Miracle-dz/UniFAR-FTUs huggingface dataset:
Sources of Cancer Neoantigens beyond Single-Nucleotide Variants

The success of checkpoint blockade therapy against cancer has unequivocally shown that cancer cells can be effectively recognized by the immune system and eliminated. However, the identity of the cancer antigens that elicit protective immunity remains to be fully explored. Over the last decade, most of the focus has been on somatic mutations derived from non-synonymous single-nucleotide variants (SNVs) and small insertion/deletion mutations (indels) that accumulate during cancer progression. Mutated peptides can be presented on MHC molecules and give rise to novel antigens or neoantigens, which have been shown to induce potent anti-tumor immune responses. A limitation with SNV-neoantigens is that they are patient-specific and their accurate prediction is critical for the development of effective immunotherapies. In addition, cancer types with low mutation burden may not display sufficient high-quality [SNV/small indels] neoantigens to alone stimulate effective T cell responses. Accumulating evidence suggests the existence of alternative sources of cancer neoantigens, such as gene fusions, alternative splicing variants, post-translational modifications, and transposable elements, which may be attractive novel targets for immunotherapy. In this review, we describe the recent technological advances in the identification of these novel sources of neoantigens, the experimental evidence for their presentation on MHC molecules and their immunogenicity, as well as the current clinical development stage of immunotherapy targeting these neoantigens.
Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation

The pathogenesis of type 2 diabetes (T2D) is highly related to the abnormal self-assembly of the human islet amyloid polypeptide (hIAPP) into amyloid aggregates. To inhibit hIAPP aggregation is considered a promising therapeutic strategy for T2D treatment. Melatonin (Mel) was reported to effectively impede the accumulation of hIAPP aggregates and dissolve preformed fibrils. However, the underlying mechanism at the atomic level remains elusive. Here, we performed replica-exchange molecular dynamics (REMD) simulations to investigate the inhibitory effect of Mel on hIAPP oligomerization by using hIAPP20–29 octamer as templates. The conformational ensemble shows that Mel molecules can significantly prevent the β-sheet and backbone hydrogen bond formation of hIAPP20–29 octamer and remodel hIAPP oligomers and transform them into less compact conformations with more disordered contents. The interaction analysis shows that the binding behavior of Mel is dominated by hydrogen bonding with a peptide backbone and strengthened by aromatic stacking and CH–π interactions with peptide sidechains. The strong hIAPP–Mel interaction disrupts the hIAPP20–29 association, which is supposed to inhibit amyloid aggregation and cytotoxicity. We also performed conventional MD simulations to investigate the influence and binding affinity of Mel on the preformed hIAPP1–37 fibrillar octamer. Mel was found to preferentially bind to the amyloidogenic region hIAPP20–29, whereas it has a slight influence on the structural stability of the preformed fibrils. Our findings illustrate a possible pathway by which Mel alleviates diabetes symptoms from the perspective of Mel inhibiting amyloid deposits. This work reveals the inhibitory mechanism of Mel against hIAPP20–29 oligomerization, which provides useful clues for the development of efficient anti-amyloid agents.
Coupled trajectory optimization and tuning of tracking controllers for parafoil generator

ABSTRACT The high-altitude wind power generation (HAWPG) parafoil is an innovative generator with remarkable environmental benefits. Due to the unique trajectory shape, there is an inherent coupling between the pitch and yaw channels, which imposes severe difficulties in the trajectory optimization and tracking controller design. To deal with this intrinsic problem, the trajectory optimization and tracking of the HAWPG parafoil are provided in a comprehensive manner. By using the pseudospectral method (PSM), the parametric optimal trajectory, which has the maximum net power generation, can be obtained. To satisfactorily track this trajectory, well-tuned trajectory controllers are needed to ensure the desired generation performance for the strong coupling dynamics between the two channels. The deep deterministic policy gradient (DDPG) algorithm is applied to the joint tuning of two conventional PID controllers for strongly coupled nonlinear dynamics. A reasonable cost function is established in this process. The mappings between the errors and control gains for the two channels can then be obtained. The gain tuning results are interpretable and well match the empirical knowledge. The simulations are carried out and the comparisons are performed with regard to multiple uncertainties and perturbations. The effectiveness of the proposed method can be illustrated.
Optimal Participation of RES Aggregators in Energy and Ancillary Services Markets

