gebhart/patrepeval huggingface dataset:
Non-Sialate Inhibitor of Influenza A/WSN/33 Neuraminidase (1995)

An N1 strain of influenza A virus neuraminidase (A/WSN/33 NA) was purified and used to screen for inhibitors. As a result, a well-known tuberculostatic, 4'-formylacetanilide thiosemicarbazone (or thiacetazone), was identified. Thiacetazone is a non-sialate compound and inhibits the enzyme in a noncompetitive manner with respect to the substrate sialic acid. Mechanistic studies indicate that the inhibition was due to the competition of thiacetazone with Ca2+, which maintains N1 neuraminidase in an active conformation. The Ki for the inhibition was estimated to be about 4 microM. Equilibrium exchange experiments revealed that when purified A/WSN/33 NA was incubated with 5 microM 45CaCl2, 2 mol of 45Ca2+ ion was exchanged into each mole of NA tetramer and subsequently displaced from the enzyme upon the introduction of the inhibitor. Inhibition of plaque formation by thiacetazone in an MDCK cell culture that had been infected with the influenza A/WSN/33 virus was demonstrated. Thiacetazone was highly specific for A/WSN/33 neuraminidase, since little effect was noted when it was tested against NAs from the other strains of influenza virus or from bacteria. This compound might represent a group of non-sialate inhibitors of influenza NA that bind to a noncatalytic or an allosteric site on the enzyme.
Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. (1995)

Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the production of cytokines in bone or bone marrow. However, controversy remains on the role of candidate factors, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). As IL-1 and TNF have many additive and/or synergistic effects in bone, we tested the hypothesis that the simultaneous block of IL-1 and TNF is required to prevent the initial phase of rapid bone loss that follows ovariectomy (ovx). To this aim, rats were ovariectomized and treated for 2 weeks with either IL-1 receptor antagonist (IL-1ra), an inhibitor of IL-1, or TNF-binding protein (TNFbp), an inhibitor of TNF. Ovx increased bone marrow cell secretion of IL-1 and TNF and decreased the bone density of the distal femur, as measured by dual energy x-ray absorptiometry. Ovx-induced bone loss was decreased by both IL-1ra and TNFbp and completely prevented by simultaneous treatment with IL-1ra and TNFbp. Combined treatment with IL-1ra and TNFbp decreased urinary pyridinoline cross-links, a marker of bone resorption that reflects osteoclast number and osteoclast activity, whereas treatment with either inhibitor alone was less effective. Both IL-1ra and TNFbp decreased the number of osteoclasts on the endocortical surfaces and stimulated bone formation, but the two inhibitors had no additive effects on these indexes, suggesting that inhibition of osteoclastogenesis and stimulation of bone formation do not account for the additive bone-sparing effects of IL-1ra and TNFbp. These inhibitors had no effect in sham-operated rats, indicating that they specifically blocked estrogen-dependent events. In conclusion, these data indicate that in the early post-ovx period, IL-1 and TNF play a critical causal role in inducing bone loss and do so by stimulating bone resorption and inhibiting bone formation.
Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion. (1992)

Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression.
Activation of the NF-κB transcription factor in a T-lymphocytic cell line by hypochlorous acid (1997)

Reactive oxygen species (ROS) such as hydrogen peroxide serve as second messengers in the induction of the transcription factor NF-κB, and hence in the activation and replication of human immunodeficiency virus type 1 (HIV-1) in human cells. During inflammatory reactions, many oxidative species are produced, one of which is hypochlorous acid (HOCl), which is responsible for the microbicidal effects of activated human polymorphonuclear leukocytes. Treatment of a T-lymphocytic cell line with micromolar concentrations of HOCl promoted the appearance of transcription factor NF-κB (the heterodimer p50/p65) in the nucleus of the cells, even in the absence of de novo protein synthesis. Western blot analysis of the NF-κB inhibitory subunits (IκB) demonstrated that both IκB-α proteolysis and p105 processing were induced by the treatment. NF-κB activation was very effective when cells were subjected to hyperthermia before being treated with HOCl. Various antioxidants, such as pyrrolidine dithiocarbamate, p-bromophenacyl-bromide and nordihydroguaiaretic acid could strongly reduce NF-κB translocation, demonstrating the importance of oxidative species in the transduction mechanism. Moreover, ACH-2 cells treated with HOCl or H2O2 released tumour necrosis factor-α (TNF-α) in the supernatants. The importance of TNF-α release in NF-κB induction by HOCl or H2O2 was demonstrated by the fact that: (1) the nuclear appearance of NF-κB was promoted in untreated cells; and (2) synergism between TNF-α and HOCl was detected. Collectively, these results suggest that HOCl should be considered as an oxidative species capable of inducing NF-κB in a T-lymphocytic cell line through a transduction mechanism involving ROS, and having a long-distance effect through subsequent TNF-α release.
Cis and trans activation of adenovirus IVa2gene transcription (1985)

The transcriptional control region of the adenovirus IVa2 promoter was analyzed by cloning this promoter in front of a gene coding for bacterial chloramphenicol acetyl transferase (CATase) and estimating levels of CATase and IVa2 promoter specific RNA synthesized after transfection. To produce detectable amounts of CATase with the IVa2 promoter, an enhancer has to be present in cis. In the absence of enhancer sequences, the adenovirus E1A gene can not stimulate CATase synthesis. When cells were transfected with plasmids containing enhancer sequences and various IVa2 mutant promoters upstream of the CAT gene, we observed that CATase activity was not reduced significantly even after deletion of all sequences upstream of the RNA initiation site. Synthesis of IVa2 specific RNA was dependent on plasmids containing an enhancer (SV40 72 bp repeat) that was present in cis. In the absence of enhancer sequences, co-transfection to provide the adenovirus E1A gene in trans also stimulated IVa2 RNA synthesis. When HeLa cells were transfected with various deletion mutants with an enhancer in cis it was seen that sequences -38 to -64 base pairs upstream of the RNA initiation site are necessary for efficient transcription. The E1A gene in trans and an enhancer in cis have an additive effect on RNA synthesis from both IVa2 and major late promoters. The basis for the conflicting results between transcription and CATase synthesis is discussed.
Sonoelectrochemical Synthesis of Nanoparticles (2009)

This article reviews the nanomaterials that have been prepared to date by pulsed sonoelectrochemistry. The majority of nanomaterials produced by this method are pure metals such as silver, palladium, platinum, zinc, nickel and gold, but more recently the syntheses have been extended to include the preparation of nanosized metallic alloys and metal oxide semiconductors. A major advantage of this methodology is that the shape andsize of the nanoparticles can be adjusted by varying the operating parameters which include ultrasonic power, current density, deposition potential and the ultrasonic vs electrochemical pulse times. Together with these, it is also possible to adjust the pH, temperature and composition of the electrolyte in the sonoelectrochemistry cell.
New Aminoacyl-tRNA Synthetase Inhibitors as Antibacterial Agents (2004)

Increasing rates of bacterial resistance to known classes of antibiotics present a severe global challenge. As a consequence, the search for new chemical entities that address novel bacterial targets remains ongoing. Aminoacyl-tRNA synthetases (aa-RS) are essential enzymes for protein biosynthesis and emerged as an interesting target class in antibacterial research. These enzymes are present in all living organisms, and they are indispensable for the highly specific translation of the messenger-RNA (mRNA) template into protein via specific transfer-RNAs (tRNAs) as adapter molecules. When one aa-RS is inhibited, the corresponding tRNA is not charged and is therefore unavailable for translation. This leads to protein synthesis inhibition, which, in turn, causes cell growth arrest. Consequently, each compound that inhibits any of the aa-RS is a potential antibacterial agent. The clinical utility of this principle is proven by the natural product Ile-RS inhibitor pseudomonic acid, which is currently marketed as an antibacterial agent for topical application. Various chemical structures that inhibit aa-RS have been identified. These inhibitors have either been isolated from natural sources or have been generated synthetically. The synthetic inhibitors are modifications of natural inhibitors, derivatives of the natural synthetase substrates and reaction intermediates, or have been identified by screening of compound libraries. The recent progress achieved with these different classes of aa-RS inhibitors and their antibacterial potential in vitro and in vivo is discussed in this review.
Impact of Heparan Sulfate Binding on Transduction of Retina by Recombinant Adeno-Associated Virus Vectors (2016)

AAV has emerged as the vector of choice for gene delivery to the retina, with attention focused on developing vectors that can mediate transduction following noninvasive, intravitreal injection. HS binding has been postulated to play a role in intravitreally mediated transduction of retina. Our evaluation of the HS binding of AAV2-based variants and other AAV serotype vectors and the correlation of this property with transduction points to HS affinity as a factor controlling retinal transduction following Ivt delivery. However, HS binding is not the only requirement for improved Ivt-mediated transduction. We show that AAV2-based vectors lacking heparin binding transduce retina by subretinal injection and display a remarkable ability to transduce photoreceptors, indicating that other receptors are involved in this phenotype.
Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. (1991)

The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.
The Dalkon Shield Controversy (1975)

The recent report of 209 cases of septic spontaneous abortion and 11 maternal deaths in the United States in women using the Dalkon Shield intrauterine device (IUD) raised the question about a possible causal relationship between the IUD and pelvic sepsis. It is essential to determine whether or not this sipsis is unique to the Dalkon Shield or generic to all types of IUDs. Our studies permit the conclusion that the tail of the Dalkon Shield is structurally and functionally different from the tails of the four other IUDs tested. The unique characteristics of the Dalkon tail theoretically could provide a mechanism whereby pathogenic bacteria from the vagina enter the uterine cavity and cause sepsis.
Th1 and Th2 CD4+ Cells in the Pathogenesis of Allergic Diseases (1997)

Our understanding of the molecular and genetic etiologies of allergic disorders, which affect 20%-30% of the general population, has greatly improved over the past several years. Previously, research focused on examination of immediate hypersensitivity reactions, initiated by the cross-linking of IgE molecules on the surface of mast cells/basophils, resulting in the release of a host of mediators, which cause symptoms typified by acute anaphylaxis. Although there has been substantial progress in understanding the molecular biology of mast cell and basophil activation and of the regulation of IgE synthesis, recent studies have shifted attention to the cellular and molecular mechanisms that cause a broader allergic inflammatory response and underlie the more chronic and severe symptoms of allergy and asthma. In this report, we will review a substantial body of recent experimental work that has provided the basis for our new understanding of the allergic inflammatory response and the pathogenesis of allergic diseases. We will describe the recent progress in defining the immunological basis for allergic disease, and how subsets of helper CD4+ T cells secreting a specific array of cytokines (Th2 cytokines) regulate/cause allergic inflammation. We will review the cell biology of Th2 cells, the role of Th2 cells in allergic disease, and biological, genetic, and therapeutic mechanisms that influence the differentiation of CD4+ T cells and enhance or suppress cytokine synthesis in Th2 cells. These mechanisms control the expression of allergic diseases, which occur in some but not all individuals following environmental exposure to allergens.
Cellulose Beads:  a New Versatile Solid Support for Microwave- Assisted Synthesis. Preparation of Pyrazole and Isoxazole Libraries (2003)

The synthesis of libraries of substituted pyrazoles and isoxazoles has been developed via in situ generation of polymer-bound enaminones. The synthetic protocol makes use of commercially available aniline cellulose, a low-cost and versatile biopolymer, under very mild conditions. This new support allowed us to carry out reactions in polar solvents under both conventional heating and MW irradiation without degradation of the polymer. The reaction between cellulose-bound enaminone and hydroxylamine or hydrazines to afford the target heterocycles in high yields directly in solution is the key step. The support can be conveniently recycled.
Postmenopausal hormone use and cholecystectomy in a large prospective study. (1994)

Women using postmenopausal hormones are at an increased risk of cholecystectomy. Women and their physicians should consider the spectrum of risks and benefits when deciding whether to take hormones.
The Early Post-War Boom and its Aftermath (1993)

Prior to the Second World War, much urban as well as rural property was owned by a relatively small number of aristocratic families who in most cases had owned the land for centuries. Indeed, despite the impact that the payment of death duties has had in splitting up the old estates, the aristocracy nowadays still hold large amounts of both urban and rural property, with four large estates — Grosvenor, Howard de Walden, Cadogan and Portman — owning some of the most valuable property in central London. Large tracts of urban and rural property are also owned by the Crown and by institutions such as the Oxford and Cambridge colleges, trade guilds and the churches. The Church of England is one of the largest landowners in the UK, with property comprising over half of its investment portfolio.
Integrated optical channel waveguides in silicon using SiGe alloys (1991)

Different techniques for fabrication of single-mode waveguides in silicon by etching and indiffusion are reported. Minimum propagation losses around 3dB/cm at a wavelength of 1. 3Lm have been achieved.
Depression-Inducing and Antidepressive Effects of Neuroleptics (1983)

