Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Simulations Identify Pyrrolidine-2,3-Dione Derivatives as Novel Inhibitors of Cdk5/p25 Complex to Attenuate Alzheimer’s Pathology

Mechanistically, neurotoxic insults provoke Ca2+-mediated calpain activation, which cleaves the cytoplasmic region of membrane-embedded p35 and produces its truncated form p25. Upon physical interaction, cyclin-dependent kinase 5 (Cdk5) and p25 forms hyperactivated Cdk5/p25 complex and causes severe neuropathological aberrations including hyperphosphorylated tau-mediated neurofibrillary tangles formation, Alzheimer’s symptoms, and neuronal death. Therefore, the inhibition of Cdk5/p25 complex may relieve p-tau-mediated Alzheimer’s pathology. Herein, computational simulations have identified pyrrolidine-2,3-dione derivatives as novel inhibitors of Cdk5/p25 complex. A ligand-based pharmacophore was designed and employed as 3D query to retrieve drug-like molecules from chemical databases. By molecular docking, drug-like molecules obtaining dock score > 67.67 (Goldcore of the reference compound) were identified. Molecular dynamics simulation and binding free energy calculation retrieved four pyrrolidine-2,3-dione derivatives as novel candidate inhibitors of Cdk5/p25. The root means square deviation of Cdk5/p25 in complex with candidate inhibitors obtained an average value of ~2.15 Å during the 30 ns simulation period. Molecular interactions analysis suggested that each inhibitor occupied the ATP-binding site of Cdk5/p25 and formed stable interactions. Finally, the binding free energy estimation suggested that each inhibitor had lowest binding energy than the reference compound (−113.10 kJ/mol) to recapitulate their strong binding with Cdk5/p25. Overall, these inhibitors could mitigate tau-mediated Alzheimer’s phenotype.
Expression, purification and characterization of a phyAm-phyCs fusion phytase

The phyAm gene encoding acid phytase and optimized neutral phytase phyCs gene were inserted into expression vector pPIC9K in correct orientation and transformed into Pichia pastoris in order to expand the pH profile of phytase and decrease the cost of production. The fusion phytase phyAm-phyCs gene was successfully overexpressed in P. pastoris as an active and extracellular phytase. The yield of total extracellular fusion phytase activity is (25.4±0.53) U/ml at the flask scale and (159.1±2.92) U/ml for high cell-density fermentation, respectively. Purified fusion phytase exhibits an optimal temperature at 55 °C and an optimal pH at 5.5∼6.0 and its relative activity remains at a relatively high level of above 70% in the range of pH 2.0 to 7.0. About 51% to 63% of its original activity remains after incubation at 75 °C to 95 °C for 10 min. Due to heavy glycosylation, the expressed fusion phytase shows a broad and diffuse band in SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). After deglycosylation by endoglycosidase H (EndoHf), the enzyme has an apparent molecular size of 95 kDa. The characterization of the fusion phytase was compared with those of phyCs and phyAm.
Flow Battery Storage Application with Wind Power

It is technically practical to apply electricity storage to wind generation to improve availability, to increase the amount of wind generation that may be installed on the grid without risking system voltage instability, to increase throughput of existing grid infrastructure, and to yield various ancillary benefits such as reduced system losses and improved power factor control. The integrated approach of applying energy storage to wind generation also yields economic returns in specialized cases such as island systems and wind farm repowering projects with paybacks and rates of return that may be commercially attractive. Benefits of such storage-coupled wind applications accrue in both directions, providing ride-through and transient mitigation from the perspective of the wind farm during grid disturbances
A Class of High-Rate Low-Complexity Error-Detecting RLL Codes

We present a new methodology for the construction of high-rate channel modulation run-length-limited RLL codes. Simple modulation encoders and decoders are constructed, with low error propagation during decoding. They combine partial error detection capability (PED) to boost the performance of a concatenated outer Error Correction Code (ECC) [1]. Moreover, current systems are using low redundancy ECC, and the overall rate is mainly determined by the inner modulation code rate, which critically is to be maintained high. Code rates, for example, 16/17, 24/25 and higher are achievable, with efficiency exceeding 0.94 and 0.96, respectively. The proposed fixed length block decodable codes, are generalized schemes of the type for.
The Effect of Ballistic Exercise as Pre-Activation for 100 m Sprints

