Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Molecule Agents Targeting PD-1 Checkpoint Pathway for Cancer Immunotherapy: Mechanisms of Action and Other Considerations for Their Advanced Development

Pioneering success of antibodies targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has changed the outlook of cancer therapy. Although these antibodies show impressive durable clinical activity, low response rates and immune-related adverse events are becoming increasingly evident in antibody-based approaches. For further strides in cancer immunotherapy, novel treatment strategies including combination therapies and alternate therapeutic modalities are highly warranted. Towards this discovery and development of small molecule, checkpoint inhibitors are actively being pursued, and the efforts have culminated in the ongoing clinical testing of orally bioavailable checkpoint inhibitors. This review focuses on the small molecule agents targeting PD-1 checkpoint pathway for cancer immunotherapy and highlights various chemotypes/scaffolds and their characterization including binding and functionality along with reported mechanism of action. The learnings from the ongoing small molecule clinical trials and crucial points to be considered for their clinical development are also discussed.
DC/DC Converters for Multiterminal HVDC Systems: Based on Modular Multilevel Converter

The increase in the energy demand has resulted in searching for new energy sources. Due to the increased prices of fossil fuels and the environmental issues, renewable energy sources has become popular in Europe. Renewable energy generation such as wind, solar and wave has point-to-point connections with the main grid. In order to minimize the disadvantages of renewable energy sources like energy fluctuations, multi-terminal systems are favoured interconnecting energy generation stations among them with the main grid. The long distance interconnection especially for offshore wind farms and intercontinental connections is not possible with traditional alternating current (AC) technology because of the limited power transfer. Therefore, high voltage direct current (HVDC) technology is considered as the main element for the future multi-terminal grid. The conversion between AC and DC is preferred via voltage source converters (VSC) as they offer more flexible power control compared to traditional current source converters in other words line commutated converters (LCC). HVDC power transmission schemes have been constructed depending on the technology of the time, which means that there is no standardization in voltage levels and configurations of the HVDC schemes. Therefore, the connection of such systems operating at different voltage levels and/or in different schemes such as monopole and bipolar systems for the future multi-terminal DC grids requires DC/DC converters. Although the voltage level and the configurations are the same for both DC systems, DC/DC converter may be required for the power flow control in multi-terminal DC grid. The modular multilevel converter (MMC) seems as the most suitable converter in this application due to its advantages such as low switching losses, high scalability and modularity. MMC control structures are introduced and front-to-front connection of two MMC forming a DC/AC/DC converter is modelled and simulated for different applications such as interconnecting systems with same voltage levels, different voltage levels or different configurations in this study. The passive element sizes of MMC submodules are also compared for different AC side frequency as the component sizes can be decreased thanks to the increase in the AC frequency which has a disadvantage of higher switching losses. Moreover, the designed converters are tested in multi-terminal DC grids to check their performance and functionality.
Semi-auto labeling device for 6Dof object pose estimation

In this work, we propose to generate the supervised training dataset for 6-DoF object pose estimation algorithm, with trivial human labor. A semi-auto labelling board is designed so that its pose can be estimated accurately with a learned deep model. For a training sequence with more than 1000 frames, one only needs to manually mark the key points of the object for 2-5 frames and the ground-truth pose of the object can be calculated automatically for the whole sequence. In the experiment, we prove that the state-of-the-art pose estimation method can be trained well with only 20-50 human-labelled images and the yielded model performs better than the model learned based on the manually labelled dataset with more than 800 images.
A unified modeling and control design for precision transmission system with friction and backlash

The structural flexibility, nonlinear friction, and backlash are the major factors limiting the control performance of precision transmission systems. If uncompensated, these factors compromise the positioning and tracking accuracy of precision transmission systems and even cause limit cycles and oscillation. In this article, a framework for integrated design from dynamic modeling to controller design is proposed. A multi-state dynamic model is presented, which can unify the modeling for a multi-state, discontinuous system including the motor state, the motion state, the mechanical contact state, and the friction state. Then, a control design method related to the dynamic modeling using perturbation separation of the model parameters is presented. Using the proposed modeling method, a continuous dynamic model is established to include all different partition models. The model comprehensively describes the mechanical and electrical characteristics of the precision transmission system. A robust controller is designed using the proposed control method. Experimental results demonstrate that the proposed modeling method is accurate and the proposed control method significantly improves accuracy and robustness of the controller compared to traditional control methods.
Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model

Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by spontaneous and elicited paroxysms of electric-shock-like or stabbing pain in a region of the face. The epigenetic regulation of TN is still obscure. In current study, a rat TN model subject to carbamazepine (CBZ) treatment was established, and transcriptome- and genome-scale profiling of H3K9ac and HDAC3 was performed by RNA-seq and ChIP-seq. We observed that H3K9ac levels in the trigeminal ganglion were lower in the TN rats compared with those in the control, and CBZ treatment led to recovery of H3K9ac levels. Further, we found that HDAC3 was overactivated, which interfered with H3K9 acetylation due to higher phosphorylation in TN compared with that in the control. Finally, the phosphokinase leucine-rich repeat kinase 2 (LRRK2) was demonstrated to contribute to HDAC3 activity via the MAPK signaling pathway. Taken together, we identified a regulatory mechanism in which the phosphate groups transferred from activated ERK and LRRK2 to HDAC3 caused genome-scale deacetylation at H3K9 and resulted in the silencing of a large number of genes in TN. The kinases or important enzymes within this regulatory axis may represent important targets for TN therapy and prevention.
EXPERIMENTAL STUDY OF MAGNUS EFFECT OVER AN AIRCRAFT WING

We present this paper as an experimental study of employing Magnus Effect in an aircraft wing. The scope and interest of study of Magnus Effect and its application in Aerospace Engineering is widely increasing all over the world to make use of the Magnus Force for enhanced Lift by Drag Ratio. Most of the trials weren't successful due to the heavy Drag Force produced by large cylinders, even though sufficient Lift Force was generated. The main stereotypical apprehension of Magnus Effect is that it could be applied only over symmetrical bodies like a spinning ball(sphere), or a cylinder or a disc. We suggest an idea to be applied differently by maintaining a constant circumferential speed over an airfoil profile. We propose to initiate the project work by considering a symmetrical airfoil and study it’s aerodynamic characteristics and make an attempt in extending it's performing envelope by implementing Magnus Effect. Our intention is to provide the constant circumferential speed over the airfoil skin is by compositing a treadmill like motion contributed by a series of rollers fastened over a chain track and driven by a stepper motor. The Rollers coupled Treadmill spins in a clockwise direction, when air passes over the upper surface of the airfoil, it will be pushed down, due to the energy provided by the treadmill motion imparted to the airflow. This apparently make the air below the airfoil denser and eventually leading to a pressure rise in the lower surface of the airfoil. Consequently, the supplemented acceleration of airflow over the upper surface of the airflow results in a greater pressure difference between both the surfaces of airfoil. Thus we are generating surplus Lift Force and minimize Drag Force by implementing Magnus Effect over the aircraft wing. We term this entire approach as Flo-Lapse. Our Pilot Studies and predictions make it seem that this idea will wide open many avenues for production of augmented Lift/Drag Ratio, wielding of shorter wingspan, probability of initiating a Vertical Take-Off for Unmanned Aerial Vehicles, or production of Lift at Zero Airspeed. A probable condition of the Cruise phase of a flight profile, where in the aircraft is at maximum speed, the incoming airstream can be used to reverse the Flo-Lapse approach and serve the purpose of an energy solution. We suggest that optimising the circumferential speed, we can have better L/D Ratios and delay early stalling of wing.
Action detection system for alerting drivers using computer vision

Nowadays, the increasing number of careless drivers on the road has resulted in more accident cases. Driver’s decisions and behaviors are the key to maintain road safety. However, many drivers tend to do secondary tasks like playing with their phone, adjusting radio player, eating or drinking, answering phone calls, and worse case is reading phone texts. In previous efforts, many kinds of approaches had been introduced to try to solve the task to recognize and capture potential problem related to careless driving inside the car. In this project, the work will mainly focus on the driver's secondary task recognition using the action detection method. A camera will be set up inside the car for the real-time extract of driver’s action. The video will undergo a process to extract out the human pose frames without background, called human pose estimator framework. Inside this framework, raw images will be input into a convolutional neural network (CNN) that computes human key-point's activation maps. After, that key-point's coordinate will be computed using the output activation maps and drawn on a new blank frame. Then the frames will be input into classification CNN network for the action classification. If an action performed by driver is considered a dangerous secondary task, alert will be given. The proposed framework was able to achieve a higher speed compared to other people's framework if it is being run on Raspberry Pi CPU. It is able to detect 10 different driver actions where only talking to passengers and normal driving will not trigger the buzzer to give alert to driver.
Performance evaluation of Viterbi decoded binary and non-binary linear block codes in flat fading channels

In recent years, much attention has been given to the decoding of linear block codes by means of trellis decoding algorithms, such as the Bahl-Cocke-Jelinek-Raviv (BCJR) and Viterbi algorithms. Not only do these algorithms support soft in. put decoding, but also the application of channel state information for improved decoding performances in fading channel environments. This paper presents a performance evaluation, based on an extensive simulation study, of Viterbi decoded binary Hamming and non-binary Reed-Solomon block codes under flat fading channel conditions with varying Doppler frequencies and line-of-sight signal strengths. Special attention is given to the influence of channel state information on the bit error rate performance.
A Machine Learning-based Course Enrollment Recommender System

: As an integral component of human society, higher education has been undergoing a transformation in multiple aspects, such as administrative reorganization, pedagogical reform, and technological innovation. To line up with the latest trends, many institutions constantly update their curriculum, which poses challenges to students and their advisors. This paper proposes a machine learning-based course enrollment recommender system that aims to make personalized suggestions to students who expect to take classes in the upcoming semester. Using matrix factorization as the core algorithm, the model exploits several available types of information, including student course enrollment history and other contextual features, such as prerequisite restrictions, course meeting times, instructional methods, and course instructors. The system not only helps students but also facilitates their advisors’ work. Our experimental results show that the recommended courses were highly relevant while providing plenty of options to students.
Biblical Approach to Development: A Theological Reflection from the Perspective of Burkan Pentadic Criticism

The subject of development has been approached from different academic disciplines mainly from sociological, economic, political and anthropological perspectives. Not much has been written about the subject of development within theological scholarship. The reason is that the church and for that matter, traditional theological scholarship has focused on personal piety and discipleship instead of social responsibility and development. Subsequently many have come to think that the Bible has less to say about development. The main aim of this article is to offer a biblically informed systematic approach to the subject of development. It argues that the Bible provides a useful guide on what it means to develop. Using the method of Burkan Pentadic Criticism to analyse the biblical teaching on the essentials of development, this paper maintains that the Bible and for that matter, the biblical teaching on development, should shape the human understanding, worldview and attitudes about development. Keywords: Development, Worldview, Bible, stewardship, Pentadic Criticism, shalom.
The Role of Embodied Simulation and Visual Imagery in Emotional Contagion with Music

Emotional contagion has been explained as arising from embodied simulation. The two most accepted theories of music-induced emotions presume a mechanism of internal mimicry: the BRECVEMA framework proposes that the melodic aspect of music elicits internal mimicry leading to the induction of basic emotions in the listener, and the Multifactorial Process Model proposes that the observation or imagination of motor expressions of the musicians elicits muscular and neural mimicry, and emotional contagion. Two behavioral studies investigated whether, and to what extent, mimicry is responsible for emotion contagion, and second, to what extent context for affective responses in the form of visual imagery moderates emotional responses. Experiment 1 tested whether emotional contagion is influenced by mimicry by manipulating explicit vocal and motor mimicry. In one condition, participants engaged in mimicry of the melodic aspects of the music by singing along with the music, and in another, participants engaged in mimicry of the musician’s gestures when producing the music, by playing along (“air guitar”-style). The experiment did not find confirmatory evidence for either hypothesized simulation mechanism, but it did provide evidence of spontaneous visual imagery consistent with the induced and perceived emotions. Experiment 2 used imagined rather than performed mimicry, but found no association between imagined motor simulation and emotional intensity. Emotional descriptions read prior to hearing the music influenced the type of perceived and induced emotions and support the prediction that visual imagery and associated semantic knowledge shape listeners’ affective experiences with music. The lack of evidence for the causal role of embodied simulation suggests that current theorization of emotion contagion by music needs refinement to reduce the role of simulation relative to other mechanisms. Evidence for induction of affective states that can be modulated by contextual and semantic associations suggests a model of emotion induction consistent with constructionist accounts.
Model-Based Control Strategies to Enhance Energy Flexibility in Electrically Heated School Buildings

This paper presents a general methodology to model and activate the energy flexibility of electrically heated school buildings. The proposed methodology is based on the use of archetypes of resistance–capacitance thermal networks for representative thermal zones calibrated with measured data. Using these models, predictive control strategies are investigated with the aim of reducing peak demand in response to grid requirements and incentives. A key aim is to evaluate the potential of shifting electricity use in different archetype zones from on-peak hours to off-peak grid periods. Key performance indicators are applied to quantify the energy flexibility at the zone level and the school building level. The proposed methodology has been implemented in an electrically heated school building located in Québec, Canada. This school has several features (geothermal heat pumps, hydronic radiant floors, and energy storage) that make it ideal for the purpose of this study. The study shows that with proper control strategies through a rule-based approach with near-optimal setpoint profiles, the building’s average power demand can be reduced by 40% to 65% during on-peak hours compared to a typical profile.
Design, Synthesis, and Antifungal Activity of Novel Benzimidazole Derivatives Bearing Thioether and Carbamate Moieties

In this study, a series of benzimidazole derivatives bearing thioether and carbamate moieties have been synthesized and evaluated for their in vitro antifungal activity against Cytospora mandshurica, Thanatephorus cucumeris, Botrytis cinerea, Verticillium daliae, Phytophthora infestans, and Gibberella zeae by the mycelium growth rate method. The result of bioassay demonstrated that most of the compounds had certain antifungal activity. Especially, compound E11 revealed better antifungal activity against Verticillium daliae and Phytophthora infestans at 50 μg/mL, with the inhibition rates of 70% and 75%, respectively, than those of albendazole (38% and 61%, respectively). To the best of our knowledge, it is the first study on the synthesis and antifungal activity of benzimidazole derivatives containing thioether and carbamate moieties.
Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naïve Patients

Schizophrenia is a severe and chronic mental illness usually diagnosed in adolescents and young adults. Many studies indicate that oxidative stress causes membrane dysfunction and cell damage, which is implicated in the pathophysiology of schizophrenia. The purpose of our study was to evaluate oxidative stress markers (the main primary products of lipid peroxidation, lipid hydroperoxides (LOOH), and end products of lipid peroxidation, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and Ferric Reducing Ability of Plasma (FRAP)) in the plasma of patients with the first episode of schizophrenia in drug-naïve patients (22 men and 12 women aged 17–29). The control group (Ctrl) comprised 26 healthy subjects (19 men and 7 women, aged 18–30 years). The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Analyses of the oxidative stress variables revealed an increased level of SOD (U/mL) in subjects with schizophrenia versus control group. In addition, lipid damage measured as LOOHs µ (mol/L) and MDA was significantly higher in patients with schizophrenia in comparison to control subjects. There was a positive correlation between MDA µmol/L and PANSS P and a positive correlation between C-reactive protein (CRP) and the PANSS P scale. The elevated level of superoxide dismutase in patients with the first episode of schizophrenia can be explained by compensatory mechanisms to counteract oxidative stress. Malondialdehyde can be used as a simple biomarker of low-grade systemic inflammation associated with oxidative stress. A positive correlation between CRP and PANSS P scale and MDA and PANSS P scale may indicate a significant relationship between the development of low-grade inflammation and damage associated with oxidative stress in the development of the first symptoms of schizophrenia.
Combined Microbiome and Metabolome Analysis Reveals a Novel Interplay Between Intestinal Flora and Serum Metabolites in Lung Cancer

As the leading cause of cancer death, lung cancer seriously endangers human health and quality of life. Although many studies have reported the intestinal microbial composition of lung cancer, little is known about the interplay between intestinal microbiome and metabolites and how they affect the development of lung cancer. Herein, we combined 16S ribosomal RNA (rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC-MS) technology to analyze intestinal microbiota composition and serum metabolism profile in a cohort of 30 lung cancer patients with different stages and 15 healthy individuals. Compared with healthy people, we found that the structure of intestinal microbiota in lung cancer patients had changed significantly (Adonis, p = 0.021). In order to determine how intestinal flora affects the occurrence and development of lung cancer, the Spearman rank correlation test was used to find the connection between differential microorganisms and differential metabolites. It was found that as thez disease progressed, L-valine decreased. Correspondingly, the abundance of Lachnospiraceae_UCG-006, the genus with the strongest association with L-valine, also decreased in lung cancer groups. Correlation analysis showed that the gut microbiome and serum metabolic profile had a strong synergy, and Lachnospiraceae_UCG-006 was closely related to L-valine. In summary, this study described the characteristics of intestinal flora and serum metabolic profiles of lung cancer patients with different stages. It revealed that lung cancer may be the result of the mutual regulation of L-valine and Lachnospiraceae_UCG-006 through the aminoacyl-tRNA biosynthesis pathway, and proposed that L-valine may be a potential marker for the diagnosis of lung cancer.