Creation and Divine Providence in Plotinus

In this paper, we argue that Plotinus denies deliberative forethought about the physical cosmos to the demiurge on the basis of certain basic and widely shared Platonic and Aristotelian assumptions about the character of divine thought. We then discuss how Plotinus can nonetheless maintain that the cosmos is «providentially» ordered

Creation and Divine Providence in Plotinus

In this paper, we argue that Plotinus denies deliberative forethought about the physical cosmos to the demiurge on the basis of certain basic and widely shared Platonic and Aristotelian assumptions about the character of divine thought. We then discuss how Plotinus can nonetheless maintain that the cosmos is «providentially» ordered

Involvement of JAK/STAT Signaling and a Basement Membrane-Associated Protein during Air Sac Primordium Development in Drosophila Melanogaster

Tumor metastasis currently presents the greatest obstacle for effective cancer remediation. Metastatic growth necessitates both degradation of a specialized form of extracellular matrix (ECM) known as the basement membrane (BM) and the invasion of surrounding tissues thereafter. The thoracic air sacs of fruit flies (Drosophila melanogaster), which develop and operate in a fashion comparable to the human lung, provide a unique model for identifying and characterizing factors that contribute to its own development as well as tumoral invasion. We investigated the involvement of both Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signaling and a BMassociated protein during the development of air sac primordia (ASPs), the precursors to Drosophila air sacs. We find that JAK/STAT signaling occurs in ASP tip cells and that misexpression of core pathway components via the GAL4/UAS system negatively impacts ASP development. Further, we identify Unpaired 2 (Upd2) as the primary activating ligand for JAK/STAT activity in the ASP. Knockdown of the BM-associated protein using GAL4 drivers associated with a fibroblast growth factor (FGF) receptor gene, breathless (btl), and segment polarity gene, patched (ptc), prevented larval development beyond the second larval instar (L2). Knockdown of the BM-associated protein in the wing also produced bristle defects, but its overexpression did not have an effect anywhere other than in the ASP, where the proportion of mutant phenotypes increased significantly (p \u3c .0001) in response. Finally, we find that collagen IV localization was unaffected by knockdown of the BM-associated protein. Together, our data constitute a significant step forward in understanding the role of both this BM-associated protein and JAK/STAT signaling in the ASP and similar mammalian structures

Assessing the Impact of Non-Differential Genotyping Errors on Rare Variant Tests of Association

Background/Aims: We aim to quantify the effect of non-differential genotyping errors on the power of rare variant tests and identify those situations when genotyping errors are most harmful. Methods: We simulated genotype and phenotype data for a range of sample sizes, minor allele frequencies, disease relative risks and numbers of rare variants. Genotype errors were then simulated using five different error models covering a wide range of error rates. Results: Even at very low error rates, misclassifying a common homozygote as a heterozygote translates into a substantial loss of power, a result that is exacerbated even further as the minor allele frequency decreases. While the power loss from heterozygote to common homozygote errors tends to be smaller for a given error rate, in practice heterozygote to homozygote errors are more frequent and, thus, will have measurable impact on power. Conclusion: Error rates from genotype-calling technology for next-generation sequencing data suggest that substantial power loss may be seen when applying current rare variant tests of association to called genotypes

Highly oriented nonepitaxially grown \u3ci\u3eL\u3c/i\u3e1\u3csub\u3e0\u3c/sub\u3e FePt films

A method of preparing nonepitaxially grown, highly textured L10 FePt thin films is described. A nearly perfect (001) texture was obtained by direct deposition of FePt films on Corning 7059 glass substrates and subsequent rapid thermal annealing. The ordering and orientation of the L10-phase FePt grains were controlled by the initial as-deposited film structure, and also by the annealing process. Magnetic measurements reveal large perpendicular anisotropy for these (001) textured films. The substrates and processes used for nonepitaxial growth of L10 ordered FePt films are much more compatible with practical applications than those grown epitaxially

Orientation-controlled nonepitaxial L1\u3csub\u3e0\u3c/sub\u3e CoPt and FePt films

We report results on highly oriented, face-centered tetragonal ordered CoPt and FePt thin films grown nonepitaxially by directly depositing films on thermally oxidized Si substrates and subsequent annealing. By controlling the thickness, composition, and annealing conditions, and/or depositing a proper underlayer, nearly perfect (001)-oriented CoPt and FePt films can be obtained. Magnetic measurements reveal large perpendicular anisotropy for such films

Leveraging Sanofi intensified ICB platform to enable early process development for a labile and hard-to-express molecule

Within the biopharmaceutics industry, tremendous progress has been made in the implementation of early development antibody platforms to achieve high volumetric productivity and consistent product quality for novel therapies. More recently, development of new modalities provide opportunities for advancing exciting new therapeutic possibilities. However, many of these modalities present new upstream and downstream development challenges, e.g., low expression, labile molecules, low recovery, and unreliable product quality. The resulting additional development requirements increase the timelines for demonstrating Proof of Concept and may even prohibit certain therapeutic candidates from reaching the clinic at all. The Sanofi ICB platform provides opportunities to increase productivity and improve product quality, enabling manufacture of new entities previously inaccessible. Here, we present a case study of such a situation, in which the ICB platform is applied to an early-stage, labile, hard to express molecule produced from non-CHO mammalian cells. A combination of upstream and downstream high-throughput technologies have been incorporated to rapidly define a process sufficient for first-in-human studies. Process intensification enables adequate material generation within an acceptable number of batches for both development and clinical manufacturing. This case study demonstrates the strategy of using intensified perfusion platform for non-antibody modalities to support a diverse portfolio for our evolving industry

Evaluation of well designs to improve access to safe and clean water in rural Tanzania

The objective of this study was to examine three well designs: drilled wells (20–30 m deep), closed dug wells (\u3e5 m deep), and hand-dug open wells (\u3c5 m deep), to determine the water quality for improving access to safe and clean water in rural communities. Heterotrophic plate count (HPC), total coliforms (TC), Escherichia coli (E. coli) and turbidity, were used to assess the water quality of 97 wells. Additionally, the study looked at the microflora diversity of the water, focusing on potential pathogens using outgrowth, PCR, and genome sequencing for 10 wells. Concentrations of TC for the open dug wells (4 × 104 CFU/100 mL) were higher than the drilled (2 × 103 CFU/100 mL) and closed dug wells (3 × 103 CFU/100 mL). E. coli concentration for drilled and closed dug wells was \u3c22 MPN (most probable number)/100 mL, but higher for open wells (\u3e154 MPN/100 mL). The drilled well turbidity (11 NTU) was within the standard deviation of the closed well (28 NTU) compared to open dug wells (49 NTU). Drilled and closed wells had similar microbial diversity. There were no significant differences between drilled and closed dug wells. The covering and lining of hand-dug wells should be considered as an alternative to improve access to safe and clean water in rural communities

A comparison across non-model animals suggests an optimal sequencing depth for de novo transcriptome assembly

Background: The lack of genomic resources can present challenges for studies of non-model organisms. Transcriptome sequencing offers an attractive method to gather information about genes and gene expression without the need for a reference genome. However, it is unclear what sequencing depth is adequate to assemble the transcriptome de novo for these purposes. Results: We assembled transcriptomes of animals from six different phyla (Annelids, Arthropods, Chordates, Cnidarians, Ctenophores, and Molluscs) at regular increments of reads using Velvet/Oases and Trinity to determine how read count affects the assembly. This included an assembly of mouse heart reads because we could compare those against the reference genome that is available. We found qualitative differences in the assemblies of whole-animals versus tissues. With increasing reads, whole-animal assemblies show rapid increase of transcripts and discovery of conserved genes, while single-tissue assemblies show a slower discovery of conserved genes though the assembled transcripts were often longer. A deeper examination of the mouse assemblies shows that with more reads, assembly errors become more frequent but such errors can be mitigated with more stringent assembly parameters. Conclusions: These assembly trends suggest that representative assemblies are generated with as few as 20 million reads for tissue samples and 30 million reads for whole-animals for RNA-level coverage. These depths provide a good balance between coverage and noise. Beyond 60 million reads, the discovery of new genes is low and sequencing errors of highly-expressed genes are likely to accumulate. Finally, siphonophores (polymorphic Cnidarians) are an exception and possibly require alternate assembly strategies

Promoting Social Behaviour in Reducing Peak Electricity Consumption Using Multi-Agent Systems

As we move towards an energy system based on renewable energy sources, we need to consider their inflexibility to meet sudden peaks in demand. It is therefore important to reduce the peak load placed on our energy system. For individual households this means spreading out the use of high-powered appliances, such as dishwashers and washing machines, throughout the day. Traditional approaches to this problem have relied on differential pricing set by a centralised utility company, but this mechanism has not been effective in promoting widespread shifting of appliance usage. Our previous research investigated a decentralised mechanism where agents receive an initial allocation of time-slots to use their appliances, which they can then exchange with other agents. This was found to be an effective approach to reducing the peak load within a community energy system when we introduced social capital, the tracking of favours given and received, in order to incentivise agents to act flexibly by accepting exchanges that do not immediately benefit them. This system encouraged self-interested agents to learn socially beneficial behaviour in order to earn social capital that they could later use to improve their own performance. In this paper we expand this work by implementing real world household appliance usage data in order to ensure that our mechanism could adapt to the challenging demand needs of real households. We also demonstrate how smaller and more diverse populations can optimise more effectively than larger community energy systems and better overcome the challenges of real-world demand peaks