gebhart/patrepeval huggingface dataset:
Development of an Amine Dehydrogenase for Synthesis of Chiral Amines (2012)

A leucine dehydrogenase has been successfully altered through several rounds of protein engineering to an enantioselective amine dehydrogenase. Instead of the wild-type α-keto acid, the new amine dehydrogenase now accepts the analogous ketone, methyl isobutyl ketone (MIBK), which corresponds to exchange of the carboxy group by a methyl group to produce chiral (R)-1,3-dimethylbutylamine.
Post‐transcriptional silencing of chalcone synthase in Petunia by inverted transgene repeats (1997)

Summary To induce post‐transcriptional silencing of flower pigmentation genes by homologous sense transgenes in transgenic petunias, it is not necessary for the transgenes to be highly transcribed. Even promoterless transgenes can induce silencing. Here it is shown that in these cases silencing is mediated by multimeric transgene/T‐DNA loci in which the T‐DNAs are arranged as inverted repeats (IRs). With the transgene constructs used, monomeric T‐DNA loci are unable to confer silencing even though they modulate IR‐induced silencing. IRsfs with the silencing sequences proximal to the centre (IR c ) induce a more severe silencing than IRs with these sequences distal to the centre (IR n ). Somatic reversion of silencing, as observed in a side branch of one of the chalcone synthase ( Chs ) transformants, was associated with a deletion of the IR locus from L1 cells, the meristematic cell layer that expresses the endogenous Chs genes in the flower corolla. Taken together, these data indicate that the post‐transcriptional silencing mechanism can be activated by inverted transgene repeats. It is also shown that a silent IR UidA—ChsA locus silences the expression of a monomeric 35S promoter‐driven UidA—ChsA transgene only in corollas where the endogenous Chs genes are highly transcribed. These results are consistent with a model in which an IR, by virtue of its palindromic sequence organization, is able to promote the production of aberrant RNA s from the endogenous homologs as a result of ectopic pairing.
Optimizing kd-trees for scalable visual descriptor indexing (2010)

In this paper, we attempt to scale up the kd-tree indexing methods for large-scale vision applications, e.g., indexing a large number of SIFT features and other types of visual descriptors. To this end, we propose an effective approach to generate near-optimal binary space partitioning and need low time cost to access the nodes in the query stage. First, we relax the coordinate-axis-alignment constraint in partition axis selection used in conventional kd-trees, and form a partition axis with the great variance by combining a few coordinate axes in a binary manner for each node, which yields better space partitioning and requires almost the same time cost to visit internal nodes during the query stage thanks to cheap projection operations. Then, we introduce a simple but very effective scheme to guarantee the partition axis of each internal node is orthogonal to or parallel with those of its ancestors, which leads to efficient distance computation between a query point and the cell associated with each node and yields fast priority search. Compared with the conventional kd-trees, our approach takes a little more tree construction time, but obtains much better nearest neighbor search performance. Experimental results on large scale local patch indexing and image search with tiny images show that our approach outperforms the state-of-the-art kd-tree based indexing methods.
T cell receptor genes do not rearrange or express functional transcripts in natural killer cells of scid mice. (1987)

The lineage of natural killer (NK) cells is poorly understood. To examine the relationship between NK cells and cells of the T lineage we have examined purified NK cells from a mutant mouse strain (scid) with severe combined immunodeficiency. Approximately 40% of the lymphoid cells in the spleens of scid mice expressed the NK-specific marker NK-2.1. All NK activity of the scid spleen cells could be accounted for by the NK-2.1+ population, similar to results obtained by using normal C57BL/6 X DBA/2 (B6D2F1) mice. Sorted NK-2.1+ cells proliferated in response to human recombinant interleukin 2 (r-IL 2) but not to concanavalin A (Con A), and were maintained in culture for 2 to 3 wk. Cultured NK-2.1+ cells displayed a cell surface phenotype (Asialo-GM1+, Thy-1.2+, L3T4-, Lyt-2-) and lytic activity similar to that described for freshly isolated NK cells of normal mice. Furthermore, T cell receptor (TCR) genes of the TCR-gamma and TCR-beta loci were in germline configuration, and no functional transcripts of TCR-gamma, TCR-beta, or TCR-alpha were detected. We propose that the expression of the TCR is not necessary for functional NK activity, and NK cells are distinct from both mature cytotoxic T lymphocytes and the earliest identifiable T cells.
Molecular Mechanisms of Death-Receptor-Mediated Apoptosis (2001)

