gebhart/patrepeval huggingface dataset:
Vasculotide, an Angiopoietin-1 mimetic, ameliorates several features of experimental atopic dermatitis-like disease (2016)

The AT-Derm phenotype in these animals is driven through dysregulation of Tie2 receptor signalling and is augmented by supplemental Ang2-dependent stimulation. Overexpression of Ang1 or treatment with VT produced a similar amelioration of the phenotype supporting the contention that VT and Ang1 have a similar mechanism of action on the Tie2 receptor and can both counteract the signalling driven by Ang2. Our results also support a possible role for Tie2-signalling in the development of eosinophilic diseases and that activation of Tie2 may directly or indirectly modulate the differentiation of eosinophils, which express Tie2. In summary, these data support the hypothesis that this AT-Derm mouse model is driven by dysregulation of the Tie2 signalling pathway and increased Ang2 levels can aggravate it, whereas it can be reversed by either Ang1-overexpression or VT treatment. Moreover, our data supports the contention that VT acts as an Angiopoietin-1 mimetic and may provide a novel entry point for Tie2-agonist-based therapies for atopic diseases.
Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers (2015)

A highly glycosylated, trimeric envelope glycoprotein (Env) mediates HIV-1 cell entry. The high density and heterogeneity of the glycans shield Env from recognition by the immune system, but paradoxically, many potent broadly neutralizing antibodies (bNAbs) recognize epitopes involving this glycan shield. To better understand Env glycosylation and its role in bNAb recognition, we characterized a soluble, cleaved recombinant trimer (BG505 SOSIP.664) that is a close structural and antigenic mimic of native Env. Large, unprocessed oligomannose-type structures (Man8-9GlcNAc2) are notably prevalent on the gp120 components of the trimer, irrespective of the mammalian cell expression system or the bNAb used for affinity purification. In contrast, gp41 subunits carry more highly processed glycans. The glycans on uncleaved, non-native oligomeric gp140 proteins are also highly processed. A homogeneous, oligomannose-dominated glycan profile is therefore a hallmark of a native Env conformation and a potential Achilles' heel that can be exploited for bNAb recognition and vaccine design.
Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy (2009)

The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer.
Broadband moth-eye antireflection coatings fabricated by low-cost nanoimprinting (2009)

Subwavelength scale antireflection moth-eye structures in silicon were fabricated by a wafer-scale nanoimprint technique and demonstrated an average reflection of 1% in the spectral range from 400 to 1000 nm at normal incidence. An excellent antireflection property out to large incident angles is shown with the average reflection below 8% at 60°. Pyramid array gave an almost constant average reflection of about 10% for an incident angle up to 45° and concave-wall column array produced an approximately linear relation between the average reflection and the incident angles. The technique is promising for improving conversion efficiencies of silicon solar cells.
Controlling the Response Characteristics of Luminescent Porphyrin Plastic Film Sensors for Oxygen (1997)

Two porphyrins, platinum(II) octaethylporphyrin (Pt-OEP) and palladium(II) octaethylporphyrin (Pd-OEP), are incorporated into a wide variety of different encapsulating matricies and tested as oxygen sensors. The excited state lifetimes of the two porphyrins are quite different, 0.091 ms for Pt-OEP and 0.99 ms for Pd-OEP, and Pt-OEP-based oxygen sensors are found to be much less sensitive than Pd-OEP-based ones to quenching by oxygen. Two major response characteristics of an oxygen sensor are (i) its sensitivity toward oxygen and (ii) its response and recovery times when exposed to an alternating atmosphere of nitrogen and air. The response characteristics of a range of Pt-OEP, and Pd-OEP-based oxygen sensors were determined using cellulose acetate butyrate (CAB), poly(methyl methacrylate) (PMMA), and PMMA/CAB polymer blends as the encapsulating media. Pt-OEP and Pd-OEP oxygen sensors have better response characteristics (i.e., more sensitive and lower response and recovery times) when CAB is used as the encapsulating medium rather than PMMA. For both Pt-OEP- and Pd-OEP-based oxygen sensors, in either polymer, increasing the level of tributyl phosphate plasticizer improves the response characteristics of the final oxygen-sensitive film. Pt-OEP in different unplasticized PMMA/CAB blended films produced a range of oxygen sensors in which the response characteristics improved with increasing level of CAB present.
A Floristic Study of the Vascular Plants of Kharimkotan, Kuril Islands (2006)

