gebhart/patrepeval huggingface dataset:
Helper-Dependent Adenovirus Vectors Elicit Intact Innate but Attenuated Adaptive Host Immune Responses In Vivo (2004)

Helper-dependent adenovirus (HD-Ad) vectors with all adenoviral genes deleted mediate very long-term expression of therapeutic transgenes in a variety of animal models of disease. These vectors are associated with reduced toxicity and improved safety relative to traditional early region 1 deletion first-generation Ad (FG-Ad) vectors. Many studies have clearly demonstrated that FG-Ad vectors induce innate and adaptive immune responses in vivo; however, a comprehensive analysis of host immune responses to HD-Ad vectors has not yet been performed. In DBA/2 mice, intravenous injection of HD-Ad vectors encoding LacZ (HD-AdLacZ) or a murine secreted alkaline phosphatase (HD-AdSEAP) induced an early expression of inflammatory cytokine and chemokine genes in the liver, including interferon-inducible protein 10, macrophage inflammatory protein 2, and tumor necrosis factor alpha, and were expressed in a pattern similar to that induced by FG-Ad vectors encoding AdSEAP. Like AdSEAP, and consistent with the pattern of cellular gene expression, HD-AdLacZ and HD-AdSEAP induced the recruitment of CD11b-positive leukocytes to the transduced liver within hours of administration. AdSEAP also induced a second phase of liver inflammation, consisting of inflammatory gene expression and CD3-positive lymphocytic infiltrates 7 days posttransduction. In contrast, beyond 24 h no infiltrates or expression of inflammatory genes was detected in the livers of mice receiving HD-AdSEAP. Despite the lack of liver inflammation at 7 days, Ad-specific cytotoxic T lymphocytes could be detected in mice receiving HD-AdSEAP. This lack of liver inflammation was not due to reduced transduction since levels of transgene expression and the amounts of vector DNA in the liver were equivalent in mice receiving HD-AdSEAP and AdSEAP. These results demonstrate that HD-Ad vectors induce intact innate but attenuated adaptive immune responses in vivo.
Endogenous Unsaturated C18 N-Acylethanolamines Are Vanilloid Receptor (TRPV1) Agonists (2005)

The endogenous C18 N-acylethanolamines (NAEs) N-linolenoylethanolamine (18:3 NAE), N-linoleoylethanolamine (18:2 NAE), N-oleoylethanolamine (18:1 NAE), and N-stearoylethanolamine (18:0 NAE) are structurally related to the endocannabinoid anandamide (20:4 NAE), but these lipids are poor ligands at cannabinoid CB(1) receptors. Anandamide is also an activator of the transient receptor potential (TRP) vanilloid 1 (TRPV(1)) on primary sensory neurons. Here we show that C18 NAEs are present in rat sensory ganglia and vascular tissue. With the exception of 18:3 NAE in rat sensory ganglia, the levels of C18 NAEs are equal to or substantially exceed those of anandamide. At submicromolar concentrations, 18:3 NAE, 18:2 NAE, and 18:1 NAE, but not 18:0 NAE and oleic acid, activate native rTRPV(1) on perivascular sensory nerves. 18:1 NAE does not activate these nerves in TRPV(1) gene knock-out mice. Only the unsaturated C18 NAEs elicit whole cell currents and fluorometric calcium responses in HEK293 cells expressing hTRPV(1). Molecular modeling revealed a low energy cluster of U-shaped unsaturated NAE conformers, sharing several pharmacophoric elements with capsaicin. Furthermore, one of the two major low energy conformational families of anandamide also overlaps with the cannabinoid CB(1) receptor ligand HU210, which is in line with anandamide being a dual activator of TRPV(1) and the cannabinoid CB(1) receptor. This study shows that several endogenous non-cannabinoid NAEs, many of which are more abundant than anandamide in rat tissues, activate TRPV(1) and thus may play a role as endogenous TRPV(1) modulators.
Carbon‐Nanotube‐Film Microheater on a Polyethylene Terephthalate Substrate and Its Application in Thermochromic Displays (2011)

