gebhart/patrepeval huggingface dataset:
‘Undifferentiated progenitor cells’ in focal nodular hyperplasia of the liver (1996)

Focal nodular hyperplasia is a tumour like lesion, characterized by a central fibrous scar with irradiating fibrous septa that surround hyperplastic nodules and contain multiple bile ductules. The origin of the bile ductular structures is not clear. Recently, we found evidence for the existence of human counterparts of rat oval cells (potential stem cells) that have the ability of differentiating towards both bile duct cells and hepatocytes. These cells were found in regenerating human liver as well as in chronic cholestatic conditions. Because cholestatic features are seen in focal nodular hyperplasia, we initiated an immunohistochemical study on 23 surgical specimens using antibodies specific for cytokeratins 7 and 19 (bile duct type cytokeratins), OV6 (rat oval cell marker), chromogranin-A (shown to be positive in reactive bile ductules and human oval-like cells) and neural cell adhesion molecule--NCAM (shown to be positive in reactive bile ductules) to investigate whether 'undifferentiated progenitor cells' are also present in focal nodular hyperplasia. Electronmicroscopy was applied in five cases. Bile ductules invariably showed immunoreactivity for CK7 and 19, OV6, chromogranin-A and NCAM. In addition, small individual cells with an oval nucleus and a small rim of cytoplasm, in the vicinity of the septa, were immunoreactive for chromogranin-A, CK7 and 19 and OV6. These cells were hardly recognizable on routine light microscopy. Clusters of periseptal hepatocytes, seemingly in continuity with bile ductular structures, had a transitional phenotype: they stained positive for chromogranin-A, CK7 and OV6 and sometimes formed liver cell rosettes. The number of OV6-positive hepatocytes was greater than the number of chromogranin-A and CK7 positive hepatocytes. This indicates that, in human liver, OV-6 is not purely a marker of progenitor cells. Ultrastructurally, small immature cells, highly resembling rat oval cells, were recognized in the vicinity of septa. In addition, transitional cells displaying characteristics both of hepatocytes and bile duct cells were also present. These results confirm the presence of 'undifferentiated progenitor cells' in focal nodular hyperplasia and suggest that the ductular reaction in these lesions results, at least partly, from activation of these cells.
Protein-free cell culture on an artificial substrate with covalently immobilized insulin. (1996)

Insulin was immobilized on a surface-hydrolyzed poly(methyl methacrylate) film. Chinese hamster ovary cells overexpressing human insulin receptors were cultured on the film in the absence of serum or soluble proteins. Small amounts of immobilized insulin (1-10% of the required amount of free insulin) were sufficient to stimulate cell proliferation. In addition, the maximal mitogenic effect of immobilized insulin was greater than that of free insulin. Immobilized insulin activated the insulin receptor and downstream signaling proteins, and this activation persisted for longer periods than that obtained with free insulin, probably explaining the greater mitogenic effect of the immobilized insulin. Finally the immobilized-insulin film was usable repeatedly without marked loss of activity.
[Investigation of radiation safety management of nuclear medicine facilities in Japan; contamination of radioactivity in the draining-water system. A Working Group of Japanese Society of Nuclear Medicine for the Guidelines of Nuclear Medicine Therapy]. (1999)

Radiation safety management condition in Japanese nuclear medicine facilities were investigated by the questionnaire method. The first questionnaire was asked in all Japanese 1,401 Nuclear Medicine facilities. Answers from 624 institutes (44.5%) were received and analyzed. The radiation-safety management in nuclear medicine institutes was considered to be very well performed everyday. Opinion for the present legal control of nuclear medicine institutes was that the regulation in Japan was too strict for the clinical use of radionuclides. The current regulation is based on the assumption that 1% of all radioactivity used in nuclear medicine institutes contaminates into the draining-water system. The second questionnaire detailing the contamination of radioactivity in the draining-water system was sent to 128 institutes, and 64 answers were received. Of them, 42 institutes were considered to be enough to evaluate the contamination of radioactivity in the draining-water system. There was no difference between 624 institutes answered to the first questionnaire and 42 institutes, where the radioactivity in the draining-water system was measured, in the distribution of the institute size, draining-water system equipment and the radioactivity measuring method, and these 42 institutes seemed to be representative of Japanese nuclear medicine institutes. Contamination rate of radioactivity into the draining system was calculated by the value of radioactivity in the collecting tank divided by the amount of radionuclides used daily in each institute. The institutes were divided into two categories on the basis of nuclear medicine practice pattern; type A: in-vivo use only and type B: both in-vivo and in-vitro use. The contamination rate in 27 type A institutes did not exceed 0.01%, whereas in 15 type B institutes the contamination rate distributed widely from undetectable to above 1%. These results indicated that the present regulation for the draining-water system, which assumed that 1% of all radioactivity used in nuclear medicine institutes contaminated into draining-water system, should be reconsidered in nuclear medicine facilities where radionuclides are used only in in-vivo studies.
Experimental and Theoretical Studies on Stereo- and Regioselectivity in Intramolecular Nitrone−Alkene Cycloaddition of Hept-6-enoses Derived from Carbohydrates (2006)

