gebhart/patrepeval huggingface dataset:
Altered conformation of the p53 protein in myeloid leukemia cells and mitogen-stimulated normal blood cells. (1992)

Expression of the normal p53 gene promotes cell differentiation, maturation and apoptosis. The mutant p53 gene, which does not function normally, is frequently expressed at elevated levels in tumor cells [for review see Lane, D.P. & Benchimol, S. (1990). Genes Dev., 4, 1-8]. We have analysed the expression of and mutational change in the p53 gene in the peripheral blood cells of 49 primary acute myeloid leukemia (AML) patients. The p53 protein levels were elevated in 37 patients (75%) when measured by immunoprecipitation with antibodies PAb1801 and PAb421, which recognize both normal and mutant forms of the protein. The p53 protein from 32 of these 37 patients was immunoprecipitated by PAb240, which recognizes a conformation of p53 protein associated with point mutations. However, point mutations were detected by single-stranded conformation polymorphism (SSCP) assay and direct sequencing in only three patients at codons 178, 245, 273 and 290. Growth stimulation of normal lymphocytes also generated p53 which was immunoprecipitable by PAb240. Thus, alteration of p53 conformation, rather than acquisition of point mutations, could be the mechanism underlying the increased proliferation of myeloid cells in most AML patients.
Voltage-operated calcium channels in small cell lung carcinoma cell lines: pharmacological, functional, and immunological properties. (1990)

Different subtypes of voltage-operated calcium channels (VOCCs) are expressed in different tissues and can be distinguished by functional and pharmacological criteria. One type of high voltage-activated calcium channel, specifically recognized by the peptide neurotoxin omega-conotoxin (omega CTx), is expressed only in neurons. Seven different human small cell lung carcinoma (SCC) cell lines were also found to bind 125I-omega CTx. The binding was specific, saturable, and of high affinity. 125I-omega CTx binding was not antagonized by the calcium channel ligands verapamil, nitrendipine, and diltiazem. There was a correlation between the amount of toxin binding and the detection of depolarization-induced calcium fluxes studied with the fluorimetric probe Fura2. Fura2 experiments also demonstrated that, in addition to omega CTx-sensitive calcium channels, SCC cell lines also expressed omega CTx-insensitive calcium channels, which were antagonized by nitrendipine and verapamil. 125I-omega CTx-labeled VOCCs from SCC cells were, furthermore, precipitated by anti-VOCC autoantibodies obtained from patients affected by the Lambert-Eaton myasthenic syndrome, a neuromuscular disease often associated with SCC. The present findings further indicate the presence of neuronal molecules with important biological function on SCC plasma membrane and add new insights into the pathogenetic mechanism of autoimmune neurological paraneoplastic diseases, like Lambert-Eaton myasthenic syndrome.
Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27 (2004)

Polycomb group (PcG) complexes 2 and 3 are involved in transcriptional silencing. These complexes contain a histone lysine methyltransferase (HKMT) activity that targets different lysine residues on histones H1 or H3 in vitro. However, it is not known if these histones are methylation targets in vivo because the human PRC2/3 complexes have not been studied in the context of a natural promoter because of the lack of known target genes. Here we report the use of RNA expression arrays and CpG-island DNA arrays to identify and characterize human PRC2/3 target genes. Using oligonucleotide arrays, we first identified a cohort of genes whose expression changes upon siRNA-mediated removal of Suz12, a core component of PRC2/3, from colon cancer cells. To determine which of the putative target genes are directly bound by Suz12 and to precisely map the binding of Suz12 to those promoters, we combined a high-resolution chromatin immunoprecipitation (ChIP) analysis with custom oligonucleotide promoter arrays. We next identified additional putative Suz12 target genes by using ChIP coupled to CpG-island microarrays. We showed that HKMT-Ezh2 and Eed, two other components of the PRC2/3 complexes, colocalize to the target promoters with Suz12. Importantly, recruitment of Suz12, Ezh2 and Eed to target promoters coincides with methylation of histone H3 on Lys 27.
Analysis of the inductive turn-off of double gate MOS controlled thyristors (1996)

High voltage inductive turn-off of double gate MOS Controlled Thyristors (MCTs) are analyzed using two-dimensional numerical simulations. Analysis shows that beside the significantly improved maximum controllable current and reduced switching loss, the electric field distribution in these devices has two peaks during inductive turn-off, enabling the maximum turn-off power density to be twice as high as that of the single gate devices. This observation also applies to other double gate bipolar power devices such as double gate Insulated Gate Bipolar Transistors (IGBTs).
RNA ligands to human nerve growth factor (1995)

High affinity RNA ligands to human nerve growth factor (NGF) were selected from pools of random RNA using SELEX [Tuerk, C. and Gold, L. (1990) Science, 249, 505-510]. Nerve growth factor, which is a protein required for the development of neurons, is not known to bind nucleic acids as part of its natural function. We describe two of the selected RNA molecules in detail. One of them is highly structured, folding into a pseudoknot with an additional hairpin-loop; this structure provides salt-resistant binding to NGF. The other is unstructured and elevated salt concentrations inhibit its binding. These molecules compete with each other for NGF binding. Our RNAs may furnish useful diagnostic tools for the study of an important neurotrophic protein; additionally, they illustrate another example of the potential for nucleic acids to take part in novel binding interactions.
On-chip measurements of cell compressibility via acoustic radiation (2011)

Measurements of mechanical properties of biological cells are of great importance because changes in these properties can be strongly associated with the progression of cell differentiation and cell diseases. Although state of the art methods, such as atomic force microscopy, optical tweezers and micropipette aspiration, have been widely used to measure the mechanical properties of biological cells, all these methods involve direct contact with the cell and the measurements could be affected by the contact or any local deformation. In addition, all these methods typically deduced the Young's modulus of the cells based on their measurements. Herein, we report a new method for fast and direct measurement of the compressibility or bulk modulus of various cell lines on a microchip. In this method, the whole cell is exposed to acoustic radiation force without any direct contact. The method exploits the formation of an acoustic standing wave within a straight microchannel. When the polystyrene beads and cells are introduced into the channel, the acoustic radiation force moves them to the acoustic pressure node and the movement speed is dependent on the compressibility. By fitting the experimental and theoretical trajectories of the beads and the cells, the compressibility of the cells can be obtained. We find that the compressibility of various cancer cells (MCF-7: 4.22 ± 0.19 × 10(-10) Pa(-1), HEPG2: 4.28 ± 0.12 × 10(-10) Pa(-1), HT-29: 4.04 ± 0.16 × 10(-10) Pa(-1)) is higher than that of normal breast cells (3.77 ± 0.09 × 10(-10) Pa(-1)) and fibroblast cells (3.78 ± 0.17 × 10(-10) Pa(-1)). This work demonstrates a novel acoustic-based method for on-chip measurements of cell compressibility, complementing existing methods for measuring the mechanical properties of biological cells.
Catalytic and non-catalytic domains of the Fujinami sarcoma virus P130gag-fps protein-tyrosine kinase distinguished by the expression of v-fps polypeptides in Escherichia coli. (1987)

While protein-tyrosine kinases share a region of sequence identity corresponding to their kinase domains, the specific elements essential for catalysis, substrate binding and substrate specificity are largely undefined. The P130gag-fps transforming protein of Fujinami avian sarcoma virus is a cytoplasmic tyrosine kinase with a complex structure that includes a C-terminal kinase domain. To identify the precise N-terminal border of the v-fps catalytic region and to assess its interactions with non-catalytic domains, C-terminal v-fps polypeptide fragments of decreasing size were expressed in E. coli as trpE-v-fps hybrid proteins. All such polypeptides containing 263 or more residues derived from the C-terminus of P130gag-fps (i.e. residues 920-1182) were enzymatically active as tyrosine kinases. They autophosphorylated at physiological sites in vivo and phosphorylated exogenous substrates such as enolase and poly(glu,tyr) at tyrosine in vitro. Deletion of a further five amino acids from P130gag-fps residues 920-925 abolished all enzymatic activity. This deletion coincides with the predicted N-terminus of the v-fps ATP-binding site at residue 922. These data indicate that the N-terminal border of the ATP-binding site defines the start of the minimal v-fps tyrosine kinase catalytic domain, and show that this minimal domain is competent to bind substrates. More N-terminal non-catalytic sequences appear to functionally interact with the catalytic domain.
The burden and outcomes associated with dehydration among US elderly, 1991. (1994)

Hospitalization of elderly people with dehydration is a serious and costly medical problem. Attention should be focused on understanding predisposing factors and devising strategies for prevention.
Molecular cloning of a 46-kilodalton surface antigen (P46) gene from Mycoplasma hyopneumoniae: direct evidence of CGG codon usage for arginine (1995)

The DNA sequence of the gene encoding the early and specific 46-kDa surface antigen (P46) of Mycoplasma hyopneumoniae has been determined. The P46 gene, encoding a putative lipoprotein, contained three TGA codons and a single CGG codon in a 1,257-bp open reading frame. Edman degradation of peptide fragments showed that at least one TGA codon encodes tryptophan and that the CGG codon, which has been reported to be nonsense or unassigned in other mycoplasmas, is used for arginine in M. hyopneumoniae.
Syntrophic Degradation of Cadaverine by a Defined Methanogenic Coculture (2009)

A novel, strictly anaerobic, cadaverine-oxidizing, defined coculture was isolated from an anoxic freshwater sediment sample. The coculture oxidized cadaverine (1,5-diaminopentane) with sulfate as the electron acceptor. The sulfate-reducing partner could be replaced by a hydrogenotrophic methanogenic partner. The defined coculture fermented cadaverine to acetate, butyrate, and glutarate plus sulfide or methane. The key enzymes involved in cadaverine degradation were identified in cell extracts. A pathway of cadaverine fermentation via 5-aminovaleraldehyde and crotonyl-coenzyme A with subsequent dismutation to acetate and butyrate is suggested. Comparative 16S rRNA gene analysis indicated that the fermenting part of the coculture belongs to the subphylum Firmicutes but that this part is distant from any described genus. The closest known relative was Clostridium aminobutyricum, with 95% similarity.
Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows Photoreceptor Cell Degeneration (2015)

Allele-specific ASO-mediated knockdown of mutant P23H rhodopsin expression slowed the rate of photoreceptor degeneration and preserved the function of photoreceptor cells in eyes of the P23H rhodopsin transgenic rat. Our data indicate that ASO treatment is a potentially effective therapy for the treatment of retinitis pigmentosa.
Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). (2002)

The inadvertent fusion of the bcr gene with the abl gene results in a constitutively active tyrosine kinase (Bcr-Abl) that transforms cells and causes chronic myelogenous leukemia. Small molecule inhibitors of Bcr-Abl that bind to the kinase domain can be used to treat chronic myelogenous leukemia. We report crystal structures of the kinase domain of Abl in complex with two such inhibitors, imatinib (also known as STI-571 and Gleevec) and PD173955 (Parke-Davis). Both compounds bind to the canonical ATP-binding site of the kinase domain, but they do so in different ways. As shown previously in a crystal structure of Abl bound to a smaller variant of STI-571, STI-571 captures a specific inactive conformation of the activation loop of Abl in which the loop mimics bound peptide substrate. In contrast, PD173955 binds to a conformation of Abl in which the activation loop resembles that of an active kinase. The structure suggests that PD173955 would be insensitive to whether the conformation of the activation loop corresponds to active kinases or to that seen in the STI-571 complex. In vitro kinase assays confirm that this is the case and indicate that PD173955 is at least 10-fold more inhibitory than STI-571. The structures suggest that PD173955 achieves its greater potency over STI-571 by being able to target multiple forms of Abl (active or inactive), whereas STI-571 requires a specific inactive conformation of Abl.
Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival (2003)

