gebhart/patrepeval huggingface dataset:
Impact of PEG Chain Length on the Physical Properties and Bioactivity of PEGylated Chitosan/siRNA Nanoparticles in Vitro and in Vivo (2017)

PEGylation of cationic polyplexes is a promising approach to enhance the stability and reduce unspecific interaction with biological components. Herein, we systematically investigate the impact of PEGylation on physical and biological properties of chitosan/siRNA polyplexes. A series of chitosan-PEG copolymers (CS-PEG2k, CS-PEG5k and CS-PEG10k) were synthesized with similar PEG mass content but with different molecular weight. PEGylation with higher molecular weight and less grafting degree resulted in smaller and more compacted nanoparticles with relatively higher surface charge. PEGylated polyplexes showed distinct mechanism of endocytosis, which was macropinocytosis and caveolae-dependent and clathrin-independent. In vitro silencing efficiency in HeLa and H1299 cells was significantly improved by PEGylation and CS-PEG5k/siRNA achieved the highest knockdown efficiency. Efficient silence of ribonucleotide reductase subunit M2 (RRM2) in HeLa cells by CS-PEG5k/siRRM2 significantly induced cell cycle arrest and inhibited cell proliferation. In addition, PEGylation significantly inhibited macrophage phagocytosis and unspecific interaction with red blood cells (RBCs). Significant extension of in vivo circulation was achieved only with high molecular weight PEG modification (CS-PEG10k), whereas all CS/siRNA and CS-PEG/siRNA nanoparticles showed similar pattern of biodistribution with major accumulation in liver and kidney. These results imply that PEGylation with higher molecular weight PEG and less grafting rate is a promising strategy to improve chitosan/siRNA nanocomplexes performance both in vitro and in vivo.
Follistatin Is a Modulator of Gonadal Tumor Progression and the Activin-Induced Wasting Syndrome in Inhibin-Deficient Mice (2000)

Inhibins and activins are dimeric proteins belonging to the transforming growth factor-β superfamily. Follistatin is an activin-binding protein that antagonizes the function of activin via binding to its β-subunits. Previously, we demonstrated that mice deficient in inhibin develop ovarian and testicular sex cord-stromal tumors of granulosa and Sertoli cell origin, with 100% penetrance as early as 4 weeks of age. Overproduction of activins in the serum directly causes a cachexia-like wasting syndrome that results in lethality of these mice at an early stage after the onset of the tumors. In an independent set of studies, overexpression of mouse follistatin using the mouse metallothionein I promoter in transgenic mice led to gonadal defects and eventual infertility, primarily due to local effects of follistatin in these tissues. Activin has a positive growth effect on gonadal tumor cells in culture and directly causes the cancer cachexia-like syndrome in inhibin-deficient mice via interaction with activin receptor type IIA in livers and stomachs. We therefore hypothesized that an activin antagonist such as follistatin can act as a physiological modifier, either locally or via the serum, to block the activin-mediated cancer cachexia-like syndrome in inhibin-deficient mice and/or slow the progression of gonadal cancers in these mice. To test this hypothesis, we generated mice that are homozygous mutant for the inhibin α null allele (i.e.inham1/inham1) and carry the mouse metallothionein I follistatin (MT-FS) transgene. Our results show that gonadal tumors that are histologically similar in most, but not all, cases to the tumors in inhibin-deficient mice develop in these inham1/inham1, MT-FS+ mice. However, inham1/inham1, MT-FS+ mice exhibit a less severe wasting syndrome, lower serum activin levels, and a statistically significant prolonged survival in a number of cases compared with mice deficient in inhibin alone. Thus, follistatin can act as a modulator of tumor growth and the activin-induced cancer cachexia-like syndrome in inhibin-deficient mice.
Molecular Cloning and Expression of a Functional Snake Venom Vascular Endothelium Growth Factor (VEGF) from theBothrops insularis Pit Viper (2001)

