Dominance Relationships of Cycloheximide-Resistant Mutants of Schizophyllum commune Fr.

We have isolated several mutants of Schizophyllum commune Fr. able to grow on media containing cycloheximide in concentrations up to 30 mg/L. Genetic analyses of the resistant phenotypes show them to be due to the action of a single gene located on the first linkage group between the A-mating type factor and a gene for an adenine requirement (ade-ll). We have analyzed the growth and development of dikaryons made homoallelic for either the resistant or sensitive alleles as well as the heteroallelic dikaryon. These dikaryons showed different abilities to fruit when placed on media containing various concentrations of cycloheximide. Homoallelic sensitive strains failed to grow on any concentration of cycloheximide tested(\u3e 1 mg/L). Homoallelic resistant strains grew and fruited on all concentrations of cycloheximide up to 30 mg/ L. Heteroallelic dikaryons showed a response that was dose-dependent for fruiting, but not growth. As the concentration of cycloheximide was increased, these heteroallelic colonies showed a progressive loss of ability to form fruiting bodies and at concentrations greater than 30 mg/L, they gave rise to homokaryons as outgrowths from the colony edge. These homokaryons were all of the nuclear genotype associated with the original resistant component of the dikaryon

Innovative mechanism for measuring the mass properties of an object

The Kennedy Space Center Robotics Group recently completed development and testing on a novel approach to measure the mass properties of a rigid body. This unique design can measure the payload's weight, mass center location, and moments of inertia about three orthogonal axes. Furthermore, these measurements only require a single torque sensor and a single angular position sensor

Ecological interactions and coexistence are predicted by gene expression similarity in freshwater green algae

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136696/1/jec12759_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136696/2/jec12759.pd

Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice

Allograft transplantation requires chronic immunosuppression, but there is no effective strategy to evaluate the long-term maintenance of immunosuppression other than assessment of graft function. The ability to monitor naive alloreactive T cells would provide an alternative guide for drug therapy at early, preclinical stages of graft rejection and for evaluating tolerance-inducing protocols. To detect and quantify naive alloreactive T cells directly ex vivo, we used the unique ability of naive T cells to rapidly produce TNF-alpha but not IFN-gamma. Naive alloreactive T cells were identified by the production of TNF-alpha after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-gamma. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-alpha-producing cells was predictive for rejection in an in vivo cytotoxicity assay and correlated with skin allograft rejection. Naive alloreactive T cells were also detected in humans, suggesting clinical relevance. We conclude that rapid production of TNF-alpha can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection

Flexible Session Management in a Distributed Environment

Many secure communication libraries used by distributed systems, such as SSL, TLS, and Kerberos, fail to make a clear distinction between the authentication, session, and communication layers. In this paper we introduce CEDAR, the secure communication library used by the Condor High Throughput Computing software, and present the advantages to a distributed computing system resulting from CEDAR's separation of these layers. Regardless of the authentication method used, CEDAR establishes a secure session key, which has the flexibility to be used for multiple capabilities. We demonstrate how a layered approach to security sessions can avoid round-trips and latency inherent in network authentication. The creation of a distinct session management layer allows for optimizations to improve scalability by way of delegating sessions to other components in the system. This session delegation creates a chain of trust that reduces the overhead of establishing secure connections and enables centralized enforcement of system-wide security policies. Additionally, secure channels based upon UDP datagrams are often overlooked by existing libraries; we show how CEDAR's structure accommodates this as well. As an example of the utility of this work, we show how the use of delegated security sessions and other techniques inherent in CEDAR's architecture enables US CMS to meet their scalability requirements in deploying Condor over large-scale, wide-area grid systems

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance