gebhart/patrepeval huggingface dataset:
Expression of stem cell factor and c-kit in human neuroblastoma. The Children's Cancer Group (1994)

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Because melanocytes derive from neural crest cells, the role of SCF and c-kit was investigated in the neural crest-derived childhood tumor neuroblastoma. Using reverse transcription-polymerase chain reaction analysis, simultaneous expression of steady-state mRNA for the SCF ligand and its receptor c-kit was found in 14 of 14 (100%) human neuroblastoma cell lines and clones and in 8 of 18 (45%) human neuroblastoma tumor samples. Functional blockade of c-kit receptors in the cell lines SK-N-BE(2) and SH-SY5Y using the mouse monoclonal anti-c-kit antibody SR-1 resulted in a significant decrease in cellular growth rate when measured by either 3H-thymidine incorporation or clonogenicity. In addition, higher levels of c-kit mRNA expression were associated with parental neuroblastoma cell lines and subclones with a neuronal (N) differentiation phenotype, whereas lower levels of c-kit mRNA were associated with neuroblastoma cell line subclones having a schwannian/glial/melanocytic pattern of differentiation. However, the differentiation phenotype of neuroblastoma cell lines was not directly altered when c-kit expression was blocked using the SR-1 antibody. In summary, these data indicate that c-kit receptor expression may play a significant role in the growth regulation of the two neuroblastoma cell lines examined and suggest that c-kit may also play a similar role in neuroblastoma growth regulation in vivo. Simultaneous expression of SCF and c-kit mRNA in both neuroblastoma cell lines and tumors implies that c-kit may act as part of an autocrine growth loop in conjunction with endogenous production of SCF in this disease.
PNA for One-Base Differentiating Protection of DNA from Nuclease and Its Use for SNPs Detection (2003)

By the combination of peptide nucleic acid (PNA) with single-stranded DNA specific nucleases, alteration of a single base to another in DNA has been detected with high accuracy. Only the DNAs in DNA/PNA duplexes involving a mismatch are efficiently hydrolyzed by these enzymes, whereas fully matching sequences are kept intact. This difference is visually scored by adding 3,3'-diethylthiadicarbocyanine, which changes its color from blue to purple upon binding to DNA/PNA duplexes. These findings are applied to the convenient and straightforward detection of single nucleotide polymorphisms (SNPs). When the target site in the sample DNA is completely complementary with the PNA, a notable amount of DNA/PNA duplex remains and thus the solution exhibits purple color. In the presence of even one mismatch between PNA and DNA, however, the DNA is completely digested by the enzyme and therefore the dye shows its intrinsic blue color. The SNPs in the apolipoprotein E gene of human DNA have been successfully genotyped by this method.
Engineered Proteolytic Nanobodies Reduce Aβ Burden and Ameliorate Aβ-Induced Cytotoxicity (2010)

Deposition of beta-amyloid (Abeta) is considered an important early event in the pathogenesis of Alzheimer's disease (AD), and reduction of Abeta levels in the brain could be a viable therapeutic approach. A potentially noninflammatory route to facilitate clearance and reduce toxicity of Abeta is to degrade the peptide using proteolytic nanobodies. Here we show that a proteolytic nanobody engineered to cleave Abeta at its alpha-secretase site has potential therapeutic value. The Asec-1A proteolytic nanobody, derived from a parent catalytic light chain antibody, prevents aggregation of monomeric Abeta, inhibits further aggregation of preformed Abeta aggregates, and reduces Abeta-induced cytotoxicity toward a human neuroblastoma cell line. The nanobody also reduces toxicity induced by overexpression of the human amyloid precursor protein (APP) in a Chinese hamster ovary (CHO) cell line by cleaving APP at the alpha-secretase site which precludes formation of Abeta. Targeted proteolysis of APP and Abeta with catalytic nanobodies represents a novel therapeutic approach for treating AD where potentially harmful side effects can be minimized.
Recent Advances in Lewis Acid Catalyzed Diels−Alder Reactions in Aqueous Media (2001)

Recently the aqueous medium has attracted the interest of organic chemists, and many, sometimes surprising, discoveries have been made. Among the organic reactions investigated in aqueous medium, the Diels−Alder cycloaddition has been the most widely studied because of its great importance in the synthetic and theoretical fields. The Diels−Alder reaction is greatly enhanced by Lewis acid catalysis, and this review illustrates recent significant results in this field when the reaction is performed in aqueous medium.
Synergism Between Mycophenolate Mofetil and Cyclosporine in Preventing Graft-Versus-Host Disease Among Lethally Irradiated Dogs Given DLA-Nonidentical Unrelated Marrow Grafts (1998)

Abstract Mycophenolate mofetil (MMF) was evaluated either alone or combined with cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts. Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four groups were studied for GVHD prevention: six dogs in group 1 received MMF 10 mg/kg twice daily subcutaneously (SC) on days 0 to 27. They died between 8 to 28 days from infection or GVHD; survival was better than that of 72 controls given no immunosuppression (P = .04), but not different from 19 dogs given CSP. Four dogs in group 2 received MMF as described, along with CSP at 10 to 15 mg/kg twice daily on days 0 to 27. They died at 6 to 98 days from CSP-associated toxicity, weight loss, or infection. Nine dogs in group 3 received MMF SC twice daily 6 mg/kg/d for 3 days, followed by 10 mg/kg twice daily until day 27, along with CSP as described; four died between 7 to 106 days with intussusception, infection, or GVHD, and five became long-term survivors. Six dogs in group 4 received shortened MMF (21 days) and reduced doses of CSP given through day 100. Three died with GVHD or infection between days 38 to 119, and three became long-term survivors. Results support the notion of synergism between MMF and CSP, as evidenced by stable graft-host tolerance in greater than 50% of dogs.
Novel zirconium complexes of amine bis(phenolate) ligands. Remarkable reactivity in polymerization of hex-1-ene due to an extra donor arm (2000)

Zirconium complexes of two dianionic amine bis(phenolate) ligands have been synthesized, their X-ray structures solved, and their activity as hex-1-ene polymerization catalysts studied; upon treatment with B(C6F5)3, an octahedral [ONNO]Zr(CH2Ph)2 complex, having an extra N-donor group on a side arm, shows exceptionally high polymerization activity and yields a high molecular weight poly(hex-1-ene), whereas a related pentacoordinate [ONO]Zr(CH2Ph)2 complex, having no extra donor group, shows only poor activity as a polymerization catalyst.
Enzyme-Triggered Self-Assembly of Peptide Hydrogels via Reversed Hydrolysis (2006)

We demonstrate that proteases can be used to selectively trigger the self-assembly of peptide hydrogels via reversed hydrolysis.
Efficient scalar quantization of exponential and Laplacian random variables (1996)

This paper presents solutions to the entropy-constrained scalar quantizer (ECSQ) design problem for two sources commonly encountered in image and speech compression applications: sources having the exponential and Laplacian probability density functions. We use the memoryless property of the exponential distribution to develop a new noniterative algorithm for obtaining the optimal quantizer design. We show how to obtain the optimal ECSQ either with or without an additional constraint on the number of levels in the quantizer. In contrast to prior methods, which require a multidimensional iterative solution of a large number of nonlinear equations, the new method needs only a single sequence of solutions to one-dimensional nonlinear equations (in some Laplacian cases, one additional two-dimensional solution is needed). As a result, the new method is orders of magnitude faster than prior ones. We show that as the constraint on the number of levels in the quantizer is relaxed, the optimal ECSQ becomes a uniform threshold quantizer (UTQ) for exponential, but not for Laplacian sources. We then further examine the performance of the UTQ and optimal ECSQ, and also investigate some interesting alternatives to the UTQ, including a uniform-reconstruction quantizer (URQ) and a constant dead-zone ratio quantizer (CDZRQ).
Alanine dehydrogenases from two Bacillus species with distinct thermostabilities: molecular cloning, DNA and protein sequence determination, and structural comparison with other NAD(P)+-dependent dehydrogenases (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlanine dehydrogenases from two Bacillus species with distinct thermostabilities: molecular cloning, DNA and protein sequence determination, and structural comparison with other NAD(P)+-dependent dehydrogenasesShunichi Kuroda, Katsuyuki Tanizawa, Hidehiko Tanaka, Kenji Soda, and Yonekazu SakamotoCite this: Biochemistry 1990, 29, 4, 1009–1015Publication Date (Print):January 30, 1990Publication History Published online1 May 2002Published inissue 30 January 1990https://pubs.acs.org/doi/10.1021/bi00456a025https://doi.org/10.1021/bi00456a025research-articleACS PublicationsRequest reuse permissionsArticle Views240Altmetric-Citations54LEARN 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
A new chip-level differential detection system for DS-CDMA (2003)

In this paper we mathematically prove that if the original spreading Pseudo-Noise (PN) code is an m-sequence or a Gold-sequence, then the chip-by-chip differential decoding (CBCDD) sequence of the original PN code is a cyclic shift version of the original PN sequence. By utilizing this property, we design a new chip-level differential detection system for DS-CDMA, which does not require any chip-level differential encoding in the transmitter. We demonstrate simplicity of implementation and robust operation in the presence of carrier frequency shift.
Signal bias removal for robust telephone based speech recognition in adverse environments (2002)

A speech signal transmitted through a telephone channel often encounters variable conditions which significantly deteriorate the performance of state-of-the-art HMM-based speech recognition systems. Undesirable components due to ambient noise and channel interference, as well as different sound pick-up equipments, render the recognizer unsuitable for real-world applications. This paper presents a signal bias removal method based on the maximum likelihood estimation for the minimization of these undesirable effects. The proposed method, integrated into a discrete density HMM, is applied to telephone speech recognition where the contamination due to ambient noise and channel distortion are assumed to be unknown. Experimental results are presented for speaker-independent connected digit recognition which demonstrate a reduction in the word error rate by up to 40%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of a Nontoxic Monophosphoryl Lipid A (1987)

Gram-negative bacterial endotoxins constitute some of the strongest immunologic adjuvants known. Precluding their use as adjuvants in humans has been the exquisite toxicity of these compounds in extraordinarily small amounts. With the acquisition of precise knowledge of the structure of the active moiety, detoxifying procedures have been developed. These have resulted in the isolation of a monophosphoryl lipid A with a much reduced toxicity that retains the capacity to act as an adjuvant in young mice as well as in immunodeficient aging mice.
Site-specific enzymic incorporation of an unnatural base, N6-(6-aminohexyl)isoguanosine, into RNA (1993)

An efficient enzymatic method is described for the sequence-specific incorporation of a functionalizable modified base into RNA molecules. A deoxy-5-methylisocytidine (d^(Me)isoC) in the DNA template directs the T7 RNA polymerase incorporation of N^6-(6-aminohexyl)isoguanosine (6-AH-isoG) into the transcribed RNA product. The misincorporation of isoGTP derivatives opposite T is eliminated in the presence of ATP, and the misincorporation of A opposite d^(Me)isoC is negligible in the presence of isoGTP derivatives. The isolated yield of RNA products using modified templates is approximately 50% that for reactions using natural templates. A post-transcriptional modification of the reactive primary amino group with N-hydroxysuccinimide-activated biotin or the dianhydride of ethylenediaminetetraacetic acid affords site-specifically modified RNA sequences suitable for further studies. This method for the generation of RNA molecules containing a primary amine suitable for post-transcriptional modification should be useful for mapping the structure of folded RNA polymers and RNA-protein complexes by affinity cleavage and affinity labeling.
Preparation of a [60]fullerene derivative containing a fused seven-membered ring (1998)

[60]Fullerene reacts with 1,8-bis(bromomethyl)naphthalene in the presence of KI/18-crown-6 to form a C60 derivative with a seven-membered ring fused to a [6,6] junction.
A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins (2011)

The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
Thrombosis in paroxysmal nocturnal hemoglobinuria (2013)

The most frequent and feared complication of paroxysmal nocturnal hemoglobinuria (PNH) is thrombosis. Recent research has demonstrated that the complement and coagulation systems are closely integrated with each influencing the activity of the other to the extent that thrombin itself has recently been shown to activate the alternative pathway of complement. This may explain some of the complexity of the thrombosis in PNH. In this review, the recent changes in our understanding of the pathophysiology of thrombosis in PNH, as well as the treatment of thrombosis, will be discussed. Mechanisms explored include platelet activation, toxicity of free hemoglobin, nitric oxide depletion, absence of other glycosylphosphatidylinositol-linked proteins such as urokinase-type plasminogen activator receptor and endothelial dysfunction. Complement inhibition with eculizumab has a dramatic effect in PNH and has a major impact in the prevention of thrombosis as well as its management in this disease.
New Aspects of Siglec Binding Specificities, Including the Significance of Fucosylation and of the Sialyl-Tn Epitope (2000)

The siglecs (sialic acid-binding immunoglobulin superfamily lectins) are immunoglobulin superfamily members recognizing sialylated ligands. Most prior studies of siglec specificities focused on alpha2-3- and alpha2-6-sialyllactos(amin)es and on one or two of the siglecs at a time. Here, we explore several new aspects of specificities of the first six reported siglecs, using sialylated glycans presented in multivalent form, on synthetic polyacrylamide backbones, or on mucin polypeptides. First, we report that binding of siglec-1 (sialoadhesin), siglec-3 (CD33), siglec-4a (myelin-associated glycoprotein), and siglec-5 to alpha2-3 sialyllactosamine is affected markedly by the presence of an alpha1-3-linked fucose. Thus, while siglecs may not interfere with selectin-mediated recognition, fucosylation could negatively regulate siglec binding. Second, in contrast to earlier studies, we find that siglec-3 prefers alpha2-6-sialyllactose. Third, siglec-5 binds alpha2-8-linked sialic acid, making it the siglec least specific for linkage recognition. Fourth, siglecs-2 (CD22), -3, -5, and -6 (obesity-binding protein 1) showed significant binding to sialyl-Tn (Neu5Acalpha2-6-GalNAc), a tumor marker associated with poor prognosis. Fifth, siglec-6 is an exception among siglecs in not requiring the glycerol side chain of sialic acid for recognition. Sixth, all siglecs require the carboxyl group of sialic acid for binding. Finally, the presentation of the sialyl-Tn epitope and/or more extended structures that include this motif may be important for optimal recognition by the siglecs. This was concluded from studies using ovine, bovine, and porcine submaxillary mucins and Chinese hamster ovary cells transfected with ST6GalNAc-I and/or the mucin polypeptide MUC1.
A Nevv Method of Third-Order Intermodulation Reduction in Nonlinear Microwave Systems (1986)

Third-order intermodulation distortion (IMD (3)) of some microwave systems has been analyzed using Vollterra series. In this paper, theoretical results which have been calculated with a nonlinear FET model show that third-order intermodulation prodgcts of two input signals at f/sub 1/ and f/sub 2/ can be reduced by several orders of magnitude (in fact, theoretically, IMD (3) should be reduced to zero), with a low-frequency feedback at f/sub 1/- f/sub 2/, when the amplitude and the phase of this feedback are correctly chosen. To verify this prediction, a circuit has been realized and measurements have been made on a one-stage FET amplifier. First results confirm our analysis. Experimental measurements show a 12-dB decrease of intermodulation products with our method.
A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent (2007)

The most abundant and biologically active green tea catechin, (-)-epigallocatechin-3-gallate or (-)-EGCG, has been shown to act as a proteasome inhibitor and tumor cell death inducer. However, (-)-EGCG is unstable under physiologic conditions and has poor bioavailability. Previously, in an attempt to increase the stability of (-)-EGCG, we introduced peracetate protections to its reactive hydroxyl groups and showed that this peracetate-protected (-)-EGCG [Pro-EGCG (1); formerly named compound 1] could be converted into (-)-EGCG under cell-free conditions. In the current study, we provide evidence that when cultured human breast cancer MDA-MB-231 cells were treated with Pro-EGCG (1), (-)-EGCG was not only converted but also accumulated, accompanied by enhanced levels of proteasome inhibition, growth suppression, and apoptosis induction, compared with cells treated with natural (-)-EGCG. To investigate the potential use of Pro-EGCG (1) as a novel prodrug that converts to a cellular proteasome inhibitor and anticancer agent in vivo, MDA-MB-231 tumors were induced in nude mice, followed by treatment with Pro-EGCG (1) or (-)-EGCG for 31 days. Results of this in vivo study showed a significant inhibition of breast tumor growth by Pro-EGCG (1), compared with (-)-EGCG, associated with increased proteasome inhibition and apoptosis induction in tumor tissues. In conclusion, we have shown that Pro-EGCG (1) increases the bioavailability, stability, and proteasome-inhibitory and anticancer activities of (-)-EGCG in human breast cancer cells and tumors, suggesting its potential use for cancer prevention and treatment.
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome (2017)

Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375 .).
Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy (2019)

The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the application of CAR-T cells has been limited by antigen escape and on-target, off-tumor toxicities. Therefore, it may be a potentially effective strategy to select appropriate targets and to combine multi-antigen-targeted CAR-T cells with "OR", "AND" and "NOT" Boolean logic gates. We summarize the current limitations of CAR-T cells as well as the efficacy and safety of logic-gated CAR-T cells in antitumor therapy. This review will help to explore more optimized strategies to expand the CAR-T cell therapeutic window.
High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. (1979)

A set of vector DNAs (Y vectors) useful for the cloning of DNA fragments in Saccharomyces cerevisiae (yeast) and in Escherichia coli are characterized. With these vectors, three modes of yeast transformation are defined. (i) Vectors containing yeast chromosomal DNA sequences (YIp1, YIp5) transform yeast cells at low frequency (1--10 colonies per microgram) and integrate into the genome by homologous recombination; this recombination is reversible. (ii) Hybrids containing endogenous yeast plasmid DNA sequences (YEp2, YEp6) transform yeast cells at much higher frequency (5000--20,000 colonies per microgram). Such molecules replicate autonomously with an average copy number of 5--10 covalently closed circles per yeast cell and also replicate as a chromosomally integrated structure. This DNA may be physically isolated in intact form from either yeast or E. coli and used to transform either organism at high frequency. (iii) Vectors containing a 1.4-kilobase yeast DNA fragment that includes the centromere linked trp1 gene (YRp7) transform yeast with an efficiency of 500--5000 colonies per microgram; such molecules behave as minichromosomes because they replicate autonomously but do not integrate into the genome. The uses of Y vectors for the following genetic manipulations in yeast are discussed: isolation of genes; construction of haploid strains that are merodiploid for a particular DNA sequence; and directed alterations of the yeast genome. General methods for the selection and the analysis of these events are presented.