Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic alterations drive brain metastases formation in colorectal cancer: The role of IRS2

Colorectal cancer (CRC) is currently the fourth leading etiology of brain metastasis (BM). Yet, mechanisms supporting the formation of CRC BM are mostly unknown. In order to identify drivers that lead to tropism and adaptation of CRC cells to the brain environment, we analyzed an extensive genomic database, consisting of over 36,000 human CRC primary and metastasis samples. Several genomic alterations specific for BM were noted, among them increased prevalence of insulin receptor substrate 2 (IRS2) amplification, observed in 7.6% of BM, compared to only 2.9% of primary tumors or other metastatic sites (p<7E-05). This observation was validated by Immunohistochemistry studies of human clinical samples, showing increased expression of IRS2 protein in BM. IRS2 is a cytoplasmic adaptor mediating effects of insulin and IGF-1 receptors and is involved in more aggressive behavior of different cancer types. In order to study the ability of IRS2 to promote growth of CRC cells under brain microenvironment conditions, we employed an in vitro system consisting of cultured human astrocytes or their conditioned media. Indeed, IRS2-overexpressed CRC cells survived better and formed larger 3D spheres when grown in brain-mimicking conditions, while IRS2-silenced CRC cells showed a mirror image. Similarly, In vivo studies, using intracranial CRC BM mouse model, demonstrated that IRS2-overexpressed cells generated larger brain lesions, while silencing IRS2 dramatically decreased tumor outgrowth and extended survival. Transcriptomic analysis revealed enrichment of oxidative phosphorylation (OXPHOS) and Wnt/β-catenin pathways by IRS2. Indeed, IRS2-expressing cells showed increased mitochondrial activity and glycolysis-independent viability. Furthermore, IRS2-expressing cells had increased β-catenin transcriptional activity, and either β-catenin inhibition or IRS2 inhibition in IRS2-expressing cells decreased their viability, β-catenin transcriptional activity, and mitochondrial activity. These data suggest involvement of IRS2 in modulating OXPHOS through β-catenin. Exploiting this mechanism as a potential vulnerability allowed us to develop novel treatment strategies against CRC BM. NT219 is a novel IRS1/2 inhibitor already being tested in clinical trials. Treatment of mice harboring CRC BM with NT219 and 5-flourouracil reduced tumor growth and prolonged mice survival. These data reveal, for the first time, the unique genomic profile of CRC BM and imply the IRS2 role in promoting CRC BM. These effects may be mediated, at least in part, by modulation of the β-catenin and OXPHOS pathway. These findings may pave the way for clinical trials evaluation this novel IRS2-based strategy for the treatment of CRC BM. Accession no GSE203017 and here is the link: https://www.ncbi. nlm.nih. gov/geo/query/acc.cgi? acc=GSE203017
Genome-Wide Association and Genomic Prediction of Growth Traits in the European Flat Oyster (Ostrea edulis)

The European flat oyster (Ostrea edulis) is a bivalve mollusc that was once widely distributed in Europe and represented an important food resource for humans for centuries. Populations of O. edulis experienced a severe decline across their biogeographic range mainly due to anthropogenic activities and disease outbreaks. To restore the economic and ecological benefits of European flat oyster populations, extensive protection and restoration efforts are in place within Europe. In line with the increasing interest in supporting restoration and oyster farming through the breeding of stocks with enhanced performance, the present study aimed to evaluate the potential of genomic selection for improving growth traits in a European flat oyster population obtained from successive mass-spawning events. Four growth-related traits were evaluated: total weight (TW), shell height (SH), shell width (SW) and shell length (SL). The heritability of the growth traits was moderate-low, with estimates of 0.45, 0.37, 0.22, and 0.32 for TW, SH, SW and SL, respectively. A genome-wide association analysis revealed a largely polygenic genetic architecture for the four growth traits, with two distinct QTLs detected on chromosome 4. To investigate whether genomic selection can be implemented in flat oyster breeding at a reduced cost, the utility of low-density SNP panels (down to 100 SNPs) was assessed. Genomic prediction accuracies using the full density panel were high (>0.83 for all traits). The evaluation of the effect of reducing the number of markers used to predict genomic breeding values revealed that similar selection accuracies could be achieved for all traits with 2K SNPs as for a full panel containing 4,577 SNPs. Only slight reductions in accuracies were observed at the lowest SNP density tested (i.e. 100 SNPs), likely due to a high relatedness between individuals being included in the training and validation sets during cross-validation. Overall, our results suggest that the genetic improvement of growth traits in oysters is feasible. Nevertheless, and although low-density SNP panels appear as a promising strategy for applying GS at a reduced cost, additional populations with different degrees of genetic relationship should be assessed to derive estimates of prediction accuracies to be expected in practical breeding programmes.
Thermodynamic analysis of thermophotovoltaic systems used in waste heat recovery systems: an application

