gebhart/patrepeval huggingface dataset:
DoesO-GlcNAc play a role in neurodegenerative diseases? (2005)

There are several lines of evidence that the modification of proteins by cytosolic- and nuclear-specific O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is closely related to neuropathologies, particularly Alzheimer's disease. Several neuronal proteins have been identified as being modified with O-GlcNAc; these proteins could form part of the inclusion bodies found, for example, in the most frequently observed neurologic disorder (i.e., Alzheimer's disease; Tau protein and beta-amyloid peptide are the well known aggregated proteins). O-GlcNAc proteins are also implicated in synaptosomal transport (e.g., synapsins and clathrin-assembly proteins). Inclusion bodies are partly characterized by a deficiency in the ubiquitin-proteasome system, avoiding the degradation of aggregated proteins. From this perspective, it appears interesting that substrate proteins could be protected against proteasomal degradation by being covalently modified with single N-acetylglucosamine on serine or threonine, and that the proteasome itself is modified and regulated by O-GlcNAc (in this case the turnover of neuronal proteins correlates with extracellular glucose). Interestingly, glucose uptake and metabolism are impaired in neuronal disorders, and this phenomenon is linked to increased phosphorylation. In view of the existence of the dynamic interplay between O-GlcNAc and phosphorylation, it is tempting to draw a parallel between the use of glucose, O-GlcNAc glycosylation and phosphorylation. Lastly, the two enzymes responsible for O-GlcNAc dynamism (i.e., O-GlcNAc transferase and glucosaminidase) are both enriched in the brain and genes that encode the two enzymes are located in two regions that are found to be frequently mutated in neurologic disorders. The data presented in this review strongly suggest that O-GlcNAc could play an active role in neurodegenerative diseases.
Distinct molecular forms of β-catenin are targeted to adhesive or transcriptional complexes (2004)

Beta-catenin plays essential roles in both cell-cell adhesion and Wnt signal transduction, but what precisely controls beta-catenin targeting to cadherin adhesive complexes, or T-cell factor (TCF)-transcriptional complexes is less well understood. We show that during Wnt signaling, a form of beta-catenin is generated that binds TCF but not the cadherin cytoplasmic domain. The Wnt-stimulated, TCF-selective form is monomeric and is regulated by the COOH terminus of beta-catenin, which selectively competes cadherin binding through an intramolecular fold-back mechanism. Phosphorylation of the cadherin reverses the TCF binding selectivity, suggesting another potential layer of regulation. In contrast, the main cadherin-binding form of beta-catenin is a beta-catenin-alpha-catenin dimer, indicating that there is a distinct molecular form of beta-catenin that can interact with both the cadherin and alpha-catenin. We propose that participation of beta-catenin in adhesion or Wnt signaling is dictated by the regulation of distinct molecular forms of beta-catenin with different binding properties, rather than simple competition between cadherins and TCFs for a single constitutive form. This model explains how cells can control whether beta-catenin is used independently in cell adhesion and nuclear signaling, or competitively so that the two processes are coordinated and interrelated.
Binary search trees for generalized measurements (2008)

Generalized quantum measurements (positive operator valued measures or probability operator measures) are important for optimally extracting information for quantum communication and computation. The standard realization via the Neumark extension requires extensive resources in the form of operations in an extended Hilbert space. For an arbitrary measurement, we show how to construct a binary search tree with a depth logarithmic in the number of possible outcomes. This could be implemented experimentally by coupling the measured quantum system to a probe qubit which is measured, and then iterating.
Batch effects and the effective design of single-cell gene expression studies (2017)

Single-cell RNA sequencing (scRNA-seq) can be used to characterize variation in gene expression levels at high resolution. However, the sources of experimental noise in scRNA-seq are not yet well understood. We investigated the technical variation associated with sample processing using the single-cell Fluidigm C1 platform. To do so, we processed three C1 replicates from three human induced pluripotent stem cell (iPSC) lines. We added unique molecular identifiers (UMIs) to all samples, to account for amplification bias. We found that the major source of variation in the gene expression data was driven by genotype, but we also observed substantial variation between the technical replicates. We observed that the conversion of reads to molecules using the UMIs was impacted by both biological and technical variation, indicating that UMI counts are not an unbiased estimator of gene expression levels. Based on our results, we suggest a framework for effective scRNA-seq studies.
Identification of a previously unknown human collagen chain, alpha 1(XV), characterized by extensive interruptions in the triple-helical region. (1992)

A previously unknown collagen cDNA clone, PF19, was isolated from a human placenta library. The 2.1-kilobase insert has a complete open reading frame of 709 amino acids that includes 12 amino acids of the NH2-terminal domain, a principally collagenous region of 577 residues, and 120 residues of the noncollagenous COOH terminus. The collagenous part of the sequence encoded by PF19 is characterized by 13 interruptions ranging in size from 2 to 45 amino acids. Within four interruptions are consensus sequences for attachment of serine-linked glycosaminoglycans and asparagine-linked oligosaccharides suggesting that this collagen may be extensively glycosylated. A synthetic decapeptide representing a sequence at the beginning of the COOH-terminal noncollagenous domain was used to prepare an antibody in rabbits. This antiserum detected a 125-kDa bacterial collagenase-sensitive protein in Western blots of HeLa cell lysate. Consistent with the size of the collagen chain, Northern blot hybridization revealed a major transcript of 5.3 kilobases and two minor ones of 4.7 and 4.4 kilobases that are present in cultured human fibroblasts but absent from umbilical vein endothelial cells. We propose that the previously unidentified polypeptide described in this report be designated the alpha 1 chain of type XV collagen.
Apparent heterogeneity of human megakaryocyte colony‐ and thrombopoiesis‐stimulating factors: studies on urinary extracts from patients with aplastic anaemia and idiopathic thrombocytopenic purpura (1982)

Megakaryocyte colon-stimulating factor (MEG-CSF) in the urinary extracts from patients wit aplastic anaemia (AA) revealed two distinct peaks of activity on Sephadex G-200 gel filtration with apparent molecular weights of 155,000 and 76,000. Both fractions induced significant thrombocytosis in peripheral blood and megakaryocytosis in the spleen of rats. Heterogeneity of MEG-CSF was also found in the extracts from the urine of patients with idiopathic thrombocytopenic purpura. The higher molecular weight MEG-CSF was significantly reduced when the gel filtration was performed under the dissociating conditions. Ion-exchange chromatography indicated that the higher molecular weight MEG-CSF had a different charge from the lower molecular weight MEG-CSF. These results suggest that the apparent heterogeneity of MEG-CSF is due to interaction of MEG-CSF with other proteins in the urinary extracts.
VXA: A Virtual Architecture for Durable Compressed Archives (2006)

Data compression algorithms change frequently, and obsolete decoders do not always run on new hardware and operating systems, threatening the long-term usability of content archived using those algorithms. Re-encoding content into new formats is cumbersome, and highly undesirable when lossy compression is involved. Processor architectures, in contrast, have remained comparatively stable over recent decades. VXA, an archival storage system designed around this observation, archives executable decoders along with the encoded content it stores. VXA decoders run in a specialized virtual machine that implements an OS-independent execution environment based on the standard x86 architecture. The VXA virtual machine strictly limits access to host system services, making decoders safe to run even if an archive contains malicious code. VXA's adoption of a "native" processor architecture instead of type-safe language technology allows reuse of existing "hand-optimized" decoders in C and assembly language, and permits decoders access to performance-enhancing architecture features such as vector processing instructions. The performance cost of VXA's virtualization is typically less than 15% compared with the same decoders running natively. The storage cost of archived decoders, typically 30-130KB each, can be amortized across many archived files sharing the same compression method.
Directed Evolution of Nucleic Acid Enzymes (2004)

Just as Darwinian evolution in nature has led to the development of many sophisticated enzymes, Darwinian evolution in vitro has proven to be a powerful approach for obtaining similar results in the laboratory. This review focuses on the development of nucleic acid enzymes starting from a population of random-sequence RNA or DNA molecules. In order to illustrate the principles and practice of in vitro evolution, two especially well-studied categories of catalytic nucleic acid are considered: RNA enzymes that catalyze the template-directed ligation of RNA and DNA enzymes that catalyze the cleavage of RNA. The former reaction, which involves attack of a 2'- or 3'-hydroxyl on the alpha-phosphate of a 5'-triphosphate, is more difficult. It requires a comparatively larger catalytic motif, containing more nucleotides than can be sampled exhaustively within a starting population of random-sequence RNAs. The latter reaction involves deprotonation of the 2'-hydroxyl adjacent to the cleavage site, resulting in cleaved products that bear a 2',3'-cyclic phosphate and 5'-hydroxyl. The difficulty of this reaction, and therefore the complexity of the corresponding DNA enzyme, depends on whether a catalytic cofactor, such as a divalent metal cation or small molecule, is present in the reaction mixture.
From the Newsstand (2004)

Review of Internet-related stories in IEEE, Computer Society, and trade press.
[The relationship between the change of mitochondria and the fertility in CMS line of sorghum after heat shock]. (2000)

The mitochondria of anther in pollen mother cell stage of cytoplasmic male sterility (CMS) line 3197A in sorghum were extracted after heat shock. The number of the mitochondria was measured by flow cytometer and some isoenzymes were analyzed by PAGE combined with stain for enzyme activity. The result of mitochondria quantity measurement shows that the number of the mitochondria in CMS line 3197A increased greatly up to 4.5 folds after heat shock. The analysis of isoenzymes also demonstrates that the type of isoenzyme in CMS line is in consistent with maintainer line. The study denoted the change of the quantity of mitochondria after heat shock and the relationship between this change and the fertility in sorghum.
The copper-chelating agent, trientine, attenuates liver enzyme-altered preneoplastic lesions in rats by angiogenesis suppression (2003)

It has been shown that angiogenesis plays an important role not only in tumor growth, but also in carcinogenesis. We previously reported that the copper-chelating agent, trientine dihydrochloride (trientine), exerted strong anti-angiogenic activity and inhibited hepatocellular carcinoma (HCC) tumor growth. The aim of the current study was to elucidate the effect of trientine on liver enzyme-altered preneoplastic lesions in rats, especially in conjunction with angiogenesis alteration in the liver. In a diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis model, trientine treatment, even at a clinically comparable low dose, significantly suppressed glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions associated with a decrease in copper content in the liver. Trientine also markedly suppressed neovascularization in the liver to a similar level as that of development of the preneoplastic lesions. On the contrary, the proliferative cell nuclear antigen (PCNA)-positive cells were not altered with or without trientine treatment. These results suggested that the copper-chelating agent, trientine, exerted chemopreventive effects against rat liver carcinogenesis due to the suppression of angiogenesis, and suggest that it might be useful clinically as a chemopreventive agent of HCC.
The Effect of Nicotine on Reproduction and Attachment of Human Gingival Fibroblasts In Vitro (1993)

The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal.
High‐yield isolation of murine microglia by mild trypsinization (2003)

Microglia can be isolated with high purity but low yield by shaking off loosely adherent cells from mixed glial cultures. Here we describe a new technique for isolating microglia with an average yield close to 2,000,000 microglial cells/mouse pup, more than five times higher than that of the shaking method. Confluent mixed glial cultures are subjected to mild trypsinization (0.05-0.12%) in the presence of 0.2-0.5 mM EDTA and 0.5-0.8 mM Ca2+. This results in the detachment of an intact layer of cells containing virtually all the astrocytes, leaving undisturbed a population of firmly attached cells identified as >98% microglia. These almost pure microglial preparations can be kept in culture for weeks and show proliferation and phagocytosis. Treatment with macrophage colony-stimulating factor and lipopolysaccharide, alone or in the presence of interferon gamma, induces typical microglial responses in terms of proliferation, morphological changes, nuclear factor-kappaB translocation, NO, and tumor necrosis alpha release and phagocytosis. This method allows for the preparation of highly enriched mouse or rat microglial cultures with ease and reproducibility. Because of its high yield, it can be especially convenient when high amounts of microglial protein/mRNA are required or in cases in which the starting material is limited, such as microglial cultures from transgenic animals.
Kallikrein-kinin system in diabetic patients. (1988)

Various factors in the kallikrein-kinin (K-K) system were examined in diabetic patients, and their clinical significance was evaluated. The plasma prekallikrein level was slightly increased in the entire diabetic group, but was decreased in the patients with microangiopathy. While the plasma kallikrein-like activity was increased in the diabetic patients. The urinary glandular kallikrein activity was decreased in the diabetic patients, and was significantly correlated with the urinary C-peptide level. High-molecular-weight kininogen was increased in the entire diabetic group. In the patients with microangiopathy its level was significantly lower than in diabetic patients without microangiopathy. Low-molecular-weight kininogen was increased significantly in the diabetic patients. These results suggest that the glandular K-K system is suppressed in diabetic patients and the plasma K-K system in those patients is activated according to the degree of impairment of glucose metabolism, and that changes in the plasma levels of its components are associated with those in the components of the coagulation system.
Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response (2017)

Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (<i>IDH2</i>) occur in many cancers, including ∼12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite <i>R</i>-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML (rrAML) patients with m<i>IDH2</i> in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear. Here, we measured 2-HG, m<i>IDH2</i> allele burden, and co-occurring somatic mutations in sequential patient samples from the clinical trial and correlated these with clinical response. Furthermore, we used flow cytometry to assess inhibition of mIDH2 on hematopoietic differentiation. We observed potent 2-HG suppression in both R140 and R172 m<i>IDH2</i> AML subtypes, with different kinetics, which preceded clinical response. Suppression of 2-HG alone did not predict response, because most nonresponding patients also exhibited 2-HG suppression. Complete remission (CR) with persistence of m<i>IDH2</i> and normalization of hematopoietic stem and progenitor compartments with emergence of functional m<i>IDH2</i> neutrophils were observed. In a subset of CR patients, m<i>IDH2</i> allele burden was reduced and remained undetectable with response. Co-occurring mutations in NRAS and other MAPK pathway effectors were enriched in nonresponding patients, consistent with RAS signaling contributing to primary therapeutic resistance. Together, these data support differentiation as the main mechanism of enasidenib efficacy in relapsed/refractory AML patients and provide insight into resistance mechanisms to inform future mechanism-based combination treatment studies.
Serum anti-p53 antibodies in patients with lung cancer. (2000)

Antibodies against the p53 protein are produced by some cancer patients. In some tumour entities, the presence of p53 autoantibodies have been linked to poorer survival. This study was designed to assess the prevalence and prognostic implications of p53 autoantibodies in patients with lung cancer. Serum samples of 180 patients were tested for antibodies against p53 protein using an ELISA. We studied 134 patients with primary lung cancer [histology: small cell lung carcinoma (SCLC) n=35; non-small cell lung carcinoma (NSCLC) n=99]. The control group consisted of 46 patients without lung cancer. In 17/134 (12.6%) of the cancer patients, p53 autoantibodies were detected (4/35 SCLC, 13/99 NSCLC). Most of the positive results were found in advanced stages of NSCLC (stage I-IIIA: 1/34; stage IIIB/IV: 12/65). One of the 46 control patients tested positive. Statistical analysis of survival shows no correlation with p53 antibody status in SCLC, but a significant correlation with shorter survival in NSCLC (p=0.01). After correction for stage of disease this correlation remains significant (stage IIIB/IV: p=0.02). In our series, the presence of anti-p53 autoantibodies is almost exclusively linked to the presence of malignant disease. Prognosis for patients with NSCLC, but not SCLC seems to be linked to the p53 autoantibody status.
Absence of a structural basis for intracellular recognition and differential localization of nuclear and plasma membrane-associated forms of simian virus 40 large tumor antigen. (1986)

The simian virus 40 large tumor antigen (T-ag) is found in both the nuclei (nT-ag) and plasma membranes (mT-ag) of simian virus 40-infected or -transformed cells. It is not known how newly synthesized T-ag molecules are recognized, sorted, and transported to their ultimate subcellular destinations. One possibility is that these events depend upon structural differences between nT-ag and mT-ag. To test this possibility, we compared the structures of nT-ag and mT-ag from simian virus 40-infected cells. No differences between the two forms of T-ag were detected by migration in polyacrylamide gels, by Staphylococcus aureus V8 partial proteolytic mapping of methionine- or proline-containing peptides, or by two-dimensional tryptic peptide mapping of methionine-containing peptides. The carboxy-terminal, methionine-containing tryptic peptide was identified in the two-dimensional maps and was shown to be identical in nT-ag and mT-ag. Thus, a structural basis for the recognition and differential localization of T-ags could not be demonstrated. The carboxy terminus of the T-ag encoded by mutant dlA2413 is derived from the alternate open reading frame of the simian virus 40 early region, in analogy with the theoretical early gene product, T*-ag. We used this mutant to identify peptides unique to T*-ag. None of these peptides were detected in maps of mT-ag; only wild-type T-ag-specific peptides were found. These findings suggest that T*-ag does not represent the membrane-associated form of T-ag, but that mT-ag is encoded within the same reading frame used for nT-ag.
Restriction of placental function alters heart development in the sheep fetus (2007)

Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110-125 days of gestation (term: 150 +/- 3 days). PR fetuses with a mean gestational Po(2) < 17 mmHg were defined as hypoxic. At postmortem (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.