gebhart/patrepeval huggingface dataset:
When replication forks stop (1994)

DNA synthesis is an accurate and very processive phenomenon, yet chromosome replication does not proceed at a constant rate and progression of the replication fork can be impeded. Several structural and functional features of the template can modulate the rate of progress of the replication fork. These include DNA secondary structures, DNA damage and occupied protein-binding sites. In addition, prokaryotes contain sites where replication is specifically arrested. DNA regions at which the replication machinery is blocked or transiently slowed could be particularly susceptible to genome rearrangements. Illegitimate recombination, a ubiquitous phenomenon which may have dramatic consequences, occurs by a variety of mechanisms. The observation that some rearrangements might be facilitated by a pause in replication could provide a clue in elucidating these processes. In support of this, some homologous and illegitimate recombination events have already been correlated with replication pauses or arrest sites.
Redundancy of signal and anchor functions in the NH2-terminal uncharged region of influenza virus neuraminidase, a class II membrane glycoprotein (1988)

Class II membrane glycoproteins share a common topology of the NH2 terminus inside and the COOH terminus outside the cell. Their transport to the cell surface is initiated by the function of a single hydrophobic domain near the NH2 terminus. This functional domain serves both as an uncleaved signal sequence and as a transmembrane anchor. We examined the signal and anchor functions of influenza virus neuraminidase, a prototype class II membrane glycoprotein, by deletion analysis of its long, uncharged amino-terminal region. The results presented here show that the entire stretch of 29 uncharged amino acids (7 to 35) is not required for either a signal sequence or an anchor sequence function. On the basis of translocation and membrane stability data for different mutants, we suggest that the first 20 amino acid residues (7 to 27) are likely to provide the hydrophobic core for these functions and that within this putative subdomain some sequences are more efficient than the other sequences in providing a translocation function. Finally, it appears that neuraminidase and its mutant proteins are translocated with the proper orientation, regardless of the characteristics of the flanking sequences.
Short report: 4-Aminopyridine--a new drug tested in the treatment of Eaton-Lambert syndrome (1977)

A 67 year old man with the myasthenic syndrome associated with small cell bronchogenic carcinoma was treated with a new drug, 4-aminopyridine. The muscle weakness showed marked improvement and electrophysiological examinations demonstrated restoration of neuromuscular transmission.
Control of ring junction stereochemistry via radical cyclization (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTControl of ring junction stereochemistry via radical cyclizationGilbert Stork and Michael KahnCite this: J. Am. Chem. Soc. 1985, 107, 2, 500–501Publication Date (Print):January 1, 1985Publication History Published online1 May 2002Published inissue 1 January 1985https://pubs.acs.org/doi/10.1021/ja00288a038https://doi.org/10.1021/ja00288a038research-articleACS PublicationsRequest reuse permissionsArticle Views1176Altmetric-Citations165LEARN 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
Analytical Characteristics of a Noninvasive Gene Expression Assay for Pigmented Skin Lesions (2016)

We previously reported clinical performance of a novel noninvasive and quantitative PCR (qPCR)-based molecular diagnostic assay (the pigmented lesion assay; PLA) that differentiates primary cutaneous melanoma from benign pigmented skin lesions through two target gene signatures, LINC00518 (LINC) and preferentially expressed antigen in melanoma (PRAME). This study focuses on analytical characterization of this PLA, including qPCR specificity and sensitivity, optimization of RNA input in qPCR to achieve a desired diagnostic sensitivity and specificity, and analytical performance (repeatability and reproducibility) of this two-gene PLA. All target qPCRs demonstrated a good specificity (100%) and sensitivity (with a limit of detection of 1-2 copies), which allows reliable detection of gene expression changes of LINC and PRAME between melanomas and nonmelanomas. Through normalizing RNA input in qPCR, we converted the traditional gene expression analyses to a binomial detection of gene transcripts (i.e., detected or not detected). By combining the binomial qPCR results of the two genes, an improved diagnostic sensitivity (raised from 52%- 65% to 71% at 1 pg of total RNA input, and to 91% at 3 pg of total RNA input) was achieved. This two-gene PLA demonstrates a high repeatability and reproducibility (coefficient of variation <3%) and all required analytical performance characteristics for the commercial processing of clinical samples.
Salicylate Triggers Heat Shock Factor Differently than Heat (1995)

Sodium salicylate has the unusual property of partially inducing the human heat shock response (Jurivich, D. A., Sistonen, L., Kroes, R., and Morimoto, R. I. (1992) Science 255, 1243-1245). Salicylate induces the DNA binding state of the human heat shock transcription factor (HSF), but this is insufficient to elevate heat shock gene expression. Because it is not known how HSF enhances heat shock gene expression, further analysis of the transcriptionally inert, salicylate-induced HSF was undertaken to potentially identify components of the heat shock response that are necessary for full transcriptional induction. Like thermal stress, exposure of HeLa cells to salicylate led to the induction of HSF1 into a DNA-bound state. Despite continued exposure of cells to salicylate, HSF1.DNA binding attenuated much more rapidly than a continuous heat shock. Western blot analysis revealed that the salicylate-induced form of HSF1 was not hyperphosphorylated like the heat-induced form. Furthermore, supershifts of the HSF1 bound to an heat shock element (HSE) oligonucleotide by monoclonal antibodies to phosphoamino acids revealed that salicylate induced threonine phosphorylation of HSF1, whereas heat led to a predominance of HSF1 serine phosphorylation. These data suggest that salicylate-independent signals are necessary to convert HSF1 into a transactivator of heat shock gene expression and that brief acquisition of DNA binding by this factor is insufficient to maximally enhance transcription.
Sequence Alterations Can Mask Each Other’s Presence during Screening with SSCP or Heteroduplex Analysis: BRCA Genes as Examples (2000)

For mutation detection, various screening techniques are widely used because DNA sequencing, the gold-standard method, is still considered to be expensive and laborious for high-throughput screening. Single-strand conformation polymorphism (SSCP) analysis, heteroduplex analysis (HA) and their variant techniques are popular and frequently used for this purpose. It is widely accepted that when searching for unknown sequence variations, any revealed distinct pattern should always be sequenced. We give examples here of the BRCA1 and BRCA2 genes where the SSCP/HA techniques can produce ambiguous predictions if used to detect known genetic variants compared to positive controls. Using direct DNA sequencing, we provide evidence that in such cases, mutations or polymorphisms can mask each other's presence. This phenomenon can often influence the results of any DNA testing because genetic variations such as single-nucleotide polymorphisms occur frequently in the human genome. We suggest that even in the case of known electrophoretic patterns of well-characterized genetic alterations, every sequence alteration should be confirmed by direct DNA sequencing, especially if genetic testing is carried out for diagnostic purposes.
Stable Phase Equilibrium of the Aqueous Ternary System Li + //Cl - ,borate- H 2 O at 348 K (2014)

The Sichuan Basin,with an area of about 20×104 km2,is situated at 102.5°~110°E and 27.67°~32.67°N.The underground brine resources in Sichuan basin are a type of comprehensive liquid mineral resource.Pingluo
A Novel Approach for Nucleic Acid Delivery Into Cancer Cells (2012)

Our new approach, based on the use of a dynamic gradient magnetic field, enhanced the transfection efficiency and had a less cytotoxic effect on prostate cancer cells in comparison with the standard magnetofection and lipofection.
Inhibition of Alzheimer's Amyloidosis by Peptides That Prevent β-Sheet Conformation (1996)

Amyloid beta-peptide (A beta) is a major fibrillar component of neuritic plaques in Alzheimer's disease (AD) brains and is related to the pathogenesis of the disease. We hypothesized that amyloid formation could be inhibited by peptides homologous to A beta (position 17-21) with a similar degree of hydrophobicity, but with a very low propensity to adopt a beta-sheet conformation by incorporating proline residues (anti-beta-sheet peptides or beta-sheet inhibitors). An 11-residue peptide with these characteristics binds to A beta, inhibits A beta fibril formation and partially disaggregates preformed fibrils in vitro. Shorter anti-beta-sheet peptides and analogs containing D-amino acids are also able to inhibit A beta fibrillogenesis. The latter are more resistant to proteolytic degradation and may serve as a starting point to design more efficient peptides derivatives to inhibit amyloidogenesis in vivo.
Occurrence, mechanisms and analytical applications of electrogenerated chemiluminescence. A review (1994)

The occurrence, mechanisms, and practicalities of the electrogeneration of chemiluminescence are described with reference to applications in analytical chemistry. The general theory of electron transfer excitation mechanisms is discussed with respect to organic reactions in aprotic media, and extended to include inorganic complexes and clusters. Analytical applications are classified according to the excitation mechanism, i.e., organic and inorganic systems, established chemiluminescence reactions initiated electrochemically, and cathodic luminescence at semiconductor electrodes.
Fundamental neuroscience : images (1999)

Fundamental Neuroscience is the only comprehensive text that defies the full scope of neuroscience. Developed in accordance with results of extensive reviews by neuroscience instructors, and in co-operation with the Association of Neuroscience Departments and Programs (ANDP), this text is divided into seven integrated sections.
Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis (2015)

clinicaltrials.gov NCT01335464 and NCT01335477.
Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor alphavbeta3-integrin expression. (2004)

This study demonstrated the suitability of a PEG moiety for improving the in vivo kinetics of a 64Cu-RGD peptide tracer without compromising the tumor-targeting ability and specificity of the peptide. Systematic investigations of the effects of the size and geometry of PEG on tumor targeting and in vivo kinetics will lead to the development of radiotracers suitable for clinical applications such as visualizing and quantifying alphav-integrin expression by PET. In addition, the same ligand labeled with therapeutic radionuclides may be applicable for integrin-targeted internal radiotherapy.
Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp 120 (1990)

Amino acid sequences inducing neutralizing antibodies to HIV-1 were sought. Murine monoclonal antibodies (MAbs) were characterized by their reactivity with the envelope precursor gp160 or the Escherichia coli recombinant DNA products pB1 and pE3 representing the carboxy- and amino-terminal halves of mature envelope gp120. Fine mapping of the MAb determinants was performed using defined 15-mer synthetic peptides spanning the entire envelope gp120 region of HIV-1. One group of MAbs recognizes epitopes (amino acids 304-323) occurring in a small region with variable and conserved amino acid sequences of gp120. These MAbs mediate neutralization of the HIV-1 strain HTLV-IIIB (HIV-1IIIB) which was used for immunization. Nine out of 11 primary HIV-1 isolates were neutralized well or moderately well. In addition, prominent serological reactivity was noted with peptide sequences of strains of various European or American origins, but not with two HIV-1 strains of African origin. The cross-reactivity contrasts with previously described type-specific reactions to other sequences of this region. The reactivity to the short conserved site GPGR with its flanking amino acids may explain the broad sequence cross-reactivity seen with our neutralizing MAbs. Two other MAbs recognize conserved epitopes (amino acids 79-103) situated in the amino-terminal region of gp120. These MAbs did not neutralize HIV-1IIIB.
Down-regulation of Aurora B kinase induces cellular senescence in human fibroblasts and endothelial cells through a p53-dependent pathway (2011)

Aurora B kinase (Aurora-B) functions in chromosome segregation and cleavage of polar spindle microtubules. However, its role in cellular senescence remains elusive. Here, we investigated Aurora-B effects on cellular senescence in human fibroblasts and endothelial cells. Aurora-B levels were reduced during replicative senescence and premature senescence by adriamycin. Aurora-B overexpression in old cells partially reversed senescence phenotypes. In contrast, Aurora-B down-regulation accelerated cellular senescence. p53 knockdown but not p16 knockdown inhibited cellular senescence by Aurora-B reduction. These results suggest that Aurora-B might function in the regulation of cellular senescence of human primary cells via a p53-dependent pathway.
Query reformulation for content based multimedia retrieval in MARS (2003)

Unlike traditional database management systems, in content-based multimedia retrieval databases, it is difficult for users to express their exact information need directly in a precise query. A typical interface allows users to express their information need using examples of objects similar to the ones they wish to retrieve. Such a user interface, however, requires mechanisms to learn the query representation from the examples. In this paper, we describe the query refinement framework implemented in the Multimedia Analysis and Retrieval System (MARS) for learning query representations using relevance feedback. The proposed framework uses a query expansion approach towards modifying the query representation in which relevant objects are added to the query. Furthermore, query reweighting techniques are used to adjust similarity functions.
Gene regulation during late embryogenesis: the RY motif of maturation‐specific gene promoters is a direct target of the FUS3 gene product (2000)

The Arabidopsis mutants fus3 and abi3 show pleiotropic effects during embryogenesis including reduced levels of transcripts encoding embryo-specific seed proteins. To investigate the interaction between the B3-domain-containing transcription factors FUS3 and ABI3 with the RY cis-motif, conserved in many seed-specific promoters, a promoter analysis as well as band-shift experiments were performed. The analysis of promoter mutants revealed the structural requirements for the function of the RY cis-element. It is shown that both the nucleotide sequence and the alternation of purin and pyrimidin nucleotides (RY character) are essential for the activity of the motif. Further, it was shown that FUS3 and ABI3 can act independently of each other in controlling promoter activity and that the RY cis-motif is a target for both transcription factors. For FUS3, which is so far the smallest known member of the B3-domain family, a physical interaction with the RY motif was established. The functional and biochemical data demonstrate that the regulators FUS3 and ABI3 are essential components of a regulatory network acting in concert through the RY-promoter element to control gene expression during late embryogenesis and seed development.
Market-Oriented Programming and its Application to Power Load Management (1998)

Market-oriented programming is a new approach to design and implementation of resource allocation mechanisms in computer systems. It has its roots in different disciplines, such as economics and computer science (in particular the area of multi-agent systems). This thesis is divided into two different parts, focusing on: 1) central foundations and mechanisms of market-oriented programming, and 2) the use of market-oriented programming in practical applications. Market-oriented programming is seen as a programming paradigm based on abstractions such as prices and demands. Concepts, terminology and theory from micro-economics form the foundations of the paradigm. Central aspects of these foundations are investigated and some new insights are presented. Furthermore, some relations between standard optimization/resource allocation approaches and markets are described, and novel theorems are introduced. A plethora of algorithms (some stemming from mathematical optimization and numerical analysis, and some new) for the main computational problem of market-oriented programming - the computation of general equilibrium - are described, analyzed and compared. Some issues of self-interested agents in market-oriented programming are also investigated. A published, and generally recognized, market-oriented approach to the application building climate control is analyzed in some detail. A new approach to this application, based on market-oriented programming, is introduced and shown to be superior to the analyzed approach in many ways. The case study pinpoints a number of potential pitfalls as well as advantages of market-oriented approaches to this and other applications. A second investigated application is power load management, i.e. the management of loads at the customers' side for obtaining more efficient energy systems management. The basis of the application is described and a new market-oriented approach is introduced and analyzed. The approach is shown to have a number of advantages compared to existing approaches to this problem. The main conclusion of the thesis is that there are some potential pitfalls of market-oriented programming, but when used with care it provides a highly natural and efficient means for resource allocation in computer systems.
TGFß and IL-10: inhibitory cytokines regulating immunity and the response to infection (2000)

A complex interplay between cytokines provides plasticity to our systems of host defense and immune surveillance, but also presents a tremendous challenge to our understanding of the host immune response. These cytokines are typically pleiotropic. They may amplify their own expression, influence the production of other cytokines and effector molecules, and exert an end-effect that is often defined by the array of other signals acting in their presence. Determining those participants which negatively regulate these effector responses may enable us to manipulate the exaggerated response, whether to pathogens or to self, and to enhance an ineffective response by interfering with their activity.
The role of U2AF35 and U2AF65 in enhancer-dependent splicing (2001)

Splicing enhancers are RNA sequence elements that promote the splicing of nearby introns. The mechanism by which these elements act is still unclear. Some experiments support a model in which serine-arginine (SR)-rich proteins function as splicing activators by binding to enhancers and recruiting the splicing factor U2AF to an adjacent weak 3' splice site. In this model, recruitment requires interactions between the SR proteins and the 35-kDa subunit of U2AF (U2AF35). However, more recent experiments have not supported the U2AF recruitment model. Here we provide additional evidence for the recruitment model. First, we confirm that base substitutions that convert weak 3' splice sites to a consensus sequence, and therefore increase U2AF binding, relieve the requirement for a splicing activator. Second, we confirm that splicing activators are required for the formation of early spliceosomal complexes on substrates containing weak 3' splice sites. Most importantly, we find that splicing activators promote the binding of both U2AF65 and U2AF35 to weak 3' splice sites under splicing conditions. Finally, we show that U2AF35 is required for maximum levels of activator-dependent splicing. We conclude that a critical function of splicing activators is to recruit U2AF to the weak 3' splice sites of enhancer-dependent introns, and that efficient enhancer-dependent splicing requires U2AF35.
[Treatment monitoring of patients with uterine cancer with and without progression by free serum amino acids]. (1989)

We determined 10 free serum amino acids by automatic chromatographic analyses in continuous steps in tumour monitoring of 51 patients with cancer of the uterine body. There were 39 patients without and 12 patients with recurrent disease. We found an elevation of aspartic acid, glutaminic acid, tyrosine and phenylalanine in continuous monitoring. Glycine, alanine, valine and leucine have an increased level in pretherapeutic value, too. A monitoring with amino acids in metaphylaxis is possible.
Lung mechanics following antigen challenge of Ascaris suum-sensitive rhesus monkeys (1976)

Pulmonary resistance (RL) breathing air and a helium-oxygen mixture (He-O2) dynamic compliance (Cdyn), respiratory frequency (f), subdivisions of lung volume, and static deflation pressure-volume (PV) curves were measured before and after bronchial challenge with Ascaris suum antigen in six rhesus monkeys with varying skin reactivity to this antigen. The animals were lightly anesthetized with pentobarbital sodium, intubated, and studied in a volume displacement body plethysmograph, transpulmonary pressure being measured with an esophageal balloon technique. With the animals breathing spontaneously antigen was delivered with a De Vilbiss ultrasonic nebulizer and RL was determined by the method of electrical subtraction. With challenge, three monkeys showed no response and three persistently demonstrated significant bronchonconstriction (peak RL 700+/-100% control) with a decreased response to He-O2 suggesting combined central and peripheral airway narrowing. Responding monkeys also developed tachypnea (f 210+/-8% control) and a fall in Cdyn (18+/-6% control) but no significant changes in total lung capacity and its subdivisions, or in static PV curves were seen. We conclude that this primate model shows important similarities to and differences from human asthma.