Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of RIPK1 Markedly Exacerbates Murine Immune-Mediated Liver Injury through Massive Apoptosis of Hepatocytes, Independent of Necroptosis and Inhibition of NF-κB

Receptor-interacting protein kinase (RIPK)1 has an essential role in the signaling pathways triggered by death receptors through activation of NF-κB and regulation of caspase-dependent apoptosis and RIPK3/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. We examined the effect of RIPK1 antisense knockdown on immune-mediated liver injury in C57BL/6 mice caused by α-galactosylceramide (αGalCer), a specific activator for invariant NKT cells. We found that knockdown of RIPK1 markedly exacerbated αGalCer-mediated liver injury and induced lethality. This was associated with increased hepatic inflammation and massive apoptotic death of hepatocytes, as indicated by TUNEL staining and caspase-3 activation. Pretreatment with zVAD.fmk, a pan-caspase inhibitor, or neutralizing Abs against TNF, almost completely protected against the exacerbated liver injury and lethality. Primary hepatocytes isolated from RIPK1-knockdown mice were sensitized to TNF-induced cell death that was completely inhibited by adding zVAD.fmk. The exacerbated liver injury was not due to impaired hepatic NF-κB activation in terms of IκBα phosphorylation and degradation in in vivo and in vitro studies. Lack of RIPK1 kinase activity by pretreatment with necrostatin-1, a RIPK1 kinase inhibitor, or in the RIPK1 kinase-dead knock-in (RIPK1D138N) mice did not exacerbate αGalCer-mediated liver injury. Furthermore, RIPK3-knockout and MLKL-knockout mice behaved similarly as wild-type control mice in response to αGalCer, with or without knockdown of RIPK1, excluding a switch to RIPK3/MLKL-mediated necroptosis. Our findings reveal a critical kinase-independent platform role for RIPK1 in protecting against TNF/caspase-dependent apoptosis of hepatocytes in immune-mediated liver injury.
GTP Hydrolysis by eRF3 Facilitates Stop Codon Decoding during Eukaryotic Translation Termination

ABSTRACT Translation termination in eukaryotes is mediated by two release factors, eRF1 and eRF3. eRF1 recognizes each of the three stop codons (UAG, UAA, and UGA) and facilitates release of the nascent polypeptide chain. eRF3 is a GTPase that stimulates the translation termination process by a poorly characterized mechanism. In this study, we examined the functional importance of GTP hydrolysis by eRF3 in Saccharomyces cerevisiae. We found that mutations that reduced the rate of GTP hydrolysis also reduced the efficiency of translation termination at some termination signals but not others. As much as a 17-fold decrease in the termination efficiency was observed at some tetranucleotide termination signals (characterized by the stop codon and the first following nucleotide), while no effect was observed at other termination signals. To determine whether this stop signal-dependent decrease in the efficiency of translation termination was due to a defect in either eRF1 or eRF3 recycling, we reduced the level of eRF1 or eRF3 in cells by expressing them individually from the CUP1 promoter. We found that the limitation of either factor resulted in a general decrease in the efficiency of translation termination rather than a decrease at a subset of termination signals as observed with the eRF3 GTPase mutants. We also found that overproduction of eRF1 was unable to increase the efficiency of translation termination at any termination signals. Together, these results suggest that the GTPase activity of eRF3 is required to couple the recognition of translation termination signals by eRF1 to efficient polypeptide chain release.
A maximum power point tracking controller for thermoelectric generators

Thermoelectric generators (TEGs) directly convert heat energy into electricity for power-supplying sensors and other portable electronic devices. In this paper, a maximum power point tracking (MPPT) controller in the modified perturb and observe (P&O) algorithm was designed on the basis of analyzing the output characteristics of the TEG modules. The MPPT controller consists of a voltage sensor, a current sensor, a microcontroller and a SEPIC converter, which keeps the operating point of the thermoelectric generator tracking the maximum power point (MPP). The thermoelectric generator was heated to generate electricity, and a supercapacitor accumulated that energy. Experimental results using the MPPT controller present that the thermoelectric generator's output voltage achieves around 5 V, the output power achieves upward of 2W when the temperature difference ΔT=75°C and the operating point of the thermoelectric generator accurately tracks the MPP with a tracking efficiency of 99.8%; the charging power can be improved 89.65%.
The Amino Acid Sequence of the Tryptophan‐Containing Subunit (α‐Subunit) of Bovine Brain S‐100 Protein

Abstract: The tryptophan‐containing subunit (α‐subunit) of bovine brain S‐100 protein was purified from a S‐aminoethyl derivative of S‐100a protein, and its amino acid sequence was determined. The α‐subunit contained 93 residues, including one tryptophan, and had a molecular weight of 10,400. The sequence shows an extensive homology (58% identity) to the sequence of another “tryptophan‐free” subunit (β‐subunit) found in both S‐100a and S‐100b protein, and has a calcium binding site characteristic of the “E‐F hand” proteins, such as calmodulin or troponin C. The tryptophan residue is located at position 90 which is presumably adjacent to the C‐terminal end of the α‐helix following the calcium binding loop, and thus appears likely to serve as a specific probe in structure‐function studies of S‐100a protein.
HLA class II similarities in Iranian Kurds and Azeris

The genetic relationship between Kurds and Azeris of Iran was investigated based on human leukocyte antigen (HLA) class II profiles. HLA typing was performed using polymerase chain reaction/restriction fragment‐length polymorphism (PCR/RFLP) and PCR/sequence‐specific primer (PCR/SSP) methods in 100 Kurds and 100 Azeris. DRB1*1103/04, DQA1*0501 and DQB1*0301 were the most common alleles and DRB1*1103/04‐DQA1*0501‐DQB1*0301 was the most frequent haplotype in both populations. No significant difference was observed in HLA class II allele distribution between these populations except for DQB1*0503 which showed a higher frequency in Kurds. Neighbor‐joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1 and DQB1 allele frequencies showed a strong genetic tie between Kurds and Azeris of Iran. The results of amova revealed no significant difference between these populations and other major ethnic groups of Iran. No close genetic relationship was observed between Azeris of Iran and the people of Turkey or Central Asians. According to the current results, present‐day Kurds and Azeris of Iran seem to belong to a common genetic pool.
Hematopoiesis in the Elderly

Abstract The effect of age on the hematopoietic system has always been an area of clinical interest. Alterations in lymphocyte immunophenotype and function with age have been clearly demonstrated as has a decrease in neutrophil function. However, controversy continues to surround the significance of unexplained anaemia in the elderly patient and the extent to which this could be a physiological occurrence. The weight of evidence from animal and human studies would suggest that anaemia is not a physiological occurrence but may have a multifactorial pathogenesis. Are older patients therefore, appropriate candidates for high dose therapy, including autologous stem cell transplantation? The loss of telomeric DNA from hematopoietic progenitor cells with aging implies that stem cell collections from an older patient may have compromised replicative capacity with a reduced response to hematopoietic growth factors. Recent studies, however, show that age is not an obstacle for the collection of a stem cell product, which is capable of restoring normal hematopoietic function. A study of autologous stem cell transplantation has shown comparable neutrophil and platelet recovery times between younger and older patients.
Low-cost Photometric sensing for Maximum PV power generation

The Constant Voltage Maximum Power Point Technique (MPPT) method has the drawback of measuring the open circuit voltage Voc of the Photo voltaic (PV) panel by disconnecting it from the balance of the system. To reduce the circuit complexity, this paper proposes a remedial measure to identify the peak power operating point from the Low cost Photometric Sensor. The measured photometric quantity is to be converted into a radiometric quantity in terms of the irradiance. Hence the mathematical model is developed to estimate Voc through photometric measurement. Now the constant voltage method can be used to determine the Maximum Power Point from 0.76 percentage of Voc. The developed mathematical model endorses to find MPPT without disconnecting the PV panel in the real time PV power generation. The effectiveness of the proposed method is verified through experiments under various weather conditions.
A role for lysyl oxidase regulation in the control of normal collagen deposition in differentiating osteoblast cultures

Differentiation of phenotypically normal osteoblast cultures leads to formation of a bone‐like extracellular matrix in vitro. Maximum collagen synthesis occurs early in the life of these cultures, whereas insoluble collagen deposition occurs later and is accompanied by a diminished rate of collagen synthesis. The mechanisms that control collagen deposition seem likely to include regulation of extracellular collagen biosynthetic enzymes, but expression patterns of these enzymes in differentiating osteoblasts has received little attention. The present study determined the regulation of lysyl oxidase as a function of differentiation of phenotypically normal murine MC3T3‐E1 cells at the level of RNA and protein expression and enzyme activity. In addition, the regulation of BMP‐1/mTLD mRNA levels that encodes procollagen C‐proteinases was assayed. The role of lysyl oxidase in controlling insoluble collagen accumulation was further investigated in inhibition studies utilizing β‐aminopropionitrile, a specific inhibitor of lysyl oxidase enzyme activity. Results indicate that lysyl oxidase is regulated as a function of differentiation of MC3T3‐E1 cells, and that the maximum increase in lysyl oxidase activity precedes the most efficient phase of insoluble collagen accumulation. By contrast BMP‐1/mTLD is more constitutively expressed. Inhibition of lysyl oxidase in these cultures increases the accumulation of abnormal collagen fibrils, as determined by solubility studies and by electron microscopy. Taken together, these data support that regulation of lysyl oxidase activity plays a key role in the control of collagen deposition by osteoblast cultures. Copyright © 2004 Wiley‐Liss, Inc.
Optimizing the Identification of Digital Predistorters for Improved Power Amplifier Linearization Performance

Digital predistortion (DPD) is a cost-effective method to linearize power amplifiers (PAs) in modern wireless transceivers. In block-based predistortion, which is a two-step process involving DPD identification and linearization, the linearization performance is related to the PA output power during identification. In this brief, we investigate this relation and find the optimum PA output power in the identification for the best linearization performance. A scaling factor is applied to the input signal to control the PA output power during the identification. Since the optimum PA output power for the identification is expected to depend on the probability density function (pdf) of the input signal magnitude and the PA response, we choose signals with different pdfs and a PA with different linearity settings for our study. The factors that affect the linearization performance are identified and we explain how they lead to different linearization performances for different PA responses and pdfs of the input signal magnitude. Measurements using a PA that operates at 900 MHz with two different Universal Mobile Telecommunications System signals were carried out. The linearization performance is quantified as the mean squared error (MSE) between the input and output signals. Depending on the pdf of the input signal magnitude, we found MSE improvements between 2 and 10 dB if the optimum PA output power is chosen during the identification.
A Spatiotemporal Oriented Energy Network for Dynamic Texture Recognition

This paper presents a novel hierarchical spatiotemporal orientation representation for spacetime image analysis. It is designed to combine the benefits of the multilayer architecture of ConvNets and a more controlled approach to spacetime analysis. A distinguishing aspect of the approach is that unlike most contemporary convolutional networks no learning is involved; rather, all design decisions are specified analytically with theoretical motivations. This approach makes it possible to understand what information is being extracted at each stage and layer of processing as well as to minimize heuristic choices in design. Another key aspect of the network is its recurrent nature, whereby the output of each layer of processing feeds back to the input. To keep the network size manageable across layers, a novel cross-channel feature pooling is proposed. The multilayer architecture that results systematically reveals hierarchical image structure in terms of multiscale, multiorientation properties of visual spacetime. To illustrate its utility, the network has been applied to the task of dynamic texture recognition. Empirical evaluation on multiple standard datasets shows that it sets a new state-of-the-art.
Active Learning Applied to RCS Computations With Nonuniform Sampling Using Different Objective Functions

An active learning framework is introduced to reduce the number of frequencies and angles one must consider for wideband monostatic scattering computations or measurements. This method is used to optimally select those frequencies and angles that would be most informative, resulting in nonuniform sampling and often a reduced number of points (vis-agrave-vis uniform sampling). In this paper we focus on jointly two-dimensional optimal sampling in frequency and incident angle thetas for monostatic scattering. The method consists of two basic steps. One step involves estimation of model parameters using a least-square (LS) algorithm. The next step is to optimally choose the next point (frequency and thetas) for analysis by the computational model or experiment. This new point is selected with the goal of reducing uncertainty in the parametric model (quantified via the Fisher information matrix). Iterating these two steps, a sequence of numerical computations or measurements are performed, each at the most informative point for learning the parameters of the associated simpler parametric model. This idea is demonstrated here in the context of reducing the number of points (frequencies and orientations) at which a computational model must be employed. And in order to avoid repeatedly gathering samplings at the edge of the input space, an alternative objective function is applied which makes the actively selected points closer to a region of interest
Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP.

PURPOSE Retinitis pigmentosa GTPase regulator (RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. METHODS An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. RESULTS Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. CONCLUSIONS AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted.
Robust Expansion of Viral Antigen-specific CD4+ and CD8+ T Cells for Adoptive T Cell Therapy Using Gene-modified Activated T Cells as Antigen Presenting Cells

Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated with CMV-specific T cells, but current in vitro techniques using dendritic cells as antigen-presenting cells are time-consuming and expensive. To simplify the production of clinical grade CMV-specific T cells, we evaluated gene-modified activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily produced source of APCs to boost CD4+ and CD8+ T-cell responses against the immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant CMV pp65 gene were used to stimulate the expansion of autologous T cells. After 10 to 14 days, the T cell lines were tested for antigen specificity by using the flow cytometric intracellular detection of interferon-γ after stimulation for 6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids. Under optimal conditions, this technique induced a median 766-fold and a 652-fold expansion of pp65-specific CD4+ and CD8+ responder cells, respectively, in 15 T cell lines. In 13 of 15 T cell lines, over 106 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5×106 peripheral blood mononuclear cells, representing an over 3-log increase. These data indicate that T-APCs efficiently boost pp65-specific CD4+ and CD8+ T cell numbers to clinically useful levels. The approach has the advantage of using a single leukocyte collection from the donor to generate large numbers of CMV-specific T cells within a total 3-week culture period using only one stimulation of antigen.
Grexit news and stock returns

ABSTRACT During the first 8 months of 2015, there was an ongoing debate about whether or not Greece should remain in the euro area. Using an event study approach, we quantify the effects of Grexit-related statements made by six important euro area politicians (Merkel, Schaeuble, Tsipras, Varoufakis, Juncker, and Schulz) on intraday stock returns in Germany, Greece, and the euro area during the period of 1 January 2015–19 August 2015. We show that positive statements indicating that a Grexit is less likely lead to higher returns, and negative statements to lower returns. The overall impact of negative statements is more pronounced. The cumulative absolute effects on stock returns are sizeable as the statements contribute to a variation of up to 58 percentage points in the ATHEX. These large effects are of particular relevance as our study only captures an 8-month snapshot of the Greek Government debt crisis.
Comparative study of piezoelectric materials properties for green energy harvesting from vibration

This article provides a study of the relation between the parameters characterizing piezoelectric material's properties relevant for energy harvesting from cantilever-based energy-harvesting devices (EHD), harvesting energy from vibrational motion. Furthermore, the performance of some piezoelectric materials has been compared with respect to their output power. The mathematical model of a cantilever-based bimorph has been used to analyze the behavior of the systems and subsequent comparison of their performance with respect to different materials.
A Novel Time Series Approach for Predicting the Long-Term Popularity of Online Videos

Predicting the video popularity is an essential part of fast growing online media services. It is beneficial to an array of domains, from targeted advertising, personalized recommendation, to traffic load optimization. However, popularity prediction is a challenge problem due to the uncertainty of information cascade. In this paper, we treat the popularity of online videos as time series over the given periods and propose a novel time series model for popularity prediction. The proposed model is based on the correlation between early and future popularity series. Instead of inferring the precise view counts for a video, this paper focuses on accurately identifying the most popular videos based on the predicted popularity, because it is of the most interest to service providers. Experimental result on real world data have demonstrated that the proposed model outperforms several existing popularity prediction models.
Association of HLA alleles and clinical features in patients with synovitis of recent onset.

OBJECTIVE To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset. METHODS The HLA alleles A, B, C, DRbeta1, and DQbeta1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints. At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n = 244). RESULTS Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RF+) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45). The presence of 2 SE alleles or an associated DQbeta1*0301 (DQ7) or DQbeta1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DRbeta1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12% versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. CONCLUSION This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients.