gebhart/patrepeval huggingface dataset:
Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: Activation of Toll-like receptor 7 (2003)

Certain C8-substituted and N7, C8-disubstituted guanine ribonucleosides comprise a class of small molecules with immunostimulatory activity. In a variety of animal models, these agents stimulate both humoral and cellular immune responses. The antiviral actions of these guanosine analogs have been attributed to their ability to induce type I IFNs. However, the molecular mechanisms by which the guanosine analogs potentiate immune responses are not known. Here, we report that several guanosine analogs activate Toll-like receptor 7 (TLR7). 7-Thia-8-oxoguanosine, 7-deazaguanosine, and related guanosine analogs activated mouse immune cells in a manner analogous to known TLR ligands, inducing cytokine production in mouse splenocytes (IL-6 and IL-12, type I and II IFNs), bone marrow-derived macrophages (IL-6 and IL-12), and in human peripheral blood leukocytes (type I IFNs, tumor necrosis factor alpha and IL-12). The guanosine congeners also up-regulated costimulatory molecules and MHC I/II in dendritic cells. Genetic complementation studies in human embryonic kidney 293 cells confirmed that the guanosine analogs activate cells exclusively via TLR7. The stimulation of TLR7 by the guanosine analogs in human cells appears to require endosomal maturation because inhibition of this process with chloroquine significantly reduced the downstream activation of NF-kappaB. However, TLR8 activation by R-848 and TLR2 activation by [S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-R-Cys-S-Ser-Lys4-OH, trihydrochloride)] were not inhibited by chloroquine, whereas TLR9 activation by CpG oligodeoxynucleotides was abolished. In summary, we present evidence that guanosine analogs activate immune cells via TLR7 by a pathway that requires endosomal maturation. Thus, the B cell-stimulating and antiviral activities of the guanosine analogs may be explained by their TLR7-activating capacity.
Historical review: megakaryopoiesis and thrombopoiesis (2008)

The study of thrombopoiesis has evolved greatly since an era when platelets were termed "the dust of the blood," only about 100 years ago. During this time megakaryocytes were identified as the origin of blood platelets; marrow-derived megakaryocytic progenitor cells were functionally defined and then purified; and the primary regulator of the process, thrombopoietin, was cloned and characterized and therapeutic thrombopoietic agents developed. During this journey we continue to learn that the physiologic mechanisms that drive proplatelet formation can be recapitulated in cell-free systems and their biochemistry evaluated; the molecular underpinnings of endomitosis are being increasingly understood; the intracellular signals sent by engagement of a large number of megakaryocyte surface receptors have been defined; and many of the transcription factors that drive megakaryocytic fate determination have been identified and experimentally manipulated. While some of these biologic processes mimic those seen in other cell types, megakaryocytes and platelets possess enough unique developmental features that we are virtually assured that continued study of thrombopoiesis will yield innumerable clinical and scientific insights for many decades to come.
Are Active Microbiological Surveillance and Subsequent Isolation Needed to Prevent the Spread of Methicillin-Resistant Staphylococcus aureus? (2005)

Surveillance cultures and genotyping of MRSA and MSSA isolates demonstrated the absence of cross-transmission among patients in the MICU, despite ongoing introduction of these pathogens. Reporting culture results and isolating colonized patients, as suggested by some guidelines, would have falsely suggested the success of such infection-control policies.
In vitro and in vivo effector function of rat IgG2a monoclonal anti-S. mansoni antibodies. (1982)

Rat IgG2a monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with S. mansoni for 5 wk and IR983F nonsecreting rat myeloma cells. The cell supernatants of one particular IgG2a-producing clone (IPL Sm1) as well as ascitic fluids induced by this clone revealed anti-S. mansoni activity detected by immunofluorescence on schistosoma sections. In vitro studies of the effector function of such antibodies revealed that the rat IgG2a monoclonal antibodies mediated high levels of rat eosinophil-dependent cytotoxic effect against S. mansoni schistosomula, similar to that obtained with 5-week infected rat serum. Passive transfer experiments carried out with IPL Sm1 ascitic fluid showed a significant level of passive protection against a challenge infection. These results indicate a possible use of the monoclonal antibodies in analyzing in vivo functions of IgG2a antibodies, as well as in isolating potentially protective target antigens.
Binary error probabilities on Earth-space links subject to scintillation fading (1985)

