REGULATION OF THE INNATE IMMUNE RESPONSES AUTOPHAGY AND INFLAMMASOME ACTIVATION DURING BACTERIAL INFECTION

Autophagy is an innate anti-microbial host defense that maintains tissue homeostasis. Autophagy is negatively regulated by the nutrient-sensing mTORC1 complex. In this study, we examined the regulatory mechanisms of autophagy and inflammasome activation during Ehrlichia infection. Monocytic Ehrlichia is a Gram negative intracellular bacterial pathogen that causes fatal human monocytic ehrlichiosis. Ehrlichia lacks LPS, but induces inflammasome activation leading to acute liver damage. In humans, the potentially fatal human monocytic ehrlichiosis (HME) mimics sepsis and toxic shock-like syndrome [1, 2], making Ehrlichia a viable model system for these conditions in the absence of LPS. During virulent Ehrlichia infection confocal data shows that autophagy increased with infection, despite clear activation of the autophagy inhibitor mTORC1. This is likely due to a balance of mTORC1 dependent and independent autophagy. Employing bone marrow derived macrophages (BMM) from mice deficient in MyD88 and TLR9 we reveal a novel signaling pathway for IOE mediated autophagy regulation and inflammasome activation centered around IFNβ production. We have previously shown that the virulent Ehrlichia strain Ixodes ovatus Ehrlichia (IOE) expresses higher levels of IFNβ than the avirulent strain Ehrlichia muris (EM) [3]. When IFNβ is added to BMM mTORC1 activation increases, a phenomenon further increased when IFNβ is added to IOE infected BMM. Both IOE and IFNβ mediated mTORC1 activation are abrogated by knockout of the TLR9 receptor. This placed IFNβ upstream of TLR9 in the IOE mediated mTORC1 signaling pathway. As both TLR9 is activated by dsDNA, we have hypothesized that these receptors are activated by mitochondrial DNA released in response to IFNβ mediated DAMP production. These data suggest that LPS-negative Ehrlichia regulates autophagy with mTORC1, and that this mTORC1 activation is achieved via IFNβ mediated TLR9. Our findings reveal a novel regulation of autophagy and the inflammasome in macrophages via MyD88 and mTORC1 during infection with intracellular pathogens

Experimental investigation on pore size distribution and drying kinetics during lyophilization of sugar solutions

[EN] The pore structure is a decisive factor for the process efficiency and product quality of freeze dried products. In this work the two-dimensional ice crystal structure was investigated for maltodextrin solutions with different concentrations by a freeze drying microscope. The resulting drying kinetics was investigated for different pore structures. Additionally the three-dimensional pore structure of the freeze dried samples was measured by µ-computed tomography and the pore size distribution was quantified by image analysis techniques. The two- and three-dimensional pore size distributions were compared and linked to the drying kinetics.Foerst, P.; Lechner, M.; Vorhauer, N.; Schuchmann, H.; Tsotsas, E. (2018). Experimental investigation on pore size distribution and drying kinetics during lyophilization of sugar solutions. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1415-1422. https://doi.org/10.4995/IDS2018.2018.7310OCS1415142

Beurling primes with large oscillation

A Beurling generalized number system is constructed having integer counting function N B ( x ) = κ x + O ( x θ ) with κ >0 and 1/2 (4/ e )(1− θ ). The construction uses elements of classical analytic number theory and probability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46253/1/208_2005_Article_638.pd

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate

Salmon Lake Residents Interview, May 7, 1988

Each interviewee recalls when he or she first saw Salmon Lake. They reminiscence about people and events that played a part in the Lake\u27s history.https://scholarworks.umt.edu/mtcommunities_oralhistory/1012/thumbnail.jp