gebhart/patrepeval huggingface dataset:
High Affinity and Specific Binding of HIV-1 TAR RNA by a Tat-Derived Oligourea (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHigh Affinity and Specific Binding of HIV-1 TAR RNA by a Tat-Derived OligoureaN. Tamilarasu, Ikramul Huq, and Tariq M. RanaView Author Information Department of Pharmacology Robert Wood Johnson Medical School 675 Hoes Lane, Piscataway, New Jersey 08854 Cite this: J. Am. Chem. Soc. 1999, 121, 7, 1597–1598Publication Date (Web):February 4, 1999Publication History Received4 November 1998Published online4 February 1999Published inissue 1 February 1999https://pubs.acs.org/doi/10.1021/ja983822thttps://doi.org/10.1021/ja983822trapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views298Altmetric-Citations52LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Equilibrium constant,Genetics,Nucleic acid structure,Peptides and proteins,Pharmacology Get e-Alerts
Use of Real-Time PCR and Fluorimetry To Detect Lamivudine Resistance-Associated Mutations in Hepatitis B Virus (1999)

Very rapid amplification of DNA by PCR in small volumes can be continuously monitored by the detection of the binding of probes with a rapid cycler with built-in fluorometric detection. Primers were designed to amplify approximately 100 bp of the polymerase gene of hepatitis B virus (HBV) spanning codon 550, where mutations associated with resistance to lamivudine invariably occur. Four hybridization probes were synthesized: one was 3' labelled with fluorescein and hybridized upstream of codon 550. The others were 5' labelled with Cy5 and 3' labelled with biotin and spanned codon 550. The Cy5-labelled oligonucleotides contained either wild-type (ATG) or mutant (GTG or ATT) sequences. A Cy5-labelled probe and either the fluorescein-labelled probe or Sybr Green 1 (a compound that fluoresces when bound to double-stranded DNA) were included in each PCR. After completion of the amplification by using a LightCycler (Idaho Technology), the temperature at which the Cy5 probe melted from the product was determined in a melt program that took ca. 3 min. Pre- and posttreatment samples from eight patients (five chronic and three transplant) who failed lamivudine treatment were amplified, and the presence of mutations in codon 550 was determined by ABI sequencing and by using the LightCycler; in some cases PCR products were also cloned, and multiple clones were sequenced. Concordant results were obtained in all cases. We found the LightCycler to be better at resolving the sequences of genomic mixtures; for example, two samples showed a sequence at codon 550 of (A/G)T(G/T), which was found by fluorimetry to be mixtures of GTG and ATT but no ATG, and this finding was confirmed by the sequencing of clones. However, this approach was not more sensitive than population sequencing for the detection of the presence of mixtures. Overall, this pilot study has demonstrated an approach that could be an extremely rapid and economical method for the detection of lamivudine resistance-associated mutations in HBV.
ChemInform Abstract: Diels‐Alder Reaction of 2‐Aryl‐1‐methylisoindoles with N‐Substituted Maleimides. (1989)

Abstract Diels‐Alder reaction of the isoindoles (III) with the maleimides (IV) under kinetic control gives the endo‐adducts (V).
High-Availability Algorithms for Distributed Stream Processing (2005)

Stream-processing systems are designed to support an emerging class of applications that require sophisticated and timely processing of high-volume data streams, often originating in distributed environments. Unlike traditional data-processing applications that require precise recovery for correctness, many stream-processing applications can tolerate and benefit from weaker recovery guarantees. In this paper, we study various recovery guarantees and pertinent recovery techniques that can meet the correctness and performance requirements of stream-processing applications. We discuss the design and algorithmic challenges associated with the proposed recovery techniques and describe how each can provide different guarantees with proper combinations of redundant processing, checkpointing, and remote logging. Using analysis and simulations, we quantify the cost of our recovery guarantees and examine the performance and applicability of the recovery techniques. We also analyze how the knowledge of query network properties can help decrease the cost of high availability.
Sulfatases, Trapping of the Sulfated Enzyme Intermediate by Substituting the Active Site Formylglycine (1998)

Sulfatases contain an active site formylglycine residue that is generated by post-translational modification. Crystal structures of two lysosomal sulfatases revealed significant similarity to the catalytic site of alkaline phosphatase containing a serine at the position of formylglycine. To elucidate the catalytic mechanism of sulfate ester hydrolysis, the formylglycine of arylsulfatases A and B was substituted by serine. These mutants upon incubation with substrate were covalently sulfated at the introduced serine. This sulfated enzyme intermediate was stable at pH 5. At alkaline pH it was slowly hydrolyzed. These characteristics are analogous to that of alkaline phosphatase which forms a phosphoserine intermediate that is stable at pH 5, but is hydrolyzed at alkaline pH. In wild-type sulfatases the hydroxyl needed for formation of the sulfated enzyme intermediate is provided by the aldehyde hydrate of the formylglycine. The second, non-esterified hydroxyl of the aldehyde hydrate is essential for rapid desulfation of the enzyme at acidic pH, which most likely occurs by elimination. The lack of this second hydroxyl in the serine mutants explains the trapping of the sulfated enzyme intermediate. Thus, in acting as a geminal diol the formylglycine residue allows for efficient ester hydrolysis in an acidic milieu.
Utilization of Genomic Signatures to Identify Phenotype-Specific Drugs (2009)

Genetic and genomic studies highlight the substantial complexity and heterogeneity of human cancers and emphasize the general lack of therapeutics that can match this complexity. With the goal of expanding opportunities for drug discovery, we describe an approach that makes use of a phenotype-based screen combined with the use of multiple cancer cell lines. In particular, we have used the NCI-60 cancer cell line panel that includes drug sensitivity measures for over 40,000 compounds assayed on 59 independent cells lines. Targets are cancer-relevant phenotypes represented as gene expression signatures that are used to identify cells within the NCI-60 panel reflecting the signature phenotype and then connect to compounds that are selectively active against those cells. As a proof-of-concept, we show that this strategy effectively identifies compounds with selectivity to the RAS or PI3K pathways. We have then extended this strategy to identify compounds that have activity towards cells exhibiting the basal phenotype of breast cancer, a clinically-important breast cancer characterized as ER-, PR-, and Her2- that lacks viable therapeutic options. One of these compounds, Simvastatin, has previously been shown to inhibit breast cancer cell growth in vitro and importantly, has been associated with a reduction in ER-, PR- breast cancer in a clinical study. We suggest that this approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes that can augment the conventional strategies of target-based screens.
MAP Kinase Pathways in Neuronal Cell Death (2008)

The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogen-activated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen-activated protein kinases activated by extracellular stimuli including stress, are a major focus. Knock-out mouse studies have demonstrated that removing particular JNK genes can reduce the severity in various disease scenarios, including those which are used to model Parkinson's disease and cerebral ischemia. In addition, activation of JNKs can be seen in human disease tissue. In this review we bring together the evidence for JNK being an important regulator of neuronal loss and outline the advancement of small molecule inhibitors for future therapeutic intervention.
J.R.R. Tolkien: A Lifetime of Fantasy (1998)

Being Part of the Solution Carol Blackburn Copyright © 1998 The Johns Hopkins University
Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule (2004)

The Abeta1-42 peptide that is overproduced in Alzheimer's disease (AD) from a large precursor protein has a normal amino acid sequence but, when liberated, misfolds at neutral pH to form "protofibrils" and fibrils that are rich in beta-sheets. We find that these protofibrils or fibrils are toxic to certain neuronal cells that carry Ca-permeant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Disrupting the structure of the Abeta1-42 fibrils and protofibrils might lead to the discovery of molecules that would be very useful in the treatment of AD. A high-throughput screen of a library of >3,000 small molecules with known "biological activity" was set up to find compounds that efficiently decrease the beta-sheet content of aggregating Abeta1-42. Lead compounds were characterized by using thioflavin T (ThT) as a beta-sheet assay. The most effective of six compounds found was 4,5-dianilinophthalimide (DAPH) under the following conditions: DAPH at low micromolar concentrations abolishes or greatly reduces previously existing fully formed Abeta1-42 fibrils, producing instead amorphous materials without fibrils but apparently containing some protofibrils and smaller forms. Coincubation of the Abeta1-42 peptide with DAPH produces either amorphous materials or empty fields. Coincubation of DAPH and Abeta1-42 greatly reduces the beta-sheet content, as measured with ThT fluorescence, and produces a novel fluorescent complex with ThT. When the Abeta1-42 peptide was coincubated with DAPH at very low micromolar concentrations, the neuronal toxicity mentioned above (Ca(2+) influx) was eliminated. Clearly, DAPH is a promising candidate for AD therapy.
A sequence-comparison statistic and algorithm (1973)