Polyethylene terephthalate (PET) is used as the substrate of a carbon nanotube (CNT)-film heater to improve its mechanical robustness. The thermal response is improved by using thin PET and downsizing the CNT-film area. Thermal response times from room temperature to 100 °C of 2 and 5 s are achieved. An addressable microheater array is fabricated and used in thermochromic displays. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor (2007)

Mitochondrial antiviral signaling protein (MAVS) is an essential component of virus-activated signaling pathways that induce protective IFN responses. Its localization to the outer mitochondrial membrane suggests an important yet unexplained role for mitochondria in innate immunity. Here, we show that hepatitis A virus (HAV), a hepatotropic picornavirus, ablates type 1 IFN responses by targeting the 3ABC precursor of its 3C(pro) cysteine protease to mitochondria where it colocalizes with and cleaves MAVS, thereby disrupting activation of IRF3 through the MDA5 pathway. The 3ABC cleavage of MAVS requires both the protease activity of 3C(pro) and a transmembrane domain in 3A that directs 3ABC to mitochondria. Lacking this domain, mature 3C(pro) protease is incapable of MAVS proteolysis. HAV thus disrupts host signaling by a mechanism that parallels that of the serine NS3/4A protease of hepatitis C virus, but differs in its use of a stable, catalytically active polyprotein processing intermediate. The unique requirement for mitochondrial localization of 3ABC underscores the importance of mitochondria to host control of virus infections within the liver.
Sortases and pilin elements involved in pilus assembly of Corynebacterium diphtheriae (2004)

Corynebacterium diphtheriae SpaA pili are composed of three pilin subunits, SpaA, SpaB and SpaC. SpaA, the major pilin protein, is distributed uniformly along the pilus shaft, whereas SpaB is observed at regular intervals, and SpaC seems to be positioned at the pilus tip. Pilus assembly in C. diphtheriae requires the pilin motif and the C-terminal sorting signal of SpaA, and is proposed to occur by a mechanism of ordered cross-linking, whereby pilin-specific sortase enzymes cleave precursor proteins at sorting signals and involve the side-chain amino groups of pilin motif sequences to generate covalent linkages between pilin subunits. We show here that two elements of SpaA pilin precursor, the pilin motif and the sorting signal, are together sufficient to promote the polymerization of an otherwise secreted protein by a process requiring the function of the sortase A gene (srtA). Five other sortase genes are dispensable for SpaA pilus assembly. Further, the incorporation of SpaB into SpaA pili requires a glutamic acid residue within the E box motif of SpaA, a feature that is found to be conserved in other Gram-positive pathogens that encode sortase and pilin subunit genes with sorting signals and pilin motifs. When the main fimbrial subunit of Actinomyces naeslundii type I fimbriae, FimA, is expressed in corynebacteria, C. diphtheriae strain NCTC13129 polymerized FimA to form short fibres. Although C. diphtheriae does not depend on other actinomycetal genes for FimA polymerization, this process involves the pilin motif and the sorting signal of FimA as well as corynebacterial sortase D (SrtD). Thus, pilus assembly in Gram-positive bacteria seems to occur by a universal mechanism of ordered cross-linking of precursor proteins, the multiple conserved features of which are recognized by designated sortase enzymes.
Enzymatic and chemical cleavage methods (1999)

Cleavage-based methods of mutation detection offer a simple and intuitive means to detect and in most cases locate mutations within DNA fragment sizes ranging from 500 to 1500 bases. Their main advantages as a presequencing screening technology when scanning for unknown mutations is the potential to increase throughput by multiplexing. Combined with lower reagent costs per sample, mutation scanning methods offer significant advantages over currently available sequencing techniques and are likely to be of increasing importance as genomic sequence data becomes more readily available. Although enzymatic methods offer the advantages of simpler and less hazardous protocols, at present the most robust cleavage methods are based around chemical methods.
Exploring instruction-fetch bandwidth requirement in wide-issue superscalar processors (1999)

