Nonlinear modal coupling in a high-stress doubly-clamped nanomechanical resonator

We present results from a study of the nonlinear intermodal coupling between different flexural vibrational modes of a single high-stress, doubly-clamped silicon nitride nanomechanical beam. The measurements were carried out at 100 mK and the beam was actuated using the magnetomotive technique. We observed the nonlinear behavior of the modes individually and also measured the coupling between them by driving the beam at multiple frequencies. We demonstrate that the different modes of the resonator are coupled to each other by the displacement induced tension in the beam, which also leads to the well known Duffing nonlinearity in doubly-clamped beams.Comment: 15 pages, 7 figure

Dissipation due to tunneling two-level systems in gold nanomechanical resonators

We present measurements of the dissipation and frequency shift in nanomechanical gold resonators at temperatures down to 10 mK. The resonators were fabricated as doubly-clamped beams above a GaAs substrate and actuated magnetomotively. Measurements on beams with frequencies 7.95 MHz and 3.87 MHz revealed that from 30 mK to 500 mK the dissipation increases with temperature as $T^{0.5}$, with saturation occurring at higher temperatures. The relative frequency shift of the resonators increases logarithmically with temperature up to at least 400 mK. Similarities with the behavior of bulk amorphous solids suggest that the dissipation in our resonators is dominated by two-level systems

Three Conservation Applications of Astronaut Photographs of Earth: Tidal Flat Loss (Japan), Elephant Impacts on Vegetation (Botswana), and Seagrass and Mangrove Monitoring (Australia)

NASA photographs taken from low Earth orbit can provide information relevant to conservation biology. This data source is now more accessible due to improvements in digitizing technology, Internet file transfer, and availability of image processing software. We present three examples of conservation-related projects that benefited from using orbital photographs. (1) A time series of photographs from the Space Shuttle showing wetland conversion in Japan was used as a tool for communicating about the impacts of tidal flat loss. Real-time communication with astronauts about a newsworthy event resulted in acquiring current imagery. These images and the availability of other high resolution digital images from NASA provided timely public information on the observed changes. (2) A Space Shuttle photograph of Chobe National Park in Botswana was digitally classified and analyzed to identify the locations of elephant-impacted woodland. Field validation later confirmed that areas identified on the image showed evidence of elephant impacts. (3) A summary map from intensive field surveys of seagrasses in Shoalwater Bay, Australia was used as reference data for a supervised classification of a digitized photograph taken from orbit. The classification was able to distinguish seagrasses, sediments and mangroves with accuracy approximating that in studies using other satellite remote sensing data. Orbital photographs are in the public domain and the database of nearly 400,000 photographs from the late 1960s to the present is available at a single searchable location on the Internet. These photographs can be used by conservation biologists for general information about the landscape and in quantitative applications

Audio mixing in a tri-port nano-electro-mechanical device

We report on experiments performed on a cantilever-based tri-port nano-electro-mechanical (NEMS) device. Two ports are used for actuation and detection through the magnetomotive scheme, while the third port is a capacitively coupled gate electrode. By applying a low frequency voltage signal on the gate, we demonstrate mixing in the mechanical response of the device, even for {\it low magnetomotive drives, without resorting to conduction measurements through the NEMS}. The technique can thus be used in particular in the linear regime, as an alternative to nonlinear mixing, for normal conducting devices. An analytic theory is presented reproducing the data without free parameter

Intact landscape promotes gene flow and low genetic structuring in the threatened Eastern Massasauga Rattlesnake

