Miracle-dz/UniFAR-FTUs huggingface dataset:
Transposon-mediated generation of BCR-ABL1-expressing transgenic cell lines for unbiased sensitivity testing of tyrosine kinase inhibitors

Point mutations in the ABL1 kinase domain are an important mechanism of resistance to tyrosine kinase inhibitors (TKI) in BCR-ABL1-positive and, as recently shown, BCR-ABL1-like leukemias. The cell line Ba/F3 lentivirally transduced with mutant BCR-ABL1 constructs is widely used for in vitro sensitivity testing and response prediction to tyrosine kinase inhibitors. The transposon-based Sleeping Beauty system presented offers several advantages over lentiviral transduction including the absence of biosafety issues, faster generation of transgenic cell lines, and greater efficacy in introducing large gene constructs. Nevertheless, both methods can mediate multiple insertions in the genome. Here we show that multiple BCR-ABL1 insertions result in elevated IC50 levels for individual TKIs, thus overestimating the actual resistance of mutant subclones. We have therefore established flow-sorting-based fractionation of BCR-ABL1-transformed Ba/F3 cells facilitating efficient enrichment of cells carrying single-site insertions, as demonstrated by FISH-analysis. Fractions of unselected Ba/F3 cells not only showed a greater number of BCR-ABL1 hybridization signals, but also revealed higher IC50 values for the TKIs tested. The data presented highlight the need to carefully select transfected cells by flow-sorting, and to control the insertion numbers by FISH and real-time PCR to permit unbiased in vitro testing of drug resistance.
SAR Imagery Simulation of Ship Based on Electromagnetic Calculations and Sea Clutter Modelling for Classification Applications

Ship detection and classification with space-borne SAR has many potential applications within the maritime surveillance, fishery activity management, monitoring ship traffic, and military security. While ship detection techniques with SAR imagery are well established, ship classification is still an open issue. One of the main reasons may be ascribed to the difficulties on acquiring the required quantities of real data of vessels under different observation and environmental conditions with precise ground truth. Therefore, simulation of SAR images with high scenario flexibility and reasonable computation costs is compulsory for ship classification algorithms development. However, the simulation of SAR imagery of ship over sea surface is challenging. Though great efforts have been devoted to tackle this difficult problem, it is far from being conquered. This paper proposes a novel scheme for SAR imagery simulation of ship over sea surface. The simulation is implemented based on high frequency electromagnetic calculations methods of PO, MEC, PTD and GO. SAR imagery of sea clutter is modelled by the representative K-distribution clutter model. Then, the simulated SAR imagery of ship can be produced by inserting the simulated SAR imagery chips of ship into the SAR imagery of sea clutter. The proposed scheme has been validated with canonical and complex ship targets over a typical sea scene.
Contribution of small conductance K+ channels to sinoatrial node pacemaker activity: insights from atrial‐specific Na+/Ca2+ exchange knockout mice

Repolarizing currents through K+ channels are essential for proper sinoatrial node (SAN) pacemaking, but the influence of intracellular Ca2+ on repolarization in the SAN is uncertain. We identified all three isoforms of Ca2+‐activated small conductance K+ (SK) channels in the murine SAN. SK channel blockade slows repolarization and subsequent depolarization of SAN cells. In the atrial‐specific Na+/Ca2+ exchanger (NCX) knockout mouse, cellular Ca2+ accumulation during spontaneous SAN pacemaker activity produces intermittent hyperactivation of SK channels, leading to arrhythmic pauses alternating with bursts of pacing. These findings suggest that Ca2+‐sensitive SK channels can translate changes in cellular Ca2+ into a repolarizing current capable of modulating pacemaking. SK channels are a potential pharmacological target for modulating SAN rate or treating SAN dysfunction, particularly under conditions characterized by abnormal increases in diastolic Ca2+.
Implementing Co-Regulated Feeding with Mothers of Preterm Infants

