gebhart/patrepeval huggingface dataset:
Gonadotropin-releasing hormone (GnRH) agonist triptorelin inhibits estradiol-induced serum response element (SRE) activation and c-fos expression in human endometrial, ovarian and breast cancer cells (2004)

The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.
Network-Based Information Brokers (1995)

ions and assumptions that will enable the agent to retrieve information that is relevant to a query. . Methods for appropriately combining and summarizing retrieved information. Building such brokers as ad hoc, monolithic applications will not scale, and the resulting brokers will not be able to interoperate with the new protocols and services being developed for the Internet. Technical Approach Our approach in this project is to enable the construction and maintenance of domain-specific information brokers by developing . Detailed specifications of a broker system architecture. . A broker shell that implements the broker architecture and contains implementations of all the architecture&amp;apos;s domain-independent brokering facilities. . A domain and source modeling tool kit for developing and maintaining a broker&amp;apos;s domainspecific expertise. . Two example brokers: a broker in the Electronic Commerce testbed being built in the CommerceNet project, and a broker in the pharmaceutical domain for...
Synthesis (and Alternative Proof of Configuration) of the Scyphostatin C(1‘)−C(20‘) Trienoyl Fragment (2000)

[reaction--see text] Each of four diastereomers of structure 2, corresponding to the lipophilic side chain of scyphostatin (1), were prepared. Careful analysis of their NMR spectral data and comparison with those of the natural product corroborates the recently reported (Org. Lett. 2000, 2, 505) stereochemical assignment. A strategy for the stereoselective synthesis of 2 has been achieved.
Self-sharpening tip integrated on micro cantilevers with self-exciting piezoelectric sensor for parallel atomic force microscopy (1997)

Arrays of cantilevers with integrated self-sharpening tips and self-exciting piezoelectric sensors have been fabricated using monocrystalline silicon micromachining. During the fabrication process, tips are first formed with a wet etching technique allowing a good homogeneity of tip shape over a whole wafer and then protected with a local thick silicon dioxide layer. Single cantilevers have been used to achieve atomic force microscopy images of grids with periods of 0.25, 1, and 5 μm and with height differences of 100, 15, and 180 nm, respectively.
Effects of Mycobacterial Cell Wall‐DNA Complex (MCC), Alendronate and Pamidronate on Canine Osteosarcoma Cell Lines (2005)

Introduction: MCC, a cell wall composition prepared from Mycobacterium phlei ., inhibits the proliferation and induces apoptosis in a wide range of tumor cells. Bisphosphonates have been reported to inhibit the proliferation of canine osteosarcoma cell lines. In this study, we have determined the activity of MCC alone and in combination with the bisphosphonates alendronate and pamidronate on canine osteosarcoma cell lines. Methods: Canine osteosarcoma cell lines D17 and D22 were incubated with different concentrations of MCC (0.01–100 μg/ml) and suboptimal concentrations of alendronate and pamidronate for 72 hours. Cellular proliferation was measured by MTT reduction. Nuclear DNA condensation was determined using with Hoescht 33258 staining, and apoptosis by flow cytometry using active‐caspase‐3/PE and anti‐cleaved‐PARP/FITC antibodies. Results: MCC inhibited the proliferation of both canine osteosarcoma D17 and D22 cell lines in a concentration‐dependent manner. The IC 50 for D17 cells was 3.9 μg/ml and for D22 cells 44.4 μg/ml. Cells incubated with 100 μg/ml MCC were positive for Hoescht staining, active caspase‐3 and cleaved PARP, indicative of cell death by apoptosis. The addition of alendronate or pamidronate was found to potentiate the apoptosis‐inducing activity of MCC. Maximal activity was observed when 5 μM alendronante or 10 μM pamidronate were used in combination with 100 μg/ml MCC. Conclusion: MCC inhibits the proliferation and induces apoptosis in canine osteosarcoma cell lines in vitro . This anticancer activity can be potentiated by the use of alendronate and pamidronate. These data support the development of MCC as a therapeutic agent for the treatment of canine osteosarcoma.
Preliminary core set of domains and reporting requirements for longitudinal observational studies in rheumatology. (1999)

Observational and longitudinal observational studies (LOS) provide essential information about the course and outcome of rheumatic disorders that cannot be provided by randomized controlled trials, and they constitute the major clinical scientific communication in rheumatology. There has been no consensus as to the full and appropriate content of LOS. This report defines a core set of domains and reporting requirements for LOS. At the 1998 OMERACT IV Conference a consensus process evaluated the literature of rheumatology in light of the constructs, variables, and outcomes of rheumatology by using introductory lectures, nominal groups, and plenary sessions. The result of this process was to identify 5 "core" domains that should be included in every LOS: Health Status, Disease Process, Damage, Mortality, and Toxicity/Adverse Reactions. Two additional domains, Work Disability and Costs, were recognized as important, but need not be used in all LOS. Eleven subdomains were identified that divided the domains into convenient clinical and conceptual units. A set of reporting requirements was also determined. The core recommendations, which follow on the WHO ICIDH-2 outline, are not disease-specific; the substitution of different "disease process" and "damage" measures make them suitable for many rheumatic disorders. The core set is intended to serve as a core for LOS in almost all rheumatic conditions.
Quantitative analysis of effects causing nonlinear position response in position-sensitive photodetectors (1982)