There is no standard treatment for patients with unresectable hepatocellular carcinoma (HCC). Survival benefits derived from medical interventions are controversial. The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival. Randomized controlled trials (RCTs) that were published as full papers assessing survival for primary treatments of HCC were included. MEDLINE, the Cochrane Library, CANCERLIT, and a manual search from 1978 to May 2002 were used. The primary end point was survival, and the secondary end point was response to treatment. Estimates of effect were calculated according to the random effects model. Sensitivity analysis included methodological quality. We identified 61 randomized trials, but only 14 met the criteria to perform a meta-analysis assessing arterial embolization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with control (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.89; P =.017). Sensitivity analysis showed a significant benefit of chemoembolization with cisplatin or doxorubicin (OR, 0.42; 95% CI, 0.20-0.88) but none with embolization alone (OR, 0.59; 95% CI, 0.29-1.20). Overall, treatment induced objective responses in 35% of patients (range, 16%-61%). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI, 0.36-1.13; P =.13), and only low-quality scale trials suggested 1-year improvement in survival. In conclusion, chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Treatment with tamoxifen does not modify the survival of patients with advanced disease.
MUC18, a melanoma-progression associated molecule, and its potential role in tumor vascularization and hematogenous spread. (1994)

The MUC18 protein, a member of the immunoglobulin superfamily and related to several adhesion molecules, shows an expression pattern in human malignant melanoma which is closely associated with tumor progression and the onset of metastasis. To determine the expression pattern of MUC18 in normal human tissues, immunohistochemical analysis was performed on frozen sections of a variety of normal human tissues using monoclonal antibodies against three different epitopes. This analysis showed that expression of MUC18 is limited to smooth muscle cells and to vascular endothelium. No reactivity could be observed with epithelial cells or with quiescent or activated hemopoetic cells. Smooth muscle cells in lung, skin, and in the gastrointestinal tract express MUC18 as does vascular smooth muscle, whereas myocardium or skeletal muscle appeared negative. Comparison of MUC18 staining with that of the panendothelial marker CD31 showed that MUC18 is expressed on the endothelia of a subset of blood capillaries and in tumor vessels but is absent on the endothelium of arterial vessels and large veins. The regulation of MUC18 expression was investigated in vascular smooth muscle cells and endothelial cells cultured in vitro. These studies revealed induction of the gene in endothelial cells upon proliferation. The observation that the MUC18 protein is not only present on melanoma cells but also on the endothelia of blood vessels penetrating primary and metastatic melanomas suggests a complex involvement of this potential cell adhesion molecule in tumor angiogenesis and metastasis.
An Efficient System for Cap- and Poly(A)-Dependent Translation In Vitro (2004)

The 3' poly(A) tail of eukaryotic messenger RNAs (mRNAs) acts synergistically with the 5' cap structure to enhance translation. This phenomenon has been explained by the simultaneous binding of poly(A)-binding protein (PABP) and a cap-binding protein (eIF4E) to eIF4G that results in the circularization of the mRNA (closed-loop model). We developed a robust cell-free protein synthesis system to study poly(A)-dependent translation. In nuclease-treated extracts of Krebs-2 ascites cells, the mRNA poly(A) tail and the cap structure synergistically stimulate translation. We also describe an efficient procedure for depleting PABP from translation extracts. Greater than 98% of PABP can be depleted from extracts by preincubation with either of the PABP-interacting proteins (Paip2 or Paip1) coupled to beads, and these depleted extracts fail to support efficient translation of poly(A)+ mRNAs. Translation activity is restored to depleted extracts by the addition of recombinant PABP.
Clonal expansion of T cells infiltrating in the airways of non-atopic asthmatics (2000)

