gebhart/patrepeval huggingface dataset:
Mutational definition of the human immunodeficiency virus type 1 Rev activation domain (1991)

Replication of human immunodeficiency virus type 1 requires the functional expression of the virally encoded Rev protein. The binding of this nuclear trans activator to its viral target sequence, the Rev-response element, induces the cytoplasmic expression of unspliced viral mRNAs. Mutation of the activation domain of Rev generates inactive proteins with normal RNA binding capabilities that inhibit wild-type Rev function in a trans-dominant manner. Here, we report that the activation domain comprises a minimum of nine amino acids, four of which are critically spaced leucines. The preservation of this essential sequence in other primate and nonprimate lentivirus Rev proteins indicates that this leucine-rich motif has been highly conserved during evolution. This conclusion, taken together with the observed permissiveness of a variety of eukaryotic cell types for Rev function, suggests that the target for the activation domain of Rev is likely to be a highly conserved cellular protein(s) intrinsic to nuclear mRNA transport or splicing.
The FLP protein of the yeast 2-microns plasmid: expression of a eukaryotic genetic recombination system in Escherichia coli. (1983)

The FLP gene of the yeast 2-microns plasmid is involved in a site-specific recombination event that results in the inversion of a set of sequences within the plasmid. This gene has been cloned and expressed in Escherichia coli. Expression of the FLP gene results in efficient recombination within the bacterial cell, which is specific for plasmids containing at least one 2-microns plasmid recombination site. This work demonstrates that (i) FLP protein is actively involved in 2-microns plasmid recombination; (ii) no other factors specific to yeast are required for the reaction; (iii) FLP protein acts efficiently in trans; (iv) FLP protein will promote site-specific insertion and deletion reactions in addition to the inversion reaction; and (v) FLP-promoted recombination is not dependent upon any DNA structural features unique to yeast chromatin.
Cloning and characterization of nanB, a second Streptococcus pneumoniae neuraminidase gene, and purification of the NanB enzyme from recombinant Escherichia coli (1996)

Streptococcus pneumoniae is believed to produce more than one form of neuraminidase, but there has been uncertainty as to whether this is due to posttranslational modification of a single gene product or the existence of more than one neuraminidase-encoding gene. Only one stable pneumococcal neuraminidase gene (designated nanA) has been described. In the present study, we isolated and characterized a second neuraminidase gene (designated nanB), which is located close to nanA on the pneumococcal chromosome (approximately 4.5kb downstream). nanB was located on an operon separate from that of nanA, which includes at least five other open reading frames. NanB has a predicted size of 74.5 kDa after cleavage of a 29-amino-acid signal peptide. There was negligible amino acid homology between NanA and NanB, but NanB did exhibit limited homology with the sialidase of Clostridium septicum. NanB was purified from recombinant Escherichia coli and found to have a pH optimum of 4.5, compared with 6.5 to 7.0 for NanA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis suggested that NanB has a molecular size of approximately 65 kDa. The discrepancy between this estimate and the size predicted from the nucleotide sequence is most likely a consequence of C-terminal processing or anomalous electrophoretic behavior.
Nanomaterial transfer using hot embossing for flexible electronic devices (2006)

We demonstrate hot embossing to pattern carbon nanotubes (CNTs) on flexible substrates. Patterns of CNTs grown on both microtextured and flat silicon templates were transferred into polymer substrates, with good replication of both the CNT patterns and surface relief features. The transferred CNTs formed a highly entangled network with electrical resistance of 1kΩ–9MΩ, depending on growth and embossing conditions. The electrical properties showed a strong sensitivity to both light and temperature. This dry transfer process shows promise for high throughput manufacturing of nanomaterial-based flexible electronic devices.
Lupus Antibody Tops Cancer Cells (2012)

A lupus causing anti-DNA antibody penetrates living cells and targets DNA repair for therapeutic advantage in human cancer cells.
Distribution of Reducible 4-Hydroxynonenal Adduct Immunoreactivity in Alzheimer Disease is Associated with APOE Genotype (1998)

