In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

The application of bacterial metagenomic analysis as biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and Controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed with QIIME2 pipeline. We applied logistic regression for adjusting differences attributable to sex, age and body mass index and compared diagnostic accuracy of our gut signatures with other previously published. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44) and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminoccocaeae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1) were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application to our population of two other published panels. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Despite UAV multi-target detection exhibits considerable developmental potential worldwide, it suffers distinct challenges compared with traditional tasks in this field. These challenges include insufficient feature extraction capabilities for small targets, limited capabilities for multi-dimensional feature fusion, as well as constraints on hardware computation parameters. Especially in mission scenarios such as disaster detection, these challenges will be further amplified. Consequently, this paper introduces SSE-YOLO, an innovative YOLO framework algorithm specially designed to address these challenges. To enhance the model's feature extraction capability, we employ the SPDConv module to replace the original Conv in the backbone section, utilizing depth-separable convolution instead of traditional convolution pooling. Concurrently, we eliminate the SPPF module at the bottom and address a new Separate Kernel Attention Pyramid Pooling (SKAPP) module, substantially enhancing the feature fusion capability at the model's core. Moreover, to address the challenge of multi-dimensional feature fusion, we replace the Concat module of the neck and head with E-BiFPN, transmitting feature information from the backbone to the lower network through four CBS blocks, which effectively resolves the issue of lost contextual information in the model. Meanwhile, SSE-YOLO undergoes ablation experiments on the VisDrone2019 dataset to evaluate its effectiveness against alternative methods, and experimental results illustrate the model's exceptional precision in detecting UAV targets. In comparison to models with comparable experimental accuracy, SSE-YOLO requires remarkably fewer parameters. On the VisDrone2019-DET-test-dev dataset, SSE-YOLO enhances mAP by 17.3%, with a 42.5% reduction in the parameter amounts. Therefore, the proposed method effectively tackles the challenge of reconciling low parameters and high accuracy, presenting a novel pathway for deep learning-based UAV multi-target detection.

We investigated by Real-time PCR and end point PCR the presence of 10 potential zoonotic viruses in 91 small mammals sold as pets in pet shops of Southern Italy. The animals were analysed for: aichivirus, sapovirus, astrovirus, hepatitis A virus, noroviruses (GI and GII), rotavirus, circovirus, coronaviruses. Among the 9 species of small mammals analysed (golden hamsters, Java squirrels, mongolian gerbils, peruvian guinea pigs, pet mice, pet rats, dwarf rabbits, african hedgehogs and sugar gliders) 12 pet rats, 11 pet mice and 1 golden hamster tested positive to a PCR amplifying a conserved gene (RdRp) of coronavirus. However further characterizaton by sequencing gave not conclusive results. A pet rat resulted instead positive to aichivirus and its sequence showed similarity with a murine kobuvirus-1 strain identified in China. To our knowledge, this is the first study reporting the detection of aichivirus in rodents in Italy, the virus probably introduced through the importation of animals from Asia. Since living in close contact to humans, expecially with children, the continuous monitoring of the small mammals is very important to avoid the spread of new pathologies among animals and humans and further investigation is desirable in order to safeguard public health.

Repairing of small and isolated delamination area in carbon fiber reinforced polymer (CFRP) without significantly altering the composite structure is studied in this research. A small drilled hole was introduced at the center of the delamination section of CFRP, providing the channel for epoxy infill of sharp delamination cracks. The pressureless infill repair was achieved through the capillary action of an acetone-diluted resin solution (without hardener) with CNT reinforcement, e.g., 89 m/m% of acetone, 10 m/m% of resin and 1m/m% of CNT. Such an acetone-rich resin pre-coating (RPC) solution is easy to prepare and apply to the drilled hole area. Curing of CNT-toughened resin infill was induced by filling the small-drilled hole with a resin-hardener mixture toughened by CNT/Aramid pulp. The effectiveness of delamination repair with curing periods of two weeks and three months were compared. Flexural strength measurements indicated that 77% (potentially 100%) of the restoration was achievable.

The biodiversity of the State National Natural Park (SNNP) "Buiratau" has not been studied, as it is young in Kazakhstan. The purpose of our study was an independent botanical and geographical study of the vegetation cover of the SNNP "Buiratau". This study have been carried out using the method route-reconnaissance and identifying plants, according to plant guide “Flora of Kazakhstan” (1999), “Key to Plants of Central Asia” (1974). The results showed that depending on the geographical location (Kazakh highland, steppe zone) of the SNNP "Buiratau" territory this natural complex has a very diverse botanical feature. In these types of vegetation of this territory, there are both Red Data Book and rare and endemic plants, such as black alder and birch forests, the peculiarity of which is that some species (Alnus glutinosa (L) Gaertn, Betula Kirghisorum Sav. - Rysz.) are listed in the Red book and very few. Medicinal, plant species and their resource potential are an important component of the flora. The analysis showed that the SNNP "Buiratau" is a unique natural environment, which is characterized by 10 species of plants listed in the Red Book, and 26 species of rare and endangered species.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial to mesenchymal transition (ETM) thus promoting the colonization of distant sites that in turn sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short reviews we will give an overview of the most recent advances related to three main large families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, integrin antagonists and small interfering (siRNAs). Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

Genetic susceptibility in psoriasis is a topic of interest in the initiative to improve targeted treatment strategies. In this review, we discuss genes linked to psoriasis and the available treatment options in context of targeting respective gene products implicated in the pathogenesis of psoriasis. In order to identify relevant genetic markers and treatments, we developed a literature search utilizing PubMed, Google Scholar, MEDLINE, and Web of Science with keywords, including genetic susceptibility to psoriasis, genetics and psoriasis, psoriasis treatments, biologics treatments in psoriasis. Articles in English from database inception to 1/1/23, were included. Case reports and series were excluded. Gene variant forms commonly implicated in the pathogenesis of psoriasis include those encoding for interleukins, interferons, and other mediators involved in inflammatory pathways, such as JAK/STAT, NFk-B, and others. Most commonly utilized treatments for psoriasis include drugs that target inflammatory markers like IL23, IL12, IL17, and TNF-a. TYK2 inhibition has been discussed as an emerging treatment strategy. Multiple genes are linked to the pathogenesis of psoriasis. This understanding may provide an avenue for further development of pharmacologic strategies targeting underlying genetic pathways. Genetically guided treatment may also allow for greater understanding in the selection of biologics.

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases as well as microvascular eye diseases. Established hypertension leads to chronic vasoconstriction of small arteries as well as to decreased lumen diameter and thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was first demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alteration in small resistance arteries; however microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events, possessing, therefore, a prognostic relevance. New, non-invasive techniques, such as Scanning Laser Doppler Flowmetry or Adaptive Optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in term of cardio- and cerebrovascular events. A rarefaction of capillary network has also been reported in hypertension which may contribute to flow reduction and impairment in oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might concur to microvascular angina, stroke, and renal dysfunction. In addition, they could be a marker useful in monitoring the beneficial effect of antihypertensive treatment. Also conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. The review will address the possible relations between structural microvascular alterations and hypertension-mediated organ damage and their potential improvement with antihypertensive treatment.

Considering the differences between the European and African continents concerning the management of the mining production sector, we decided to carry out this study with the main objective of demonstrating that, in Africa, mining can positively change the quality of life of the populations where it develops and, at the same time, it is possible to respect the environment, which is our main wealth. To achieve these objectives, it is necessary to present the mining activity of the continent, emphasizing both the negative aspects and its strong points. The most important thing is to make a good diagnosis of the situation, which will allow us to cure our "patient", that is, African mining production.

Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive spinal cord disorder with no effective treatment. There is much of interest in developing potential biomarkers for predicting the pathogenesis of HAM/TSP disorder. This study used Illumina massive parallel sequencing (MPS) technology to assess the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1 infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Using various bioinformatics tools, the sRNA MPS reads were aligned, annotated, and profiled. There were 251 known and 50 potential novel sRNAs among the 402 detected sRNAs in the HAM and ASP groups versus the HC group. Sixty-eight known sRNAs were found to be significantly different between the ASP and HAM groups. In HAM vs ASP subjects, 88 mature miRNAs were downregulated. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The top seven deregulated miRS target genes were linked to a variety of biological processes and molecular functions. Relevant reactome pathways to our findings provide a rich source of data and an opportunity to further understand sRNA regulation and function in HTLV-1 pathophysiology.

