Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid‐β up‐regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age‐related macular degeneration

One of the earliest signs of age‐related macular degeneration (AMD) is the formation of drusen which are extracellular deposits beneath the retinal pigmented epithelium (RPE). To investigate the relationship between drusen and AMD, we focused on amyloid β (Aβ), a major component of drusen and also of senile plaques in the brain of Alzheimer's patients. We previously reported that Aβ was accumulated in drusen‐like structure in senescent neprilysin gene‐disrupted mice. The purpose of this study was to investigate the influence of Aβ on factor B, the main activator of the complement alternative pathway. The results showed that Aβ did not directly modulate factor B expression in RPE cells, but increased the production of monocyte chemoattractant protein‐1 (MCP‐1). Aβ also increased the production of IL‐1β and TNF‐α in macrophages/microglia, and exposure of RPE cells to IL‐1β and TNF‐α significantly up‐regulated factor B. Co‐cultures of RPE cells and macrophages/microglia in the presence of Aβ significantly increased the expression of factor B in RPE. These findings indicate that cytokines produced by macrophages/microglia that were recruited by MCP‐1 produced in RPE cells stimulated by Aβ up‐regulate factor B in RPE cells. Thus, a combined mechanism exists for Aβ‐induced for the activation of the complement alternative pathway in the subretinal space; cytokine‐induced up‐regulation of activator factor B and dysfunction of the inhibitor factor I by direct binding to Aβ as suggested in our earlier study. J. Cell. Physiol. 220: 119–128, 2009. © 2009 Wiley‐Liss, Inc.
Fast Statistical Full-Chip Leakage Analysis for Nanometer VLSI Systems

In this article, we present a new full-chip statistical leakage estimation considering the spatial correlation condition (strong or weak). The new algorithm can deliver linear time, O(N), time complexity, where N is the number of grids on chip. The proposed algorithm adopts a set of uncorrelated virtual variables over grid cells to represent the original physical random variables and the cell size is determined by the spatial correlation length. In this way, each physical variable is always represented by virtual variables locally. We prove the number of neighbor cells for each grid cell is not related to the condition of spatial correlation (from no correlation to 100% correlated), which leads to linear time complexity in terms of number of gates. We compute the gate leakage by the orthogonal polynomials-based collocation method. The total leakage of a whole chip can be computed by simply summing up the coefficients of corresponding orthogonal polynomials in each grid cell. Furthermore, we develop a look-up table to cache statistical information for each type of gate instead of calculating leakage for every single instance of gate on a chip. As a result, a new statistical leakage characterization in Standard Cell Library (SCL) is put forward. Furthermore, an incremental analysis algorithm is proposed to update the chip-level statistical leakage information efficiently after a few changes are made. The proposed method has no restrictions on static leakage models, or types of leakage distributions. The large circuit examples in 45nm CMOS process demonstrate the proposed algorithm is 1000X faster than a recently proposed grid-based method with similar accuracy and many orders of magnitude times speedup over the Monte Carlo method. Experimental results also show the incremental analysis provides about 10X further speedup. We expect the incremental analysis could achieve more speedup over the full leakage analysis for larger problem sizes.
MicroRNA-125b Functions as a Tumor Suppressor in Hepatocellular Carcinoma Cells

MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3′ UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.
Two-dimensional Model of Fluid Flow and Distribution of Nutrient Concentration in a Microfluidic Device

Abstract: During the past few years, the process of miniaturisation in the field of biochemical laboratory equipment led to the introduction of the so-called “lab-on-a-chip” microdevices, which combine separate functional units into a complex, multifunctional apparatus. Fluid dynamics plays an essential role in the development of such equipment, since frequently the major part of chemical analysis is based on soluble analytes. In this work, we consider a device for the analysis of cell growth under different conditions. In this device, dozens of cell spots absorb the nutrient (analyte) from the liquid medium. The concentration of the analyte must be strictly controlled to maintain a specific microenvironment. A two-dimensional model for the flow field and the distribution of concentration of the analyte is developed taking into account the geometrical shape of the spot with a simplified absorption model. The dependence of the results on the controlling parameters is investigated in order to determine the influence of the presence of the cell spot on the distribution of the analyte.
High angular resolution light field reconstruction with coded-aperture mask

