Rectification by charging -- the physics of contact-induced current asymmetry in molecular conductors

We outline the qualitatively different physics behind charging-induced current asymmetries in molecular conductors operating in the weakly interacting self-consistent field (SCF) and the strongly interacting Coulomb Blockade (CB) regimes. A conductance asymmetry arises in SCF because of the unequal mean-field potentials that shift a closed-shell conducting level differently for positive and negative bias. A very different current asymmetry arises for CB due to the unequal number of open-shell excitation channels at opposite bias voltages. The CB regime, dominated by single charge effects, typically requires a computationally demanding many-electron or Fock space description. However, our analysis of molecular Coulomb Blockade measurements reveals that many novel signatures can be explained using a {{simpler}} orthodox model that involves an incoherent sum of Fock space excitations and {\it{hence treats the molecule as a metallic dot or an island}}. This also reduces the complexity of the Fock space description by just including various charge configurations only, thus partially underscoring the importance of electronic structure, while retaining the essence of the single charge nature of the transport process. We finally point out, however, that the inclusion of electronic structure and hence well-resolved Fock space excitations is crucial in some notable examples.Comment: 12 pages, 10 figure

BRAF(V600) inhibition alters the microRNA cargo in the vesicular secretome of malignant melanoma cells

The BRAF inhibitors vemurafenib and dabrafenib can be used to treat patients with metastatic melanomas harboring BRAF(V600) mutations. Initial antitumoral responses are often seen, but drug-resistant clones with reactivation of the MEK-ERK pathway soon appear. Recently, the secretome of tumor-derived extracellular vesicles (EVs) has been ascribed important functions in cancers. To elucidate the possible functions of EVs in BRAF-mutant melanoma, we determined the RNA content of the EVs, including apoptotic bodies, microvesicles, and exosomes, released from such cancer cells after vemurafenib treatment. We found that vemurafenib significantly increased the total RNA and protein content of the released EVs and caused significant changes in the RNA profiles. RNA sequencing and quantitative PCR show that cells and EVs from vemurafenib-treated cell cultures and tumor tissues harvested from cell-derived and patient-derived xenografts harbor unique miRNAs, especially increased expression of miR-211-5p. Mechanistically, the expression of miR-211-5p as a result of BRAF inhibition was induced by increased expression of MITF that regulates the TRPM1 gene resulting in activation of the survival pathway. In addition, transfection of miR-211 in melanoma cells reduced the sensitivity to vemurafenib treatment, whereas miR-211-5p inhibition in a vemurafenib resistant cell line affected the proliferation negatively. Taken together, our results show that vemurafenib treatment induces miR-211-5p up-regulation in melanoma cells both in vitro and in vivo, as well as in subsets of EVs, suggesting that EVs may provide a tool to understand malignant melanoma progression.1114sciescopu

P/2010A2 LINEAR - I: An impact in the Asteroid Main Belt

Comet P/2010A2 LINEAR is a good candidate for membership with the Main Belt Comet family. It was observed with several telescopes (ESO NTT, La Silla; Gemini North, Mauna Kea; UH 2.2m, Mauna Kea) from 14 Jan. until 19 Feb. 2010 in order to characterize and monitor it and its very unusual dust tail, which appears almost fully detached from the nucleus; the head of the tail includes two narrow arcs forming a cross. The immediate surroundings of the nucleus were found dust-free, which allowed an estimate of the nucleus radius of 80-90m. A model of the thermal evolution indicates that such a small nucleus could not maintain any ice content for more than a few million years on its current orbit, ruling out ice sublimation dust ejection mechanism. Rotational spin-up and electrostatic dust levitations were also rejected, leaving an impact with a smaller body as the favoured hypothesis, and ruling out the cometary nature of the object. The impact is further supported by the analysis of the tail structure. Finston-Probstein dynamical dust modelling indicates the tail was produced by a single burst of dust emission. More advanced models, independently indicate that this burst populated a hollow cone with a half-opening angle alpha~40degr and with an ejection velocity v_max ~ 0.2m/s, where the small dust grains fill the observed tail, while the arcs are foreshortened sections of the burst cone. The dust grains in the tail are measured to have radii between a=1-20mm, with a differential size distribution proportional to a^(-3.44 +/- 0.08). The dust contained in the tail is estimated to at least 8x10^8kg, which would form a sphere of 40m radius. Analysing these results in the framework of crater physics, we conclude that a gravity-controlled crater would have grown up to ~100m radius, i.e. comparable to the size of the body. The non-disruption of the body suggest this was an oblique impact.Comment: 15 pages, 11 figures, in pres

An integrative review exploring decision-making factors influencing mental health nurses in the use of restraint

Introduction: While mechanical and manual restraint as an institutional method of control within mental health settings may be perceived to seem necessary at times, there is emergent literature highlighting the potential counter-therapeutic impact of this practice for patients as well as staff. Nurses are the professional group who are most likely to use mechanical and manual restraint methods within mental health settings. In-depth insights to understand what factors influence nurses’ decision-making related to restraint use are therefore warranted. Aim: To explore what influences mental health nurses’ decision-making in the use of restraint. Method: An integrative review using Cooper’s framework was undertaken. Results: Eight emerging themes were identified: ‘safety for all’, ‘restraint as a necessary intervention’, ‘restraint as a last resort’, ‘role conflict’, ‘maintaining control’, ‘staff composition’, ‘knowledge and perception of patient behaviours’, and ‘psychological impact’. These themes highlight how mental health nurses’ decision-making is influenced by ethical and safety responsibilities, as well as, interpersonal and staff-related factors. Conclusion: Research to further understand the experience and actualization of ‘last resort’ in the use of restraint and to provide strategies to prevent restraint use in mental health settings are needed

Optimizing differential identifiability improves connectome predictive modeling of cognitive deficits from functional connectivity in Alzheimer's disease

Functional connectivity, as estimated using resting state functional MRI, has shown potential in bridging the gap between pathophysiology and cognition. However, clinical use of functional connectivity biomarkers is impeded by unreliable estimates of individual functional connectomes and lack of generalizability of models predicting cognitive outcomes from connectivity. To address these issues, we combine the frameworks of connectome predictive modeling and differential identifiability. Using the combined framework, we show that enhancing the individual fingerprint of resting state functional connectomes leads to robust identification of functional networks associated to cognitive outcomes and also improves prediction of cognitive outcomes from functional connectomes. Using a comprehensive spectrum of cognitive outcomes associated to Alzheimer's disease (AD), we identify and characterize functional networks associated to specific cognitive deficits exhibited in AD. This combined framework is an important step in making individual level predictions of cognition from resting state functional connectomes and in understanding the relationship between cognition and connectivity

Assembly of Protein Building Blocks Using a Short Synthetic Peptide

Combining proteins or their defined domains offers new enhanced functions. Conventionally, two proteins are either fused into a single polypeptide chain by recombinant means or chemically cross-linked. However, these strategies can have drawbacks such as poor expression (recombinant fusions) or aggregation and inactivation (chemical cross-linking), especially in the case of large multifunctional proteins. We developed a new linking method which allows site-oriented, noncovalent, yet irreversible stapling of modified proteins at neutral pH and ambient temperature. This method is based on two distinct polypeptide linkers which self-assemble in the presence of a specific peptide staple allowing on-demand and irreversible combination of protein domains. Here we show that linkers can either be expressed or be chemically conjugated to proteins of interest, depending on the source of the proteins. We also show that the peptide staple can be shortened to 24 amino acids still permitting an irreversible combination of functional proteins. The versatility of this modular technique is demonstrated by stapling a variety of proteins either in solution or to surfaces

RNA-interference in rice against Rice tungro bacilliform virus results in its decreased accumulation in inoculated rice plants

Rice tungro is a viral disease seriously affecting rice production in South and Southeast Asia. Tungro is caused by the simultaneous infection in rice of Rice tungro bacilliform virus (RTBV), a double-stranded DNA virus and Rice tungro spherical virus (RTSV), a single-stranded RNA virus. To apply the concept of RNA-interference (RNAi) for the control of RTBV infection, transgenic rice plants expressing DNA encoding ORF IV of RTBV, both in sense as well as in anti-sense orientation, resulting in the formation of double-stranded (ds) RNA, were raised. RNA blot analysis of two representative lines indicated specific degradation of the transgene transcripts and the accumulation of small molecular weight RNA, a hallmark for RNA-interference. In the two transgenic lines expressing ds-RNA, different resistance responses were observed against RTBV. In one of the above lines (RTBV-O-Ds1), there was an initial rapid buildup of RTBV levels following inoculation, comparable to that of untransformed controls, followed by a sharp reduction, resulting in approximately 50-fold lower viral titers, whereas the untransformed controls maintained high levels of the virus till 40 days post-inoculation (dpi). In RTBV-O-Ds2, RTBV DNA levels gradually rose from an initial low to almost 60% levels of the control by 40 dpi. Line RTBV-O-Ds1 showed symptoms of tungro similar to the untransformed control lines, whereas line RTBV-O-Ds2 showed extremely mild symptoms