A capillary valve for microfluidic systems.

Microfluidic systems are becoming increasingly complicated as the number of applications grows. The use of microfluidic systems for chemical and biological agent detection, for example, requires that a given sample be subjected to many process steps, which requires microvalves to control the position and transport of the sample. Each microfluidic application has its own specific valve requirements and this has precipitated the wide variety of valve designs reported in the literature. Each of these valve designs has its strengths and weaknesses. The strength of the valve design proposed here is its simplicity, which makes it easy to fabricate, easy to actuate, and easy to integrate with a microfluidic system. It can be applied to either gas phase or liquid phase systems. This novel design uses a secondary fluid to stop the flow of the primary fluid in the system. The secondary fluid must be chosen based on the type of flow that it must stop. A dielectric fluid must be used for a liquid phase flow driven by electroosmosis, and a liquid with a large surface tension should be used to stop a gas phase flow driven by a weak pressure differential. Experiments were carried out investigating certain critical functions of the design. These experiments verified that the secondary fluid can be reversibly moved between its 'valve opened' and 'valve closed' positions, where the secondary fluid remained as one contiguous piece during this transport process. The experiments also verified that when Fluorinert is used as the secondary fluid, the valve can break an electric circuit. It was found necessary to apply a hydrophobic coating to the microchannels to stop the primary fluid, an aqueous electrolyte, from wicking past the Fluorinert and short-circuiting the valve. A simple model was used to develop valve designs that could be closed using an electrokinetic pump, and re-opened by simply turning the pump off and allowing capillary forces to push the secondary fluid back into its stowed position

Engineered Nanostructures for High Thermal Conductivity Substrates

In the DARPA Thermal Ground Plane (TGP) program[1],we are developing a new thermal technology that will enable a monumental thermal technological leap to an entirely new class of electronics, particularly electronics for use in high-tech military systems. The proposed TGP is a planar, thermal expansion matched heat spreader that is capable of moving heat from multiple chips to a remote thermal sink. DARPA’s final goals require the TGP to have an effective conductivity of 20,000 W/mK, operate at 20g, with minimal fluid loss of less than 0.1%/year and in a large ultra-thin planar package of 10cmx20cm, no thicker than 1mm. The proposed TGP is based on a heat pipe architecture[2], whereby the enhanced transport of heat is made possible by applying nanoengineered surfaces to the evaporator, wick, and condenser surfaces. Ultra-low thermal resistances are engineered using superhydrophilic and superhydrophobic nanostructures on the interior surfaces of the TGP envelope. The final TGP design will be easily integrated into existing printed circuit board manufacturing technology. In this paper, we present the transport design, fabrication and packaging techniques, and finally a novel fluorescence imaging technique to visualize the capillary flow in these nanostructured wicks.United States. Defense Advanced Research Projects Agency (SSC SD Contract No. N66001-08-C-2008

Long-term impacts of invasive species on a native top predator in a large lake system

1. Declining abundances of forage fish and the introduction and establishment of non-indigenous species have the potential to substantially alter resource and habitat exploitation by top predators in large lakes. 2. We measured stable isotopes of carbon (δ13C) and nitrogen (δ15N) in field-collected and archived samples of Lake Ontario lake trout (Salvelinus namaycush) and five species of prey fish and compared current trophic relationships of this top predator with historical samples. 3. Relationships between δ15N and lake trout age were temporally consistent throughout Lake Ontario and confirmed the role of lake trout as a top predator in this food web. However, δ13C values for age classes of lake trout collected in 2008 ranged from 1.0 to 3.9‰ higher than those reported for the population sampled in 1992. 4. Isotope mixing models predicted that these changes in resource assimilation were owing to the replacement of rainbow smelt (Osmerus mordax) by round goby (Neogobius melanostomus) in lake trout diet and increased reliance on carbon resources derived from nearshore production. This contrasts with the historical situation in Lake Ontario where δ13C values of the lake trout population were dominated by a reliance on offshore carbon production. 5. These results indicate a reduced capacity of the Lake Ontario offshore food web to support the energetic requirements of lake trout and that this top predator has become increasingly reliant on prey resources that are derived from nearshore carbon pathways

Pushdown automata in statistical machine translation

This article describes the use of pushdown automata (PDA) in the context of statistical machine translation and alignment under a synchronous context-free grammar. We use PDAs to compactly represent the space of candidate translations generated by the grammar when applied to an input sentence. General-purpose PDA algorithms for replacement, composition, shortest path, and expansion are presented. We describe HiPDT, a hierarchical phrase-based decoder using the PDA representation and these algorithms. We contrast the complexity of this decoder with a decoder based on a finite state automata representation, showing that PDAs provide a more suitable framework to achieve exact decoding for larger synchronous context-free grammars and smaller language models. We assess this experimentally on a large-scale Chinese-to-English alignment and translation task. In translation, we propose a two-pass decoding strategy involving a weaker language model in the first-pass to address the results of PDA complexity analysis. We study in depth the experimental conditions and tradeoffs in which HiPDT can achieve state-of-the-art performance for large-scale SMT. </jats:p

Chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the leading cause of renal allograft loss in paediatric renal transplant recipients. CAN is the result of immunological and nonimmunological injury, including acute rejection episodes, hypoperfusion, ischaemia reperfusion, calcineurin toxicity, infection and recurrent disease. The development of CAN is often insidious and may be preceded by subclinical rejection in a well-functioning allograft. Classification of CAN is histological using the Banff classification of renal allograft pathology with classic findings of interstitial fibrosis, tubular atrophy, glomerulosclerosis, fibrointimal hyperplasia and arteriolar hyalinosis. Although improvement in immunosuppression has led to greater 1-year graft survival rates, chronic graft loss remains relatively unchanged and opportunistic infectious complications remain a problem. Protocol biopsy monitoring is not current practice in paediatric transplantation for CAN monitoring but may have a place if new treatment options become available. Newer immunosuppression regimens, closer monitoring of the renal allograft and management of subclinical rejection may lead to reduced immune injury leading to CAN in the paediatric population but must be weighed against the risk of increased immunosuppression and calcineurin inhibitor nephrotoxicity

Ephemeris and hazard assessment for near-Earth asteroid (101955) Bennu based on OSIRIS-REx data

Small bodies such as the near-Earth asteroid Bennu drift in their orbit due to thermal radiation forces (the Yarkovsky effect). Ground-based observations have indicated a nonzero probability of Bennu impacting Earth, depending on how its orbit evolves. Thus, among the goals of the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission to Bennu were to precisely measure the Yarkovsky effect and refine the impact hazard assessment for this body. Here we address these objectives. Using OSIRIS-REx spacecraft tracking data, we derive meter-level constraints on the distance between Earth and Bennu from January 2019 to October 2020. While these data greatly improve the knowledge of the trajectory of Bennu, they also require an unprecedented fidelity for the modeling of an asteroid’s trajectory. In particular, special care is needed to take into account the contribution of 343 small-body perturbers and the uncertainty in their masses. Radiation effects such as the Poynting–Robertson drag, so far only considered for interplanetary dust dynamics, now become a consideration for modeling the trajectory of a 500-m asteroid such as Bennu. By employing a thermophysical model based on OSIRIS-REx’s characterization of Bennu, we estimate a semimajor axis drift of−284.6 ± 0.2m/yr (signal-to-noise ratio∼1400) at epoch 2011 January 1 caused by the Yarkovsky effect. The largest source of modeling error is solar wind drag, which may lower the magnitude of the semimajor axis drift from the Yarkovsky effect by up to 0.16 m/yr. The Yarkovsky-related semimajor axis drift varies by roughly±1m/yr as the orbit of Bennu evolves due to planetary perturbations from 1900 to 2135. The Yarkovsky thermophysical model proves to be extremely accurate by predicting a bulk density estimate within 0.1% of that estimated through gravity science analysis. Compared to the information available before the OSIRIS-REx mission, the knowledge of the circumstances of the scattering Earth encounter that will occur in 2135 improves by a factor of 20, thus allowing us to rule out many previously possible impact trajectories. However, there remain some impact trajectories compatible with the data. Prior to the spacecraft encounter, the overall impact probability through 2200 was 3.7 × 10−4 (1 in 2700). As a result of our analysis, the cumulative impact probability through 2300 becomes 5.7 × 10−4 (1 in 1750) and the most significant individual impact solution is for September 2182, with an impact probability of 3.7 × 10−4 (1 in 2700). Both Bennu and (29075) 1950 DA have a Palermo scale value of −1.42 and share the distinction as the currently most hazardous object in the asteroid catalog

Survey of Activated FLT3 Signaling in Leukemia

Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia

Relationship of Optimism and Suicidal Ideation in Three Groups of Patients at Varying Levels of Suicide Risk

Optimism has been associated with reduced suicidal ideation, but there have been few studies in patients at high suicide risk. We analyzed data from three study populations (total N=319) with elevated risk of suicide: (1) patients with a recent acute cardiovascular event, (2) patients hospitalized for heart disease who had depression or an anxiety disorder, and (3) patients psychiatrically hospitalized for suicidal ideation or following a suicide attempt. For each study we analyzed the association between optimism (measured by the Life-Orientation Test-Revised) and suicidal ideation, and then completed an exploratory random effects meta-analysis of the findings to synthesize this data. The meta-analysis of the three studies showed that higher levels of self-reported optimism were associated with a lower likelihood of suicidal ideation (odds ratio [OR]=.89, 95% confidence interval [CI]=.85-.95, z=3.94, pz=3.57, pz=3.61,