Miracle-dz/UniFAR-FTUs huggingface dataset:
Amphiphilic Degradable Polymer/Hydroxyapatite Compositesas Smart Bone Tissue Engineering Scaffolds: A Dissertation

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle mineral component in bone. This dissertation describes the development of smart bone tissue engineering scaffolds composed of the biodegradable amphiphilic polymer poly(D,L-lactic acid-co-ethylene glycol-co- D,L-lactic acid) (PELA) and HA. Electrospun nanofibrous HA-PELA scaffolds exhibited improved handling characteristics and bioactivity over conventional HApoly( D,L-lactic acid) composites. Electrospun HA-PELA was hydrophilic, elastic, stiffened upon hydration, and supported the attachment and osteogenic differentiation of rat bone marrow stromal cells (MSCs). These in vitro properties translated into robust bone formation in vivo using a critical-size femoral defect model in rats. Spiral-wrapped HA-PELA scaffolds, loaded with MSCs or a lowdose of recombinant human bone morphogenetic protein-2, templated bone formation along the defect. As an alternate approach, PELA and HA-PELA were viii rapid prototyped into three-dimensional (3-D) macroporous scaffolds using a consumer-grade 3-D printer. These 3-D scaffolds have differential cell adhesion characteristics, swell and stiffen upon hydration, and exhibit hydration-induced self-fixation in a simulated confined defect. HA-PELA also exhibits thermal shape memory behavior, enabling the minimally invasive delivery and rapid (>3 sec) shape recovery of 3-D scaffolds at physiologically safe temperatures (~ 50oC). Overall, this dissertation demonstrates how the rational selection of FDA approved materials with synergistic interactions results in smart biomaterials with high potential for clinical translation.
Video genre estimation from relationship between motion and facial features using SLPCCA

In this paper, we propose an efficient video genre estimation method based on the relationship between facial features and motion features. In the proposed method, we utilize supervised locality preserving canonical correlation analysis (SLPCCA), which is derived in the proposed method, to maximize the correlation between facial features and motion features. Moreover, by using SLPCCA, we can consider not only the correlation but also class information. Finally, by applying Support Vector Machine (SVM) to the SLPCCA-based feature vectors, we realize a successful video genre estimation. Experimental results show the effectiveness of our method.
The Role of Noncoding RNA Pseudouridylation in Nuclear Gene Expression Events

Pseudouridine is the most abundant internal RNA modification in stable noncoding RNAs (ncRNAs). It can be catalyzed by both RNA-dependent and RNA-independent mechanisms. Pseudouridylation impacts both the biochemical and biophysical properties of RNAs and thus influences RNA-mediated cellular processes. The investigation of nuclear-ncRNA pseudouridylation has demonstrated that it is critical for the proper control of multiple stages of gene expression regulation. Here, we review how nuclear-ncRNA pseudouridylation contributes to transcriptional regulation and pre-mRNA splicing.
An updated analysis of respiratory tract cells at risk for formaldehyde carcinogenesis

Abstract Study of the mode of action (MOA) relating exposure to a given chemical with an associated adverse outcome is an iterative process with each iteration driven by new understandings of the relevant biology. Here, we revisit a previously described, MOA-based clonal growth model of the human respiratory tract cancer risk associated with formaldehyde inhalation. Changes reflect a better understanding of populations of cells at risk of carcinogenic transformation in the pharynx, larynx and respiratory bronchiolar portions of the human respiratory tract and inclusion of basal cells in the pool of cells at risk. The focus of this report is not on cancer risk per se, but rather on the sensitivity of model parameters and predicted risks to alternative descriptions of the fraction of cells at risk for carcinogenic transformation. For a population of formaldehyde-exposed nonsmokers, revised specification of cells at risk resulted in changes in both parameter estimates and in predicted risks. Compared to our previous assessment, predicted additional risks were up to 87% greater at exposure levels ≤1 ppm, but up to about 130% lower at high exposure levels (2–5 ppm). While this work should not be considered an update to MOA-based risk assessments for formaldehyde described previously, it illustrates the sensitivity of parameter estimates and risk predictions to the quantitative specification of cells at risk of carcinogenic transformation and, therefore, the motivation for describing the relevant biology as accurately as possible.
Cost analysis of a prospective multi-site cohort study of palliative care consultation teams for adults with advanced cancer: Where do cost-savings come from?

