gebhart/patrepeval huggingface dataset:
MicroRNA Expression in Cytogenetically Normal Acute Myeloid Leukemia (2008)

A microRNA signature in molecularly defined, high-risk, cytogenetically normal AML is associated with the clinical outcome and with target genes encoding proteins involved in specific innate-immunity pathways.
Improved FDTD subgridding algorithms via digital filtering and domain overriding (2005)

In numerical simulations of Maxwell's equations for problems with disparate geometric scales, it is often advantageous to use grids of varying densities over different portions of the computational domain. In simulations involving structured finite-difference time-domain (FDTD) grids, this strategy is often referred as subgridding (SG). Although SG can lead to major computational savings, it is known to cause instabilities, spurious reflections, and other accuracy problems. In this paper, we introduce two strategies to combat these problems. First, we present an overlapped SG (OSG) approach combined with digital filters (in space). OSG can recover standard SG (SSG) schemes but it is based upon a more general, explicit separation between interpolation/decimation operations and the FDTD field update itself. This allows for a better classification of errors associated with the subgrid interface. More importantly, digital filters and phase matching techniques can be then employed to combat those errors. Second, we introduce SG with a domain overriding (SG-DO) strategy, consisting of overlapped (sub)grid regions that contain auxiliary (buffer) subdomains with perfectly matched layers (PML) to allow explicit control on the reflection and transmission properties at SG interfaces. We provide two-dimensional (2-D) numerical examples showing that residual errors from 2-D SG-DO FDTD simulations can be significantly reduced when compared to SSG schemes.
Enhancement of tumor lysate- and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein. (2001)

We have evaluated whether the addition of a foreign helper protein, keyhole limpet hemocyanin (KLH), can augment the efficacy of tumor lysate-pulsed dendritic cells and peptide-pulsed DC immunizations in vivo. Besides being used as a "surrogate antigen" in approaches to measure immunological response in cancer patients, KLH is also an immunogenic carrier protein to elicit T-cell help. Using the D5 subline of B16 melanoma, we demonstrate that DCs pulsed with both KLH and tumor lysate mediate enhanced immune priming and rejection of established metastases in vivo, which is dependent on host-derived T cells. Interleukin 2 augments the enhancement afforded by KLH, as measured by cure rates and overall survival, in the absence of autoimmune depigmentation. KLH added to DC immunizations markedly enhances tumor-specific T cell production of IFN-gamma. D5 melanoma exposed to similar levels of IFN-gamma results in substantial expression of MHC class I molecules. DCs pulsed with KLH and mouse tyrosinase-related protein-2 peptide results in enhanced reduction of B16 melanoma metastases; the effect is most pronounced in a setting where tyrosinase-related protein-2 peptide-pulsed DCs alone are completely ineffective. Collectively, these findings demonstrate that KLH addition to tumor antigen-pulsed DC immunizations can augment IFN-gamma production and enhance in vivo antitumor activity.
Reactivation of solids from furnace injection of limestone for sulfur dioxide control (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactivation of solids from furnace injection of limestone for sulfur dioxide controlWojciech. Jozewicz, John C. S. Chang, Theodore G. Brna, and Charles B. SedmanCite this: Environ. Sci. Technol. 1987, 21, 7, 664–670Publication Date (Print):July 1, 1987Publication History Published online1 May 2002Published inissue 1 July 1987https://doi.org/10.1021/es00161a007Request reuse permissionsArticle Views83Altmetric-Citations36LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions (2016)

MicroRNAs (miRNAs) are small non-coding RNAs (∼22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2-8) of miRNA. Recent advances in a transcriptome-wide method of mapping miRNA binding sites (Ago HITS-CLIP) elucidated that a large portion of miRNA-target interactions in vivo are mediated not only through the canonical "seed sites" but also via non-canonical sites (∼15-80%), setting the stage to expand and determine their properties. Here we focus on recent findings from transcriptome-wide non-canonical miRNA-target interactions, specifically regarding "nucleation bulges" and "seed-like motifs". We also discuss insights from Ago HITS-CLIP data alongside structural and biochemical studies, which highlight putative mechanisms of miRNA target recognition, and the biological significance of these non-canonical sites mediating marginal repression.
Localized current field hyperthermia in carcinoma of the cervix: 3-D computer simulation of SAR distribution (1999)

