Miracle-dz/UniFAR-FTUs huggingface dataset:
Polo-like kinase-1 Inhibitors and the Antiandrogen Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling

Abiraterone, a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC), slows disease progression by abrogating androgen synthesis and antagonizing the androgen receptor (AR). We report that inhibitors of the mitotic kinase Plk1, including the clinically active third-generation Plk1 inhibitor onvansertib, when co-administered with abiraterone, synergistically kill cancer cells from a wide variety of tumor types in an androgen-independent manner, both in vitro and in vivo. Abiraterone treatment alone results in defects in mitotic spindle orientation, failure of complete chromosome condensation, and upregulation of mitosis and mitotic-spindle related gene sets independently of its effects on AR signaling. These effects, while mild following abiraterone monotherapy, result in profound sensitization to the anti-mitotic effects of Plk1 inhibition, leading to spindle assembly checkpoint-dependent mitotic cell death and entosis. In a murine PDX model of mCRPC, combined onvansertib and abiraterone resulted in enhanced mitotic arrest and dramatic inhibition of tumor cell growth compared to either agent alone. STATEMENT OF SIGNIFICANCE A phase 2 clinical trial is underway (NCT03414034) testing combined Plk1 inhibitor onvansertib and abiraterone in mCRPC patients with nascent abiraterone resistance. Our work establishes a mechanistic basis for that trial and indicates that combined abiraterone and onvansertib co-treatment may have broad utility for cancer treatment beyond mCRPC.
Small-molecule inhibitors targeting prokaryotic ClpQ protease in Plasmodium display anti-malarial efficacies against blood and liver stages

The ATP-dependent ClpQY system is a prokaryotic proteasome-like machinery in the mitochondrion of malaria parasite, Plasmodium. This protease system is identified as a validated target for malaria intervention. Here we have identified drug-like small chemical compounds, pyrimidotriazine derivatives, as specific inhibitors of P. falciparum ClpQ (PfClpQ) having effective parasiticidal efficacies on asexual and liver stages. Screening of the ‘Malaria Box’ compound library, using a robust in vitro activity assay, identified a hit compound targeting the PfClpQ protease with IC50 at ~750nM. Further, Structure-Activity Relationship (SAR) analysis, using a small library of derivatives of the hit compound, identified three potential lead compounds, ICGEB-L1, ICGEB-L2 and ICGEB-L3, which inhibited enzyme activity with IC50 in 100-200nM ranges. The three lead compounds effectively inhibited in vitro asexual stage parasite growth in similar concentration ranges with ~100-fold selectivity over mammalian cell line; in addition, these compounds effectively inhibited in vitro growth and maturation of hepatocytic stage parasites with EC50 in low nano-molar ranges. These compounds were found to effectively block the development of trophozoite stages to schizont stage, concurrently arresting development and segregation of parasite mitochondria, in asexual as well as hepatocytic stages of the parasite. These morphological and developmental effects of the drugs on parasites mimic the data from genetic ablation of PfClpQ. Importantly, all three compounds showed significant in vivo anti-parasitic efficacies on blood stages of P. berghei mouse malaria model. Overall these results suggest that these PfClpQ targeting compounds are promising candidates to develop new anti-malarials.
Car license plate detection method for Malaysian plates-styles by using a web camera

