gebhart/patrepeval huggingface dataset:
A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells (2006)

The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I-restricted immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101 that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results demonstrate that AML leukemic blasts can in principle process and present immunogenic FLT3-ITD neoepitopes. Therefore, FLT3-ITD represents a potential candidate target antigen for the immunotherapy of AML.
Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. (1997)

Inactivation of the cyclin-dependent kinase inhibitors p16INK4A and p15INK4B are frequent alterations in neoplasia, often resulting from homozygous deletion or promoter region hypermethylation. We have analyzed both modes of inactivation of p15INK4B and p16INK4A in the major types of adult and pediatric hematological malignancies. Hypermethylation of p15INK4B, without alteration of p16INK4A, was an almost universal finding in adult acute myelogenous leukemia, and occurred very frequently in adult acute lymphocytic leukemia and pediatric acute myelogenous leukemia and acute lymphocytic leukemia. In contrast, neither p15INK4B nor p16INK4A were inactivated in any stage of chronic myelogenous leukemia. Hypermethylation of p16INK4A, often without alterations of p15INK4B, was found in non-Hodgkin's lymphoma and was much more frequent in cases with high-grade than low-grade histology. Enriched normal bone marrow stem cells had no detectable promoter region methylation of these genes, as analyzed by a newly developed PCR method. Remarkably distinct patterns of inactivation of p15INK4B and p16INK4A characterize different types of hematological malignancy, and alterations in these tumor suppressor genes are one of the most common alterations in hematological malignancies.
Cardiac Sarcoplasmic Reticulum Calcium Leak: Basis and Roles in Cardiac Dysfunction (2011)

Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease.
Changes in chromosomal proteins in colon cancer.The complexity and DNA-binding properties of tumor-associated proteins and evidence for their association with the malignant state in human colonic epithelium (1977)

The properties of two classes of nonhistone nuclear proteins (NHNP) whose appearance has been correlated with the process of carcinogenesis in the colonic epithelium of rats given 1,2-dimethylhydrazine (DMH) have been investigated. NHNP isolated from adenocarcinomas of the colon were tested for their binding to homologous DNA. The tumor-specific protein class TNP1 (molecular weight ca. 44,000) shows high affinity for DNA while the second class of tumor-specific proteins (TNP2; molecular weight ca. 62,000) does not bind to DNA. When tumor chromatin is subjected to a limited digestion with DNAse I under conditions that are known to preferentially digest active genes, the TNP1 proteins are selectively released, suggesting that this protein fraction is associated with the actively transcribing portions of the genome. The complexity of both tumor-specific protein classes has also been analyzed by two-dimensional gel electrophoresis. This method reveals a high degree of complexity both in TNP1 and TNP2. Protein classes similar to TNP1 and TNP2 that are also found in human colonic adenocarcinomas are not detectable in polyps from familial polyposis-affected patients at times when no sign of malignancy has yet appeared.
III. Yeast sequencing reports. Corrected sequence for the right telomere of Saccharomyces cerevisiae chromosome III (1994)

A comparison of the sequences of telomere regions from several yeast chromosomes revealed an apparent cloning artifact for the right end of chromosome III. An integrating vector containing G1-3T telomere sequences was used to clone the right end of chromosome III from a strain related to S288C. The sequence of this clone confirmed that the published sequence was incorrect and demonstrated that the right telomere region of chromosome III is similar to other telomeres.
Field emission from a single nanomechanical pillar (2007)

We measured field emission from a silicon nanopillar mechanically oscillating between two electrodes. The pillar has a height of about 200 nm and a diameter of 50 nm, allowing resonant mechanical excitations at radio frequencies. The tunnelling barriers for field emission are mechanically modulated via displacement of the gold island on top of the pillar. We present a rich frequency-dependent response of the emission current in the frequency range of 300–400 MHz at room temperature. Modified Fowler–Nordheim field emission is observed and attributed to the mechanical oscillations of the nanopillar.
Factors affecting rhythm after the maze procedure for atrial fibrillation. (1996)

Results favor earlier performance of the procedure before these risk factors develop, after which omission of the procedure or extensive left atrial plication may be appropriate. This requires further study.
Sulphated compounds attenuate β-amyloid toxicity by inhibiting its association with cells (1995)

Agents that interfere with the toxic effects of beta-amyloid protein may be therapeutically useful against Alzheimer's disease. We reported recently that several sulphated glycosaminoglycans and sulphonated dyes attenuate the toxic effects of beta-amyloid fragments beta 25-35 and beta 1-40 in two clonal cell lines. We now demonstrate that this protective effect is due to interference with beta-amyloid cell association rather than effects on beta-amyloid structure. Using an enzyme-linked immunoabsorbance assay to detect cell-associated beta 1-40, we found in a range of compounds a strong correlation between inhibition of HeLa cell association of beta 1-40 and attenuation of cellular toxicity as measured by inhibition of 3-[4,5-dimethylthia-zol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction. In contrast, effects on peptide structure, as measured by Congo red binding, were generally inconsistent with the attenuating effects of the compounds on cellular toxicity. These results suggest that by binding beta-amyloid these agents prevent its interaction with cells.
Cationic Liposomes for Gene Delivery: From Biophysics to Biological Applications (2003)

The use of an efficient carrier for nucleic acid-based medicines is considered to be a determinant factor for the successful application of gene therapy. The drawbacks associated with the use of viral vectors, namely those related with safety problems, have prompted investigators to develop alternative methods for gene delivery, cationic lipid-based systems being the most representative. Despite extensive research in the last decade on the use of cationic liposomes as gene transfer vectors and the development of elegant strategies to enhance their biological activity, these systems are still far from being viable alternatives to the use of viral vectors in gene therapy. In this review considerations are made regarding the structure-activity relationships of cationic liposome/DNA complexes and the key formulation parameters influencing the features of lipoplexes are presented and discussed in terms of their effect on biological activity. Particular emphasis is given to the interaction of the lipoplexes with serum components as well as to novel strategies developed to circumvent difficulties that may emerge upon iv administration of the complexes. Finally, since the ability of the lipoplexes to be stored while preserving their transfection activity is a crucial issue for the repeated use of such carriers, approaches reported on the improvement of their physical stability are also reviewed.
Efficient gene transfer into various mammalian cells, including non-hepatic cells, by baculovirus vectors. (1997)

A baculovirus (Autographa californica nucleopolyhedrovirus) vector containing a strong promoter, the CAG promoter, was developed to introduce foreign genes into mammalian cells. Recombinant baculoviruses carrying a reporter gene under the control of the CAG promoter were inoculated into various mammalian cell lines. High-level expression was observed not only in hepatocytes but also in other non-hepatic cell lines tested. Expression of the reporter gene was detected even 14 days after infection. The infectious titre of the recovered baculoviruses decreased significantly after infection, indicating that the baculoviruses did not replicate in mammalian cells. We then compared the efficiencies of gene expression by the baculovirus vector with that of a replication-defective adenovirus vector by using the same expression unit. The same level of expression was observed in HepG2, HeLa and COS7 cells by both vectors. Efficient expression and proper processing were observed in mammalian cells infected with baculoviruses carrying genes coding for structural regions of hepatitis C virus. These results suggest that the baculovirus vector is a good tool for gene delivery into various mammalian cells in order to study the function of foreign genes.
Molecular Cloning of CoA Synthase (2002)

Coenzyme A functions as a carrier of acetyl and acyl groups in living cells and is essential for numerous biosynthetic, energy-yielding, and degradative metabolic pathways. There are five enzymatic steps in CoA biosynthesis. To date, molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals has been only reported for pantothenate kinase. In this study, we present cDNA cloning and functional characterization of CoA synthase. It has an open reading frame of 563 aa and encodes a protein of approximately 60 kDa. Sequence alignments suggested that the protein possesses both phosphopantetheine adenylyltransferase and dephospho-CoA kinase domains. Biochemical assays using wild type recombinant protein confirmed the gene product indeed contained both these enzymatic activities. The presence of intrinsic phosphopantetheine adenylyltransferase activity was further confirmed by site-directed mutagenesis. Therefore, this study describes the first cloning and characterization of a mammalian CoA synthase and confirms this is a bifunctional enzyme containing the last two components of CoA biosynthesis.
Simultaneous Measurement of 19 Components in Serum‐Containing Animal Cell Culture Media by Fourier Transform Near‐Infrared Spectroscopy (2001)

