Miracle-dz/UniFAR-FTUs huggingface dataset:
Impacts of hydrodynamic conditions and microscale surface roughness on the critical shear stress to develop and thickness of early‐stage Pseudomonas putida biofilms

Biofilms can increase pathogenic contamination of drinking water, cause biofilm‐related diseases, alter the sediment erosion rate, and degrade contaminants in wastewater. Compared with mature biofilms, biofilms in the early‐stage have been shown to be more susceptible to antimicrobials and easier to remove. Mechanistic understanding of physical factors controlling early‐stage biofilm growth is critical to predict and control biofilm development, yet such understanding is currently incomplete. Here, we reveal the impacts of hydrodynamic conditions and microscale surface roughness on the development of early‐stage Pseudomonas putida biofilm through a combination of microfluidic experiments, numerical simulations, and fluid mechanics theories. We demonstrate that early‐stage biofilm growth is suppressed under high flow conditions and that the local velocity for early‐stage P. putida biofilms (growth time < 14 h) to develop is about 50 μm/s, which is similar to P. putida's swimming speed. We further illustrate that microscale surface roughness promotes the growth of early‐stage biofilms by increasing the area of the low‐flow region. Furthermore, we show that the critical average shear stress, above which early‐stage biofilms cease to form, is 0.9 Pa for rough surfaces, three times as large as the value for flat or smooth surfaces (0.3 Pa). The important control of flow conditions and microscale surface roughness on early‐stage biofilm development, characterized in this study, will facilitate future predictions and managements of early‐stage P. putida biofilm development on the surfaces of drinking water pipelines, bioreactors, and sediments in aquatic environments.
Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2

Abstract Aims Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. Methods and results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM–10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3–10 µM (by 20–32%/25–30%/44–45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3–3 µM. Conclusion A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS.
Multigrid Method for 2D Helmholtz Equation using Higher Order Finite Difference Scheme Accelerated by Krylov Subspace

A sixth-order compact difference scheme is applied with uniform mesh sizes in different coordinate directions to discretize a two dimensional Helmholtz equation. Multigrid method is designed to solve the resulting sparse linear systems. Numerical results are conducted to test the accuracy and performance of the sixth-order compact difference scheme with multigrid method and to compare it with the standard second-order difference scheme and fourth-order compact difference scheme. The errors norms L 2 is used to establish efficiency and accuracy of the proposed scheme
A Semi-Empirical Surface Pressure Spectrum Model for Airfoil Trailing-Edge Noise Prediction

A semi-empirical model to determine the wall pressure frequency spectrum beneath a two-dimensional, pressure gradient turbulent boundary-layer is presented. The model is derived based on the experimental wall pressure data of various research groups. The experimental database includes both the equilibrium flat plate and non-equilibrium airfoil boundary-layer flow cases and covers a large range of Reynolds numbers, 1.0 times 103 < Reδ2 < 3.0 times 104. The enhanced model is a combination of the modified Chase-Howe, Goody and Rozenberg models, and is a simple function of the ratio of pressure and timescales of the outer to inner part of the boundary-layer. The key advantage of the present model is that it incorporates the Reynolds number, the boundary-layer loading as well as pressure gradient effects through an amplitude scaling function and timescale ratio, and compares well to the experimental data. Spectral features of the detailed measurement data and various scaling behavior of the wall pressure spectrum are elaborately investigated. A summary of the results on the applicability and limitation of the model for various test cases is discussed. The enhanced model is further applied to develop an airfoil turbulent boundary-layer trailing-edge interaction (TBL-TE) far-field noise prediction scheme. Prediction results are compared with the well established experimental database and encouraging results are found. The enhanced Wall Pressure Fluctuation (WPF) as well as trailing-edge noise spectra models accuracy for the maximum noise level is in ±2dB range for the test cases examined. The model can be applied further for acoustic airfoil design and optimization and in various aeroacoustic applications.
Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19

