Miracle-dz/UniFAR-FTUs huggingface dataset:
Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

Background: Smoke components can generate 1) oxidative stress; 2) complement activation; 3) endoplasmic reticulum stress; and 4) lipid dysregulation. Results: In smoke-exposed RPE cells all four measures were activated, and reversed by antioxidants and blocking alternative complement pathway signaling. Conclusion: Oxidative stress and complement act synergistically in age-related macular degeneration (AMD) pathogenesis. Significance: Identifying mechanisms of lipid deposition will aid to develop new therapeutic approaches for AMD. Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD.
Gender Differences in Cardiac Ischemic Injury and Protection—Experimental Aspects

This review summarizes some available information on gender differences of myocardial injury with particular attention to experimental approach. It has been observed that significant gender differences exist already in normal heart. They involve among others cardiac growth, contractile function, calcium metabolism and function of mitochondria. Differences, characteristic of the normal myocardium, generate the logical presumption of the different reaction of the male and female heart to various pathogenic factors. Most of the experimental studies confirm the clinical observations: increased resistance of the female heart to ischemia/reperfusion injury was shown in dogs, rats, mice and rabbits. Furthermore, gender differences in the ischemic tolerance of the adult myocardium can be influenced by interventions (e.g. hypoxia) imposed during the early phases of ontogenetic development. The already high tolerance of the adult female heart can be increased by adaptation to chronic hypoxia and ischemic preconditioning. It seems that the protective effect depends on age: it was absent in young, highly tolerant heart but it appeared with the decrease of natural resistance during aging. Both experimental and clinical studies have indicated that female gender influences favorably also the remodeling and the adaptive response to myocardial infarction. It follows from the data available that male and female heart differs significantly in many parameters under both physiological and pathological conditions. Detailed molecular and cellular mechanisms of these differences are still unknown; they involve genomic and non-genomic effects of sex steroid hormones, particularly the most frequently studied estrogens. The cardiovascular system is, however, influenced not only by estrogens but also by other sex hormones, e.g. androgens. Moreover, steroid hormone receptors do not act alone but interact with a broad array of co-regulatory proteins to alter transcription. The differences are so important that they deserve serious consideration in clinical practice in search for proper diagnostic and therapeutic procedures.
Meaning in life, resilience, and psychological well-being among children affected by parental HIV

ABSTRACT Meaning in life has been posited to improve psychological well-being. People facing adversities can reduce psychological distress through pursuing a sense of purpose in life. However, the effectiveness of meaning in life in promoting psychological well-being has been found varied, and what factors may affect the function of meaning in life remain unclear. In this paper, the authors suggest that resilience, the positive adaptation during or following significant adversity, can strengthen the protective effects of meaning in life on psychological well-being. To test this hypothesis, we analyzed data from a sample of 518 vulnerable children of parents living with HIV about their meaning in life, resilience, depression, and loneliness. Results showed that resilience moderated the relationship between meaning in life and depression, and between meaning in life and loneliness. Meaning in life was associated with lower levels of depression and loneliness among children high in resilience, in comparison to children low in resilience. Future interventions targeting meaning in life and well-being should consider children’s resilience, which can allow for better individualization of the treatment.
Isolation of St. Louis encephalitis virus from adult Dermacentor variabilis (Acari: Ixodidae).

St. Louis encephalitis (SLE) virus was isolated from adult Dermacentor variabilis ticks removed from a Raccoon (Procyon lotor) captured in Memphis, Tennessee, USA, on 24 May 1979. Neutralizing antibody against SLE virus was detected in mammals from the same area. The epidemiologic significance of the isolate is unknown.
Feature-preserving mesh denoising via attenuated bilateral normal filtering and quadrics

In this paper, we propose a two phase feature-preserving mesh denoising algorithm. The first phase consists of modified bilateral filtering applied on field of face normals. The range filtering is affected by gradual attenuation of the standard deviation of normal differences along with subsequent iteration. We also provide a method for automatic estimation of the bilateral filter parameters without user interaction. Filtering process is followed by reconstruction of the mesh vertex positions from a given field of face normals. Our method is based on geometric fact that every vertex should lie within all tangent planes that locally support one of its neighbouring triangles. We use quadrics to encode squared distances to the planes defined by filtered normals and centroids of the faces from 1-ring neighbourhood of considered vertex. New vertex positions are identified by minimizing quadric error metric. Our tests have shown that this iteration scheme converges faster than gradient descent algorithm. Sharp features are well preserved which will be documented on several CAD-like models.
Intranasal Loteprednol Etabonate in Healthy Male Subjects: Pharmacokinetics and Effects on Endogenous Cortisol

Loteprednol etabonate (LE) is a glucocorticoid soft drug that is currently in development for intranasal use. The main objectives of this study were to examine the pharmacokinetics and potential effects on systemic cortisol of two intranasal suspension formulations of LE and to compare these findings with placebo and fluticasone propionate (FP, Flonase®) control treatments. In this randomized, double‐blind (except for FP), parallel‐group study (n = 8/group), all subjects received for 14 days once daily in the morning two puffs of the following nasal spray formulations into each nostril: LE 0.1% (400 μg/day), LE 0.2% (800 μg/day), FP 0.05% (200 μg/day), and placebo. Drug trough levels were determined on days 1, 5, 12, 13, and 14, and a full pharmacokinetic profile was established on day 14, and 24‐hour serum cortisol profiles were assessed prior to treatment (i.e., at baseline) and after the last dose. All subjects completed the protocol without treatment‐emergent adverse findings. All formulations were rapidly absorbed (tmax less than 1 h). The rather short mean terminal half‐lives of 2.2 ± 1.5 hours and 1.8 ± 1.0 hours for LE 400 μg and LE 800 μg, respectively, and 4.2 ±1.8 hours for the 200‐μg FP treatment explained the lack of any accumulation. Mean peak concentrations (Cmax) were 139 ± 57 pg/mL with LE 400 μg and 164 ± 54 pg/mL with LE 800 μg and thus fairly independent from dose. The 200‐μg FP treatment resulted in a Cmax of only 15.5 ± 5.9 pg/mL. Mean measured AUC0‐t values (193 ± 87 pg/h/mL−1, 300 ± 183 pg/h/mL−1, and 40 ± 34 pg/h/ mL‐−1 for LE 400 μg, LE 800 μg, and FP 200 μg, respectively) showed high variability and suggested nonlinear pharmacokinetics for the LE formulations, indicative of a less complete systemic uptake of LE from the 0.2% concentration. None of the treatments (LE 400 μg, LE 800 μg, and FP 200 μg) showed evidence for serum cortisol suppression when compared with placebo, respectively. The uptake and systemic exposure appears less complete from the 0.2% LE concentration, which principally favors this formulation for further clinical development.
Enhancing RGB CNNs with depth

Most current approaches for recognition in RGB-D images fall in either the late fusion or the early fusion category. A drawback of the early fusion scheme is its inapplicability when one of the modalities is absent at test time. On the other hand, a late fusion of features does not allow the correlated nature of modalities to be exploited effectively. Recent approaches using Deep Learning are not immune to these problems either. In this work, we propose a simple, yet elegant method towards combining early and late fusion of colour and depth information when training deep Convolutional Neural Networks (CNNs). We show that when fine-tuning CNNs, an intermediate depth pre-training step provides a significant jump in colour recognition accuracy. The trends are observed consistently over several benchmark RGB-D datasets.
The microbial flora of the rumen of cows fed hay and high cereal rations and its relationship to the rumen fermentation.

Summary. The rumen microbial population associated with feeding cows 3 rations, hay alone, 20% hay/80% flaked maize and 20% hay/80% rolled barley has been examined. The differences between the hay and the cereal rations were considerable but between the cereal rations only slight. Both cereal rations provoked & large drop in the proportion of butyrivibrios, and a rise in the proportion of selenomonads, peptostreptococci, lactobacilli and bifidobacteria. The importance of these and other changes occurring in the microbial flora are discussed in relation to their possible effect on the products of the rumen fermentation.
Comparative proteome analysis and thermal stress induced changes in the embryo of poly- and bi-voltine strains of Bombyx mori

Proteins are the ultimate operating molecules producing the physiological effect in all the stages of an organism. As a consequence, proteome of the embryo play a pivotal role in determining the biological structures besides cellular organization and morphogenetic movements that occur during embryo development. But, changes in the environment temperature for few hours whether that alter the embryo development, protein expression and hatching of infants are unknown in Bombyx mori L. Hence, eggs of poly- and bi-voltine breeds were exposed to heat shock temperature of 35, 40 and 45°C for 2 h to measure tolerance level and differential expression of proteins in different age of the embryos. To facilitate comparative analysis among different breeds a comprehensive proteome map was constructed considering protein profile of different day’s embryos. Interestingly, ~10 to 21 protein bands were recorded during embryo development - from ovipostion till hatching - along with few new protein bands on day-6, which were differ in their intensity in different silkworm strains. Interestingly, no change in the protein pattern was observed in different days embryos exposed to thermal stress at 35 and 40°C. But degradation of 18 and 19 kDa proteins were recorded in all the days of embryos exposed to 45°C while four major protein bands remain unaltered. Further, the percent of hatching was slightly declined in 35 and 40°C and zero hatching was recorded in all the stages of eggs HS at 45°C. This clearly indicates that differential expression/degradation of proteins as a response to thermal stress not only influences the growth and development but also determine hatching of embryo. Accordingly, we suggest that embryonic protein map constructed in the present study shall be a valid reference for comparative analysis and hatching of embryos as one of the key traits to measure the rate of thermotolerance in the existing or new strains/breeds of B. mori.
The poor performance of TMM on microRNA-Seq.

