gebhart/patrepeval huggingface dataset:
Patterns of tumor metastasis: organ selectivity in the spread of cancer cells. (1988)

More than a century ago, Fuchs recognized that although tumors varied in their propensity for metastasis, there was, as well, discrimination in the different organs of the body, some providing a more fertile soil for growth for specific tumors than others. Paget dramatized this clear distinction between the intrinsic properties of the cancer cell and the properties of the host when he expanded on the analogy between tumors and plants: "When a plant goes to seed, its seeds are carried in all directions; but they can only live and grow if they fall on congenial soil." Paget is almost apologetic as he contrasts the work of those that study the 'seed' to his own work on the 'soil': "The best work in the pathology of cancer is done by those who...are studying the nature of the seed. They are like scientific botanists; and he who turns over the records of cases of cancer is only a ploughman, but his observations of the properties of the soil may also be useful." In a time where the primary emphasis in cancer research is at the level of gene expression, of regulation and of epigenetic modification of the "seed," those individuals, such as Pauli and Lee, who study the properties of the host environment should not be ignored. Not only are the observations of the 'soil' useful, they provide essential information without which we will not be able to understand the nature of the metastatic process.
Alfred P. Sloan Jr. prize. Studies and prospectives of the protein kinase C family for cellular regulation (1989)

Studies and Prospectives of
CD248: Reviewing its Role in Health and Disease (2012)

CD248, also known as endosialin or tumor endothelial marker-1 (TEM-1), is a C-type lectin-like domain (CTLD) containing cell surface glycoprotein that is expressed by stromal cells of proliferating tissues during embryogenesis and postnatally in tumors and inflammatory lesions. Loss-of-function studies in mice support the notion that CD248 promotes tumor growth and inflammation, observations that are stimulating interest in evaluating this molecule as a therapeutic target. In spite of these advances, the mechanisms by which CD248 modulates cancer and inflammation remain largely enigmatic. This review highlights our current understanding of CD248, its structure, pattern of expression, regulation and function in various disease processes.
A Soluble Truncated Form of the Mer Tyrosine Kinase Inhibits Gas6 Activity in Platelets and Monocytes. (2004)

Abstract Several receptor tyrosine kinases generate soluble ligand binding domains either by proteolytic cleavage of the extracellular domain or differential splicing yielding in a truncated RNA transcript. Mer is a member of a receptor tyrosine kinase family which includes Axl and Tyro-3. All three members of this family have an extracellular domain which includes two immunoglobulin and two fibronectin type III motifs. Mer, Axl, and Tyro-3 are transforming in vitro in numerous cell types and are overexpressed in several different human cancers. In addition, Mer, Axl, and Tyro-3 and the common ligand Gas6 are all expressed in platelets and directly affect platelet activation and clot stability. We have found that the 205 kD Mer protein in platelets and monocytes is post-translationally processed by cleavage of the extracellular domain via a TACE-like metalloprotease. The cleavage results in a soluble extracellular domain protein (approximately 150kD) and a membrane-bound kinase domain. The proteolytic cleavage of Mer can be enhanced by LPS and PMA, and specifically inhibited by a TAPI, a TACE inhibitor. Significant amounts of the soluble Mer protein are present in human and mouse serum. The soluble Mer protein directly binds the ligand Gas6, and inhibits Gas6 stimulation of full-length Mer. Gas6, related to anticoagulant protein S, is also a ligand for Axl and Tyro-3. The cleavage of Mer may represent a mechanism of directly regulating the numerous functions of Gas6 including promoting platelet adhesion and clot stability, stimulating cell proliferation, inducing cell adhesion and chemotaxis, and preventing apoptosis. Furthermore, the ability of soluble Mer to inhibit Gas6 activity in platelets may provide a potential novel therapeutic intervention in the treatment of clotting disorders.
Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2 (1982)

Monoclonal antibodies secreted by six hybridomas and recognizing antigenic sites on glycoproteins gC, gAB, gD, gE, and gF of herpes simplex virus type 2 were examined for their ability to protect BALB/c mice from lethal infection by the virus. Administration of monoclonal antibodies to individual glycoproteins intraperitoneally 3 h before footpad challenge with 10 times the 50% lethal dose of virus protected between 35 and 75% of the mice, except for one of two monoclonal antibodies recognizing antigens on gC. The antibodies did not neutralize virus in vitro and protected A/J mice deficient in the fifth component of complement as efficiently as complement-sufficient BALB/c mice. A good correlation was found between protection and titers of monoclonal antibodies assessed by antibody-dependent cell-mediated cytolysis. The results indicate that any of the glycoproteins can serve as antigens for a protective immune response. In addition, the data are compatible with protection being mediated by an antibody-dependent cell-mediated cytolysis mechanism.
Marcadores genéticos en equinos (1997)

The efficiency of genetic markers (GM), to be applied in veterinary practice (filiation verification, identification, breed specificity, diagnosis and prevention of neonatal isoerthrolysis) is evaluated by the Polymorphic Information Content (PIC). MG allows the study and evaluation of the maintenance of genetic biodiversity of breeds. MG in equine breeds present a different distribution of their gene frequencies, as well as the presence of alleles specific to certain breeds.
Implantable Baclofen Pump as an Adjuvant in Treatment of Pressure Sores (2003)

Currently, the success of ulcer treatment is limited by the high recurrence and complication rates. Spasticity is an important contributing factor to ulcer recurrence, and intrathecal baclofen is an effective method to reduce spasticity. Spasticity creates friction, shear, and mobility impairment resulting in wound dehiscence, flap loss, infection, and hematoma. Spasticity can be managed pharmacologically and surgically; baclofen is the drug of choice. Baclofen inhibits spasticity by blocking excitatory neurotransmitters in the spinal dorsal horn. Intrathecal baclofen maximizes the dose delivered to spinal receptors and minimizes the side effects associated with oral baclofen. Case reports of intrathecal baclofen used in patients with pressure sores demonstrate the use of intrathecal baclofen to improve reconstructive outcomes in spastic patients.
Automated Question Answering From Lecture Videos: NLP vs. Pattern Matching (2005)

This paper explores the feasibility of automated question answering from lecture video materials used in conjunction with PowerPoint slides. Two popular approaches to question answering are discussed, each separately tested on the text extracted from videotaped lectures: 1) the approach based on Natural Language Processing (NLP) and 2) a self-learning probabilistic pattern matching approach. The results of the comparison and our qualitative observations are presented. The advantages and shortcomings of each approach are discussed in the context of video applications for e-learning or knowledge management.
Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide. (1999)

Nitric oxide (NO)*, the principal airborne pollutant generated from combustion processes such as gas stoves, tobacco smoke, and burning of fossil fuels, is being tested as a therapeutic agent in clinical trials. A prior morphometric study of rats exposed for 9 weeks to 0.5 parts per million (ppm) NO demonstrated focal degeneration of the alveolar interstitium and increased numbers of fenestrated alveolar septa (Mercer et al. 1995). The limited size and distribution of defects in this NO exposure did not alter alveolar surface area or other morphometric indicators of lung function, but were of interest as the responses to inhaled NO appeared to differ from those produced by other oxidants such as ozone (O3) and nitrogen dioxide (NO2). Nitric oxide exposures at the same concentration and duration as prior morphometric studies of O3 and NO2 were necessary in order to make a comparison. This was the purpose of the current study in which F344 rats were exposed for 6 weeks to air, 2 ppm NO, or 6 ppm NO. Following exposure, the lungs of NO- and air-exposed rats were preserved and prepared for electron microscopy. The lungs of replicate groups were lavaged and analyzed for protein content and antioxidants. Ultrastructural alterations due to exposure were determined by quantitative morphometric analyses and serial-section counts of the number of alveolar fenestrae. In contrast to the prior study of NO, there was no significant difference in the number of alveolar fenestrae/lung between control and NO-exposed groups. Morphometric analysis of the 6 ppm NO-exposure group demonstrated a significant increase from controls in the percentage of epithelial basement membrane covered by type II epithelial cells and a significant increase in the number of type II epithelial cells and airspace macrophages. At 2 ppm, only the percentage of epithelial basement membrane covered by type II epithelial cells was significant. No significant differences were found in lavage protein or in lavage ascorbic acid or glutathione content between clean-air controls and NO-exposed groups. Overall, the proinflammatory responses by type II epithelial cells and airspace macrophages following inhaled NO were comparable to those of O3 and NO2. These results, derived from experiments using significantly higher concentrations than in the prior study, demonstrate that inhaled NO produces a pattern of injury similar to that of other oxidants.
Os8N3 is a host disease-susceptibility gene for bacterial blight of rice (2006)

