gebhart/patrepeval huggingface dataset:
Synthesis and Expression of Tissue Factor Pathway Inhibitor by Serum-stimulated Fibroblasts, Vascular Smooth Muscle Cells and Cardiac Myocytes (1999)

Tissue factor pathway inhibitor (TFPI) plays an important role in regulating tissue factor (TF)-initiated blood coagulation. Since serum stimulation of fibroblasts, vascular smooth muscle cells and cardiac myocytes in culture increases the expression of TF mRNA and antigen (Ag) in these cells, we hypothesized that serum may also induce increased synthesis of TFPI in these cells to regulate the TF-induced extravascular clotting at an injury site. To test this concept, we used primary isolates of the following human cell types - fetal and adult lung fibroblasts, pulmonary and aortic smooth muscle cells, and cardiac myocytes. Serum-stimulation of these cells resulted in an increased expression of TF mRNA and Ag (8 to 10-fold). Upon serum stimulation, expression of TFPI mRNA and Ag was also increased in these cells. However, the increase in TFPI-Ag (6 to 8-fold) was significantly greater than the TFPI mRNA (2 to 3-fold). Notably, increased expression of TFPI persisted after the TF expression had declined. Further, increased synthesis of TFPI initially led to the saturation of heparin-releasable binding sites. TFPI-Ag was detected by Western blotting, 35S-metabolic labeling and activity assays on the conditioned media, heparin-released material from cells, and in cell lysates. TFPI-Ag was also detected by immunofluorescence staining of cells. Actinomycin D partially whereas cycloheximide completely prevented the serum-induced increased expression of TFPI synthesis by these cells, suggesting control primarily at the translational but some at the transcriptional level as well. The Mr of undegraded TFPI in all cases was approximately 45 kDa and was of full length. TFPI synthesized locally by fibroblasts, vascular smooth muscle cells and cardiac myocytes could play a significant role in regulating TF-initiated extravascular clotting especially since plasma TFPI that may be available at the injury site lacks a portion of the carboxyl segment and is a less efficient inhibitor.
Theoretical Estimation of Leakage Current in II-VI Heterostructure Lasers (1992)

II-VI heterostructures studied in terms of lasing properties up to now have been mostly common-anion or common-cation heterostructures, where the band offsets are localized either in the conduction band or in the valence band. This paper deals with a leakage current in this sort of p-i-n heterostructure under forward bias. It is shown that the leakage current does not necessarily depend on the band offset, but principally depends on the energy-gap difference between the active layer and the cladding layer. This result leads to the expectation that the above heterostructures with the nearly flat band structures either in the conduction band or in the valence band will be applicable as II-VI laser materials. Quantitative comparison between the radiative recombination current and the leakage current was also performed on the laser diode structure.
Identification of Target Genes for the Ewing's Sarcoma EWS/FLI Fusion Protein by Representational Difference Analysis (1995)

The EWS/FLI-1 fusion gene results from the 11;22 chromosomal translocation in Ewing's sarcoma. The product of the gene is one of a growing number of structurally altered transcription factors implicated in oncogenesis. We have employed a subtractive cloning strategy of representational difference analysis in conjunction with a model transformation system to identify genes transcribed in response to EWS/FLI. We have characterized eight transcripts that are dependent on EWS/FLI for expression and two transcripts that are repressed in response to EWS/FLI. Three of the former were identified by sequence analysis as stromelysin 1, a murine homolog of cytochrome P-450 F1 and cytokeratin 15. Stromelysin 1 is induced rapidly after expression of EWS/FLI, suggesting that the stromelysin 1 gene may be a direct target gene of EWS/FLI. These results demonstrate that expression of EWS/FLI leads to significant changes in the transcription of specific genes and that these effects are at least partially distinct from those caused by expression of germ line FLI-1. The representational difference analysis technique can potentially be applied to investigate transformation pathways activated by a broad array of genes in different tumor systems.
Optimizing Change Request Scheduling in IT Service Management (2008)

Enterprises of today face the challenge of managing large, complex IT eco-systems consisting of software applications, servers, network routers, and other type of resources. Change management, especially scheduling of changes, is known to be one of the most challenging problems in managing IT operations. In this paper, we propose an optimization model for IT change scheduling that takes into account the constraints and cost factors typically encountered in a service provider environment. In particular, we formulate the model in a way that can be solved using standard mathematical programming techniques (i.e., mixed integer programming). This not only results in strictly optimal solutions, but also provides a scalable means for scheduling a large set of change requests with complex constraints. Furthermore, having a computational efficient optimization solution facilitates the study of the scheduling sensitivity with respect to parameter inaccuracy and leads to more robust change schedules. Finally, we demonstrate the effectiveness of the proposed approach in an IT change management example which is built using insights from a large service delivery account and over two hundred thousand change instances.
Comparative effects of combretastatin A-4 disodium phosphate and 5,6-dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal tissues (2001)

CA4DP and DMXAA produced a selective and significant reduction in tumour perfusion, but the pattern of change was different. These results suggest how these vascular targeting drugs should be combined with more conventional therapies.
Inactivation of human gamma-glutamylcysteine synthetase by cystamine. Demonstration and quantification of enzyme-ligand complexes. (1978)

Human erythrocyte gamma-glutamylcysteine synthetase is inactivated by the disulfide cystamine (2,2'-dithiobis-(ethylamine)) at pH 8.2 with a rate constant of 1020 min-1 mM-1. Magnesium ion and various combinations of substrates and products confer differing degrees of protection against cystamine inactivation, thus allowing the detection and quantification of certain enzyme-ligand interactions. By measuring inactivation rates as a function of ligand concentrations in incomplete reaction mixtures, we have obtained evidence for the following complexes: enzyme . Mg2+; enzyme . Mg2+ . MgATP2-; enzyme . Mg2+ . L-glutamate; enzyme . Mg2+ . MgATP2- . L-glutamate; enzyme . Mg2+ . L-gamma-glutamyl-L-alpha-aminobutyrate. The data also imply the existence of enzyme . (Mg2+)2 . MgATP2- . L-glutamate and several enzyme forms resulting from the weak binding to L-alpha-aminobutyrate. The methods used permit the calculation of cystamine inactivation rates for most of these enzyme forms and also give values for the equilibrium constants describing their formation.
Phosphorylation of Xenopus mitogen-activated protein (MAP) kinase kinase by MAP kinase kinase kinase and MAP kinase. (1993)

Xenopus 45-kDa mitogen-activated protein (MAP) kinase kinase (MAPKK) is a serine/threonine/tyrosine kinase, which activates MAP kinase (MAPK) by phosphorylating its threonine and tyrosine residues. MAPKK is active only when its threonine and/or serine residues are phosphorylated. We have identified from Xenopus eggs two protein kinases responsible for phosphorylation of MAPKK. The two kinases are separated by Sephacryl S-300 gel filtration chromatography. The higher molecular weight kinase phosphorylates MAPKK previously dephosphorylated and inactivated by phosphatase 2A treatment on mainly serine and slightly threonine residues, and reactivates the MAPKK, and is thus assumed to work as MAPKK kinase (MAPKKK) in vivo. The lower molecular weight kinase, identified as MAPK, phosphorylates the dephosphorylated MAPKK on mainly threonine and faintly serine residues, but does not reactivate the MAPKK activity. As Xenopus MAPKK contains a single phosphorylation consensus sequence (PXT388P) for MAPK in the C-terminal region, this T388 residue may be a major phosphorylation site catalyzed by MAPK. Thus, Xenopus MAPKK is phosphorylated in mature oocytes by not only an upstream kinase, MAPKKK, but also a downstream kinase, MAPK.
A vipox virus-vectored Japanese encephalitis virus vaccines: use as vaccine candidates in combination with purified subunit immunogens (1994)

An avipox virus, canarypox (ALVAC), which is naturally host-range restricted, was used to construct recombinants encoding the Japanese encephalitis virus (JEV) prM, E and NS1 genes (vCP107) and prM and E genes (vCP140). Mice immunized with these recombinant viruses produced JEV neutralizing antibodies and were protected from lethal JEV challenge. Protection was also observed in mice immunized with a subunit vaccine candidate, consisting of extracellular particles (EPs; RNA-free subviral membrane vesicles containing prM/M and E proteins) derived from HeLa cell cultures infected with a JEV-vaccinia recombinant. Mice primed with vCP107 and boosted with EPs had higher antibody levels than mice immunized twice with EPs alone, although the levels were comparable to that obtained in mice immunized twice with the recombinant virus. Mice immunized with a mixture of recombinant virus (vCP107) plus EPs had neutralizing antibody titres higher than mice immunized with the recombinant virus or EPs alone.
Monitoring Bacterial Community of Human Gut Microbiota Reveals an Increase in Lactobacillus in Obese Patients and Methanogens in Anorexic Patients (2009)

Lactobacillus species are widely used as growth promoters in the farm industry and are now linked to obesity in humans. The study of the bacterial flora in anorexic patients revealed an increase in M. smithii. This increase might represent an adaptive use of nutrients in this population.
Direct antenna modulation: analysis, design, and experiment (2006)

In this paper, a symmetrical 1.5 GHz patch antenna has been designed, constructed, simulated and experimentally fine-tuned to be the radiating element in the experiment to implement direct antenna modulation. With a resonant bandwidth of about 30 MHz (using a 10 dB or better return-loss standard), there is significant room for improvement that direct antenna modulation can offer to the information bandwidth of the system. By driving the antenna at resonance and directly modulating it with an integrated Schottky diode being biased by an external pulse train, the frequency of this external modulating signal is predicted to far exceed the resonant bandwidth of the antenna and still produce a clear demodulated waveform at the receiving end of a basic communication system
Voice Operated Transducer for the Disabled (1980)

Most systems for enabling a disabled individual to control an electrical device use the sip and puff technique or mechanically operated switches or levers. A system usable by a patient with severe tremor is described, in which tongue clicks are used to control a tape recorder. These clicks are found to be easily separable from voice frequencies by means of a simple high-pass filter. The user selects the various modes of the tape recorder by emitting specified numbers of clicks in a selected time period.
Consensus molecular subtypes (CMS) as a marker for treatment and disease biology in metastatic colorectal cancer (CRC). (2020)

4089 Background: Consensus molecular subtypes (CMS) categorize colorectal cancer (CRC) into groups based on gene transcription and are prognostic in early-stage and first-line metastatic settings. Their impact on treatment history is unknown. We hypothesized that the best prognosis CMS2 would have higher utilization of liver-directed therapies and maintenance chemotherapy over the worst prognosis CMS4. Methods: Primary surgical resection specimens were annotated for CMS on a translational protocol in a 5FU-refractory metastatic CRC population. Specimens that had neoadjuvant chemotherapy or radiation were excluded. CMS1, CMS3 and indeterminate CMS were also excluded. Liver-directed therapies were defined as any surgery, direct injection of cytotoxics or microspheres, radiation or radiofrequency ablation. Multiple occurrences of liver-directed therapies or maintenance chemotherapy in the same patient were recorded once for statistical tests of association. Results: CMS1 (7.4%), CMS3 (8.2%) and indeterminate calls (4.1%) accounted for 20% of all samples tested. There were 43 (44%) CMS2 and 55 (56%) CMS4 patients eligible. Age, stage at diagnosis, mismatch repair and RAS mutational status were similar in both groups. Left-sided tumors were more common in CMS2 (79%) than CMS4 (42%), p = .001. The median overall survival (OS) from stage IV diagnosis was 40 [34 - 51] versus (vs) 28 [21 – 33] months (p &lt; .0001) for CMS2 vs CMS4 respectively. Liver-directed therapy was greater in CMS2 (53%) vs CMS4 (31%), p = .024. The number further increased when multiple treatments in a single patient were taken into account. Microsphere injection, radiation and liver surgery combined with RFA were the most skewed towards CMS2 over CMS4. No difference in median OS was seen from first liver-directed therapy in CMS2 vs CMS4 (29 vs 27 months, p = .31). There was a trend towards greater maintenance chemotherapy in CMS2 (47%) vs CMS4 (29%), p = .076. Conclusions: Better prognosis with CMS2 is consistent with other studies. Significantly increased liver-directed therapy was observed in CMS2. Selection criteria for liver-directed therapy such as slowly progressing, oligometastatic and hepatic-confined disease may be enriching for CMS2 and gives insight into the natural history of this subtype.
Identification and Characterization of the Protein Encoded by the Human N- myc Oncogene (1986)

The human N-myc gene is related to the c-myc proto-oncogene, and has been shown to have transforming potential in vitro. Many studies have reported amplification of N-myc in human neuroblastoma and retinoblastoma cell lines. In primary tumors, amplification of the gene was found to correlate directly with behavior of the tumor. Specific restriction fragments of a partial complementary DNA clone of N-myc from LA-N-5 human neuroblastoma cells were placed into a bacterial expression vector for the purpose of producing antigens representative of the N-myc protein. Rabbits immunized with these antigens produced antisera that recognized a protein of 62-64 kilodaltons in neuroblastoma cells. By several criteria, this protein appears to be part of the same proto-oncogene family as the c-myc protein. Moreover, the antisera to fragments of this protein were capable of histochemically identifying malignant cells in clinical specimens.
End-to-end equalization experiments in amplified WDM lightwave systems (1993)

It is experimentally verified that signal-to-noise ratio equalization in amplified wavelength-multiplexed lightwave systems can be achieved by adjusting input optical signal powers according to a simple algorithm. The experiment involved four channels spaced by 2 nm transmitted through 550 km of fiber with the aid of eight erbium-doped optical amplifiers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Double knockdown of α1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC (2007)

Our results suggest that FUT8 and GMD collaborate synergistically in the process of intracellular oligosaccharide fucosylation. We also demonstrated that double knockdown of FUT8 and GMD in antibody-producing cells could serve as a new strategy for producing next-generation therapeutic antibodies fully lacking core fucosylation and with enhanced ADCC. This approach offers tremendous cost- and time-sparing advantages for the development of next-generation therapeutic antibodies.
Resveratrol Stimulates Mitochondrial Bioenergetics to Protect Retinal Pigment Epithelial Cells From Oxidative Damage (2013)

Our results indicate that RSV, a major polyphenol found in red wine, exerts protection against acrolein-induced cytotoxicity in human ARPE-19 cells via increases in the mitochondrial bioenergetics. In addition, the antioxidant effect of RSV may contribute to protection against laser-induced CNV in animals exposed to CS. Therefore, RSV might be beneficial for treatment of acrolein-induced or CS-evoked RPE degeneration.
The role of peptides in blood‐brain barrier nanotechnology (2007)

The blood-brain barrier (BBB) regulates the passage of molecules between the bloodstream and the brain. Overcoming the difficulty of delivery drugs to specific areas of the brain is a major challenge. The BBB exerts a neuroprotective function as it hinders the delivery of diagnostic and therapeutic agents to the brain. Here, we provide an overview of the way in which peptides and nanotechnology are being exploited in tandem to address this problem. Peptides can be used as specialised coatings able to transport nanoparticles with specific properties, such as targeting. The nanoparticle can also carry a peptide drug. Furthermore, peptides can be used in less conventional approaches such as all-peptide nanoparticles. In summary, the combined use of peptides and nanotechnology offers tremendous hope in the treatment of brain disorders.
Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab (2008)

Our data suggest that the IL-8 A-251T polymorphism may be a molecular predictor of response to bevacizumab-based chemotherapy. The CXCR2 C+785T, VEGF C+936T single nucleotide polymorphisms and the AM 3' dinucleotide repeat polymorphisms may be molecular markers for PFS in ovarian cancer patients.
Electroporation of Cell Membranes: A Review (1996)

The study of the electroporation on biomembranes has become one of the most exciting topics in the biophysical and biotechnological areas. Researchers all over the world have been focused on four major areas: measurements of transmembrane potential (TMP); dynamics of electroporation such as time sequence, properties of electropores such as size, structure, and population; membrane permeabilization and breakdown theory; and the effects of secondary factors such as ions type and cell growth stage on electroporation. This article reviews some of the recent discoveries and theories on this subject. Studies on TMP and pore dynamics remain a difficult task. Since the area of electroporation on a biomembrane is small (less than 0.1% of total surface area) and the time sequence of electropores is in the submicrosecond range measuring devices with subtle detection and time resolution are required. While more and more studies have shown the formation sequence of electropore(s) at specific locations on various biomembranes, the pore(s) widening process and the subsequent membrane breakdown mechanisms remain controversial. The influence of electromechanical stress or transmembrane potential on membrane discharge and rupture seems to be a function of various factors such as membrane properties, external medium, and the protocols of electroporators.
Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor (2016)

Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non-tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome-mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protein analysis were performed by real-time PCR and Western blot. IL8 and MMP9 secretions were evaluated by ELISA. Exosomes were isolated from CML cells and blood samples of CML patients. Here, we show that LAMA84 and CML patients' exosomes contain amphiregulin (AREG), thus activating epidermal growth factor receptor (EGFR) signalling in stromal cells. EGFR signalling increases the expression of SNAIL and its targets, MMP9 and IL8. We also demonstrated that pre-treatment of HS5 with LAMA84 exosomes increases the expression of annexin A2 that promotes the adhesion of leukaemic cells to the stromal monolayer, finally supporting the growth and invasiveness of leukaemic cells. Leukaemic and stromal cells establish a bidirectional crosstalk: exosomes promote proliferation and survival of leukaemic cells, both in vitro and in vivo, by inducing IL8 secretion from stromal cells. We propose that this mechanism is activated by a ligand-receptor interaction between AREG, found in CML exosomes, and EGFR in bone marrow stromal cells.
Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia (2005)

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.