During the generation of abundant expressed sequence tags from the Viperidae snake Bothrops insularis venom glands, we identified for the first time a cDNA coding for a putative vascular endothelial growth factor-like (VEGF-like) protein. The deduced primary sequence, after complete sequencing of the longest snake venom VEGF (svVEGF) cDNA, displayed similarity with vertebrate VEGFs and with the hypotensive factor from Vipera aspis venom. Its cDNA was subcloned, expressed in Escherichia coli with a His(6) tag as an insoluble monomer, and purified by Ni(2+)-affinity chromatography after 8 m urea extraction. Antiserum against svVEGF was generated and tested in Western blot against proteins from snake venoms and cellular extracts. The mature svVEGF appears to be ubiquitously distributed throughout snake venoms and was also confirmed by Northern blot studies of other related Viperidae species and by cDNA cloning of svVEGF from Bothrops jararaca pit viper. The produced recombinant protein dimerizes after refolding processes and was biologically characterized, showing ability to increase vascular permeability. These results established that svVEGF is a novel and important active toxin during the early stages of bothropic snake bite envenoming and represents a new member of the VEGF family of proteins.
Fluorescence Polarization: Past, Present and Future (2003)

Fluorescence polarization was first observed in 1920 and during the next few decades the theoretical foundations of the phenomenon were clearly established. In the last two decades of the 20(th) century, fluorescence polarization became one of the most prevalent methods used in clinical and biomedical sciences. In this article we review the history of fluorescence polarization, its theoretical foundations and some of the more important practical developments, which helped to popularize the method. We also discuss important, but often misunderstood, practical considerations including the wavelength dependence of the limiting polarization and the effect of energy transfer on polarization. The present state of fluorescence polarization, both in pure research as well as in the applied biosciences is also reviewed. Finally, we speculate on possible future developments in the field, such as the use of multi-photon techniques.
Evaluation of β‐cell mass and function in the Göttingen minipig (2007)

Increased knowledge about beta-cell mass and function is important for our understanding of the pathophysiology of type 2 diabetes (T2DM). The relationship between the two is difficult to study in humans, whereas animal models allow studies of consequences of, for example, reduction of beta-cell mass and induction of obesity and procurement of the pancreas for histological examination. An overview of results obtained in the Göttingen minipig in relation to beta-cell function, and mass is provided here. Effects of a primary reduction of beta-cell mass have indicated that not all of the defects of pulsatile insulin secretion in human T2DM can be explained by reduced beta-cell mass. Furthermore, induction of obesity has shown deterioration of beta-cell function and morphological changes in the pancreas. As in humans, obesity leads to an increased beta-cell volume in the minipig, and based on the increased number of islets, neogenesis of islets is an important factor in expansion of beta-cell mass in this species. Measurement of beta-cell function as an estimate of beta-cell mass is, at present, the only method possible in humans, and this approach has been validated using lean and obese minipigs with a range of beta-cell mass. The effects on beta-cell function and mass of obesity of longer duration and/or more pronounced hyperglycaemia remains to be determined, but the models developed so far represent a valuable tool for such investigations.
Blocking Hedgehog Survival Signaling at the Level of the GLI Genes Induces DNA Damage and Extensive Cell Death in Human Colon Carcinoma Cells (2011)