Software was developed for the 3D simulation of SAR distribution for a 500 kHz localized current field hyperthermia system to be used in patients with carcinoma of the cervix. This hyperthermia system was specifically designed for use with a modified Fletcher-Suit intracavitary applicator. It consists of software modules for data input, tetrahedral grid generation and a numerical calculation of SAR distribution using an adaptive, multilevel finite element code. The AVS (Advanced Visual System, Inc.) system was used for the visual presentation of the results. A quasi-static approach was employed for the determination of SAR distribution. Results of the performed numerical tests were presented and they showed an important, clinically relevant ability to obtain a selective power deposition. This selective power deposition depended on the applicator geometry, i.e. the distance between the components of a Fletcher-Suit applicator and their relative position and the use of different modes of excitation.
Aluminum in Parenteral Nutrition Solution—Sources and Possible Alternatives (1986)

The extent of aluminum (Al) contamination in parenteral nutrition (PN) solutions for infants is not known. Aluminum was measured in 136 samples from various commercially available components that are used with PN. Results showed Al content varied widely among different components. The same chemical may have a different Al content depending on the manufacturer. However, Al contents were similar among lots from the same manufacturer for the same chemical. Aluminum contamination was arbitrarily classified as high (greater than 500 micrograms Al/liter), intermediate (51-500 micrograms Al/liter) or low (less than or equal to 50 micrograms Al/liter). The high group included most calcium and phosphorus containing salts, 1 multivitamin preparation, folic acid, ascorbic acid and concentrated (25%) albumin. The intermediate group included sodium lactate, potassium phosphates, zinc and chromium chloride, multitrace metal preparation, and 5% plasma protein. The low group included amino acids, sterile water and dextrose water, chloride salts of sodium, potassium, calcium, copper and chromium, sodium phosphates, magnesium sulphate, zinc sulphate, vitamin B12, vitamin K1, 1 multivitamin preparation, soybean oil emulsion and heparinized (2 U/ml) saline. PN solutions made from high Al components may contain up to 300 micrograms Al/liter. Calcium gluconate contributed greater than 80% of the total Al load from PN. Lowering of Al content in calcium gluconate in addition to use of specific low Al components offers the opportunity to significantly lower the Al concentration of the final PN solution and theoretically may achieve an Al content as low as 12 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Single-molecule detection by two-photon-excited fluorescence (1995)

We present a technique for observing single fluorophore molecules in solution. A mode-locked laser beam is focused into the solution, thereby defining a two-photon excitation volume localized in three dimensions. Molecules diffusing into and out of this volume produce fluorescence bursts, which are detected with a high signal-to-background ratio. The theoretical foundations for the technique are laid out, including the attendant fluorescence rate distribution, and agree with experimental results obtained for Rhodamine B molecules in water.
Stereoselective synthesis of [5'-2H1][5'-13C]nucleosides (2002)

An approach to a synthesis of stereoselective 5'-monodeuterated nucleoside combined with 13C label is described. A preparation of (5R)-D-[5-(2)H1;5-(13)C]ribose derivative of 1,2:5,6-di-O-isopropyliden-alpha-D-allofranose was successfully achieved by a 13C Wittig reaction using Ph3P13CH3I-BuLi to 5-oxoribose derivative and subsequent transformation into D-[5-(13)C]ribose derivative with an AD reaction, selective acylation, oxidation with NaIO4, and a stereoselective deuteride transfer reaction from Alpine-Borane-d to 5-oxo-D-[5-(13)C]ribose derivative as the main reaction. (5'R)-[5'-(2)H1;5'-(13)C]nucleosides were synthesized in the established manner from this 5-(13)C/2H1-double-labeled ribose.
Greater frequency of CD5-negative CD8+ T cells against human immunodeficiency virus type 1 than other viruses is consistent with adaptation to antigenic variation (2014)