The antidepressive and anxiolytic efficacy of flupenthixol has been investigated in numerous controlled and open trials involving patients with endogenous, reactive as well as senile depressions. When administered at a mean daily single or multiple dose of 1-2 mg, flupenthixol proved to be a very effective and well-tolerated antidepressant. As opposed to some of the currently available antidepressants, flupenthixol has a rapid onset of action which is often displayed within the first 2-3 days following its application. Flupenthixol decanoate has also a pronounced antidepressive and anxiolytic effect which appears to be adequate enough for treating mild to moderately severe syndromes of depression. This depot neuroleptic has been given at a fortnightly dosage ranging between 2.5 and 30 mg. However, if the aspect of efficacy in relation to tolerance has to be taken in to consideration, then 5 mg are apt to be an appropriate dose. Patients with an agitated depression and/or suicide ideation should, however, be excluded from therapy with this drug. Extrapyramidal movement disorders which may appear during treatment are a disadvantage of this medication. Apparently such disorders are rarely encountered if the dose is kept below 10 mg. Other untoward effects are very seldom indeed. A final and conclusive judgement on the possible application of flupenthixol decanoate in the prophylaxis of phases in patients with bipolar and periodical depressions is as yet not feasible. Further clinical trials are necessary before flupenthixol decanoate can be classified as a possible 'depot antidepressant'.
File Distribution Efficiencies: cfengine Versus rsync (2001)

This papers reports on a preliminary investigation of the performance of cfengine and rsync for file distribution for the purposes of system maintenance. It focuses on two aspects of file distribution: the transfer during an initial copy from a master server to a client, and the file verification of the client's files against the server's files. It is shown that for larger file transfers rsync performs better, while cfengine manages smaller transfers better.
Noradrenaline activation of neurotrophic pathways protects against neuronal amyloid toxicity (2010)

Degeneration of locus coeruleus (LC) noradrenergic forebrain projection neurons is an early feature of Alzheimer's disease. The physiological consequences of this phenomenon are unclear, but observations correlating LC neuron loss with increased Alzheimer's disease pathology in LC projection sites suggest that noradrenaline (NA) is neuroprotective. To investigate this hypothesis, we determined that NA protected both hNT human neuronal cultures and rat primary hippocampal neurons from amyloid-beta (Abeta(1-42) and Abeta(25-35)) toxicity. The noradrenergic co-transmitter galanin was also effective at preventing Abeta-induced cell death. NA inhibited Abeta(25-35)-mediated increases in intracellular reactive oxygen species, mitochondrial membrane depolarization, and caspase activation in hNT neurons. NA exerted its neuroprotective effects in these cells by stimulating canonical beta(1) and beta(2) adrenergic receptor signaling pathways involving the activation of cAMP response element binding protein and the induction of endogenous nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Treatment with functional blocking antibodies for either NGF or BDNF blocked NA's protective actions against Abeta(1-42) and Abeta(25-35) toxicity in primary hippocampal and hNT neurons, respectively. Taken together, these data suggest that the neuroprotective effects of noradrenergic LC afferents result from stimulating neurotrophic NGF and BDNF autocrine or paracrine loops via beta adrenoceptor activation of the cAMP response element binding protein pathway.
Characterization of the Binding of Serum Amyloid P to Laminin (1997)

Serum amyloid P (SAP) is a member of the pentraxin family. These are evolutionarily conserved proteins made up of five noncovalently bound identical subunits that are arranged in a flat pentameric disc. Although a variety of activities have been attributed to SAP and other pentraxins, their biological functions remain unclear. In humans SAP is a constitutive serum protein that is synthesized by hepatocytes. It is encoded by a single copy gene on chromosome 1. SAP is a component of all amyloid plaques and is also a normal component of a number of basement membranes including the glomerular basement membrane. The association and distribution of SAP within the glomerular basement membrane are altered or completely disrupted in a number of nephritides (e.g. Alport's Syndrome, type II membranoproliferative glomerulonephritis, and membranous glomerulonephritis). In the present study the binding of SAP to laminin was characterized. SAP binds to human laminin and merosin as well as mouse and rat laminins. The binding of SAP to mouse laminin is saturable and calcium-dependent. The Kd of this interaction is 2. 74 x 10(-7) M, with a SAP/laminin molar ratio of 1:7.1. Competition binding assays indicate that the binding of SAP to laminin is inhibited by both SAP and its analog, C-reactive protein, as well as phosphatidylethanolamine. In turbidity assays SAP enhanced the polymerization of laminin in a concentration-dependent manner. However, SAP did not alter the ability of laminin to serve as a cell adhesion substrate. Previous observations indicating that SAP binds to extracellular matrix components such as type IV collagen, proteoglycans, and fibronectin in concert with the data presented here suggest that SAP may play an important role in determining the structure of those basement membranes with which it is associated.