gebhart/patrepeval huggingface dataset:
Diffusive Dynamics of Vesicles Tethered to a Fluid Supported Bilayer by Single-Particle Tracking (2006)

We recently introduced a method to tether intact phospholipid vesicles onto a fluid supported lipid bilayer using DNA hybridization (Yoshina-Ishii, C.; Miller, G. P.; Kraft, M. L; Kool, E. T.; Boxer, S. G. J. Am. Chem. Soc. 2005, 127, 1356-1357). Once tethered, the vesicles can diffuse in two dimensions parallel to the supported membrane surface. The average diffusion coefficient, D, is typically 0.2 microm(2)/s; this is 3-5 times smaller than for individual lipid or DNA-lipid conjugate diffusion in supported bilayers. In this article, we investigate the origin of this difference in the diffusive dynamics of tethered vesicles by single-particle tracking under collision-free conditions. D is insensitive to tethered vesicle size from 30 to 200 nm, as well as a 3-fold change in the viscosity of the bulk medium. The addition of macromolecules such as poly(ethylene glycol) reversibly stops the motion of tethered vesicles without causing the exchange of lipids between the tethered vesicle and supported bilayer. This is explained as a depletion effect at the interface between tethered vesicles and the supported bilayer. Ca ions lead to transient vesicle-vesicle interactions when tethered vesicles contain negatively charged lipids, and vesicle diffusion is greatly reduced upon Ca ion addition when negatively charged lipids are present both in the supported bilayer and tethered vesicles. Both effects are interesting in their own right, and they also suggest that tethered vesicle-supported bilayer interactions are possible; this may be the origin of the reduction in D for tethered vesicles. In addition, the effects of surface defects that reversibly trap diffusing vesicles are modeled by Monte Carlo simulations. This shows that a significant reduction in D can be observed while maintaining normal diffusion behavior on the time scale of our experiments.
Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on resting and activated human peripheral blood leucocytes (2006)

The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are widely expressed on human lymphoid and non-lymphoid cells. This study aimed to compare systematically levels of CReg expression by different leucocyte subsets and to determine whether levels were increased following activation in vitro. Levels of each CReg protein were similar on freshly isolated monocytes and all major lymphocyte subsets, except that CD4(+) cells expressed significantly less CD46 than CD8(+) cells (P < 0.05) while the reverse was observed for CD55 (P < 0.02). CD56(+) cells, predominantly natural killer cells, expressed significantly lower levels of CD59 than T cells (P < 0.02). CD45RO(+) cells had higher levels of surface CD46 and CD59, but lower levels of CD55, than CD45RO(-) cells (P < 0.02); CD25(+) cells also expressed significantly less CD55 than CD25(-) cells (P < 0.002). Neutrophils expressed higher levels of CD59, but lower levels of CD55, than monocytes. Following activation with phytohaemagglutinin, CD46 was up-regulated on all leucocyte subsets with the exception of CD56(+) cells. Both CD55 and CD59 were also markedly up-regulated on monocytes, and CD55 expression was greater on CD8(+) than CD4(+) cells following activation (P < 0.02). Lipopolysaccharide treatment did not significantly alter B-cell expression of CReg proteins whereas CD55 and CD59, but not CD46, were significantly up-regulated on monocytes (P < 0.02). These observations that CReg proteins are up-regulated on certain activated leucocyte subsets indicate that levels would be increased following immune responses in vivo. This could enhance both protection against local complement activation at inflammatory sites and also the immunoregulatory properties of these leucocytes.
Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. (1995)

The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified. We show here that in a central nervous system-derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa protein that regulates ligand binding to the low density lipoprotein receptor-related protein (LRP). Anti-LRP antibody also completely abolished the neurite-promoting effect of apoE3. Understanding isoform-specific cell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease pathogenesis.
Fine and Predictable Tuning of TALEN Gene Editing Targeting for Improved T Cell Adoptive Immunotherapy (2017)

Using a TALEN-mediated gene-editing approach, we have previously described a process for the large-scale manufacturing of "off-the-shelf" CAR T cells from third-party donor T cells by disrupting the gene encoding TCRα constant chain (TRAC). Taking advantage of a previously described strategy to control TALEN targeting based on the exclusion capacities of non-conventional RVDs, we have developed highly efficient and specific nucleases targeting a key T cell immune checkpoint, PD-1, to improve engineered CAR T cells' functionalities. Here, we demonstrate that this approach allows combined TRAC and PDCD1 TALEN processing at the desired locus while eliminating low-frequency off-site processing. Thus, by replacing few RVDs, we provide here an easy and rapid redesign of optimal TALEN combinations. We anticipate that this method can greatly benefit multiplex editing, which is of key importance especially for therapeutic applications where high editing efficiencies need to be associated with maximal specificity and safety.
Ion transport mechanisms in native human retinal pigment epithelium. (1992)

