gebhart/patrepeval huggingface dataset:
Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: directed apoptotic events in vascular endothelial cells. (2003)

The serine protease granzyme B (GrB; 25 kDa) is capable of inducing apoptosis through both caspase-dependent and caspase-independent mechanisms. We designed a novel vascular-targeting fusion construct designated as GrB/vascular endothelial growth factor (VEGF)121, which is composed of a non-heparin-binding isoform of VEGF and the proapoptotic pathway enzyme GrB fused via a short, flexible tether (G4S). The chimeric fusion gene was then cloned into a bacterial vector, and the protein was expressed in Escherichia coli and purified by nickel-NTA metal affinity chromatography. Western blotting confirmed incorporation of both VEGF121 and GrB proteins into the construct. GrB/VEGF121 specifically bound (ELISA) to porcine aortic endothelial (PAE)/FLK-1 cells overexpressing the FLK-1/KDR receptor but not to cells overexpressing the FLT-1 receptor. Immunofluoresence studies showed that the GrB moiety of GrB/VEGF121 was delivered efficiently and rapidly into the cytosol of PAE/FLK-1 cells but not into that of PAE/FLT-1 cells after 4 h treatment with GrB/VEGF121. Treatment of cells with GrB/VEGF121 showed that the IC50 was approximately 10 nM against PAE/FLK-1 cells; however, there were no cytotoxic effects observed on PAE/FLT-1 cells at doses up to 200 nM. GrB/VEGF121 induced apoptotic events specifically on PAE/FLK-1 as assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay, DNA laddering, and cytochrome c release from mitochondria. In addition, the fusion construct mediated the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase in target endothelial cells within 4 h after treatment. In conclusion, delivery of the human proapoptotic pathway enzyme GrB to tumor vascular endothelial cells or to tumor cells may have significant therapeutic potential and represents a potent new class of targeted therapeutic agents with a unique mechanism of action.
Periurethral Teflon Injection: a Simple Treatment for Urinary Incontinence (1983)

The follow-up of 28 patients with urinary incontinence treated with periurethral Teflon injection revealed significant improvement in 53.6% and complete cure in 21.4%. Patients most likely to benefit were those with weak sphincters and stable detrusors. The method is quick and safe and requires only a brief hospital stay. It is suitable for patients in whom conventional operative techniques have failed or in whom surgery is best avoided on medical grounds.
Nanocomposites of Chitin Whiskers from Riftia Tubes and Poly(caprolactone) (2002)

Nanocomposite materials were obtained from a colloidal suspension of high aspect ratio β chitin whiskers as the reinforcing phase and poly(caprolactone) as the matrix. The chitin whiskers, prepared by acid hydrolysis of Riftia tubes, consisted of slender parallelepiped rods with an aspect ratio close to 120. A procedure was optimized to prepare a latex of poly(caprolactone). After mixing and stirring the two aqueous suspensions, solid films were obtained by either freeze-drying and hot-pressing or casting and evaporating the preparations. An amorphous poly(styrene-co-butyl acrylate) latex was also used as a model matrix. The thermal and mechanical properties of the resulting films were evaluated. The reinforcing effect of chitin whiskers is discussed on the basis of different types of mechanical models, and it is concluded that these whiskers form a rigid network assumed to be governed by a percolation mechanism. The formation of this network allows the thermal stabilization of the material for temperatures higher than the melting temperature of the poly(caprolactone).
An open‐label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function (2014)

Plasma migalastat clearance decreased as degree of renal impairment increased. Data from the migalastat HCl clinical program will guide dosing and intervals for patients with Fabry disease with renal impairment.
Simultaneous Real-Time Detection of Motor Imagery and Error-Related Potentials for Improved BCI Accuracy (2008)

Brain-computer interfaces (BCIs), as any other interaction modality based on physiological signals and body channels (e.g., muscular activity, speech and gestures), are prone to errors in the recognition of subject's intent. An elegant approach to improve the accuracy of BCIs consists of a verification procedure directly based on the presence of error-related potentials (ErrP) in the EEG recorded right after the occurrence of an error. Two healthy volunteer subjects with little prior BCI experience participated in a real-time human-robot interaction experiment where they were asked to mentally move a cursor towards a target that can be reached within a few steps using motor imagery. These experiments confirm the previously reported presence of a new kind of ErrP. These Interaction ErrP exhibit a first sharp negative peak followed by a positive peak and a second broader negative peak (~270, ~330 and ~430 ms after the feedback, respectively). The objective of the present study was to simultaneously detect erroneous responses of the interface and classifying motor imagery at the level of single trials in a real-time system. We have achieved online an average recognition rate of correct and erroneous single trials of 84.7% and 78.8%, respectively. The off-line post-analysis showed that the BCI error rate without the integration of ErrP detection is around 30% for both subjects. However, when integrating ErrP detection, the average online error rate drops to 7%, multiplying the bit rate by more than 3. These results show that it's possible to simultaneously extract in real-time useful information for mental control to operate a brain-actuated device as well as correlates of cognitive states such as error-related potentials to improve the quality of the brain-computer interaction.
Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease (2012)

