Therapeutic potential of extracellular vesicles

Extracellular vesicles (EV) have emerged as important mediators of intercellular communication. By their origin, we can find vesicles derived from plasma membrane such as microvesicles, ectosomes, and membrane particles or exosomes, which originate in the endosomal membrane compartment. They contain numerous proteins, lipids, and even nucleic acids like mRNA and miRNA that can affect the cells that encounter these structures in complex ways. The EV have recently gained interest for their therapeutic potential both as a treatment itself and as a biomarker of several pathologies. The research lines involving EV cover a wide range of aspects from basic research on the EV biology to the manipulation or monitoring of EV for therapeutic purposes

Compositional Variations in Apatite and Petrogenetic Significance: Examples from Peraluminous Granites and Related Pegmatites and Hydrothermal Veins from the Central Iberian Zone (Spain and Portugal)

Apatite can be used as an archive of processes occurring during the evolution of granitic magmas and as a pegmatite exploration tool. With this aim, a detailed compositional study of apatite was performed on different Variscan granites, pegmatites and quartz veins from the Central Iberian Zone. Manganese in granitic apatite increases with increasing evolution degree. Such Mn increase would not be related to changes in the fO(2) during evolution but rather to a higher proportion of Mn in residual melts, joined to an increase in SiO2 content and peraluminosity. In the case of pegmatitic apatite, the fO(2) and the polymerization degree of the melts seem not to have influenced the Mn and Fe contents but the higher availability of these transition elements and/or the lack of minerals competing for them. The subrounded Fe-Mn phosphate nodules, where apatite often occurs in P-rich pegmatites and P-rich quartz dykes, probably crystallized from a P-rich melt exsolved from the pegmatitic melt and where Fe, Mn and Cl would partition. The low Mn and Fe contents in the apatite from the quartz veins may be attributed either to the low availability of these elements in the late hydrothermal fluids derived from the granitic and pegmatitic melts, or to a high fO(2). The Rare Earth Elements, Sr and Y are the main trace elements of the studied apatites. The REE contents of apatite decrease with the evolution of their hosting rocks. The REE patterns show in general strong tetrad effects that are probably not related to the fluids' activity in the system. On the contrary, the fluids likely drive the non-CHARAC behavior of apatite from the most evolved granitic and pegmatitic units. Low fO(2) conditions seem to be related to strong Eu anomalies observed for most of the apatites associated with different granitic units, barren and P-rich pegmatites. The positive Eu anomalies in some apatites from leucogranites and Li-rich pegmatites could reflect their early character, prior to the crystallization of feldspars. The increase in the Sr content in apatite from Li-rich pegmatites and B-P +/- F-rich leucogranites could be related to problems in accommodating this element in the albite structure, favoring its incorporation into apatite. The triangular plots sigma REE-Sr-Y and U-Th-Pb of apatites, as well as the Eu anomaly versus the TE1,3 diagram, seem to be potentially good as petrogenetic indicators, mainly for pegmatites and, to a lesser extent, for granites from the CIZ

Charm Production in DPMJET

In this work, charm production in the {\sc dpmjet} hadronic jet simulation is compared to experimental data. Since the major application of {\sc dpmjet} is the simulation of cosmic ray-induced air showers, the version of the code integrated in the CORSIKA simulation package has been used for the comparison. Wherever necessary, adjustments have been made to improve agreement between simulation and data. With the availability of new muon/neutrino detectors that combine a large fiducial volume with large amounts of shielding, investigation of prompt muons and neutrinos from cosmic ray interactions will be feasible for the first time. Furthermore, above $\gtrsim 100$ TeV charmed particle decay becomes the dominant background for diffuse extraterrestrial neutrino flux searches. A reliable method to simulate charm production in high-energy proton-nucleon interactions is therefore required.Comment: 10 pages, to be published in JCA

Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids

A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6- substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed

Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study

Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD

An Electrochemical Study of Frustrated Lewis Pairs: A Metal-free Route to Hydrogen Oxidation

[Image: see text] Frustrated Lewis pairs have found many applications in the heterolytic activation of H(2) and subsequent hydrogenation of small molecules through delivery of the resulting proton and hydride equivalents. Herein, we describe how H(2) can be preactivated using classical frustrated Lewis pair chemistry and combined with in situ nonaqueous electrochemical oxidation of the resulting borohydride. Our approach allows hydrogen to be cleanly converted into two protons and two electrons in situ, and reduces the potential (the required energetic driving force) for nonaqueous H(2) oxidation by 610 mV (117.7 kJ mol(–1)). This significant energy reduction opens routes to the development of nonaqueous hydrogen energy technology

Wavelength calibration for OSIRIS/GTC* tunable filters

OSIRIS (Optical System for Imaging and low Resolution Integrated Spectroscopy) is the first light instrument of the Gran Telescopio Canarias (GTC). It provides a flexible and competitive tunable filter (TF). Since it is based on a Fabry-Perot interferometer working in collimated beam, the TF transmission wavelength depends on the position of the target with respect to the optical axis. This effect is non-negligible and must be accounted for in the data reduction. Our paper establishes a wavelength calibration for OSIRIS TF with the accuracy required for spectrophotometric measurements using the full field of view (FOV) of the instrument. The variation of the transmission wavelength $\lambda(R)$ across the FOV is well described by $\lambda(R)=\lambda(0)/\sqrt{1+(R/f_2)^2}$, where $\lambda(0)$ is the central wavelength, $R$ represents the physical distance from the optical axis, and $f_2=185.70\pm0.17\,$mm is the effective focal length of the camera lens. This new empirical calibration yields an accuracy better than 1\,\AA\ across the entire OSIRIS FOV ($\sim$8\arcmin$\times$8\arcmin), provided that the position of the optical axis is known within 45 $\mu$m ($\equiv$ 1.5 binned pixels). We suggest a calibration protocol to grant such precision over long periods, upon re-alignment of OSIRIS optics, and in different wavelength ranges. This calibration differs from the calibration in OSIRIS manual which, nonetheless, provides an accuracy $\lesssim1$\AA\, for R\lesssim 2\arcmin.Comment: 22 pages, 7 figures, accepted for publication in PAS

The impact of different strategies to handle missing data on both precision and bias in a drug safety study: a multidatabase multinational population-based cohort study

BACKGROUND: Missing data are often an issue in electronic medical records (EMRs) research. However, there are many ways that people deal with missing data in drug safety studies. AIM: To compare the risk estimates resulting from different strategies for the handling of missing data in the study of venous thromboembolism (VTE) risk associated with antiosteoporotic medications (AOM). METHODS: New users of AOM (alendronic acid, other bisphosphonates, strontium ranelate, selective estrogen receptor modulators, teriparatide, or denosumab) aged ≥50 years during 1998–2014 were identified in two Spanish (the Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria [BIFAP] and EpiChron cohort) and one UK (Clinical Practice Research Datalink [CPRD]) EMR. Hazard ratios (HRs) according to AOM (with alendronic acid as reference) were calculated adjusting for VTE risk factors, body mass index (that was missing in 61% of patients included in the three databases), and smoking (that was missing in 23% of patients) in the year of AOM therapy initiation. HRs and standard errors obtained using cross-sectional multiple imputation (MI) (reference method) were compared to complete case (CC) analysis – using only patients with complete data – and longitudinal MI – adding to the cross-sectional MI model the body mass index/smoking values as recorded in the year before and after therapy initiation. RESULTS: Overall, 422/95,057 (0.4%), 19/12,688 (0.1%), and 2,051/161,202 (1.3%) VTE cases/participants were seen in BIFAP, EpiChron, and CPRD, respectively. HRs moved from 100.00% underestimation to 40.31% overestimation in CC compared with cross-sectional MI, while longitudinal MI methods provided similar risk estimates compared with cross-sectional MI. Precision for HR improved in cross-sectional MI versus CC by up to 160.28%, while longitudinal MI improved precision (compared with cross-sectional) only minimally (up to 0.80%). CONCLUSIONS: CC may substantially affect relative risk estimation in EMR-based drug safety studies, since missing data are not often completely at random. Little improvement was seen in these data in terms of power with the inclusion of longitudinal MI compared with cross-sectional MI. The strategy for handling missing data in drug safety studies can have a large impact on both risk estimates and precision

Saturation of electrical resistivity

Resistivity saturation is observed in many metallic systems with a large resistivity, i.e., when the resistivity has reached a critical value, its further increase with temperature is substantially reduced. This typically happens when the apparent mean free path is comparable to the interatomic separations - the Ioffe-Regel condition. Recently, several exceptions to this rule have been found. Here, we review experimental results and early theories of resistivity saturation. We then describe more recent theoretical work, addressing cases both where the Ioffe-Regel condition is satisfied and where it is violated. In particular we show how the (semiclassical) Ioffe-Regel condition can be derived quantum-mechanically under certain assumptions about the system and why these assumptions are violated for high-Tc cuprates and alkali-doped fullerides.Comment: 16 pages, RevTeX, 15 eps figures, additional material available at http://www.mpi-stuttgart.mpg.de/andersen/saturation

Variation and ethnic inequalities in treatment of common mental disorders before, during and after pregnancy : combined analysis of routine and research data in the Born in Bradford cohort

BACKGROUND: Common mental disorders (CMD) such as anxiety and depression during the maternal period can cause significant morbidity to the mother in addition to disrupting biological, attachment and parenting processes that affect child development. Pharmacological treatment is a first-line option for moderate to severe episodes. Many women prescribed pharmacological treatments cease them during pregnancy but it is unclear to what extent non-pharmacological options are offered as replacement. There are also concerns that treatments offered may not be proportionate to need in minority ethnic groups, but few data exist on treatment disparities in the maternal period. We examined these questions in a multi-ethnic cohort of women with CMD living in Bradford, England before, during and up to one year after pregnancy. METHODS: We searched the primary care records of women enrolled in the Born in Bradford cohort for diagnoses, symptoms, signs ('identification'), referrals for treatment, non-pharmacological and pharmacological treatment and monitoring ('treatment') related to CMD. Records were linked with maternity data to classify women identified with a CMD as treated prior to, and one year after, delivery. We examined rates and types of treatment during pregnancy, and analysed potential ethnic group differences using adjusted Poisson and multinomial logistic regression models. RESULTS: We analysed data on 2,234 women with indicators of CMD. Most women were discontinued from pharmacological treatment early in pregnancy, but this was accompanied by recorded access to non-drug treatments in only 15 % at the time of delivery. Fewer minority ethnic women accessed treatments compared to White British women despite minority ethnic women being 55-70 % more likely than White British women to have been identified with anxiety in their medical record. CONCLUSIONS: Very few women who discontinued pharmacological treatment early in their pregnancy were offered other non-pharmacological treatments as replacement, and most appeared to complete their pregnancy untreated. Further investigation is warranted to replicate the finding that minority ethnic women are more likely to be identified as being anxious or having anxiety and understand what causes the variation in access to treatments