A statistic is proposed for the comparison of ordered sequences of objects when the aim is to slot together the sequences. An algorithm is suggested for attempting to find the best pairwise fit.
Highly Effective Contact Antimicrobial Surfaces via Polymer Surface Modifiers (2007)

Contact antimicrobial coatings with poly(alkylammonium) compositions have been a subject of increasing interest in part because of the contribution of biocide release coatings to antibiotic resistance. Herein, a concept for antimicrobial coatings is developed on the basis of the thermodynamically driven surface concentration of soft block side chains. The concept incorporates structural and compositional guidance from naturally occurring antimicrobial proteins and achieves compositional economy via a polymer-surface modifier (PSM). To implement this concept, polyurethanes were prepared having random copolymer 1,3-propylene oxide soft blocks with alkylammonium and either trifluoroethoxy or PEGlyted side chains. Six carbon (C6) and twelve carbon (C12) alkylammonium chain lengths were used. The PSMs were first tested as 100% coatings and were highly effective against aerosol challenges of Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). To evaluate the surface concentration, solutions containing 2 wt % PSM with a conventional polyurethane were evaporatively coated onto glass slides. These 2% PSM coatings were tested against aerosol challenges of Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria (107 CFU/mL/30 min). A copolymer soft block containing trifluorethoxy (89 mol %) and C-12 alkylammonium (11 mol %) side chains gave the highest biocidal effectiveness in 30 min: 2 wt %, Gram(+/-) bacteria, 100% kill, and 3.6-4.4 log reduction. A zone of inhibition test showed no biocide release for PSMs and PSM-modified compositions. Characteristics that contribute to concept validation include good hard block/soft block phase separation, a cation/co-repeat group ratio mimicking natural biocidal proteins, a semifluorinated "chaperone" aiding in alkylammonium surface concentration, and a low Tg for the alkylammonium soft block.
Therapeutic cancer targeting peptides (2002)

Antitumor monoclonal antibodies have shown clinical promise as cancer cell surface targeting agents. More tumor targeting antibodies are likely to be approved by the FDA in the next few years. However, there are two major limitations in antibody-targeted therapy: large size and nonspecific uptake of the antibody molecules by the liver and the reticuloendothelial system. These result in poor tumor penetration of antibody pharmaceuticals and dose-limiting toxicity to the liver and bone marrow. Peptides are excellent alternative targeting agents for human cancers, and they may alleviate some of the problems with antibody targeting. In the last decade, several investigators have successfully used combinatorial library methods to discover cell surface binding peptides that may be useful for cancer targeting. The phage-display library technique and the "one-bead one-compound" combinatorial library method are the two approaches that have been used. Cancer cell surface receptors or endothelial cell surface receptors of the neovasculature are the two popular therapeutic targets for cancer. Results from preclinical studies with some peptides are encouraging in their targeting potential.
Cytogenetic studies on human myeloma cell lines (1987)

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.
Study on stable equilibrium of levitated impeller in rotary pump with passive magnetic bearings (2006)

It is widely acknowledged that the permanent maglev cannot achieve stable equilibrium; the authors have developed, however, a stable permanent maglev centrifugal blood pump. Permanent maglev needs no position detection and feedback control of the rotor, nevertheless the eccentric distance (ED) and vibration amplitude (VA) of the levitator have been measured to demonstrate the levitation and to investigate the factors affecting levitation. Permanent maglev centrifugal impeller pump has a rotor and a stator. The rotor is driven by stator coil and levitated by two passive magnetic bearings. The rotor position is measured by four Hall sensors, which are distributed evenly and peripherally on the end of the stator against the magnetic ring of the bearing on the rotor. The voltage differences of the sensors due to different distances between the sensors and the magnetic ring are converted into ED. The results verify that the rotor can be disaffiliated from the stator if the rotating speed and the flow rate of the pump are large enough, that is, the maximal ED will reduce to about half of the gap between the rotor and the stator. In addition, the gap between rotor and stator and the viscosity of the fluid to be pumped also affect levitation. The former has an optimal value of approximately 2% of the radius of the rotor. For the latter, levitation stability is better with higher viscosity, meaning smaller ED and VA. The pressure to be pumped has no effect on levitation.
A comparison between next-generation sequencing and ASO-qPCR for minimal residual disease detection in multiple myeloma. (2013)

8601 Background: Although molecular CR in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual which is laborious and time-consuming. The usage of the LymphoSIGHT method, a next-generation sequencing (NGS)-based platform, may overcome these challenges and increase sensitivity and specificity. We compared the LymphoSIGHT approach with ASO-qPCR for minimal residual disease (MRD) detection in autografts in the autologous peripheral blood stem cell transplantation (ASCT) setting. Methods: Seventeen Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a PR or CR after ASCT. Bone marrow (BM) slides from 13 MM patients and fresh BM cells from 4 MM patients at diagnosis as well as autografts were obtained for DNA extraction. Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. The presence of the myeloma clonotype was then assessed in follow-up samples. Results: MRD in autografts was detected in 6 of 17 (35%) by ASO-qPCR and 13 of 17 (76%) by NGS. When MRD was assessed by NGS, 6 MRD (+) cases received post-ASCT therapy while 4 MRD (-) cases and 7 MRD (+) cases were followed without post-ASCT therapy. The MRD (-) cases tended to show a better PFS than the MRD (+) cases with post-ASCT therapy (P = 0.26) and those without post-ASCT therapy (P = 0.09) although overall survival rates were comparable among the three groups. There was no difference in PFS between MRD (-) and MRD (+) cases when MRD was assessed by ASO-qPCR (P = 0.6). These studies will be extended in 30 additional MM patients, and results will be presented. Conclusions: MRD-negativity in autografts revealed by NGS may be more closely associated with durable remission of MM than that revealed by ASO-qPCR.
On satisfying timing constraints in hard-real-time systems (1993)

The authors explain why pre-run-time scheduling is essential if one wishes to guarantee that timing constraints will be satisfied in a large complex hard-real-time system. They examine some of the major concerns in pre-run-time scheduling and consider what formulations of mathematical scheduling problems can be used to address those concerns. This work provides a guide to the available algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analyzing Feature Significance from Various Systems for Mass Diagnosis (2006)

This paper compares a few classification models for mass classification and analyzes the feature significance for mass classification using various models. It involves a few algorithms for feature selection and also analyzes the individual feature significance. The comparison of classification models is based on the same datasets for mass diagnosis.
Comparative Transoral Dural Closure Techniques: A Canine Model (1988)

A watertight dural closure is difficult to achieve after transoral-transclival operation for ventral intradural lesions at the craniocervical junction. These procedures have a high morbidity and mortality from cerebrospinal fluid (CSF) fistula, meningitis, and abscess. We used a canine model to test three different techniques of dural closure after transoral intradural operation: primary suture closure, laser patch weld, and fibrin glue patch closures. The primary suture closure technique was inadequate. All eight leaked CSF at the time of operation, and five had radiographic leaks and were incompetent at autopsy. All seven of the laser closures leaked CSF at operation, yet only one was incompetent at autopsy. The fibrin glue technique was superior and provided a solid seal at operation, even with repeated Valsalva maneuvers to 40 mm Hg. The immediate and persistent seal at operation is clinically significant because it may prevent CSF leak, meningitis, and abscess formation in human patients after transoral surgery. Fibrin glue is excellent for repairing complex dural defects and merits evaluation in clinical trials.
[The influence of irradiation into the wear behaviour of polyethylene (author's transl)]. (1979)

Irradiated specimens of UHMW-PE have been tested by a "Pin-on-disc"-method against a metal pin. Increasing irradiation doses are leading to obviously increasing wear-rates. Irradiation in presence of nitrogen gives no advantage in comparison to normal air as an crosslinking agents, concerning tribological properties.
Painful Boney Metastases (2013)

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics.