gebhart/patrepeval huggingface dataset:
The major immunogenic epitopes of Epstein-Barr virus (EBV) nuclear antigen 1 are encoded by sequence domains which vary among nasopharyngeal carcinoma biopsies and EBV-associated cell lines. (1999)

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a protein expressed consistently in EBV-infected cells and EBV-associated malignant tissues. A panel of monoclonal antibodies (MAbs) was generated against the C terminus of EBNA-1 and evaluated for the detection of EBNA-1 in different cell lines. The epitopes recognized were mapped. Since sequence variations of EBNA-1 have been reported in nasopharyngeal carcinoma (NPC) tissues and in infected healthy individuals, the ability of these MAbs to recognize a recombinant protein derived from an NPC biopsy was also analysed. MAb 4H11 appeared to react with EBNA-1 sequences from different sources, whereas MAbs 5C11, 5F12 and 8F6 failed to recognize a recombinant EBNA-1 protein cloned from an NPC patient. Using different recombinant EBNA-1 fragments in an immunoblot format, this study demonstrates that the domain bounded by amino acids 408 and 498 is very immunogenic in mice in that epitopes in this region are recognized by various MAbs. Amino acid sequences of EBNA-1 were also deduced from nucleotide sequences amplified from three Burkitt's lymphoma cell lines, two spontaneous lymphoblastoid cell lines, two NPC biopsies and one NPC hybrid cell line, NPC-KT, and compared to the sequence from B95-8. The amino acid sequence of EBNA-1 in Akata is almost identical to that in an NPC biopsy, except for amino acid 585. The results of this study indicate that the immunogenic epitopes of EBNA-1 are highly variable.
Diurnal variation affects age-related profile in skin thickness. (2002)

We have previously demonstrated that over the course of each day there are changes in skin thickness that can be measured by B-mode ultrasonography. This suggests that there is a shift in dermal fluid from the face toward the legs by gravity, resulting in a diurnal variation in skin thickness. Therefore, age-dependent profiles in skin thickness were evaluated by B-mode ultrasonography in the morning or in the afternoon for 130 normal Japanese females aged 18-83 years. Three areas of the face (the forehead, the corners of the eye, and the cheeks) were measured as distinctively sun-exposed areas while the flexion side of the forearm was measured as a weakly sun-exposed area. A weak correlation between skin thickness and age was found in all areas measured (positive for the forehead, the corners of the eye, and the cheeks; negative for forearms) in the morning but not in the afternoon, when only a weak positive correlation was observed in the cheek. These results indicate that when measuring skin thickness, an appropriate time for taking measurements should be selected with consideration of the movements of dermal fluid over the course of each day.
Intelligent code completion with Bayesian networks. (2016)

Code completion is an integral part of modern Integrated Development Environments (IDEs). Developers often use it to explore Application Programming Interfaces (APIs). It is also useful to reduce the required amount of typing and to help avoid typos. Traditional code completion systems propose all type-correct methods to the developer. Such a list is often very long with many irrelevant items. More intelligent code completion systems have been proposed in prior work to reduce the list of proposed methods to relevant items.This work extends one of these existing approaches, the Best Matching Neighbor (BMN) algorithm. We introduce Bayesian networks as an alternative underlying model, use additional context information for more precise recommendations, and apply clustering techniques to improve model sizes. We compare our new approach, Pattern-based Bayesian Networks (PBN), to the existing BMN algorithm. We extend previously used evaluation methodologies and, in addition to prediction quality, we also evaluate model size and inference speed.Our results show that the additional context information we collect improves prediction quality, especially for queries that do not contain method calls. We also show that PBN can obtain comparable prediction quality to BMN, while model size and inference speed scale better with large input sizes.
A 3D sidewall flash EPROM cell and memory array (1993)

