gebhart/patrepeval huggingface dataset:
Impaired Granulocytic Differentiation In Vitro in Hematopoietic Cells Lacking Retinoic Acid Receptors α1 and γ (1998)

Transcripts for the retinoic acid receptors (RARs) alpha1, alpha2, gamma1, and gamma2 were found in the granulocytic lineage (Gr-1+ cells) through semiquantitative polymerase chain reaction (PCR) analysis. The screening of single cell cDNA libraries derived from hematopoietic progenitors also showed the presence of RARalpha and, to a lesser extent, RARgamma transcripts in committed granulocyte (colony-forming unit-granulocyte [CFU-G]) or granulocyte-macrophage (CFU-GM) colony-forming cells. The contribution of RARalpha1 and gamma to hematopoietic cell differentiation was therefore investigated in mice bearing targeted disruption of either one or both of these loci. Because RARgamma and RARalpha1gamma compound null mutants die shortly after birth, bone marrow cells were collected from fetuses at 18.5 days postcoitum (dpc) and evaluated for growth and differentiation in culture in the presence of Steel factor (SF), interleukin-3 (IL-3), and erythropoietin (Epo). The frequency of colony-forming cells from bone marrow populations derived from RARalpha1/gamma double null mice was not significantly different from that of RARgamma or RARalpha1 single nulls or from wild-type controls. In addition, the distribution of erythroid, granulocyte, and macrophage colonies was comparable between hematopoietic cells from all groups, suggesting that lineage commitment was not affected by the lack of RARalpha1 and/or RARgamma. Colony cells were then harvested individually and evaluated by morphologic criteria. While terminal granulocyte differentiation was evident in wild-type cells and colonies from either single null mutant, colonies derived from RARalpha1-/-gamma-/- bone marrow populations were blocked at the myelocyte and, to a lesser extent, at the metamyelocyte stages, whereas erythroid and macrophage differentiation was not affected. Together, these results indicate that both RARalpha1 and gamma are required for terminal maturation in the granulocytic lineage in vitro, but appear to be dispensable for the early stages of hematopoietic cell development. Our results raise the possibility that in acute promyelocytic leukemia (APL), the RARalpha fusion proteins cause differentiation arrest at a stage when further maturation requires not only RARalpha, but also RARgamma. Finally, bone marrow cells appear to differentiate normally in vivo, suggesting an effective compensation mechanism in the RARalpha1/gamma double null mice.
A quadruple subharmonic phase-conjugating array for secure picosatellite crosslinks (2004)

A retrodirective array for use in secure picosatellite networks is presented. This is the first reported array that uses quadruple subharmonic mixing which relaxes the requirements on a high-frequency local oscillator. The array demonstrates circular polarization and two-dimensional retrodirectivity for a free-floating satellite environment. Bistatic radiation-pattern measurements demonstrate the effectiveness of the design.
Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine (2012)

Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the low frequency of HSV-1-specific T cells have hampered the search for the most effective T cell antigens for inclusion in a candidate vaccine. We have now developed what we believe to be novel methods to efficiently generate a genome-wide map of the responsiveness of HSV-1-specific T cells, and demonstrate the applicability of these methods to a second complex microbe, vaccinia virus. We used cross-presentation and CD137 activation-based FACS to enrich for polyclonal CD8+ T effector T cells. The HSV-1 proteome was prepared in a flexible format for analyzing both CD8+ and CD4+ T cells from study participants. Scans with participant-specific panels of artificial APCs identified an oligospecific response in each individual. Parallel CD137-based CD4+ T cell research showed discrete oligospecific recognition of HSV-1 antigens. Unexpectedly, the two HSV-1 proteins not previously considered as vaccine candidates elicited both CD8+ and CD4+ T cell responses in most HSV-1-infected individuals. In this era of microbial genomics, our methods - also demonstrated in principle for vaccinia virus for both CD8+ and CD4+ T cells - should be broadly applicable to the selection of T cell antigens for inclusion in candidate vaccines for many pathogens.
CYP92B1, A Cytochrome P450, Expressed in Petunia Flower Buds, That Catalyzes Monooxidation of Long-Chain Fatty Acids (2002)