The effective performance of wide-issue superscalar processors depends on many parameters, such as branch prediction accuracy, available instruction-level parallelism, and instruction-fetch bandwidth. This paper explores the relations between some of these parameters, and more particularly, the requirement in instruction-fetch bandwidth. We introduce new enhancements to boost effectively the instruction-fetch bandwidth of conventional fetch engines. However, experiments strongly show that performance improves less for a given instruction-fetch bandwidth gain as the base fetch bandwidth increases. At the level of bandwidth exhibited by the proposed schemes, the performance improvement is small. This clearly brings to light potential relations between the fetch bandwidth and the other parameters. We provide a model to explain this behaviour and quantify some relations. Based on the experimental observation that the available parallelism in an instruction window of size N grows as the square root /spl radic/N, we derive from the model that the instruction fetch bandwidth requirement increases as the square root of the distance between mispredicted branches. We also show that the instruction fetch bandwidth requirement increases linearly with the parallelism available in a fixed-size instruction window.
Active dielectric metasurface based on phase‐change medium (2016)

Abstract We propose all‐dielectric metasurfaces that can be actively re‐configured using the phase‐change material Ge 2 Sb 2 Te 5 (GST) alloy. With selectively controlled phase transitions on the composing GST elements, metasurfaces can be tailored to exhibit varied functionalities. Using phase‐change GST rod as the basic building block, we have modelled metamolecules with tunable optical response when phase change occurs on select constituent GST rods. Tunable gradient metasurfaces can be realized with variable supercell period consisting of different patterns of the GST rods in their amorphous and crystalline states. Simulation results indicate a range of functions can be delivered, including multilevel signal modulating, near‐field coupling of GST rods, and anomalous reflection angle controlling. This work opens up a new space in exploring active meta‐devices with broader applications that cannot be achieved in their passive counterparts with permanent properties once fabricated. image
Isolation of a cDNA clone for the human HLA-DR antigen alpha chain by using a synthetic oligonucleotide as a hybridization probe. (1982)

We have used a synthetic 20-nucleotide hybridization probe to isolate a cDNA clone encoding the alpha chain of the HLA-DR antigen from a cDNA library constructed from membrane-bound poly(A)+ mRNA. A set of synthetic 11-nucleotide fragments, potentially complementary to the codons for amino acids 11-14 of the HLA-DR alpha chain, were used to prime a cDNA synthesis reaction on various poly(A)+ mRNA templates. Extension of the primers in the presence of a single dideoxynucleotide triphosphate resulted in an 18-nucleotide cDNA product whose sequence corresponded to the NH2-terminal amino acids of the HLA-DR alpha chain. An oligonucleotide was synthesized based on this sequence information and its specificity for HLA-DR alpha mRNA was confirmed by primer extension and blot analysis. The cDNA library made from mRNA from the lymphoblastoid cell line CA-SC was probed with 32P-labeled cDNA synthesized on poly(A)+ mRNA from a B-cell line (CA-SC) or from a T-cell line (Molt-4) to enrich for B-cell-specific clones. A set of cDNA clones that hybridized preferentially with the B-cell probe was screened with the 32P-labeled 20-nucleotide probe. The cDNA clone isolated by this procedure is 1,100 nucleotides long; the nucleotide sequence of the 5' end of the cDNA insert corresponds to the amino acid sequence of the HLA-DR alpha chain. Hybridization of this cDNA clone to genomic blots suggests that the HLA-DR alpha chain is encoded by a single-copy gene. One of the restriction endonucleases used in genomic DNA digests reveals a restriction fragment polymorphism.
Bortezomib and sirolimus inhibit the chronic active antibody-mediated rejection in experimental renal transplantation in the rat (2010)

BZ and SRL represent promising drugs with anti-humoral activity in the situation of an already established chronic humoral or mixed alloimmune response after renal transplantation.
Reactive Oxygen Species Mediate Virus-induced STAT Activation (2004)

Respiratory syncytial virus (RSV) is the leading cause of epidemic respiratory tract illness in children in the United States and worldwide. RSV infection of airway epithelial cells induces formation of reactive oxygen species (ROS), whose production mediates the expression of cytokines and chemokines involved the immune/inflammatory responses of the lung. In this study, we have investigated the role of ROS in RSV-induced signal transducers and activators of transcription (STAT) activation and interferon regulatory factor (IRF) gene expression in human airway epithelial cells. Our results indicate that RSV replication induces IRF-1 and -7 gene transcription, a response abrogated by antioxidants. RSV infection induces binding of STAT to the IRF-1 gamma-interferon-activated sequence (GAS) and IRF-7 interferon-stimulated responsive element (ISRE). STAT1 and STAT3 bind IRF-1 GAS, whereas STAT1, STAT2, IRF-1, and IRF-9 bind IRF-7 ISRE. Antioxidant treatment blocks RSV-induced STAT binding to both the IRF-1 GAS and IRF-7 ISRE by inhibition of inducible STAT1 and STAT3 tyrosine phosphorylation, suggesting that RSV-induced ROS formation is required for STAT activation and IRF gene expression. Although protein tyrosine phosphorylation is necessary for RSV-induced STAT activation, Janus kinase and Src kinase activation do not mediate this effect. Instead, RSV infection inhibits intracellular tyrosine phosphatase activity, which is restored by antioxidant treatment. Pharmacological inhibition of tyrosine phosphatases induces STAT activation. Together, these results suggest that modulation of phosphatases could be an important mechanism of virus-induced STAT activation. Treatment of alveolar epithelial cells with the NAD(P)H oxidase inhibitor diphenylene iodonium abolishes RSV-induced STAT activation, indicating that NAD(P)H oxidase-produced ROS are required for downstream activation of the transcription factors IRF and STAT in virus-infected airway epithelial cells.
The Hippocampal Formation (2006)

This chapter begins with a brief discussion of the reasons behind the interest of scientists in the hippocampus. It then considers the importance of studying the hippocampus on its own, followed by discussion of the contemporary era of hippocampal research that started in the 1960s. An overview of the subsequent chapters is presented.
Contraception in mares heteroimmunized with pig zonae pellucidae (1989)

Ten fertile feral mares and 6 domestic horses (4 fertile mares, 1 infertile mare, 1 gelding) were immunized with heat-solubilized pig zonae pellucidae by 4 injections equivalent to 2000 or 5000 zonae each at 2-4-week intervals and a booster injection of 20,000 zonae 6-10 months after the last of the initial inoculations. The immune response was reflected by high antibody levels as measured by an enzyme-linked immunosorbent assay (ELISA) using immobilized pig zona antigen. In-vivo inhibition of fertility occurred in 12 (86%) of the 14 fertile mares studied and persisted for a minimum of 7 months. Repeated mating of the fertile domestic mares resulted in conception when anti-pig zona antibody concentrations had decreased from initial peak absorbance ratios (greater than 1.0) to relatively lower levels (0.64 or less with one exception). An indirect immunofluorescence assay, revealed a considerably lower cross-reactive antibody titre with horse oocytes as compared to pig oocytes. Clinical, endocrinological and histological analyses of the ovaries and their function following regained fertility after immunization revealed no abnormalities. One mare remained infertile.
Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in surgically resectable stage III non-small cell lung cancer (2010)

The purpose of this study was to evaluate the prognostic value of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in patients with stage III non-small cell lung cancer (NSCLC). A total of 188 consecutive patients with pathologic stage III NSCLC were retrospectively reviewed. The expression of LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF) as well as microvessel density (MVD) were evaluated immunohistochemically and correlated with the prognosis of patients after complete resection of the tumor. Positive expression of LAT1 and CD98 was noted in 58% (109/188) and 50% (94/188) of the cases, respectively (p=0.1473). A positive rate of LAT1 expression was significantly higher in squamous cell carcinoma (SQC) (90%, 48/53) and large-cell carcinoma (LCC) (100%, 12/12) than in adenocarcinoma (AC) (40%, 49/123). Moreover, a positive rate of LAT1 with CD98 expression was also significantly higher in SQC (74%, 39/53) and LCC (75%, 9/12) than AC (34%, 42/123). LAT1 expression was significantly higher in patients with mediastinal lymph node metastases than in patients without, and was significantly correlated with CD98, Ki-67 labeling index, VEGF and MVD. The 5-year survival rates of LAT1-positive and -negative patients and CD98-positive and -negative patients were 27.9 and 40.6% (p=0.0033), respectively, and 24.1 and 43.6% (p=0.0004), respectively. Multivariate analysis confirmed that positive expression of LAT1 and CD98 was an independent factor predicting a poor prognosis. In conclusion, the overexpression of LAT1 and CD98 is a pathological factor for predicting the prognosis of patients with surgically resectable stage III NSCLC.
Identification of subdominant CTL epitopes of the GP100 melanoma-associated tumor antigen by primary in vitro immunization with peptide-pulsed dendritic cells (1997)

The gp100 melanoma-associated tumor Ag was selected as a model system to study the diversity of human antitumor cytotoxic T cell responses. First, peptides corresponding to dominant gp100 HLA-A2.1-restricted CTL epitopes were tested using lymphocytes from normal volunteers and an in vitro priming protocol that uses peptide-pulsed dendritic cells as APCs and IL-7 and IL-10 as immune-enhancing cytokines. High CTL activity toward both peptide-pulsed target cells and gp100+ melanoma cells was obtained with four out of five peptides tested. Second, HLA-A2.1-binding peptides from gp100 that do not appear to represent CTL epitopes in melanoma patients were also tested for their capacity to induce CTL using the in vitro priming protocol. Three of six peptides tested induced CTL in lymphocytes from normal volunteers. One of these peptides was also immunogenic for lymphocytes derived from a melanoma patient in remission. Because these three CTL epitopes were not recognized in the natural immune response in melanoma patients but do appear as immunogens when peptides are used to induce the T cell response, they may be considered as typical "subdominant" epitopes. The results are discussed in the context of the usefulness of this approach to detail the immunologic potential of a given tumor-associated Ag and its relevance for the design of effective immune-based therapies.
Pulsed second-harmonic generation in nonlinear, one-dimensional, periodic structures (1997)

We present a numerical study of second-harmonic (SH) generation in a one-dimensional, generic, photonic band-gap material that is doped with a nonlinear ${\ensuremath{\chi}}^{(2)}$ medium. We show that a 20-period, 12-\ensuremath{\mu}m structure can generate short SH pulses (similar in duration to pump pulses) whose energy and power levels may be 2--3 orders of magnitude larger than the energy and power levels produced by an equivalent length of a phase-matched, bulk medium. This phenomenon comes about as a result of the combination of high electromagnetic mode density of states, low group velocity, and spatial phase locking of the fields near the photonic band edge. The structure is designed so that the pump pulse is tuned near the first-order photonic band edge, and the SH signal is generated near the band edge of the second-order gap. This maximizes the density of available field modes for both the pump and SH field. Our results show that the ${\ensuremath{\chi}}^{(2)}$ response is effectively enhanced by several orders of magnitude. Therefore, mm- or cm-long, quasi-phase-matched devices could be replaced by these simple layered structures of only a few micrometers in length. This has important applications to high-energy lasers, Raman-type sources, and frequency up- and down-conversion schemes.
Purification of a Thermostable DNA Polymerase from a Thermotoga Speciesa (1990)

Most of the initial studies on the fundamental cellular process of biosynthesis and repair of deoxyribonucleic acid (DNA) have been carried out on the bacterium&#13;\nEscherichia coli.¹When a single-stranded DNA template is provided with a primer, the 5’ - 3’ polymerase copies the template in the presence of deoxyribonucleotide triphosphates and a divalent cation, for example, Mg²⁺.
Detection of BOLD changes by means of a frequency‐sensitive trueFISP technique: preliminary results (2001)

A new method is introduced to detect magnetic field modulation arising from brain activation-induced BOLD effects. This approach uses a two-dimensional high-bandwidth, high-resolution conventional gradient-echo steady-state imaging sequence known as TrueFISP. The ability to visualize changes in oxygen saturation comes from the fact that the method is sensitive to the local field. As is well known, as the oxygen saturation changes so does the local field associated with the venous blood. We demonstrate that it is possible to visualize not only venous blood with this approach on a macroscopic level for major veins, but also to measure conventional oscillatory like signal changes during activated and resting states. Unfortunately, the method has two major drawbacks. First, a long TR is needed to maximize signal changes and, second, the field must be very well shimmed or numerous experiments need to be run to find the activation, as the signal response is sensitive to the starting frequency in the resting state. Nevertheless, these images can be compared directly with anatomical images collected with the same method without the need for distortion correction.