gebhart/patrepeval huggingface dataset:
Rationally designed fluorogenic protease reporter visualizes spatiotemporal dynamics of apoptosis in vivo (2015)

Fluorescence resonance energy transfer-based reporters have been widely used in imaging cell signaling; however, their in vivo application has been handicapped because of poor signal. Although fluorogenic reporters overcome this problem, no such reporter of proteases has been demonstrated for in vivo imaging. Now we have redesigned an infrared fluorescent protein so that its chromophore incorporation is regulated by protease activity. Upon protease activation, the infrared fluorogenic protease reporter becomes fluorescent with no requirement of exogenous cofactor. To demonstrate biological applications, we have designed an infrared fluorogenic executioner-caspase reporter, which reveals spatiotemporal coordination between cell apoptosis and embryonic morphogenesis, as well as dynamics of apoptosis during tumorigenesis in Drosophila. The designed scaffold may be used to engineer reporters of other proteases with specific cleavage sequence.
Structures of the oligosaccharides present at the three asparagine-linked glycosylation sites of human IgD. (1983)

The complete amino acid sequence of the human myeloma IgD:WAH has been determined and the sites of asparagine glycosylation identified as residues 354, 445, and 496 (Takahashi, N., Tetaert, D., Debuiere, B., Lin, L.-C., and Putnam, F. W. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 2850-2854). We have determined the structures of the oligosaccharides at each of these positions. Asn 354 bears oligosaccharides exclusively of the high mannose type containing from 5 to 9 mannose residues. Twenty per cent of the oligosaccharides at this site contain 1 glucose residue at the terminus of the branch emanating from the alpha 1 leads to 3-linked core mannose which is believed to reflect incomplete processing of the triglucosyl-high mannose oligosaccharide intermediate following transfer from dolichol to nascent peptide. Asn 445 and Asn 496 bear exclusively dibranched complex oligosaccharide structures; 30-40% of these molecules contain a bisecting GlcNAc-linked beta 1 leads to 4 to the innermost core mannose residue. At Asn 445, 40% of both the bisected and nonbisected oligosaccharides contain 1 residue of fucose on the Asn-linked GlcNAc and 50% bear a single N-acetylneuraminic acid residue. The oligosaccharides at Asn 496 are devoid of sialic acid and fucose. Thus, IgD:WAH is notable for the presence of virtually unprocessed oligosaccharide structures (glucosylated high mannose) on the same peptide backbone as extensively processed complex type molecules. The finding that each of the 3 Asn glycosylation sites of IgD:WAH bears either exclusively a complex or a high mannose type oligosaccharide indicates that there is considerable specificity in the glycosylation process. These oligosaccharides, nonetheless, display extensive microheterogeneity at each location.
Localization of the labile disulfide bond between SU and TM of the murine leukemia virus envelope protein complex to a highly conserved CWLC motif in SU that resembles the active-site sequence of thiol-disulfide exchange enzymes (1997)

Previous studies have indicated that the surface (SU) and transmembrane (TM) subunits of the envelope protein (Env) of murine leukemia viruses (MuLVs) are joined by a labile disulfide bond that can be stabilized by treatment of virions with thiol-specific reagents. In the present study this observation was extended to the Envs of additional classes of MuLV, and the cysteines of SU involved in this linkage were mapped by proteolytic fragmentation analyses to the CWLC sequence present at the beginning of the C-terminal domain of SU. This sequence is highly conserved across a broad range of distantly related retroviruses and resembles the CXXC motif present at the active site of thiol-disulfide exchange enzymes. A model is proposed in which rearrangements of the SU-TM intersubunit disulfide linkage, mediated by the CWLC sequence, play roles in the assembly and function of the Env complex.
The Ischemic Penumbra: A New Opportunity for Neuroprotection (2006)

The development of acute stroke therapies has yielded only limited success and many failures in multiple clinical trials. The target of acute stroke therapy is that portion of the ischemic region that is still potentially salvageable, i.e. the ischemic penumbra. Neuroprotective drugs have the potential to prevent a portion of the ischemic penumbra from evolving into infracted tissue and designing trials that target neuroprotective drugs at patients with persistent penumbra should enhance the likelihood of a positive outcome. Currently, diffusion and perfusion MRI has the potential to approximate the location and persistence of the ischemic penumbra and can be used in clinical trials to select appropriate patients for inclusion and to evaluate a meaningful treatment effect. Perfusion CT may also have similar capabilities. Use of these imaging modalities in clinical trials and ultimately in clinical practice will likely help in the development and utilization of novel neuroprotective drugs.
Appraisal of anti-idiotypic antibodies in the treatment of solid tumors in humans. (1992)