Animal cell cultures generate maximal amounts of desired products when maintained in a controlled environment with low and constant concentrations of nutrients and wastes. Traditionally this has involved slow addition of glucose and glutamine; however, recent studies have indicated that a number of low concentration amino acids are required to prevent initiation of apoptosis. Therefore, optimal control of animal cell cultures will likely require measurement of a large number of chemical components. We present here the evaluation of a near-infrared spectroscopic (NIRS) monitoring scheme to quantify 19 cellular nutrients and wastes in culture medium with and without serum. The components include glucose, lactate, ammonia, pyruvate, glutamine, and 14 other amino acids. Spectroscopic calibrations were generated for a synthetic version of a standard culture medium (DMEM) in which the concentrations of 17 DMEM components and ammonia and lactate were varied in a random fashion. This randomization provides a stringent evaluation of the measurement scheme. Reasonably accurate measurements of these 19 components could be accomplished in the absence or presence of 10% horse serum by volume with percent errors ranging from 3% to 37%. Analytes with concentrations as low as 0.3 mM could be reliably quantified. The presence of serum, when properly included in the calibration, has little effect on measurement error. These results provide an important step toward application of NIRS for monitoring the large number of varying components of animal cell cultivations.
Application of Spinal Ablative Techniques for the Treatment of Benign Chronic Painful Conditions (2002)

Ablative spinal techniques offer pain relief for many patients, but the use of these methods should be considered carefully in the light of available nondestructive procedures that may achieve similar goals with potentially lower morbidities.
The Impact of Computerized Physician Order Entry on Medication Error Prevention (1999)

Computerized POE substantially decreased the rate of non-missed-dose medication errors. A major reduction in errors was achieved with the initial version of the system, and further reductions were found with addition of decision support features.
Studies on cytochrome c-heparin interactions by differential scanning calorimetry (1994)

The effects of heparin on the thermotropic properties of ferricytochrome c have been studied using high-sensitivity differential scanning calorimetry. Saturating concentrations of heparin at low ionic strength induced an important shift of the transition temperature Tm from 84.1 degrees C to 59.8 degrees C. This was accompanied by unusually large cooperativity of thermal denaturation of this complex, indicating strong intermolecular interactions between protein molecules. The destabilization of cytochrome c when mixed with heparin was not observed at high ionic strength, under which conditions complex was not formed.
Intranasal vaccination with poly(lactide‐co‐glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization (2008)

These results demonstrate that i.n. immunization with peptide T-PLGA microparticles is effective in preventing subsequent allergic sensitization to Ole e 1. Our data indicate that peptide-PLGA microparticles may be promising candidates for the design of nasal vaccines against allergic diseases in humans.
A simple synthesis of 8‐(trifluoromethyl)‐2,3,5,6,11,12,14,15‐octahydro‐1H,4H,10H, 13H‐diquinolizino[9,9a,1‐bc:9′,9a',1‐hi] xanthylium perchlorate, an efficient dye (1977)

Abstract A one‐step procedure is described for the preparation of the title compound I, an efficient laser dye operating in the red region.
In Situ Production of Ozone in Water Using a Membrel Electrolyzer (1985)

The application of solid polymer electrolyte or Membrel water electrolysis cells with anodes for anodic generation of ozone in electrolyte‐free water is reported. Maximum yields were obtained at a temperature of 25°–30°C and a current density of 1.0–1.3 Acm−2. The current efficiency was not found to depend on ozone concentration in the feed water. Both, the perfluorinated membrane and the anode do not show any degradation of performance after 2500h of operation. The excellent stability and performance of the cell are correlated with properties of the membrane and its interface with the anode: exclusive transference of electric current by protons; absence of convection in the electrolyte; high oxygen oversaturation in the vicinity of the electrode.
Quantum Dots on Gold: Electrodes For Photoswitchable Cytochrome c Electrochemistry (2006)

A photoswitchable arrangement for direct electrochemistry of the redox protein cytochrome c can result from the application of CdSe/ZnS quantum dots on gold electrodes. “On/off” responses can be realized through photoexcitation of the quantum dots. Electrode illumination resulted in stepwise heterogeneous electron transfer from the electrode via the semiconductor particles to the heme proteins (see figure). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2296/2006/z500441_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Uterus-derived growth substances: possible implications for human uterus physiology and pathophysiology (review). The Group for Gynecological Investigation. (1991)

The presence of mitogens and inhibitors in myometrial, endometrial and leiomyoma extracts was documented. Growth substances of human uterus extracts were sensitive to tryptic digestion and were acid stable. Mitogens and inhibitors were retained and could be eluted from cartridges of octadecylsilyl-silica by 80% acetonitrile. Reverse-phase high performance liquid chromatography (r-HPLC) could separate mitogens from inhibitors. In addition, r-HPLC profiles revealed eluates of myometrial and leiomyoma extracts containing mitogens with preferential activity for either osteoblasts or myoblast-like cells, respectively. The presence of mitogens and inhibitors in human uterine extracts suggests a possible involvement of these growth substances in the regulation of various physiological and pathophysiological processes of human uterus.
Selective Inhibition of PI3K/Akt/mTOR Signaling Pathway Regulates Autophagy of Macrophage and Vulnerability of Atherosclerotic Plaque (2014)