Electrophysiologic techniques were used to characterize the electrical properties and the ion transport mechanisms at the apical and basolateral membranes of the human retinal pigment epithelium (RPE). These experiments used fresh native tissue from adult donor and fetal eyes. In the upper range, adult donor RPE had an apical membrane resting potential (VA) of approximately equal to -60 mV and a transepithelial potential (TEP) and resistance (Rt) of 3.5 mV and 148 omega.cm2, respectively. The means were at least 50% of these values. In RPE from fetuses of gestational age 19-23 wk, VA was -56 +/- 4 mV, TEP was 2.2 +/- 1.5 mV, Rt was 206 +/- 151 omega.cm2, and the ratio of apical to basolateral resistance was 0.70 +/- 0.50 (mean +/- standard deviation; n = 15). The apical membrane of the adult donor and fetal RPE contains a large relative K+ conductance (TK > 0.3) that is barium blockable. In fetal RPE, there is evidence for separate K+ and Cl- conductive mechanisms at the basolateral membrane. However, the evidence for the Cl- conductance is indirect. The fetal RPE apical membrane, but not the basolateral membrane, contains a ouabain-sensitive mechanism that exhibits two distinct phases of apical depolarization. The first, rapid phase suggests that the pump is electrogenic. The apical membrane of fetal RPE contains a bumetanide-sensitive mechanism and a receptor activated by nanomolar amounts of epinephrine. In fetal RPE, step changes in apical [K+]o between 5 and 2 mmol/l produced a delayed basolateral membrane hyperpolarization that in situ generates the fast oscillation trough of the electroretinogram.
A Thermodynamic Scale for the .beta.-Sheet Forming Tendencies of the Amino Acids (1994)

The results of a study to measure the beta-sheet forming propensities of the 20 naturally occurring amino acids are presented. The protein host for these studies is the 56 amino acid B1 domain of staphylococcal IgG binding protein G [Fahnestock, S.R., Alexander, P., Nagle, J., & Filpula, D. (1986) J. Bacteriol. 167, 870-880]. This protein was selected because it exhibits a reversible two-state thermal denaturation transition and its structure is known at high resolution. A suitable guest position in the protein was identified, and its neighboring environment was modified to minimize the potential for artifactual interactions. All 20 amino acids were individually substituted at the guest site, and their effect on the protein's thermal stability was determined. NMR was used to verify the structural integrity of several of the proteins with different amino acid substitutions at the guest site. The results of these studies provide a thermodynamic scale for the relative beta-sheet forming propensities of the amino acids that shows a clear correlation with the beta-sheet preferences derived from statistical surveys of proteins of known structure.
Biosynthesis of Thiamin I: The Function of the thiE Gene Product (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of Thiamin I: The Function of the thiE Gene ProductAllyson D. Backstrom, R. Austin S. McMordie, and Tadhg P. BegleyCite this: J. Am. Chem. Soc. 1995, 117, 8, 2351–2352Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ja00113a025https://doi.org/10.1021/ja00113a025research-articleACS PublicationsRequest reuse permissionsArticle Views208Altmetric-Citations42LEARN 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
Relationship of active site topology to substrate specificity for cytochrome P450terp (CYP108). (1994)

Earlier studies have shown that the reactions of cytochrome P450 with arylhydrazines yield aryl-iron complexes, and that oxidative migration of the aryl groups to the pyrrole nitrogens of the heme provides information on the active site topology. Comparison of cytochromes P450terp (CYP108), P450cam (CYP101), and P450BM-3 (CYP102) by this method suggests that the active site of P450terp is effectively more sterically restricted than those of the other two enzymes and is primarily open above pyrrole ring D of the heme group. This experimental model of the P450terp active site differs from that deduced by x-ray crystallography, which shows that pyrrole ring C is also relatively open. The results suggest that aryl shifts can be used to probe conformations of the active site other than that trapped in the crystal state. Identification of the product formed from alpha-terpineol by P450terp shows that the enzyme exclusively hydroxylates the most sterically accessible, allylically activated position. The enzyme also oxidizes substituted thioanisoles and styrenes unrelated to alpha-terpineol to the corresponding sulfoxides and epoxides. In the case of 4-methylthioanisole and 4-methylstyrene, methyl hydroxylation competes effectively with sulfoxidation and epoxidation in the reaction catalyzed by P450terp but not those catalyzed by P450BM-3 or P450cam. Comparison of the stereoselectively of thioanisole sulfoxidation and styrene epoxidation by P450terp, P450cam, and P450BM-3 shows that P450terp is the most, and P450BM-3 the least, stereospecific. The stereospecificity of thioanisole sulfoxidation by P450terp depends on the electronic nature of the para-substituent and rises from an (R):(S) ratio of 20:80 for p-MeO to a value of < 01:99 for p-CN. The (R):(S) ratio for the epoxides produced by P450terp is approximately 90:10 for the two substituents investigated. Cytochromes P450cam and P450BM-3 are much less stereoselective. A model is suggested by the stereochemical and topological data for the binding of substrates in P450terp.
American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 (2009)