A promising new sidewall flash EPROM (electrically programmable read-only memory) cell has been implemented in a novel memory array to demonstrate the potential of this cell for shrinking future generations of ultrahigh-density, high-performance flash EPROM arrays. The sidewall flash EPROM cell is a 3-D, single transistor, floating gate memory cell that is fabricated on the sidewalls of a narrow silicon pillar. Current flows vertically along the sidewalls of the pillar from the top of the pillar (drain), to the base of the pillar (source). Because both the source and the word lines lie buried beneath the surface of the wafer, the sidewall EPROM realizes extremely small cell size, approaching the theoretical minimum cell size dictated by the lithography dependent pitch. The sidewall EPROM cell becomes increasingly attractive as EPROM scaling continues down into the deep submicron regime. This is because the channel length of the memory transistor remains the same as geometries are scaled and only the width decreases. Another significant advantage is that isolation between cells is inherent in this approach and is not a concern when scaling.
Advances and Future Prospects of Spin-Transfer Torque Random Access Memory (2010)

Spin-transfer torque random access memory (STT-RAM) is a potentially revolutionary universal memory technology that combines the capacity and cost benefits of DRAM, the fast read and write performance of SRAM, the non-volatility of Flash, and essentially unlimited endurance. In order to realize a small cell size, high speed and achieve a fully functional STT-RAM chip, the MgO-barrier magnetic tunnel junctions (MTJ) used as the core storage and readout element must meet a set of performance requirements on switching current density, voltage, magneto-resistance ratio (MR), resistance-area product (RA), thermal stability factor (¿) , switching current distribution, read resistance distribution and reliability. In this paper, we report the progress of our work on device design, material improvement, wafer processing, integration with CMOS, and testing for a demonstration STT-RAM test chip, and projections based on modeling of the future characteristics of STT-RAM.
Lysis of HIV-1-infected cells and inhibition of viral replication by universal receptor T cells (1997)

Increasing evidence suggests that HIV-1-specific cytotoxic T lymphocytes (CTLs) are a key host immune response to HIV-1 infection. Generation of CTL responses for prevention or therapy of HIV-1 infection has several intrinsic technical barriers such as antigen expression and presentation, the varying HLA restrictions between different individuals, and the potential for viral escape by sequence variation or surface molecule alteration on infected cells. A strategy to circumvent these limitations is the construction of a chimeric T cell receptor containing human CD4 or HIV-1-specific Ig sequences linked to the signaling domain of the T cell receptor zeta chain (universal T cell receptor). CD8+ CTLs transduced with this universal receptor can then bind and lyse infected cells that express surface HIV-1 gp120. We evaluated the ability of universal-receptor-bearing CD8+ cells from a seronegative donor to lyse acutely infected cells and inhibit HIV-1 replication in vitro. The kinetics of lysis and efficiency of inhibition were comparable to that of naturally occurring HIV-1-specific CTL clones isolated from infected individuals. Further study will be required to determine the utility of these cells as a therapeutic strategy in vivo.
Spatial learning deficit in transgenic mice that conditionally over‐express GSK‐3β in the brain but do not form tau filaments (2002)

Deregulation of glycogen synthase kinase-3 (GSK-3) activity in neurones has been postulated as a key feature in Alzheimer's disease (AD) pathogenesis. This was further supported by our recent characterization of transgenic mice that conditionally over-express GSK-3beta in hippocampal and cortical neurones. These mice, designated Tet/GSK-3beta, showed many of the biochemical and cellular aspects of AD neuropathology such as tau hyperphosphorylation and somatodendritic localization, decreased nuclear beta-catenin, neuronal death and reactive gliosis. Tet/GSK-3beta mice, however, did not show tau filament formation up to the latest tested age of 3 months at least. Here we report spatial learning deficits of Tet/GSK-3beta mice in the Morris water maze. In parallel, we also measured the increase in GSK-3 activity while further exploring the possibility of tau filament formation in aged mice. We found a significant increase in GSK-3 activity in the hippocampus of Tet/GSK-3beta mice whereas no tau fibrils could be found even in very old mice. These data reinforce the hypothesis of GSK-3 deregulation in AD pathogenesis, and suggest that Tet/GSK-3beta mice can be used as an AD model and, most remarkably, can be used to test the therapeutic potential of the selective GSK-3 inhibitors that are currently under development. Additionally, these experiments suggest that destabilization of microtubules and alteration of intracellular metabolic pathways contribute to AD pathogenesis independent of toxicity triggered by the aberrant tau deposits.
Protamine-Fragment Peptides Fused to an SV40 Nuclear Localization Signal Deliver Oligonucleotides That Produce Antisense Effects in Prostate and Bladder Carcinoma Cells (2002)