With the advent of bulk volumes of renewable energy, RES aggregators have evolved into key market players of the energy industry. This paper presents a holistic approach to derive the optimal offering strategy of a price-taker RES aggregator in the day-ahead energy and ancillary services markets. The day-ahead, the ancillary services and the real-time balancing market functions are modeled in detail. Fundamental imbalance settlement mechanisms are examined, namely Single Pricing, Two Price settlement and Dual Pricing. Several sources of uncertainty are considered affecting the day-ahead market prices, the ancillary services prices, the imbalance prices and the actual production of the RES aggregator. To cope with these uncertainties, a stochastic risk-constrained optimization model is formulated for the aggregator's optimal bidding. A realistic application in the Greek power system allows for examining the motivations for strategic bidding and accurate forecasting in each imbalance pricing scheme. The interplay between the energy and the ancillary services offers is analyzed, to examine the RES aggregator's motivations to bid for ancillary services.
Research on Application of Fama-French Three-Factor Model in Asset Allocation

As the index of living standard is rising in the recent decades, more and more people join the stock market or have the demand to allocate their assets. That stimulates the appearance of the capital asset pricing model, the Fama-French model, and some other models that are helpful for asset allocation. This paper combs through the development of these models by doing the literature reviews. After listing several examples of expansion to the models, it is natural to conclude that the following research in this field might focus on the specialty of the Fama-French model in different countries and areas or come up with some new factors that influence asset pricing. Also, frequent application of the Fama-French model in the stock market would be consistent in the future with a probable trend of adding some new methods such as artificial neural networks. This paper attempts to introduce some traditional asset pricing models like CAPM and the Fama-French model, along with their expansion in aspects of adding factors or new tools in recent years, then provide a suggestion of specific and innovative research.
Impact of Physical Learning Environment on University Students’ Academic Engagement in an Online Learning Setting during Covid-19: Evidence from a Sri Lankan University

The restrictions imposed due to the outbreak of Coronavirus 2019 led to a paradigm shift in terms of the learning arrangements. In such a situation, since curfew was imposed in Sri Lanka, the universities commenced their all-academic activities using different virtual platforms such Zoom and MS Teams to continue teaching and learning process. Active student engagement is vital for the success of the process. However, evidence shows that the level of student engagement is low in academic activities in an online learning setting and the studies that explored the impact of the physical environment on this situation are rare. Therefore, this study aims to study the impact of ambient and spatial attributes in the physical environment on the level of students’ academic engagement in an online learning setting. Data were collected from a purposive sample of 238 undergraduates of University of Sri Jayewardenepura, Sri Lanka and were analyzed using Structural Equation Modeling with AMOS. The model fit assessment, path coefficient estimation and hypotheses testing were done at the data analysis. The study finding empirically validate the impact of ambient and spatial attributes of the physical environment on student engagement in an online learning setting. Out of ambient attributes, noise and lighting level were recorded as the most influencing factor while size and shape of the study area were recorded as highly influencing factors out of spatial attributes. The impact of air quality, layout and pattern on student engagement was found insignificant. The study finding broadens the components taken as physical resources considered in the Engagement Theory and provide insights for students, university officials, housing developers and policy makers on the importance of the physical learning environment for the student academic engagement in an online leaning setting
Human–hippo conflicts in Kenya during 1997–2008: vulnerability of a megaherbivore to anthropogenic land use changes

Rising human population and the associated demand for more land, water and other natural resources are intensifying conflicts between people and wildlife worldwide. We investigated the nature, intensity, seasonality, spatial and temporal patterns in human–hippo conflict incidences reported from wildlife stations Kenya-wide over a 12-year period spanning 1997–2008. Overall, 4493 human–hippo conflict incidences were recorded, representing a mean rate of 4.46 ± 0.29 incidences per month. The conflict incidences increased by 1285% from 1997 to 2008, resulting in 937 peak incidences reported in 2008. Number of conflict incidences differed among conservation regions, with incidences increasing during severe droughts and over time. Crop damage was the most commonly reported type of conflict. Wildlife managers attended to 90% of all reported conflict incidences. Hippo mortality increased linearly with increasing conflict incidences, portending a precarious future for hippos outside protected areas of Kenya. This dramatic rise in human–hippo conflicts is a consequence of fundamental land use changes around wetland habitats.
A Polyclonal Selex Aptamer Library Directly Allows Specific Labelling of the Human Gut Bacterium Blautia producta without Isolating Individual Aptamers

Recent studies have demonstrated that changes in the abundance of the intestinal bacterium Blautia producta, a potential probiotic, are closely associated with the development of various diseases such as obesity, diabetes, some neurodegenerative diseases, and certain cancers. However, there is still a lack of an effective method to detect the abundance of B. producta in the gut rapidly. Especially, DNA aptamers are now widely used as biometric components for medical testing due to their unique characteristics, including high chemical stability, low production cost, ease of chemical modification, low immunogenicity, and fast reproducibility. We successfully obtained a high-affinity nucleic acid aptamer library (B.p-R14) after 14 SELEX rounds, which efficiently discriminates B. producta in different analysis techniques including fluorometric suspension assays or fluorescence microscopy from other major gut bacteria in complex mixtures and even in human stool samples. These preliminary findings will be the basis towards aptamer-based biosensing applications for the fast and reliable monitoring of B. producta in the human gut microbiome.
Is music on the wane? A small mixed methods study exploring musical learning in the school reception class in the East of England

Abstract This small-scale mixed methods study sought to explore the nature of the musical learning in the Reception year. Research data from the questionnaires (n = 39) provide some evidence that little has changed over the last two decades in some aspects of the music provision for children aged 4 and 5 years. However, interviews with eight Reception teachers revealed some unexpected findings on account of some contemporary barriers. Qualitative data suggest that children’s entitlement to develop their innate musicality within the Foundation stage curriculum may be at risk, as some teachers find the challenges of ‘fitting it all’ is difficult to accomplish.
Assessing Sustainable Green Areas based on Ecological Niche Role in Urban Education Institute

Green areas are so critical in urban communities for making environments healthier and more livable. The objectives of this study were to assess sustainable green areas and to study their ecological niches in an urban education institute. Rajamangala University of Technology Isan (RMUTI) at Nakhonratchasima City Municipality (NCM) was selected as the study area. The spatial assessment of sustainable green areas used guidelines of the policy action plan for sustainable urban green area management by the Office of Natural Resources and Environmental Policy and Planning (ONEP) and then sustainable green areas were analyzed by the Ecological Niche Model (ENM) in Biomapper to check the distribution and durability of the existing trees to the current environment.The study found that sustainable green area in RMUTI at NCM is about 54.23% with 1,176 trees, which is in accordance with the policy action plan of ONEP that has suggested at least 30% of the land parcel being the sustainable green area in urban education institute. In the area of RMUTI, we mostly found type 2 (multiple-use) and type 3 (environmental preservation), respectively. Such two-green type was not only confirmed by assessing the highest accuracy of ENM (AVI and CVI =1.00) but they also preferred niche factors: annual precipitation for type 2 and annual temperature for type 3. Consequently, tree distribution in type 2 and 3 will have more ability of highly sustainable green areas than other green types. These results are explicitly showed that if green type has many distributions of studied trees, it will be a possibility of sustainable green areas. Furthermore, knowledge of ENM will help to plan the suitable tree species to right green areas and their current environment. Consequently, this study can be an example for assessing sustainable green areas-based ENM and implementing in other urban education institutes.
Advanced Molecular Tweezers with Lipid Anchors against SARS-CoV-2 and Other Respiratory Viruses

The COVID-19 pandemic caused by SARS-CoV-2 presents a global health emergency. Therapeutic options against SARS-CoV-2 are still very limited but urgently required. Molecular tweezers are supramolecular agents that destabilize the envelope of viruses resulting in a loss of viral infectivity. Here, we show that first-generation tweezers, CLR01 and CLR05, disrupt the SARS-CoV-2 envelope and abrogate viral infectivity. To increase the antiviral activity, a series of 34 advanced molecular tweezers were synthesized by insertion of aliphatic or aromatic ester groups on the phosphate moieties of the parent molecule CLR01. A structure-activity relationship study enabled the identification of tweezers with a markedly enhanced ability to destroy lipid bilayers and to suppress SARS-CoV-2 infection. Selected tweezer derivatives retain activity in airway mucus and inactivate the SARS-CoV-2 wildtype and variants of concern as well as respiratory syncytial, influenza, and measles viruses. Moreover, inhibitory activity of advanced tweezers against respiratory syncytial virus and SARS-CoV-2 was confirmed in mice. Thus, potentiated tweezers are broad-spectrum antiviral agents with great prospects for clinical development to combat highly pathogenic viruses.
An Artificial Intelligence Approach to Guiding the Management of Heart Failure Patients Using Predictive Models: A Systematic Review

Heart failure (HF) is one of the leading causes of mortality and hospitalization worldwide. The accurate prediction of mortality and readmission risk provides crucial information for guiding decision making. Unfortunately, traditional predictive models reached modest accuracy in HF populations. We therefore aimed to present predictive models based on machine learning (ML) techniques in HF patients that were externally validated. We searched four databases and the reference lists of the included papers to identify studies in which HF patient data were used to create a predictive model. Literature screening was conducted in Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition and MEDLINE. The protocol of the current systematic review was registered in the PROSPERO database with the registration number CRD42022344855. We considered all types of outcomes: mortality, rehospitalization, response to treatment and medication adherence. The area under the receiver operating characteristic curve (AUC) was used as the comparator parameter. The literature search yielded 1649 studies, of which 9 were included in the final analysis. The AUCs for the machine learning models ranged from 0.6494 to 0.913 in independent datasets, whereas the AUCs for statistical predictive scores ranged from 0.622 to 0.806. Our study showed an increasing number of ML predictive models concerning HF populations, although external validation remains infrequent. However, our findings revealed that ML approaches can outperform conventional risk scores and may play important role in HF management.
The computational turn in online mental health research: A systematic review