Anti-idiotypic antibodies may be valuable in the induction of antitumor immunity in two ways--they can serve as a ready source of antigen when the appropriate TAA is difficult or impossible to purify. More importantly, regulatory anti-idiotypic antibodies can activate specific T-helper cells, bringing all the components of cellular immunity to bear on neoplastic process. Although the results in studies in animals have demonstrated resistance to tumor challenge after immunization with anti-idiotypic antibodies, studies of humans with advanced malignancies have failed to produce substantial clinical results. Nevertheless, immunization with anti-idiotypic antibodies has influenced some tumors. These studies represent important, initial steps toward understanding the immune network and modulating it in favor of the host, against human tumors. As a continued understanding of the immune network evolves and strategies for activating and suppressing specific immune responses are developed, it should be possible to design vaccines for specific uses. Although current anti-idiotypic vaccines do not seem promising for the treatment of established solid tumors in humans, we can look with anticipation to studies of polyvalent vaccines for the prevention of carcinoma in high risk groups.
Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain. (1992)

We have analyzed the in vitro phosphorylation of tau protein by Ca2+/calmodulin-dependent protein kinase, casein kinase II, and proline-directed serine/threonine protein kinase. These kinases phosphorylate tau protein in sites localized in different regions of the molecule, as determined by peptide mapping analyses. Focusing on the phosphorylation of tau by protein kinase C, it was calculated as an incorporation of 4 mol of phosphate/mol of tau. Limited proteolysis assays suggest that the phosphorylation sites could be located within the tubulin-binding domain. Direct phosphorylation of synthetic peptides corresponding to the cysteine-containing tubulin-binding region present in both fetal and adult tau isoforms demonstrates that serine 313 is modified by protein kinase C. Phosphorylation of the synthetic peptide by protein kinase C diminishes its binding to tubulin, as compared with the unphosphorylated peptide.
Testosterone supplementation improves spatial and verbal memory in healthy older men (2001)

The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.
Efficient computations of encodings for quantum error correction (1997)

We show how, given any set of generators of the stabilizer of a quantum code, an efficient gate array that computes the code words can be explicitly constructed. For an $n$-qubit code whose stabilizer has $d$ generators, the resulting gate array consists of $O(\mathrm{nd})$ operations, and converts $k$-qubit data (where $k=n\ensuremath{-}d)$ into $n$-qubit code words.
Rules for Making Human Tumor Cells (2002)

The apparent complexity of the genetic, biochemical, and physiological changes in cancer cells threatens to stall the elucidation of the origins of cancer and the development of new treatments for malignant diseases. The authors propose a considerably simplified scheme in which only five alterations are required to transform cells from a normal to a malignant phenotype.
Cyclic AMP- and Cyclic GMP-dependent Protein Kinases Differ in Their Regulation of Cyclic AMP Response Element-dependent Gene Transcription (1999)

The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs). Although both the type Ibeta cGMP-dependent protein kinase (cGKIbeta) and the type II cAMP-dependent protein kinase (cAKII) phosphorylated the cytoplasmic substrate VASP (vasodilator- and A kinase-stimulated phosphoprotein) to a similar extent, cyclic nucleotide regulation of CRE-dependent transcription was at least 10-fold higher in cAKII-transfected cells than in cGKIbeta-transfected cells. Overexpression of each kinase in mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme. As reported previously, the catalytic (C) subunit of cAKII translocated to the nucleus following activation by 8-bromo-cyclic AMP. However, cGKIbeta did not translocate to the nucleus upon activation by 8-bromo-cyclic GMP. Replacement of an autophosphorylated serine (Ser79) of cGKIbeta with an aspartic acid resulted in a mutant kinase with constitutive kinase activity in vitro and in vivo. The cGKIbetaS79D mutant localized to the cytoplasm and was only a weak activator of CRE-dependent gene transcription. However, an amino-terminal deletion mutant of cGKIbeta was found in the nucleus as well as the cytoplasm and was a strong activator of CRE-dependent gene transcription. These data suggest that the inability of cGKs to translocate to the nucleus is responsible for the differential ability of cAKs and cGKs to activate CRE-dependent gene transcription and that nuclear redistribution of cGKs is not required for NO/cGMP regulation of gene transcription.
Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. (1986)

There is a great need for substances that can act as adjuvants on local mucosal immune responses to perorally (p.o.) administered immunogens and which could be included in future oral vaccines. In this study we show that in mice cholera toxin (CT) is a potent adjuvant on enteric mucosal immune responses to related (cholera B subunit) as well as unrelated (KLH) antigens presented by the p.o. route. The adjuvant action of CT was dose-dependent and was achieved only when CT was given p.o. and together with the antigen. Both priming (memory induction) and boosting of the gut mucosal immune system by the oral route were greatly potentiated by CT. High numbers of specific antibody-producing cells as well as substantial mucosal memory in the lamina propria were stimulated by p.o. priming immunizations if CT adjuvant was included. Anamnestic responses could be elicited by a single p.o. booster immunization for at least 10 weeks and probably much longer. The adjuvant action of CT is suggested to involve activation of adenylate cyclase and cyclic AMP-mediated signals with differential effects on B and regulatory T intestinal lymphocytes. The adjuvant-active dose of CT, 100-500 ng, was lower than the immunogenic dose (2 micrograms) and much below the p.o. dose needed for detectable net fluid secretion in mouse intestine (5-10 micrograms). Cholera B subunit (10 micrograms) administered p.o. together with 500 ng of CT was 50 times more effective in stimulating gut mucosal anti-toxin responses compared with B subunit vaccine alone. Our results suggest that CT or substances that use similar adjuvant mechanisms may substantially increase the mucosal immunogenicity and efficacy of non-replicating oral vaccines.
Nucleophilic substitutions of unactivated vinyl halides with alkanethiolate anions in hexamethylphosphoramide (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleophilic substitutions of unactivated vinyl halides with alkanethiolate anions in hexamethylphosphoramideMarcello Tiecco, Lorenzo Testaferri, Marco Tingoli, Donatella Chianelli, and Mauela MontanucciCite this: J. Org. Chem. 1983, 48, 25, 4795–4800Publication Date (Print):December 1, 1983Publication History Published online1 May 2002Published inissue 1 December 1983https://pubs.acs.org/doi/10.1021/jo00173a003https://doi.org/10.1021/jo00173a003research-articleACS PublicationsRequest reuse permissionsArticle Views902Altmetric-Citations41LEARN 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
Hole Compensation Mechanism of P-Type GaN Films (1992)

Low-resistivity p-type GaN films, which were obtained by N 2 -ambient thermal annealing or low-energy electron-beam irradiation (LEEBI) treatment, showed a resistivity as high as 1×10 6 Ω·cm after NH 3 -ambient thermal annealing at temperatures above 600°C. In the case of N 2 -ambient thermal annealing at temperatures between room temperature and 1000°C, the low-resistivity p-type GaN films showed no change in resistivity, which was almost constant between 2 Ω·cm and 8 Ω·cm. These results indicate that atomic hydrogen produced by NH 3 dissociation at temperatures above 400°C is related to the hole compensation mechanism. A hydrogenation process whereby acceptor-H neutral complexes are formed in p-type GaN films was proposed. The formation of acceptor-H neutral complexes causes hole compensation, and deep-level and weak blue emissions in photoluminescence.
Structural and Biochemical Characterization of the Wild Type PCSK9-EGF(AB) Complex and Natural Familial Hypercholesterolemia Mutants (2008)

PCSK9 regulates low density lipoprotein receptor (LDLR) levels and consequently is a target for the prevention of atherosclerosis and coronary heart disease. Here we studied the interaction, of LDLR EGF(A/AB) repeats with PCSK9. We show that PCSK9 binds the EGF(AB) repeats in a pH-dependent manner. Although the PCSK9 C-terminal domain is not involved in LDLR binding, PCSK9 autocleavage is required. Moreover, we report the x-ray structure of the PCSK9DeltaC-EGF(AB) complex at neutral pH. Compared with the low pH PCSK9-EGF(A) structure, the new structure revealed rearrangement of the EGF(A) His-306 side chain and disruption of the salt bridge with PCSK9 Asp-374, thus suggesting the basis for enhanced interaction at low pH. In addition, the structure of PCSK9DeltaC bound to EGF(AB)(H306Y), a mutant associated with familial hypercholesterolemia (FH), reveals that the Tyr-306 side chain forms a hydrogen bond with PCSK9 Asp-374, thus mimicking His-306 in the low pH conformation. Consistently, Tyr-306 confers increased affinity for PCSK9. Importantly, we found that although the EGF(AB)(H306Y)-PCSK9 interaction is pH-independent, LDLR(H306Y) binds PCSK9 50-fold better at low pH, suggesting that factors other than His-306 contribute to the pH dependence of PCSK9-LDLR binding. Further, we determined the structures of EGF(AB) bound to PCSK9DeltaC containing the FH-associated D374Y and D374H mutations, revealing additional interactions with EGF(A) mediated by Tyr-374/His-374 and providing a rationale for their disease phenotypes. Finally, we report the inhibitory properties of EGF repeats in a cellular assay measuring LDL uptake.
Cadet: A High Data Rate Software Defined Radio for SmallSat Applications (2012)

The government and private sectors are showing more interest in SmallSats for a wider range of missions. However, mission planners are discovering that even relatively simple missions are generating significant amounts of data, and that a communication infrastructure that supports high data rates must be considered early in mission conceptualization and project planning. In answer to these emerging communication needs, L-3 Communications, in conjunction with Utah State University – Space Dynamics Laboratory, developed the Cadet Radio for the Dynamic Ionosphere CubeSat Experiment (DICE) space weather program. DICE was successfully launched in October 2011, and the Cadet radios are currently down-linking mission data at 3 Mbps to the NASA Wallops Island ground station and the SRI ground station in Palo Alto, California. Cadet was designed from the ground up as a very low size, weight, and power (SWAP) software defined radio (SDR). It was also conceived as an element of a communication infrastructure which would be adaptable to various mission needs, and provide an affordable solution through a common core design. The ground communication infrastructure must also be included in SmallSat mission planning. Further community development of an integrated ground infrastructure will greatly improve the effectiveness and affordability of future SmallSat missions.
Rory Nicol (2010)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Rory Nicol Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Large-area Projection HAN-mode Multicolor TFT-addressed LCD (1989)

Abstract A liquid crystal multicolor projection display using a TFT-addressed hybrid-aligned nematic (HAN) cell without a color filter has been developed. Compared to a TFT color LCD with an RGB color filter, it has such advantages as five times brighter display and three times higher resolution.
CD40 AND CD154 IN CELL-MEDIATED IMMUNITY (1998)

CD40-CD154-mediated contact-dependent signals between B and T cells are required for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154 interactions are however also important in many other cell systems. CD40 is expressed by a large variety of cell types other than B cells, and these include dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in immune responses. Recently published studies indicate that CD40-CD154 interactions can influence T cell priming and T cell-mediated effector functions; they can also upregulate costimulatory molecules and activate macrophages, NK cells, and endothelia as well as participate in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. This review focuses on the role of the CD40-CD154 system in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
Juvenile myelomonocytic leukemia with less aggressive clinical course and KRAS mutation (2008)

This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1545-5009/suppmat . Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Aggressive management of doxorubicin-induced cardiomyopathy associated with 'low' doses of doxorubicin (1994)

There is a dose-effect relationship between doxorubicin and the incidence of symptomatic cardiac failure. It is generally thought that doses below 500-550 mg/m2 are safe but, when objective measures of cardiac function are used, it becomes apparent that degrees of cardiac failure occur at doses below this. We present here the case histories of two patients who developed very severe cardiac failure at cumulative doses well below 500 mg/m2 but who survived their initial cardiac illness due to aggressive intervention. In one case, the patient was successfully treated by orthotopic cardiac transplantation.
Novel complementation cell lines derived from human lung carcinoma A549 cells support the growth of E1-deleted adenovirus vectors. (1996)

Replication-defective E1-deleted adenoviruses are attractive vectors for gene therapy or live vaccines. However, manufacturing methods required for their pharmaceutical development are not optimized. For example, the generation of E1-deleted adenovirus vectors relies on the complementation functions present in 293 cells. However, 293 cells are prone to the generation of replication competent particles as a result of recombination events between the viral DNA and the integrated adenovirus sequences present in the cell line. We report here that human lung A549 cells transformed with constitutive or inducible E1-expression vectors support the replication of E1-deficient adenoviruses. E1A transcription was elevated in most of the cell lines, and E1A proteins were expressed at levels similar to those of 293 cells. However, the levels of expression of E1A did not correlate with the efficiencies of complementation of E1-deleted viruses in A549 clones, since some clones complemented replication in the absence of induction of E1A expression. In addition, complementation of E1-deficient adenoviruses did not require expression of the E1B 55-kDa protein. Although these cell lines contain the coding and cis-acting regulatory sequences of the structural protein IX gene, they are not able to complement viruses in which this gene has been deleted. In contrast to 293 cells, such new complementation cell lines do not contain the left end of the adenoviral genome and thus represent a significant improvement over the currently used 293 cells, in which a single recombination event is sufficient to yield replication competent adenovirus.