A review of variable-pitch propellers and their control strategies in aerospace systems

The relentless pursuit of aircraft flight efficiency has thrust variable-pitch propeller technology into the forefront of aviation innovation. This technology, rooted in the ancient power unit of propellers, has found renewed significance, particularly in the realms of unmanned aerial vehicles and urban air mobility. This underscores the profound interplay between visionary aviation concepts and the enduring utility of propellers. Variable-pitch propellers are poised to be pivotal in shaping the future of human aviation, offering benefits such as extended endurance, enhanced maneuverability, improved fuel economy, and prolonged engine life. However, with additional capabilities come new technical challenges. The development of an online adaptive control of variable-pitch propellers that does not depend on an accurate dynamic model stands as a critical imperative. Therefore, a comprehensive review and forward-looking analysis of this technology is warranted. This paper introduces the development background of variable-pitch aviation propeller technology, encompassing diverse pitch angle adjustment schemes and their integration with various engine types. It places a central focus on the latest research frontiers and emerging directions in pitch control strategies. Lastly, it delves into the research domain of constant speed pitch control, articulating the three main challenges confronting this technology: inadequacies in system modeling, the intricacies of propeller-engine compatibility, and the impact of external, time-varying factors. By shedding light on these multifaceted aspects of variable-pitch propeller technology, this paper serves as a resource for aviation professionals and researchers navigating the intricate landscape of future aircraft development

Adaptive Model Predictive Control for Engine-Driven Ducted Fan Lift Systems using an Associated Linear Parameter Varying Model

Ducted fan lift systems (DFLSs) powered by two-stroke aviation piston engines present a challenging control problem due to their complex multivariable dynamics. Current controllers for these systems typically rely on proportional-integral algorithms combined with data tables, which rely on accurate models and are not adaptive to handle time-varying dynamics or system uncertainties. This paper proposes a novel adaptive model predictive control (AMPC) strategy with an associated linear parameter varying (LPV) model for controlling the engine-driven DFLS. This LPV model is derived from a global network model, which is trained off-line with data obtained from a general mean value engine model for two-stroke aviation engines. Different network models, including multi-layer perceptron, Elman, and radial basis function (RBF), are evaluated and compared in this study. The results demonstrate that the RBF model exhibits higher prediction accuracy and robustness in the DFLS application. Based on the trained RBF model, the proposed AMPC approach constructs an associated network that directly outputs the LPV model parameters as an adaptive, robust, and efficient prediction model. The efficiency of the proposed approach is demonstrated through numerical simulations of a vertical take-off thrust preparation process for the DFLS. The simulation results indicate that the proposed AMPC method can effectively control the DFLS thrust with a relative error below 3.5%

Logistic Regression Analysis of Factors Influencing the Effectiveness of Intensive Sound Masking Therapy in Patients with Tinnitus

Objectives: To investigate factors influencing the effectiveness intensive sound masking therapy on tinnitus using Logistic Regression Analysis. Design: The study used a retrospective cross-section analysis. Participants: 102 patients with tinnitus were recruited at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China. Intervention: Intensive sound masking therapy was used as an intervention approach for patients with tinnitus. Primary and secondary outcome measures: participants underwent audiological investigations and tinnitus pitch and loudness matching measurements, followed by intensive sound masking therapy. The Tinnitus Handicap Inventory (THI) was used as the outcome measure pre- and post-treatment. Multivariate logistic regression was performed to investigate the association of demographic and audiological factors with effective therapy. Results: According to the THI score changes pre-and post-sound masking intervention, fifty-one participants were categorised into an effective group, the remaining 51 participants were placed in a non-effective group. Those in the effective group were significantly younger than those in the non-effective group (p=0.012). Significantly more participants had flat audiogram configurations in the effective group (p=0.04). Multivariable logistic regression analysis showed that age (OR=0.96, 95% CI: 0.93, 0.99, p=0.007), audiometric configuration (p=0.027) and THI score pre-treatment (OR=1.04, 95% CI: 1.02, 1.07, p<0.001) were significantly associated with therapeutic effectiveness. Further analysis showed that patients with flat audiometric configurations were 5.45 times more likely to respond to intervention than those with high-frequency steeply sloping audiograms (OR=5.45, 95% CI: 1.67, 17.86, p=0.005). Conclusion: Audiometric configuration, age and THI scores appear to be predictive for the effectiveness of sound masking treatment. Gender, tinnitus characteristics and hearing threshold measures seem not to be related to treatment effectiveness. Further randomized control study is needed to provide further evidence of the effectiveness of prognostic factors in tinnitus interventions

MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas.

Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results: We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions: Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level

Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer

Cordycepin is widely considered a direct tumor-suppressive agent. However, few studies have investigated as the effect of cordycepin therapy on the tumor microenvironment (TME). In our present study, we demonstrated that cordycepin could weaken the function of M1-like macrophages in the TME and also contribute to macrophage polarization toward the M2 phenotype. Herein, we established a combined therapeutic strategy combining cordycepin and an anti-CD47 antibody. By using single-cell RNA sequencing (scRNA-seq), we showed that the combination treatment could significantly enhance the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. In addition, the combination treatment could regulate the proportion of CD8+ T cells to prolong the progression-free survival (PFS) of patients with digestive tract malignancies. Finally, flow cytometry validated the changes in the proportions of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs). Collectively, our findings suggested that the combination treatment of cordycepin and the anti-CD47 antibody could significantly enhance tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. In addition, the PFS in patients with digestive tract malignancies would be prolonged by regulating CD8+ T cells

Influence of Audiovisual Training on Horizontal Sound Localization and Its Related ERP Response

The objective was to investigate the influence of audiovisual training on horizontal sound localization and the underlying neurological mechanisms using a combination of psychoacoustic and electrophysiological (i.e., event-related potential, ERP) measurements on sound localization. Audiovisual stimuli were used in the training group, whilst the control group was trained using auditory stimuli only. Training sessions were undertaken once per day for three consecutive days. Sound localization accuracy was evaluated daily after training, using psychoacoustic tests. ERP responses were measured on the first and last day of tasks. Sound localization was significantly improved in the audiovisual training group when compared to the control group. Moreover, a significantly greater reduction in front-back confusion ratio for both trained and untrained angles was found between pre- and post-test in the audiovisual training group. ERP measurement showed a decrease in N1 amplitude and an increase in P2 amplitude in both groups. However, changes in late components were only found in the audiovisual training group, with an increase in P400 amplitude and decrease in N500 amplitude. These results suggest that the interactive effect of audiovisual localization training is likely to be mediated at a relatively late cognitive processing stage

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Configuration Interaction Methods to Predictions on Photophysical Properties of Organic Materials

Electronic structure methods are routinely applied to molecular systems to provide chemical insights. Accessing accurate models, however, still requires careful tuning and sizable computational resources. This work focuses on the development of methods and strategies that enable the calculations of various excited state properties on larger systems than ever before. The first three chapters focus on the spin-flip configuration interaction family of methods. Chapter II introduces the new implementation of the spin-flip method that can predict charge-transfer state properties with mid- to large-size systems, with a challenging example of a theoretically designed molecular system to harvest multiple electrons from strongly correlated multiexciton states on a single chromophore, quinoidal bithiophene, which has shown from prior studies to be a good intramolecular singlet fission candidate. Using the newly implemented tool, the study implies that electron transfer between the two molecules occurs from the multiexciton state into an excited charge transfer state. This indicates that two-electron transfer may happen sequentially, thus increasing the electron transfer yield of the singlet fission process. The spin-flip methodology is then extended to enable spin-orbit coupling calculations in Chapter III, where benchmark models and specific applications to organic triplet emitters will be given. A detailed analysis of a system that combines a purely organic triplet emitter with the excited-state intramolecular proton transfer (ESIPT) mechanism shows large spin-orbit coupling values between singlet and triplet excited states. This creates viable intersystem crossing transition channels to populate the triplet state. Similarly, the study also shows that the ESIPT triplet emitter, with a large spin-orbit coupling value between the ground and the lowest triplet excited state, shows fast phosphorescence rate. These large intersystem crossing and phosphorescence rates thus make the ESIPT triplet emitter system one of the brightest phosphors. To further explore challenges of computing excited state properties, Chapter IV provide more insight into the solvent effect to the molecular systems, where an implementation of polarizable continuum model is described with an additional benchmark system, perylenediimide (PDI) dimer. The inclusion of the solvent effect in two geometries of PDI dimer suggests that dielectric stabilization creates excitonic trap states in one geometry by breaking symmetry and localizing charge, which outcompetes the multiexciton state and results in consequent relaxation back to the ground state. Therefore, the study, with the implemented solvation description, will show that a promising route to improving efficiency of singlet fission in PDI dimer systems is to find dimer geometries in which single-directional charge transfer is inhibited in the solvent, which may be achieved by suppressing broken symmetry and avoiding polar solvent environments. In general, implementations and calculations on charge transfer state analysis in solar cells, spin-orbit couplings for predicting intersystem crossing pathways and solvent effects of organic material systems that newly implemented in this work can all provide evidence to explain the mechanisms of solar cell and semiconductor materials from a theoretical perspective. While there is still a lot to be done before the computational methods could be applied to a wide variety of large systems, the various methods investigated and extended here show significant promise, especially with the benchmark and actual experimental molecular systems that presented in the chapters, as these systems are indeed applicable to any configuration interaction methods.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/174197/1/hanjiej_1.pd

MECHANISTIC STUDIES ON NEDD4 FAMILY HECT E3 UBIQUITIN LIGASES

The NEDD4 family HECT (homologous to E6AP C terminus) E3 ligases contain nine enzymes that catalyze the ubiquitination of numerous important proteins including tumor suppressor PTEN and transcription factors Oct4 and EGR2. The NEDD4 ubiquitination enzymes therefore impact many cellular events and need to be tightly controlled. Dysregulation of NEDD4 enzymes is associated with many pathologies like cancer and neurodegenerative diseases. NEDD4 protein architecture includes an N-terminal C2 domain, followed by two to four WW domains and culminating in a C-terminal HECT domain. Previous work from our lab has demonstrated that a linker region between two of the WW domains can undergo an intra-molecular interaction with catalytic HECT domain, serving an auto-inhibitory role. In this thesis, we investigated the molecular mechanisms of this auto-regulatory linker and found that the linker auto-inhibition can be relieved by either linker phosphorylation, which disrupts the linker-HECT interaction. Moreover, we found that linker autoinhibition can be overcome by the NEDD4 family member binding with allosteric activators like NDFIP1 and ubiquitin variants. We have also demonstrated that the NEDD4 family member WWP1 K740N/N745S germline variants, associated with cancer, do not relieve auto-inhibition as suggested in a recent clinical study. Furthermore, we performed substrate screening with a phosphor-mimetic/activated form of the NEDD4 family member WWP2 using protein microarrays. We have identified a group of new potential WWP2 protein substrates from this screening and followed up on three of these, the autophagy receptors NDP52, OPTN and SQSTM1. In vitro and in vivo, we demonstrated that WWP2 ubiquitinates these autophagy receptors and plays an important role in regulating mitophagy. In addition, in this thesis work, we developed two chemical strategies to site-specifically modify proteins of interest for biochemical studies. Firstly, we developed an N-terminal labeling method with NHS ester compounds, which shows high specificity. We applied this strategy to study WWP2 autoubiquitination and E2-E3 molecular interaction. Secondly, we adapted a recently developed technique for chemically-ubiquitinating protein of interest using ubiquitin hydrazide mimics. We expanded its application to other proteins, including ubiquitin-conjugating enzyme E2 and HECT E3 ligases. We applied the generated E2-Ub or E3-Ub as enzyme intermediate state mimics to study the HECT E3 catalytic mechanisms. Our data support a model in which the HECT-Ub intermediate undergoes a conformational switch from an inverted T shape to an L shape, which reduces the E3 affinity for the E2. This model accounts for an efficient turnover process that allows for rapid E2 recycling and enhanced substrate ubiquitination