151 research outputs found
A topological insulator surface under strong Coulomb, magnetic and disorder perturbations
Three dimensional topological insulators embody a newly discovered state of
matter characterized by conducting spin-momentum locked surface states that
span the bulk band gap as demonstrated via spin-resolved ARPES measurements .
This highly unusual surface environment provides a rich ground for the
discovery of novel physical phenomena. Here we present the first controlled
study of the topological insulator surfaces under strong Coulomb, magnetic and
disorder perturbations. We have used interaction of iron, with a large Coulomb
state and significant magnetic moment as a probe to \textit{systematically test
the robustness} of the topological surface states of the model topological
insulator BiSe. We observe that strong perturbation leads to the
creation of odd multiples of Dirac fermions and that magnetic interactions
break time reversal symmetry in the presence of band hybridization. We also
present a theoretical model to account for the altered surface of BiSe.
Taken collectively, these results are a critical guide in manipulating
topological surfaces for probing fundamental physics or developing device
applications.Comment: 14 pages, 4 Figures. arXiv admin note: substantial text overlap with
arXiv:1009.621
MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations
The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML
Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia
The clinical significance of aberrant promoter methylation of the
canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4,
sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor
gene Wnt5a, belonging to the non-canonical Wnt signaling pathway,
was investigated in a large series of 75 patients with Philadelphia
chromosome-positive acute lymphoblastic leukemia by methylationspecific
polymerase chain reaction. At least one methylated gene
was observed in cells from 66% (49/75) of patients (methylated
group). Disease-free survival and overall survival at 9 years were 51
and 40%, respectively, for the unmethylated group and 3 and 2%,
respectively, for the methylated group (both P < 0.0001). Multivariate
analysis demonstrated that the Wnt methylation profile was an
independent prognostic factor predicting disease-free survival
(P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation
of promoter-associated CpG islands in the Wnt signaling pathway is
very common in Philadelphia chromosome-positive acute lymphoblastic
leukemia and potentially defines subgroups with distinct
clinical characteristics
Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia
Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy.
Although CTA genes are expressed in some normal tissues, such as the testis,
this immunologically protected site lacks MHC I expression and as such, does not
present self antigens to T cells. To date, CTA genes have been shown to be expressed
in a range of solid tumors via demethylation of their promoter CpG islands, but rarely
in chronic myeloid leukemia (CML) or other hematologic malignancies
Entanglement study of the 1D Ising model with Added Dzyaloshinsky-Moriya interaction
We have studied occurrence of quantum phase transition in the one-dimensional
spin-1/2 Ising model with added Dzyaloshinsky-Moriya (DM) interaction from bi-
partite and multi-partite entanglement point of view. Using exact numerical
solutions, we are able to study such systems up to 24 qubits. The minimum of
the entanglement ratio R \tau 2/\tau 1 < 1, as a novel estimator of
QPT, has been used to detect QPT and our calculations have shown that its
minimum took place at the critical point. We have also shown both the
global-entanglement (GE) and multipartite entanglement (ME) are maximal at the
critical point for the Ising chain with added DM interaction. Using matrix
product state approach, we have calculated the tangle and concurrence of the
model and it is able to capture and confirm our numerical experiment result.
Lack of inversion symmetry in the presence of DM interaction stimulated us to
study entanglement of three qubits in symmetric and antisymmetric way which
brings some surprising results.Comment: 18 pages, 9 figures, submitte
Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia
Aberrant genome-wide hypomethylation is thought to be
related to tumorigenesis by promoting genomic instability.
Since DNA methylation is considered an important mechanism
for the silencingof retroelements, hypomethylation
in human tumors may lead to their reactivation. However,
the role of DNA hypomethylation in chronic myeloid
leukemia (CML) remains to be elucidated. In this study,
the methylation status of the LINE-1 (L1) retrotransposon
promoter was analysed in CML samples from the chronicphase
(CP, n¼140) and the blast crisis (BC, n¼47). L1
hypomethylation was significantly more frequent in BC
(74.5%) than in CP (38%) (Po0.0001). Furthermore,
L1 hypomethylation led to activation of both ORF1 sense
transcription (Po0.0001) and c-MET gene antisense
transcription (Po0.0001), and was significantly associated
with high levels of BCR–ABL (P¼0.02) and
DNMT3b4 (P¼0.001) transcripts. Interestingly, in
CP-CML, extensive L1 hypomethylation was associated
with poorer prognosis in terms of cytogenetic response
to interferon (P¼0.004) or imatinib (P¼0.034) and
progression-free survival (P¼0.005). The above results
strongly suggest that activation of both sense and
antisense transcriptions by aberrant promoter hypomethylation
of the L1 elements plays a role in the progression
and clinical behavior of the CML
Hedgehog Spin-texture and Berry's Phase tuning in a Magnetic Topological Insulator
Understanding and control of spin degrees of freedom on the surfaces of
topological materials are key to future applications as well as for realizing
novel physics such as the axion electrodynamics associated with time-reversal
(TR) symmetry breaking on the surface. We experimentally demonstrate
magnetically induced spin reorientation phenomena simultaneous with a
Dirac-metal to gapped-insulator transition on the surfaces of manganese-doped
Bi2Se3 thin films. The resulting electronic groundstate exhibits unique
hedgehog-like spin textures at low energies, which directly demonstrate the
mechanics of TR symmetry breaking on the surface. We further show that an
insulating gap induced by quantum tunnelling between surfaces exhibits spin
texture modulation at low energies but respects TR invariance. These spin
phenomena and the control of their Fermi surface geometrical phase first
demonstrated in our experiments pave the way for the future realization of many
predicted exotic magnetic phenomena of topological origin.Comment: 38 pages, 18 Figures, Includes new text, additional datasets and
interpretation beyond arXiv:1206.2090, for the final published version see
Nature Physics (2012
Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia
Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL).
Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL
samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly,
the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect
activation of TP53 pathway with 5-aza-29-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells.
The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly
diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of
the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p,0.001) rate being an
independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the
multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of
ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or
activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL
Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells
Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB-MNCs) of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses.info:eu-repo/semantics/publishedVersio
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