gebhart/patrepeval huggingface dataset:
Characterization of Some Molecular Mechanisms Governing Autoactivation of the Catalytic Domain of the Anaplastic Lymphoma Kinase (2007)

NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of anaplastic large cell lymphoma cases. It derives from the t(2;5)(p23;q35) chromosomal translocation that fuses the catalytic domain of the tyrosine kinase, anaplastic lymphoma kinase (ALK), with the dimerization domain of the ubiquitously expressed nucleophosmin (NPM) protein. Dimerization of the ALK kinase domain leads to its autophosphorylation and constitutive activation. Activated NPM/ALK stimulates downstream survival and proliferation signaling pathways leading to malignant transformation. Herein, we investigated the molecular mechanisms of autoactivation of the catalytic domain of ALK. Because kinases are typically regulated by autophosphorylation of their activation loops, we systematically mutated (Tyr --> Phe) three potential autophosphorylation sites contained in the "YXXXYY" motif of the ALK activation loop, and determined the effect of these mutations on the catalytic activity and biological function of NPM/ALK. We observed that mutation of both the second and third tyrosine residues (YFF mutant) did not affect the kinase activity or transforming ability of NPM/ALK. In contrast, mutation of the first and second (FFY), first and third (FYF), or all three (FFF) tyrosine residues impaired both kinase activity and transforming ability of NPM/ALK. Furthermore, a DFF mutant, in which the aspartic residue introduces a negative charge similar to a phosphorylated tyrosine, possessed catalytic activity similar to the YFF mutant. Together, our findings indicate that phosphorylation of the first tyrosine of the YXXXYY motif is necessary for the autoactivation of the ALK kinase domain and the transforming activity of NPM/ALK.
The Effect of Polyvinylpyrrolidine on the Stability of Taurolidine (1997)

In an aqueous solution, taurolidine reversibly degrades to taurultam, hydroxymethyltaurultam, taurineamide, and formaldehyde. The objectives of this research were to investigate the mechanism of polyvinylpyrrolidine (PVP)-induced taurolidine stabilization by measuring the effect of PVP on the rate and extent of formaldehyde release from taurolidine and its decomposition products, the ionization of taurineamide, and the NMR and FT-IR spectra of taurineamide. PVP was found to a) increase the rate constant for taurultam formation from taurineamide and formaldehyde, b) decrease the apparent pKa of taurineamide, and c) alter the NMR and FT-IR taurineamide spectra. The effect of PVP on the stability of taurolidine was to increase the stability of its primary degradation product, taurultam, which, in turn increased taurolidine stability because taurultam was reversibly formed from taurolidine. Furthermore, the increased stability of taurultam in acidic, aqueous PVP solutions was due to an increased rate of taurultam formation from its primary degradation products: taurineamide and formaldehyde. The rate constant for taurultam formation increased three-fold in the presence of 5% PVP. The rate increase was caused by the interaction of unprotonated taurineamide with PVP. The estimated taurineamide-PVP association constant was 1800 M-1. This interaction decreased the concentration of unreactive/protonated taurineamide while increasing the concentration of unprotonated/associated substrate which was found to be fivefold less reactive than the free/unprotonated amine.
Bacillus thuringiensis Enzyme-Digested Delta Endotoxin: Effect on Cultured Insect Cells (1976)

Cells from three insect cell lines responded to the enzyme-digested delta endotoxin of Bacillus thuringiensis with swelling, lysis, and vesicle formation. Sufficient toxin was taken up in 1 minute to cause half-maximal cell damage. Cytoxic activity was neutralized by specific antiserum to the endotoxin.
The Ferric Chloride Oxidation of 5-Substituted o-Semidines and the Polarographic Properties of the Products (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Ferric Chloride Oxidation of 5-Substituted o-Semidines and the Polarographic Properties of the ProductsAlfred P. Kottenhahn, Eddie T. Seo, and Hosmer W. StoneCite this: J. Org. Chem. 1963, 28, 11, 3114–3120Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jo01046a043https://doi.org/10.1021/jo01046a043research-articleACS PublicationsRequest reuse permissionsArticle Views148Altmetric-Citations9LEARN 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
Pax3/Pax7 mark a novel population of primitive myogenic cells during development (2005)

