755 research outputs found
The Unconsoled: The Modern Rogue Trapped in Traumas
Ryder, the protagonist in the novel, suffers many traumatic experiences during his childhood. Though these traumas shadow his life, he doesnāt narrate them directly in the novel. Instead, he unfolds his own experiences through othersā traumatic stories: traumas in Borisā childhood, in Stephenās youth, and in Brodskyās middle-age. Besides, in his adulthood, Ryder reperforms his experienced traumas upon his son Boris and his wife Sophie, which leads to tragedies to both himself and his family. Through his narration, he unconsciously uncovers his own traumatic pain that deprives him of controlling his life. Like the rogue in modern society, he can neither find any consolation from others nor give any consolation to others. To some extent, what Ryder experiences reflects the existing conditions of the unconsoled people in the west in 20th century with endless helplessness and loneliness.
Mechanisms of chiral plasmonics -- scattering, absorption and photoluminescence
Chirality is a concept that one object is not superimposable on its mirror
image by translation and rotation. In particular, chiral plasmonics have been
widely investigated due to the their excellent optical chiral properties, and
have led to numerous applications such as optical polarizing element etc. In
this study, we develop a model based on the concept of the interaction between
harmonic oscillators to investigate and explain the optical chiral mechanisms
of strongly coupled metal nanoparticles (MNPs). The chirality of the
scattering, absorption, and photoluminescence spectra are carefully discussed
in detail. The results show that the chirality of the system originates not
only from the orientations of the MNPs, but also from the different eigen
parameters between them. Specifically, the derived three factors contribute to
the chirality: the symmetry, the coupling strength, and the coherent
superposition of the emitted electric field. This work provides a deeper
understanding on the chiral plasmonics and may guide relevant applications in
theory.Comment: 8 pages, 8 figure
Unified Treatment for Scattering, Absorption, and Photoluminescence of coupled Metallic Nanoparticles with Vertical Polarized Excitation
Optical properties of coupled metallic particles (MNPs) have been widely
reported due to their unique characteristics such as peak shift/splitting of
the coupling spectra and electromagnetic enhancement at sub-wavelength scale,
etc. In a previous work, we have investigated the coupling spectra of two
coupled MNPs with parallel polarized excitation. In this study, we investigate
the vertical polarization case in detail. Different from the parallel one, the
vertical one has its unique properties: (a) three coupling coefficients; (b)
positive coupling terms in the coupling equations; (c) blue-shifts of the peaks
with the increasing coupling strength for identical MNPs spectra, including
scattering, absorption, and photoluminescence. Comparison with published
experimental results shows the validity of this model. This work provides a
deeper understanding on the optical properties of coupled MNPs and is
beneficial to relevant applications.Comment: 7 pages, 5 figure
A Psychoanalytical Approach to Nathaniel Hawthorneās āEthan Brandā
Psychoanalytical criticism to literary works is one of the important ways to uncover the depths of authorās thinking, which also contributes to readersā understanding of actions, characteristics, plots or even endings of characters in the novel. From the perspective of psychoanalysis, this article focuses on Nathaniel Hawthorneās short story āEthan Brandā written by him in 1850 to analyze Hawthorneās unconscious intention of creating this story and the reasons of why he writes in that way instead of another
The Mechanisms of HOXA9-Mediated Oncogenic Transformation
Hox genes encode a family of homeodomain-containing transcription factors that are critical for body plan specification and tissue morphogenesis during embryonic development. Hoxa9, in particular, is required for adult hematopoiesis in which it promotes stem cell renewal and expansion. Most importantly, Hoxa9 is commonly dysregulated in various types of acute leukemia, including acute myeloid leukemia (AML), and T- and B-precursor acute lymphoblastic leukemia (B-ALL and T-ALL). Together with its co-factor MEIS1, HOXA9 plays a causal role in driving leukemic transformation. Hoxa9 dysregulation is also linked to various types of solid tumors, and both gain and loss of function have been implicated in tumorigenesis. Despite its central role, the mechanism through which HOXA9 mediates oncogenic transformation remains poorly understood.
Previous work in our lab found that in a HOXA9/MEIS1-driven AML cell line, HOXA9 primarily binds to promoter-distal regions of the genome. Its target regions predominately carry the epigenetic signatures indicative of active enhancers. A substantial portion of HOXA9 binding sites are co-occupied by lineage-determining factors, such as C/EBPĪ± and PU.1. However, it remains unknown 1) whether HOXA9 drives the formation of active enhancers and globally alters the enhancer landscape; 2) whether HOXA9 strictly acts downstream of other transcription factors, or it can play a pioneer role and acts upstream of all other transcription factors and chromatin regulators; 3) if its regulatory functions are conserved in other cell lineages.
To address these questions, I show that in the myeloid lineage, HOXA9/MEIS1-transformed cells are characterized by significant alterations of the enhancer landscape and exhibit prominent emergence of de novo enhancers. These de novo enhancers are absent of enhancer modifications in any hematopoietic cells, and are associated with activation of a leukemia-specific transcription program. HOXA9 acts as a pioneer factor at these de novo regions and is required for the recruitment of myeloid lineage factor C/EBPĪ± while it is dispensable for the formation of the normal hematopoietic enhancers. Together, these results suggest an active role of HOXA9 in altering enhancer landscapes during leukemic transformation.
To explore the mechanisms of HOXA9-mediated enhancer formation, I assessed the role of the histone H3K4 methyltransferase MLL3/MLL4 complex in this alteration of enhancer landscape. Using immunoprecipitation and ChIP-seq analysis, I found physical interaction between HOXA9 and the MLL3/MLL4 complex. In addition, I determined that the MLL3/MLL4 complex is required for formation of de novo enhancers, as well as for in vivo leukemogenesis driven by HOXA9/MEIS1. Collectively, these findings provide strong evidence for an essential role for the MLL3/MLL4 complex in HOXA9-mediated leukemic transformation.
I have also collected preliminary data pertaining to HOXA9ās function in other cell lineages. I found that HOXA9 localizes to active enhancer regions in B-lineage leukemia cells and reshape the enhancer landscape; hence, confirming HOXA9ās enhancer binding characteristics. Furthermore, I discovered that HOXA9 efficiently blocks the adipogenic program in pre-adipocytes by preventing the upregulation of the key adipogenesis factor, Pparg. These data highlight a coherent role for HOXA9 in regulating gene expression and modulating cellular differentiation across different lineages.
In summary, this dissertation reveals a previously uncharacterized role of HOXA9 in leukemogenesis and cellular transformation, and provides a strong rationale for targeting the HOXA9-collaborating chromatin modulators, as well as the leukemia-specific enhancers, for the therapeutic development of acute leukemia.PHDMolecular & Cellular PathologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138797/1/yuqings_1.pd
HoxA9 binds and represses the Cebpa +8 kb enhancer
C/EBPĪ± plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPĪ±-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9
Selective Adsorption and Separation of (ā)-Epigallocatechin Gallate (EGCG) based on Silica Gel Surface Molecularly Imprinted Polymers
AbstractTo separate and enrich EGCG from a mixture of tea catechins, the molecular imprinted polymers (MIPs) were synthesized on silica gel by surface molecular imprinting technique and characterized with Fourier transform infrared spectroscopy (FT-IR), elemental analysis and scanning electronic microscopy (SEM). MIPs exhibited favorable recognition, better selectivity for EGCG than the other monomers, and the descending order was EGCG, (+)-catechin (C), (ā)-epicatechin (EC), (ā)-epigallocatechin (EGC), (ā)-catechin gallate (CG) and (ā)-gallocatechin gallate (GCG). These results demonstrated that MIPs could realize the separation and enrichment of EGCG in real sample
Deterministic and Unambiguous Dense Coding
Optimal dense coding using a partially-entangled pure state of Schmidt rank
and a noiseless quantum channel of dimension is studied both in
the deterministic case where at most messages can be transmitted with
perfect fidelity, and in the unambiguous case where when the protocol succeeds
(probability ) Bob knows for sure that Alice sent message , and when
it fails (probability ) he knows it has failed. Alice is allowed any
single-shot (one use) encoding procedure, and Bob any single-shot measurement.
For a bound is obtained for in terms of the largest
Schmidt coefficient of the entangled state, and is compared with published
results by Mozes et al. For it is shown that is strictly
less than unless is an integer multiple of , in which case
uniform (maximal) entanglement is not needed to achieve the optimal protocol.
The unambiguous case is studied for , assuming for a
set of messages, and a bound is obtained for the average
\lgl1/\tau\rgl. A bound on the average \lgl\tau\rgl requires an additional
assumption of encoding by isometries (unitaries when ) that are
orthogonal for different messages. Both bounds are saturated when is a
constant independent of , by a protocol based on one-shot entanglement
concentration. For it is shown that (at least) messages can
be sent unambiguously. Whether unitary (isometric) encoding suffices for
optimal protocols remains a major unanswered question, both for our work and
for previous studies of dense coding using partially-entangled states,
including noisy (mixed) states.Comment: Short new section VII added. Latex 23 pages, 1 PSTricks figure in
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