gebhart/patrepeval huggingface dataset:
N-terminal methionine-specific peptidase in Salmonella typhimurium. (1987)

Crude extracts of a multiply peptidase-deficient strain of Salmonella typhimurium contain an aminopeptidase that specifically removes N-terminal methionine from peptides. This activity shows pronounced specificity for the peptide's second amino acid. Methionine is removed from peptides with alanine, threonine, or glycine in this position but not when the second amino acid is leucine or methionine. The activity is stimulated by Co2+ and is inhibited by EDTA. Mutations that lead to overproduction (up to 30-fold) of the activity have been obtained by selecting for growth on Met-Gly-Gly as a methionine source. These mutations map at approximately 3 map units, phage P22 cotransducible with leu. The overproducer mutations are dominant to wild type, and duplication of the wild-type allele of the locus leads to a gene dosage effect on peptidase levels. This suggests that the locus of the overproducer mutations may be the structural gene for the peptidase. NaDodSO4/PAGE shows an increased level of a single protein (34 kDa) in the overproducer mutant. This protein is highly enriched in a purified preparation of the peptidase. The specificity of this enzyme suggests that it is involved in the cleavage of methionine from newly synthesized peptide chains. This activity can specifically remove methionine from the N terminus of a completed protein. Treatment of purified, unprocessed (N-terminal methionine) interleukin 1 beta with the purified peptidase results in removal of N-terminal methionine with no additional alterations. N-terminal processing of at least this protein can occur after translation is complete. We propose to call this enzyme peptidase M (methionine-specific aminopeptidase).
Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma (2009)

Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.
Sorafenib plus daily low-dose temozolomide for relapsed glioblastoma: a phase II study. (2013)

This combination of sorafenib and temozolomide was feasible and safe, showing some activity in patients with relapsed GBM.
Use of 1‐(m‐aminophenyl)flavazoles for the preparation of immunogens with oligosaccharide determinant groups. A method is described for the preparation of immunogens with oligosaccharide determinant groups (1971)

Abstract A method is described for the preparation of immunogens with oligosaccharide determinant groups. The method, which consists of conversion of the sugar into its 1‐(maminophenyl)flavazole and subsequent azo‐coupling to protein, has been elaborated with various oligosaccharides of the isomaltose‐, maltose‐, and cellobiose‐series. It requires unsubstituted hydroxyl groups on positions 2 and 3 adjacent to the reducing end of the sugar and appears to be especially suited for oligosaccharides having a polymerization degree between 3 and 8. The procedure does not necessitate protection of the sugar hydroxyl groups. Oligosaccharide‐flavazole‐azo‐edestin conjugates have been tested for immunogenicity in rabbits. Specific anti‐oligosaccharide antibodies were formed in all instances. High titres of dextranspecific antibodies were obtained upon immunization with an isomaltoheptaose‐flavazole‐azo‐edestin conjugate. Further applications of the method will be discussed.
Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model (2021)

The availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) threat. Here, we have assessed the immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidates BBV152A, BBV152B, and BBV152C in Syrian hamsters. Three dose vaccination regimes with vaccine candidates induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamster was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology, and robust humoral immune response. These findings confirm the immunogenic potential of the vaccine candidates and further protection of hamsters challenged with SARS-CoV-2. Of the three candidates, BBV152A showed the better response.
Shift of Clinical Human Immunodeficiency Virus Type 1 Isolates from X4 to R5 and Prevention of Emergence of the Syncytium-Inducing Phenotype by Blockade of CXCR4 (1999)

The emergence of X4 human immunodeficiency virus type 1 (HIV-1) strains in HIV-1-infected individuals has been associated with CD4(+) T-cell depletion, HIV-mediated CD8(+) cell apoptosis, and an impaired humoral response. The bicyclam AMD3100, a selective antagonist of CXCR4, selected for the outgrowth of R5 virus after cultivation of mixtures of the laboratory-adapted R5 (BaL) and X4 (NL4-3) HIV strains in the presence of the compound. The addition of AMD3100 to peripheral blood mononuclear cells infected with X4 or R5X4 clinical HIV isolates displaying the syncytium-inducing phenotype resulted in a complete suppression of X4 variants and a concomitant genotypic change in the V2 and V3 loops of the envelope gp120 glycoprotein. The recovered viruses corresponded genotypically and phenotypically to R5 variants in that they could no longer use CXCR4 as coreceptor or induce syncytium formation in MT-2 cells. Furthermore, the phenotype and genotype of a cloned R5 HIV-1 virus converted to those of the R5X4 virus after prolonged culture in lymphoid cells. However, these changes did not occur when the infected cells were cultured in the presence of AMD3100, despite low levels of virus replication. Our findings indicate that selective blockade of the CXCR4 receptor prevents the switch from the less pathogenic R5 HIV to the more pathogenic X4 HIV strains, a process that heralds the onset of AIDS. In this article, we show that it could be possible to redirect the evolution of HIV so as to impede the emergence of X4 strains or to change the phenotype of already-existing X4 isolates to R5.
Texture Synthesis Using Convolutional Neural Networks (2015)

Here we introduce a new model of natural textures based on the feature spaces of convolutional neural networks optimised for object recognition. Samples from the model are of high perceptual quality demonstrating the generative power of neural networks trained in a purely discriminative fashion. Within the model, textures are represented by the correlations between feature maps in several layers of the network. We show that across layers the texture representations increasingly capture the statistical properties of natural images while making object information more and more explicit. The model provides a new tool to generate stimuli for neuroscience and might offer insights into the deep representations learned by convolutional neural networks.
The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13. (1992)

Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein that is bound to immobilized FK506. As expected, the NH2-terminal sequences of the 60-kDa protein from these two species were found to be nearly the same. We were surprised to discover, however, that the sequence of the human protein was identical to that of Hsp56, a heat shock protein of unknown function that has been shown to be a component of several steroid receptor complexes. Further analysis of the calf thymus protein revealed a peptide with homology to a region near the COOH terminus of both FKBP-12 and FKBP-13. It would appear, therefore, that this 60-kDa protein, or as we refer to it provisionally, "Hsp56," could have the capacity to bind FK506 directly. These observations lead us to speculate that "Hsp56" may mediate immunosuppression and inhibition of T-cell proliferation by FK506 and may do so via a cytosolic signal transduction pathway separate, but not necessarily exclusive, from that of FKBP-12 and FKBP-13.
Antibodies Stage a Comeback in Cancer Treatment (1998)

In 1982, an immunologist reported vanquishing cancer in a patient using antibodies custom-designed to attack his own lymphoma cells, but in subsequent testing of other antibodies, the effects in humans didn9t match those in mice and unexpected toxicity even killed patients, bringing clinical trials to an abrupt halt. Now, the U.S. Food and Drug Administration has approved an antilymphoma antibody, and just last week, researchers announced some success with an antibody tailored to fight recalcitrant breast cancers that is nearing regulatory approval. But researchers caution that antibodies will never replace conventional cancer chemotherapy drugs; in fact, results so far show that they may work best when combined with those drugs.
Identification of the ice‐binding face of antifreeze protein from Tenebrio molitor (2002)

The beetle Tenebrio molitor produces several isoforms of a highly disulfide-bonded beta-helical antifreeze protein with one surface comprised of an array of Thr residues that putatively interacts with ice. In order to use mutagenesis to identify the ice-binding face, we have selected an isoform that folds well and is tolerant of amino acid substitution, and have developed a heating test to monitor refolding. Three different types of steric mutations made to the putative ice-binding face reduced thermal hysteresis activity substantially while a steric mutation on an orthogonal surface had little effect. NMR spectra indicated that all mutations affected protein folding to a similar degree and demonstrated that most of the protein folded well. The large reductions in activity associated with steric mutations in the Thr array strongly suggest that this face of the protein is responsible for ice binding.
Synthesis of C7,C7‘-Ethylene- and C7,C7‘-Methylene-Bridged C2-Symmetric Bis(indenyl)zirconium and -titanium Dichlorides (1998)

We have prepared several novel metallocenes bridged at the 7,7‘-positions of the indenyl moiety. The new metallocenes include the methylene-bridged [dl-bis(4,6-dimethylinden-7-yl)methylidene]titanium dichloride (20) and [dl-bis(4,6-dimethylinden-7-yl)methylidene]zirconium dichloride (21), which were prepared from m-xylene. In addition, [dl-1,2-bis(4-methylinden-7-yl)ethylidene]- and [dl-1,2-bis(4-isopropylinden-7-yl)ethylidene]zirconium dichlorides (dl-12a and dl-12b) and [dl-1,2-bis(4-isopropylinden-7-yl)ethylidene]titanium dichloride (dl-13) were synthesized from p-cymene and p-xylene, respectively. The structures of metallocene dichlorides dl-12a, dl-12b, and dl-13 were determined by X-ray crystallography and found to have C1 symmetry in the solid state but in solution exhibit C2 symmetry, as seen in the 1H NMR spectra at room temperature.
Moment based 3D edge operator for anisotropic image (1992)

A moment-based operator for 3D edge detection has been already proposed for isotropic description of medical data sets. This paper presents its generalization to anisotropic volume data. Two solutions, based on implicit "deformation" and "interpolation" model, are briefly described. This comparison is conducted on real data and discussed.
Photoactivatable and Photoconvertible Fluorescent Probes for Protein Labeling (2010)

Photosensitive probes are powerful tools to study cellular processes with high temporal and spatial resolution. However, most synthetic fluorophores suited for biomolecular imaging have not been converted yet to appropriate photosensitive analogues. Here we describe a generally applicable strategy for the generation of photoactivatable and photoconvertible fluorescent probes that can be selectively coupled to SNAP-tag fusion proteins in living cells. Photoactivatable versions of fluorescein and Cy3 as well as a photoconvertible Cy5-Cy3 probe were prepared and coupled to selected proteins on the cell surface, in the cytosol, and in the nucleus of cells. In proof-of-principle experiments, the photoactivatable Cy3 probe was used to characterize the mobility of a lipid-anchored cell surface protein and of a G protein coupled receptor (GPCR). This work establishes a generally applicable strategy for the generation of a large variety of different photosensitive fluorophores with tailor-made properties for biomolecular imaging.
Purification and characterization of an activity from Saccharomyces cerevisiae that catalyzes homologous pairing and strand exchange. (1987)

An activity that catalyzes the formation of joint molecules from linear M13mp19 replicative form DNA and circular M13mp19 viral DNA was purified 1000- to 2000-fold from mitotic Saccharomyces cerevisiae cells. The activity appeared to reside in a Mr 132,000 polypeptide. The reaction required that the substrates be homologous and also required Mg2+. There was no requirement for ATP. The reaction required stoichiometric amounts of protein and showed a cooperative dependence on protein concentration. Electron microscopic analysis of the joint molecules indicated they were formed by displacement of one strand of the linear duplex by the single-stranded circular molecule. This analysis also showed that heteroduplex formation started at the 3'-homologous end of the linear duplex strand followed by extension of the hybrid region toward the 5'-homologous end of the linear duplex strand (3'-to-5' direction).
The physiologic role of interleukin-3, interleukin-5, granulocyte-macrophage colony-stimulating factor, and the βc receptor system (1998)

Gene knockout techniques in the mouse have provided a unique opportunity to examine physiologic gene function. The phenotypes of mutant mice have resulted in a number of predicted as well as totally unexpected results, the latter perhaps providing the most valuable insight into otherwise unexplored biology. An excellent example to illustrate these points are gene knockout studies of interleukin (IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the receptor system that cells use to bind these ligands. The role of IL-5 appears to be largely restricted to eosinophil biology, fulfilling expectations. However, the vivo function of GM-CSF, IL-3, and their receptor interaction has been more surprising. Neither cytokine nor their combination play an essential or even detectable role in primary bone marrow hematopoiesis, Instead, both IL-3 and GM-CSF play more specialized roles on certain cell subsets, basophil and mast cells, and alveolar macrophages, respectively. This review discusses recent findings with these mice, and based on these results, suggests a more appropriate view of the role of these cytokines and receptors in the hierarchy of molecular events leading to hematopoiesis.
Photoaffinity labeling of parathyroid hormone receptors in clonal rat osteosarcoma cells. (1988)

A photoreactive derivative of a sulfur-free bovine parathyroid hormone (PTH) analogue, [Nle8,N-epsilon-(4-azido-2-nitrophenyl)Lys13,Nle18,Tyr34]bovine PTH-(1-34)-NH2 (NAP-NlePTH), was purified from the products of the reaction of [Nle8,Nle18,Tyr34]bovine PTH-(1-34)-NH2 (NlePTH) with 4-fluoro-3-nitro-phenylazide and was used to identify binding components of the PTH receptor in clonal rat osteosarcoma cells (ROS 17/2.8). The purified analogue, NAP-NlePTH, is a fully active agonist in three different ROS 17/2.8 cell bioassays: 1) specific binding to saturable PTH receptors; 2) stimulation of cyclic AMP accumulation; and 3) inhibition of cellular alkaline phosphatase activity; this analogue gave dose response curves parallel to and 25-33% as potent as its parent molecule, NlePTH. Radioiodinated NAP-NlePTH (125I-labeled NAP-NlePTH) retained maximal receptor-binding potency. Radioligand saturation studies in intact cells showed that the Kd of PTH receptors for the photoligand was slightly less than that for 125I-labeled NlePTH (2.8 and 0.8 nM, respectively), but that the Bmax was essentially identical for both radioligands (8 fmol/10(5) cells). Photoaffinity labeling of ROS 17/2.8 cells revealed several 125I-labeled macromolecular components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One predominant 125I-labeled band, having an apparent Mr of 80,000 daltons (including Mr = 4,347 ligand; hereafter referred to as the Mr = 80,000 protein), was consistently demonstrated in both reducing and nonreducing conditions. Its labeling was completely inhibited by coincubation with NlePTH (10 nM) at 26-fold molar excess to the photoligand, but not by biologically inactive PTH fragments or unrelated hormone. Labeling of several other macromolecular components persisted in the presence of NlePTH (1 microM). Only the labeling of the Mr = 80,000 protein showed saturation kinetics for photoaffinity labeling; the dose of 125I-labeled NAP-NlePTH (0.8 nM) to half-saturate labeling of the Mr = 80,000 protein was close to the Kd (2.8 nM) of specific binding of the photoligand to receptors in intact ROS 17/2.8 cells. Pretreatment of the cells with NlePTH and dexamethasone led to the predicted proportional decrease or increase, respectively, in labeling of the Mr = 80,000 protein. Our data, using a highly purified photoactive derivative of PTH, having carefully defined chemical and biological properties, show a plasma membrane component of Mr = 80,000 in ROS 17/2.8 cells that possesses the affinity, binding capacity, and physiological characteristics of the PTH receptor.
Differential Expression of Somatostatin Receptors, P44/42 MAPK, and mTOR Activation in Medulloblastomas and Primitive Neuroectodermal Tumors (2013)

Recently, somatostatin receptors (SSR) have been identified on medulloblastomas and proposed as a new target for chemotherapy including inhibitory somatostatin analogs. Activation of SSRs inhibit growth, in part, by activating phosphatases that dephosphorylate/deactivate growth stimulatory signaling of the MEK1-p44/42 MAPK and PI3K-Akt-mTOR pathways. These SSR-inhibited signaling pathways have not been characterized or correlated with SSR expression in medulloblastomas or primitive neuroectodermal tumors (PNETs), yet may represent additional targets for combined chemotherapy. We evaluated the distribution and extent of SSR1 and SSR2 expression and correlated it with activation of downstream MEK1-p44/42 MAPK and PI3K-Akt-mTOR pathways in medulloblastomas and PNETs. Sections from 22 medulloblastomas and 9 PNETs were compared using immunohistochemistry with monoclonal antibodies to SSR1, SSR2, p44/42 MAPK, phosphorylated p44/42 MAPK, and phosphorylated mTOR. SSR1 was detected in 50% of medulloblastomas, extensive in 46%, and similar in classic, desmoplastic, and large cell/anaplastic subtypes. SSR1 was detected in 78% of PNETs and extensive in the majority. SSR2 was found in 18% of medulloblastomas and 33% of PNETs. Activated/phosphorylated pMAPK 44/42 was detected in 82% of medulloblastomas, all subtypes, and in 62.5% of PNETs with coexpression of SSR1 in one third. Activated/phosphorylated mTOR was found in only 18% of medulloblastomas but in 88% of PNETs. SSR1 coexpression with activated/phosphorylated mTOR was identified in 75% of PNETs. These findings suggest that addition of an mTOR inhibitor may potentiate growth inhibitory effects of SSR agonists in the treatment of PNETs. Immunohistochemical identification of mTOR activation/phosphorylation in biopsies of initial and treatment-resistant PNETs may facilitate development of clinical trials and therapeutic decisions.
Introduction (1999)

Sociology is the most ambitious of all the social sciences. It is concerned with all that happens to people in terms of their relations with each other and the scope of its inquiries can range from things such as the mass movement of populations over centuries to two commuters catching each other's eye on the morning train to work The key idea of sociology is that the lives of individuals cannot be understood apart from the social contexts in which they live. This chapter aims to introduce readers to the idea of 'sociological thinking', Illustrate the importance of theory for all sociological research and outline the key areas of applied sociological research around which this book is organized. it should help you understand: The key questions sociologists ask about human societies Why all social research is theory dependent What the central areas of applied sociological research are The relationship of sociology to modernity
The synthetic neuroactive steroid SGE-516 reduces seizure burden and improves survival in a Dravet syndrome mouse model (2017)

Dravet syndrome is an infant-onset epileptic encephalopathy with multiple seizure types that are often refractory to conventional therapies. Treatment with standard benzodiazepines like clobazam, in combination with valproate and stiripentol, provides only modest seizure control. While benzodiazepines are a first-line therapy for Dravet syndrome, they are limited by their ability to only modulate synaptic receptors. Unlike benzodiazepines, neuroactive steroids potentiate a wider-range of GABA<sub>A</sub> receptors. The synthetic neuroactive steroid SGE-516 is a potent positive allosteric modulator of both synaptic and extrasynaptic GABA<sub>A</sub> receptors. Prior work demonstrated anticonvulsant activity of SGE-516 in acute seizure assays in rodents. In this study, we evaluated activity of SGE-516 on epilepsy phenotypes in the Scn1a <sup>+/-</sup> mouse model that recapitulates many features of Dravet syndrome, including spontaneous seizures, premature death and seizures triggered by hyperthermia. To evaluate SGE-516 in Scn1a <sup>+/-</sup> mice, we determined the effect of treatment on hyperthermia-induced seizures, spontaneous seizure frequency and survival. SGE-516 treatment protected against hyperthermia-induced seizures, reduced spontaneous seizure frequency and prolonged survival in the Scn1a <sup>+/-</sup> mice. This provides the first evidence of SGE-516 activity in a mouse model of Dravet syndrome, and supports further investigation of neuroactive steroids as potential anticonvulsant compounds for refractory epilepsies.
Estimating Oral Toxicity of Slow-Acting Toxicants Against Subterranean Termites (Isoptera: Rhinotermitidae) (1994)

Journal Article Estimating Oral Toxicity of Slow-Acting Toxicants Against Subterranean Termites (Isoptera: Rhinotermitidae) Get access Nan-Yao Su, Nan-Yao Su Ft. Lauderdale Research and Education Center, University of Florida, Institute of Food and Agricultural Sciences, Ft. Lauderdale, FL 33314 Search for other works by this author on: Oxford Academic PubMed Google Scholar Masahiko Tokoro, Masahiko Tokoro Ft. Lauderdale Research and Education Center, University of Florida, Institute of Food and Agricultural Sciences, Ft. Lauderdale, FL 33314 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rudolf H. Scheffrahn Rudolf H. Scheffrahn Ft. Lauderdale Research and Education Center, University of Florida, Institute of Food and Agricultural Sciences, Ft. Lauderdale, FL 33314 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 87, Issue 2, 1 April 1994, Pages 398–401, https://doi.org/10.1093/jee/87.2.398 Published: 01 April 1994 Article history Received: 10 May 1993 Accepted: 08 November 1993 Published: 01 April 1994