gebhart/patrepeval huggingface dataset:
Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease. (1991)

The rapid identification of mutations causing Tay-Sachs disease requires the capacity to readily screen the regions of the HEXA gene most likely to be affected by mutation. We have sequenced the portions of the introns flanking each of the 14 HEXA exons in order to specify oligonucleotide primers for the PCR-dependent amplification of each exon and splice-junction sequence. The amplified products were analyzed, by electrophoresis in nondenaturing polyacrylamide gels, for the presence of either heteroduplexes, derived from the annealing of normal and mutant DNA strands, or single-strand conformational polymorphisms (SSCP), derived from the renaturation of single-stranded DNA. Five novel mutations from Tay-Sachs disease patients were detected: a 5-bp deletion of TCTCC in IVS-9; a 2-bp deletion of TG in exon 5; G78 to A, giving a stop codon in exon 1; G533 to T in exon 5, producing the third amino acid substitution detected at this site; and G to C at position 1 of IVS-2, expected to produce abnormal splicing. In addition, two mutations, (G1496 to A in exon 13 and a 4-bp insertion in exon 11) that have previously been reported were identified.
Clinical Use of Irinotecan:Current Status and Future Considerations (1997)

Irinotecan (CPT-11, Camptosar), a semisynthetic, water-soluble derivative of the plant alkaloid camptothecin, is a drug which has undergone extensive clinical investigation worldwide. It is, at this time, commercially available in the United State for the treatment of fluorouracil-refractory colorectal cancer. In this review, I will discuss the current approved clinical use, discus the issues of toxicity and its management, and consider some of the ongoing clinical investigations which are exploring possible future uses for this agent.
Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase 2 gene family (2014)

Soybean oil is high in polyunsaturated fats and is often partially hydrogenated to increase its shelf life and improve oxidative stability. The trans-fatty acids produced through hydrogenation pose a health threat. Soybean lines that are low in polyunsaturated fats were generated by introducing mutations in two fatty acid desaturase 2 genes (FAD2-1A and FAD2-1B), which in the seed convert the monounsaturated fat, oleic acid, to the polyunsaturated fat, linoleic acid. Transcription activator-like effector nucleases (TALENs) were engineered to recognize and cleave conserved DNA sequences in both genes. In four of 19 transgenic soybean lines expressing the TALENs, mutations in FAD2-1A and FAD2-1B were observed in DNA extracted from leaf tissue; three of the four lines transmitted heritable FAD2-1 mutations to the next generation. The fatty acid profile of the seed was dramatically changed in plants homozygous for mutations in both FAD2-1A and FAD2-1B: oleic acid increased from 20% to 80% and linoleic acid decreased from 50% to under 4%. Further, mutant plants were identified that lacked the TALEN transgene and only carried the targeted mutations. The ability to create a valuable trait in a single generation through targeted modification of a gene family demonstrates the power of TALENs for genome engineering and crop improvement.
Prolate Spheroidal Wave Functions, Fourier Analysis, and Uncertainty-V: The Discrete Case (1978)

A discrete time series has associated with it an amplitude spectrum which is a periodic function of frequency. This paper investigates the extent to which a time series can be concentrated on a finite index set and also have its spectrum concentrated on a subinterval of the fundamental period of the spectrum. Key to the analysis are certain sequences, called discrete prolate spheroidal sequences, and certain functions of frequency called discrete prolate spheroidal functions. Their mathematical properties are investigated in great detail, and many applications to signal analysis are pointed out.
Hedgehog Signaling Promotes Prostate Xenograft Tumor Growth (2004)

During fetal prostate development, Sonic hedgehog (Shh) expression by the urogenital sinus epithelium activates Gli-1 expression in the adjacent mesenchyme and promotes outgrowth of the nascent ducts. Shh signaling is down-regulated at the conclusion of prostate ductal development. However, a survey of adult human prostate tissues reveals substantial levels of Shh signaling in normal, hyperplasic, and malignant prostate tissue. In cancer specimens, the Shh expression is localized to the tumor epithelium, whereas Gli-1 expression is localized to the tumor stroma. Tight correlation between the levels of Shh and Gli-1 expression suggests active signaling between the tissue layers. To determine whether Shh-Gli-1 signaling could be functionally important for tumor growth and progression, we performed experiments with the LNCaP xenograft tumor model and demonstrated that: 1). Shh expressed by LNCaP tumor cells activates Gli-1 expression in the tumor stroma, 2). genetically engineered Shh overexpression in LNCaP cells leads to increased tumor stromal Gli-1 expression, and 3). Shh overexpression dramatically accelerates tumor growth. These data suggest that hedgehog signaling from prostate cancer cells to the stroma can elicit the expression of paracrine signals, which promote tumor growth.
Fast algorithms for discrete and continuous wavelet transforms (1992)