The effect of blocking groups and stereochemistry of the substituents on the regio- and stereoselectivity in intramolecular nitrone-alkene cycloaddition (INAC) of hept-6-enoses are reported. L-ribo-Hept-6-enose 12 and D-lyxo-hept-6-enose 15, both containing a 2,3-O-isopropylidene blocking group, and L-xylo-hept-6-enose 23 and D-arabino-hept-6-enose 30, both with a 2,3-O-trans-diacetal blocking group, were prepared from D-ribose and D-arabinose, respectively. With N-alkyl hydroxylamine, lactols 12 and 15 underwent an INAC reaction to give cis-fused isoxazolidines exclusively whereas lactols 23 and 30 gave a mixture of cis-, trans-fused isoxazolidines (cyclohexanols) and bridged isoxazolidines (cycloheptanols). With the 2,3-O-trans-diacetal protecting group, the bridged bicyclo[4.2.1]isoxazolidines (cycloheptanols), via the endo mode of INAC cyclization, were synthesized for the first time from unbranched sugar derivatives 23 and 30. The stereochemical outcomes of these reactions were rationalized on the basis of transition state energies obtained by computation. The present INAC showed trivial temperature, but significant solvent dependence. For lactols 23 and 30, performing the INAC in 2-propanol gave the best yields of fused isoxazolidines (cyclohexanols) whereas in dichloromethane afforded the best yields of bridged isoxazolidines (cycloheptanols).
A High Molecular Weight Melanoma-Associated Antigen–Specific Chimeric Antigen Receptor Redirects Lymphocytes to Target Human Melanomas (2010)

Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen-restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3zeta activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, was non-MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies.
Iterative multiuser detection for coded CDMA signals in AWGN and fading channels (2000)

A new iterative receiver for joint detection and decoding of code division multiple access (CDMA) signals is presented. The new scheme is based on a combination of the minimum mean square error (MMSE) criterion and the turbo processing principle by Hagenauer (see Proc. Int. Symp. Turbo Codes and Related Topics, Brest, France, p.1-9, 1997). The complexity of the new scheme is of polynomial order in the number of users. The new scheme is applicable to two situations: (a) when the receiver is capable of decoding the signals from all users and (b) when the receiver is only capable of decoding the signals from a subset of users. In the first scenario, we establish that the proposed receiver achieves superior performance to the iterative soft interference cancellation technique under certain conditions. On the other hand, in the second scenario, we argue that the proposed receiver outperforms both the iterative soft interference canceler and the iterative maximum a posteriori (MAP) receiver because of its superior near-far resistance. For operation over fading channels, the estimation of the complex fading parameters for all users becomes an important ingredient in any multiuser detector. In our scheme, the soft information provided by the decoders is used to enhance this estimation process. Two iterative soft-input channel estimation algorithms are presented: the first is based on the MMSE criterion, and the second is a lower-complexity approximation of the first. The proposed multiuser detection algorithm(s) are suitable for both terrestrial and satellite applications of CDMA.
Chemistry and antiinflammatory activities of prodolic acid and related 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-alkanoic acids. 1 (1975)

The synthesis and antiinflammatory activities of a series of 23 novel 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-alkanoic acids are described and some relationships between structure and activity are discussed. One of these compounds, 1,3,4,9-tetrahydro-1-propylpyrano[3,4-b]indole-1-acetic acid (prodolic acid, USAN), has been selected for further studies.
Mortality Impact of Hypothermia After Cavitary Explorations in Trauma (2009)

Postoperative hypothermia is common in critically injured patients requiring cavitary surgery and is an independent predictor of mortality. The impact of measures to maintain or restore normothermia in the operating room warrants further investigation.
A "brick" caching scheme for 3D medical imaging (2005)

This paper presents a "brick" caching scheme for a broad range of 3D medical imaging algorithms, which achieves a cache hit ratio of 100% and significantly reduces the total data-flow from the system memory to the caches, thus reducing the memory bandwidth requirement of the system. With data indexing and duplication, this scheme supports multiple parallel memory access required in most 3D imaging algorithms. Brick prefetching strategy fetches data into the cache before they are used, therefore preventing the stall of the processing pipeline. The applications of the caching scheme in FDK cone beam reconstruction and 3D image registration were presented as examples. This caching scheme will be used in our FPGA-based 3D medical imaging coprocessor and it can also be applied to other FPGA-based 3D imaging accelerators.
Hepcidin Levels and Their Determinants in Different Types of Myelodysplastic Syndromes (2011)

Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic non-transferrin-bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiation factor 15 did not appear as a primary hepcidin regulator in this series. If confirmed, these results may help to calibrate future treatments with chelating agents and/or hepcidin modulators in MDS patients.
Randomized Trial of Human Milk Cream as a Supplement to Standard Fortification of an Exclusive Human Milk-Based Diet in Infants 750-1250 g Birth Weight (2014)

Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group. HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants.
PSD-95 is required for activity-driven synapse stabilization (2007)

The activity-dependent regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and the stabilization of synapses are critical to synaptic development and plasticity. One candidate molecule implicated in maturation, synaptic strengthening, and plasticity is PSD-95. Here we find that acute knockdown of PSD-95 in brain slice cultures by RNAi arrests the normal development of synaptic structure and function that is driven by spontaneous activity. Surprisingly, PSD-95 is not necessary for the induction and early expression of long-term potentiation (LTP). However, knockdown of PSD-95 leads to smaller increases in spine size after chemically induced LTP. Furthermore, although at this age spine turnover is normally low and LTP produces a transient increase, in cells with reduced PSD-95 spine turnover is high and remains increased after LTP. Taken together, our data support a model in which appropriate levels of PSD-95 are required for activity-dependent synapse stabilization after initial phases of synaptic potentiation.
Requirement for an initial signal from the membrane-proximal region of the interleukin 2 receptor γ <sub>c</sub> chain for Janus kinase activation leading to T cell proliferation (1997)

The interleukin 2 receptor (IL-2R) generates proliferative signals in T lymphocytes by ligand-induced heterodimerization of two chains, IL-2Rbeta and gamma(c), which associate with the tyrosine kinases Jak1 and Jak3, respectively. Genetic and molecular studies have demonstrated that Jak3 is essential for mitogenic signaling by the gamma(c) chain; because it is also the only molecule known to associate with gamma(c), we speculated that Jak3 might be sufficient for signaling by this chain. Therefore, fusion proteins were constructed in which all or part of the cytoplasmic domain of gamma(c) was replaced by Jak3. Signaling was evaluated in the IL-2-dependent T cell line CTLL-2 using chimeric IL-2Rbeta and gamma(c) chains that bind and are activated by the cytokine granulocyte-macrophage colony-stimulating factor. Chimeric gamma(c) chains containing only Jak3 in the cytoplasmic domain failed to mediate proliferation of CTLL-2 cells, but addition of a conserved membrane-proximal (PROX) domain of gamma(c) in tandem with Jak3 fully reconstituted gamma(c) function. The requirement for the PROX domain reflected an essential role in the activation of Jak3 in vivo. Despite lacking defined catalytic motifs, PROX induced an early Jak-independent signal, including tyrosine phosphorylation of IL-2Rbeta and the tyrosine phosphatase SHP-2. The results define the minimal signaling components of gamma(c) and suggest a new mechanism by which the IL-2R initiates signaling in response to ligand.
Mandatory security in object-oriented database systems (1989)

A multilevel secure object-oriented data model (using the ORION data model) is proposed for which mandatory security issues in the context of a database system is discussed. In particular the following issues are dealt with: (1) the security policy for the system, (2) handling polyinstantiation, and (3) handling the inference problem. A set of security properties that has been established in this paper is more complete than those that have been proposed previously. Finally we describe how certain security constraints are handled by our model.
<i>N</i><sup>6</sup>-Cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA), a Very Selective Agonist with High Affinity for the Human Adenosine A<sub>1</sub> Receptor (2003)

Four subtypes of adenosine receptors are currently known, that is, A(1), A(2A), A(2B), and A(3) receptors. Interestingly, quite substantial species differences exist especially between human and rat A(3) receptors. As a result, ligands such as CCPA, which are very selective for the rat A(1) receptor versus the human A(3) receptor, are substantially less selective when the human A(1) and A(3) receptors are compared. New 2-substituted and 2,N(6)-disubstituted adenosines were synthesized, and their affinities for the human adenosine A(1), A(2A), A(2B), and A(3) receptors were determined. Although large substituents on the C2-position are generally thought to yield adenosine A(2A) receptor selective ligands, the reported series of 2-triazeno-substituted adenosines had a very high affinity for the A(1) receptor. For example, 2-(3-phenylaminocarbonyltriazene-1-yl)adenosine had an affinity of 6.1 +/- 1.3 nM for the human adenosine A(1) receptor. Introduction of a diphenethyl substituent at the N(6)-position of this compound resulted in a high-affinity agonist, 3.1 +/- 0.9 nM, for the human adenosine A(1) receptor with 316- and 45-fold selectivity versus the human A(2A) and human A(3) receptors, respectively. The most selective, high-affinity human adenosine A(1) receptor agonist was the disubstituted compound N(6)-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA). TCPA had an affinity of 2.8 +/- 0.8 nM for the human adenosine A(1) receptor and was 75-fold and 214-fold selective versus the human A(2A) and human A(3) receptors, respectively. In addition, TCPA was a full agonist and inhibited the forskolin-induced cAMP production of CHO cells stably transfected with the human adenosine A(1) receptor with an IC(50) of 1.5 +/- 0.5 nM.
Stereoselective synthesis of 3-alkylated glutamic acids: application to the synthesis of secokainic acid (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective synthesis of 3-alkylated glutamic acids: application to the synthesis of secokainic acidIsabelle Jako, Pierre Uiber, Andre Mann, Camille Georges Wermuth, Thierry Boulanger, Bernadette Norberg, Guy Evrard, and Francois DurantCite this: J. Org. Chem. 1991, 56, 19, 5729–5733Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/jo00019a055https://doi.org/10.1021/jo00019a055research-articleACS PublicationsRequest reuse permissionsArticle Views290Altmetric-Citations47LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Histone Deacetylase Inhibitors Enhance <i>Candida albicans</i> Sensitivity to Azoles and Related Antifungals: Correlation with Reduction in <i>CDR</i> and <i>ERG</i> Upregulation (2002)

Histone acetylation and deacetylation play important roles in eukaryotic gene regulation. Several histone deacetylase (HDA) inhibitors have been characterized, including trichostatin A (TSA), apicidin, and sodium butyrate. We tested their effects on Candida albicans in vitro growth, heat sensitivity, and germ tube formation; minimal effects were observed. However, there was a dramatic effect of TSA on C. albicans sensitivity to the azoles fluconazole, itraconazole, and miconazole. Similar effects were observed with other HDA inhibitors and with the antifungals terbinafine and fenpropimorph, which target, as do azoles, enzymes in the ergosterol biosynthetic pathway. In contrast, HDA inhibitors had minimal effect on the activities of amphotericin B, flucytosine, and echinocandin, which have unrelated targets. Specifically, addition of 3 micro g of TSA/ml lowered the itraconazole MIC for five susceptible C. albicans isolates an average of 2.7-fold at 24 h, but this increased to >200-fold at 48 h. Thus, the primary effect of TSA was a reduction in azole trailing. TSA also enhanced itraconazole activity against Candida parapsilosis and Candida tropicalis but had no effect with four less related yeast species. To examine the molecular basis for these effects, we studied expression of ERG genes (encoding azole and terbinafine targets) and CDR/MDR1 genes (encoding multidrug transporters) in C. albicans cells treated with fluconazole or terbinafine with or without TSA. Both antifungals induced to various levels the expression of ERG1, ERG11, CDR1, and CDR2; addition of TSA reduced this upregulation 50 to 100%. This most likely explains the inhibition of azole and terbinafine trailing by TSA and, more generally, provides evidence that trailing is mediated by upregulation of target enzymes and multidrug transporters.