gebhart/patrepeval huggingface dataset:
Comparison of Shiga-like toxin I B-subunit expression and localization in Escherichia coli and Vibrio cholerae by using trc or iron-regulated promoter systems (1993)

Shiga-like toxin I (SLT-I) B-subunit expression was examined by using the trc promoter in two different constructs, pSBC32 and pSBC54, in which 710 bp of DNA downstream of the B subunit in pSBC32 was deleted. The trc promoter in pSBC54 was replaced also with the SLT-I iron-regulated promoter to create a third plasmid, pSBC61. SLT-I B-subunit expression was examined from all three plasmids following transfer into Escherichia coli JM105 and the cholera toxin A-subunit gene deletion mutant Vibrio cholerae 0395-N1. The SLT-I B subunit was expressed from all constructs. pSBC61 was regulated by elemental iron and produced equivalent amounts of SLT-I B subunit from both E. coli and V. cholerae. In contrast to the cholera toxin B subunit, virtually all released into the medium, the SLT-I B subunit was predominantly cell associated in the pSBC61 constructs. Both pSBC32 and pSBC54 were inducible with isopropyl-beta-D-thiogalactopyranoside (IPTG) in the E. coli background but not the V. cholerae background; however, when E. coli cultures were allowed to grow for 24 h, the yield of SLT-I B subunit was not increased by IPTG induction. Both pSBC32 and -54 expressed more SLT-I B subunit in the V. cholerae host than in the E. coli host. Scale-up to a 9.9-liter fermentor culture of V. cholerae 0395 N1 (pSBC32) resulted in the isolation of 220 mg of SLT-I B. The purified B subunit was identical, in terms of binding to Vero cells, stoichiometry after chemical cross-linking, and ability to inhibit cytotoxicity of intact Shiga toxin, to native SLT-I B subunit from E. coli O157:H7.
Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents (2011)

Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of diaryl ether based thiazolidenediones, which function as selective ligands against this receptor. Series optimization provided several potent analogues that inhibit the recruitment of a coactivator peptide fragment in in vitro biochemical assays (IC(50) < 150 nM) and cellular two-hybrid reporter assays against the ligand binding domain (IC(50) = 1-5 μM). A cocrystal structure of the ligand-binding domain of ERRα with lead compound 29 revealed the presence of a covalent interaction between the protein and ligand, which has been shown to be reversible. In diet-induced murine models of obesity and in an overt diabetic rat model, oral administration of 29 normalized insulin and circulating triglyceride levels, improved insulin sensitivity, and was body weight neutral. This provides the first demonstration of functional activities of an ERRα ligand in metabolic animal models.
QUANTITATIVE COMPARISON OF METHODS OF ADMINISTERING PHYSOSTIGMINE (1943)

Physostigmine, because of its potent parasympathomimetic action, has retained an important position in ophthalmic therapy since first used as a miotic by Laqueur (1876).<sup>1</sup>It is administered usually in an aqueous solution and less frequently in an ointment or lamella. The official preparation is physostigmine salicylate, although the sulfate, which possesses similar pharmacologic properties, is also available. This paper presents a comparison of the effectiveness of the various methods of local application, including iontophoresis and the use of a wetting agent. new method, its relative advantages and disadvantages must be carefully balanced. As part of the evaluation it is desirable to know the amount of drug entering the eye. Therefore a quantitative estimation was made of the physostigmine content of the aqueous humor of the rabbit's eye with different methods of application. No local or general deleterious effects were noted with any of the procedures described. A temporary corneal
Detection of Verotoxin‐Producing Escherichia coli O157:H7 by Multiplex Polymerase Chain Reaction (1998)

We constructed primers for multiplex polymerase chain reaction (PCR) to detect verotoxin-producing Escherichia coli (VTEC) O157:H7. The multiplex PCR primers were designed from the sequence of the flagellin structural gene of Escherichia coli flagellar type H7 (GenBank under accession number L07388), and from the sequence of the rfbE gene of Escherichia coli O157:H7 (GenBank under accession number S83460). In addition to these primers, we used a primer pair reported by Karch and Meyer (J. Clin. Microbiol. 27: 2751-2757, 1989) to amplify various VT genes from VTEC. All of the examined specimens (18 isolates) of VT-producing E. coli O157:H7 showed a positive result by the multiplex PCR test with the three sets of primers. The sensitivity of detection for VT-producing E. coli O157:H7 was shown to be at least 3,000 cells per PCR tube.
Coordination and communication between the p53 and IGF-1–AKT–TOR signal transduction pathways (2006)

Over the past 10 years the signal transduction networks for p53, IGF-1-AKT, and TOR pathways have been assembled in worms, flies, and mammals, and their functions elucidated. In the past 1-2 years a number of genes and their proteins have been identified that permit extensive communication and coordination between these pathways. These three pathways are involved in sensing and integrating signals arising from nutrient and growth factor availability, signals from sensory and sexual organs, and intrinsic and extrinsic stress signals. In turn these pathways regulate cell growth, proliferation, and death. These networks are central to our understanding of a variety of physiological and pathological conditions, including cancer, diabetes, and longevity.
High throughput synthesis and screening of chalcogenide materials for data storage (2005)

We have analyzed protein patterns of human nasal lavage fluid (NLF) with two-dimensional gel electrophoresis (2-DE) and identified several proteins (such as transthyretin, Clara Cell protein 16, lipocalin-1, cystatin S, cystatin SN, immunoglobulin binding factor, statherin, calgranulin B, prolactin-inducible protein, and zinc-alpha2-glycoprotein) by N-terminal amino acid sequencing and matrix-assisted laser desorption/ionizationtime of flight (MALDI-TOF) mass spectrometry. To investigate whether airway irritation causes alterations in NLF 2-DE patterns, we compared epoxy workers with airway irritation (n=8) and healthy controls (n=6) before and after 2 h exposure to the epoxy chemical, dimethylbenzylamine (DMBA, 100 microg/m3) in an exposure chamber. A 25 kDa protein with pI 5.5 was found to be altered in the NLF 2-DE patterns; a trypsin digest of the 2-DE spot analyzed by MALDI-TOF and expressed sequence tags (ESTs) determined after post-source decay (PSD) identified the protein as palate lung and nasal epithelial clone (PLUNC). In controls, the levels of NLF-PLUNC were generally lower after 2 h exposure, whereas in epoxy workers, the levels were increased three- to twentyfold after exposure. The human gene sequence for PLUNC was just recently reported and so far no biofunctional data are available. Our results suggest that PLUNC is involved in the airway inflammatory response after exposure to irritants.
An introduction to the sequence rule: A system for the specification of absolute configuration (1964)

This paper describes the relatively simple methods that suffice for specifying the absolute configuration of the majority of optically active organic compounds - those containing asymmetric carbon atoms.
OUTPLACEMENT COUNSELLING AT SMITHKLINE BEECHAM (1990)

The merger of two giant pharmaceutical businesses inevitably affects staff motivation and morale. Whether leaving or staying, staff need support in these circumstances to enable them to cope with the effects of major change. A model for addressing this problem is explored and the beneficial results — personal commitment, job satisfaction, enhanced performance — emphasised.
Complement-Dependent Apoptosis and Inflammatory Gene Changes in Murine Lupus Cerebritis (2005)

The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, CR1-related y (Crry), administered both as an overexpressing Crry transgene and as Crry-Ig. Prominent deposition of complement proteins C3 and C9 in brains of MRL/lpr mice was indicative of complement activation and was significantly reduced by Crry. Apoptosis was determined in brain using different independent measures of apoptosis, including TUNEL staining, DNA laddering, and caspase-3 activity, all of which were markedly increased in lupus mice and could be blocked by inhibiting complement with Crry. Complement activation releases inflammatory mediators that can induce apoptosis. The mRNA for potentially proinflammatory proteins such as TNFR1, inducible NO synthase, and ICAM-1 were up-regulated in brains of lupus mice. Crry prevented the increased expression of these inflammatory molecules, indicating that the changes were complement dependent. Furthermore, microarray analysis revealed complement-dependent up-regulation of glutamate receptor (AMPA-GluR) expression in lupus brains, which was also validated for AMPA-GluR1 mRNA and protein. Our results clearly demonstrate that apoptosis is a prominent feature in lupus brains. Complement activation products either directly and/or indirectly through TNFR1, ICAM-1, inducible NO synthase, and AMPA-GluR, all of which were altered in MRL/lpr mouse brains, have the potential to induce such apoptosis. These findings present the exciting possibility that complement inhibition is a therapeutic option for lupus cerebritis.
Preferential expression of IL-2 receptor subunits on memory populations within CD4+ and CD8+ T cells. (1991)

Using anti-Tac and anti-Mik-beta 1 monoclonal antibodies to alpha and beta subunits of the interleukin-2 receptor (IL-2R), respectively, a marked difference in expression of IL-2R subunits on blood CD4+ and CD8+ T cells was demonstrated between adults and newborns. In the adult blood, reciprocal expression of IL-2R alpha and IL-2R beta was observed in CD4+ and CD8+ T cells. Some CD4+ T cells expressing IL-2R alpha were often detected, but IL-2R beta + CD4+ cells were very few. On the other hand, CD8+ T cells expressed significant IL-2R beta but little IL-2R alpha. In marked contrast to adult individuals, both CD4+ and CD8+ T cells from the newborns, which seemed to consist mainly of naive populations, showed only negligible expression of IL-2R subunits. It was found that IL-2R subunits appeared to be preferentially expressed on CD4+ and CD8+ T cells with memory phenotypes in the adult blood. Isolated memory (CD45RO+) CD4+ and CD8+ T cells, unlike naive (CD45RO-) ones, were able to proliferate in response to exogenous IL-2 as well as the recall antigen. The present results suggest that IL-2R subunits expressed on circulating T-cell subsets may play an important role in memory T-cell function.
The microbiome of the chicken gastrointestinal tract (2012)

The modern molecular biology movement was developed in the 1960s with the conglomeration of biology, chemistry, and physics. Today, molecular biology is an integral part of studies aimed at understanding the evolution and ecology of gastrointestinal microbial communities. Molecular techniques have led to significant gains in our understanding of the chicken gastrointestinal microbiome. New advances, primarily in DNA sequencing technologies, have equipped researchers with the ability to explore these communities at an unprecedented level. A reinvigorated movement in systems biology offers a renewed promise in obtaining a more complete understanding of chicken gastrointestinal microbiome dynamics and their contributions to increasing productivity, food value, security, and safety as well as reducing the public health impact of raising production animals. Here, we contextualize the contributions molecular biology has already made to our understanding of the chicken gastrointestinal microbiome and propose targeted research directions that could further exploit molecular technologies to improve the economy of the poultry industry.
Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases (2000)

There is growing evidence to support the use of motor cortex stimulation (MCS) in the management of patients with chronic neuropathic pain. A prospective audit of ten patients using a modified staged technique for motor cortex implantation provides further evidence for the analgesic effectiveness of this technique. Ten patients suffering from phantom limb pain (n=3), post stroke pain (n=5), post traumatic neuralgia secondary to gunshot injury to the brain stem (n=1) and brachyalgia secondary to neuro-fibromatosis (n=150% pain relief) and long-term benefit in 4/5 of patients who initially responded to intermittent cortical stimulation (longest follow up 31 months after implantation). Of those patients who benefited two had post stroke pain, two phantom limb pain and one post-traumatic neuralgia. We conclude that motor cortex stimulation is an effective analgesic intervention in some patients with chronic neuropathic pain, but it is difficult if not impossible to predict those patients who may respond to treatment prior to implantation. Randomised controlled trials are now urgently needed to test the effectiveness of motor cortex stimulation under double-blind conditions.
The Potent Anti-HIV Protein Cyanovirin-N Contains Two Novel Carbohydrate Binding Sites That Selectively Bind to Man8 D1D3 and Man9 with Nanomolar Affinity:  Implications for Binding to the HIV Envelope Protein gp120 (2001)

