gebhart/patrepeval huggingface dataset:
Ras-induced Epigenetic Inactivation of the RRAD (Ras-related Associated with Diabetes) Gene Promotes Glucose Uptake in a Human Ovarian Cancer Model (2014)

RRAD (Ras-related associated with diabetes) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras-regulated transcriptome and epigenome were profiled by comparing T29H (a Ras(V12)-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through reduced representation bisulfite sequencing and digital gene expression. We found that Ras(V12)-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated, and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine resulted in demethylation in the RRAD promoter and restored RRAD expression in T29H cells. Additionally, treatment with farnesyltransferase inhibitor FTI277 resulted in restored RRAD expression and inhibited DNA methytransferase expression and activity in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting that RRAD is a tumor suppressor gene. Our results indicate that Ras(V12)-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis.
A Magnetically Separable, Highly Stable Enzyme System Based on Nanocomposites of Enzymes and Magnetic Nanoparticles Shipped in Hierarchically Ordered, Mesocellular, Mesoporous Silica (2005)

Multifunctional nanocomposites (M-CLEAs) of enzymes and magnetic nanoparticles (M-NPs) were fabricated in hierarchically ordered, mesocellular, mesoporous silica (HMMS; see Figure) by a simple process involving the co-adsorption of enzyme molecules and magnetic nanoparticles into HMMS followed by glutaraldehyde (GA) treatment. These nanocomposites are magnetically separable and highly stable and active. In particular, M-CLEA–lipase shows no decrease of lipase activity at all in the presence of proteases. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2421/2005/z500245_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.
Semisynthesis of a Homogeneous Glycoprotein Enzyme: Ribonuclease C: Part 2 (2009)

Active RNase glycoprotein from three pieces: The glycoprotein enzyme ribonuclease C, which contains a complex saccharide N-glycan, was synthesized by sequential native chemical ligation. An optimized ligation and isolation protocol allowed the efficient assembly and refolding of the 124 amino acid enzyme.
Aggregation-induced emission: phenomenon, mechanism and applications (2009)

It is textbook knowledge that chromophore aggregation generally quenches light emission. In this feature article, we give an account on how we observed an opposite phenomenon termed aggregation-induced emission (AIE) and identified the restriction of intramolecular rotation as a main cause for the AIE effect. Based on the mechanistic understanding, we developed a series of new fluorescent and phosphorescent AIE systems with emission colours covering the entire visible spectral region and luminescence quantum yields up to unity. We explored high-tech applications of the AIE luminogens as, for example, fluorescence sensors (for explosive, ion, pH, temperature, viscosity, pressure, etc.), biological probes (for protein, DNA, RNA, sugar, phospholipid, etc.), immunoassay markers, PAGE visualization agents, polarized light emitters, monitors for layer-by-layer assembly, reporters for micelle formation, multistimuli-responsive nanomaterials, and active layers in the fabrication of organic light-emitting diodes.
PEGylation and Multimerization of the Anti-p185HER-2 Single Chain Fv Fragment 4D5 (2006)

A major goal in antibody design for cancer therapy is to tailor the pharmacokinetic properties of the molecule according to specific treatment requirements. Key parameters determining the pharmacokinetics of therapeutic antibodies are target specificity, affinity, stability, and size. Using the p185HER-2 (HER-2)-specific scFv 4D5 as model system, we analyzed how changes in molecular weight and valency independently affect antigen binding and tumor localization. By employing multimerization and PEGylation, four different antibody formats were generated and compared with the scFv 4D5. First, dimeric and tetrameric miniantibodies were constructed by fusion of self-associating, disulfide-linked peptides to the scFv 4D5. Second, we attached a 20-kDa PEG moiety to the monovalent scFv and to the divalent miniantibody at the respective C terminus. In all formats, serum stability and full binding reactivity of the scFv 4D5 were retained. Functional affinity, however, did change. An avidity increase was achieved by multimerization, whereas PEGylation resulted in a 5-fold decreased affinity. Nevertheless, the PEGylated monomer showed an 8.5-fold, and the PEGylated dimer even a 14.5-fold higher tumor accumulation than the corresponding scFv, 48 h post-injection, because of a significantly longer serum half-life. In comparison, the non-PEGylated bivalent and tetravalent miniantibodies showed only a moderate increase in tumor localization compared with the scFv, which correlated with the degree of multimerization. However, these non-PEGylated formats resulted in higher tumor-to-blood ratios. Both multimerization and PEGylation represent thus useful strategies to tailor the pharmacokinetic properties of therapeutic antibodies and their combined use can additively improve tumor targeting.
An empirical study of the naive Bayes classifier (2001)

The naive Bayes classifier greatly simplify learning by assuming that features are independent given class. Although independence is generally a poor assumption, in practice naive Bayes often competes well with more sophisticated classifiers. Our broad goal is to understand the data characteristics which affect the performance of naive Bayes. Our approach uses Monte Carlo simulations that allow a systematic study of classification accuracy for several classes of randomly generated problems. We analyze the impact of the distribution entropy on the classification error, showing that low-entropy feature distributions yield good performance of naive Bayes. We also demonstrate that naive Bayes works well for certain nearlyfunctional feature dependencies, thus reaching its best performance in two opposite cases: completely independent features (as expected) and functionally dependent features (which is surprising). Another surprising result is that the accuracy of naive Bayes is not directly correlated with the degree of feature dependencies measured as the classconditional mutual information between the features. Instead, a better predictor of naive Bayes accuracy is the amount of information about the class that is lost because of the independence assumption. 1
Oligo(2,6‐anthrylene)s: Acene–Oligomer Approach for Organic Field‐Effect Transistors (2003)

Oligo(2,6-anthrylene) wie 1 und ihre Dihexylderivate, synthetisiert durch Suzuki-Kupplung (siehe Schema), wurden genutzt, um organische Feldeffekttransistoren (OFETs) herzustellen. Die Löcherbeweglichkeit dieser Anthracenoligomere kann bis zu 0.18 cm2 V−1 s−1 betragen. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2003/z50527_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.
Pathogenesis and Pharmacology of Epilepsy in the Lithium‐pilocarpine Model (2007)

To try to identify the critical structures during epileptogenesis, we used the lithium-pilocarpine model that reproduces most clinical and neuropathological features of temporal lobe epilepsy (TLE). We used imaging techniques as well as a disease modifying approach and pharmacological strategy. With [14C]-2-deoxyglucose autoradiography, we assessed changes in cerebral glucose utilization. T2-weighted magnetic resonance imaging (MRI, 4.7 T) allowed follow-up of structures involved in epileptogenesis. A potential disease-modifying effect was studied using preconditioning with brief seizures (amygdala kindling, maximal electroshocks) and pharmacological strategies including vigabatrin (250 mg/kg), caffeine (0.3 g/L in drinking water), topiramate (10-60 mg/kg), pregabalin (50 mg/kg followed by 10 mg/kg), or RWJ-333369 (10-120 mg/kg). In adult and PN21 rats that became epileptic, entorhinal, and piriform cortices were the initial structures exhibiting significant signal changes on MRI scans, from 6 h after status epilepticus (SE) onset, reflecting neuronal death. In PN21 rats that did not become epileptic, no signal occurred in parahippocampal cortices. In hippocampus, MRI signal change appeared 36-48 h after SE, and progressively worsened to sclerosis. During the latent and chronic phases, the metabolic level in the hilus of adult and PN21 epileptic rats was normal although neuronal loss reached 60-75%. Protection limited to CA1 and/or CA3 (caffeine, topiramate, vigabatrin, amygdala kindling) did not affect the latency to spontaneous seizures. Protection limited to the entorhinal and piriform cortices (pregabalin) delayed epileptogenesis. The combined protection of Ammon's horn and parahippocampal cortices (RWJ-333369) prolonged the latency before the onset of seizures in a dose-dependent manner or, in some cases, prevented the epilepsy. The entorhinal and piriform cortices are critically involved in the early phase of the epileptogenesis while the hilus may initiate and/or maintain epileptic seizures. Pharmacological protection of the basal cortices is necessary for a beneficial disease-modifying effect but this must be combined with protection of the hippocampus to prevent epileptogenesis in this model of TLE.
Criteria for diagnosing Parkinson's disease (1992)

Parkinson's disease evolves slowly, and there is current interest in exploring the earliest stages of the disorder, because of new approaches to studying pathogenesis and developing potential neuroprotective treatment. Recognizing early Parkinson's disease is not easy. The certainty of diagnosis increases as the disease advances. To address the problem of identifying Parkinson's disease in its initial phases of clinical expression, we propose the following designated levels of confidence for the diagnosis: (1) clinically possible, (2) clinically probable, and (3) clinically definite. Laboratory support for the diagnosis may be applied to each category. Criteria are provided as a framework underpinning this classification.
Severe Early-Onset Polyneuropathy in Insulin-Dependent Diabetes Mellitus (1992)

