Understanding the Interactions of Developing Thymocytes and Antigen Presenting Cells in the Thymic Medulla

Various thymic APC subsets have been invoked in deletional tolerance and Treg cell induction, but previous studies either assessed total T cell numbers or used TCR transgenic lines, obscuring roles that individual thymic APC subsets might serve for particular antigen-specific T cell populations. Utilizing T cell receptor sequencing, we found that medullary thymic epithelial cells (mTECs) and bone marrow-derived (BM) APCs delete or select unique conventional and Treg cell TCR repertoires, demonstrating distinct roles for these APCs. We show that BM APCs and mTECs each contribute to Aire-dependent T cell tolerance development, albeit through either cooperative or autologous antigen presentation respectively, and that cooperative antigen transfer is likely performed by thymic CD8+ DCs. Using our established TCR sequencing approach, In addition, we sought to understand CD8+ DC-mediated cooperative antigen presentation further. We quantified the extent of CD8+ DC-dependent Treg cell and negative selection and the proportion of this selection that is achieved through Aire-dependent cooperative antigen transfer. We also found that CD36 expression by CD8+ DCs facilitates Aire-dependent cooperative antigen transfer both in vivo and via TCR sequencing. Finally, we found that in the absence of thymic CD8+ DCs or CD36 expression; direct allo-tolerance fails to develop leading to catastrophic acute GVHD

An Environmental Impact Assessment of Perfluorocarbon Thermal Working Fluid Use On Board Crewed Spacecraft

The design and operation of crewed spacecraft requires identifying and evaluating chemical compounds that may present reactivity and compatibility risks with the environmental control and life support (ECLS) system. Such risks must be understood so that appropriate design and operational controls, including specifying containment levels, can be instituted or an appropriate substitute material selected. Operational experience acquired during the International Space Station (ISS) program has found that understanding ECLS system and environmental impact presented by thermal control system working fluids is imperative to safely operating any crewed space exploration vehicle. Perfluorocarbon fluids are used as working fluids in thermal control fluid loops on board the ISS. Also, payload hardware developers have identified perfluorocarbon fluids as preferred thermal control working fluids. Interest in using perfluorocarbon fluids as thermal control system working fluids for future crewed space vehicles and outposts is high. Potential hazards associated with perfluorocarbon fluids are discussed with specific attention given to engineering assessment of ECLS system compatibility, compatibility testing results, and spacecraft environmental impact. Considerations for perfluorocarbon fluid use on crewed spacecraft and outposts are summarized

Finite temperature effective action, AdS_5 black holes, and 1/N expansion

We propose a phenomenological matrix model to study string theory in AdS_5 \times S_5 in the canonical ensemble. The model reproduces all the known qualitative features of the theory. In particular, it gives a simple effective potential description of Euclidean black hole nucleation and the tunnelling between thermal AdS and the big black hole. It also has some interesting predictions. We find that there exists a critical temperature at which the Euclidean small black hole undergoes a Gross-Witten phase transition. We identify the phase transition with the Horowitz-Polchinski point where the black hole horizon size becomes comparable to the string scale. The appearance of the Hagedorn divergence of thermal AdS is due to the merger of saddle points corresponding to the Euclidean small black hole and thermal AdS. The merger can be described in terms of a cusp (A_3) catastrophe and divergences at the perturbative string level are smoothed out at finite string coupling using standard techniques of catastrophe theory.Comment: 41 pages, 3 eps figures, uses harvma

SCHEMA Recombination of a Fungal Cellulase Uncovers a Single Mutation That Contributes Markedly to Stability

A quantitative linear model accurately (R^2 = 0.88) describes the thermostabilities of 54 characterized members of a family of fungal cellobiohydrolase class II (CBH II) cellulase chimeras made by SCHEMA recombination of three fungal enzymes, demonstrating that the contributions of SCHEMA sequence blocks to stability are predominantly additive. Thirty-one of 31 predicted thermostable CBH II chimeras have thermal inactivation temperatures higher than the most thermostable parent CBH II, from Humicola insolens, and the model predicts that hundreds more CBH II chimeras share this superior thermostability. Eight of eight thermostable chimeras assayed hydrolyze the solid cellulosic substrate Avicel at temperatures at least 5 °C above the most stable parent, and seven of these showed superior activity in 16-h Avicel hydrolysis assays. The sequence-stability model identified a single block of sequence that adds 8.5 °C to chimera thermostability. Mutating individual residues in this block identified the C313S substitution as responsible for the entire thermostabilizing effect. Introducing this mutation into the two recombination parent CBH IIs not featuring it (Hypocrea jecorina and H. insolens) decreased inactivation, increased maximum Avicel hydrolysis temperature, and improved long time hydrolysis performance. This mutation also stabilized and improved Avicel hydrolysis by Phanerochaete chrysosporium CBH II, which is only 55–56% identical to recombination parent CBH IIs. Furthermore, the C313S mutation increased total H. jecorina CBH II activity secreted by the Saccharomyces cerevisiae expression host more than 10-fold. Our results show that SCHEMA structure-guided recombination enables quantitative prediction of cellulase chimera thermostability and efficient identification of stabilizing mutations

Inner-sphere vs. outer-sphere reduction of uranyl supported by a redox-active, donor-expanded dipyrrin

The uranyl(VI) complex UO2Cl(L) of the redox-active, acyclic diimino-dipyrrin anion, L− is reported and its reaction with inner- and outer-sphere reductants studied. Voltammetric, EPR-spectroscopic and X-ray crystallographic studies show that chemical reduction by the outer-sphere reagent CoCp2 initially reduces the ligand to a dipyrrin radical, and imply that a second equivalent of CoCp2 reduces the U(VI) centre to form U(V). Cyclic voltammetry indicates that further outer-sphere reduction to form the putative U(IV) trianion only occurs at strongly cathodic potentials. The initial reduction of the dipyrrin ligand is supported by emission spectra, X-ray crystallography, and DFT; the latter also shows that these outer-sphere reactions are exergonic and proceed through sequential, one-electron steps. Reduction by the inner-sphere reductant [TiCp2Cl]2 is also likely to result in ligand reduction in the first instance but, in contrast to the outer-sphere case, reduction of the uranium centre becomes much more favoured, allowing the formation of a crystallographically characterised, doubly-titanated U(IV) complex. In the case of inner-sphere reduction only, ligand-to-metal electron-transfer is thermodynamically driven by coordination of Lewis-acidic Ti(IV) to the uranyl oxo, and is energetically preferable over the disproportionation of U(V). Overall, the involvement of the redox-active dipyrrin ligand in the reduction chemistry of UO2Cl(L) is inherent to both inner- and outer-sphere reduction mechanisms, providing a new route to accessing a variety of U(VI), U(V), and U(IV) complexes

Structural variation, dynamics, and catalytic application of palladium(II) complexes of di-N-heterocyclic carbene-amine ligands

A series of palladium(II) complexes incorporating di-NHC-amine ligands has been prepared and their structural, dynamic and catalytic behaviour investigated. The complexes [trans-(k(2)-(CN)-C-tBu(Bn)CN(Bn)C-tBu)PdCl2] (12) and [trans-(kappa(2)-(CN)-C-Mes(H)C-Mes)PdCl2] (13) do not exhibit interaction between the amine nitrogen and palladium atom respectively. NMR spectroscopy between - 40 and 25 degrees C shows that the di-NHC-amine ligand is flexible expressing C-s symmetry and for 13 rotation of the mesityl groups is prevented. In the related C-1 complex [(kappa(3)-(CN)-C-tBu(H)C-tBu)PdCl][CI] (14) coordination of NHC moieties and amine nitrogen atom is observed between -40 and 25 degrees C. Reaction between 12 - 14 and two equivalents of AgBF4 in acetonitrile gives the analogous complexes [trans-(kappa(2)-(CN)-C-tBu(Bn)C-tBu)PdCl2] (12) and [trans-(kappa(CN)-C-2Mes(H)C-Mes)PdCl2] (13) do not exhibit interaction between the amine nitrogen and palladium atom respectively. NMR spectroscopy between -40 ans 25 degrees C shows the di-NHC-amine ligand is flexible expressing C-s symmetry and for 13 rotation of the mesityl groups is prevented. In the related C-1 complex [kappa(3)-(CN)-C-tBu(H)C-tBu)PdCI][CI] (14) coordination of NHC moieties and amine nitrogen atom is observed between -40 and 25 degrees C.Reaction between 12-14 and two equivalents of AgBF4 in acetonitrile gives the analogous complexes [trans-(kappa(2)-(CN)-C-tBu(H)(CPd)-Pd-tBu(MeCN)(2)][BF4](2) (15), [trans-(kappa(CN)-C-2Mes(H)C-Mes)Pd(MeCN)(2)[BF4](2 (16)) and [(kappa(3)-(CN)-C-tBu(H)C-tBu)Pd(MeCN)][BF4](2) (17) indicating that ligand structure determines amine coordination. The single crystal X-ray structures of 12, 17 and two ligand imidazolium salt precursors C-tBu(H)N(Bn)C(H) (tBu)][CI](2) (2) and [C-tBu(H) N(H)C(H)(tBu)][BPh4](2) (4) have been determined. Complexes 12-14 and 15-17 have been shown to be active precatalysts for Heck and hydroamination reactions respectively

Selfish or altruistic? An analysis of alarm call function in wild capuchin monkeys, Cebus apella nigritus

Alarm calls facilitate some antipredatory benefits of group living but may endanger the caller by attracting the predator's attention. A number of hypotheses invoking kin selection and individual selection have been proposed to explain how such behaviour could evolve. This study tests eight hypotheses for alarm call evolution by examining the responses of tufted capuchin monkeys to models of felids, perched raptors and vipers. Specifically, this study examines: (1) differences between individuals in their propensity to call in response to different threat types, (2) whether there is an audience effect for alarm calling and (3) the response of conspecifics to alarms. Results indicate that the benefits likely to be afforded to the caller vary with stimulus type. Alarm calling in response to felids is most likely selfish, with calls apparently directed towards both the predator and potential conspecific mobbers. Alarm calling in response to vipers attracts additional mobbers as well, but also appears to be driven by kin selection in the case of males and parental care benefits in the case of females. Alarm responses to perched raptors are rare, but seem to be selfish, with callers benefiting by recruiting additional mobbers

SUSTAINABLE GREYWATER FILTRATION ON A RESIDENTIAL SCALE

Gemstone Team PURIFYThis project proposes a sustainable greywater filtration system for residential-scale water reuse. Recycled greywater can be used in toilet water, outdoor irrigation, car washing, and clothes washing, reducing the demand for potable water. Although pilot-scale systems have been demonstrated for greywater recycling, residential-scale applications remain unexplored, as treatment options on a residential scale are limited. This project designed and implemented a residential-scale greywater filtration system into reACT, the University of Maryland’s 2017 Solar Decathlon House. The system was constructed within the constraints of the Solar Decathlon, with an emphasis on sustainability. It used several filtration methods, including micron, mineral sand, activated carbon, and ultraviolet disinfection. Multi-phase water testing was conducted to evaluate pH, turbidity, chemical oxygen demand, total organic carbon, and total nitrogen. The prototype proved capable of functioning in a real-world setting and filtering water to meet several non-potable urban reuse standards