38 research outputs found
Emergence of bound states in ballistic magnetotransport of graphene antidots
An experimental method for detection of bound states around an antidot formed
from a hole in a graphene sheet is proposed by measuring the ballistic two
terminal conductances. In particularly, we consider the effect of bound states
formed by magnetic field on the two terminal conductance and show that one can
observe Breit-Wigner like resonances in the conductance as a function of the
Fermi level close to the energies of the bound states. In addition, we develop
a new numerical method in which the computational effort is proportional to the
linear dimensions, instead of the area of the scattering region beeing typical
for the existing numerical recursive Green's function method.Comment: 7 pages, 6 figure
Demonstration of a Melanoma-Specific CD44 Alternative Splicing Pattern That Remains Qualitatively Stable, but Shows Quantitative Changes during Tumour Progression
The role of CD44 in the progression of human melanoma has mostly been characterised by qualitative changes in
expression of its individual variable exons. These exons however, may be expressed to form a number of molecules, the
alternative splice variants of CD44, which may be structurally and functionally different. Using real-time PCR measurements
with variable exon specific primers we have determined that all are expressed in human melanoma. To permit comparison
between different tumours we identified a stable CD44 variable exon (CD44v) expression pattern, or CD44 ‘fingerprint’. This
was found to remain unchanged in melanoma cell lines cultured in different matrix environments. To evaluate evolution of
this fingerprint during tumour progression we established a scid mouse model, in which the pure expression pattern of
metastatic primary tumours, circulating cells and metastases, non-metastatic primary tumours and lung colonies could be
studied. Our analyses demonstrated, that although the melanoma CD44 fingerprint is qualitatively stable, quantitative
changes are observed suggesting a possible role in tumour progression
Thermopower in hBN/graphene/hBN superlattices
Thermoelectric effects are highly sensitive to the asymmetry in the density
of states around the Fermi energy and can be exploited as probes of the
electronic structure. We experimentally study thermopower in high-quality
monolayer graphene, within heterostructures consisting of complete hBN
encapsulation and 1D edge contacts, where the graphene and hBN lattices are
aligned. When graphene is aligned to one of the hBN layers, we demonstrate the
presence of additional sign reversals in the thermopower as a function of
carrier density, directly evidencing the presence of the moir\'e superlattice.
We show that the temperature dependence of the thermopower enables the
assessment of the role of built-in strain variation and van Hove singularities
and hints at the presence of Umklapp electron-electron scattering processes. As
the thermopower peaks around the neutrality point, this allows to probe the
energy spectrum degeneracy. Further, when graphene is double-aligned with the
top and bottom hBN crystals, the thermopower exhibits features evidencing
multiple cloned Dirac points caused by the differential super-moir\'e lattice.
For both cases we evaluate how well the thermopower agrees with Mott's
equation. Finally, we show the same superlattice device can exhibit a
temperature-driven thermopower reversal from positive to negative and vice
versa, by controlling the carrier density. The study of thermopower provides an
alternative approach to study the electronic structure of 2D superlattices,
whilst offering opportunities to engineer the thermoelectric response on these
heterostructures.Comment: 9 pages, 3 figure
Recommended from our members
Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection.
The complex immunopathology ofMycobacterium tuberculosis(Mtb) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb. After preliminary screening, CFP10 (32-39), GlfT2 (4-12), HBHA (185-194), and PPE15 (1-15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb-sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure-activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate (Pal-CGHP) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System
A Chemocentric Approach to the Identification of Cancer Targets
A novel chemocentric approach to identifying cancer-relevant targets is introduced. Starting with a large chemical collection, the strategy uses the list of small molecule hits arising from a differential cytotoxicity screening on tumor HCT116 and normal MRC-5 cell lines to identify proteins associated with cancer emerging from a differential virtual target profiling of the most selective compounds detected in both cell lines. It is shown that this smart combination of differential in vitro and in silico screenings (DIVISS) is capable of detecting a list of proteins that are already well accepted cancer drug targets, while complementing it with additional proteins that, targeted selectively or in combination with others, could lead to synergistic benefits for cancer therapeutics. The complete list of 115 proteins identified as being hit uniquely by compounds showing selective antiproliferative effects for tumor cell lines is provided
Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells
BACKGROUND: Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. METHODS: Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model. RESULTS: All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment. CONCLUSIONS: Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors
Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells.
While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells