Stentz, D. A., Vita, Engineer's Council for Professional Development

NPS 1959 Professors in Engineer's Council for Professional DevelopmentNPS 1959 Professors in Engineer's Council for Professional Developmen

Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease

The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI-related diseases, including inflammatory bowel disease (IBD), therefore identifying host-microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study BEV-host interactions, we examined the influence of BEVs generated by the gut commensal bacterium, Bacteroides thetaiotaomicron, on host immune cells. Single-cell RNA sequencing data and host-microbe protein-protein interaction networks were used to predict the effect of BEVs on dendritic cells, macrophages and monocytes focusing on the Toll-like receptor (TLR) pathway. We identified biological processes affected in each immune cell type and cell-type specific processes including myeloid cell differentiation. TLR pathway analysis highlighted that BEV targets differ among cells and between the same cells in healthy versus disease (ulcerative colitis) conditions. The in silico findings were validated in BEV-monocyte co-cultures demonstrating the requirement for TLR4 and Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP) in BEV-elicited NF-kB activation. This study demonstrates that both cell-type and health status influence BEV-host communication. The results and the pipeline could facilitate BEV-based therapies for the treatment of IBD

Sampling-based Algorithms for Optimal Motion Planning

During the last decade, sampling-based path planning algorithms, such as Probabilistic RoadMaps (PRM) and Rapidly-exploring Random Trees (RRT), have been shown to work well in practice and possess theoretical guarantees such as probabilistic completeness. However, little effort has been devoted to the formal analysis of the quality of the solution returned by such algorithms, e.g., as a function of the number of samples. The purpose of this paper is to fill this gap, by rigorously analyzing the asymptotic behavior of the cost of the solution returned by stochastic sampling-based algorithms as the number of samples increases. A number of negative results are provided, characterizing existing algorithms, e.g., showing that, under mild technical conditions, the cost of the solution returned by broadly used sampling-based algorithms converges almost surely to a non-optimal value. The main contribution of the paper is the introduction of new algorithms, namely, PRM* and RRT*, which are provably asymptotically optimal, i.e., such that the cost of the returned solution converges almost surely to the optimum. Moreover, it is shown that the computational complexity of the new algorithms is within a constant factor of that of their probabilistically complete (but not asymptotically optimal) counterparts. The analysis in this paper hinges on novel connections between stochastic sampling-based path planning algorithms and the theory of random geometric graphs.Comment: 76 pages, 26 figures, to appear in International Journal of Robotics Researc

Coupling 3D Geomechanics to Classical Petroleum System Simulation

Geomechanical models of classical petroleum system simulators are limited to 1D phenomenological laws relating porosity to vertical effective stress. In order to overcome this limitation, a 3D poromechanical model is integrated in the sedimentary basin simulation by applying an iterative coupling scheme between a conventional basin code and a mechanical finite element code. This paper presents the porous material constitutive law specifically devised to deal with basin modeling, together with essential aspects of the mechanical code implementation and explicit coupling workflow. The numerical procedure is first verified according to a semi-analytical solution and then compared to an implicit academic code. Finally, a 3D synthetic case demonstrates the importance of incorporating 3D geomechanics to basin simulation. The results show that tectonic compression may significantly contribute to overpressure development and natural fracturing of seal rocks, contrary to the standard procedures of petroleum system simulation which are unable to capture such effect

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all Gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn’s disease (CD) or ulcerative colitis (UC). Results: In healthy individuals, Bt OMVs stimulated significant (p<0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p<0.001 and p<0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103 + DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p<0.01 and p<0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). Conclusions: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

BACKGROUND: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC). RESULTS: In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103+ DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). CONCLUSIONS: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients. Video Abstract

Top quark mass measurement using the template method at CDF

We present a measurement of the top quark mass in the lepton+jets and dilepton channels of $t\bar{t}$ decays using the template method. The data sample corresponds to an integrated luminosity of 5.6 fb$^{-1}$ of $p\bar{p}$ collisions at Tevatron with $\sqrt{s}=1.96$ TeV, collected with the CDF II detector. The measurement is performed by constructing templates of three kinematic variables in the lepton+jets and two kinematic variables in the dilepton channel. The variables are two reconstructed top quark masses from different jets-to-quarks combinations and the invariant mass of two jets from the $W$ decay in the lepton+jets channel, and a reconstructed top quark mass and $m_{T2}$, a variable related to the transverse mass in events with two missing particles, in the dilepton channel. The simultaneous fit of the templates from signal and background events in the lepton+jets and dilepton channels to the data yields a measured top quark mass of $M_{top} = 172.1 \pm 1.1(stat) \pm 0.9(syst).$Comment: submitted to Phys. Rev.

Search for the standard model Higgs boson decaying to a bbˉb\bar{b} pair in events with no charged leptons and large missing transverse energy using the full CDF data set

We report on a search for the standard model Higgs boson produced in association with a vector boson in the full data set of proton-antiproton collisions at $\sqrt{s} = 1.96$ TeV recorded by the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45 fb$^{-1}$. We consider events having no identified charged lepton, a transverse energy imbalance, and two or three jets, of which at least one is consistent with originating from the decay of a $b$ quark. We place 95% credibility level upper limits on the production cross section times standard model branching fraction for several mass hypotheses between 90 and $150 \mathrm{GeV}/c^2$. For a Higgs boson mass of $125 \mathrm{GeV}/c^2$, the observed (expected) limit is 6.7 (3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let