gebhart/patrepeval huggingface dataset:
T-antigen mutant activities in vivo: roles of p53 and pRB binding in tumorigenesis of the choroid plexus. (1992)

To study the mechanism by which SV40 large T antigen transforms cells under physiological conditions, we analysed several mutant forms of T antigen for their ability to induce cell proliferation and tumorigenesis in transgenic mice. These mutant proteins, which differ in their ability to form complexes with the tumor suppressors pRB and p53, were analysed under conditions in which wild-type T antigen induces choroid plexus papillomas as a result of uniform proliferation of the entire choroid plexus epithelium. The results presented here show that binding of T antigen to p53 is not required for induction of choroid plexus tumors. However, tumorigenesis does appear to require the binding of T antigen to pRB/p107. An additional activity, resident in the amino-terminal one-fifth of the protein, may also play a role. These experiments indicate the importance of whole-animal assays in determining the molecular basis of transformation, since each of these mutants possessed similar transformation phenotypes in culture but showed distinct phenotypes in the choroid plexus of the animal.
Bruton's tyrosine kinase: oncotarget in myeloma (2012)

Our findings therefore provide a strong rationale for investigating Btk inhibitors in MM and WM to target both tumor cells and their supporting BM microenvironment and thereby both suppress tumor cell growth and abrogate MM-induced bone disease.
Intensive medical treatment of severe acute pancreatitis (1981)

Abstract Therapeutic measurements for acute pancreatitis depend on the severity of the disease and its complications. Since complications of acute pancreatitis may develop at any time, patients should be admitted to an intensive care unit for assessment (and frequent reassessment) of the severity of the disease and of the development of complications; they should remain in the intensive care unit for the first 48 hours at least, even if no signs of shock are apparent. The only exceptions to this rule are mild cases without signs of peritonitis. Basic therapy should include relief of pain, total fasting, nasogastric suction, parenteral replacement of fluids, electrolyte, albumin, and blood, and antibiotics. Hyperglycemia should be corrected and heparin should be given in cases of disseminated intravascular coagulation. In renal insufficiency, peritoneal dialysis is important, and in respiratory complications, humidified oxygen or artificial ventilation including positive end expiratory pressure therapy should be applied. Although the effect of peritoneal dialysis has been proven only in animal experiments and in retrospective studies in man, it is recommended in severe cases for shock therapy and for correction of electrolyte imbalance when ascites is present, even before anuria occurs.
Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. (1988)

In contrast to euthymic (nu/+) BALB/c mice, athymic nude (nu/nu) BALB/c mice fail to control the visceral intracellular replication of Leishmania donovani, do not generate the macrophage-activating lymphokine IFN-gamma, and show little or no granulomatous tissue response. To characterize the T cell requirement for successful defense against L. donovani, nude mice were first reconstituted with unfractionated nu/+ immune spleen cells, which readily conferred the capacity to control and eliminate visceral (hepatic) L. donovani. In reconstituted mice, acquired resistance was paralleled by the ability of spleen cells to generate high levels of leishmanial Ag-stimulated IFN-gamma and the development of well formed liver granulomas. In contrast, nude mice reconstituted with either L3T4+- or Lyt-2+-enriched immune spleen cells alone failed to control visceral parasite replication and did not develop effective granulomas despite the finding that transfer of L3T4+ cells largely and Lyt-2+ cells partially restored the capacity to secrete IFN-gamma. To determine whether both T cell subsets were also required in a normal host, nu/+ BALB/c mice were treated with cell-depleting anti-L3T4 and anti-Lyt-2 mAb. Depletion of either T cell subset inhibited the acquisition of resistance to L. donovani and impaired the tissue granulomatous response. Thus, successful T cell-dependent host defense towards intracellular L. donovani and the tissue expression (granulomas) of this mechanism appear to require both L3T4+ and Lyt-2+ cells. A primary role for the L3T4+ cell may be IFN-gamma production; the role of the Lyt-2+ cell and the precise interaction of the two T cell subsets remain to be identified.
Site-Directed ELISA Identifies a Highly Antigenic Region of the Simian Immunodeficiency Virus Transmembrane Glycoprotein (1988)

The transmembrane glycoprotein (gp32) of the simian immunodeficiency virus (SIV) contains a highly antigenic region that includes amino acid residues 606-628. A synthetic peptide representing this region was highly immunoreactive with sera from SIV-infected primates in a site-directed enzyme-linked immunosorbent assay (ELISA). This reactivity extended across four primate species from three genera and identified infection with at least two distinct isolates of SIV. This site-directed ELISA represents a simple, accessible method with broad specificity for screening large numbers of primates for antibodies against SIV.
Noncritical quasiphase-matched second harmonic generation in LiB3O5 crystal at room temperature (1992)

Noncritical quasiphase-matched (NQPM) second harmonic generation (SHG) in LBO crystal at room temperature is reported. It is observed that the SHG conversion efficiency increases approximately as the square of the number of LBO sheets. The dependence of SHG conversion efficiency on incident angle and the intensity of the fundamental wave at 1064 nm were also measured. Using a 4 mm thick NQPM LBO frequency doubler, a maximum conversion efficiency of 12% is obtained at a pump intensity of 0.254 GW/cm2.
Assembly and Post-Modification of a Metal–Organic Nanotube for Highly Efficient Catalysis (2012)

A metal-organic nanotube (MONT) was synthesized by linking up the bent organic ligands and the tetra-coordinated zinc cations under mild conditions. Structural analysis revealed that the MONT has a very large exterior wall diameter of 4.91 nm and an interior channel diameter of 3.32 nm. Interlocking of the nanotubes gives rise to a 3D chiral framework containing 1D helical cylindered channels with diameter of 2.0 nm. The MONT has very interesting property by synergizing the functionality of nanotubes, metal-organic frameworks (MOFs), and N-heterocyclic carbenes (NHCs). The dye adsorption experiments demonstrate that the channels of the MONTs are accessible to large reagents typically used for catalysis. The postmodification of the MONT can be easily operated by unmarking the imidazolium moieties in the channel walls, which was conducted as a highly active heterogeneous catalyst for Suzuki-Miyaura and Heck coupling reactions, hydrogenation of olefins and nitrobenzene, while the constituent elements are less efficient for these reactions under the same conditions.
Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo (2014)

Loss of cochlear hair cells in mammals is currently believed to be permanent, resulting in hearing impairment that affects more than 10% of the population. Here, we developed two genetic strategies to ablate neonatal mouse cochlear hair cells in vivo. Both Pou4f3(DTR/+) and Atoh1-CreER™; ROSA26(DTA/+) alleles allowed selective and inducible hair cell ablation. After hair cell loss was induced at birth, we observed spontaneous regeneration of hair cells. Fate-mapping experiments demonstrated that neighboring supporting cells acquired a hair cell fate, which increased in a basal to apical gradient, averaging over 120 regenerated hair cells per cochlea. The normally mitotically quiescent supporting cells proliferated after hair cell ablation. Concurrent fate mapping and labeling with mitotic tracers showed that regenerated hair cells were derived by both mitotic regeneration and direct transdifferentiation. Over time, regenerated hair cells followed a similar pattern of maturation to normal hair cell development, including the expression of prestin, a terminal differentiation marker of outer hair cells, although many new hair cells eventually died. Hair cell regeneration did not occur when ablation was induced at one week of age. Our findings demonstrate that the neonatal mouse cochlea is capable of spontaneous hair cell regeneration after damage in vivo. Thus, future studies on the neonatal cochlea might shed light on the competence of supporting cells to regenerate hair cells and on the factors that promote the survival of newly regenerated hair cells.
Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake (2003)