Early-onset symptomatic polyneuropathy in patients with diabetes mellitus is characterized by the loss of both myelinated and unmyelinated nerve fibers. Spontaneous axonal regeneration is remarkably frequent, even when neuropathy is severe.
TCL1 is activated by chromosomal rearrangement or by hypomethylation (2001)

TCL1 is an oncogene activated by recurrent reciprocal translocations at chromosome segment 14q32.1 in the most common of the mature T-cell malignancies, T-cell prolymphocytic leukemia. It acts to transport Akt1 to the nucleus and enhance Akt1's serine-threonine kinase activity. TCL1 is also expressed in the B-cell malignancy, Burkitt's lymphoma (BL). However, 14q32.1 breakpoints have not been detected in BL, and we therefore investigated in more detail how expression was activated. No evidence for rearrangement near TCL1 was found in BL. Instead, a NotI site adjacent to the TATA box in the TCL1 promoter was found to be unmethylated. By contrast, tumor cell lines not expressing TCL1 were fully methylated at this NotI site, while normal somatic cells were hemimethylated. We also found that TCL1 was expressed in B-cell chronic lymphocytic leukemia (CLL) and the related disorder splenic lymphoma with villous lymphocytes (unlike in normal mature B-cells), and that the NotI site was unmethylated on both alleles. This correlation of repression and methylation was tested in vitro. When cells with both alleles methylated at the NotI site were demethylated, TCL1 expression was induced. These data provide evidence that in mature B-cell malignancies there is an alternative mechanism of TCL1 activation that apparently involves loss of methylation of one promoter allele. We discuss the significance of this for CLL tumorigenesis and for genomewide hypomethylation in CLL.
A Test of the Adaptive Plasticity Hypothesis Using Transgenic and Mutant Plants Disabled in Phytochrome-Mediated Elongation Responses to Neighbors (1995)

Many plants display characteristic phytochrome-mediated stem elongation responses to crowding and vegetation shade, commonly referred to as the shade avoidance syndrome. We tested the hypothesis that this elongation is a form of adaptive plasticity by comparing the relative performance at high and low density of wild-type plants and transgenic and mutant plants in which the shade avoidance response was disabled. Transgenic tobacco plants in which elongation in response to neighbors was blocked by expression of the oat PHYA gene had decreased relative fitness when grown in competition with elongated wild-type plants. In contrast, constitutively elongated Brassica ein mutant plants, deficient in light-stable phytochrome, had lower fitness relative to nonelongated wild type at low density than in competition with elongated wild type at high density. The observation that phytochrome-mediated elongation is advantageous in dense stands, but disadvantageous for uncrowded plants, indicates that a response to foliage shade allows plants to develop an appropriate morphology for the level of competition they experience. This observation supports the adaptive plasticity hypothesis for this ecologically important trait.
hCAP‐18, a cathelin/pro‐bactenecin‐like protein of human neutrophil specific granules (1995)

A 19 kDa protein was identified in specific granules of human neutrophils. A full-length cDNA clone was isolated from a human CML cDNA library, based on amino-acid sequences of isolated tryptic fragments. This clone includes the recently identified cDNA for FALL-39/CAP-18. Aminoacid sequences of proteolytic fragments derived both from the conserved N-terminal cathelin-like region and the highly variable C-terminal region characteristic of this family of bactericidal, LPS binding proteins, were in complete agreement with the sequence deduced from the cDNA. Thus, the 19 kDa protein is hCAP-18, stored as a 'pro-peptide' in specific granules.
Corneal cell proteins and ocular surface pathology (1999)

