198 research outputs found
Heterochromatin protein 1α mediates development and aggressiveness of neuroendocrine prostate cancer
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathological feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC. Longitudinal analysis using our unique, first-in-field PDX model of adenocarcinoma-to-NEPC transdifferentiation revealed that, among those 36 heterochromatin-related genes, heterochromatin protein 1α (HP1α) expression increased early and steadily during NEPC development and remained elevated in the developed NEPC tumor. Its elevated expression was further confirmed in multiple PDX and clinical NEPC samples. HP1α knockdown in the NCI-H660 NEPC cell line inhibited proliferation, ablated colony formation, and induced apoptotic cell death, ultimately leading to tumor growth arrest. Its ectopic expression significantly promoted NE transdifferentiation in adenocarcinoma cells subjected to androgen deprivation treatment. Mechanistically, HP1α reduced expression of androgen receptor (AR) and RE1 silencing transcription factor (REST) and enriched the repressive trimethylated histone H3 at Lys9 (H3K9me3) mark on their respective gene promoters. These observations indicate a novel mechanism underlying NEPC development mediated by abnormally expressed heterochromatin genes, with HP1α as an early functional mediator and a potential therapeutic target for NEPC prevention and management
Recommended from our members
Balancing the popularity bias of object similarities for personalised recommendation
Network-based similarity measures have found wide applications in recommendation algorithms and made signicant contributions for uncovering users' potential interests. However, existing measures are generally biased in terms of popularity, that the popular objects tend to have more common neighbours with others and thus are considered more similar to others. Such popularity bias
of similarity quantification will result in the biased recommendations, with either poor accuracy or poor diversity. Based on the bipartite network modelling of the user-object interactions, this paper firstly calculates the expected number of common neighbours of two objects with given popularities in random networks. A Balanced Common Neighbour similarity index is accordingly developed
by removing the random-driven common neighbours, estimated as the expected number, from the total number. Recommendation experiments in three data sets show that balancing the popularity bias in a certain degree can significantly improve the recommendations' accuracy and diversity
simultaneously
Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism
This article reviews the application of the non-equilibrium Green's function
formalism to the simulation of novel photovoltaic devices utilizing quantum
confinement effects in low dimensional absorber structures. It covers
well-known aspects of the fundamental NEGF theory for a system of interacting
electrons, photons and phonons with relevance for the simulation of
optoelectronic devices and introduces at the same time new approaches to the
theoretical description of the elementary processes of photovoltaic device
operation, such as photogeneration via coherent excitonic absorption,
phonon-mediated indirect optical transitions or non-radiative recombination via
defect states. While the description of the theoretical framework is kept as
general as possible, two specific prototypical quantum photovoltaic devices, a
single quantum well photodiode and a silicon-oxide based superlattice absorber,
are used to illustrated the kind of unique insight that numerical simulations
based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape
Direct Measurements of the Branching Fractions for and and Determinations of the Form Factors and
The absolute branching fractions for the decays and
are determined using singly
tagged sample from the data collected around 3.773 GeV with the
BES-II detector at the BEPC. In the system recoiling against the singly tagged
meson, events for and events for decays are observed. Those yield
the absolute branching fractions to be and . The
vector form factors are determined to be
and . The ratio of the two form
factors is measured to be .Comment: 6 pages, 5 figure
Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta
Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector,
the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are
measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and
(7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure
Partial Wave Analysis of
BES data on are presented. The
contribution peaks strongly near threshold. It is fitted with a
broad resonance with mass MeV, width MeV. A broad resonance peaking at 2020 MeV is also required
with width MeV. There is further evidence for a component
peaking at 2.55 GeV. The non- contribution is close to phase
space; it peaks at 2.6 GeV and is very different from .Comment: 15 pages, 6 figures, 1 table, Submitted to PL
BESII Detector Simulation
A Monte Carlo program based on Geant3 has been developed for BESII detector
simulation. The organization of the program is outlined, and the digitization
procedure for simulating the response of various sub-detectors is described.
Comparisons with data show that the performance of the program is generally
satisfactory.Comment: 17 pages, 14 figures, uses elsart.cls, to be submitted to NIM
Measurement of branching fractions for the inclusive Cabibbo-favored ~K*0(892) and Cabibbo-suppressed K*0(892) decays of neutral and charged D mesons
The branching fractions for the inclusive Cabibbo-favored ~K*0 and
Cabibbo-suppressed K*0 decays of D mesons are measured based on a data sample
of 33 pb-1 collected at and around the center-of-mass energy of 3.773 GeV with
the BES-II detector at the BEPC collider. The branching fractions for the
decays D+(0) -> ~K*0(892)X and D0 -> K*0(892)X are determined to be BF(D0 ->
\~K*0X) = (8.7 +/- 4.0 +/- 1.2)%, BF(D+ -> ~K*0X) = (23.2 +/- 4.5 +/- 3.0)% and
BF(D0 -> K*0X) = (2.8 +/- 1.2 +/- 0.4)%. An upper limit on the branching
fraction at 90% C.L. for the decay D+ -> K*0(892)X is set to be BF(D+ -> K*0X)
< 6.6%
The pole in
Using a sample of 58 million events recorded in the BESII detector,
the decay is studied. There are conspicuous
and signals. At low mass, a large
broad peak due to the is observed, and its pole position is determined
to be - MeV from the mean of six analyses.
The errors are dominated by the systematic errors.Comment: 15 pages, 6 figures, submitted to PL
Measurements of the Mass and Full-Width of the Meson
In a sample of 58 million events collected with the BES II detector,
the process J/ is observed in five different decay
channels: , , (with ), (with
) and . From a combined fit of all five
channels, we determine the mass and full-width of to be
MeV/ and
MeV/.Comment: 9 pages, 2 figures and 4 table. Submitted to Phys. Lett.
- …