We published our third-party comparison of seven different normalization methods that were previously employed in microarray analysis, and TMM, a method developed by Robinson and Oshlack (2010) for RNA-Seq analysis, in the context of microRNA sequencing (miRNA-Seq). We used various evaluation metrics (MSE, KS statistics, ROC curves, linear regression, and differential expression test similarities) on two independent public miRNA-Seq profiling results that had qPCR results for validation. Based on the results that used relevant R packages at the time of publication, we found (Garmire and Subramaniam 2012) that quantile and lowess normalization worked the best on the two public data sets, whereas the normalization step documented in TMM, at the time of manuscript preparation, performed the worst among all methods compared. This publication caught a tremendous amount of interest from Robinson and colleagues. They incorrectly stated many factsconcerningboththeirsoftware,whichwasmadeavailable publicly and subsequently revised, and our analysis, both in private communications as well as in their Divergent Views paper in RNA. We feel obligated to straighten the records and facts to the readers on several questions that Robinson and colleagues raised in their Divergent Views. For software that is actively being developed, such as edgeR, which uses the TMM method in their original paper, we look forward to additional improvements, such as the changes that are made in their code supplemented to their Divergent Views. Theauthorsfirstquestionedthereproducibilityofouranalysis. To answer this question, we must point out that the authors changed the software and user guidelines since the preparation of our manuscript. The changes in MSE from TMM in their Supplemental Figure 1 come from the changes intheir method. Whilepreparingthispublication,weactively sought the opinions of Robinson and colleagues given the results in Figure 3 of our recent publication (Garmire and Subramaniam 2012). We asked Robinson and colleagues directly if one should reverse the order of the numerator and denominator in calculating the normalization factor documented in their original Genome Biology paper (since we observed that doing so would improve MSE of TMM slightly). Unfortunately, Robinson and colleagues did not directly answer us, but we were pointed to their online example, which was consistent with their publication. We therefore used the normalizationfactorasdescribedbyRobinsonandcolleagues. Thisnormalizationfactorwasuseddirectlyintheirearlierversion of user guideline (dated October 14, 2010; a copy of this guidelineissubmittedtotheEditorwiththisDivergentViews
CEACAM is not necessary for Neisseria gonorrhoeae to adhere to and invade female genital epithelial cells

Neisseria gonorrhoeae has a repertoire of up to 11 opacity‐associated (Opa) proteins that are adhesins. Most Opa proteins adhere to CEACAM antigens and when CEACAM molecules are present on the surface of transfected epithelial cells their binding by Opa is thought to induce invasion of these cells by gonococci. In this study, we investigated whether several malignant epithelial cell lines, normal cervical and fallopian tube epithelial cell cultures, as well as normal fallopian tube tissue express several of the CEACAM molecules, and whether gonococci use these molecules for adherence and invasion of these female genital epithelial cells. A primary cervical cell culture and metastatic cervical cell line ME180 both expressed CEACAM as shown by whole cell ELISA and flow cytometry, and increased the surface expression of total CEACAM during incubation with Opa+ gonococci. Opa+ gonococci both adhered to and invaded these cells; CEACAM‐specific monoclonal antibody (MAb) partially abolished this interaction. Two primary fallopian epithelial tube cell cultures, a primary cervical cell culture and two malignant cell lines, HEC‐1‐B and HeLa, did not express CEACAM nor was CEACAM mRNA present. No evidence of either intracellular or secreted extracellular CEACAM was found with HEC‐1‐B and HeLa cells. Opa+ gonococci both adhered to and invaded CEACAM non‐expressing cells; however, Opa+ gonococcal association with these non‐expressing cell lines could not be inhibited with CEACAM‐specific MAb. These data show that CEACAM is not always expressed on female genital epithelial cells and is not essential for gonococcal adherence and invasion. However, when CEACAM is expressed, Opa+ gonococci exploit it for the adherence to and invasion of these cells.
A 2GHz 0.25μm SiGe BiCMOS Oscillator with Flip-Chip Mounted BAW Resonator