In higher plants, long-chain fatty acid hydroperoxides are intermediates in the synthesis of a diverse group of bioactive compounds. We used the reverse trascriptase-polymerase chain reaction to isolate a gene responsible for the oxidization of fatty acids from Petunia hybrida. A P450 cDNA not isolated earlier, CYP92B1, contained an open reading frame predicted to encode a polypeptide consisting of 510 amino acid residues. The transcript of the cyp92B1 gene was expressed at a high level in the early stage of flower development. CYP92B1 cDNA was expressed in a yeast, Saccharomyces cerevisiae, and recombinant yeast microsomes containing CYP92B1, a hemoprotein, metabolized lauric acid, linoleic acid, and linolenic acid.
A Variational Analysis of Stochastic Gradient Algorithms (2016)

Stochastic Gradient Descent (SGD) is an important algorithm in machine learning. With constant learning rates, it is a stochastic process that, after an initial phase of convergence, generates samples from a stationary distribution. We show that SGD with constant rates can be effectively used as an approximate posterior inference algorithm for probabilistic modeling. Specifically, we show how to adjust the tuning parameters of SGD such as to match the resulting stationary distribution to the posterior. This analysis rests on interpreting SGD as a continuous-time stochastic process and then minimizing the Kullback-Leibler divergence between its stationary distribution and the target posterior. (This is in the spirit of variational inference.) In more detail, we model SGD as a multivariate Ornstein-Uhlenbeck process and then use properties of this process to derive the optimal parameters. This theoretical framework also connects SGD to modern scalable inference algorithms; we analyze the recently proposed stochastic gradient Fisher scoring under this perspective. We demonstrate that SGD with properly chosen constant rates gives a new way to optimize hyperparameters in probabilistic models.
Very sparse random projections (2006)

There has been considerable interest in random projections, an approximate algorithm for estimating distances between pairs of points in a high-dimensional vector space. Let A in Rn x D be our n points in D dimensions. The method multiplies A by a random matrix R in RD x k, reducing the D dimensions down to just k for speeding up the computation. R typically consists of entries of standard normal N(0,1). It is well known that random projections preserve pairwise distances (in the expectation). Achlioptas proposed sparse random projections by replacing the N(0,1) entries in R with entries in -1,0,1 with probabilities 1/6, 2/3, 1/6, achieving a threefold speedup in processing time.We recommend using R of entries in -1,0,1 with probabilities 1/2√D, 1-1√D, 1/2√D for achieving a significant √D-fold speedup, with little loss in accuracy.
Control of sp2/sp3 Carbon Ratio and Surface Chemistry of Nanodiamond Powders by Selective Oxidation in Air (2006)

The presence of large amounts of nondiamond carbon in detonation-synthesized nanodiamond (ND) severely limits applications of this exciting nanomaterial. We report on a simple and environmentally friendly route involving oxidation in air to selectively remove sp(2)-bonded carbon from ND. Thermogravimetric analysis and in situ Raman spectroscopy shows that sp(2) and sp(3) carbon species oxidize with different rates at 375-450 degrees C and reveals a narrow temperature range of 400-430 degrees C in which the oxidation of sp(2)-bonded carbon occurs with no or minimal loss of diamond. X-ray absorption near-edge structure spectroscopy detects an increase of up to 2 orders of magnitude in the sp(3)/sp(2) ratio after oxidation. The content of up to 96% of sp(3)-bonded carbon in the oxidized samples is comparable to that found in microcrystalline diamond and is unprecedented for ND powders. Transmission electron microscopy and Fourier transform infrared spectroscopy studies show high purity 5-nm ND particles covered by oxygen-containing surface functional groups. The surface functionalization can be controlled by subsequent treatments (e.g., hydrogenization). In contrast to current purification techniques, the air oxidation process does not require the use of toxic or aggressive chemicals, catalysts, or inhibitors and opens avenues for numerous new applications of nanodiamond.
Requirements for successful immunotherapy and chemoimmunotherapy of a murine model of ovarian cancer. (1981)

A comprehensive study of nonspecific immunotherapy has been conducted in an established murine model of ovarian cancer in order to determine the relative effectiveness of commonly used bacterial immunostimulants, the importance of the route and schedule of administration of these agents, and their effects in combination with chemotherapy. Implants of 10(5) or 10(6) ovarian tumor cells i.p. kill all syngeneic C3HeB/FeJ mice within 25 days. Corynebacterium parvum (700 microgram/mouse i.p. 24 hr after a 10(5) tumor cell inoculum) cures 75% of the mice; in contrast, neither i.v. nor s.c. administration improves survival rates. After the same tumor challenge, Bacillus Calmette-Guérin was minimally effective at extremely high doses only, while the methanol extraction residue of B. Calmette-Guérin was ineffective. Two days after an implant of 10(6) tumor cells, neither cyclophosphamide, nor cis-diamminedichloroplastinum(II) (cisplatin), nor C. parvum increased survival. Combination of C. parvum with cyclophosphamide or cisplatin resulted in a synergism shown by the 40 and 60% cure rates, respectively. However, combination of C. parvum with an active agent, doxorubicin, resulted in toxicity even in untumored animals. This study demonstrates that therapeutic efficacy of immunotherapy depends critically on the choice of an appropriate agent and route of administration and, to a lesser extent, on the dose and schedule used. The observation provides a rationale for carefully conducted Phase I and Phase II studies of treatment with bacterial immunostimulants, alone or in combination with chemotherapy, in human ovarian cancer.
Construction of adenovirus expression vectors by site-directed in vivo recombination. (1982)

We developed a method for conveniently positioning foreign DNA at many preselected sites in the adenoviral genome by a combination of in vitro and in vivo recombination. Using this technique, we constructed a set of recombinant viruses that contain the SV40 A gene downstream from the adenovirus tripartite leader. One of these hybrid viruses, Ad-SVR26, contains the A gene close to and downstream from both the major late promoter and the first segment of the tripartite leader. The transcripts encoded by the inserted SV40 DNA are highly overproduced in infected cells; they initiate at the adenoviral late promoter and terminate at the SV40 polyadenylation site. Several novel splice acceptor sites in the SV40 sequences are used in the processing of the primary transcript to produce six different species of spliced RNA. The synthesis of T antigen in Ad-SVR26-infected cells requires the use of novel AUG initiation codons present within the SV40 coding region or adenoviral sequences that normally form part of the intron between the first and second segments of the tripartite leader. The level of T antigen expression is not as high as the level of mRNA production. The usage of these new AUG triplets or the absence of the complete adenovirus tripartite leader sequence may account for the low efficiency of translation.
Parallel thermodynamic analysis of duplexes on oligodeoxyribonucleotide microchips (1998)

A microchip method has been developed for massive and parallel thermodynamic analyses of DNA duplexes. Fluorescently labeled oligonucleotides were hybridized with oligonucleotides immobilized in the 100 x 100 x 20 mum gel pads of the microchips. The equilibrium melting curves for all microchip duplexes were measured in real time in parallel for all microchip duplexes. Thermodynamic data for perfect and mismatched duplexes that were obtained using the microchip method directly correlated with data obtained in solution. Fluorescent labels or longer linkers between the gel and the oligonucleotides appeared to have no significant effect on duplex stability. Extending the immobilized oligonucleotides with a four-base mixture from the 3'-end or one or two universal bases (5-nitroindole) from the 3'- and/or 5'-end increased the stabilities of their duplexes. These extensions were applied to increase the stabilities of the duplexes formed with short oligonucleotides in microchips, to significantly lessen the differences in melting curves of the AT- and GC-rich duplexes, and to improve discrimination of perfect duplexes from those containing poorly recognized terminal mismatches. This study explored a way to increase the efficiency of sequencing by hybridization on oligonucleotide microchips.
Nucleoside conformation is determined by the electronegativity of the sugar substituent (1980)

The proton and 13C NMR spectra of uridine, deoxyuridine and four 2' substituted uridines (dUn, dUz, dUcl and dUfl) are reported. A linear relationship between the electronegativity of the 2'-substituent and the carbon-13 chemical shift of C2' is observed. Taking into account the effect of electronegativity by using the correction proposed by Karplus or by Jankowski, the proton-proton coupling constants have been used to compute the conformational equilibria of the six uridines. It is shown that the contribution of the N form (3'-endo -2'-exo) increases with the electronegativity of the 2' substituent. Thus dUfl contains some 85% N form in solution. - Applying similar corrections to published data in the adenosine series, a similar correlation is observed. This observation, that the most polar substituent pulls the pucker to its side, holds also for 3'-substituted compounds, like cordycepin (3'dAdo) and 3'-deoxy-3'-amino-adenosine. It is suggested that the influence of the electronegativity could be the dominating effect of nucleoside conformations and would also hold for arabinosides and xylosides. This effect should therefore also be the principal force which determines the differences between DNA and RNA.
Angiogenesis and cigarette smoking in squamous cell lung carcinomas: an immunohistochemical study of 28 cases. (1999)

Angiogenesis in tumors is influenced by several factors which in turn are associated with chemoresistance or radioresistance. Moreover, the tumors of smokers are known to be relatively resistant to chemotherapy. This investigation attempts to determine whether or not a relationship exists between cigarette smoking and angiogenesis in lung cancer. Tumor samples from 14 non-smokers and 14 heavy cigarette smokers were selected for this study. The populations were matched for age, sex and tumor stage. Resistance to doxorubicin, microvessel density, the expression of vascular endothelial growth factor (VEGF) and thrombospondin (TSP) were analyzed in both populations. Tumors of smokers were more frequently resistant to doxorubicin in vitro, had lower vessel counts and a reduced expression of VEGF compared to tumors of nonsmokers. In contrast, TSP was significantly increased in the tumors of smokers. These data show that angiogenesis in lung tumors is linked to a patient's smoking habits.
Preparative Manipulation of Gold Nanoparticles by Reversible Binding to a Polymeric Solid Support (2005)

A preparative scheme is presented for controlled modification of gold nanoparticles (NPs) by using reversible binding to a polymeric solid support through boronic acid chemistry. Octanethiol-capped Au NPs were bound to a boronic acid functionalized resin by custom-synthesized bifunctional linker molecules. The NPs were chemically released from the resin to the solution, with one (or a few) linker molecules embedded in their capping layer. This was confirmed by rebinding the linker-derivatized NPs to a boronic resin, exploiting the reversibility of the boronic acid/diol chemistry. The same scheme was employed to demonstrate a new method for affinity separation of NPs by means of a solid-phase reaction. The use of boronic acid provides versatility and chemical reversibility, while the polymeric solid support affords the separation and preparative aspects. The method presented here may be useful in various facets of NP handling, manipulation, and separation.
Optical isomerism and biological activity of pharmaceutical preparations (2012)

The paper considers the relationship between optical isomerism and the pharmacological activity of pharmaceutical preparations.
Hepatocyte Growth Factor-induced Scatter of Madin-Darby Canine Kidney Cells Requires Phosphatidylinositol 3-Kinase (1995)

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that induces mitogenesis, motility, invasion, and morphogenesis of several epithelial and endothelial cell lines in culture. The receptor for HGF/SF has been identified as the Met tyrosine kinase. To investigate the signaling pathways that are involved in these events, we have generated chimeric receptors containing the extracellular domain of the colony-stimulating factor-1 (CSF-1) receptor fused to the transmembrane and intracellular domains of the Met receptor (MET). Madin-Darby canine kidney (MDCK) epithelial cells expressing the CSF-MET chimera dissociate and scatter in response to CSF-1. However, cells expressing a mutant CSF-MET receptor containing a phenylalanine substitution for tyrosine 1356 were unable to scatter or form branching tubules following stimulation with CSF-1. Tyrosine 1356 is essential for the recruitment of multiple substrates including the p85 subunit of PI3-kinase, phospholipase C gamma, and Grb2. In this study, we have investigated the role of PI3-kinase and a downstream target of PI3-kinase, pp70S6K, in the induction of MDCK cell scatter in response to HGF/SF. Our results demonstrate that following stimulation with HGF/SF, activation of PI3-kinase but not pp70S6K is essential for MDCK cell scatter.
Characterization of the genes for the hexagonally arranged surface layer proteins in protein-producing Bacillus brevis 47: complete nucleotide sequence of the middle wall protein gene (1988)

Bacillus brevis 47 contains two surface (S)-layer proteins, termed the outer wall protein (OWP) and the middle wall protein (MWP), which form a hexagonal array in the cell wall. The MWP and OWP genes are contained in the 9-kilobase-pair (kbp) BclI fragment and constitute an operon under coordinate control of their expression. The nucleotide sequence of a 3.8-kbp EcoRI-SacI fragment containing the entire MWP gene has been determined in this study. Together with the DNA sequence of the promoter region for the MWP-OWP gene operon (H. Yamagata, T. Adachi, A. Tsuboi, M. Takao, T. Sasaki, N. Tsukagoshi, and S. Udaka, J. Bacteriol. 169:1239-1245, 1987) and that of the OWP gene (A. Tsuboi, R. Uchihi, R. Tabata, Y. Takahashi, H. Hashiba, T. Sasaki, H. Yamagata, N. Tsukagoshi, and S. Udaka, J. Bacteriol. 168:365-373, 1986), the complete nucleotide sequence of the MWP-OWP gene operon has been determined. The MWP gene encodes a secretory precursor of the MWP, consisting of a total of 1,053 amino acid residues with a signal peptide of 23 amino acid residues at its amino-terminal end. Bacillus subtilis harboring the MWP gene synthesized an immunoreactive polypeptide with almost the same molecular weight as the authentic MWP, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The amino acid compositions deduced from the MWP and OWP genes were similar to the chemical amino acid compositions of other S-layer proteins in the predominance of acidic amino acids compared with basic amino acids and in the very low content of sulfur-containing amino acids. The acidic nature of the MWP and OWP was confirmed by isoelectric focusing on polyacrylamide gels. In addition, circular dichroism spectra indicated that the S-layer proteins in B. brevis 47 were composed of approximately 30% beta-sheet and 5% alpha-helical structures, with the remainder of the polypeptide backbone being aperiodic in nature.
High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma (2006)

Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.
VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis (1996)

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is thought to function by interacting with two high-affinity receptors, flk-1 and flt-1. In an adult heart, angiogenesis can occur in a number of pathological conditions, including atherosclerosis, hypertrophy, and infarction. To determine the role played by VEGF, flk-1, and flt-1 in this process in vivo, we studied the expression of the growth factor and its receptors in a rat infarct model. After an acute myocardial infarction, we observed an initial rapid (1h) rise in VEGF (275%), flk-1 (375%), and flt-1 (400%) mRNA expression throughout the entire heart. Initial diffuse induction of VEGF, flk-1, and flt-1 expression in the left ventricle was later replaced by an increase predominantly limited to perimyocardial infarction area where angiogenesis was taking place. In situ hybridization showed at 6 h after infarction, viable myocytes adjacent to the infarct zone expressed markedly increased amounts of VEGF. At both 6 and 24 h, microvessels at the infarct edge overexpressed both flk-1 and flt-1 mRNAs; at 3 and 7 days new vessels infiltrating the infarct also overexpressed both receptors and continued for as late as 6 wk. In summary, acute myocardial infarction is accompanied by rapid and prolonged increase in expression of VEGF and its receptors with characteristic spatial and temporal kinetic. These findings suggest that the VEGF/VEGF receptor system plays an important role in the angiogenesis and stromal deposition associated with myocardial infarction.
Cofactor regeneration in polymersome nanoreactors: enzymatically catalysed Baeyer–Villiger reactions (2011)

Enzymatically catalysed Baeyer–Villiger reactions were successfully performed making use of our novel cofactor regenerating nanoreactors. The system is based on intrinsically porous polymeric vesicles loaded with enzymes that are able to regenerate the cofactor NADPH.