A fully integrated paperfluidic molecular diagnostic chip for the extraction, amplification, and detection of nucleic acids from clinical samples

Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples through immunoassays; however, the detection of many disease targets relies on the much higher sensitivity and specificity achieved via nucleic acid amplification tests (NAAT). The steps involved in NAAT have recently begun to be explored in paper matrices, and our group, among others, has reported on paper-based extraction, amplification, and detection of DNA and RNA targets. Here, we integrate these paper-based NAAT steps into a single paperfluidic chip in a modular, foldable system that allows for fully integrated fluidic handling from sample to result. We showcase the functionality of the chip by combining nucleic acid isolation, isothermal amplification, and lateral flow detection of human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in less than 1 hour for rapid, early detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, and offering the potential for a point-of-care molecular diagnostic platform even in remote and resource-limited settings.U54 EB015403 - NIBIB NIH HHS; U54 EB015408 - NIBIB NIH HHS; U54-EB015403-S1 - NIBIB NIH HH

The Evolution and Extratropical Transition of Tropical Cyclones from a GPM, ISS LIS and GLM Perspective

Not much is known about the evolution of lightning within extra-tropical cyclones traversing the mid-latitudes, especially its oceans. To facilitate such studies we combine a recently constructed precipitation features (PF) database obtained from the Global Precipitation Measurement (GPM) mission constellation of satellites with lightning observations from the Geostationary Lightning Mapper (GLM) onboard GOES-16 and the Lightning Imaging Sensor (LIS) onboard the International Space Station (ISS). The goal of this study is to provide a new observationally-based view of the tropical to extra-tropical transition and its impact on lightning production. Such data fusion approaches, as presented here, will also be important in future satellite studies of convective precipitation

Проектування та оптимізація конструкцій гумових віброізоляторів силосних конструкцій

Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For Francisella tularensis, many genes of the Francisella pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of F. tularensis; five selected FPI mutants thereof, i.e., Delta iglA, Delta iglC, Delta iglG, Delta iglI, and Delta pdpE strains; and Listeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC(-/-) BMDM, MyD88(-/-) BMDM, J774 cells, or HeLa cells, LVS, Delta pdpE and Delta iglG mutants, and L. monocytogenes replicated efficiently in all five cell types, whereas the Delta iglA and Delta iglC mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC(-/-) BMDM, and HeLa cells. In contrast to the rapid replication in other cell types, L. monocytogenes showed no replication in MyD88(-/-) BMDM and LVS showed no replication in either BMDM or MyD88(-/-) BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment per se are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection.Originally included in thesis in manuscript form.</p

Denoising Diffusion Restoration Tackles Forward and Inverse Problems for the Laplace Operator

Diffusion models have emerged as a promising class of generative models that map noisy inputs to realistic images. More recently, they have been employed to generate solutions to partial differential equations (PDEs). However, they still struggle with inverse problems in the Laplacian operator, for instance, the Poisson equation, because the eigenvalues that are large in magnitude amplify the measurement noise. This paper presents a novel approach for the inverse and forward solution of PDEs through the use of denoising diffusion restoration models (DDRM). DDRMs were used in linear inverse problems to restore original clean signals by exploiting the singular value decomposition (SVD) of the linear operator. Equivalently, we present an approach to restore the solution and the parameters in the Poisson equation by exploiting the eigenvalues and the eigenfunctions of the Laplacian operator. Our results show that using denoising diffusion restoration significantly improves the estimation of the solution and parameters. Our research, as a result, pioneers the integration of diffusion models with the principles of underlying physics to solve PDEs.Comment: 29 page

Strain-induced superconductivity in Sr2IrO4

Multi-orbital quantum materials with strong interactions can host a variety of novel phases. In this work we study the possibility of interaction-driven superconductivity in the iridate compound Sr$_2$IrO$_4$ under strain and doping. We find numerous regimes of strain-induced superconductivity in which the pairing structure depends on model parameters. Spin-fluctuation mediated superconductivity is modeled by a Hubbard-Kanamori model with an effective particle-particle interaction, calculated via the random phase approximation. Magnetic orders are found using the Stoner criterion. The most likely superconducting order we find has $d$-wave pairing, predominantly in the total angular momentum, $J=1/2$ states. Moreover, an $s_{\pm}$-order which mixes different bands is found at high Hund's coupling, and at high strain anisotropic $s$- and $d$-wave orders emerge. Finally, we show that in a fine-tuned region of parameters a spin-triplet $p$-wave order exists. The combination of strong spin-orbit coupling, interactions, and a sensitivity of the band structure to strain proves a fruitful avenue for engineering new quantum phases.Comment: 26 pages, 21 figure

The Extratropical Transition of Tropical Storm Cindy From a GLM, ISS LIS and GPM Perspective

The distribution of lightning with respect to tropical convective precipitation systems has been well established in previous studies and more recently by the successful Tropical Rainfall Measuring Mission (TRMM). However, TRMM did not provide information about precipitation features poleward of +/-38 deg latitude. Hence we focus on the evolution of lightning within extra-tropical cyclones traversing the mid-latitudes, especially its oceans. To facilitate such studies, lightning data from the Geostationary Lightning Mapper (GLM) onboard GOES-16 was combined with precipitation features obtained from the Global Precipitation Measurement (GPM) mission constellation of satellites

RADIUS: Risk-Aware, Real-Time, Reachability-Based Motion Planning

Deterministic methods for motion planning guarantee safety amidst uncertainty in obstacle locations by trying to restrict the robot from operating in any possible location that an obstacle could be in. Unfortunately, this can result in overly conservative behavior. Chance-constrained optimization can be applied to improve the performance of motion planning algorithms by allowing for a user-specified amount of bounded constraint violation. However, state-of-the-art methods rely either on moment-based inequalities, which can be overly conservative, or make it difficult to satisfy assumptions about the class of probability distributions used to model uncertainty. To address these challenges, this work proposes a real-time, risk-aware reachability based motion planning framework called RADIUS. The method first generates a reachable set of parameterized trajectories for the robot offline. At run time, RADIUS computes a closed-form over-approximation of the risk of a collision with an obstacle. This is done without restricting the probability distribution used to model uncertainty to a simple class (e.g., Gaussian). Then, RADIUS performs real-time optimization to construct a trajectory that can be followed by the robot in a manner that is certified to have a risk of collision that is less than or equal to a user-specified threshold. The proposed algorithm is compared to several state-of-the-art chance-constrained and deterministic methods in simulation, and is shown to consistently outperform them in a variety of driving scenarios. A demonstration of the proposed framework on hardware is also provided

Stair Negotiation Made Easier using Novel Interactive Energy-Recycling Assistive Stairs

Here we show that novel, energy-recycling stairs reduce the amount of work required for humans to both ascend and descend stairs. Our low-power, interactive, and modular steps can be placed on existing staircases, storing energy during stair descent and returning that energy to the user during stair ascent. Energy is recycled through event-triggered latching and unlatching of passive springs without the use of powered actuators. When ascending the energy-recycling stairs, naive users generated 17.4 ± 6.9% less positive work with their leading legs compared to conventional stairs, with the knee joint positive work reduced by 37.7 ± 10.5%. Users also generated 21.9 ± 17.8% less negative work with their trailing legs during stair descent, with ankle joint negative work reduced by 26.0 ± 15.9%. Our low-power energy-recycling stairs have the potential to assist people with mobility impairments during stair negotiation on existing staircases

Associations between polygenic risk, negative symptoms, and functional connectome topology during a working memory task in early-onset schizophrenia

Working memory (WM) deficit in schizophrenia is thought to arise from a widespread neural inefficiency. However, we do not know if this deficit results from the illness-related genetic risk and influence the symptom burden in various domains, especially in patients who have an early onset illness. We used graph theory to examine the topology of the functional connectome in 99 subjects (27 early-onset schizophrenia (EOS), 24 asymptomatic siblings, and 48 healthy subjects) during an n-back task, and calculated their polygenic risk score (PRS) for susceptibility to schizophrenia. Linear regression analysis was used to test associations of the PRS, clinical symptoms, altered connectomic properties, and WM accuracy in EOS. Indices of small-worldness and segregation were elevated in EOS during the WM task compared with the other two groups; these connectomic aberrations correlated with increased PRS and negative symptoms. In patients with higher polygenic risk, WM performance was lower only when both the connectomic aberrations and the burden of negative symptoms were higher. Negative symptoms had a stronger moderating role in this relationship. Our findings suggest that the aberrant connectomic topology is a feature of WM task performance in schizophrenia; this relates to higher polygenic risk score as well as higher burden of negative symptoms. The deleterious effects of polygenic risk on cognition are played out via its effects on the functional connectome, as well as negative symptoms

Lightning Enriched Global Precipitation Feature Database

The Tropical Rainfall Measurement Mission (TRMM) has provided a wealth of insight about lightning and precipitation in the tropics. However TRMM did not provide coverage outside the tropics and sub-tropics (i.e., beyond 38latitude), and hence it was unable to sample the lightning activity and precipitation features over a large fraction of mid-latitude continents and oceans, including extratropical cyclone storm tracks. The Global Precipitation Measurement (GPM) mission picks up where TRMM left off in that it provides information on precipitation features in the mid-and high latitudes (up to 65N/S). However, GPM lacks a lightning instrument that can provide additional insights into mid-latitude thunderstorm activity and distribution. Hence we integrate observations from coincident the ISS Lightning Imaging Sensor (LIS) and the World Wide Lightning Location Network (WWLLN) observations with measurements from the GPM constellation of satellites, in particular to extend the existing GPM Precipitation Feature (PF) database so its data parameters are similar to that of the TRMM PF database (i.e., precipitation + lighting). Currently, WWLLN and ISS-LIS lightning have been collocated into precipitation features defined from GPM core satellite and constellation satellites observations