Sialic acid-binding immunoglobulin-like lectins (siglecs) are expressed predominantly in the haemopoietic and immune systems and exhibit specificities for both the linkage and the nature of sialic acids in N-glycans, O-glycans and glycolipids. Several siglecs, including sialoadhesin (Sn, siglec-1) and siglec-5, bind to NeuAcalpha2,3Gal, a terminal capping structure that can also be displayed on the lipopolysaccharide (LPS) of Neisseria meningitidis (Nm). In the present study, we examined the potential of siglecs expressed on cells of the immune system to function as receptors for sialylated Nm. We used sialylated and non-sialylated LPS derivatives of two serogroups (A and B) of Nm in this study. Using recombinant chimeric soluble receptors, siglec-transfected cell lines and macrophages from wild-type and Sn-deficient mice, we observed that sialylated but not non-sialylated variants of either genetic background were specifically recognized by Sn and siglec-5, whereas other siglecs examined were ineffective. In addition, macrophages expressing Sn, as well as transfectants expressing Sn or siglec-5, bound and phagocytosed sialylated bacteria in a siglec- and sialic acid-dependent manner. This study demonstrates that Nm LPS sialylation can lead to increased bacterial susceptibility to phagocytic uptake, a phenomenon in direct contrast to previously reported protective effects of LPS sialylation.
Studies in the Sphingolipids Series. IV.1 Determination of the Configuration of the Amino Carbon Atom in Sphingosine2 (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies in the Sphingolipids Series. IV.1 Determination of the Configuration of the Amino Carbon Atom in Sphingosine2M. PROSTENIK, M. MUNK-WEINERT, and D. E. SUNKOCite this: J. Org. Chem. 1956, 21, 4, 406–409Publication Date (Print):April 1, 1956Publication History Published online1 May 2002Published inissue 1 April 1956https://pubs.acs.org/doi/10.1021/jo01110a007https://doi.org/10.1021/jo01110a007research-articleACS PublicationsRequest reuse permissionsArticle Views48Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Evolved Policy Gradients (2018)

We propose a metalearning approach for learning gradient-based reinforcement learning (RL) algorithms. The idea is to evolve a differentiable loss function, such that an agent, which optimizes its policy to minimize this loss, will achieve high rewards. The loss is parametrized via temporal convolutions over the agent's experience. Because this loss is highly flexible in its ability to take into account the agent's history, it enables fast task learning. Empirical results show that our evolved policy gradient algorithm (EPG) achieves faster learning on several randomized environments compared to an off-the-shelf policy gradient method. We also demonstrate that EPG's learned loss can generalize to out-of-distribution test time tasks, and exhibits qualitatively different behavior from other popular metalearning algorithms.
Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's β‐amyloid precursor protein (1998)

A distinctive tract of all the forms of Alzheimer's disease is the extracellular deposition of a 40-42/43 amino acid-long peptide derived from the so-called beta-amyloid precursor protein (APP). This is a membrane protein of unknown function, whose short cytosolic domain has been recently demonstrated to interact with several proteins. One of these proteins, named Fe65, has the characteristics of an adaptor protein; in fact, it possesses three protein-protein interaction domains: a WW domain and two PID/PTB domains. The interaction with APP requires the most C-terminal PID/PTB domain, whereas the WW domain is responsible for the interaction with various proteins, one of which was demonstrated to be the mammalian homolog of the Drosophila enabled protein (Mena), which in turn interacts with the cytoskeleton. The second PID/PTB domain of Fe65 binds to the CP2/LSF/LBP1 protein, which is an already known transcription factor. The other proteins interacting with the cytosolic domain of APP are the G(o) heterotrimeric protein, APP-BP1 and X11. The latter interacts with APP through a PID/PTB domain and possesses two other protein-protein interaction domains. The small size of the APP cytodomain and the overlapping of its regions involved in the binding of Fe65 and X11 suggest the existence of competitive mechanisms regulating the binding of the various ligands to this cytosolic domain. In this short review the possible functional roles of this complex protein network and its involvement in the generation of Alzheimer's phenotype are discussed.
Characterization of the human Ly‐6 antigens, the newly annotated member Ly‐6K included, as molecular markers for head‐and‐neck squamous cell carcinoma (2002)

The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPI-anchored surface proteins, of which some show tissue-restricted expression patterns. To identify novel human HNSCC-associated Ly-6 members with squamous cell-associated expression patterns, we performed comprehensive gene-screening consisting of BLAST searches within GenBank databases, followed by expression analysis. Using this approach, the Ly-6K gene could be annotated as a novel member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K, PSCA, GML, RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal and malignant squamous cells and in peripheral blood and bone marrow cells, thus limiting its applicability as an HNSCC-associated marker. In contrast, besides the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected. These data justify further evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of HNSCC.
Generation of a flanking sequence‐tag database for activation‐tagging lines in japonica rice (2005)

We have generated 47,932 T-DNA tag lines in japonica rice using activation-tagging vectors that contain tetramerized 35S enhancer sequences. To facilitate use of those lines, we isolated the genomic sequences flanking the inserted T-DNA via inverse polymerase chain reaction. For most of the lines, we performed four sets of amplifications using two different restriction enzymes toward both directions. In analyzing 41,234 lines, we obtained 27,621 flanking sequence tags (FSTs), among which 12,505 were integrated into genic regions and 15,116 into intergenic regions. Mapping of the FSTs on chromosomes revealed that T-DNA integration frequency was generally proportional to chromosome size. However, T-DNA insertions were non-uniformly distributed on each chromosome: higher at the distal ends and lower in regions close to the centromeres. In addition, several regions showed extreme peaks and valleys of insertion frequency, suggesting hot and cold spots for T-DNA integration. The density of insertion events was somewhat correlated with expressed, rather than predicted, gene density along each chromosome. Analyses of expression patterns near the inserted enhancer showed that at least half the test lines displayed greater expression of the tagged genes. Whereas in most of the increased lines expression patterns after activation were similar to those in the wild type, thereby maintaining the endogenous patterns, the remaining lines showed changes in expression in the activation tagged lines. In this case, ectopic expression was most frequently observed in mature leaves. Currently, the database can be searched with the gene locus number or location on the chromosome at http://www.postech.ac.kr/life/pfg/risd. On request, seeds of the T(1) or T(2) plants will be provided to the scientific community.
A 5′ intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1–2% of the Caucasian population (2005)

The P2X(7) gene is important for the innate immune response but known polymorphisms do not explain all subjects with loss of P2X(7) function. A splice site mutation (g-->t) was found at position +1 of the first intron of the P2X(7) gene in 7 of 336 Caucasians and 1 of 39 subjects of Indian ethnicity. All eight subjects were heterozygous for the uncommon 1513A-->C polymorphism of the P2X(7) gene. RT-PCR and sequencing showed the splice site mutation was on the 1513C allele in the Caucasians and on the 1513A allele in the Indian subject. The splice site mutation is an inherited polymorphism and gives rise to a P2X(7) null allele in 1-2% of the Caucasian population.
Synthesis of Functionalized Organotrifluoroborates via the 1,3-Dipolar Cycloaddition of Azides (2006)

[reaction: see text] We have successfully prepared potassium azidoalkyltrifluoroborates from the corresponding halogen compounds in 94-98% yields through a nucleophilic substitution reaction with NaN(3). In the presence of various alkynes and Cu(I) as a catalyst, these azidotrifluoroborates easily formed 1,4-disubstituted organo-[1,2,3]-triazol-1-yl-trifluoroborates in 85-98% yields. This method was then developed into a facile one-pot synthesis for the preparation of various organo-[1,2,3]-triazol-1-yl-trifluoroborates using haloalkyltrifluoroborates as the starting materials.
Termination of DNA synthesis by novel 3'-modifieddeoxyribonucleoside 5'-triphosphates (1994)

Eight 3'-modified-dNTPs were synthesized and tested in two different DNA template assays for incorporation activity. From this enzymatic screen, two 3'-O-methyl-dNTPs were shown to terminate DNA syntheses mediated by a number of polymerases and may be used as alternative terminators in Sanger sequencing. 3'-O-(2-Nitrobenzyl)-dATP is a UV sensitive nucleotide and was shown to be incorporated by several thermostable DNA polymerases. Base specific termination and efficient photolytic removal of the 3'-protecting group was demonstrated. Following deprotection, DNA synthesis was reinitiated by the incorporation of natural nucleotides into DNA. The identification of this labile terminator and the demonstration of a one cycle stop-start DNA synthesis are initial steps in the development of a novel sequencing strategy.
A Practical Cytopathic Effect/Dye-Uptake Interferon Assay for Routine Use in the Clinical Laboratory (1985)

The clinical value of interferon (IFN) level determinations has been demonstrated, but a practical assay procedure for routine use in the diagnostic laboratory has not been available. The authors examined the susceptibility of five cell lines (WISH, HEp-2, Vero, A549, and WI-26VA4) to vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV), and compared the response of these cells to the inhibitory activity of IFN-alpha and IFN-gamma for the respective viral cytopathic effect (CPE). The WISH-EMCV system was the most sensitive for IFN-alpha, and was approximately as sensitive as the HEp-2-VSV system for IFN-gamma. WISH cells were found to be significantly more sensitive for both IFN-alpha and IFN-gamma when EMCV, instead of VSV, was used (P less than 0.001). Therefore, the latter system served as the basis for developing a CPE dye-uptake procedure that was found to be considerably more rapid but slightly less sensitive than the conventional technic. However, both procedures were equally reproducible and should be suitable for automation.