Allelomimesis as universal clustering mechanism for complex adaptive systems

Animal and human clusters are complex adaptive systems and many are organized in cluster sizes $s$ that obey the frequency-distribution $D(s)\propto s^{-\tau}$. Exponent $\tau$ describes the relative abundance of the cluster sizes in a given system. Data analyses have revealed that real-world clusters exhibit a broad spectrum of $\tau$-values, $0.7\textrm{(tuna fish schools)}\leq\tau\leq 2.95\textrm{(galaxies)}$. We show that allelomimesis is a fundamental mechanism for adaptation that accurately explains why a broad spectrum of $\tau$-values is observed in animate, human and inanimate cluster systems. Previous mathematical models could not account for the phenomenon. They are hampered by details and apply only to specific systems such as cities, business firms or gene family sizes. Allelomimesis is the tendency of an individual to imitate the actions of its neighbors and two cluster systems yield different $\tau$ values if their component agents display different allelomimetic tendencies. We demonstrate that allelomimetic adaptation are of three general types: blind copying, information-use copying, and non-copying. Allelomimetic adaptation also points to the existence of a stable cluster size consisting of three interacting individuals.Comment: 8 pages, 5 figures, 2 table

Measurement of glomerular filtration rate reveals that subcapsular injection of shear‐thinning hyaluronic acid hydrogels does not impair kidney function in mice

The continued development of minimally invasive therapeutic implants, such as injectable hydrogels, necessitates the concurrent advancement of methods to best assess their biocompatibility via functional outcomes in vivo. Biomaterial implants have been studied to treat kidney disease; however, assessment of biocompatibility has been limited to biomarker and histological assessments. Techniques now exist to measure kidney function serially in vivo in murine studies via transcutaneous measurements of glomerular filtration rate (tGFR). In this study, adult male and female wild-type BalbC mice underwent right unilateral nephrectomy. The remaining solitary left kidney was allowed 4 weeks to recover via compensatory hypertrophy, after which subcapsular injection of either saline or shear-thinning hyaluronic acid hydrogel was performed. Serial tGFR measurements before and after treatment were used to assess the effect of hydrogel injection on kidney filtration. Urine and serum biomarkers of kidney function, and kidney histology were also quantified. Hydrogel injection did not affect kidney function, as assessed by tGFR. Results were in agreement with standard metrics of serum and urine biomarkers of injury as well as histological assessment of inflammation. The model developed provides a direct functional assessment of implant compatibility for the treatment of kidney disease and impact on kidney function

The Chemical Compositions of Non-Variable Red and Blue Field Horizontal Branch Stars

We present a new detailed abundance study of field red horizontal branch (RHB) and blue horizontal branch (BHB) non-variable stars. High resolution and high S/N echelle spectra of 11 RHB and 12 BHB were obtained with the McDonald 2.7 m telescope, and the RHB sample was augmented by reanalysis of spectra of 25 stars from a recent survey. We derived stellar atmospheric parameters based on spectroscopic constraints, and computed relative abundance ratios for 24 species of 19 elements. The species include Si II and Ca II, which have not been previously studied in RHB and BHB (Teff < 9000 K) stars. The abundance ratios are generally consistent with those of similar-metallicity field stars in different evolutionary stages. We estimated the masses of the RHB and BHB stars by comparing their Teff--log g positions with HB model evolutionary tracks. The mass distribution suggests that our program stars possess masses of ~0.5 Msun. Finally, we compared the temperature distributions of field RHB and BHB stars with field RR Lyraes in the metallicity range -0.8 >~ [Fe/H] >~ -2.5. This yielded effective temperatures estimates of 5900K and 7400 K for the red and blue edges of the RR Lyrae instability strip.Comment: Accepted to A

Supersymmetry Breaking from a Calabi-Yau Singularity

We conjecture a geometric criterion for determining whether supersymmetry is spontaneously broken in certain string backgrounds. These backgrounds contain wrapped branes at Calabi-Yau singularites with obstructions to deformation of the complex structure. We motivate our conjecture with a particular example: the $Y^{2,1}$ quiver gauge theory corresponding to a cone over the first del Pezzo surface, $dP_1$. This setup can be analyzed using ordinary supersymmetric field theory methods, where we find that gaugino condensation drives a deformation of the chiral ring which has no solutions. We expect this breaking to be a general feature of any theory of branes at a singularity with a smaller number of possible deformations than independent anomaly-free fractional branes.Comment: 32 pages, 6 figures, latex, v2: minor changes, refs adde

Multiplexed gene expression analysis of HLA class II-associated podoconiosis implicates chronic immune activation in its pathogenesis

Background Podoconiosis is a tropical lymphoedema of the leg resulting from barefoot exposure to irritant volcanic soils. Approximately 4 million people are affected, mainly in African highland regions. The pathogenesis of this neglected tropical disease is still largely unknown, although HLA class II (HLAII) polymorphisms are associated with the disease. Methods NanoString technology was used to assess expression of 579 immune-related genes in formalin-fixed and paraffin-embedded lymph node archival samples from podoconiosis patients and unaffected controls. Results Forty-eight genes were upregulated and 21 downregulated in podoconiosis samples compared with controls. Gene ontology analysis showed differentially expressed genes to be closely related to major histocompatibility complex protein, cytokine and TNF receptor binding genes. Pathway enrichment analysis revealed involvement of lymphocyte activation, adaptive immunity, cytokine signalling, antigen processing and the IL-12 pathways. Conclusions This exploratory study reports a multiplex gene expression analysis in podoconiosis and shows upregulation of pro-inflammatory transcripts compatible with the notion of local, chronic immune activation in this HLAII-associated disease. Implicated pathways will inform future research into podoconiosis immunopathogenesis

Genetic topography and cortical cell loss in Huntington's disease link development and neurodegeneration

Cortical cell loss is a core feature of Huntington Disease (HD), beginning many years before clinical motor diagnosis, during the premanifest stage. However, it is unclear how genetic topography relates to cortical cell loss. Here, we explore the biological processes and cell types underlying this relationship and validate this using cell-specific post-mortem data. Eighty premanifest participants on average 15 years from disease onset and 71 controls were included. Using volumetric and diffusion MRI we extracted HD-specific whole brain maps where lower grey matter volume and higher grey matter mean diffusivity, relative to controls, were used as proxies of cortical cell loss. These maps were combined with gene expression data from the Allen Human Brain Atlas (AHBA) to investigate the biological processes relating genetic topography and cortical cell loss. Cortical cell loss was positively correlated with the expression of developmental genes (i.e. higher expression correlated with greater atrophy and increased diffusivity) and negatively correlated with the expression of synaptic and metabolic genes that have been implicated in neurodegeneration. These findings were consistent for diffusion MRI and volumetric HD-specific brain maps. As wild type Huntingtin is known to play a role in neurodevelopment, we explored the association between wild type Huntingtin (HTT) expression and developmental gene expression across the AHBA. Co-expression network analyses in 134 human brains free of neurodegenerative disorders was also performed. HTT expression was correlated with the expression of genes involved in neurodevelopment while co-expression network analyses also revealed that HTT expression was associated with developmental biological processes. Expression weighted cell-type enrichment (EWCE) analyses were used to explore which specific cell-types were associated with HD cortical cell loss and these associations were validated using cell specific single nucleus RNAseq (snRNAseq) data from post-mortem HD brains. The developmental transcriptomic profile of cortical cell loss in preHD was enriched in astrocytes and endothelial cells, while the neurodegenerative transcriptomic profile was enriched for neuronal and microglial cells. Astrocyte-specific genes differentially expressed in HD post-mortem brains relative to controls using snRNAseq were enriched in the developmental transcriptomic profile, while neuronal and microglial-specific genes were enriched in the neurodegenerative transcriptomic profile Our findings suggest that cortical cell loss in preHD may arise from dual pathological processes, emerging as a consequence of neurodevelopmental changes, at the beginning of life, followed by neurodegeneration in adulthood, targeting areas with reduced expression of synaptic and metabolic genes. These events result in age-related cell death across multiple brain cell types

Brane Tilings and Exceptional Collections

Both brane tilings and exceptional collections are useful tools for describing the low energy gauge theory on a stack of D3-branes probing a Calabi-Yau singularity. We provide a dictionary that translates between these two heretofore unconnected languages. Given a brane tiling, we compute an exceptional collection of line bundles associated to the base of the non-compact Calabi-Yau threefold. Given an exceptional collection, we derive the periodic quiver of the gauge theory which is the graph theoretic dual of the brane tiling. Our results give new insight to the construction of quiver theories and their relation to geometry.Comment: 46 pages, 37 figures, JHEP3; v2: reference added, figure 13 correcte

Prolonged acute kidney injury exacerbates lung inflammation at 7 days post‐acute kidney injury

Patients with acute kidney injury (AKI) have increased mortality; data suggest that the duration, not just severity, of AKI predicts increased mortality. Animal models suggest that AKI is a multisystem disease that deleteriously affects the lungs, heart, brain, intestine, and liver; notably, these effects have only been examined within 48 h, and longer term effects are unknown. In this study, we examined the longer term systemic effects of AKI, with a focus on lung injury. Mice were studied 7 days after an episode of ischemic AKI (22 min of renal pedicle clamping and then reperfusion) and numerous derangements were present including (1) lung inflammation; (2) increased serum proinflammatory cytokines; (3) liver injury; and (4) increased muscle catabolism. Since fluid overload may cause respiratory complications post-AKI and fluid management is a critical component of post-AKI care, we investigated various fluid administration strategies in the development of lung inflammation post-AKI. Four different fluid strategies were tested - 100, 500, 1000, or 2000 μL of saline administered subcutaneously daily for 7 days. Interestingly, at 7 days post-AKI, the 1000 and 2000 μL fluid groups had less severe AKI and less severe lung inflammation versus the 100 and 500 μL groups. In summary, our data demonstrate that appropriate fluid management after an episode of ischemic AKI led to both (1) faster recovery of kidney function and (2) significantly reduced lung inflammation, consistent with the notion that interventions to shorten AKI duration have the potential to reduce complications and improve patient outcomes