Click Chemistry with Polymers, Dendrimers, and Hydrogels for Drug Delivery

This is a post-peer-review, pre-copyedit version of an article published in Pharmaceutical Research. The final authenticated version is available online at: https://doi.org/10.1007/s11095-012-0683-yDuring the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug deliveryThis work was financially supported by the Spanish Ministry of Science and Innovation (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037)S

Early Carboniferous synorogenic basins evolution of the Ossa-Morena and

The stratigraphic record of the Early Carboniferous in Iberia reveals that synorogenic deposition was important and occurred simultaneously in basins influenced by extension and contraction with gravitational instability. In NW Iberia (Galicia – Trás-os-Montes Zone) contraction was dominant and the deposition took place in a forebulge outwards from the nappe stacking front. Here, synorogenic deposits were strongly affected by folding and thrusting as they were imbricated and incorporated in the allochthonous pile. In a different way, in SW Iberia (Ossa-Morena Zone) synorogenic deposition was influenced by extension and happened simultaneously with the onset of significant magmatism

The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance

Adaptive immune responses depend on the capacity of T cells to target specific antigens. As similar antigens can be expressed by pathogens and host cells, the question naturally arises of how can T cells discriminate friends from foes. In this work, we suggest that T cells tolerate cells whose proliferation rates remain below a permitted threshold. Our proposal relies on well-established facts about T-cell dynamics during acute infections: T-cell populations are elastic (they expand and contract) and they display inertia (contraction is delayed relative to antigen removal). By modelling inertia and elasticity, we show that tolerance to slow-growing populations can emerge as a population-scale feature of T cells. This result suggests a theoretical framework to understand immune tolerance that goes beyond the self versus non-self dichotomy.M.A.H. has been partially supported by MINECO grant no. MTM2014-53156. The rest of the authors have not received any particular financial support for this work

Cognitive Performance and Morning Levels of Salivary Cortisol and α-Amylase in Children Reporting High vs. Low Daily Stress Perception

The aim of the present study was to assess the effects of daily stress perception on cognitive performance and morning basal salivary cortisol and alpha-amylase levels in healthy children aged 9-12. Participants were classified by whether they had low daily perceived stress (LPS, n = 27) or a high daily perceived stress (HPS, n = 26) using the Children Daily Stress Inventory (CDSI). Salivary cortisol and alpha-amylase were measured at awakening and 30 minutes later. Cognitive performance was assessed using the Cognitive Drug Research assessment system. The HPS group exhibited significantly poorer scores on speed of memory (p < .05) and continuity of attention (p < .05) relative to the LPS group. The HPS group also showed significantly lower morning cortisol levels at awakening and at +30 minutes measures in comparison with the LPS group (p < .05), and mean morning cortisol levels were negatively correlated with speed of memory (p < .05) in the 53 participants. No significant differences were observed between both groups in alpha-amylase levels. These findings suggest that daily perceived stress in children may impoverish cognitive performance via its modulating effects on the HPA axis activit

Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD)

Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD). HIV promotion of an M1 antigen presenting cell (APC) - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (Aβ) protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner. CD45 is a protein tyrosine phosphatase receptor which negatively regulates CD40L-CD40-induced microglial M1 activation; an effect leading to the promotion of an M2 phenotype better suited to phagocytose and clear Aβ. Moreover, this CD45 mediated activation state appears to dampen harmful cytokine production. As such, this property of microglial CD45 as a regulatory "off switch" for a CD40-promoted M1, APC-type microglia activation phenotype may represent a critical therapeutic target for the prevention and treatment of neurodegeneration, as well as microglial dysfunction, found in patients with HAD

La reforma de la formación inicial del profesorado de ciencias de secundaria: propuesta de un diseño del currículo basado en competencias

El principal objetivo de este trabajo es proponer un mecanismo de selección de competencias específicas para la formación inicial del profesorado de ciencias experimentales, contando para ello con distintas fuentes relevantes para dicha formación. Con tal fin hemos hecho uso de un procedimiento consistente en ir incorporando de forma crítica las competencias procedentes de las siguientes fuentes curriculares: los modelos de formación inicial del profesorado vigentes en la literatura educativa, el currículo actual de ciencias en la educación secundaria obligatoria en España, el Programa internacional de evaluación PISA, la opinión del profesorado en activo mediante una encuesta cuyos resultados más relevantes son mostrados, las concepciones epistemológicas del profesorado, la profesionalización docente y las demandas que genera y, finalmente, la dimensión social de la ciencia.The primary objective of this paper is to propose a mechanism for selecting specific competences for preservice science teacher training, referring to relevant sources for such training. To this end we have used an trans-disciplinary procedure consistent with incorporating critical competences from the following curricular sources: Models of current preservice teacher training in educational literature, the current curriculum of Science in Compulsory Secondary Education in Spain, the Program for International Student Assessment (PISA), the views of in-service secondary school teachers (through a survey whose most relevant results are given), teachers' epistemological conceptions, the professionalization of teaching and the demands it generates and, finally the social dimension of science

Asynchronous processing for latent fingerprint identification on heterogeneous CPU-GPU systems

Latent fingerprint identification is one of the most essential identification procedures in criminal investigations. Addressing this task is challenging as (i) it requires analyzing massive databases in reasonable periods and (ii) it is commonly solved by combining different methods with very complex data-dependencies, which make fully exploiting heterogeneous CPU-GPU systems very complex. Most efforts in this context focus on improving the accuracy of the approaches and neglect reducing the processing time. Indeed, the most accurate approach was designed for one single thread. This work introduces the fastest methodology for latent fingerprint identification maintaining high accuracy called Asynchronous processing for Latent Fingerprint Identification (ALFI). ALFI fully exploits all the resources of CPU-GPU systems using asynchronous processing and fine-coarse parallelism for analyzing massive databases. Our approach reduces idle times in processing and exploits the inherent parallelism of comparing latent fingerprints to fingerprint impressions. We analyzed the performance of ALFI on Linux and Windows operating systems using the well-known NIST/FVC databases. Experimental results reveal that ALFI is in average 22x faster than the state-of-the-art algorithm, reaching a value of 44.7x for the best-studied case

Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: Implications for HIV-associated neurocognitive disorders

Up to 50% of long-term HIV infected patients, including those with systemically well-controlled infection, commonly experience memory problems and slowness, difficulties in concentration, planning, and multitasking. Deposition of Aβ plaques is also a common pathological feature of HIV infection. However, it is not clear whether this accumulation is due to AD-like processes, HIV-associated immunosuppression, Tat protein-induced Aβ elevations, and/or the effects of single highly active antiretroviral therapy (ART). Here we evaluated the effects of several ART medications (Zidovudine, Lamivudine, Indinavir, and Abacavir) alone and in combination on: 1) Aβ1-40, 42 generation in murine N2a cells transfected with the human "Swedish" mutant form of APP; 2) microglial phagocytosis of FITC-Aβ1-42 peptides in cultured murine N9 microglia. We report for the first time that these antiretroviral compounds (10 μM) generally increase Aβ generation (~50-200%) in SweAPP N2a cells and markedly inhibit microglial phagocytosis of FITC-Aβ1-42 peptides in murine microglia. The most significant amyloidogenic effects were observed with combined ART (p < 0.05); suggesting certain ART medications may have additive amyloidogenic effects when combined. As these antiretroviral compounds are capable of penetrating the blood brain barrier and reaching the concentrations employed in the in vitro studies, these findings raise the possibility that ART may play a casual role in the elevated Aβ found in the brains of those infected with HIV. Therefore these compounds may consequently contribute to cognitive decline observed in HIV associated neurocognitive disorders (HAND)