Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular sites involved in the biogenesis of bile canaliculi in hepatic cells.

Studies in hepatoma cells and hepatocytes have revealed that the biogenesis of bile canalicular membrane involves microvilli-lined vesicles (MLV), which are formed in well differentiated cells. The vesicles grow as a function of time and are presumably vectorially transported to cell surface contact sites of attached cells. We demonstrate that a fluorescent head group-labeled lipid analog, N-(lissamine rhodamine B sulfonyl)phosphatidylethanolamine (N-Rh-PE), after its exogenous insertion into the plasma membrane of HepG2 cells at 4 degrees C, accumulates in these microvilli-lined vesicles at 37 degrees C. This shows that the MLV are a target for plasma membrane-derived lipids. Furthermore, also the Golgi apparatus is involved in the formation of the vesicles. After initial accumulation of the fluorescent sphingolipid precursor, 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoic acid (C6-NBD)-ceramide in the Golgi apparatus at 37 degrees C, prolonged incubation at 37 degrees C results in the appearance of NBD fluorescence in the microvilli-lined vesicles. The transport route for the Golgi-derived material to the developing bile canalicular vesicle is not an indirect pathway, i.e. involving transcytosis via the basolateral plasma membrane. This could be demonstrated by including bovine serum albumin (BSA) in the incubation media, a lipid scavenger that will remove any C6-NBD-lipids exposed at the basolateral membrane. At these conditions, lipid trafficking between the Golgi complex and MLV still occurred. We further demonstrate that the targeting from the Golgi apparatus to the bile canaliculus is also operational in isolated human hepatocytes. The latter results suggests that the Golgi complex is involved in both the formation of bile canaliculi and in bile secretion in fully differentiated cells.
Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection

ABSTRACT To understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and the mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with host CTL responses in six linked transmission pairs. HIV-1 sequences corresponding to full-length p17 and p24 gag were generated by 454 pyrosequencing for all pairs near the time of transmission, and seroconverting partners were followed for a median of 847 days postinfection. T-cell responses were screened by gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous peptide sets reflecting any Gag variant present in at least 5% of sequence reads in the individual's viral population. While we found little evidence for the occurrence of CTL reversions, CTL escape processes were found to be highly dynamic, with multiple epitope variants emerging simultaneously. We found a correlation between epitope entropy and the number of epitope variants per response (r = 0.43; P = 0.05). In cases in which multiple escape mutations developed within a targeted epitope, a variant with no fitness cost became fixed in the viral population. When multiple mutations within an epitope achieved fitness-balanced escape, these escape mutants were each maintained in the viral population. Additional mutations found to confer escape but undetected in viral populations incurred high fitness costs, suggesting that functional constraints limit the available sites tolerable to escape mutations. These results further our understanding of the impact of CTL escape and reversion from the founder virus in HIV infection and contribute to the identification of immunogenic Gag regions most vulnerable to a targeted T-cell attack. IMPORTANCE Rapid diversification of the viral population is a hallmark of HIV-1 infection, and understanding the selective forces driving the emergence of viral variants can provide critical insight into the interplay between host immune responses and viral evolution. We used deep sequencing to comprehensively follow viral evolution over time in six linked HIV transmission pairs. We then mapped T-cell responses to explore if mutations arose due to adaption to the host and found that escape processes were often highly dynamic, with multiple mutations arising within targeted epitopes. When we explored the impact of these mutations on replicative capacity, we found that dynamic escape processes only resolve with the selection of mutations that conferred escape with no fitness cost to the virus. These results provide further understanding of the complicated viral-host interactions that occur during early HIV-1 infection and may help inform the design of future vaccine immunogens.
Improving software-reduced touchscreen latency

The latency of current mobile devices' touchscreens is around 100ms and has widely been explored. Latency down to 2ms is noticeable, and latency as low as 25ms reduces users' performance. Previous work reduced touch latency by extrapolating a finger's movement using an ensemble of shallow neural networks and showed that predicting 33ms into the future increases users' performance. Unfortunately, this prediction has a high error. Predicting beyond 33ms did not increase participants' performance, and the error affected the subjective assessment. We use more recent machine learning techniques to reduce the prediction error. We train LSTM networks and multilayer perceptrons using a large data set and regularization. We show that linear extrapolation causes an 116.7% higher error and the previously proposed ensembles of shallow networks cause a 26.7% higher error compared to the LSTM networks. The trained models, the data used for testing, and the source code is available on GitHub.
Oral implant surfaces: Part 2--review focusing on clinical knowledge of different surfaces.

PURPOSE This article reviews clinical knowledge of selected oral implant surfaces. MATERIALS AND METHODS The surfaces most commonly used in clinical practice, marketed by the five largest oral implant companies, are identified; their clinical documentation was scrutinized following a strict protocol. Experimental knowledge of the surfaces is briefly summarized. Retrospective, prospective, and comparative clinical studies were analyzed separately, as were studies of implants in conjunction with bone grafts. RESULTS TiUnite anodized surfaces are clinically documented in 1- to 2-year follow-up studies at best, with failures at about 3%. Sandblasted and acid-etched SLA surfaces are documented with good clinical results for up to 3 years. Osseotite dual acid-etched implants are documented with good clinical results for up to 5 years. Frialit-2 sandblasted and etched implants are positively documented for about 3 years in one study only. The Tioblast implant is the only design documented for survival over 10 years of follow-up and success over 7 years of follow-up. CONCLUSION Generally, oral implants are introduced clinically without adequate clinical documentation. Implant companies initiate clinical documentation after product launch. The standards of clinical reporting have improved over the years. Proper long-term reports have been published for only one surface, Tioblast.
Pdx1 and controlled culture conditions induced differentiation of human amniotic fluid‐derived stem cells to insulin‐producing clusters

This study investigated the differentiation of human amniotic fluid‐derived stem cells (hAFSCs) into insulin‐producing clusters in vitro. Adenovirally‐delivered mouse Pdx1 (Ad‐Pdx1) induced human Pdx1 expression in hAFSCs and enhanced the coordinated expression of downstream β‐cell markers. When Ad‐Pdx1‐transduced hAFSCs were sequentially treated with activin A, bFGF and nicotinamide and the culture plate surface coated with poly‐l‐ornithine, the expression of islet‐associated human mRNAs for Pdx1, Pax6, Ngn3 and insulin was increased. C‐peptide ELISA confirmed that Ad‐Pdx1‐transduced hAFSCs processed and secreted insulin in a manner consistent with that pathway in pancreatic β‐cells. To sustain the β‐cell‐like phenotype and investigate the effect of three‐dimensional (3D) conformation on the differentiation of hAFSCs, Pdx1‐transduced cells were encapsulated in alginate and cultured long‐term under serum‐free conditions. Over 2 weeks, partially differentiated hAFSC clusters increased in size and increased insulin secretion. Taken together, these data demonstrate that ectopic Pdx1 expression initiates pancreatic differentiation in hAFSCs and that a β‐cell‐like phenotype can be augmented by culture conditions that mimic the stromal components and 3D geometry associated with pancreatic islets. Copyright © 2012 John Wiley & Sons, Ltd.
TDP‐43 toxicity is mediated by the unfolded protein response‐unrelated induction of C/EBP homologous protein expression

Transactive response DNA‐binding protein‐43 (TDP‐43) neuronal toxicity plays an essential role in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin‐positive inclusions. In our previous study, we showed that low‐grade overexpression of TDP‐43, which is thought to mimic the gain‐of‐function of TDP‐43, caused neuronal death, mediated by the upregulation of Bim and the downregulation of Bcl‐xL in vitro. In this study, we show that TDP‐43 overexpression caused the upregulation of C/EBP‐homologous protein (CHOP) and that disruption of the CHOP gene markedly attenuated TDP‐43‐induced cell death. These results indicate that increases in CHOP expression contribute to TDP‐43‐induced cell death. We also show that the TDP‐43‐induced upregulation of CHOP expression is mediated by both the upregulation of the mRNA level of CHOP and the attenuation of thedegradation of CHOP, which is independent on the PERK/eIF2α/ATF4 or other pathway related to the unfolded protein response (UPR) to endoplasmic reticulum stress. This study provides the first example of the CHOP‐mediated cell death that is independent of the UPR. © 2011 Wiley Periodicals, Inc.
Human intravenous immunoglobulin (IVIG) preparations degranulate human neutrophils in vitro

IVIG preparations have biological effects in vivo that are not fully understood. Possible effects include the property to stimulate Fc receptors on various cell types. To study whether IVIG may interact with neutrophils we developed an in vitro system, in which neutrophils, in whole blood or purified, were incubated with IVIG and assessed for degranulation by measuring the release of elastase and lactoferrin in culture medium. All commercially available IVIG preparations tested induced degranulation of neutrophils when incubated for 2 h at therapeutically relevant concentrations. In studies with blocking antibodies against Fc receptors (FcR), this degranulation was shown to be dependent on FcγRII, whereas FcγRIII had no effect. Experiments with purified neutrophils as well as binding experiments with labelled IVIG preparations indicated that neutrophil degranulation resulted from a direct interaction of IVIG with neutrophils. Using gel filtration fractions, it was found that polymeric and dimeric IgG present in IVIG was mainly responsible for the degranulation. We suggest that degranulation of neutrophils may contribute to the (side)effects of IVIG treatment in vivo.
Prophylactic Intravesical Chemotherapy to Prevent Bladder Tumors after Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinomas: A Systematic Review and Meta-Analysis

Introduction: Intravesical recurrence after treatment of primary upper urinary tract urothelial carcinomas (UUT-UCs) is common. While intravesical instillation is widely used to prevent recurrence after transurethral resection for primary bladder tumors, there is still no consensus on the prophylactic capability of intravesical chemotherapy in preventing bladder tumor recurrence after surgery for UUT-UCs. Methods: A meta-analysis of the published results of clinical trials was performed to compare radical surgery alone or surgery plus postoperative intravesical chemotherapy. The primary end point was to determine the percentage of patients with recurrence in the different groups. Results: Our study includes five trials with recurrence information on 614 patients. During follow-up, 55 of 268 (20.5%) patients who received postoperative instillation had bladder recurrence compared to 127 of 346 (36.7%) patients who had no adjuvant treatment - a decrease of 41% in the odds of recurrence with chemotherapy (odds ratio 0.48, 95% confidence interval 0.33-0.69, p = 0.0001). No serious adverse events were reported. Subgroup analyses were temporarily unavailable. Conclusions: Postoperative intravesical chemotherapy significantly decreases the risk of bladder recurrence after nephroureterectomy for primary UUT-UCs. Postoperative intravesical instillation is considered the treatment of choice after nephroureterectomy.
Portable computer vision-based cardiac estimation as a teaching aid

The prevalence of pervasive computing has made computing platforms more portable and has introduced an array of sensors that are useful for many applications. The potential of these sensors are finally being realized in many fields. One area that is especially benefiting from these sensors is the field of the biometrics. However, we are still grappling with user acceptance issues such as intrusiveness and hygiene problems, which stifle the uptake of the technology. This study investigates the potential of using one of the more common sensors, a portable device camera, and using it to assist educators. By implementing a system that captures heart rate in a novel manner, a basic affective biometric system is formed that requires no contact and is portable. The system segments relevant areas that highlight blood flow in the face, extrapolates heart rate variability through color space changes. By analyzing the extent of color change, a cardiac waveform can be formed with a QRS complex derivative, which can be used for the task of sentiment classification. The sentiment derived can then be used by an educator to inform them of any potential uncertainty during their teaching in real-time. Abrupt changes in sentiment can then be addressed during the class, thereby improving the potential uptake of concepts taught in a classroom. The study validates that it is possible to derive heart rate variability using a camera, it also shows that using this heart rate for basic sentiment classification is feasible using a portable device even with limited resources and it warrants more attention.
THE RELATIONSHIP BETWEEN THE STOCK PRICES AND FINANCIAL RATIOS: EVIDENCE FROM THE PRAGUE STOCK EXCHANGE AND THE POLISH STOCK EXCHANGE

Stock prices and their fluctuations are analyzed by investors and analytics due to the possibility of achievement the capital earnings. Many variables can affect development of the stock prices; the main categories are macroeconomic factors, industrial variables, and company characteristics. This paper is focused on company characteristics that reflect success of business activities of individual companies. The object of the paper is to investigate the existence of a relationship between selected financial ratios and stock prices of selected manufacturing companies listed on the Prague Stock Exchange and the Polish Stock Exchange. The semi-annual data is analyzed over the 2006 – 2017 period. The long-term relationship between the selected financial ratios and stock prices is examined by using the Johansen cointegration test. The existence of short-term cointegration linkages is analyzed using the Vector Error Correction Model (VECM). The findings show that there are sporadic relationships between the stock prices and financial ratios. It seems that investors could be interested in macroeconomic factors, industry variables or they do not have a relevant education to evaluate the financial information.
Modeling Tumor Treating Fields (TTFields) application in single cells during metaphase and telophase

