gebhart/patrepeval huggingface dataset:
N-Glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on host stress response, production yield and vaccine potential (2015)

Plant-based transient overexpression systems enable rapid and scalable production of subunit vaccines. Previously, we have shown that cholera toxin B subunit (CTB), an oral cholera vaccine antigen, is N-glycosylated upon expression in transgenic Nicotiana benthamiana. Here, we found that overexpression of aglycosylated CTB by agroinfiltration of a tobamoviral vector causes massive tissue necrosis and poor accumulation unless retained in the endoplasmic reticulum (ER). However, the re-introduction of N-glycosylation to its original or an alternative site significantly relieved the necrosis and provided a high CTB yield without ER retention. Quantitative gene expression analysis of PDI, BiP, bZIP60, SKP1, 26Sα proteasome and PR1a, and the detection of ubiquitinated CTB polypeptides revealed that N-glycosylation significantly relieved ER stress and hypersensitive response, and facilitated the folding/assembly of CTB. The glycosylated CTB (gCTB) was characterized for potential vaccine use. Glycan profiling revealed that gCTB contained approximately 38% plant-specific glycans. gCTB retained nanomolar affinity to GM1-ganglioside with only marginal reduction of physicochemical stability and induced an anti-cholera holotoxin antibody response comparable to native CTB in a mouse oral immunization study. These findings demonstrated gCTB's potential as an oral immunogen and point to a potential role of N-glycosylation in increasing recombinant protein yields in plants.
Homologous recombination of copackaged retrovirus RNAs during reverse transcription (1992)

According to prevailing models, the high frequency of recombination in retroviruses occurs during reverse transcription of two genetically different genomes copackaged into virion particles. This view has been tested in our studies of the mechanism of recombination within homologous sequences of two retroviral genomes during a single round of virus replication and in the absence of helper virus. The recombination substrates were Moloney murine leukemia virus-based vectors, each of which contains an altered defective neomycin gene (neo) under the transcriptional control of the 5' long terminal repeat; the 3' sequences of each construct contain either the Moloney murine leukemia virus or simian virus 40 large-T polyadenylation sequence. One neo gene contained a linker insertion mutation at the 5' end (neo minus), and the other contained a deletion and linker insertion at the 3' end (neo delta 3). Each of the mutant neo constructs was introduced into the packaging helper cell line psi 2 by sequential cotransfection, and individual psi 2 double transformants were selected. Supernatant fluids from the cloned psi 2 double transformants were used to infect NIH 3T3 cells, and recombinant neo+ proviruses were detected by their ability to confer G418 resistance during infection of NIH 3T3 cells. Our results show that (i) recombination between a homologous sequence of about 560 bp occurred with a frequency of about 10(-4) per virus replication cycle; (ii) recombination occurred only after the viral RNAs had been packaged into particles, i.e., recombination between the two vector DNAs or between viral RNAs prior to packaging was not detected; and (iii) copackaging of two different genomic RNAs as a heterodimer is a prerequisite for recombination. Furthermore, our results indicate that recombination can occur during the DNA negative-strand synthesis of reverse transcription.
L-5-Hydroxytryptophan Versus Placebo in Childhood Migraine Prophylaxis: A Double-Blind Crossover Study (1986)

L-5HTP was tested versus placebo in a double-blind crossover study of 27 migraine children aged 6-12 years, who recorded their headaches in a headache diary for 1 month. Twenty-one patients subsequently started the trial. The mean daily dose of L-5HTP was 5 mg/kg body weight, and each treatment period with either L-5HTP or placebo lasted 12 weeks. In group A (L-5HTP-placebo; 10 patients) and group B (placebo-L-5HTP; 11 patients) both L-5HTP and placebo led to a significant reduction of the migraine index and frequency of migraine attacks during the 3rd month of each treatment period. However, we found a treatment X period interaction because the efficacy determinants decreased significantly during the first and the second treatment periods in both groups irrespective of the sequence of treatments. No differences were found between L-5HTP (first period of group A) and placebo (first period of group B).
Management of Urinary Tract Injuries Following Total Hysterectomy (2018)

Objective: This study elaborated on the clinical experience of patients who underwent urologic management due to urologic complications after receiving a total hysterectomy at a regional hospital. Materials and methods: A total of 696 female patients received the four types of total hysterectomy including total abdominal hysterectomy, transvaginal hysterectomy, lapaparoscopic hysterectomy or robotic hysterectomy for variant gynecologic pathologies. Only 22 cases (3.2%) had urologic procedures performed during or after the operations from 2012/1/1 to 2016/6/30. Results: Of the 22 cases, thirteen (1.9%) received a series of conservative managements only, including cystoscopy, ureteroscopy, endoscopic ureterotomy, ureteral catheterization or double J stenting during the follow-up period. Nine more complicated cases (1.3%) eventually had definitive management, including repair of the urinary bladder rupture, repair of the vesicovaginal fistula, ureteroureterostomy or ureteroneocystostomy. However, five of these nine cases had both conservative and definitive management. The mean delay interval between the initial management and gynecologic procedure was 19.3 days. For definitive management and the gynecologic procedure, the period was 52.8 days. Conclusions: Compared to previous studies, the incidence of urologic injuries following a total hysterectomy in our hospital was similar. From the paper review, it seems early recognition does not improve the outcome but we found a 100% good outcome in patients with definitive management. Copyright © 2017, Taiwan Urological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
On the Application of Importance Sampling to the Simulation of Digital Satellite and Multihop Links (1984)

Importance sampling is one of the more useful techniques for reducing the number of samples required in Monte Carlo simulation. In the communication context, it has been applied and discussed in conjunction with single-hop digital systems. The purpose of this paper is to extend the method of application of importance sampling to multihop digital communication systems, with particular reference to the two-hop, or satellite, case. The situation is examined both for the case when the receiver is nonlinear and for when it is linear.
A destination prediction method using driving contexts and trajectory for car navigation systems (2009)

Car navigation systems provide the best route to a destination quickly and effectively. However, during daily driving, this information is not necessary since drivers already know the route to the destination very well. In addition, it is time-consuming for drivers to input the destination. Thus, our research group has proposed a new car navigation system that provides information related to the destination by predicting the user's destination automatically. We propose the use of a new method that predicts the destination on the basis of the driving trajectory and the contexts in which the user drives. A system that uses our method knows the destination without user interaction and provides information related to the correct destination.
Determination of Irreversible Ischemia by Xenon-Enhanced Computed Tomographic Monitoring of Cerebral Blood Flow in Patients with Symptomatic Vasospasm (1989)

In patients with subarachnoid hemorrhage, delayed neurological deficits, often followed by infarction, are believed to result from ischemia caused by vasospasm. Cerebral blood flow (CBF) data have been useful in predicting the risk of vasospasm in these patients and in distinguishing those deficits caused by vasospasm. Although CBF thresholds for infarction have been established in animals, few clinical studies have correlated CBF values with neurological symptoms and infarction. To assess the sensitivity to ischemia provided by xenon-enhanced computed tomography (Xe/CT) of CBF and to define the clinical significance of specific values that it measures, we compared the clinical, CT, and Xe/CT findings on CBF in 51 patients with subarachnoid hemorrhage caused by ruptured aneurysms. Each patient had 1 to 6 Xe/CT studies. Fourteen patients had symptomatic vasospasm. In all 14, the first post deficit Xe/CT study found abruptly reduced CBF, either regionally or globally. In 9 of these 14 patients, flow values fell below 15 ml/100 g/min in 2 or more adjacent 2-cm cortical regions of interest, and in all 9, concurrent follow-up CT scans showed infarction in these regions. Eight of the 9 had paralysis and a severe sensory deficit. No patient whose CBF remained above 18 ml/100 g/min developed infarction. The blood flow studies caused neither significant complications nor neurological deterioration. The Xe/CT CBF method appears very sensitive to the early detection of symptomatic vasospasm. In most patients with subarachnoid hemorrhage, this noninvasive technique can replace angiography to delineate the location and severity of vasospasm, and may be useful in predicting the development of infarction.
Dose‐dependent response of gamma irradiation on mechanical properties and related biochemical composition of goat bone‐patellar tendon‐bone allografts (1995)

