The entangling side of the Unruh-Hawking effect

We show that the Unruh effect can create net quantum entanglement between inertial and accelerated observers depending on the choice of the inertial state. This striking result banishes the extended belief that the Unruh effect can only destroy entanglement and furthermore provides a new and unexpected source for finding experimental evidence of the Unruh and Hawking effects.Comment: 4 pages, 4 figures. Added Journal referenc

Asymmetric interaction of neuropeptidase activities between cortico-limbic structures, plasma and cardiovascular function after unilateral dopamine depletions of the nigrostriatal system

In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior. The study of the activity of neuropeptide regulatory enzymes (neuropeptidases, NPs) is illustrative. We have observed that the left and right brain areas interact intra- and inter-hemispherically, as well as with peripheral tissues or with physiological parameters such as blood pressure or with behaviors such as turning preference. To obtain data that reflect this integrative behavior, we simultaneously analyzed the impact of left or right brain DA depletion on the activity of various NPs in corticolimbic regions of the left and right hemispheres, such as the medial prefrontal cortex, amygdala and hippocampus, as well as on the plasma activity of the same aminopeptidase activities (APs) and on systolic blood pressure (SBP). Intra- and inter-hemispheric interactions as well as the interactions of NPs from the left or right hemispheres were analyzed with the same plasma APs and the SBP obtained from sham and from left or right lesioned rats. The results demonstrate a complex profile depending on the hemisphere considered. They definitively confirm an asymmetric neurovisceral integration and reveal a higher level of inter-hemispheric corticolimbic interactions including with SBP after left dopamine depletion

Environmental screening tools for assessment of infrastructure plans based on biodiversity preservation and global warming (PEIT, Spain).

Most Strategic Environmental Assessment (SEA) research has been concerned with SEA as a procedure, and there have been relatively few developments and tests of analytical methodologies. The first stage of the SEA is the ‘screening’, which is the process whereby a decision is taken on whether or not SEA is required for a particular programme or plan. The effectiveness of screening and SEA procedures will depend on how well the assessment fits into the planning from the early stages of the decision-making process. However, it is difficult to prepare the environmental screening for an infrastructure plan involving a whole country. To be useful, such methodologies must be fast and simple. We have developed two screening tools which would make it possible to estimate promptly the overall impact an infrastructure plan might have on biodiversity and global warming for a whole country, in order to generate planning alternatives, and to determine whether or not SEA is required for a particular infrastructure plan

Synthesis and properties of 2′-deoxy-2′,4′-difluoroarabinose-modified nucleic acids

© 2015 American Chemical Society. We report the synthesis, thermal stability, and RNase H substrate activity of 2′-deoxy-2′,4′-difluoroarabino-modified nucleic acids. 2′-Deoxy-2′,4′-difluoroarabinouridine (2,′4′-diF-araU) was prepared in a stereoselective way in six steps from 2′-deoxy-2′-fluoroarabinouridine (2′-F-araU). NMR analysis and quantum mechanical calculations at the nucleoside level reveal that introduction of 4′-fluorine introduces a strong bias toward the North conformation, despite the presence of the 2′-βF, which generally steers the sugar pucker toward the South/East conformation. Incorporation of the novel monomer into DNA results on a neutral to slightly stabilizing thermal effect on DNA-RNA hybrids. Insertion of 2′,4′-diF-araU nucleotides in the DNA strand of a DNA-RNA hybrid decreases the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage of the complement RNA strand compared to that for an all-DNA strand or a DNA strand containing the corresponding 2′-F-araU nucleotide units, consistent with the notion that a 4′-fluorine in 2′-F-araU switches the preferred sugar conformation from DNA-like (South/East) to RNA-like (North).Peer Reviewe

Exploring structure–activity relationships in photodynamic therapy anticancer agents based on Ir(III)-COUPY conjugates

Photodynamic therapy holds great promise as a non-invasive anticancer tool against drug-resistant cancers. However, highly effective, non-toxic, and reliable photosensitizers with operability under hypoxic conditions remain to be developed. Herein, we took the advantageous properties of COUPY fluorophores and cyclometalated Ir(III) complexes to develop novel PDT agents based on Ir(III)-COUPY conjugates with the aim of exploring structure–activity relationships. The structural modifications carried out within the coumarin scaffold had a strong impact on the photophysical properties and cellular uptake of the conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity under green light irradiation, which was attributed to the photogeneration of ROS, while remaining non-toxic in the dark. Among them, two hit conjugates showed excellent phototherapeutic indexes in cisplatin-resistant A2780cis cancer cells, both in normoxia and in hypoxia, suggesting that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting COUPY dyes and transition metal complexes could effectively tackle in vitro acquired resistance to cisplatin