BACKGROUND Despite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia. METHODS We performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data. RESULTS CarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality. CONCLUSIONS Unsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP. FUNDING National Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.
Class A capsid assembly modulator RG7907 clears HBV-infected hepatocytes through core-dependent hepatocyte death and proliferation

Background and Aims: Effective therapies leading to a functional cure for chronic hepatitis B are still lacking. Class A capsid assembly modulators (CAM-As) are an attractive modality to address this unmet medical need. CAM-As induce aggregation of the HBV core protein (HBc) and lead to sustained HBsAg reductions in a chronic hepatitis B mouse model. Here, we investigate the underlying mechanism of action for CAM-A compound RG7907. Approach and Results: RG7907 induced extensive HBc aggregation in vitro, in hepatoma cells, and in primary hepatocytes. In the adeno-associated virus (AAV)–HBV mouse model, the RG7907 treatment led to a pronounced reduction in serum HBsAg and HBeAg, concomitant with clearance of HBsAg, HBc, and AAV-HBV episome from the liver. Transient increases in alanine transaminase, hepatocyte apoptosis, and proliferation markers were observed. These processes were confirmed by RNA sequencing, which also uncovered a role for interferon alpha and gamma signaling, including the interferon-stimulated gene 15 (ISG15) pathway. Finally, the in vitro observation of CAM-A–induced HBc–dependent cell death through apoptosis established the link of HBc aggregation to in vivo loss of infected hepatocytes. Conclusions: Our study unravels a previously unknown mechanism of action for CAM-As such as RG7907 in which HBc aggregation induces cell death, resulting in hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response. This represents a promising approach to attain a functional cure for chronic hepatitis B.
Unsteady flow fields in a high specific speed centrifugal pump

The unsteady flow fields within a non-cavitating high specific speed centrifugal pump (cos=l.l) were the object of an experimental, numerical, and theoretical investigation in which new signal analysis techniques for unsteady phenomena analysis were implemented. Three particular aspects were subject to detailed concentration, all known to be problematic in the pump industry, • part load behavior and impeller flow recirculation, • unsteady impeller blade loading, • acoustic generation. Part Load Behavior and Impeller Flow Recirculation The measured characteristics for the high specific speed centrifugal pump revealed distinct discontinuities in part load operation and were shown to coincide with abrupt unsteady flow field changes in the pump. These discontinuities occurred at different threshold volume fluxes when increasing or decreasing the pump discharge and make up a hysteresis loop. Discrepancies in the magnitude of the pressure discontinuities and shaft power discontinuities indicated, shown theoretically to be plausible, the commencement/cessation of dissipater mechanisms within the flow as the recirculation commences/ceases. Transient behavior of the hysteresis in the pump pressure discharge characteristic was evaluated as a function of changing volume flux rate experimentally and accordingly theoretically. Quasi steady behavior was found for Id^/dfkO.OOSs"1. A 2nd order nonlinear dependence on the changing volume flux rate was determined for the change in useful hydraulic power during the commencement/cessation of the impeller recirculation. The pump impeller pressure discharge characteristic was evaluated experimentally and numerically by taking the difference between the integrated impeller outlet and impeller inlet total pressure. The experimental and numerical characteristics agree well including the volume flux location and magnitude of the pressure discontinuities in the hysteresis loop. Experimental and numerical comparisons are made at the impeller inlet/ outlet with emphasis on the changing flow field in the hysteresis loop flow regime and its coupling to the onset of recirculation flow zones. This combined application of numerical and experimental tools provided insight for the hysteresis flow field of a pump impeller and for abrupt changes in the associated unsteady flow field.
Effects of combining feedback and hypothesis-testing on the quality of simulated child sexual abuse interviews with avatars among Chinese university students

Previous research has shown that simulation training using avatars with repeated feedback improves child sexual abuse interview quality. The present study added a hypothesis-testing intervention and examined if the combination of two interventions, feedback and hypothesis-testing, would improve interview quality compared to no intervention and to either intervention alone. Eighty-one Chinese university students were randomly assigned to a control, feedback, hypothesis-testing, or the combination of feedback and hypothesis-testing group and conducted five simulated child sexual abuse interviews online. Depending on the assigned group, feedback on the outcome of the cases and question types used in the interview were provided after each interview, and/or the participants built hypotheses based on preliminary case information before each interview. The combined interventions group and feedback group showed a higher proportion of recommended questions and correct details from the 3rd interview onward compared to the hypothesis-building and control groups. The difference between the number of correct conclusions was not significant. hypothesis-testing alone exacerbated the use of non-recommended questions over time. The results show that hypothesis-testing may impact question types used negatively but not when combined with feedback. The potential reasons for hypothesis-testing alone not being effective and the differences between the present and previous studies were discussed.
A new method for mapping detector material in situ and a matrix element approach to the search for heavy di-muon resonances at the LHC

The Standard Model of particle physics has proven to be a very successful theory to describe the fundamental interactions and elementary particles observed in nature. The discovery of a Higgs boson in 2012 by the Atlas and CMS experiments at the LHC has been the ultimate confirmation of the predictions of the theory. However, this model does not have answers to everything at the fundamental level. For example, the inclusion of the gravitational force and the hierarchy problem are among the questions awaiting to be answered. Moreover, it is believed that the fundamental forces could be unified into a single force. Many new theoretical models that address these problems predict the existence of new heavy particles at the TeV scale and even new extra space dimensions. An experimentally and particularly appealing final state to search for these new phenomena at the LHC collider is the di-muon final state. However, no evidence for such new particles has been found so far, indicating that these particles might be heavier and produced at a lower rate than expected. By improving the reconstruction and analysis techniques, the sensitivity of these searches can be enhanced. This thesis presents the results of research performed along both of these lines. First, a new method for mapping the distribution of detector material has been developed and applied to the inner tracker detector of the CMS experiment. The method exploits the scattering of charged particles off the nuclei of the material of a high-energy physics experiment to infer the distribution of the material itself. The method is easily applicable and its accuracy is comparable to that of more traditional methods. The method also proves to be complementary to such traditional methods in that it suffers from different sources of uncertainty. Second, a matrix element based analysis approach has been developed and tested to improve the sensitivity for a discovery of a di-muon resonance. It is found that the analysis method is robust, reliable and advantageous to use in the searches at the LHC.
Nutri-microbiome epidemiology, an emerging field to disentangle the interplay between nutrition and microbiome for human health

Abstract Diet and nutrition have a substantial impact on the human microbiome, and interact with the microbiome, especially gut microbiome, to modulate various diseases and health status. Microbiome research has also guided the nutrition field to a more integrative direction, becoming an essential component of the rising area of precision nutrition. In this review, we provide a broad insight into the interplay among diet, nutrition, microbiome, and microbial metabolites for their roles in the human health. Among the microbiome epidemiological studies regarding the associations of diet and nutrition with microbiome and its derived metabolites, we summarize those most reliable findings and highlight evidence for the relationships between diet and disease-associated microbiome and its functional readout. Then, the latest advances of the microbiome-based precision nutrition research and multidisciplinary integration are described. Finally, we discuss several outstanding challenges and opportunities in the field of nutri-microbiome epidemiology.
Particle tracking microrheology of protein solutions

Video-based particle tracking microrheology that requires ∼2 μl per sample is used to measure the viscosity of protein solutions of monoclonal antibodies. Direct imaging provides an immediate assessment of probe stability and the validity of the microrheology measurement. Precise measurements are made by choosing a displacement lag time that is a balance between minimizing tracking error while maximizing the number of sampled particle displacements. The excess kurtosis α2 of the probe displacement probability distribution and its test statistic Zα2 are used to set the optimal lag time. The viscosity is calculated by fitting a Gaussian distribution to the sampled displacements. Microrheology viscosities for two monoclonal antibody solutions are in good agreement with bulk rheology. Using a similar comparison of the microrheology of sucrose solutions with a correlation relating viscosity and concentration, an analysis of covariance (p = 0.941) demonstrates the high accuracy of small volume microrheology mea.
The Schottky barrier transistor in emerging electronic devices

This paper explores how the Schottky barrier (SB) transistor is used in a variety of applications and material systems. A discussion of SB formation, current transport processes, and an overview of modeling are first considered. Three discussions follow, which detail the role of SB transistors in high performance, ubiquitous and cryogenic electronics. For high performance computing, the SB typically needs to be minimized to achieve optimal performance and we explore the methods adopted in carbon nanotube technology and two-dimensional electronics. On the contrary for ubiquitous electronics, the SB can be used advantageously in source-gated transistors and reconfigurable field-effect transistors (FETs) for sensors, neuromorphic hardware and security applications. Similarly, judicious use of an SB can be an asset for applications involving Josephson junction FETs.
Protective mucosal and systemic immunity induced by virus-like particles expressing Toxoplasma gondii cyst wall protein

Toxoplasma gondii host cellular invasion factors such as the rhoptry proteins, micronemal antigens, or other subcellular compartment proteins have shown limited vaccine efficacies. T. gondii cyst wall protein (CST1) as a cyst persistence factor is critical for cyst wall integrity and bradyzoite persistence. Here, we generated influenza virus-like particles (VLPs) expressing the T. gondii CST1 and evaluated the mucosal as well as systemic immunities induced by VLPs. Intranasal immunization with the VLPs induced parasite-specific IgG and IgA antibody responses in sera and intestines. VLP immunization showed higher levels of germinal center B cell response and antibody-secreting cell (ASC) response upon challenge infection, indicating memory B cell response was induced. VLP-immunized mice showed a significant reduction of cyst counts and lower levels of pro-inflammatory cytokines (IFN-γ, IL-6) production in the brain upon T. gondii ME49 challenge infection compared to unimmunized control. Thus, VLP immunization protected mice from the lethal dose challenge infection with T. gondii ME49 and did not incur bodyweight loss. These results indicated that T. gondii CST1 containing VLPs can induce mucosal and systemic immunity and also suggest its developmental potential as an effective vaccine candidate against T. gondii infection.
Prevalence of alcohol-associated liver disease: a systematic review and meta-analysis

Background: Alcohol-associated liver disease (ALD) is a common cause of morbidity and premature mortality. To date, there has been no systematic synthesis of the prevalence of ALD. This systematic review was done with the aim of reporting the prevalence of ALD across different health care settings. Methods: PubMed and EMBASE were searched for studies reporting the prevalence of ALD in populations subjected to a universal testing process. Single-proportion meta-analysis was performed to estimate the prevalence of all ALD, alcohol-associated fatty liver, and alcohol-associated cirrhosis, in unselected populations, primary care, and among patients with alcohol-use disorder (AUD). Results: Thirty-five studies were included reporting on 513,278 persons, including 5968 cases of ALD, 18,844 cases of alcohol-associated fatty liver, and 502 cases of alcohol-associated cirrhosis. In unselected populations, the prevalence of ALD was 3.5% (95% CI, 2.0%–6.0%), the prevalence in primary care was 2.6% (0.5%–11.7%), and the prevalence in groups with AUD was 51.0% (11.1%–89.3%). The prevalence of alcohol-associated cirrhosis was 0.3% (0.2%–0.4%) in general populations, 1.7% (0.3%–10.2%) in primary care, and 12.9% (4.3%–33.2%) in groups with AUD. Conclusions: Liver disease or cirrhosis due to alcohol is not common in general populations and primary care but very common among patients with coexisting AUD. Targeted interventions for liver disease such as case finding will be more effective in at-risk populations.