1,458 research outputs found
WWP1 knockout in mice exacerbates obesity-related phenotypes in white adipose tissue but improves whole-body glucose metabolism
Soliton excitations in halogen-bridged mixed-valence binuclear metal complexes
Motivated by recent stimulative observations in halogen (X)-bridged binuclear
transition-metal (M) complexes, which are referred to as MMX chains, we study
solitons in a one-dimensional three-quarter-filled charge-density-wave system
with both intrasite and intersite electron-lattice couplings. Two distinct
ground states of MMX chains are reproduced and the soliton excitations on them
are compared. In the weak-coupling region, all the solitons are degenerate to
each other and are uniquely scaled by the band gap, whereas in the
strong-coupling region, they behave differently deviating from the scenario in
the continuum limit. The soliton masses are calculated and compared with those
for conventional mononuclear MX chains.Comment: 9 pages, 10 figures embedded, to be published in J. Phys. Soc. Jpn.
71, No. 1 (2002
Synthetic DNA immunotherapy in biochemically relapsed prostate cancer
Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).
Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks.
Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50).
Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)
Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut
Fish larval development, not least the spectacular
process of flatfish metamorphosis, appears to be
under complex endocrine control, many aspects of
which are still not fully elucidated. In order to obtain
data on the functional development of two major
endocrine glands, the pituitary and the thyroid, during
flatfish metamorphosis, histology, immunohistochemistry
and in situ hybridization techniques were applied on
larvae of the Atlantic halibut (Hippoglossus hippoglossus),
a large, marine flatfish species, from hatching
through metamorphosis. The material was obtained
from a commercial hatchery. Larval age is defined as
day-degrees (D =accumulated daily temperature from
hatching). Sporadic thyroid follicles are first detected in
larvae at 142 D (27 days post-hatch), prior to the
completion of yolk sack absorption. Both the number
and activity of the follicles increase markedly after yolk
sack absorption and continue to do so during subsequent
development. The larval triiodothyronine (T3)
and thyroxine (T4) content increases, subsequent to yolk
absorption, and coincides with the proliferation of thyroid
follicles. A second increase of both T3 and T4 occurs
around the start of metamorphosis and the T3 content
further increases at the metamorphic climax. Overall,
the T3 content is lower than T4. The pituitary gland can
first be distinguished as a separate organ at the yolk sack
stage. During subsequent development, the gland becomes
more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia
(PI). The first sporadic endocrine pituitary cells are observed
at the yolk sack stage, somatotrophs (growth
hormone producing cells) and somatolactotrophs (somatolactin
producing cells) are first observed at 121 D
(23 days post-hatch), and lactotrophs (prolactin producing
cells) at 134 D (25 days post-hatch). Scarce
thyrotrophs are evident after detection of the first thyroid
follicles (142 D ), but coincident with a phase in
which follicle number and activity increase (260 D ).
The somatotrophs are clustered in the medium ventral
region of the PD, lactotrophs in the anterior part of the
PD and somatolactotrophs are scattered in the mid and
posterior region of the pituitary. At around 600 D ,
coinciding with the start of metamorphosis, somatolactotrophs
are restricted to the interdigitating tissue of the
NH. During larval development, the pituitary endocrine
cells become more numerous. The present data on thyroid
development support the notion that thyroid hormones
may play a significant role in Atlantic halibut
metamorphosis. The time of appearance and the subsequent
proliferation of pituitary somatotrophs, lactotrophs,
somatolactotrophs and thyrotrophs indicate at
which stages of larval development and metamorphosis
these endocrine cells may start to play active regulatory
roles.This work has been carried out within the
projects ‘‘Endocrine Control as a Determinant of Larval Quality in
Fish Aquaculture’’ (CT-96-1422) and ‘‘Arrested development: The
Molecular and Endocrine Basis of Flatfish Metamorphosis’’
(Q5RS-2002-01192), with financial support from the Commission
of the European Communities. However, it does not necessarily
reflect the Commission’s views and in no way anticipates its future
policy in this area. This project was further supported by the
Swedish Council for Agricultural and Forestry Research and Pluriannual
funding to CCMAR by the Portuguese Science and
Technology Council
Enzootic bovine leukosis accompanied by splenomegaly in an 8-month-old calf
ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗIn this report, an 8-month-old calf (crossbred, Holstein × Japanese Black) developed fever and accompanied abomasum displacement. Blood chemical test showed remarkably high values of white blood cell count and heteromorphic lymphocytes. In pathological appraisal, enlarged splenomegaly and swelling of the lymph nodes were observed. Histopathological examination revealed invasion of tumor cells derived from B1 cells into systemic lymph nodes, liver and spleen. The provirus loads of bovine leukemia virus (BLV) was 1,439 copies per 10 ng DNA by using real time PCR. In conclusion, this case was diagnosed as bovine leukemia caused by BLV infection with a huge splenomegaly
Cosmic Evolution of Stellar-mass Black Hole Merger Rate in Active Galactic Nuclei
Binary black hole mergers encode information about their environment and the
astrophysical processes that led to their formation. Measuring the redshift
dependence of their merger rate will help probe the formation and evolution of
galaxies and the evolution of the star formation rate. Here we compute the
cosmic evolution of the merger rate for stellar-mass binaries in the disks of
Active Galactic Nuclei (AGNs). We focus on recent evolution out to redshift
, covering the accessible range of current Earth-based gravitational-wave
observatories. On this scale, the AGN population density is the main
contributor to redshift-dependence. We find that the AGN-assisted merger rate
does not meaningfully evolve with redshift, differentiating this channel from
field binaries and some other dynamical formation scenarios.Comment: 6 pages, 2 figure
Effect of liquid elasticity on the behaviour of high-speed focused jets
We investigate the effect of highly contrasting non-Newtonian liquid properties on the formation of liquid jets with a focused shape. By using two nozzle-free ejection techniques, mechanically impact- and laser-induced, fast jets of a highly elastic (sodium polyacrylate) and weakly elastic (xanthan-gum) diluted polymer solutions are generated. A unique high-speed effect is encountered at the jet ejection onset of the highly elastic solution. Its jet-tip speed is on average 1.4 times faster in comparison to a Newtonian (glycerin/water) and the weakly elastic liquids. We explain this effect occurring as a result of the high viscoelasticity of the sodium polyacrylate solution. Additionally, a 'bungee jumper' jet behaviour (Morrison and Harlen in Rheol Acta 49(6):619-632, 2010) is observed in a regime of high speed (10 20 mPa s) not previously examined. We additionally characterise the viscoelastic non-breakup jet limit using the Bazilevskii et al. (Fluid Dyn 40(3):376-392, 2005) ejection criterion. Herein, the extensional rheological parameters are measured implementing a novel DoS-CaBER technique (Dinic et al. in Lab Chip 17(3):460-473, 2017). Our findings may influence results of inkjet printing technologies and recent nozzle-free ejection systems for ejecting liquids with non-Newtonian properties.Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
Japan Society for the Promotion of Science
Grants-in-Aid for Scientific Research (KAKENHI)
17H01246
20H00223
ANID FONDECYT, Chile
320009
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