Support expansion C∗\mathrm C^*-algebras

We consider operators on $L^2$ spaces that expand the support of vectors in a manner controlled by some constraint function. The primary objects of study are $\mathrm C^*$-algebras that arise from suitable families of constraints, which we call support expansion $\mathrm C^*$-algebras. In the discrete setting, support expansion $\mathrm C^*$-algebras are classical uniform Roe algebras, and the continuous version featured here provides examples of "measurable" or "quantum" uniform Roe algebras as developed in a companion paper. We find that in contrast to the discrete setting, the poset of support expansion $\mathrm C^*$-algebras inside $\mathcal B(L^2(\mathbb R))$ is extremely rich, with uncountable ascending chains, descending chains, and antichains

UAS for Public Safety: Active Threat Recognition

The Center for Homeland Defense and Security identified an increase of active threat events, such as mass shootings, annually since 1999. Literature suggests that 90% of shootings were over before law enforcement arrived at the scene and the first responder response was limited to “surround and contain” until Special Weapons and Tactics Teams (SWAT) arrived on the scene. Using Unmanned Aircraft Systems (UAS) to detect which individual was the threat and type of weapon used can provide useful information to increase the speed of the response for first-on-scene rather than waiting for SWAT if the type of weapon was known. A UAS equipped with a full spectrum sensor compared traditional red-green-blue (RGB) images to near-infrared (NIR) images in a simulated active threat scenario. A true positive rate (TPR) metric was used to measure the percentage of correctly-detected weapons consisting of either a knife, pistol, rifle, shotgun, or shovel at slant range distances of 25-, 50-, 75-, and 100-feet respectively. A convenience sample of 102 survey participants, recruited from constituents of the Airborne Public Safety Association (APSA) and DRONERESPONDERS was conducted to observe 48 randomly-presented images to determine which type of weapon was detected. The results suggest that survey participants could correctly detect weapons at a 12% greater rate with the NIR sensor than the RGB sensor; however, the pistol had the largest difference in TPR between NIR and RGB sensors. The pistol had an increased probability of detection by 33% when using the NIR sensor compared to an RGB sensor. Additionally, differences were also observed between slant range distances. The closest distance of 25 feet showed a 42% increase in participants’ ability to correctly determine the weapon type compared to the 100-foot slant range distance. Therefore, using a NIR sensor-equipped UAS at flying a maximum slant range distance of 50 feet may help a first-responder determine the type of weapon before SWAT arrives on the scene

Prone ventilation in COVID-19 acute respiratory distress syndrome: Case report of two patients from Ethiopia

The COVID-19 pandemic is one of the largest health crises that the world has ever seen, infecting forty million people and killing more than 1 million to date. The disease has imposed a significant demand on health care resources due to the increased number and severely ill patients visiting facilities each day. Since there is no effective cure for COVID-19, supportive management with oxygen, steroids, anticoagulation, and prone positioning remains the major interventions. Prone ventilation is known to have a mortality benefit in intubated patients with acute respiratory distress syndrome (ARDS). However, studies on its role in intubated patients with COVID-19 ARDS (CARDS) are very scarce in resource-limited settings like Africa. We describe two patients with CARDS who were successfully treated with invasive mechanical ventilation, prone ventilation, and standard supportive care

Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non‐native polyketide substrates. Reactions pairing wildtype PKS modules with non‐native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non‐cognate TE domains was severely reduced. In contrast, non‐native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wild‐type polyketide synthases with non‐native substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of non‐native substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/3/anie202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/2/anie202004991_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/1/anie202004991.pd

Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non‐native polyketide substrates. Reactions pairing wildtype PKS modules with non‐native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non‐cognate TE domains was severely reduced. In contrast, non‐native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wild‐type polyketide synthases with non‐native substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of non‐native substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/2/ange202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/1/ange202004991.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/3/ange202004991_am.pd

Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane

The cell surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS). The network of charges and sugars provided by the dense packing of LPS molecules in the outer leaflet of the outer membrane interferes with the entry of hydrophobic compounds into the cell, including many antibiotics. In addition, LPS can be recognized by the immune system and plays a crucial role in many interactions between bacteria and their animal hosts. LPS is synthesized in the inner membrane of Gram-negative bacteria, so it must be transported across their cell envelope to assemble at the cell surface. Over the past two decades, much of the research on LPS biogenesis has focused on the discovery and understanding of Lpt, a multi-protein complex that spans the cell envelope and functions to transport LPS from the inner membrane to the outer membrane. This paper focuses on the early steps of the transport of LPS by the Lpt machinery: the extraction of LPS from the inner membrane. The accompanying paper (May JM, Sherman DJ, Simpson BW, Ruiz N, Kahne D. 2015 Phil. Trans. R. Soc. B 370, 20150027. (doi:10.1098/rstb.2015.0027)) describes the subsequent steps as LPS travels through the periplasm and the outer membrane to its final destination at the cell surface.Chemistry and Chemical Biolog

Lipopolysaccharide transport to the cell surface: periplasmic transport and assembly into the outer membrane

Gram-negative bacteria possess an outer membrane (OM) containing lipopolysaccharide (LPS). Proper assembly of the OM not only prevents certain antibiotics from entering the cell, but also allows others to be pumped out. To assemble this barrier, the seven-protein lipopolysaccharide transport (Lpt) system extracts LPS from the outer leaflet of the inner membrane (IM), transports it across the periplasm and inserts it selectively into the outer leaflet of the OM. As LPS is important, if not essential, in most Gram-negative bacteria, the LPS biosynthesis and biogenesis pathways are attractive targets in the development of new classes of antibiotics. The accompanying paper (Simpson BW, May JM, Sherman DJ, Kahne D, Ruiz N. 2015 Phil. Trans. R. Soc. B 370, 20150029. (doi:10.1098/rstb.2015.0029)) reviewed the biosynthesis of LPS and its extraction from the IM. This paper will trace its journey across the periplasm and insertion into the OM.Chemistry and Chemical Biolog

Decoupling catalytic activity from biological function of the ATPase that powers lipopolysaccharide transport

Gram-negative bacteria contain an unusual outer membrane that prevents the entry of most currently available antibiotics. This membrane contains a complex glycolipid, LPS, on the exterior. It is not understood how such a large molecule, which can contain hundreds of sugars and six fatty acyl chains, is transported across the cell envelope from its site of synthesis in the cytoplasmic membrane to the cell surface. Using a combination of genetics, biochemistry, and structural biology, we characterized residues in the protein that powers LPS transport to gain mechanistic insight into how ATP hydrolysis is coupled to the biological function of the transporter. These tools help us understand how to design antibiotics targeting this essential pathway.Chemistry and Chemical Biolog