The importance of small urban green areas has increased in the context of rapid urbanization and densification of the urban tissue. The analysis of these areas through remote sensing has been limited due to the low spatial resolution of freely available satellite images. We propose a timeseries analysis on 3 m resolution Planet images, using GEOBIA and vegetation indices, with the aim of extracting and assessing the quality of small urban green areas in two different climatic and biogeographical regions – temperate (Bucharest, Romania) and mediterranean (Athens, Greece). Our results have shown high accuracy (over 91%) regarding the extraction of small urban green areas in both cities, across all analysed images. The timeseries analysis showed consistency in location for around 55% of the identified surfaces throughout the entire period. The vegetation indices registered higher values in the temperate region, due to the vegetation characteristics and the planning of the two cities. For the same reasons, the increase in vegetation density and quality, as a result of the distance from the city centre and the decrease in the density of built-up areas is more obvious in Athens. The proposed method provides valuable insights in the distribution and quality of small urban green areas at city level and can represent the ground basis for many analyses, currently limited by poor spatial resolution.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

Nicotine exposure may affect NSCLC is associated with lung cancer in humans. Whether nicotine exhibits carcinogenesis promoted activities in tumor growth still unknown. Nicotine is known to have dichotomous effects on cancer biology, acting like a pro- or anti-carcinogenesis agent. There are different functions between adenocarcinoma and squamous NSCLC cancer cells. Excess generation of nicotine may inhibit mitochondrial metabolism, protein modification, and DNA cleavage. Materials and Methods: We used the H520 NSCLC line obtained from human lung epithelial cells to detected nicotine growth and toxicity using MTT assay and western blotting. The concentration of nicotine stimulated cell growth to correspond to low concentration, while high concentration was cytotoxic. Results: According to MTT assay results, at 1.0 μM nicotine has significantly enhanced the H520 cell viability (%). Nicotine induced lung cancer carcinogenesis through mechanisms of α7nAchR, EGFR, HDAC2/4/5, Cyclin D/Cyclin E, Bcl-2, p-Akt, and inflammatory proteins of NF-KappaB and COX2 increases at 1.0 μM. Apoptosis proteins were decreases at 1.0 μM nicotine by p21, p27, c-jun, and p38α using western blotting. Nicotine stimulates tumor growth is mediated through α7nicotinic-acetylcholine receptors (α7nAChR), possibly involving inflammation. On the other hand, at high nicotine concentrations (> 1.0 μM) with consistent cytotoxic effects and appeared to be due to direct cell kill. Nicotine can prevent apoptosis induced by NSCLC. Conclusion: Therefore, the effects on chemotherapeutics by NSCLC malignant cell lines, nicotine in concentrations as low as 1.0 μM decreased. These mechanisms are responsible for the genotoxic effects caused by nicotine. This leads to downstream effects on decreased apoptosis, increased cell proliferation and transformation. The malignant NSCLC cells respond to the treatment with nicotine in lung cancer, the nicotine-mediated induction of growth may provide one of its links to α7nAchR or EGFR.

Australian regional areas are now receiving significant numbers of migrants from the African continent. Predominantly Anglo-Saxon communities perceive these ‘newcomers’ as physically and culturally different. Asking, however, how African migrants themselves construct relationships with local communities and build a sense of belonging in regional and rural areas is a very different question. This paper explores South Sudanese migrants’experiences conceptualising their sense of belonging in a small county town: Castlemaine, Victoria. Focus group discussions show that even with the welcoming atmosphere and support from the local community, South Sudanese migrants are still attracted to metropolitan environments that have greater diversity, feeling more at home in such settings. Using the theoretical background of a stranger, this paper argues the cities allow strangers be un-noticed letting them feel at ‘home’. Findings from the study show settings with greater diversity encourage negotiating difference openly and easing power imbalances among different groups.Finally, the locality of Castlemaine, within easy commuting distance to metropolitan Melbourne and suburbs, is considered in relation to hypermobility reducing the capacity to construct ‘bridging capital’ within such local communities.

Microbial contamination is now more common than chemical contamination in Tibet, and water-borne microbes can cause a number of diseases that threaten public health. Thus, in order to clarify the spatiotemporal distribution of bacteria in small watersheds for which there is no data in Tibet, we set up four sampling points along an upstream-downstream transect of the Xincang River Basin. We collected 239 water samples in 2014 and 2015, and evaluated their total constituent numbers of bacteria (TB) and coliforms (TC). The results of this study show that the microbial contamination of the Xincang River Basin is mild-to-moderate in terms of TB and TC contents, and that these concentrations vary significantly in different seasons. Results show that in summer TB and TC concentrations in the downstream section of this river were highest and that microbial contamination was most serious. Data also demonstrate that precipitation is the most important factor underlying increases in TB and TC concentrations during the summer months; both these variables are significantly correlated with precipitation, while animal husbandry and domestic sewage are the main sources of microbial contamination overall. The results of this study are likely to reflect the basic characteristics of small watersheds for which there is no data to some extent, and are thus of significant practical importance for protecting their ecological environments and promoting sustainable development.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/ 18F]exchange reaction over IDIF in dimethylsulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7±3% radiochemical yield in a 20 minutes reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t>10 min post administration), rapid accumulation in the liver, long circulation time and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

Skin melanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream prometastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds the potential to prevent metastasis however, these networks entail complex feedback and feedforward regulatory motifs among various regulatory layers, which make it difficult to identify druggable components. To this end, computational approaches such as mathematical modeling and virtual screening are important tools to unveil the dynamics of these signaling networks and identify critical components that could be further explored as therapeutic targets. Herein, we integrated a well-established E2F1-mediated epithelial-mesenchymal transition (EMT) map with transcriptomics data from E2F1-expressing melanoma cells to reconstruct a core regulatory network underlying aggressive melanoma. Using logic-based in silico perturbation experiments of a core regulatory network, we identified that simultaneous perturbation of Protein kinase B (AKT1) and oncoprotein murine double minute 2 (MDM2) drastically reduces EMT in melanoma. Using the structures of the two protein signatures, virtual screening strategies were performed with the FDA-approved drug library. Thus, by combining drug repurposing and computer-aided drug design techniques, followed by molecular dynamics simulation analysis identified two potent drugs (Cialis and Finasteride) that can efficiently inhibit AKT1 and MDM2 protein signatures respectively, and with better therapeutic properties. We proposed that these two drugs could be considered for the development of therapeutic strategies for the management of aggressive melanoma.

This article presents a low-cost insurance system developed for small-hold farms in disaster-prone regions, primarily using free Earth Observation (EO) data and Free Open Source Software (FOSS) – collectively termed sustainable geoinformatics - with a proprietary mobile phone app that enables verification. The study examined 30 farms in Risaralda department, Colombia. A Digital Elevation Model (12.5m pixels) from the ALOS PALSAR satellite sensor was used with a Geographical Information System (GIS) to map the terrain, drainage and geohazards of each farming district. Google Earth Engine (GEE) was used to carry out Time Series Analysis of 15 EO and weather datasets for 1998 to 2020. This analysis enabled the levels of risk from hydrometeorological hazards to be determined for each farm of the study, providing key data for the setting of insurance premiums. A parametric insurance product was piloted using GPS-tagged, time-stamped mobile phone photos to verify crop health. Key features of this insurance system are its low operational cost and rapid damage verification, relative to conventional approaches to farm insurance. It is an affordable form of insurance for small-scale farmers, with the rapid verification and payment of claims. This relatively fast, low-cost and affordable approach to insurance for small-scale farming enhances sustainable development by enabling policy-holder farmers to recover more quickly from disasters.

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

The purpose of this study is to investigate the failure mechanism and preventive strengthening methods of prefabricated full length small box girder (PSBG) under car explosion. After damage analysis during blast loads using the commercial software Autodyn, three strengthening methods are presented to improve the blast mitigation performance. The results show that the failure modes and bearing capacity are significantly different with various strengthening measures. Adhering U-shaped steel plate can effectively enhance the shear performance of PSBG under blast loads. Strengthening the bottom of the upper flange of box girder with steel plate can effectively mitigate the local bending failure, and enhance the overall flexural capacity during car explosion.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Climate change is unpredictable and can change rapidly or over time; anthropogenic stressors work synergistically to strengthen their impact on vulnerable ecosystems and the fisheries sector. This study documented the past occurrence of extreme climate change impacts, such as supertyphoon Pablo (ST: Bopha), which severely affected Baganga, Davao Oriental, about ten years ago. A mixed-methods data collection was used, combining semi-structured interviews with small-scale fishers (N=120) in four fishing villages and focus group discussions (N=4, participated by about 4 focus groups) on assessing the impacts and their adaptation after climatic events occurred. Our findings indicate that the four selected fishing villages were exposed to common factors of climate change events that destroyed many lives and their livelihood. Including a decrease in catch per trip and the fishing operations disruption (98%). However, due to the impact of the supertyphoon, small-scale fishers in Baganga developed psychological distress (emotional 44% and physical 24%) due to the extreme event or disaster and economic losses (32%). In order to survive, their adaptation strategies relied on government and non-government-provided provisions and projects, e.g., planting trees, constructing a sea wall with wave breakers, cash for work, and tourism as an alternative livelihood. Despite this, our study revealed that the community had limited knowledge on the impacts of climate change, lack clear management goals especially for fishers, and the widespread use of illegal fishing gears. The local government must strongly implement rules, policies, and adaptation measures that will contribute to better and more resilient communities. This can help them to withstand future shocks and provide sustainable fisheries resources that will benefit all the fishers. The study will be useful to policymakers, disaster management group and organization that will help assist affected communities highly affected by climatic events.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

The sustainability of agroecological systems, biodiversity protection, animal welfare and consumer demand for higher-quality products from alternative and extensive farming methods, have reinforced interest in local breeds that are well adapted to low-input environments. However, food safety needs to be safeguarded to reinforce consumer confidence. The aim of this study was to conduct a preliminary investigation on the occurrence of Salmonella spp. in eggshells, hen’s cloaca and litter materials from autochthonous Portuguese laying hens raised in a semi-extensive system for small-scale production. A total of 279 samples were obtained, with 63 samples from the “Preta Lusitânica” breed, and 72 samples each from the remaining autochthonous breeds, namely “Branca”, “Amarela” and “Pedrês Portuguesa”. None (0%) of the samples analyzed were positive for Salmonella spp.. To the best of our knowledge, these are the first results of Salmonella evaluation from hen’s cloaca, eggshells, and litter materials in autochthonous Portuguese chickens, suggesting that a semi-extensive production system can contribute to better food security and a lower risk to public health and the environment.

Zoonotic abortive diseases represent a significant health and economic risk for national public health. This cross-sectional survey was conducted from April to October 2021 among 200 selected small ruminant farmers in the three northern regions of Cameroon. Data collection was done through questionnaires administered by exchange with the herder and responses were coded and recorded on an Excel spreadsheet. The data were then analyzed with R software, version 2.13.0. An ANOVA test was used to assess significant differences in mean of Knowledge, Attitudes, Practices and Perception of zoonotic risks (KAPP) scores between regions. Pearson correlations were used to calculate the association between KAPP scores within regions. Small ruminant farmers surveyed had low mean scores for knowledge of abortive Toxoplasmosis and Chla-mydophilosis (0.1 ± 0.2), desirable attitude (0.32 ± 0.07), appropriate practice (0.36 ± 0.13) in managing abortion, and positive perception of zoonotic risks of Toxoplasmosis and Chlamydo-philosis in small ruminants (0.12 ± 0.33), respectively. KAPP was significantly (p<0.01) and posi-tively associated with knowledge (r=0.98) and risk perception (r=0.99). However, attitudes (r=0.06), practices (r=0.05) and risk perception of toxoplasmosis (r=0.07) and Chlamydophilosis (r=0.08) were not associated with farmers' knowledge. This study revealed significant knowledge gaps, low levels of desired attitudes, and high-risk behavioral practices. These results therefore call for capacity building of health professionals and farmers to better integrate the One Health concept in the management of neglected zoonotic diseases.

We have recently introduced the possibility of performing operando small-angle X-ray scattering measurements using a novel industrially relevant injection moulding system for plastics. We show that useful time-resolving measurements can be performed with a time-cycle of 1s and we highlight the possible steps to reduce this to 0.5s. We show how we can use the transmission measurements to provide a time-marker when plastic first enters the mould cavity in the region probed by the incident X-ray beam. We show the opportunities provided by this experimental stage mounted on the NCD-SWEET beamline at ALBA to probe the reproducibility of the injection moulding system on different scales. The design of the equipment allows the development of the structure and the morphology to be evaluated in different parts of mould cavity and we evaluate any differences in a rectangular mould cavity. We identify future prospects for this equipment in terms of novel mould heating and cooling systems and the opportunities for quantitatively evaluating radical approaches to injection moulding technology.

Alfalfa is an important forage crop around the world. LncRNAs are considered to be a class of functional biomacromolecules, while little is known about lncRNAs in alfalfa. In this study, RNAs from different tissues of alfalfa were sequenced and anlyzed with full-length transcriptome sequencing technology, yielding the full-length transcripts dataset of alfalfa. Based on sequencing and public RNA-seq data, lncRNAs of alfalfa were predicted genome-wide by CPC2 and PLEK. The results showed most lncRNAs shared low sequence conservation with those in other plant species, part of which seems originate from plastid genome. We also identified 88563 lncRNAs, approximately 99.8% of total lncRNAs, with possibility of coding small ORFs using two prediction tools. Our research generated the biggest sequence set of alfalfa lncRNAs, and revealed some plastid originated lncRNAs with high sequence conservation.

Blast charge initiation procedures have a significant impact on both mining safety and production rates. In this study, the inventory benefit of an electric initiation system was investigated to assess its influence on both fragmentation and blast-induced damages. The Wipfrag software's was used to examine the size distribution and productivity of 12 small-scale blasts initiated by both non-electric and electric detonators. All blast rounds was initiated with plain type of electric and NONEL detonators. The average burden, spacing, stemming length, and charge weight were, respectively, 0.85 m, 1.10 m, 0.66m, and 1.1kg. The results showed that the mesh through which 80% of the blast fragments will pass for the electric blast is smaller than the mesh through which the material products from the NONEL blast will pass. The results also demonstrate that the generated blast-induced ground vibration (PPV) from all blast rounds for electric blast varies from 0.4–1.2 mm/s and 80–105dB, while that for non-electric blast ranges from 0.05–0.2mm/s and 72–95dB. As a result, the electric blast initiation technique was found to produce good fragmentation, with a higher percentage of optimum fragment sizes on spec than non-electrically initiated blasts.

We develop the theory of Heyting locally small spaces, including Stone-like dualities such as a new version of Esakia duality and a system of concrete isomorphisms and equivalences. In such a way, we continue building tame topology, realising Grothendieck's ideas. We use up-spectral spaces and define the standard up-spectralification of a Kolmogorov locally small space. This research gives more understanding of locally definable spaces over structures with topologies.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

Small boat fishers are often the lifeblood of remote coastal communities in Iceland, contributing to employment, jobs and economic prosperity. This study conducts exploratory but highly practical research into the efficiency of onboard catch handling practices by Icelandic small boat fishers using fish handling tools called automatic jigging machines. Using applied research methods, this study researches whether standardisation of operations could be applied to make catch handling practices on small boats more time and resource efficient, leading to reduced waste, a consistently higher quality product, and potential increases in economic efficiency and sustainability. Thematic analysis, value stream mapping, flow analysis and Kaizen ideology were adopted to identify gaps and continuous improvement opportunities to standardise processes, leading to exemplary performance. Eight core recommendations are identified, seven of which are classed as straight-forward, ‘do now’ measures according to a Kaizen Priority Matrix. These include human and technological interventions in the areas of safety, organisational arrangements, hygiene, fish handling and bleeding, and cooling. Questionnaire responses reveal four main themes of importance to the sub-sector: changes in recent decades; the importance of small boat fishers; education and improvement; and the particularities of the sub-industry. The latter include the perception of a ‘race against time’ to land the catch, an issue that sometimes contributes to sub-optimal catch handling practices. Although this study has decidedly practical connotations for small boat fishers, its outcomes are also likely to be of interest to academics, particularly those focused on the organisational management of natural resources and general applications of the project management methodology and applied research methods as a means of solving practical problems in everyday life.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

In the past few decades, the tourism sector has emerged as a significant economic activity in island nations, particularly in tropical regions. However, most of the tropical islands face similar constraints. National and international tourists visit the SIDS including A & N Islands and contribute to the GDP to significant share. The Covid-19 outbreaks in SIDs including A & N islands shows that number of people infected were less as compared to metros or big cities. However, tourism activities completely stopped due to lockdown resulting in decreasing tourist’s arrival, declined GDP and per capita income of SIDs to greater extent. The information gathered from various sources, mass media and net analysed and interpreted in this chapter. Due to Covid-19 tourist’s arrival declined which has serious consequences on the livelihood of islander. Our analysis revealed A&N Islands deficit in energy available at from different sources by 18.26%. However, they are surplus in protein. The burden of high expenditure coupled with poor infrastructure makes them more vulnerable in the circumstance of pandemic outbreaks. This outbreak has created the question of survival due to loss of jobs, halted economic activates, psychological, health unrest and livelihood threats among the depending people of these Island nations. Therefore, government interventions and subsidized package is very much essential to revive the tourism industry.

Land degradation is a critical issue globally putting our future generations at risk. The decrease in farm productivity over the years is evidence of land degradation severity in Nepal. Among the many strategies in place, agroforestry, which is an integrated tree-based farming, is widely recommended to address this productivity issue. This paper thoroughly examines what influences the choice of agroforestry adoption by farmers and what discourages the adoption. For this, a total of 288 households were surveyed using a structured questionnaire. Two agroforestry practices were compared with conventional agriculture with the help of the Multinomial Logistic Regression (MNL) model. The likelihood of adoption was found to be influenced by gender; the male-headed households were more likely to adopt the tree-based farming practice. Having a source of off-farm income was positively associated with the adoption decision of farmers. Area of farmland was found being the major constraint to agroforestry adoption for smallholder farmers. Some other variables that affected positively included livestock herd size, provision of extension service, home-to- forest distance, farmers’ group membership and awareness of farmers about environmental benefits of agroforestry. Irrigation was another adoption constraint that the study area farmers were faced with. The households with means of transport and with larger family (household) size were found to be reluctant towards agroforestry adoption. A collective farming practice could be a strategy to engage the smallholder farmers in agroforestry.

Mediterranean catchments are characterized by significant spatial and temporal hydrological variability caused by the interaction of natural as well human-induced abiotic and biotic factors. This study investigates the (non-)linearity rainfall-runoff relationship at multiple temporal scales in representative small Mediterranean catchments (i.e., < 10 km2) to achieve a better understanding of the hydrological response. Rainfall-runoff relationship was evaluated in 44 catchments at annual and event –203 events in 12 of these 44 catchments– scales. A linear rainfall-runoff relation was observed at annual scale with higher scatter in pervious than impervious catchments. Larger scattering was observed at event scale, although pervious lithology and agricultural land use promoted significant rainfall-runoff linear relations in winter and spring. These relationships were particularly analysed during five hydrological years in Es Fangar catchment (3.35 km2; Mallorca, Spain) as a temporal downscaling to assess intra-annual variability in which antecedent wetness conditions played a significant role in runoff generation.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Currently, Korea is experiencing localized extreme rainfall, which accounts for more than 80% of flood-related disasters, and is increasing in small river basins, where more than 60% of flood-related casualties occur. These events are caused by climate change and geological factors and their impact is becoming more severe. As a result, an effective measurement system is required to mitigate their impact, particularly in small stream basins that are especially vulnerable due to their steep slopes, small catchment areas, and lack of maintenance and management capacity. In addition, a Flood Early Warning Framework (FEWF) that forecasts discharge and depth during flood events is crucial for reducing casualties. Therefore, this research is focused on developing the FEWF using the nomograph and rating curve methods, which are established by the robust constrained nonlinear equation solver and are suitable for small streams. The FEWF is evaluated using real-time data observed over 7-years period from the Closed-circuit Television-based Automatic Discharge Measurement Technology (CADMT), and the results show that the FEWF is effective in forecasting discharge and depth during flood events. The use of CADMT technology for real-time data can develop an accurate and reliable FEWF, which can help mitigate the impacts of extreme rainfall events and reduce the number of flood-related casualties in small stream basins.

For better export performance in cross border e-commerce, a contingency model integrates e-commerce into traditional export marketing strategy (EMS) with internal and external determinants of EMS. However, EMS of Micro, small, and medium-sized enterprises (MSMEs) is understudied. This study validates and modifies existing model for MSMEs. As a qualitative study, multiple sources of data including interviews, internal documents, and group discussions were used regarding business cases of entrepreneurs and supporting organizations in Mongolia and Korea. This research suggets contingency model for MSMEs with modified factors and different strategies in each factor. Specifically, intermal determinants are managerial capability, product competitiveness, and strategic marketing orientation. External determinants are export market competitivceness, export market infrastructure and entry barriers. EMS for MSMEs consists of the same factors with the original model but come up with different strategies. Theoretical and managerial implications were discussed.

More than 700 thousand human deaths from mosquito bites are observed annually in the world. It is more than 2 times the number of annual murders in the world. In this regard, the invention of new more effective methods of protection against mosquitoes is necessary. In this article for the first time, comprehensive studies of mosquito neutralization using machine vision and a 1 W power laser are considered. Developed laser installation with Raspberry Pi that changing the direction of the laser with a galvanometer. We developed a program for mosquito tracking in real. The possibility of using deep neural networks, Haar cascades, machine learning for mosquito recognition was considered. We considered in detail the classification problems of mosquitoes in images. A recommendation is given for the implementation of this device based on a microcontroller for subsequent use as part of an unmanned aerial vehicle. Any harmful insects in the fields can be used as objects for control.

A multimodal detection system with complementary capabilities for efficient detection was developed for impurity detection. The system consisted of a visible light camera, a multispectral camera, image correction and registration algorithms. It can obtain spectral feature and color feature at the same time, and has higher spatial resolution than a single spectral camera. This system was applied to detect impurities in Pu ’er tea to verify its high efficiency. The spectral and color features of each pixel in the images of Pu ’er tea were obtained by this system and used for pixel classification. The experimental results show that the accuracy of Support Vector Machine (SVM) model based on combined features is 93%, which is 7% higher than that based on only spectral features. By applying median filtering algorithm and contour detection algorithm to the label matrix extracted from pixel-classified images, 8 impurities except hair were detected successfully. Moreover, taking advantage of the high resolution of visible light camera, small impurities can be clearly imaged. By comparing the segmented color image with the pixel-classified image, small impurities such as hair could be detected successfully. Finally, it is proved that the system can obtain multiple images to allow a more detailed and comprehensive understanding of the detected items, and has excellent ability to detect small impurities.

In this paper, four probability functions are compared with the purpose of establishing a methodology to improve the accuracy of the estimated wind energy in a desert city in northwestern Mexico. For the statistical modeling, 3 time series of wind speed data were used, corresponding to the years 2017, 2018, and 2019, recorded with a sonic anemometer at a sampling frequency of 10 Hz. From these, the analysis is performed with different stationarity periods (5, 30, 60, and 600 seconds). The estimation of the parameters characterizing the probability density functions was performed using different methods; the statistical models were evaluated by the coefficient of determination and the Nash-Sutcliffe efficiency coefficient, while their accuracy by the measured quadratic error, the mean square error, the mean absolute error, and the mean absolute percentage error. It was found that Weibull with the energy pattern factor method and Gamma using the method of moments were the probability density functions that best describe the statistical behavior of the wind speed and, therefore, better estimate the energy generated, so it is concluded that the proposed methodology will allow having greater confidence, both in the estimation of the wind speed and in the small wind energy available for its use.

A systematic review and meta-analysis were conducted to estimate the prevalence of chlamydiosis in small ruminants. The study included 133 publications that reported the presence of Chlamydia abortus in 109 and 74 studies in sheep and goats from 45 countries. The prevalence of chlamydiosis was estimated at global, regional, and national levels using meta-analyses of proportions. Meta-regression and cumulative meta-analyses were also performed. Globally, the prevalence of chlamydiosis in sheep and goats was estimated at 20.1% (95% CI: 17.8-22.4) and 14.4% (11.6-17.4), respectively. For sheep, chlamydiosis prevalence was heterogeneous at regional and national levels. South Asia had the highest prevalence (30.6%) and East Asia and Pacific the lowest (14.0%). Nationally, chlamydiosis was more prevalent in Romania, Hungary, and Germany (range 53.3-87.0%) compared to Costa Rica, Australia, and Zimbabwe (4.7-5.2%). Among goats, chlamydiosis prevalence was similar across regions (10.4-19.7%), but varied significantly among countries, 0.0% in Romania and Australia and 91.7% in Bosnia and Herzegovina. In both species, sample size, number of diagnostic techniques, and latitude were significant covariates. Prevalence varied widely in the first decades of publications before stabilizing. Our study found a high prevalence of chlamydiosis in small ruminants, with the pathogen being distributed globally but heterogeneously across countries.

Renewable Energy Communities (RECs), strongly sustained by the European Community as a viable way to fasten low carbon transition, slowly develop in Italy for regulatory . This study delves into the framework of RECs and explores the perspective of the specifically small and medium industries in the Lombardy region of Italy through a survey. Our findings reveal that while SMEs exhibit interest in RECs, there is a notable gap in knowledge and engagement. We argue that the active involvement of Public Administration Bodies (PABs) is crucial in disseminating information about RECs and highlighting their benefits. The survey results, elaborated through a non-parametric test (Mann-Whitney U test) indicate that PABs play a pivotal role in influencing SMEs' perceptions and willingness to participate in RECs. The data suggest that more direct and effective communication strategies by PABs could significantly enhance SMEs' understanding and involvement in RECs. This research underscores the need for targeted and strategic efforts by PABs to foster a more informed and proactive approach among SMEs towards renewable energy initiatives. Such endeavors could be instrumental in accelerating the adoption of RECs, contributing to a more sustainable and resilient energy future.

