gebhart/patrepeval huggingface dataset:
Pyramidal parametrics (1983)

The mapping of images onto surfaces may substantially increase the realism and information content of computer-generated imagery. The projection of a flat source image onto a curved surface may involve sampling difficulties, however, which are compounded as the view of the surface changes. As the projected scale of the surface increases, interpolation between the original samples of the source image is necessary; as the scale is reduced, approximation of multiple samples in the source is required. Thus a constantly changing sampling window of view-dependent shape must traverse the source image. To reduce the computation implied by these requirements, a set of prefiltered source images may be created. This approach can be applied to particular advantage in animation, where a large number of frames using the same source image must be generated. This paper advances a “pyramidal parametric” prefiltering and sampling geometry which minimizes aliasing effects and assures continuity within and between target images. Although the mapping of texture onto surfaces is an excellent example of the process and provided the original motivation for its development, pyramidal parametric data structures admit of wider application. The aliasing of not only surface texture, but also highlights and even the surface representations themselves, may be minimized by pyramidal parametric means.
Calcitriol-Induced Apoptosis in LNCaP Cells Is Blocked ByOverexpression of Bcl-21 (2000)

While the role of vitamin D in bone and mineral metabolism has been investigated extensively, the role of the vitamin D receptor in other tissues is less well understood. 1,25-Dihydroxyvitamin D3 (calcitriol) can act as a differentiating agent in normal tissues and can inhibit the growth of many cancer cell lines including LNCaP prostate cancer cells. We have shown previously that calcitriol causes LNCaP cell accumulation in the G0/G1 phase of the cell cycle. In this study, we demonstrate that calcitriol also induces apoptosis of LNCaP cells. The calcitriol-induced apoptosis is accompanied by a down-regulation of Bcl-2 and Bcl-X(L) proteins, both of which protect cells from undergoing apoptosis. Other proteins important in apoptotic control, Bax, Mcl-1, and Bcl-X(S), are unaffected by calcitriol treatment. We find that overexpression of Bcl-2 blocks calcitriol-induced apoptosis and reduces, but does not eliminate, calcitriol-induced growth inhibition. We conclude that both regulation of cell cycle and the apoptotic pathway are involved in calcitriol action in prostate cancer cells.
Isolation and characterization of a rat liver alkaline phosphatase gene (1989)

Structural analysis of 55 nearly full-length cDNA clones revealed heterogeneity in the 5'-untranslated regions of rat liver alkaline phosphatase mRNAs. The 5' extremities diverged into two totally unrelated sequence stretches at the position 88 nucleotides upstream of the initiation codon ATG. These two sequences, referred to as E1 and E2, were assigned on the genome about 36,000 base pairs (36 kbp) and 10 kbp upstream, respectively, of the exon coding for the 5'-most part of the common region. The gene consisted of 13 exons, including E1 and E2, and spanned about 56 kbp. The 11 exons (E3 to E13) following E1 and E2 were shared in common by the E1-type and the E2-type mRNAs. Analyses by S1 nuclease mapping and primer extension revealed the presence of two independent transcription-initiation sites specific to each of the E1 and E2 sequences. These results are interpreted as indicating a possible alternative usage of two leader exons, hence the presence of two independent promoters. Structural features of these putative promoters are described in the context of transcriptional fundamental and regulatory cis-elements.
A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism (2020)

In this interventional clinical trial in BTHS, daily administration of elamipretide led to improvement in BTHS symptoms.
Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition (2018)

Free accessAbstractFirst published online January 25, 2018Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd editionAll Articleshttps://doi.org/10.1177/0333102417738202
Myristoylated Naked2 Antagonizes Wnt-β-Catenin Activity by Degrading Dishevelled-1 at the Plasma Membrane (2010)

In Drosophila, naked cuticle is an inducible antagonist of the Wnt-beta-catenin pathway, likely acting at the level of Dishevelled (Dsh/Dvl), an essential component of this pathway. The mechanism by which naked cuticle and its two vertebrate orthologs, Naked1 (NKD1) and Naked2 (NKD2), inhibit Dvl function is unknown. NKD2 is myristoylated, a co-translational modification that leads to its plasma membrane localization. In contrast, myristoylation-deficient G2A NKD2 is cytoplasmic. Herein we show that the ability of Nkd2/NKD2 to antagonize Wnt-beta-catenin activity during zebrafish embryonic development and in mammalian HEK293 cells is myristoylation-dependent. NKD2 and Dvl-1 interact and co-localize at the lateral membrane of polarized epithelial cells. In reciprocal overexpression and siRNA knockdown experiments, NKD2 and Dvl-1 destabilize each other via enhanced polyubiquitylation; this effect is also dependent upon Naked2 myristoylation. Cell fractionation and ubiquitylation assays indicate that endogenous NKD2 interacts with a slower migrating, ubiquitylated form of Dvl-1 in plasma membrane fractions. These results provide a mechanism by which NKD2 antagonizes Wnt signaling: myristoylated NKD2 interacts with Dvl-1 at the plasma membrane, and this interaction leads to their mutual ubiquitin-mediated proteasomal degradation.
Aggregate hierarchy in soils (1991)

