A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Late Major Hemoptysis After Lung Volume Reduction With Coils Induced by Dual Antiaggregation Therapy.

Lung-volume reduction using coils is an effective and safe treatment for selected patients presenting severe emphysema and hyperinflation. Most complications occur during the first 30 days after the procedure. Although frequent, hemoptysis is usually transient and minor. Antiaggregation therapy is common in patients with emphysema who, very often, have additional tobacco-associated comorbidities. Aspirin is considered safe for most major interventions; however, clopidogrel is mainly contraindicated and considered an exclusion criterion. We present a case of life-threatening hemoptysis caused by dual antiaggregation therapy "accidentally" introduced 3 months after the procedure. So far no recommendations exist on the optimal therapeutic strategy after lung-volume reduction with coils.

Abstenció diferencial, vot dual i vot diferencial a L'Hospitalet de Llobregat : Estudi sobre el comportament electoral a L'Hospitalet de Llobregat entre 1979 i 2014

Aquest treball presenta un anàlisi sobre el comportament electoral a L'Hospitalet de Llobregat entre 1979 i 2014, en relació als diferents nivells de participació electoral i les diferències en el vot a partits que es produeixen segons l'àmbit de la convocatòria electoral.

Concepts and Reference. Defending a Dual Theory of Natural Kind Concepts

In this thesis I argue that the psychological study of concepts and categorisation, and the philosophical study of reference are deeply intertwined. I propose that semantic intuitions are a variety of categorisation judgements, determined by concepts, and that because of this, concepts determine reference. I defend a dual theory of natural kind concepts, according to which natural kind concepts have distinct semantic cores and non-semantic identification procedures. Drawing on psychological essentialism, I suggest that the cores consist of externalistic placeholder essence beliefs. The identification procedures, in turn, consist of prototypes, sets of exemplars, or possibly also theory-structured beliefs. I argue that the dual theory is motivated both by experimental data and theoretical considerations. The thesis consists of three interrelated articles. Article I examines philosophical causal and description theories of natural kind term reference, and argues that they involve, or need to involve, certain psychological elements. I propose a unified theory of natural kind term reference, built on the psychology of concepts. Article II presents two semantic adaptations of psychological essentialism, one of which is a strict externalistic Kripkean-Putnamian theory, while the other is a hybrid account, according to which natural kind terms are ambiguous between internalistic and externalistic senses. We present two experiments, the results of which support the strict externalistic theory. Article III examines Fodor’s influential atomistic theory of concepts, according to which no psychological capacities associated with concepts constitute them, or are necessary for reference. I argue, contra Fodor, that the psychological mechanisms are necessary for reference.

DFM(A)- aspects for a horn antenna design

In this paper aspects of design for manufacturability and assembly (DFMA) are applied to the design of coaxially fed standard gain horn antenna for 1.70 - 2.60 GHz. Possibilities to utilize cross-technological approach method is examined. Methods of DFMA for laser processing are covered and practical design guides and methods are developed. Antenna construction for easy manufacturing and specialized performance is shown. Required dimensions and tolerances are discussed and suitable materials for laser processing are selected.

Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells

Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.

El "Asilo del Port" de Barcelona

El pasado 15 de mayo de 2010, realizamos un acto de recordatorio y de homenaje, de amigos y amigas, de personas que lo valorábamos y respetábamos, de educadores y educadoras sociales que nos consideramos sus discípulos, de Toni Julià, que había muerto hacía unos meses, a comienzos del verano de 2009. Y lo hicimos en el espacio emblemático que en 1977 ocupaba 'el Asilo del Port' del ayuntamiento de Barcelona y que ahora ocupa, en parte, la escuela Bàrkeno. El Asilo del Port, nombre con el que era conocido en los años 70 por los vecinos del Barrio de la Marina del Prat Vermell, estaba situado en la calle Cisell, en lo que había sido, hasta su anexión a Barcelona,"la Marina" del municipio de Sants (3). Era un centro-institución municipal de muy larga trayectoria, entre los de la Beneficencia de la ciudad de Barcelona. Y en 1977 actuó como base de operaciones logística del nacimiento de los 'Colectivos Infantiles del Ayuntamiento de Barcelona', experiencia pionera en el proceso de renovación de la acción socioeducativa con la infancia del inicio de la democracia en España. (4) En este artículo queremos ofrecer algunos elementos que nos ayuden a ubicar, dentro de la historia de la acción social de la ciudad de Barcelona, las diferentes funciones y el recorrido de esta institución, el Asilo del Port. Y de paso, rescatar alguna anécdota relacionada con Toni Julià.

Vid frågornas port

Soitinnus: sekakuoro. (SATB)

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.

Principals intercanvis de mercaderies entre València Port i la Xina en el període 1996-2014

La present memòria es planteja com una aportació a la comprensió de les últimes dos dècades de relacions comercials amb la Xina des del port de València, en fase d'integració amb el de Sagunt i Gandia, i el seu hinterland constituït a més de pel País Valencià per una àrea que abasta tota la zona est i central de la Península Ibèrica. La Xina és el país protagonista d'entre les economies emergents en l'actualitat, així l'estudi analitza, des d'una perspectiva eminentment valenciana, quins són els principals intercanvis de mercaderies entre València Port i els principals ports de la Xina.

Alargamento da distribuição de massa molar de polímeros sintetizados com catalisadores metalocênicos dual-site

The main topics related to the use of dual-site catalysts in the production of polymers with broad molecular weight distribution are reviewed. The polymerization using dual-site catalysts is more economical and allows to produce a higher quality product than other processes, such as polymer blend and multistage reactors. However, the formulation of these catalysts is quite complicated since the same catalyst must produce distinct polymer grades. In addition, the release of patents concerning the combination of metallocenes and new technologies for polymerization shows that polymerization processes using dual-site catalysts are of current industrial interest.