Two major risk factors for late-onset familial and sporadic Alzheimer disease (AD), a leading cause of dementia worldwide, are increasing age and inheritance of the epsilon4 allele of the apolipoprotein E gene (APOE4). Several isoform-specific effects of apoE have been proposed; however, the mechanisms by which apoE isoforms influence the pathogenesis of AD are unknown. Also associated with AD is increased lipid peroxidation in the regions of the brain most damaged by disease. 4-hydroxynonenal (HNE), the most potent neurotoxic product of lipid peroxidation, is thought to be deleterious to cells through reactions with protein nucleophiles. We tested the hypothesis that accumulation of the most common forms of HNE-protein adducts, borohydride-reducible adducts, is associated with AD and examined whether there was a relationship to APOE. Our results demonstrated that reducible HNE adducts were increased in the hippocampus, entorhinal cortex, and temporal cortex of patients with AD. Furthermore, our data showed that the pattern of reducible HNE adduct accumulation was related to APOE genotype; AD patients homozygous for APOE4 had pyramidal neuron cytoplasmic accumulation of reducible HNE adducts, while AD APOE3 homozygotes had both pyramidal neuron and astrocyte accumulation of reducible HNE adducts. This is in contrast to our previous observations that a distinct HNE protein adduct, the pyrrole adduct, accumulates on neurofibrillary tangles in AD patients. We conclude that APOE genotype influences the cellular distribution of increased reducible HNE adduct accumulation in AD.
Autism, Alzheimer disease, and fragile X (2011)

The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-β peptide (Aβ), Aβ precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted α form of the amyloid-β precursor protein (sAPPα) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPα levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPα level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPα and production of insoluble Aβ would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.
XOMA 052, an Anti-IL-1β Monoclonal Antibody, Improves Glucose Control and β-Cell Function in the Diet-Induced Obesity Mouse Model (2010)

Recent evidence suggests that IL-1beta-mediated glucotoxicity plays a critical role in type 2 diabetes mellitus. Although previous work has shown that inhibiting IL-1beta can lead to improvements in glucose control and beta-cell function, we hypothesized that more efficient targeting of IL-1beta with a novel monoclonal antibody, XOMA 052, would reveal an effect on additional parameters affecting metabolic disease. In the diet-induced obesity model, XOMA 052 was administered to mice fed either normal or high-fat diet (HFD) for up to 19 wk. XOMA 052 was administered as a prophylactic treatment or as a therapy. Mice were analyzed for glucose tolerance, insulin tolerance, insulin secretion, and lipid profile. In addition, the pancreata were analyzed for beta-cell apoptosis, proliferation, and beta-cell mass. Mice on HFD exhibited elevated glucose and glycated hemoglobin levels, impaired glucose tolerance and insulin secretion, and elevated lipid profile, which were prevented by XOMA 052. XOMA 052 also reduced beta-cell apoptosis and increased beta-cell proliferation. XOMA 052 maintained the HFD-induced compensatory increase in beta-cell mass, while also preventing the loss in beta-cell mass seen with extended HFD feeding. Analysis of fasting insulin and glucose levels suggests that XOMA 052 prevented HFD-induced insulin resistance. These studies provide new evidence that targeting IL-1beta in vivo could improve insulin sensitivity and lead to beta-cell sparing. This is in addition to previously reported benefits on glycemic control. Taken together, the data presented suggest that XOMA 052 could be effective for treating many aspects of type 2 diabetes mellitus.
Role of complement in renal tubular damage (1995)

Deposition of immunoglobulins, complement proteins C1q, C3c, C3d, C4, C5, C6, C7, C8, C9, and terminal complement complex neoantigens in the renal tubulointerstitium was studied in serial sections by immunofluorescence microscopy. Renal tissue from 45 cases with various glomerular diseases, including 8 controls, was studied. The patients were divided into groups; one with tubulointerstitial lesions (24 cases) and the other without (13 cases). The immunoproteins were deposited mainly in the tubular basement membrane and blood vessels. Compared with controls there was a significantly increased staining score for C5 to C9 in the tubular basement membrane in both disease groups. However, the increase in terminal complement complex neoantigens score was significant only in the disease group with tubulo interstitial lesions. The changes in C3d score were not significant. Serial sections showed consistent and heavy ribbon-like deposits of complement proteins C3d, C5 to C9, and terminal complement complex neoantigens in corresponding locations of the segments of tubular basement membrane, mainly in the disease group with tubulointerstitial lesions and especially in the damaged tubules. These findings suggest that in situ activation of the complement cascade leads to the deposition of terminal complement complex neoantigens. Complement activation in the basal area of the tubules may, therefore, be an important pathogenetic mechanism in tubulointerstitial damage.
The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody (2010)

T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti-PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1(+) MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.
Efficient execution of memory access phases using dataflow specialization (2015)

This paper identifies a new opportunity for improving the efficiency of a processor core: memory access phases of programs. These are dynamic regions of programs where most of the instructions are devoted to memory access or address computation. These occur naturally in programs because of workload properties, or when employing an in-core accelerator, we get induced phases where the code execution on the core is access code. We observe such code requires an OOO core's dataflow and dynamism to run fast and does not execute well on an in-order processor. However, an OOO core consumes much power, effectively increasing energy consumption and reducing the energy efficiency of in-core accelerators.
Persistent issues in the application of virtual environment systems to training (2002)

The flexible constellation of technologies that comprise virtual environment (VE) systems provide many new opportunities for training. However, the lessons learned from decades of research in flight and driving simulation seem largely forgotten. This review recalls a set of long-term issues that will constrain the application of VE systems to training. In particular, the issues of cost effectiveness, interface usability, transfer of training, transfer theory, and training feedback are addressed. Training and research decisions that do not consider these issues are likely to result in programs and recommendations that do little to efficiently improve skills and knowledge.
Inhibitory effects of ω‐3 polyunsaturated fatty acids on receptor‐mediated non‐selective cation currents in rat A7r5 vascular smooth muscle cells (1997)

1. The effects of omega-3 polyunsaturated fatty acids on receptor-mediated non-selective cation current (Icat) and K+ current were investigated in aortic smooth muscle cells from foetal rat aorta (A7r5 cells). The whole-cell voltage clamp technique was employed. 2. With a K(+)-containing solution, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 30 microM) produced an outward current at a holding potential of -40 mV. This response was inhibited by tetraethylammonium (20 mM) or Cs+ in the patch pipette solution, and the reversal potential of the EPA-induced current followed the K+ equilibrium potential in a near Nernstian manner. 3. Under conditions with a Cs(+)-containing pipette solution, both vasopressin and endothelin-1 (100 nM) induced a long-lasting inward current at a holding potential of -60 mV. The reversal potential of these agonist-induced currents was about +0 mV, and was not significantly altered by the replacement of the extracellular or intracellular Cl+ concentration, suggesting that the induced current was a cation-selective current (Icat). 4. La3+ and Cd2+ (1 mM) completely abolished these agonist-induced Icat, but nifedipine (10 microM) failed to inhibit it significantly. 5. omega-3 polyunsaturated fatty acids (3-100 microM), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist-induced Icat in a concentration-dependent manner. The potency of the inhibitory effect was EPA > DHA > DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 microM. 6. Arachidonic and linoleic acids (10, 30 microM) showed a smaller inhibitory effect compared to omega-3 fatty acids. Also, oleic and stearic acids (30 microM) did not show a significant inhibitory effect on Icat. 7. A similar inhibitory action of EPA was observed when Icat was activated by intracellularly applied GTP gamma S in the absence of agonists, suggesting that the site of action of omega-3 fatty acids is not located on the receptor. 8. These results demonstrate that omega-3 polyunsaturated fatty acids can activate a K+ current and also effectively inhibit receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells. Thus, the data suggest that omega-3 fatty acids may play an important role in the regulation of vascular tone.
Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer (2005)

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (> 75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P < 0.001). Using specific thresholds, patients with > or = 25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.
HydraFS: a high-throughput file system for the HYDRAstor content-addressable storage system (2010)

