gebhart/patrepeval huggingface dataset:
Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation (1999)

ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation.
Simultaneous Quantification of Tacrolimus and Sirolimus, in Human Blood, by High-Performance Liquid Chromatography???Tandem Mass Spectrometry (2000)

In this paper the authors present a validated method for the simultaneous analysis of tacrolimus and sirolimus in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry. Blood samples (500 microL) were prepared by C18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring. The assay was linear for both compounds over the range 0.25-100 microg/L (r2 > 0.996, n = 7). At the limit of quantification (0.25 microg/L), for both sirolimus and tacrolimus, the interday imprecision was < 3% and the analytical recovery was between 97.0% and 102%, respectively. The interbatch and intrabatch coefficients of variation of the method for both analytes, at the three quality control concentrations (0.5, 20, and 80 microg/L), were < 16% and < 10%, respectively. The analytical recovery, at the three control concentrations, ranged from 99.2% to 104% of the nominal concentration. The mean absolute recovery (+/- standard deviation) of tacrolimus, sirolimus, and internal standard was 82 +/- 7%, 89 +/- 12%, and 77 +/- 8%, respectively (n = 12). In conclusion, the method presented can be used for simultaneous determination of tacrolimus and sirolimus and will aid in pharmacokinetic studies and therapeutic drug monitoring of these drugs. Furthermore, this method has economic benefits in the clinical setting where these drugs are coadministered.
Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and IκB Kinase ϵ (2009)

TANK-binding kinase 1 (TBK1) and IkappaB kinase epsilon (IKKepsilon) regulate the production of Type 1 interferons during bacterial and viral infection, but the lack of useful pharmacological inhibitors has hampered progress in identifying additional physiological roles of these protein kinases and how they are regulated. Here we demonstrate that BX795, a potent and relatively specific inhibitor of TBK1 and IKKepsilon, blocked the phosphorylation, nuclear translocation, and transcriptional activity of interferon regulatory factor 3 and, hence, the production of interferon-beta in macrophages stimulated with poly(I:C) or lipopolysaccharide (LPS). In contrast, BX795 had no effect on the canonical NFkappaB signaling pathway. Although BX795 blocked the autophosphorylation of overexpressed TBK1 and IKKepsilon at Ser-172 and, hence, the autoactivation of these protein kinases, it did not inhibit the phosphorylation of endogenous TBK1 and IKKepsilon at Ser-172 in response to LPS, poly(I:C), interleukin-1alpha (IL-1alpha), or tumor necrosis factor alpha and actually enhanced the LPS, poly(I:C), and IL-1alpha-stimulated phosphorylation of this residue. These results demonstrate that the phosphorylation of Ser-172 and the activation of TBK1 and IKKepsilon are catalyzed by a distinct protein kinase(s) in vivo and that TBK1 and IKKepsilon control a feedback loop that limits their activation by LPS, poly(I:C) and IL-1alpha (but not tumor necrosis factor alpha) to prevent the hyperactivation of these enzymes.
American Jukebox: The Classic Years (1990)

Photographs depict full-sized jukeboxes, wall boxes, table models, and speakers manufactured by Wurlitzer, Rock-Ola, Seeburg, and other leading jukebox manufacturers from 1937 to 1948.
Ionizing Radiation and Chemotherapeutic Drugs Induce Apoptosis in Lymphocytes in the Absence of FAS or Fadd/Mort1 Signaling (2000)

Ionizing radiation and cytotoxic drugs used in the treatment of cancer induce apoptosis in many cell types, including tumor cells. It has been reported that tumor cells treated with anticancer drugs increase surface expression of Fas ligand (FasL) and are killed by autocrine or paracrine apoptosis signaling through Fas (Friesen, C., I. Herr, P.H. Krammer, and K.-M. Debatin. 1996. Nat. Med. 2:574-577). We show that lymphocytes that cannot be killed by FasL, such as those from Fas-deficient lpr mice or transgenic mice expressing a dominant negative mutant of Fas-associated death domain protein (FADD/MORT1), are as sensitive as normal lymphocytes to killing by gamma radiation or the cytotoxic drugs cis-platin, doxorubicin, and etoposide. In contrast, p53 deficiency or constitutive expression of Bcl-2 markedly increased the resistance of lymphocytes to gamma radiation or anticancer drugs but had no effect on killing by FasL. Consistent with these observations, lpr and wild-type T cells both had a reduced capacity for mitogen-induced proliferation after drug treatment, whereas bcl-2 transgenic or p53-deficient T cells retained significant clonogenic potential. These results demonstrate that apoptosis induced by ionizing radiation or anticancer drugs requires p53 and is regulated by the Bcl-2 protein family but does not require signals transduced by Fas and FADD/MORT1.
Accumulation of Muscle Ankyrin Repeat Protein Transcript Reveals Local Activation of Primary Myotube Endcompartments during Muscle Morphogenesis (1997)

The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236-10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793-804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers.
Controlled Intracellular Release of Doxorubicin in Multidrug-Resistant Cancer Cells by Tuning the Shell-Pore Sizes of Mesoporous Silica Nanoparticles (2011)

In this work, hollow mesoporous silica nanoparticles (HMSNs) with three pore sizes were manufactured to control the drug release rate, and the biological roles of these HMSNs were evaluated in multidrug-resistant (MDR) cancer cells. As novel pore-size-controllable inorganic materials, HMSNs showed negligible cytotoxicity and efficient cellular uptake toward drug-sensitive MCF-7 and drug-resistant MCF-7/ADR cells. Doxorubicin (DOX)-loaded HMSNs (DMSNs) not only demonstrated effective drug loading and a pH-responsive drug release character but also exhibited pore-size-dependent and sustained drug release performance in both in vitro and intracellular drug release experiments. In addition, DMSNs exhibited pore-size-dependent anticancer activity against MCF-7/ADR cells. DMSNs with larger pore size could mediate more cellular uptake of DOX and faster intracellular drug release, which led to more intracellular drug accumulation and stronger MDR-reversal effects. The MDR-overcoming mechanism could be due to the efficient cellular uptake, P-gp inhibition, and ATP depletion. These results demonstrate that HMSNs could be a very promising drug delivery system for pore-size-controllable drug release and cancer MDR reversion.
Recombinant horseradish peroxidase: Production and analytical applications (2015)

Horseradish peroxidase is a key enzyme in bio- and immunochemical analysis. New approaches in functional expression of the peroxidase gene in E. coli cells and the subsequent refolding of the resulting protein yield a recombinant enzyme that is comparable in its spectral and catalytic characteristics to the native plant peroxidase. Genetic engineering approaches allow production of recombinant peroxidase conjugates with both protein antigens and Fab antibody fragments. The present article reviews the use of recombinant horseradish peroxidase as the marker enzyme in ELISA procedures as well as in amperometric sensors based on direct electron transfer.
Laser trimming adjustment of waveguide birefringence in silica integrated-optic ring resonators (1989)

Precise control of waveguide birefringence between TM and TE modes is required for various integrated-optic devices with a desired polarization dependence or independence.1 This paper describes laser trimming of amorphous silicon stress-applying films on silica waveguides for adjusting waveguide birefringence. A practical application to polarization-insensitive optical ring resonators is also presented.
Revelle revisited: Buffer factors that quantify the response of ocean chemistry to changes in DIC and alkalinity (2010)

We derive explicit expressions of the Revelle factor and several other buffer factors of interest to climate change scientists and those studying ocean acidification. These buffer factors quantify the sensitivity of CO 2 and H + concentrations ([CO 2 ] and [H + ]) and CaCO 3 saturation (Ω) to changes in dissolved inorganic carbon concentration (DIC) and alkalinity (Alk). The explicit expressions of these buffer factors provide a convenient means to compare the degree of buffering of [CO 2 ], [H + ], and Ω in different regions of the oceans and at different times in the future and to gain insight into the buffering mechanisms. All six buffer factors have roughly similar values, and all reach an absolute minimum when DIC = Alk (pH ∼ 7.5). Surface maps of the buffer factors generally show stronger buffering capacity in the subtropical gyres relative to the polar regions. As the dissolution of anthropogenic CO 2 increases the DIC of surface seawater over the next century, all the buffer factors will decrease, resulting in a much greater sensitivity to local variations in DIC and Alk. For example, diurnal and seasonal variations in pH and Ω caused by photosynthesis and respiration will be greatly amplified. Buffer factors provide convenient means to quantify the effect that changes in DIC and Alk have on seawater chemistry. They should also help illuminate the role that various physical and biological processes have in determining the oceanic response to an increase in atmospheric CO 2 .
P27 GENISTEIN INHIBITS GLUTAMATE-INDUCED APOPTOSIS IN PRIMARY NEURONAL CELL CULTURES OF MOUSE BRAIN CORTEX AND CEREBELLUM (2006)

Kajta, Malgorzataa; Domin, Helenab; Grynkiewicz, Grzegorzc; Lason, Wladyslawa Author Information
MR imaging and metallic implants for anterior cruciate ligament reconstruction: Assessment of ferromagnetism and artifact (1992)

Magnetic resonance (MR) imaging is contraindicated for patients with certain ferromagnetic implants, primarily because of potential risks related to movement or dislodgment of the devices. An additional problem with metallic implants is the potential image distortion that may affect the interpretation of the MR study. Since MR imaging is frequently useful for the evaluation of postoperative anterior cruciate ligament (ACL) reconstruction, the ferromagnetic qualities and artifacts associated with MR imaging were determined for five metallic orthopedic implants commonly used for this surgery. Only the Perfix interference screw displayed a substantial deflection force and caused extensive signal loss. Images of the knee of one patient with two Perfix screws in place were not interpretable because of the image distortion caused by these implants. Therefore, alternative nonferromagnetic implants should be considered for reconstruction of the ACL.
Radiotracer measurements as a sensitive tool for the detection of metal penetration in molecular-based organic electronics (2005)

The metallization of organic thin films is a crucial point in the development of molecular electronics. However, there is no method established yet to detect trace amounts of metal atoms in those thin films. Radiotracer measurements can quantify even very small amounts of material penetrating into the bulk, in our case less than 0.01% of a monolayer. Here, the application of this technique on two different well-characterized organic thin film systems (diindenoperylene and pentacene) is demonstrated. The results show that Ag is mainly adsorbed on the surface, but indicate that already at moderate deposition temperatures Ag can penetrate into the organic thin films and agglomerate at the film/substrate interface.
Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats (2009)

BMSCs prevent arrested alveolar and vascular growth in part through paracrine activity. Stem cell-based therapies may offer new therapeutic avenues for lung diseases that currently lack efficient treatments.
HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration (2006)

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10(-11). Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.
Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women (2015)

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.
An Aptly Positioned Azido Group in the Spacer of a Protein Cross‐Linker for Facile Mapping of Lysines in Close Proximity (2007)

Cross-links between amino acid residues in close proximity can provide distance constraints for the validation of models of the 3D structure proteins. The mapping of cross-links by the identification of linked peptides in proteolytic digests is facilitated by cleavable cross-linkers that enable isolation of the cleavage products while preserving information about the linkage. We present an amine-specific cross-linker, bis(succinimidyl)-3-azidomethyl glutarate (BAMG), that fulfils these requirements. Two parallel reaction pathways are induced by tris(carboxyethyl)phosphine (TCEP) in cross-linked peptides from BAMG-treated cytochrome c. One pathway leads to cleavage of the cross-linked species, while in the other the azido group of BAMG is reduced to an amino group without cleavage. Cross-linked peptides and peptides modified by partially hydrolysed BAMG yield distinct sets of TCEP-induced reaction products. These can be isolated by reversed-phase diagonal chromatography and identified by mass spectrometry to reveal the identity of the parent compounds. The ease with which cross-link-derived reaction products can be isolated and identified indicates that the mapping of cross-links in complex biological assemblies and mixtures of protein complexes might become feasible in the near future.
Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury* (2009)

These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.
Disruption of the Na+ion binding site as a mechanism for positive allosteric modulation of the mu-opioid receptor (2014)

Positive allosteric modulation of the mu-opioid receptor (MOPr), the site of action of all clinically used opioids, represents a potential approach for the management of pain. We recently reported on positive allosteric modulators of MOPr (mu-PAMs), a class A G protein coupled receptor (GPCR). This study was designed to examine the mechanism of allostery by comparing the degree to which opioid ligand structure governs modulation. To do this we examined the interaction of the mu-PAM, BMS-986122, with a chemically diverse range of MOPr orthosteric ligands. Generally, for full agonists BMS-986122 enhanced the binding affinity and potency to activate G protein with no alteration in the maximal effect. In contrast, lower efficacy agonists including morphine were insensitive to alterations in binding affinity and showed little to no change in potency to stimulate G protein. Instead, there was an increase in maximal G protein stimulation. Antagonists were unresponsive to the modulatory effects of BMS-986122. Sodium is a known endogenous allosteric modulator of MOPr and alters orthosteric agonist affinity and efficacy. The sensitivity of an orthosteric ligand to BMS-986122 was strongly correlated with its sensitivity to NaCl. In addition, BMS-986122 decreased the ability of NaCl to modulate agonist binding in an allosteric fashion. Overall, BMS-986122 displayed marked probe dependence that was based upon the efficacy of the orthosteric ligand and can be explained using the Monod-Wyman-Changeux two-state model of allostery. Furthermore, disruption of the Na(+) ion binding site may represent a common mechanism for allosteric modulation of class A GPCRs.
Parallel confocal detection of single molecules in real time (2008)

The confocal detection principle is extended to a highly parallel optical system that continuously analyzes thousands of concurrent sample locations. This is achieved through the use of a holographic laser illumination multiplexer combined with a confocal pinhole array before a prism dispersive element used to provide spectroscopic information from each confocal volume. The system is demonstrated to detect and identify single fluorescent molecules from each of several thousand independent confocal volumes in real time.
Genetic Architecture of Maize Kernel Composition in the Nested Association Mapping and Inbred Association Panels (2011)

The maize (Zea mays) kernel plays a critical role in feeding humans and livestock around the world and in a wide array of industrial applications. An understanding of the regulation of kernel starch, protein, and oil is needed in order to manipulate composition to meet future needs. We conducted joint-linkage quantitative trait locus mapping and genome-wide association studies (GWAS) for kernel starch, protein, and oil in the maize nested association mapping population, composed of 25 recombinant inbred line families derived from diverse inbred lines. Joint-linkage mapping revealed that the genetic architecture of kernel composition traits is controlled by 21-26 quantitative trait loci. Numerous GWAS associations were detected, including several oil and starch associations in acyl-CoA:diacylglycerol acyltransferase1-2, a gene that regulates oil composition and quantity. Results from nested association mapping were verified in a 282 inbred association panel using both GWAS and candidate gene association approaches. We identified many beneficial alleles that will be useful for improving kernel starch, protein, and oil content.