The cornea is a transparent and avascular tissue that functions as the major refractive structure for the eye. A wide variety of growth factors, chemokines, cytokines and their receptors are synthesized by corneal epithelial and stromal cells, and are found in tears. These molecules function in corneal wound healing and in inflammatory responses. Proteoglycans and glycoproteins are essential for normal corneal function, both at the air-epithelial interface and within the extracellular matrix. The ocular MUC mucins may play roles in forming the mucus layer of the tear film, in regulating tear film spread, and in inhibiting the adhesion of pathogens to the ocular surface. Lumican, keratocan and mimecan are the major keratan sulfate proteoglycans of the corneal stroma. They are essential, along with other proteoglycans and interfibrillar proteins, including collagens type VI and XII, for the maintenance of corneal transparency. Corneal epithelial cells interact with a specialized extracellular matrix structure, the basement membrane, composed of a specific subset of collagen type IV and laminin isoforms in addition to ubiquitous extracellular matrix molecules. Matrix metalloprotein-ases have been identified in normal corneal tissue and cells and may play a role in the development of ulcerative corneal diseases. Changes in extracellular matrix molecule localization and synthesis have been noted in other types of corneal diseases as well, including bullous keratopathy and keratoconus.
A new approach to the study of the base-excision repair pathway using methoxyamine. (1985)

This paper describes the use of methoxyamine to study the enzymatic reactions catalyzed by uracil-DNA glycosylase and by AP (apurinic/apyrimidinic) endodeoxyribonuclease isolated from mammalian cells. [14C]Methoxyamine permits one to follow the formation of AP sites in a uracil-containing polydeoxyribonucleotide incubated with calf thymus uracil-DNA glycosylase. The number of methoxyamine-reacted AP sites is equal to that of uracil released. Methoxyamine has no effect on the uracil-DNA glycosylase activity and may be added together with the enzyme in order to block the AP sites and prevent the degradation of the polynucleotide by the AP endonucleases that may be present in a crude preparation. Addition of methoxyamine to AP sites prevents not only the enzymatic hydrolysis of the adjacent phosphodiester bond but also the degradation of the polynucleotide by NaOH. This protective effect disappears after methoxyamine is removed by acetaldehyde.
Self-Assembled, Deterministic Carbon Nanotube Wiring Networks This work was funded by the Office of Naval Research, DARPA, and an NSF-FRG grant. (2002)

A “minimal-lithography” technique for chemically assembling small deterministic crossbars of single-walled carbon nanotube (SWNT) ropes: The formation of electrically conducting crossbar circuits with 8 to 14 junctions (see picture) from a suspension of SWNTs is described. The critical structural parameters of the circuits were controlled by chemically directed self-assembly, rather than lithographic patterning, and all steps were carried out under ambient conditions. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18100_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.
Stimulation of Natural Killer T Cells by Glycolipids (2013)

Natural killer T (NKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type.
Parallelization and characterization of SIFT on multi-core systems (2008)

This paper parallelizes and characterizes an important computer vision application -Scale Invariant Feature Transform (SIFT) both on a Symmetric Multiprocessor (SMP) platform and a large scale Chip Multiprocessor (CMP) simulator. SIFT is an approach for extracting distinctive invariant features from images and has been widely applied. In many computer vision problems, a real-time or even super-real-time processing capability of SIFT is required. To meet the computation demand, we optimize and parallelize SIFT to accelerate its execution on multi-core systems. Our study shows that SIFT can achieve a 9.7x ~ llx speedup on a 16 -core SMP system. Furthermore, Single Instruction Multiple Data (SIMD) and cache-conscious optimization bring another 85% performance gain at most. But it is still three times slower than the real-time requirement for High-Definition Television (HDTV) image. Then we study the performance of SIFT on a 64 -core CMP simulator. The results show that for HDTV image, SIFT can achieve an excellent speedup of 52 x and run in real-time finally. Besides the parallelization and optimization work, we also conduct a detailed performance analysis for SIFT on those two platforms. We find that load imbalance significantly limits the scalability and SIFT suffers from intensive burst memory bandwidth requirement on the 16 -core SMP system. However, on the 64 -core CMP simulator the memory pressure is not high due to the shared last-level cache (LLC) which accommodates tremendous read-write sharing in SIFT. Thus it does not affect the scaling performance. In short, understanding the characterization of SIFT can help identify the program bottlenecks and give us further insights into designing better systems.
APOLIPOPROTEIN E POLYMORPHISM AND NEUROLOGICAL OUTCOME AFTER CARDIOPULMONARY RESUSCITATION (1999)

Society Of Critical Care Medicine 29Th Educational And Scientific Symposium; Orlando, Florida, Usa; February 11-15, 2000: Poster Presentations
Phosphorylation of the Small Heat Shock-related Protein, HSP20, in Vascular Smooth Muscles Is Associated with Changes in the Macromolecular Associations of HSP20 (1999)

Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC20) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC20. These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.