177 research outputs found
The window period of NEUROGENIN3 during human gestation
The basic helix-loop-helix transcription factor, NEUROG3, is critical in causing endocrine commitment from a progenitor cell population in the developing pancreas. In human, NEUROG3 has been detected from 8 weeks postconception (wpc). However, the profile of its production and when it ceases to be detected is unknown. In this study we have defined the profile of NEUROG3 detection in the developing pancreas to give insight into when NEUROG3- dependent endocrine commitment is possible in the human fetus. Immunohistochemistry allowed counting of cells with positively stained nuclei from 7 wpc through to term. mRNA was also isolated from sections of human fetal pancreas and NEUROG3 transcription analyzed by quantitative reverse transcription and polymerase chain reaction. NEUROG3 was detected as expected at 8 wpc. The number of NEUROG3-positive cells increased to peak levels between 10 wpc and 14 wpc. It declined at and after 18 wpc such that it was not detected in human fetal pancreas at 35-41 wpc. Analysis of NEUROG3 transcription corroborated this profile by demonstrating very low levels of transcript at 35-41 wpc, more than 10-fold lower than levels at 12-16 wpc. These data define the appearance, peak and subsequent disappearance of the critical transcription factor, NEUROG3, in human fetal pancreas for the first time. By inference, the window for pancreatic endocrine differentiation via NEUROG3 action opens at 8 wpc and closes between 21 and 35 wpc
- and -hypernuclei
- and -hypernuclei are studied in the quark-meson
coupling (QMC) model. Comparisons are made with the results for
-hypernuclei studied in the same model previously. Although the scalar
and vector potentials felt by the , and in
the corresponding hypernuclei multiplet which has the same baryon numbers are
quite similar, the wave functions obtained, e.g., for state, are
very different. The baryon density distribution in
Pb is much more pushed away from the center than that for
the in Pb due to the Coulomb force. On the contrary,
the baryon density distributions in -hypernuclei are
much larger near the origin than those for the in the corresponding
-hypernuclei due to its heavy mass. It is also found that level
spacing for the single-particle energies is much smaller than that
for the and .Comment: Latex, 14 pages, 4 figures, text was extended, version to appear in
Phys. Rev.
Experimental and Theoretical Challenges in the Search for the Quark Gluon Plasma: The STAR Collaboration's Critical Assessment of the Evidence from RHIC Collisions
We review the most important experimental results from the first three years
of nucleus-nucleus collision studies at RHIC, with emphasis on results from the
STAR experiment, and we assess their interpretation and comparison to theory.
The theory-experiment comparison suggests that central Au+Au collisions at RHIC
produce dense, rapidly thermalizing matter characterized by: (1) initial energy
densities above the critical values predicted by lattice QCD for establishment
of a Quark-Gluon Plasma (QGP); (2) nearly ideal fluid flow, marked by
constituent interactions of very short mean free path, established most
probably at a stage preceding hadron formation; and (3) opacity to jets. Many
of the observations are consistent with models incorporating QGP formation in
the early collision stages, and have not found ready explanation in a hadronic
framework. However, the measurements themselves do not yet establish
unequivocal evidence for a transition to this new form of matter. The
theoretical treatment of the collision evolution, despite impressive successes,
invokes a suite of distinct models, degrees of freedom and assumptions of as
yet unknown quantitative consequence. We pose a set of important open
questions, and suggest additional measurements, at least some of which should
be addressed in order to establish a compelling basis to conclude definitively
that thermalized, deconfined quark-gluon matter has been produced at RHIC.Comment: 101 pages, 37 figures; revised version to Nucl. Phys.
Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour
Purpose: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor a kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a >fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, third and later lines of therapy. Methods: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150 mg QD could dose escalate to 150 mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150 mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150 mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively. Results: Of 142 patients with GIST receiving ripretinib 150 mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3 and 4.6 months for patients on second-, third-and >fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar. Conclusion: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Experimentele farmacotherapi
Experimental Lagos bat virus infection in straw-colored fruit bats: A suitable model for bat rabies in a natural reservoir species
Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable m
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