This deficit in CD5 expression selective for HIV-specific CD8(+) T cells is consistent with in vivo adaptation to low avidity HIV peptide variants and has potential consequences for CD8(+) T cell expansion, cross-reactivity and autoreactivity.
Temporal delivery of multiple growth factors from polymer scaffolds to enhance neovascularization. (2004)

Therapeutic angiogenesis holds great promise as a therapy to treat ischemic diseases and reduce damage to affected tissues. The complex nature of the angiogenic cascade requires the coordination of numerous cell types and various factors, several challenges with current growth factor delivery approaches have been identified. They include limited growth factor exposure time to the host tissue, systemic presence of the factor, and lack of vessel maturation due to single factor administration. To date, neovascularization approaches in many pre-clinical and clinical trials have focused on the initial stages of blood vessel formation. Although blood vessel formation is crucial to battle ischemia due to arterial occlusion, maintaining the new vascular network is vital to the establishment of a meaningful and lasting therapy. In this thesis, an inductive tissue engineering approach was employed utilizing a polymeric, macroporous scaffold to deliver vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), and the angiopoietins-1 and -2 (Ang1, Ang2) in a temporal manner to promote new blood vessel formation and enhance maturation. The ability of a poly(lactide-co-glycolide) (PLG) system to locally release bioactive factors with distinct kinetics, <italic> in vitro</italic> and <italic>in vivo</italic>, was dependent on the protein incorporation method and polymeric properties. Direct protein incorporation into the PLG matrix positioned the factor predominantly adjacent to the pore, allowing it to be released quickly. In contrast, pre-encapsulating the protein prior to matrix fabrication deeply embeds the protein in the polymer resulting in a slower release rate. Using this polymeric system in a subcutaneous mouse model, the dual rapid release of VEGF and Ang2 provided an additive benefit in blood vessel formation. Rapid delivery of VEGF + Ang2, followed by a delayed release of PDGF and Ang1, individually or concurrently, promoted vessel maturation without significantly reducing the density of the newly formed vascular network. In contrast, releasing PDGF + Ang1 at the same time as VEGF + Ang2, reduced vessel density. Both VEGF and VEGF + Ang2 greatly limited necrosis and restored partial blood perfusion in hind limbs of SCID mice subjected to severe ischemia. These studies expose the importance of temporal interactions between these angiogenic molecules on vessel formation and maturation. The results may allow one to control the development of a functional and stable vascular bed in ischemic tissues and improve therapeutic neovascularization.
Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow (2004)

Abstract Plasma cells (PCs) represent the final stage of B-cell differentiation and are devoted to the production of immunoglobulin (Ig). Perturbations to their development can result in human disorders characterized by PC expansion and hypergammaglobulinemia. Ig-secreting cells (ISCs) have been identified in secondary lymphoid tissues and bone marrow (BM). Most ISCs in lymphoid tissue are short-lived; in contrast, ISCs that migrate to the BM become long-lived PCs and continue to secrete immunoglobulin for extended periods. However, a small population of long-lived PCs has been identified in rodent spleen, suggesting that PCs may persist in secondary lymphoid tissue and that the spleen, as well as the BM, plays an important role in maintaining long-term humoral immunity. For these reasons, we examined ISCs in human spleen and identified a population that appears analogous to long-lived rodent splenic PCs. Human splenic ISCs shared morphologic, cellular, molecular, and functional characteristics with long-lived PCs in BM, demonstrating their commitment to the PC lineage. Furthermore, the detection of highly mutated immunoglobulin V region genes in splenic ISCs suggested they are likely to be antigen-selected and to secrete high-affinity immunoglobulin. Thus, our results suggest that splenic ISCs have an important role in humoral immunity and may represent the affected cell type in some B-cell dyscrasias.
Discovery of Novel Bruton’s Tyrosine Kinase Inhibitors Using a Hybrid Protocol of Virtual Screening Approaches Based on SVM Model, Pharmacophore and Molecular Docking (2012)

Bruton's tyrosine kinase has emerged as a potential target for the treatment for B-cell malignancies and autoimmune diseases. Discovery of Bruton's tyrosine kinase inhibitors has thus attracted much attention recently. In this investigation, we introduced a hybrid protocol of virtual screening methods including support vector machine model-based virtual screening, pharmacophore model-based virtual screening and docking-based virtual screening for retrieving new Bruton's tyrosine kinase inhibitors from commercially available chemical databases. Performances of the hybrid virtual screening approach were evaluated against a test set, which results showed that the hybrid virtual screening approach significantly shortened the overall screening time, and considerably increased the hit rate and enrichment factor compared with the individual method (SB-VS, PB-VS and DB-VS) or their combinations by twos. This hybrid virtual screening approach was then applied to screen several chemical databases including Specs (202,408 compounds) and Enamine (980,000 compounds) databases. Thirty-nine compounds were selected from the final hits and have been shifted to experimental studies.
Two cases of successful treatment of locally advanced non-small cell lung cancer with induction chemo-radiotherapy using weekly carboplatin and paclitaxel. (2002)

局所進行非小細胞肺癌に, carboplatinとpaclitaxelの少量分割投与と放射線併用術前治療が奏効した2例を報告する.症例1は71歳男性.右肺上葉にcT3N2M0の扁平上皮癌を, 左肺S6にcTINM0M0の肺癌疑いの病巣を認めた.CBDCA (AUC1.25) とTXL (70mg/m2) をweeklyに6週投与後, 右腫瘍に放射線照射40Gyを行い奏効した.照射後発症した放射線性肺臓炎, 帯状疱疹の軽快後, 右肺上葉切除術, 6週後に, 左肺S6区域切除術を施行した.左右肺共に扁平上皮癌であった.周術期に重篤な合併症は認めなかった.症例2は65歳女性.cT4N2M0の左肺下葉腺癌にて, CBDCA (AUC1.25) とTXL (70mg/m2) のweekly投与を2週行い更にTXLを40mg/m2に減量し4週投与と放射線照射50Gyを同時施行後, 左肺全摘術を施行した.周術期に重篤な合併症は認めなかった.CBDCAとTXLによる放射線照射併用した術前治療は本症例に対し奏効し副作用も容認しうる範囲内であった事より局所進行非小細胞肺癌に対し有効な治療法であると期待できる.
Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space (2019)

Immunodominant T cell epitopes preferentially targeted in multiple individuals are the critical element of successful vaccines and targeted immunotherapies. However, the underlying principles of this "convergence" of adaptive immunity among different individuals remain poorly understood. To quantitatively describe epitope immunogenicity, here we propose a supervised machine learning framework generating probabilistic estimates of immunogenicity, termed "immunogenicity scores," based on the numerical features computed through sequence-based simulation approximating the molecular scanning process of peptides presented onto major histocompatibility complex (MHC) by the human T cell receptor (TCR) repertoire. Notably, overlapping sets of intermolecular interaction parameters were commonly utilized in MHC-I and MHC-II prediction. Moreover, a similar simulation of individual TCR-peptide interaction using the same set of interaction parameters yielded correlates of TCR affinity. Pathogen-derived epitopes and tumor-associated epitopes with positive T cell reactivity generally had higher immunogenicity scores than non-immunogenic counterparts, whereas thymically expressed self-epitopes were assigned relatively low scores regardless of their immunogenicity annotation. Immunogenicity score dynamics among single amino acid mutants delineated the landscape of position- and residue-specific mutational impacts. Simulation of position-specific immunogenicity score dynamics detected residues with high escape potential in multiple epitopes, consistent with known escape mutations in the literature. This study indicates that targeting of epitopes by human adaptive immunity is to some extent directed by defined thermodynamic principles. The proposed framework also has a practical implication in that it may enable to more efficiently prioritize epitope candidates highly prone to T cell recognition in multiple individuals, warranting prospective validation across different cohorts.
An endoplasmic reticulum retrieval signal sequence promotes MHC class I--presentation of exogenous CTL epitope peptides (2006)

Objective To detect the effect of an endoplasmic reticulum (ER) retrieval signal peptide on MHC class Ⅰ-associated antigen presentation of exogenous CTL epitope peptides. Methods Three peptides were synthesized, which were the minimal CTL epitope peptide OVA_ 257-264 , OVA_ 257-264 -KDEL (with an ER retrieval signal Lys-Asp-Glu-Leu sequence at the carboxyl-terminus of OVA_ 257-264 ), and OVA_ 257-268 (with four naturally extended residues TEWT at the carboxyl terminus of OVA_ 257-264 ). Flow cytometric analysis was used to detect time-dependent kinetics of MHC class Ⅰ antigen presentation by APC fed with these peptides. Results The exogenous peptides which were artificially fused with a carboxyl-terminal KDEL sequence, could be efficiently presented by intracellular MHC class Ⅰ molecules, and retain the capacity of APCs to display surface MHC/peptide complexes for a prolonged period. Conclusion The ER retrieval signal modification can be regarded as a novel method for targeting exogenous peptides into the intracellular MHC class Ⅰ presentation pathway, and may improve the molecule design of CTL epitope based-peptide vaccines.
Directed Evolution of Bacillus subtilis Lipase A by Use of Enantiomeric Phosphonate Inhibitors: Crystal Structures and Phage Display Selection (2005)

Phage display can be used as a protein-engineering tool for the selection of proteins with desirable binding properties from a library of mutants. Here we describe the application of this method for the directed evolution of Bacillus subtilis lipase A, an enzyme that has important properties for the preparation of the pharmaceutically relevant chiral compound 1,2-O-isopropylidene-sn-glycerol (IPG). PCR mutagenesis with spiked oligonucleotides was employed for saturation mutagenesis of a stretch of amino acids near the active site. After expression of these mutants on bacteriophages, dual selection with (S)-(+)- and (R)-(-)-IPG stereoisomers covalently coupled to enantiomeric phosphonate suicide inhibitors (SIRAN Sc and Rc inhibitors, respectively) was used for the isolation of variants with inverted enantioselectivity. The mutants were further characterised by determination of their Michaelis-Menten parameters. The 3D structures of the Sc and Rc inhibitor-lipase complexes were determined and provided structural insight into the mechanism of enantioselectivity of the enzyme. In conclusion, we have used phage display as a fast and reproducible method for the selection of Bacillus lipase A mutant enzymes with inverted enantioselectivity.
Prospects for Clinical Application of Electronic-Nose Technology to Early Detection of Mycobacterium tuberculosis in Culture and Sputum (2006)

Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) is time-consuming and operator dependent and lacks sensitivity. A new method is urgently needed. We investigated the potential of an electronic nose (EN) (gas sensor array) comprising 14 conducting polymers to detect different Mycobacterium spp. and Pseudomonas aeruginosa in the headspaces of cultures, spiked sputa, and sputum samples from 330 culture-proven and human immunodeficiency virus-tested TB and non-TB patients. The data were analyzed using principal-component analysis, discriminant function analysis, and artificial neural networks. The EN differentiated between different Mycobacterium spp. and between mycobacteria and other lung pathogens both in culture and in spiked sputum samples. The detection limit in culture and spiked sputa was found to be 1 x 10(4) mycobacteria ml(-1). After training of the neural network with 196 sputum samples, 134 samples (55 M. tuberculosis culture-positive samples and 79 culture-negative samples) were used to challenge the model. The EN correctly predicted 89% of culture-positive patients; the six false negatives were the four ZN-negative and two ZN-positive patients. The specificity and sensitivity of the described method were 91% and 89%, respectively, compared to culture. At present, the reasons for the false negatives and false positives are unknown, but they could well be due to the nonoptimized system used here. This study has shown the ability of an electronic nose to detect M. tuberculosis in clinical specimens and opens the way to making this method a rapid and automated system for the early diagnosis of respiratory infections.
Effect of Mobile Phase Additives on the Resolution of Four Bioactive Compounds by RP-HPLC (2010)

The use of mobile phase additives enhances the separation and resolution of the bioactive compounds on the C(18) column. Chlorogenic acid, caffeic acid, rutin, and scoparone from Herba Artemisiae Scopariae were investigated as the target compounds. Acetic acid, triethylamine, inorganic salts, and several ionic liquids were added as mobile phase additives into methanol/water (40:60, v/v). The result revealed that a mobile phase with 0.01 mol/L of ionic liquid [BMIM][BF(4)] enabled the optimum separation of the four target compounds.