We study electrohydrodynamic (EHD) linear (in)stability of microfluidic channel flows, i.e. the stability of interface between two-shearing viscous (perfect) dielectrics exposed to an electric field in large aspect ratio microchannels. We then apply our results to particular microfluidic systems known as electroosmotic (EO) pumps. Our results are detailed analytical expressions for the growth rate of two-dimensional EHD modes in Couette-Poiseuille flows in the limit of small Reynolds number ($R$); the expansions to both zeroth- and first-order-$R$ are considered. The growth rates are complicated functions of viscosity-, height-, density- and dielectric-constant ratio, as well as of wavenumbers and voltages, and to our knowledge have not been presented before in literature. To make the results more useful, e.g., for voltage-control EO pump operations, we also derive equations for the impending voltages of the neutral stability curves that divide stable from unstable regions in voltage-wavenumber stability diagrams. The voltage equations and the stability diagrams are given for all wavenumbers. We finally outline the flow regimes in which our first-order-$R$ voltage corrections could potentially be experimentally measured. Our work gives the insight into the coupling mechanism between electric field and shear flow in parallel-planes channel flows, correcting an erroneous attempt from literature. Our general analysis enables us also to refine the renowned instability mechanism due to viscosity stratification, i.e., the case of pure shear instability, when the first-order-$R$ voltage correction equals zero.

In recent times, a great interest has been motivated in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, lupane-type triterpenes are phytochemicals that exert significant activities against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose‐limiting toxic effects and chemoresistance. Herein, we investigated the structure-activity relationship of six pentacyclic triterpenes: oleanolic acid (OleA), ursolic acid (UrA), asiatic acid (AsA), betulinic acid (BeA), betulin (Betu), lupeol (Lupe), on NSCLC A549 cells. From our studies, we confirmed that all these triterpenes showed cytotoxicity in the mid µM range, where BeA showed the strongest effect. Then, we determined that most of these triterpenes induced S-phase and G2/M phase cycle arrest, reactive oxygen species, mitochondrial depolarization, and caspase 3 activation. For chemoresistance markers, we elucidated that most triterpenes downregulated STAT3 and PDL1 genes. In contrast, ursane-type UrA and AsA also induced DNA damage, reactive nitrogen species and autophagy. These results showed that even slight structural changes in these triterpenes can influence the cellular response and mechanistic pathways. This study opens promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Wool quality and yield are important economic traits of livestock. In this study, the skin tissues of the upper scapula of Super Merino sheep (SM) and Small-Tailed Han sheep (STH) during the growing period were studied. Differentially expressed (DE) long non-coding RNAs (lncRNAs) and messenger RNAs (mRNA) were identified via histopathological observation and high-throughput RNA sequencing. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze differentially expressed genes. Reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify nine selected DE lncRNAs and five DE mRNAs. Significant differences were found in the expression levels of LOC114113396 (KRTAP15-1), CRABP1, KRT10, KRTAP1-3, KRTAP4.3, KRT2, FGF1, IGF-1, and KIT in SM and STH skin tissues. These results indicate that these mRNAs may play an important role in the growth and development of hair follicles and the regulation of hair fiber traits. Differentially expressed lncRNA target genes and mRNAs were mainly enriched in biological processes and pathways related to skin development and fiber traits, which is consistent with previous studies. LncRNA MSTRG.9225.1, MSTRG.124320.1, MSTRG.96951.1, MSTRG.91685.1, MSTRG.122229.1, MSTRG.89255.1, MSTRG.98769.1, and MSTRG.84658.1 may indirectly participate in the growth and development of sheep hair follicles and the regulation of hair fiber diameter by regulating the expression of their respective target genes. These candidate lncRNAs and mRNAs may provide a basis for the study of sheep hair follicle growth and development and hair fiber traits.

Mercury emissions from small-scale coal-fired boilers are still a serious environmental problem in Poland and the Czech Republic. The publication presents the results of mercury emission tests conducted using five different small-scale coal-fired boilers and five different coal fuels. The research was carried out under laboratory conditions, but also using residential users' heating devices. They covered a wide range of operational parameters, both energy and emission. It was shown that more than 94% of the mercury contained in coal fuel undergoing combustion is emitted into the atmosphere with the volatile products of combustion (including dust), and the amount of emissions is strongly dependent on the original mercury content of the fuel. One solution to the problem of mercury emissions from small-scale coal-fired boilers may be to replace traditional coal with low-emission carbon fuels. The paper shows that mercury emissions from burning such fuels are many times lower than from burning coal. The widespread use of low-emission carbon fuels in individual heating systems in Poland and the Czech Republic would reduce mercury emissions to the atmosphere by up to 90% compared to the current level of emissions generated by individual heating systems in these countries.

The images captured by UAVs during inspection often contain numerous small targets related to transmission lines, which are critical and vulnerable elements for ensuring the safe operation of these lines. However, due to various factors such as the small size of the targets, low resolution, complex background, and potential line aggregation, achieving accurate and real-time detection becomes challenging. To address these issues, this paper proposes a detection algorithm called P2-ECA-EIOU-YOLOv5 (P2E-YOLOv5). Firstly, in order to address the challenges posed by the complex background and environmental interference that impact small targets, an ECA attention module is integrated into the network. This module effectively enhances the network's focus on small targets while concurrently mitigating the influence of environmental interference. Secondly, considering the characteristics of small target size and low resolution, a new high-resolution detection head is introduced, which is more sensitive to small targets. Lastly, the network utilizes the EIOU-Loss as the regression Loss function to improve the positioning accuracy of small targets, as they tend to aggregate. Experimental results demonstrate that the proposed P2E-YOLOv5 detection algorithm achieves an accuracy P of 96.0% and an average accuracy (mAP) of 97.0% for small target detection in transmission lines.

Infrared detection plays an important role in the military, aerospace, and other fields, which has the advantages of all-weather, high stealth, and strong anti-interference. However, infrared dim small target detection suffers from complex backgrounds, low signal-to-noise ratio, blurred targets with small area percentages, and other challenges. In this paper, we proposed a multiscale YOLOv5-AFAM algorithm to realize high-accuracy and real-time detection. Aiming at the problem of target intra-class feature difference and inter-class feature similarity, the Adaptive Fusion Attention Module - AFAM was proposed to generate feature maps that are calculated to weigh the features in the network and make the network focus on small targets. This paper proposed a multiscale fusion structure to solve the problem of small and variable detection scales in infrared vehicle targets. In addition, the downsampling layer is improved by combining Maxpool and convolutional downsampling to reduce the number of model parameters and retain the texture information. For multiple scenarios, we constructed an infrared dim and small vehicle target detection dataset, ISVD. The multiscale YOLOv5-AFAM was conducted on the ISVD dataset, compared to YOLOv7, mAP@0.5 achieves a small improvement while the parameters are only 17.98% of it. By contrast with the YOLOv5s model, mAP@0.5 was improved by 4.3% with a 6.6% reduction in the parameters. Experiments results demonstrate that the multiscale YOLOv5-AFAM has a higher detection accuracy and detection speed on infrared dim and small vehicles.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in the Kolikoro and Sikasso regions are available, hence the interest in investigating the different species of small rodents and insectivores, and their role in the transmission of pathogens to humans. The study aims to identify commensal small mammal species circulating in Faladjè and Bougouni areas, and likely to represent major risks of epidemic disease emergence. Sessions of trapping were carried out in December 2016 in Faladjè and Bougouni with wire mesh traps type “Besançon tous services” (BTS) baited with peanut butter and/or onion. All animals captured were identified morphologically. Out of 123 small rodents and insectivores captured in 674 trap nights, 75 (60.97%) were from Faladjè and 48 (39.02%) from Bougouni, Of these, six species of small rodents belong to the family Muridae (Mastomys erythroleucus, Mastomys natalensis, Rattus rattus, Praomys daltoni, Gerbilliscus gambianus, Taterillus gracilis) and two species of insectivores associated with the genus Crocidura spp. belong to the family Soricidae and Erinaceidae (Crocidura cf olivieri and Atelerix cf albiventris) respectively. There is low specific diversity within these two stands, but the variation in relative abundance is significant (binomial test, p = 0.018 ˂ 0.05) between the Faladjè and Bougouni stands of small mammals. Mastomys erythroleucus was the most dominant species (57.33%, 43/75) in the Faladjè settlement and R. rattus dominated (37.5%,18/48) that of Bougouni. These two species of small mammals are potentially involved in the transmission of bacteria, parasites and pathogenic viruses to humans.

The ever-growing repertoire of genomic techniques continues to expand our understanding of true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbour robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in annotation and characterization of such proteins, yet many challenges remain to fully understand the pervasive nature of small proteins and their impact on bacterial biology. In this work we review recent developments in the dynamic field of bacterial genome reannotation, catalogue important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.