Many bacterial diseases of plants depend on the interaction of type III effector genes of the pathogen and disease-susceptibility genes of the host. The host susceptibility genes are largely unknown. Here, we show that expression of the rice gene Os8N3, a member of the MtN3 gene family from plants and animals, is elevated upon infection by Xanthomonas oryzae pv. oryzae strain PXO99(A) and depends on the type III effector gene pthXo1. Os8N3 resides near xa13, and PXO99(A) failed to induce Os8N3 in rice lines with xa13. Silencing of Os8N3 by inhibitory RNA produced plants that were resistant to infection by strain PXO99(A) yet remained susceptible to other strains of the pathogen. The effector gene avrXa7 from strain PXO86 enabled PXO99(A) compatibility on either xa13- or Os8N3-silenced plants. The findings indicate that Os8N3 is a host susceptibility gene for bacterial blight targeted by the type III effector PthXo1. The results support the hypothesis that X. oryzae pv. oryzae commandeers the regulation of otherwise developmentally regulated host genes to induce a state of disease susceptibility. Furthermore, the results support a model in which the pathogen induces disease susceptibility in a gene-for-gene manner.
Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells (1997)

Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine thought to play a major role in recruiting monocytes to the atherosclerotic plaque. Tissue factor (TF), the initiator of coagulation, is found in the atherosclerotic plaque, macrophages, and human aortic smooth muscle cells (SMC). The exposure of TF during plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the accumulation of TF mRNA and protein in SMC and in THP-1 myelomonocytic leukemia cells. MCP-1 also induces TF activity on the surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled to a Gi-protein. Chelation of intracellular calcium and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a Kd similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that they possess a distinct MCP-1 receptor. These data suggest that in addition to being a chemoattractant, MCP-1 may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells.
Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells. (1985)

Highly purified, Escherichia coli-derived recombinant human tumor necrosis factor (TNF) was labeled with 125I and employed to determine receptor binding, internalization, and intracellular degradation in murine L929 cells (highly sensitive to the cytotoxic action of TNF) and in diploid human FS-4 cells (resistant to TNF cytotoxicity). 125I-labeled TNF bound specifically to high-affinity receptors on both L929 and FS-4 cells. Scatchard analysis of the binding data indicated the presence of 2200 binding sites per L929 cell and 7500 binding sites per FS-4 cell. The calculated dissociation constants are 6.1 X 10(-10) M and 3.2 X 10(-10) M for L929 and FS-4 cells, respectively. In both L929 and FS-4 cells, incubation at 37 degrees C resulted in a rapid internalization of the bulk of the cell-bound TNF, followed by the appearance of trichloroacetic acid-soluble 125I radioactivity in the tissue culture medium, due to degradation of TNF. Degradation but not cellular uptake of TNF was inhibited in the presence of chloroquine (an inhibitor of lysosomal proteases) in both L929 and FS-4 cells, suggesting that degradation occurs intracellularly, probably within lysosomes. These results show that resistance of FS-4 cells to TNF cytotoxicity is not due to a lack of receptors or their inability to internalize and degrade TNF.
TRPM4 Regulates Calcium Oscillations After T Cell Activation (2004)

TRPM4 has recently been described as a calcium-activated nonselective (CAN) cation channel that mediates membrane depolarization. However, the functional importance of TRPM4 in the context of calcium (Ca2+) signaling and its effect on cellular responses are not known. Here, the molecular inhibition of endogenous TRPM4 in T cells was shown to suppress TRPM4 currents, with a profound influence on receptor-mediated Ca2+ mobilization. Agonist-mediated oscillations in intracellular Ca2+ concentration ([Ca2+]i), which are driven by store-operated Ca2+ influx, were transformed into a sustained elevation in [Ca2+]i. This increase in Ca2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca2+ oscillations, with downstream effects on cytokine production in T lymphocytes.
Transcriptional profiling reveals regulated genes in the hippocampus during memory formation (2002)

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.
TRAIL and its receptors as targets for cancer therapy (2004)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, which can induce apoptotic cell death in a variety of tumor cells by engaging the death receptors DR4 and DR5, while sparing most normal cells. Preclinical studies in mice and non-human primates have shown the potential utility of recombinant soluble TRAIL and agonistic anti-DR5 or DR4 antibodies for cancer therapy. Moreover, we have recently revealed a vital role for endogenously expressed TRAIL in immunosurveillance of developing and metastatic tumors. In this review, we summarize recent knowledge about TRAIL and its receptors as promising targets for cancer therapy.
Tumor-Reactive CD8+ T Cells in Metastatic Gastrointestinal Cancer Refractory to Chemotherapy (2013)

