gebhart/patrepeval huggingface dataset:
A Novel Series of 2,5-Substituted Tryptamine Derivatives as Vascular 5HT1B/1D Receptor Antagonists (1997)

The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or ethylene-linked 5-side chain. Careful design of new molecules based on a proposed pharmacophoric model of the 5HT1B-like receptor has resulted in the discovery of ethyl 3-[2-(dimethylamino)ethyl]-5-[2-(2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate (40), a highly potent, silent, competitive, and selective antagonist which shows affinity at the vascular 5HT1B-like receptors only. Changes to the size of the 2-ester substituent have a significant effect on affinity at the 5HT1B-like receptor and other receptors. Prudent placement of the carbonyl substituent in the heterocycle of the 5-side chain is crucial for good affinity and selectivity over the 5HT2A and other receptors. Several key structural and electronic features were identified which are crucial for producing antagonism within a tryptamine-based series. An electron deficient indole ring system appears essential in order to achieve antagonism, and this is achieved by the inclusion of electron-withdrawing groups at the 2-position of the indole ring. The molecule displacement within the receptor resulting from the inclusion of the bulky 2-substituents also enhances antagonism as this results in the removal of the pi electron density of the indole ring from the region of the receptor normally occupied by the indole ring of 5HT. There also appears to be a structural requirement on the side chain incorporating the protonatable nitrogen, and this is achieved by the inclusion of the bulky 2-ester group which neighbors the 3-ethylamine side chain.
Application of space–time duality to ultrahigh-speed optical signal processing (2013)

Manipulation and characterization of information using ultrafast optical signals is critical for numerous applications in telecommunications, biology, quantum information science, spectroscopy, and atomic and molecular physics. Femtosecond pulsed laser sources are available over a wide range of wavelengths and repetition rates, which enable the generation, transmission, and characterization of information at bandwidths beyond 1&#xA0;THz. In this article, we review the concept of space&#x2013;time duality as a system design tool for ultrafast optical processing and characterization. The combination of this design framework with recent advances in nonlinear optical devices enables the realization of highly complex signal processing systems that can generate, characterize, and manipulate arbitrary and non-repetitive optical waveforms at unprecedented processing speeds.
p54nrb is a component of the snRNP-free U1A (SF-A) complex that promotes pre-mRNA cleavage during polyadenylation (2005)

The U1 snRNP-A (U1A) protein has been known for many years as a component of the U1 snRNP. We have previously described a form of U1A present in human cells in significant amounts that is not associated with the U1 snRNP or U1 RNA but instead is part of a novel complex of non-snRNP proteins that we have termed snRNP-free U1A, or SF-A. Antibodies that specifically recognize this complex inhibit in vitro splicing and polyadenylation of pre-mRNA, suggesting that this complex may play an important functional role in these mRNA-processing activities. This finding was underscored by the determination that one of the components of this complex is the polypyrimidine-tract-binding protein-associated splicing factor, PSF. In order to further our studies on this complex and to determine the rest of the components of the SF-A complex, we prepared several stable HeLa cell lines that overexpress a tandem-affinity-purification-tagged version of U1A (TAP-tagged U1A). Nuclear extract was prepared from one of these cell lines, line 107, and affinity purification was performed along with RNase treatment. We have used mass spectrometry analysis to identify the candidate factors that associate with U1A. We have now identified and characterized PSF, p54(nrb), and p68 as novel components of the SF-A complex. We have explored the function of this complex in RNA processing, specifically cleavage and polyadenylation, by performing immunodepletions followed by reconstitution experiments, and have found that p54(nrb) is critical.
The POZ domain: a conserved protein-protein interaction motif. (1994)

We describe a novel zinc finger protein, ZID (zinc finger protein with interaction domain). At its amino terminus ZID contains a 120-amino-acid conserved motif present in a large family of proteins that includes both the otherwise unrelated zinc finger proteins, such as Ttk, GAGA, and ZF5, and a group of poxvirus proteins: We therefore refer to this domain as the POZ (poxvirus and zinc finger) domain. The POZ domains of ZID, Ttk, and GAGA act to inhibit the interaction of their associated finger regions with DNA. This inhibitory effect is not dependent on interactions with other proteins and does not appear dependent on specific interactions between the POZ domain and the finger region. The POZ domain acts as a specific protein-protein interaction domain: The POZ domains of ZID and Ttk can interact with themselves but not with each other, POZ domains from ZF5, or the viral protein SalF17R. However, the POZ domain of GAGA can interact efficiently with the POZ domain of Ttk. In transfection experiments, the ZID POZ domain inhibits DNA binding in NIH-3T3 cells and appears to localize the protein to discrete regions of the nucleus. We discuss the implications of multimerization for the function of POZ domain proteins.
Design of a multiplexing grating for color holographic waveguide (2015)

Volume holographic gratings have been used in waveguide displays to implement full-color three-dimensional imaging. Among these, multiplexing gratings are advanced in low energy losses and simple manufacture technologies when used as couplers of color hologram waveguides. A multiplexing holographic grating is designed to realize a uniform red, green, and blue diffraction efficiency and eliminate stray light to the largest extent. Results indicate that the red, green, and blue light incident normal to the grating could be successfully in-coupled into the planar waveguide for total internal reflection with high peak diffraction efficiency, similar energy output, and little stray light. We also analyze the effect of the technical tolerance, including gating thickness, index modulation, grating period, slanted angle, and incident angle. This analysis could help to minimize the optical system and improve the color image quality of waveguide displays.
Mesoscopic structural organization in fluorinated room temperature ionic liquids (2018)

The presence of fluorous tails in room-temperature ionic liquids imparts new properties to their already rich spectrum of appealing features. The interest towards this class of compounds that are of ionic nature with melting point less than 25 °C is accordingly growing; in particular, compounds bearing relatively long fluorous tails have begun to be considered. In this invited presentation, we show recent results arising from the systematic study of structural properties of a series of fluorinated room temperature ionic liquids, with growing fluorous chain length. At odd with the current understanding of this class of compounds, we show experimentally that they are characterized by the presence of segregated fluorous domains whose size depends on the fluorous chain length. This experimental finding, based on the synergic use of X-ray and neutron scattering, provides a structural scenario at the mesoscopic spatial scale that is in agreement with the recent state of the art molecular dynamic simulations. We speculate on the potential role of this significant compartmentalization of the bulk liquid phase into different nanoscale domains, as relevant in a series of applications including separation, solubility, catalysis, and so forth.
Does the Naked Fluoride Ion Exist? (1992)

Of course in a chemical environment the F − ion cannot exist —this is the answer to the question in the title of this highlight. But in 1991 two reagents were described that make an almost naked fluoride ion available. K. O. Christl et al. synthesized for the first time pure Me 4 N + F − , from which complex fluoro anions with high coordination numbers can be prepared (for example, [XeF 5 ] − and [IF 8 ] − ). R. Schwesinger et al. succeeded in preparing anhydrous [(Me 2 N) 3 PNP (NMe 2 ) 3 ] + F − , which has an extremely large cation–anion distance and promises to be a useful reagent in organic synthesis.
P-Selectin Glycoprotein Ligand-1 (PSGL-1) on T Helper 1 but Not on T Helper 2 Cells Binds to P-Selectin and Supports Migration into Inflamed Skin (1997)

We have shown recently that mouse Th1 cells but not Th2 cells are selectively recruited into inflamed sites of a delayed-type hypersensitivity (DTH) reaction of the skin. This migration was blocked by monoclonal antibodies (mAb) against P- and E-selectin. Here we show that Th1 cells bind to P-selectin via the P-selectin glycoprotein ligand-1 (PSGL-1). This is the only glycoprotein ligand that was detectable by affinity isolation with a P-selectin-Ig fusion protein. Binding of Th1 cells to P-selectin, as analyzed by flow cytometry and in cell adhesion assays, was completely blocked by antibodies against PSGL-1. The same antibodies blocked partially the migration of Th1 cells into cutaneous DTH reactions. This blocking activity, in combination with that of a mAb against E-selectin, was additive. PSGL-1 on Th2 cells, although expressed at similar levels as on Th1 cells, did not support binding to P-selectin. Thus, the P-selectin-binding form of PSGL-1 distinguishes Th1 cells from Th2 cells. Furthermore, PSGL-1 is relevant for the entry of Th1 cells into inflamed areas of the skin. This is the first demonstration for the importance of PSGL-1 for mouse leukocyte recruitment in vivo.
APRIL-Deficient Mice Have Normal Immune System Development (2004)

APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL(-/-) mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.
Low-melting sugar–urea–salt mixtures as solvents for Diels–Alder reactions (2005)

Sweet solutions are obtained upon heating mixtures of simple carbohydrates, urea and inorganic salts to moderate temperatures, to give new chiral media for organic reactions.
Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells. (1994)

To understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.
Delineation of an Active Fragment and Poly(l-proline) II Conformation for Candidacidal Activity of Bactenecin 5 (1996)

Bactenecin 5 and its fragments [BN22 (1-22), BN16 (7-22), and BC24 (20-43)] were synthesized by solid-phase methods. Their antifungal activities on Candida albicans have been studied and compared with those of the native bactenecin 5. The conformational preferences of these peptides in aqueous and nonaqueous solutions and in lipid vesicles were examined by circular dichroism. The highly active N-terminal fragment (BN16) was examined in aqueous solution using 500 MHz two-dimensional NMR. Bactenecin 5 and its fragments are potent candidacidal agents against C. albicans. The N-terminal fragments (BN22 and BN16) of bactenecin 5 are relatively more active than the C-terminal fragment BC24, especially at lower concentrations. The N-terminal region (7-22) which retains the activity of the whole molecule appears to be the functional domain for candidacidal activity. The CD spectra of bactenecin 5 and its fragments are reminiscent of the CD spectrum of poly(L-proline) type II structure in aqueous and nonaqueous solutions and also in lipid vesicles. The temperature dependence of NH chemical shifts and 1H/2H exchange effect on amide resonances suggest the absence of intramolecularly hydrogen-bonded NH groups. The coupling constant (JNH-CalphaH) values, conformational restriction offered by the Pro residues (phi = -60 degrees +/- 15 degrees), the set of medium- and short-range nuclear Overhauser effects observed for the active N-terminal fragment (BN16), and the restrained structure calculation using DIANA suggest that poly(L-proline) type II conformers of the peptide molecules could be significantly populated in aqueous solution. The ability of bactenecin peptides to induce disruption of lipid vesicles correlates well with their activity. Our results suggest that poly(L-proline) type II structure may, indeed, be the biologically active conformation for candidacidal activity of bactenecin peptides.
Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. (1995)

The gene product of the recently cloned mouse obese gene (ob) is important in regulating adipose tissue mass. ob RNA is expressed specifically by mouse adipocytes in vivo in each of several different fat cell depots, including brown fat. ob RNA is also expressed in cultured 3T3-442A preadipocyte cells that have been induced to differentiate. Mice with lesions of the hypothalamus, as well as mice mutant at the db locus, express a 20-fold higher level of ob RNA in adipose tissue. These data suggest that both the db gene and the hypothalamus are downstream of the ob gene in the pathway that regulates adipose tissue mass and are consistent with previous experiments suggesting that the db locus encodes the ob receptor. In db/db and lesioned mice, quantitative differences in expression level of ob RNA correlated with adipocyte lipid content. The molecules that regulate expression level of the ob gene in adipocytes probably are important in determining body weight, as are the molecules that mediate the effects of ob at its site of action.
Biochemistry and biomechanics of healing tendon (1998)

Biochemistry and biomechanics of healing tendon: Part II. effects of combined laser therapy and electrical stimulation. Med. Sci. Sports Exerc., Vol. 30, No. 6, pp. 794-800, 1998. Purpose: In previous studies we demonstrated that early mechanical loading and laser photo-stimulation independently promoted tendon healing. Thus, we tested the hypothesis that a combination of laser phototherapy and mechanical load would further accelerate healing of experimentally tenotomized and repaired rabbit Achilles tendons. Methods: Following surgical tenotomy and repair, the tendons of experimental and control rabbits were immobilized in polyurethane casts for 5 d. The repaired tendons of experimental rabbits received mechanical load via electrical stimulation-induced contraction of the triceps surae for 5 d. In addition, experimental tendons were treated with daily doses of 1 J·cm−2 low intensity helium-neon laser throughout the 14-d experimental period. Results: The combination of laser photostimulation and mechanical load increased the maximal stress, maximal strain, and Young's modulus of elasticity of the tendons 30, 13, and 33%, respectively. However, MANOVA revealed no statistically significant differences in these biomechanical indices of repair of control and experimental tendons. Biochemical assays showed a 32% increase in collagen levels (P < 0.05) and an 11% decrease in mature cross-links in experimental tendons compared with that in controls (P > 0.05). Electron microscopy and computer morphometry revealed no significant differences in the morphometry of the collagen fibers and no visible differences in the ultrastructure of cellular and matrical components of control and experimental tendons. Conclusions: These findings indicate that the combination of laser photostimulation and early mechanical loading of tendons increased collagen production, with marginal biomechanical effects on repaired tendons.
A single naturally processed measles virus peptide fully dominates the HLA-A*0201-associated peptide display and is mutated at its anchor position in persistent viral strains (2000)

We studied the natural MHC class I display of measles virus (MV) epitopes. Peptide ligands associated with HLA-A*0201 were purified from a B lymphoblastoid cell line prior to and after infection with MV. Infection-induced peptides were revealed using microcapillary reversed phase high performance liquid chromatography electrospray ionization/mass spectrometry (microLC-ESI/MS) by subtraction of the "infected" and "uninfected" ion traces. Three naturally processed viral epitopes derived from different MV proteins were identified through tandem MS sequencing. These peptides were expressed at widely divergent levels of HLA-peptide complexes, but had similar binding capacities to HLA-A*0201. The most abundant viral peptide species, identified as residues 84-92 (KLWESPQEI) of the MV nonstructural C protein, was expressed at an unprecedented high density (> 10(5) copies per cell) and was immunogenic in HLA-A2/Kb-transgenic mice. Furthermore, natural mutants of this epitope, occurring in persistent lethal MV strains, were shown to have lost their HLA-A*0201 binding capacity. Thus, here we report for the first time the direct discovery through microLC-ESI/MS of a uniquely dominant viral HLA class I ligand, KLWESPQEI, with features eligible for immune selection pressure.
Molecular analysis of the recF gene of Escherichia coli. (1984)

We analyzed the nucleotide sequence of a 1.325-kilobase region of wild-type Escherichia coli containing a functional recF gene and six Tn3 mutations that inactivate recF. The analysis shows a potentially translatable reading frame of 1071 nucleotides, which is interrupted by all six insertions. A protein of 40.5 kilodaltons would result from translation of the open reading frame, and a radioactive band of protein of an apparent molecular weight of approximately 40 kilodaltons was seen by the maxicell method using a recF+ plasmid. Putative truncated peptides were seen when two recF::Tn3 mutant plasmids were used. Differential expression of dnaN and recF from a common promoter was noted. recF332::Tn3 was transferred to the chromosome where, in hemizygous condition, it produced UV sensitivity indistinguishable from that produced by two presumed recF point mutations.
Placenta growth factor stimulates the growth of Philadelphia chromosome positive acute lymphoblastic leukemia cells by both autocrine and paracrine pathways (2005)

Vascular endothelial growth factor (VEGF) and its associated molecule, placenta growth factor (PlGF) are now known to support normal hematopoiesis, and leukemia cell growth. In this study, expression of VEGF and PlGF in acute lymphoblastic leukemia (ALL) cells was examined by real time reverse transcription-polymerase chain reaction in 20 patient samples. Expression of PlGF was more intense in Philadelphia chromosome positive (Ph(+)) ALL than in Ph(-) ALL cases. On the other hand, expression level of VEGF was not different between Ph(+) and Ph(-) cases. Then, PlGF was added to the two ALL cell lines, CRL1929 (Ph(+)), and Nalm6 (Ph(-)). The PlGF stimulated the growth of CRL1929 in time- and dose-dependent manners, although the growth of Nalm6 was not affected by PlGF. The growth stimulation of CRL1929 by PlGF was confirmed by the increase of S phase cells. And the growth promoting effect of PlGF on CRL1929 was cancelled by simultaneous addition of VEGFR1/Fc (which binds to PlGF and abrogates its function), but was not cancelled by VEGFR2/Fc (which does not bind to PlGF). Then, addition of VEGFR1/Fc to the simple culture of CRL1929 demonstrated growth inhibitory effect. These observations demonstrated that PlGF stimulates the growth of Ph(+) ALL cells by both autocrine and paracrine pathways. Finally, PlGF-VEGFR1 loop might be a therapeutic target to improve the prognosis of Ph(+) ALL.
Heteronuclear decoupling in rotating solids (1995)

A simple two pulse phase modulation (TPPM) scheme greatly reduces the residual linewidths arising from insufficient proton decoupling power in double resonance magic angle spinning (MAS) experiments. Optimization of pulse lengths and phases in the sequence produces substantial improvements in both the resolution and sensitivity of dilute spins (e.g., 13C) over a broad range of spinning speeds at high magnetic field. The theoretical complications introduced by large homo- and heteronuclear interactions among the spins, as well as the amplitude modulation imposed by MAS, are explored analytically and numerically. To our knowledge, this method is the first phase-switched sequence to exhibit improvement over continuous-wave (cw) decoupling in a strongly coupled homogeneous spin system undergoing sample spinning.