Purpose:The purpose of this study is to describe implementation of the Co-Regulated Feeding Intervention (CoReg), when provided by mothers and guided by intervention nurses trained in methods of guided participation (GP). Co-regulated feeding intervention aims to prevent stress during feeding and ease the challenge very preterm (VP) infants experience coordinating breathing and swallowing during the early months. Guided participation is a participatory learning method to guide the complex learning required for mothers. Study Design and Methods:Sixteen mothers of 17 VP infants participated. Each mother received a median of five intervention sessions during the infant's transition to oral feeding. Intervention field notes, audio recordings of the sessions, and video recordings of the nurse-guided feedings were reviewed, organized, and content analyzed to evaluate implementation. Results:The co-regulated feeding intervention was well received by mothers; enrollment, participation, and retention rates were high. Most mothers chose to spread out the intervention sessions across the transition period. Scheduling sessions was the greatest barrier. Mothers had competing demands and infant readiness to eat could not be predicted. The top five issues identified as needing attention by the mother or nurse included reading cues, coregulating breathing, providing motoric stability, regulating milk flow, and providing rest periods. Main GP strategies included joint attention with the mother to the dyad's feeding challenges, auditory assessment of breathing and swallowing, and reflection with planning for future feedings using video playback. Clinical Implications:Nurse presence while mothers feed affords rich opportunities to guide coregulated, cue-based feeding. Co-regulated feeding intervention would be enhanced if mothers are guided by the bedside nurse.
Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB). Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2), significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.
Quality Assessment for Image Coding Based on Matching Pursuit

Valuation of image coding relies on not only the efficiency of the coding, but also the quality of the coded image. We present a new objective quality assessment metric for image coding based on matching pursuit. First of all, we get the characteristics of the most important structure by projecting the reference image onto the base functions from a dictionary using matching pursuit. Secondly, we process the reference image and gain the structure information of the images in the order of importance, projecting the images onto the structural characteristics. Finally the objective quality score is given by comparing the differences of structure information between the reference and coded images. Experimental results show that the proposed approach is well consistent with the subjective quality score.
Early-Life Stress Does Not Aggravate Spatial Memory or the Process of Hippocampal Neurogenesis in Adult and Middle-Aged APP/PS1 Mice

Life-time experiences are thought to influence the risk to develop the neurodegenerative disorder Alzheimer’s disease (AD). In particular, early-life stress (ES) may modulate the onset and progression of AD. There is recent evidence by our group and others that AD-related neuropathological progression and the associated neuroimmune responses are modulated by ES in the classic APPswe/PS1dE9 mouse model for AD. We here extend our previous study on ES mediated modulation of neuropathology and neuroinflammation and address in the same cohort of mice whether ES accelerates and/or aggravates AD-induced cognitive decline and alterations in the process of adult hippocampal neurogenesis (AHN), a form of brain plasticity. Chronic ES was induced by limiting bedding and nesting material during the first postnatal week and is known to induce cognitive deficits by 4 months in wild type (WT) mice. The onset of cognitive decline in APP/PS1 mice generally starts around 6 months of age. We here tested mice at ages 2–4 months to study acceleration and at ages 8–10 months for aggravation of the APP/PS1 phenotype. ES-exposed WT and APP/PS1 mice were able to perform the object recognition (ORT) and location tasks (OLT) at 2 months of age. Interestingly, at 3 months, ES induced impairments in the performance of the OLT in WT, but not in APP/PS1 mice. APP/PS1 mice exhibited alterations in hippocampal cell proliferation and differentiation, but ES exposure did not further change this. At 9 months, APP/PS1 mice exhibited impaired performance in the Morris Water Maze (MWM) task, as well as reductions in markers of the AHN process, which were not further modulated by ES exposure. In addition, we observed a so far unreported hyperactivity in ES-exposed mice at 8 months of age, which hampered assessment of cognitive functions in the ORT and OLT. In conclusion, while ES has been reported to modulate AD neuropathology and neuroinflammation before, it failed to accelerate or aggravate the decline in cognition or the process of AHN in APP/PS1 mice at ages 2–4 and 8–10 months. Future studies are needed to unravel how ES might affect the vulnerability to develop AD.
Is exercise-based cardiac rehabilitation effective? A systematic review and meta-analysis to re-examine the evidence