CD4+ T cells are thought to play an important role in airway inflammation in both atopic and non-atopic asthma. However, the mechanism by which T cells are activated in non-atopic asthma, where there is no causative antigen identified, is unknown. To elucidate this issue, we analysed T cell receptor (TCR) Vbeta gene clonotypes of T cells in the bronchoalveolar lavage fluids (BALF) of non-atopic asthmatics using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and a sequencing method. We found that the numbers of TCR Vbeta gene clonotypes of T cells in the BALF of non-atopic asthmatics were significantly increased compared with those of peripheral blood lymphocytes (PBL). We also found that there were several shared amino acid motifs in complementarity-determining region 3 (CDR3) of TCR Vbeta genes from those T cell clones in BALF of non-atopic asthmatics, whereas these shared motifs were not found in the same Vbeta family genes from PBL in the patients. Moreover, a conserved amino acid sequence was detected in two patients who shared a common HLA-DR allele. These results indicate that the infiltrating T cells in the airways of non-atopic asthmatics recognize relatively limited epitopes of antigens and are clonally expanded by antigen-driven stimulation.
The mystery of nonclassical protein secretion (2003)

Most of the examples of protein translocation across a membrane (such as the import of classical secretory proteins into the endoplasmic reticulum, import of proteins into mitochondria and peroxisomes, as well as protein import into and export from the nucleus), are understood in great detail. In striking contrast, the phenomenon of unconventional protein secretion (also known as nonclassical protein export or ER/Golgi-independent protein secretion) from eukaryotic cells was discovered more than 10 years ago and yet the molecular mechanism and the molecular identity of machinery components that mediate this process remain elusive. This problem appears to be even more complex as several lines of evidence indicate that various kinds of mechanistically distinct nonclassical export routes may exist. In most cases these secretory mechanisms are gated in a tightly controlled fashion. This review aims to provide a comprehensive overview of our current knowledge as a basis for the development of new experimental strategies designed to unravel the molecular machineries mediating ER/Golgi-independent protein secretion. Beyond solving a fundamental problem in current cell biology, the molecular analysis of these processes is of major biomedical importance as these export routes are taken by proteins such as angiogenic growth factors, inflammatory cytokines, components of the extracellular matrix which regulate cell differentiation, proliferation and apoptosis, viral proteins, and parasite surface proteins potentially involved in host infection.
Information retrieval from hypertext: update on the dynamic medical handbook project (1989)

This paper attempts to provide a perspective from which to develop a more complete theory of information retrieval from hypertext documents. Viewing hypertexts as large information spaces, we compare two general classes of navigation methods, classes we call local and global. We argue that global methods necessitate some form of “index space” conceptually separate from the hypertext “document space”. We note that the architectures of both spaces effect the ease with which one can apply various information retrieval algorithms. We identify a number of different index space and document space architectures and we discuss some of the associated trade-offs between hypertext functionality and computational complexity. We show how some index space architectures can be exploited for enhanced information retrieval, query refinement, and automated reasoning. Through analysis of a number of prototype systems, we discuss current limitations and future potentials for various hypertext information retrieval structures.
High-brightness gallium nitride nanowire UV–blue light emitting diodes (2007)

We report on high-brightness GaN nanowire UV–blue light emitting diodes (LEDs), which are fabricated by coupling of n-GaN nanowires and p-GaN substrates using two assembly methods, random dispersion (RD) and dielectrophoresis assisted assembly deposition (DAAD). These GaN nanowire LEDs have bright UV–blue emission (411–437 nm) from the n-GaN nanowire/p-GaN substrate junction and the light emission is strong enough to be observed with the naked eye even for a single GaN nanowire LED. The results reported here should have significant implications for the fabrication of highly efficient, low-cost UV–blue LEDs with low power consumption, as compared to conventional thin-film based GaN LEDs.
PREDICTING PROSTATE CANCER BEHAVIOR USING TRANSCRIPT PROFILES (2004)

Gene expression profiles offer an opportunity for acquiring molecular determinants correlating with clinical outcome. With rare exceptions these profiles have yet to be validated or used in prospective studies. Future research will benefit from assessments of intratumor heterogeneity and host factors such as the immune response and hormonal milieu. The prospective validation of predictive models will serve to prove usefulness in the clinical arena.