Genetic structuring of wild populations is dependent on environmental, ecological, and life-history factors. The specific role environmental context plays in genetic structuring is important to conservation practitioners working with rare species across areas with varying degrees of fragmentation. We investigated fine-scale genetic patterns of the federally threatened Eastern Massasauga Rattlesnake (Sistrurus catenatus) on a relatively undisturbed island in northern Michigan, USA. This species often persists in habitat islands throughout much of its distribution due to extensive habitat loss and distance-limited dispersal. We found that the entire island population exhibited weak genetic structuring with spatially segregated variation in effective migration and genetic diversity. The low level of genetic structuring contrasts with previous studies in the southern part of the species' range at comparable fine scales (~7 km), in which much higher levels of structuring were documented. The island population's genetic structuring more closely resembles that of populations from Ontario, Canada, that occupy similarly intact habitats. Intrapopulation variation in effective migration and genetic diversity likely corresponds to the presence of large inland lakes acting as barriers and more human activity in the southern portion of the island. The observed genetic structuring in this intact landscape suggests that the Eastern Massasauga is capable of sufficient interpatch movements to reduce overall genetic structuring and colonize new habitats. Landscape mosaics with multiple habitat patches and localized barriers (e.g., large water bodies or roads) will promote gene flow and natural colonization for this declining species

Improving accuracy of nanothermal measurements via spatially distributed scanning thermal microscope probes

Advances in material design and device miniaturization lead to physical properties that may significantly differ from the bulk ones. In particular, thermal transport is strongly affected when the device dimensions approach the mean free path of heat carriers. Scanning Thermal Microscopy (SThM) is arguably the best approach for probing nanoscale thermal properties with few tens of nm lateral resolution. Typical SThM probes based on microfabricated Pd resistive probes (PdRP) using a spatially distributed heater and a nanoscale tip in contact with the sample provide high sensitivity and operation in ambient, vacuum, and liquid environments. Although some aspects of the response of this sensor have been studied, both for static and dynamic measurements, here we build an analytical model of the PdRP sensor taking into account finite dimensions of the heater that improves the precision and stability of the quantitative measurements. In particular, we analyse the probe response for heat flowing through a tip to the sample and due to probe selfheating and theoretically and experimentally demonstrate that they can differ by more than 50%, hence introducing significant correction in the SThM measurements. Furthermore, we analyzed the effect of environmental parameters such as sample and microscope stage temperatures and laser illumination, which allowed reducing the experimental scatter by a factor of 10. Finally, varying these parameters, we measured absolute values of heat resistances and compared these to the model for both ambient and vacuum SThM operations, providing a comprehensive pathway improving the precision of the nanothermal measurements in SThM

The Mitochondrial Protease LonP1 Promotes Proteasome Inhibitor Resistance in Multiple Myeloma

Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to treat this incurable cancer. These drugs interfere with the main pathway of protein degradation and lead to the accumulation of damaged proteins inside cells. Despite promising initial responses, multiple myeloma cells eventually become drug resistant in most patients. The biology behind relapsed/refractory multiple myeloma is complex and poorly understood. Several studies provide evidence that in addition to the proteasome, mitochondrial proteases can also contribute to protein quality control outside of mitochondria. We therefore hypothesized that mitochondrial proteases might counterbalance protein degradation in cancer cells treated with proteasome inhibitors. Using clinical and experimental data, we found that overexpression of the mitochondrial matrix protease LonP1 (Lon Peptidase 1) reduces the efficacy of proteasome inhibitors. Some proteasome inhibitors partially crossinhibit LonP1. However, we show that the resistance effect of LonP1 also occurs when using drugs that do not block this protease, suggesting that LonP1 can compensate for loss of proteasome activity. These results indicate that targeting both the proteasome and mitochondrial proteases such as LonP1 could be beneficial for treatment of multiple myeloma

Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways by NE. These NE-regulated pathways are critical for cell-to-cell contact and motility and consistent with the delay in metastasis in NE-/- mice. To evaluate whether pharmacologic inhibition of NE inhibited pulmonary metastasis and phenotypically mimicked PyMT NE-/- mice, we utilized AZD9668, a clinically available and specific NE inhibitor. We found AZD9668 treated PyMT-NE+/+ mice showed significantly reduced lung metastases, improved recurrence-free, metastasis-free and overall survival, and their tumors showed similar molecular alterations as those observed in PyMT-NE-/- tumors. Finally, we identified a NE-specific signature that predicts recurrence and metastasis in patients with breast cancer. Collectively, our studies suggest that genetic ablation and pharmacologic inhibition of NE reduces metastasis and extends survival of mouse models of breast cancer, providing rationale to examine NE inhibitors as a treatment strategy for the clinical management of patients with metastatic breast cancer