gebhart/patrepeval huggingface dataset:
Phage Display of RNA Binding Zinc Fingers from Transcription Factor IIIA (1997)

Zinc fingers in transcription factor IIIA (TFIIIA) contribute differentially to RNA and DNA binding affinity. We investigated whether the same putative alpha-helix amino acids in TFIIIA zinc fingers are essential for both RNA and DNA binding. In published structures, zinc fingers make DNA base contacts through amino acids -1, +2, +3, and +6 of the recognition helix. Alanine substitution at these four positions were made in TFIIIA RNA binding zinc fingers, tz4-7 and DNA binding zinc fingers, tz1-3. Substitution in zinc fingers 4 or 6 of tz4-7 reduced RNA affinity 77- and 38-fold, respectively, whereas substitution in zinc fingers 5 or 7 had little effect. DNA binding affinity of tz1-3 was eliminated by alanine substitution in any one zinc finger. We determined which amino acids supported RNA binding by phage display of a library of zinc finger 4 mutants. Lysine at helix position -1 of zinc finger 4 was conserved in all selected tz4-7 fusions. Point mutation of Lys-1 to alanine in zinc finger 4 reduced tz4-7 RNA affinity 30-fold. We propose that RNA binding by TFIIIA shows similarity to DNA binding in the use of the recognition helix. Helix positions -1 and +2 may have particular significance for RNA binding.
Synthese von Isothiocyanatocarbonsäurechloriden aus Lactamen (1975)

Isothiocyanate (2) , die im gleichen Molekül eine Carbonsäurechlorid‐Gruppe enthalten und daher für die Synthese niedermolekularer und polymerer Derivate von ω‐Aminocarbonsäuren von Interesse sind, bilden sich erstaunlich leicht aus den Lactamen (1) . magnified image
GANP enhances the efficiency of mRNA nuclear export in mammalian cells (2010)

Nuclear export of mRNPs is mediated by transport factors such as NXF1 that bind mRNPs and mediate their translocation through the central channel of nuclear pores (NPC) using transient interactions with FG-nucleoporins. A number of nuclear factors enhance the efficiency of this process by concentrating mRNPs at the nuclear face of the pores. Although this enhancement has been explored mainly with the yeast TREX-2 complex, recent work has indicated that mammalian cells employ GANP (Germinal-centre Associated Nuclear Protein) for efficient mRNP nuclear export and for efficient recruitment of NXF1-containing mRNPs to NPCs. GANP is constructed from several domains that show local homology to FG-nucleoporins, the yeast mRNA export factor Sac3p and the mammalian MCM3 acetyltransferase. Whereas yeast TREX-2 is located primarily at nuclear pores, some GANP is located in the nuclear interior in addition to that found at the pores. GANP depletion inhibits bulk mRNA export, resulting in retention of mRNPs and NXF1 in punctate foci within the nucleoplasm, consistent with GANP's being an integral component of the mammalian mRNA export machinery. Here, we discuss the model for GANP function presented in our recent paper and its implications for the mechanism of mRNA export in mammalian cells.
Anticandida Activity Is Retained in P-113, a 12-Amino-Acid Fragment of Histatin 5 (2001)

Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.
A time-invariant principle of genome evolution (2010)

Uncovering general principles of genome evolution that are time-invariant and that operate in germ and somatic cells has implications for genome-wide association studies (GWAS), gene therapy, and disease genomics. Here we investigate the relationship between structural alterations (e.g., insertions and deletions) and single-nucleotide substitutions by comparing the following genomes that diverged at different times across germ- and somatic-cell lineages: (i) the reference human and chimpanzee genome (in million years), (ii) the reference human and personal genomes (in tens of thousands of years), and (iii) structurally altered regions in cancer and genetically engineered cells (in days). At the species level, genes with structural alteration in nearby regions show increased single-nucleotide changes and tend to evolve faster. In personal genomes, the single-nucleotide substitution rate is higher near sites of structural alteration and decreases with increasing distance. In human cancer cell populations and in cells genetically engineered using zinc-finger nucleases, single-nucleotide changes occur frequently near sites of structural alterations. We present evidence that structural alteration induces single-nucleotide changes in nearby regions and discuss possible molecular mechanisms that contribute to this phenomenon. We propose that the low fidelity of nonreplicative error-prone repair polymerases, which are used during insertion or deletion, result in break-repair-induced single-nucleotide mutations in the vicinity of structural alteration. Thus, in the mutational landscape, structural alterations are linked to single-nucleotide changes across different time scales in both somatic- and germ-cell lineages. We discuss implications for genome evolution, GWAS, disease genomics, and gene therapy and emphasize the need to investigate both types of mutations within a single framework.
Passive GPS-Free Navigation for Small UAVs (2005)

A method for passive GPS-free navigation of a small Unmanned Aerial Vehicle with a minimal sensor suite (limited to an inertial measurement unit and a monocular camera) is presented. The navigation task is cast as a Simultaneous Localization and Mapping (SLAM) problem. While SLAM has been the subject of a great deal of research, the highly non-linear system dynamics and limited sensor suite available in this application presents a unique set of challenges which have not previously been addressed. In this particular application solutions based on Extended Kalman Filters have been shown to diverge and alternate techniques are required. In this paper an Unscented Kalman Filter is applied to the navigation problem, which leads to a consistent estimate of vehicle and feature states. This paper presents: (a) simulation results showing mapping and navigation in three dimensions; (b) preliminary hardware test results showing navigation and mapping using an off-the-shelf inertial measurement unit and camera in a laboratory environment.
The Amino Acid Sequence of a κ Type Bence-Jones Protein (1969)

The amino acid sequence of the human κ Bence-Jones protein Ag containing 214 residues has been determined by a combination of four procedures: sequence analysis of the tryptic and of the chymotryptic peptides of the carboxymethylated protein described earlier and partial sequence analysis of the tryptic peptides of the aminoethylated protein and of the peptic peptides of the oxidized protein described herein. The tryptic peptides from the aminoethylated protein account for the total amino acid content and provide some necessary overlaps. Analysis of two of these peptides and of one of the peptic cysteic acid peptides has yielded the previously missing sequence for positions 19 through 32. There are two analogous disulfide bridges: one connecting Cys-23 and Cys-88 and one connecting Cys-134 and Cys-194. Comparison to the provisional sequences of other human κ Bence-Jones proteins has verified the concept that the NH2-terminal half of κ light chains is prone to variation in sequence whereas the COOH-terminal half has a fixed sequence except for one hereditary variation. Many of the differences in sequence in the NH2-terminal portion of κ-chains are not attributable to single point mutations. The various genetic mechanisms proposed to explain the variability in sequence of immunoglobulin light chains are discussed.
The First Agmatine/Cadaverine Aminopropyl Transferase: Biochemical and Structural Characterization of an Enzyme Involved in Polyamine Biosynthesis in the Hyperthermophilic Archaeon Pyrococcus furiosus (2007)

We report here the characterization of the first agmatine/cadaverine aminopropyl transferase (ACAPT), the enzyme responsible for polyamine biosynthesis from an archaeon. The gene PF0127 encoding ACAPT in the hyperthermophile Pyrococcus furiosus was cloned and expressed in Escherichia coli, and the recombinant protein was purified to homogeneity. P. furiosus ACAPT is a homodimer of 65 kDa. The broad substrate specificity of the enzyme toward the amine acceptors is unique, as agmatine, 1,3-diaminopropane, putrescine, cadaverine, and sym-nor-spermidine all serve as substrates. While maximal catalytic activity was observed with cadaverine, agmatine was the preferred substrate on the basis of the k(cat)/K(m) value. P. furiosus ACAPT is thermoactive and thermostable with an apparent melting temperature of 108 degrees C that increases to 112 degrees C in the presence of cadaverine. Limited proteolysis indicated that the only proteolytic cleavage site is localized in the C-terminal region and that the C-terminal peptide is not necessary for the integrity of the active site. The crystal structure of the enzyme determined to 1.8-A resolution confirmed its dimeric nature and provided insight into the proteolytic analyses as well as into mechanisms of thermal stability. Analysis of the polyamine content of P. furiosus showed that spermidine, cadaverine, and sym-nor-spermidine are the major components, with small amounts of sym-nor-spermine and N-(3-aminopropyl)cadaverine (APC). This is the first report in Archaea of an unusual polyamine APC that is proposed to play a role in stress adaptation.
The synthesis of a carbohydrate-like dihydrooxazine and tetrahydrooxazine as putative inhibitors of glycoside hydrolases: A direct synthesis of isofagomine (2002)

