Miracle-dz/UniFAR-FTUs huggingface dataset:
A FUZZY-BASED FACE TRACKING SCHEME

In this paper, a technique is presented to locate and track the facial areas in videophone-type sequences. The proposed face localization methodconsists of essentially two components: i) a color processing unit, and ii) a fuzzy-based shape and color analysis module. The color processing component utilizes the distribution of skin-tones in the HSV color space to obtain an initial set of candidate regions or objects. The latter shape and color analysis module is used to correctly identify the facial regions when falsely detected objects are extracted. A number of fuzzy membership functions are devised to provide information about each object’s shape, orientation, location, and average hue. An aggregation operator (cid:12)nally combines these measures and correctly selects the facial area. The suggested approach is robust with regards to di(cid:11)erent skin types, and various types of object or background motion within the scene. Furthermore, the algorithm can be implemented at a low computational complexity due to the binary nature of the operations involved.
Persistent Human KIT Receptor Signaling Disposes Murine Placenta to Premature Differentiation Resulting in Severely Disrupted Placental Structure and Functionality

Activating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3–6 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo.
A Shift in Glycerolipid Metabolism Defines the Follicular Fluid of IVF Patients with Unexplained Infertility

Follicular fluid (FF) constitutes the microenvironment of the developing oocyte. We recently characterized its lipid composition and found lipid signatures of positive pregnancy outcome after in vitro fertilization (IVF). In the current study, we aimed to test the hypothesis that unexplained female infertility is related to lipid metabolism, given the lipid signature of positive-outcome IVF patients we previously found. Assuming that FF samples from IVF patients with male factor infertility can represent a non-hindered metabolic microenvironment, we compared them to FF taken from women with unexplained infertility. FF from patients undergoing IVF was examined for its lipid composition. We found highly increased triacylglycerol levels, with a lower abundance of monoacylglycerols, phospholipids and sphingolipids in the FF of patients with unexplained infertility. The alterations in the lipid class accumulation were independent of the body mass index (BMI) and were altogether kept across the age groups. Potential lipid biomarkers for pregnancy outcomes showed a highly discriminative abundance in the FF of unexplained infertility patients. Lipid abundance distinguished IVF patients with unrecognized infertility and provided a potential means for the evaluation of female fertility.
Eicosapentaenoic acid limitation decreases weight and fecundity of the invading predator Bythotrephes longimanus

Bythotrephes longimanus is an invasive predatory cladoceran that is negatively impacting North American zooplankton in the Laurentian Great Lakes and on the Canadian Shield. Concurrently, algal community composition, which affects zooplankton food quality, is changing in many lakes of the Canadian Shield. The n-3 fatty acid eicosapentaenoic acid (EPA) is highly retained in Bythotrephes, but the effects of EPA limitation on Bythotrephes’ population dynamics are unknown. To test the hypothesis that EPA limitation results in decreased weight and fecundity of Bythotrephes, the green alga Scenedesmus obliquus was cultured in the laboratory, split into EPA-enriched lines and un-enriched controls, then fed to Daphnia ambigua, which were in turn offered to juvenile Bythotrephes. Bythotrephes consuming EPA-enriched daphniids were heavier and had larger clutch sizes than those consuming control daphniids. Both diets supported ontogenesis, but not brood release, of Bythotrephes. To understand why laboratory-reared Bythotrephes did not release broods, we compared their fatty acid profiles with those of field-collected specimens, and found that they were EPA impoverished compared with field-collected conspecifics. Our results suggest that EPA availability influences Bythotrephes population dynamics, establishment success and impacts in nature.
Screening and Evaluation of Novel Compounds against Hepatitis B Virus Polymerase Using Highly Purified Reverse Transcriptase Domain

Hepatitis B virus (HBV) polymerase seems to be very hard to express and purify sufficiently, which has long hampered the generation of anti-HBV drugs based on the nature of the polymerase. To date, there has been no useful system developed for drug screening against HBV polymerase. In this study, we successfully obtained a highly purified reverse transcriptase (RT) domain of the polymerase, which has a template/primer and substrate binding activity, and established a novel high-throughput screening (HTS) system using purified RT protein for finding novel polymerase inhibitors. To examine whether the assay system provides reliable results, we tested the small scale screening using pharmacologically active compounds. As a result, the pilot screening identified already-known anti-viral polymerase agents. Then, we screened 20,000 chemical compounds and newly identified four hits. Several of these compounds inhibited not only the HBV RT substrate and/ template/primer binding activity, but also Moloney murine leukemia virus RT activity, which has an elongation activity. Finally, these candidates did show to be effective even in the cell-based assay. Our screening system provides a useful tool for searching candidate inhibitors against HBV.
Displacement of Slow-Turnover DNA Glycosylases by Molecular Traffic on DNA

In the base excision repair pathway, the initiating enzymes, DNA glycosylases, remove damaged bases and form long-living complexes with the abasic DNA product, but can be displaced by AP endonucleases. However, many nuclear proteins can move along DNA, either actively (such as DNA or RNA polymerases) or by passive one-dimensional diffusion. In most cases, it is not clear whether this movement is disturbed by other bound proteins or how collisions with moving proteins affect the bound proteins, including DNA glycosylases. We have used a two-substrate system to study the displacement of human OGG1 and NEIL1 DNA glycosylases by DNA polymerases in both elongation and diffusion mode and by D4, a passively diffusing subunit of a viral DNA polymerase. The OGG1–DNA product complex was disrupted by DNA polymerase β (POLβ) in both elongation and diffusion mode, Klenow fragment (KF) in the elongation mode and by D4. NEIL1, which has a shorter half-life on DNA, was displaced more efficiently. Hence, both possibly specific interactions with POLβ and nonspecific collisions (KF, D4) can displace DNA glycosylases from DNA. The protein movement along DNA was blocked by very tightly bound Cas9 RNA-targeted nuclease, providing an upper limit on the efficiency of obstacle clearance.
Visual Field Estimation by Probabilistic Classification

The gold standard clinical tool for evaluating visual dysfunction in cases of glaucoma and other disorders of vision remains the visual field or threshold perimetry exam. Administration of this exam has evolved over the years into a sophisticated, standardized, automated algorithm that relies heavily on specifics of disease processes particular to common retinal disorders. The purpose of this study is to evaluate the utility of a novel general estimator applied to visual field testing. A multidimensional psychometric function estimation tool was applied to visual field estimation. This tool is built on semiparametric probabilistic classification rather than multiple logistic regression. It combines the flexibility of nonparametric estimators and the efficiency of parametric estimators. Simulated visual fields were generated from human patients with a variety of diagnoses, and the errors between simulated ground truth and estimated visual fields were quantified. Error rates of the estimates were low, typically within 2 dB units of ground truth on average. The greatest threshold errors appeared to be confined to the portions of the threshold function with the highest spatial frequencies. This method can accurately estimate a variety of visual field profiles with continuous threshold estimates, potentially using a relatively small number of stimuli.
Blockchain-Enabled Contextual Online Learning Under Local Differential Privacy for Coronary Heart Disease Diagnosis in Mobile Edge Computing

Due to the increasing medical data for coronary heart disease (CHD) diagnosis, how to assist doctors to make proper clinical diagnosis has attracted considerable attention. However, it faces many challenges, including personalized diagnosis, high dimensional datasets, clinical privacy concerns and insufficient computing resources. To handle these issues, we propose a novel blockchain-enabled contextual online learning model under local differential privacy for CHD diagnosis in mobile edge computing. Various edge nodes in the network can collaborate with each other to achieve information sharing, which guarantees that CHD diagnosis is suitable and reliable. To support the dynamically increasing dataset, we adopt a top-down tree structure to contain medical records which is partitioned adaptively. Furthermore, we consider patients’ contexts (e.g., lifestyle, medical history records, and physical features) to provide more accurate diagnosis. Besides, to protect the privacy of patients and medical transactions without any trusted third party, we utilize the local differential privacy with randomised response mechanism and ensure blockchain-enabled information-sharing authentication under multi-party computation. Based on the theoretical analysis, we confirm that we provide real-time and precious CHD diagnosis for patients with sublinear regret, and achieve efficient privacy protection. The experimental results validate that our algorithm outperforms other algorithm benchmarks on running time, error rate and diagnosis accuracy.
A Local Approach for Computing Smooth B-Spline Surfaces for Arbitrary Quadrilateral Base Meshes

We present a method for approximating surface data of arbitrary topology by a model of smoothly connected B-spline surfaces. Most of the existing solutions for this problem use constructions with limited degrees-of-freedom or they address smoothness between surfaces in a post-processing step, often leading to undesirable surface behavior in proximity of the boundaries. Our contribution is the design of a local method for the approximation process. We compute a smooth B-spline surface approximation without imposing restrictions on the topology of a quadrilateral base mesh defining the individual B-spline surfaces, the used B-spline knot vectors, or the number of B-spline control points. Exact tangent plane continuity can generally not be achieved for a set of B-spline surfaces for an arbitrary underlying quadrilateral base mesh. Our method generates a set of B-spline surfaces that lead to a nearly tangent plane continuous surface approximation and is watertight, i.e., continuous. The presented examples demonstrate that we can generate B-spline approximations with differences of normal vectors along shared boundary curves of less than one degree. Our approach can also be adapted to locally utilize other approximation methods leading to higher orders of continuity.
Analysis of Gastrointestinal Responses Revealed Both Shared and Specific Targets of Zinc Oxide and Carbadox in Weaned Pigs

Antibiotics and pharmacological zinc supplementation were commonly used as growth promoters for several decades in the swine industry before being limited because of public health and environmental concerns. Further, the physiological and metabolic responses associated with their growth promotion effects are unclear. To characterize these responses induced by pharmacological zinc supplementation (2500 mg/kg) and carbadox (55 mg/kg), 192 post-weaning pigs were fed basal and test diets for 43 days. Compared with basal, pharmacological zinc and carbadox independently improved growth performance. Pharmacological zinc increased gastric mucosa thickness compared with basal zinc, while carbadox increased intestinal villus:crypt ratio compared with non-carbadox. Pharmacological zinc and carbadox independently reduced interleukin (IL)-1β concentration compared with basal zinc and non-carbadox. Pharmacological zinc increased IL-1RA:IL-1 ratio by 42% compared with basal zinc, while carbadox tended to increase the IL-10 and IL10:IL-12 ratio compared with non-carbadox. Carbadox increased fecal concentrations of histidine and lysine compared with non-carbadox. The independent effect of pharmacological zinc and carbadox on morphology and nutrient metabolism, and their shared effect on immunity may contribute to the additive effect on growth promotion. These results further confirmed the concept that growth promotion is multifactorial intervention. Therefore, elucidating growth-promoting effects and searching for alternatives should include wide-spectrum evaluation.
Episodic Breathlessness with and without Background Dyspnea in Advanced Cancer Patients Admitted to an Acute Supportive Care Unit

Aim: To characterize episodic breathlessness (EB) in patients with advanced cancer, and to determine factors influencing its clinical appearance. Methods: A consecutive sample of advanced cancer patients admitted to an acute palliative care unit was surveyed. Continuous dyspnea and EB were measured by a numerical scale. The use of drugs used for continuous dyspnea and EB was recorded. Patients were asked about the characteristics of EB (frequency, intensity, duration and triggers). The Multidimensional dyspnea profile (MDP), the Brief dyspnea inventory (BDI), the Athens sleep scale (AIS) and the Hospital Anxiety and Depression Scale (HADS) were also administered. Results: From 439 advanced cancer patients surveyed, 34 and 27 patients had EB, without and with background dyspnea, respectively. The mean intensity and the number of episodes were higher in patients with background dyspnea (p < 0.0005 and p = 0.05, respectively). No differences in duration were observed. Most episodes lasted <10 min. A recognizable cause triggering EB was often found. The presence of both background dyspnea and EB was associated with higher values of MDP and BDI. EB was independently associated with frequency and intensity of background dyspnea (OR = 20.9, 95% CI (Confidence interval) 9.1–48.0; p < 0.0005 and OR = 1.97, 95% CI 1.09–3.58; p = 0.025, respectively) and a lower Karnofsky level (OR = 0.96, 95%CI 0.92–0.98, p = 0.05). Discussion: EB may occur in patients with and without continuous dyspnea, and is often induced by physical and psychological factors. EB intensity is higher in patients with continuous dyspnea. The duration was often so short that the use of drugs, as needed, may be too late, unless administered pre-emptively when the trigger was predictable.
Post-Translational Modifications of Extracellular Proteasome

The ubiquitin-proteasome system (UPS) is one of the major protein degradation pathways in eukaryotic cells. Abnormal functioning of this system has been observed in cancer and neurological diseases. The 20S proteasomes, essential components of the UPS, are present not only within the cells but also in the extracellular space, and their concentration in blood plasma has been found to be elevated and dependent upon the disease state, being of prognostic significance in patients suffering from cancer, liver diseases, and autoimmune diseases. However, functions of extracellular proteasomes and mechanisms of their release by cells remain largely unknown. The main mechanism of proteasome activity regulation is provided by modulation of their composition and post-translational modifications (PTMs). Moreover, diverse PTMs of proteins are known to participate in the loading of specific elements into extracellular vesicles. Since previous studies have revealed that the transport of extracellular proteasomes may occur via extracellular vesicles, we have set out to explore the PTMs of extracellular proteasomes in comparison to cellular counterparts. In this work, cellular and extracellular proteasomes were affinity purified and separated by SDS-PAGE for subsequent trypsinization and matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) analysis. In total, we could identify 64 and 55 PTM sites in extracellular and cellular proteasomes, respectively, including phosphorylation, ubiquitination, acetylation, and succinylation. We observed novel sites of acetylation at K238 and K192 of the proteasome subunits β2 and β3, respectively, that are specific for extracellular proteasomes. Moreover, cellular proteasomes show specific acetylation at K227 of α2 and ubiquitination at K201 of β3. Interestingly, succinylation of β6 at the residue K228 seems not to be present exclusively in extracellular proteasomes, whereas both extracellular and cellular proteasomes may also be acetylated at this site. The same situation takes place at K201 of the β3 subunit where ubiquitination is seemingly specific for cellular proteasomes. Moreover, crosstalk between acetylation, ubiquitination, and succinylation has been observed in the subunit α3 of both proteasome populations. These data will serve as a basis for further studies, aimed at dissection of the roles of extracellular proteasome-specific PTMs in terms of the function of these proteasomes and mechanism of their transport into extracellular space.
In silico structural analysis of sequences containing 5-hydroxymethylcytosine reveals its potential as binding regulator for development, ageing and cancer-related transcription factors

ABSTRACT The presence of 5-hydroxymethyl cytosine in DNA has been previously associated with ageing. Using in silico analysis of normal liver samples we presently observed that in 5-hydroxymethyl cytosine sequences, DNA methylation is dependent on the co-presence of G-quadruplexes and palindromes. This association exhibits discrete patterns depending on G-quadruplex and palindrome densities. DNase-Seq data show that 5-hydroxymethyl cytosine sequences are common among liver nucleosomes (p < 2.2x10−16) and threefold more frequent than nucleosome sequences. Nucleosomes lacking palindromes and potential G-quadruplexes are rare in vivo (1%) and nucleosome occupancy potential decreases with increasing G-quadruplexes. Palindrome distribution is similar to that previously reported in nucleosomes. In low and mixed complexity sequences 5-hydroxymethyl cytosine is frequently located next to three elements: G-quadruplexes or imperfect G-quadruplexes with CpGs, or unstable hairpin loops (TCCCAY6TGGGA) mostly located in antisense strands or finally A-/T-rich segments near these motifs. The high frequencies and selective distribution of pentamer sequences (including TCCCA, TGGGA) probably indicate the positive contribution of 5-hydroxymethyl cytosine to stabilize the formation of structures unstable in the absence of this cytosine modification. Common motifs identified in all total 5-hydroxymethyl cytosine-containing sequences exhibit high homology to recognition sites of several transcription factor families: homeobox, factors involved in growth, mortality/ageing, cancer, neuronal function, vision, and reproduction. We conclude that cytosine hydroxymethylation could play a role in the recognition of sequences with G-quadruplexes/palindromes by forming epigenetically regulated DNA ‘springs’ and governing expansions or compressions recognized by different transcription factors or stabilizing nucleosomes. The balance of these epigenetic elements is lost in hepatocellular carcinoma.
On Diversity in Image Captioning: Metrics and Methods

Diversity is one of the most important properties in image captioning, as it reflects various expressions of important concepts presented in an image. However, the most popular metrics cannot well evaluate the diversity of multiple captions. In this paper, we first propose a metric to measure the diversity of a set of captions, which is derived from latent semantic analysis (LSA), and then kernelize LSA using CIDEr (R. Vedantam et al., 2015) similarity. Compared with mBLEU (R. Shetty et al., 2017), our proposed diversity metrics show a relatively strong correlation to human evaluation. We conduct extensive experiments, finding there is a large gap between the performance of the current state-of-the-art models and human annotations considering both diversity and accuracy; the models that aim to generate captions with higher CIDEr scores normally obtain lower diversity scores, which generally learn to describe images using common words. To bridge this “diversity” gap, we consider several methods for training caption models to generate diverse captions. First, we show that balancing the cross-entropy loss and CIDEr reward in reinforcement learning during training can effectively control the tradeoff between diversity and accuracy of the generated captions. Second, we develop approaches that directly optimize our diversity metric and CIDEr score using reinforcement learning. These proposed approaches using reinforcement learning (RL) can be unified into a self-critical (S. J. Rennie et al., 2017) framework with new RL baselines. Third, we combine accuracy and diversity into a single measure using an ensemble matrix, and then maximize the determinant of the ensemble matrix via reinforcement learning to boost diversity and accuracy, which outperforms its counterparts on the oracle test. Finally, inspired by determinantal point processes (DPP), we develop a DPP selection algorithm to select a subset of captions from a large number of candidate captions. The experimental results show that maximizing the determinant of the ensemble matrix outperforms other methods considerably improving diversity and accuracy.