gebhart/patrepeval huggingface dataset:
Point mutations of the N‐ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia (1994)

Oncogene mutations are frequently found in several tumour types and, among these, point mutations of the ras gene are particularly significant. A predominance of N-ras mutations has been found in the bone marrow DNA of patients with myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML). On the other hand, increased levels of plasma DNA have previously been observed in patients suffering from various malignant diseases. In the present work we have investigated, by polymerase chain reaction (PCR), point mutations of the N-ras gene in the DNA of plasma, blood cells and bone marrow of 10 patients suffering from AML or MDS. The different ras mutations detected in five cases were always present in the plasma DNA while sometimes absent in the DNA of peripheral blood cells or bone marrow. This indicates that a bone marrow biopsy or aspiration does not necessarily contain all the malignant clones involved in the disease. Plasma could thus prove to be an easily accessible and useful material for detection and monitoring of myeloid disorders.
The Scaffolding Adapter Gab1 Mediates Vascular Endothelial Growth Factor Signaling and Is Required for Endothelial Cell Migration and Capillary Formation (2006)

Vascular endothelial growth factor (VEGF) is involved in the promotion of endothelial cell proliferation, migration, and capillary formation. These activities are mainly mediated by the VEGFR2 receptor tyrosine kinase that upon stimulation, promotes the activation of numerous proteins including phospholipase Cgamma (PLCgamma), phosphatidylinositol 3-kinase (PI3K), Akt, Src, and ERK1/2. However, the VEGFR2-proximal signaling events leading to the activation of these targets remain ill defined. We have identified the Gab1 adapter as a novel tyrosine-phosphorylated protein in VEGF-stimulated cells. In bovine aortic endothelial cells, Gab1 associates with VEGFR2, Grb2, PI3K, SHP2, Shc, and PLCgamma, and its overexpression enhances VEGF-dependent cell migration. Importantly, silencing of Gab1 using small interfering RNAs leads to the impaired activation of PLCgamma, ERK1/2, Src, and Akt; blocks VEGF-induced endothelial cell migration; and perturbs actin reorganization and capillary formation. In addition, co-expression of VEGFR2 with Gab1 mutants unable to bind SHP2 or PI3K in human embryonic kidney 293 cells and bovine aortic endothelial cells mimics the defects observed in Gab1-depleted cells. Our work thus identifies Gab1 as a novel critical regulatory component of endothelial cell migration and capillary formation and reveals its key role in the activation of VEGF-evoked signaling pathways required for angiogenesis.
Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity (2004)

The "BH3-only" proapoptotic BCL-2 family members initiate the intrinsic apoptotic pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member is important for the cytokine-mediated homeostasis of hematopoietic cells. We show here that the phosphorylation status of BIM controls its proapoptotic activity. IL-3, a hematopoietic survival factor, induces extracellular signal-regulated kinase/mitogen-activated protein kinase-mediated phosphorylation of BIM on three serine sites (S55, S65, and S100). After IL-3 withdrawal, only nonphosphorylated BIM interacts with the multidomain proapoptotic effector BAX. Phosphorylation of BIM on exposure of cells to IL-3 dramatically reduces the BIM/BAX interaction. A nonphosphorylatable BIM molecule (S55A, S65A, and S100A) demonstrates enhanced interaction with BAX and enhanced proapoptotic activity. Thus, ERK/mitogen-activated protein kinase-dependent phosphorylation of BIM in response to survival factor regulates BIM/BAX interaction and the pro-death activity of BIM.
Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis. (1990)

The incidence of serum antibodies to human low-density lipoprotein, to oxidized low-density lipoprotein, and to ceroid extracted from human atheroma was assessed in 100 subjects using an adaptation of the enzyme-linked immunosorbent assay technique. Patients with chronic periaortitis, subclinical chronic periaortitis, and ischemic heart disease, and "elderly control" individuals were compared with young, healthy adults. Provided that precautions were taken to prevent oxidation of the low-density lipoprotein during the assay, antibodies were not found to native human low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid, usually both, were detected in all 20 patients with clinical chronic periaortitis, in 17 of 20 patients with subclinical chronic periaortitis, in 12 of 20 patients with ischemic heart disease, and in 10 of 20 elderly control subjects. Binding inhibition studies showed cross-reactions between oxidized low-density lipoprotein and ceroid. Western blotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that in some patients with clinical chronic periaortitis, these antibodies were directed against breakdown products of apolipoprotein B that resulted from oxidation of low-density lipoprotein. Antibodies to oxidized low-density lipoprotein or ceroid were not detected in healthy young adults. These findings show that chronic periaortitis is accompanied by autoallergy to ceroid, which is probably at least partly composed of low-density lipoprotein oxidized within the human atherosclerotic plaque, and that a number of middle-aged and elderly people without chronic periaortitis also have such antibodies.
Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells (2002)

Reaction to certain motifs in bacterial DNA is an important function of natural immunity. For example, single stranded oligonucleotides (ODN) containing the motif "not C, unmethylated C, G, not G" are powerful mitogens and apoptosis inhibitors for mouse spleen B cells. But replacing GCGTT or ACGTT with GCGGG or ACGGG converted a stimulatory 15-mer ODN into an inhibitory ODN. All inhibitory ODN had three consecutive G, and a fourth G increased inhibitory activity, but a deazaguanosine substitution to prevent planar stacking did not affect activity. Inhibitory ODN blocked apoptosis protection and cell-cycle entry induced by stimulatory ODN, but not that induced by lipopolysaccharide, anti-CD40 or anti-IgM+IL-4. ODN-driven up-regulation of cyclin D(2), c-Myc, c-Fos, c-Jun and Bcl(XL) and down-regulation of cyclin kinase inhibitor p27(kip1) were all blocked by inhibitory ODN. The relative potency of a series of stimulatory and inhibitory ODN was the same for all readouts measured. Interference with uptake of stimulatory ODN could not account for their inhibitory effects. Even if addition of inhibitory ODN was delayed several hours, partial inhibition of stimulatory ODN effects occurred. Inhibitory ODN hold potential as antidotes for excessive ODN stimulation in the clinical setting and provide an important tool for studying ODN recognition.
Adaptive phase change metamaterials for infrared aperture control (2011)

This paper discusses the use of chalcogenide phase change materials to create tunable metamaterials as potential candidates for application to adaptive coded aperture control in the infrared. Phase change materials exhibit large and reversible changes in optical properties (&Delta;n, &Delta;k) when switched between the amorphous and crystalline phases. Thermally-induced phase transitions from the insulating amorphous to the conductive crystalline state can be controlled through external means, facilitating the design of reconfigurable metamaterial devices that operate with ultrafast response times. In this work, robust global stochastic optimization algorithms were combined with full-wave electromagnetic simulation tools to design periodic subwavelength chalcogenide nanostructured arrays to meet the specified device performance goals in each phase. The measured optical properties (n, k) of deposited chalcogenide thin films and nanofabrication constraints were incorporated into the optimization algorithm to guarantee that the designed nanostructures could be manufactured. By choosing the appropriate cost functions, adaptive metamaterials were designed to switch between transmissive and reflective, transmissive and absorptive, and reflective and absorptive states. These design demonstrations represent a significant step forward in the development of adaptive infrared metamaterials.
Kinetics of Escherichia coli destruction by microwave irradiation (1992)

The kinetics of destruction of Escherichia coli cells suspended in a solution by microwave irradiation with a microwave oven were studied. During radiation at several powers, the temperature of 0.01 M phosphate buffer (PB), pH 7.0, in a glass beaker increased linearly at a rate of A (degrees Centigrade per second) according to the exposure time. When E. coli cells suspended in PB were exposed in the same beaker, the number of viable cells decreased according to the exposure time and the power used. The survival curve was approximated to a set of three linear parts. For each part, a rate constant of destruction (k) and an extrapolated starting temperature (T0) at several powers were estimated. Thereafter, the relationships between A and k and between A and T0 were studied. When a flat petri dish was used, the A value of exposed PB was lower and bacterial destruction was inhibited; the survival curve was similar to a curve predicted from the A value by using the relationships between the parameters. As the concentration of salt in the solution increased (from 0 to 1.35 M), the A value decreased and bacterial destruction was more suppressed. No remarkable difference between the destruction profiles for microwave exposure and conventional heating, which had the potential to generate an equal A value, was detected. These results showed that the parameter A of an irradiated solution is essential when kinetics of bacterial destruction by microwave exposure are studied and that the destruction profile can be interpreted mostly by means of thermal effects.
11-cis-Retinal Reduces Constitutive Opsin Phosphorylation and Improves Quantum Catch in Retinoid-deficient Mouse Rod Photoreceptors (2002)

