Device Discovery in Frequency Hopping Wireless Ad Hoc Networks

This research develops a method for efficient discovery of wireless devices for a frequency hopping spread spectrum, synchronous, ad hoc network comprised of clustered sub-networks. The Bluetooth wireless protocol serves as the reference protocol. The development of a discovery, or outreach, method for scatternets requires the characterization of performance metrics of Bluetooth piconets, many of which are unavailable in literature. Precise analytical models characterizing the interference caused to Bluetooth network traffic by inquiring devices, the probability mass function of packet error rates between arbitrary pairs of Bluetooth networks, and Bluetooth discovery time distribution are developed. Based on the characterized performance metrics, three scatternet outreach methods are developed and compared. Outreach methods which actively inquire on a regular basis, as proposed in literature, are shown to produce lower goodput, have greater mean packet delay, require more power, and cause significant delays in discovery. By passively remaining available for outreach, each of these disadvantages is avoided

Allosteric Activation of the Par-6 PDZ Via a Partial Unfolding Transition

Proteins exist in a delicate balance between the native and unfolded states, where thermodynamic stability may be sacrificed to attain the flexibility required for efficient catalysis, binding, or allosteric control. Partition-defective 6 (Par-6) regulates the Par polarity complex by transmitting a GTPase signal through the Cdc42/Rac interaction binding PSD-95/Dlg/ZO-1 (CRIB-PDZ) module that alters PDZ ligand binding. Allosteric activation of the PDZ is achieved by local rearrangement of the L164 and K165 side chains to stabilize the interdomain CRIB:PDZ interface and reposition a conserved element of the ligand binding pocket. However, microsecond to millisecond dynamics measurements revealed that L164/K165 exchange requires a larger rearrangement than expected. The margin of thermodynamic stability for the PDZ domain is modest (∼3 kcal/mol) and further reduced by transient interactions with the disordered CRIB domain. Measurements of local structural stability revealed that tertiary contacts within the PDZ are disrupted by a partial unfolding transition that enables interconversion of the L/K switch. The unexpected participation of partial PDZ unfolding in the allosteric mechanism of Par-6 suggests that native-state unfolding may be essential for the function of other marginally stable proteins

Click Chemistry to Probe Hsp90: Synthesis and Evaluation of a Series of Triazole Containing Novobiocin Analogues

A series of triazole-containing novobiocin analogues has been designed, synthesized and their inhibitory activity determined. These compounds contain a triazole ring in lieu of the amide moiety present in the natural product. The anti-proliferative effects of these compounds were evaluated against two breast cancer cell lines (SKBr-3 and MCF-7), and manifested activities similar to their amide-containing counterparts. In addition, Hsp90-dependent client protein degradation was observed via western blot analysis, further supporting a common mode of Hsp90 inhibition for both structural classes

Where Do We Go From Here? A Summary of Issues of Concern and Recommendations Developed During the Panel Discussion of the Large Pelagic Fishes Symposium

One of the goals of the Large Pelagic Fishes Symposium was to provide a forum for development of a list of Issues of Concern regarding large pelagic fishes and their fisheries in the Caribbean and Gulf of Mexico region. During the Symposium and ensuing Panel Discussion, it became clear that the level of consciousness concerning large pelagic fishes is of equal importance to that of other regional fisheries such as reef fishes and conch/lobster. Four major issues of concern regarding large pelagic fishes in the region surfaced during the Symposium. The Symposium Committee recommends that future resources and energy should be addressed to these identified concerns: 1) Fisheries policy-advisors and managers are not getting information from scientists in a timely fashion; 2) Approaches to reduce overfishing and its negative effects need to be strengthened; 3) Insufficient attention is being paid to instituting effective regional management; and 4) Initiatives to engage fishers in management processes and to help find solutions are inadequate. Panel members and Symposium participants made a number of recommendations for addressing each of these issues. The recommendations related to helping resolve each issue of concern are listed

Reconstitution of dynein transport to the microtubule plus end by kinesin

Cytoplasmic dynein powers intracellular movement of cargo toward the microtubule minus end. The first step in a variety of dynein transport events is the targeting of dynein to the dynamic microtubule plus end, but the molecular mechanism underlying this spatial regulation is not understood. Here, we reconstitute dynein plus-end transport using purified proteins from S. cerevisiae and dissect the mechanism using single-molecule microscopy. We find that two proteins–homologs of Lis1 and Clip170–are sufficient to couple dynein to Kip2, a plus-end-directed kinesin. Dynein is transported to the plus end by Kip2, but is not a passive passenger, resisting its own plus-end-directed motion. Two microtubule-associated proteins, homologs of Clip170 and EB1, act as processivity factors for Kip2, helping it overcome dynein's intrinsic minus-end-directed motility. This reveals how a minimal system of proteins transports a molecular motor to the start of its track. DOI: http://dx.doi.org/10.7554/eLife.02641.00

Gambogic Acid, a Natural Product Inhibitor of Hsp90

A high-throughput screening of natural product libraries identified (−)-gambogic acid (1), a component of the exudate of Garcinia harburyi, as a potential Hsp90 inhibitor, in addition to the known Hsp90 inhibitor celastrol (2). Subsequent testing established that 1 inhibited cell proliferation, brought about the degradation of Hsp90 client proteins in cultured cells, and induced the expression of Hsp70 and Hsp90, which are hallmarks of Hsp90 inhibition. Gambogic acid also disrupted the interaction of Hsp90, Hsp70, and Cdc37 with the heme-regulated eIF2α kinase (HRI, an Hsp90-dependent client) and blocked the maturation of HRI in vitro. Surface plasmon resonance spectroscopy indicated that 1 bound to the N-terminal domain of Hsp90 with a low micromolar Kd, in a manner that was not competitive with the Hsp90 inhibitor geldanamycin (3). Molecular docking experiments supported the posit that 1 binds Hsp90 at a site distinct from Hsp90s ATP binding pocket. The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors

Variation of a Lightning NOx Indicator for National Climate Assessment

During the past couple of years, an analysis tool was developed by the NASA Marshall Space Flight Center (MSFC) for the National Climate Assessment (NCA) program. The tool monitors and examines changes in lightning characteristics over the conterminous US (CONUS) on a continual basis. In this study, we have expanded the capability of the tool so that it can compute a new climate assessment variable that is called the Lightning NOx Indicator (LNI). Nitrogen oxides (NOx = NO + NO2) are known to indirectly influence our climate, and lightning NOx is the most important source of NOx in the upper troposphere (particularly in the tropics). The LNI is derived using Lightning Imaging Sensor (LIS) data and is computed by summing up the product of flash area x flash brightness over all flashes that occur in a particular region and period. Therefore, it is suggested that the LNI is a proxy to lightning NOx production. Specifically, larger flash areas are consistent with longer channel length and/or more energetic channels, and hence more NOx production. Brighter flashes are consistent with more energetic channels, and hence more NOx production. The location of the flash within the thundercloud and the optical scattering characteristics of the thundercloud are of course complicating factors. We analyze LIS data for the years 2003-2013 and provide geographical plots of the time-evolution of the LNI in order to determine if there are any significant changes or trends between like seasons, or from year to year