gebhart/patrepeval huggingface dataset:
Purification and properties of 2-aminoadipate: 2-oxoglutarate aminotransferase from bovine kidney (1989)

Previous studies with rat kidney preparations indicated that 2-aminoadipate aminotransferase (AadAT) and kynurenine aminotransferase (KAT) activities are properties of a single protein. We found that bovine kidney contains an appreciable amount of AadAT activity, but lacks KAT activity. AadAT from bovine and rat kidney extracts were purified to electrophoretic homogeneity. The purification procedure included fractionation with (NH1)2SO1, heat treatment, DEAE-cellulose chromatography and hydroxyapatite chromatography. Physical and kinetic properties, such as pH optima, Km for substrates, Mr, electrophoretic mobility and inhibition by dicarboxylic acids of bovine kidney AadAT, were similar to those of the rat kidney enzyme. However, bovine kidney AadAT differed from rat kidney AadAT in substrate specificity, amino acid composition and stability when stored. The titration curve of bovine kidney AadAT was also different from that of the rat kidney enzyme. The results suggest that bovine kidney AadAT may have some structural similarity to rat kidney AadAT and that the structural differences observed between the two enzymes may explain the absence of KAT activity in bovine kidney.
Fluorènacènes et fluorènaphènes. Synthèses dans la série des indéno‐fluorènes VIII. Méthyl‐3‐, diméthyl‐1,4‐, diméthyl‐1,3‐et triméthyl‐1,3,4‐cis‐fluorènacène (1958)

Abstract Les dérivés suivants du cis ‐fluorènacène ont été synthétisés en six étapes à partir de l'acide méthyl‐3‐dibromo‐4,6‐benzoïque: le méthyl‐3‐ cis ‐fluorèn‐acène ou méthyl‐6′‐[indéno‐2′, 1′:2,3‐fluorène], le diméthyl‐1,4‐ cis ‐fluorèn‐acène ou diméthyl‐4′,7′‐[indéno‐2′,1′:2,3‐fluorène], le diméthyl‐1,3‐ cis ‐fluo‐rènacène ou diméthyl‐4′,6′‐[indéno‐2′,1′:2,3‐fluorène] et le triméthyl‐1,3,4‐ cis ‐fluorènacène ou triméthyl‐4′,6′,7′‐[indéno‐2′,1′:2,3‐fluorène]. Les rendements globaux en hydrocarbures cristallisés sont de 36–43% de la théorie.
Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma. (2002)

Interactions of CD70, a tumor necrosis factor-related cell surface ligand and its receptor, CD27, are thought to play an important role for T-, B-, and natural killer-cell activation. However, ligation of CD27 can also induce apoptosis. Human glioblastoma is paradigmatic for cancer-associated immunosuppression. We identified CD70 as a radioinducible gene in U87 MG glioma cells. A screening of a panel of human glioma cell lines revealed that 11 of 12 cell lines expressed CD70 mRNA and protein. Two human neuroblastoma cell lines did not express CD70. CD70 mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53-independent manner. No alteration in CD70 expression was observed after glioma cell exposure to cytotoxic drugs such as lomustine. CD70 protein was also detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic astrocytomas in vivo. CD27 expression was not detected in any glioma cell line, and there was no evidence for autocrine or backward signaling of the CD70 system in human glioma cells. Unexpectedly, CD70 expressed on glioma cells did not increase the immunogenicity of glioma cells in vitro. In contrast, CD70-positive glioma cells induced apoptosis in peripheral blood mononuclear cells (PBMCs) in a CD70-dependent manner. Neutralization of CD70 expressed on glioma cells prevented apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures of glioma cells and PBMCs. The effects of CD70-expressing glioma cells on PBMCs were mimicked by agonistic CD27 antibodies. Conversely, the shedding of CD27 by PBMCs was identified as a possible escape mechanism from glioma cell-induced CD70-dependent apoptosis. Thus, induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas.
Inhibition of Alpha-Smooth Muscle Actin Expression in an In Vitro Wound Healing Model by Certain Antibiotics (1999)

These studies suggest that one reason certain antimicrobials impair wound healing, is due to myofibroblast inhibition of alpha-SM actin.
Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis (2010)

Antineutrophil cytoplasmic autoantibody (ANCA) causes vascular injury that leads to small-vessel vasculitis. Patients with ANCA aberrantly express neutrophil granule-encoding genes, including 2 that encode autoantigens: proteinase 3 (PR3) and myeloperoxidase (MPO). To uncover a potential transcriptional regulatory mechanism for PR3 and MPO disrupted in patients with ANCA vasculitis, we examined the PR3 and MPO loci in neutrophils from ANCA patients and healthy control individuals for epigenetic modifications associated with gene silencing. We found that levels of the chromatin modification H3K27me3, which is associated with gene silencing, were depleted at PR3 and MPO loci in ANCA patients compared with healthy controls. Interestingly, in both patients and controls, DNA was unmethylated at a CpG island in PR3, whereas in healthy controls, DNA was methylated at a CpG island in MPO. Consistent with decreased levels of H3K27me3, JMJD3, the demethylase specific for H3K27me3, was preferentially expressed in ANCA patients versus healthy controls. In addition, we describe a mechanism for recruiting the H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) to PR3 and MPO loci mediated by RUNX3. RUNX3 message was decreased in patients compared with healthy controls, and may also be under epigenetic control. DNA methylation was increased at the RUNX3 promoter in ANCA patients. These data indicate that epigenetic modifications associated with gene silencing are perturbed at ANCA autoantigen-encoding genes, potentially contributing to inappropriate expression of PR3 and MPO in ANCA patients.
Severe Heart Failure and Early Mortality in a Double-Mutation Mouse Model of Familial Hypertrophic Cardiomyopathy (2008)

TnI-203/MHC-403 double-mutant mice develop a severe cardiac phenotype characterized by heart failure and early death. The presence of 2 disease-causing mutations may predispose individuals to a greater risk of developing severe heart failure than human FHC caused by a single gene mutation.
Regulation of ganglioside biosynthesis in the nervous system (2004)

Ganglioside biosynthesis is strictly regulated by the activities of glycosyltransferases and is necessarily controlled at the levels of gene transcription and posttranslational modification. Cells can switch between expressing simple and complex gangliosides or between different series within these two groups during brain development. The sequential biosynthesis of gangliosides in parallel enzymatic pathways, however, requires fine-tuned subcellular sequestration and orchestration of glycosyltransferases. A popular model predicts that this regulation is achieved by the vectorial organization of ganglioside biosynthesis: sequential biosynthetic steps occur with the traffic of ganglioside intermediates through subsequent subcellular compartments. Here, we review current models for the subcellular distribution of glycosyltransferases and discuss results that suggest a critical role of N-glycosylation for the processing, transport, and complex formation of these enzymes. In this context, we attempt to illustrate the regulation of ganglioside biosynthesis as well as the biological significance of N-glycosylation as a posttranslational regulatory mechanism. We also review the results of analyses of the 5' regulatory sequences of several glycosyltransferases in ganglioside biosynthesis and provide insights into how their synthesis can be regulated at the level of transcription.
Synthesis and characterization of copolymers of bromoacrylated methyl oleate (2004)

Abstract In this study, methyl oleate was bromoacrylated in the presence of N ‐bromosuccinimide and acrylic acid in one step. Homopolymers and copolymers of bromoacrylated methyl oleate (BAMO) were synthesized by free radical bulk polymerization and photopolymerization techniques. Azobisisobutyronitrile (AIBN) and 2,2‐dimethoxy‐2‐phenyl‐acetophenone were used as initiators. The new monomer BAMO was characterized by FTIR, GC‐MS, 1 H, and 13 C‐NMR spectroscopy. Styrene (STY), methylmethacrylate (MMA), and vinyl acetate (VA) were used for copolymerization. The polymers synthesized were characterized by FTIR, 1 H‐NMR, 13 C‐NMR, and differential scanning calorimetry (DSC). Molecular weight and polydispersities of the copolymers were determined by GPC analysis. Ten different feed ratios of the monomers STY and BAMO were used for the calculation of reactivity ratios. The reactivity ratios were determined by the Fineman–Ross and Kelen–Tudos methods using 1 H‐NMR spectroscopic data. The reactivity ratios were found to be r sty = 0.891 (Fineman–Ross method), 0.859 (Kelen–Tudos method); r bamo = 0.671 (Fineman–Ross method), 0.524 (Kelen–Tudos method). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2475–2488, 2004
Introduction (2015)

This introductory chapter provides a brief overview of the life and career of Harry Golden, a writer and humorist whose works exalted the “little guy”—factory workers, prostitutes, shopkeepers, and—during the time of the segregation—African Americans. Golden spun his experiences growing up in Lower East Side New York into his popular books for which he became a household name. He explored some of the biggest themes a writer can put to paper: prejudice, dignity, and the daily struggle of the working person—with slices of real life, humorously rendered. Along with such amusing cultural digressions, Golden sounded a warning for America to appreciate and accelerate its social progress in his fight against racial discrimination, which he believed was pulling down the nation and its people.
Inactivation of uPA and its receptor uPAR by 3,3′‐diindolylmethane (DIM) leads to the inhibition of prostate cancer cell growth and migration (2009)

3,3'-Diindolylmethane (DIM) has been studied for its putative anti-cancer properties, especially against prostate cancer; however, its exact mechanism of action remains unclear. We recently provided preliminary data suggesting down-regulation of uPA during B-DIM (a clinically active DIM)-induced inhibition of invasion and angiogenesis in prostate cancer cells. Since the expression and activation of uPA plays important role in tumorigenicity, and high endogenous levels of uPA and uPAR are found in advanced metastatic cancers, we investigated their role in B-DIM-mediated inhibition of prostate cancer cell growth and motility. Using PC3 cells, we found that B-DIM treatment as well as the silencing of uPA and uPAR by siRNAs led to the inhibition of cell growth and motility. Conversely, over-expression of uPA/uPAR in LNCaP and C4-2B cells resulted in increased cell growth and motility, which was effectively inhibited by B-DIM. Moreover, we found that uPA as well as uPAR induced the production of VEGF and MMP-9, and that the down-regulation of uPA/uPAR by siRNAs or B-DIM treatment resulted in the inhibition of VEGF and MMP-9 secretion which could be responsible for the observed inhibition of cell migration. Interestingly, silencing of uPA/uPAR led to decreased sensitivity to B-DIM indicating important role of uPA/uPAR in B-DIM-mediated regulation of prostate cancer cell growth and migration. Our data suggest that chemopreventive and/or therapeutic activity of B-DIM is in part due to down-regulation of uPA-uPAR leading to reduced production of VEGF/MMP-9 which ultimately leads to the inhibition of cell growth and migration of aggressive prostate cancer cells.
Sustaining Intravitreal Residence With L-Arginine Peptide-Conjugated Nanocarriers (2017)

We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.
Detecting 802.11 MAC Layer Spoofing Using Received Signal Strength (2008)

MAC addresses can be easily spoofed in 802.11 wireless LANs. An adversary can exploit this vulnerability to launch a large number of attacks. For example, an attacker may masquerade as a legitimate access point to disrupt network services or to advertise false services, tricking nearby wireless stations. On the other hand, the received signal strength (RSS) is a measurement that is hard to forge arbitrarily and it is highly correlated to the transmitter's location. Assuming the attacker and the victim are separated by a reasonable distance, RSS can be used to differentiate them to detect MAC spoofing, as recently proposed by several researchers. By analyzing the RSS pattern of typical 802.11 transmitters in a 3-floor building covered by 20 air monitors, we observed that the RSS readings followed a mixture of multiple Gaussian distributions. We discovered that this phenomenon was mainly due to antenna diversity, a widely-adopted technique to improve the stability and robustness of wireless connectivity. This observation renders existing approaches ineffective because they assume a single RSS source. We propose an approach based on Gaussian mixture models, building RSS profiles for spoofing detection. Experiments on the same testbed show that our method is robust against antenna diversity and significantly outperforms existing approaches. At a 3% false positive rate, we detect 73.4%, 89.6% and 97.8% of attacks using the three proposed algorithms, based on local statistics of a single AM, combining local results from AMs, and global multi-AM detection, respectively.
Prenatal diagnosis. Fetoscopy. (1984)