We studied the effects of gamma irradiation on the dimensions, mechanical and material properties, and mature hydroxypyridinium crosslink density of collagen in goat patellar tendon-bone specimens. Left and right patellar tendon-bone units were removed from 10 adult female goats and were bisected longitudinally. Each tendon half was frozen, and then the left halves were exposed to 4, 6, or 8 Mrad (40,000, 60,000, or 80,000 Gy) of gamma irradiation. The contralateral tendon halves served as controls (no irradiation). Each specimen then was loaded to failure in tension, and its soft-tissue midsubstance was processed to measure collagen content and hydroxypyridinium crosslink density. Dose-dependent reductions in the mechanical properties were found, including 46% (p < 0.01) and 18% (p < 0.05) reductions in maximum force and stiffness, respectively, at 4 Mrad. Similar reductions were noted in material properties, including 37% (p < 0.005) and 8% (p > 0.05) reductions in maximum stress and modulus, respectively, at 4 Mrad. These results are consistent with our previous report involving 2 and 3 Mrad (20,000 and 30,000 Gy) of exposure. We also found significant decreases in hydroxypyridinium crosslink density with 6 Mrad of irradiation (p < 0.05). However, since only one biomechanical parameter (modulus) correlated significantly with only one biochemical measure (hydroxypyridinium crosslink density) (p < 0.05), other possible mechanisms also are being explored to more fully explain these dose-dependent changes.
Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. (1997)

Multiple steps are involved in the metastasis of cancer cells from primary sites to distant organs. These steps should be considered in the design of pharmacologic approaches to prevent or inhibit the metastatic process. In the present study, we have compared the effects of inhibiting several steps involved in the bone metastatic process individually with inhibition of both together. The steps we chose were matrix metalloproteinase (MMP) secretion, likely involved in tumor cell invasion, and osteoclastic bone resorption, the final step in the process. We used an experimental model in which inoculation of human estrogen-independent breast cancer MDA-231 cells into the left cardiac ventricle of female nude mice causes osteolytic lesions in bone. To inhibit cancer invasiveness, the tissue inhibitor of the MMP-2 (TIMP-2), which is a natural inhibitor of MMPs, was overexpressed in MDA-231 cells. To inhibit bone resorption, a potent bisphosphonate, ibandronate (4 microg/mouse) was daily administered subcutaneously. Nude mice received either; (a) nontransfected MDA-231 cells; (b) nontransfected MDA231 cells and ibandronate; (c) TIMP-2-transfected MDA-231 cells; or (d) TIMP-2-transfected MDA-231 cells and ibandronate. In mice from group a, radiographs revealed multiple osteolytic lesions. However, in mice from group b or group c, osteolytic lesions were markedly decreased. Of particular note, in animals from group d receiving both ibandronate and TIMP-2-transfected MDA-231 cells, there were no radiologically detectable osteolytic lesions. Survival rate was increased in mice of groups c and d. There was no difference in local enlargement in the mammary fat pad between nontransfected and TIMP-2-transfected MDA-231 cells. These results suggest that inhibition of both MMPs and osteoclastic bone resorption are more efficacious treatment for prevention of osteolytic lesions than either alone, and suggest that when therapies are designed based on the uniqueness of the bone microenvironment and combined with several common steps in the metastatic process, osteolytic bone metastases can be more efficiently and selectively inhibited.
The specific 18-kilodalton antigen of Mycobacterium leprae is present in Mycobacterium habana and functions as a heat-shock protein. (1990)

A mAb previously thought to be specific for Mycobacterium leprae has been found to cross-react with a cultivable mycobacterium, Mycobacterium habana TMC5135. The epitope is present on a protein of identical molecular mass (18 kDa) in both species. When M. habana is subjected to heat shock, expression of the protein is significantly increased, whereas other forms of environmental stress do not increase its expression. Since immunization of mice with M. habana results in protection against infection with M. leprae, the possibility of using a molecular genetic approach to investigate the role of this protein in protective immunity is raised.
An Integrated Fluorescence Detection System in Poly(dimethylsiloxane) for Microfluidic Applications (2001)

This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (microAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-microm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 microm) colored polycarbonate filter was placed on the top of the embedded microAPD to absorb scattered excitation light before it reached the detector. The microAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (approximately 200 microm) of the microAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the microAPD (30 microm) matched the dimensions of the channels (50 microm). A blue light-emitting diode was used for fluorescence excitation. The microAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (approximately 25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications.
Sharing telematics courses - The CANDLE project (2001)

To ease the creation and use of web-based course material, some of the leading european universities and companies in the area of telematics started a project, named CANDLE (Cooperative And Network Distributed Learning Environment)1. This project has three different goals. First it plans to provide a service to coordinate the joint development of course material. To demonstrate the benefit of such a service, the second goal is to create web-based material for courses in the area of telematics. The third goal of the project is to develop a number of methods that guide authors in using the service and ease the transformation of traditional course material into reusable web-based material. This paper discusses these main goals of the CANDLE project.
Regulation of Cell Growth by Recombinant Oncostatin M (1990)

Oncostatin M is a novel growth regulator originally isolated from differentiated human histiocytic lymphoma cells and activated T-lymphocytes based on its ability to inhibit the growth of A375 melanoma cells. We report here that oncostatin M is a widely acting regulator which alters the growth and/or morphology of cells derived from a variety of cancer cell types. At picomolar concentrations, recombinant oncostatin M inhibited the growth of 13/24 tumor cell lines. Six out of 7 lung cancer cell lines were inhibited by oncostatin M, but none of 6 colon cancer cell lines were affected. Oncostatin M also stimulated the growth of some normal cells (3/6), indicating that it, like many growth regulators, is bifunctional. Oncostatin M receptors appear necessary but not sufficient for a growth response to oncostatin M, since none of the cell lines lacking receptor responded to oncostatin M, whereas many but not all cell lines with receptor responded to oncostatin M. Receptor size (Mr congruent to 150,000) was similar for cells in which growth was inhibited, stimulated, or unaffected by oncostatin M.
The FSSP database: fold classification based on structure-structure alignment of proteins (1996)

The FSSP database presents a continuously updated classification of 3-D protein folds based on an all-against-all comparison of structures currently in the Protein Data Bank (PDB) [Bernstein et al. (1977) J. Mol. Biol., 112, 535- 542]. The database currently contains an extended structural family for each of 600 representative protein chains which have <25% mutual sequence identity. The results of the exhaustive pairwise structure comparisons are reported in the form of a fold tree generated by hierarchical clustering and as a series of structurally representative sets of folds at varying levels of uniqueness. For each query structure from the representative set, there is a database entry containing structure-structure alignments with its structural neighbours in the representative set and its sequence homologs in the PDB. All alignments are based purely on the 3-D co-ordinates of the proteins and are derived by an automatic structure comparison program (Dali). The FSSP database is accessible electronically on the World Wide Web and by anonymous ftp.
Regulation of Glucagon-Like Peptide-1 Synthesis and Secretion in the GLUTag Enteroendocrine Cell Line (1998)

Glucagon-like peptide-1 (GLP-1) released from the intestine is a potent stimulator of glucose-dependent insulin secretion. To elucidate the factors regulating GLP-1 secretion, we have studied the enteroendocrine GLUTag cell line. GLP-1 secretion was stimulated in a dose-dependent fashion by activation of protein kinase A or C with forskolin or phorbol 12,13-dibutyrate, respectively (by 2.3 ± 0.5-fold at 100μ m and 4.3 ± 0.6-fold at 0.3 μm, respectively; P < 0.01–0.001). Of the regulatory peptides tested, only glucose-dependent insulinotropic peptide stimulated the release of GLP-1 (by 2.3 ± 0.2-fold at 0.1μ m; P < 0.001); glucagon was without effect, and paradoxically, the inhibitory neuropeptide somatostatin-14 increased secretion slightly (by 1.6 ± 0.3-fold at 0.01μ m; P < 0.05). In tests of several neurotransmitters, only the cholinergic agonists carbachol and bethanechol stimulated peptide secretion in a dose-dependent fashion (by 2.3 ± 0.5- and 1.7 ± 0.3-fold at 1000 μm; P < 0.05–0.001); the β-adrenergic agonist isoproterenol and the chloride channel inhibitor γ-aminobutyric acid did not affect release of GLP-1. Long chain monounsaturated fatty acids (18:1), but not saturated fatty acids (16:0), also stimulated the release of GLP-1 (by 1.7 ± 0.1-fold at 150 μm; P < 0.001). Consistent with the presence of a cAMP response element in the proglucagon gene, activation of the protein kinase A-dependent pathway with forskolin increased proglucagon messenger RNA transcript levels by 2-fold (P < 0.05); glucose-dependent insulinotropic peptide and phorbol 12,13-dibutyrate were without effect. Therefore, by comparison with results obtained using primary L cell cultures or in vivo models, GLUTag cells appear to respond appropriately to the regulatory mechanisms controlling intestinal GLP-1 secretion.
The effects of low‐dose ketamine on the prefrontal cortex and amygdala in treatment‐resistant depression: A randomized controlled study (2016)

Ketamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC.
Structural Framework for the Protein Kinase Family (1992)

Structural Framework for the Protein Kinase Family, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/cellbio/8/1/annurev.cb.08.110192.002241-1.gif
Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients (2010)

Hydroxyurea (HU) is frequently given as treatment for myelofibrosis (MF), but data on its efficacy and tolerability are scarce. The results of HU therapy were evaluated in 40 patients with hyperproliferative manifestations of primary (n = 32), post-polycythemia vera (n = 6), or post-essential thrombocythemia (n = 2) myelofibrosis. Median interval between diagnosis and HU start was 6.2 months (range 0-141.7). Reasons for treatment were constitutional symptoms (55%), symptomatic splenomegaly (45%), thrombocytosis (40%), leukocytosis (28%), pruritus (10%), and bone pain (8%). The starting dose was 500 mg/day, subsequently adjusted to the individual efficacy and tolerability. Response was bone pain 100%, constitutional symptoms 82%, pruritus 50%, splenomegaly 40%, and anemia 12.5%. According to the International Working Group for Myelofibrosis Research and Treatment criteria, clinical improvement was achieved in 16 patients (40%). Median duration of response was 13.2 months (range 3-126.2). Worsening of the anemia or appearance of pancytopenia were observed in 18 patients, requiring administration of erythropoietin-stimulating agents (n = 17) and/or danazol (n = 9). Oral or leg ulcers appeared in five patients and one had gastrointestinal symptoms. HU is an effective and generally well-tolerated therapy for the hyperproliferative manifestations of MF. The accentuation of the anemia often induced by HU is usually manageable with concomitant treatment.
ChemInform Abstract: Synthesis and Evaluation of Stilbene and Dihydrostilbene Derivatives as Potential Anticancer Agents That Inhibit Tubulin Polymerization. (1991)

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.