Miracle-dz/UniFAR-FTUs huggingface dataset:
Landscape of driver gene events, biomarkers, and druggable targets identified by whole-genome sequencing of glioblastomas

Abstract Background The survival of glioblastoma patients is poor. Median survival after diagnosis is 15 months, despite treatment involving surgical resection, radiotherapy, and/or temozolomide chemotherapy. Identification of novel targets and stratification strategies of glioblastoma patients to improve patient survival is urgently needed. Whole-genome sequencing (WGS) is the most comprehensive means to identify such DNA-level targets. We report a unique set of WGS samples along with comprehensive analyses of the glioblastoma genome and potential clinical impact of WGS. Methods Our cohort consisted of 42 glioblastoma tumor tissue and matched whole-blood samples, which were whole-genome sequenced as part of the CPCT-02 study. Somatic single-nucleotide variants, small insertions/deletions, multi-nucleotide variants, copy-number alterations (CNAs), and structural variants were analyzed. These aberrations were harnessed to investigate driver genes, enrichments in CNAs, mutational signatures, fusion genes, and potential targeted therapies. Results Tumor mutational burden (TMB) was similar to other WGS efforts (1–342 mutations per megabase pair). Mutational analysis in low TMB samples showed that the age-related CpG demethylation signature was dominant, while hyper- and ultramutated tumors had additional defective DNA mismatch repair signatures and showed microsatellite instability in their genomes. We detected chromothripsis in 24% of our cohort, recurrently on chromosomes 1 and 12. Recurrent noncoding regions only resulted in TERT promoter variants. Finally, we found biomarkers and potentially druggable changes in all but one of our tumor samples. Conclusions With high-quality WGS data and comprehensive methods, we identified the landscape of driver gene events and druggable targets in glioblastoma patients.
circ_0075943 Dominates the miR-141-3p/AK2 Network to Support the Development of Breast Carcinoma

Background Breast cancer (BC) progression is related to the disorder of circular RNAs (circRNAs). This study aims to characterize the role of circ_0075943 in BC. Methods Real-time fluorescent quantitative PCR (real-time PCR) technology was implemented to investigate circ_0075943, AK2 mRNA, and microRNA-141-3p levels. MTT, colony formation method, Transwell, and flow cytometry technique were adopted to investigate cell function. The connection between miR-141-3p and circ_0075943 or AK2 was confirmed by the dual-luciferase reporter gene or RNA immunoprecipitation (RIP). The influence on circ_0075943 in vivo was confirmed by animal experiments. Results circ_0075943 was augmented in BC cell lines and tumor specimens. Dwindling of circ_0075943 could dramatically suppress the phenotype of BC cells and induce apoptosis. MiR-141-3p is a target of circ_0075943, and its repression largely reverses the influence of knocking down circ_0075943 on cell behavior. Moreover, AK2, as a target of miR-141-3p, is augmented in BC cells and specimens. AK2 overexpression could restore the phenotype of BC cells blocked by miR-141-3p redevelopment. Moreover, knocking down circ_0075943 could suppress the growth of tumors in vivo. Conclusion The abnormal regulation of circ_0075943 participates in part of the expansion of BC by dominating the miR-141-3p/AK2 regulatory network.
Web Manifestations of Knowledge-Based Innovation Systems in the UK

This work or any part thereof has not previously been presented in any form to the University or to any other body whether for the purposes of assessment, publication or for any other purpose (unless otherwise indicated). Save for any express acknowledgments, references and/or bibliographies cited in the work, I confirm that the intellectual content of the work is the result of my own efforts and of no other person. The right of David Stuart to be identified as author of this work is asserted in accordance with ss.77 and 78 of the Copyright, Designs and Patents Act 1988. At this date copyright is owned by the author.
Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.
Stacked multicell converter (SMC): control and natural balancing

This paper presents a new control strategy to improve natural balancing properties of a stacked multicell converter (SMC) dedicated to high voltage high power applications. Another advantage of this topology is the spectral quality of the output voltage. The specific features of this converter are presented. Then the control requirements and the corresponding modulator are discussed. Finally, the study of the balancing of the capacitor voltages leads to a modified modulator.
Effect of Polymer Dissolution Temperature and Conditioning Time on the Morphological and Physicochemical Characteristics of Poly(Vinylidene Fluoride) Membranes Prepared by Non-Solvent Induced Phase Separation

This work reports on the production of poly(vinylidene fluoride) (PVDF) membranes by non-solvent induced phase separation (NIPS) using N,N-dimethylformamide (DMF) as solvent and water as non-solvent. The influence of the processing conditions in the morphology, surface characteristics, structure, thermal and mechanical properties were evaluated for polymer dissolution temperatures between 25 and 150 °C and conditioning time between 0 and 10 min. Finger-like pore morphology was obtained for all membranes and increasing the polymer dissolution temperature led to an increase in the average pore size (≈0.9 and 2.1 µm), porosity (≈50 to 90%) and water contact angle (up to 80°), in turn decreasing the β PVDF content (≈67 to 20%) with the degree of crystallinity remaining approximately constant (≈56%). The conditioning time did not significantly affect the polymer properties studied. Thus, the control of NIPS parameters proved to be suitable for tailoring PVDF membrane properties.
Operating Rules for an Off-Stream Blending Reservoir to Control Nitrate in a Municipal Water System

AbstractMunicipal water supply systems dependent on surface water sources that are susceptible to both low flows and contamination can use off-stream blending reservoirs (OSBR) both to increase their yield and avoid investments in expensive treatment technology. Three water quality operating rules (WQORs) are simulated from a retrospective planning perspective using the OSBR system that controls nitrate contamination for Pontiac, Illinois as an example case. These rules regulate pumped reservoir inflow based on (1) a maximum river concentration (Riv-CR), (2) a maximum reservoir concentration (Res-CR), and (3) a hybrid rule incorporating both maximum reservoir and river concentrations (Hyb-CR). The Hyb-CR rule typically registers the highest yield when nitrate is modeled as a conservative contaminant, while Res-CR tends to produce the highest yields when nitrate losses are considered. In general, reservoir concentration-based WQORs are effective for increasing the yield of OSBR systems that control the con.
EFFECT OF CRUSHER DUST ON ENGINEERING PROPERTIES OF LIME STABILIZED BLACK COTTON SOIL

1* The effect of crusher dust on the engineering characteristics of Black Cotton soil is presented in this paper. The soil Sample used is stabilized with 5% lime. A laboratory study was undertaken to evaluate the effect of crusher dust as a soil stabilizer. Soil sample containing 5% lime and 10% and 20% of crusher dust were prepared and compaction characteristic and California bearing ratio test were conducted as per relevant IS code of practise. The test results revealed that the compaction parameters and CBR values of the soil are improved substantially with the addition of the granite dust. The result showed the CBR value increased from 1.7% to 7.15%, the optimum moisture content have been reduced from 22% to 14.3% and the maximum dry density have been increased from 1.58 g/cc to 1.88 g/cc. The conclusion drawn from this experimental work is that the expansive clay like black cotton soil can be stabilized by the combination of lime and crusher dust to increase the stability.
Potential Factors That Trigger the Suspension of Calcium Carbonate Sediments and Whiting in a Semi-Enclosed Gulf

Whitings, the manifestation of high levels of suspended fine-grained calcium carbonate particles in the water, have been reported and studied worldwide. However, the triggering mechanism of whiting occurrences remains uncertain. The current study attempted to analyze potential factors that might account for whiting occurrences in a semi-enclosed gulf (namely the Arabian/Persian Gulf, hereinafter called the Gulf). First, spatial and temporal variability of whiting events and different potential driving factors (i.e., whiting seasonality, wind-induced mixing, sea surface temperature, and bathymetry) were explored and examined for five years (2015–2020). Second, as a general indicator of whiting occurrences in the Gulf, a whiting index (WI) was developed using time-series analysis and decision tree (DT) classification algorithm. Third, the correlation between the proposed WI and the spatial coverage of various whiting events was examined. Time-series analysis showed that whiting events during the winter season are associated with high winds that lasted for several days. Nevertheless, whiting events were rarely observed despite high wind speed and increased potential for CaCO3 precipitation in summer. This finding suggests that wind-driven forces might be potential sources for mixing water columns, resuspension of CaCO3 particles, and the appearance of whiting in the Gulf. The DT classification algorithm demonstrated that a minimum WI value of 1.1 can explain the initiation of most summer and winter whiting events. Furthermore, a Pearson correlation coefficient of 0.73 was measured between WI and the extent of whiting along the UAE and Qatar coastlines in the Gulf. The proposed WI shows a simple yet effective method for identifying and estimating the extent of whiting in the Gulf.
Returning to Radburn

The “new urbanist” vision for contemporary neighborhoods looks back to the streetscapes of the pre-automobile era for inspiration, intentionally overlooking the automobile-adaptive community design era which began in America with Clarence Stein’s and Henry Wright’s “Town for the Motor Age” Radburn1 in the late 1920s. New urbanism establishes a theoretical position fundamentally at odds with “garden city” design principles which differentiate streetscapes and community open space. New urbanists do this by downplaying or ignoring the conflict inherent in the idea that a neighborhood street should attempt to serve as civic interface while simultaneously serving as the outdoor focus for neighborhood social life. The author proposes that experimental and innovative Radburn, rather than pre-modern, pre-automobile town design, is the logical starting point for understanding how to form contemporary neighborhoods, because Radburn actually began to address the dilemma posed by the new automobility. Subsequent “garden city” experiments such as the American New Towns of the 1960s and later planned unit developments paid homage to Radburn, but abandoned particular radical aspects of the Radburn concept; thus we have not witnessed the true evolution of Radburn in North American suburbia. However, the few planned communities which did remain true to Radburn’s radicalism, such as Winnipeg, Manitoba’s postwar Wildwood Park, do reflect this evolution. This paper will address the fundamental opposition that constitutes the relationship between new urbanism and the Radburn concept, and will reveal that the present-day landscapes of Wildwood Park and of Radburn itself have evolved to offer insights for how the Radburn concept can be adapted for contemporary community planning.
Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders.
The ‘Perfect’ Conversion: Dramatic Increase in CO2 Efflux from Shellfish Ponds and Mangrove Conversion in China

Aquaculture, particularly shellfish ponds, has expanded dramatically and become a major cause of mangrove deforestation and “blue carbon” loss in China. We present the first study to examine CO2 efflux from marine aquaculture/shellfish ponds and in relation to land-use change from mangrove forests in China. Light and dark sediment CO2 efflux from shellfish ponds averaged at 0.61 ± 0.07 and 0.90 ± 0.12 kg CO2 m−2 yr−1 (= 37.67 ± 4.89 and 56.0 ± 6.13 mmol m−2 d−1), respectively. The corresponding rates (−4.21 ± 4.54 and 41.01 ± 4.15 mmol m−2 d−1) from the adjacent mangrove forests that were devoid of aquaculture wastewater were lower, while those from the adjacent mangrove forests (3.48 ± 7.83 and 73.02 ± 5.76 mmol m−2 d−1)) receiving aquaculture wastewater markedly increased. These effluxes are significantly higher than those reported for mangrove forests to date, which is attributable to the high nutrient levels and the physical disturbance of the substrate associated with the aquaculture operation. A rise of 1 °C in the sediment temperature resulted in a 6.56% rise in CO2 released from the shellfish ponds. Combined with pond area data, the total CO2 released from shellfish ponds in 2019 was estimated to be ~12 times that in 1983. The total annual CO2 emission from shellfish ponds associated with mangrove conversion reached 2–5 Tg, offsetting the C storage by mangrove forests in China. These are significant environmental consequences rather than just a simple shift of land use. Around 30% higher CO2 emissions are expected from aquaculture ponds (including shellfish ponds) compared to shellfish ponds alone. Total annual CO2 emission from shellfish ponds will likely decrease to the level reported in early 1980 under the pond area-shrinking scenario, but it will be more than doubled under the business-as-usual scenario projected for 2050. This study highlights the necessity of curbing the expansion of aquaculture ponds in valuable coastal wetlands and increasing mangrove restoration to abandoned ponds.
FLATNESS BASED CONTROL OF A DUAL COIL SOLENOID VALVE

Abstract This paper presents first results in the attempt to control a dual coil solenoid valve by means of a flatness based approach. First the modeling effort is described, then the differential flatness of the system is shown. The modeling results revealed that the system lacks controllability, when considering one coil only for actuating the valve. Therefore a suitable strategy for energizing both coils has been developed. The flatness property then is used to design feasible reference trajectories for the spool motion with the following properties: soft-landing of the spool, minimal driving current, feasible subject to voltage constraints. Simulation results demonstrate the usefulness and robustness of the approach.
Experimental study of a novel thermoelectric domestic-ventilator with heat recovery

A novel prototype thermoelectric domestic-ventilator with air-conditioning heat recovery of exhaust had been made and tested in this paper. A thermoelectric heat exchanger is integrated with a flat-fin cross-flow heat exchanger in this ventilator. This ventilator is investigated and its cooling (or heating) performance evaluated in terms of the Coefficient of Performance (COP), cooling and heating power, and being handled temperature difference of fresh air. The COP of this ventilator is found to be over 2.5 in the whole test. The optimal working parameters of this ventilator are found in the study. The potential improvement in the cooling and heating performance is also discussed in this work.
Accurate Instance Segmentation in Pediatric Elbow Radiographs

Radiography is an essential basis for the diagnosis of fractures. For the pediatric elbow joint diagnosis, the doctor needs to diagnose abnormalities based on the location and shape of each bone, which is a great challenge for AI algorithms when interpreting radiographs. Bone instance segmentation is an effective upstream task for automatic radiograph interpretation. Pediatric elbow bone instance segmentation is a process by which each bone is extracted separately from radiography. However, the arbitrary directions and the overlapping of bones pose issues for bone instance segmentation. In this paper, we design a detection-segmentation pipeline to tackle these problems by using rotational bounding boxes to detect bones and proposing a robust segmentation method. The proposed pipeline mainly contains three parts: (i) We use Faster R-CNN-style architecture to detect and locate bones. (ii) We adopt the Oriented Bounding Box (OBB) to improve the localizing accuracy. (iii) We design the Global-Local Fusion Segmentation Network to combine the global and local contexts of the overlapped bones. To verify the effectiveness of our proposal, we conduct experiments on our self-constructed dataset that contains 1274 well-annotated pediatric elbow radiographs. The qualitative and quantitative results indicate that the network significantly improves the performance of bone extraction. Our methodology has good potential for applying deep learning in the radiography’s bone instance segmentation.
Botanical, Phytochemical, Anti-Microbial and Pharmaceutical Characteristics of Hawthorn (Crataegus monogyna Jacq.), Rosaceae

Hawthorn (Crataegus monogyna Jacq.) is a wild edible fruit tree of the genus Crataegus, one of the most interesting genera of the Rosaceae family. This review is the first to consider, all together, the pharmaceutical, phytochemical, functional and therapeutic properties of C. monogyna based on numerous valuable secondary metabolites, including flavonoids, vitamin C, glycoside, anthocyanin, saponin, tannin and antioxidants. Previous reviews dealt with the properties of all species of the entire genera. We highlight the multi-therapeutic role that C. monogyna extracts could have in the treatment of different chronic and degenerative diseases, mainly focusing on flavonoids. In the first part of this comprehensive review, we describe the main botanical characteristics and summarize the studies which have been performed on the morphological and genetic characterization of the C. monogyna germplasm. In the second part, the key metabolites and their nutritional and pharmaceutical properties are described. This work could be an essential resource for promoting future therapeutic formulations based on this natural and potent bioactive plant extract.
Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans

Sexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons. In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.