gebhart/patrepeval huggingface dataset:
Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple V beta T cell receptor genes (1993)

Abstract Intestinal intraepithelial lymphocytes (IEL) are a phenotypically distinct T cell population of unknown function. The majority of human intestinal IEL express the TCR-alpha beta, the CD8 accessory molecule, and the CD45RO Ag, suggesting that they are MHC class I-restricted memory T cells. Recent analyses of the TCR alpha- and beta-chains expressed by these cells have shown marked skewing toward one or several V region genes in individual donors and revealed the presence of clonally expanded cells. In addition, functional data has suggested that the MHC class I-like CD1 molecules may be the target ligands for some human intestinal IEL clones. This report examines in detail the TCR-beta repertoire of human jejunal IEL to determine what fraction of these cells are clonally expanded and to determine whether a particular subset of V beta genes are utilized by the clonally expanded cells. The results demonstrate that the majority of IEL are derived from the expansion of a relatively few T cell clones and that these clones can utilize a large number of different V beta genes. Oligoclonal expansion is also demonstrated among lamina propria lymphocytes (LPL), with overlapping but distinct clones detected in the LPL vs the IEL populations. These results indicate that most intestinal IEL-alpha beta, and a subpopulation of LPL, are specific for a limited number of Ag and place constraints on the possible roles played by IEL in the defense against diverse environmental pathogens or in the generation of oral tolerance.
Leptin induces proliferation and anti-apoptosis in human hepatocarcinoma cells by up-regulating cyclin D1 and down-regulating Bax via a Janus kinase 2-linked pathway (2007)

Obesity serves as an important risk factor for incidences of both cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC), which is the third leading cause of cancer death worldwide. Leptin, the obesity biomarker molecule secreted systemically by body fat mass and locally by activated hepatic stellate cells, is proposed to play a certain role in HCC growth. Here, we show both proliferative and anti-apoptotic effects of leptin in HCC cells. Leptin stimulated cyclin D1 promoter activity to increase cyclin D1 protein expression, which accelerated the cell cycle progression. The reduced ratio between anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) Bcl-2 family proteins by transforming growth factor (TGF)-beta 1 caused HCC cells degradation of poly(ADP-ribose) polymerase and consequential apoptosis; whereas, leptin protected cells from apoptosis by reversing TGF-beta 1-reduced Bcl-2/Bax ratio as a result of down-regulating Bax. Any inhibitor specific for Janus kinase 2 (JAK2), phosphatidylinositol 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase 1/2 (ERK1/2) blocked these leptin functions. When intrahepatocytic JAK2 was activated by leptin, the active JAK2 afterward triggered a signaling cascade involving activations of PI3K/Akt and MEK/ERK1/2 in order of occurrence. As yet, in most cases, the crosstalks among signaling pathways primarily studied in diverse cancer cell types for mediating somatotropic effect of leptin are not well clarified and seem to be cell-type dependent. For the first time, our results demonstrate the direct effects of leptin on HCC growth and define its signal pathway with a crosstalking JAK2-PI3K/Akt-MEK/ERK1/2 connection. The identified hierarchy of intrahepatocytic leptin signaling pathway provides a clear basis potentially beneficial to make accurate and effectual strategies for facing both cirrhotic and non-cirrhotic liver carcinogenesis.
GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism (2009)

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), is the first of this new class of antihyperglycemia drugs approved to treat T2DM. GLP-1Rs are coupled to the cAMP second messenger pathway and, along with pancreatic cells, are expressed within the nervous system of rodents and humans, where receptor activation elicits neurotrophic actions. We detected GLP-1R mRNA expression in both cultured embryonic primary cerebral cortical and ventral mesencephalic (dopaminergic) neurons. These cells are vulnerable to hypoxia- and 6-hydroxydopamine-induced cell death, respectively. We found that GLP-1 and Ex-4 conferred protection in these cells, but not in cells from Glp1r knockout (-/-) mice. Administration of Ex-4 reduced brain damage and improved functional outcome in a transient middle cerebral artery occlusion stroke model. Ex-4 treatment also protected dopaminergic neurons against degeneration, preserved dopamine levels, and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our findings demonstrate that Ex-4 can protect neurons against metabolic and oxidative insults, and they provide preclinical support for the therapeutic potential for Ex-4 in the treatment of stroke and PD.
PARAID: a gear-shifting power-aware RAID (2007)

Reducing power consumption for server computers is important, since increased energy usage causes increased heat dissipation, greater cooling requirements, reduced computational density, and higher operating costs. For a typical data center, storage accounts for 27 % of energy consumption. Conventional server-class RAIDs cannot easily reduce power because loads are balanced to use all disks even for light loads. We have built the Power-Aware RAID (PARAID), which reduces energy use of commodity server-class disks without specialized hardware. PARAID uses a skewed striping pattern to adapt to the system load by varying the number of powered disks. By spinning disks down during light loads, PARAID can reduce power consumption, while still meeting performance demands, by matching the number of powered disks to the system load. Reliability is achieved by limiting disk power cycles and using different RAID encoding schemes. Based on our five-disk prototype, PARAID uses up to 34 % less power than conventional RAIDs, while achieving similar performance and reliability. 1
Saturated Fatty Acids Alter the Late Secretory Pathway by Modulating Membrane Properties (2013)

Saturated fatty acids (SFA) have been reported to alter organelle integrity and function in many cell types, including muscle and pancreatic β-cells, adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this study, using a yeast-based model that recapitulates most of the trademarks of SFA-induced lipotoxicity in mammalian cells, we demonstrate that these lipid species act at different levels of the secretory pathway. Ceramides mostly appear to modulate the induction of the unfolded protein response and the transcription of nutrient transporters destined to the cell surface. On the other hand, saturated PL, by altering membrane properties, directly impact vesicular budding at later steps in the secretory pathway, i.e. at the trans-Golgi Network level. They appear to do so by increasing lipid order within intracellular membranes which, in turn, alters the recruitment of loose lipid packing-sensing proteins, required for optimal budding, to nascent vesicles. We propose that this latter general mechanism could account for the well-documented deleterious impacts of fatty acids on the last steps of the secretory pathway in several cell types.
Rice and Butterfly Wing Effect Inspired Low Drag and Antifouling Surfaces: A Review (2014)

In this article, a comprehensive overview of the reported rice and butterfly wing effect discovered by the authors is presented with the hope to attract and inspire others in the field. Living nature has inspired researchers for centuries to solve complex engineering challenges with much attention given to unique structures, materials, and surfaces. Such challenges include drag reducing and antifouling surfaces to save energy, lives, and money. Many flora and fauna exhibit low drag and antifouling characteristics, such as shark skin and lotus leaves, due to their hierarchical microstructured morphologies. The authors have reported that rice leaves and butterfly wings combine the shark skin (anisotropic flow leading to low drag) and lotus leaf (superhydrophobic and self-cleaning) effects, producing the so-called rice and butterfly wing effect. Such surfaces have been fabricated with photolithography, soft lithography, hot embossing, and coating techniques. Fluid drag, anti-biofouling, anti-inorganic fouling, contact angle, and contact angle hysteresis results are presented to understand the role of sample morphology. Conceptual modeling provides design guidance when developing novel low drag and antifouling surfaces for medical, marine, and industrial applications.
Pulsed feeding during fed‐batch fungal fermentation leads to reduced viscosity without detrimentally affecting protein expression (2002)

The goal in this study was to determine if pulsed addition of substrate could be used to alter filamentous fungal morphology during fermentation, to result in reduced broth viscosity. In all experiments, an industrially relevant strain of Aspergillus oryzae was grown in 20-liter fermentors. As a control, cultures were fed limiting substrate (glucose) continuously. Tests were performed by altering the feeding strategy so that the same total amount of glucose was fed in repeated 300-s cycles, with the feed pump on for either 30 or 150 s during each cycle. Variables indicative of cellular metabolic activity (biomass concentration, oxygen uptake rate, base consumed for pH control) showed no significant difference between continuous and pulse-fed fermentations. In addition, there was no significant difference between total extracellular protein expression or the apparent distribution of these proteins. In contrast, fungal mycelia during the second half of pulse-fed fermentations were approximately half the size (average projected area) of fungi during fermentations with continuous addition of glucose. As a result, broth viscosity during the second half of pulse-fed fermentations was approximately half that during the second half of continuous fermentations. If these results prove to be applicable for other fungal strains and processes, then this method will represent a simple and inexpensive means to reduce viscosity during filamentous fungal fermentation.
The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy (2012)

Studies on gene therapy for hemophilia B (HB) using adeno-associated viral (AAV) vectors showed that the safety of a given strategy is directly related to the vector dose. To overcome this limitation, we sought to test the efficacy and the risk of immunogenicity of a novel factor IX (FIX) R338L associated with ∼ 8-fold increased specific activity. Muscle-directed expression of canine FIX-R338L by AAV vectors was carried out in HB dogs. Therapeutic levels of circulating canine FIX activity (3.5%-8%) showed 8- to 9-fold increased specific activity, similar to humans with FIX-R338L. Phenotypic improvement was documented by the lack of bleeding episodes for a cumulative 5-year observation. No antibody formation and T-cell responses to FIX-R338L were observed, even on challenges with FIX wild-type protein. Moreover, no adverse vascular thrombotic complications were noted. Thus, FIX-R338L provides an attractive strategy to safely enhance the efficacy of gene therapy for HB.
Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu, and carcinoembryonic antigen in patients with colorectal cancer. (2000)

The antigens epithelial cell adhesion molecule (Ep-CAM), her-2/neu, and carcinoembryonic antigen (CEA) are potential T-cell targets in antigen-specific vaccination-based cancer therapy. We performed this study to evaluate whether a natural specific T-cell response against these tumor-associated antigens (TAAs) already exists in patients with colorectal carcinoma (CRC). We used the IFN-gamma ELISPOT assay to detect circulating TAA-reactive T cells directly ex vivo in unstimulated peripheral blood mononuclear cells. We analyzed the T-cell response in peripheral blood mononuclear cells of 22 HLA-A2-positive patients with CRC and 8 HLA-A2-positive healthy subjects against 3 HLA A2-restricted peptide epitopes of the TAAs Ep-CAM (GLKAGVIAV), her-2/neu (IISAVVGIL), and CEA (YLSGANLNL). Seven of 22 patients but none of the 8 healthy subjects had T cells specifically secreting IFN-gamma in response to one to three of these antigens (n = 4, Ep-CAM; n = 5, her-2/neu; n = 6, CEA). In three of the seven responding patients, TAA-reactive T cells were further characterized by flow cytometry. In all three patients, the majority of these T cells have a CD3+CD8+IFN-gamma+CD69+CD45RA+ phenotype, resembling activated effector-type T cells. T-cell responses occurred only in patients with metastatic disease (Dukes' stages C and D). The results of this study indicate that natural T-cell responses against TAAs occur in approximately one-half of CRC patients with involvement of lymph nodes or distant metastases, but not in CRC patients with disease confined to the intestinum.
The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency (2005)

The SDH mutation database offers a valuable tool and resource for clinicians involved in the treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists needing an overview of current knowledge, and geneticists and other researchers needing a solid foundation for further exploration of both these tumor syndromes and SDHA-related phenotypes.
Wide-field-of-view adaptive optics (1992)

One of the most significant limitations to conventional atmospheric compensation systems is their very restricted field of view (FOV), generally equal to an isoplanatic patch size. A wavefront sensing and compensation concept is proposed that should allow the FOV to be increased in size by factors of ten or more. The kernel of the idea is to use wavefront measurements in several (approximately equals 9) directions separated by 100 - 200 (mu) rad to deduce an estimate of the three dimensional optical path difference (OPD) distribution in the atmosphere. The algorithms are roughly based on those used for medical tomographic imaging. Preliminary analysis indicates that from 9 measurement directions it is possible to estimate the OPD contributions from approximately six altitude layers. Once this 3-D OPD distribution is calculated, it may be used to deconvolve wide FOV short exposure images (i.e., wide FOV speckle holography) or it may be used to derive the drive signals for a suite of deformable mirrors that are conjugate to their respective altitude slices. Initial indications are that the FOV may be increased to 500 (mu) rad for a 3.5 m telescope operating at 0.8 micrometers . Further, since the OPD contribution in each layer is smaller than the full atmosphere, the requirements on the system performance are somewhat relaxed.
Near-field differential scanning optical microscope with atomic force regulation (1992)

We present the design and describe the operation of a scanning probe microscope which simultaneously provides the attractive mode force and near-field optical images of objects. In this technique, the force signal is used to track the topography, thus allowing the optical signal primarily to show variations in transmissivity. A number of results are presented on the application of the technique to imaging different samples.
DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1 (2019)

Gastric cancer (GC) is the second most prevalent carcinoma resulting in cancer-related deaths in the world, with differences among geographic areas. Although the incidence and mortality rates of GC in Asia are decreasing, the search for diverse and effective therapies of GC is still needed to be fully inquired. The present research explored the expression pattern, functional role and underlying mechanism of DLX6-AS1 in GC. Firstly, we measured DLX6-AS1 expression in GC and then found the elevated level of DLX6-AS1. To further inspect the function role of DLX6-AS1 involved in GC, we performed lost-of-function assays. The silencing of DLX6-AS1 suppressed cell proliferation, migration and EMT process of GC cells. Subsequently, we uncovered that MAP4K1 was also up-regulated in GC and could be positively regulated by DLX6-AS1. Moreover, MAP4K1 down-regulation similarly inhibited GC progression. In addition, DLX6-AS1 stabilized MAP4K1 via modulating FUS. In summary, DLX6-AS1 modulated GC progression through FUS-regulated MAP4K1. Our paper exposed the role and regulatory mechanism of DLX6-AS1 in GC, which suggested a novel and valid therapy for GC patients.
A new approach for real time moving vehicle detection (2002)

This paper proposes a method for detecting and tracking a moving vehicle on the asphalt road based on vision. The distance between the robot and a moving vehicle, velocity, and its width are estimated during the tracking process. The authors show a real time moving vehicle detection method which is enough for detecting a moving vehicle for any weather conditions including fine, partly cloudy and cloudy. Furthermore, the method is applicable for the road covered partly or completely by shadows. Stationary vehicle is also distinguished from moving one by evaluating its velocity. The proposed method detects a vehicle from a distance of 25 m with a domestic video camera and extracts its front shape in real time.
Simulation on Effects of Electrical Loading due to Interdigital Transducers in Surface Acoustic Wave Resonator (2013)

This paper investigates the effects of electrical loading due to metallic interdigital transducer (IDT) on surface acoustic wave (SAW) velocity in SAW resonators by simulation using FEM in COMSOL Multiphysics. The IDT electrodes fabricated over the piezo-substrate short circuit the parallel electric field associated with SAW under the IDT during wave propagation and affect the SAW phase velocity. The simulation considers a SAW resonator with massless infinite number of IDT fingers on Y–Z cut lithium niobate substrate. The changes in resonance frequency and SAW phase velocity of SAW resonator due to electrical loading are studied for various metallization ratios. The electric field distribution at the surface of piezo-substrate is obtained and it is observed that the short circuit of the electric field due to metallic IDT reduces the SAW phase velocity; consequently, the resonance frequency of the SAW device decreases.
Characterization of Modified Antisense Oligonucleotides in Xenopus laevis Embryos (2006)

A wide variety of modified oligonucleotides have been tested as antisense agents. Each chemical modification produces a distinct profile of potency, toxicity, and specificity. Novel cationic phosphoramidate-modified antisense oligonucleotides have been developed recently that have unique and interesting properties. We compared the relative potency and specificity of a variety of established antisense oligonucleotides, including phosphorothioates (PS), 2'-O-methyl (2'OMe) RNAs, locked nucleic acids (LNAs), and neutral methoxyethyl (MEA) phosphoramidates with new cationic N,N-dimethylethylenediamine (DMED) phosphoramidate-modified antisense oligonucleotides. A series of oligonucleotides was synthesized that targeted two sites in the Xenopus laevis survivin gene and were introduced into Xenopus embryos by microinjection. Effects on survivin gene expression were examined using quantitative real-time PCR. Of the various modified oligonucleotide designs tested, LNA/PS chimeras (which showed the highest melting temperature) and DMED/phosphodiester chimeras (which showed protection of neighboring phosphate bonds) were potent in reducing gene expression. At 40 nM, overall specificity was superior for the LNA/PS-modified compounds compared with the DMED-modified oligonucleotides. However, at 400 nM, both of these compounds led to significant degradation of survivin mRNA, even when up to three mismatches were present in the heteroduplex.
Biology of IL‐21 and the IL‐21 receptor (2004)

Interleukin-21 (IL-21) is the newest member of the common gamma-chain family of cytokines, which includes IL-2, IL-4, IL-7, IL-9, IL-13, and IL-15. Its private receptor, IL-21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding. Initial studies have demonstrated that IL-21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells. More recently, the potential therapeutic capacity of IL-21 in the treatment of cancers has been widely investigated. The biological role of IL-21 in the immune system is complex, as IL-21 has been shown to have the ability to both promote and inhibit immune responses. Overall, the current data point to IL-21 being a novel immunomodulatory cytokine, whose regulation of any given immune response is highly dependent on the surrounding environmental context.
A plant signal peptide–hepatitis B surface antigen fusion protein with enhanced stability and immunogenicity expressed in plant cells (2003)

The use of transgenic plants to express orally immunogenic protein antigens is an emerging strategy for vaccine biomanufacturing and delivery. This concept has particular suitability for developing countries. One factor that has limited the development of this technology is the relatively modest levels of accumulation of some antigenic proteins in plant tissues. We used fusion protein design to improve expression of the hepatitis B surface antigen (HBsAg) by attempting to mimic the process of HBsAg targeting to the endoplasmic reticulum of human liver cells during hepatitis B virus infection. We created a gene encoding a recombinant HBsAg modified to contain a plant signal peptide fused to its amino terminus. The signal peptide from soybean vegetative storage protein vspA (VSP alpha S) directed endoplasmic reticulum targeting of HBsAg in plant cells, but was not cleaved and resulted in enhanced VSP alpha S-HBsAg fusion accumulation. This product was more stable and presented the protective "a" antigenic determinant to significantly higher levels than unmodified native HBsAg expressed in plant cells. It also showed a greater extent of intermolecular disulfide bond formation and formation of virus-like particles. Moreover, VSP alpha S-HBsAg stimulated higher levels of serum IgG than native HBsAg when injected into mice. We conclude that HBsAg tolerates a polypeptide fusion at the amino terminus and that VSP alpha S-HBsAg is an improved antigen for plant-based expression of a subunit vaccine for hepatitis B virus.