gebhart/patrepeval huggingface dataset:
Multiple Peptide Resistance Factor (MprF)-mediated Resistance of Staphylococcus aureus against Antimicrobial Peptides Coincides with a Modulated Peptide Interaction with Artificial Membranes Comprising Lysyl-Phosphatidylglycerol (2011)

Modification of the membrane lipid phosphatidylglycerol (PG) of Staphylococcus aureus by enzymatic transfer of a l-lysine residue leading to lysyl-PG converts the net charge of PG from -1 to +1 and is thought to confer resistance to cationic antimicrobial peptides (AMPs). Lysyl-PG synthesis and translocation to the outer leaflet of the bacterial membrane are achieved by the membrane protein MprF. Consequently, mutants lacking a functional mprF gene are in particular vulnerable to the action of AMPs. Hence, we aim at elucidating whether and to which extent lysyl-PG modulates membrane binding, insertion, and permeabilization by various AMPs. Lysyl-PG was incorporated into artificial lipid bilayers, mimicking the cytoplasmic membrane of S. aureus. Moreover, we determined the activity of the peptides against a clinical isolate of S. aureus strain SA113 and two mutants lacking a functional mprF gene and visualized peptide-induced ultrastructural changes of bacteria by transmission electron microscopy. The studied peptides were: (i) NK-2, an α-helical fragment of mammalian NK-lysin, (ii) arenicin-1, a lugworm β-sheet peptide, and (iii) bee venom melittin. Biophysical data obtained by FRET spectroscopy, Fourier transform infrared spectroscopy, and electrical measurements with planar lipid bilayers were correlated with the biological activities of the peptides. They strongly support the hypothesis that peptide-membrane interactions are a prerequisite for eradication of S. aureus. However, degree and mode of modulation of membrane properties such as fluidity, capacitance, and conductivity were unique for each of the peptides. Altogether, our data support and underline the significance of lysyl-PG for S. aureus resistance to AMPs.
ChemInform Abstract: Application of Glycals to the Synthesis of Oligosaccharides: Convergent Total Syntheses of the Lewis X Trisaccharide Sialyl Lewis X Antigenic Determinant and Higher Congeners. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
LcrV Plague Vaccine with Altered Immunomodulatory Properties (2005)

Yersinia pestis, the causative agent of plague, secretes LcrV (low-calcium-response V or V antigen) during infection. LcrV triggers the release of interleukin 10 (IL-10) by host immune cells and suppresses proinflammatory cytokines such as tumor necrosis factor alpha and gamma interferon as well as innate defense mechanisms required to combat the pathogenesis of plague. Although immunization of animals with LcrV elicits protective immunity, the associated suppression of host defense mechanisms may preclude the use of LcrV as a human vaccine. Here we show that short deletions within LcrV can reduce its immune modulatory properties. An LcrV variant lacking amino acid residues 271 to 300 (rV10) elicited immune responses that protected mice against a lethal challenge with Y. pestis. Compared to full-length LcrV, rV10 displayed a reduced ability to release IL-10 from mouse and human macrophages. Furthermore, the lipopolysaccharide-stimulated release of proinflammatory cytokines by human or mouse macrophages was inhibited by full-length LcrV but not by the rV10 variant. Thus, it appears that LcrV variants with reduced immune modulatory properties could be used as a human vaccine to generate protective immunity against plague.
Naloxone increases pain induced by topical capsaicin in healthy human volunteers (2002)

Opioid receptors occur in locations of strategic importance within the central nervous system for modulation of pain. Is pain reduced by ongoing inhibition mediated by activation of these receptors? Experiments to date in which the opioid-receptor antagonist, naloxone, is administered during a painful event have yielded unclear results. Topically applied capsaicin can be used to induce tonic pain of moderate to severe intensity without tissue injury and is an ideal stimulus for studying acute pain modulation. We therefore conducted a placebo-controlled double-blind crossover study to investigate the effects of naloxone on capsaicin-induced pain (five men, four women, aged 29 +/- 5 years). Capsaicin (10%) was applied topically and subjects rated pain every 2 min. The subjects were told that any drug given to them could increase, decrease, or not change their pain sensation. Pain plateaued after 20 min. At 26 min subjects received either naloxone or placebo in double-blind fashion. At 56 min subjects received the alternative (placebo or naloxone). In a second session the order of presentation was reversed. The naloxone induced a significant increase in pain compared both to baseline (P < 0.01) and placebo (P < 0.01). The peak effect, reached at 12-20 min after naloxone delivery, was 59% greater than placebo. This experiment suggests that acute pain is actively suppressed by endogenous opioid-receptor activation.
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. (1995)

