gebhart/patrepeval huggingface dataset:
Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging (2016)

The blood-brain barrier (BBB) is partially disrupted in brain tumors. Despite the gaps in the BBB, there is an inadequate amount of pharmacological agents delivered into the brain. Thus, the low delivery efficiency renders many of these agents ineffective in treating brain cancer. In this report, we proposed an "autocatalytic" approach for increasing the transport of nanoparticles into the brain. In this strategy, a small number of nanoparticles enter into the brain via transcytosis or through the BBB gaps. After penetrating the BBB, the nanoparticles release BBB modulators, which enables more nanoparticles to be transported, creating a positive feedback loop for increased delivery. Specifically, we demonstrated that these autocatalytic brain tumor-targeting poly(amine-co-ester) terpolymer nanoparticles (ABTT NPs) can readily cross the BBB and preferentially accumulate in brain tumors at a concentration of 4.3- and 94.0-fold greater than that in the liver and in brain regions without tumors, respectively. We further demonstrated that ABTT NPs were capable of mediating brain cancer gene therapy and chemotherapy. Our results suggest ABTT NPs can prime the brain to increase the systemic delivery of therapeutics for treating brain malignancies.
Mass determination of megadalton-DNA electrospray ions using charge detection mass spectrometry (1998)

Charge detection mass spectrometry (CD-MS) has been used to determine the mass of double-stranded, circular DNA and single-stranded, circular DNA in the range of 2500 to 8000 base pairs (1.5-5.0 MDa). Simultaneous measurement of the charge and velocity of an electrostatically accelerated ion allows a mass determination of the ion, with instrument calibration determined independently of samples. Positive ion mass spectra of electrosprayed commercial DNA samples supplied in tris(hydroxymethyl)ethylenediaminetetraacetic acid buffer, diluted in 50 vol. % acetonitrile, were obtained without cleanup of the sample. A CD mass spectrum constructed from 3000 ion measurements takes 10 min to acquire and yields the DNA molecular mass directly (mass resolution = 6). The data collected represent progress toward a more automatable alternative to sizing of DNA by gel electrophoresis. In addition to the mass spectra, CD-MS generates charge versus mass plots, which provide another means to investigate the creation and fate of large electrospray ions.
Biophysical Characterization of Zinc Ejection from HIV Nucleocapsid Protein by Anti-HIV 2,2‘-Dithiobis[benzamides] and Benzisothiazolones (1996)

HIV nucleocapsid protein (NCp7) has been suggested as a possible target for 2,2'-dithiobis-[benzamide] and benzisothiazolone agents that inhibit viral replication in infected cells (Rice et al. Science 1995, 270, 1194-1197). The solution behavior of these compounds and the mechanistic events leading to removal of Zn from HIV nucleocapsid protein in vitro has been studied by electrospray ionization mass spectrometry, 500 MHz one- and two-dimensional nuclear magnetic resonance spectroscopy, and circular dichroism spectroscopy. We demonstrate that (1) Zn ejection is accompanied by formation of covalent complexes formed between the 2,2'-dithiobis[benzamide] monomers and Cys residues of Zn-depleted NCp7, (2) the rate of Zn ejection is faster for the C-terminal Zn finger and slower for the N-terminal finger, (3) Zn ejection results in a loss of structural integrity of the NCp7 protein, and (4) there is no appreciable interaction between a nonreactive isostere of the lead 2,2'-dithiobis[benzamide] and NCp7 in buffered aqueous solution. These findings are discussed in terms of the mechanism of action of Zn ejection by aromatic 2,2'-dithiobis[benzamides].
Sympathetic Vasomotor Tone Determines Blood Pressure Response to Long-Term Sibutramine Treatment (2007)

The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment.
D‐ AND L‐STEREOISOMERS OF ALLYLGLYCINE: CONVULSIVE ACTION AND INHIBITION OF BRAIN L‐GLUTAMATE DECARBOXYLASE (1977)

Abstract— DL‐Allylglycine was resolved into the L‐ and D‐stereoisomers using hog kidney acylase. Both isomers were active as convulsants after administration to mice. The dose of D‐allylglycine required to induce convulsions was greater than that of the L‐isomer. Studies on the concentration of the two isomers in brain suggest that the lower effectiveness of D‐allylglycine is partially due to its slower penetration into the brain through the blood‐brain barrier. Both isomers of allylglycine inhibited brain glutamate decarboxylase in vitro to approximately the same extent, however, in vivo L‐allylglycine inhibited the enzyme more strongly than the D isomer. Concentrations of allylglycine which caused a significant inhibition of L‐glutamate decarboxylase in vivo were ineffective in inhibiting the enzyme in vitro . Oxidation products derived from L‐ or D‐allylglycine by the action of either L‐ or D‐amino acid oxidase caused an almost complete inhibition of the enzyme in vitro . It is suggested that a common intermediate derived from the two isomers (possibly 2‐keto‐4‐pentenoic acid) is responsible for the in vivo inhibition of L‐glutamate decarboxylase and possibly also for the induction of convulsions.
Role of gap junctions in the development of the preimplantation mouse embryo (1995)

