Suppression of Conductance in a Topological Insulator Nanostep Junction

We investigate quantum transport via surface states in a nanostep junction on the surface of a 3D topological insulator that involves two different side surfaces. We calculate the conductance across the junction within the scattering matrix formalism and find that as the bias voltage is increased, the conductance of the nanostep junction is suppressed by a universal factor of 1/3 compared to the conductance of a similar planar junction based on a single surface of a topological insulator. We also calculate and analyze the Fano factor of the nanostep junction and predict that the Fano factor saturates at 1/5, five times smaller than for a Poisson process

Adiabatic quantum pumping through surface states in 3D topological insulators

We investigate adiabatic quantum pumping of Dirac fermions on the surface of a strong 3D topological insulator. Two different geometries are studied in detail, a normal metal -- ferromagnetic -- normal metal (NFN) junction and a ferromagnetic -- normal metal -- ferromagnetic (FNF) junction. Using a scattering matrix approach, we first calculate the tunneling conductance and then the adiabatically pumped current using different pumping mechanisms for both types of junctions. We explain the oscillatory behavior of the conductance by studying the condition for resonant transmission in the junctions and find that each time a new resonant mode appears in the transport window, the pumped current diverges. We also predict an experimentally distinguishable difference between the pumped current and the rectified current

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Crítica de Libros.

Sin resumen

Acute mountain sickness susceptibility and basic cognitive function after a brief simulated altitude of 4800 M

Twelve climbers with not been exposed in the last 12 months at high altitude were evaluated using verbal, spatial, reasoning and numerical tasks from Thurstone''s (1969) Primary Mental Abilities (PMA) test. These tasks were undertaken before and immediately after completing the Richalet et al. (1988) Normobaric Hypoxic (NH) test, which evaluates the acute mountain sickness (AMS) risk using a FiO2 of 11.5% during rest and exercise. A control group of eight climbers did not perform the NH test, so as to rule out the possible learning effect of the PMA test. Four participants (33%) from the experimental group were classified as having high-susceptibility to AMS. However, the PMA test performed after the NH test did not significantly differ from the one carried out before the NH test or from the cognitive abilities measured in the control group (p > .05)

Novel methylselenoesters induce programed cell death via entosis in pancreatic cancer cells

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds

Novel methylselenoesters as antiproliferative agents

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.The authors express their gratitude to the Plan de Investigación de la Universidad de Navarra, PIUNA (Ref 2014-26), “la Caixa” and “CAN” Foundations for financial support for the project. The research leading to these results has also received funding from “la Caixa” Banking Foundation and from the Asociación de Amigos de la Universidad de Navarra, to whom Nuria Díaz-Argelich wishes to expresses her gratitude

Identification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutic

The prognosis for patients with metastatic melanoma remains very poor. Constitutive signal transducer and activator of transcription 3 (STAT3) activation has been correlated to metastasis, poor patient survival, larger tumor size, and acquired resistance against vemurafenib (PLX-4032), suggesting its potential as a molecular target. We recently designed a series of isoseleno- and isothio-urea derivatives of several biologically active heterocyclic scaffolds. The cytotoxic effects of lead isoseleno- and isothio-urea derivatives (compounds 1 and 3) were studied in a panel of five melanoma cell lines, including B-RAFV600E-mutant and wild-type (WT) cells. Compound 1 (IC50 range 0.8–3.8 µM) showed lower IC50 values than compound 3 (IC50 range 8.1–38.7 µM) and the mutant B-RAF specific inhibitor PLX-4032 (IC50 ranging from 0.4 to >50 µM), especially at a short treatment time (24 h). These effects were long-lasting, since melanoma cells did not recover their proliferative potential after 14 days of treatment. In addition, we confirmed that compound 1 induced cell death by apoptosis using Live-and-Dead, Annexin V, and Caspase3/7 apoptosis assays. Furthermore, compound 1 reduced the protein levels of STAT3 and its phosphorylation, as well as decreased the expression of STAT3-regulated genes involved in metastasis and survival, such as survivin and c-myc. Compound 1 also upregulated the cell cycle inhibitor p21. Docking studies further revealed the favorable binding of compound 1 with the SH2 domain of STAT3, suggesting it acts through STAT3 inhibition. Taken together, our results suggest that compound 1 induces apoptosis by means of the inhibition of the STAT3 pathway, non-specifically targeting both B-RAF-mutant and WT melanoma cells, with much higher cytotoxicity than the current therapeutic drug PLX-4032