gebhart/patrepeval huggingface dataset:
Identification of a Functional Epitope in Plasminogen Activator Inhibitor-1, not Localized in the Reactive Center Loop (1998)

Plasminogen activator inhibitor-1 (PAI-1) is unique among the serpins because of its conformational flexibility. Previously, we have characterized monoclonal antibodies that neutralize PAI-1 activity by switching the active, inhibitory pathway into the non-inhibitory substrate pathway (10). Here, we report the identification of the epitopes for two of these antibodies, i.e. MA-55F4C12 and MA-33H1 and apply this information to explain their functional effects. Using a random PAI-1 epitope library (11), phages displaying specific PAI-1 fragments were isolated after selective screening for binding onto the respective antibodies. Competition experiments with PAI-1 demonstrated that selected phages react with the antigen-binding site of the antibodies. Comparison of the sequences of the different overlapping inserts, encoding the PAI-1 epitope, with the PAI-1 cDNA sequence revealed that both epitopes, even though not identical, are located between amino acids Glu128 and Ala156 in the PAI-1 molecule. Analysis within the three-dimensional structure of PAI-1 showed that these residues completely cover helix F, which is localized close to the major beta-sheet A. This localization provides a rational basis for explaining the mechanism of PAI-1 inactivation by both antibodies: upon binding of these antibodies to PAI-1, a stabilizing effect is induced on helix F resulting in a decrease of the kinetics of insertion of the reactive site loop into beta-sheet A during interaction with the target proteinase. This forms the molecular basis for the observed functional effects of these antibodies and fully explains why PAI-1, in the presence of these antibodies, has lost its inhibitory properties but remains succeptible to cleavage by its target proteinases. The identification and localization of these functionally important epitopes opens new perspectives for the development of pharmacological agents with PAI-1 modulating properties.
Identification of breast cancer cell line-derived paracrine factors that stimulate osteoclast activity. (1999)

Metastatic breast cancer causes destruction of significant amounts of bone, and, although bone is the most likely site of breast cancer metastasis, little is understood about interactions between tumor cells and bone-resorbing osteoclasts. We have investigated the paracrine factors produced by breast cancer cells that are involved in increasing osteoclast activity. We have determined by immunoassay that the human breast cancer cell line MDA MB 231 (231) cultured in serum-free medium secretes transforming growth factors type beta(TGF-beta) 1 and 2, macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL) -1 and -6, tumor necrosis factor alpha (TNF-alpha), insulin-like growth factor II (IGF II), and parathyroid hormone-related peptide. To determine which of these are involved in increased bone destruction, we have fractionated serum-free 231-conditioned media and measured these fractions for effects on osteoclast resorption activity using multiple activity assays. The pattern of responses was complex. Several fractions stimulated osteoclast resorption either by increasing the number of osteoclasts binding to the bone or by elevating the resorption activity of the individual osteoclasts. Other fractions inhibited osteoclast activity. Analysis of active fractions for the factors identified in the 231-conditioned medium revealed that the presence of TNF-alpha and IGF-II was restricted to separate fractions that stimulated osteoclast resorption activity. The fractions that inhibited osteoclast resorption activity contained M-CSF, IL-6, TGF-beta2, and GM-CSF. No TGF-beta1 or IL-1 was detected in any of the active fractions. Our data support the hypothesis that breast cancer cells modulate osteoclast activity using multiple regulatory factors that increase both the number of mature osteoclasts attached to the bone and the bone resorption activity of these individual osteoclasts. Once it is understood how metastatic breast cancer elevates osteoclast-mediated bone loss, effective therapies to slow the progression and/or prevent this bone loss will become possible.
The limits of the cellular capacity to mediate an estrogen response. (1992)

While steroid response is generally restricted by the availability of steroid receptors, the theoretical limits of the response are not known. We have constructed a series of cell lines that stably express the estrogen receptor (ER) at levels up to 5,000,000 ERs per cell and employed these cells to explore the limits of the estrogen response. Several reporter genes with estrogen response elements upstream of the herpes thymidine kinase promoter showed hyperbolic saturation kinetics with increasing ER. Maximum response was 10 times that seen in cell lines with receptor titers comparable to physiological levels. Half-maximal responses required 500,000 receptors per cell, and cells with 5,000,000 ERs showed greater than 90% maximum induction. Estradiol dose-response studies indicated that the receptors are limiting below 500,000 ERs per cell, but at higher ER titers there are spare receptors. In contrast to most reporters, the widely used reporter pA2-CAT, which has 200 base pairs of Xenopus vitellogenin DNA between the response element and the promoter, showed squelching at ER levels beyond 500,000 per cell. Cell lines that expressed ER above this level activated pA2-CAT with a distorted hormone dependence, where saturating ligand concentrations were inhibitory. All reporters displayed squelching when the ER was provided by transient transfection at a level that we judge is 20,000,000 per cell by extrapolation from the behavior of stable cell lines. These findings suggest that saturation of the cellular capacity to mediate an estrogen response and ER-dependent squelching occur at receptor titers well above those encountered in nature. If current models of steroid hormone action are correct, the findings also imply that estrogen response elements are occupied to very small extents under normal conditions.
Register level sort algorithm on multi-core SIMD processors (2013)

State-of-the-art hardware increasingly utilizes SIMD parallelism, where multiple processing elements execute the same instruction on multiple data points simultaneously. However, irregular and data intensive algorithms are not well suited for such architectures. Due to their importance, it is crucial to obtain efficient implementations. One example of such a task is sort, a fundamental problem in computer science. In this paper we analyze distinct memory accessing models and propose two methods to employ highly efficient bitonic merge sort using SIMD instructions as register level sort. We achieve nearly 270x speedup (525M integers/s) on a 4M integer set using Xeon Phi coprocessor, where SIMD level parallelism accelerates the algorithm over 3 times. Our method can be applied to any device supporting similar SIMD instructions.
Diffuse Interface Modeling of Droplet Impact on a Pre‐Patterned Solid Surface (2005)

Abstract Summary: The impact of a droplet on a solid surface, pre‐patterned with a barrier, was studied using a diffuse interface model. The effect of the wettability of the barrier material and the width of the barrier on droplet spreading was investigated. The results show that depending on the barrier wettability and width, the flow of the spreading droplet can be controlled and that the droplet may or may not overflow the barrier. Droplet shapes with the corresponding velocity field for different barrier contact angles at ± = 1.5. magnified image Droplet shapes with the corresponding velocity field for different barrier contact angles at ± = 1.5.
Darstellung Und Stereochemie Der 1.2.3.4‐Tetracarbonsäuren Des Cyclopentans Und Cyclohexans (1958)

Abstract Cyclopentan‐ und Cyclohexan‐tetracarbonsäure‐(1.2.3.4) können theoretisch in je 6 stereoisomeren Formen auftreten. Sie werden alle bis auf jeweils die 1 c .2 c .3 c .4 t ‐Form dargestellt. Die Umwandlungen der einzelnen Stereoisomeren ineinander werden studiert.
Host‐induced gene silencing: a tool for understanding fungal host interaction and for developing novel disease control strategies (2011)

Recent discoveries regarding small RNAs and the mechanisms of gene silencing are providing new opportunities to explore fungal pathogen-host interactions and potential strategies for novel disease control. Plant pathogenic fungi are a constant and major threat to global food security; they represent the largest group of disease-causing agents on crop plants on the planet. An initial understanding of RNA silencing mechanisms and small RNAs was derived from model fungi. Now, new knowledge with practical implications for RNA silencing is beginning to emerge from the study of plant-fungus interactions. Recent studies have shown that the expression of silencing constructs in plants designed on fungal genes can specifically silence their targets in invading pathogenic fungi, such as Fusarium verticillioides, Blumeria graminis and Puccinia striiformis f.sp. tritici. Here, we highlight the important general aspects of RNA silencing mechanisms and emphasize recent findings from plant pathogenic fungi. Strategies to employ RNA silencing to investigate the basis of fungal pathogenesis are discussed. Finally, we address important aspects for the development of fungal-derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control fungal disease.
Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation (2016)

The modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two major DNA epigenetic modifications in mammalian genomes and play crucial roles in development and pathogenesis. Little is known about the colocalization or potential correlation of these two modifications. Here we present an ultrasensitive single-molecule imaging technology capable of detecting and quantifying 5hmC and 5mC from trace amounts of DNA. We used this approach to perform single-molecule fluorescence resonance energy transfer (smFRET) experiments which measure the proximity between 5mC and 5hmC in the same DNA molecule. Our results reveal high levels of adjacent and opposing methylated and hydroxymethylated CpG sites (5hmC/5mCpGs) in mouse genomic DNA across multiple tissues. This identifies the previously undetectable and unappreciated 5hmC/5mCpGs as one of the major states for 5hmC in the mammalian genome and suggest that they could function in promoting gene expression.
Bacteroides fragilis Enterotoxin Gene Sequences in Patients with Inflammatory Bowel Disease (2000)