Clouds and aerosols in Puerto Rico ─ a new evaluation

The influence of aerosols, both natural and anthropogenic, remains a major area of uncertainty when predicting the properties and behaviour of clouds and their influence on climate. In an attempt to better understand warm cloud formation in a tropical marine environment, a period of intensive measurements took place in December 2004 in Puerto Rico, using some of the latest developments in online instrumentation such as aerosol mass spectrometers, cloud condensation nuclei counters and a hygroscopicity tandem differential mobility analyser. Simultaneous online measurements of aerosol size distributions, composition, hygroscopicity and optical properties were made near the lighthouse of Cape San Juan in the north-eastern corner of the island and at the top of East Peak mountain (1040 m a.s.l.), the two sites separated by 17 km. Additional measurements of the cloud droplet residual and interstitial aerosol properties were made at the mountain site, accompanied by measurements of cloud droplet size distributions, liquid water content and the chemical composition of cloud and rain water samples. <br><br> Both aerosol composition and cloud properties were found to be sensitive to wind sector. Air from the east-northeast (ENE) was mostly free of anthropogenic influences, the submicron fraction being mainly composed of non-sea salt sulphate, while that from the east-southeast (ESE) was found to be moderately influenced by populated islands upwind, adding smaller (&lt;100 nm), externally mixed, carbonaceous particles to the aerosol that increased the number concentrations by over a factor of 3. This change in composition was also accompanied with a reduction in the measured hygroscopicity and fractional cloud activation potential of the aerosol. At the mountain site, the average cloud droplet concentrations increased from 193 to 519 cm^&minus;3, median volume diameter decreased from 20 to 14 μm and the liquid water content increased from 0.24 to 0.31 g m^&minus;3 when the winds shifted from the ENE to ESE. Larger numbers of interstitial particles were recorded, most notably at sizes greater than 100 nm, which were absent during clean conditions. The average size of the residual particles and concentrations of cloudwater nitrate, sulphate and insoluble material increased during polluted conditions. <br><br> Previous studies in Puerto Rico had reported the presence of a significant non-anthropogenic organic fraction in the aerosols measured and concluded that this was a factor controlling the in situ cloud properties. However, this was not observed in our case. In contrast to the 1.00&plusmn;0.14 μg m^&minus;3 of organic carbon measured in 1992 and 1995, the organic matter measured in the current study of 0.17&plusmn;0.35 μg m^&minus;3 is many times lower, most of which can be attributed to anthropogenic sources. During clean conditions, the submicron aerosol was observed to be almost entirely inorganic, an observation supported by the hygroscopicity measurements. This suggests that organic aerosols from marine sources may not be completely ubiquitous (either spatially or temporally) in this environment and requires further investigation to quantify their true extent and implications, with more extensive, longer-term sampling in conjunction with wind field analyses

Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D+i 2013-2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF) and B2017/BMD-3804 MITIC-CM

Características y consecuencias de las agresiones sexuales en adolescentes consultantes en un centro de salud sexual y reproductiva

Antecedentes: La agresión sexual es un evento traumático y doloroso que afecta de manera transversal, a las víctimas de ambos sexos, de todos los niveles socioeconómicos con graves consecuencias para la salud física, psicológica y social para quienes la sufren. Objetivo: Determinar las características de las agresiones sexuales y sus consecuencias en adolescentes consultantes en un centro de atención en Salud Sexual y Reproductiva. Método: Estudio analítico de corte transversal de 573 adolescentes atendidas en un centro de medicina reproductiva (CEMERA) en el período 2003-2010 y que reportaron antecedente de abuso sexual. Se estudiaron tanto las características como las consecuencias del abuso, datos que se obtuvieron desde las fichas clínicas. Resultados: En el 86,5 % de los casos se reportó abuso sexual y en un 13,5% violación. El 48,5% de los agresores son familiares. La edad más vulnerable fue entre 5-9 años con un 41,2%. En el 39,2% el abuso sexual fue reiterado. En un 43,4% el lugar fue el propio hogar de la víctima. Un 70% reveló y de estos el 45,9% lo hizo en forma tardía. Sólo en un 19% se hizo la denuncia legal. De las adolescentes que iniciaron actividad sexual voluntaria (83,3%), un 35,4% tenía menos de 15 años. Un 11,8% reportó 3 y más parejas sexuales. Conclusión: El antecedente de abuso sexual debe ser considerado en la atención de adolescentes que consultan por salud sexual y reproductiva. El equipo de salud debe estar preparado para atender sus múltiples necesidades

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

Background: The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail. Methods: We use optical techniques, including fluorescence confocal microscopy and lifetime imaging microscopy (FLIM) both in model membranes built up as giant unilamellar vesicles (GUVs) and cultured cells. These experiments are complemented with computational studies to unravel the molecular mechanism that makes NAO cytotoxic. Results: We have obtained direct evidence that NAO promotes strong membrane adhesion of negatively charged vesicles. The attractive forces are derived from van der Waals interactions between anti-parallel H-dimers of NAO molecules from opposing bilayers. Semi-empirical calculations have confirmed the supramolecular scenario by which anti-parallel NAO molecules form a zipper of bonds at the contact region. The membrane remodeling effect of NAO, as well as the formation of H-dimers, was also confirmed in cultured fibroblasts, as shown by the ultrastructure alteration of the mitochondrial cristae. Conclusions: We conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity. General significance: Mitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy

In-flight Diagnostics in LISA Pathfinder

LISA PathFinder (LPF) will be flown with the objective to test in space key technologies for LISA. However its sensitivity goals are, for good reason, one order of magnitude less than those which LISA will have to meet, both in drag-free and optical metrology requirements, and in the observation frequency band. While the expected success of LPF will of course be of itself a major step forward to LISA, one might not forget that a further improvement by an order of magnitude in performance will still be needed. Clues for the last leap are to be derived from proper disentanglement of the various sources of noise which contribute to the total noise, as measured in flight during the PathFinder mission. This paper describes the principles, workings and requirements of one of the key tools to serve the above objective: the diagnostics subsystem. This consists in sets of temperature, magnetic field, and particle counter sensors, together with generators of controlled thermal and magnetic perturbations. At least during the commissioning phase, the latter will be used to identify feed-through coefficients between diagnostics sensor readings and associated actual noise contributions. A brief progress report of the current state of development of the diagnostics subsystem will be given as well.Peer Reviewe