Although it is theoretically possible to construct light-spot-position-sensitive photodetectors (PSD's) having perfect position-response linearity, in practice linearity is degraded by laterally inhomogeneous resistive layers, finite-conductive strips, and imperfect isolations. PSD's at 6 × 6 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> having 0.5-percent nonlinearity have been fabricated, but before making larger PSD's with less nonlinearity, e.g., for use in silicon repeaters, a quantitative analysis of the causes of nonlinearity must be made. To this end, a computer model is developed. This model is described here, and the results of calculations performed with it are discussed. Nonlinearity caused by inhomogeneity is found to be less than 1/8 of the maximum relative change in resistive layer conductivity. It further appears that finite-conductive contact strips cause less than 0.05-percent nonlinearity if the contact strips are wide enough. Nonlinearity due to imperfect isolations is important only when n-n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-</sup> or p-p <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-</sup> junctions are used. The calculations derived are found to be in good agreement with results given in the literature.
Immunity to experimental cholera. I. Protective effect of humoral IgG antitoxin demonstrated by passive immunization. (1974)

The protective role of serum IgG antitoxin was studied in dogs transfused either with whole plasma or purified serum IgG from hyperimmunized dogs. Washings of jejunal Thiry-Vella loops after plasma transfusion yielded IgG antitoxin. Furthermore, dogs transfused with antitoxic plasma were protected against intrajejunal challenge with cholera toxin and this protection could not be diminished by extensive washing of the jejunum prior to toxin challenge. Finally, intact dogs transfused with antitoxic serum IgG were highly protected against orogastric challenge with viable Vibrio cholerae. These results indicate that serum IgG can play a protective role at the surface of the gut mucosa or within its lumen. They also suggest that serum-derived antibody may exert its effect while intimately associated with the mucosa, a position in which it may be protected from rapid destruction by proteolytic enzymes.
Bacteriotherapy: the time has come (2001)

The worldwide emergence of bacterial resistance to antibacterial agents has produced a need for new methods of combating bacterial infections. This need is forced on us by the long time lag in developing new antibacterial agents. And even though new agents may be in the pipeline, they will not solve all current resistance problems. In addition, we also have to recognise that the use of antibacterial agents not only selects resistant bacteria but also disturbs normal human flora, which may itself further inhibit our defence against infection. Bacteriotherapy—using harmless bacteria to displace pathogenic organisms—is an alternative and promising way of combating infections.1

A recent paper in the BMJ by Roos et al showed how commensal α haemolytic streptococci were used to replace the normal nasopharyngeal flora in children with recurrent otitis media.2 The results were astonishing. After treatment, recurrences of otitis media fell to half of those in the control group; at three months 42% of children given streptococci in nasal spray were healthy …
Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome (2009)

Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS. (ClinicalTrials.gov number, NCT00465985.)
Targeting Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases (2006)

Malignant melanoma has a high propensity for metastatic spread, making it the most deadly form of skin cancer. B-RAF has been identified as the most mutated gene in these invasive cells and therefore an attractive therapeutic target. However, for uncertain reasons, chemotherapy inhibiting B-Raf has not been clinically effective. This has raised questions whether this pathway is important in melanoma metastasis or whether targeting a protein other than B-Raf in the signaling cascade could more effectively inhibit this pathway to reduce lung metastases. Here, we investigated the role played by (V600E)B-Raf in melanoma metastasis and showed that targeting this signaling cascade significantly reduces lung metastases. Small interfering RNA (siRNA)-mediated inhibition was used in mice to reduce expression (activity) of each member of the signaling cascade and effects on metastasis development were measured. Targeting any member of the signaling cascade reduced metastasis but inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (Mek) 1 and Mek 2 almost completely prevented lung tumor development. Mechanistically, metastatic inhibition was mediated through reduction of melanoma cell extravasation through the endothelium and decreased proliferative capacity. Targeting B-Raf with the pharmacologic inhibitor BAY 43-9006, which was found ineffective in clinical trials and seems to act primarily as an angiogenesis inhibitor, did not decrease metastasis, whereas inhibition of Mek using U0126 decreased cellular proliferative capacity, thereby effectively reducing number and size of lung metastases. In summary, this study provides a mechanistic basis for targeting Mek and not B-Raf in the mutant (V600E)B-Raf signaling cascade to inhibit melanoma metastases.
Polyglutamine-Expanded Androgen Receptors Form Aggregates That Sequester Heat Shock Proteins, Proteasome Components and SRC-1, and Are Suppressed by the HDJ-2 Chaperone (1999)

Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a polyglutamine expansion in the androgen receptor (AR). We show in transiently transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron microscopy reveals both types of aggregates to have a similar ultrastructure. ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ-2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label with antibodies recognizing the PA700 proteasome caps but not 20S core particles. These results suggest that ARQ48 accumulates due to protein misfolding and a breakdown in proteolytic processing. Furthermore, the homeostatic disturbances associated with aggregate formation may affect normal cell function.
Corticotropin and beta-endorphin: construction and analysis of recombinant DNA complementary to mRNA for the common precursor. (1979)

A cDNA fragment synthesized from mouse mRNA (ACTH/LPH mRNA) that codes for the precursor polypeptide containing corticotropin (ACTH), beta-lipotropin (LPH), and several other peptides has been cloned in bacteria. The mRNA was enriched for ACTH/LPH mRNA translational activity (to about 75%) prior to cDNA synthesis. It appears to contain about 1200 bases, of which approximately 450 bases are not translated. The cloned DNA fragment is complementary to the region of the mRNA coding for the protein fragment beta-LPH-(44--90); this contains all of the amino acids of [Met]-enkephalin (residues 61--65 of beta-LPH), most of the amino acids of beta-melanocyte-stimulating hormone, and all but the carboxy-terminal amino acid of beta-endorphin. Based on assignment of the amino acid sequence of mouse beta-LPH from the nucelic acid sequence, it appears that there is extensive homology of mouse beta-LPH with human and porcine beta-LPH. The data also establish the linkage between beta-melanocyte-stimulating hormone and beta-endorphin as a Lys-Arg sequence. It is hoped that this cloned DNA can be used as a probe to study the expression and structure of the ACTH/LPH gene.
Context-dependent Markov model structured by locus equations: Applications to phonetic classification (1994)

In this paper, a quantitative and parametric model is presented that incorporates the role of context-dependent formant transitions in phonetic decoding of speech. The idea is to use the locus equations established from speech science to constrain the model parameters so that the number of parameters for the context-dependent model reduces to the same order as that for the context-independent model. In contrast to the knowledge-based, largely qualitative approaches employing also the formant transition information, our approach allows the parameters of the phonetic classifier, including the locus-equation slopes and intercepts, in conjunction with the hidden Markov model parameters, to be subject to mathematical optimization via an effective and efficient training procedure developed in this study. Detailed analysis of the results obtained from automatic training shows that the estimates of the locus-equation slopes and intercepts are consistent with those manually derived and reported in the speech science literature. Further, the experimental results using a phonetic classifier trained on the TIMIT database demonstrate the effectiveness of our new model, measured by a 15% classification error rate reduction, in comparison with a conventional statistical phonetic classifier under identical training and testing conditions.
Why Neurons Have Thousands of Synapses, a Theory of Sequence Memory in Neocortex (2016)

Pyramidal neurons represent the majority of excitatory neurons in the neocortex. Each pyramidal neuron receives input from thousands of excitatory synapses that are segregated onto dendritic branches. The dendrites themselves are segregated into apical, basal, and proximal integration zones, which have different properties. It is a mystery how pyramidal neurons integrate the input from thousands of synapses, what role the different dendrites play in this integration, and what kind of network behavior this enables in cortical tissue. It has been previously proposed that non-linear properties of dendrites enable cortical neurons to recognize multiple independent patterns. In this paper we extend this idea in multiple ways. First we show that a neuron with several thousand synapses segregated on active dendrites can recognize hundreds of independent patterns of cellular activity even in the presence of large amounts of noise and pattern variation. We then propose a neuron model where patterns detected on proximal dendrites lead to action potentials, defining the classic receptive field of the neuron, and patterns detected on basal and apical dendrites act as predictions by slightly depolarizing the neuron without generating an action potential. By this mechanism, a neuron can predict its activation in hundreds of independent contexts. We then present a network model based on neurons with these properties that learns time-based sequences. The network relies on fast local inhibition to preferentially activate neurons that are slightly depolarized. Through simulation we show that the network scales well and operates robustly over a wide range of parameters as long as the network uses a sparse distributed code of cellular activations. We contrast the properties of the new network model with several other neural network models to illustrate the relative capabilities of each. We conclude that pyramidal neurons with thousands of synapses, active dendrites, and multiple integration zones create a robust and powerful sequence memory. Given the prevalence and similarity of excitatory neurons throughout the neocortex and the importance of sequence memory in inference and behavior, we propose that this form of sequence memory may be a universal property of neocortical tissue.
3-Benzyloxyisoxazole system in construction of tetracyclines (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-Benzyloxyisoxazole system in construction of tetracyclinesGilbert Stork and Alfred A. Hagedorn IIICite this: J. Am. Chem. Soc. 1978, 100, 11, 3609–3611Publication Date (Print):May 1, 1978Publication History Published online1 May 2002Published inissue 1 May 1978https://pubs.acs.org/doi/10.1021/ja00479a060https://doi.org/10.1021/ja00479a060research-articleACS PublicationsRequest reuse permissionsArticle Views847Altmetric-Citations61LEARN 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
Platelet GP IIIa Pl A and GP Ib Variable Number Tandem Repeat Polymorphisms and Markers of Platelet Activation in Acute Stroke (1998)

A number of polymorphisms of the platelet glycoprotein (GP) Ib-V-IX and IIb/IIIa complexes have been described, and the PlA polymorphism of GP IIIa has been associated with coronary thrombosis. We determined the levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) and the genotype distributions of PlA and a variable number tandem repeat (VNTR) polymorphism of GP 1b in subjects with acute stroke (n=609) and healthy control subjects (n=435). Levels of beta-TG were higher in patients both initially (47.4 [44.7 to 50.2] ng/mL, P<0.0001) and after 3 months (42.9 [40.3 to 45.7] ng/mL, P=0.03) compared with control subjects (39.4 [37.7 to 41.2] ng/mL). Initial levels of beta-TG were significantly higher in those who subsequently died (58.7 [52.3 to 65.8] ng/mL) compared with those still alive (42.7 [40.1 to 45.5] ng/mL, P<0.0001). In a logistic regression model, beta-TG remained an independent predictor of poststroke mortality, with an odds ratio for an increase in 10 ng/mL of 1.12 (1.03 to 1.21, P=0.006). In subjects who had never smoked, there was a significant difference in the genotype distributions of patients with atherothrombotic stroke (A1/A1=147, A1/A2=70, and A2/A2=2) compared with controls (A1/A1=165, A1/A2=47, and A2/A2=5, P=0.03). The PlA distribution of subjects with atherothrombotic stroke before the age of 50 years (A1/A1=19 and A1/A2+A2/A2=18) was also significantly different from age- and sex-matched controls (A1/A1=54 and A1/A2+A2/A2=20, P=0.02). We found no association of VNTR with stroke or poststroke mortality. These data indicate that there is a persistent state of enhanced platelet activation in subjects with acute stroke, which is associated with poststroke mortality. The increased frequency of the PlA2 allele in young subjects with atherothrombotic stroke lends further support for a role of the PlA polymorphism in acute thrombosis.
Mutagenesis of the BH3 Domain of BAX Identifies Residues Critical for Dimerization and Killing (1998)

The BCL-2 family of proteins is comprised of proapoptotic as well as antiapoptotic members (S. N. Farrow and R. Brown, Curr. Opin. Genet. Dev. 6:45-49, 1996). A prominent death agonist, BAX, forms homodimers and heterodimerizes with multiple antiapoptotic members. Death agonists have an amphipathic alpha helix, called BH3; however, the initial assessment of BH3 in BAX has yielded conflicting results. Our BAX deletion constructs and minimal domain constructs indicated that the BH3 domain was required for BAX homodimerization and heterodimerization with BCL-2, BCL-XL, and MCL-1. An extensive site-directed mutagenesis of BH3 revealed that substitutions along the hydrophobic face of BH3, especially charged substitutions, had the greatest affects on dimerization patterns and death agonist activity. Particularly instructive was the BAX mutant mIII-1 (L63A, G67A, L70A, and M74A), which replaced the hydrophobic face of BH3 with alanines, preserving its amphipathic nature. BAXmIII-1 failed to form heterodimers or homodimers by yeast two-hybrid or immunoprecipitation analysis yet retained proapoptotic activity. This suggests that BAX's killing function reflects mechanisms beyond its binding to BCL-2 or BCL-XL to inhibit them or simply displace other protein partners. Notably, BAXmIII-1 was found predominantly in mitochondrial membranes, where it was homodimerized as assessed by homobifunctional cross-linkers. This characteristic of BAXmIII-1 correlates with its capacity to induce mitochondrial dysfunction, caspase activation, and apoptosis. These data are consistent with a model in which BAX death agonist activity may require an intramembranous conformation of this molecule that is not assessed accurately by classic binding assays.
Laboratory evaluation of the efficacy and speed of kill of lotilaner (CredelioTM) against Ixodes ricinus ticks on cats (2018)

At the minimum dose rate of 6 mg/kg, lotilaner was efficacious against I. ricinus ticks. In addition, lotilaner was effective against this tick within 12 hours of treatment, reaching 100% efficacy within 24 hours. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days. By quickly killing ticks that infest cats, lotilaner has the potential to contribute to the reduction of tick-borne pathogens transmission.