Rpe65(-/-) mice produce minimal amounts of 11-cis-retinal, the ligand necessary for the formation of photosensitive visual pigments. Therefore, the apoprotein opsin in these animals has not been exposed to its normal ligand. The Rpe65(-/-) mice contain less than 0.1% of wild type levels of rhodopsin. Mass spectrometric analysis of opsin from Rpe65(-/-) mice revealed unusually high levels of phosphorylation in dark-adapted mice but no other structural alterations. Single flash and flicker electroretinograms (ERGs) from 1-month-old animals showed trace rod function but no cone response. B-wave kinetics of the single-flash ERG are comparable with those of dark-adapted wild type mice containing a full compliment of rhodopsin. Application (intraperitoneal injection) of 11-cis-retinal to Rpe65(-/-) mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein.
Control of the Molecular Weight of Polyethene in Syntheses with Bis(ylide)nickel Catalysts (1987)

Polyethenes in almost all molecular weight ranges —from polyethene waxes and hard waxes through high-density polyethene to ultrahigh molecular weight polyethene -are accessible with the aid of novel, very active bis(ylide)nickel(0) catalysts. The catalysts are prepared from bis(cyclooctadiene)nickel(0), the carbonyl-stabilized ylide ligands 1-3, and a non-stabilized ylide.
A large deletion in the matrix domain of the human immunodeficiency virus gag gene redirects virus particle assembly from the plasma membrane to the endoplasmic reticulum (1993)

Morphogenesis of retroviruses involves assembly of the structural Gag and Gag-Pol polyproteins with subsequent budding of the virus particle from the plasma membrane and proteolytic cleavage by the viral proteinase. The matrix (MA) domain, representing the N-terminal segment of Gag, plays a critical role in this process. We constructed an in-frame deletion in the MA coding region (lacking codons 16 to 99) of the human immunodeficiency virus (HIV) type 1 gag gene. Following transient transfection of the complete proviral DNA carrying the deletion, the mutant polyprotein was synthesized and proteolytically processed like the wild-type polyprotein. However, release of virus particles was reduced approximately 10-fold. The extracellular particles that were released did not contain viral glycoproteins and were noninfectious. Electron micrographs revealed budding of virus particles into the endoplasmic reticulum (ER) of transfected cells and large numbers of particles within the ER. These particles were all immature and morphologically indistinguishable from intracisternal A-type particles, a class of murine endogenous retrovirus elements. Budding structures at the plasma membrane were rarely seen and only a few extracellular particles were observed, but in contrast to those in the ER, these particles had the morphology of mature particles, similar to that of wild-type HIV, except for the lack of surface projections.
Induction of Bystander T Cell Proliferation by Viruses and Type I Interferon in Vivo (1996)

T cell proliferation in vivo is presumed to reflect a T cell receptor (TCR)-mediated polyclonal response directed to various environmental antigens. However, the massive proliferation of T cells seen in viral infections is suggestive of a bystander reaction driven by cytokines instead of the TCR. In mice, T cell proliferation in viral infections preferentially affected the CD44hi subset of CD8+ cells and was mimicked by injection of polyinosinic-polycytidylic acid [poly(I:C)], an inducer of type I interferon (IFN I), and also by purified IFN I; such proliferation was not associated with up-regulation of CD69 or CD25 expression, which implies that TCR signaling was not involved. IFN I [poly(I:C)]-stimulated CD8+ cells survived for prolonged periods in vivo and displayed the same phenotype as did long-lived antigen-specific CD8+ cells. IFN I also potentiated the clonal expansion and survival of CD8+ cells responding to specific antigen. Production of IFN I may thus play an important role in the generation and maintenance of specific memory.
Eosinophilic Esophagitis - Treatment of Eosinophilic Esophagitis with Drugs: Corticosteroids (2014)