Macrophage infiltration contributes to the instability of atherosclerotic plaques. In the present study, we investigated whether selective inhibition of PI3K/Akt/mTOR signaling pathway can enhance the stability of atherosclerotic plaques by activation of macrophage autophagy. In vitro study, selective inhibitors or siRNA of PI3K/Akt/mTOR pathways were used to treat the rabbit's peritoneal primary macrophage cells. Inflammation related cytokines secreted by macrophages were measured. Ultrastructure changes of macrophages were examined by transmission electron microscope. mRNA or protein expression levels of autophagy related gene Beclin 1, protein 1 light chain 3 II dots (LC3-II) or Atg5-Atg12 conjugation were assayed by quantitative RT-PCR or Western blot. In vivo study, vulnerable plaque models were established in 40 New Zealand White rabbits and then drugs or siRNA were given for 8 weeks to inhibit the PI3K/Akt/mTOR signaling pathway. Intravascular ultrasound (IVUS) was performed to observe the plaque imaging. The ultrastructure of the abdominal aortic atherosclerosis lesions were analyzed with histopathology. RT-PCR or Western blot methods were used to measure the expression levels of corresponding autophagy related molecules. We found that macrophage autophagy was induced in the presence of Akt inhibitor, mTOR inhibitor and mTOR-siRNA in vitro study, while PI3K inhibitor had the opposite role. In vivo study, we found that macrophage autophagy increased significantly and the rabbits had lower plaque rupture incidence, lower plaque burden and decreased vulnerability index in the inhibitors or siRNA treated groups. We made a conclusion that selective inhibition of the Akt/mTOR signal pathway can reduce macrophages and stabilize the vulnerable atherosclerotic plaques by promoting macrophage autophagy.
Stem Cell Contribution to Ovarian Development, Function, and Disease (2008)

By virtue of the fact that oocytes not only serve to produce embryos after fertilization but also can effectively reprogram adult somatic cell nuclei to a pluripotent state, much of the interest in the role of stem cells in ovarian biology has been focused on the germline. However, very recent studies have revealed that somatic stem cells may also be of considerable relevance to the study of normal ovarian function. Furthermore, stem cell dysfunction may underlie or contribute to disease states such as ovarian cancer and polycystic ovary syndrome. Our objective is to explore these concepts in greater detail, with the hope of stimulating further research efforts into understanding what role stem cells may play in the physiology and pathology of the mammalian female gonads.
Intramolecular Binding Contributes to the Activation of CDPK, a Protein Kinase with a Calmodulin-Like Domain (1996)

The activity of calmodulin-like domain protein kinase (CDPK) is regulated by the direct binding of Ca2+. Unmodified soybean CDPK alpha and a chimeric enzyme in which the calmodulin-like domain (CLD) was replaced by VU-1 calmodulin had similar values of Vmax(app) (3.19, 3.46, and 3.60, 3.93 mumol/ min/mg, respectively), and each was activated 30-70-fold by Ca2+. To determine if activation results from the binding of the CLD to the autoinhibitory (junction) domain of CDPK alpha in a manner analogous to the activation of calmodulin-dependent enzymes by calmodulin, recombinant CLD and truncation mutants of CDPK alpha were expressed in bacteria and highly purified. In blot overlays, biotinylated CLD bound to mutants containing residues 312-328 of the junction domain. In an electrophoretic mobility shift assay CLD bound synthetic peptides containing residues 318-332 in a calcium-dependent manner, providing direct evidence for binding of CLD to a site in the junction domain. Mutants of CDPK alpha from which all or part of the CLD had been deleted were constitutively inactive. Addition of 20 microM CLD to these mutants in the presence, but not the absence, of calcium stimulated their activities, but to various degrees. His6-CDPK alpha (1-328), which contained none of the CLD, was activated only 5-fold, but the activity of His6-CDPK alpha (1-398), which retained nearly half of the CLD in its sequence, was stimulated 64-fold. The latter activity approached that of unmodified CDPK alpha and was half maximal at a CLD concentration of 7 microM. Our results suggest that binding of CLD to the junction domain contributes to, but is not sufficient for activation. Although calmodulin supported full activity of the chimeric enzyme, its addition to His6-CDPK alpha (1-398) resulted in activity that was only 6% of that of the unmodified enzyme and which was half-maximal at 20 microM Arabidopsis calmodulin. These results support the conclusion that simple binding of the calmodulin-like domain to the junction domain is not sufficient for activation.