Resolving small molecule mixtures by nuclear magnetic resonance (NMR) spectroscopy has been of great interest for a long time for its precision, reproducibility and efficiency. However, spectral analyses for such mixtures are often highly challenging due to overlapping resonance lines and limited chemical shift windows. The existing experimental and theoretical methods to produce shift NMR spectra in dealing with the problem have limited applicability owing to sensitivity issues, inconsistency and / or requirement of prior knowledge. Recently, we have resolved the problem by decoupling multiplet structures in NMR spectra by the wavelet packet transform (WPT) technique. In this work, we developed a scheme for deploying the method in generating highly resolved WPT NMR spectra and predicting the composition of the corresponding molecular mixtures from their 1H NMR spectra in an automated fashion. The four-step spectral analysis scheme consists of calculating WPT spectrum, peak matching with a WPT shift NMR library, followed by two optimization steps in producing the predicted molecular composition of a mixture. The robustness of the method was tested on an augmented dataset of 1000 molecular mixtures, each containing 3 to 7 molecules. The method successfully predicted the constituent molecules with a median true positive rate of 1.0 against the varying compositions, while a median false positive rate of 0.04 was obtained. The approach can be scaled easily for much larger datasets.

Mechanical recycling of solid plastic wastes on a small-scale level can be accomplished with the correct approaches. Thermoplastics are mostly considered for mechanical recycling because of their physical properties and ease of reprocessing. This paper reviews the mechanical reprocessing techniques of selected thermoplastics (polyethylene terephthalate and polyolefins) since they constitute a significant proportion of plastics used commercially. Furthermore, necessary considerations for effective operation of small-scale plants, including energy requirements of machinery and optimisation in order to improve efficiency and product quality, are discussed. A clearer understanding and addressing of the process-related challenges will lead to successful establishment and management of small-scale mechanical recycling facilities to benefit communities. Efficient small-scale mechanical reprocessing establishments have become essential in reducing the environmental impacts of solid plastic wastes and for energy conservation.

We describe the design and fabrication of an industrial injection moulding system which can be mounted and used on the NCD-SWEET Small-angle X-Ray Scattering Beamline at ALBA. We show how highly useful time-resolved data can be obtained using this system. We are able to evaluate the fraction of material in the mould cavity and identify the first material to solidify and how this varies with the injection tem-perature. The design follows current industrial practice and provides opportunities to collect time-resolved data at several points within the mould cavity so we can build up a 4D perspective of the morphology and its temporal development. The quantitative data obtained will prove invaluable for the optimisation of the next generation of in-jection moulding techniques. This preliminary work used results from the injection moulding of a general purpose isotactic polypropylene.

In northern Thailand, the problem of small particulate matter happens every year, with the pri-mary source being agricultural weed burning and wildfire. The tourism industry is strongly impacted and has been the spotlight for the past few years. Thus, the study aims to investigate the effect of small particulate matter on tourism and related SMEs in Chiang Mai, Thailand. The data was collected from 286 entrepreneurs in the tourism and related SMEs sectors. The data was analyzed using data mining and association rule techniques. The study revealed that small particulate matter has a considerable impact on customer factors, especially the number of customers has decreased. Operational factors and prod-uct/service factors are also affected by the dust in the form of adjustments to keep the business running and the protection of the health of employees and customers. Certainly, financial factors are affected by the small particulate matter situation, both lower revenues and higher costs.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Small Island States (SIDS) are among the nations most exposed to climate change (CC) and are characterised by a high degree of vulnerability. Their special nature means there is a need for more studies focused on the limits to CC adaptation on such fragile nations, particularly in respect of their problems and constraints. This paper addressed a perceived need for research into the limitations of adaptation on SIDS, focusing on the many restrictions which are unique to them. The main research question raised by this study was that how and to what extent the challenges by human activities (e.g., agriculture and tourism) posed to coastlines of SIDS could be addressed. This paper identified and described the adaptation limits they have, by using a review of the literature and an analysis of case studies from a sample of five SIDS in the Caribbean and Pacific regions (Barbados, Trinidad and Tobago, Cook Islands, Fiji, Solomon Islands, and Tonga). The findings of this research showed that an adaptable SIDS is characterised by awareness of various values, appreciation and understanding of a diversity of impacts and vulnerabilities, and acceptance of certain losses through change. The implications of this paper are two-fold. It explains why island nations continue to suffer from the impacts of CC, and suggest some of the means via which adequate policies may support SIDS in their efforts to cope with the threats associated with a changing climate. This study concluded that, despite the technological and ecological limits (hard limits) affecting natural systems, adaptation to CC is not only limited by such complex forces, but also by societal factors (soft limits) that could potentially be overcome by more adequate adaptation strategies.

Human cytomegalovirus (HCMV) is a leading cause of severe diseases in immunocompromised individuals, including AIDS and transplanted patients, and in congenitally infected newborns. The utility of available drugs is limited by poor bioavailability, toxicity, and emergence of resistant strains. Therefore, it is crucial to identify new targets of therapeutic intervention. Among the latter, viral protein-protein interactions are becoming increasingly attractive. Since dimerization of HCMV DNA polymerase processivity factor ppUL44 plays an essential role in the viral life cycle being required for oriLyt-dependent DNA replication, we performed an in silico screening and selected 18 small molecules (SMs) potentially interfering with ppUL44 homodimerization. Antiviral assays using recombinant HCMV TB40-UL83-YFP in the presence of the selected SMs led to the identification of four active compounds. The most active one, B3, also efficiently inhibited AD169 in plaque reduction assays and impaired replication of an AD169-GFP reporter virus and its ganciclovir-resistant counterpart to a similar extent. As assessed by Western blotting experiments, treatment of infected cells with B3 specifically reduced viral gene expression starting from 48 h post infection, consistent with activity on viral DNA synthesis. Therefore, inhibition of ppUL44 dimerization could represent a new class of HCMV inhibitors, complementary to those targeting the DNA polymerase catalytic subunit or the viral terminase complex.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

After globalization, South Korea’s retail landscape has been saturated with large-scale, corporate type retails. However, recently new commercial districts composed of small retail units are returning and bringing about a change. This study sought to take note of this phenomenon and identify its features and meanings from the perspective of urban ecology. A density-distribution analysis was conducted to investigate how they were forms, and an analysis of traces on the Internet and an analysis on the types of businesses were done to identify sociocultural characteristics. Results showed that they had similar type of locations and growth patterns, that they harmoniously congregated in a form of smaller-individual stores, and that their use of similar names for their stores had an impact of branding their entire districts. It was also noted that a shared culture through social networking services served as a growth boost for their unfavorable location. The spontaneous formation of such commercial districts can be an outcome of an urban ecological process geared toward blank niches burgeoning in the current retail structure of Korea. The causes and conditions found in the cases reveal meaningful policy implications for cities facing the same urban crisis diversity.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

Since the 1970s, land subsidence has been developing rapidly in the Beijing Plain, the systematic study of its evolution mechanism is of great significance to the sustainable development of the regional economy. First, based on ENVISAT ASAT and RADARSAT2 data, the land subsidence data in Beijing Plain were obtained using permanent interferometer technology. Second, based on the GIS platform and using fishing net tools, vector data of ground settlement with different resolutions were obtained. Through a series of tests, a scale of 960 metres was selected as the research unit, and the subsidence rate of the grid was obtained from 2004 to 2015. Finally, based on the Mann-Kendall mutation test method, a trend analysis of land subsidence changes in various grids was carried out. The results showed that single-year mutation mainly distributed in the middle and lower parts of the Yongding River alluvial fan and the Chaobai River alluvial fan, mainly occurring in 2015, 2005 and 2013, respectively. The upper and middle alluvial fan of the Chaobai River, the vicinity of the emergency water source and the edge velocity of the groundwater funnel have undergone several sudden changes. Combined with hydrogeology, basic geological conditions and the impact of the South-to-North Water transfer project, we analysed the causes of the mutations in the grid. The research results can provide a basis for the study and prevention of land subsidence in this area and help to further explore the trend characteristics of land subsidence in this area.

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.