Cyanovirin-N (CVN) is a monomeric 11 kDa cyanobacterial protein that potently inactivates diverse strains of human immunodeficiency virus (HIV) at the level of cell fusion by virtue of high affinity interactions with the surface envelope glycoprotein gp120. Several lines of evidence have suggested that CVN-gp120 interactions are in part mediated by N-linked complex carbohydrates present on gp120, but experimental evidence has been lacking. To this end we screened a comprehensive panel of carbohydrates which represent structurally the N-linked carbohydrates found on gp120 for their ability to inhibit the fusion-blocking activity of CVN in a quantitative HIV-1 envelope-mediated cell fusion assay. Our results show that CVN specifically recognizes with nanomolar affinity Man(9)GlcNAc(2) and the D1D3 isomer of Man(8)GlcNAc(2). Nonlinear least squares best fitting of titration data generated using the cell fusion assay show that CVN binds to gp120 with an equilibrium association constant (K(a)) of 2.4 (+/- 0.1) x 10(7) M(-1) and an apparent stoichiometry of 2 equiv of CVN per gp120, Man(8)GlcNAc(2) D1D3 acts as a divalent ligand (2 CVN:1 Man(8)) with a K(a) of 5.4 (+/- 0.5) x 10(7) M(-1), and Man(9)GlcNAc(2) functions as a trivalent ligand (3 CVN:1 Man(9)) with a K(a) of 1.3 (+/- 0.3) x 10(8) M(-1). Isothermal titration calorimetry experiments of CVN binding to Man(9)GlcNAc(2) at micromolar concentrations confirmed the nanomolar affinity (K(a) = 1.5 (+/- 0.9) x 10(8) M(-1)), and the fitted data indicated a stoichiometry equal to approximately one (1 Man(9):1 CVN). The 1:1 stoichiometry at micromolar concentrations suggested that CVN has not only a high affinity binding site-relevant to the studies at nM concentrations-but a lower affinity site as well that facilitates cross-linking of CVN-oligomannose at micromolar concentrations or higher. The specificity of CVN for Man(8) D1D3 and Man(9) over the D1D2 isomer of Man(8) indicated that the minimum structure required for high affinity binding comprises Manalpha1 --> 2Manalpha. By following the (1)H-(15)N correlation spectrum of (15)N-labeled CVN upon titration with this disaccharide, we unambiguously demonstrate that CVN recognizes and binds to the disaccharide Manalpha1 --> 2Manalpha via two distinct binding sites of differing affinities located on opposite ends of the protein. The high affinity site has a K(a) of 7.2 (+/- 4) x 10(6) M(-1) and the low affinity site a K(a) of 6.8 (+/- 4) x 10(5) M(-1) as determined by isothermal titration calorimetry. Mapped surfaces of the carbohydrate binding sites are presented, and implications for binding to gp120 are discussed.
A case for the average-half-face in 2D and 3D for face recognition (2009)

We observe that the human face is inherently symmetric and we would like to exploit this symmetry in face recognition. The average-half-face has been previously shown to do just that for a set of 3D faces when using eigenfaces for recognition. We build upon that work and present a comparison of the use of the average-half-face to the use of the original full face with 6 different algorithms applied to two- and three-dimensional (2D and 3D) databases. The average-half-face is constructed from the full frontal face image in two steps; first the face image is centered and divided in half and then the two halves are averaged together (reversing the columns of one of the halves). The resulting average-half-face is then used as the input for face recognition algorithms. Previous work has shown that the accuracy of 3D face recognition using eigenfaces with the average-half-face is significantly better than using the full face. We compare the results using the average-half-face and the full face using six face recognition methods; eigenfaces, multi-linear principal components analysis (MPCA), MPCA with linear discriminant analysis (MPCALDA), Fisherfaces (LDA), independent component analysis (ICA), and support vector machines (SVM). We utilize two well-known 2D face database as well as a 3D face database for the comparison. Our results show that in most cases it is superior to employ the average-half-face for frontal face recognition. The consequences of this discovery may result in substantial savings in storage and computation time.
Heterogeneity of mouse myeloma gamma G globulins as revealed by enzymatic proteolysis. (1969)

The sensitivity of mouse myeloma γG globulins to enzymatic proteolysis has been investigated under several experimental conditions. γG1 was found to be more resistant to papain or tryptic cleavage than γG2d and γG2b. Minor differences were found between the reactivities of the latter two proteins. γG2b showed extremely high sensitivity to the action of pepsin. The addition of cysteine to the incubation mixtures of globulins with papain or trypsin enhanced the degree of fragmentation, but some physical and immunochemical properties of these fragments were found to be different from those of fragments obtained in the absence of cysteine. The possible role of this reducing agent has been discussed.
Dual Inhibition of Human Type 4 Phosphodiesterase Isostates by (R*,R*)-(±)-Methyl 3-Acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1-pyrrolidinecarboxylate (1998)

Purified recombinant human type 4 phosphodiesterase B2B (HSPDE4B2B) exists in both a low- and a high-affinity state that bind (R)-rolipram with Kd's of ca. 500 and 1 nM, respectively [Rocque, W. J., Tian, G., Wiseman, J. S., Holmes, W. D., Thompson, I. Z., Willard, D. H., Patel, I. R., Wisely, G. B., Clay, W. C., Kadwell, S. H., Hoffman, C. R., and Luther, M. A. (1997) Biochemistry 36, 14250-14261]. Since the tissue distribution of the two isostates may be significantly different, development of inhibitors that effectively inhibit both forms may be advantageous pharmacologically. In this study, enzyme inhibition and binding of HSPDE4B2B by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-1-pyrrolidin ecarboxylate (1), a novel inhibitor of phosphodiesterase 4 (PDE 4), were investigated. Binding experiments demonstrated high-affinity binding of 1 to HSPDE4B2B with a stoichiometry of 1:1. Inhibition of PDE activity showed only a single transition with an observed Ki similar to the apparent Kd determined by the binding experiments. Deletional mutants of HSPDE4B2B, which have been shown to bind (R)-rolipram with low affinity, were shown to interact with 1 with high affinity, indistinguishable from the results obtained with the full-length enzyme. Bound 1 was completely displaced by (R)-rolipram, and the displacement showed a biphasic transition that resembles the biphasic inhibition of HSPDE4B2B by (R)-rolipram. Theoretical analysis of the two transitions exemplified in the interaction of (R)-rolipram with HSPDE4B2B indicated that the two isostates were nonexchangeable. Phosphorylation at serines 487 and 489 on HSPDE4B2B had no effect on the stoichiometry of binding, the affinity for binding, or the inhibition of the enzyme by 1. These data further illustrate the presence of two isostates in PDE 4 as shown previously for (R)-rolipram binding and inhibition. In contrast to (R)-rolipram, where only one of the two isostates of PDE 4 binds with high affinity, 1 is a potent, dual inhibitor of both of the isostates of PDE 4. Kinetic and thermodynamic models describing the interactions between the nonexchangeable isostates of PDE 4 and its ligands are discussed.
Convenient syntheses of phosphinic analogues of γ-aminobutyric- and glutamic acids (2016)

Three-steps, one-pot synthesis of 2-amino-4-(hydroxyphosphinyl)butyric acid from dibutyl ester of vinylphosphinic acid was carried out with an overall yield of 66%. 3-Aminopropylphosphinic acid was prepared from allylamine in three steps with an overall yield of 56%. These improved protocols allowed to obtain these commercially unavailable phosphinic analogues of glutamic acid and GABA for testing on potential molecular targets.
Stability of the Sherrington-Kirkpatrick solution of a spin glass model (1978)

The stationary point used by Sherrington and Kirkpatrick (1975) in their evaluation of the free energy of a spin glass by the method of steepest descent is examined carefully. It is found that, although this point is a maximum of the integrand at high temperatures, it is not a maximum in the spin glass phase nor in the ferromagnetic phase at low temperatures. The instability persists in the presence of a magnetic field. Results are given for the limit of stability both for a partly ferromagnetic interaction in the absence of an external field and for a purely random interaction in the presence of a field.
Prevention of acute graft‐versus‐host disease by humanized anti‐CD26 monoclonal antibody (2013)

CD26 (DPP4) is a T cell costimulatory molecule as well as T cell activation marker, and CD26(+) T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD26(+) T cells in graft-versus-host disease (GVHD) target organs. To expand our in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (x-GVHD) murine model. Following intraperitoneal injection of human peripheral blood mononuclear cells into non-obese diabetic severe combined immunodeficiency/γ(c) (-/-) mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26(high) human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased x-GVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4- immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukaemia effects in studies using cotransplantation of P815 murine leukaemic cells. In addition, CD26(+) lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.