gebhart/patrepeval huggingface dataset:
Roles of Chk1 in cell biology and cancer therapy (2013)

The evolutionally conserved DNA damage response (DDR) and cell cycle checkpoints preserve genome integrity. Central to these genome surveillance pathways is a protein kinase, Chk1. DNA damage induces activation of Chk1, which then transduces the checkpoint signal and facilitates cell cycle arrest and DNA damage repair. Significant progress has been made recently toward our understanding of Chk1 regulation and its implications in cancer etiology and therapy. Specifically, a model that involves both spatiotemporal and conformational changes of proteins has been proposed for Chk1 activation. Further, emerging evidence suggests that Chk1 does not appear to be a tumor suppressor; instead, it promotes tumor growth and may contribute to anticancer therapy resistance. Recent data from our laboratory suggest that activating, but not inhibiting, Chk1 in the absence of chemotherapy might represent an innovative approach to suppress tumor growth. These findings suggest unique regulation of Chk1 in cell biology and cancer etiology, pointing to novel strategies for targeting Chk1 in cancer therapy.
Environment estimation for enhanced impedance control (2002)

Impedance control is a popular method of controlling the dynamic response a robot has to external forces. The advantage of such a control paradigm is the ability to manipulate in both unconstrained and constrained environments. Unlike hybrid control methods that attempt to control forces and motions in orthogonal directions, impedance control consists of a single control law that accommodates external forces. One problem associated with such a controller is the selection of the robot's target impedance. This paper illustrates, through analysis and experimentation, the shortcoming of improper target impedance selection. The integration of a real time estimate of the robot's environment with the impedance controller resolves this problem. Experimental results illustrate improved performance during the transition from unconstrained to constrained manipulation.
Cutting Edge: Identification of a Novel Chemokine Receptor That Binds Dendritic Cell- and T Cell-Active Chemokines Including ELC, SLC, and TECK (2000)

Searching for new receptors of dendritic cell- and T cell-active chemokines, we used a combination of techniques to interrogate orphan chemokine receptors. We report here on human CCX CKR, previously represented only by noncontiguous expressed sequence tags homologous to bovine PPR1, a putative gustatory receptor. We employed a two-tiered process of ligand assignment, where immobilized chemokines constructed on stalks (stalkokines) were used as bait for adhesion of cells expressing CCX CKR. These cells adhered to stalkokines representing ELC, a chemokine previously thought to bind only CCR7. Adhesion was abolished in the presence of soluble ELC, SLC (CCR7 ligands), and TECK (a CCR9 ligand). Complete ligand profiles were further determined by radiolabeled ligand binding and competition with >80 chemokines. ELC, SLC, and TECK comprised high affinity ligands (IC50 <15 nM); lower affinity ligands include BLC and vMIP-II (IC50 <150 nM). With its high affinity for CC chemokines and homology to CC receptors, we provisionally designate this new receptor CCR10.
Secretion of complement components of the alternative pathway (C3 and factor B) by the human alveolar type II epithelial cell line A549. (2000)

The complement system participates in the local immune system of the lung. In this study, we investigated the secretion of complement components of the alternative pathway (C3 and factor B) in the alveolar type II epithelial cell line A549. The levels of C3 and factor B protein in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). The C3 and factor B mRNA expression was assessed by reverse transcription polymerase chain reaction (RT-PCR). The addition of interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha induced a dose- and time-dependent increase in C3 and factor B secretion. The addition of IL-6 or interferon (IFN)-gamma also induced a weak but significant increase in C3 and factor B secretion. These responses at the protein level were also observed at the mRNA level. Furthermore, the combination of IL-1beta plus TNF-alpha induced a marked increase in C3 and factor B secretion. Similarly, IL-6 and IFN-gamma potently enhanced IL-1beta- or TNF-alpha-induced C3 and factor B secretion, respectively. In this study, we demonstrated C3 and factor B secretion in A549 cells, and showed that the proinflammatory cytokines, IL-1beta, IL-6, TNF-alpha and IFN-gamma, acted as potent inducers of C3 and factor B secretion. It is likely that alveolar type II epithelial cells are the local sites of complement biosynthesis, and that various cytokines act as regulators of this local immune protection system.
Development of an Agricultural Biotechnology Crop Product: Testing from Discovery to Commercialization (2012)

"Genetically modified" (GM) or "biotech" crops have been the most rapidly adopted agricultural technology in recent years. The development of a GM crop encompasses trait identification, gene isolation, plant cell transformation, plant regeneration, efficacy evaluation, commercial event identification, safety evaluation, and finally commercial authorization. This is a lengthy, complex, and resource-intensive process. Crops produced through biotechnology are the most highly studied food or food component consumed. Before commercialization, these products are shown to be as safe as conventional crops with respect to feed, food, and the environment. This paper describes this global process and the various analytical tests that must accompany the product during the course of development, throughout its market life, and beyond.
The simplest electronic ballast for HID lamps (2002)

The resonant forward-flyback (RFF) inverter is presented, analyzed theoretically and tested experimentally. It is shown that the inverter can be designed to operate under zero voltage switching (ZVS) conditions and that it acts as a current source, features that are highly compatible with HID lamp ballasting. The design guidelines and the detailed analytical expressions developed in this study were verified by computer simulation and hardware implementation. The experimental results of the study demonstrate that the arc of small 35 W and 70 W metal halide discharge lamps can be stabilized by the proposed RFF ballast when operated in the 300 kHz to 400 kHz switching frequency range and applying about 20% FM modulation. Considering the fact that the proposed ballast includes only one switching device, one magnetic component and one resonant capacitor, the RFF inverter is most likely the simplest ballast topology possible.
Comprehensive next-generation cancer genome sequencing in the era of targeted therapy and personalized oncology (2011)

DNA sequence analysis has become a significant laboratory test in oncology, permitting treatment to become increasingly personalized for both solid tumors and hematologic malignancies. Traditional approaches to sequence analysis, including Sanger sequencing, pyrosequencing and allele-specific PCR, are now widely used to guide therapy for patients diagnosed with lung and colorectal cancer as well as for melanoma, sarcomas (e.g., gastrointestinal stromal tumors) and subtypes of leukemia and lymphoma. Traditional sequence analysis has been limited in bandwidth and throughput and as a result, has been focused exclusively on testing the most common aberrations in key genes or fully sequencing single genes. The massively parallel or next-generation sequencing (NGS) approach to DNA analysis holds a number of potential advantages over the traditional methods, including the ability to fully sequence large numbers of genes (hundreds to thousands) in a single test. Furthermore, NGS can simultaneously detect deletions, insertions, copy number alterations, translocations and exome-wide base substitutions (including known hot-spot mutations) in all known cancer-related genes. However, significant challenges, particularly with respect to demands on expertise and infrastructure, will have to be overcome to translate NGS to the bedside of the cancer patient. Extensive computational expertise is required to bring NGS into clinical context, and a deep knowledge of cancer medicine and cancer biology will be required to generate truly useful, so-called 'clinically actionable' reports for clinicians. While NGS is on the cusp of being launched as a clinical test, it may be expected that the near future will continue to bring major advances in the technology that will lower the overall cost, speed up the turnaround time, increase the breadth of genome sequencing, and detect epigenetic markers and other important genomic parameters, while becoming applicable to smaller and smaller specimens, including circulating tumor cells and circulating free DNA in plasma.
[123I]beta-CIT SPECT imaging of striatal dopamine transporter binding in Tourette's disorder (1995)

These findings corroborate post-mortem results and support the hypothesis of a dysregulation in presynaptic dopamine function in Tourette's disorder.
Meal Pattern Analysis of Diet‐Induced Obesity in Susceptible and Resistant Rats (2003)

The hyperphagia of a Sprague-Dawley rat model of chronic diet-induced obesity is caused by an increase in meal size, not number. These results are an important step toward understanding the mechanisms underlying differences in feeding behavior of DIO and DR rats.
Evolution of multicellularity in Metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis (2004)

A comparison of the subcellular assignments of proteins between the unicellular Saccharomyces cerevisiae and the multicellular Drosophila melanogaster and Caenorhabditis elegans was performed using a computational tool for the prediction of subcellular localization. Nine subcellular compartments were studied: (1) extracellular domain, (2) cell membrane, (3) cytoplasm, (4) endoplasmic reticulum, (5) Golgi apparatus, (6) lysosome, (7) peroxisome, (8) mitochondria, and (9) nucleus. The transition to multicellularity was found to be characterized by an increase in the total number of proteins encoded by the genome. Interestingly, this increase is distributed unevenly among the subcellular compartments. That is, a disproportionate increase in the number of proteins in the extracellular domain, the cell membrane, and the cytoplasm is observed in multicellular organisms, while no such increase is seen in other subcellular compartments. A possible explanation involves signal transduction. In terms of protein numbers, signal transduction pathways may be roughly described as a pyramid with an expansive base in the extracellular domain (the numerous extracellular signal proteins), progressively narrowing at the cell membrane and cytoplasmic levels, and ending in a narrow tip consisting of only a handful of transcription modulators in the nucleus. Our observations suggest that extracellular signaling interactions among metazoan cells account for the uneven increase in the numbers of proteins among subcellular compartments during the transition to multicellularity.
New chemotherapeutic agents for breast cancer (1994)

The drug discovery programs of the National Cancer Institute and the pharmaceutical industry recently have provided oncologists with a wide array of new chemotherapeutic agents that have considerable potential for breast cancer treatment. Foremost among these new agents are the taxanes, of which paclitaxel and docetaxel, the only members of this class currently in clinical use, have been associated with impressive response rates in patients with metastatic disease. Importantly, they display some evidence clinically of not being cross-resistant with the anthracyclines. Efforts now are being directed toward optimizing dose and schedule in the metastatic setting while integrating these agents into standard adjuvant regimens. Other agents that have undergone Phase II testing in breast cancer include vinorelbine, edatrexate, and losoxantrone. It remains to be determined, however, whether these drugs possess substantial advantages over other members of their class. Newer compounds, such as pyrazoloacridine, ICI D1694, topoisomerase-I inhibitors, temozolomide, penclomidine, fumagillin (TNP-470), and differentiators like the retinoids, hold substantial promise because of their unique mechanisms of action; however, Phase II testing of these agents is just beginning. Although alternative approaches to treatment, such as gene therapies, monoclonal antibodies, and growth factor inhibitors, are likely to have a positive impact, it is probable that progress will best be made by combining these strategies with chemotherapy. Therefore, continuation of the search for more effective chemotherapeutic agents should remain a high priority.
KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling (2008)

Abstract Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines and the viability of CD138+ primary myeloma cells by induction of apoptosis, accompanied by an increase of acetylation of histones and activation of caspase-3, caspase-8, and caspase-9. Treatment with KD5170 caused a loss of mitochondrial membrane potential resulting in release of apoptogenic factors such as cytochrome c, Smac, and apoptosis-inducing factor. Furthermore, KD5170 induced oxidative stress and oxidative DNA damage in myeloma cells as evidenced by the up-regulation of heme oxygenase-1 and H2A.X phosphorylation. Combination of KD5170 with proteasome inhibitor bortezomib or tumor necrosis factor–related apoptosis-inducing ligand synergistically enhanced the antimyeloma activity. We further found that resistance of myeloma cells to KD5170 was associated with activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway under treatment with KD5170. Pretreatment with the mitogen-activated protein kinase inhibitor U0126 restored sensitivity to KD5170, suggesting that the combination of KD5170 with U0126 could overcome drug resistance. Growth of myeloma tumor xenografts in KD5170-treated nude mice was significantly inhibited and survival was prolonged. Histone acetylation was increased in spleen and tumor tissues of animals treated with KD5170. Our data indicate that KD5170 has potent antimyeloma activity in vitro and in vivo, which is mediated by DNA damage and mitochondrial signaling and subsequent induction of apoptosis. [Mol Cancer Ther 2008;7(6):1494–505]
Mixture Density Estimation (1999)

Gaussian mixtures (or so-called radial basis function networks) for density estimation provide a natural counterpart to sigmoidal neural networks for function fitting and approximation. In both cases, it is possible to give simple expressions for the iterative improvement of performance as components of the network are introduced one at a time. In particular, for mixture density estimation we show that a k-component mixture estimated by maximum likelihood (or by an iterative likelihood improvement that we introduce) achieves log-likelihood within order 1/k of the log-likelihood achievable by any convex combination. Consequences for approximation and estimation using Kullback-Leibler risk are also given. A Minimum Description Length principle selects the optimal number of components k that minimizes the risk bound.
Multi-feature hierarchical template matching using distance transforms (2002)

We describe a multi-feature hierarchical algorithm to efficiently match N objects (templates) with am image using distance transforms (DTs). The matching is under translation, but it can cover more general transformations by generating the various transformed templates explicitly. The novel part of the algorithm is that, in addition to a coarse-to-fine search over the translation parameters, the N templates are grouped off-line into a template hierarchy based on their similarity. This way, multiple templates can be matched simultaneously at the coarse levels of the search, resulting in various speed-up factors. Furthermore, in matching, features are distinguished by type and separate DTs are computed for each type (e.g. based on edge orientations). These concepts are illustrated in the application of traffic sign detection.
A film bulk acoustic resonator pressure sensor based on lateral field excitation (2018)

A high-sensitive thickness shear mode film bulk acoustic resonator pressure sensor based on lateral field excitation is designed with its structure simulated in environment of air and liquids. A finite element model of film bulk acoustic resonator pressure sensor structure is established to obtain frequency variation under different pressure conditions by parameter sweep method when the multi-physics fields are added to the model. The results of simulation show that the pressure sensor’s resonance frequency is 2.114 GHz and pressure sensitivity is 1200 Hz/kPa in air. In liquid environment, film bulk acoustic resonator pressure sensor displays a pressure sensitivity of 325 Hz/kPa in ethanol, 475 Hz/kPa in deionized water, and 612.5 Hz/kPa in glycerol. This film bulk acoustic resonator pressure sensor has been proved to be highly sensitive both in air and liquid environment and has the potential to be used in biomedical applications.
[Detection of Aspergillus fumigatus DNA by polymerase chain reaction in the clinical samples from individuals with pulmonary aspergillosis]. (1994)

Aspergillosis is a disastrous cause of mortality and morbidity in patients in an immunocompromised state and old lung tuberculosis. However, the diagnosis of aspergillosis remains unsettled. In the present study, we developed a test to detect the Aspergillus fumigatus DNA using polymerase chain reaction (PCR) in clinical samples including sputum and bronchial aspirations from the patients with aspergillosis. We selected 2 pairs of oligonucleotide primers and the DNA for the small subunit ribosomal RNA of aspergillus fumigatus and they were significantly amplified. Although isolation of Aspergillus DNA may reflect contamination and colonization without infection, no aspergillus DNA was found in sputum or bronchial aspirations from the patients with lung cancer or interstitial lung diseases except a case of pulmonary fibrosis associated with rheumatoid arthritis chronically received 20 mg of corticosteroid. There was a 100% correlation between the culture results and the nested PCR results in the patients with pulmonary aspergillosis. These findings indicate that PCR detection of aspergillus fumigatus might be valuable for the diagnosis of aspergillosis.
Analysis of the Repertoire Features of TCR Beta Chain CDR3 in Human by High-Throughput Sequencing (2016)

Some repertoire features could be observed in the public sequences, highly abundance clones, and long TCR CDR3 sequences, which might be helpful for further study of immune behavior and immune response.
Gene Complementation in the T Lymphocyte Proliferative Response to Poly (Glu57Lys38Tyr5): Evidence for Effects of Polymer Handling and Gene Dosage (1979)

Abstract This paper explores the difficulties encountered in demonstrating Ir gene complementation in the immune response to the synthetic terpolymer, poly(Glu57-Lys38Tyr5) [GLT5]. First, the method by which the polymer was put into solution influenced the outcome because some determinants on GLT5 were found to be sensitive to exposure to alkaline conditions. Second, the dose of antigen used for immunization was shown to be critical since mice of the H-2q haplotype failed to respond to low doses of GLT5. Third, prolonged storage of dialyzed and lyophilized GLT5 led to alterations in the solubility properties of the polymer with consequent loss of some of the antigenic determinants. Finally, differences in the genetic make up of the responding strains affected the overall response. Each responder haplotype recognized different determinants on the polymer, or the same determinant in different ways, such that variations in polymer handling appeared to influence selectively the immunogenicity and antigenicity of GLT5 for each strain. Furthermore, the critical (B10 × B10.A)F1 strain, whose response was required to demonstrate conclusively complementation, failed to respond well to certain altered preparations of the polymer in which the determinants being recognized were present in low concentration. This failure, in contrast to the high responsiveness of the genetically similar B10.A(5R) strain, was shown by the low response of [B10.A(4R) × B10.A(5R)] F1 mice to result from a gene dosage effect. However, under optimal conditions of antigen handling, (B10 × B10.A)F1 mice did respond well to GLT5, demonstrating that two complementing MHC-linked Ir genes are involved in the recognition of certain determinants on this polymer.
Identification of Mutations in the Canine von Willebrand Factor Gene Associated with Type III von Willebrand Disease (1998)

In humans, type III von Willebrand disease is caused by deletions or nonsense mutations. In dogs, the underlying genetic defects have not been determined yet. We searched for the genetic defect in four related type III deficient Dutch Kooiker dogs obtained from one breeder. Mutation analysis was performed with total RNA isolated from platelets or whole blood. The complete coding region of the vWf gene was amplified by RT-PCR and sequenced by the cycle sequencing technique. Two homozygous mutations were found, a G-->A transition at the first position of the donor splice site sequence of intron 16 (TGgtaagt-->TGataagt) and a missense mutation at nt 208 (G-->A) (1). The splice site defect resulted in the generation of a transcript containing 46bp of intron sequence and a stop codon at amino acid position 729 in the propeptide region of the vWf protein. This mutation seems to be causative for the type III phenotype. The effect of the missense mutation in exon 3 which causes a change of Val to Ile on the vWD phenotype is unclear. Probably, this transition represents a polymorphism occurring in Dutch Kooiker dogs. Both mutations were not present in 5 healthy mongrel dogs.