Miracle-dz/UniFAR-FTUs huggingface dataset:
PDE1 inhibitors: a review of the recent patent literature (2008-present)

ABSTRACT Introduction PDE1 has been demonstrated to be a potential drug target for a variety of diseases, such as Alzheimer’s disease and cardiovascular disease. In the past decades, numerous PDE1 inhibitors with structural diversities have been developed and patented by pharmaceutical companies, providing drug candidates for exploring novel disease indications of PDE1. Area covered This review aims to provide an overview of PDE1 inhibitors reported in patents from 2008 to present. Expert opinion Among current PDE1 inhibitors, only a few of them showed high selectivity over other PDEs, which might cause severe side effects in the clinic. The development of highly selective PDE1 inhibitors is still the ‘top priority’ in the following research. The selective recognition mechanism of PDE1 with inhibitors should be further elucidated by X-ray crystallography in order to provide evidence for the rational design of selective PDE1 inhibitors. In addition, PDE1 inhibitors should be applied to different clinical indications beyond CNS diseases.
Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.
Deep Video Prior for Video Consistency and Propagation

Applying an image processing algorithm independently to each video frame often leads to temporal inconsistency in the resulting video. To address this issue, we present a novel and general approach for blind video temporal consistency. Our method is only trained on a pair of original and processed videos directly instead of a large dataset. Unlike most previous methods that enforce temporal consistency with optical flow, we show that temporal consistency can be achieved by training a convolutional network on a video with Deep Video Prior (DVP). Moreover, a carefully designed iteratively reweighted training strategy is proposed to address the challenging multimodal inconsistency problem. We demonstrate the effectiveness of our approach on 7 computer vision tasks on videos. Extensive quantitative and perceptual experiments show that our approach obtains superior performance than state-of-the-art methods on blind video temporal consistency. We further extend DVP to video propagation and demonstrate its effectiveness in propagating three different types of information (color, artistic style, and object segmentation). A progressive propagation strategy with pseudo labels is also proposed to enhance DVP’s performance on video propagation. Our source codes are publicly available at https://github.com/ChenyangLEI/deep-video-prior.
Low power, low voltage on chip relaxation oscillator

ABSTRACT A low power, low voltage resistor-capacitor or relaxation oscillator circuit is proposed. The proposed relaxation oscillator works with minimum 1.1 V supply and consumes less than 3 uA average current for 128 KHz output frequency. A novel integrated comparator and bias current reference circuit ensures low current consumption and low silicon area while providing good output frequency stability across voltage and temperature variation. Capacitor trimming is used to tune the output frequency across process variation. The proposed circuit is designed in 40 nm complementary metal oxide semiconductor process and simulation and silicon measurement results are provided to show the functionality.
Can guidance during play enhance children’s learning and development in educational contexts? A systematic review and meta‐analysis

Abstract This systematic review and meta‐analysis considered evidence of guided play compared to direct instruction or free play to support children's learning and development. Interventions from 39 studies were reviewed (published 1977–2020); 17 were included in meta‐analysis (N total = 3893; M childage = 1–8 years; M girls 49.8%; M ethnicity White 41%, African American/Black 28%, Hispanic 19%). Guided play had a greater positive effect than direct instruction on early maths skills (g = 0.24), shape knowledge (g = 0.63), and task switching (g = 0.40); and than free play on spatial vocabulary (g = 0.93). Differences were not identified for other key outcomes. Narrative synthesis highlighted heterogeneity in the conceptualization and implementation of guided play across studies.
Simulation of PID Control for Vehicle Suspension Based on PSO Algorithm

Due to the problem of the PID controller when defining the three parameters,a method using the PSO algorithm was designed to optimize it.This method utilizes the global searching strategy of the PSO algorithm to optimize and design the parameters with the target function of chassis performance indexes.And then a simulation experiment was provided for the active vehicle chassis control.The results show that using the PID controller optimized by the PSO algorithm,the actively controlled vehicle chassis's performances,such as the vertical acceleration and the dynamic displacement of the suspension,can be greatly improved compared with the chassis controlled by the normal PID controller and the passive one.Meanwhile,the problem of defining the weight matrices is wess solved based on the advantage that the normal PID controller is sufficiently utilized.
Development of an efficient marker‐free soybean transformation method using the novel bacterium Ochrobactrum haywardense H1