Thermodynamic analysis of the thermophotovoltaic (TPV) system was carried out in our research and the results are presented. First, the TPV system was analyzed in three different regions. In the analysis, each part of the system is taken separately, while the whole system is handled separately. Within the thermodynamic analysis of each region, energy and exergy analysis were carried out and the system was analyzed from part to part. As a result of this method, a general energy and exergy efficiency of the whole TPV system is determined. Our results are supported by formulas. The In0.2Ga0. 8As0.18Sb0. 82 cell has a higher efficiency compared to the GaSb cell at the same source temperature. This is because the reverse saturation current and the energy band gap are low and the short-circuit current is high. If TPV systems are applied for waste heat energy potential in the Turkish iron and steel industry, the energy efficiency of GaSb cell systems is 66 192 MJ per year with energy efficiency of 2.04%, the energy efficiency of In0.2Ga0. 8As0.18Sb0. 82 cell systems is 7.31% with annual energy efficiency of 189 971 MJ can be recovered. It is aimed that the work done will be an alternative to the existing electricity generation and will form a resource for future works.
Specific detection and deletion of the Sigma-1 receptor in neurons and glial cells for functional characterization in vivo

The chaperon protein sigma-1 receptor (S1R) has been discovered over forty years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising therapeutical potential of targeting the S1R for several neurological disorders. Although intensive in vitro studies have revealed S1Rs are mainly residing at the membrane of the endoplasmic reticulum (ER), the cell-specific in vivo expression pattern of S1Rs is still unclear, mainly due to the lack of a reliable detection method which also prevented a comprehensive functional analysis. Here, first, we identified a highly specific antibody using S1R knockout (KO) mice and established an immunohistochemical protocol involving a 1% SDS antigen retrieval step. Second, we characterized the S1R expression in the mouse brain and can demonstrate that the S1R is widely expressed: in principal neurons, interneurons, and all glial cell types. Finally, we generated a novel Cre-dependent S1R conditional KO mouse (S1R flox) to study cell type-specific functions of the S1R. As a proof of concept, we successfully ablated S1R expressions in neurons or microglia employing neuronal and microglial Cre-expressing mice, respectively. In summary, we provide powerful tools to cell-specifically detect, delete and functionally characterize S1R in vivo.
Title: “Genetic and chemical disruption of Amyloid Precursor Protein processing impairs zebrafish sleep maintenance”

Sleep-wake disturbances are among the earliest symptoms of Alzheimer’s disease (AD) and contribute to disease severity. Since a major driver of AD—the accumulation of amyloid-beta (Aβ) in the brain—is modulated by sleep, a “vicious” feedforward cycle has been proposed in which Aβ buildup disrupts sleep, leading to more Aβ secretion and further worsening of sleep and AD. Consistent with this idea, mouse models of AD develop early sleep phenotypes, and sleep is acutely modulated by exogenous Aβ. However, these overexpression paradigms leave unclear whether endogenous Aβ signaling contributes to sleep regulation. To tackle this question, we generated loss of function mutations in the zebrafish orthologs of Amyloid Precursor Protein (APP) and monitored larval sleep behavior. Larvae with mutations in appa had reduced waking activity levels but normal sleep patterns, while larvae that lacked appb had reduced sleep due to an inability to maintain sleep bout durations. In addition, larvae exposed to the γ-secretase inhibitor DAPT, which inhibits Aβ production from APP, also have shorter sleep bouts at night. Although γsecretase inhibition impacts the proteolytic cleavage of many proteins, appb mutants were insensitive to the sleep bout shortening effects of DAPT, suggesting that loss of
DivIVA phosphorylation at threonine affects its dynamics and cell cycle in Deinococcus radiodurans

RqkA, a γ radiation responsive Ser/Thr quinoprotein kinase, is characterized for its role in radioresistance in Deinoocccus radiodurans. DivIVA is a cell division protein involved in determination of cell pole and division site in bacteria. RqkA phosphorylated cognate DivIVA (drDivIVA) at Threonine 19 (T19) residue located in its pole recognition motif. The phospho-mimetic replacement of T19 (T19E) functioned differently than phospho-ablative (T19A) and drDivIVA proteins. T19E-RFP expressing in wild type background showed arrest in dynamics of drDivIVA, and loss of interaction with genome segregation protein. divIVA is shown to be an essential gene in this bacterium. The allelic replacement of divIVA with T19E-RFP was not tolerated unless drDivIVA was expressed episomally while there was no effect of this replacement with T19A-RFP and drDivIVA-RFP. These results suggested that the T19 phosphorylation in drDivIVA by RqkA has affected in vivo functions of DivIVA that would render cell cycle arrest in this bacterium.
No modular shape changes in the mandible of Andean white-eared opossum (Didelphis pernigra, Linnaeus, 1758)

Morphological integration and modularity are concepts that refer to the covariation level between the components of a structure. Species of the opossums, genus Didelphis, have been the object of several taxonomic and morphometric analyses but no study has so far analysed mandibular morphological integration and modularity at a species-level. The aim of this work was to check whether the body (corpus mandibulae, mandibular corpus) and the ramus (ramus mandibulae, ascending mandibular ramus) are separate modules in Didelphis pernigra using a two-dimensional geometric morphometric approach. For this purpose, a sample of hemimandibles from 36 D. pernigra (13 males and 23 females) was analysed using 17 landmarks in lateral view. The modularity hypothesis based on different developmental origins was tested, by using the RV coefficient. Later, the integration level was assessed applying a partial least-squares analysis (PLS). The underlying aim was to know whether the traditional division between mandibular body and ramus has a modular basis, as well as the morphological integration level between these two structures. Results reflected that landmarks integration was not uniform throughout the mandible but structured into two distinct modules: ramus and body. Results allow to conclude that allometry plays an important role in shape variation in this species, and that the hypotheses of two-module organization in males cannot be confirmed. Models that accurately represent the biting mechanics will strengthen our understanding of which variables are functionally relevant and how they are relevant to performances, not only masticatories.
Clostridium scindens colonization of gnotobiotic mice promotes a chronic unresolving infection with Clostridioides difficile

The commensal Clostridium scindens has been regarded as a promising bacteriotherapeutic against Clostridioides difficile infection due to its ability to consume host factors that can promote C. difficile growth, and its production of the antimicrobial compound 1-acetyl-β-carboline. We investigated C. scindens’ protective effects against C. difficile using defined colonization studies in gnotobiotic mice. Mice infected with C. difficile develop lethal infection within 48 hours. In contrast, 88% of mice pre-colonized with C. scindens survived acute infection with delayed C. difficile colonization, lower biomass, and toxin B levels at 24 hours after infection. However, two weeks post-challenge, surviving mice showed comparable levels of cecal C. difficile vegetative and spore biomass and toxin B, as seen during acute infection. After two weeks, co-colonized mice exhibited mucosal colonic hyperplasia with focal pseudomembranes, modeling a chronic and recurrent infection state. Our findings illustrate how the commensal microbiota can modulate host and pathogen interactions leading to chonic C. difficile carriage and infection.
Investigation of thermal performance of a solar pond with external heat addition

This study addresses the method of adding heat to a salt gradient solar pond (SGSP) from external sources and investigates the thermal performance of the pond. In this case, the external heat source is solar heat collected by evacuated tube solar collectors (ETSC), and collected heat is transferred to the lower-convective zone (LCZ) of the SGSP by circulating fluid from the LCZ. Results show that heat addition from the external source enhances the thermal performance of the SGSP in terms of heat recovery and thermal efficiency but with certain constraints. The heat addition efficiency reduces with increase in aperture area of the ETSC. Also with increasing heat addition, the heat removal from the SGSP has to be increased; otherwise, the SGSP efficiency reduces rapidly. Heat removal from SGSP has to be performed keeping in mind the heat demand and the quality of heat. The latter reduces with an increase of heat extraction beyond a certain limit. Hence, optimizing the range of parameters in case of adding heat from external sources is very important for the best performance of a SGSP.
Enhancement of Edge-based Image Quality Measures Using Entropy for Histogram Equalization-based Contrast Enhancement Techniques

An Edge-based image quality measure (IQM) technique for the assessment of histogram equalization (HE)-based contrast enhancement techniques has been proposed that outperforms the Absolute Mean Brightness Error (AMBE) and Entropy which are the most commonly used IQMs to evaluate Histogram Equalization based techniques, and also the two prominent fidelity-based IQMs which are Multi-Scale Structural Similarity (MSSIM) and Information Fidelity Criterion-based (IFC) measures. The statistical evaluation results show that the Edge-based IQM, which was designed for detecting noise artifacts distortion, has a Person Correlation Coefficient (PCC) > 0.86 while the others have poor or fair correlation to human opinion, considering the Human Visual Perception (HVP). Based on HVP, this paper propose an enhancement to classic Edge-based IQM by taking into account the brightness saturation distortion which is the most prominent distortion in HE-based contrast enhancement techniques. It is tested and found to have significantly well correlation (PCC > 0.87, Spearman rank order correlation coefficient (SROCC) > 0.92, Root Mean Squared Error (RMSE) < 0.1054, and Outlier Ratio (OR) = 0%).
Diversity of durian (Durio zibethinus L.) from Nonthaburi, Thailand based on morpho-palatability characteristics and simple sequence repeat markers

a Department of Plant Science, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand. b Department of Biology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand. c Plant Genetic Conservation Project, Chitralada Villa, Dusit, Bangkok 10303, Thailand. d Faculty of Environment and Resource Studies, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand. e Horticultural Research Institute, Department of Agriculture, Ministry of Agriculture and Cooperatives, Chatuchak, Bangkok 10900, Thailand.
COPD_A_300299 909..918

1Integrative Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden; 4Boehringer Ingelheim AB, Stockholm, Sweden; 5COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden; 6Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 413 45, Sweden Introduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care. Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a codiagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators. Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥2 and CAT score <10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy. Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment.
Analysis of pH process using Model Reference Adaptive Controller

pH control plays an important role in many applications. pH value must be maintained within the allowable range so that the products produced within the safety limit. There is no particular acceptable solution to control the varying pH value. Due to high non-linearity of the process, controlling of the acid-base parameters becomes difficult. Conventional controller designed for controlling parameters does not obtain good performance. To overcome the disadvantage of conventional controller, advanced controllers like IMC based PID, adaptive techniques like Model Reference Adaptive Controller(MRAC) and Intelligent controllers like Fuzzy Logic Controller(FLC) are designed to obtain better performance. A comparative study of these controllers was done in this work.
A Novel Benzo[d,e]Chromene for Organic Light Emitting Diodes (OLEDs)

Organic light emitting diodes (OLEDs) have been known for the next generation of display technology. In this work, we synthesized four benzo[d,e]chromene derivatives (BS01-BS04) varying the position of fluorine atom for OLED application. The compounds were characterized by 1H and 13C NMR, FTIR and mass spectroscopy. Their photoluminescence properties were studied which showed the thermally activated delayed fluorescence (TADF) character from intramolecular charged transfer (ICT) transition. The compounds were used as a dopant for OLEDs in the structure of ITO/NPB/BS01-BS04/Bphen/LiF/Al. The BS02 device exhibited green colour with the current efficiency at 1.28 cd/A and the power efficiency at 0.47 Im/W.
Smart Signalization and Public Transport Priority, a First Step to Smart Mobility in a Smart City

Smarty city is a current topic, growing very fast in the last years. This concept is linked as a winning strategy to solve some major problems of big cities, like pollution, traffic jams, energy consumption, etc. Smart city is the next level, a more complex concept of the much restrictive green city, being an extension of this one, involving a better urban zone, a smaller environmental footprint, a higher penetration of ICT in the city life. A very important component of a smart city is the urban mobility, a smart mobility in a smart city. The aim of the paper is the presentation of the first step in this direction, because a smart mobility involve a smart signalization first. To reduce the traffic jam in an cross junction, an adaptive signal master plan of the intersection are used, with the help of a dedicated software.
A Deep Learning Model in a Tactical Asset Allocation Framework

In this seminar paper a Long-Short-Term-Memory Neural Network has been constructed and combined in a with the Dynamic Conditional Correlation-MGARCH model in a Minimum Variance Optimization framework to create a tactical asset allocation strategy. This was done in an attempt to improve the risk-adjusted return in a portfolio consisting of three major asset classes; Equity, Gold and Bonds. The results showed that the tactical asset allocation strategy signiﬁcantly outper-formed a passive portfolio by generating a 0.7 pct. point higher average monthly return. The ultimate performance measure to evaluate the two portfolios was chosen as the Sharp-ratio and Omega-ratio. The average Sharpe-ratio of the tactical asset allocation strategy was found to be 0.01 higher than the passive portfolio while the average Omega-ratio was 0.78 higher during the time-span of 02.01. 2019-27.9. 2019.
Design of a Battery-Ultracapacitor Hybrid Energy Storage System with Power Flow Control for an Electric Vehicle

A combination of battery and ultracapacitor as a hybrid energy storage system (HESS) of an electric vehicle (EV) can result in better acceleration performance, reduce battery charge-discharge cycle and longer driving range. This paper presents a new converter design combining triple-half-bridge (THB) and buck-boost half-bridge (BHB) converters in a battery-ultracapacitor HESS. The BHB converter is used to compensate the voltage variation of the ultracapacitor. A power management system is proposed to control the power of battery and ultracapacitor to supply the demanded power. This paper describes the operation of the proposed converter using a simplified ∆ -type primary-referred equivalent circuit. This paper also shows the simulation results verifying the dynamic response of the proposed power management system for the proposed HESS.