The treatment of benzyl 2,3-O-isopropylidene-β-L-xylopyranoside with N-hydroxyphthalimide under Mitsunobu conditions, followed by protecting-group interchange, gave benzyl 4-O-[(tert-butoxycarbonyl)amino]-2,3- O-isopropylidene-α-D-arabinoside. Mild acid hydrolysis and catalytic hydrogenolysis afforded 4-O-[(tert-butoxycarbonyl)amino]-D-arabinose that, upon heating in water, gave the dihydrooxazine [(4R,5S,6R)-5,6-dihydro-4,5-dihydroxy-6-hydroxymethyl-4H-1,2-oxazine] as a crystalline solid. A single-crystal structure determination of this solid showed it to exist in the 5 H 6 conformation. Reduction of the dihydrooxazine gave the tetrahydrooxazine [(4R,5S,6R)-4,5-dihydroxy-6-hydroxymethyl-3,4,5,6-tetrahydro-2H-1,2-oxazine]. The dihydrooxazine was an effective inhibitor of two β-glucosidases (K i = 27 and 35 µM). Benzyl 2,3-O-isopropylidene-β-L-xylopyranoside, via the derived imidazylate, was converted into a nitrile that, upon reduction and protecting-group manipulations, gave benzyl 4-C-aminomethyl-4-deoxy-α-D-arabinoside. Treatment of this amine with hydrogen and palladium-on-carbon gave isofagomine.Key words: dihydrooxazine, tetrahydrooxazine, isofagomine, iminosugars, glycosidase inhibitors.
New Medium for Blood Cultures (1969)

A new medium suitable for blood cultures is described. It contains dextrose, cysteine, iron, and magnesium, in a tris(hydroxymethyl)aminomethane buffer, and a mixture of peptones derived from animal tissues, casein, and yeast. In comparison with Trypticase Soy Broth, the growth rate constants of Staphylococcus aureus, Streptococcus (Viridans group), enterococcus, and Escherichia coli were higher in this medium, and growth appeared earlier in a significant number of clinical blood cultures.
High- and low-temperature bonding techniques for microstructures (1993)

The ability to bond together two or more silicon wafers greatly expands the variety and complexity of silicon microstructures that can be designed and fabricated. At LLNL, microstructures have been used for many years as hardware in scientific experiments. The activity has recently been expanded into other areas to include microinstruments for biomedical applications and for chemical analysis. Both high temperature (1100{degrees}C) bonding techniques have been used, depending on the application. This paper discusses these applications with emphasis on the most extensive which is the fabrication of microchannel coolers for diode arrays.
Soluble Polymers as Scaffolds for Recoverable Catalysts and Reagents (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSoluble Polymers as Scaffolds for Recoverable Catalysts and ReagentsTobin J. Dickerson, Neal N. Reed, and Kim D. JandaView Author Information Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 Cite this: Chem. Rev. 2002, 102, 10, 3325–3344Publication Date (Web):September 4, 2002Publication History Received10 April 2002Published online4 September 2002Published inissue 1 October 2002https://pubs.acs.org/doi/10.1021/cr010335ehttps://doi.org/10.1021/cr010335eresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views3933Altmetric-Citations506LEARN 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 SUBJECTS:Alcohols,Catalysts,Chemical reactions,Polymers,Reagents Get e-Alerts
Color dependent optical prefilter for the suppression of aliasing artifacts (1990)

Optical prefilters, which make use of the double-refraction effect in crystalline quartz, reduce the amount of aliasing artifacts in the displayed image of a video system. This paper describes anew class of optical prefilter that produces different amounts of blur for different colors. The chromatic variation is obtained by placing a polarization retarder between two quartz crystals. This type of filter is useful with sensors that have unequal pixel densities in the three sensed colors.
Improved Image Captioning via Policy Gradient optimization of SPIDEr (2017)

Current image captioning methods are usually trained via maximum likelihood estimation. However, the log-likelihood score of a caption does not correlate well with human assessments of quality. Standard syntactic evaluation metrics, such as BLEU, METEOR and ROUGE, are also not well correlated. The newer SPICE and CIDEr metrics are better correlated, but have traditionally been hard to optimize for. In this paper, we show how to use a policy gradient (PG) method to directly optimize a linear combination of SPICE and CIDEr (a combination we call SPIDEr): the SPICE score ensures our captions are semantically faithful to the image, while CIDEr score ensures our captions are syntactically fluent. The PG method we propose improves on the prior MIXER approach, by using Monte Carlo rollouts instead of mixing MLE training with PG. We show empirically that our algorithm leads to easier optimization and improved results compared to MIXER. Finally, we show that using our PG method we can optimize any of the metrics, including the proposed SPIDEr metric which results in image captions that are strongly preferred by human raters compared to captions generated by the same model but trained to optimize MLE or the COCO metrics.
Improved double-stranded DNA sequencing using the linear polymerase chain reaction (1989)

Journal Article Improved double-stranded DNA sequencing using the linear polymerase chain reaction Get access Vincent Murray Vincent Murray Molecular Sciences Group, Peter MacCallum Cancer Institute481 little Lonsdale Street, Melbourne, Victoria 3000, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 21, 11 November 1989, Page 8889, https://doi.org/10.1093/nar/17.21.8889 Published: 11 November 1989 Article history Accepted: 12 October 1989 Published: 11 November 1989
CD44 Regulates Hepatocyte Growth Factor-mediated Vascular Integrity (2007)

The preservation of vascular endothelial cell (EC) barrier integrity is critical to normal vessel homeostasis, with barrier dysfunction being a feature of inflammation, tumor angiogenesis, atherosclerosis, and acute lung injury. Therefore, agents that preserve or restore vascular integrity have important therapeutic implications. In this study, we explored the regulation of hepatocyte growth factor (HGF)-mediated enhancement of EC barrier function via CD44 isoforms. We observed that HGF promoted c-Met association with CD44v10 and recruitment of c-Met into caveolin-enriched microdomains (CEM) containing CD44s (standard form). Treatment of EC with CD44v10-blocking antibodies inhibited HGF-mediated c-Met phosphorylation and c-Met recruitment to CEM. Silencing CD44 expression (small interfering RNA) attenuated HGF-induced recruitment of c-Met, Tiam1 (a Rac1 exchange factor), cortactin (an actin cytoskeletal regulator), and dynamin 2 (a vesicular regulator) to CEM as well as HGF-induced trans-EC electrical resistance. In addition, silencing Tiam1 or dynamin 2 reduced HGF-induced Rac1 activation, cortactin recruitment to CEM, and EC barrier regulation. We observed that both HGF- and high molecular weight hyaluronan (CD44 ligand)-mediated protection from lipopolysaccharide-induced pulmonary vascular hyperpermeability was significantly reduced in CD44 knock-out mice, thus validating these in vitro findings in an in vivo murine model of inflammatory lung injury. Taken together, these results suggest that CD44 is an important regulator of HGF/c-Met-mediated in vitro and in vivo barrier enhancement, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin.
Immune modulation mediated by the humanized anti‐CD70 monoclonal antibody SGN‐70 (2008)

CD70 is a member of the TNF family whose interaction with its cognate receptor CD27 regulates immune effector and memory responses, and blockade of CD70‐CD27 interactions inhibits the onset of EAE and cardiac allograft rejection in mice. Immunohistochemical analysis revealed the presence of CD70+ cells in inflamed tissues of lupus, rheumatoid arthritis and Crohn's disease patients. We have developed a humanized anti‐human CD70 monoclonal antibody, SGN‐70, that can selectively deplete CD70+ antigen‐specific T cells and down‐regulate expression of cytokines and chemokines including IFN‐γ, TNF‐α, VEGF and IP‐10, as well as the co‐stimulatory molecules CD40L, 4‐1BB, ICOS and OX40. In a T‐cell directed co‐stimulation of peripheral blood lymphocyte culture system, SGN‐70 decreased expansion of both T and B cells. The differentiation of CD20+CD38+ peripheral blood B cells to CD20‐CD38+ plasmablasts was also inhibited by SGN‐70, as were levels of secreted Ig. The in vivo activity of SGN‐70 was evaluated in SCID‐huPBMC mice immunized with tetanus toxoid (TT). Treatment with SGN‐70 significantly reduced anti‐TT antibody titers compared to untreated mice or to those that received non‐binding control Ig. Altogether, our data indicate that SGN‐70 can modulate immune responses mediated by both T and B lymphocytes, and provide a rationale to test SGN‐70 clinically in autoimmune indications.
The Effects of Reduced Temperature and/or Starvation Conditions on the Radiosensitivity and Repair of Potentially Lethal Damage and Sublethal Damage in L5178Y-R and L5178Y-S Cells (1988)

Potentially lethal damage (PLD) and sublethal damage (SLD) modification in L5178Y-S(LY-S) and L5178Y-R (LY-R) cells was investigated for postirradiation holding in either plateau phase or log phase at either 25 or 37 degrees C. Incubation in both plateau and log phases increased PLD repair (PLDR) at 25 degrees C but increased PLD fixation (PLDF) at 37 degrees C in LY-S cells, with the opposite result (PLDR at 37 degrees C, PLDF at 25 degrees C) in LY-R cells. Conditioned medium (CM from plateau-phase cells) had only a slight effect on the radiosensitivity of log-phase LY-S cells. CM was highly toxic to log-phase LY-R cells even without radiation. Postirradiation incubation of log-phase cells at 25 degrees C increased PLDF between 5.5 and 18 h in LY-R cells, whereas PLDR was completed by 5.5 h in LY-S cells. Flow cytometric data show that the LY-R vs LY-S plateau-phase PLD results are not caused by a differential cell cycle distribution. Although all cell cycle stages are found in the plateau-phase cells, G1 is enriched and cells in all stages must be slowly cycling or stationary. Split doses decrease survival of LY-S cells at 37 degrees C but maintain survival at the single acute total dose level at 25 degrees C (no SLD repair (SLDR)). SLDR is observed at both 25 and 37 degrees C in LY-R cells. The results for both the split dose and delayed plating experiments are best understood in terms of competition between PLD repair and fixation with their relative contributions depending on cellular metabolism, which can be altered by changes in temperature or medium constituents. The opposite PLD results obtained for LY-S and LY-R cells suggest that radiosensitivity in these cells is determined by two different mechanisms.
High-Throughput Screening of One-Bead-One-Compound Libraries: Identification of Cyclic Peptidyl Inhibitors against Calcineurin/NFAT Interaction (2011)

One-bead-one-compound (OBOC) libraries provide a powerful tool for drug discovery as well as biomedical research. However, screening a large number of beads/compounds (>1 million) and rank ordering the initial hits (which are covalently attached to a solid support) according to their potencies still post significant technical challenges. In this work, we have integrated some of the latest technical advances from our own as well as other laboratories to develop a general methodology for rapidly screening large OBOC libraries. The methodology has been applied to synthesize and screen a cyclic peptide library that features: (1) spatially segregated beads containing cyclic peptides on the surface layer and linear encoding peptides in their interior; (2) rapid on-bead screening of the library (>1 million) by a multistage procedure (magnetic bead sorting, enzyme-linked assay, and fluorescence based screening); (3) selective release of cyclic peptides from single positive beads for solution-phase determination of their binding affinities; and (4) hit identification by partial Edman degradation/mass spectrometry (PED/MS). Screening of the library against protein phosphatase calcineurin (Cn) identified a series of cyclic peptides that bind to the substrate-docking site for nuclear factor of activated T cells (NFAT) with K(D) values of ∼1 μM. Further improvement of the affinity and specificity of these compounds may lead to a new class of immunosuppressive agents that are more selective and therefore less toxic than cyclosporine A and FK506.