Recently, license plate detection has been used in many applications especially in transportation systems. Many methods have been proposed in order to detect license plates, but most of them work under restricted conditions such as fixed illumination, stationary background, and high resolution images. License plate detection plays an important role in car license plate recognition systems because it affects the accuracy and processing time of the system. This work aims to build a Car License Plate Detection (CLPD) system at a lower cost of its hardware devices and with less complexity of algorithms' design, and then compare its performance with the local CAR Plate Extraction Technology (CARPET). As Malaysian plates have special design and they differ from other international plates, this work tries to compare two likely-design methods. The images are taken using a web camera for both the systems. One of the most important contributions in this paper is that the proposed CLPD method uses Vertical Edge Detection Algorithm (VEDA) to extract the vertical edges of plates. The proposed CLPD method can work to detect the region of car license plates. The method shows the total time of processing one 352x288 image is 47.7 ms, and it meets the requirement of real time processing. Under the experiment datasets, which were taken from real scenes, 579 out of 643 images were successfully detected. Meanwhile, the average accuracy of locating car license plate was 90%. In this work, a comparison between CARPET and the proposed CLPD method for the same tested images was done in terms of detection rate and efficiency. The results indicated that the detection rate was 92% and 84% for the CLPD method and CARPET, respectively. The results also showed that the CLPD method could work using dark images to detect license plates, whereas CARPET had failed to do so.
Simple Synthesis of CeO2 Nanoparticle Composites In Situ Grown on Carbon Nanotubes for Phenol Detection

via simple hydrothermal method, CeO2 was in-situ grown onto the CNTs to form CeO2/CNTs nanocomposites were synthesized with cerium nitrate as Ce resource. The morphology and structure were characterized by transmission electron microscopy and X-ray diffraction. The characterizations reveal that CeO2 nanoparticles are uniformly dispersed onto the surface of the pre-acidified CNTs. The electrochemical property of the synthesized nanocomposite was investigated in 0.1 M KCl electrolyte containing 2 mM [Fe(CN)6]3-/4-. The nanocomposites were employed to fabricate electrochemical sensor for phenol detection. The linear range for phenol detection measured by the differential pulse voltammetry method is 1–500 μM. The sensor also exhibits good selectivity, reproducibility and stability. When applied for the river and tap water analysis, it shows good recovery rate.
Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

DNA repair mechanisms have been proven to be essential for cells, and abnormalities in DNA repair could cause various diseases, such as cancer. However, the diversity and complexity of DNA repair mechanisms obscure the functions of DNA repair in cancers. In addition, the relationships between DNA repair, the tumor mutational burden (TMB), and immune infiltration are still ambiguous. In the present study, we evaluated the prognostic values of various types of DNA repair mechanisms and found that double-strand break repair through single-strand annealing (SSA) and nonhomologous end-joining (NHEJ) was the most prognostic DNA repair processes in gastric cancer (GC) patients. Based on the activity of these two approaches and expression profiles, we constructed a HR-LR model, which could accurately divide patients into high-risk and low-risk groups with different probabilities of survival and recurrence. Similarly, we also constructed a cancer-normal model to estimate whether an individual had GC or normal health status. The prognostic value of the HR-LR model and the accuracy of the cancer-normal model were validated in several independent datasets. Notably, low-risk samples, which had higher SSA and NHEJ activities, had more somatic mutations and less immune infiltration. Furthermore, the analysis found that low-risk samples had higher and lower methylation levels in CpG islands (CGIs) and open sea regions respectively, and had higher expression levels of programmed death-ligand 1 (PD-L1) and lower methylation levels in the promoter of the gene encoding PD-L1. Moreover, low-risk samples were characterized primarily by higher levels of CD4+ memory T cells, CD8+ naive T cells, and CD8+ TEM cells than those in high-risk samples. Finally, we proposed a decision tree and nomogram to help predict the clinical outcome of an individual. These results provide an improved understanding of the complexity of DNA repair, the TMB, and immune infiltration in GC, and present an accurate prognostic model for use in GC patients.
Astragaloside IV Ameliorates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Fecal Metabolites