A content-addressable storage (CAS) system is a valuable tool for building storage solutions, providing efficiency by automatically detecting and eliminating duplicate blocks; it can also be capable of high throughput, at least for streaming access. However, the absence of a standardized API is a barrier to the use of CAS for existing applications. Additionally, applications would have to deal with the unique characteristics of CAS, such as immutability of blocks and high latency of operations. An attractive alternative is to build a file system on top of CAS, since applications can use its interface without modification.Mapping a file system onto a CAS system efficiently, so as to obtain high duplicate elimination and high throughput, requires a very different design than for a traditional disk subsystem. In this paper, we present the design, implementation, and evaluation of HydraFS, a file system built on top of HYDRAstor, a scalable, distributed, content-addressable block storage system. HydraFS provides high-performance reads and writes for streaming access, achieving 82-100% of the HYDRAstor throughput, while maintaining high duplicate elimination.
PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma (2014)

Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma.
Engineering microbes to sense and eradicate Pseudomonas aeruginosa , a human pathogen (2011)

Synthetic biology aims to systematically design and construct novel biological systems that address energy, environment, and health issues. Herein, we describe the development of a synthetic genetic system, which comprises quorum sensing, killing, and lysing devices, that enables Escherichia coli to sense and kill a pathogenic Pseudomonas aeruginosa strain through the production and release of pyocin. The sensing, killing, and lysing devices were characterized to elucidate their detection, antimicrobial and pyocin release functionalities, which subsequently aided in the construction of the final system and the verification of its designed behavior. We demonstrated that our engineered E. coli sensed and killed planktonic P. aeruginosa, evidenced by 99% reduction in the viable cells. Moreover, we showed that our engineered E. coli inhibited the formation of P. aeruginosa biofilm by close to 90%, leading to much sparser and thinner biofilm matrices. These results suggest that E. coli carrying our synthetic genetic system may provide a novel synthetic biology-driven antimicrobial strategy that could potentially be applied to fighting P. aeruginosa and other infectious pathogens.
High Throughput Phenotyping of Blueberry Bush Morphological Traits Using Unmanned Aerial Systems (2017)

Phenotyping morphological traits of blueberry bushes in the field is important for selecting genotypes that are easily harvested by mechanical harvesters. Morphological data can also be used to assess the effects of crop treatments such as plant growth regulators, fertilizers, and environmental conditions. This paper investigates the feasibility and accuracy of an inexpensive unmanned aerial system in determining the morphological characteristics of blueberry bushes. Color images collected by a quadcopter are processed into three-dimensional point clouds via structure from motion algorithms. Bush height, extents, canopy area, and volume, in addition to crown diameter and width, are derived and referenced to ground truth. In an experimental farm, twenty-five bushes were imaged by a quadcopter. Height and width dimensions achieved a mean absolute error of 9.85 cm before and 5.82 cm after systematic under-estimation correction. Strong correlation was found between manual and image derived bush volumes and their traditional growth indices. Hedgerows of three Southern Highbush varieties were imaged at a commercial farm to extract five morphological features (base angle, blockiness, crown percent height, crown ratio, and vegetation ratio) associated with cultivation and machine harvestability. The bushes were found to be partially separable by multivariate analysis. The methodology developed from this study is not only valuable for plant breeders to screen genotypes with bush morphological traits that are suitable for machine harvest, but can also aid producers in crop management such as pruning and plot layout organization.
How Can Vaccines Against Influenza and Other Viral Diseases Be Made More Effective? (2010)

DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.
Page grammars and page parsing. A syntactic approach to document layout recognition (2002)

Describes a syntactic approach to deducing the logical structure of printed documents from their physical layout. Page layout is described by a two-dimensional grammar, similar to a context-free string grammar, and a chart parser is used to parse segmented page images according to the grammar. This process is part of a system which reads scanned document images and produces computer-readable text in a logical mark-up format such as SGML. The system is briefly outlined, the grammar formalism and the parsing algorithm are described in detail, and some experimental results are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>