The development of antisense technology has focused on improving methods for oligonucleotide delivery into cells. In the present work, we describe a novel strategy for oligonucleotide delivery based on a bifunctional peptide composed of a C-terminal protamine-fragment that contains a DNA-binding domain and an N-terminal nuclear localization signal sequence derived from the SV40 large-T antigen (The sequences of two of the peptides are R6WGR6-PKKKRKV [s-protamine-NLS] and R4SR6FGR6VWR4-PKKKRKV [l-protamine-NLS]). We demonstrated, by intrinsic fluorescence quenching, that peptides of this class form complexes with oligodeoxynucleotides. To evaluate delivery, we used a 20-mer phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated region of the PKC-alpha mRNA and G3139, an 18-mer phosphorothioate targeted to the first six codons of the human bcl-2 open reading frame, and complexed them with either of two peptides (s- or l-protamine-NLS). These peptides bind to and deliver antisense oligonucleotides to the nucleus of T24 bladder and PC3 prostate cancer cells, as demonstrated by confocal microscopy. Furthermore, as shown by Western and Northern blotting, the peptide-oligonucleotide complexes produced excellent downregulation of the expression of the complementary mRNAs, which in turn resulted in downregulation of protein expression. However, under certain circumstances (predominantly in PC3 cells), incubation of the cells with chloroquine was required to produce antisense activity. Using this strategy, PKC-alpha protein and mRNA expression in T24 and PC3 cells and bcl-2 expression in PC3 cells was reduced by approximately 75 +/- 10% at a minimum concentration of oligomer of 0.25 microM, in combination with 12-15 microM peptide. On the basis of our results, we conclude that arginine-rich peptides of this class may be potentially useful delivery vehicles for the cellular delivery of antisense oligonucleotides. This new strategy may have several advantages over other methods of oligonucleotide delivery and may complement already existing lipid-based technologies.
Genetic Subtypes in Retinitis Pigmentosa (1989)

<h3>To the Editor.</h3> —In their article in the March 1988Archives, Hunter and colleagues<sup>1</sup>state that "Attempts to elucidate the pathogeneses of these [genetic] subtypes have been confounded by studies that have considered all patients with RP [retinitis pigmentosa] as a single group," after which two RP studies of which I was one of the authors are referenced. It appears that a careful reading was not given to our articles, as Table 1 in the article on autoimmunity in hereditary retinal degeneration<sup>2</sup>illustrates the great effort the UCLA Retinitis Pigmentosa Center takes to subdivide patients with RP on a hereditary and test rationale, while our study correlating the fluorescein angiographic findings with the presence or absence of antiretinal antibodies<sup>3</sup>also looked at differences between patients with typical rod-cone vs cone-rod degeneration (type I vs type II RP, Baltimore classification). Hunter et al appear to be critical of
Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens (2001)

Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351-1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell-deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
Fuel optimal propulsive maneuver of an experimental structure exhibiting spacelike dynamics (1996)

The implementation of four fuel-optimal methods for propulsive maneuver of space structures is described. Toward this end, an experimental structure that possessed spacelike dynamics was fabricated and used to test the previously mentioned fuel optimal methods. The results given highlight the differences among fuel optimal methods for propulsive maneuver of space structures, their relative strengths and weaknesses, and the sources of
The First 1000 Dendritic Cell Vaccinees (2003)

