Fractional diffusion emulates a human mobility network during a simulated disease outbreak

From footpaths to flight routes, human mobility networks facilitate the spread of communicable diseases. Control and elimination efforts depend on characterizing these networks in terms of connections and flux rates of individuals between contact nodes. In some cases, transport can be parameterized with gravity-type models or approximated by a diffusive random walk. As a alternative, we have isolated intranational commercial air traffic as a case study for the utility of non-diffusive, heavy-tailed transport models. We implemented new stochastic simulations of a prototypical influenza-like infection, focusing on the dense, highly-connected United States air travel network. We show that mobility on this network can be described mainly by a power law, in agreement with previous studies. Remarkably, we find that the global evolution of an outbreak on this network is accurately reproduced by a two-parameter space-fractional diffusion equation, such that those parameters are determined by the air travel network.Comment: 26 pages, 4 figure

Measurement of Longitudinal Spin Transfer to Lambda Hyperons in Deep-Inelastic Lepton Scattering

Spin transfer in deep-inelastic Lambda electroproduction has been studied with the HERMES detector using the 27.6 GeV polarized positron beam in the HERA storage ring. For an average fractional energy transfer = 0.45, the longitudinal spin transfer from the virtual photon to the Lambda has been extracted. The spin transfer along the Lambda momentum direction is found to be 0.11 +/- 0.17 (stat) +/- 0.03 (sys); similar values are found for other possible choices for the longitudinal spin direction of the Lambda. This result is the most precise value obtained to date from deep-inelastic scattering with charged lepton beams, and is sensitive to polarized up quark fragmentation to hyperon states. The experimental result is found to be in general agreement with various models of the Lambda spin content, and is consistent with the assumption of helicity conservation in the fragmentation process.Comment: 8 pages, 3 figures; new version has an expanded discussion and small format change

Transport of Pb and Zn by carboxylate complexes in basinal ore fluids and related petroleum-field brines at 100°C: the influence of pH and oxygen fugacity

It is well established through field observations, experiments, and chemical models that oxidation (redox) state and pH exert a strong influence on the speciation of dissolved components and the solubility of minerals in hydrothermal fluids. log [Image: see text] –pH diagrams were used to depict the influence of oxygen fugacity and pH on monocarboxylate- and dicarboxylate-transport of Pb and Zn in low-temperature (100°C) hydrothermal ore fluids that are related to diagenetic processes in deep sedimentary basins, and allow a first-order comparison of Pb and Zn transport among proposed model fluids for Mississippi Valley-type (MVT) and red-bed related base metal (RBRBM) deposits in terms of their approximate pH and [Image: see text] conditions. To construct these diagrams, total Pb and Zn concentrations and Pb and Zn speciation were calculated as a function of log [Image: see text] and pH for a composite ore-brine with concentrations of major elements, total sulfur, and total carbonate that approximate the composition of MVT and RBRBM model ore fluids and modern basinal brines. In addition to acetate and malonate complexation, complexes involving the ligands Cl(-), HS(-), H(2)S, and OH(- )were included in the model of calculated total metal concentration and metal speciation. Also, in the model, Zn and Pb are competing with the common-rock forming metals Ca, Mg, Na, Fe, and Al for the same ligands. Calculated total Pb concentration and calculated total Zn concentration are constrained by galena and sphalerite solubility, respectively. Isopleths, in log [Image: see text] –pH space, of the concentration of Pb and concentration of Zn in carboxylate (acetate + malonate) complexes illustrate that the oxidized model fluids of T. H. Giordano (in Organic Acids in Geological Processes, ed. E. D. Pittman and M. D. Lewan, Springer-Verlag, New York, 1994, pp. 319–354) and G. M. Anderson (Econ. Geol., 1975, 70, 937–942) are capable of transporting sufficient amounts of Pb (up to 10 ppm) and Zn (up to 100 ppm) in the form of carboxylate complexes to form economic deposits of these metals. On the other hand, the reduced ore fluid models of D. A. Sverjensky (Econ. Geol., 1984, 79, 23–37) and T. H. Giordano and H. L. Barnes (Econ. Geol., 1981, 76, 2200–2211) can at best transport amounts of Pb and Zn, as carboxylate complexes, that are many orders of magnitude below the 1 to 10 ppm minimum required to form economic deposits. Lead and zinc speciation (mol% of total Pb or Zn) in the model ore fluid was calculated at specific log [Image: see text] –pH conditions along the 100, 0.01, and 0.001 ppm total Pb and total Zn isopleths. Along the 100 ppm isopleth conditions are oxidized (∑SO(4 )>> ∑H(2)S) with Pb and Zn predominantly in the form of chloride complexes under acid to mildly alkaline conditions (pH from 3 to approximately 7.5), while hydroxide complexes dominate Pb and Zn speciation under more alkaline conditions. Sulfide complexes are insignificant under these oxidized conditions. For more reduced conditions along the 0.01 and 0.001 ppm isopleths chloride complexes dominate Pb and Zn speciation in the SO(4)(2- )field and near the SO(4)(2-)-reduced sulfur boundary from pH = 4 to approximately 7.5, while hydroxide complexes dominate Pb and Zn speciation under alkaline conditions above pH = 7.5 in the SO(4)(2- )field. In the most reduced fluids (∑H(2)S >> ∑SO(4)) along the 0.01 and 0.001 isopleths, sulfide complexes account for almost 100% of the Pb and Zn in the model fluid. Acetate (monocarboxylate) complexation is significant only under conditions of chloride and hydroxide complex dominance and its effect is maximized in the pH range 5 to 7, where it complexes 2 to 2.6% of the total Pb and 1 to 1.25% of the total Zn. Malonate (dicarboxylate) complexes are insignificant along all isopleths. The speciation results from this study show that deep formation waters characterized by temperatures near 100°C, high oxidation states and ∑H(2)S < 0.03 mg L(-1 )([Image: see text] < 10(-6)), high chlorinities (~ 100000 mg L(-1)), and high but reasonable concentrations of carboxylate anions can mobilize up to 3% of the total Pb and up to 1.3% of the total Zn as carboxylate complexes. Furthermore, these percentages, under the most favorable conditions, correspond to approximately 1 to 100 ppm of these metals in solution; concentrations that are adequate to form economic deposits of these metals. However, the field evidence suggests that all of these optimum conditions for carboxylate complexation are rarely met at the same time. A comparison of the composite ore fluid compositions from this study and modern brine data shows that the ore brines, corresponding to log [Image: see text] –pH conditions based on the Anderson (1975) and Giordano (1994) model fluids, are similar in many respects to modern, high trace-metal petroleum-field brines. The principal differences between modern high trace-metal brines and the composite ore fluids of Anderson (1975) and Giordano (1994) relate to their carboxylate anion content. The reported concentrations of monocarboxylate anions (∑monocbx) and dicarboxylate anions (Edicbx) in high trace-metal petroleum-field brines (< 1 to 300 mg L(-1 )and < 1 mg L(-1), respectively) are significantly lower than the concentrations assumed in the modelled brines of this study (∑monocbx = 7 700 mg L(-1 )and ∑dicbx = 300 mg L(-1)). There are also major differences in the corresponding total chloride to carboxylate ratio (∑m(Cl)/∑m(cbx)) and monocarboxylate to dicarboxylate ratio (∑m(monocbx)/∑m(dicbx)). Modern high trace-metal brines have much higher ∑m(Cl)/∑m(cbx )values and, therefore, the contribution of carboxylate complexes to the total Pb and Zn content in these modern brines is likely to be significantly less than the 1 to 3 percent for the composite ore fluids of Anderson (1975) and Giordano (1994). The composite ore-brine based on the Giordano and Barnes (1981) MVT ore fluid is comparable to the high salinity (> 170 000 mg L(-1 )TDS) subset of modern brines characterized by low trace-metal content and high total reduced sulfur (∑H(2)S). A comparison of the Sverjensky (1984) composite ore-brine with modern petroleum-field brines in terms of ∑H(2)S and Zn content, reveals that this ore fluid corresponds to a "border-type" brine, between modern high trace-metal brines and those with low trace-metal content and high ∑H(2)S. A brine of this type is characterized by values of ∑H(2)S, ∑Zn, and/or ∑Pb within or near the 1 to 10 mg L(-1 )range. Based on brine-composition data from numerous references cited in this paper, border-type brines do exist but are rare. The model results and field evidence presented in this study are consistent with other chemical simulation studies of carboxylate complexation in modern petroleum-field brines. Thus, it appears that carboxylate complexation plays a minor, if not insignificant, role as a transport mechanism for Pb and Zn in high salinity Na–Cl and Na–Ca–Cl basinal brines and related ore fluids

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A single migrant enhances the genetic diversity of an inbred puma population

Migration is essential for maintaining genetic diversity among populations, and pumas (Puma concolor) provide an excellent model for studying the genetic impacts of migrants on populations isolated by increasing human development. In densely populated southern California, USA, puma populations on the east and west side of interstate highway 15 (I-15) have become fragmented into a small inbred population on the west side (Santa Ana Mountains) and a relatively larger, more diverse population on the east side (Eastern Peninsular Range). From 146 sampled pumas, genetic analyses indicate seven pumas crossed I-15 over the last 15 years, including four males from west to east, and three males from east to west. However, only a single migrant (named M86) was detected to have produced offspring and contribute to gene flow across the I-15 barrier. Prior to the M86 migration, the Santa Ana population exhibited inbreeding and had significantly lower genetic diversity than the Eastern Peninsular Range population. After M86 emigrated, he sired 11 offspring with Santa Ana females, decreasing inbreeding measures and raising heterozygosity to levels similar to pumas in the Eastern Peninsular Range. The emigration of M86 also introduced new alleles into the Santa Ana population, although allelic richness still remained significantly lower than the Eastern Peninsular population. Our results clearly show the benefit of a single migrant to the genetics of a small, isolated population. However, ongoing development and habitat loss on both sides of I-15 will increasingly strengthen the barrier to successful migration. Further monitoring, and potential human intervention, including minimizing development effects on connectivity, adding or improving freeway crossing structures, or animal translocation, may be needed to ensure adequate gene flow and long-term persistence of the Santa Ana puma population

Fractional Diffusion Emulates a Human Mobility Network during a Simulated Disease Outbreak

Mobility networks facilitate the growth of populations, the success of invasive species, and the spread of communicable diseases among social animals, including humans. Disease control and elimination efforts, especially during an outbreak, can be optimized by numerical modeling of disease dynamics on transport networks. This is especially true when incidence data from an emerging epidemic is sparse and unreliable. However, mobility networks can be complex, challenging to characterize, and expensive to simulate with agent-based models. We therefore studied a parsimonious model for spatiotemporal disease dynamics based on a fractional diffusion equation. We implemented new stochastic simulations of a prototypical influenza-like infection spreading through the United States' highly-connected air travel network. We found that the national-averaged infected fraction during an outbreak is accurately reproduced by a space-fractional diffusion equation consistent with the connectivity of airports. Fractional diffusion therefore seems to be a better model of network outbreak dynamics than a diffusive model. Our fractional reaction-diffusion method and the result could be extended to other mobility networks in a variety of applications for population dynamics

Supplemental Information from Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus genomes

Additional details of analysi

A single migrant enhances the genetic diversity of an inbred puma population.

Migration is essential for maintaining genetic diversity among populations, and pumas (Puma concolor) provide an excellent model for studying the genetic impacts of migrants on populations isolated by increasing human development. In densely populated southern California, USA, puma populations on the east and west side of interstate highway 15 (I-15) have become fragmented into a small inbred population on the west side (Santa Ana Mountains) and a relatively larger, more diverse population on the east side (Eastern Peninsular Range). From 146 sampled pumas, genetic analyses indicate seven pumas crossed I-15 over the last 15 years, including four males from west to east, and three males from east to west. However, only a single migrant (named M86) was detected to have produced offspring and contribute to gene flow across the I-15 barrier. Prior to the M86 migration, the Santa Ana population exhibited inbreeding and had significantly lower genetic diversity than the Eastern Peninsular Range population. After M86 emigrated, he sired 11 offspring with Santa Ana females, decreasing inbreeding measures and raising heterozygosity to levels similar to pumas in the Eastern Peninsular Range. The emigration of M86 also introduced new alleles into the Santa Ana population, although allelic richness still remained significantly lower than the Eastern Peninsular population. Our results clearly show the benefit of a single migrant to the genetics of a small, isolated population. However, ongoing development and habitat loss on both sides of I-15 will increasingly strengthen the barrier to successful migration. Further monitoring, and potential human intervention, including minimizing development effects on connectivity, adding or improving freeway crossing structures, or animal translocation, may be needed to ensure adequate gene flow and long-term persistence of the Santa Ana puma population