugs such as fluoxetine and imipramine. It is still unclear whether serotonin within the DMH plays a similar regulatory action. The results showed that intra-DMH injection of the 5-HT1A receptor agonist 8-OH-DPAT, the preferential 5-HT2A receptor agonist DOI, but not the 5-HT2C agonist MK-212, inhibited the escape reaction of male Wistar rats evoked by electrical stimulation of the DMH. Local microinjection of the 5-HT1A antagonist WAY-100635 or the preferential 5-HT2A antagonist ketanserin was ineffective. Whereas chronic (21 days) systemic treatment with imipramine potentiated the anti-escape effect of both 8-OH-DPAT and DOI, repeated administration of fluoxetine enhanced the effect of the latter agonist. The results indicate that 5-HT1A and 5-HT2A receptors within the DMH play a phasic inhibitory role upon escape expression, as previously reported in the dPAG. Facilitation of 5-HT-mediated neurotransmission in the DMH may be implicated in the mode of action of antipanic drugs.
A fully integrated 0.5-5.5 GHz CMOS distributed amplifier

A fully integrated 0.5-5.5-GHz CMOS-distributed amplifier is presented. The amplifier is a four stage design fabricated in a standard 0.6-/spl mu/m three-layer metal digital-CMOS process. The amplifier has a unity-gain cutoff frequency of 5.5 GHz, and a gain of 6.5 dB, with a gain flatness of /spl plusmn/1.2 dB over the 0.5-4 GHz band. Input and output are matched to 50 /spl Omega/, with worst-case return losses on the input and output of -7 and -10 dB, respectively. Power dissipation is 83.4 mW from a 3.0 V supply, input-referred 1-dB compression point varies from +6 dBm at 1 GHz to 8.8 dBm at 5 GHz. From a circuit standpoint, the fully integrated nature of the amplifier on the given substrate results in a heavily parasitic-laden design. Discussion emphasis is therefore placed on the practical design, modeling, and CAD optimization techniques used in the design process.
SAR image super-resolution based on TV-regularization using gradient profile prior

We propose an total variation (TV) regularization approach for the reconstruction of super-resolution synthetic aperture radar (SAR) image based on gradient profile prior. Then we design a super-resolution reconstruction algorithm via split Bregman iteration with the known degradation matrix. The evaluation index is tested on SAR images for objective assessment of the performance of SAR image super-resolution reconstruction. Experimental results show that the proposed split Bregamn super-resolution approach has good effect of noise suppression, while able to effectively maintain the SAR image content. Besides, the experimental results on real SAR scenes demonstrate its superiority to other super-resolution algorithms.
Modelling single- and tandem-bubble dynamics between two parallel plates for biomedical applications

Abstract Carefully timed tandem microbubbles have been shown to produce directional and targeted membrane poration of individual cells in microfluidic systems, which could be of use in ultrasound-mediated drug and gene delivery. This study aims at contributing to the understanding of the mechanisms at play in such an interaction. The dynamics of single and tandem microbubbles between two parallel plates is studied numerically and analytically. Comparisons are then made between the numerical results and the available experimental results. Numerically, assuming a potential flow, a three-dimensional boundary element method (BEM) is used to describe complex bubble deformations, jet formation, and bubble splitting. Analytically, compressibility and viscous boundary layer effects along the channel walls, neglected in the BEM model, are considered while shape of the bubble is not considered. Comparisons show that energy losses modify the bubble dynamics when the two approaches use identical initial conditions. The initial conditions in the boundary element method can be adjusted to recover the bubble period and maximum bubble volume when in an infinite medium. Using the same conditions enables the method to recover the full dynamics of single and tandem bubbles, including large deformations and fast re-entering jet formation. This method can be used as a design tool for future tandem-bubble sonoporation experiments.
Consistency of the Two Component Composite Modeling Framework for NBTI in Large and Small Area p-MOSFETs

Consistency of the recently proposed deterministic composite modeling framework for Negative Bias Temperature Instability (NBTI) in large area devices is verified for stochastic NBTI in small area devices. The framework has two independent and uncoupled components, interface trap generation (ΔV<sub>IT</sub>), and hole trapping in pre-existing defects (ΔV<sub>HT</sub>). The time evolution of mean threshold voltage shift (ΔV <sub>T</sub>), from multiple ultra-fast measurements in small area devices under diverse stress and recovery conditions, is predicted by the deterministic composite framework. It is shown that although the physical mechanism of NBTI remains the same as the device area is scaled, there can be significant differences in the relative ΔV<sub>IT</sub> and Δ V<sub>HT</sub> contribution to ΔV<sub>T</sub> between large and small area devices, which can alter the overall model parameters. A stochastic simulation framework, fully consistent with the deterministic framework, is developed, which is shown to predict experimentally measured mean time evolution of ΔV<sub>T</sub> in small area devices.
Both Arabidopsis TATA binding protein (TBP) isoforms are functionally identical in RNA polymerase II and III transcription in plant cells: evidence for gene‐specific changes in DNA binding specificity of TBP.

Promoters of pol II and pol III transcribed U‐snRNA genes in plants have identical sequence elements comprised of a −30 TATA box and an upstream sequence element (USE), located four or three helical turns upstream of the TATA box in pol II and pol III genes, respectively; it is this difference in element spacing that determines the RNA polymerase specificity of the gene. We are interested in identifying factors binding to U‐snRNA gene promoters and their role in selection of RNA polymerase. In this work we have investigated possible differences in the activity of the two TATA binding proteins (TBPs) encoded by two different TBP genes of Arabidopsis. Using mutant TBPs with altered DNA binding specificity, similar to those described previously in yeast, we show that two Arabidopsis TBP isoforms are equally active with both pol II and pol III U‐snRNA genes and with an mRNA gene transfected into plant protoplasts. In contrast to yeast, where modified TBP permits transcription only from promoters containing the TGTAAA mutant of the consensus (TATAAA) TATA element, altered Arabidopsis TBPs also suppress other TATA box mutants. Similar results were obtained with human and yeast TBP mutants expressed in plant cells. Interestingly, in several cases suppression of different TATA box mutants by altered TBPs was gene or RNA polymerase specific suggesting that assembly of TBP into specific complexes containing different TBP‐associated factors may alter DNA binding specificity of the protein.
Automated tracking of tumor-stroma morphology in microtissues identifies functional targets within the tumor microenvironment for therapeutic intervention

Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of complex cell cultures has been lacking. Here, we have developed a novel automated pipeline to model tumor-stroma interplay, track motility and quantify morphological changes of 3D co-cultures, in real-time live-cell settings. The platform consists of microtissues from prostate cancer cells, combined with CAFs in extracellular matrix that allows biochemical perturbation. Tracking of fibroblast dynamics revealed that CAFs guided the way for tumor cells to invade and increased the growth and invasiveness of tumor organoids. We utilized the platform to determine the efficacy of inhibitors in prostate cancer and the associated tumor microenvironment as a functional unit. Interestingly, certain inhibitors selectively disrupted tumor-CAF interactions, e.g. focal adhesion kinase (FAK) inhibitors specifically blocked tumor growth and invasion concurrently with fibroblast spreading and motility. This complex phenotype was not detected in other standard in vitro models. These results highlight the advantage of our approach, which recapitulates tumor histology and can significantly improve cancer target validation in vitro.