Summary We have discovered a novel bacterium, Ochrobactrum haywardense H1 (Oh H1), which is capable of efficient plant transformation. Ochrobactrum is a new host for Agrobacterium‐derived vir and T‐DNA‐mediated transformation. Oh H1 is a unique, non‐phytopathogenic species, categorized as a BSL‐1 organism. We engineered Oh H1 with repurposed Agrobacterium virulence machinery and demonstrated Oh H1 can transform numerous dicot species and at least one monocot, sorghum. We generated a cysteine auxotrophic Oh H1‐8 strain containing a binary vector system. Oh H1‐8 produced transgenic soybean plants with an efficiency 1.6 times that of Agrobacterium strain AGL1 and 2.9 times that of LBA4404Thy‐. Oh H1‐8 successfully transformed several elite Corteva soybean varieties with T0 transformation frequency up to 35%. In addition to higher transformation efficiencies, Oh H1‐8 generated high‐quality, transgenic events with single‐copy, plasmid backbone‐free insertion at frequencies higher than AGL1. The SpcN selectable marker gene is excised using a heat shock‐inducible excision system resulting in marker‐free transgenic events. Approximately, 24.5% of the regenerated plants contained only a single copy of the transgene and contained no vector backbone. There were no statistically significant differences in yield comparing T3 null‐segregant lines to wild‐type controls. We have demonstrated that Oh H1‐8, combined with spectinomycin selection, is an efficient, rapid, marker‐free and yield‐neutral transformation system for elite soybean.
Recombinant HNP-1 Produced by Escherichia coli Triggers Bacterial Apoptosis and Exhibits Antibacterial Activity against Drug-Resistant Bacteria

Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical application has been hampered by the difficulty of mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that recombinant protein expression combined with ultrafiltration may be a simple and cost-effective solution to HNP-1 production. ABSTRACT Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical applications have been hampered by challenges during mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that Escherichia coli expressing full-length preproHNP-1 secretes a soluble form of HNP-1, which can be recovered from the total cell lysate after isopropyl thio-β-d-galactoside (IPTG) induction and ultrafiltration. Label-free quantitative proteomics and co-immunoprecipitation experiments revealed that HNP-1 induces cell apoptosis in bacteria by causing DNA and membrane damage. Notably, we found that HNP-1 disrupts the DNA damage response pathway by interfering with the binding of RecA to single-stranded DNA (ssDNA). Further experiments demonstrated that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results indicated that recombinant protein expression may be a simple and cost-effective solution to produce HNP-1 and that RecA inhibition via HNP-1 may serve as an alternative strategy to counteract antibiotic resistance. IMPORTANCE Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical application has been hampered by the difficulty of mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that recombinant protein expression combined with ultrafiltration may be a simple and cost-effective solution to HNP-1 production. We further found that HNP-1 induces bacterial apoptosis and prevents its SOS repair pathway from binding to the RecA protein, which may be a new antibacterial mechanism. In addition, we showed that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results provide new insights into the production and antibacterial mechanism of HNP-1, both of which may promote its clinical application.
Updating sentences lists for assessment speech perception

ABSTRACT Purpose Adapt a list of sentences for a speech intelligibility test. Methods A speech material data base consisting of 200 phonetically balanced sentences was analyzed and partially updated. In the first stage, 60 reviewers, specialists in linguistics and speech and hearing science, analyzed the sentences in relation to the parameters of familiarity, meaning and predictability using an on-line questionnaire. Cronbach's Alpha coefficient was used to analyze the internal consistency of the questionnaire. In the second stage, the reviewers analyzed whether they were in accordance with the criteria indicated by the literature for the construction of sentences. Results In the first stage, the responses of 15 reviewers who completed the entire questionnaire were analyzed. Agreement between reviewers was high for all criteria. 71 sentences were recommended for modification in the first stage, with predictability being the most indicated parameter as requiring change. In the second stage, 28 more sentences were selected for adjustment, with the presence of a proper name in the sentence being the most frequently cited criterion. Conclusion It was possible to adapt a list of sentences in order to provide speech language therapists with a free of charge speech perception protocol. It is hoped that this new test can assist in standardizing assessment for normal hearing adults and individuals with hearing loss in Brazilian Portuguese.
Cardio-psycho-metabolic outcomes of bariatric surgery: design and baseline of the WAS trial

Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled Würzburg Adipositas Studie (WAS) trial compares the effects of Roux-en-Y gastric bypass (RYGB) vs psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and the quality of life (QoL) (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6–12 months. Thereafter, the patients were randomized and followed through month 12 to collect the primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac MRI), functional brain MRI, psychometric scales, and endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m2) exhibiting a relevantly compromised exercise capacity (median peakVO2 18.3 mL/min/kg) and the QoL (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on the cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB.
Reinforcement Learning-Based Model-Free Controller for Feedback Stabilization of Robotic Systems

This article presents a reinforcement learning (RL) algorithm for achieving model-free control of robotic applications. The RL functions are adapted with the least-square temporal difference (LSTD) learning algorithms to develop a model-free state feedback controller by establishing linear quadratic regulator (LQR) as a baseline controller. The classical least-square policy iteration technique is adapted to establish the boundary conditions for complexities incurred by the learning algorithm. Furthermore, the use of exact and approximate policy iterations estimates the parameters of the learning functions for a feedback policy. To assess the operation of the proposed controller, the trajectory tracking and balancing control problems of unmanned helicopters and balancer robotic applications are solved for real-time experiment. The results showed the robustness of the proposed approach in achieving trajectory tracking and balancing control.
A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans

Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic. ABSTRACT Infection of Cryptococcus neoformans is one of the leading causes of morbidity and mortality, particularly among immunocompromised patients. However, currently available drugs for the treatment of C. neoformans infection are minimal. Here, we report SP1, a peptide derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Saccharomyces cerevisiae, efficiently kills C. neoformans and Cryptococcus gattii. SP1 causes damages to the capsule. Unlike many antimicrobial peptides, SP1 does not form pores on the cell membrane of C. neoformans. It interacts with membrane ergosterol and enters vacuole possibly through membrane trafficking. C. neoformans treated with SP1 show the apoptotic phenotypes such as imbalance of calcium ion homeostasis, reactive oxygen increment, phosphatidylserine exposure, and nuclear fragmentation. Our data imply that SP1 has the potential to be developed into a treatment option for cryptococcosis. IMPORTANCE Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic. However, amphotericin B has rather high renal toxicity, and tolerance to these drugs are quicky developed. The peptide SP1 derived from baker’s yeast GAPDH shows antifungal function to kill Cryptococcus neoformans and Cryptococcus gattii efficiently with a high specificity, even for the drug-resistant strains. Our data demonstrate that SP1 induces the apoptosis-like death of Cryptococcus neoformans at low concentrations. The finding of this peptide may shed light on a new direction to treat cryptococcosis.
Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at day 140. Fetal testes from day 140 pregnant ewes that were exposed transiently for 80-day periods during early (0–80 days), mid (30–110 days), or late (60–140 days) pregnancy had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance, and lowered testosterone; collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation are associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.
A Segmentation Scheme for Knowledge Discovery in Human Activity Spotting

Spotting the target activity in a sequence of activities and transitions without applying a predetermined window size is a challenging task. The sliding window method, which is the typical approach in segmenting the continuous data stream, operates with optimal segment sizes chosen considering the type and duration of the activities. Nevertheless, activity type and duration are usually unknown to the detection unit in practice. In this study, we proposed the nonpredetermined size windowing (NSW) scheme to spot the target activity performed in a sequence of unseen activities. NSW is built on classifying progress-based features in multilayer training and prediction stages where the time-domain progress is expressed in terms of polynomials. Thus, it operates without incorporating the information regarding duration and type of the activities. We verified our method with a proof-of-concept use case where data are acquired by a single wrist-worn 3-D accelerometer. We compared our method against fixed size windowing performed with varying window sizes and feature extraction schemes; windowed energy, peak frequency, Shannon entropy, and wavelet entropy. Our method outperforms the compared schemes, reaching a median accuracy of 89% and a median true positive rate of 1 in both intrasubject and intersubject cases based on an independent test set where each test instance contains a sequence of nine different activities.
Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the Host

Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. ABSTRACT Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host’s harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen. IMPORTANCE Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. Surprisingly, very little is known about the iron acquisition mechanisms in this species. This study represents the first report on the involvement of the S. epidermidis iron-regulated loci hts and fhuC in biofilm formation under host relevant conditions and, most importantly, in survival within the host. Ultimately, these findings highlight iron acquisition and these loci in particular, as potential targets for future therapeutic strategies against biofilm-associated S. epidermidis infections.
Women of Color Student Survivors’ Perceptions of Campus Sexual Assault Prevention Programming

This article presents a qualitative study of 44 Women of Color undergraduate student survivors’ perceptions of campus sexual assault prevention programming using the framework of standpoint theory. Participants held perceptions concerning online training prior to college, the in-person presentations they attended during new student orientation, and the lack of information relayed through prevention programs about sexual assault perpetration. Findings highlight the need for continued research investigating the standpoints of Women of Color students to better inform implementation of prevention efforts.