Objectives To determine the contemporary effectiveness of exercise-based cardiac rehabilitation (CR) in terms of all-cause mortality, cardiovascular mortality and hospital admissions. Data sources Studies included in or meeting the entry criteria for the 2016 Cochrane review of exercise-based CR in patients with coronary artery disease. Study eligibility criteria Randomised controlled trials (RCTs) of exercise-based CR versus a no-exercise control whose participants were recruited after the year 2000. Study appraisal and synthesis methods Two separate reviewers independently screened the characteristics of studies. One reviewer quality appraised any new studies and assessed their risk of bias using the Cochrane Collaboration’s recommended risk of bias tool. Data were reported as the risk difference (95% CI). Results We included 22 studies with 4834 participants (mean age 59.5 years, 78.4% male). We found no differences in outcomes between exercise-based CR and a no-exercise control at their longest follow-up period for: all-cause mortality (19 studies; n=4194; risk difference 0.00, 95% CI −0.02 to 0.01, P=0.38) or cardiovascular mortality (9 studies; n=1182; risk difference −0.01, 95% CI −0.02 to 0.01, P=0.25). We found a small reduction in hospital admissions of borderline statistical significance (11 studies; n=1768; risk difference −0.05, 95% CI −0.10 to −0.00, P=0.05). Conclusions and implications of key findings Our analysis indicates conclusively that the current approach to exercise-based CR has no effect on all-cause mortality or cardiovascular mortality, when compared with a no-exercise control. There may be a small reduction in hospital admissions following exercise-based CR that is unlikely to be clinically important. PROSPERO registration number CRD42017073616.
Towards a Marketplace of Open Source Software Data

Development, distribution and use of open source software comprise a market of data (source code, bug reports, documentation, number of downloads, etc.) from projects, developers and users. This large amount of data hampers people to make sense of implicit links between software projects, e.g., Dependencies, patterns, licenses. This context raises the question of what techniques and mechanisms can be used to help users and developers to link related pieces of information across software projects. In this paper, we propose a framework for a marketplace enhanced using linked open data (LOD) technology for linking software artifacts within projects as well as across software projects. The marketplace provides the infrastructure for collecting and aggregating software engineering data as well as developing services for mining, statistics, analytics and visualization of software data. Based on cross linking software artifacts and projects, the marketplace enables developers and users to understand the individual value of components and their relationship to bigger software systems. Improved understanding creates new business opportunities for software companies: users will be able to analyze and compare projects, developers can increase the visibility of their products, and hosts may offer plugins and services over the data to paying customers.
A Low-Power Parallel Architecture for Finite Galois Field GF(2m) Arithmetic Operations for Elliptic Curve Cryptography

In this paper, a parallel, power-efficient and scalable word-based crypto architecture is proposed that performs the operations required for scalar point multiplication including add, multiplication and inversion operations on GF(2) operands. The proposed architecture distinguishes itself from exiting architectures, including our prior architecture, by the fact that its resource usage and power-consumption is based on the input data. Hence, such architecture might be used for various operand sizes without modifying or reconfiguring the underlying hardware. The architecture has also the ability to perform several different operations in parallel when each operation requires a small key size which significantly increases the overall performance and throughput of the system. In the absence of parallel requests, the remaining unused modules will be turned off in order to save power. The experimental results show significant improvement in the timing, throughput and energy performances with a slight overhead in the circuit area.
Activity-dependent trafficking of lysosomes in dendrites and dendritic spines

In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic &agr;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins.
Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis

Background Accumulating evidence showed that high expression of toll like receptor 4 (TLR4) was significantly associated with the outcome of patients with solid cancers. However, other studies failed to draw a similar conclusion. Thus, a systematic meta-analysis was performed to assess the prognostic value of TLR4 in solid tumors. Results Data from 15 studies and 1294 patients were enrolled. Among the 15 studies, 14 studies demonstrated the association between overall survival(OS) and TLR4 expression, and 7 studies described the relationship between disease-free survival(DFS) and TLR4 expression. High expression of TLR4 was significantly associated with poor OS (pooled hazard ratio (HR) = 2.05; 95% confidence interval (CI) (1.49, 2,49), P < 0.001). The results of meta regression analysis indicated that the subgroups of ethnic (PD = 0.924), tumor type (PD = 0.669), HR obtained method (PD = 0.945), analysis type (PD = 0.898), and cut-off value(PD = 0.835) were not the resource of heterogeneity. Moreover, patients with elevated TLR4 had a significantly worse DFS (pooled HR = 1.79; 95% CI (1.11, 2.88), P < 0.05). Materials and Methods We searched PubMed, Embase and the Cochrane Library (last update by April 18, 2017) to identify literatures evaluating the value of TLR4 in cancer patients. Combined hazard ratios (HRs) for OS and DFS were assessed using fixed-effects models and random effects models respectively. Conclusions The meta-analysis suggests that elevated expression of TLR4 is associated with poor OS and shorter DFS of patients with solid tumors. The results indicate that TLR4, as a novel prognostic biomarker in solid tumors, could potentially help to improve treatment decision-making of solid tumors in clinical.
Effect of surface conditions and strain hardening on the passivity breakdown of 304 stainless steel

Electrical and electrochemical properties of the passive layer formed on 304L austenitic stainless steel are investigated by means of both conductive atomic force microscopy in air and electrochemical atomic force microscopy in chloride-containing media. The maps of local electrical conductivity of the oxide overlayer exhibit different patterns depending on the surface conditions after mechanical or electrochemical polishing. In particular, the passive film covering strain-hardened regions reveals a higher electrical conductivity. The local enhancement of the electrical conduction is explained by local changes of the stoichiometry of the passive film. Moreover, the highly conductive regions lead to a local breakdown of the native oxide in chloride-containing media and favor the initiation of localized pits.
Can the Enterococcus faecalis identified in the root canals of primary teeth be a cause of failure of endodontic treatment?

Abstract Objective: This study investigated the presence of Enterococcus faecalis in primary teeth with primary root canal infections and related to the possible failure of pulpectomy outcome after 36 months. Material and methods: Root canal samples were obtained from 25 out of 244 patients using the sterile paper cone method. The identification of E. faecalis was done with culture and molecular tests using species-specific 16S rRNA gene-based polymerase chain reaction (PCR). After 36 months, the pulpectomy outcome was evaluated. Results: Enterococcus faecalis was found in five (20%) samples, and dental caries were the cause of primary infection in all of them. Pulpectomy outcome was evaluated only in teeth that completed the entire clinical protocol and were followed up to 36 months (n = 8). From these, 75% (n = 6) were successful and 25% (n = 2) failed. E. faecalis was present in 50% of both successful and failed cases. Conclusions: Enterococcus faecalis was not related to the failure of endodontic treatment of primary teeth.
Can’t Get it Out of My Mind: A Systematic Review of Predictors of Intrusive Memories of Distressing Events

Intrusive memories, when persistent and distressing, are theorized to underlie a range of transdiagnostic psychological symptoms and associated impairment. However, little is known about factors predicting the development and persistence of intrusive memories. The aim of this systematic review is to evaluate the literature on pre-event, event-based, and post-event predictors of intrusive memories. A systematic review was conducted, searching for studies that examined intrusive, event-based memories. One hundred and six articles were identified from PsycInfo, PubMed, and Medline databases. Experimental and prospective studies with clinical (N = 14) and nonclinical (N = 92) samples were critically reviewed, provided the inclusion of an analogue stressor with nonclinical samples, and that intrusive memories frequency and/or distress were assessed as primary dependent variables. Pre-existing psychopathology and pre-event appraisal style appear to predict intrusive memories (small to medium effects), whereas trait dissociation did not predict intrusive memories. Of studies examining event-based predictors, higher data-driven processing appears to predict intrusive memories with generally large effects. Post-event negative appraisals consistently predicted intrusive memories (medium to large effects), and preliminary evidence suggests higher post-event conceptual processing predicting fewer intrusive memories. This review synthesizes findings regarding a broad range of pre-event, event-based, and post-event factors that may influence the development of intrusive memories. Methodological issues of current paradigms and the lack of emphasis on memory retrieval processes limit our understanding of what predicts intrusive memory persistence. These limitations are particularly important given that individuals typically seek treatment for distressing intrusive memories once a memory has been fully consolidated, where retrieval processes are of utmost importance.
UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease

Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as vascular damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, and can contribute to vascular repair as well as to cardiovascular pathologies such as intimal hyperplasia/restenosis in coronary artery and arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity. UHRF1 expression correlated with the development of vascular pathologies associated with modulation of noncoding RNAs, such as microRNAs. miR-145 — pivotal in regulating VSMC plasticity, which is reduced in vascular diseases — was found to control Uhrf1 mRNA translation. In turn, UHRF1 triggered VSMC proliferation, directly repressing promoters of cell-cycle inhibitor genes (including p21 and p27) and key prodifferentiation genes via the methylation of DNA and histones. Local vascular viral delivery of Uhrf1 shRNAs or Uhrf1 VSMC-specific deletion prevented intimal hyperplasia in mouse carotid artery and decreased vessel damage in a mouse model of aortic aneurysm. Our study demonstrates the fundamental role of Uhrf1 in regulating VSMC phenotype by promoting proliferation and dedifferentiation. UHRF1 targeting may hold therapeutic potential in vascular pathologies.