Skeletal muscle serves as a paradigm for the acquisition of cell fate, yet the relationship between primitive cell populations and emerging myoblasts has remained elusive. We identify a novel population of resident Pax3+/Pax7+, muscle marker-negative cells throughout development. Using mouse mutants that uncouple myogenic progression, we show that these Pax+ cells give rise to muscle progenitors. In the absence of skeletal muscle, they apoptose after down-regulation of Pax7. Furthermore, they mark the emergence of satellite cells during fetal development, and do not require Pax3 function. These findings identify critical cell populations during lineage restriction, and provide a framework for defining myogenic cell states for therapeutic studies.
Neuroprotective Effects of Leptin Against Ischemic Injury Induced by Oxygen-Glucose Deprivation and Transient Cerebral Ischemia (2007)

Leptin is neuroprotective against ischemic neuronal injury. Our findings suggest that leptin is a legitimate candidate for the treatment of ischemic stroke.
Historical overview of the treatment of rheumatoid arthritis with an emphasis on methotrexate. (1996)

We have reviewed the treatment of rheumatoid arthritis (RA) in pertinent selected literature with a focus on methotrexate (MTX). Considerable progress has been made over the last 120 years since the introduction of salicylates to treat rheumatic symptoms. Most slow acting antirheumatic drugs became widely used in the years after the second world war. MTX became widely accepted in the 1980s although early reports of its use predate that time. The historical perspective of the development of agents to treat RA indicates that most significant advances are concentrated in the last 45 years, especially the last 15 years. This trend will likely continue.
A controlled study of Tourette syndrome. II. Conduct. (1987)

To assess conduct in Tourette syndrome (TS), 47 controls, 246 TS patients, 17 attention-deficit-disorder (ADD), and 15 ADD patients with minor tics or a family history of TS (ADD 2(0) TS) were compared for the following behaviors: running away from home, lying, stealing, starting fires, vandalism, being in trouble with the law, fighting, shouting at parents or peers, attacking others, lack of respect for adults, short temper, hurting animals, feeling full of hate, being unable to stop fighting, and problems with drugs and alcohol. With the exception of running away from home and being in trouble with the law, TS patients were significantly different from controls in all other behaviors. When the components were combined for a total conduct score, only one (2.1%) of the controls had a score greater than 13, and he had TS. By contrast, 35% of the TS patients had scores greater than 13 (P less than .0005). The correlation coefficient between the total conduct score and ADD score was .48. Although the presence of ADD was an important factor in determining conduct in TS, other factors such as depression and compulsive behavior also played a contributing role. There was little correlation between the total conduct score and the number of tics. It is estimated that among non-economically disadvantaged children, 10%-30% of conduct disorder may be due to the presence of a TS gene.
B7-H1 Up-Regulation on Myeloid Dendritic Cells Significantly Suppresses T Cell Immune Function in Patients with Chronic Hepatitis B (2007)

Although dysfunctional dendritic cells contribute to inadequate adaptive immunity in chronic hepatitis B (CHB), underlying molecular mechanisms remain largely undefined. In this study, we examined B7-H1 expression on circulating myeloid dendritic cells (mDCs) in 46 CHB patients, 10 autoimmune hepatitis patients, and 10 healthy subjects as control. We found that B7-H1 expression is significantly up-regulated on circulating mDCs of CHB and autoimmune hepatitis patients compared with healthy individuals. The B7-H1 up-regulation was significantly correlated with an elevation of serum alanine aminotransaminase levels and plasma viral load. In addition, in vitro, both IFN-alpha and IFN-gamma could strongly stimulate mDCs to express B7-H1. More importantly, elevated B7-H1 expression is also closely associated with the suppression of T cell immune function. In vitro blockade of B7-H1 signaling could not only down-regulate IL-10 and up-regulate IL-12 production by mDCs, but also enhance mDC-mediated allostimulatory capacity and cytokine production of T cells. Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-gamma production by autologous hepatitis B virus-specific T cells. These new findings suggested that chronic inflammation may contribute to B7-H1 up-regulation on mDCs in CHB patients, which potentially cause defective hepatitis B virus-specific T cell function and viral persistence. Our findings further support the notion that the blockade of B7-H1 may represent a novel therapeutic approach for this disease.
Site-Specific Antibody–Polymer Conjugates for siRNA Delivery (2013)

We describe here the development of site-specific antibody-polymer conjugates (APCs) for the selective delivery of small interference RNAs (siRNAs) to target cells. APCs were synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded p-acetyl phenylalanine (pAcF). The APCs all showed binding affinity comparable to that of HER2 as their native counterparts and no significant cellular cytotoxicity. Mutant S202-pAcF Fab and Q389-pAcF IgG polymer conjugates specifically delivered siRNAs to HER2(+) cells and mediated potent gene silencing at both the mRNA and protein levels. However, a mutant A121-pAcF IgG polymer conjugate, despite its high binding affinity to HER2 antigen, did not induce a significant RNA interference response in HER2(+) cells, presumably due to steric interference with antigen binding and internalization. These results highlight the importance of conjugation site on the activity of antibody-polymer-based therapeutics and suggest that such chemically defined APCs may afford a useful targeted delivery platform for siRNAs or other nucleic acid-based therapies.
Myriad Applications of Circulating Cell-Free DNA in Precision Organ Transplant Monitoring (2017)

Solid organ transplantation remains the preferred treatment for many end-stage organ diseases, but complications due to acute rejection and infection occur frequently and undermine its long-term benefits. Monitoring of the health of the allograft is therefore a critically important component of post-transplant therapy. Here, we review several emerging applications of circulating cell-free DNA (cfDNA) in the post-transplant monitoring of rejection, infection, and immunosuppression. We further discuss the cellular origins and salient biophysical properties of cfDNA. A property of cfDNA that has been prominent since its discovery in the late 1940s is its ability to yield surprises. We review recent insights into the epigenetic features of cfDNA that yet again provide novel opportunities for transplant monitoring.
Analysis and visualization of SSH attacks using honeypots (2013)

In the field of computer security, honeypots are systems aimed at deceiving malicious users who launch attacks against the servers and network infrastructure of various organizations. They can be deployed as protection mechanisms to an organization's real systems, or as research units to study and analyze the methods employed by individual hackers. In this paper we present the results of a research honeypot's operation, which undertook the role of a web trap for attackers who target the SSH service in order to gain illegal server access. The fake system has remained online and fully operational during a course of several consequent months, capturing attacks and logging all malicious activity. During this assessment it was shown that honeypots remain very effective tools in gathering information about SSH attacks. Furthermore, we observed that attackers are constantly targeting servers in the wild employing ready-to-use tools and dictionaries, while their post-compromise actions include mostly pivoting and IRC-related activities. Lastly we present a visualization tool aimed at helping security researchers during the analysis and conclusions drawing phases, for use with the same SSH honeypot implementation software as outlined in this work.
Porta-person (2007)

This paper describes a telepresence device called Porta-Person. This is the first project in a larger initiative known as the Connected Conference Room, which aims to improve the user experience for remote people connected to meetings taking place in conference rooms. The Porta-Person is designed to enhance a sense of social presence for remote meeting participants. It does this by providing a high-fidelity audio connection and a remotely controlled telepresence display with video or animation.
Intelligent control of the Intelledex 605T robot manipulator (1988)

The authors present the results of the experiments which indicate how controlled robotic motion might be achieved through pattern-based paradigms, implemented for real-time operation on the Intelledex 605T robot manipulator with artificial neural nets (ANN). Previous attempts at pattern-based control have often failed, primarily because of the need for storage of an enormous number of training-set patterns and the long times required for pattern processing. It is demonstrated that these problems can be overcome through use of artificial neural networks implemented by parallel distributed processing. The feedforward Rumelhart net is investigated for the constrained robot manipulator. The robot arm, with two degrees of freedom, must move its end effector toward an observed target in the presence of disturbances. Such a control action need not be programmed in detail. Presented with a small number of training situations, the ANN can generalize and perform in many different situations. Preliminary results obtained using an Intelledex 605T and an IBM PC/AT are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cell Biology by the Numbers (2015)

A Top 25 CHOICE 2016&nbsp;Title, and recipient of the CHOICE Outstanding Academic Title (OAT) Award. How much energy is released in ATP hydrolysis? How many mRNAs are in a cell? How genetically similar are two random people? What is faster, transcription or translation?Cell Biology by the Numbers explores these questions and dozens of others provid
Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor (1996)

4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC50s up to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this "supra-additive" effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.
Protein Kinase C Controls Microtubule-based Traffic but Not Proteasomal Degradation of c-Met (2003)

Upon hepatocyte growth factor stimulation, its receptor c-Met is rapidly internalized via clathrin-coated vesicles and traffics through an early endosomal compartment. We show here that c-Met accumulates progressively in perinuclear compartments, which in part include the Golgi. The c-Met content in the Golgi is principally the newly synthesized precursor form and, to a lesser extent, the internalized, recycling c-Met. By following the trafficking of c-Met inside the cell using a semi-automatic procedure and using inhibition or activation of protein kinase C (PKC) and microtubule depolymerizing agents, we show that PKC positively controls the trans-cytosolic movement of c-Met along microtubules. In parallel to its traffic, internalized c-Met is progressively degraded by a proteasome-sensitive mechanism; the lysosomal pathway does not play a substantial role. Inhibition or promotion of c-Met traffic to the perinuclear compartment does not alter the kinetics of proteasome-dependent c-Met degradation. Thus susceptibility to proteasomal degradation is not a consequence of post-endocytic traffic. The data define a PKC-controlled traffic pathway for c-Met that operates independently of its degradative pathway.
An Inhibitor of Ribosomal Peptidyl Transferase Using the Transition-State Analogy (1995)

The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide modification. The Ki's of structural homologues of CCdApPuro suggest that both the CCdA and puromycin moieties participate in binding. Thus, CCdApPuro appears to bridge the A- and P-sites of the ribosome, implying that substrates are juxtaposed with a geometry suitable for direct reaction during peptidyl transfer.
Pramlintide as An Adjunct to Insulin in Patients with Type 2 Diabetes in A Clinical Practice Setting Reduced A1C, Postprandial Glucose Excursions, And Weight (2007)

In this uncontrolled, open-label setting, pramlintide initiation while reducing mealtime insulin, followed by insulin dose optimization, resulted in improvements in postprandial glucose excursions and A1C. These improvements in glycemic control were accompanied by weight loss.
Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis (2014)

Microscopic pathological heterogeneity in IPF lung tissue corresponds to specific gene expression patterns related to bronchiolisation and lymphoid aggregates. MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF.
Purification and Characterization of Thrombopoietin1 (1995)

A thrombopoietic factor, termed thrombopoietin (TPO), was highly purified directly from the plasma of sublethally irradiated 1,100 rats by measuring the production of megakaryocytes from a highly enriched population of rat megakaryocyte progenitor cells (CFU-MK). The rat plasma TPO is a glycoprotein and strongly hydrophobic. The total activity and purification yields obtained were about 29% and 1.49 x 10(8), respectively. The amino acid sequences of the two peptide fragments prepared from the purified 19 kDa TPO were analyzed, and used for the cloning of rat and human TPO cDNAs. It was found that the 19 kDa TPO was truncated but comprised at least 163 amino acids. The sequence of human TPO cDNA revealed that the TPO was identical to the c-Mpl ligand. Both rat and human TPOs expressed in COS-1 cells exhibited significant activity toward the CFU-MK in vitro, and were active in stimulating platelet production in mice. These results indicate that a thrombopoietic factor originally found in the irradiated rat plasma is a ligand for the rat c-Mpl.
Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging☆ (2004)

Although neurocognitive decline after CABG is mostly transient, memory impairment can persist for months. New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline.
Reactions of phosphorus compounds. Preparation of cyclopropylidene compounds from cyclopropyltriphenylphosphonium bromide (1966)

E. E. Schweizer and J. G. Thompson, Chem. Commun. (London), 1966, 666 DOI: 10.1039/C19660000666
E1A-induced Processing of Procaspase-8 Can Occur Independently of FADD and Is Inhibited by Bcl-2 (1998)

Expression of the 243-residue form of the adenovirus E1A protein in the absence of other viral proteins triggers apoptosis by a pathway that requires p53. This pathway includes processing and activation of initiator procaspase-8, redistribution of cytochrome <i>c</i>, and activation of procaspase-3. Bcl-2 functions at or upstream of procaspase-8 processing to inhibit all of these events and prevent cell death. This contrasts with the anti-apoptotic influence of Bcl-2 family proteins in the cell death pathway induced by Fas ligand or tumor necrosis factor (TNF), in which Bcl-2 typically acts downstream of Fas/TNFR1-mediated activation of caspase-8. Moreover, E1A induces procaspase-8 processing and cell death in cells deleted of FADD, an adaptor protein critical for Fas/TNFR1 activation of caspase-8. The results indicate that E1A is capable of activating caspase-8 by a Bcl-2-inhibitable pathway that does not involve autocrine stimulation of FADD-dependent death receptor pathways.
Expression of raf oncogenes activates the PEA1 transcription factor motif. (1989)

PEA1 (AP1) motif transcription enhancer activity was stimulated by v-raf and more efficiently by activated c-raf-1 or A-raf than by their normal counterparts, in agreement with a role for PEA1 in transformation by raf. Mutations in the ATP-binding site of v-raf prevented activation, suggesting that phosphorylation is somehow required.