Undermining and Strengthening Social Networks through Network Modification

Social networks have well documented effects at the individual and aggregate level. Consequently it is often useful to understand how an attempt to influence a network will change its structure and consequently achieve other goals. We develop a framework for network modification that allows for arbitrary objective functions, types of modification (e.g. edge weight addition, edge weight removal, node removal, and covariate value change), and recovery mechanisms (i.e. how a network responds to interventions). The framework outlined in this paper helps both to situate the existing work on network interventions but also opens up many new possibilities for intervening in networks. In particular use two case studies to highlight the potential impact of empirically calibrating the objective function and network recovery mechanisms as well as showing how interventions beyond node removal can be optimised. First, we simulate an optimal removal of nodes from the Noordin terrorist network in order to reduce the expected number of attacks (based on empirically predicting the terrorist collaboration network from multiple types of network ties). Second, we simulate optimally strengthening ties within entrepreneurial ecosystems in six developing countries. In both cases we estimate ERGM models to simulate how a network will endogenously evolve after intervention

The determination of planetary structure in tidally relaxed inclined systems

[Abridged] The recent discovery of a transiting planet on a non-circular orbit with a massive highly eccentric companion orbiting HAT-P-13 offers the possibility of probing the structure of the short-period planet. The ability to do this relies on the system being in a quasi-equilibrium state in the sense that the eccentricities are constant on the usual secular timescale, and decay on a timescale which is much longer than the age of the system. Since the equilibrium eccentricity is effectively a function only of observable system parameters and the unknown Love number of the short-period planet, the latter can be determined with accurate measurements of the planet's eccentricity and radius. However, this analysis relies on the unlikely assumption that the system is coplanar. Here we generalize our recent analysis of this fixed-point phenomenon to mutually inclined systems and show that the fixed point of coplanar systems is replaced by a limit cycle, with the average value of the eccentricity decreasing and its amplitude of variation increasing with increasing mutual inclination. This behaviour significantly reduces the ability to unambiguously determine the Love number of the short-period planet if the mutual inclination is higher than around 10^o. We show that for Q-values less than 10^6, the HAT-P-13 system cannot have a mutual inclination between 54 and 126^o because Kozai oscillations coupled with tidal dissipation would act to quickly move the inclination outside this range, and that the behaviour of retrograde systems is the mirror image of that for prograde systems. We derive a relationship between the equilibrium radius of the short-period planet, its Q-value and its core mass, and show that given current estimates of e_b and the planet radius, the HAT-P-13 system is likely to be close to coplanar [...]Comment: 24 pages, 14 figures, Accepted for publication in MNRAS. **NOTE REFINED PREDICTION FOR MUTUAL INCLINATIO

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species

Stem Cell Emergence and Hemopoietic Activity Are Incompatible in Mouse Intraembryonic Sites

In the mouse embryo, the generation of candidate progenitors for long-lasting hemopoiesis has been reported in the paraaortic splanchnopleura (P-Sp)/aorta-gonad-mesonephros (AGM) region. Here, we address the following question: can the P-Sp/AGM environment support hemopoietic differentiation as well as generate stem cells, and, conversely, are other sites where hemopoietic differentiation occurs capable of generating stem cells? Although P-Sp/AGM generates de novo hemopoietic stem cells between 9.5 and 12.5 days post coitus (dpc), we show here that it does not support hemopoietic differentiation. Among mesoderm-derived sites, spleen and omentum were shown to be colonized by exogenous cells in the same fashion as the fetal liver. Cells colonizing the spleen were multipotent and pursued their evolution to committed progenitors in this organ. In contrast, the omentum, which was colonized by lymphoid-committed progenitors that did not expand, cannot be considered as a hemopoietic organ. From these data, stem cell generation appears incompatible with hemopoietic activity. At the peak of hemopoietic progenitor production in the P-Sp/AGM, between 10.5 and 11.5 dpc, multipotent cells were found at the exceptional frequency of 1 out of 12 total cells and 1 out of 4 AA4.1+ cells. Thus, progenitors within this region constitute a pool of undifferentiated hemopoietic cells readily accessible for characterization

Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2

Background: The adapter proteins SLP-76 and LAT have been shown to play critical roles in the activation of PLCc2 in platelets downstream of GPVI/FcRc and the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation of SLP-76. Objective: In the present study, we have compared the role of Gads alongside that of LAT following activation of the major platelet glycoprotein receptors using mice deficient in the two adapter proteins. Results: Gads was found to be required for the efficient onset of aggregation and secretion in response to submaximal stimulation of GPVI and CLEC-2, but to be dispensable for activation following stronger stimulation of the two receptors. Gads was also dispensable for spreading induced through integrin aIIbb3 or the GPIb–IX–V complex.Further, Gads plays a negligible role in aggregate formation on collagen at an arteriolar rate of shear. In stark contrast, platelets deficient in the adapter LAT exhibit a marked decrease in aggregation and secretion following activation of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at arteriolar shear. Conclusions: The results demonstrate that Gads plays a key role in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and CLEC-2 whereas LAT is required for full activation over a wider range of agonist concentrations. These results reveal the presence of a Gads-independent pathway of platelet activation downstream of LAT