Several algorithms are reviewed for computing various types of wavelet transforms: the Mallat algorithm (1989), the 'a trous' algorithm, and their generalizations by Shensa. The goal of this work is to develop guidelines for implementing discrete and continuous wavelet transforms efficiently, and to compare the various algorithms obtained and give an idea of possible gains by providing operation counts. Most wavelet transform algorithms compute sampled coefficients of the continuous wavelet transform using the filter bank structure of the discrete wavelet transform. Although this general method is already efficient, it is shown that noticeable computational savings can be obtained by applying known fast convolution techniques, such as the FFT (fast Fourier transform), in a suitable manner. The modified algorithms are termed 'fast' because of their ability to reduce the computational complexity per computed coefficient from L to log L (within a small constant factor) for large filter lengths L. For short filters, smaller gains are obtained: 'fast running FIR (finite impulse response) filtering' techniques allow one to achieve typically 30% savings in computations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins (2001)

The docking protein FRS2 is a major downstream effector that links fibroblast growth factor (FGF) and nerve growth factor receptors with the Ras/mitogen-activated protein kinase signaling cascade. In this report, we demonstrate that FRS2 also plays a pivotal role in FGF-induced recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase). We demonstrate that tyrosine phosphorylation of FRS2alpha leads to Grb2-mediated complex formation with the docking protein Gab1 and its tyrosine phosphorylation, resulting in the recruitment and activation of PI3-kinase. Furthermore, Grb2 bound to tyrosine-phosphorylated FRS2 through its SH2 domain interacts primarily via its carboxyl-terminal SH3 domain with a proline-rich region in Gab1 and via its amino-terminal SH3 domain with the nucleotide exchange factor Sos1. Assembly of FRS2alpha:Grb2:Gab1 complex induced by FGF stimulation results in activation of PI3-kinase and downstream effector proteins such as the S/T kinase Akt, whose cellular localization and activity are regulated by products of PI3-kinase. These experiments reveal a unique mechanism for generation of signal diversity by growth factor-induced coordinated assembly of a multidocking protein complex that can activate the Ras/mitogen-activated protein kinase cascade to induce cell proliferation and differentiation, and PI3-kinase to activate a mediator of a cell survival pathway.
The Chemistry of Methyl Vinyl Ketone. II. Reactions with Esters, β-Keto Esters, Malonic Ester, Amines, Tar Bases, and Inorganic Salts (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Methyl Vinyl Ketone. II. Reactions with Esters, β-Keto Esters, Malonic Ester, Amines, Tar Bases, and Inorganic SaltsNorman C. Ross and Robert LevineCite this: J. Org. Chem. 1964, 29, 8, 2346–2350Publication Date (Print):August 1, 1964Publication History Published online1 May 2002Published inissue 1 August 1964https://doi.org/10.1021/jo01031a059RIGHTS & PERMISSIONSArticle Views664Altmetric-Citations16LEARN 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 (607 KB) Get e-Alerts Get e-Alerts
Reactions of dinitrogen pentoxide and nitrogen dioxide with 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (1991)

The reactions of gaseous dinitrogen pentoxide (N2O5) and nitrogen dioxide (NO2) with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC) coated on the inside surface of a glass reaction cell were studied at 298 K. Unsaturated phosphatidylcholines are significant components of pulmonary surfactant in the alveolar region of the lung and hence serve as a simple model to examine reactions of pulmonary surfactant with these oxidant air pollutants. Using high-performance liquid chromatography (HPLC), Fourier transform infrared and fast atom bombardment mass spectroscopy, the major products of reactions of POPC with N2O5 and NO2 were separated and identified. In the POPC-N2O5 reaction using either air or helium as a buffer gas, the nitronitrate, vinyl nitro and allylic nitro derivatives, as well as a small amount of the trans-isomer of the starting material, were obtained. The nature of the products obtained from the POPC-NO2 reaction depends on the concentration of NO2 as well as whether air is present. At low NO2 concentrations (PNO2/N2O4 less than or equal to 3.8 Torr) in air or in helium, the trans-isomer of POPC was formed almost exclusively. At higher NO2 concentrations (PNO2/N2O4 greater than or equal to 20 Torr) in helium, the dinitro, vinyl nitro and nitro alcohol derivatives were formed. In the presence of air (or 24% 18O2 in helium), a nitronitrate and a dinitronitrate were additional products. Mechanisms for the formation of the observed products and implications for the inhalation of oxides of nitrogen are discussed.
Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA (2014)

Duchenne muscular dystrophy (DMD) is an inherited X-linked disease caused by mutations in the gene encoding dystrophin, a protein required for muscle fiber integrity. DMD is characterized by progressive muscle weakness and a shortened life span, and there is no effective treatment. We used clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)-mediated genome editing to correct the dystrophin gene (Dmd) mutation in the germ line of mdx mice, a model for DMD, and then monitored muscle structure and function. Genome editing produced genetically mosaic animals containing 2 to 100% correction of the Dmd gene. The degree of muscle phenotypic rescue in mosaic mice exceeded the efficiency of gene correction, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle. With the anticipated technological advances that will facilitate genome editing of postnatal somatic cells, this strategy may one day allow correction of disease-causing mutations in the muscle tissue of patients with DMD.
Novel Intramolecular Reactivity of Oximes:  Synthesis of Cyclic and Spiro-Fused Imines (2007)

Under conventional heat (135-145 degrees C) or microwave irradiation and 1 equiv of acetic anhydride, ortho-substituted aryl-oximes undergo a novel sp3 C-H activated cyclization to produce the corresponding isoindoles, and aliphatic oximes afford the corresponding dihydropyrroles. The cyclization occurs with various substrates in good yield (46-82%) leading to unique spiro-fused and cyclic imines. An initial mechanistic investigation suggests the reaction occurs via a nitrenium or vinyl nitrene intermediate. [reaction: see text]
Structural and Kinetic Characterization of Escherichia coli TadA, the Wobble-Specific tRNA Deaminase (2006)

The essential tRNA-specific adenosine deaminase catalyzes the deamination of adenosine to inosine at the wobble position of tRNAs. This modification allows for a single tRNA species to recognize multiple synonymous codons containing A, C, or U in the last (3'-most) position and ensures that all sense codons are appropriately decoded. We report the first combined structural and kinetic characterization of a wobble-specific deaminase. The structure of the Escherichia coli enzyme clearly defines the dimer interface and the coordination of the catalytically essential zinc ion. The structure also identifies the nucleophilic water and highlights residues near the catalytic zinc likely to be involved in recognition and catalysis of polymeric RNA substrates. A minimal 19 nucleotide RNA stem substrate has permitted the first steady-state kinetic characterization of this enzyme (k(cat) = 13 +/- 1 min(-)(1) and K(M) = 0.83 +/- 0.22 microM). A continuous coupled assay was developed to follow the reaction at high concentrations of polynucleotide substrates (>10 microM). This work begins to define the chemical and structural determinants responsible for catalysis and substrate recognition and lays the foundation for detailed mechanistic analysis of this essential enzyme.
Changes of perceived control after kidney transplantation: a prospective study (2017)

A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation.
AIDS Retrovirus (ARV-2) Clone Replicates in Transfected Human and Animal Fibroblasts (1986)

A molecular clone of the AIDS-associated retrovirus (ARV-2) was transfected into human T lymphocyte and monocyte cell lines as well as mouse, mink, monkey, and human fibroblast lines. A replicating virus with cytopathic and biologic properties of ARV-2 was recovered from all the cell lines. The animal and human fibroblast cells are resistant to direct infection by ARV, and in these experiments virus production in the fibroblast lines, especially mouse, was reduced compared to human lymphocytes. However, human fibroblasts were more permissive to virus expression than mouse cells. These results show that, whereas the primary block to ARV infection in certain cells may occur at the cell surface, intracellular mechanisms can also participate in controlling virus replication. The results have relevance to vaccine development and encourage further work with modified molecular clones to examine regions of the ARV genome necessary for cytopathology and replication.
Simplified 13C-urea breath test for detection of helicobacter pylori infection (2001)

The UBT-Lite formulation of the 13C-UBT proved to be an improved version of the U.S. standard 13C-UBT offering less expensive ingredients, shorter test duration, and a simplified breath test collection method, without sacrificing accuracy.
Secure location information management in cellular radio systems (2002)

To ensure reachability of mobile subscribers, cellular radio networks (GSM, IS-41) store location information usually in a home location register (HLR) and in a visitor location register (VLR). To trace mobile users, the network operator just has then to read in these registers. This is considered as a violation of the data security requirement confidentiality. Neither potential communication partners nor third parties should be able to record moving tracks of users without their explicit consent. We propose two new methods that allow the storing of subscribers' exact location information in central databases but still guarantee their privacy. These methods are the "anonymous-subscriber" strategy (AS) and the "anonymity classes" strategy (AC). AS and AC methods protect the subscriber's location information and do not neglect performance considerations. The basic idea of these new strategies is to permit entries of exact location information only if the subscriber remains anonymous. We show that the new procedures can be realized as extensions to the GSM-system. For this purpose they have been specified according to the GSM recommendations methodology and a simulation program using the OPNET Tool, has been developed. Finally, we discuss the influence of the new methods on the network performances.
Phenotypic knockout of HIV type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1 infection (1997)

A genetic defect in a CC-chemokine receptor (CCR)-5, the principal coreceptor for the macrophage-tropic HIV type 1 (HIV-1), recently was found to naturally protect CCR-5-defective, but healthy, individuals from HIV-1 infection. In this study, we mimic the natural resistance of the CCR-5-defective individuals by designing a strategy to phenotypically knock out CCR-5. The inactivation of the CCR-5 coreceptor is accomplished by targeting a modified CC-chemokine to the endoplasmic reticulum to block the surface expression of newly synthesized CCR-5. The lymphocytes transduced to express the intracellular chemokine, termed "intrakine," were found to be viable and resistant to macrophage-tropic HIV-1 infection. Thus, this gene-based intrakine strategy targeted at the conserved cellular receptor for the prevention of HIV-1 entry should have significant advantages over currently described approaches for HIV-1 therapy.
In Situ Detection of Specific p53 Mutations in Cultured Cells Using the Amplification Refractory Mutation System Polymerase Chain Reaction (2000)

Accurate molecular detection of genetic mutations involved in tumorigenesis has been based predominantly on analysis of extracted DNA, but this does not provide detailed information on the location, number, type or clonal distribution of mutated cells and their precise anatomic location and clonal distribution. This study has used a sensitive and specific application of the amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) in situ, combined with in situ hybridization to localize and identify cells with defined p53 mutations. The ARMS-PCR was performed in situ in SW480 cells in suspension and in cells either cultured or cytospun onto glass slides. Amplified mutant DNA PCR products were detected in SW480 cells using digoxigenin-labeled probes, visually identifying cells harboring specific mutations in the p53 gene. In situ hybridization alone of the mutant cells without the amplification step was negative. Normal human fibroblasts or endothelial cells were refractory to in situ amplification. This reaction was mutation-specific as CEM cells with different p53 mutations reacted negatively. Mutant messenger RNA (mRNA) in tumor cells was also selectively amplified in situ by ARMS-PCR following reverse transcription (RT). This study demonstrates the potential of in situ ARMS-PCR or RT-ARMS-PCR for mutation analysis in situ and could have useful clinical applications.
Acceleration and inhibition of lipid oxidation by heme compounds (1969)

Abstract The acceleration and inhibition of unsaturated fatty acid oxidation by heme compounds was followed in model systems with an oxygen analyzer. The linoleate to heme molar ratios for maximum catalysis were 100 for hemin and catalase, 250 for metmyoglobin, 400 for cytochrome c and 500 for methemoglobin. With heme concentrations of 2 to 4 times the optimum catalytic amount, no oxidation occurred. Rapid heme destruction was observed with catalyzing ratios of lipid to heme, but with inhibitory ratios a stable red compound formed, believed to be a lipid hydroperoxide derivative of the heme. The ratios of lipid to metmyoglobin for maximum acceleration varied with the pH. Linolenate was much less sensitive to heme catalysis than linoleate. Colorless products of heme degradation had a marked antioxidant effect. A possible mechanism for the antioxidant effect of hemes is advanced, based on the formation of stable heme peroxide complexes or stable heme radicals, or both, during the early stages of oxidation. Prooxidant activity is believed to occur only when the peroxide to heme ratio is so high that the oxidation of the hemes goes beyond the initial stages.
Synthesis of replica mesostructures by the nanocasting strategy (2005)

Since mesoporous silicates (M41S) were first discovered in the early 1990s, organic–inorganic assembly combined with sol–gel processes by using surfactants as structure-directing agents had been considered to be the major pathway for creating mesoscaled periodic materials. However, unfortunately, many mesostructured materials could not be prepared by the sol–gel process. Nanocasting, using highly ordered mesoporous silica as a template, has brought forward incredible possibilities in preparing novel mesostructured materials, and has led to a great number of ordered nanowire arrays with: a) small diameter (<10 nm); b) large surface areas (up to 2500 m2 g-1) and uniform mesopores (1.5–10 nm); c) tunable 2-D or 3-D mesostructures; d) controlled morphology such as spheres, rods, films, and monoliths; and e) different components including carbon, metals, metal oxides and metal sulfides. We intend to review the results of research into replica mesostructures by nanocasting in recent years from the viewpoint of synthesis. Detailed synthetic processes are described, and problems that are often encountered in the procedure are discussed with several solutions. Many mesostructured replicas are introduced, sorted by their components, including synthetic methods, characteristics of the materials, applications and future challenges. Finally, a simple view of the prospects in this area is provided.