In this paper, the spatial distribution of stony desertification characteristics and its influencing factors in Karst areas in different sampling scales are studied using a grid sampling method based on geographic information system (GIS) technology and geo-statistics, with the rock bareness rate obtained through sampling with 150m × 150m grids in the Houzhai River Basin being taken as the original data and five grid scales (300m × 300m, 450m × 450m, 600m × 600m, 750m × 750m, and 900m × 900m) as the subsample sets. The results show that the rock bareness rate does not vary much from one sampling scale to another while average values of the five sub-samples all fluctuate around the average value of the entire set. As the sampling scale is expanding, the maximum value and the average value of rock bareness rate are decreasing gradually, with a gradual increase in the coefficient of variability. In the scale of 150m × 150m, the areas of minor stony desertification, medium stony desertification, and major stony desertification in the Houzhai River Basin are 7.81 km2, 4.50 km2, and 1.87 km2, respectively. The spatial variability of stony desertification on small scales is influenced by many factors, and that on medium scales is jointly influenced by gradient, rock contents, and rock bareness rate. On large scales, the spatial variability of stony desertification is mainly influenced by soil thickness and rock bareness rate.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

In small-scale hydropower scheme, the most important component is electro-mechanical equipment. Since cost contribution of this component is high because hydrokinetic projects require negligible civil works. Turbine and alternator contribute major fraction of the hydrokinetic projects. Thus, there is a requirement to estimates the electromechanical equipment cost for the hydrokinetic hydropower scheme. The present paper investigates design parameters of the hydrokinetic turbines and intends to develop cost correlation which depends on most critical parameters of hydropower sites such as velocity and power capacity. In this present work, three zero head turbines are considered including straight blade Darrieus, two Stage Savonius, and Gorlov Helical. The size and cost of major components have been calculated based on material, manufacturing, research and design, and assembly costs. Based on cost and site parameters, cost correlation has been developed. The obtained cost has been validated with available zero head turbines in the market and installed projects. A techno-economic analysis has been carried out to select economical hydrokinetic turbine for river and canal application.

Artisanal and small-scale gold mining (ASGM) has been an important source of income for communities in the Madre de Dios River Basin in Peru for hundreds of years. However, in recent decades, the scale of ASGM activities in the region has increased dramatically, and exposures to a variety of occupational and environmental hazards related to ASGM, including mercury, are becoming more widespread. The aims of our study were to: (1) examine patterns in the total hair mercury level of human participants in several communities in the region and compare these results to the 2.2 µg/g total hair mercury level equivalent to the World Health Organization (WHO) Expert Committee of Food Additives (JECFA)’s Provisional Tolerable Weekly Intake (PTWI); and (2), to measure the mercury levels of paco (Piaractus brachypomus) fish raised in local aquaculture ponds, in order to compare these levels to the EPA Fish Tissue Residue Criterion of 0.3 µg Hg/g fish (wet weight). We collected hair samples from 80 participants in four communities (one control and three where ASGM activities occurred) in the region, and collected 111 samples from fish raised in 24 local aquaculture farms. We then analyzed the samples for total mercury. Total mercury levels in hair were statistically significantly higher in the mining communities than in the control community, and increased with increasing distance away from the Madre de Dios headwaters (as the crow flies), did not differ by sex, and frequently exceeded the reference level. Regression analyses indicated that higher hair mercury levels were associated with residence in ASGM communities. The analysis of paco fish samples found no samples that exceeded the EPA tissue residue criterion. Collectively, these results align with other recent studies showing that ASGM activities are associated with elevated human mercury exposure. The fish farmed through the relatively new process of aquaculture in ASGM areas appeared to have little potential to contribute to human mercury exposure. More research is needed on human health risks associated with ASGM to discern occupational, residential, and nutritional exposure, especially through tracking temporal changes in mercury levels as fish ponds age, and assessing levels in different farmed fish species. Additionally, research is needed to definitively determine that elevated mercury levels in humans and fish result from the elemental mercury from mining, rather than from a different source, such as the mercury released from soil erosion during deforestation events from mining or other activities.

This paper presents an optimal design for the inner current control loop of the continuous current conduction mode (CCM) power factor correction (PFC) stage, which it can be used as the front stage of the two stages alternating current-direct current (AC-DC) telecom power supply. Conventional single-phase CCM-PFC boost converter usually implemented with using of the proportional-integral (PI) controllers in both of the voltage and current control loops, to regulate the output DC voltage to the specified value, moreover to maintains the input current follows the input voltage which offers converter with high power factor (P.F) and low current total harmonic distortion (THD). However, due to the slow dynamic response of the PI controller at the zero-crossing point of the input supply current, input current can’t fully follow the input voltage which leads to high THD. Digitally controlled PFC converter with an optimal design of the inner current control loop using doubly control loops IP controller to reduce the THD and to offer input current with unity P.F was performed in this paper. Furthermore, for the economic design of the digitally control PFC converter, two isolated AC and DC voltage sensors are proposed and designed for the interfacing with the microcontroller unit (MCU). PSIM software was used to test the converter performance with using the proposed designed current controllers and isolated voltage sensors. High power density digitally controlled telecom PFC stage with P.F of about 99.93%, full load efficiency of about 98.70% and THD less 5.50% is achieved in this work.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Recently, the Integrated Air Defense System (IADS) has become vital for the defense system as the military defense system is vital for national security. Placing Integrated Air Defense System batteries among locations to protect locations assets is a crucial problem because optimal solutions are needed for interceptor missiles to intercept attacker missiles for maximizing protection of assets across locations or places. In this research, the procedures of using network algorithms along with developing several network algorithms are going to be demonstrated to develop a model for sequential development of seven network securing strategies of placing Surface to Air Missile (SAM) batteries to maximize the protection of assets across locations (based on given asset values) by generating optimal solutions through computation to destroy maximum attacker missiles by using minimum interceptor missiles with given intercept probability. This network securing strategies can be implemented not only for Integrated Air Defense System (IADS) planning but also Counter Air (CA) planning as Integrated Air Defense System (IADS) is conducted with defensive counter air supported by attack operations in offensive counter air.

Outcome of redo-mitral valve replacement in the small mitral annulus with the use of the chimney technology is not well documented. From 2019 to 2020, 77 consecutive patients underwent redo-mitral valve replacement with the use of the chimney technology because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. Mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. Preoperative Mitral valve mean gradient was 18.07 ± 9.40 mmHg. Postoperative mitral prosthesis size 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. Mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg and at follow-up echocardiogram performed at 3 years after the procedure was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while 4-year survival was 89.3% with no reoperation. Use of the chimney technology in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable intraoperatively and over time.

Proposed study aims to investigate the digital transformation of Greek small and medium enterprises (SMEs), with a particular focus on their digital maturity and the strategic and organizational factors contributing to digital transformation. The research issue of digital transformation is attracting considerable interest among academics and business practicians since COVID-19 accelerated the procedure of implementing Industry’s 4.0 principles all over global economies. Quantitative research on 147 Greek SMEs revealed most important issues on how these businesses implement digital transformation, factors accelerating or decelerating the process, barriers and expected outcomes. Research enlights how SMEs face the transition to digital business and reveals the factors that can facilitate the whole process. Results can be valuable for stakeholders enabled to digital transformation process from both business and academic point of view, while there exist aspects that can contribute to policy makers / motivation developers in state’s level as well.

Pancreatic ductal adenocarcinoma (PDAC) is a ravaging disease whose poor prognosis requires a more detailed understanding of its biology to foster the development of effective therapies. The unsatisfactory results of treatments targeting cell proliferation and its related mechanisms suggested to rather focus on the inflammatory tumor microenvironment (TME). Here, we discuss the role of cancer secreted proteins in the complex TME tumor-stroma crosstalk, to sched lights on druggable molecular targets for the development of innovative, safer and more efficient therapeutic strategies.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

Recently, there has been renewed interest in the performance, functionality, and sustainability of traditional small-scale storage interventions (check dams, farm bunds and tanks) used across India for the improvement of local water security. The Central Groundwater Board of India is en-couraging the construction of such interventions for the alleviation of water scarcity. It is of critical importance to understand the hydrological effect of these interventions at basin scales to maximise their effectiveness. The quantification of small-scale interventions in hydrological modelling is often neglected, especially in large-scale modelling exercises. A bespoke version of the GWAVA model was developed to assess the impact of interventions on the water balance of the Cauvery Basin and two smaller sub-catchments. Model results demonstrate that farm bunds appear to have a negligible effect on the estimated average annual simulated streamflow at the outlets of the two sub-catchments and the basin whereas tanks and check dams have a more significant effect. In-terventions generally were found to increase evaporation losses across the catchment. The model adaption used in this study provides a step-change in the conceptualisation and quantification of the consequences of small-scale storage interventions in large- or basin-scale hydrological models.