This study provides detailed mRNA expression patterns of various claudins throughout the human gastrointestinal tract. Analysis of expression levels of claudins in patients with CD, active and inactive UC shows that changes in expression are confined to specific intestinal segments and strongly depend on inflammatory activity.
Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. (1994)

E2F-1, the first gene product identified among a family of E2F transcription factors, is thought to play a critical role in G1/S progression of the cell cycle. Transcriptional activities of E2F are modulated during the cell cycle, mainly by the formation of complexes between E2F and several key regulators of cell cycle such as the retinoblastoma protein and related proteins. To further understand the roles of E2F in the cell cycle progression, we have overexpressed exogenous E2F-1 by using a tetracycline-controlled expression system. We have found that the induced expression of E2F-1 in Rat-2 fibroblasts promotes S-phase entry and subsequently leads to apoptosis. The apoptosis occurs in an E2F-1 dose-dependent manner. Cells resistant to the induction of apoptosis have lost the ability to express exogenous E2F-1. Cells growing in low serum are more sensitive to the E2F-1-mediated cell death. Overexpression of E2F-1 mutants that impair DNA binding or transactivation does not alter cell cycle progression or induce apoptosis. These results define a novel pathway to apoptosis and demonstrate that premature S-phase entry is associated with apoptotic cell death.
Targeting Oncogenic ALK: A Promising Strategy for Cancer Treatment (2011)

Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and hematologic tumors. Novel drugs targeting this tyrosine kinase receptor are under development, and early clinical trials are showing promising activity in non-small cell lung cancer patients with ALK+ tumors. Here, we review the structure and function of the ALK receptor, the mechanisms associated with its deregulation in cancer, methods for ALK detection in tumor samples, its potential as a new marker for candidate patient selection for tailored therapy, and novel drugs under development that target ALK.
Biosynthesis of collagen and its alterations in pathological states. (1976)

The biosynthesis of collagen involves a number of unique post-translational modifications which are catalyzed by many specific enzymes. The main steps in collagen biosynthesis are transcription and translation, hydroxylations of prolyl and lysyl residues, glycosylations of hydroxylysyl residues, chain association and disulphide bonding, triple helix formation, secretion of procollagen into the extracellular matrix, conversion of procollagen into collagen, specific aggregation of collagen molecules and crosslink formation. Information about these modifications has rapidly increased during recent years, and initial information is available about the regulation and possibilities of specific pharmacological control of collagen biosynthesis at the level of these stages. Elucidation of the biochemical defect in an inborn error of collagen biosynthesis in man was reported for the first time in 1972 and subsequently several additional defects have been characterized. Alterations in collagen biosynthesis are also found during growth and ageing, as well as in many acquired pathological states: data about the nature of such changes in now rapidly accumulating.
Microinjected glutathione reductase crystals as indicators of the redox status in living cells (1999)

The flavoenzyme glutathione reductase catalyses electron transfer reactions between two major intracellular redox buffers, namely the NADPH/NADP+ couple and the 2 glutathione/glutathione disulfide couple. On this account, microcrystals of the enzyme were tested as redox probes of intracellular compartments. For introducing protein crystals into human fibroblasts, different methods (microinjection, particle bombardment and optical tweezers) were explored and compared. When glutathione reductase crystals are present in a cytosolic environment, the transition of the yellow Eox form to the orange-red 2-electron reduced charge transfer form, EH2, is observed. Taking into account the midpoint potential of the Eox/EH2 couple, the redox potential of the cytosol was found to be < -270 mV at pH 7.4 and 37 degrees C. As a general conclusion, competent proteins in crystalline--that is signal-amplifying--form are promising probes for studying intracellular events.
Service independent operations systems (2002)

The key to the success of intelligent networks (IN) is the capability to design, develop, and deploy new and innovative services quickly and in a cost effective manner. The service creation environment (SCE) for a programmable service control point (SCP) and service circuit node (SCN) provides a set of powerful capabilities to quickly design and develop new services on these platforms. A significant research and development effort has been spent on these technologies and these areas have been the focus of various standards committees. However, an important parameter for reducing time to market is the capability to offer new services to end-users. This requires the capability to quickly trial the services and to be able to offer these services in a consistent and integrated manner once the trial is successful. This capability involves managing the operations required for the new services in a consistent and secure manner over one or more networks. This often ignored area of the IN operations is the topic of our discussion.
The Polycondensation of Cyclohexylsilanetriol (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Polycondensation of CyclohexylsilanetriolJohn F. Brown Jr. and Lester H. Vogt Jr.Cite this: J. Am. Chem. Soc. 1965, 87, 19, 4313–4317Publication Date (Print):October 1, 1965Publication History Published online1 May 2002Published inissue 1 October 1965https://pubs.acs.org/doi/10.1021/ja00947a016https://doi.org/10.1021/ja00947a016research-articleACS PublicationsRequest reuse permissionsArticle Views1466Altmetric-Citations247LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A spectral-temporal method for pitch tracking (2006)

In this paper, a new spectral/temporal method is described for robust pitch tracking for both high quality and telephone speech. A previous version of this algorithm was presented as YAAPT (Kasi and Zahorian, 2002) [10]. In the current paper, a novel method is presented for spectral pitch tracking, using nonlinear processing to partially restore the potentially missing fundamental frequency. A frequency domain modified autocorrelation is used to determine the spacing between harmonic peaks in the spectrum. The frequency domain spectral track is then used to refine time-domain pitch candidates obtained using the “NCCF or Normalized Cross Correlation” reported by Talkin [1]. Dynamic programming is used to find the “best” pitch track among all the candidates, using both local and transition costs. The algorithm was evaluated using the Keele pitch extraction reference database.
Noninvasive imaging of protein–protein interactions in living subjects by using reporter protein complementation and reconstitution strategies (2002)

In this study we have developed bioluminescence-imaging strategies to noninvasively and quantitatively image protein-protein interactions in living mice by using a cooled charge-coupled device camera and split reporter technology. We validate both complementation and intein-mediated reconstitution of split firefly luciferase proteins driven by the interaction of two strongly interacting proteins, MyoD and Id. We use transient transfection of cells and image MyoD-Id interaction after induction of gene expression in cell culture and in cells implanted into living mice. Techniques to study protein-protein interactions in living subjects will allow the study of cellular networks, including signal transduction pathways, as well as development and optimization of pharmaceuticals for modulating protein-protein interactions.
Role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. II. Down-regulation of macrophage-mediated cytotoxicity by tumor-derived granulocyte-macrophage colony-stimulating factor (1991)

Peritoneal elicited macrophages (PEM) from mammary tumor-bearing mice have a decreased capacity to become cytotoxic against syngeneic, allogeneic, and xenogeneic target cells upon in vitro stimulation with LPS, as compared with PEM of normal mice. A regulatory mechanism other than PG release is suggested because the addition of both indomethacin and LPS to macrophage cultures from tumor-bearing mice caused no changes in their cytotoxic capability. Because tumor products have been implicated in the down-regulation of immune responses, we investigated whether pretreatment with supernatants from the tumor cell line DA-3, derived from the in vivo mammary adenocarcinoma D1-DMBA-3, affects the cytolytic capacity of macrophages. This treatment inhibits, in a dose-dependent fashion, the ability of stimulated normal PEM to kill target cells. Partial purification of DA-3 cell line supernatant showed that most of the inhibitory activity was exerted by factors with a molecular mass greater than 10 kDa and less than 30 kDa. However, slight inhibition could also be observed with fractions containing molecules less than 10 kDa. The data suggest that more than one factor released by the mammary tumor cells may be involved in the down-regulation of macrophage-mediated cytotoxicity. Because the DA-3 cells constitutively produce granulocyte-macrophage CSF (GM-CSF), which has a molecular mass of 27 kDa, we pretreated PEM from normal mice in vitro with rGM-CSF for 24 h. This resulted in a dose-dependent decrease in their capacity to kill tumor target cells upon LPS stimulation. Furthermore, PEM from normal mice injected with rGM-CSF for 25 days displayed a profound decrease in their cytolytic ability against DA-3 targets upon in vitro stimulation with increasing amounts of LPS. The pretreatment of PEM from normal mice with a combination of DA-3 cell supernatants and specific anti-GM-CSF partially neutralized the inhibitory effect of the DA-3 supernatant on macrophage tumoricidal capability. These results indicate that tumor-derived GM-CSF is an important factor involved in the decreased macrophage cytotoxicity during mammary adenocarcinoma progression.
The Influenza B Virus Hemagglutinin Head Domain Is Less Tolerant to Transposon Mutagenesis than That of the Influenza A Virus (2018)

Influenza A and B viruses can continuously evade humoral immune responses by developing mutations in the globular head of the hemagglutinin (HA) that prevent antibody binding. However, the influenza B virus HA over time displays less antigenic variation despite being functionally and structurally similar to the influenza A virus HA. To determine if the influenza B virus HA is under constraints that limit its antigenic variation, we performed a transposon screen to compare the mutational tolerance of the currently circulating influenza A virus HAs (H1 and H3 subtypes) and influenza B virus HAs (B/Victoria87 and B/Yamagata88 antigenic lineages). A library of insertional mutants for each HA was generated and deep sequenced after passaging to determine where insertions were tolerated in replicating viruses. The head domains of both viruses tolerated transposon mutagenesis, but the influenza A virus head was more tolerant to insertions than the influenza B virus head domain. Furthermore, all five of the known antigenic sites of the influenza A virus HA were tolerant of 15 nucleotide insertions, while insertions were detected in only two of the four antigenic sites in the influenza B virus head domain. Our analysis demonstrated that the influenza B virus HA is inherently less tolerant of transposon-mediated insertions than the influenza A virus HA. The reduced insertional tolerance of the influenza B virus HA may reveal genetic restrictions resulting in a lower capacity for antigenic evolution.<b>IMPORTANCE</b> Influenza viruses cause seasonal epidemics and result in significant human morbidity and mortality. Influenza viruses persist in the human population through generating mutations in the hemagglutinin head domain that prevent antibody recognition. Despite the similar selective pressures on influenza A and B viruses, influenza A virus displays a higher rate and breadth of antigenic variability than influenza B virus. A transposon mutagenesis screen was used to examine if the reduced antigenic variability of influenza B virus was due to inherent differences in mutational tolerance. This study demonstrates that the influenza A virus head domain and the individual antigenic sites targeted by humoral responses are more tolerant to insertions than those of influenza B virus. This finding sheds light on the genetic factors controlling the antigenic evolution of influenza viruses.
Bovine Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Cooperatively Antagonize Alpha/Beta Interferon-Induced Antiviral Response (2000)

The functions of bovine respiratory syncytial virus (BRSV) nonstructural proteins NS1 and NS2 were studied by generation and analysis of recombinant BRSV carrying single and double gene deletions. Whereas in MDBK cells the lack of either or both NS genes resulted in a 5,000- to 10,000-fold reduction of virus titers, in Vero cells a moderate (10-fold) reduction was observed. Interestingly, cell culture supernatants from infected MDBK cells were able to restrain the growth of NS deletion mutants in Vero cells, suggesting the involvement of NS proteins in escape from cytokine-mediated host cell responses. The responsible factors in MDBK supernatants were identified as type I interferons by neutralization of the inhibitory effect with antibodies blocking the alpha interferon (IFN-alpha) receptor. Treatment of cells with recombinant universal IFN-alpha A/D or IFN-beta revealed severe inhibition of single and double deletion mutants, whereas growth of full-length BRSV was not greatly affected. Surprisingly, all NS deletion mutants were equally repressed, indicating an obligatory cooperation of NS1 and NS2 in antagonizing IFN-mediated antiviral mechanisms. To verify this finding, we generated recombinant rabies virus (rRV) expressing either NS1 or NS2 and determined their IFN sensitivity. In cells coinfected with NS1- and NS2-expressing rRVs, virus replication was resistant to doses of IFN which caused a 1,000-fold reduction of replication in cells infected with wild-type RV or with each of the NS-expressing rRVs alone. Thus, BRSV NS proteins have the potential to cooperatively protect an unrelated virus from IFN-alpha/beta mediated antiviral responses. Interestingly, BRSV NS proteins provided a more pronounced resistance to IFN in the bovine cell line MDBK than in cell lines of other origins, suggesting adaptation to host-specific antiviral responses. The findings described have a major impact on the design of live recombinant BRSV and HRSV vaccines.
Nucleophilic Addition of Nitrogen to Aryl Cations: Mimicking Titan Chemistry (2013)

The reactivity of aryl cations toward molecular nitrogen is studied systematically in an ion trap mass spectrometer at 10(2) Pascal of nitrogen, the pressure of the Titan main haze layer. Nucleophilic addition of dinitrogen occurs and the nature of aryl group has a significant influence on the reactivity, through inductive effects and by changing the ground state spin multiplicity. The products of nitrogen activation, aryldiazonium ions, react with typical nitriles, aromatic amines, and alkynes (compounds that are relevant as possible Titan atmosphere constituents) to form covalently bonded heterocyclic products. Theoretical calculations at the level [DFT(B3LYP)/6-311++G(d,p)] indicate that the N2 addition reaction is exothermic for the singlet aryl cations but endothermic for their triplet spin isomers. The -OH and -NH2 substituted aryl ions are calculated to have triplet ground states, which is consistent with their decreased nitrogen addition reactivity. The energy needed for the generation of the aryl cations from their protonated precursors (ca. 340 kJ/mol starting with protonated aniline) is far less than that required to directly activate the nitrogen triple bond (the lowest energy excited state of N2 lies ca. 600 kJ/mol above the ground state). The formation of aza-aromatics via arene ionization and subsequent reactions provide a conceivable route to the genesis of nitrogen-containing organic molecules in the interstellar medium and Titan haze layers.