Canonical Hedgehog (HH) signaling is characterized by Smoothened (Smo)-dependent activation of the transcription factors Gli1 and Gli2, which regulate HH target genes. In human colon carcinoma cells, treatment with the Gli small-molecule inhibitor GANT61 induces extensive cell death in contrast to the Smo inhibitor cyclopamine. Here we elucidate cellular events upstream of cell death elicited by GANT61, which reveal the basis for its unique cytotoxic activity in colon carcinoma cells. Unlike cyclopamine, GANT61 induced transient cellular accumulation at G(1)-S (24 hours) and in early S-phase (32 hours), with elevated p21(Cip1), cyclin E, and cyclin A in HT29 cells. GANT61 induced DNA damage within 24 hours, with the appearance of p-ATM and p-Chk2. Pharmacologic inhibition of Gli1 and Gli2 by GANT61 or genetic inhibition by transient transfection of the Gli3 repressor (Gli3R) downregulated Gli1 and Gli2 expression and induced γH2AX, PARP cleavage, caspase-3 activation, and cell death. GANT61 induced γH2AX nuclear foci, while transient transfection of Gli3R showed expression of Gli3R and γH2AX foci within the same nuclei in HT29, SW480, and HCT116. GANT61 specifically targeted Gli1 and Gli2 substantiated by specific inhibition of (i) direct binding of Gli1 and Gli2 to the promoters of target genes HIP1 and BCL-2, (ii) Gli-luciferase activity, and (iii) transcriptional activation of BCL-2. Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells.
Similar patterns of hypomethylation in the β‐hydroxy‐β‐methylglutaryl coenzyme a reductase gene in hepatic nodules induced by different carcinogens (1994)

Our earlier studies demonstrated that the beta-hydroxy-beta-methylglutaryl coenzyme A (HMG CoA) reductase gene is hypomethylated and overexpressed in hepatic nodules initiated by 1,2-dimethylhydrazine (1,2-DMH). The study presented here examined whether the pattern of DNA methylation of the HMG CoA reductase gene in hepatic nodules reflected carcinogen-DNA interaction during initiation. Accordingly, hepatic nodules were generated in male Fischer 344 rats with either 1,2-DMH or aristolochic acid (AA), which interact predominantly with the guanine and adenine bases in DNA, respectively. DNA from individual nodules was restricted with HpaII, MspI, and HhaI, and the fragments obtained were hybridized to a cDNA probe for HMG CoA reductase. The results indicated that the hypomethylation pattern in the reductase gene in the nodules initiated with these two carcinogens was similar, although they interacted with different bases in the DNA. The question still remained whether the DNA fragments obtained by digesting the two sets of nodules with the restriction endonucleases were from the same domains in the genome of HMG CoA reductase. To examine this, probes for the different domains of the HMG CoA reductase gene were generated from the cDNA using the restriction enzyme Accl. Three probes were obtained: (i) a 5'-end fragment corresponding to the membrane-spanning region, (ii) a second fragment corresponding to the 3'-end of the protein, and (iii) a third fragment spanning the region between (i) and (ii). Each of these probes was radiolabeled and hybridized to the HpaII- and HhaI-generated fragments from the DNA of hepatic nodules initiated with 1,2-DMH and AA. Irrespective of the carcinogen used for initiation, hypomethylation occurred in all three domains of the gene. More important, the pattern of hypomethylation was similar in the nodules initiated by the two carcinogens. Furthermore, an overall similarity was seen in the hypomethylation patterns in the c-myc and c-Ha-ras genes in the DNA of nodules initiated with either 1,2-DMH or AA. These results raise the possibility that the pattern of hypomethylation established in the hepatic nodules may not directly reflect the interaction between the initiating carcinogen and DNA but may represent a unique phenotype of hepatic nodules.
Development of definitive endoderm from embryonic stem cells in culture (2004)

The cellular and molecular events regulating the induction and tissue-specific differentiation of endoderm are central to our understanding of the development and function of many organ systems. To define and characterize key components in this process, we have investigated the potential of embryonic stem (ES) cells to generate endoderm following their differentiation to embryoid bodies (EBs) in culture. We found that endoderm can be induced in EBs, either by limited exposure to serum or by culturing in the presence of activin A (activin) under serum-free conditions. By using an ES cell line with the green fluorescent protein (GFP) cDNA targeted to the brachyury locus, we demonstrate that endoderm develops from a brachyury(+) population that also displays mesoderm potential. Transplantation of cells generated from activin-induced brachyury(+) cells to the kidney capsule of recipient mice resulted in the development of endoderm-derived structures. These findings demonstrate that ES cells can generate endoderm in culture and, as such, establish this differentiation system as a unique murine model for studying the development and specification of this germ layer.
Dynamics of organic compound extraction from water using liquid-coated fused silica fibers (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of organic compound extraction from water using liquid-coated fused silica fibersDerek. Louch, Safa. Motlagh, and Janusz. PawliszynCite this: Anal. Chem. 1992, 64, 10, 1187–1199Publication Date (Print):May 15, 1992Publication History Published online1 May 2002Published inissue 15 May 1992https://pubs.acs.org/doi/10.1021/ac00034a020https://doi.org/10.1021/ac00034a020research-articleACS PublicationsRequest reuse permissionsArticle Views1616Altmetric-Citations510LEARN 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
Uncertainty Relation for Smooth Entropies (2011)

Uncertainty relations give upper bounds on the accuracy by which the outcomes of two incompatible measurements can be predicted. While established uncertainty relations apply to cases where the predictions are based on purely classical data (e.g., a description of the system's state before measurement), an extended relation which remains valid in the presence of quantum information has been proposed recently [Berta et al., Nature Phys. 6, 659 (2010)]. Here, we generalize this uncertainty relation to one formulated in terms of smooth entropies. Since these entropies measure operational quantities such as extractable secret key length, our uncertainty relation is of immediate practical use. To illustrate this, we show that it directly implies security of quantum key distribution protocols. Our security claim remains valid even if the implemented measurement devices deviate arbitrarily from the theoretical model.
Structural tuning of color chromaticity through nonradiative energy transfer by interspacing CdTe nanocrystal monolayers (2009)

We proposed and demonstrated architectural tuning of color chromaticity by controlling photoluminescence decay kinetics through nonradiative Förster resonance energy transfer in the heterostructure of layer-by-layer spaced CdTe nanocrystal (NC) solids. We achieved highly sensitive tuning by precisely adjusting the energy transfer efficiency from donor NCs to acceptor NCs via controlling interspacing between them at the nanoscale. By modifying decay lifetimes of donors from 12.05 to 2.96 ns and acceptors from 3.68 to 14.57 ns, we fine-tuned chromaticity coordinates from (x,y)=(0.575,0.424) to (0.632, 0.367). This structural adjustment enabled a postsynthesis color tuning capability, alternative or additive to using the size, shape, and composition of NCs.
Bacterial Lipopolysaccharide Activates Nuclear Factor-κB through Interleukin-1 Signaling Mediators in Cultured Human Dermal Endothelial Cells and Mononuclear Phagocytes (1999)

Bacterial lipopolysaccharide (LPS)-mediated immune responses, including activation of monocytes, macrophages, and endothelial cells, play an important role in the pathogenesis of Gram-negative bacteria-induced sepsis syndrome. Activation of NF-kappaB is thought to be required for cytokine release from LPS-responsive cells, a critical step for endotoxic effects. Here we investigated the role and involvement of interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) signal transducer molecules in LPS signaling in human dermal microvessel endothelial cells (HDMEC) and THP-1 monocytic cells. LPS stimulation of HDMEC and THP-1 cells initiated an IL-1 receptor-like NF-kappaB signaling cascade. In transient cotransfection experiments, dominant negative mutants of the IL-1 signaling pathway, including MyD88, IRAK, IRAK2, and TRAF6 inhibited both IL-1- and LPS-induced NF-kappaB-luciferase activity. LPS-induced NF-kappaB activation was not inhibited by a dominant negative mutant of TRAF2 that is involved in TNF signaling. LPS-induced activation of NF-kappaB-responsive reporter gene was not inhibited by IL-1 receptor antagonist. TLR2 and TLR4 were expressed on the cell surface of HDMEC and THP-1 cells. These findings suggest that a signal transduction molecule in the LPS receptor complex may belong to the IL-1 receptor/toll-like receptor (TLR) super family, and the LPS signaling cascade uses an analogous molecular framework for signaling as IL-1 in mononuclear phagocytes and endothelial cells.
Ribonuclease T1 is stabilized by cation and anion binding (1988)

The stability of the folded conformation of ribonuclease T1 is increased by 0.8, 1.8, and 3.3 kcal/mol in the presence of 0.1 M NaCl, MgCl2, and Na2HPO4, respectively. This remarkable increase in the conformational stability results primarily from the preferential binding to the native protein of one Mg2+ or two Na+ ions at cation-binding sites and by the binding of one HPO4(2-) ion at an anion-binding site. Only modest binding constants, 6.2 (Na+), 155 (Mg2+), and 282 M-1 (HPO4(2-)), are required to account for the enhanced stability. One important goal of the modification of proteins through genetic engineering is to increase their stability. Our results suggest that the creation of specific cation- and anion-binding sites on the surface of a protein through amino acid substitutions might be a generally useful way of achieving this goal. The design of these sites will be aided by the recent availability of detailed structural information on cation- and anion-binding sites.
Activation of protein kinase C by tyrosine phosphorylation in response to H 2 O 2 (1997)

Protein kinase C (PKC) isoforms, alpha, betaI, and gamma of cPKC subgroup, delta and epsilon of nPKC subgroup, and zeta of aPKC subgroup, were tyrosine phosphorylated in COS-7 cells in response to H2O2. These isoforms isolated from the H2O2-treated cells showed enhanced enzyme activity to various extents. The enzymes, PKC alpha and delta, recovered from the cells were independent of lipid cofactors for their catalytic activity. Analysis of mutated molecules of PKC delta showed that tyrosine residues, which are conserved in the catalytic domain of the PKC family, are critical for PKC activation induced by H2O2. These results suggest that PKC isoforms can be activated through tyrosine phosphorylation in a manner unrelated to receptor-coupled hydrolysis of inositol phospholipids.
Frequency Control Requirements for Reliable Interconnection Frequency Response (2018)

In light of changes in how electricity is being both generated and consumed, the Department of Energyâs Lawrence Berkeley National Laboratory (Berkeley Lab) has written a new report analyzing challenges facing the nationâs electric grid and making recommendations for ensuring continued reliability. The report was prepared for the Federal Energy Regulatory Commission (FERC), Office of Electric Reliability, to support ongoing FERC and industry efforts to ensure reliable interconnection frequency response for the three major interconnections in the United States: the Eastern, Western, and Texas Interconnections.\n\nThe purpose of this study (and its supporting supplemental reports) is to support policymaker and industry understanding of the physical requirements for reliable interconnection frequency response, which is the collective ability of the power system to respond to sudden loss events, such as the loss of a large generator. \n\nGrid reliability depends on controlling the power system frequency so that it remains within pre-established, safe operating bounds. Reliability is threatened when a large electric generator or generators experiences a problem and automatically disconnects from the power system; the loss of generation causes an immediate decline in power system frequency. If the remaining, still-connected generators do not respond and rapidly arrest the decline in frequency, power system frequency may decline below established, safe operating bounds and trigger automatic, emergency load shedding to avoid a cascading blackout.\n\nThe study builds on an earlier study for FERC conducted in 2010.
HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. (1993)

E7 is the major transforming protein of human papillomavirus type 16 (HPV16). It has been found to associate with the retinoblastoma protein Rb1. We investigated whether HPV16 E7 protein was associated with other cellular proteins, in particular with those involved in cell cycle control. Immunoprecipitates from CaSki cell extracts with an anti E7 monoclonal antibody contained a histone H1 kinase. Recombinant E7, synthesized in yeast, when mixed with protein extracts from epithelial cells bound histone H1 kinase activity in vitro. The in vivo and the in vitro-formed E7-kinase complex had the same periodicity of activity during the cell cycle, being most active in S and G2/M. Immunoblotting of E7 immunoprecipitates with an antibody raised against the p33CDK2, revealed a 33 kDa protein band not detected by an anti-p34cdc2 antibody, suggesting that the E7-associated kinase activity is due to the p33CDK2. The interaction appears to be via cyclin A, since probing of similar immunoblots showed a 50 kDa band corresponding to cyclin A. The association of E7 with cyclin A appeared to be direct, not involving Rb 1 or other proteins.