Groundwater is an important resource for many countries and its scarcity is a major concern in small territories, especially in the islands where the constant extraction is creating a high risk of public calamity. This issue has been increasing because of the anthropogenic activities and the climate change and it has called the attention of scientists and stakeholders in order to assess the sustainability of the water management system, and therefore, to establish strategies for a more sustainable water use. San Andres island was taking as case study and a description of the water balance was carried out in order to understand the management system. Then, a water system sustainability assessment was performed with indicators such as water security, water quality, drinking water, sanitation, infrastructure, climate robustness, biodiversity, attractiveness, and governance, according to the City Blueprint Methodology. The result for the 24 evaluated indicators was a score of 3.2, whose interpretation is “an unsustainable water management”. The qualitative assessment was the base to propose water security, water quality, and governance strategies to improve the water management in the island. The assessment and its discussions are relevant for the water management in small islands across the world whose economy is based on the tourism and whose water security is at a high risk.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

ABSTRACT This study focused for socio-economic benefit of Western shoreline of Lake Ziway ecosystem. The data collected from two woredas they are Adami Tulu Jidu Kombolch (ATJK) and Dugda woreda of fishermen and small scale irrigation users. Lake Ziway great importance food and water for both groups of respondents and additionally sources of raw material, energy, cultivation, organic fertilizers, genetic and medicinal plants. Lake Ziway also has a major economic benefit for both groups of respondents. The sampled fishermen cached mean amount of 2,524Kg per year with minimum and maximum amount of fish 504Kg and 16,800Kg per year respectively and with this fish catching they got average income of 51,398 Birr ($2,570) per year with range of 7,200 Birr ($360) and 288,000 Birr ($14,400) per year. As like of fishermen small scale irrigation also got economic benefit with their production of cereal crops, fruits and vegetables. They produce in average 13.47Quintal of cereal crop and 69.56Quintal of fruits and vegetables per year and they got average income of 7,727 Birr ($386) and with range of 13,714 Birr ($686) per year respectively. this incurred that wetland ecosystem has a lot of socio-economic benefit for the people live near by specially for developing countries like Ethiopia they are more dependent on natural ecosystem like of Lake Ziway. Because of its high importance, we have to protect and conserve and use sustainably of Lake Ziway and similar wetland ecosystems. Key Words: Wetland ecosystem service; Lake Ziway; Socioeconomic benefit; Fishermen; Small scale irrigation users

Small island developing states (SIDS) traditionally face a set of challenges like the narrow economic structure, environmental issues, and dependence on a few ranges of economic activities forcing them to open the economy to the exterior. Therefore, their development model, like in Cape Verde depends on migration, remittances, dependence on aid, tourism, and state employment. The current research offers an insight about the nature of Cape Verde’s economy as a SIDS and the degree to which its economy depends on tourism and government services, both of which are supported through aid programs. Understanding Cape Verde’s development model is important to clarify the challenges the country faces, and its development needs to gather a long-term resilience and to understand if it is changing from a MIRAB (Migrations, Remittances, Aid and Bureaucracy) model into another one.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

: Molecular targeting strategies have been used for years to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping that in mind, it is essential to know the role of each enzyme in a particular metabolic pathway. In this review, we are providing in-depth knowledge of various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase, which are associated with multiple types of cancer that depend on ceramide metabolism. Focus has also been given to discussing physicochemical properties of well-studied inhibitors of natural products origin and their related structures for these enzymes. Targeting ceramide metabolism exhibited promise in mono and combination therapies at preclinical stages to prevent cancer progression and paved the way for the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide metabolizing enzymes will help the medicinal chemist to design potent and selective small molecules for treating cancer progression at various levels.

Recently, federated learning (FL) has been receiving great attention as an effective machine learning method to avoid the security issue in raw data collection as well as to distribute the computing load to edge devices. However, even though wireless communications is a essential part for implementing FL in edge networks, there have been a few works that analyze the effect of wireless networks on FL. In this paper, we investigate FL in small-cell networks where multiple base stations (BSs) and users are located according to homogeneous Poisson point process (PPP) with different densities. We comprehensively analyze the effects of geographic node deployment on the model aggregation in FL on the basis of stochastic geometry-based analysis. We derive the closed-form expressions of coverage probability with tractable approximations and discuss the minimum required BS density for achieving a target model aggregation rate in small-cell networks. Our analysis and simulation results provide insightful information for understanding the behaviors of FL in small-cell networks, and it can be exploited as a guideline for designing the network facilitating the wireless FL.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Change detection with heterogeneous remote sensing images (Hete-CD) plays an important role in practical applications, especially when homogenous remote sensing images are unavailable. However, bitemporal heterogeneous remote sensing images (HRSIs) cannot compare directly to measure change magnitude, and many deep learning methods require large amounts of samples to train the module. Moreover, labeling many samples for land cover change detection with HRSIs is time-consuming and labor-intensive. Therefore, acquiring satisfactory performance of Hete-CD remains a challenge for deep learning networks with very small training samples. In this study, we promote a novel deep-learning framework for Hete-CD to obtain satisfactory performance while the initial samples are very small. We initially design a multiscale network with select kernel-attention module to focus on capturing different change targets with various sizes and shapes. Then, a simple yet effective non-parametric sample-enhanced algorithm based on the Pearson correlation coeffi-cient is promoted to explore potential samples around each initial sample. Finally, the proposed network and sample-enhanced algorithm are fused into one iterative framework to improve the change detection performance with very small samples. Experimental results conducted on four pairs of actual HRSIs indicated that the proposed framework can achieve competitive accuracies with very small samples for initialization when compared with some state-of-the-art methods. For example, the improvement is approximately 3.38% and 1.99% when compared with the selected traditional methods and deep learning methods, respectively.

Infrared dim and small target detection is a key technology of various detection tasks. However, due to the lack of shape, texture, and other information, it is a challenging task to detect dim and small targets. Recently, since many traditional algorithms ingore global information of infrared images, they generate some false alarms in complicated environments. To address this problem, in this paper, a coarse-to-fine deep learning-based method is proposed to detect dim and small targets. Firstly, a coarse-to-fine detection framework integrating deep learning and background prediction is applied for detecting targets. The framework contains of coarse detection module and fine detection module. In coarse detection stage, Region Proposal Network (RPN) is employed to generate masks in target candidate regions. Then, for further optimize the result, inpainting is utilized to predict the background by the global semnantic of images. In this paper, inpainting algorithm with a mask aware dynamic filtering module is incorporated into the fine detection stage to estimate background in candidate target areas. Finally, compared with existing algorithms, the experimental results indicate that the proposed framework have effective detection capability and robustness for complex surroundings.

One of the stated goals of the Common Agricultural Policy reforms has been to provide a fairer distribution of payments across and within Member States, but little progress has been accomplished, with about 20% of farmers receiving 80% of the total amount of Direct Payments. The structural factors that underlie this inequity, notably the preponderance of specific types of farming systems, are investigated in this research. A logit model was developed using Agricultural Census data at the Commune level, using the evolution of the percentage of farmers receiving Direct Payments in Portugal as the dependent variable. The findings reveal that the local importance of arable crops (cereals) and cattle farming systems, as well as the existence of larger farms and younger farmers, all contributed to farmers' increasing access to DP between 2009 and 2019. In traditional Mediterranean farming systems, however, access to DP has been restricted to a smaller proportion of farmers. However, there appears to have been some redistribution in the previous two CAP programming cycles, from bigger to smaller farmers, older to younger farmers, and from olives, cereals, and cattle to other types of production, notably vineyards.

Phagosomal escape and intracellular survival, often accompanied by Small Colony Variants (SCVs) formation, are typical features of infections caused by S. aureus. The survival in macro-phages favours S. aureus dissemination and complicates treatment. RAW 264.7 murine macro-phages infected with S. aureus USA300 and treated with erythromycin and 20mM carnosine, alone and in combination, were used as experimental model. SCVs were isolated from all treat-ment conditions, but only those undergoing the pressure of combined erythromycin and carnosine for 48 hours were stable for at least six passages on blood agar. Nucleic acid extraction was car-ried out for S. aureus USA300 wild-type and stable SCVs. Whole Genome Sequencing (WGS) was performed using Illumina DNA Prep and Illumina MiSeq, and quantitative reverse transcription PCR was performed. WGS analysis did not yield mutations pointing to differences between S. au-reus USA300 and stable SCVs, therefore the focus was shifted to evaluating gene expression vari-ations. Genes such as zur, mntR, uhpt, fur, sdrE were shown to be significantly up-regulated in SCVs compared to S. aureus USA300 wild-type, suggesting a global change that allows adapta-tion to intracellular persistence, including protection from inflammatory response and evasion of the immune system.

The DNA methylation profile of breast cancer differs from that in healthy tissue and can be used as a diagnostic and prognostic biomarker. Aim of the study: to compare gene methylation in small malignant breast tumors less than 2 cm and in healthy tissue and fibroadenoma. Methylation of the following 15 genes was studied: MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, TIMP3. Methods: analysis was made by our modified MS-HRM method followed confirmation of the results by pyrosequencing. The genes were selected from publications that studied DNA methylation in breast cancer with high genome coverage. The study group included 48 samples of breast cancer, the control group included 24 samples of fibroadenoma and 24 samples of healthy tissue. Results: significant differences were found in methylation of 8 genes: CCDC181, GSM2, ITPRIPL1, ZNF177, CACNA1E, DLGAP2, TIMP3 (all р<0.001), and PRDM14 (р=0.002). The most accurate diagnostic value, based on logistic regression, was shown with the compound of two genes – CCDC181 and ZNF177 (AUC=0.99) in pyrosequencing analysis. Conclusion: small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissue and benign proliferative lesions.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.