This document is the first update of the American College of Gastroenterology (ACG) colorectal cancer (CRC) screening recommendations since 2000. The CRC screening tests are now grouped into cancer prevention tests and cancer detection tests. Colonoscopy every 10 years, beginning at age 50, remains the preferred CRC screening strategy. It is recognized that colonoscopy is not available in every clinical setting because of economic limitations. It is also realized that not all eligible persons are willing to undergo colonoscopy for screening purposes. In these cases, patients should be offered an alternative CRC prevention test (flexible sigmoidoscopy every 5-10 years, or a computed tomography (CT) colonography every 5 years) or a cancer detection test (fecal immunochemical test for blood, FIT).
Plasmonic nanocavity arrays for enhanced efficiency in organic photovoltaic cells (2008)

We demonstrate enhanced power conversion efficiency in organic photovoltaic (OPV) cells incorporated into a plasmonic nanocavity array. The nanocavity array is formed between a patterned Ag anode and an unpatterned Al cathode. This structure leads to the confinement of optical energy and enhanced absorption in the OPV. Devices characterized under simulated solar illumination show a 3.2-fold increase in power conversion efficiency compared to OPVs with unpatterned Ag anodes. The observed enhancement is also reflected in the external quantum efficiency, and the spectral response is consistent with optical finite-difference time-domain simulations of the structure.
ANT-on-YARDS: FPGA/MPU hybrid architecture for telecommunication data processing (1998)

This paper presents a novel system architecture that combines tightly coupled field programmable gate arrays (FPGA's) and a microprocessing unit (MPU) that we have developed. This system architecture comprises three main programmable devices which yield high flexibility. These devices are a reduced instruction set computer (RISC)-type MPU with memories, programmable interconnection devices, and FPGA's. This system supports various styles of coupling between the FPGA's and the MPU which makes several data processing operations more effective. Furthermore, we indicate the most suitable applications for the system. They are telecommunication data processes involving complex protocol operations and network control algorithms. In this paper, two applications of the system are given. One is for operation, administration, and management (OAM) cell processing on an asynchronous transfer mode (ATM) network. The other is a dynamic remote reconfiguration protocol that enables the functions of the transport data processing system to be updated or changed on-line.
Recent Advances in Glycosylation Modifications in the Context of Therapeutic Glycoproteins (2012)

Glycosylation is one of the most complex post-translation modifications, commonly found in many cell surface and secreted eukaryotic proteins. 1-2% of the human transcriptome encodes proteins that link to glycosylation. Many protein-based biotherapeutics approved or in clinical trials are glycoproteins. The oligosaccharides covalently attached to therapeutic glycoproteins pose biological benefits as well as manufacturing challenges. The present chapter reviews the structure and function of glycosylation, glycoform patterns observed for the biotherapeutic proteins produced by various host systems, and analytic methods for the characterization of glycoforms. Recent advances in utilizing glycosylation as a strategy to improve biotherapeutics properties are also discussed.
Exertional Collapse and Sudden Death Associated with Sickle Cell Trait (1996)

The most serious complication of sickle cell trait (SCT) is sudden death during exertion. SCT often remains unrecognized in the 2.5 million African Americans affected. Exertional collapse and sudden death associated with SCT is characterized by rhabdomyolysis, heat stroke, and cardiac arrhythmia. There is a 40-fold increased risk of sudden death in affected soldiers during military basic training and there are many cases reported in athletes during preseason training. There have been no cases reported in soldiers beyond basic training. In the case presented, a soldier with 3 years of military service succumbed to SCT-associated sudden death during physical fitness testing.
The effect of plasma transfusion on morbidity and mortality: a systematic review and meta‐analysis (2010)

Very-low-quality evidence suggests that plasma infusion in the setting of massive transfusion for trauma patients may be associated with a reduction in the risk of death and multiorgan failure. A survival benefit was not demonstrated in most other transfusion populations.
Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors (2001)

These data suggest that the expression of survivin may be upregulated during an early step of tumorigenesis and during the development of cancer by reducing the cancer cell apoptosis.
Ultraviolet B but not Ultraviolet A Radiation Initiates Melanoma (2004)

Cutaneous malignant melanoma is one of the fastest increasing cancers with an incidence that has more than doubled in the last 25 years. Sunlight exposure is strongly implicated in the etiology of cutaneous malignant melanoma and the UV portion of the sunlight spectrum is considered responsible. Data are, however, conflicting on the roles of ultraviolet B [UVB; 280-320 nanometers (nm)] and ultraviolet A (UVA; 320-400 nm), which differ in their ability to initiate DNA damage, cell signaling pathways and immune alterations. To address this issue, we have used specialized optical sources, emitting isolated or combined UVB or UVA wavebands or solar simulating radiation, together with our hepatocyte growth factor/scatter factor-transgenic mouse model of UV-induced melanoma that uniquely recapitulates human disease. Only UVB-containing sources initiated melanoma. These were the isolated UVB waveband (>96% 280-320 nm), the unfiltered F40 sunlamp (250-800 nm) and the solar simulator (290-800 nm). Kaplan-Meier survival analysis indicated that the isolated UVB waveband was more effective in initiating melanoma than either the F40 sunlamp or the solar simulator (modified log rank P < 0.02). The latter two sources showed similar melanoma effectiveness (P = 0.38). In contrast, transgenic mice irradiated with either the isolated UVA waveband (>99.9% 320-400 nm, 150 kJ/m2), or an F40 sunlamp filtered to remove > 96% of the UVB, responded like unirradiated control animals. We conclude that, within the constraints of this animal model, UVB is responsible for the induction of mammalian cutaneous malignant melanoma whereas UVA is ineffective even at doses considered physiologically relevant. This finding may have major implications with respect both to risk assessment from exposure to solar and artificial UVB, and to development of effective protection strategies against melanoma induction by UVB. Moreover, these differences in wavelength effectiveness can now be exploited to identify UV pathways relevant to melanomagenesis.
High‐molecular‐weight Fibronectin Synthesized by Adenoid Cystic Carcinoma Cells of Salivary Gland Origin (1999)

To understand the morphogenesis of characteristic cribriform structures and the frequent invasion of salivary adenoid cystic carcinomas (ACC) along such basement membrane-rich structures as peripheral nerves, we have isolated fibronectin (FN) from the culture media of ACC3 cells established from a parotid ACC and characterized its glycosylation and alternative splicing status. FN isolated from ACC3 cells (ACC-FN) showed a molecular mass of 315 kDa in SDS-PAGE and was less heterogeneous and larger than plasma FN (pFN) or FNs from other cell sources. Differential enzymatic treatments of immunoprecipitated ACC-FN with neuraminidase, peptide-N-glycosidase F and endo-alpha-N-acetylgalactosaminidase revealed that ACC-FN was composed of a polypeptide chain of 270 kDa, with 10 kDa each of N-linked and O-linked oligosaccharide chains. Reverse transcription polymerase chain reaction (RT-PCR), in-situ hybridization, and immunofluorescence studies showed that most ACC-FNs contained ED-A, ED-B and IIICS regions in the molecules. This alternative splicing status of ACC-FN seemed to contribute to its less heterogeneous and larger molecular form. Cell attachment assay demonstrated that ACC-FN was more potent than pFN in adhesion of ACC3 cells. The results indicated that ACC-FN may function as a substrate for attachment of ACC3 cells, or that ACC3 cells trap and retain ACC-FN in their pericellular space. This isoform of FN may play an important role in the mode of invasion of ACC and the formation of stromal pseudocysts in the characteristic cribriform structure of ACC.
Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1 (2006)

The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in response to activation of the MAPK (mitogen-activated protein kinase) pathways. This phosphorylation triggers a series of molecular events that convert Elk-1 from a transcriptionally silent state into a highly active state and then back to a basal level. At the same time, activation of the ERK (extracellular-signal-regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO (small ubiquitin-related modifier). As SUMO imparts repressive properties on Elk-1, ERK-mediated SUMO loss leads to de-repression at the same time as the ERK pathway promotes activation of Elk-1. Thus a two-step mechanism is employed to convert Elk-1 into its fully activated state. Here, the molecular events underlying these changes in Elk-1 status, and the role of PIASxalpha [protein inhibitor of activated STAT (signal transducer and activator of transcription) xalpha] as a co-activator that facilitates this process, are discussed.
Molecular cloning and DNA sequencing of the Escherichia coli K-12 ald gene encoding aldehyde dehydrogenase (1991)

The gene ald, encoding aldehyde dehydrogenase, has been cloned from a genomic library of Escherichia coli K-12 constructed with plasmid pBR322 by complementing an aldehyde dehydrogenase-deficient mutant. The ald region was sequenced, and a single open reading frame of 479 codons specifying the subunit of the aldehyde dehydrogenase enzyme complex was identified. Determination of the N-terminal amino acid sequence of the enzyme protein unambiguously established the identity and the start codon of the ald gene. Analysis of the 5'- and 3'-flanking sequences indicated that the ald gene is an operon. The deduced amino acid sequence of the ald gene displayed homology with sequences of several aldehyde dehydrogenases of eukaryotic origin but not with microbial glyceraldehyde-3-phosphate dehydrogenase.