Apoptosis, also called "programmed cell death", can be induced by a variety of stimuli including activation of death receptors by the corresponding death ligands. Death receptors are a subgroup of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily and are characterized by a death domain, which is required for signal transduction. Upon apoptosis induction, caspases, a family of aspartyl-specific cysteine proteases, are activated, which are the main executioners of apoptosis. Finally, specific death substrates are cleaved, resulting in the morphologic features of apoptosis. Depending on the cell type, activation of mitochondria is of central significance for apoptosis induction. This signaling pathway can be modulated by different pro- and anti-apoptotic proteins such as Bax and Bcl-2, which are localized at the mitochondria. Furthermore, apoptosis initiation can be prevented at the death receptor level by FLICE (caspase-8)-inhibitory proteins (FLIPs). Deregulation of apoptosis is associated with diseases like cancer, autoimmunity, and AIDS. Therefore, the elucidation of cell death pathways and the identification of modulators of apoptosis have many therapeutic implications.
Antileukemia effect of c- myc N3′→P5′ phosphoramidate antisense oligonucleotides in vivo (1997)

In vitro, uniformly modified oligonucleotide N3'-->P5' phosphoramidates are apparently more potent antisense agents than phosphorothioate derivatives. To determine whether such compounds are also effective in vivo, severe combined immunodeficiency mice injected with HL-60 myeloid leukemia cells were treated systemically with equal doses of either phosphoramidate or phosphorothioate c-myc antisense or mismatched oligonucleotides. Compared with mice treated with mismatched oligodeoxynucleotides, the peripheral blood leukemic load of mice treated with the antisense sequences was markedly reduced, and such effects were associated with significantly prolonged survival of the antisense-treated mice. Moreover, with each of three different treatment schedules (100, 300, or 900 microg/day for 6 consecutive days), survival of the phosphoramidate-treated mice was significantly longer than that of the phosphorothioate-treated mice. Both phosphoramidate and phosphorothioate oligonucleotides were efficiently taken up by leukemic cells in vivo and were capable of specifically down-regulating c-Myc expression. Moreover, tissue distribution of the phosphoramidate derivatives was undistinguishable from that of the phosphorothioate derivatives. Collectively, these studies suggest that phosphoramidate oligonucleotides can serve as potent and specific antisense agents in the treatment of human leukemia and probably of other malignancies.
Waveguide hologram fingerprint entry device (1996)

The recording and entry of fingerprints into the local and na- tional databases is increasingly relying on optics to simplify and speed up this process. A prototype device for the entry of fingerprints that uses a waveguide hologram as part of the scheme for illuminating the finger is described. The use of the waveguide hologram enables reduction in the size, weight, and energy consumption of a fingerprint entry device (or live scan device). The entry device then becomes highly portable and thus useful in many office and field applications. Coupled with electronic or optical processing and storage along with telephone or radio trans- mission of the captured fingerprints, rapid identification of individuals be- comes a realizable goal. The components required for the prototype ho- lographic fingerprint entry device (HoloFED) including the light source, the illumination waveguide hologram, the imaging system and the stor- age, and processing system are discussed. Examples of fingerprints captured are shown. The trade-offs necessary for the implementation of the prototype are object-to-image distance, optical efficiency, weight, and cost. © 1996 Society of Photo-Optical Instrumentation Engineers.
Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype. (1994)

We have characterized the structure and function of RNA sequences that direct beta-cytoplasmic actin mRNA to the cell periphery were mapped to two segments of 3'-untranslated region by expression of LacZ/beta-actin chimeric mRNAs in chicken embryo fibroblasts (CEFs). A 54-nt segment, the "RNA zipcode," and a homologous but less active 43-nt segment each localized beta-galactosidase activity to the leading lamellae. This zipcode contains the full activity, and mutations or deletions within it reduce, but do not eliminate, its activity, indicating that several motifs contribute to the activity. Two of these motifs, when multimerized, can regenerate almost full activity. These sequences are highly conserved in evolution, since the human beta-actin zipcode, positioned identically in the 3'UTR localizes equally well in chicken cells. Complementary phosphorothioate oligonucleotides against the zipcode delocalized endogenous beta-actin mRNA, whereas those complementary to the region just outside the zipcode, or sense oligonucleotides, did not. Actin mRNA or protein levels were unaffected by the antisense treatments, but a dramatic change in lamellipodia structure, and actin stress fiber organization was observed using the same antizipcode oligonucleotides which delocalized the mRNA. Hence, discrete 3'UTR sequences direct beta-actin isoform synthesis to the leading lamellae and affect cell morphology, presumably through the actin cytoskeleton.
New Growth-Regulating Compounds. I. Summary of Growth-Inhibitory Activities of Some Organic Compounds as Determined by Three Tests (1946)