The flora of Kharimkotan, the middle Kuril Islands, had not been known prior to field work performed under the auspices of the International Kuril Island Project (IKIP) in 1996 and 2000. A first checklist of the vascular plants including the old specimens collected by Tatewaki in 1930, is provided here. The list represents 46 families, 121 genera, 182 species, and 4 subspecies for the island. Dominant families are; Asteraceae (17 spp.), Poaceae (17 spp.), Cyperaceae (17 spp.), Brassicaceae (10 spp.), Rosaceae (10 spp.) and Ericaceae (10 spp.). The outline of the vegetation of Kharimkotan is also given.
Water-Soluble Prodrugs of the Human Immunodeficiency Virus Protease Inhibitors Lopinavir and Ritonavir (2009)

We studied the synthesis, cleavage rates, and oral administration of prodrugs of the HIV protease inhibitors (PIs) lopinavir and ritonavir. Phosphate esters attached directly to the central hydroxyl groups of these PIs did not demonstrate enzyme-mediated cleavage in vitro and did not provide measurable plasma levels of the parent drugs in vivo. However, oxymethylphosphate (OMP) and oxyethylphosphate (OEP) prodrugs provided improved rates of cleavage, high levels of aqueous solubility, and high plasma levels of the parent drugs when dosed orally in rats and dogs. Dosing unformulated capsules containing the solid prodrugs led to plasma levels equivalent to those observed for dosing formulated solutions of the parent drugs. A direct synthetic process for the preparation of OMP and OEP prodrugs was developed, and the improved synthetic method may be applicable to the preparation of analogous soluble prodrugs of other drug classes with limited solubility.
A phenomenological description of strain relaxation in GexSi1−x/Si(100) heterostructures (1989)

We describe how in situ observation of strain relaxation of Gex Si1−x /Si(100) heterostructures in a transmission electron microscope enable us to obtain the fundamental parameters which describe the nucleation, propagation, and interaction of misfit dislocations. Activation energies and prefactors are obtained for the nucleation and propagation processes for x in the range 0.20–0.35, and a simple model to account for dislocation interactions is developed. These measured parameters are then incorporated into a predictive model of strain relaxation which successfully reproduces experimental data. This model relies only upon parameters which can be directly measured.
A Signaling Network in Phenylephrine-Induced Benign Prostatic Hyperplasia (2009)

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology characterized by prostatic enlargement and coinciding with distinctive alterations in tissue histomorphology. To identify the molecular mechanisms underlying the development of BPH, we conducted a DNA microarray study using a previously described animal model in which chronic alpha(1)-adrenergic stimulation by repeated administration of phenylephrine evokes histomorphological changes in the rat prostate that resemble human BPH. Bioinformatic tools were applied to microarray data obtained from prostate tissue to construct a network model of potentially relevant signal transduction pathways. Significant involvement of inflammatory pathways was demonstrable, including evidence for activation of a TGF-beta signaling cascade. The heterodimeric protein clusterin (apolipoprotein J) was also identified as a prominent node in the network. Responsiveness of TGF-beta signaling and clusterin gene and protein expression were confirmed independently of the microarray data, verifying some components of the model. This is the first attempt to develop a comprehensive molecular network for histological BPH induced by adrenergic activation. The study also implicated clusterin as a novel biochemical target for therapy.
Complementary Function and Integrated Wiring of the Evolutionarily DistinctDrosophilaOlfactory Subsystems (2011)

To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.
Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid. (1994)

Certain phosphatidic/plasmanic/plasmenic acid (PA) species function as lipid intermediates in cell activation and may function directly as intracellular signaling molecules. PA can also be dephosphorylated to 1,2-diradyl-sn-glycerol by phosphatidate phosphohydrolase. Treatment of various cell types, including murine P388 monocytic leukemia cells, with bacterial lipopolysaccharide rapidly stimulates large increases in PA and PA-derived diradylglycerol. Pentoxifylline, 1-(5-oxohexyl)-3,7-dimethylxanthine, inhibits lipopolysaccharide-stimulated formation of PA in P388 cells at high concentrations (IC50 = 500 microM). Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline in humans and is > 800-fold more active as an inhibitor of PA formation than pentoxifylline (IC50 = 0.6 microM). Lisofylline does not inhibit lipopolysaccharide-induced activation of phosphatidylinositol-specific phospholipase C and generation of phosphatidylinositol-derived diradylglycerol. Lisofylline but not pentoxifylline protects BALB/c mice from endotoxin lethality when administered 4 hr after lipopolysaccharide. This protective effect is independent of either agent's effect on suppression of plasma tumor necrosis factor alpha. These data suggest that inhibitors of PA formation may have significant clinical potential in the treatment of sepsis and septic shock.
A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid (2007)

The phenotype and function of murine dendritic cells (DCs) are primarily studied using bone-marrow-derived DCs (BM-DCs), but may be hampered by the heterogeneous phenotype of BM-DCs due to their differential state of maturation. Here we characterize a newly established murine DC line (SP37A3) of myeloid origin. During maintainance in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and M-CSF, SP37A3 cells resemble immature DCs characterized by low expression of major histocompatibility complex (MHC) II and costimulatory molecules and low T-cell stimulatory capacity. Upon stimulation, SP37A3 cells acquire a mature phenotype and activate naive T cells as potently as BM-DCs. Similar to BM-DCs, SP37A3 cells activated in the presence of dexamethasone-induced regulatory T cells, which were anergic upon restimulation and suppressed proliferation of naive T cells. This tolerogenic state was reflected by lower expression levels of costimulatory molecules and proinflammatory cytokines compared with mature cells, as well as up-regulated expression of FcgammaRIIB and interleukin-1RA (IL-1RA). SP37A3 cells were responsive to dexamethasone even when applied at later time points during activation, suggesting functional plasticity. Thus, DC line SP37A3 represents a suitable model to study functions of immature and mature as well as tolerogenic myeloid DCs, circumventing restrictions associated with the use of primary DCs and BM-DCs.
Slit Protein-mediated Inhibition of CXCR4-induced Chemotactic and Chemoinvasive Signaling Pathways in Breast Cancer Cells (2004)

Slit, which mediates its function by binding to the Roundabout (Robo) receptor, has been shown to regulate neuronal and CXCR4-mediated leukocyte migration. Slit-2 was shown to be frequently inactivated in lung and breast cancers because of hypermethylation of its promoter region. Furthermore, the CXCR4/CXCL12 axis has been reported recently to be actively involved in breast cancer metastasis to target organs such as lymph nodes, lung, and bone. In this study, we sought to characterize the effect of Slit (=Slit-2) on the CXCL12/CXCR4-mediated metastatic properties of breast cancer cells. We demonstrate here that breast cancer cells and tissues derived from breast cancer patients express Robo 1 and 2 receptors. We also show that Slit treatment inhibits CXCL12/CXCR4-induced breast cancer cell chemotaxis, chemoinvasion, and adhesion, the fundamental components that promote metastasis. Slit had no significant effect on the CXCL12-induced internalization process of CXCR4. In addition, characterization of signaling events revealed that Slit inhibits CXCL12-induced tyrosine phosphorylation of focal adhesion components such as RAFTK/Pyk2 at residues 580 and 881, focal adhesion kinase at residue 576, and paxillin. We found that Slit also inhibits CXCL12-induced phosphatidylinositol 3-kinase, p44/42 MAP kinase, and metalloproteinase 2 and 9 activities. However, it showed no effect on JNK and p38 MAP kinase activities. To our knowledge, this is the first report to analyze in detail the effect of Slit on breast cancer cell motility as well as its effect on the critical components of the cancer cell chemotactic machinery. Studies of the Slit-Robo complex may foster new anti-chemotactic approaches to block cancer cell metastasis.
DNA Labeling Index and Structure of the Rat Mammary Gland as Determinants of Its Susceptibility to Carcinogenesis<xref ref-type="fn" rid="FN2">2</xref> (1978)

Journal Article DNA Labeling Index and Structure of the Rat Mammary Gland as Determinants of Its Susceptibility to Carcinogenesis Get access Jose Russo, Jose Russo 3Experimental Pathology Laboratory, Depanment of Biology, Michigan Cancer Foundation, 110 East Warren Ave., Detroit, Mich. 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar Irma H. Russo Irma H. Russo 3Experimental Pathology Laboratory, Depanment of Biology, Michigan Cancer Foundation, 110 East Warren Ave., Detroit, Mich. 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 6, December 1978, Pages 1451–1459, https://doi.org/10.1093/jnci/61.6.1451 Published: 01 December 1978 Article history Received: 05 January 1978 Revision received: 23 June 1978 Accepted: 06 July 1978 Published: 01 December 1978
Color quantization of images (1991)

The authors develop algorithms for the design of hierarchical tree structured color palettes incorporating performance criteria which reflect subjective evaluations of image quality. Tree structured color palettes greatly reduce the computational requirements of the palette design and pixel mapping tasks, while allowing colors to be properly allocated to densely populated areas of the color space. The algorithms produce higher-quality displayed images and require fewer computations than previously proposed methods. Error diffusion techniques are commonly used for displaying images which have been quantized to very few levels. Problems related to the application of error diffusion techniques to the display of color images are discussed. A modified error diffusion technique is shown to be easily implemented using the tree structured color palettes developed earlier.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
IgA Complexes in Plasma and Synovial Fluid of Patients with Rheumatoid Arthritis Induce Neutrophil Extracellular Traps via FcαRI (2016)