We identified enterotoxigenic Bacteroides fragilis in stool specimens of patients with inflammatory bowel disease and other gastrointestinal disorders. The organism was detected in 11 (13.2%) of 83 patients with inflammatory bowel disease. Of 57 patients with active disease, 19.3% were toxin positive; none of those with inactive disease had specimens positive for enterotoxigenic Bacteroides fragilis gene sequences.
Reconstitution of Neuronal Cdc2-like Kinase from Bacteria-expressed Cdk5 and an Active Fragment of the Brain-specific Activator (1995)

Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subunit which is derived from a brain-specific 35-kDa novel protein, p35 (Lew, J., Huang, Q.-Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H. (1994) Nature 371, 423-426). Three truncated forms of p35 including the one corresponding to the 25-kDa subunit of the kinase have been expressed in Escherichia coli and shown to activate a bacteria-expressed Cdk5 with equal efficacy. The shortest truncated form of p35, p21, spanning amino acid residues 88 to 291, has been used to reconstitute active Cdk5 kinase and to characterize the activation reaction. The purified kinase displays similar specific enzyme activity and similar phosphorylation site specificity as the neuronal Cdc2-like kinase purified from bovine brain. Bovine brain extract contains Cdk5 uncomplexed with p35 or p25 which has also been found to be activated by p21 or p25. The results substantiate the previous suggestion that p35 is a specific Cdk5 activator. Several observations suggest that, unlike other well characterized Cdc2-like kinases whose activities depend on the phosphorylation of the catalytic subunits at a specific site by a distinct kinase, the reconstituted Cdk5/p21 does not depend on the phosphorylation of Cdk5 for activity. The reconstitution of the highly active Cdk5 kinase was achieved without requiring any other kinase in the reconstitution reaction. The possibility of autophosphorylation of Cdk5 on the putative activation site has been ruled out as no phosphorylation occurred on Cdk5 during the enzyme reaction. The rate and extent of the kinase reconstitution were not significantly affected by Mg2+ ATP.
Development of the thermionic valve (1990)

Compared with the situation immediately preceding the Second World War, the overall picture by 1945 was that of much greater diversification. Highly specialised, costly devices, capable of generating extremely high powers, existed at one end of the spectrum, and mass-produced low-cost miniature receiving valves at the other. It was in the latter area that semiconductor diodes had established themselves at the expense of the thermionic valve, as a detector of microwave frequencies. Later developments, involving the transistor, have since almost entirely replaced the vacuum tube as a low-power, low cost mass produced device. It has not however been possible to replace the specialised high-power high-frequency transmitting devices, such as the klystron, magnetron and travelling-wave tube by any solid-state equivalent.
Integrin-associated Protein Is a Receptor for the C-terminal Domain of Thrombospondin (1996)

The C-terminal "cell-binding domain" (CBD) of thrombospondin-1 (TS1) is a binding site for many cell types. Cell-binding peptides based on the sequence RFYVVM from the CBD of TS1 affinity label a 52-kDa cell surface glycoprotein, which we show is integrin-associated protein (IAP or CD47). IAP associates with alpha v beta 3 and thereby modulates the activity of several integrins. Cells that express IAP bind strongly to TS1, the CBD, and its active cell-binding peptides while IAP negative cells do not. The 52-kDa protein is affinity labeled on IAP-positive but not IAP-negative cells, and monoclonal antibodies against IAP specifically immunoprecipitate the affinity-labeled 52-kDa protein from lysates of IAP-positive cells. Consistent with the association of IAP with alpha v beta 3 integrin, the labeled 52-kDa protein is immunoprecipitated by an anti-alpha v beta 3 antibody. Endothelial cells exhibit chemotaxis toward TS1 (at concentrations above 10 nM) and RFYVVM peptides. Chemotaxis to both agents is specifically inhibited by a function blocking anti-IAP monoclonal antibody. These data establish IAP (CD47) as a receptor for the CBD of TS1 and suggest a mechanism for the well established effects of the CBD on cell motility.
Multilayer exchange spring media for magnetic recording (2006)

The concept of exchange spring media is extended from two layers to N layers. The coercive field of the multilayer structure decreases with 1∕N while the energy barrier is only determined by the magnetic properties of the hardest layer. A 25nm thick trilayer has a 7.5 times smaller coercive field (1.4T) as a single layer at the same thermal stability and for the same value of the magnetization. A continuous variation of the anisotropy in the recording media reduces the coercive field by a factor of 10 for a layer thickness of 25nm.
5,8-Disubstituted 1-aminotetralins. Class of compounds with a novel profile of central nervous system activity (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT5,8-Disubstituted 1-aminotetralins. Class of compounds with a novel profile of central nervous system activityReinhard Sarges, James R. Tretter, Stanley S. Tenen, and Albert WeissmanCite this: J. Med. Chem. 1973, 16, 9, 1003–1011Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/jm00267a010https://doi.org/10.1021/jm00267a010research-articleACS PublicationsRequest reuse permissionsArticle Views340Altmetric-Citations21LEARN 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
Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity (2004)

DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)-containing complexes.
Substrate protection against inactivation of the mammalian polyamine-transport system by 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide (1996)

Mammalian polyamine transporters have not thus far been biochemically characterized. Since essential carboxy groups in the polyamine carrier might participate in the transport process, the ability of two different carbodi-imides to affect [3H]spermidine uptake was assessed in Chinese hamster ovary cells. Both the hydrophobic 1,3-dicyclohexylcarbodi-imide (DCC) and the more polar 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide (EDC) irreversibly inhibited spermidine transport with EC50 values of 11 +/- 4 and 96 +/- 16 microM after 30 min at 22 degrees C respectively. Prior treatment with EDC in the absence of substrate decreased both the Vmax and K(m) for spermidine uptake in a time- and concentration-dependent manner. Spermidine-transport inactivation by EDC (1 mM) was temperature-dependent, with 60 and 90% inhibition observed after 10 min at 22 and 37 degrees C respectively. Spermine (10 microM) almost fully protected against spermidine-transport inactivation by EDC at 22 degrees C, and decreased the rate of inactivation at 37 degrees C by about 80%. Putrescine, spermidine and spermine were all effective in protecting against EDC-mediated inactivation of [3H]spermidine and [3H]putrescine uptake at 22 degrees C with EC50 values estimated at 10, 1 and less than 1 microM respectively. The nucleophile glycine ethyl ester (up to 50 mM) prevented the inhibition brought about by 1 mM EDC. Inhibition by 1 mM EDC was greater at pH 7.2 than at pH 5.8 (89 +/- 3 compared with 44 +/- 5%), whereas the converse was true for 100 microM DCC (81 +/- 3 compared with 92 +/- 5%). On the other hand, spermine did not protect against inactivation of spermidine uptake by DCC. Moreover, DCC, but not EDC, inhibited Na(+)-dependent amino acid uptake. The present data indicate that (i) EDC and DCC inhibit polyamine transport through distinct mechanisms, (ii) substrate binding occludes one or several carboxy groups lying in a polar environment of the carrier and (iii) these carboxyl residues might be activated by EDC to crosslink a neighbouring nucleophile side group, resulting in a conformation of the polyamine carrier which is inactive for transport.
ElasticFusion: Dense SLAM Without A Pose Graph (2015)

We present a novel approach to real-time dense visual SLAM. Our system is capable of capturing comprehensive dense globally consistent surfel-based maps of room scale environments explored using an RGB-D camera in an incremental online fashion, without pose graph optimisation or any postprocessing steps. This is accomplished by using dense frame-tomodel camera tracking and windowed surfel-based fusion coupled with frequent model refinement through non-rigid surface deformations. Our approach applies local model-to-model surface loop closure optimisations as often as possible to stay close to the mode of the map distribution, while utilising global loop closure to recover from arbitrary drift and maintain global consistency.
Effect of ADP and Ionic Strength on the Kinetic and Motile Properties of Recombinant Mouse Myosin V (2000)

Mouse myosin V is a two-headed unconventional myosin with an extended neck that binds six calmodulins. Double-headed (heavy meromyosin-like) and single-headed (subfragment 1-like) fragments of mouse myosin V were expressed in Sf9 cells, and intact myosin V was purified from mouse brain. The actin-activated MgATPase of the tissue-purified myosin V, and its expressed fragments had a high V(max) and a low K(ATPase). Calcium regulated the MgATPase of intact myosin V but not of the fragments. Both the MgATPase activity and the in vitro motility were remarkably insensitive to ionic strength. Myosin V and its fragments translocated actin at very low myosin surface densities. ADP markedly inhibited the actin-activated MgATPase activity and the in vitro motility. ADP dissociated from myosin V subfragment 1 at a rate of about 11.5 s(-1) under conditions where the V(max) was 3.3 s(-1), indicating that, although not totally rate-limiting, ADP dissociation was close to the rate-limiting step. The high affinity for actin and the slow rate of ADP release helps the myosin head to remain attached to actin for a large fraction of each ATPase cycle and allows actin filaments to be moved by only a few myosin V molecules in vitro.
Increased Hepatic Insulin Action in Diet-Induced Obese Mice Following Inhibition of Glucosylceramide Synthase (2010)

These results indicate that GSL inhibition in obese mice primarily results in an increase in insulin action in the liver, and suggests that GSLs may have an important role in hepatic insulin resistance in conditions of obesity.