Background: Studies report cost-savings from hospital-based palliative care consultation teams compared to usual care only, but drivers of observed differences are unclear. Aim: To analyse cost-differences associated with palliative care consultation teams using two research questions: (Q1) What is the association between early palliative care consultation team intervention, and intensity of services and length of stay, compared to usual care only? (Q2) What is the association between early palliative care consultation team intervention and day-to-day hospital costs, compared to a later intervention? Design: Prospective multi-site cohort study (2007–2011). Patients who received a consultation were placed in the intervention group, those who did not in the comparison group. Intervention group was stratified by timing, and groups were matched using propensity scores. Setting/participants: Adults admitted to three US hospitals with advanced cancer. Principle analytic sample contains 863 patients (nUC = 637; nPC EARLY = 177; nPC LATE = 49) discharged alive. Results: Cost-savings from early palliative care accrue due to both reduced length of stay and reduced intensity of treatment, with an estimated 63% of savings associated with shorter length of stay. A reduction in day-to-day costs is observable in the days immediately following initial consult but does not persist indefinitely. A comparison of early and late palliative care consultation team cost-effects shows negligible difference once the intervention is administered. Conclusion: Reduced length of stay is the biggest driver of cost-saving from early consultation for patients with advanced cancer. Patient- and family-centred discussions on goals of care and transition planning initiated by palliative care consultation teams may be at least as important in driving cost-savings as the reduction of unnecessary tests and pharmaceuticals identified by previous studies.
Stopping Conventional Showering Decreases Pseudomonas Infections in left Ventricular Assist Device Patients

Background Left ventricular assist device (LVAD) exit-site infections represent a major challenge in the era of modern LVADs. Infections caused by Pseudomonas are particularly difficult to treat due to limited antibiotic susceptibility. We hypothesized that keeping the LVAD exit site dry while bathing could result in reduced incidence of Pseudomonas infections. Methods Starting in April 2013, all patients who underwent placement of HeartMate II (HM II) LVAD were instructed not to take conventional showers and to keep the exit site dry while bathing. We retrospectively reviewed patients who underwent HeartMate II LVAD implantation at our institution. Overall and Pseudomonas exit-site infections were compared between two groups: Group 1 was implanted with an LVAD prior to intervention (4/1/2013) and Group 2 after the intervention. Both groups were subjected to cumulative hazard analysis and compared using log-rank test. Results From November 2006 to September 2015, 283 patients underwent HM II LVAD placement at a single institution (Group 1, 163 patients; Group 2, 120 patients). Median age was 59 years (interquartile range [IQR] 50–65), and 57 (20%) were female. Overall, driveline infection was noted in 86 (30%) patients. Pseudomonas was the causative or coexisting organism in 16 (6%) patients. Median days to infection were 347 (IQR, 162–568). Driveline infection was identified in 69 (42%) patients in Group 1 and 17 (14 %) in Group 2. Pseudomonas was an infectious organism in 15 (9%) patients of Group 1 and one (1%) patient of Group 2. The incidence of Pseudomonas exit-site infections (p = 0.077) decreased substantially after the intervention. Conclusions Stopping conventional showering may reduce the rate of Pseudomonas LVAD exit-site infections. Additional, multi-institutional data are needed to further evaluate these findings.
Efficient Computation of the Skyline Cube

Skyline has been proposed as an important operator for multi-criteria decision making, data mining and visualization, and user-preference queries. In this paper. we consider the problem of efficiently computing a SKYCUBE, which consists of skylines of all possible non-empty subsets of a given set of dimensions. While existing skyline computation algorithms can be immediately extended to computing each skyline query independently, such "shared-nothing" algorithms are inefficient. We develop several computation sharing strategies based on effectively identifying the computation dependencies among multiple related skyline queries. Based on these sharing strategies, two novel algorithms, Bottom-Up and Top-Down algorithms, are proposed to compute SKYCUBE efficiently. Finally, our extensive performance evaluations confirm the effectiveness of the sharing strategies. It is shown that new algorithms significantly outperform the naive ones.
The need for ‘representative task design’ in evaluating efficacy of skills tests in sport: A comment on Russell, Benton and Kingsley (2010)

Abstract Russell, Benton and Kingsley (2010) recently suggested a new association football test comprising three different tasks for the evaluation of players' passing, dribbling and shooting skills. Their stated intention was to enhance ‘ecological validity’ of current association football skills tests allowing generalisation of results from the new protocols to performance constraints that were ‘representative’ of experiences during competitive game situations. However, in this comment we raise some concerns with their use of the term ‘ecological validity’ to allude to aspects of ‘representative task design’. We propose that in their paper the authors confused understanding of environmental properties, performance achievement and generalisability of the test and its outcomes. Here, we argue that the tests designed by Russell and colleagues did not include critical sources of environmental information, such as the active role of opponents, which players typically use to organise their actions during performance. Static tasks which are not representative of the competitive performance environment may lead to different emerging patterns of movement organisation and performance outcomes, failing to effectively evaluate skills performance in sport.
Robust autonomous flight and mission management for MAVs in GPS-denied environments

This paper addresses the problem of autonomous flight in GPS-denied environments. We present our systematic solution with integrated hardware and software design, robust state estimation and mission management. A micro aerial vehicle (MAV) equipped with 2D laser scanner, camera, on-board computer and flight controller is designed and constructed to realize our flight missions. The 2D laser-based localization and Kalman filter-based sensor fusion provide a robust state estimation for the MAV. We also design a task tree-based mission management method to handle a complete mission with multiple tasks. Moreover, vision-based detection algorithms complement various tasks, such as target searching and precision landing. Extensive experimental results demonstrate the robustness and effectiveness of the overall integrated system. It was also validated by our championship winning in Singapore Amazing Flight Machine Competition (SAFMC) 2017.
Mapping and Evaluation of NDVI Trends from Synthetic Time Series Obtained by Blending Landsat and MODIS Data around a Coalfield on the Loess Plateau

The increasingly intensive and extensive coal mining activities on the Loess Plateau pose a threat to the fragile local ecosystems. Quantifying the effects of coal mining activities on environmental conditions is of great interest for restoring and managing the local ecosystems and resources. This paper generates dense NDVI (Normalized Difference Vegetation Index) time series between 2000 and 2011 at a spatial resolution of 30 m by blending Landsat and MODIS (Moderate Resolution Imaging Spectroradiometer) data using the Spatial and Temporal Adaptive Reflectance Fusion Model (STARFM) and further evaluates its capability for mapping vegetation trends around a typical coalfield on the Loss Plateau. Synthetic NDVI images were generated using (1) STARFM-generated NIR (near infrared) and red band reflectance data (scheme 1) and (2) Landsat and MODIS NDVI images directly as inputs for STARFM (scheme 2). By comparing the synthetic NDVI images with the corresponding Landsat NDVI, we found that scheme 2 consistently generated better results (0.70 < R2 < 0.76) than scheme 1 (0.56 < R2 < 0.70) in this study area. Trend analysis was then performed with the synthetic dense NDVI time series and the annual maximum NDVI (NDVImax) time series. The accuracy of these trends was evaluated by comparing to those from the corresponding MODIS time series, and it was concluded that both the trends from synthetic/MODIS NDVI dense time series and synthetic/MODIS NDVImax time series (2000–2011) were highly consistent. Compared to trends from MODIS time series, trends from synthetic time series are better able to capture fine scale vegetation changes. STARFM-generated synthetic NDVI time series could be used to quantify the effects of mining activities on vegetation, but the test areas should be selected with caution, as the trends derived from synthetic and MODIS time series may be significantly different in some areas.
Enhanced dependency of KRAS‐mutant colorectal cancer cells on RAD51‐dependent homologous recombination repair identified from genetic interactions in Saccharomyces cerevisiae

Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti‐EGFR‐targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS‐mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS‐mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling. We found that KRAS mutation resulted in slowing and stalling of the replication fork and accumulation of DNA damage. Moreover, we found that KRAS‐mutant HCT116 cells have an increase in MYC‐mediated RAD51 expression with a corresponding increase in RAD51 recruitment to irradiation‐induced DNA double‐strand breaks (DSBs) compared to genetically complemented isogenic cells. MYC depletion using RNA interference significantly reduced IR‐induced RAD51 foci formation and HRR. On the contrary, overexpression of either HA‐tagged wild‐type (WT) MYC or phospho‐mutant S62A increased RAD51 protein levels and hence IR‐induced RAD51 foci. Likewise, depletion of RAD51 selectively induced apoptosis in HCT116‐mutant cells by increasing DSBs. Pharmacological inhibition targeting HRR signaling combined with PARP inhibition selectivity killed KRAS‐mutant cells. Interestingly, these differences were not seen in a second isogenic pair of KRAS WT and mutant cells (DLD‐1), likely due to their nondependency on the KRAS mutation for survival. Our data thus highlight a possible mechanism by which KRAS‐mutant‐dependent cells drive HRR in vitro by upregulating MYC‐RAD51 expression. These data may offer a promising therapeutic vulnerability in colorectal cancer cells harboring otherwise nondruggable KRAS mutations, which warrants further investigation in vivo.
Petri Net Siphon Analysis and Graph Theoretic Measures for Identifying Combination Therapies in Cancer

Epidermal Growth Factor Receptor (EGFR) signaling to the Ras-MAPK pathway is implicated in the development and progression of cancer and is a major focus of targeted combination therapies. Physiochemical models have been used for identifying and testing the signal-inhibiting potential of targeted therapies; however, their application to larger multi-pathway networks is limited by the availability of experimentally-determined rate and concentration parameters. An alternate strategy for identifying and evaluating drug-targetable nodes is proposed. A physiochemical model of EGFR-Ras-MAPK signaling is implemented and calibrated to experimental data. Essential topological features of the model are converted into a Petri net and nodes that behave as siphons—a structural property of Petri nets—are identified. Siphons represent potential drug-targets since they are unrecoverable if their values fall below a threshold. Centrality measures are then used to prioritize siphons identified as candidate drug-targets. Single and multiple drug-target combinations are identified which correspond to clinically relevant drug targets and exhibit inhibition synergy in physiochemical simulations of EGF-induced EGFR-Ras-MAPK signaling. Taken together, these studies suggest that siphons and centrality analyses are a promising computational strategy to identify and rank drug-targetable nodes in larger networks as they do not require knowledge of the dynamics of the system, but rely solely on topology.
Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5–21.4, p < 0.01 and OR 4.8, 95% CI 1.9–11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4–0.6, p < 0.01 and β 1.9, 95% CI 0.6–3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.
Iterative Refinement of Approximate Posterior for Training Directed Belief Networks

Recent advances in variational inference that make use of an inference or recognition network for training and evaluating deep directed graphical models have advanced well beyond traditional variational inference and Markov chain Monte Carlo methods. These techniques offer higher flexibility with simpler and faster inference; yet training and evaluation still remains a challenge. We propose a method for improving the per-example approximate posterior by iterative refinement, which can provide notable gains in maximizing the variational lower bound of the log likelihood and works with both continuous and discrete latent variables. We evaluate our approach as a method of training and evaluating directed graphical models. We show that, when used for training, iterative refinement improves the variational lower bound and can also improve the log-likelihood over related methods. We also show that iterative refinement can be used to get a better estimate of the log-likelihood in any directed model trained with mean-field inference.
Functional analysis of serine acetyltransferase from Mycobacterium smegmatis

Serine acetyltransferase (CysE) is involved in L‐cysteine biosynthesis in Mycobacterium, and it is important for the self‐defense mechanism of the bacteria. Mycobacterium tuberculosis CysE (Rv2335) has been identified as a serine acetyltransferase, and it is orthologous to Mycobacterium smegmatis MSMEG_5947. In this study, the MSMEG_5947 gene was cloned, expressed, and identified as a serine acetyltransferase. To investigate the function of M. smegmatis CysE, a MSMEG_5947 knockout mutant strain (M. sm‐ΔM_5947) was generated through homologous recombination. The growth and morphological characteristics of this strain were studied using growth curves and electron microscopy, respectively. M. sm‐ΔM_5947 grew slower than M. smegmatis mc2155. Electron microscopy revealed that the lack of the M. smegmatis CysE protein caused drastic morphological changes. Therefore, deletion of the serine acetyltransferase retards the growth of the Mycobacterium, but serine acetyltransferase expression is not essential for the survival of the bacteria.
Reliability of Pain Measurements Using Computerized Cuff Algometry: A DoloCuff Reliability and Agreement Study

Computerized pneumatic cuff pressure algometry (CPA) using the DoloCuff is a new method for pain assessment. Intra‐ and inter‐rater reliabilities have not yet been established. Our aim was to examine the inter‐ and intrarater reliabilities of DoloCuff measures in healthy subjects.