Effects of electric fields on biological cells have been extensively studied but primarily in the low and high frequency regimes. Low frequency AC fields have been investigated for applications to nerve and muscle stimulation or to examine possible environmental effects of 60 Hz excitation. High frequency fields have been studied to understand tissue heating and tumor ablation. Biological effects at intermediate frequencies (in the 100-500 kHz regime) have only recently been discovered and are now being used clinically to disrupt cell division, primarily for the treatment of recurrent glioblastoma multiforme. In this study, we develop a computational framework to investigate the mechanisms of action of these Tumor Treating Fields (TTFields) and to understand in vitro findings observed in cell culture. Using Finite Element Method models of isolated cells we show that the intermediate frequency range is unique because it constitutes a transition region in which the intracellular electric field, shielded at low frequencies, increases significantly. We also show that the threshold at which this increase occurs depends on the dielectric properties of the cell membrane. Furthermore, our models of different stages of the cell cycle and of the morphological changes associated with cytokinesis show that peak dielectrophoretic forces develop within dividing cells exposed to TTFields. These findings are in agreement with in vitro observations, and enhance our understanding of how TTFields disrupt cellular function.
[Virological and serological surveys for H9N2 subtype of influenza A virus in chickens and men in Shenzhen city].

OBJECTIVE To understand the distribution of influenza A H9N2 virus in chickens and men in Shenzhen area. METHODS Virus isolation was performed in embryonated hen s eggs with routine method. The antibody to H9N2 virus was detected with micro-hemagglutination inhibition (HI) test, then the results were checked by using the neutralization assay in MDCK cells. RESULTS Totally 27 strains of influenza A H9N2 virus were isolated from chickens in farm markets in Shenzhen, whereas no H9N2 virus was isolated from men. Approximately 26% of human sera with the HI titers > or =20 to H9N2 virus were detected. However only 7% of chicken sera with the HI titers > or =20 to H9N2 virus were detected. Meanwhile the HI titer and (MGT) of antibody to H9N2 virus in human sera increased with age. It was also found that there was a close relationship between HI antibody titer to H9N2 virus in human sera and occupation. CONCLUSIONS The distribution of influenza A H9N2 virus in chicken and men in Shenzhen was rather wide. The human H9N2 virus infection probably derived from chicken H9N2 virus.
Effective suppression method for 2nd nonlinear signals of SAW devices

Linearity performances are getting one of the most important characteristics of surface acoustic wave (SAW) duplexers because nonlinear signals generated in RF front-end of cellar phone handsets deteriorate the receiver sensitivities significantly. In this paper, the generation mechanisms of the 2nd order nonlinear signals of SAW resonators/duplexers on a 42°Y-X LiTaO3 substrate and an effective suppression method for them are discussed. The crystalline asymmetry properties of substrates are focused on as the one possibility of the occurrence factor of the 2nd order nonlinear signals. Additionally, based on this hypothesis, an interdigital transducer (IDT) design which realizes the cancellation of the crystalline asymmetry effect is proposed to improve the linearity. As the result, the 2nd order harmonics level of the one-port SAWresonators and the 2nd order intermodulation distortion (IMD2) levels of the SAW duplexers have been improved up to about 25dBm and 20dBm, respectively.
Calmodulin-like skin protein is downregulated in human cerebrospinal fluids of Alzheimer’s disease patients with apolipoprotein E4; a pilot study using postmortem samples

Abstract Objective: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer’s disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood–cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients. Methods: Mice were intraperitoneally injected with 5 nmol of recombinant human CLSP. At 1h after the injection, the mice were sacrificed for the analysis of the existence of human CLSP in blood and interstitial fluid (ISF)-containing brain samples. Using postmortem CSF samples, we next determined the concentrations of CLSP in CSFs of human AD and control cases. Results: Intraperitoneally administered recombinant human CLSP circulated in the blood stream and reached the brain interstitial fluid. The concentrations of CLSP in CSFs of human AD and control cases are sufficient to exhibit the CLSP activity. Although the concentrations of CLSP in CSFs were not significantly different between AD and control cases, the concentrations of CLSP are lower in the AD cases with the apolipoprotein E4 genotype than in the AD cases without the apolipoprotein E4 genotype. Discussion: The first result indicates that CLSP enters the central nervous system through the blood–brain barrier. The second result suggests that CLSP functions in the human brains. The third result may exclude the possibility that the downregulation of the CLSP level is involved in the AD pathogenesis. The last result may contribute to the better understanding of the AD pathogenesis from the standpoint of the apolipoprotein E genotype.
Research for equilateral triangle optical resonators

An important feature for the Micro-resonator is the quality factor. This Paper presents a new equilateral triangle micro-resonator (ETR) design, simulates the spectral response by FDTD method, then calculates the quality factor (Q factor), and compare the results with the micro-ring resonator (MR) with similar footprint. The simulation results show that the quality factor of ETR at the side length of 6um is more than 10 times larger than that of the MR which has the same area as ETR on the same material platform. We also show that the output of an ETR with an opening to the output waveguide is more efficient, besides the increasing of quality factor by 26% at a wavelength of 1.48um.