Aim Gut microbiota is of crucial importance to cardiac health. Astragaloside IV (AS-IV) is a main active ingredient of Huangqi, a traditional edible and medicinal herb that has been shown to have beneficial effects on cardiac fibrosis (CF). However, it is still uncertain whether the consumption of AS-IV alleviates cardiac fibrosis through the gut microbiota and its metabolites. Therefore, we assessed whether the anti-fibrosis effect of AS-IV is associated with changes in intestinal microbiota and fecal metabolites and if so, whether some specific gut microbes are conducive to the benefits of AS-IV. Methods Male C57BL-6J mice were subcutaneously injected with isoprenaline (ISO) to induce cardiac fibrosis. AS-IV was administered to mice by gavage for 14 days. The effects of AS-IV on cardiac function, myocardial enzyme, cardiac weight index (CWI), and histopathology of ISO-induced CF mice were investigated. Moreover, 16S rRNA sequencing was used to establish gut-microbiota profiles. Fecal-metabolites profiles were established using the liquid chromatograph-mass spectrometry (LC-MS). Results AS-IV treatment prevented cardiac dysfunction, ameliorated myocardial damage, histopathological changes, and cardiac fibrosis induced by ISO. AS-IV consumption increased the richness of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella. AS-IV also modulated gut metabolites in their feces. Among 141 altered gut metabolites, amino acid production was sharply changed. Furthermore, noticeable correlations were found between several specific gut microbes and altered fecal metabolites. Conclusions An increase of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella abundance, and modulation of amino acid metabolism, may contribute to the anti-fibrosis and cardiac protective effects of Astragaloside IV.
Seed Size Variation of Trees and Lianas in a Tropical Forest of Southeast Asia: Allometry, Phylogeny, and Seed Trait - Plant Functional Trait Relationships

Seed size is a key trait for understanding and predicting ecological processes in a plant community. In a tropical forest, trees and lianas are major components driving ecosystem function and biogeochemical processes. However, seed ecological research on both components remains limited, particularly phylogenetic patterns and relationships with other traits. Here, we compiled a unique dataset of seed size (seed mass and geometrical size metrics) based on collections of more than 5,200 seeds of 196 woody plant species, covering >98 and 70% of tree and liana stems, respectively, located on a 30-ha plot in a tropical evergreen forest in central Thailand. We aimed to (1) develop allometric equations among seed size metrics to predict seed mass; (2) examine phylogenetic influence on seed size variation; and (3) examine relationships among seed traits and several other functional plant traits. Our allometric equations relating seed mass, seed volume, and width were well-fitted with data (R2= 0.94, 0.87 respectively). A phylogenetic signal test found that seed size was randomly distributed across the phylogeny. To study the functional trait relationships, we separately tested seed size data of the tree and liana communities (146 and 50 species, respectively), against mean body size of frugivores, successional niches, leaf, and structural traits. For the tree community, seed size was significantly related to mean body size of frugivores, which we believe is a basic driver of seed size because it is related to the gape width affecting dispersal effectiveness. Nearly all leaf traits were significantly positively correlated with seed size (p < 0.03). The significant positive correlation of leaf area and greenness suggested the high-energy demand of large-seeded species. We found a strong positive correlation between seed size and leaf toughness, suggesting a coordination between seed size and leaf defense. However, all these patterns disappeared in the same analysis applied to the liana community. Liana seed size variation was lower than that of trees, perhaps because lianas grow in relatively more uniform conditions in the forest canopy. Frugivore size was the strongest driver of seed size variation. Our study shows a surprising contrast between trees and lianas that is worth further investigation.
Distributed formation control for autonomous robots

This thesis addresses several theoretical and practical problems related to formation-control of autonomous robots. Formation-control aims to simultaneously accomplish the tasks of forming a desired shape by the robots and controlling their coordinated collective motion. This kind of robot performance is a cornerstone in the emerging field of swarm robotics, in particular with applications in precision agriculture, coverage of sport/art events, communication networks, area surveillance or vehicle platooning for energy efficiency and many others. One of the most important outcomes of this thesis is that the provided algorithms are completely distributed. This means that there is no central unit commanding the robots, but they have their own intelligence which allows them to make their own decisions based only on the local information. A distributed scheme entails a striking feature about the scalability and maintenance of a team of robots. Moreover, we also address the scenario of having wrongly calibrated sensors, which has a profound impact in the performance of the robots. The provided algorithms make the robots robust against such a practical and very common problem in real applications.
Psychosomatic Symptoms in Terminally Ill Cancer Patients and Its Relation With Using Complementary and Alternative Medicines: A Cross-Sectional Study in Southeast Iran