The benefits of warm-up in sports performance has received a special interest in the current literature. However, there is a large gap of knowledge about the tasks to be performed, specifically in the real competitive environment. The purpose of the study was to verify the acute effects of a warm-up including ballistic exercises in 100 m running performance. In addition, a second 100 m trial was assessed to better understand the warm-up effects in training and competition. Eleven men (25.4 ± 6.2 years of age, 1.76 ± 0.08 m of height, 78.2 ± 8.6 kg of body mass) were submitted to three different protocols, in a randomized order: no warm-up (NWU), typical warm-up (WU) and WU complemented with ballistic exercises (PAP). Biomechanical, physiological and psychophysiological variables were assessed. Differences were found between the three conditions assessed in the first 100 m sprint with 7.4% and 7.6% faster performances after the WU and PAP, compared to NWU. Stride length was higher in the second part of the 100 m after PAP compared with WU. These results highlight the positive effects of warm-up for sprinting performance. The inclusion of ballistic exercises, besides being used to improve sprint performance, can increase stride length in the final of the 100 m race.
Are engineering students decreasing? A Spanish case study

There is an idea that engineering degrees are experiencing a decrease in number of students. This is a fact that has concerned many worldwide engineering societies. The reasons may be based in a loss of motivation among students to begin a difficult career, in spite of great expectations jobs proposed from the society. However, this paper offers some data that could change this thought, particularly in Spain. Figures, demographical statistics, students' opinions and university data can give an answer to the question of enrollment and provide some conclusions why engineering careers are less demanded from students. Is it real or just myth?
Control system design for an Automatic Emergency Braking system in a sedan vehicle

The Automatic Emergency Braking (AEB) systems in vehicles is one of the technologies suggested by NHTSA to be included in vehicles by default. This article presents the dynamic model of the vehicle that should be considered to design control of EAB system. After that, the design of a classic controller is presented, following of some results of simulations, which let to identify variables to measure the comfort of automatic braking, and when and in which conditions the ABS systems act over an action of AEB. Finally, the Architecture of the implementation of the braking over CAN Networks is presented.
Nuclear actin and Mrtfs control disuse muscle atrophy via Srf activity regulation Running title : The actin / Mrtfs / Srf axis controls disuse atrophy

Skeletal muscle atrophy is a debilitating process associated with a wide variety of conditions including inactivity, disease and aging. Here, we demonstrate that the actin/Mrtfs/Srf pathway is specifically downregulated in muscle atrophy induced by disuse in mice. We show in vivo that the abolition of mechanical signals leads to rapid accumulation of G-actin in myonuclei and export of the Srf coactivator Mrtf-A, resulting in Mrtfs/Srf-dependent transcription decrease that contributes to atrophy. We demonstrate that inhibition of the actin/Mrtfs/Srf axis by overexpression of nuclear non-polymerizable actin, pharmacological inhibition of Mrtfs/Srf and muscle-specific Srf deletion worsens denervation-induced atrophy. Conversely, maintenance of high Srf or Mrtfs activity in denervated muscle, through overexpression of constitutively active derivatives, counteracts atrophy. Altogether, our data provide new mechanistic insights into the control of muscle mass upon disuse atrophy by the actin/Mrtfs/Srf pathway, highlighting Srf as a key mediator of mechanotransduction in muscle. Jo ur na l o f C el l S ci en ce A cc ep te d m an us cr ip t
Adherence to Clinical Trial Supported Evaluation of Optic Neuritis

ABSTRACT Purpose: The Optic Neuritis Treatment Trial showed that an MRI of the brain is a powerful predictor of developing multiple sclerosis (MS). However, surveys of practitioners suggest that the recommended use of imaging is not consistently followed in practice. With this study, we aim to assess the rate at which newly diagnosed optic neuritis (ON) patients receive brain MRIs. Methods: This is a retrospective cohort study using administrative medical claims data from a large, national US insurer. All incident cases from 2000 to 2016 of ON in patients without MS were assessed. The primary outcome was a comparison of patterns of MRI scanning usage following diagnosis of ON. Secondary outcomes evaluated steroid treatment and progression to MS. Results: Of 2865 qualified ON patients, 1755 (61.3%) received a brain MRI. At 1 year follow-up, 629 (30.3%) patients had progressed to MS, a rate that increased slightly to 34.3% (366 patients) within a 3-year period of their initial ON diagnosis. A total of 520 (18.2%) patients received intravenous steroids, and 383 (13.4%) received oral steroids within 30 days of the ON diagnosis. Conclusion: Across the United States, a surprisingly low number of individuals obtain a brain MRI following onset of ON, suggesting that physicians may not be fully assessing the risk of MS.
Racial Segregation Across U.S. Nursing Homes: A Systematic Review of Measurement and Outcomes.

BACKGROUND AND OBJECTIVES Nursing homes remain subjected to institutional racial segregation in the United States. However, a standardized approach to measure segregation in nursing homes does not appear to be established. A systematic review was conducted to identify all formal measurement approaches to evaluate racial segregation among nursing home facilities, and to then identify the association between segregation and quality of care in this context. RESEARCH DESIGN AND METHODS PubMed, Scopus, and Web of Science databases were searched (January 2018) for publications relating to nursing home segregation. Following the PRISMA guidelines, studies were included that formally measured racial segregation of nursing homes residents across facilities with regional-level data. RESULTS Eight studies met the inclusion criteria. Formal segregation measures included the Dissimilarity Index, Disparities Quality Index, Modified Thiel's Entropy Index, Gini coefficient, and adapted models. The most common data sources were the Minimum Data Set (MDS; resident-level), the Certification and Survey Provider Enhanced Reporting data (CASPER; facility-level), and the Area Resource File/ U.S. Census Data (regional-level). Most studies showed evidence of racial segregation among U.S. nursing home facilities and documented a negative impact of segregation on racial minorities and facility-level quality outcomes. DISCUSSION AND IMPLICATIONS The measurement of racial segregation among nursing homes is heterogeneous. While there are limitations to each methodology, this review can be used as a reference when trying to determine the best approach to measure racial segregation in future studies. Moreover, racial segregation among nursing homes remains a problem and should be further evaluated.
Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition

Significance Identifying components of breast milk that influence postnatal development though their effects on the gut microbiota and immune system could provide new therapeutic approaches for childhood undernutrition, including heretofore treatment-refractory linear growth faltering (stunting). Plasma biomarkers of osteoclast-mediated bone resorption and osteoblast-driven bone formation in stunted Bangladeshi children provided evidence for elevated osteoclastic activity. Gnotobiotic mice, colonized with a stunted infant’s gut microbiota, exhibited decreased bone resorption when consuming diets supplemented with a purified bovine oligosaccharide mixture dominated by sialylated structures found in human breast milk. Supplementation decreased osteoclastogenesis while sparing osteoblast activity; the microbiota, intestinal cell populations, and immune mediators contribute to these responses. The influence of milk oligosaccharides on the gut microbiota–bone axis has diagnostic and therapeutic implications. Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting. To characterize interactions among the gut microbiota, human milk oligosaccharides (HMOs), and osteoclast and osteoblast biology, young germ-free mice were colonized with cultured bacterial strains from a 6-mo-old stunted infant and fed a diet mimicking that consumed by the donor population. Adding purified bovine sialylated milk oligosaccharides (S-BMO) with structures similar to those in human milk to this diet increased femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses. Comparisons of germ-free and colonized mice revealed S-BMO-dependent and microbiota-dependent increases in cecal levels of succinate, increased numbers of small intestinal tuft cells, and evidence for activation of a succinate-induced tuft cell signaling pathway linked to Th2 immune responses. A prominent fucosylated HMO, 2′-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects. These results underscore the need to further characterize the balance between, and determinants of, osteoclastic and osteoblastic activity in stunted infants/children, and suggest that certain milk oligosaccharides may have therapeutic utility in this setting.
Speed and Phase Adjacent Cross-Coupling Synchronous Control of Multi-Exciters in Vibration System Considering Material Influence

