gebhart/patrepeval huggingface dataset:
Pigment content of cultured human melanocytes does not correlate with tyrosinase message level (1991)

Tyrosinase is considered to be the rate-limiting enzyme for the biosynthesis of melanin in epidermal melanocytes, and thus tyrosinase activity is thought to be a major regulatory step in melanogenesis. To determine whether the rate of pigment production was controlled at the level of tyrosinase gene expression, we developed a culture system capable of generating large populations of pure human melanocytes and then measured both melanin content as determined spectrophotometrically by absorption at 475 nm and mRNA levels as detected by hybridization with cloned cDNA Pmel 34, encoding human tyrosinase. We examined the relationship between pigment content and tyrosinase mRNA levels among human melanoma and melanocyte lines with very different levels of basal pigmentation; between two clones of a single human melanoma line, one pigmented and one amelanotic; and sequentially in melanocytes before and after simulation with isobutylmethylxanthine to increase melanin content per cell. Using Northern blot analysis and in-situ hybridization we found no correlation between tyrosinase message levels and melanin content, suggesting that posttranscriptional regulation of tyrosinase and/or other events determine the rate of pigment synthesis in human melanocytes.
Aluminum Is Put on Trial as a Vaccine Booster (2000)

PUBLIC HEALTHSAN JUAN, PUERTO RICO-- Complaints about vaccine safety and debate over a mysterious muscle ailment have prompted researchers to take a fresh look at the use of aluminum adjuvants, which are used to cause the immune system to react earlier, more potently, and more persistently to the antigen contained in the vaccine. This month, as some 70 scientists gathered here for 2 days of often vigorous discussion of the findings about the muscle ailment, a larger question hung over the gathering: Will aluminum be the next battleground in the vaccine wars?
Innovation through Collaborative Partnerships: Creating the MSN News for iPad App at VanceInfo Technologies (2013)

This teaching case focuses on a collaborative project between a major software and services outsourcing company in China (VanceInfo Technologies) and one of its major Western clients (Microsoft Inc.). VanceInfo and Microsoft had been engaged in a long-term client/vendor relationship since 1997 and the project had been the result of this long-term partnership arrangement. The project was deemed quite successful and innovative; hence it provided an opportunity to determine how collaborative innovation could work between two remote and culturally different supply chain partners and how the lessons from this project could be used to inform SSO providers of ways in which they could move up the value chain to more client-focused value added services. The case looks in-depth at the actual working practices that enabled the distributed Microsoft/VanceInfo team to produce a market-led innovative product. Agile methods were highly integral to the functioning of those work practices and are quite carefully scrutinised from the point of view of how they were adapted for use in a distributed, cross-cultural environment. Users of the case study will be asked to formulate answers to several questions geared towards providing general guidelines that SSO providers can follow to achieve similar successful outcomes.
Impact of Immune Complex Size and Glycosylation on IgG Binding to Human FcγRs (2013)

IgG molecules are widely used as therapeutic agents either in the form of intact Abs or as Fc fusion proteins. Although efficient binding of the IgG Fc fragment to cellular FcγRs may be essential to achieve a high cytolytic activity, it may be advantageous for other applications to limit or abolish this interaction. Genetic or biochemical approaches have been used to generate these non-FcγR-binding IgG variants. By using soluble versions of FcγRs and monomeric versions of these altered IgG molecules, it was demonstrated that these IgG variants no longer bind to FcγRs. Importantly, however, these assays do not reflect the physiologic interaction of IgG with low-affinity cellular FcγRs occurring in the form of multimeric immune complexes. In this study, we investigated how the size of an immune complex can affect the interaction of normal and various versions of potentially non-FcγR-binding IgG variants with cellular FcγRs. We show that neither the D265A mutation nor EndoS treatment resulting in IgG molecules with only one N-acetylglucosamine and a fucose residue was fully able to abolish the interaction of all IgG subclasses with cellular FcγRs, suggesting that IgG subclass-specific strategies are essential to fully interfere with human FcγR binding.
Junctional Adhesion Molecule, a Novel Member of the Immunoglobulin Superfamily That Distributes at Intercellular Junctions and Modulates Monocyte Transmigration (1998)

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.
Topographical control of cell behaviour: II. multiple grooved substrata (1990)

Electronics miniaturization techniques have been used to fabricate substrata to study contact guidance of cells. Topographical guidance of three cell types (BHK, MDCK and chick embryo cerebral neurones) was examined on grooved substrata of varying dimensions (4-24 microns repeat, 0.2-1.9 microns depth). Alignment to within 10 degrees of groove direction was used as our criterion for guidance. It was found that repeat spacing had a small effect (alignment is inversely proportional to spacing) but that groove depth proved to be much more important in determining cell alignment, which increased with depth. Measurements of cell alignment and examination by scanning electron microscopy showed that BHK cells and MDCK cells interacted differently with grooved substrata, and also that the response of MDCK cells depended on whether or not the cells were isolated or part of an epithelial cell island. Guidance by a multiple topographical cue is greater than could be predicted from cells' reactions to a single cue (Clark et al. Development 99: 439-448, 1987). Substratum topography is considered to be an important cue in many developmental processes. Cellular properties such as cytoskeletal organisation, cell adhesion and the interaction with other cells are discussed as being factors determining a cells susceptibility to topography.
Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity (2010)

As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.
Monitoring the Trafficking of Adoptively Transferred Antigen- Specific CD8-Positive T Cells In Vivo , Using Noninvasive Luminescence Imaging (2007)

Understanding of the trafficking of antigen-specific CD8(+) T cells in vivo will provide insight about how our immune system controls infectious diseases and cancers. In the current study we used a luciferase-expressing human papillomavirus type 16 (HPV-16) E7-specific CD8(+) T cell for adoptive transfer to control E7-expressing TC-1 tumor cells. We used noninvasive luminescence imaging to monitor the trafficking of E7-specific CD8(+) T cells over time. We also boosted the luciferase-expressing E7-specific CD8(+) T cells in vivo, using E7-expressing vaccinia. We found that injected E7-specific T cells preferentially migrated to the E7-expressing tumor site but not to the E7-negative control tumor site, and increased in number at the tumor site over time. In addition, vaccination with E7-expressing vaccinia led to a significant increase in the number of E7-specific CD8(+) T cells at the tumor site, resulting in a significant antitumor effect compared with vaccination with wild-type vaccinia. Thus, our data suggest that the antitumor effects generated by adoptive transfer of E7-specific CD8(+) T cells can be significantly enhanced by vaccination with E7-expressing vaccinia and that our system represents a plausible approach to investigate the trafficking and biology of antigen-specific T cells in vivo.
Cationic surfactants : physical chemistry (1990)

Focusing on the solution physical chemistry and surface properties of cationic surfactants, three major sections examine the properties of cationic surfactants themselves both in solution and at interfaces, the interactions of cationic surfactants with other materials, and applications of cationic s
Human TCR That Incorporate CD3ζ Induce Highly Preferred Pairing between TCRα and β Chains following Gene Transfer (2008)

TCR gene therapy is adversely affected by newly formed TCRalphabeta heterodimers comprising exogenous and endogenous TCR chains that dilute expression of transgenic TCRalphabeta dimers and are potentially self-reactive. We have addressed TCR mispairing by using a modified two-chain TCR that encompasses total human CD3zeta with specificities for three different Ags. Transfer of either TCRalpha:CD3zeta or beta:CD3zeta genes alone does not result in surface expression, whereas transfer of both modified TCR chains results in high surface expression, binding of peptide-MHC complexes and Ag-specific T cell functions. Genetic introduction of TCRalphabeta:zeta does not compromise surface expression and functions of an endogenous TCRalphabeta. Flow cytometry fluorescence resonance energy transfer and biochemical analyses demonstrate that TCRalphabeta:CD3zeta is the first strategy that results in highly preferred pairing between CD3zeta-modified TCRalpha and beta chains as well as absence of TCR mispairing between TCR:CD3zeta and nonmodified TCR chains. Intracellular assembly and surface expression of TCR:CD3zeta chains is independent of endogenous CD3gamma, delta, and epsilon. Taken together, our data support the use of TCRalphabeta:CD3zeta to prevent TCR mispairing, which may provide an adequate strategy to enhance efficacy and safety of TCR gene transfer.
Construction of an Excisable Bacterial Artificial Chromosome Containing a Full-Length Infectious Clone of Herpes Simplex Virus Type 1: Viruses Reconstituted from the Clone Exhibit Wild-Type Properties In Vitro and In Vivo (2002)

In recent years, several laboratories have reported on the cloning of herpes simplex virus type 1 (HSV-1) genomes as bacterial artificial chromosomes (BACs) in Escherichia coli and on procedures to manipulate these genomes by using the bacterial recombination machinery. However, the HSV-BACs reported so far are either replication incompetent or infectious, with a deletion of one or more viral genes due to the BAC vector insertion. For use as a multipurpose clone in research on HSV-1, we attempted to generate infectious HSV-BACs containing the full genome of HSV-1 without any loss of viral genes. Our results were as follows. (i) E. coli (YEbac102) harboring the full-length HSV-1 genome (pYEbac102) in which a BAC flanked by loxP sites was inserted into the intergenic region between U(L)3 and U(L)4 was constructed. (ii) pYEbac102 was an infectious molecular clone, given that its transfection into rabbit skin cells resulted in production of infectious virus (YK304). (iii) The BAC vector sequence was almost perfectly excisable from the genome of the reconstituted virus YK304 by coinfection of Vero cells with YK304 and a recombinant adenovirus, AxCANCre, expressing Cre recombinase. (iv) As far as was examined, the reconstituted viruses from pYEbac102 could not be phenotypically differentiated from wild-type viruses in vitro and in vivo. Thus, the viruses grew as well in Vero cells as did the wild-type virus and exhibited wild-type virulence in mice on intracerebral inoculation. (v) The infectious molecular clone pYEbac102 is in fact useful for mutagenesis of the HSV-1 genome by bacterial genetics, and a recombinant virus carrying amino acid substitutions in both copies of the alpha0 gene was generated. pYEbac102 will have multiple applications to the rapid generation of genetically engineered HSV-1 recombinants in basic research into HSV-1 and in the development of HSV vectors in human therapy.
Aortic Dissection: New Frontiers in Diagnosis and Management (2003)

C ardiovascular disease is the leading cause of death in most Western societies and is increasing steadily in many developing countries. Aortic diseases constitute an emerging share of the burden. New diagnostic imaging modalities, longer life expectancy in general, longer exposure to elevated blood pressure, and the proliferation of modern noninvasive imaging modalities have all contributed to the growing awareness of acute and chronic aortic syndromes. ] Both parts may help to better integrate the complexities of acute aortic syndromes.
The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival (2015)

study question: What is the role of microRNA-451 (miR-451) in human endometriotic tissue? summary answer: miR451 expression was elevated in endometriotic lesion tissue. MiR451 modulated the expression of macrophage migration inhibitory factor and limited cell survival.
Role of a highly conserved YPITP motif in 2‐oxoacid:ferredoxin oxidoreductase. (2001)

2-Oxoacid:ferredoxin oxidoreductase from Sulfolobus sp. strain 7, an aerobic and thermoacidophilic crenoarchaeon, catalyses the coenzyme A-dependent oxidative decarboxylation of pyruvate and 2-oxoglutarate, a cognate Zn-7Fe-ferredoxin serving as an electron acceptor. It comprises two subunits, a (632 amino acids) and b (305 amino acids). To further elucidate its structure and function, we constructed a gene expression system. The wild-type recombinant enzyme was indistinguishable from the natural one in every criterion investigated. A series of variants was constructed to elucidate the role of the YPITP-motif (residues 253-257) in subunit a, which is conserved universally in the 2-oxoacid:ferredoxin oxidoreductase (OFOR) family. Single amino-acid replacements at Y253 and P257 by other amino acids caused a drastic loss of enzyme activity. T256, the hydroxyl group of which has been proposed to be essential for binding of the 2-oxo group of the substrate in the Desulfovibrio africanus enzyme, was unexpectedly replaceable with Ala, the kcat and Km for 2-oxoglutarate being approximately 33% and approximately 51%, respectively, as compared with that of the wild-type enzyme. Replacement at other positions resulted in a significant decrease in the kcat of the reaction while the Km for 2-oxoacid was only slightly affected. Thus, the YPITP-motif is essential for the turnover of the reaction rather than the affinity toward 2-oxoacid.
A reliable plasma marker of platelet activation: Does it exist? (2002)

Despite the clear importance of the platelet in various conditions and diseases, there are few opportunities to assess the physiological and pathological functions of this cell. Those without access to a flow cytometer or platelet aggregometer rely on secreted or release products of the platelet. Principle among these molecules are alpha granule components beta thromboglobulin and platelet factor four, and membrane constituents such as P selectin, gpV and glycocalicin. However, notwithstanding the ease of measurement of these markers (i.e., by ELISA) each one has its own particular disadvantage, mostly of methodology and specificity. Nevertheless, if our goal is to improve our ability to recognize and treat subjects with thrombotic disorders, then additional studies on these molecules may prove to be a sound investment.
Biosynthesis of Sphingolipid Bases (1968)

Abstract In the presence of TPNH, particulate cell-free preparations from Hansenula ciferri convert palmityl coenzyme A and serine-14C to labeled dihydrosphingosine and sphingosine. Both the free bases and their dinitrophenyl derivatives migrated identically with authentic standards on thin layer chromatograms. The identity of sphingosine, not previously reported as a biosynthetic product in yeast, was further confirmed by its catalytic reduction to dihydrosphingosine and by recrystallization of its triacetyl derivative to constant specific radioactivity in the presence of unlabeled authentic carrier. Both the biosynthetic sphingosine and dihydrosphingosine have the erythro configuration. In the absence of added TPNH, no sphingosine or dihydrosphingosine is formed by this system. Instead, two less stable, labeled compounds are formed, (a) 2-amino-1-hydroxyoctadecan-3-one (3-ketodihydrosphingosine), and (b) a compound which may be the 3-keto analogue of sphingosine. These intermediates are converted either enzymatically in the presence of TPNH or nonenzymatically with sodium borohydride to dihydrosphingosine and sphingosine. The most prominent labeled component of the mixture on acetylation chromatographs identically with authentic N-acetyl-3-ketodihydrosphingosine. Like the pyridoxal-P-dependent over-all reaction leading to dihydrosphingosine (1), formation of the labile intermediate, but not its reduction to dihydrosphingosine, is inhibited by cysteine. On the basis of these experiments, synthesis of dihydrosphingosine appears to proceed by a pyridoxal-P-dependent condensation of palmityl-CoA with serine to yield 3-ketodihydrosphingosine. TPNH-dependent reduction of this 3-keto intermediate then leads to dihydrosphingosine. The origin of other sphingolipid bases is discussed. 2-Hexadecenoate, but not α-hydroxypalmitate, replaces palmitate as a substrate in this crude cell-free system, but does not change the distribution of products. Phytosphingosine, the major sphingolipid base excreted by the growing yeast, is not formed in the cell-free system.
MicroRNA: an Emerging Therapeutic Target and Intervention Tool (2008)

MicroRNAs (miRNAs) are a class of short non-coding RNAs with posttranscriptional regulatory functions. To date, more than 600 human miRNAs have been experimentally identified, and estimated to regulate more than one third of cellular messenger RNAs. Accumulating evidence has linked the dysregulated expression patterns of miRNAs to a variety of diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases and viral infections. MiRNAs provide its particular layer of network for gene regulation, thus possessing the great potential both as a novel class of therapeutic targets and as a powerful intervention tool. In this regard, synthetic RNAs that contain the binding sites of miRNA have been shown to work as a "decoy" or "miRNA sponge" to inhibit the function of specific miRNAs. On the other hand, miRNA expression vectors have been used to restore or overexpress specific miRNAs to achieve a long-term effect. Further, double-stranded miRNA mimetics for transient replacement have been experimentally validated. Endogenous precursor miRNAs have also been used as scaffolds for the induction of RNA interference. This article reviews the recent progress on this emerging technology as a powerful tool for gene regulation studies and particularly as a rationale strategy for design of therapeutics.
[Structure of eremosamine--an amino sugar from the antibiotic eremomycin]. (1988)

A new amino sugar named eremosamine was isolated from hydrolysate of eremomycin, an antibiotic belonging to the group of polycyclic glycopeptides. Crystalline derivatives of the amino sugar i. e. methyleremosaminide and methyl-N,O-acetyleremosaminide (alpha- and beta-anomers) were prepared. The data on PMR study and optic properties of the compounds showed that eremosamine had the structure of 2,3,6-tridesoxy-3-amino-3-C-methyl-L-arabinohexose.
Simulation and analysis of a high-efficiency silicon optoelectronic modulator based on a Bragg mirror (2001)

We describe the operating principle of a silicon optoelectronic modulator based on the plasma dispersion effect used in conjunction with a distributed Bragg reflector, which converts the phase shift, in- duced by the free carriers injected by a P-i-N diode, into variations of its reflectivity. The device is integrated in a low-loss silicon-on-insulator waveguide. Two different approaches in the driving schemes are pro- posed. Moreover, we show how it is possible to reach a theoretical 100% modulation depth by exploiting in a concurrent way both the variations of the refractive index and the increased optical absorption. An exhaustive description of the optical structure and its guiding properties, together with the analysis of the electrical behavior of the modulator, is given. Finally, a comparison with other interferometric structures is analyzed, and it is shown how this kind of modulator exhibits satisfactory charac- teristics in terms of dissipated power and reduced occupation of area on a chip. © 2001 Society of Photo-Optical Instrumentation Engineers.