An RF oscillator consisting of a BAW resonator on top of a SiGe BiCMOS IC is presented. The circuit achieves a phase noise of -124dBc/Hz at 100kHz carrier offset, -160dBc/Hz floor and supply pushing of 65ppm/V while consuming 12mW in an IC footprint of 0.043mm2.
Muscle imaging in clinical practice: diagnostic value of muscle magnetic resonance imaging in inherited neuromuscular disorders

Purpose of reviewThis review reports on the use of muscle magnetic resonance imaging as a clinical and research tool in inherited neuromuscular disorders. Recent findingsSeveral papers published during the past few years have reported on the value of muscle magnetic resonance imaging in detecting patterns of muscle involvement in various muscular dystrophies and other inherited myopathies. The patterns of muscle involvement observed on muscle magnetic resonance imaging are often specific for distinct genetic entities. SummaryOur review of the literature suggests that muscle magnetic resonance imaging can provide information that is useful in clinical practice and may be used as an additional tool in a diagnostic flow chart to select appropriate genetic and biochemical investigations.
CRISPR/Cas9: An RNA‐guided highly precise synthetic tool for plant genome editing

CRISPR/Cas9 is a newly developed and naturally occurred genome editing tool, which is originally used by bacteria for immune defence. In the past years, it has been quickly employed and modified to precisely edit genome sequences in both plants and animals. Compared with the well‐developed zinc finger nucleases (ZFNs) and transcription activator‐like effector nucleases (TALENs), CRISPR/Cas9 has lots of advantages, including easier to design and implement, higher targeting efficiency, and less expensive. Thus, it is becoming one of the most powerful tools for knockout of an individual gene as well as insertion of one gene and/or control of gene transcription. Studies have shown that CRISPR/Cas9 is a great tool to edit many genes in a variety of plant species, including the model plant species as well as agriculturally important crops, such as cotton, maize, wheat, and rice. CRISPR/Cas9‐based genome editing can be used for plant functional studies and plant improvement to yield, quality, and tolerance to environmental stress.
Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus

The association between BK virus infection and hemorrhagic cystitis (HC) in hematopoietic stem cell transplant (HSCT) recipients is well established. However, BK virus-associated HC has not been described in liver transplant (LT) recipients. We present a case of BK virus-associated HC in a LT recipient. Our patient presented with worsening liver function tests 2 years after transplantation and was found to have acute cellular rejection. He was treated with increased immunosuppression and subsequently developed hematuria. He was eventually diagnosed with BK virus-associated HC.
Cervical Sagittal Alignment in Scheuermann Disease

Study Design. Retrospective evaluation of radiographs. Objective. The aim of this study was to assess sagittal cervical balance in patients with the two types Scheuermann disease (SD). Summary of Background Data. The structural hyperkyphosis characterizing SD may be localized in the thoracic (SDT) or thoraco-lumbar (SDTL) spine segments. This may affect sagittal cervical balance. Methods. Seventy-one patients (41 males and 30 females), aged 16.3 ± 3.8 years with SD, were enrolled into the study. On standing lateral long-cassette radiographs, the following measurements were made: C0-2 angle, C2-7 angle (CL), C1-C2 angle, relative rotation angle (RRA)—measured at levels from C2 to C7, cervical tilt (CT), thoracic inlet angle (TIA), T1 slope, neck tilt (NT), C0-angle, cranial offset (CO), and cranial tilt (CRT). Comparison with t test was performed with significance level P < 0.05. Results. There were 38 SDT and 33 SDTL patients. In SDT, the T1 slope was significantly greater than that in SDTL (38.1° vs. 28.9°; P = 0.0002), and consequently CL (−19.8° vs. −8.9°; P = 0.0160), CT (29.8° vs. 24.3°; P = 0.0190), and TIA (81.9° vs. 71.1°; P = 0.0022) in SDT were significantly greater as well. The difference in CL was expressed mainly in C6-C5 (−4.8° vs. −1.4°; P = 0.0146) and C5-C4 (−4.4°; vs. −1.5° P = 0.0464) segments. There were no significant differences in proximal cervical lordosis: C0-2 angle (−21.6° vs. −20.8°; P = 0.7597), C1-C2 angle (−30.8°vs. −27.5°; P = 0.1746), C3-C2 (−5.4° vs. −5.1°; P = 0.7976), and C4-C3 (3.5° vs. −1.5°; P = 0.1464) segments. There was no significant difference in cranial parameters C0-angle, CRT, and CO. Conclusion. Scheuermann disease type has an influence on cervical sagittal balance. Localization of structural kyphosis affects the T1 slope as well as C2-C7 lordosis, cervical tilt, and thoracic inlet angle. Significant difference in C2-C7 lordosis in comparison to similar C0-2 lordosis demonstrates that compensation is present in subaxial cervical spine. Position of the head center of gravity is not dependent on the SD type. Level of Evidence: 4