Autoantibodies, including rheumatoid factor (RF), are an important characteristic of rheumatoid arthritis (RA). Interestingly, several studies reported a correlation between the presence of IgA autoantibodies and worse disease course. We demonstrated previously that triggering the IgA Fc receptor (FcαRI) on neutrophils results in neutrophil recruitment and the release of neutrophil extracellular traps (NETs). Because this can lead to tissue damage, we investigated whether IgA immune complexes in plasma and synovial fluid of RA patients activate neutrophils. RF isotypes were measured with ELISA, and immune complexes were precipitated using polyethylene glycol 6000. Isolated neutrophils were incubated with immune complexes, and activation and release of NETs were determined in the presence or absence of FcαRI-blocking Abs. Plasma and SF of RA patients contained IgM, IgG, and IgA RFs. Patient plasma IgA RF and IgM RF showed a strong correlation. No uptake of IgM and minimal endocytosis of IgG immune complexes by neutrophils was observed, in contrast to avid uptake of IgA complexes. Incubation of neutrophils with immune complexes resulted in the production of reactive oxygen species, as well as the release of NETs, lactoferrin, and chemotactic stimuli. Importantly, activation of neutrophils was reduced when FcαRI was blocked. Neutrophils were activated by IgA immune complexes, which suggests that neutrophils play a role in inducing joint damage in RA patients who have IgA autoantibody complexes, thereby increasing the severity of disease. Blocking FcαRI inhibited neutrophil activation and, as such, may represent an additional attractive novel therapeutic strategy for the treatment of RA.
Spatial heterodyne spectroscopy: a novel interferometric technique for ground-based and space astronomy (1990)

The theoretical principles and technical feasibility of spatial heterodyne spectroscopy (SHS) for astronomical observations are explored. The SHS setup is basically a Michelson interferometer with the mirrors replaced by diffraction gratings; wavelength-dependent Fizeau fringes are recorded and Fourier analyzed to obtain a high-resolution spectrum even at relatively low spatial frequencies. Two all-reflection SHS instruments are described and illustrated with diagrams, and laboratory test results using CCD detectors for both visible and UV measurements are presented, indicating resolving powers of about 75,000 and 70,000, respectively. Also discussed are the advantages and limitations of SHS vis a vis other Fourier-transform spectroscopic methods.
Identification of residues critical for toxicity in Clostridium perfringens phospholipase C, the key toxin in gas gangrene (2000)

Clostridium perfringens phospholipase C (PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. The toxic activities of genetically engineered alpha-toxin variants harboring single amino-acid substitutions in three loops of its C-terminal domain were studied. The substitutions were made in aspartic acid residues which bind calcium, and tyrosine residues of the putative membrane-interacting region. The variants D269N and D336N had less than 20% of the hemolytic activity and displayed a cytotoxic potency 103-fold lower than that of the wild-type toxin. The variants in which Tyr275, Tyr307, and Tyr331 were substituted by Asn, Phe, or Leu had 11-73% of the hemolytic activity and exhibited a cytotoxic potency 102- to 105-fold lower than that of the wild-type toxin. The results demonstrated that the sphingomyelinase activity and the C-terminal domain are required for myotoxicity in vivo and that the variants D269N, D336N, Y275N, Y307F, and Y331L had less than 12% of the myotoxic activity displayed by the wild-type toxin. This work therefore identifies residues critical for the toxic activities of C. perfringens PLC and provides new insights toward understanding the mechanism of action of this toxin at a molecular level.
Strategies for on-chip sub-nanosecond signal capture and timing measurements (2002)

Two strategies for on-chip signal capture and characterization are described. The first is an extension of an integrated mixed-signal test core that has the ability to provide time and frequency domain measurements. This extension consists of a Delay Locked Loop (DLL) based timing module that through an undersampling algorithm provides high effective sampling rates for arbitrary, high bandwidth, periodic signals. The second is a time to digital converter (TDC) based on a Vernier Delay Line (VDL). This circuit can sample digital signals at very fine time intervals, and produce an on-chip jitter cumulative distribution function (CDF) from which a jitter histogram may be extracted. Both techniques were successfully demonstrated using a prototype IC in a 0.35 /spl mu/m CMOS process.