Background Cancer patients face various problems and complications, which they address through various complementary and alternative medicines (CAM). The aim of this study was to investigate the relationship between CAM and psychosomatic symptoms in terminally ill cancer patients. Methods This cross-sectional study was performed on 221 terminally ill cancer patients (based on metastatic stage and according to the physicin diagnosis) in southeastern Iran. Convenience sampling was used to select terminally ill cancer patients. Using questionnaires like the demographic and clinical information questionnaire, Edmonton Symptom Assessment Scale (ESAS), Hospital Anxiety and Depression Scale (HADS), CAM questionnaire and satisfaction with the use of CAM, the researcher was able to compile a comprehensive picture of the population. Results The mean age of the participants was 51.66 ± 13.34 years. The majority of the samples were female, married, educated, and unemployed. The mean score for the physical symptoms of the participants according to ESAS was 22.25 ± 17.57 which was less than the midpoint of the scale (the possible score of ESAS was 0–100). Only 2.7% (n = 6) and 0.9% (n = 2) of the participants had mild and moderate anxiety, respectively, and the other participants' anxiety levels were normal. Only 7.7% (n = 17) and 4.1% (n = 9) of the participants had mild and moderate depression, respectively, and the other participants' depression levels were normal. Last year, 87.3% of the participants used at least one type of CAM. Aside from prayer, 42.1% of the participants used at least one type of CAM in the last year. Prayer was used by 83.7% of the participants, medicinal plants by 35.8%, massage by 9.5%, dietary supplements by 3.6%, wet cupping by 3.2%, relaxation and meditation by 2.7%, dry cupping by 2.4%, and acupuncture by 0.5%. The common reason for using CAM was to reduce the stress and anxiety caused by cancer and to treat it. There were no significant differences in physical and psychological symptoms between the CAM-users and non-CAM users. Conclusion Patients with cancer have a relatively low level of psychosomatic symptoms, and the primary reason for using CAM was to relieve stress and anxiety associated with cancer and treat it. However, psychosomatic symptoms were the same for CAM and non-CAM users. Because so many people with cancer use CAM, future studies should look into why and how CAM is used.
Green Finance, Innovation and the Energy-Environment-Climate Nexus

After the Paris Climate Conference (COP21), carbon neutrality and environmental sustainability have become the consensus of many countries. Technological innovation and green finance are the essential factors that can help to realize clean energy transition, carbon emission reduction and climate change mitigation. To investigate the pathways for sustainable development, this study includes innovation and green finance into simultaneous equations models within energy-environment-climate nexus. We examine the dynamic relationships for a sample of 49 countries with green bonds issued for the period 2007–2019. The results confirm that there are bidirectional relationships among renewable energy consumption, environmental pollution and climate change. Innovation can significantly promote renewable energy consumption, reduce CO2 emissions and mitigate climate change. Green finance can effectively alleviate environmental pollution and climate change. Accelerating the development of green finance is the primary motivation for sustainable development. Green finance moderates the relationship between innovation and energy-environment-climate nexus. The positive impact of innovation on renewable energy consumption is enhanced by higher level of green finance. When the development of green finance is high, innovation has a greater negative influence on CO2 emissions, and the impact of innovation on climate change is weakened.
The Global and Western Indian Ocean Dispersal of House Geckos From Asia Using Historical and Mitochondrial DNA Perspectives

