Frequency Response Based Repetitive Control for Periodic Coefficient Systems Motivated by Cam Followers

Cam follower systems are generally designed to operate at a fixed speed or a range of fixed speeds. However manufacturing defects, wear, or a change of design goals may require altering the camshaft speed to produce a follower trajectory which is not possible using a fixed speed. The follower trajectory may also be optimized for some performance criteria such as minimizing vibration and wear. Like most real world systems, the differential equations governing a cam follower system are nonlinear. A common approach for controlling a nonlinear system is to first linearize the system about a nominal operating point, then apply linear control laws. In many cases, such as the cam follower system, one can create a trajectory and numerically solve the nonlinear system for the inputs required to follow it. Linearizing about this solution creates a linear time varying system whose states are deviations from the desired solution. The speed trajectory in the cam follower system is periodic, which results in a linear system with periodic coefficients. Repetitive control creates control systems that aim to converge to zero tracking error following a periodic command, or aim to completely cancel the effects of a periodic disturbance. Using the inverse of the steady state frequency response as a compensator has been shown to be very effective for linear time invariant systems. That idea is applied here to linear time periodic systems. The periodic state matrices lend themselves well to frequency domain representations, which can be used to construct a matrix form of the steady state frequency response. The first law studied in this work analyzes a moving window implementation which monitors the output errors and previous commands to create an update to the change in the command for the current time step using the inverse of the steady state frequency response matrix. Asymptotic convergence conditions for zero tracking error are derived. When the number of samples in one period is not an integer number, the moving window method is not feasible without interpolation. Therefore a second method based on the projection algorithm from adaptive control is developed and analyzed. In linear constant coefficient systems, one generally needs to incorporate a frequency cutoff filter to robustify to high frequency model error. The additional intricacies of designing a cutoff filter for periodic systems is considered, aiming to handle the fact that for periodic coefficient systems, addressing error components below the intended cutoff can excite harmonics above the cutoff. The control laws developed in this work are applicable to any nonlinear system which may be linearized about a periodic trajectory. Development of these control laws is motivated by improving the performance of a cam follower system. Additional improvements in cam follower behavior can be done through parameter optimization. This includes optimizing a nonlinear follower spring such that it provides just sufficient force to maintain contact while reducing the load on the cam

Cardiogenol C can induce Mouse Hair Bulge Progenitor Cells to Transdifferentiate into Cardiomyocyte-like Cells

<p>Abstract</p> <p>Background</p> <p>Hair bulge progenitor cells (HBPCs) are multipotent stem cells derived from the bulge region of mice vibrissal hairs. The purified HBPCs express CD34, K15 and K14 surface markers. It has been reported that HBPCs could be readily induced to transdifferentiate into adipocytes and osteocytes. However, the ability of HBPCs to transdifferentiate into cardiomyocytes has not yet been investigated.</p> <p>Methodology/Principal Findings</p> <p>The cardiomyogenic potential of HBPCs was investigated using a small cell-permeable molecule called Cardiogenol C. We established that Cardiogenol C could induce HBPCs to express transcription factors GATA4, Nkx2.5 and Tbx5, which are early specific markers for pre-cardiomyogenic cells. In prolonged cultures, the Cardiogenol C-treated HBPCs can also express muscle proteins, cardiac-specific troponin I and sarcomeric myosin heavy chain. However, we did not observe the ability of these cells to functionally contract. Hence, we called these cells cardiomyocyte-like cells rather than cardiomyocytes. We tried to remedy this deficiency by pre-treating HBPCs with Valproic acid first before exposing them to Cardiogenol C. This pretreatment inhibited, rather than improved, the effectiveness of Cardiogenol C in reprogramming the HBPCs. We used comparative proteomics to determine how Cardiogenol C worked by identifying proteins that were differentially expressed. We identified proteins that were involved in promoting cell differentiation, cardiomyocyte development and for the normal function of striated muscles. From those differentially expressed proteins, we further propose that Cardiogenol C might exert its effect by activating the Wnt signaling pathway through the suppression of Kremen1. In addition, by up-regulating the expression of chromatin remodeling proteins, SIK1 and Smarce1 would initiate cardiac differentiation.</p> <p>Conclusions/Significance</p> <p>In conclusion, our CD34⁺/K15⁺HBPCs could be induced to transdifferentiate into cardiomyocyte-like cells using a small molecule called Cardiogenol C. The process involves activation of the Wnt signaling pathway and altered expression of several key chromatin remodeling proteins. The finding is clinically significant as HBPCs offer a readily accessible and autologous source of progenitor cells for cell-based therapy of heart disease, which is one of major killers in developed countries.</p

Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions

Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse embryonic stem cells leads to their exit from self-renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream transcriptional factor of the Nodal/Activin pathway, followed by massively parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression

Microorganism Profiles of Penile Prosthesis Removed for Infection, Erosion, and Mechanical Malfunction Based on Next-Generation Sequencing.

BACKGROUND: Next-generation sequencing (NGS) is an emerging technology that may allow for more sensitive and sophisticated microbial testing of the microbiota of penile prostheses (PP). AIM: To describe the microorganism profiles of PP explanted for infection, erosion, and mechanical malfunction using NGS. METHODS: All patients who underwent PP removal by two physicians at two institutions were identified. Differences in alpha diversity (ie, number of species detected, species diversity across samples) and microbiome compositional profiles (Bray-Curtis community dissimilarities) across samples were assessed using ANOVA and PERMANOVA, respectively. OUTCOMES: Number of species detected, species diversity across samples, and microbiome compositional profiles. RESULTS: A total of 83 patients who underwent device removal for infection (n = 8, 10%), erosion (n = 5, 6%), and mechanical malfunction (n = 70, 84%) were included. When considering all devices, 56% (n = 48) of NGS and 29% (n = 24) of standard cultures resulted positive for presence of microorganisms. Culture only detected the most abundant NGS species in 62.5% (n = 5) of infected devices. Species richness and microbiome compositional profiles varied by surgical indication, but not by age, race, diabetes status, or implant duration. Most frequent organisms by surgical indication were Pseudomonas aeruginosa (infection), Staphylococcus epidermidis (erosion), and Escherichia coli (mechanical malfunction). The highest relative abundance organisms were P aeruginosa (infection), Corynebacterium jeikeium (erosion), and E coli (mechanical malfunction). CLINICAL IMPLICATIONS: Identifying microbiome profiles of PP removed for infection, erosion, and mechanical malfunction may guide the selection of peri-operative antibiotics and PP antibiotic coatings or hydrophilic dip solutions for each individual scenario. STRENGTHS AND LIMITATIONS: While this is the first study to utilize next-generation sequencing to evaluate penile prosthesis biofilm, the clinical significance of these findings has yet to be determined. A prospective, randomized trial aimed at evaluating the clinical significance of NGS in patients with PP infection is currently underway. CONCLUSION: NGS testing identified distinct microbiome profiles of PP removed for infection, erosion, and mechanical malfunction. Chung PH, Leong JY, Phillips CD, Henry GD. Microorganism Profiles of Penile Prosthesis Removed for Infection, Erosion, and Mechanical Malfunction Based on Next-Generation Sequencing. J Sex Med 2022;19:356-363

How COVID-19 changed clinical research strategies: a global survey

Objective Clinical research has faced new challenges during the COVID-19 pandemic, leading to excessive operational demands affecting all stakeholders. We evaluated the impact of COVID-19 on clinical research strategies and compared different adaptations by regulatory bodies and academic research institutions in a global context, exploring what can be learned for possible future pandemics. Methods We conducted a cross-sectional online survey and identified and assessed different COVID-19-specific adaptation strategies used by academic research institutions and regulatory bodies. Results All 19 participating academic research institutions developed and followed similar strategies, including preventive measures, manpower recruitment, and prioritisation of COVID-19 projects. In contrast, measures for centralised management or coordination of COVID-19 projects, project preselection, and funding were handled differently amongst institutions. Regulatory bodies responded similarly to the pandemic by implementing fast-track authorisation procedures for COVID-19 projects and developing guidance documents. Quality and consistency of the information and advice provided was rated differently amongst institutions. Conclusion Both academic research institutions and regulatory bodies worldwide were able to cope with challenges during the COVID-19 pandemic by developing similar strategies. We identified some unique approaches to ensure fast and efficient responses to a pandemic. Ethical concerns should be addressed in any new decision-making process

Accommodating stormwater storage structure in the veranda of shop building

This paper describes the investigation to place water storage structure under the veranda of a shop building. A veranda is a commercial building feature in Southeast Asia with a narrow walkway about 3 m wide. Given the small space’s limited capability to hold rainwater from the building roof, a draining tank is, therefore, a more viable choice. Rainwaters flow in and out the tank simultaneously with an outlet control that enables water storage within. A modular-based stormwater storage system that could be assembled under the veranda was selected. Storm Water Management Model version 5.0 was used to model the system. The modular-based system's availability of field test data allowed calibration and verification exercises using the mentioned software and yielded R Square values between 0.97-0.99. As such, the parameters of the system as a storage unit were applied in the modelling of the same system in the veranda. Two cases were presented. The water storage structure was modelled in a single shop lot and a partial commercial area with six units of shop lots and surrounding streets. Modelling the single shop lot with 60% of its roof directing waters to the water storage structure was predicted to reduce 25-30% of its peak values comparing the post-development hydrographs with and without the intervention. The partial commercial area modelling yielded only 0.4-10% prediction in its reduction, suggesting additional intervention was required

Surface Acoustic Wave Ammonia Sensors Based on ST-cut Quartz under Periodic Al Structure

Surface acoustic wave (SAW) devices are key components for sensing applications. SAW propagation under a periodic grating was investigated in this work. The theoretical method used here is the space harmonic method. We also applied the results of SAW propagation studied in this work to design a two-port resonator with an Al grating on ST-cut quartz. The measured frequency responses of the resonator were similar to the simulation ones. Then, the chemical interface of polyaniline/WO3 composites was coated on the SAW sensor for ammonia detection. The SAW sensor responded to ammonia gas and could be regenerated using dry nitrogen

Antibody stabilization for thermally accelerated deep immunostaining

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining

Shot Noise in Mesoscopic Conductors

Theoretical and experimental work concerned with dynamic fluctuations has developed into a very active and fascinating subfield of mesoscopic physics. We present a review of this development focusing on shot noise in small electric conductors. Shot noise is a consequence of the quantization of charge. It can be used to obtain information on a system which is not available through conductance measurements. In particular, shot noise experiments can determine the charge and statistics of the quasiparticles relevant for transport, and reveal information on the potential profile and internal energy scales of mesoscopic systems. Shot noise is generally more sensitive to the effects of electron-electron interactions than the average conductance. We present a discussion based on the conceptually transparent scattering approach and on the classical Langevin and Boltzmann-Langevin methods; in addition a discussion of results which cannot be obtained by these methods is provided. We conclude the review by pointing out a number of unsolved problems and an outlook on the likely future development of the field.Comment: 99 two-column pages; 38 .eps figures included. Submitted to Physics Reports. Many minor improvements; typos corrected; references added and update