gebhart/patrepeval huggingface dataset:
Specific detection of DNA and RNA targets using a novel isothermal nucleic acid amplification assay based on the formation of a three-way junction structure (2001)

The formation of DNA three-way junction (3WJ) structures has been utilised to develop a novel isothermal nucleic acid amplification assay (SMART) for the detection of specific DNA or RNA targets. The assay consists of two oligonucleotide probes that hybridise to a specific target sequence and, only then, to each other forming a 3WJ structure. One probe (template for the RNA signal) contains a non-functional single-stranded T7 RNA polymerase promoter sequence. This promoter sequence is made double-stranded (hence functional) by DNA polymerase, allowing T7 RNA polymerase to generate a target-dependent RNA signal which is measured by an enzyme-linked oligosorbent assay (ELOSA). The sequence of the RNA signal is always the same, regardless of the original target sequence. The SMART assay was successfully tested in model systems with several single-stranded synthetic targets, both DNA and RNA. The assay could also detect specific target sequences in both genomic DNA and total RNA from Escherichia coli. It was also possible to generate signal from E.coli samples without prior extraction of nucleic acid, showing that for some targets, sample purification may not be required. The assay is simple to perform and easily adaptable to different targets.
One Process to Reap Them All (2017)

Ubiquitous mobile platforms such as Android rely on managed language run-time environments, also known as language virtual machines (VMs), to run a diverse range of user applications (apps). Each app runs in its own private VM instance, and each VM makes its own private local decisions in managing its use of processor and memory resources. Moreover, the operating system and the hardware do not communicate their low-level decisions regarding power management with the high-level app environment. This lack of coordination across layers and across apps restricts more effective global use of resources on the device.
Immunohistochemical detection and quantitation of P-glycoprotein in multiple drug-resistant human myeloma cells: association with level of drug resistance and drug accumulation (1989)

Using several multiple drug-resistant human myeloma cell lines as standards, we developed an immunohistochemical staining technique and means of quantitating P-glycoprotein in individual myeloma cells. The level of staining intensity for P-glycoprotein in individual myeloma cells was quantitated by measuring the average optical density of each cell with a microscopic computerized cell analysis system. Using this system, we observed that the level of P-glycoprotein for individual cells within a cell population of known drug sensitivity was very homogeneous (coefficient of variation less than or equal to 13%). Analysis of cell lines with gradually increasing levels of multidrug resistance (8226/S, 8226/Dox6 and 8226/Dox40) demonstrated a close association between the level of resistance to doxorubicin, defined by the mean lethal dose (D0) and the amount of P-glycoprotein on individual cells determined by the optical density (r = 0.82, P less than 0.0005). Intracellular doxorubicin (DOX) accumulation in the individual cell lines was inversely related to the level of drug resistance expressed as D0. P-glycoprotein was also detected in the marrow-derived myeloma cells of patients with drug refractory disease using immunohistochemical staining. The amount of P-glycoprotein in the cells of one patient was directly compared to the amount found in the simultaneously stained standard cell lines (8226/Dox6 and 8226/Dox40) by comparing the optical densities for individual cells. Using this immunohistochemical technique to detect and quantitate P-glycoprotein in patient myeloma cells and comparing it to standard multidrug resistant myeloma cell lines may be of value in determining the contribution of P-glycoprotein to clinical drug resistance in patients with multiple myeloma.
Resistance to CDK2 Inhibitors Is Associated with Selection of Polyploid Cells in CCNE1 -Amplified Ovarian Cancer (2013)

These findings suggest that cyclinE1/CDK2 is an important therapeutic target in HGSC, but that resistance to CDK2 inhibitors may emerge due to upregulation of CDK2 target protein and through preexisting cellular polyploidy.
Novel Synthesis of the Main Central 2,3,6-Trisubstituted Pyridine Skeleton [Fragment A-B-C] of a Macrobicyclic Antibiotic, Cyclothiazomycin (2002)

Abstract The useful synthesis of the main central 2,3,6-trisubstituted pyridine skeleton [the protected Fragment A-B-C] of a macrobicyclic antibiotic, cyclothiazomycin, was first accomplished. First, the 2-[2-(2-substituted thiazol-4-yl)]-4,5-dihydrothiazole-4-carboxylate [Fragment A derivative], attached to the 6-substituent of the main pyridine skeleton, was synthesized by two consecutive thiazolations of the protected Ser thioamide derivative with 3-bromopyruvate, and then thiazolination of the C-terminal Ser residue of the sequence. Secondly, an efficient synthesis of the central 2-(2-{2-[(1R)-1-aminoethyl]pyridin-6-yl}thiazol-4-yl)-4,5-dihydrothiazole-4-carboxylate [Fragment B derivative] was also achieved by thiazolation of the formyl group of the 2-(1-aminoethyl)-6-formylpyridine derivative, and then thiazolination. Thirdly, a convenient synthesis of the protected dehydrotetrapeptide [Fragment C derivative], which is bound to the 2-substituent of the pyridine skeleton, was attained by the usual stepwise elongation of the appropriate α-amino acids and β-elimination of a Thr residue of the sequence. Finally, the facile fragment condensation of the three Fragments thus obtained gave the protected Fragment A-B-C derivative via Fragment A-B. Furthermore, the configurational structures of the three Fragments (A, B, and C) were also investigated.
CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4. (1993)

Type 1 and type 2 cloned T helper (Th) cells are believed to require different antigen-presenting cell (APC)-derived costimuli for proliferation. In the case of Th1-cloned T cells, CD28 signaling costimulates production of autocrine interleukin 2 (IL-2). Th2 cells produce their autocrine growth factor, IL-4, without costimulation, but require APC-derived costimuli, or IL-1, to respond to IL-4. Here we demonstrate that engagement of CD28 on Th2 cells with anti-CD28 antibody or with APC-associated B7 costimulates Th2 responsiveness to IL-4 but does not affect IL-4 or IL-2 production by Th2 cells. Costimulation of Th2 cells via CD28 appears to involve the induction of IL-1 production by Th2 cells, which acts in an autocrine fashion to induce IL-4 responsiveness. These results suggest that CD28-induced costimulation plays an important role in responses mediated by both types of Th cells.
Attention, intentions, and the structure of discourse (1986)

In this paper we explore a new theory of discourse structure that stresses the role of purpose and processing in discourse. In this theory, discourse structure is composed of three separate but interrelated components: the structure of the sequence of utterances (called the linguistic structure), a structure of purposes (called the intentional structure), and the state of focus of attention (called the attentional state). The linguistic structure consists of segments of the discourse into which the utterances naturally aggregate. The intentional structure captures the discourse-relevant purposes, expressed in each of the linguistic segments as well as relationships among them. The attentional state is an abstraction of the focus of attention of the participants as the discourse unfolds. The attentional state, being dynamic, records the objects, properties, and relations that are salient at each point of the discourse. The distinction among these components is essential to provide an adequate explanation of such discourse phenomena as cue phrases, referring expressions, and interruptions.The theory of attention, intention, and aggregation of utterances is illustrated in the paper with a number of example discourses. Various properties of discourse are described, and explanations for the behavior of cue phrases, referring expressions, and interruptions are explored.This theory provides a framework for describing the processing of utterances in a discourse. Discourse processing requires recognizing how the utterances of the discourse aggregate into segments, recognizing the intentions expressed in the discourse and the relationships among intentions, and tracking the discourse through the operation of the mechanisms associated with attentional state. This processing description specifies in these recognition tasks the role of information from the discourse and from the participants' knowledge of the domain.
Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process. (1984)

We have constructed phage lambda and plasmid DNA substrates (lambda tk2 and ptk2) that contain two defective herpesvirus thymidine kinase (tk) genes that can be used to detect homologous recombination during the transfer of DNA into mouse L cells deficient in thymidine kinase activity. The recombination event reconstructs a wild-type tk gene and is scored because it converts Tk- cells to Tk+. Using this system, we have shown that (i) both intramolecular and intermolecular homologous recombination can be detected after gene transfer; (ii) the degree of recombination decreases with decreasing tk gene homology; and (iii) the efficiency of recombination can be stimulated 10- to 100-fold by cutting the tk2 DNA with restriction enzymes at appropriate sites relative to the recombining sequences. Based on the substrate requirements for these recombination events, we propose a model to explain how recombination might occur in mammalian cells. The essential features of the model are that the cut restriction site ends are substrates for cellular exonucleases that degrade DNA strands. This process exposes complementary strands of the two defective tk genes, which then pair. Removal of unpaired DNA at the junction between the paired and unpaired regions permits a gap repair process to reconstruct an intact gene.
Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors (2006)

CD30 is a member of the tumor necrosis factor receptor family. Overexpression of CD30 on some neoplasms versus its limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Anaplastic large-cell lymphoma (ALCL) represents a heterogeneous group of aggressive non-Hodgkin lymphomas characterized by the strong expression of CD30. We investigated the therapeutic efficacy of HeFi-1, a mouse IgG1 monoclonal antibody, which recognizes the ligand-binding site on CD30, and humanized anti-Tac antibody (daclizumab), which recognizes CD25, in a murine model of human ALCL. The ALCL model was established by intravenous injection of karpas299 cells into nonobese diabetic/severe combined immuno-deficient (SCID/NOD) wild-type or SCID/NOD Fc receptor common gamma chain-deficient (FcRgamma(-/-)) mice. HeFi-1, given at a dose of 100 microg weekly for 4 weeks, significantly prolonged survival of the ALCL-bearing SCID/NOD wild-type and SCID/NOD FcRgamma(-/-) mice (P < .01) as compared with the control groups. In vitro studies showed that HeFi-1 inhibited the proliferation of karpas299 cells, whereas daclizumab did not inhibit cell proliferation. We demonstrated that the expression of FcRgamma on polymorphonuclear leukocytes and monocytes was not required for HeFi-1-mediated tumor growth inhibition in vivo, although it was required for daclizumab.
P3‐225: Whole‐genome SNP linkage screen for dementia in the midwestern U.S. Amish (2008)

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. While evidence for an underlying genetic etiology of AD is strong, it has proven to be quite challenging to elucidate. The APOE gene accounts for less than half of the susceptibility and thus other genetic factors are likely to be involved. Genetic heterogeneity is a major complicating factor hindering further gene identification. To overcome this problem and maximize our power to identify AD risk genes, we are studying the genetically isolated and well-defined Amish populations of middle Ohio and northern Indiana. To date we have enrolled over 1550 Amish individuals with over 100 of these having either probable or possible dementia. We have undertaken a whole-genome SNP linkage screen (Illumina Linkage Panel IVb) using 672 Amish individuals (103 with AD) within 21 sub-pedigrees ranging in total size from 18 to 157 individuals. We performed both 2-pt linkage analysis (using dominant and recessive models within the Superlink program) and a novel test of association using the MQLS test (by Thornton & McPeek), on 5,645 SNPs. Preliminary linkage analysis found 162 SNPs with 2-pt lod scores >1.0. Suggestive linkage to AD was found for 18 SNPs across 16 independent loci (2-pt lod scores >2.0: 1q, 2p, 2q, 3q22, 3q26, 4q, 5q, 7q, 8p, 13q, 14q23, 14q24, 16p, 18q, 20q, 21q). The MQLS test also identified 284 SNPs with nominally significant p-values (p≤0.05). Subsequently, we utilized the Simwalk program to perform multipoint linkage analysis for multiple 3-SNP sliding windows across each of the regions identified by the 2-pt analysis. Five of these regions continued to demonstrate strong evidence for linkage (1q, 3q22, 5q, 18q, and 21q), with three of these also demonstrating MQLS p-values ≤0.05 (1q, 3q22, 18q). Additional follow-up of these more narrowed regions is currently ongoing. Our genome scan suggests that a number of regions within our Amish population may contain AD susceptibility genes, with the strongest current evidence suggesting involvement of chr 1q, 3q, and 18q.
Chitotriosidase, a chitinase, and the 39‐kDa human cartilage glycoprotein, a chitin‐binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages (1998)

In various mammals, enzymatically active and inactive members of family 18 glycosyl hydrolases, containing chitinases, have been identified. In man, chitotriosidase is the functional chitinolytic enzyme, whilst the homologous human cartilage 39-kDa glycoprotein (HC gp-39) does not exhibit chitinase activity and its function is unknown. This study establishes that HC gp-39 is a chitin-specific lectin. It is experimentally demonstrated that a single amino acid substitution in the catalytic centre of the 39-kDa isoform of chitotriosidase, which generates a similar sequence to that in HC gp-39, results in a loss of hydrolytic activity and creates the capacity to bind to chitin. The possible implication of the finding for chitinolytic and chitin-binding proteins that are produced in high quantities by activated macrophages are discussed.
Neutrophils produce biologically active macrophage inflammatory protein-3α (MIP-3α) / CCL20 and MIP-3β / CCL19 (2001)

Macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we have reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GROalpha/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3alpha/CCL20 and MIP-3beta/CCL19 when cultured with either LPS or TNF-alpha. We also report that MIP-3alpha/CCL20 and MIP-3beta/CCL19 production by LPS-stimulated neutrophils is negatively modulated by IL-10. Remarkably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion were dramatically suppressed by anti-MIP-3alpha/CCL20 and anti-MIP-3beta/CCL19 neutralizing antibodies, indicating that MIP-3alpha/CCL20 and MIP-3beta/CCL19 present in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the ability of neutrophils to produce MIP-3alpha/CCL20 and MIP-3beta/CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immune response.
N‐linked glycosylation is an important parameter for optimal selection of cell lines producing biopharmaceutical human IgG (2009)

We studied the variations in N-linked glycosylation of human IgG molecules derived from 105 different stable cell lines each expressing one of the six different antibodies. Antibody expression was based on glutamine synthetase selection technology in suspension growing CHO-K1SV cells. The glycans detected on the Fc fragment were mainly of the core-fucosylated complex type containing zero or one galactose and little to no sialic acid. The glycosylation was highly consistent for the same cell line when grown multiple times, indicating the robustness of the production and glycan analysis procedure. However, a twofold to threefold difference was observed in the level of galactosylation and/or non-core-fucosylation between the 105 different cell lines, suggesting clone-to-clone variation. These differences may change the Fc-mediated effector functions by such antibodies. Large variation was also observed in the oligomannose-5 glycan content, which, when present, may lead to undesired rapid clearance of the antibody in vivo. Statistically significant differences were noticed between the various glycan parameters for the six different antibodies, indicating that the variable domains and/or light chain isotype influence Fc glycosylation. The glycosylation altered when batch production in shaker was changed to fed-batch production in bioreactor, but was consistent again when the process was scaled from 400 to 5,000 L. Taken together, the observed clone-to-clone glycosylation variation but batch-to-batch consistency provides a rationale for selection of optimal production cell lines for large-scale manufacturing of biopharmaceutical human IgG.
Size-Dependent Melting Properties of Small Tin Particles: Nanocalorimetric Measurements (1996)

For the first time, the latent heat of fusion $\ensuremath{\Delta}{H}_{m}$ for Sn particles formed by evaporation on inert substrate with radii ranging from 5 to 50 nm has been measured directly using a novel scanning nanocalorimeter. A particle-size-dependent reduction of $\ensuremath{\Delta}{H}_{m}$ has been observed. An ``excluded volume'' is introduced to describe the latent heat of fusion from the enhanced surface melting of small particles. Melting point depression has also been found by our nanocalorimetric technique.
Cryo-Transmission Electron Microscopy Confirms Controlled Synthesis of Cadmium Sulfide Nanocrystals within Lecithin Vesicles (1998)

Size-quantized CdS nanocrystals of controlled dimensions are synthesized within monodisperse egg lecithin vesicles made by detergent depletion. Cryo-transmission electron microscopy (cryo-TEM) enables imaging in situ both of the vesicle wall and of the encapsulated nanocrystal. Cryo-TEM images confirm that only one particle per vesicle forms and that nanocrystal diameter is determined by the number of Cd2+ ions initially encapsulated. These micrographs further show that the particles adsorb to the inner surface of the vesicle membrane, which suggests that crystal growth and particle core structure could be controlled through manipulation of vesicle bilayer chemistry.
MPEG-4 Low Delay Audio Coding Based on the AAC Codec (1999)

Perceptual audio coding is known to deliver high sound quality even at low bit rates for a broad range of audio signals. However, the total delay of the encoder/decoder chain is usually considerably higher than acceptable for two-way communication applications, such as teleconferencing. This paper discusses the primary sources of algorithmic delay in a perceptual audio codec and describes an MPEG~2 AAC-derived codec which was optimized for very low delay and accepted as the baseline of development for low-delay coding in MPEG-4 version 2 audio.
Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus (2013)

Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).
Three‐dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy (2012)

The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.
Sequential production of interferon-γ by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of α-galactosylceramide (2002)

The antimetastatic effect of the CD1d-binding glycolipid, alpha-galactosylceramide (alpha-GalCer), is mediated by NK1.1(+)T (NKT) cells; however, the mechanisms behind this process are poorly defined. Although it has been shown to involve NK cells and interferon-gamma (IFN-gamma) production, the way these factors collaborate to mediate effective tumor rejection and the importance of other factors characteristic of NKT cell and NK cell activation are unknown. Using gene-targeted mice and antibody treatments, the critical need for interleukin 12 (IL-12), IFN-gamma, and NK cells has been shown in the antimetastatic activity of alpha-GalCer in the lungs and the liver. By contrast, in lung and liver metastasis models, cytotoxic molecules expressed by NK cells and NKT cells (perforin, Fas ligand, and tumor necrosis factor-related apoptosis-inducing ligand) and an NKT cell-secreted cytokine, IL-4, were not necessary for the antitumor activity of alpha-GalCer. Like IL-12, IL-18 was required for optimal serum IFN-gamma induction and control of lung metastases by alpha-GalCer. IL-18 was unnecessary for alpha-GalCer-related suppression of liver metastases. Most importantly, after adoptive transfer of alpha-GalCer-reactive NKT cells or NK cells into NKT cell-deficient, IFN-gamma-deficient, or RAG-1-deficient mice, it was demonstrated that the sequential production of IFN-gamma by NKT cells and NK cells was absolutely required to reconstitute the antimetastatic activity of alpha-GalCer.