E6-AP is a 100-kDa cellular protein that interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53 tumor-suppressor protein for ubiquitin-mediated proteolysis. E6-AP is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. The amino acid sequence of E6-AP shows similarity to a number of protein sequences over an approximately 350-aa region corresponding to the carboxyl termini of both E6-AP and the E6-AP-related proteins. Of particular note is a conserved cysteine residue within the last 32-34 aa, which in E6-AP is likely to be the site of ubiquitin thioester formation. Two of the E6-AP-related proteins, a rat 100-kDa protein and a yeast 95-kDa protein (RSP5), both of previously unknown function, are shown here to form thioesters with ubiquitin. Mutation of the conserved cysteine residue of these proteins destroys their ability to accept ubiquitin. These data strongly suggest that the rat 100-kDa protein and RSP5, as well as the other E6-AP-related proteins, belong to a class of functionally related E3 ubiquitin-protein ligases, defined by a domain homologous to the E6-AP carboxyl terminus (hect domain).
Multiple Ink Nanolithography: Toward a Multiple-Pen Nano-Plotter (1999)

The formation of intricate nanostructures will require the ability to maintain surface registry during several patterning steps. A scanning probe method, dip-pen nanolithography (DPN), can be used to pattern monolayers of different organic molecules down to a 5-nanometer separation. An "overwriting" capability of DPN allows one nanostructure to be generated and the areas surrounding that nanostructure to be filled in with a second type of "ink."
A Rapid Isolation of the Unknown 5'-Flanking Sequence of Human CENP-B cDNA with Polymerase Chain Reactions. (1991)

We rapidly and efficiently isolated the 5'-region of cDNA encoding the N-terminal region of human centromere antigen B (CENP-B) including an ATG methionine codon by polymerase chain reactions (PCR). The unknown 5'-flanking sequence of the cDNA was amplified using an adaptor-sequence ligated to the 5' end as a universal primer sequence. To locate the target fragments, we did an additional PCR with another set of two internal primers using samples of the size-fractionated products as templates, rather than using the conventional hybridization procedure. This approach can further be applied to the analysis of other unknown flanking sequences of cDNA or genomic DNA.
New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse (2008)

These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.
Human apolipoprotein A-I prevents atherosclerosis associated with apolipoprotein[a] in transgenic mice. (1994)

Elevated levels of apolipoprotein[a] (apo[a]) and apolipoprotein A-I (apoA-I) are associated, respectively, with increased and decreased atherosclerosis risk, in both humans and transgenic mice. To investigate the interactions of these two important lipid-associated proteins, we assessed the effect of expression of human apoA-I and apo[a] transgenes, both singularly and together, on murine atherogenesis. Mice expressing the apo[a] transgene have a lipoprotein profile similar to nontransgenic controls, yet have significantly increased susceptibility to diet-induced atherosclerosis. Compared to mice expressing only the apo[a] transgene, mice expressing both apo[a] and apoA-I transgenes have twofold greater high density lipoprotein (HDL) concentrations and approximately a 20-fold decrease in development of early atherosclerotic lesions. The finding of decreased atherosclerosis in the setting of elevated apo[a] and apoA-I suggests that elevations of apoA-I and HDL have a dominant effect in reducing atherosclerosis susceptibility in various settings, including those not associated with alterations of plasma lipids.
The odds of immunotherapy success (2015)

Mutation load correlates with the response of melanomas to immunotherapy [Also see Report by Van Allen et al. ]
The hydrocarbon breath test in the study of lipid peroxidation: principles and practice. (1992)

Lipid peroxidation has gained increasing interest in recent years as one of the more prominent features of free radical-induced damage in biology. The study of lipid peroxidation might increase our understanding of the etiology and pathophysiology of a great number of diseases. Ethane and pentane are among the numerous end-products of lipid peroxidation and although they represent only a small and possibly variable proportion of the total amount of peroxidized polyunsaturated fatty acids, their determination in head space or exhaled breath enables accurate assessment of oxidative stress both in vitro and in vivo. To date, the number of studies utilizing the hydrocarbon breath test as a marker of lipid peroxidation in humans is small. Technical difficulties are among the main reasons for the limited use of this method. An appropriate washout period, the use of the right materials, the scrupulous avoidance of air contamination, adequate preinjection concentrations of the samples, and a sensitive gas chromatographic technique enable the accurate and reproducible measurement of hydrocarbons in human breath. The hydrocarbon breath test provides a noninvasive and extremely sensitive instrument for the assessment of oxidative stress status in adults as well as in children.
Efficient Contrast Enhancement Using Adaptive Gamma Correction With Weighting Distribution (2012)

This paper proposes an efficient method to modify histograms and enhance contrast in digital images. Enhancement plays a significant role in digital image processing, computer vision, and pattern recognition. We present an automatic transformation technique that improves the brightness of dimmed images via the gamma correction and probability distribution of luminance pixels. To enhance video, the proposed image-enhancement method uses temporal information regarding the differences between each frame to reduce computational complexity. Experimental results demonstrate that the proposed method produces enhanced images of comparable or higher quality than those produced using previous state-of-the-art methods.
Novel potassium channel openers: synthesis and pharmacological evaluation of new N-(substituted-3-pyridyl)-N'-alkylthioureas and related compounds (1994)

This report describes the synthesis and pharmacological evaluation of a series of novel potassium channel openers related to the pinacidil-type compounds. Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated for their effects on both the inhibition of spontaneous mechanical activity in rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the structure-activity relationship for this series of compounds was discussed. Good correlation between in vitro and iv antihypertensive activity was observed for these compounds. Among them, cyanoguanidines bearing a conformationally rigid unit such as a norbornyl group generally possessed potent activity in both in vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N"-(1-methyl-2-norbornyl)guanidine (23d) was identified as a more potent potassium channel opener in vitro (EC100 = 3 x 10(-8) M) than pinacidil (EC100 = 10(-7) M).
Infectious Complications in Patients Undergoing Marrow Transplantation: A Prospective Randomized Study of the Additional Effect of Decontamination and Laminar Air Flow Isolation among Patients Receiving Prophylactic Systemic Antibiotics (1987)

99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF + PSA, 49 patients). Only 1 patient (3%) in the LAF + PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p less than 0.005). Three patients (6%) in the LAF + PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p = 0.06). There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival. We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period.
Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation (2004)

Extracellular nucleotides play an important role in thrombosis and inflammation, triggering a range of effects such as platelet activation and recruitment, endothelial cell activation, and vasoconstriction. CD39, the major vascular nucleoside triphosphate diphosphohydrolase (NTPDase), converts ATP and ADP to AMP, which is further degraded to the antithrombotic and anti-inflammatory mediator adenosine. Deletion of CD39 renders mice exquisitely sensitive to vascular injury, and CD39-null cardiac xenografts show reduced survival. Conversely, upregulation of CD39 by somatic gene transfer or administration of soluble NTPDases has major benefits in models of transplantation and inflammation. In this study we examined the consequences of transgenic expression of human CD39 (hCD39) in mice. Importantly, these mice displayed no overt spontaneous bleeding tendency under normal circumstances. The hCD39 transgenic mice did, however, exhibit impaired platelet aggregation, prolonged bleeding times, and resistance to systemic thromboembolism. Donor hearts transgenic for hCD39 were substantially protected from thrombosis and survived longer in a mouse cardiac transplant model of vascular rejection. These thromboregulatory manifestations in hCD39 transgenic mice suggest important therapeutic potential in clinical vascular disease and in the control of serious thrombotic events that compromise the survival of porcine xenografts in primates.
Prostaglandin E2 Receptor, EP3, Is Induced in Diabetic Islets and Negatively Regulates Glucose- and Hormone-Stimulated Insulin Secretion (2013)

BTBR mice develop severe diabetes in response to genetically induced obesity due to a failure of the β-cells to compensate for peripheral insulin resistance. In analyzing BTBR islet gene expression patterns, we observed that Pgter3, the gene for the prostaglandin E receptor 3 (EP3), was upregulated with diabetes. The EP3 receptor is stimulated by prostaglandin E2 (PGE2) and couples to G-proteins of the Gi subfamily to decrease intracellular cAMP, blunting glucose-stimulated insulin secretion (GSIS). Also upregulated were several genes involved in the synthesis of PGE2. We hypothesized that increased signaling through EP3 might be coincident with the development of diabetes and contribute to β-cell dysfunction. We confirmed that the PGE2-to-EP3 signaling pathway was active in islets from confirmed diabetic BTBR mice and human cadaveric donors, with increased EP3 expression, PGE2 production, and function of EP3 agonists and antagonists to modulate cAMP production and GSIS. We also analyzed the impact of EP3 receptor activation on signaling through the glucagon-like peptide (GLP)-1 receptor. We demonstrated that EP3 agonists antagonize GLP-1 signaling, decreasing the maximal effect that GLP-1 can elicit on cAMP production and GSIS. Taken together, our results identify EP3 as a new therapeutic target for β-cell dysfunction in T2D.
Development of Cation/Anion “Interaction” Scales for Ionic Liquids through ESI-MS Measurements (2006)

Electrospray ionization mass spectrometry applied to ionic liquids allowed the study of loosely bonded supramolecules, originating from these organic salts. Based on the observation that ionic liquids formed cationic [C(q+1)X(q)](+) and anionic [C(q)X(q+1)](-) supramolecular aggregates, we have investigated mixed networks, formed by different cations coordinated to a selected anion or by different anions bonded to a given cation, i.e., [C1...X...C2](+) and [X1...C...X2](-), with the aim to build a scale of the cation-anion interaction strength. The qualitative order of intrinsic bond strength to Br- was found to be the following: [emim](+) > [bmim](+) > [mor1,2](+) > [hmim]+ > [omim](+) > [mor1,4](+) > [bupy](+) > [bpyrr](+) > [picol](+) > [bm(2)im](+) > [TBA](+). Similarly, the interaction energies to 1-butyl-3-methylimidazolium (bmim) species envisaged two classes of anions: species tightly coordinated to the cationic moiety that include CF3COO(-), Br(-), N(CN)2(-), and BF4(-) and anions loosely interacting with the alkylimidazolium species such as OTf(-), PF6(-), and Tf2N(-).
A new method for side pumping of double-clad fiber sources (2003)

We report a new method for pumping of double-clad, rare-earth-doped fiber sources using diode lasers, diode bars, or fiber-coupled pump sources. In this technique, the pump beam is launched by reflection from a mirror that is embedded in a channel cut into the inner cladding. The mirror may be curved to reduce the divergence of the pump beam, thereby allowing the use of highly divergent pump sources and low-numerical-aperture inner claddings. Additional advantages include high coupling efficiency, little loss of brightness in coupling the pump beam, relatively low sensitivity to misalignment, no obstruction of the fiber ends, no loss for light propagating in the core, simplicity (low parts count), compact and rugged packaging, scalability to high power, and low cost. Because of the large alignment tolerances, the technique is uniquely well suited to the direct coupling of the output of a diode bar into one or more double-clad fibers. We present a detailed description and characterization of the technique. We also describe the performance of Yb-doped and Er-Yb-doped fiber amplifiers constructed with this method, including amplifiers with saturated output powers of 5.2 W (1064-nm wavelength) and 2.6 W (1550 nm) when pumped with two laser diodes.
5G Radio Access: Requirements, Concept and Experimental Trials (2015)

Currently, many operators worldwide are deploying Long Term Evolution (LTE) to provide much faster access with lower latency and higher efficiency than its predecessors 3G and 3.5G. Meanwhile, the service rollout of LTE-Advanced, which is an evolution of LTE and a “true 4G” mobile broadband, is being underway to further enhance LTE performance. However, the anticipated challenges of the next decade (2020s) are so tremendous and diverse that there is a vastly increased need for a new generation mobile communications system with even further enhanced capabilities and new functionalities, namely a fifth generation (5G) system. Envisioning the development of a 5G system by 2020, at DOCOMO we started studies on future radio access as early as 2010, just after the launch of LTE service. The aim at that time was to anticipate the future user needs and the requirements of 10 years later (2020s) in order to identify the right concept and radio access technologies for the next generation system. The identified 5G concept consists of an efficient integration of existing spectrum bands for current cellular mobile and future new spectrum bands including higher frequency bands, e.g., millimeter wave, with a set of spectrum specific and spectrum agnostic technologies. Since a few years ago, we have been conducting several proof-of-concept activities and investigations on our 5G concept and its key technologies, including the development of a 5G real-time simulator, experimental trials of a wide range of frequency bands and technologies and channel measurements for higher frequency bands. In this paper, we introduce an overview of our views on the requirements, concept and promising technologies for 5G radio access, in addition to our ongoing activities for paving the way toward the realization of 5G by 2020.
Blocking Mast Cell–Mediated Type I Hypersensitivity in Experimental Allergic Conjunctivitis by Monocyte Chemoattractant Protein-1/CCR2 (2009)

Stimulation of the co-stimulatory axis of CCR2 by MCP-1 is essentially required for mast cell-mediated hypersensitivity reactions in mouse eyes.
Novel association of a diverse range of genes with renal cell carcinoma as identified by differential display (2000)

We have used differential-display PCR (DD-PCR) to compare renal-cell carcinoma (RCC) and normal kidney gene expression with the aim of identifying genes specifically associated with RCC. Using a modified DD-PCR approach, which was non-radioactive, quicker and simpler than the conventional method, 24 cDNA samples were clearly up- or down-regulated in RCC tissue from 4 patients. Fourteen of these showed high similarity to a number of known genes. Eight of these cDNA clones were chosen for further analysis. These were a regulator of G-protein signalling (RGS-5), Notch-3, Na,K-ATPase alpha subunit, HLA class II antigen, ETS-like protein, transforming growth factor beta-stimulated clone (TSC-22), bladder cancer-related protein (BC10) and adipophilin. Semi-quantitative RT-PCR using specific primers to each of these genes confirmed differential expression in 67% to 83% of a further 12 RCC and normal kidney paired samples from 7 of the 8 cDNA clones. Northern analysis further confirmed the up-regulation in expression of RGS-5 and Notch-3 in RCC. Further characterisation of these differentially expressed genes should lead to a better understanding of the changes that occur at the molecular level during RCC development and progression.