External fluctuations in front dynamics with inertia: The overdamped limit

We study the dynamics of fronts when both inertial effects and external fluctuations are taken into account. Stochastic fluctuations are introduced as multiplicative noise arising from a control parameter of the system. Contrary to the non-inertial (overdamped) case, we find that important features of the system, such as the velocity selection picture, are not modified by the noise. We then compute the overdamped limit of the underdamped dynamics in a more careful way, finding that it does not exhibit any effect of noise either. Our result poses the question as to whether or not external noise sources can be measured in physical systems of this kind.Comment: 4 pages, 1 figure, accepted for publication in European Physical Journal

On the Generalized Kramers Problem with Oscillatory Memory Friction

The time-dependent transmission coefficient for the Kramers problem exhibits different behaviors in different parameter regimes. In the high friction regime it decays monotonically ("non-adiabatic"), and in the low friction regime it decays in an oscillatory fashion ("energy-diffusion-limited"). The generalized Kramers problem with an exponential memory friction exhibits an additional oscillatory behavior in the high friction regime ("caging"). In this paper we consider an oscillatory memory kernel, which can be associated with a model in which the reaction coordinate is linearly coupled to a nonreactive coordinate, which is in turn coupled to a heat bath. We recover the non-adiabatic and energy-diffusion-limited behaviors of the transmission coefficient in appropriate parameter regimes, and find that caging is not observed with an oscillatory memory kernel. Most interestingly, we identify a new regime in which the time-dependent transmission coefficient decays via a series of rather sharp steps followed by plateaus ("stair-like"). We explain this regime and its dependence on the various parameters of the system

Sorting of mesoscopic particles driven through periodic potential landscapes

Sorting of colloidal particles of different sizes is of importance in the transport and delivery of such particles in biological, materials science, and other technological contexts. A successful methodology involves the flow of a mixture of particles over designer surfaces presenting a periodic array of traps (optical tweezers) or microfabricated obstacles. The trajectories of the particles over these surfaces deviate from the direction of flow as the particles are attracted (traps) or repelled (obstacles) by the features of the landscape. The deviation of the particles from that of the flow depends on particle size (or on some other particle characteristic) and hence the particles can be sorted according to trajectory direction. On the basis of extensive numerical simulations, we present a unified view of these methodologies and discuss the effects of system parameters such as the magnitude and direction of the flow on the sorting efficacy.Peer ReviewedPreprin

Generation of short and long range temporal correlated noises

We present the implementation of an algorithm to generate Gaussian random noises with prescribed time correlations that can be either long or short ranged. Examples of Langevin dynamics with short and long range noises are presented and discussed.Comment: 7 pages, 6 figs, submitted to J. Comp. Phy

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial

Ibrutinib; Mantle cell lymphomaIbrutinib; Linfoma de células del mantoIbrutinib; Limfoma de cèl·lules de mantellPURPOSE The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. METHODS This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 < 30%, and largest tumor diameter ≤ 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg/m2. Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria. RESULTS Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia. CONCLUSION Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases.The funding for the IMCL-2015 was obtained through unrestricted Janssen Clinical Investigator-Initiated Study (IIS) Research Support

Momentum dependence of spin-orbit interaction effects in single-layer and multi-layer transition metal dichalcogenides

One of the main characteristics of the new family of two-dimensional crystals of semiconducting transition metal dichalcogenides (TMDs) is the strong spin-orbit interaction, which makes them very promising for future applications in spintronics and valleytronics devices. Here we present a detailed study of the effect of spin-orbit coupling (SOC) on the band structure of single-layer and bulk TMDs, including explicitly the role of the chalcogen orbitals and their hybridization with the transition metal atoms. To this aim, we combine density functional theory (DFT) calculations with a Slater-Koster tight-binding (TB) model. Whereas most of the previous TB models have been restricted to the K and K' points of the Brillouin zone (BZ), here we consider the effect of SOC in the whole BZ, and the results are compared to the band structure obtained by DFT methods. The TB model is used to analyze the effect of SOC in the band structure, considering separately the contributions from the transition metal and the chalcogen atoms. Finally, we present a scenario where, in the case of strong SOC, the spin/orbital/valley entanglement at the minimum of the conduction band at Q can be probed and be of experimental interest in the most common cases of electron-doping reported for this family of compounds

Further Characterization of the Electrogenicity and pH Sensitivity of the Human Organic Anion-Transporting Polypeptides OATP1B1 and OATP1B3

Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential (ΔΨ) was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability increased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differently the specific transport of taurocholic acid (TCA) and estradiol 17β-d-glucuronide (E217βG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin (K+-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin (protonophores), and amiloride (Na+/H+-inhibitor) and cation replacement in the medium were studied with fluorescent probes for measuring substrate uptake (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and ΔΨ [DilC1(5)]. The results suggest that activity of these three carriers is sodium/potassium-independent and affected differently by changes in pHo and ΔΨ: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude of ΔΨ. Moreover, electrophysiological measurements revealed the existence of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA, E217βG, and estrone-3-sulfate. Furthermore, a leakage of Na+ through OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic transporters whose activity may be strongly affected under circumstances of displacement of local pH

Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation

Autophagy and exosome secretion play important roles in a variety of physiological and disease states, including the development of age‐related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways of activation. Low oxidative damage in ARPE‐19 cells, alters both autophagy and exosome biogenesis. Moreover, oxidative stress modifies the protein and genetic cargo of exosomes, possibly affecting the fate of surrounding cells. In order to understand the connection between these two mechanisms and their impact on angiogenesis, stressed ARPE‐19 cells were treated with a siRNA‐targeting Atg7, a key protein for the formation of autophagosomes. Subsequently, we observed the formation of multivesicular bodies and the release of exosomes. Released exosomes contained VEGFR2 as part of their cargo. This receptor for VEGF—which is critical for the development of new blood vessels—was higher in exosome populations released from stressed ARPE‐19. While stressed exosomes enhanced tube formation, exosomes became ineffective after silencing VEGFR2 in ARPE‐19 cells and were, consequently, unable to influence angiogenesis. Moreover, vessel sprouting in the presence of stressed exosomes seems to follow a VEGF‐independent pathway. We propose that abnormal vessel growth correlates with VEGFR2‐expressing exosomes release from stressed ARPE‐19 cells, and is directly linked to autophagy