gebhart/patrepeval huggingface dataset:
Intracellular Delivery Strategies for Antisense Phosphorodiamidate Morpholino Oligomers (2000)

Antisense oligonucleotides inhibit gene expression by interfering with transcription, translation, or splicing. They show great potential as gene-specific, nontoxic therapy for a wide variety of diseases. They are also powerful tools to study gene function as well as for validation of therapeutic targets. Even with compelling evidence of activity in vivo, the majority of cell types in culture require technologies capable of efficiently delivering antisense oligonucleotides into the cytosolic/nuclear compartment of the cells in culture. Phosphorodiamidate morpholino oligomers (PMO) are a new generation of antisense oligomers with high specificity and efficacy. They inhibit translation of targeted mRNA by steric blockade. Different methods were evaluated for efficient delivery of PMO into the cells in culture. Efficacy was compared using the PMO targeted to the 5'-untranslated region (5'-UTR) of alpha-globin-luciferase reporter fusion gene mRNA. A functional assay based on the lunciferase reporter system was used to measure efficacy. The fluorescence-activated cell sorting (FACS) method was used for quantitative determination of PMO uptake into the cells. Physical methods, such as scrape-loading, syringe-loading, and osmotic-loading, provided efficient transfer of PMO into the cells, which resulted in higher efficacy. These procedures caused minimal damage to the cells. Cell permeabilization with streptolysin O did not improve the cell uptake of PMO. Complexation with cationic lipids, Lipofectin and Lipofectamine (GIBCO-BRL, Gaithersburg, MD) also failed to enhance the uptake of PMO. We conclude that physical methods are optimal for the delivery of neutrally charged PMO into cells in culture. Further, these methods do not leave residual material that may interfere with the interpretation of targeted gene function.
Patient-Specific ECG Classification Based on Recurrent Neural Networks and Clustering Technique (2017)

In this paper, we propose a novel patient-specific electrocardiogram (ECG) classification algorithm based on the recurrent neural networks (RNN) and density based clustering technique. We use RNN to learn time correlation among ECG signal points and to classify ECG beats with different heart rates. Morphology information including the present beat and the T wave of former beat is fed into RNN to learn underlying features automatically. Clustering method is employed to find representative beats as the training data. Evaluated on the MIT-BIH Arrhythmia Database, the experimental results show that proposed algorithm achieves the state-of-the-art classification performance.
Design and Evaluation of a Uniform Flow Microreactor (2010)

This paper proposes a design method to provide uniform flow in a microreactor. Uniform momentum approach is adopted with 10 pillars before and after the chamber having a different slope inlet channel. The slope and number of pillars are two factors to make a uniform flow in the microreactor, covering the hexagonal gold layer. The CFD analysis about the designed microreactor is carried out and the velocity vector field measurements are made in the fabricated microreactor by micro PIV technique. The uniformity of microreactor flow was confirmed by both numerical simulation and experimental results.
beta2-Adrenoceptor Density of Human Lymphocytes After Nitroprusside-Induced Hypotension (1995)

The present study was undertaken to assess the influence of nitroprusside-induced hypotension on beta 2-adrenoceptor density. Twenty-four patients undergoing nose-septum corrections under general anesthesia were allocated randomly to a nitroprusside or control group. beta 2-Receptor density on lymphocytes was measured by binding studies using (-)125-iodocyanopindolol. Lymphocyte subpopulations B, T, Thelper, Tsuppressor, and natural killer cells were determined simultaneously by flow cytometry. Five of 12 nitroprusside-treated patients developed significant intraoperative increases of epinephrine levels (+69% versus preoperatively) which were not seen in the remaining seven patients. In these five patients, beta 2-receptor density of unfractionated lymphocytes was 26% lower (P < 0.05) on the first day after surgery compared with preoperative values. Since no changes in proportions of lymphocyte subpopulations were observed, these results are not caused by redistribution phenomena inducing a decrease of subsets with a high number of beta receptors. These findings suggest that beta 2-adrenergic responsiveness might be diminished after nitroprusside treatment in some patients.
Induction of Robust Type-I CD8+ T-cell Responses in WHO Grade 2 Low-Grade Glioma Patients Receiving Peptide-Based Vaccines in Combination with Poly-ICLC (2014)

The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade 2 glioma patients. These results warrant further evaluations of this approach. Clin Cancer Res; 21(2); 286-94. ©2014 AACR.
Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4. (1991)

Wolf-Hirschhorn syndrome is a clinically recognizable, multiple congenital anomaly syndrome usually associated with terminal deletion of the short arm of chromosome 4. A girl with clinical features of Wolf-Hirschhorn syndrome did not show an obvious deletion of chromosome 4, and a molecular defect was suspected. RFLPs of genomic DNA from the proband and her parents were studied using DNA probes from the distal region of chromosome 4p. Fluorescence in situ hybridization using a cosmid p847.351 containing the fragment 847 E-C was performed to investigate the possibility of a subtle translocation. Cytogenetic analyses done on the child and on both parents did not conclusively reveal abnormalities of chromosome 4. Molecular studies using two probes mapped to distal 4p showed the absence of the maternal haplotype in the child. These findings are thus consistent with a molecular deletion of 4p and confirm the diagnosis of Wolf-Hirschhorn syndrome. Cytogenetic experiments involving fluorescence in situ hybridization showed that the mother carried a subtle translocation between chromosomes 4 and 19, 46,XX,t(4,19)(p16.3; p13.3), which resulted in an unbalanced form in the child. Chorionic villus sampling for prenatal diagnosis in a subsequent pregnancy showed the fetus to be unaffected. This provides the first evidence, in chromosome 4p, of a molecular deletion due to a subtle, inherited translocation leading to the Wolf-Hirschhorn phenotype. Such subtle translocations may become an important mechanism for some recurrent genetic defects.
The Cell Biology of Parasitism in Trypanosoma brucei: Insights and Drug Targets from Genomic Approaches? (2002)

The African trypanosome, Trypanosoma brucei exhibits a complex, digenetic life cycle that alternates between the tsetse fly vector and the mammalian host. The life cycle is characterised by a complex series of cell type differentiations and variations in metabolism. In addition the trypanosome exhibits a particular cell biology that has become adapted for its role as a parasite. This article places some of these areas in a frame-work that considers the role of cellular processes in parasitism. I rehearse some conclusions from recent studies and provide hyphotheses and suggestions for future work. Areas debated include: cell surface protein expression, cell differentiation, endomembrane trafficking and protein targeting, the cytoskeleton,flagellum functions in motility, attachment and plasma membrane differentiation, organelle specialisations, control of cell cycle, parasite/host, parasite/parasite and parasite/vector interactions. The review also focuses on the likely impact of the genome project and reverse genetics in providing greater insight to these cellular processes and how, if coordinated with some alan by scientists and funding agencies, this may provide novel targets for future drug development.
The C‐Terminus of the β Protein is Critical in Amyloidogenesisa (1993)

The beta amyloid protein found in extracellular deposits in Alzheimer's disease (AD) is heterogeneous at its C-terminus; proteins ending at residues 40, 42, and 43 have been identified in neuritic deposits, while protein in vascular amyloid appears to end at residue 39 or 40. Studies of synthetic beta proteins (beta 1-39, beta 1-40, beta 1-42), and model peptides (beta 26-39, beta 26-40, beta 26-42, beta 26-43) demonstrate that amyloid formation is a nucleation-dependent phenomenon. Peptides ending at residues 39 or 40 were kinetically soluble for hours to days, while peptides ending at residues 42 or 43 aggregated immediately; all eventually reached similar thermodynamic solubility. The kinetically soluble variants could be seeded with the kinetically insoluble variants. The secondary structure of beta 26-39 fibrils was different from that of beta 26-42 fibrils, however, seeding beta 26-39 with beta 26-42 produces mixed fibrils with structure similar to beta 26-42. These results suggest that neuritic plaques may be seeded by their minor component; this may determine the structure and properties of amyloid in AD.
TransientBoost: On-line boosting with transient data (2010)

For on-line learning algorithms, which are applied in many vision tasks such as detection or tracking, robust integration of unlabeled samples is a crucial point. Various strategies such as self-training, semi-supervised learning and multiple-instance learning have been proposed. However, these methods are either too adaptive, which causes drifting, or biased by a prior, which hinders incorporation of new (orthogonal) information. Therefore, we propose a new on-line learning algorithm (TransientBoost), which is highly adaptive but still robust. This is realized by using an internal multi-class representation and modeling reliable and unreliable data in separate classes. Unreliable data is considered transient, hence we use highly adaptive learning parameters to adapt to fast changes in the scene while errors fade out fast. In contrast, the reliable data is preserved completely and not harmed by wrong updates. We demonstrate our algorithm on two different tasks, i.e., object detection and object tracking showing that we can handle typical problems considerable better than existing approaches. To demonstrate the stability and the robustness, we show long-term experiments for both tasks.
Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. (1985)