Theoretical estimates are derived of the average probability 〈Pb〉 of bit error rate that would occur for a binary CPSK signal on an Earth-space link in the presence of scintillation fading and additive white Gaussian noise. Strong scintillations are shown to produce a significant degradation in 〈Pb〉. Experimental results of the signal amplitude distribution obtained on a 7.1° elevation satellite downlink lead to values of 〈Pb〉 against 〈Eb/No〉 which agree well with the results obtained using the theoretical Moulsley-Vilar distribution (1982).
Delayed Triphenyltetrazolium Chloride Staining Remains Useful for Evaluating Cerebral Infarct Volume in a Rat Stroke Model (1997)

Sixteen of 24 Sprague-Dawley rats with permanent middle cerebral artery occlusion for 24 hours were subjected to immediate or 8-hour delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining (n = 8 at each time point); the other 8 animals were subjected to immediate or 8-hour delayed measurement of succinate dehydrogenase activity (n = 4 at each time point). The TTC staining was of good quality good in all animals, and the infarcted region could be distinguished easily from normal tissue. There was no significant difference in corrected infarct volume between the two groups (263.8 +/- 43.1 versus 264.4 +/- 54.8 mm3 [mean +/- standard deviation]). The activity of succinate dehydrogenase was not significantly different when normal or infarcted tissue was measured immediately after death or with an 8 hour delay, although less activity was detected at both time points in the infarcted tissue. These results demonstrate that an 8-hour delay of TTC staining is reliable for evaluating brain infarct volume in a rat stroke model and this probably is attributable to the slow deterioration of mitochondrial enzyme activity in nonischemic brain over this time period.
Isolation and Characterization of a Coagulation Factor Xa Inhibitor from Black Fly Salivary Glands (1990)

We have discovered and characterized a novel coagulation factor Xa inhibitor from the salivary gland of the black fly, Simulium vittatum. Salivary glands were surgically dissected from the flies and a crude salivary gland extract was tested for inhibition of a number of coagulation assays. The gland extract inhibited both thrombin and factor Xa. To purify further the factor Xa inhibitor, a factor Xa affinity column was utilized. Final purification of the black fly factor Xa inhibitor was achieved by reverse-phase C8 microbore high pressure liquid chromatography. Inhibition of factor Xa was nearly stoichiometric by the purified inhibitor with no inhibitor of thrombin detected. SDS-polyacrylamide gel electrophoresis indicated the inhibitor had a molecular weight of 18,000 and sequence analysis of the inhibitor revealed a blocked amino terminus. These data indicate that the blood-sucking black fly has evolved a highly potent inhibitor of mammalian coagulation factor Xa to disrupt its host normal hemostatic clotting mechanisms.
Extensive and Prolonged Restoration of Dystrophin Expression with Vivo-Morpholino-Mediated Multiple Exon Skipping in Dystrophic Dogs (2012)

Duchenne muscular dystrophy (DMD) is a severe and the most prevalent form of muscular dystrophy, characterized by rapid progression of muscle degeneration. Antisense-mediated exon skipping is currently one of the most promising therapeutic options for DMD. However, unmodified antisense oligos such as morpholinos require frequent (weekly or bi-weekly) injections. Recently, new generation morpholinos such as vivo-morpholinos are reported to lead to extensive and prolonged dystrophin expression in the dystrophic mdx mouse, an animal model of DMD. The vivo-morpholino contains a cell-penetrating moiety, octa-guanidine dendrimer. Here, we sought to test the efficacy of multiple exon skipping of exons 6-8 with vivo-morpholinos in the canine X-linked muscular dystrophy, which harbors a splice site mutation at the boundary of intron 6 and exon 7. We designed and optimized novel antisense cocktail sequences and combinations for exon 8 skipping and demonstrated effective exon skipping in dystrophic dogs in vivo. Intramuscular injections with newly designed cocktail oligos led to high levels of dystrophin expression, with some samples similar to wild-type levels. This is the first report of successful rescue of dystrophin expression with morpholino conjugates in dystrophic dogs. Our results show the potential of phosphorodiamidate morpholino oligomer conjugates as therapeutic agents for DMD.
Neurotrophin‐4/5, brain‐derived neurotrophic factor, and neurotrophin‐3 promote survival of cultured vestibular ganglion neurons and protect them against neurotoxicity of ototoxins (1995)

The ability of neurotrophin-4/5 (NT-4/5), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF) to promote survival of postnatal rat vestibular ganglion neurons (VGNs) was examined in dissociated cell cultures. Of the four neurotrophins, NT-4/5 and BDNF were equally effective but more potent than NT-3 in promoting the survival of VGNs. In contrast, NGF showed no detectable effects. As expected, TrkB-IgG (a fusion protein of extracellular domain of TrkB and Fc domain of human immunoglobulin G) specifically inhibited the survival-promoting, effects by NT-4/5 or BDNF and TrkC-IgG fusion protein completely blocked that of NT-3. Immunohistochemistry with TrkB, TrkA, and p75 antisera revealed that VGNs made TrkB and p75 proteins, but not TrkA protein. Ototoxic therapeutic drugs such as cisplatin and gentamicin often induce degeneration of hair cells and ganglion neurons in both auditory and vestibular systems that leads to impairment of hearing and balance. When cisplatin and gentamicin were added to the dissociated VGN culture in which the hair cells were absent, additional cell death of VGNs was induced, suggesting that the two ototoxins may have a direct neurotoxic effect on ganglion neurons in addition to their known toxicity on hair cells. However, if the cultures were co-treated with neurotrophins, NT-4/5, BDNF, and NT-3, but not NGF, prevented or reduced the neurotoxicity of the two ototoxins. Thus, the three neurotrophins are survival factors for VGNs and are implicated in the therapeutic prevention of VGN loss caused by injury and ototoxins.
Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. (1984)

To examine myc protein products in the wide variety of human tumor cells having alterations of the c-myc locus, we have prepared an antiserum against a synthetic peptide corresponding to the predicted C-terminal sequence of the human c-myc protein. This antiserum (anti-hu-myc 12C) specifically precipitated two proteins of 64 and 67 kilodaltons in quantities ranging from low levels in normal fibroblasts to 10-fold-higher levels in Epstein-Barr virus-immortalized and Burkitt's lymphoma cell lines, to 20- to 60-fold-higher levels in cell lines having amplified c-myc. The p64 and p67 proteins were found to be highly related by partial V8 proteolytic mapping, and both were demonstrated to be encoded by the c-myc oncogene, using hybrid-selected translation of myc-specific RNA. In addition, the p64 protein was specifically precipitated from cells transfected with a translocated c-myc gene. Both p64 and p67 were found to be nuclear phosphoproteins with extremely short half-lives. In tumor cell lines having alterations at the c-myc locus due to amplification or translocation, we observed a significant change in the expression of p64 relative to p67 when compared with normal or Epstein-Bar virus-immortalized cells.
Early changes in limb buds of chick embryos after thalidomide treatment. (1966)

Since the first observations of hypoplastic and aplastic thalidomide deformities in infants (McBride, 1961; Lenz, 1962), the literature on this subject has grown to many hundreds of communications. Experimental investigations in almost all cases have been undertaken to show whether thalidomide and its metabolites have any teratogenic effects in experimental animals. Numerous review papers are available on this subject, e.g. Giroud, Tuchmann-Duplessis & Mercier-Parot (1962), Somers (1963), and Salzgeber & Wolff (1964).

Chick embryos did not seem for some time to be suitable for experimental production of typical thalidomide deformities. However, Kemper (1962 a, b ), Yang, Yang & Liang (1962). Boylen, Home & Johnson (1963) and Leone (1963) have shown that thalidomide can produce a whole range of ectromelian deformities provided that it is introduced into the egg at a particular period of embryonic development.
Effect of the preparation route, PEG and annealing on the phase stability of Fe3O4nanoparticles and their magnetic properties (2011)

Fe3O4 nanoparticles are synthesised via two different methods: (1) co-precipitation of Fe2+ and Fe3+ ions and (2) oxidative alkaline hydrolysis of Fe2+ ions under atmospheric pressure using different protective agents (PEG 200 and PEG 3000) and urea as a base. The preparation method and the polyethylene glycol (PEG) used are concurrently affecting the phase stability of the formation of the iron oxides: the co-precipitation method using PEG 200 (E4a) or PEG 3000 (E4b) leads to the formation of different ratios of Fe2O3 and Fe3O4, whereas the oxidative hydrolysis of Fe2+ using PEG 200 gives Fe3O4 (E2) powder as a major product. The average crystallites size of E4a and E4b is almost identical, i.e. around 19 nm but the saturation magnetisation of E4b is three times larger than that of E4a. The sample E2 shows the highest saturation magnetisation value 74 emu/g, with an average crystallites size of 71 nm. Transmission electron microscopy analysis confirmed that the E2 sample shows the presence of needles crystals with typical sizes around 10 and 50 nm and its selected area diffraction (SAD) shows a typical diffraction of the spinel structure of magnetite. On the other hand, E4b sample shows elongated nanoparticles with typical sizes around 24 nm and its SAD confirmed the presence of a mixture of Fe2O3 and Fe3O4 as many dispersed spots were obtained.
All-fiber video distribution (AFVD) systems using SCM and EDFA techniques (1993)

this paper describe the design and performance of all-fiber video distribution (AFVD) systems based on AM/FM FDM subcarrier multiplexing (SCM) and erbium-doped fiber amplifiers (EDFAs). The impact of applying EDFAs to SCM analog video distribution systems is investigated. AM/FM hybrid systems, which can simultaneously distribute 11 AM TV channels and 50 FM TV channels are proposed and discussed. Four-stage amplifier-branch transmission experiments are introduced. The construction and performance of a newly designed 50-channel FM tuner are also presented.
A lactose fia-biosensor system for monitoring and process control (2004)

In this work an enzymatic lactose biosensor composed of the immobilized enzymes b-galactosidase and glucose oxidase was developed. Oxygen consumption during the reaction catalyzed by these enzymes was detected. The biosensor was integrated into an FIA (flow injection analysis) system that allows measurement of lactose on-line in less than three minutes. This biosensor was used to monitor lactose concentration during the production of b-galactosidase by the yeast Kluyveromyces marxianus from cheese whey. The sensor showed good stability after four months and after almost 7000 measurements had been performed. The analytical curve was linear in the range of lactose concentration from 1 to 30 g/L.
Gene synthesis, expression, structures, and functional activities of site-specific mutants of ubiquitin. (1987)

To study the structure and function of ubiquitin we have chemically synthesized a ubiquitin gene that encodes the amino acid sequence of animal ubiquitin, inserting a series of restriction enzyme sites that divide the gene into eight "mutagenesis modules." A series of site-specific mutations were constructed to selectively perturb various regions of the molecule. The mutant genes were expressed in a large quantity of Escherichia coli, and the modified proteins were purified. To determine the structural effects of the amino acid substitutions, the solution structure of ubiquitin was investigated by two-dimensional NMR and each of the mutant proteins were screened for structural perturbations. With one exception, virtually no changes were seen other than at the point of mutation. Functional studies of the mutant proteins with the ubiquitin-activating enzyme E1 and in the reticulocyte protein degradation assay were used to identify regions of the molecule important to ubiquitin's activity in intracellular proteolysis.
Biochemical Markers in Synovial Fluid Identify Early Osteoarthritis of the Glenohumeral Joint (1996)

The objective of this study on the glenohumeral joint was to assess the (1) accuracy of clinical diagnosis of osteoarthritis compared with arthroscopic diagnosis, and (2) the ability of biochemical markers in synovial fluid to detect osteoarthritis. Patients (96) were examined clinically and the preoperative diagnosis of osteoarthritis was recorded. At surgery (arthroscopy or arthroplasty), the glenohumeral joint was inspected for signs of osteoarthritis, and the joint osteoarthritis grade (I-IV) was recorded. At surgery, synovial fluid lavage was obtained from the joint, and later analyzed to determine levels of aggrecan components: total sulfated glycosaminoglycan and keratan sulfate epitope, link protein and the chondroitin sulfate epitope recognized by antibody 3B3 (3B3(-)). Compared with arthroscopic diagnosis of osteoarthritis, the results showed that the clinical diagnosis did not wrongly identify joints without osteoarthritis, and was always able to identify joints with advanced (Grade IV) osteoarthritis. Grade II osteoarthritis was rarely identified (10% of the time), and Grade III osteoarthritis was identified 50% of the time. Biochemical assessment of the synovial fluid showed that the catabolic markers (sulfated glycosaminoglycan, keratan sulfate and link protein) were elevated in fluids from joints with moderate (Grade III) and advanced osteoarthritis (Grade IV), and the 3B3(-) epitope was elevated in Grades II, III, and IV. These results show that arthroscopic diagnosis for osteoarthritis, of the glenohumeral joint is particularly useful for early and moderate osteoarthritis, where clinical (nonarthroscopic) diagnosis is poor, and that biochemical analysis of the synovial fluids corresponds well to arthroscopic diagnosis of shoulder osteoarthritis.
Novel medical wired palpation device: A validation study of material properties (2013)

The lack of haptic feedback during Minimally Invasive Surgery (MIS) can be potentially dangerous, and has been a factor in preventing a wider application of MIS. A Wired Palpation Device (WPD), which is designed to provide the surgeon with soft tissue viscoelasticity information during MIS, can be an appealing solution to this challenge. As a novel device, the validation of its functionality is critical before being put into actual usage. In this paper, a procedure assessing the effectiveness of the WPD in characterizing soft tissue material properties was introduced. Strain creep indentation tests were performed using the WPD method on four different synthetic tissue samples, followed by standard stress relaxation indentation tests on the same samples. The results showed that the WPD was reliable in characterizing the long-term material response when compared to the traditional method (an average of 5.21% difference), but may still need improvement in its capability of capturing short-term transient soft tissue response.
Cibenzoline Has an Inhibitory Effect on Vasorelaxation Mediated by Adenosine Triphosphate-Sensitive K+ Channels in the Rat Carotid Artery (2001)

In isolated rat carotid artery, cibenzoline (10(-6) to 10(-5) M) reduced vasorelaxation to levcromakalim in a concentration-dependent fashion. These results suggest that from the clinically relevant concentrations, a novel class Ia antiarrhythmic drug, cibenzoline, impairs carotid vasodilation mediated by adenosine triphosphate-sensitive K(+) channels.
A Structure-based Approach to Designing Non-natural Peptides That Can Activate Anti-melanoma Cytotoxic T Cells (1999)

Tumor antigens presented by major histocompatibility complex (MHC) class I molecules and recognized by CD8(+) cytotoxic T lymphocytes (CTLs) may generate an efficient antitumor immune response after appropriate immunization. Antigenic peptides can be used in vivo to induce antitumor or antiviral immunity. The efficiency of naked peptides may be greatly limited by their degradation in the biological fluids. We present a rational, structure-based approach to design structurally modified, peptidase-resistant and biologically active analogues of human tumor antigen MAGE-1.A1. This approach is based on our understanding of the peptide interaction with the MHC and the T cell receptor and its precise degradation pathway. Knowledge of these mechanisms led to the design of a non-natural, minimally modified analogue of MAGE-1.A1, [Aib2, NMe-Ser8]MAGE-1.A1, which was highly peptidase-resistant and bound to MHC and activated MAGE-1.A1-specific anti-melanoma CTLs. Thus, we showed that it is possible to structurally modify peptide epitopes to obtain analogues that are still specifically recognized by CTLs. Such analogues may represent interesting leads for antitumor synthetic vaccines.
GLUTs and Mammalian Sperm Metabolism (2010)

Mammalian cells use glucides as a substrate that can be catabolized through glycolitic pathways or oxidative phosphorylation, used as a source of reducing potential, or used for anabolic aims. An important role in supplying cells with energy is played by different membrane proteins that can actively (sodium-dependent glucose transporters) or passively (glucose transporters; GLUT) transport hexoses through the lipidic bilayer. In particular, GLUTs are a family of 13 proteins that facilitate the transport of sugars and have a peculiar distribution in different tissues as well as a particular affinity for substrates. These proteins are also present in mature sperm cells, which, in fact, need carriers for uptake energetic sources that are important for maintaining cell basic activity as well as specific functions, such as motility and fertilization ability. Likewise, several GLUTs have been studied in various mammalian species (man, bull, rat, mouse, boar, dog, stallion, and donkey) to point out both their actual presence or absence and their localization on plasma membrane. The aim of this work is to give an overall picture of the studies available on GLUTs in mammalian spermatozoa at this moment, pointing out the species peculiarity, the possible role of these proteins, and the potential future research on this item.