Digital trace data and computational methods are increasingly being used by researchers to study mental health phenomena (i.e. psychopathology and well-being) in social media. Computer-assisted mental health research is not simply a continuation of previous studies, but rather raises ethical, conceptual and methodological issues that are critical to behavioural science but have not yet been systematically explored. Based on a systematic review of n = 147 studies, we reveal a multidisciplinary field of research that has grown immensely since 2010, spanning the humanities, social sciences, and engineering. We find that a substantial majority of studies in our sample lack a standardized form of ethical consideration, focus on specific constructs and have a rather narrow focus on specific social media platforms. Based on our findings, we discuss how computational elements have influenced mental health research, highlight academic gaps and suggest promising directions for future studies.
Short Range Scaling Laws of Quantum Gases With Contact Interactions

The probability amplitude for $N$ particles in a quantum gas with negligible range of interparticle interaction potentials to come to a small region of size $r$ scales like $r^\gamma$. It is shown that $\gamma$ is quantitatively related to the ground state energy of these $N$ fermions in the unitarity limit, confined by an isotropic harmonic potential. For large $N$, the short range density distribution of these $N$ particles is predominantly the same as the Thomas-Fermi profile of the gas in the unitarity limit confined by such a harmonic potential. These results may shed light on strongly interacting ultracold atomic Fermi gases, in a trap or on an optical lattice.
The Use of Intra-Operative Brilliance Amplifier by Novice Surgeons to Improve Bone Tunnels Placement in Anterior Cruciate Ligament Reconstruction during Residency Curriculum: Useful or Not?

Objective: Our objective was to evaluate the contribution of the use of intra-operative fluoroscopy on tunnels positioning during the Anterior Cruciate Ligament (ACL) reconstruction. Methods: Between January 2020 and June 2022, a total of 8 ACL reconstructions by the Kenneth Jones (KJ) technique were performed by the same young orthopedic surgeon. Fluoroscopy was used intraoperatively to control the position of the guidewire before bone tunnels reaming. It was available for use in 4 cases who constituting the Fluoroscopy Assisted Reconstruction Group (FARG). Post operatively, we assessed on plane radiographs the interference screws position of the four patients constituting the Fluoroscopy Free Reconstruction Group (FFRG). The measurements of the two groups were compared and analyzed using a Wilcoxon matched-pairs signed-ranks test. Results: Of the 4 patients operated on using intra operative fluoroscopy, imaging allowed us to reposition the tibial and femoral guide wires before reaming in all cases (100%). In the second group (FFRG) of patients (n=4), operated without fluoroscopy, post-operative screw positions were in all patients (100%), more anterior in the tibia and more posterior in the femur than the usual position of bone tunnels of ACL reconstruction. Conclusion: In order to increase the precision of the bone tunnels placement during ACL ligamentoplasty in the hands of novice orthopedic surgeon, intraoperative fluoroscopy constitutes a considerable aid tool.
Motivational Drivers of Temporal Dynamics in Postretirement Work

Abstract Objectives Many retirees continue to work in retirement, but the temporal dynamics of this process are not well understood. This article examined the extent to which retirees increase, decrease, and exit their work engagement over time. We hypothesized that different motives for postretirement work—financial, social, personal, and organizational—have differential affects on changes in work extent. Methods We analyzed 7 waves of the HEalth, Aging and Retirement Transitions in Sweden study (n = 3,123). Postretirement work was defined as working for pay while receiving pension benefits. Changes in work extent were estimated with multistate models and examined in relation to the 4 motives. Results Results showed a gradual decrease in work extent following retirement. Financial motives increased the likelihood to take up more work and decreased the likelihood to reduce work hours. Social motives increased the likelihood to reduce and exit work, while personal motives decreased the likelihood for those same pathways. Organizational (demand-driven) motives increased the likelihood to stop working. Discussion Our findings suggest that financial motives constitute an important driver for taking up more work in retirement, while motives related to the personal meaning of work explain why retirees maintain their level of engagement over time. The social function of work, on the other hand, may be gradually replaced by social activities outside of work, resulting in a gradual disengagement from work. Finally, demand-driven motives appear insufficient to remain in the labor force, highlighting the need to acknowledge the diversity of motives for continuing to work.