Environmental challenges to operationalisation of South African rainfall enhancement

Most of the atmospheric moisture in systems moving across South Africa leaves the sub-continent as the weather systems move out over the ocean, only a tenth of it falls on the landmass as rain. An increase in the efficiency of the atmospheric moisture delivery system by means of rainfall enhancement is therefore an attractive concept. Rainfall enhancement functions by either providing additional Cloud Condensation Nuclei or Ice forming Nuclei that will beneficially influence the precipitation formation process, improving the efficiency of moisture to rainfall conversion. Systematic South African research into rainfall enhancement started in the 1970s. The South African Rainfall Enhancement Programme (SAREP), initiated in the late 1990\'s, is the most recent in a series of studies and was the first semi-operational rainfall enhancement project to occur in South Africa as a response to drought conditions. In a recent study (DWAF, 2004 in prep) to finalise SAREP and provide guidance on operationalising rainfall enhancement, it was recommended that environmental impact assessment must be undertaken before this technology is implemented further. Rainfall enhancement falls specifically within the jurisdiction of the National Water Act (NWA) and the National Environmental Management Act (NEMA). A licence to undertake rainfall enhancement activities is required from the Minister of Water Affairs and Forestry after an appropriate environmental impact assessment has been undertaken to inform his decision. This paper proposes an approach to fulfil the legal requirements for operationalising future rainfall enhancement. The interaction between the science of rainfall enhancement and the ability of scientific disciplines to determine relevant environmental impacts, to appropriately inform the decision-making process, is specifically highlighted. The data requirements identified by scientists during the study varies in duration and resource needs and does not differentiate between ongoing scientific research and the requisite information required for informed decision making. This paper contemplates an approach which provides for holistic and co-ordinated investigation of South African rainfall enhancement into the future. Water SA Vol. 30 (5) 2005: pp.88-9

Enhancing of accuracy assessment for forest above-ground biomass estimates obtained from remote sensing via hypothesis testing and overfitting evaluation

The evaluation of accuracy is essential for assuring the reliability of ecological models. Usually, the accuracy of above-ground biomass (AGB) predictions obtained from remote sensing is assessed by the mean differences (MD), the root mean squared differences (RMSD), and the coefficient of determination (R^2) between observed and predicted values. In this article we propose a more thorough analysis of accuracy, including a hypothesis test to evaluate the agreement between observed and predicted values, and an assessment of the degree of overfitting to the sample employed for model training. Using the estimation of forest AGB from LIDAR and spectral sensors as a case study, we compared alternative prediction and variable selection methods using several statistical measures to evaluate their accuracy. We showed that the hypothesis tests provide an objective method to infer the statistical significance of agreement. We also observed that overfitting can be assessed by comparing the inflation in residual sums of squares experienced when carrying out a cross-validation. Our results suggest that this method may be more effective than analysing the deflation in R^2. We proved that overfitting needs to be specifically addressed since, in light of MD, RMSD and R^2 alone, predictions may apparently seem reliable even in clearly unrealistic circumstances, for instance when including too many predictor variables. Moreover, Theil’s partial inequality coefficients, which are employed to resolve the proportions of the total errors due to the unexplained variance, the slope and the bias, may become useful to detect averaging effects common in remote sensing predictions of AGB. We concluded that statistical measures of accuracy, precision and agreement are necessary but insufficient for model evaluation. We therefore advocate for incorporating evaluation measures specifically devoted to testing observed-versus-predicted fit, and to assessing the degree of overfitting

GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.

Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington's disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain

Identification of storage conditions stabilizing extracellular vesicles pre

Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS-HAT). We report that PBS-HAT buffer facilitates clearly improved short-term and long-term EV preservation for samples stored at -80°C, stability throughout several freeze-thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule – single vesicle level by fluorescence correlation spectroscopy and single particle imaging

Extracellular vesicles (EV) convey biological information by transmitting macromolecules between cells and tissues and are of great promise as pharmaceutical nanocarriers, and as therapeutic per se. Strategies for customizing the EV surface and cargo are being developed to enable their tracking, visualization, loading with pharmaceutical agents and decoration of the surface with tissue targeting ligands. While much progress has been made in the engineering of EVs, an exhaustive comparative analysis of the most commonly exploited EV-associated proteins, as well as a quantification at the molecular level are lacking. Here, we selected 12 EV-related proteins based on MS-proteomics data for comparative quantification of their EV engineering potential. All proteins were expressed with fluorescent protein (FP) tags in EV-producing cells; both parent cells as well as the recovered vesicles were characterized biochemically and biophysically. Using Fluorescence Correlation Spectroscopy (FCS) we quantified the number of FP-tagged molecules per vesicle. We observed different loading efficiencies and specificities for the different proteins into EVs. For the candidates showing the highest loading efficiency in terms of engineering, the molecular levels in the vesicles did not exceed ca 40–60 fluorescent proteins per vesicle upon transient overexpression in the cells. Some of the GFP-tagged EV reporters showed quenched fluorescence and were either non-vesicular, despite co-purification with EVs, or comprised a significant fraction of truncated GFP. The co-expression of each target protein with CD63 was further quantified by widefield and confocal imaging of single vesicles after double transfection of parent cells. In summary, we provide a quantitative comparison for the most commonly used sorting proteins for bioengineering of EVs and introduce a set of biophysical techniques for straightforward quantitative and qualitative characterization of fluorescent EVs to link single vesicle analysis with single molecule quantification

Positive Psychology in Sales: Integrating Psychological Capital

As positive psychology moves into the workplace, researchers have been able to demonstrate the desirable impact of positive organizational behavior. Specifically, psychological capital (PsyCap) improves employee attitudes, behaviors, and performance. Advancing PsyCap in sales research is important given the need for a comprehensive positive approach to drive sales performance, offset the high cost of salesperson turnover, improve cross-functional sales interfaces, and enrich customer relationships. The authors provide an integrative review of PsyCap, discuss its application in sales, and advance an agenda for future research. Research prescriptions are organized according to individual-level, intra-organizational, and extra-organizational outcomes pertinent to the sales field