An Alfisol, a Mollisol and an Oxisol were fractionated into different particle sizes after a range of disaggregating treatments from gentle to vigorous. The Alfisol and the Mollisol appeared to break down in steps; macroaggregates &amp;gt;250 µm diameter breaking down to microaggregates 20-250 µm diameter before particles &amp;lt;20 µm were released. Vigorous disruption led to particle size distributions similar to those obtained by classical methods used to determine particle size distributions. The Oxisol was stable to rapid wetting treatments but when aggregate disruption was initiated by vigorous treatments particles &amp;lt;20 µm diameter were released and there was no evidence of aggregate hierarchy. Scanning electron microscopy of particles of different sizes showed distinctly single grain particles and aggregates. The microscopic studies indicated the potential role of roots and hyphae in the stabilization of larger aggregates, and for fragments of roots as nuclei for smaller aggregates. Plant debris was not visible in aggregates &amp;lt;20 µm but clay microstructure was evident. It is suggested that aggregate hierarchy occurs in Alfisols and Mollisols because organic materials are the dominant stabilizing agents in larger aggregates but in the Oxisol oxides are dominant stabilizing agents and prevent the expression of aggregate hierarchy caused by organic materials.
Sialyllactose suppress TNF‐α stimulated IL‐8 secretion in vitro (2009)

Background Intestinal epithelial cells play an important role in mucosal immune reactions via production and expression of chemokines such as interleukin‐8 (IL‐8) being involved in carbohydrate mediated neutrophil adhesion and infiltration. Sialylated milk oligosaccharides have previously been shown to inhibit these inflammatory processes. Methods The aim of this study was to examine the inhibitory effect of sialyllactose (SL) on IL‐8 production via mitogen‐activated protein kinases (MAPK) and nuclear factor‐kappa B (NF‐kB) in TNF‐alpha‐stimulated human colon epithelial cells (HT‐29). HT29 cells were stimulated with TNF‐alpha in the presence or absence of 3′‐ and 6′‐SL. IL‐8 secretion was determined by ELISA and expression of IL‐8 and NF‐kB p65 by real time PCR. MAPK activation was assessed using a proteome profiler array. Results 3′‐ and 6′‐SL (1 mg/mL) suppressed IL‐8 mRNA expression (35.8 ± 5.4% and 38.6 ± 6.3% of controls) and secretion (66.8 ± 4.1% and 76.8 ± 8.4% of controls, respectively). Furthermore, SL significantly inhibited the TNF‐alpha induced phosphorylation of the MAPK ERK1/2 and p38‐delta as well as the expression of NF‐kB p65. Conclusions These observations suggest that milk oligosaccharides may reveal an anti‐inflammatory potential on intestinal epithelial cells possibly by interfering with the signaling pathway downstream of the ligand/receptor binding.
Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluaton of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimidazolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases (1989)

A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD-inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects.
Kinetics of T-cell receptor binding to peptide/I-Ek complexes: correlation of the dissociation rate with T-cell responsiveness. (1994)

Recognition by T-cell antigen receptors (TCRs) of processed peptides bound to major histocompatibility complex (MHC) molecules is required for the initiation of most T-lymphocyte responses. Despite the availability of soluble forms of TCRs and MHC heterodimers, this interaction has proven difficult to study directly due to the very low affinity. We report here on the kinetics of TCR binding to peptide/MHC complexes in a cell-free system using surface plasmon resonance. The apparent association rates for the interactions of related peptide/MHC complexes to one such TCR are relatively slow (900-3000 M-1.s-1) and dissociation rates are very fast (0.3-0.06 s-1) with t1/2 of 2-12 s at 25 degrees C. The calculated affinity of the engineered soluble molecules compares well with previously reported competition data for native TCRs or competition data reported here for native peptide/MHC complexes, indicating that these soluble heterodimers bind in the same manner as the original molecules expressed on cells. We also find that the peptide variants which give weaker T-cell stimulatory responses have similar affinities but distinctly faster dissociation rates compared with the original peptide (when loaded onto the MHC molecule) and that this later property may be responsible for their lower activity. This has implications for both downstream signaling events and models of TCR-peptide antagonists.
Stabilizer Quantum Error Correction Toolbox for Superconducting Qubits (2013)

We present a general protocol for stabilizer operator measurements in a system of N superconducting qubits. Using the dispersive coupling between the qubits and the field of a resonator as well as single qubit rotations, we show how to encode the parity of an arbitrary subset of M ≤ N qubits, onto two quasiorthogonal coherent states of the resonator. Together with a fast cavity readout, this enables the efficient measurement of arbitrary stabilizer operators without locality constraints.
Quantitative Characterization of Obliquely Deposited Substrates of Gold by Atomic Force Microscopy:  Influence of Substrate Topography on Anchoring of Liquid Crystals (1999)

We report the use of atomic force microscopy (AFM) to characterize quantitatively the structural anisotropy within ultrathin (thickness of ∼10 nm) obliquely deposited films of gold and thereby calculate the influence of this anisotropy on the orientations of liquid crystals (LCs) supported on these surfaces. Whereas visual inspection of AFM images (real space or reciprocal space) reveals no obvious structural anisotropy within these gold films, a quantitative analysis of the AFM profiles does show a subtle level of anisotropy on wavelengths comparable to the lateral dimensions of the gold grains (∼30 nm). Our analysis reveals the root-mean-square (rms) slope of the surface topography to be ∼1° greater in a direction parallel to the direction of deposition of the gold as compared to the perpendicular direction. We also demonstrate the rms curvature of the grains of gold to be greatest in a direction parallel to deposition. Because the amplitude of the surface roughness (∼2 nm) is small compared to its wavelength (∼30 nm), the influence of the surface roughness on the orientations of supported LCs can be described through an elastic mechanism of anchoring. By combining the multimode Berreman-de Gennes model for the elastic free energy density of a nematic LC with AFM profiles of the topography of obliquely deposited gold films, we calculate the azimuthal anchoring energy of the supported LC to be ∼0.015 mJ/m2, a value that is consistent with estimates of anchoring energies obtained by fabrication of twisted nematic LC cells. The results reported in this paper provide a route to the characterization of surfaces with designed levels of anisotropy suitable for control of the anchoring of LCs. This capability will, we believe, find application in studies aimed at exploring the use of LCs for amplification and transduction of events of molecular recognition (e.g., antigen−antibody) at surfaces.
Space to think (2010)

Space supports human cognitive abilities in a myriad of ways. The note attached to the side of the monitor, the papers spread out on the desk, diagrams scrawled on a whiteboard, and even the keys left out on the counter are all examples of using space to recall, reveal relationships, and think. Technological advances have made it possible to construct large display environments in which space has real meaning. This paper examines how increased space affects the way displays are regarded and used within the context of the cognitively demanding task of sensemaking. A pair of studies were conducted demonstrating how the spatial environment supports sensemaking by becoming part of the distributed cognitive process, providing both external memory and a semantic layer.
Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. (1993)

Exendin-4 purified from Heloderma suspectum venom shows structural relationship to the important incretin hormone glucagon-like peptide 1-(7-36)-amide (GLP-1). We demonstrate that exendin-4 and truncated exendin-(9-39)-amide specifically interact with the GLP-1 receptor on insulinoma-derived cells and on lung membranes. Exendin-4 displaced 125I-GLP-1, and unlabeled GLP-1 displaced 125I-exendin-4 from the binding site at rat insulinoma-derived RINm5F cells. Exendin-4 had, like GLP-1, a pronounced effect on intracellular cAMP generation, which was reduced by exendin-(9-39)-amide. When combined, GLP-1 and exendin-4 showed additive action on cAMP. They each competed with the radio-labeled version of the other peptide in cross-linking experiments. The apparent molecular mass of the respective ligand-binding protein complex was 63,000 Da. Exendin-(9-39)-amide abolished the cross-linking of both peptides. Exendin-4, like GLP-1, stimulated dose dependently the glucose-induced insulin secretion in isolated rat islets, and, in mouse insulinoma beta TC-1 cells, both peptides stimulated the proinsulin gene expression at the level of transcription. Exendin-(9-39)-amide reduced these effects. In conclusion, exendin-4 is an agonist and exendin-(9-39)-amide is a specific GLP-1 receptor antagonist.
Engineering TGF-β Traps: Artificially Dimerized Receptor Ectodomains as High-affinity Blockers of TGF-β Action (2008)

Receptor ectodomain-based ligand traps are a new class of candidate therapeutics that can be optimized using protein engineering approaches that are built on an understanding of the interactions between natural receptors and their ligands. We present here a summary of our characterization of TGF-β ligand-receptor interactions using primarily surface plasmon resonance (SPR)-based biosensor analyses. The results of those studies lead us to hypothesize that artificial dimerization of TGF-β receptor ectodomains may provide a bridged-binding avidity effect that promotes stable binding and increased ligand trapping potency. We confirmed this by utilizing a de novo designed heterodimerizing coiled-coil peptide system to generate, and compare in a systematic manner, monomeric and dimeric versions of soluble TGF-β receptor ectodomains. Finally, we discuss how the potency and specificity of artificially dimerized receptor ectodomain-based traps may compare favorably with other classes of TGF-β pathway inhibitors.
Gene Transfer Methods for Plants and Cell Cultures (2007)

Agrobacterium-mediated gene transfer provides a routine and efficient gene transfer system for a variety of plant species. As this biological vector does not, however, function with important plant species, numerous alternative approaches have been studied. Of those, direct gene transfer into protoplasts, microinjection and biolistics have been demonstrated to be effective. Others, for example, viral vectors, agroinfection, liposome injection and electrophoresis may have special merits, although transgenic plants have not been produced by these techniques yet. From methods based on pollen transformation, the pollen tube pathway, pollen maturation, incubation of dry seeds, incubation of tissues, liposome fusion with tissues, macroinjection, laser treatment and electroporation of tissues no proof of integrative transformation is available, so far, and it is difficult to envisage how these approaches will ever produce transgenic cells and plants. We discuss (a) why Agrobacterium does not function with all plants, (b) what merits and disadvantages we see for the effective methods, (c) what possibilities we foresee for some of the other approaches, and (d) why we do not expect the remaining ones to be successful.
Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. (1978)

MCF-7 cells of human breast cancer origin responded to estradiol (E) treatment with increased levels of progesterone receptor (PgR) showing that human breast cells which have undergone malignant changes can continue to synthesize a specific protein under hormone control. These results were obtained by studying the effects of addition and withdrawal of E on PgR synthesis and correlating this with estrogen receptor (ER) binding translocation nuclear processing reactions and restoration of unoccupied ER. In cells treated 1-5 days with E (.001-100 nM) basal PgR levels (.3-.7 pmol/mg of deoxyribonucleic acid) increased 3-6 fold. PgR response was dose-dependent with .1 nM E (a physiologic dose) the maximal effective dose. Growth and induction of PgR by .1 nM E was suppressed by an antiestrogen Tamoxifen at 10000-fold molar excess (1 mcgM) but was reversed by supraphysiological E (10 nM) which reduced the molar excess of Tamoxifen to only 100-fold. In this cell line ER unoccupied by hormone was not restricted to the cytoplasm (Rc) since a portion of the cellular receptor can also be found in the nucleus in unoccupied form (RN). The level of PgR induction correlated with the extent of Rc binding and translocation and also with the extent of Rn binding. At .1 nM E 85% of Rc and Rn were depleted and PgR was maximally stimulated. The levels of PgR also paralleled processing of bound ER (RnE) appearing in the nucleus. Processing during which a new steady-state level of RnE was achieved appeared to be a saturable event. At low E doses despite Rc and Rn binding of E RnE failed to accumulate and total ER decreased. The loss approached 70% at .1 nM E. But at higher E doses some nuclear receptor remained unprocessed and RnE levels increased. The processing effect was rapid beginning within 10 minutes of E addition and completed by 5 hours. Processed RnE levels were seen before PgR induction and during maintenance of induced PgR states. In estrogen withdrawn cells PgR fell in parallel with end of processing and restoration of Rc and Rn.
High-power Yb-doped multicore ribbon fiber laser (2005)

A highly elongated double-clad ribbon fiber that comprises a pure-silica inner cladding with transverse dimensions of approximately 1.4 mm by 0.23 mm with a linear array of ten ytterbium-doped cores has been fabricated and operated in a simple laser configuration pumped by two diode stacks. The fiber laser yielded 320 W of output power at a center wavelength of 1045 nm in a combined beam with beam propagation factors of approximately 2 (perpendicular to the array) and approximately 150 (parallel to the array) for 576 W of launched pump power. The slope efficiency with respect to absorbed pump power was 62%. The prospects for further power scaling and improved beam quality and efficiency are discussed.
Ultrafast electron diffraction with radio-frequency compressed electron pulses (2012)

We report on the complete characterization of time resolution in an ultrafast electron diffraction (UED) instrument based on radio-frequency electron pulse compression. The temporal impulse response function of the instrument was determined directly in pump-probe geometry by performing electron-laser pulse cross-correlation measurements using the ponderomotive interaction. With optimal settings, a stable impulse response of 334±10 fs was measured at a bunch charge of 0.1 pC (6.24 × 105 electrons/pulse); a dramatic improvement compared to performance without pulse compression. Phase stability currently limits the impulse response of the UED diffractometer to the range of 334–500 fs, for bunch charges ranging between 0.1 and 0.6 pC.
Role of KEAP1 / NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance (2016)

We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86-101. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.
Salivary testosterone in postmenopausal women with rheumatoid arthritis. (1998)

Testosterone in saliva is a useful indicator for monitoring androgenic status in women with RA.