gebhart/patrepeval huggingface dataset:
Phase I Trial of Antigen-Specific Gene Therapy Using a Recombinant Vaccinia Virus Encoding MUC-1 and IL-2 in MUC-1-Positive Patients With Advanced Prostate Cancer (2004)

MUC-1 is overexpressed on many tumor cells. In addition, aberrant glycosylation of MUC-1 on human tumors leads to exposure of cryptic peptide epitopes that play a role in tumor immunity. As such, it has been identified as a potential target for immunotherapy. The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose, safety of a multiple-dose regimen, and the immunologic effect of vaccinia virus expressing MUC-1 and IL-2 genes (VV/MUC-1/IL-2) in patients with advanced prostate cancer. Five x 10(5), 5 x 10(6), and 5 x 10(7) plaque-forming units (pfu) of vaccinia viruses were used in the dose-escalating study. Viruses were given via intramuscular injection, and clinical response and immune function modulation were analyzed. No grade 3 or 4 toxicity was observed. Objective clinical response was observed after the fourth injection (0.3 ng/mL) in only one patient who received an intermediate dose of virus. Systemic immune modulation in this patient included (1) up-regulation of IL-2 (CD25) and T cell (TcR alphabeta) receptors, (2) increase in the CD4/CD8 ratio (2.5-fold) (3) augmentation of T-helper type 1 cell (TH1) (interferon-gamma and tumor necrosis factor-alpha) but not TH2 (IL-4) cytokine mRNA expression, (4) induction of natural killer cell activity and MHC independent MUC-1 specific cytotoxic T-cell activity, and (5) normalization of mRNA expression of T-cell-associated signal transduction molecules TcR-zeta and p56lck. These results suggest that VV/MUC-1/IL-2 gene therapy with a maximum tolerated dose of 5 x 10(7) pfu is safe and well tolerated.
Dual Inhibition of NOX2 and Receptor Tyrosine Kinase by BJ-1301 Enhances Anticancer Therapy Efficacy via Suppression of Autocrine-Stimulatory Factors in Lung Cancer (2017)

NADPH oxidase-derived reactive oxygen species (ROS) potentiate receptor tyrosine kinase (RTK) signaling, resulting in enhanced angiogenesis and tumor growth. In this study, we report that BJ-1301, a hybrid of pyridinol and alpha-tocopherol, exerts anticancer effects by dual inhibition of NADPH oxidase and RTK activities in endothelial and lung cancer cells. BJ-1301 suppresses ROS production by blocking translocation of NADPH oxidase cytosolic subunits to the cell membrane, thereby inhibiting activation. The potency of RTK inhibition by BJ-1301 was lower than that of sunitinib (a multi-RTK inhibitor), but the inhibition of downstream signaling pathways (e.g., ROS generation) and subsequent biological changes (e.g., NOX2 induction) by BJ-1301 was superior. Consistently, BJ-1301 inhibited cisplatin-resistant lung cancer cell proliferation more than sunitinib did. In xenograft chick or mouse tumor models, BJ-1301 inhibited lung tumor growth, to an extent greater than that of sunitinib or cisplatin. Treatments with BJ-1301 induced regression of tumor growth, potentially due to downregulation of autocrine-stimulatory ligands for RTKs, such as TGFα and stem cell factor, in tumor tissues. Taken together, the current study demonstrates that BJ-1301 is a promising anticancer drug for the treatment of lung cancer. <i>Mol Cancer Ther; 16(10); 2144-56. ©2017 AACR</i>.
Future directions for the field of oncolytic virotherapy: a perspective on the use of vaccinia virus (2004)

Oncolytic virotherapy is an emerging biotherapeutic platform based on genetic engineering of viruses capable of selectively infecting and replicating within cancer cells. Such viruses have been found to be both safe and to produce antitumour effects in a number of Phase I and II clinical trials. Early work in this field has been pioneered with strains of adenovirus which, although well suited to gene therapy approaches, have displayed certain limitations in their ability to directly destroy and spread through tumour tissues, particularly after systemic administration. Investigators have subsequently been examining the feasibility of using a variety of different viruses as oncolytic agents. Vaccinia virus is perhaps the most widely administered and successful medical product in history; it displays many of the qualities thought necessary for an effective antitumour agent and is particularly well characterised in people due to its role in the eradication of smallpox. Vaccinia has a short life cycle and rapid spread, strong lytic ability, inherent systemic tumour targeting, a large cloning capacity and well-defined molecular biology. In addition, the virus produces no known disease in humans, has been delivered safely to millions of people and has already demonstrated antitumoural efficacy in trials with vaccine strains. These qualities, along with strategies for further improving the safety and antitumour effectiveness of vaccinia, will be discussed in relation to the broad spectrum of clinical experience already achieved with this virus in cancer therapy.
The COG database: new developments in phylogenetic classification of proteins from complete genomes (2001)

The database of Clusters of Orthologous Groups of proteins (COGs), which represents an attempt on a phylogenetic classification of the proteins encoded in complete genomes, currently consists of 2791 COGs including 45 350 proteins from 30 genomes of bacteria, archaea and the yeast Saccharomyces cerevisiae (http://www.ncbi.nlm.nih. gov/COG). In addition, a supplement to the COGs is available, in which proteins encoded in the genomes of two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and shared with bacteria and/or archaea were included. The new features added to the COG database include information pages with structural and functional details on each COG and literature references, improvements of the COGNITOR program that is used to fit new proteins into the COGs, and classification of genomes and COGs constructed by using principal component analysis.
[Development of liquid phase immunoassay system using magnetic nanoparticles]. (2007)

Biological immunoassay is a major detection system of biological materials from patient samples. Our group has been developing a highly sensitive immunoassay system using magnetic nanoparticles made from Fe3O4. Since unbound magnetic markers randomly move in solvent due to Brownian motion, there is no magnetic signal from unbound magnetic markers; therefore, the separation of bound from unbound markers (B/F separation) is not required. This advantage means that the detection time is greatly decreased in comparison with a normal method using fluorescent/enzyme reagent. In this paper, we describe the configuration of the developed system and demonstrate the performance of the detection of magnetic nanoparticles.
Relationship of Dietary Fat to Age-Related Maculopathy in the Third National Health and Nutrition Examination Survey (2001)

Age-related maculopathy was not significantly associated with dietary fat in this large cross-sectional survey.
Current Trends in Telemedicine for Retinopathy of Prematurity (2017)

Retinopathy of Prematurity (ROP) is a vasoproliferative disease of the retina in premature infants that can progress to blindness. Clinical ROP management standards have been established by seminal studies such as the Cryotherapy for ROP (CRYO-ROP) and Early Treatment for ROP (ET-ROP) trials, and have significantly decreased the incidence of poor visual outcomes in ROP. However, ROP continues to be a leading cause of childhood blindness worldwide.
Going both ways: Immune regulation via CD1d-dependent NKT cells (2004)

NKT cells are a unique T lymphocyte sublineage that has been implicated in the regulation of immune responses associated with a broad range of diseases, including autoimmunity, infectious diseases, and cancer. In stark contrast to both conventional T lymphocytes and other types of Tregs, NKT cells are reactive to the nonclassical class I antigen-presenting molecule CD1d, and they recognize glycolipid antigens rather than peptides. Moreover, they can either up-or downregulate immune responses by promoting the secretion of Th1, Th2, or immune regulatory cytokines. This review will explore the diverse influences of these cells in various disease models, their ability to suppress or enhance immunity, and the potential for manipulating these cells as a novel form of immunotherapy.
The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. (2002)

The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells (MECs). One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence. However, the precise genetic changes that are responsible for this event in MECs is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc cooperating oncoprotein, can bypass senescence, extend the replicative life span, and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines. Overexpression of Bmi-1 in MECs led to activation of human telomerase reverse transcriptase (hTERT) transcription and induction of telomerase activity. Telomerase induction by Bmi-1 was an early event in the extension of the replicative life span and immortalization. Bmi-1 was not overexpressed in hTERT-immortalized MECs, suggesting that Bmi-1 functions upstream of hTERT. Although, c-Myc has been reported to induce telomerase in MECs, Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT promoter. Deletion analysis of the Bmi-1 protein suggested that the RING finger, as well as a conserved helix-turn-helix-turn domain, were required for its ability to induce telomerase and immortalize MECs. These data suggest that Bmi-1 regulates telomerase expression in MECs and plays a role in the development of human breast cancer.
Panel Commentary - The Road Ahead (2003)

believe that September 11th proved beyond any reasonable doubt that international treaties and other negotiated documents are not sufficient, by themselves, to win the War on Terrorism. I was in the Pentagon when the attack came and there is no doubt in my mind that the Pentagon and the United States were attacked with weapons of mass effects. Some 3,200 people from more than 90 countries throughout the world died on that day.2 This was an attack on democracy, on liberty and on religious freedom. This was not the first armed attack by these terrorists on these core American values either. This was one of a continuing series of attacks, beginning in 1993, if not before, with the first World Trade Center bombing. These armed attacks included the 1998 embassy attacks in Kenya and Tanzania and continued with the tragic attack on USS Cole in 2000. For me then, it is interesting to consider the concept of preemption or anticipatory self-defense while in the middle of an armed conflict as these two concepts do not seem well juxtaposed at times. In World War II and the Gulf
High aspect-ratio holographic photoresist gratings (1988)

Holographic gratings with periods as small as 700 nm, rectangular profiles with linewidths of <120 nm, and depths of 1.2 microm (aspect ratio of 10) have been formed using positive photoresist on Si substrates and visible laser exposure (488 nm). Similar aspect ratios have been achieved at a 400-nm period using 334-nm exposing radiation. A simple exposure and development model, which accounts for the large aspect ratios and predicts the grating fabrication limits, is presented.
Context Encoding for Semantic Segmentation (2018)

Recent work has made significant progress in improving spatial resolution for pixelwise labeling with Fully Convolutional Network (FCN) framework by employing Dilated/Atrous convolution, utilizing multi-scale features and refining boundaries. In this paper, we explore the impact of global contextual information in semantic segmentation by introducing the Context Encoding Module, which captures the semantic context of scenes and selectively highlights class-dependent featuremaps. The proposed Context Encoding Module significantly improves semantic segmentation results with only marginal extra computation cost over FCN. Our approach has achieved new state-of-the-art results 51.7% mIoU on PASCAL-Context, 85.9% mIoU on PASCAL VOC 2012. Our single model achieves a final score of 0.5567 on ADE20K test set, which surpass the winning entry of COCO-Place Challenge in 2017. In addition, we also explore how the Context Encoding Module can improve the feature representation of relatively shallow networks for the image classification on CIFAR-10 dataset. Our 14 layer network has achieved an error rate of 3.45%, which is comparable with state-of-the-art approaches with over 10 times more layers. The source code for the complete system are publicly available.
Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis (2013)

Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.
Fungicides Acting on Oxidative Phosphorylation (2011)

This chapter contains sections titled: The Biochemistry of Oxidative Phosphorylation: A Multiplicity of Targets for Crop Protection Chemistry Strobilurins and Other Complex III Inhibitors Succinate Dehydrogenase Inhibitors Uncouplers of Oxidative Phosphorylation NADH Inhibitors (Complex I) References
Role of the NF-kB Pathway in the Pathogenesis of Human Disease States (2001)

The NF-kappaB family consists of a group of inducible transcription factors which regulate immune and inflammatory responses and protect cells from undergoing apoptosis in response to cellular stress. A number of signal transduction cascades can activate the NF-kappaB pathway to result in the translocation of the NF-kappaB proteins from the cytoplasm to the nucleus where they activate the expression of specific cellular genes. In this review, we discuss cellular genes which are regulated by NF-kappaB and disease states which are associated with constitutive activation of the NF-kappaB pathway. Strategies to prevent prolonged activation of the NF-kappaB pathway are also discussed.
Iterative multiuser detection for CDMA with FEC: near-single-user performance (1998)

This paper introduces an iterative multiuser receiver for direct sequence code-division multiple access (DS-CDMA) with forward error control (FEC) coding. The receiver is derived from the maximum a posteriori (MAP) criterion for the joint received signal, but uses only single-user decoders. Iterations of the system are used to improve performance, with dramatic effects. Single-user turbo code decoders are utilized as the FEC system and a complexity study is presented. Simulation results show that the performance approaches single-user performance even for moderate signal-to-noise ratios.
Antigens recognized on human tumors by cytolytic T lymphocytes: Towards vaccination? (1995)

It has been known for many years that cytolytic T lymphocytes that specifically recognize the tumor cells of the same patient can be derived from the blood of melanoma patients. Several of the antigens recognized by these antitumor T lymphocytes have now been completely identified. Some of them are sufficiently tumor-specific to envision their use as antitumor vaccines in selected cancer patients.
Monitoring the Effect of the Floating Hotel on the Water Quality of John Brewer Reef (1993)

This communication describes a water quality compliance assessment program carried out during the Floating Hotel's stay at John Brewer Reef in the central part of the Great Barrier Reef Lagoon. Assessments were made of the waste water treatment plant and disposal operations, and the water quality of the lagoon. Numerous technical problems existed with the operation of the treatment plant, so that the effluent breached permit requirements on many occasions, particularly during the early establishment phase. It was recommended that sludge, waste water and brine wastes should be returned to the mainland. No significant difference in water quality occurred between hotel and control sites, suggesting that the hotel had no significant effect on the water quality parameters measured. When the water quality of the lagoon was however assessed during the presence and absence of Trichodesmium, a blue-green alga which blooms prolifically in the Great Barrier Reef, it was found that this organism significantly affected water quality of the lagoon. It was concluded that in any reef water quality monitoring programme, specific attention should be given to assessing whether Trichodesmium is present. Failure to take account of this can be detrimental to the developer.
IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms (2012)

Interferon regulatory factor (IRF)-2 is a transcription factor involved in type I (IFN- α/β) signaling. It has been reported that IRF-2 deficiency results in various immune dysfunctions. However, the role of IRF-2 in B-cell functions needs to be elucidated. Unlike wild-type (WT) B cells, IRF-2(-/-) B2 cells were refractory to anti-IgM, but not LPS. Such a defect in proliferation was dependent on IFN- α/β receptor (IFNAR). Marginal zone B cells increased in the proportion relative to B2 cells in IRF-2(-/-) mice produced IgM normally to LPS stimulation. However, IRF-2(-/-) B2 cells were defective in IgM production in an IFNAR-independent manner, although both B-cell subsets differentiated phenotypically to plasma cells at elevated efficiencies. Class switch recombination of IRF-2(-/-) B2 cells by LPS plus IL-4 was also impaired. Their reduced IgM production was conceivably due to an inefficient up-regulation of Blimp-1. Consistent with these in vitro observations, specific antibody production in vivo to a T-dependent antigen by B2 cells was severely impaired in IRF-2(-/- )mice. However, a low, but significant, level of IgG was detected at a late time point, and this IgG exhibited comparable binding affinity to that in WT mice. Follicular helper T-cell development and germinal center formation were normal. A similar tendency was observed when µ chain(-/-) mice were reconstituted with IRF-2(-/- )B cells. These results revealed a multi-faceted role of IRF-2 in the function of B cells, particularly B2 cells, through regulating proliferation in an IFNAR-dependent manner and antibody production via up-regulation of Blimp-1.
Microbial Biofilms and Chronic Wounds (2017)

Background is provided on biofilms, including their formation, tolerance mechanisms, structure, and morphology within the context of chronic wounds. The features of biofilms in chronic wounds are discussed in detail, as is the impact of biofilm on wound chronicity. Difficulties associated with the use of standard susceptibility tests (minimum inhibitory concentrations or MICs) to determine appropriate treatment regimens for, or develop new treatments for use in, chronic wounds are discussed, with alternate test methods specific to biofilms being recommended. Animal models appropriate for evaluating biofilm treatments are also described. Current and potential future therapies for treatment of biofilm-containing chronic wounds, including probiotic therapy, virulence attenuation, biofilm phenotype expression attenuation, immune response suppression, and aggressive debridement combined with antimicrobial dressings, are described.
Faceting Kinetics of Stepped Si(113) Surfaces: A Time-Resolved X-Ray Scattering Study (1995)

