gebhart/patrepeval huggingface dataset:
Molecular causes of colon cancer (2002)

Cells in a developing embryo communicate with each other through a limited number of intercellular signalling pathways, of which the Wnt signalling pathway is one. Little is known about the function of Wnt signalling beyond that in embryogenesis. However, recent insights into the molecular etiology of colon cancer have implied a central role for the Wnt signalling pathway. The malignant transformation of colorectal epithelium is well defined, leading to adenoma and sequentially carcinoma formation. Several genes that regulate the Wnt pathway are mutated in cancer of the human colon and other organs. All of these mutations lead to the inappropriate activation of the pathway, which instructs the cell to divide unrestrictedly. These insights now allow the Wnt pathway to be exploited as a new target for drug development in colon cancer.
Cytotoxic Cs in Immunodeficient Athymic Mice (1994)

A studies of cytotoxic cells in athymic nude mice demonstrate higher cytotoxic activity of NK cells and macrophages than in their euthymic counterparts. The higher level of endogenous cytotoxic activity can be considered as complementary to the deficiency or lack of thymus dependent T lymphocytes and their functions. However, with increased age of mice some T lymphocytes and their functions can be demonstrated. By stimulation of splenocytes and lymph node cells in vitro with IL-2 or anti CD3 antibody cytotoxic activity towards P-815 (NK resistant, LAK sensitive) target cells can be generated. There exist data, which indicate that the cytotoxic activity is exerted by extrathymic pre-T lymphocytes with TcR gamma delta antigenic phenotype. The differences in transplantability of human tumors in athymic nude mice cannot be explained by defect in antigen recognition and in immune response of athymic nude mice, recipients of the xenografted material. The biological relevance in vivo of high endogenous cytotoxicity of NK cells observed in many strains of athymic nude mice remains obscure. The availability of new immunodeficient mouse models, e.g. scid mice deficient in B and T lymphocytes and with low level of NK cells, in which not only xenografted human tumor grow but human lymphoid cell can be transplanted as well, opens new and broader experimental possibilities, in which new preclinical immunotherapeutical approaches can be applied.
The significance of OX40 and OX40L to T‐cell biology and immune disease (2009)

OX40 (CD134) and its binding partner, OX40L (CD252), are members of the tumor necrosis factor receptor/tumor necrosis factor superfamily and are expressed on activated CD4(+) and CD8(+) T cells as well as on a number of other lymphoid and non-lymphoid cells. Costimulatory signals from OX40 to a conventional T cell promote division and survival, augmenting the clonal expansion of effector and memory populations as they are being generated to antigen. OX40 additionally suppresses the differentiation and activity of T-regulatory cells, further amplifying this process. OX40 and OX40L also regulate cytokine production from T cells, antigen-presenting cells, natural killer cells, and natural killer T cells, and modulate cytokine receptor signaling. In line with these important modulatory functions, OX40-OX40L interactions have been found to play a central role in the development of multiple inflammatory and autoimmune diseases, making them attractive candidates for intervention in the clinic. Conversely, stimulating OX40 has shown it to be a candidate for therapeutic immunization strategies for cancer and infectious disease. This review provides a broad overview of the biology of OX40 including the intracellular signals from OX40 that impact many aspects of immune function and have promoted OX40 as one of the most prominent costimulatory molecules known to control T cells.
Multimodal Representation of Advertisements Using Segment-level Autoencoders (2018)

Automatic analysis of advertisements (ads) poses an interesting problem for learning multimodal representations. A promising direction of research is the development of deep neural network autoencoders to obtain inter-modal and intra-modal representations. In this work, we propose a system to obtain segment-level unimodal and joint representations. These features are concatenated, and then averaged across the duration of an ad to obtain a single multimodal representation. The autoencoders are trained using segments generated by time-aligning frames between the audio and video modalities with forward and backward context. In order to assess the multimodal representations, we consider the tasks of classifying an ad as funny or exciting in a publicly available dataset of 2,720 ads. For this purpose we train the segment-level autoencoders on a larger, unlabeled dataset of 9,740 ads, agnostic of the test set. Our experiments show that: 1) the multimodal representations outperform joint and unimodal representations, 2) the different representations we learn are complementary to each other, and 3) the segment-level multimodal representations perform better than classical autoencoders and cross-modal representations -- within the context of the two classification tasks. We obtain an improvement of about 5% in classification accuracy compared to a competitive baseline.
G Protein Activation by Serotonin Type 4 Receptor Dimers (2011)

The discovery that class C G protein-coupled receptors (GPCRs) function as obligatory dimeric entities has generated major interest in GPCR oligomerization. Oligomerization now appears to be a common feature among all GPCR classes. However, the functional significance of this process remains unclear because, in vitro, some monomeric GPCRs, such as rhodopsin and β(2)-adrenergic receptors, activate G proteins. By using wild type and mutant serotonin type 4 receptors (5-HT(4)Rs) (including a 5-HT(4)-RASSL) expressed in COS-7 cells as models of class A GPCRs, we show that activation of one protomer in a dimer was sufficient to stimulate G proteins. However, coupling efficiency was 2 times higher when both protomers were activated. Expression of combinations of 5-HT(4), in which both protomers were able to bind to agonists but only one could couple to G proteins, suggested that upon agonist occupancy, protomers did not independently couple to G proteins but rather that only one G protein was activated. Coupling of a single heterotrimeric G(s) protein to a receptor dimer was further confirmed in vitro, using the purified recombinant WT RASSL 5-HT(4)R obligatory heterodimer. These results, together with previous findings, demonstrate that, differently from class C GPCR dimers, class A GPCR dimers have pleiotropic activation mechanisms.
Enzyme Coupled Immunoassay of Insulin Using a Novel Coupling Reagent (1976)

A novel coupling reagent, meta-maleimidobenzoyl N-hydroxysuccinimide ester was synthesized. Using this reagent, insulin was conjugated very easily with beta-D-galactosidase [EC 3.2.1.23] in neutral, aqueous solution. No reduction of the enzyme activity was observed during the coupling procedure. The competitive bindings of the conjugate and insulin to anti-insulin serum were tested. The results indicated that the conjugate has enough immune reactivity for use in enzyme coupled immunoassay. Using this assay 20-800 pg of insulin were detectable.
Relationship Between Periodontal Disease, Tooth Loss, and Carotid Artery Plaque (2003)

Our data suggest that tooth loss is a marker of past periodontal disease in this population and is related to subclinical atherosclerosis, thereby providing a potential pathway for a relationship with clinical events.
Coupled Effects of Hydrodynamics and Biogeochemistry on Zn Mobility and Speciation in Highly Contaminated Sediments (2015)

Porewater transport and diagenetic reactions strongly regulate the mobility of metals in sediments. We executed a series of laboratory experiments in Gust chamber mesocosms to study the effects of hydrodynamics and biogeochemical transformations on the mobility and speciation of Zn in contaminated sediments from Lake DePue, IL. X-ray absorption spectroscopy (XAS) indicated that the oxidation of surficial sediments promoted the formation of more mobile Zn species. Bulk chemical measurements of porewater, overlying water, and sediment also suggested that this process liberated aqueous metals to porewater and facilitated Zn efflux to the overlying water. In addition, sediment resuspension events increased the release of aqueous metals to both surficial porewater and the overlying water column. XAS analysis indicated that resuspension increased dissolution of Zn-sequestering mineral phases. These results show that both steady slow porewater transport and rapid episodic resuspension are important to the release of metal from fine-grained, low-permeability contaminated sediments. Thus, information on metals speciation and mobility under time-varying overlying flow conditions is essential to understanding the long-term behavior of metals in contaminated sediments.
Homology-Integrated CRISPR–Cas (HI-CRISPR) System for One-Step Multigene Disruption in Saccharomyces cerevisiae (2014)

One-step multiple gene disruption in the model organism Saccharomyces cerevisiae is a highly useful tool for both basic and applied research, but it remains a challenge. Here, we report a rapid, efficient, and potentially scalable strategy based on the type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas) system to generate multiple gene disruptions simultaneously in S. cerevisiae. A 100 bp dsDNA mutagenizing homologous recombination donor is inserted between two direct repeats for each target gene in a CRISPR array consisting of multiple donor and guide sequence pairs. An ultrahigh copy number plasmid carrying iCas9, a variant of wild-type Cas9, trans-encoded RNA (tracrRNA), and a homology-integrated crRNA cassette is designed to greatly increase the gene disruption efficiency. As proof of concept, three genes, CAN1, ADE2, and LYP1, were simultaneously disrupted in 4 days with an efficiency ranging from 27 to 87%. Another three genes involved in an artificial hydrocortisone biosynthetic pathway, ATF2, GCY1, and YPR1, were simultaneously disrupted in 6 days with 100% efficiency. This homology-integrated CRISPR (HI-CRISPR) strategy represents a powerful tool for creating yeast strains with multiple gene knockouts.
Low power resonant optical excitation of an optomechanical cavity (2011)

We demonstrate the actuation of a double beam opto-mechanical cavity with a sinusoidally varying optical input power. We observe the driven mechanical motion with only 200 nW coupled to the optical cavity mode. We also investigate the pump power dependence of the radio-frequency response for both the driving power and the probe power. Finally, we investigate the dependence of the amplitude of the mechanical motion on mechanical cavity quality factor.
A multiresolution framework for dynamic deformations (2002)

We present a novel framework for the dynamic simulation of elastic deformable solids. Our approach combines classical finite element methodology with a multiresolution subdivision framework in order to produce fast, easy to use, and realistic animations. We represent deformations using a hierarchical basis constructed using volumetric subdivision. The subdivision framework provides topological flexibility and the hierarchical basis allows the simulation to add detail where it is needed. Since volumetric parameterization is difficult for complex models, we support the embedding of objects in domains that are easier to parameterize.
Expression in COS cells of a mouse—human chimaeric B72.3 antibody (1987)

B72.3 is a mouse hybridoma cell-line secreting an IgG1 antibody which recognises an epitope on a tumour-associated antigen, TAG-72. This high molecular weight mucin-like molecule is found on a variety of human neoplasms, including colon, breast and ovarian carcinomas. Chimaeric immunoglobulin genes with the B72.3 specificity have been constructed by joining the mouse variable regions from cDNA clones to human genomic constant regions using recombinant DNA techniques. The chimaeric heavy and light chain immunoglobulin genes were placed under the control of a strong viral promoter, and co-transfected into COS-1 cells. SDS-PAGE analysis of the 35S-labelled products demonstrated that the transiently expressed antibodies were correctly synthesised and assembled. The specific binding characteristics of the parent B72.3 antibody were retained by the chimaeric antibody in an antigen-based ELISA. This system gave sufficiently high transient expression of the chimaeric antibody molecules to allow rapid physical and immunological characterisation of the engineered gene products.
한국 여성의 정치적 대표성에 관한 연구 (2019)

본 연구의 목적은 한국 여성의 정치적 대표성을 제고하기 위한 전략을 제시하는 것이다. 이를 위해 여성의 정치적 대표성에 관한 선행연구와 통계자료를 분석하여 여성의 과소대표성의 요인을 검토하였다. 여성의 과소대표성에 영향을 미치는 요인으로는 사회·경제적 요인, 문화적 요인, 정치 구조적 요인이 있다. 한국 여성의 정치적 대표성을 높이기 위해 두 가지 유형의 전략을 제시하였다. 첫째, 공급 측면의 전략은 정치의식을 높이기 위한 민주시민교육의 활성화와 여성정치교육 확대이다. 둘째, 수요 측면의 전략은 정치의 장에서 여성을 위한 공정한 기회를 제공하는 것에 초점을 둔다. 정치에서 여성이 적절한 대표성을 갖는 것은 여성의 권익 증진뿐만 아니라 한국 사회의 민주주의 발전을 위해 중요하다. 후속연구에서는 한국 여성의 양적 대표성과 실질적 대표성의 연관성에 관한 검토가 이루어져야 한다.
Inducible Site-Directed Recombination in Mouse Embryonic Stem Cells (1996)

The site-directed recombinase Cre can be employed to delete or express genes in cell lines or animals. Clearly, the ability to control remotely the activity of this enzyme would be highly desirable. To this end we have constructed expression vectors for fusion proteins consisting of the Cre recombinase and a mutated hormone-binding domain of the murine oestrogen receptor. The latter still binds the anti-oestrogen drug tamoxifen but no longer 17 beta-oestradiol. We show here that in embryonic stem cells expressing such fusion proteins, tamoxifen can efficiently induce Cre-mediated recombination, thereby activating a stably integrated LacZ reporter gene. In the presence of either 10 microM tamoxifen or 800 nM 4-hydroxy-tamoxifen, recombination of the LacZ gene is complete within 3-4 days. By placing a tamoxifen-binding domain on both ends of the Cre protein, the enzymatic activity of Cre can be even more tightly controlled. Transgenic mice expressing such an tamoxifen-inducible Cre enzyme may thus provide a new and useful genetic tool to mutate or delete genes at specific times during development or in adult animals.
The potential of microfluidic water-in-oil droplets in experimental biology (2009)