Eosinophilic esophagitis (EoE) is defined as a chronic immune/antigen-mediated esophageal disease characterized by clinical symptoms of esophageal dysfunction and histologically by eosinophil-predominant infiltration of the esophagus mucosa. Treatment of EoE should therefore lead to improvement of clinical symptoms and a histological decrease of eosinophilic inflammation. Topical corticosteroids (tCS; fluticasone, budesonide) have been demonstrated to be effective in treating EoE and therefore represent first-line therapy. To date, there is no approved therapy in the world for EoE. This is the reason why EoE patients are treated with medication such as inhalers or aqueous nebulizer solutions, which have to be swallowed. After administration, patients are not allowed to eat or drink for 45 min in order for the esophagus to become well coated so that the topical anti-inflammatory effect is maximized. For adults there are different dose ranges: fluticasone propionate 440-880 μg/day twice daily, budesonide 2 mg/day divided dose for inducing remission over a period of 4 to 8 weeks. Since EoE is a chronic disease known to relapse after termination of medication, maintenance therapy seems to be valuable, but there is no evidence from controlled studies with long-term follow-up. In several randomized trials, both tCS have been able to show a good safety profile. Candida esophagitis and oral candidiasis present the most common side effects of topical steroid therapy. At the moment, no data about tCS and long-term safety in EoE are available.
The block move sum normal moveout correction (1975)

Abstract A new normal moveout technique designated Block Move Sum (BMS) is described. In theory it better approximates the ideal inverse NMO process than do currently utilized techniques. Data blocks are corrected as units thus eliminating trace stretching and reducing trace distortion. The proposed correction and two common production methods are applied to both synthetic and real data and compared. Crosscorrelations calculated from synthetic seismogram data suggest the BMS method creates the least signal distortion. For field CDP data, the BMS does improve signal resolution for events at early times.
Secondary Structure and Structure-Activity Relationships of Peptides Corresponding to the Subunit Interface of Herpes Simplex Virus DNA Polymerase (2000)

The interaction of the catalytic subunit of herpes simplex virus DNA polymerase with the processivity subunit, UL42, is essential for viral replication and is thus a potential target for antiviral drug discovery. We have previously reported that a peptide analogous to the C-terminal 36 residues of the catalytic subunit, which are necessary and sufficient for its interaction with UL42, forms a monomeric structure with partial alpha-helical character. This peptide and one analogous to the C-terminal 18 residues specifically inhibit UL42-dependent long chain DNA synthesis. Using multidimensional (1)H nuclear magnetic resonance spectroscopy, we have found that the 36-residue peptide contains partially ordered N- and C-terminal alpha-helices separated by a less ordered region. A series of "alanine scan" peptides derived from the C-terminal 18 residues of the catalytic subunit were tested for their ability to inhibit long-chain DNA synthesis and by circular dichroism for secondary structure. The results identify structural aspects and specific side chains that appear to be crucial for interacting with UL42. These findings may aid in the rational design of new drugs for the treatment of herpesvirus infections.
Identification of Pirin, a Novel Highly Conserved Nuclear Protein (1997)

In this article we describe the molecular cloning of Pirin, a novel highly conserved 32-kDa protein consisting of 290 amino acids. Pirin was isolated by a yeast two-hybrid screen as an interactor of nuclear factor I/CCAAT box transcription factor (NFI/CTF1), which is known to stimulate adenovirus DNA replication and RNA polymerase II-driven transcription. Pirin mRNA is expressed weakly in all human tissues tested. About 15% of all Pirin cDNAs contain a short 34-base pair insertion in their 5'-untranslated regions, indicative of alternative splicing processes. Multiple Pirin transcripts are expressed in skeletal muscle and heart. Western blots and immunoprecipitations employing monoclonal anti-Pirin antibodies reveal that Pirin is a nuclear protein. Moreover, confocal immunofluorescence experiments demonstrate a predominant localization of Pirin within dot-like subnuclear structures. Homology searches using the BLAST algorithm indicate the existence of Pirin homologues in mouse and rat. The N-terminal half of Pirin is significantly conserved between mammals, plants, fungi, and even prokaryotic organisms. Genomic Southern and Western blots demonstrate the presence of Pirin genes and their expression, respectively, in all mammalian cell lines tested. The expression pattern, the concentrated localization in subnuclear structures, and its interaction with NFI/CTF1 in the two-hybrid system classify Pirin as a putative NFI/CTF1 cofactor, which might help to gain new insights in NFI/CTF1 functions.
Water and Molecular Weight Effects on Glass Transitions in Amorphous Carbohydrates and Carbohydrate Solutions (1991)

ABSTRACT The effects of water, freeze‐concentration and effective molecular weight (M e ) on glass transition (T g ) of maltose and maltodextrins were studied, and methods to predict T g were used to establish state diagrams. T g of maximally freeze‐concentrated solutes (T′ g ) and onset of ice melting (T′ m ) increased with M e , and for high molecular weight polysaccharides T′ g and T′ m were predicted to have the same temperature value. Ice formation at T′ g &lt;T &lt; T′ m was time dependent. Unfrozen water in maximally freeze‐concentrated matrices was about 20% independently of M e . The state diagrams can be used to evaluate physical state of frozen and dehydrated foods.
Cop 1 Therapy for Multiple Sclerosis (1987)

Multiple sclerosis is an inflammatory disease of the central nervous system in which infiltrating lymphocytes (predominantly T cells) and macrophages lead to degradation of the myelin sheath. The leading hypothesis about the causation of multiple sclerosis is that it is an autoimmune disease linked in some way to a viral infection.1 , 2 Nonetheless, despite extensive investigation, neither pathogenic autoreactive T cells or antibodies nor a virus has been shown to have a clear role in the disease process.2 Clinically, multiple sclerosis may be categorized as being of the exacerbating–remitting type, in which discrete episodes of neurologic dysfunction are followed by recovery, . . .
Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin (1990)

A factor has been identified in extracts from human HeLa and hamster V79 cells that retards the electrophoretic mobility of several DNA restriction fragments modified with the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin). Binding of the factor to cisplatin-modified DNA was sensitive to pretreatment with proteinase K, establishing that the factor is a protein. Gel mobility shifts were observed with probes containing as few as seven Pt atoms per kilobase of duplex DNA. By competition experiments the dissociation constant, Kd, of the protein from cisplatin-modified DNA was estimated to be (1-20) X 10(-10) M. Protein binding is selective for DNA modified with cisplatin, [Pt(en)Cl2] (en, ethylenediamine), and [Pt(dach)Cl2] (dach, 1,2-diaminocyclohexane) but not with chemotherapeutically inactive trans-diamminedichloroplatinum(II) or monofunctionally coordinating [Pt(dien)Cl]Cl (dien, diethylenetriamine) complexes. The protein also does not bind to DNA containing UV-induced photoproducts. The protein binds specifically to 1,2-intrastrand d(GpG) and d(ApG) cross-links formed by cisplatin, as determined by gel mobility shifts with synthetic 110-bp duplex oligonucleotides; these modified oligomers contained five equally spaced adducts of either cis-[Pt(NH3)2d(GpG) or cis-[Pt(NH3)2d(ApG)]. Oligonucleotides containing the specific adducts cis-[Pt(NH3)2d(GpTpG)], trans-[Pt(NH3)2d(GpTpG)], or cis-[Pt(NH3)2(N3-cytosine)d(G)] were not recognized by the protein. The apparent molecular weight of the protein is 91,000, as determined by sucrose gradient centrifugation of a preparation partially purified by ammonium sulfate fractionation. Binding of the protein to platinum-modified DNA does not require cofactors but is sensitive to treatment with 5 mM MnCl2, CdCl2, CoCl2, or ZnCl2 and with 1 mM HgCl2.(ABSTRACT TRUNCATED AT 250 WORDS)