Since its introduction just over a decade ago, fetoscopy has become an effective procedure for the diagnosis of at least 50 congenital abnormalities. It can also be employed as an aid to therapeutic interventions in utero.
TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence (2001)

TENB2 encodes a putative transmembrane proteoglycan, related to the EGF/heregulin family of growth factors and follistatin, which has been identified through the application of a differential display technique to a xenograft model of prostate cancer. Northern analysis and competitive PCR were used to demonstrate significantly increased TENB2 expression (p = 0.0003) on the acquisition of androgen independence in the model system. TENB2 is also overexpressed in clinical prostate carcinoma vs. its benign counterpart (p < 0.0001), with particular prominence in high-grade tumours, and shows a high degree of tissue specificity, being detected on a multitissue Northern array exclusively in brain and prostate material. Studies of recombinant protein expression demonstrate that TENB2 is a chondroitin sulphate proteoglycan. The presence of an EGF and 2 follistatin domains suggests a role in the regulation of growth factor signalling either as a ligand precursor, a membrane-bound receptor or as a binding protein for growth factors. These data are indicative of a significant role for TENB2 in the progression of poorly differentiated tumour types, with implications for prostate cancer detection, prognosis and therapy.
Soluble CD59 Expressed from an Adenovirus In Vivo Is a Potent Inhibitor of Complement Deposition on Murine Liver Vascular Endothelium (2011)

Inappropriate activation of complement on the vascular endothelium of specific organs, or systemically, underlies the etiology of a number of diseases. These disorders include atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, atherosclerosis, age-related macular degeneration, diabetic retinopathy, and transplant rejection. Inhibition of the terminal step of complement activation, i.e. formation of the membrane attack complex, using CD59 has the advantage of retaining the upstream processes of the complement cascade necessary for fighting pathogens and retaining complement's crucial role in tissue homeostasis. Previous studies have shown the necessity of membrane targeting of soluble CD59 in order for it to prove an effective inhibitor of complement deposition both in vitro and in vivo. In this study we have generated an in vivo model of human complement activation on murine liver vascular endothelium. This model should prove useful for the development of anti-complement therapies for complement-induced pathologies of vascular endothelium. Using this model, we have demonstrated the viability of a non membrane-targeted soluble CD59 to significantly inhibit complement deposition on the endothelium of murine liver vasculature when expressed in vivo from an adenovirus. This result, unanticipated based on prior studies, suggests that the use of non membrane-targeted sCD59 as an anti-complement therapy be re-visited.
Heterotrimerization of the Growth Factor Receptors erbB2, erbB3, and Insulin-like Growth Factor-I Receptor in Breast Cancer Cells Resistant to Herceptin (2010)

Primary and acquired resistance to the breast cancer drug trastuzumab (Herceptin) is a significant clinical problem. Here, we report enhanced activation of downstream signaling pathways emanating from the growth factor receptors erbB2, erbB3, and insulin-like growth factor-I receptor (IGF-IR) in trastuzumab-resistant breast cancer cells. Interactions between IGF-IR and erbB2 or erbB3 occur exclusively in trastuzumab-resistant cells, where enhanced erbB2-erbB3 interactions are also observed. Moreover, these three receptors form a heterotrimeric complex in resistant cells. erbB3 or IGF-IR knockdown by short hairpin RNA-mediated strategies upregulates p27(kip1), inactivates downstream receptor signaling, and resensitizes resistant cells to trastuzumab. Our findings reveal a heterotrimer complex with a key role in trastuzumab resistance. On the basis of our results, we propose that trastuzumab resistance in breast cancer might be overcome by therapeutic strategies that jointly target erbB3, erbB2, and IGF-IR.
Signal Transduction Pathways Regulated by Mitogen-activated/Extracellular Response Kinase Kinase Kinase Induce Cell Death (1996)

Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress-activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation characteristic of apoptosis. Expression of activated MEKK enhanced the apoptotic response to ultraviolet irradiation, indicating that MEKK-regulated pathways sensitize cells to apoptotic stimuli. Inducible expression of activated MEKK stimulated the transactivation of c-Myc and Elk-1. Activated Raf, the serine-threonine protein kinase that activates the ERK members of the MAPK family, stimulated Elk-1 transactivation but not c-Myc; expression of activated Raf does not induce any of the cellular changes associated with MEKK-mediated cell death. Thus, MEKK selectively regulates signal transduction pathways that contribute to the apoptotic response.
High-level expression and purification of secreted forms of herpes simplex virus type 1 glycoprotein gD synthesized by baculovirus-infected insect cells (1994)

Two forms of herpes simplex virus glycoprotein gD were recombined into Autographa californica nuclear polyhedrosis virus (baculovirus) and expressed in infected Spodoptera frugiperda (Sf9) cells. Each protein was truncated at residue 306 of mature gD. One form, gD-1(306t), contains the coding sequence of Patton strain herpes simplex virus type 1 gD; the other, gD-1(QAAt), contains three mutations which eliminate all signals for addition of N-linked oligosaccharides. Prior to recombination, each gene was cloned into the baculovirus transfer vector pVT-Bac, which permits insertion of the gene minus its natural signal peptide in frame with the signal peptide of honeybee melittin. As in the case with many other baculovirus transfer vectors, pVT-Bac also contains the promoter for the baculovirus polyhedrin gene and flanking sequences to permit recombination into the polyhedrin site of baculovirus. Each gD gene was engineered to contain codons for five additional histidine residues following histidine at residue 306, to facilitate purification of the secreted protein on nickel-containing resins. Both forms of gD-1 were abundantly expressed and secreted from infected Sf9 cells, reaching a maximum at 96 h postinfection for gD-1(306t) and 72 h postinfection for gD-1(QAAt). Secretion of the latter protein was less efficient than gD-1(306t), possibly because of the absence of N-linked oligosaccharides from gD-1(QAAt). Purification of the two proteins by a combination of immunoaffinity chromatography, nickel-agarose chromatography, and gel filtration yielded products that were > 99% pure, with excellent recovery. We are able to obtain 20 mg of purified gD-1(306t) and 1 to 5 mg of purified gD-1(QAAt) per liter of infected insect cells grown in suspension. Both proteins reacted with monoclonal antibodies to discontinuous epitopes, indicating that they retain native structure. Use of this system for gD expression makes crystallization trials feasible.
A C-μTesla Protocol for Sensor Networks (2008)

A sensor network has one or more base stations that talk to a large set of sensors, where the sensor life depends a small battery that consumes most power during communication. Before this network can be applied, many security problems must be solved, yet traditional security protocols usually need a lot of communication overhead. Recently, the μTesla protocol was proposed to address the authentication problem which ensures that no adversaries can impersonate the legal sender to control the sensors. The protocol adds a 24-bytes MAC (Message Authentication Code) to each 30-bytes message, where the MAC is based on the symmetric technique but can achieve the asymmetric property. The protocol is applied to a general case that a sensor can either compute the MAC to authenticate the message or just skip the MAC to see the message content. In this paper, we propose a C-μTesla protocol for a specific case where a sensor wants to authenticate all messages. We reduce the overhead from 30 bytes to 4 bytes, by asking the sender to encrypt all messages without creating any MACs, so that a sensor authenticate messages through decryption. And each message adds a 4-bytes Cyclic Redundancy Check (CRC) before encryption, so that a modified encrypted message will not pass the CRC after decryption. Moreover, the CμTesla protocol introduces a new confidentiality property that allows no adversaries to hear information of the sender through putting a fabricated sensor.