The comprehensive characterisation of complex parameter space in '-omics' technologies requires high-throughput systems. In vitro compartmentalisation of reactions in water-in-oil droplets combines the necessary ability to carry out large numbers of experiments under controlled conditions with quantitative readout, and has recently advanced towards automation by generating droplets in microfluidic devices. Some approaches based on these principles are already familiar (e.g. emulsion PCR for sequencing), others, including directed evolution or cell-based assays, are in advanced stages of development--and proof-of-principle experiments are appearing for a whole range of applications in diagnostics, cellomics, proteomics, drug discovery and systems and synthetic biology. This review describes the current state-of-the-art, notes salient features of successful experiments and extrapolates in the direction of more highly integrated systems.
Hydrothermal Treatment of Nanoparticle Thin Films for Enhanced Mechanical Durability (2008)

The mechanical durability of nanoporous all-nanoparticle and polymer-nanoparticle layer-by-layer (LbL) films (80-150 nm thick) on both glass and polycarbonate substrates has been greatly enhanced by hydrothermal treatment (124-134 degrees C). Polymer-nanoparticle films were more durable than all-nanoparticle films after hydrothermal treatment. The optical properties of nanoporous antireflection (AR) films were exploited in an abrasion test (25-100 kPa normal stress) to quantify the extent of abrasive wear observed qualitatively by scanning electron microscopy (SEM). Marginal damage was observed under optimal reinforcement conditions. Untreated films not only delaminated from the surface completely but also damaged their underlying glass and polycarbonate substrates during testing. The nature of the substrate was found to play an important role in determining abrasion resistance, regardless of the level of particle fusion in the film. The low-temperature process enables in situ mechanical reinforcement of otherwise delicate nanoparticle assemblies on plastic substrates. Tribochemical wear was found to planarize the nanoscale surface texture of these films, similar to what is observed in chemo-mechanical polishing (CMP). This finding is useful for anyone trying to make robust superhydrophobic or superhydrophilic coatings. To our knowledge, this is the first report on hydrothermal reinforcement of LbL films.
Characterization of Serum Netralization Response to the Human Immunodeficiency Virus (HIV) (1987)

To determine the clinical significance of human neutralizing antibodies to the human immunodeficiency virus (HIV), we measured serum neutralization in patients with different clinical outcomes following HIV infection. Serum neutralization titers ranged from less than 1:5 to 1:100. The neutralization response after HIV infection appeared slow, with neutralization titers remaining low, at or below 1:5, at 7 months following seroconversion. Comparison of 78 HIV seropositive subjects with AIDS, AIDS-related complex, or no symptoms failed to reveal any significant differences in titer which correlated with clinical status. However, a greater proportion of AIDS patients with Kaposi's sarcoma (11/12) had neutralization titers of 1:20 or greater than did AIDS patients with opportunistic infections (2/11). Serum samples were analyzed by Western blot for their reactivity to specific viral proteins. Clinical status could not be predicted by a particular serological profile. However, sera which reacted with the HIV major envelope glycoprotein gp120 tended to have higher neutralization titers, suggesting that gp120 may be a target of anti-HIV neutralizing antibody in man.
An Approach for Characterization and Purification of a Human Monoclonal Hybridoma Antibody (1989)

An IgG human-human monoclonal hybridoma antibody, AML-19, reactive with human myeloid cells of non-malignant and malignant origin has been produced by fusion of blood mononuclear cells from a patient with acute myeloid leukemia (AML) and the human B-lymphoma cell line RH-L4. The monoclonal antibody (MAb) AML-19 was purified from hybridoma supernatant by primarily anion-exchange chromatography, in order to separate the AML-19 MAb from contaminating immunoglobulin (Ig), e.g. bovine Ig and MAb derived from the parental fusion partner, and followed by immunoaffinity chromatography. This purification method gave the highest yield and purity of the AML-19 MAb. The isoelectric point (pI) of the MAb was estimated to be 5. Inhibition assays indicate an apparent dissociation constant (Kd) corresponding to 4 x 10(-9) M and an affinity constant (Ka) to 2.5 x 10(8)M-1 to K562 erythroleukemia cells. Scatchard plot demonstrated a linear slope as a manifestation of monoclonality and a low number of AML-19 specific epitopes, estimated to 1500 per cell.
Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. (1997)

This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.
HUMAN VASCULAR ENDOTHELIAL CELLS IN CULTURE (1974)

Human endothelial cells, obtained by collagenase treatment of term umbilical cord veins, were cultured using Medium 199 supplemented with 20% fetal calf serum. Small clusters of cells initially spread on plastic or glass, coalesced and grew to form confluent monolayers of polygonal cells by 7 days. Cells in primary and subcultures were identified as endothelium by the presence of Weibel-Palade bodies by electron microscopy. A morphologically distinct subpopulation of cells contaminating some primary endothelial cultures was selectively subcultured, and identified by ultrastructural criteria as vascular smooth muscle. Autoradiography of endothelial cells after exposure to [(3)H]thymidine showed progressive increases in labeling in growing cultures beginning at 24 h. In recently confluent cultures, labeling indices were 2.4% in central closely packed regions, and 53.2% in peripheral growing regions. 3 days after confluence, labeling was uniform, being 3.5 and 3.9% in central and peripheral areas, respectively. When small areas of confluent cultures were experimentally "denuded," there were localized increases in [(3)H]thymidine labeling and eventual reconstitution of the monolayer. Liquid scintillation measurements of [(3)H]thymidine incorporation in primary and secondary endothelial cultures in microwell trays showed a similar correlation of DNA synthesis with cell density. These data indicate that endothelial cell cultures may provide a useful in vitro model for studying pathophysiologic factors in endothelial regeneration.
Performance of Five Commercially Available Tooth Color‐Measuring Devices (2007)

In the clinical setting, the Easyshade and Ikam systems were the most reliable. The other devices tested were more reliable in vitro than in vivo.
110GHz rapid, continuous tuning from an optical parametric oscillator pumped by a fiber-amplified DBR diode laser (2005)

A singly-resonant continuous-wave optical parametric oscillator (cw-OPO) pumped by a fiber-amplified diode laser is described. Tuning of the pump source allowed the OPO output to be tuned continuously, without mode-hops, over 110 GHz in 29 ms. Discontinuous pump tuning over 20 nm in the region of 3.4 microm was also obtained. The rapid and continuous idler tuning was demonstrated by the measurement of a methane absorption spectrum. We believe this to be the first example of a singly-resonant OPO pumped by a fiber-amplified diode laser and the mode-hop free tuning range to be the highest reported for a cw-OPO.
Integration of location services in the Open Distributed Office (1994)

Matrix metalloproteinases (MMPs) are a large family of extracellular or membrane-bound proteases. Their ability to cleave extracellular matrix (ECM) proteins has implicated a role in ECM remodeling to affect cell fate and behavior during development and in pathogenesis. We have shown previously that membrane-type 1 (MT1)-MMP [corrected] is coexpressed temporally and spatially with the MMP gelatinase A (GelA) in all cell types of the intestine and tail where GelA is expressed during Xenopus laevis metamorphosis, suggesting a cooperative role of these MMPs in development. Here, we show that Xenopus GelA and MT1-MMP interact with each other in vivo and that overexpression of MT1-MMP and GelA together in Xenopus embryos leads to the activation of pro-GelA. We further show that both MMPs are expressed during Xenopus embryogenesis, although MT1-MMP gene is expressed earlier than the GelA gene. To investigate whether the embryonic MMPs play a role in development, we have studied whether precocious expression of these MMPs alters development. Our results show that overexpression of both MMPs causes developmental abnormalities and embryonic death by a mechanism that requires the catalytic activity of the MMPs. More importantly, we show that coexpression of wild type MT1-MMP and GelA leads to a cooperative effect on embryonic development and that this cooperative effect is abolished when the catalytic activity of either MMP is eliminated through a point mutation in the catalytic domain. Thus, our studies support a cooperative role of these MMPs in embryonic development, likely through the activation of pro-GelA by MT1-MMP.