We have taken several approaches to study the role of gap junctional communication during preimplantation mouse development. Firstly, the normal expression pattern of gap junctions has been characterized using immunostaining in conjunction with laser scanning confocal microscopy. Changes in junctional distribution have been correlated with developmental events. We have gone on to study development and junctional organization in mice which naturally exhibit reduced cell to cell communication (DDK syndrome), and in normal mice in which gap junction permeability has been artificially manipulated. Furthermore, anti-peptide antibodies have been tested for their ability to block gap junction communication and for the effects of such a block on subsequent development. Collectively, the results demonstrate that gap junctional communication plays an important role in the maintenance of compaction and the differentiation of an organized epithelium within an embryo, features which are vital for preimplantation development to progress successfully.
Cloning and expression of heat-labile enterotoxin operon of an enterotoxigenic human Escherichia coli strain. (1989)

Plasmid pJY11 of the Escherichia coli H10407 strain was isolated and completely digested with restriction endonuclease PstI in order to isolate the heat-labile enterotoxin (LT) operon. The resulting fragments were then separated by electrophoresis on agarose gel, and the location of the LT region in pJY11 was determined by Southern hybridization. The LT region was found to be located on a 5.3 kb fragment of pJY11. This fragment was recovered and subsequently ligated to PstI-linearized pUC8 DNA. After transformation and selection, a clone that effectively expressed LT was obtained. Biological and immunological assays showed the LT synthesized by this clone to be biologically and immunologically identical to that synthesized by the parent E. coli strain H10407; the LT production level of this recombinant strain was 15 times greater.
Photocrosslinkable polysaccharides forin situ hydrogel formation (2000)

In situ photopolymerization is an exciting new technique for tissue engineering. Two photocrosslinkable polysaccharides composed of alginate and hyaluronan are described that upon photolysis form soft, flexible, and viscoelastic hydrogels. The degree of methacrylate modification and thus covalent affects mechanical properties such as swelling, compression, and creep compliance. Significant swelling is observed in aqueous solution; these hydrogels can swell up to 14 times their dry weight. Both hydrogels exhibit low phase angles and (G*) values indicative of viscoelastic materials. The hyaluronan based hydrogel is stronger and more resilient than the corresponding alginate gel. SEM and AFM studies on both hydrogels show smooth and uniform surfaces at the macroscopic level with salient features observed only on the nanometer scale. Rapid polymerization by an optical trigger allows for controlled in situ photopolymerization in a minimally invasive manner, indicating that these hydrogels are relevant for biomedical applications such as sealing wounds and reconstructing soft tissues.
Mass Spectrometric Investigations of Drug-Receptor Interactions (1993)

Mass spectrometric (MS) detection of biologically important noncovalent complexes is reviewed within, the scope of on-going studies on this topic from this laboratory. The merits of ion spray MS and tandem MS are demonstrated in this area with examples that show systematic studies of several receptor-ligand, enzyme-substrate, and enzyme-product complexes associated with both an established well-characterized biological system (lysozyme hydrolysis of N-acetylglucosamine) and an important modern receptor-ligand complex (FKBP-FK-506 and FKBP-rapamycin). These examples and recent applications of negative ion MS and MS/MS with DNA adducts, heme-globin complexes, and antibiotic-binding proteins suggest an exciting new area of applications for MS that have not been previously available to investigators.
High speed DNA denaturation using microheating devices (2013)

Denaturation is a first step for further treatment of DNA and is expected to be carried out rapidly on an integrated chip. A microheater is a promising device for the denaturation because of easiness for fabrication and operation. In the present study, we fabricated a microheater and thermometers on a coverslip and investigated response of temperature to application of voltage. In addition, our experiment and simulation proved local heating at an aimed area. Finally, we demonstrated denaturation of DNA in buffer solution, the result of which proved that the DNA around the heater denatured within 60 ms.
Rearrangements of a 2-vinylaziridine (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRearrangements of a 2-vinylaziridinePeter ScheinerCite this: J. Org. Chem. 1967, 32, 8, 2628–2630Publication Date (Print):August 1, 1967Publication History Published online1 May 2002Published inissue 1 August 1967https://pubs.acs.org/doi/10.1021/jo01283a063https://doi.org/10.1021/jo01283a063research-articleACS PublicationsRequest reuse permissionsArticle Views322Altmetric-Citations63LEARN 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
Herpes simplex virus type 1 immediate early protein IE63 shuttles between nuclear compartments and the cytoplasm. (1997)