A time-resolved x-ray scattering study is presented of the faceting kinetics of a Si surface misoriented by $2.1\ifmmode^\circ\else\textdegree\fi{}$ from the cubic [113] direction towards [001]. Following a quench from a one-phase region of the phase diagram into a two-phase region, a grooved superstructure forms and subsequently coarsens in time. For times between one and several hundred seconds, the surface morphology is self-similar at different times, with a characteristic groove size ( $L$) varying as a power law versus time ( $t$): ${L\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}L}_{0}{t}^{0.164\ifmmode\pm\else\textpm\fi{}0.021}$. At later times, the groove size approaches a limiting value.
The FIP3-Rab11 Protein Complex Regulates Recycling Endosome Targeting to the Cleavage Furrow during Late Cytokinesis (2004)

An integral part of cell division is the separation of daughter cells via cytokinesis. There is now good evidence that the completion of cytokinesis requires coordinated membrane trafficking to deliver new membrane to the tip of the furrow and to complete the abscission. Here we have examined membrane traffic in cytokinesis and describe several novel observations. First, we show that Rab11- and FIP3-containing recycling endosomes accumulate near the cleavage furrow and are required for successful completion of cytokinesis. Second, we demonstrate that the Rab11-FIP3 protein complex is intimately involved in the delivery of endosomes to the cleavage furrow. Significantly, although FIP3 recruitment to endosomes is Rab11 dependent, we find that the targeting of FIP3 to the midbody is independent of Rab11. Third, we show that the Rab11-FIP3 complex is required for a late stage of cytokinesis, possibly abscission. Finally, we demonstrate that localization of FIP3 is subject to substantial spatial and temporal regulation. These data provide the first detailed analysis of recycling endosomes in cell division and provide a new model for membrane traffic to the furrow. We propose that the dynamic Rab11-FIP3 interaction controls the delivery, targeting, and fusion of recycling endosomes with furrow during late cytokinesis and abscission.
Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes (2007)

Adipose tissue is a source of multipotent stem cells that can be easily isolated, selected, and induced into mature, transplantable hepatocytes. The fact that they are easy to procure ex vivo in large numbers makes them an attractive tool for clinical studies in the context of establishing an alternative therapy for liver dysfunction.
Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain α-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen (1989)

Antimitochondrial autoantibodies recognizing 68 to 74 and 50 to 52 kD inner membrane mitochondrial antigens are characteristically present in sera of patients with primary biliary cirrhosis. The biochemical identification of the antigens, however, has remained elusive. We report herein that the 52 kD antigen is the dihydrolipoamide acyltransferase of the branched-chain alpha-keto acid dehydrogenase complex. This was demonstrated by three experiments through the use of recombinant fusion protein expressed in Escherichia coli from a cDNA insert encoding the human autoantigen. First, 33 of 37 primary biliary cirrhosis patients exhibiting reactivity toward the 50 to 52 kD mitochondrial antigen by immunoblotting also showed reactivity toward the recombinant fusion protein. Second, absorption of primary biliary cirrhosis sera with recombinant fusion protein, but not with an irrelevant recombinant clone, the F-specific rat liver antigen, was effective in absorbing out reactivity against the 50 to 52 kD mitochondrial antigen but not the 68 to 74 kD antigen. Third, complete removal of reactivity toward all four different isoelectric point polypeptides at 50 to 52 kD was observed in two-dimensional gel analysis. Furthermore, primary biliary cirrhosis sera were analyzed with mitochondria from three sources, rat liver, human placenta and bovine heart, in order to compare reactivity patterns and to determine precisely the comparative molecular weights of the autoantigens in the three species. The availability of recombinant autoantigens will provide improved diagnostic tests and, more importantly, will allow definite issues in primary biliary cirrhosis to be studied, including identification of immunodominant epitopes, the significance of autoantigen recognition and the establishment of autoreactive T cell clones.