Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Nanocarbon-Based photovoltaics

Carbon materials are excellent candidates for photovoltaic solar cells: they are Earth-abundant, possess high optical absorption, and superior thermal and photostability. Here we report on solar cells with active layers made solely of carbon nanomaterials that present the same advantages of conjugated polymer-based solar cells - namely solution processable, potentially flexible, and chemically tunable - but with significantly increased photostability and the possibility to revert photodegradation. The device active layer composition is optimized using ab-initio density functional theory calculations to predict type-II band alignment and Schottky barrier formation. The best device fabricated is composed of PC70BM fullerene, semiconducting single-walled carbon nanotubes and reduced graphene oxide. It achieves a power conversion efficiency of 1.3% - a record for solar cells based on carbon as the active material - and shows significantly improved lifetime than a polymer-based device. We calculate efficiency limits of up to 13% for the devices fabricated in this work, comparable to those predicted for polymer solar cells. There is great promise for improving carbon-based solar cells considering the novelty of this type of device, the superior photostability, and the availability of a large number of carbon materials with yet untapped potential for photovoltaics. Our results indicate a new strategy for efficient carbon-based, solution-processable, thin film, photostable solar cells

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Pharmacokinetic and pharmacodynamic properties of SOL1:a novel dual inhibitor of neutral endopeptidase and endothelin converting enzyme

AbstractAimsThe pharmacological profile of the novel putative neutral endopeptidase (NEP) and endothelin converting enzyme (ECE) inhibitor SOL1 was examined.Main methodsThe enzyme inhibitory profile of SOL1 was established in vitro. The pharmacokinetic and pharmacodynamic profile was determined in rodents in vivo.Key findingsIn vitro, at neutral pH, 10μM SOL1 inhibited NEP-1, NEP-2, and ECE-1 by 99%, 94% and 75%, respectively. The IC50s were 25, 25 and 3200nmol/L, respectively. In anesthetized rats, SOL1 inhibited blood pressure (BP) responses to big-ET-1 and ET-1(1–31) with ED50s of 1.9 and 0.03mg/kg, corresponding to plasma EC50s of 4.6 and 0.1μmol/L, respectively. Pharmacokinetics of SOL1 were examined after single injections in mice and rats. In these species, the estimated clearance of SOL1 varied between 5 and 9ml/kg.min and T1/2 between 20 and 60min. Steady state kinetics of SOL1 were examined after continuous s.c. infusions of SOL1 for 3weeks at 50mg/kg.day in DOCA-salt hypertensive rats. This treatment lowered BP by 22mmHg. Steady state concentrations of SOL1 in plasma were 3.9μmol/L. In heart, lung, and kidney the concentrations of SOL1 were 0.4, 1.8, and 20.5μmol/kg, respectively. About 63% of the daily dose was retrieved unaltered in the urine.SignificanceThese data indicate that SOL1 is primarily a NEP inhibitor in vitro as well as in vivo. Given the preferential renal accumulation and renal clearance of SOL1 additional ECE-1 inhibition in the kidney may have contributed to its chronic BP lowering effects in the DOCA-salt hypertensive rat model