Packed hybrid silica nanoparticles as sorbents with thermo-switchable surface chemistry and pore size for fast extraction of environmental pollutants

Thermoresponsive poly(N-isopropylacrylamide)-grafted silica nanoparticles (SiNPs) have been synthesized and fully characterized by ATR-FTIR, TGA, HRTEM, BET and DLS analysis. Hybrid solid phase extraction (SPE) beds with tuneable pore size and switchable surface chemistry were prepared by packing the polymergrafted nanoparticles inside SPE cartridges. The cartridges were tested by checking the thermoregulated elution of model compounds, namely methylene blue, caffeine and amoxicillin. Extraction of the analytes and regeneration of the interaction sites on the sorbent surface was carried out entirely in water solution by changing the external temperature below and above the lower critical solution temperature (LCST) of the polymer. The results demonstrate that the elution of model compounds depends on the temperature-regulated size of the inter-particle voids and on the change of surface properties of the PNIPAM-grafted nanoparticles from hydrophilic to hydrophobic

Complete Resolution of Erythrodermic Psoriasis in an HIV and HCV Patient Unresponsive to Antipsoriatic Treatments after Highly Active Antiretroviral Therapy (Ritonavir, Atazanavir, Emtricitabine, Tenofovir).

Background: Psoriasis is a chronic, inflammatory disease affecting 2–3% of the worldwide population, and it may worsen with HIV or be detected as HIV cutaneous manifestation. HIV-related psoriasis shows a severe and prolonged clinical course with more frequent exacerbations. The management of this condition is challenging because immunomodulating and immunosuppressant agents may have variable and partial efficacy, and therefore, antiretroviral treatment represents a potential adjunctive therapeutic option. Results: In the case we report, the HIV test was shown to be crucial for driving the therapeutic approach. Indeed, antiretroviral agents have been proven to be effective in the treatment of HIV+ psoriasis as first-line therapy. Conclusion: The HIV test should be considered in high-risk patients affected by severe psoriasis and resistant to conventional and biological treatments

Weekly epirubicin plus lonidamine in advanced breast carcinoma

: Lonidamine has been demonstrated to potentiate the cytotoxic activity of several antineoplastic drugs, for example anthracyclines. Moreover, epirubicin is considered one of the most active drugs in advanced breast cancer, although optimal dose and schedule remains to be defined. In the present study we have treated 51 patients with advanced breast cancer with a combination of lonidamine (450 mg/day orally from day 1 throughout treatment) and epirubicin (25 mg/m2 i.v.) administered according to a weekly schedule for 24 weeks. Objective responses were observed in 29 out of 51 patients (57%; CR 16%, PR 41%). Liver metastases responded in eight out of 12 evaluable patients (67%). Average response duration was 12.4 months and median overall survival was 23 months (range 1-90+). Toxicity was negligible. The combination of weekly epirubicin and lonidamine is feasible and active in advanced breast cancer patients

hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA11a and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA11a isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA11a is involved in these resistance mechanisms. The specific hMENA11a depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA11a phosphorylation and affected its localization. At the functional level, we found that hMENA11a sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA11a silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA11a contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA11a in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA11a expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA11a activity could represent a new target for antiproliferative therapies in breast cancer

Synergistic interactions between kainate and mGlu receptors regulate bouton Ca2+ signalling and mossy fibre LTP

It is currently unknown why glutamatergic presynaptic terminals express multiple types of glutamate receptors. We have addressed this question by studying both acute and long-term regulation of mossy fibre function in the hippocampus. We find that inhibition of both mGlu1 and mGlu5 receptors together can block the induction of mossy fibre LTP. Furthermore, mossy fibre LTP can be induced by the pharmacological activation of either mGlu1 or mGlu5 receptors, provided that kainate receptors are also stimulated. Like conventional mossy fibre LTP, chemically-induced mossy fibre LTP (chem-LTPm) depends on Ca2+ release from intracellular stores and the activation of PKA. Similar synergistic interactions between mGlu receptors and kainate receptors were observed at the level of Ca2+ signalling in individual giant mossy fibre boutons. Thus three distinct glutamate receptors interact, in both an AND and OR gate fashion, to regulate both immediate and long-term presynaptic function in the brain

Bell inequalities as constraints on unmeasurable correlations

The interpretation of the violation of Bell-Clauser-Horne inequalities is revisited, in relation with the notion of extension of QM predictions to unmeasurable correlations. Such extensions are compatible with QM predictions in many cases, in particular for observables with compatibility relations described by tree graphs. This implies classical representability of any set of correlations , , , and the equivalence of the Bell-Clauser-Horne inequalities to a non void intersection between the ranges of values for the unmeasurable correlation associated to different choices for B. The same analysis applies to the Hardy model and to the "perfect correlations" discussed by Greenberger, Horne, Shimony and Zeilinger. In all the cases, the dependence of an unmeasurable correlation on a set of variables allowing for a classical representation is the only basis for arguments about violations of locality and causality.Comment: Some modifications have been done in order to improve clarity of presentation and comparison with other approache

The anticipation, perception of affective touch in women with, recovered from Anorexia Nervosa

Disruptions in reward processing and anhedonia have long been observed in Anorexia Nervosa (AN). Interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialized, interoceptive C-tactile system originating at the periphery, or a more top-down mechanism in the processing of tactile pleasantness remains debated. Here, we investigated differences between patients with and recovered from AN and healthy controls in the perception of pleasantness of touch delivered in a CT-optimal versus a CT-non-optimal manner, and in their top-down, anticipatory beliefs about the perceived pleasantness of touch. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic touch applied to theforearmof 27 women with AN, 24 women who have recovered and 30 healthy controls using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than healthy controls, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in the perception of CT-optimal touch were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, tactile anhedonia in AN might persist as a trait even after otherwise successful recovery of AN and it is not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of tactile pleasantness

Observing the corona and inner heliosphere with Parker Solar Probe

The recently launched Parker Solar Probe (PSP) mission is expected to provide unprecedented views of the solar corona and inner heliosphere. In addition to instruments devoted to taking measurements of the local solar wind, the spacecraft carries a visible imager: the Wide-field Imager for Solar PRobe (WISPR). WISPR will take advantage of the proximity of the spacecraft to the Sun to perform local imaging of the near-Sun environment. WISPR will observe coronal structures at high spatial and time resolutions, although the observed plane-of-sky will rapidly change because of the fast transit at the perihelia. We present a concise description of the PSP mission, with particular regard to the WISPR instrument, discussing its main scientific goals, targets of observations, and outlining the possible synergies with current and upcoming space missions

Observations of a pulse driven cool polar jet by SDO/AIA

Context. We observe a solar jet at north polar coronal hole (NPCH) using SDO AIA 304 {\deg}A image data on 3 August 2010. The jet rises obliquely above the solar limb and then retraces its propagation path to fall back. Aims. We numerically model this observed solar jet by implementing a realistic (VAL-C) model of solar temperature. Methods. We solve two-dimensional ideal magnetohydrodynamic equations numerically to simulate the observed solar jet. We consider a localized velocity pulse that is essentially parallel to the background magnetic field lines and initially launched at the top of the solar photosphere. The pulse steepens into a shock at higher altitudes, which triggers plasma perturbations that exhibit the observed features of the jet. The typical direction of the pulse also clearly exhibits the leading front of the moving jet. Results. Our numerical simulations reveal that a large amplitude initial velocity pulse launched at the top of the solar photosphere produces in general the observed properties of the jet, e.g., upward and backward average velocities, height, width, life-time, and ballistic nature. Conclusions. The close matching between the jet observations and numerical simulations provides first strong evidence for the formation of this jet by a single velocity pulse. The strong velocity pulse is most likely generated by the low- atmospheric reconnection in the polar region which results in triggering of the jet. The downflowing material of the jet most likely vanishes in the next upcoming velocity pulses from lower solar atmosphere, and therefore distinctly launched a single jet upward in the solar atmosphere is observed.Comment: 8 pages, 4 figures, A&