This paper addresses the problem of phase and speed synchronization control of multi-exciters in vibration system considering material influence. Aiming at the synchronous control problem of the exciters, first, the dynamic model of the vibration system excited by multi-exciters considering the force of material is established. Considering the existence of coupling dynamics characteristic between adjacent exciters, an accurate controller combined with adjacent cross-coupling control (ACCC) strategy and an adaptive global sliding mode algorithm (AGSMC) is proposed to control the vibration system. The stability of the ACCC strategy controller is verified through the Lyapunov stability theorem. The ACCC strategy controller proposed in this paper is compared with the master-slave strategy controller by a numerical method. The results show that the proposed ACCC strategy and the AGSMC algorithm controller can reduce speed overshoot during the start-up phase of the induction motor and the chattering when the speed is stable, and improve the control accuracy. The ACCC strategy controller controls the multi-exciters in the vibration system considering the nonlinear force of material, so that the zero phase difference between adjacent exciters moves synchronously. Finally, in the vibration system, the influence of tracking speed and parameter error on the ACCC strategy controller is discussed. It shows that the ACCC strategy controller is robust to system parameter variation and error-disturbance.
Fast ICA and JADE Algorithms for DS-CDMA

This paper introduces application of Independent Component Analysis (ICA) in communication field for Direct Sequence Code Division Multiple Access (DS-CDMA) in symbol estimation, where ICA is statistical method for source separation based on independence between sources, and the paper developed a way to solve the ambiguities of ICA. We used ICA as a detector and it is simulated using MATLAB in downlink DS-CDMA. Fast ICA and JADE algorithms which are ICA algorithms are introduced for symbol detection for different number of users and different number of symbols. A comparison between the two algorithms is also made, the results are compared with results of conventional detection The results showed that ICA detection can solve symbol detection. The ICA detection after solving ambiguities using the proposed way gives better results than conventional detection
Solar PV interface to Grid-Tie Inverter with Current Referenced Boost Converter

A Solar Photovoltaic (PV) array may be interfaced with the Grid-Tie Inverter (GTI) either by direct connection or through a Boost Converter. In case of direct connection of PV with GTI the string voltage has to be maintained at the specified DC link Voltage level according to the Maximum Power Point (MPP) and the input range of the GTI by connecting the required number of PV panels to the string. In this case the Maximum Power Point tracking is done by giving the current reference to the inverter control and the response of the tracking may be limited by the inner current loops. Instead we can use a Boost converter to perform the dual function of stepping up the voltage and tracking the maximum power point. A Current Referenced Boost Converter has been proposed in this work in which the control is PWM mode with current feedback. The plant model is derived and a PI controller is tuned to satisfy the performance and stability requirements. The current referenced controller works well for Partially Shaded conditions and also has the ability to control the PV power by operating the PV array at any current reference in case of excess energy generation.
Computational Design for Inflated Shape of a Modular Soft Robotic Actuator

A soft robotic actuator of modular construction has been designed where multiple repeated asymmetric deforming units are connected in series to alter the final deformed shape. Using a Genetic Algorithm that can change the orientation of each articulating unit by 180°, a combination of orientations is calculated to yield what best resembles the desired profile that is specified by means of a continuous function. To improve simulation run times for the finite element analyses, a reduced order model is presented where the 3D model is simplified to that of a 2D plane strain approximation. This preliminary work shows that by using an advanced computational design tool interesting behaviour can be achieved whilst using only a very simple asymmetric deforming modular unit. A physical actuator was manufactured and the deformation compared to the numerical models.
Pharmacodynamic study of radium-223 in men with bone metastatic castration resistant prostate cancer

Background Radium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment. Methods We conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues. Results We enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC. Conclusions Osteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy.
Automatically-Tuned Damping Injection for Stable Bilateral Control Under Time Delay

Bilateral control is one of the methods to realize a teleoperation with force feedback. However, communication time delay seriously deteriorates operationality and stability of bilateral control. Although 3-channel bilateral control has been proposed to improve operationality, the system becomes unstable in contact motion. Damping injection is an effective method to stabilize the contact motion by producing viscous force. However, this method produces large operational force and deteriorates operationality. Many researchers tried to inject damping without deteriorating operationality. However, their methods are affected by several situations/factors such as delay time or operator's motion speed. As a result, their methods require a redesigning procedure in order to deal with such situations/factors. In this paper, automatically-tuned damping injection is proposed to stabilize the contact motion in 3-channel bilateral control. In the proposed method, damping gain is automatically determined by monitoring the Lyapunov stability of the force control. The effectiveness of the proposed method is verified by experiments.