In the past decade, light field imaging has greatly extended the imaging capabilities of traditional photography. However, the applications of light field imaging are limited by the aliasing artifacts due to the plenoptic sampling trade-off between angular and spatial domains. We propose to use a coded aperture light field camera instead of the traditional one, which can get more angular information without losing spatial resolution. To that end, we exploit a theoretical model to explain the relationship between light field and the raw data captured by the sensor. Then, we design a mask to code the rays using compressive sensing. Last, the sparse characteristic of light field in gradient domain and the corresponding optimization methods are utilized to reconstruct the high angular resolution light field. Experimental results on synthetic data and real data demonstrate that our system can obtain high angular resolution light field by producing a low-aliasing refocused image and high PSNR multi-view images.
Asymmetric Thermal Structure for Frequency Stabilized Two-Mode Lasers

In order to improve the frequency stabilization and the anti-interference ability of two-mode power-balance lasers, the asymmetric thermal structure made up of several thermal transfer layers with different heat transfer coefficient is proposed. Through the heat isolation effect of the middle layer in the structure, the laser has asymmetric thermal responses to electric heater control and air interference. So the anti-interference ability of the system is improved by keeping a low speed in air disturbance while keeping a high speed in thermal stabilization. Several experiments were made with two-mode laser to prove the effectiveness of the proposed method. The experimental results indicate that, frequency stability of the two-mode power-balance laser based on asymmetric thermal structure can be locked in 4.1×10-10 in ordinary lab condition, while it becomes 1.9×10-9 where the air velocity is 1m/s.
Biomimetic synthesis of the calcineurin phosphatase inhibitor dibefurin.

Dibefurin is a Ci -symmetric natural product that acts as an inhibitor of calcineurin phosphatase. A six-step synthesis of this compound is reported, which features an oxidative dimerization of the aromatic polyketide epicoccine as the key step. Dibefurin is proposed to be related to epicolactone, a complex yet racemic fungal metabolite that has recently been discovered. Attempts to access epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that is formed through a hetero-Diels-Alder reaction of a para-quinone methide with an ortho-quinone.
N-glycosylation converts non-glycoproteins into mannose receptor ligands and reveals antigen-specific T cell responses in vivo

N-glycosylation is generally accepted to enhance the immunogenicity of antigens because of two main reasons. First, the attachment of glycans enables recognition by endocytic receptors like the mannose receptor (MR) and hence increased uptake by dendritic cells (DCs). Second, foreign glycans are postulated to be immunostimulatory and their recognition could induce DC activation. However, a direct comparison between the immunogenicity of N-glycosylated vs. de-glycosylated proteins in vivo and a direct effect of N-glycosylated antigens on the intrinsic capacity of DCs to activate T cells have not been assessed so far. To analyze whether enforced N-glycosylation is a suited strategy to enhance the immunogenicity of non-glycosylated antigens for vaccination studies, we targeted non-glycoproteins towards the MR by introduction of artificial N-glycosylation using the methylotrophic yeast Komagataella phaffii (previously termed Pichia pastoris). We could demonstrate that the introduction of a single N-X-S/T motif was sufficient for efficient MR-binding and internalization. However, addition of N-glycosylated proteins neither influenced DC maturation nor their general capacity to activate T cells, pointing out that enforced N-glycosylation does not increase the immunogenicity of the antigen per se. Additionally, increased antigen-specific cytotoxic T cell responses in vivo after injection of N-glycosylated compared to de-glycosylated proteins were observed but this effect strongly depended on the epitope tested. A beneficial effect of N-glycosylation on antibody production could not be detected, which might be due to MR-cross-linking on DCs and to concomitant differences in IL-6 production by CD4+ T cells. These observations point out that the effect of N-glycosylation on antigen immunogenicity can vary between different antigens and therefore might have important implications for the development of vaccines using K. phaffii.
Systems modelling ageing: from single senescent cells to simple multi-cellular models

Systems modelling has been successfully used to investigate several key molecular mechanisms of ageing. Modelling frameworks to allow integration of models and methods to enhance confidence in models are now well established. In this article, we discuss these issues and work through the process of building an integrated model for cellular senescence as a single cell and in a simple tissue context.
The Adolescent Brain Cognitive Development Study.

The Adolescent Brain Cognitive Development (ABCD) Study is a longitudinal, observational study of over 10,000 youth recruited at 21 sites through-out the United States. School-based recruiting strategies are used to enroll a diverse cohort of 9-and 10-year-old children with the goal of following youth for at least 10 years. A team of epidemiolo-gists and biostatisticians has designed the sampling methods to ensure that the cohort resembles the U.S. population as closely as possible on sociode-mographic variables. Comprehensive biennial assessments and more limited interim assessments measure health, mental health, neurocognition, family, cultural, and environmental variables; substance use, genetic, and other biomarkers; and structural and functional brain development. A full descrip-tion of these protocols, with lists of the instruments and methods used for each assessment domain, can be reached from the Scientists page of the ABCD Study website (ABCDStudy.org).
RhoD Binds the Rab5 Effector Rabankyrin‐5 and has a Role in Trafficking of the Platelet‐derived Growth Factor Receptor

RhoD is a member of the classical Rho GTPases and it has essential roles in the regulation of actin dynamics. RhoD localizes to early endosomes and recycling endosomes, which indicates its important role in the regulation of endosome trafficking. Here, we show that RhoD binds to the Rab5 effector Rabankyrin‐5, and RhoD and Rabankyrin‐5 colocalize to Rab5‐positive endosomes, which suggests a role for Rabankyrin‐5 in the coordination of RhoD and Rab5 in endosomal trafficking. Interestingly, depletion of RhoD using siRNA techniques interfered with the internalization of the PDGFβ receptor and the subsequent activation of the downstream signaling cascades. Our data suggest that RhoD and Rabankyrin‐5 have important roles in coordinating RhoD and Rab activities during internalization and trafficking of activated tyrosine kinase receptors.
Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study

Background:Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. Methods:We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. Results:MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. Discussion:Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.
Predicting Comorbidities Using Resampling and Dynamic Bayesian Networks with Latent Variables

Comorbidities such as hypertension and lipid metabolism are often associated in diseases such as diabetes, and the early prediction of these is of great value when trying to manage progression. This is the start of a project to model multiple comorbidities in diabetes using dynamic Bayesian networks with latent variables in order to stratify patient cohorts. In this paper, we demonstrate some initial results on a dataset where the class imbalance problem poses an issue due to the rare occurrence of different individual comorbidities on a visit-by-visit basis. This is dealt with using a bootstrap technique that has been specifically designed for longitudinal data where the occurrence of the positive class occurs far less than the negative.
Design of a High Performance Carry Generation Circuit for Ternary Full Adder Using CNTFET

The Full Adder is one of the most important and basic units of arithmetic logics which is used to design many complex circuits. Further, ternary logic is a promising alternative to the conventional binary logic in VLSI design as it provides the advantages of reduced interconnects, higher operating speeds and smaller chip area. The present work aims to design high performance ternary full adder (TFA) by using carbon nanotube field effect transistors (CNTFET). The proposed TFA designs were simulated using HSPICE to obtain critical delay, power delay product (PDP) and maximum operating frequency. Further the circuit performance also has been compared with recently reported TFA. The factors which are considered for comparison are transistor count, delay, PDP and maximum operating frequency. The comparison results infer that the proposed TFA gives outstanding performance as compared to the reported one. The proposed TFA has been demonstrated delay, PDP and maximum operating frequency improvement up to 29%, 20% and 39% respectively. The transistor counts for the proposed circuits are also reduced by almost 15%.
Verified security of redundancy-free encryption from Rabin and RSA

Verified security provides a firm foundation for cryptographic proofs by means of rigorous programming language techniques and verification methods. EasyCrypt is a framework that realizes the verified security paradigm and supports the machine-checked construction and verification of cryptographic proofs using state-of-the-art SMT solvers, automated theorem provers and interactive proof assistants. Previous experiments have shown that EasyCrypt is effective for a posteriori validation of cryptographic systems. In this paper, we report on the first application of verified security to a novel cryptographic construction, with strong security properties and interesting practical features. Specifically, we use EasyCrypt to prove in the Random Oracle Model the IND-CCA security of a redundancy-free public-key encryption scheme based on trapdoor one-way permutations. Somewhat surprisingly, we show that even with a zero-length redundancy, Boneh's SAEP scheme (an OAEP-like construction with a single-round Feistel network rather than two) converts a trapdoor one-way permutation into an IND-CCA-secure scheme, provided the permutation satisfies two additional properties. We then prove that the Rabin function and RSA with short exponent enjoy these properties, and thus can be used to instantiate the construction we propose to obtain efficient encryption schemes. The reduction that justifies the security of our construction is tight enough to achieve practical security with reasonable key sizes.
Spoiler alert: Machine learning approaches to detect social media posts with revelatory information

Spoilers---critical plot information about works of fiction that "spoil" a viewer's enjoyment---have prompted elaborate conventions on social media to allow readers to insulate themselves from spoilers. However, these solutions depend on the conscientiousness and rigor of Internet posters and are thus an imperfect system. We create an automatic alternative that could alert users when a piece of text contains a spoiler. An automated spoiler detector serves not only as an additional protection against spoilers, but it also contributes to important problems in computational linguistics. We develop a new dataset of spoilers gathered from social media and create automatic classifiers using machine learning techniques. After establishing baseline performance using lexical features, we develop metadata-based features that substantially improve performance on the spoiler detection task.
BCI-based control of electric wheelchair

BCI (Brain-computer Interface) has been attracting attention as an interface to connect the brain to external devices. However, it is essential to establish methods to recognize the brain state accurately in order to implement BCI, and a number of challenges still remain. Here, we suggest a novel BCI system that accurately recognizes and isolates emotions like delight, anger, sorrow, and pleasure using an Emotion Fractal Analysis Method (EFAM), which can quantify emotions based on data obtained by electroencephalography, and control an electric wheelchair using the information. With this method, a high average rate of recognizing emotions (delight, anger, sorrow, and pleasure) of 55-60% and markedly high rate of isolating them of over 97% can be achieved. We developed the BCI circuit to control an electric wheelchair based on data on emotions obtained in realtime by EFAM. Using this circuit, the speed of an electric wheelchair can be adjusted by the intensity of emotions.
Control of hmu Heme Uptake Genes in Yersinia pseudotuberculosis in Response to Iron Sources

Despite the mammalian host actively sequestering iron to limit pathogenicity, heme (or hemin when oxidized) and hemoproteins serve as important sources of iron for many bloodborne pathogens. The HmuRSTUV hemin uptake system allows Yersinia species to uptake and utilize hemin and hemoproteins as iron sources. HmuR is a TonB-dependent outer membrane receptor for hemin and hemoproteins. HmuTUV comprise a inner membrane ABC transporter that transports hemin and hemoproteins from the periplasmic space into the bacterial cytoplasm, where it is degraded by HmuS. Here we show that hmuSTUV but not hmuR are expressed under iron replete conditions, whereas hmuR as well as hmuSTUV are expressed under iron limiting conditions, suggesting complex transcriptional control. Indeed, expression of hmuSTUV in the presence of inorganic iron, but not in the presence of hemin, requires the global regulator IscR acting from a promoter in the intergenic region between hmuR and hmuS. This effect of IscR appears to be direct by binding a site mapped by DNaseI footprinting. In contrast, expression of hmuR under iron limiting conditions requires derepression of the ferric uptake regulator Fur acting from the hmuR promoter, as Fur binding upstream of hmuR was demonstrated biochemically. Differential expression by both Fur and IscR would facilitate maximal hemin uptake and utilization when iron and heme availability is low while maintaining the capacity for periplasmic removal and cytosolic detoxification of heme under a wider variety of conditions. We also demonstrate that a Y. pseudotuberculosis ΔiscR mutant has a survival defect when incubated in whole blood, in which iron is sequestered by heme-containing proteins. Surprisingly, this phenotype was independent of the Hmu system, the type III secretion system, complement, and the ability of Yersinia to replicate intracellularly. These results suggest that IscR regulates multiple virulence factors important for Yersinia survival and growth in mammalian tissues and reveal a surprising complexity of heme uptake expression and function under differing conditions of iron.