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Some of the most visible expressions of human culture are illustrated architecturally. Unfortunately for archaeologists, the architecture being studied is not always visible and must be inferred from soil inconsistencies or charred remains. This study deals with research into roughly a millennium of Native American architecture in the Southeast and includes research on the variation of construction techniques employed both above and below ground. Most of the architecture discussed is that of domestic houses with some emphasis on large public buildings and sweat lodges. The authors use an array of methods and techniques in examining native architecture including experimental archaeology, ethnohistory, ethnography, multi-variant analysis, structural engineering, and wood science technology. A major portion of the work, and probably the most important in terms of overall significance, is that it addresses the debate of early Mississippian houses and what they looked like above ground and the changes that occurred both before and after the arrival of Europeans. Contributors:Dennis B. BlantonTamira K. Brennan Ramie A. GougeonTom H. GreshamVernon J. Knight Jr. Cameron H. Lacquement Robert H. Lafferty, IIIMark A. McConaughyNelson A. Reed Robert J. ScottLynne P. Sullivan

Some of the most visible expressions of human culture are illustrated architecturally. Unfortunately for archaeologists, the architecture being studied is not always visible and must be inferred from soil inconsistencies or charred remains. This study deals with research into roughly a millennium of Native American architecture in the Southeast and includes research on the variation of construction techniques employed both above and below ground. Most of the architecture discussed is that of domestic houses with some emphasis on large public buildings and sweat lodges. The authors use an array of methods and techniques in examining native architecture including experimental archaeology, ethnohistory, ethnography, multi-variant analysis, structural engineering, and wood science technology. A major portion of the work, and probably the most important in terms of overall significance, is that it addresses the debate of early Mississippian houses and what they looked like above ground and the changes that occurred both before and after the arrival of Europeans.   Contributors : Dennis B. Blanton Tamira K. Brennan  Ramie A. Gougeon Tom H. Gresham Vernon J. Knight Jr.  Cameron H. Lacquement  Robert H. Lafferty, III Mark A. McConaughy Nelson A. Reed  Robert J. Scott Lynne P. Sullivan

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis. A series of compounds are discovered for the treatment of visceral leishmaniasis, and cdc2-related kinase 12 (CRK12) is identified as the probable primary drug target.

Traumatic brain injury (TBI) elicits the immediate production of proinflammatory cytokines which participate in regulating the immune response. While the mechanisms of adaptive immunity in secondary injury are well characterized, the role of the innate response is unclear. Recently, the NLR inflammasome has been shown to become activated following TBI, causing processing and release of interleukin-1β (IL-1β). The inflammasome is a multiprotein complex consisting of nucleotide-binding domain and leucine-rich repeat containing proteins (NLR), caspase-1, and apoptosis-associated speck-like protein (ASC). ASC is upregulated after TBI and is critical in coupling the proteins during complex formation resulting in IL-1β cleavage. To directly test whether inflammasome activation contributes to acute TBI-induced damage, we assessed IL-1β, IL-18, and IL-6 expression, contusion volume, hippocampal cell death, and motor behavior recovery in Nlrp1 −/−, Asc −/−, and wild type mice after moderate controlled cortical impact (CCI) injury. Although IL-1β expression is significantly attenuated in the cortex of Nlrp1 −/− and Asc −/− mice following CCI injury, no difference in motor recovery, cell death, or contusion volume is observed compared to wild type. These findings indicate that inflammasome activation does not significantly contribute to acute neural injury in the murine model of moderate CCI injury.

This multicenter, randomized trial compared the effect of continuous renal-replacement therapy at two different levels of intensity on 90-day mortality among critically ill adults with acute kidney injury. The higher-intensity therapy did not reduce mortality at 90 days. This trial compared the effect of continuous renal-replacement therapy at two different levels of intensity on mortality among critically ill adults with acute kidney injury. The higher-intensity therapy did not reduce mortality at 90 days. Acute kidney injury is associated with substantial morbidity and mortality. 1 It is a common finding among patients in the intensive care unit (ICU) 2 and is an independent predictor of mortality. 3 Acute kidney injury severe enough to result in the use of renal-replacement therapy affects approximately 5% of patients admitted to the ICU and is associated with a mortality rate of 60%. 4 The optimal approach to renal-replacement therapy, as well as the optimal intensity and timing of such therapy, in critically ill patients remains unclear. In one single-center, randomized, controlled study in which continuous renal-replacement therapy was the sole treatment approach, . . .

Visceral leishmaniasis (VL) causes significant mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. We describe the development of a novel anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of VL, has suitable physicochemical, pharmacokinetic and toxicological properties for further development and has been declared a preclinical candidate. Detailed mode of action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a novel, druggable, target for VL.