Herpes simplex virus type 1 (HSV-1) immediate early protein IE63, an essential nuclear protein, is pleiotropic in function and, at the post-transcriptional level, inhibits RNA splicing, interacts with cellular splicing small nuclear ribonucleoprotein particles (snRNPs), binds RNA and prevents the nucleocytoplasmic transport of intron-containing mRNAs. Here it is reported that IE63 is a nucleocytoplasmic shuttle protein able to travel from snRNP- and RNA-rich nuclear foci to the cytoplasm, where it accumulates during actinomycin D treatment. This newly identified property suggests that IE63 facilitates nuclear export of HSV-1 transcripts, in addition to retaining intron-containing transcripts in the nucleus. The mechanism by which IE63 controls RNA export has yet to be defined.
Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1 (1997)

We have investigated the ability of Sf-caspase-1 and two mammalian caspases, caspase-1 and caspase-3, to induce apoptosis in Spodoptera frugiperda Sf-21 insect cells. While the transient expression of the pro-Sf-caspase-1 did not induce apoptosis, expression of the pro-domain deleted form, p31, or coexpression of the two subunits of mature Sf-caspase-1, p19 and p12, induced apoptosis in Sf-21 cells. The behavior of Sf-caspase-1 resembled that of the closely related mammalian caspase, caspase-3, and contrasted with that of the mammalian caspase-1, the pro-form of which was active in inducing apoptosis in Sf-21 cells. The baculovirus caspase inhibitor P35 blocked apoptosis induced by active forms of all three caspases. In contrast, members of the baculovirus inhibitor of apoptosis (IAP) family failed to block active caspase-induced apoptosis. However, during viral infection, expression of OpIAP or CpIAP blocked the activation of pro-Sf-caspase-1 and the associated induction of apoptosis. Thus, the mechanism by which baculovirus IAPs inhibit apoptosis is distinct from the mechanism by which P35 blocks apoptosis and involves inhibition of the activation of pro-caspases like Sf-caspase-1.
Control of macrophage lineage populations by CSF‐1 receptor and GM‐CSF in homeostasis and inflammation (2011)

There is recent interest in the role of monocyte/macrophage subpopulations in pathology. How the hemopoietic growth factors, macrophage-colony stimulating factor (M-CSF or CSF-1) and granulocyte macrophage (GM)-CSF, regulate their in vivo development and function is unclear. A comparison is made here on the effect of CSF-1 receptor (CSF-1R) and GM-CSF blockade/depletion on such subpopulations, both in the steady state and during inflammation. In the steady state, administration of neutralizing anti-CSF-1R monoclonal antibody (mAb) rapidly (within 3-4 days) lowered, specifically, the number of the more mature Ly6C(lo) peripheral blood murine monocyte population and resident peritoneal macrophages; it also reduced the accumulation of murine exudate (Ly6C(lo)) macrophages in two peritonitis models and alveolar macrophages in lung inflammation, consistent with a non-redundant role for CSF-1 (or interleukin-34) in certain inflammatory reactions. A neutralizing mAb to GM-CSF also reduced inflammatory macrophage numbers during antigen-induced peritonitis and lung inflammation. In GM-CSF gene-deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil dynamics in antigen-induced peritonitis suggested that GM-CSF was acting, in part, systemically to maintain the inflammatory reaction. A model is proposed in which CSF-1R signaling controls the development of the macrophage lineage at a relatively late stage under steady state conditions and during certain inflammatory reactions, whereas in inflammation, GM-CSF can be required to maintain the response by contributing to the prolonged extravasation of immature monocytes and neutrophils. A correlation has been observed between macrophage numbers and the severity of certain inflammatory conditions, and it could be that CSF-1 and GM-CSF contribute to the control of these numbers in the ways proposed.
Morphological changes of autoclaved autogenic bone implantation and autoclaved autogenic bone supplemented with allogenic demineralized bone matrix in rat parietal bone. (1996)

The healing process of resected, autoclaved (121 degrees C, 20 minutes) and re-implanted bone in the rat parietal bone was compared with that of autoclaved bone that was supplemented with allogenic bone matrix (AAA-bone), using a scanning electron microscope and a light microscope. In the implant without AAA-bone, bone union and replacement of the autoclaved bone was seen at 2 weeks after implantation. There was no evidence of any inflammatory reaction around the autoclaved bone. The implant was gradually replaced by the new bone. In the implant with AAA-bone, the new bone formation around the implanted bone was more abundant than that of the implant without AAA-bone. An inflammatory reaction was also observed after 1 week. The replacement of the implant with AAA-bone was inferior to the nonsupplemented group. The reason for the poor replacement was the disturbance of the blood supply in the implant by abundant new bone formation. In these results, the autoclaved bone re-implantation was an excellent bone substitute with osteoconductive ability and biocompatibility. The implantation with AAA-bone was good for the new bone formation, but the position and the technique of supplement with AAA-bone have to be more deeply investigated.
Security issues and concerns with the Internet (1995)

Draws its topicality and relevance from the fact that not only is the Internet widely publicized in all the media but also there are many stories regarding problems with its security. Provides a primer on the history, terminology, tools and common uses of the Internet. Identifies the most prevalent threats to security posed by using the Internet and discusses some of the traditional and emerging approaches to ensuring the security and integrity of data on the Internet.
Cas9 cleavage assay for pre-screening of sgRNAs using nicking triggered isothermal amplification (2016)

CRISPR/Cas9 is a highly efficient genome engineering tool, yet its off-target effects and sequence-dependent cleavage activity across different sgRNAs remain major concerns for its application. Here, we propose a nicking triggered exponential amplification reaction (NTEXPAR), a fast and sensitive <i>in vitro</i> method, to detect the double strand DNA cleaved by down to 10 pM Cas9 with a linear range of 100 pM to 20 nM. With this newly developed amplification method, Cas9 cleavage activity can be quantified in 40 min and the optimal sgRNA design for specific target sequence can be successfully determined. Using the pre-screened sgRNA, we are able to distinguish single nucleotide mismatch in a gene silencing experiment. This fluorescence based isothermal assay provides a versatile tool for the pre-screening of sgRNAs to achieve highly specific and highly efficient CRISPR/Cas9 genome editing.
Delayed Neuroprotective Effect of Insulin-Like Growth Factor-I After Experimental Transient Focal Cerebral Ischemia Monitored With MRI (2001)

Continuous treatment with intraventricularly and subcutaneously administered IGF-I achieved a long-lasting neuroprotective effect as early as 24 hours after ischemia as measured by MRI. Therefore, IGF-I may represent a new approach to the treatment of focal cerebral ischemia.
Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging (2007)

The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration, and it is involved in several human vascular pathologies including atherosclerosis and vascular restenosis. During intima layer thickening, HA increases dramatically in the neointima extracellular matrix. Aging is one of the major risk factors for the insurgence of vascular diseases, in which smooth muscle cells (SMCs) play a role by determining neointima formation through their migration and proliferation. Therefore, we established an in vitro aging model consisting of sequential passages of human aortic smooth muscle cells (AoSMCs). Comparing young and aged cells, we found that, during the aging process in vitro,HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2 and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA receptor CD44. In aged cells, we also observed increased CD44 signaling that consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged AoSMCs migrated faster than young cells, and such migration could be modulated by HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited AoSMCs migration. These results indicate that, during aging, HA can modulate cell migration involving CD44-mediated signaling through ERK1/2. These data suggest that age-related HA accumulation could promote SMC migration and intima thickening during vascular neointima formation.
High-Throughput Cervical Cancer Screening Using Intracellular Human PapillomavirusE6andE7mRNA Quantification by Flow Cytometry (2005)

The Papanicolaou (Pap) test, based solely on the morphologic examination of exfoliated cells from the cervix, has reduced deaths due to cervical cancer by 74% in the United States during the past 40 years. During that time, the molecular mechanisms of cervical cancer have largely been elucidated. Taken together, these observations have identified a need for a high-throughput cervical cancer screening assay. We report the development of a high-throughput assay consisting of simultaneous immunophenotyping and ultrasensitive in situ hybridization for human papillomavirus (HPV) E6 and E7 messenger RNA (mRNA). This assay can be performed in less than 3 hours directly from liquid-based cervical cytology specimens. Overall, HPV fluorescence in situ hybridization (FISH) for E6 and E7 mRNA demonstrated 83.3% sensitivity and 91.3% specificity for high-grade squamous intraepithelial lesions compared with the Pap test in 231 liquid-based cytology samples from 2 cohorts. In a subset of these samples, HPV FISH demonstrated higher sensitivity and specificity than Hybrid Capture (Digene, Gaithersburg, MD) for high-risk genotypes.
Isolation and Characterization of a Gene Encoding a PR-1-Like Protein from Arabidopsis thaliana (1991)

The hypersensitive (resistance) response to infection by pathogens is accompanied by the synthesis of a variety of host proteins, several of which are termed PR3 proteins. Although the activities of some PR proteins suggest that they are anti- fungal agents (5, 6), the functions of other families of PRs, including the PR-I proteins, are unknown. The PR-I proteins have been well characterized in terms of sequence, cellular localization, and synthesis in tobacco and tomato. Circum- stantial evidence suggests that they may be involved in both the hypersensitive response and systemic acquired resistance (for reviews, see refs. 1 and 3), and recently it has been demonstrated that they are also synthesized during normal floral development in tobacco (7).