1. The literature relating to the testing of organic compounds for growth- regulating activity on plants has been reviewed chronologically. 2. Three methods have been devised, whereby inhibitory activity at high dilution can be determined and evaluated. All depend on elongation or weight changes subsequent to treatment. The activity of the compounds under test are expressed as a percentage of the inhibition brought about concurrently by 2,4-dichlorophenoxyacetic acid as a common reference material. The plant materials used are germinating corn and young kidney-bean plants. 3. One thousand and sixty organic compounds, almost all synthesized expressly for this work, were submitted to test by the three methods. The data obtained have been assembled in groups on the basis of activity in reducing elongation of the primary root of germinating corn as compared with the reference material. 4. The significance and interpretation of the tests are discussed. Compounds showing high activity are indicated as promising for use as herbicides.
An Essential Role for DNA Adenine Methylation in Bacterial Virulence (1999)

Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam- mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam- derivatives of these pathogens may serve as live attenuated vaccines.
1H and 13C NMR spectral assignments of some natural abietane diterpenoids (2003)

Abstract An NMR study of 11 naturally occurring abietane diterpenoids is described. In addition to one‐dimensional NMR methods, including DPFGSE 1D‐NOE spectra, two‐dimensional shift‐correlated experiments [ 1 H, 1 H COSY, 1 H, 13 C‐gHSQC 1 J (C,H) and 1 H, 13 C‐gHMBC n J (C,H) ( n = 2 and 3)] were used for the complete and unambiguous 1 H and 13 C chemical shift assignments of these substances. Copyright © 2003 John Wiley &amp; Sons, Ltd.
A mutation of the beta 2-adrenergic receptor impairs agonist activation of adenylyl cyclase without affecting high affinity agonist binding. Distinct molecular determinants of the receptor are involved in physical coupling to and functional activation of Gs. (1990)

Activation of guanyl nucleotide regulatory proteins (G proteins) by hormones and neurotransmitters appears to require the formation of high affinity agonist-receptor-G protein ternary complexes. In the case of the beta 2-adrenergic receptor, multiple regions of the molecule have been implicated in coupling to the stimulatory G protein Gs. This finding raises the possibility that discrete regions of the receptor mediate ternary complex formation, whereas different loci may be involved in other aspects of G protein activation. To date, however, mutagenesis studies with the beta 2-adrenergic receptor have not clarified this question since mutant receptors with impaired abilities to activate Gs have generally possessed a diminished capacity to form the ternary complex as assessed in binding assays. We have expressed in a mammalian cell line a mutant beta 2-adrenergic receptor comprising a seven-amino acid deletion in the carboxyl-terminal region of its third cytoplasmic loop (D267-273), a region proposed to be critically involved in coupling to Gs. When tested with beta-adrenergic agonists, the maximal adenylyl cyclase response mediated by this mutant receptor was less than one-half of that seen with the wild-type receptor. Nevertheless, D267-273 exhibited high affinity agonist binding identical to that of the wild-type receptor. In addition, agonist-induced sequestration of the receptor, a property not mediated by Gs, was also normal. These findings indicate that the formation of high affinity agonist-receptor-Gs complexes is not sufficient to fully activate Gs. Instead, an additional stimulatory signal appears to be required from the receptor. Our data thereby suggest that the molecular determinants of the beta 2-adrenergic receptor involved in formation of the ternary complex are not identical to those that transmit the agonist-induced stimulatory signal to Gs.
Chromosome Breaks and Genomic Instability (2000)

Tumorigenesis is known to result from multiple genetic changes. Although endogenous and environmental insults can damage DNA, cellular mechanisms exist to repair various forms of damage or to kill those cells irreparably damaged. Hence, the accumulation of numerous genetic changes that would lead to cancer in normal cells is extremely rare. Nevertheless, disruption of a DNA repair pathway has the potential to expedite tumorigenesis by resulting in a cell that is hypermutable. Multiple pathways exist to repair the various forms of DNA damage that can cause mutagenesis. Recent studies have demonstrated a key role for homologous recombination in DNA repair, in particular in the repair chromosomal double-strand breaks. This review summarizes those studies and discusses how disruption of homologous recombination pathways can create genetic instability.
Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail (2006)

Members of the fibroblast growth factor family bind to one or more of the four closely related membrane-spanning FGF receptors. In addition to signaling through the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have studied the ability of the four FGF receptors to facilitate translocation of exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted from FGFR1 without abolishing translocation, whereas the C-terminal tail of the FGFRs, constituted by approximately 50 amino acids downstream of the kinase domain, plays a crucial role in FGF-1 translocation. Three amino acids residues within the C-terminal tail were found to be of particular importance for translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were sufficient to enable the receptor to support FGF-1 translocation. The results demonstrate a striking diversity in function of the four FGFRs determined by their C-terminal domain.
High-energy ‘composite’ layered manganese-rich cathode materials via controlling Li2MnO3 phase activation for lithium-ion batteries (2012)

The 'composite' layered materials for lithium-ion batteries have recently attracted great attention owing to their large discharge capacities. Here, the 0.5Li(2)MnO(3)·0.5LiMn(0.42)Ni(0.42)Co(0.16)O(2)'composite' layered manganese-rich material is prepared and characterized by the synchrotron X-ray powder diffraction (SXPD). The relationship between its electrochemical performance and its 'composite' components, the Li(2)MnO(3) phase activation process during cycling and the cycle stability of this material at room temperature are elucidated based on its kinetic controlled electrochemical properties, dQ/dV curves and Raman scattering spectroscopies associated with different initial charge-discharge current densities (5 mA g(-1), 20 mA g(-1) and 50 mA g(-1)), cut-off voltages (4.6 V and 4.8 V) and cycle numbers (50 cycles and 150 cycles). Furthermore, its reaction pathways are tracked via a firstly introduced integrated compositional phase diagram of four components, Li(2)MnO(3), LiMn(0.42)Ni(0.42)Co(0.16)O(2), MO(2) (M = Mn(1-α-β)Ni(α)Co(β); 0 ≤α≤ 5/12, 0 ≤β≤ 1/6) and LiMnO(2), which turns out to be a very important guiding tool for understanding and utilizing this 'composite' material.
Development of hRad51–Cas9 nickase fusions that mediate HDR without double-stranded breaks (2019)

In mammalian cells, double-stranded DNA breaks (DSBs) are preferentially repaired through end-joining processes that generally lead to mixtures of insertions and deletions (indels) or other rearrangements at the cleavage site. In the presence of homologous DNA, homology-directed repair (HDR) can generate specific mutations, albeit typically with modest efficiency and a low ratio of HDR products:indels. Here, we develop hRad51 mutants fused to Cas9(D10A) nickase (RDN) that mediate HDR while minimizing indels. We use RDN to install disease-associated point mutations in HEK293T cells with comparable or better efficiency than Cas9 nuclease and a 2.7-to-53-fold higher ratio of desired HDR product:undesired byproducts. Across five different human cell types, RDN variants generally result in higher HDR:indel ratios and lower off-target activity than Cas9 nuclease, although HDR efficiencies remain strongly site- and cell type-dependent. RDN variants provide precision editing options in cell types amenable to HDR, especially when byproducts of DSBs must be minimized.
PEI1, an Embryo-Specific Zinc Finger Protein Gene Required for Heart-Stage Embryo Formation in Arabidopsis (1998)

We used virtual subtraction, a new gene isolation strategy, to isolate several genes of interest that are expressed in Arabidopsis embryos. These genes have demonstrated biological properties or have the potential to be involved in important biological processes. One gene isolated by virtual subtraction is PEI. It encodes a protein containing a Cys3His zinc finger domain associated with a number of animal and fungal transcription factors. In situ hybridization results showed that PEI1 is expressed throughout the embryo from globular to late cotyledon stage. Transgenic Arabidopsis plants expressing a PEI1 antisense gene produced white seeds in which embryo development did not progress through heart stage. Aberrant embryos failed to form cotyledons, but the embryonic root appeared to be normal. Aberrant embryos did not turn green, and the expression of genes involved in photomorphogenesis was drastically attenuated. In culture, aberrant embryos did not form true leaves, but root formation was apparently normal. These results suggest that PEI1 is an embryo-specific transcription factor that plays an important role during Arabidopsis embryogenesis, functioning primarily in the apical domain of the embryo.
High-Affinity TCRs Generated by Phage Display Provide CD4+ T Cells with the Ability to Recognize and Kill Tumor Cell Lines (2007)

We examined the activity of human T cells engineered to express variants of a single TCR (1G4) specific for the cancer/testis Ag NY-ESO-1, generated by bacteriophage display with a wide range of affinities (from 4 microM to 26 pM). CD8(+) T cells expressing intermediate- and high-affinity 1G4 TCR variants bound NY-ESO-1/HLA-A2 tetramers with high avidity and Ag specificity, but increased affinity was associated with a loss of target cell specificity of the TCR gene-modified cells. T cells expressing the highest affinity TCR (K(D) value of 26 pM) completely lost Ag specificity. The TCRs with affinities in the midrange, K(D) 5 and 85 nM, showed specificity only when CD8 was absent or blocked, while the variant TCRs with affinities in the intermediate range-with K(D) values of 450 nM and 4 microM-demonstrated Ag-specific recognition. Although the biological activity of these two relatively low-affinity TCRs was comparable to wild-type reactivity in CD8(+) T cells, introduction of these TCR dramatically increased the reactivity of CD4(+) T cells to tumor cell lines.