This study provides a basis for the development of immunotherapy for patients with advanced gastrointestinal malignancies by first establishing the presence of naturally occurring tumor-reactive CD8(+) TIL at the molecular level.
Materials and growth issues for high-performance nonpolar and semipolar light-emitting devices (2012)

Growth of InGaN/GaN light-emitting devices on nonpolar or semipolar planes offers a viable approach to reducing or eliminating the issues associated with polarization-related electric fields present in c-plane III-nitride heterostructures. Although progress in device performance has been rapid since the introduction of high-quality free-standing nonpolar and semipolar GaN substrates, a full appreciation of the materials challenges unique to nonpolar and semipolar III-nitride semiconductors has been slower to emerge. Only recently have researchers begun to understand issues such as the origins of the pyramidal hillocks typically observed on nominally on-axis m-plane GaN films, the effects of m-plane substrate misorientation on surface morphology and device performance, the mechanics of anisotropic cracking in tensile strained m-plane AlGaN films, the formation of basal-plane stacking faults in long-wavelength m-plane InGaN quantum wells, and the mechanisms for stress relaxation in semipolar AlGaN and InGaN films. In this paper, we review the materials and growth issues unique to high-performance nonpolar and semipolar light-emitting devices grown on high-quality free-standing GaN substrates and provide an outlook for the opportunities and challenges that lie ahead.
Comprehensive genomic characterization defines human glioblastoma genes and core pathways (2008)

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
High-Performance Communication Networks (1999)

Contents 1 Wireless Networks 1 1.1 Introduction ...................................... 1 1.1.1 History of Wireless Networks ........................ 2 1.1.2 Wireless Data Vision ............................. 5 1.1.3 Technical Challenges ............................. 7 1.2 The Wireless Channel ................................. 8 1.2.1 Path loss ................................... 9 1.2.2 Shadow Fading ................................ 10 1.2.3 Multipath Flat-fading and Intersymbol Interference ............. 11 1.2.4 Doppler Frequency Shift ........................... 12 1.2.5 Interference .................................. 13 1.2.6 Infrared versus Radio ............................ 13 1.2.7 Capacity Limits of Wireless Channels .................... 14 1.3 Link Level Design .................................. 15 1.3.1 Modulation Techniques ............................ 15 1.3.2 Channel Coding and Link Layer Retransmission .............. 16 1.3.3 Flat-Fading Countermeasures ..
LOXL2-Mediated Matrix Remodeling in Metastasis and Mammary Gland Involution (2011)

More than 90% of cancer patient mortality is attributed to metastasis. In this study, we investigated a role for the lysyl oxidase-related enzyme lysyl oxidase-like 2 (LOXL2) in breast cancer metastasis, in both patient samples and in vivo models. Analysis of a published microarray data set revealed that LOXL2 expression is correlated with metastasis and decreased survival in patients with aggressive breast cancer. In immunocompetent or immunocompromised orthotopic and transgenic breast cancer models we showed that genetic, chemical or antibody-mediated inhibition of LOXL2 resulted in decreased metastasis. Mechanistic investigations revealed that LOXL2 promotes invasion by regulating the expression and activity of the extracellular proteins tissue inhibitor of metalloproteinase-1 (TIMP1) and matrix metalloproteinase-9 (MMP9). We found that LOXL2, TIMP1, and MMP9 are coexpressed during mammary gland involution, suggesting they function together in glandular remodeling after weaning. Finally, we found that LOXL2 is highly expressed in the basal/myoepithelial mammary cell lineage, like many other genes that are upregulated in basal-like breast cancers. Our findings highlight the importance of LOXL2 in breast cancer progression and support the development of anti-LOXL2 therapeutics for the treatment of metastatic breast cancer.
EDFA gain flattening using long-period fibre gratings based on the electric arc technique (2001)

We have flattened the gain spectrum of a commercial Erbium-doped fibre amplifier, obtaining a curve with approximately 3 dB of ripple, from 1524 nm to 1551 nm, using long-period fibre gratings as equalising optical filters. The fabrication principle of the long-period fibre grating is based on the electric arc technique.