Seven species of house geckos occur across the scattered islands of the Indian Ocean. Two of these, Hemidactylus frenatus and H. parvimaculatus are both widespread and possess distribution profiles that suggest pre-European, or perhaps natural dispersal to some islands. Of these, only H. frenatus currently has sufficient molecular data to begin exploring dispersal patterns. This species is one of the most successful reptile colonists, as demonstrated by its global, pantropical distribution. While in some areas, such as Australia and continental South America, its dispersal patterns are both recent and well-known, early historical records of Hemidactylus in the Indian Ocean islands suggest earlier and/or potentially non-human-mediated dispersals. Here, we reviewed the historical literature and combined those reports with an assessment of mitochondrial DNA diversity of a global sampling of H. frenatus samples that included modern and museum specimens. Our results corroborate previous studies and demonstrate the relatively high diversity within this species’ native range in Southeast Asia. In addition, the phylogenetic analysis suggests both a potential cryptic species complex, as well as global geographic structuring of different H. frenatus mitochondrial lineages. This has important implications for many comparative studies of this complex. Frequent and ongoing dispersals and colonizations complicate the identification of potentially older migration patterns. Further assessments including additional samples and analyses of additional genetic markers are necessary to disentangle older from more recent dispersals within this intriguing species.
A Fly in the Ointment: How to Predict Environmentally Driven Phenology of an Organism That Partially Regulates Its Microclimate

Phenological models representing physiological and behavioral processes of organisms are used to study, predict, and optimize management of ecological subsystems. One application of phenological models is the prediction of temporal intervals associated with the measurable physiological development of arthropods, for the purpose of estimating future time points of interest such as the emergence of adults, or estimating past time points such as the arrival of ovipositing females to new resources. The second of these applications is of particular use in the conduct of forensic investigations, where the time of a suspicious death must be estimated on the basis of evidence, including arthropods with measurable size/age, found at the death scene. Because of the longstanding practice of using necrophagous insects to estimate time of death, standardized data and methods exist. We noticed a pattern in forensic entomological validation studies: bias in the values of a model parameter is associated with improved model fit to data, for a reason that is inconsistent with how the models used in this practice are interpreted. We hypothesized that biased estimates for a threshold parameter, representing the lowest temperature at which insect development is expected to occur, result in models’ accounting for behavioral and physiological thermoregulation but in a way that results in low predictive reliability and narrowed applicability of models involving these biased parameter estimates. We explored a more realistic way to incorporate thermoregulation into insect phenology models with forensic entomology as use context, and found that doing so results in improved and more robust predictive models of insect phenology.
A Social Norms and Identity Approach to Increasing Fruit and Vegetable Intake of Undergraduate Students in the United Kingdom

This study investigated the influence of descriptive norm messages that either communicated that university students eat a sufficient amount of fruit and vegetable (F&V) or that they do not, on F&V consumption, and whether or not any effects are moderated by student identification. An online 2 (Norm: “Sufficient”/“Insufficient”) × 2 (Identification: “Low”/“High”) experimental design was employed. Infographics containing “sufficient”/“insufficient” F&V intake descriptive norms were presented. An identification manipulation was employed to create “high”/“low” student identifiers. F&V intake intentions were assessed after the manipulations; self-reported F&V intake was reported at 2 days post-intervention. Undergraduate students in the United Kingdom (N = 180) reported their intake intentions, of which 112 (62%) completed the behavioral follow-up. Participants were predominantly white female students from Scottish universities, mean age 20.4 (±1.6) years. Baseline mean F&V consumption was high (4.5 ± 2.8). There were no significant main effects of Norm or Identification manipulations on F&V intentions and intake. Significant norm × identification interactions were revealed for fruit intake intentions and vegetable intake at follow-up, indicating half-portion differences (~40 g) between groups. Ironic effects were observed for “high” identifiers, who neither intended to, nor acted in accordance with group norms; “low” student identifiers intended to and followed group norms, whereby the “sufficient”/“low” group intended to consume significantly more fruit portions and consumed more vegetables than the “insufficient”/“low” group. Given the half-portion differences between groups resulting from the norm × identification interactions, future research on a larger sample of young adults with low F&V intake is warranted to further explore the conditions under which moderating effects of identification are observed and the underlying mechanisms.