Dendritic cells (DCs) are potent antigen-presenting cells that have the ability to stimulate primary T cell antitumor immune responses in animals and humans. Since the first published clinical trial of dendritic cell vaccination in 1995, 98 studies describing more than 1000 vaccinees have been published in peer-reviewed medical journals or presented at the annual meetings of the American Society for Clinical Oncology, the American Association of Cancer Research, or the American Society of Hematology. Trials have been performed in 15 countries. Trials included patients with more than two dozen tumor types; most trials studied patients with malignant melanoma, prostate cancer, colorectal carcinoma, or multiple myeloma, using autologous DCs pulsed with synthetic antigens or idiotype antibodies. The DC vaccines were also prepared by pulsing DCs with tumor lysates or RNA, by transfection with tumor DNA, or by creating tumor cell/DC fusions. Various approaches to vaccine cell numbers, length of vaccine program, site of vaccination, frozen preservation of vaccine, and use of a maturations step for DCs were used. Adverse effects associated with DC vaccination were uncommon; most were mild and self-limited and none were serious. Clinical responses were observed in approximately half the trials. The DC vaccination may provide a safe approach to cancer immunotherapy that can overcome the limited reach and immunogenicity of peptide vaccines.
Incremental synthesis (1994)

A small change in the input to logic synthesis may cause a large change in the output implementation. This is undesirable if a designer has some investment in the old implementation and does not want it perturbed more than necessary. We describe a method that solves this problem by reusing gates from the old implementation, and restricting synthesis to the modified portions only.
Potentiating and suppressive IgE-binding factors are expressed by a single cloned gene. (1987)

We have investigated expression of an IgE-binding factor (IgE-BF) cDNA in both COS-7 monkey kidney cells and Chinese hamster ovary cells. Transient expression of the IgE-BF clone in either cell type yielded IgE-BF, which potentiated an in vitro IgE response and had an affinity for lentil lectin. In contrast, when the transient expression experiments were carried out in the presence of tunicamycin, the factors no longer bound to lentil lectin. Moreover, IgE-BF expressed under these conditions suppressed an in vitro IgE response. IgE-BF lacking affinity for lentil lectin and suppressing the IgE response also resulted from transient expression of the IgE-BF gene in the presence of glycosylation inhibiting factor, a phospholipase inhibitory protein. Thus, IgE-BF that either potentiate or suppress the IgE response can be expressed from a single cloned gene; the difference in biological activities appears to be determined principally by the type of glycosylation of the common polypeptide chain. Previous work showed that IgE-BF bears an antigenic determinant recognized by the anti-Ia monoclonal antibody OX3. IgE-BF produced in the presence of tunicamycin, and IgE-BF expressed from a mutant cDNA lacking one of two carbohydrate-attachment sites, lacked the OX3 determinant. Thus, the OX3 determinant on IgE-BF appears to be associated with a site of N-linked glycosylation.
A microfluidic model of the blood–brain barrier to study permeabilization by pulsed electric fields (2017)

Pulsed electric fields interact with the blood-brain barrier (BBB) and have been shown to increase the BBB permeability under some pulsing regimes. Pulsed electric fields may enhance drug delivery to the brain by disrupting the integrity of the BBB and allowing otherwise impermeable drugs to reach target areas. Microfluidic, in vitro models offer an alternative platform for exploring the impact of pulsed electric fields on the BBB because they create physiologically relevant microenvironments and eliminate the confounding variables of animal studies. We developed a microfluidic platform for real-time measurement of BBB permeability pre- and post-treatment with pulsed electric fields. Permeability is measured optically by the diffusion of fluorescent tracers across a monolayer of human cerebral microcapillary endothelial cells (hCMECs) cultured on a permeable membrane. We found that this device is able to capture real-time permeability of hCMEC monolayers for both reversible and irreversible electroporation pulsing regimes. Furthermore, preliminary testing of deep brain stimulation pulsing regimes reveals possible impacts on BBB integrity. This device will enable future studies of pulsed electric field regimes for improved understanding of BBB permeabilization.
SUMO Modification of Heterogeneous Nuclear Ribonucleoproteins (2004)

Small ubiquitin-related modifiers (SUMOs) are proteins that are posttranslationally conjugated to other cellular proteins, particularly those that localize and function in the nucleus. Enzymes regulating SUMO modification localize in part to nuclear pore complexes (NPCs), indicating that modification of some proteins may occur as they are translocated between the nucleus and the cytoplasm. Substrates that are regulated by SUMO modification at NPCs, however, have not been previously identified. Among the most abundant cargos transported through NPCs are the heterogeneous nuclear ribonucleoproteins (hnRNPs). HnRNPs are involved in various aspects of mRNA biogenesis, including regulation of pre-mRNA splicing and nuclear export. Here, we demonstrate that two subsets of hnRNPs, the hnRNP C and M proteins, are substrates for SUMO modification. We demonstrate that the hnRNP C proteins are modified by SUMO at a single lysine residue, K237, and that SUMO modification at this site decreases their binding to nucleic acids. We also show that Nup358, a SUMO E3 ligase associated with the cytoplasmic fibrils of NPCs, enhances the SUMO modification of the hnRNP C and M proteins. Based on our findings, we propose that SUMO modification of the hnRNP C and M proteins may occur at NPCs and facilitate the nucleocytoplasmic transport of mRNAs.
CT-measured regional specific volume change reflects regional ventilation in supine sheep (2008)

Computer tomography (CT) imaging techniques permit the noninvasive measurement of regional lung function. Regional specific volume change (sVol), determined from the change in lung density over a tidal breath, should correlate with regional ventilation and regional lung expansion measured with other techniques. sVol was validated against xenon (Xe)-CT-specific ventilation (sV) in four anesthetized, intubated, mechanically ventilated sheep. Xe-CT used expiratory gated axial scanning during the washin and washout of 55% Xe. sVol was measured from the tidal changes in tissue density (H, houndsfield units) of lung regions using the relationship sVol = [1,000(Hi - He)]/[He(1,000 + Hi)], where He and Hi are expiratory and inspiratory regional density. Distinct anatomical markings were used to define corresponding lung regions of interest between inspiratory, expiratory, and Xe-CT images, with an average region of interest size of 1.6 +/- 0.7 ml. In addition, sVol was compared with regional volume changes measured directly from the positions of implanted metal markers in an additional animal. A linear relationship between sVol and sV was demonstrated over a wide range of regional sV found in the normal supine lung, with an overall correlation coefficient (R(2)) of 0.66. There was a tight correlation (R(2) = 0.97) between marker-measured volume changes and sVol. Regional sVol, which involves significantly reduced exposure to radiation and Xe gas compared with the Xe-CT method, represents a safe and efficient surrogate for measuring regional ventilation in experimental studies and patients.
Two Outer Membrane Lipoproteins from Histophilus somni Are Immunogenic in Rabbits and Sheep and Induce Protection against Bacterial Challenge in Mice (2012)

Histophilus somni is an economically important pathogen of cattle and other ruminants and is considered one of the key components of the bovine respiratory disease (BRD) complex, the leading cause of economic loss in the livestock industry. BRD is a multifactorial syndrome, in which a triad of agents, including bacteria, viruses, and predisposing factors or "stressors," combines to induce disease. Although vaccines against H. somni have been used for many decades, traditional bacterins have failed to demonstrate effective protection in vaccinated animals. Hence, the BRD complex continues to produce strong adverse effects on the health and well-being of stock and feeder cattle. The generation of recombinant proteins may facilitate the development of more effective vaccines against H. somni, which could confer better protection against BRD. In the present study, primers were designed to amplify, clone, express, and purify two recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are structural proteins of the outer bacterial membrane. The results presented here demonstrate, to our knowledge for the first time, that when formulated, an experimental vaccine enriched with these two recombinant lipoproteins generates high antibody titers in rabbits and sheep and exerts a protective effect in mice against septicemia induced by H. somni bacterial challenge.