gebhart/patrepeval huggingface dataset:
Investigating RNA polymerase II carboxyl‐terminal domain (CTD) phosphorylation (2003)

Phosphorylation of RNA polymerase II's largest subunit C-terminal domain (CTD) is a key event during mRNA metabolism. Numerous enzymes, including cell cycle-dependent kinases and TFIIF-dependent phosphatases target the CTD. However, the repetitive nature of the CTD prevents determination of phosphorylated sites by conventional biochemistry methods. Fortunately, a panel of monoclonal antibodies is available that distinguishes between phosphorylated isoforms of RNA polymerase II's (RNAP II) largest subunit. Here, we review how successful these tools have been in monitoring RNAP II phosphorylation changes in vivo by immunofluorescence, chromatin immunoprecipitation and immunoblotting experiments. The CTD phosphorylation pattern is precisely modified as RNAP II progresses along the genes and is involved in sequential recruitment of RNA processing factors. One of the most popular anti-phosphoCTD Igs, H5, has been proposed in several studies as a landmark of RNAP II molecules engaged in transcription. Finally, we discuss how global RNAP II phosphorylation changes are affected by the physiological context such as cell stress and embryonic development.
Hepatitis B virus‐induced defect of monocyte‐derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape (2003)

Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from patients with chronic hepatitis B virus (HBV) infection are functionally impaired. In our present study MoDC from healthy subjects were propagated in vitro and inoculated with HBV particles to investigate the precise mechanisms that underly MoDC dysfunction. T-cell proliferation assays revealed an impaired allostimulatory capacity of HBV-inoculated MoDC (HBV-MoDC) as well as a lower potential of stimulating autologous T cells against a recall antigen in comparison to control-MoDC. Interleukin-2, tumour necrosis factor-alpha and interferon-gamma production by T cells in proliferation assays with HBV-MoDC was significantly lower than with control-MoDC and correlated with lower IL-12 production in HBV-MoDC cultures. The presence of the nucleoside analogue lamivudine (3TC), an inhibitor of HBV replication, restored impaired allostimulatory function of HBV-MoDC and up-regulated major histocompatibility complex class II expression. These results show that HBV infection compromises the antigen-presenting function of MoDC with concomitant impairment of T helper cell type 1 responses. This may play an important role for viral immune escape leading to chronic HBV infection. However, 3TC treatment can overcome HBV-MoDC-related T-cell hyporeactivity and this underscores its important role in enhanced immune responses to HBV.
Factor VIII Products and Inhibitor Development in Severe Hemophilia A (2013)

Recombinant and plasma-derived factor VIII products conferred similar risks of inhibitor development, and the content of von Willebrand factor in the products and switching among products were not associated with the risk of inhibitor development. Second-generation full-length recombinant products were associated with an increased risk, as compared with third-generation products. (Funded by Bayer Healthcare and Baxter BioScience.).
Differential regulation and expression of jun, c-fos and c-myc proto-oncogenes during mouse liver regeneration and after inhibition of protein synthesis. (1990)

In order to obtain information in vivo about the possible relationships between early response gene products, we have analysed the expression of c-myc, c-fos and jun proto-oncogenes in regenerating mouse liver. We show that c-myc, c-fos, jun B, c-jun and jun D mRNA expression is transiently increased soon after partial hepatectomy, jun and fos expression being induced earlier (30 min) than that of c-myc (1-2 h). C-fos, jun B and c-jun mRNA expression is dramatically enhanced (50 fold) while that of jun D and c-myc is weaker (less than 10 fold), but lasts longer. Moreover, the relative contributions of transcriptional and post-transcriptional regulations are unique for each proto-oncogene analysed. These results suggest that following the growth signal delivered by partial hepatectomy, the five proto-oncogenes analysed are all involved in the progression of hepatocytes through G1; however, due to their differential regulation and kinetics, they might play different roles in the changes in gene expression that occur during the transition from quiescence to proliferation. When protein synthesis is inhibited by injection of cycloheximide, the expression of c-myc, c-fos, jun B, c-jun and jun D mRNA is also transiently increased. Although this increase is mainly due to post-transcriptional mechanisms, c-myc, c-jun, jun D and, to a lesser extent, jun B transcription is enhanced, suggesting that labile repressor-like molecules may inhibit transcription of these genes in the quiescent liver. Moreover, the kinetics of c-myc, c-fos and jun mRNA induction are not identical, showing that different components are involved in their turnover or stability.
5-Halogenated pyrimidine lesions within a CpG sequence context mimic 5-methylcytosine by enhancing the binding of the methyl-CpG-binding domain of methyl-CpG-binding protein 2 (MeCP2) (2005)

Perturbations in cytosine methylation signals are observed in the majority of human tumors; however, it is as yet unknown how methylation patterns become altered. Epigenetic changes can result in the activation of transforming genes as well as in the silencing of tumor suppressor genes. We report that methyl-CpG-binding proteins (MBPs), specific for methyl-CpG dinucleotides, bind with high affinity to halogenated pyrimidine lesions, previously shown to result from peroxidase-mediated inflammatory processes. Emerging data suggest that the initial binding of MBPs to methyl-CpG sequences may be a seeding event that recruits chromatin-modifying enzymes and DNA methyltransferase, initiating a cascade of events that result in gene silencing. MBD4, a protein with both methyl-binding and glycosylase activity demonstrated repair activity against a series of 5-substituted pyrimidines, with the greatest efficiency against 5-chlorouracil, but undetectable activity against 5-chlorocytosine. The data presented here suggest that halogenated pyrimidine damage products can potentially accumulate and mimic endogenous methylation signals.
TheRPackagegeepackfor Generalized Estimating Equations (2006)

This paper describes the core features of the R package geepack, which implements the generalized estimating equations (GEE) approach for fitting marginal generalized linear models to clustered data. Clustered data arise in many applications such as longitudinal data and repeated measures. The GEE approach focuses on models for the mean of the correlated observations within clusters without fully specifying the joint distribution of the observations. It has been widely used in statistical practice. This paper illustrates the application of the GEE approach with geepack through an example of clustered binary data.
From the EIC: The changing face of IC design and its industry. (2003)

Verruciform xanthomas are rare lesions affecting 0.025-0.5% of the population. They present as an asymptomatic, slow growing solitary lesion on the oral mucosa. Commonly misdiagnose as squamous cell carcinoma, verruca vulgaris, leukoplakia, and lichen planus. Presented is a 22 year old male with a painful verruciform xanthoma on the posterior ear lobe in a prior ear piercing.
Compartmental organization of the ventral striatum of the rat: Immunohistochemical distribution of enkephalin, substance P, dopamine, and calcium‐binding protein (1989)

In the caudate-putamen of the rat a patch/matrix organization can be recognized on the basis of the immunohistochemical distribution of several markers, which include enkephalin, substance P, dopamine, and calcium-binding protein. In the present experiments the distributional relations of these markers were investigated in the nucleus accumbens. The distribution of enkephalin fibers shows different inhomogeneities according to their location in the nucleus. Rostrally, heavily labeled areas stand out against a moderately stained background, whereas caudally, in medial and ventral parts of the nucleus, lightly stained areas delineate regions in the moderately stained neuropil. In the distribution of substance P, areas with high staining intensity were observed in the medial and ventral parts of the nucleus accumbens. Inhomogeneities in the distribution of strong dopamine immunoreactivity consist of weakly immunoreactive areas throughout the rostrocaudal extent of the nucleus accumbens and extremely heavily labeled areas in the medial and ventral parts of the nucleus. Calcium-binding protein immunoreactivity can only be detected in dorsal parts of the nucleus. The generally intense immunostaining for calcium-binding protein is interspersed with "blanks" of weak immunoreactivity. The heavily and moderately labeled enkephalin areas each maintain specific relations with inhomogeneities in the distribution of substance P, dopamine, and calcium-binding protein. Rostrally, the heavily labeled enkephalin areas coincide with areas strongly immunostained for calcium-binding protein and with lightly stained areas in the dopamine and substance P immunoreactivity patterns. In the same region lightly stained areas in the enkephalin distribution match heavily labeled substance P areas. Caudally, in the border region of the nucleus accumbens and the caudate-putamen, the heavily labeled enkephalin areas are either related to "blanks" or to the intense staining regions in the calcium-binding protein immunoreactivity distribution. The moderately labeled enkephalin areas caudomedially in the nucleus accumbens are in register with the heavily labeled regions in the distribution of substance P and with the extremely heavily labeled regions in the distribution of dopamine. Relations with connectivity are discussed and the inhomogeneities are compared to those in the caudate-putamen. It is concluded that in the ventral striatum either one patch and one matrix compartment exist with different immunohistochemical relationships or there are several compartments with different immunohistochemical characteristics and different input-output relations.
Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor (2013)

The urokinase receptor (uPAR) is a cell-surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here, we evaluate the binding and biological activity of a new class of pyrrolidinone and piperidinone compounds, along with derivatives of previously-identified pyrazole and propylamine compounds. Competition assays revealed that the compounds displace a fluorescently labeled peptide (AE147-FAM) with inhibition constant (Ki ) values ranging from 6 to 63 μM. Structure-based computational pharmacophore analysis followed by extensive explicit-solvent molecular dynamics (MD) simulations and free energy calculations suggested the pyrazole-based and piperidinone-based compounds adopt different binding modes, despite their similar two-dimensional structures. In cells, pyrazole-based compounds showed significant inhibition of breast adenocarcinoma (MDA-MB-231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but piperidinone-containing compounds exhibited no cytotoxicity even at concentrations of 100 μM. One pyrazole-based compound impaired MDA-MB-231 invasion, adhesion, and migration in a concentration-dependent manner, while the piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix metalloprotease-9 (gelatinase) activity in a concentration-dependent manner, while the piperidinone showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF-κB signaling, while pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that the effect of the pyrazole-based compound on proliferation was due to cell killing through an apoptotic mechanism. The compounds identified represent valuable leads in the design of further derivatives with higher affinities and potential probes to unravel the protein-protein interactions of uPAR.
Cutting Edge: IFN-Inducible ELR− CXC Chemokines Display Defensin-Like Antimicrobial Activity (2001)

Recent reports highlighted the chemotactic activities of antimicrobial peptide defensins whose structure, charge, and size resemble chemokines. By assaying representative members of the four known families of chemokines we explored the obverse: whether some chemokines exert antimicrobial activity. In a radial diffusion assay, only recombinant monokine induced by IFN-gamma (MIG/CXCL9), IFN-gamma-inducible protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), members of the IFN-gamma-inducible tripeptide motif Glu-Leu-Arg (ELR)(-) CXC chemokines, were antimicrobial against Escherichia coli and Listeria monocytogenes. Similar to human defensins, antimicrobial activities of the chemokines were inhibited by 50 and 100 mM NaCl. The concentration of MIG/CXCL9 and IP-10/CXCL10 released from IFN-gamma-stimulated PBMC in 24 h were, respectively, 35- and 28-fold higher than from unstimulated cells. Additionally, the amounts of chemokines released per monocyte suggest that, in tissues with mononuclear cell infiltration, IFN-gamma-inducible chemokines may reach concentrations necessary for microbicidal activity. IFN-gamma-inducible chemokines may directly inactivate microbes before attracting other host defense cells to the area of infection.
Thermostability in endoglucanases is fold-specific (2011)

Here, we provide fold-specific guidelines to control thermostability in endoglucanases that will aid in making production of biofuels from plant biomass more efficient.
Simple high-performance exploding wire opening switch (2007)

High-efficiency simple, compact and robust opening switches capable of generating hundreds of kV are key elements in the development of autonomous explosivelydriven pulsed power sources. The paper presents results of the first phase of development of such an opening switch, based on exploding wire technology. By implementing a matched inductor in the circuit and optimising the wire parameters, a very compact and robust device is capable of generating reproducibly 240 kV. Full details of the system are given together with experimental data and theoretical predictions.
Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis (2008)

On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.
Glomerular Basement Membrane (1998)

Glomerular basement membrane (GBM) plays a crucial function in the ultrafiltration of blood plasma by the kidney. This function is impaired in Alport syndrome, a hereditary disorder that is caused by mutations in the gene encoding type IV collagen, but it is not known how the mutations lead to a defective GBM. In the present study, the supramolecular organization of type IV collagen of GBM was investigated. This was accomplished by using pseudolysin (EC 3.4.24.26) digestion to excise truncated triple-helical protomers for structural studies. Two distinct sets of truncated protomers were solubilized, one at 4 degrees C and the other at 25 degrees C, and their chain composition was determined by use of monoclonal antibodies. The 4 degrees C protomers comprise the alpha1(IV) and alpha2(IV) chains, whereas the 25 degrees C protomers comprised mainly alpha3(IV), alpha4(IV), and alpha5(IV) chains along with some alpha1(IV) and alpha2(IV) chains. The structure of the 25 degrees C protomers was examined by electron microscopy and was found to be characterized by a network containing loops and supercoiled triple helices, which are stabilized by disulfide cross-links between alpha3(IV), alpha4(IV), and alpha5(IV) chains. These results establish a conceptual framework to explain several features of the GBM abnormalities of Alport syndrome. In particular, the alpha3(IV). alpha4(IV).alpha5(IV) network, involving a covalent linkage between these chains, suggests a molecular basis for the conundrum in which mutations in the gene encoding the alpha5(IV) chain cause defective assembly of not only alpha5(IV) chain but also the alpha3(IV) and alpha4(IV) chains in the GBM of patients with Alport syndrome.
Procedural modeling of architecture (2006)

Article Share on Procedural modeling of architecture Author: Peter Wonka Arizona State University Arizona State UniversityView Profile Authors Info & Claims SIGGRAPH '06: ACM SIGGRAPH 2006 CoursesJuly 2006 Pages 17–83https://doi.org/10.1145/1185657.1185713Online:30 July 2006Publication History 5citation84DownloadsMetricsTotal Citations5Total Downloads84Last 12 Months19Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Multiple Serotonergic Mechanisms Contributing to Sensitization inAplysia: Evidence of Diverse Serotonin Receptor Subtypes (2003)

The neurotransmitter serotonin (5-HT) plays an important role in memory encoding in Aplysia. Early evidence showed that during sensitization, 5-HT activates a cyclic AMP-protein kinase A (cAMP-PKA)-dependent pathway within specific sensory neurons (SNs), which increases their excitability and facilitates synaptic transmission onto their follower motor neurons (MNs). However, recent data suggest that serotonergic modulation during sensitization is more complex and diverse. The neuronal circuits mediating defensive reflexes contain a number of interneurons that respond to 5-HT in ways opposite to those of the SNs, showing a decrease in excitability and/or synaptic depression. Moreover, in addition to acting through a cAMP-PKA pathway within SNs, 5-HT is also capable of activating a variety of other protein kinases such as protein kinase C, extracellular signal-regulated kinases, and tyrosine kinases. This diversity of 5-HT responses during sensitization suggests the presence of multiple 5-HT receptor subtypes within the Aplysia central nervous system. Four 5-HT receptors have been cloned and characterized to date. Although several others probably remain to be characterized in molecular terms, especially the Gs-coupled 5-HT receptor capable of activating cAMP-PKA pathways, the multiplicity of serotonergic mechanisms recruited into action during learning in Aplysia can now be addressed from a molecular point of view.
Transcutaneous Electrical Stimulation of the Recurrent Laryngeal Nerve in Monkeys (1987)

The recurrent laryngeal nerve (RLN) of four anesthetized adult Macaca fascicularis monkeys was stimulated by applying current with blunt electrodes placed unilaterally and bilaterally on the intact neck skin along the tracheoesophageal groove. The stimulus consisted of 2.5- to 4.0-mA cathodal pulses, each of 1-ms duration, beginning at a frequency of 10 Hz and increasing by 10-Hz increments to 100 Hz. Unilateral stimulation from 10 to 30 Hz resulted in a graded vocal cord abduction, with the maximal glottic aperture occurring at 30 Hz. Stimulation above 30 Hz produced a graded cord adduction, with nearly complete glottic closure at 100 Hz; bilateral stimulation yielded similar results, with total glottic closure at 100 Hz. Confirmation of the RLN as mediator of this frequency-dependent cord motion was achieved by surgically isolating it and attaining identical results with direct stimulation. No cardiopulmonary alterations were observed in any trial. Transcutaneous electrical stimulation of the RLN seems to be a relatively safe, reliable, and noninvasive method of controlling vocal cord position and thereby the glottic airway in monkeys.
5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats (1994)

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.
Mechanism by which caffeine potentiates lethality of nitrogen mustard. (1982)

Caffeine is synergistic with many DNA-damaging agents in increasing lethality to mammalian cells. The mechanism is not well understood. Our results show that caffeine potentiates the lethality of the nitrogen mustard 2-chloro-N-(2-chloroethyl)-N-methylethanamine (HN2) by inducing damaged cells to undergo mitosis before properly repairing lesions in their DNA. Treatment with low doses of HN2 (0.5 microM for 1 hr) caused little lethality in baby hamster kidney cells (90% survival). These cells were arrested in G2 shortly after treatment with HN2 as shown by flow microfluorimetry and autoradiography. After an arrest of 6 hr, HN2-treated cells began to move into mitosis and from then on behaved like normal cells. Repair synthesis was shown to continue during the G2 arrest by using synchronized cells pulse labeled with [3H]thymidine after HN2 treatment and autoradiography. Caffeine (2mM) increased the lethality of HN2 by 5- to 10-fold. It prevented the G2 arrest. Caffeine did not prevent these HN2-treated cells from entering or completing S phase but rather allowed them to divide without finishing the repair processes and as a consequence caused nuclear fragmentation after mitosis. Caffeine-induced nuclear fragmentation and enhanced lethality were proportional, as shown with dose--response curves and time dependence. In addition, both lethality and nuclear fragmentation were abolished by low doses of cycloheximide, an inhibitor of protein synthesis.