An unusual protein was isolated from acid extracts of normal human pancreas and pancreatic secretion in the form of uniform 7-10-nm long single threads without visible axial periodicity or other structure, as seen in the electron microscope. It accounts for as much as 300 micrograms/ml in some pancreatic secretions as measured by specific radioimmunoassay. The protein undergoes a freely reversible, pH dependent, globule-fibril transformation, being stable in the fibril form between pH 5.4 and 9.2. The monomer at acid pH has an apparent molecular weight of approximately 14,000 and consists of a single polypeptide chain, the amino acid composition of which is rich in aromatic amino acids and lacks carbohydrate, fatty acid, and phosphate. The amino acid sequence of 45 residues from the amino terminus shows no homology with any other reported protein sequences other than that of the A chain of the bovine pancreas thread protein (reported elsewhere). A sensitive radioimmunoassay employing monoclonal antibodies against human pancreatic thread protein failed to detect the antigen in a wide range of human tissues other than pancreas, nor was the antigen measurable in normal human sera. Immunohistochemistry utilizing these antibodies revealed the antigen as a component of the cytoplasm of some but not all the pancreatic acinar cells. A physiologic function has not yet been determined for this protein.
Syntheses and Spectral Properties of Functionalized, Water-Soluble BODIPY Derivatives (2008)

The objective of this work was to form water-soluble 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives. Sulfonation conditions were developed for several BODIPY dyes to give the monosulfonated products 1a-3a and the disulfonated products 1b-3b. Compounds 1 are functionalized with an aryl iodide for organometallic couplings. Similarly, 2 has an aromatic bromide but also two chlorine atoms that could be replaced via SNAr reactions. The amine 3 is amenable to couple to biomolecules via acylation reactions. A diazotization/azide reaction sequence was used to convert the amines 3 into azides 4; the latter may be functionalized via click reactions as illustrated by conversion of 4b into 5. Compound 5 was designed to have an acid-functional group to facilitate activation and coupling to amines. Spectral data for these materials indicate they are highly fluorescent probes in aqueous environments.
Site-Specific and Stoichiometric Stealth Polymer Conjugates of Therapeutic Peptides and Proteins (2016)

As potent and selective therapeutic agents, peptides and proteins are an important class of drugs, but they typically have suboptimal pharmacokinetic profiles. One approach to solve this problem is their conjugation with "stealth" polymers. Conventional methods for conjugation of this class of polymers to peptides and proteins are typically carried out by reactions that have poor yield and provide limited control over the site of conjugation and the stoichiometry of the conjugate. To address these limitations, new chemical and biological approaches have been developed that provide new molecular tools in the bioconjugation toolbox to create stealth polymer conjugates of peptides and proteins with exquisite control over their properties. This review article highlights these recent advances in the synthesis of therapeutic peptide- and protein-stealth polymer conjugates.
Mechanism of Ribose 2‘-Group Discrimination by an RNA Polymerase (1997)

The mechanism by which T7 RNA polymerase (RNAP) discriminates between rNTP and dNTP substrates has been characterized. During transcript elongation T7 RNAP uses rNTPs 70-80-fold more efficiently than dNTPs. Discrimination of the hydrogen-bonding character of the ribose 2'-substituent contributes a largely Km-mediated factor of approximately 20 to this preference for rNTPs. Discrimination of 2'-substituent H-bonding character appears to be made through a hydrogen bond to the hydroxyl group of tyrosine 639. This hydrogen bond makes little net contribution to either rNTP ground or transition state binding energy apparently because it is balanced by the energy of desolvation of the tyrosine hydroxyl. This mechanism may reflect a strategy to facilitate translocation by minimizing contributions from polymerase-NMP moiety interactions to NTP binding energy so as to minimize the affinity of the NTP binding site for the 3'-NMP of the product nucleic acid.
Histone arginine methylation (2010)

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code.
Xanthomonas oryzae pv. Oryzae Avirulence Genes Contribute Differently and Specifically to Pathogen Aggressiveness (2000)

Genomic copies of three Xanthomonas oryzae pv. oryzae avirulence (avr) genes, avrXa7, avrXal0, and avrxa5, and four homologous genes, aB3.5, aB3.6, aB4.3, and aB4.5, were mutagenized individually or in combination to study the roles of avr genes in one component of pathogen fitness, i.e., aggressiveness or the amount of disease X. oryzae pv. oryzae causes in susceptible rice lines. These X. oryzae pv. oryzae genes are members of the highly related Xanthomonas avrBs3 gene family. Compared to the wild-type strain, X. oryzae pv. oryzae strains with mutations in avrXa7, avrxa5, and the four homologous genes caused shorter lesions on rice line IR24, which contains no resistance genes relevant to the wild-type strain. The contribution of each gene to lesion length varied, with avrXa7 contributing the most and avrXal0 showing no measurable effect on aggressiveness. The functional, plasmidborne copies of avrXa7, aB4.5, and avrxa5 restored aggressiveness only to strains with mutations in avrXa7, aB4.5, and avrxa5, respectively. Mutations in avrXa7 were not complemented by plasmids carrying any other avr gene family members. These data indicate that some, but not all, avr family members contribute to pathogen aggressiveness and that the contributions are quantitatively different. Furthermore, despite their sequence similarity, the aggressiveness functions of these gene family members are not interchangeable. The results suggest that selection and pyramiding resistance genes can be guided by the degree of fitness penalty that is empirically determined in avr gene mutations.
RelB Modulation of IκBα Stability as a Mechanism of Transcription Suppression of Interleukin-1α (IL-1α), IL-1β, and Tumor Necrosis Factor Alpha in Fibroblasts (1999)

Members of the NF-kappaB/RelB family of transcription factors play important roles in the regulation of inflammatory and immune responses. RelB, a member of this family, has been characterized as a transcription activator and is involved in the constitutive NF-kappaB activity in lymphoid tissues. However, in a previous study we observed an overexpression of chemokines in RelB-deficient fibroblasts. Here we show that RelB is an important transcription suppressor in fibroblasts which limits the expression of proinflammatory mediators and may exert its function by modulating the stability of IkappaBalpha protein. Fibroblasts from relb(-/-) mice overexpress interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in response to lipopolysaccharide (LPS) stimulation. These cells have an augmented and prolonged LPS-inducible IKK activity and an accelerated degradation which results in a diminished level of IkappaBalpha protein, despite an upregulated IkappaBalpha mRNA expression. Consequently, NF-kappaB activity was augmented and postinduction repression of NF-kappaB activity was impaired in these cells. The increased kappaB-binding activity and cytokine overexpression was suppressed by introducing RelB cDNA or a dominant negative IkappaBalpha into relb(-/-) fibroblasts. Our findings suggest a novel transcription suppression function of RelB in fibroblasts.
The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors. (1994)

The t(10;14) chromosomal translocation of T-cell acute lymphoblastic leukemia joins the T-cell receptor delta gene to a region upstream of a diverged homeobox-containing gene called HOX11. To better understand the pathogenetic role of HOX11 in leukemogenesis, post 5-fluorouracil-treated murine bone marrow cells were infected with a replication-defective retrovirus bearing the gene. Constitutive expression of HOX11 in hematopoietic precursors yielded cell lines at high frequency consisting of immature cells belonging to the myeloid lineage. HOX11-transformed cell lines displayed a strict dependence on IL-3 for their survival and proliferation in culture and were not leukemogenic. The results support the hypothesis that the transforming capacity of HOX11 derives from its ability to alter the expression of genes regulating hematopoietic differentiation and that secondary mutations promoting cell survival or stimulating proliferation are required for progression to malignancy. The findings further suggest that the oncogenic activity of HOX11 might not be restricted to T-cell leukemias in humans.
Frame Bit Allocation for H.264 Using Cauchy-Distribution Based Source Modelling (2006)

Based on the observation that a Cauchy density is more accurate in estimating the distribution of the AC coefficients than the traditional Laplacian density for H.264 video coders, a rate model with improved accuracy is derived. Using the new rate model, a frame bit-allocation algorithm for the rate control of an H.264 video coder is developed. Extensive analysis with carefully selected anchor video sequences demonstrates a 0.43 dB average PSNR improvement over the JM 8.4 rate control algorithm, and a 0.27 dB average PSNR improvement over the TM5-based bit-allocation algorithm that has recently been proposed for H.264 by S. Ma et al. (see Proc. 2003 Int. Conf. Image Process., ICIP '03, vol.3, p.793-6, 2003). The analysis also demonstrates 20% and 60% reductions in PSNR variation among the encoded pictures when compared to the JM 8.4 rate control algorithm and the TM5-based bit-allocation algorithm, respectively.
Distannoxane as reverse micelle-type catalyst: novel solvent effect on reaction rate of transesterification (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDistannoxane as reverse micelle-type catalyst: novel solvent effect on reaction rate of transesterificationJunzo Otera, Shinji Ioka, and Hitosi NozakiCite this: J. Org. Chem. 1989, 54, 17, 4013–4014Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/jo00278a002https://doi.org/10.1021/jo00278a002research-articleACS PublicationsRequest reuse permissionsArticle Views451Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts