8 research outputs found
Robotic Restoration: Restoration of stucco ornaments by means of in-situ additive manufacturing
No full textThe preservation and restoration of intricate stucco ornaments, which are part of our collect cultural Heritage, is under threat due to a diminishing number of skilled restoration plasterers. The highly physically demanding- and labour intensive nature of this work makes it unsustainable for the human body and advocates for a more sustainable alternative restoration method for the future. Digital Fabrication has the potential to offer such an alternative method. While 3D scanning, digital repair and 3D printing are all proven technologies, stucco ornament restoration often requires an on site fabrication solution directly onto a ceiling or wall due to the brittle nature of prefab stucco elements. The research explores how an in-situ 3D printing technique can be developed for the restoration of stucco ornaments by focussing on three main topics: 1) developing gypsum-based 3D printing materials, which are compatible to gypsum ceilings and comply with criteria for extrusion based 3D printing; 2) Designing and prototyping 3D printing tools including an extruder and material delivery system; 3) Conceptualizing a Restoration Robot Platform with which the developed printing material can be used with the developed 3D printing tools, for on site stucco ornament restoration. The insights gained from the development of the printing material and printing process are integrated into digital fabrication software used in practise, through a proposed plug-in and workflow.Architecture, Urbanism and Building Sciences | Building Technology | Sustainable Desig
SMAR1 suppresses the cancer stem cell population via hTERT repression in colorectal cancer cells
No full textOne of the hallmarks of a cancer cell is the ability for indefinite proliferation leading to the immortalization of the cell. Activation of several signaling pathways leads to the immortalization of cancer cells via the reactivation of enzyme telomerase (hTERT). hTERT is active in germ cells, stem cells and also cancer cells. An earlier report from our lab suggests that SMAR1, a tumor suppressor protein, is significantly downregulated in the higher grades of colorectal cancers. Our study identifies SMAR1 as a transcriptional repressor of hTERT. We find that SMAR1 interacts with HDAC1/mSin3a co-repressor complex at the hTERT promoter and brings about HDAC1-mediated transcriptional repression of the promoter. Most solid tumors including colorectal cancer reactivate hTERT expression as it confers several advantages to the cancer cells like increased proliferation and angiogenesis. One of these non-canonical functions of hTERT is inducing the pool of cancer stem cell population. We find that in the CD133HighCD44High cancer stem cells population, SMAR1 expression is highly diminished leading to elevated hTERT expression. We also find that knockdown of SMAR1 promotes total CD133+CD44+ population and impart enhanced sphere-forming ability to the colorectal cancer cells. SMAR1 also inhibits invasion and metastasis in colorectal cancer cell lines via repression of hTERT. Our study provides evidence that downregulation of SMAR1 causes activation of hTERT leading to an increase in the cancer stem cell phenotype in colorectal cancer cells
AI-enabled crime intelligence extraction: enhancing law enforcement capabilities through deep and dark web analysis and data correlation
No full textThe emergence of anonymity services and the dark web presents a complex landscape where user privacy must be balanced with the need to combat illicit activities. To address this challenge, a Python-based dark web-watching crawler was developed using the Tor network to gather and store a large volume of dark website addresses. This system leverages the Scrapy framework for web crawling to extract specific crime-related information from dark websites, which is then stored in a MongoDB database for analysis. The crawler algorithms analyze the collected data to identify patterns of criminal behavior, and the results are visualized using word cloud diagrams and histograms to create an intuitive interface for real-time monitoring of dark web crimes. This monitoring system aims to enhance law enforcement's ability to detect and respond to illegal activities on the dark web, contributing to efforts to combat human trafficking, illegal information transactions, and the sale of drugs and firearms. The development of this system underscores the importance of leveraging technology to address the dual challenges of user privacy and criminal activity in anonymous online environments. Several machine learning models such as Naive Bayes, decision tree, logistic regression, random forest, KNN were tried for classifying the data from legitimate and dark net websites. Highest accuracy 99% was obtained with Random Forest algorithm. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2025
Tumor suppressor SMAR1 regulates PKM alternative splicing by HDAC6-mediated deacetylation of PTBP1
No full textBackground
Highly proliferating cancer cells exhibit the Warburg effect by regulation of PKM alternative splicing and promoting the expression of PKM2. Majority of the alternative splicing events are known to occur in the nuclear matrix where various MARBPs actively participate in the alternative splicing events. SMAR1, being a MARBP and an important tumor suppressor, is known to regulate the splicing of various cancer-associated genes. This study focuses on the regulation of PKM alternative splicing and inhibition of the Warburg effect by SMAR1.
Methods
Immunohistochemistry was performed in breast cancer patient samples to establish the correlation between SMAR1 and PKM isoform expression. Further, expression of PKM isoforms upon modulation in SMAR1 expression in breast cancer cell lines was quantified by qRT-PCR and western blot. The acetylation status of PTBP1 was estimated by immunoprecipitation along with its enrichment on PKM pre-mRNA by CLIP in SMAR1 knockdown conditions. The role of SMAR1 in tumor metabolism and tumorigenesis was explored by in vitro enzymatic assays and functional assays upon SMAR1 knockdown. Besides, in vivo tumor formation by injecting adeno-SMAR1-transduced MDA-MB-231 cells in NOD/SCID mice was performed.
Results
The expression profile of SMAR1 and PKM isoforms in breast cancer patients revealed that SMAR1 has an inverse correlation with PKM2 and a positive correlation with PKM1. Further quantitative PKM isoform expression upon modulation in SMAR1 expression also reflects that SMAR1 promotes the expression of PKM1 over tumorigenic isoform PKM2. SMAR1 deacetylates PTBP1 via recruitment of HDAC6 resulting in reduced enrichment of PTBP1 on PKM pre-mRNA. SMAR1 inhibits the Warburg effect, tumorigenic potential of cancer cells, and in vivo tumor generation in a PKM2-dependent manner.
Conclusions
SMAR1 regulates PKM alternative splicing by causing HDAC6-dependent deacetylation of PTBP1, resulting in reduced enrichment of PTBP1 on PKM pre-mRNA. Additionally, SMAR1 suppresses glucose utilization and lactate production via repression of PKM2 expression. This suggests that tumor suppressor SMAR1 inhibits tumor cell metabolism and tumorigenic properties of cancer cells via regulation of PKM alternative splicing
Photo-Induced Cytotoxicity and Anti-Metastatic Activity of Ruthenium(II)-Polypyridyl Complexes Functionalized with Tyrosine or Tryptophan
No full textThe synergistic effect of oxygen, light, and photosensitizer (PS) has found applications in medicine for the treatment of cancer through photodynamic therapy (PDT). Induction of apoptosis to cancerous cells will prevent tumor metastasis that spreads cancer cells to the neighboring organs/tissues. Herein, we report the two apoptotic Ru(II)–polypyridyl complexes that are functionalized with pendant amino acid moieties tyrosine (1) and tryptophan (2), respectively. These two water soluble complexes were found to interact strongly (K1a = (1.18 ± 0.28) × 105 M−1 and K2a = (1.57 ± 0.77) × 105 M−1) with CT-DNA. Isothermal titration calorimetry (ITC) studies revealed that these complexes bind to CT-DNA through an entropically driven process. Both the complexes showed photo-induced cytotoxicity and exhibit apoptotic activity under photo-irradiation conditions. The comet assay indicated that these complexes can damage cellular DNA, which is attributed to the significant build-up of 1O2 level even on irradiation with low intensity light (10 J cm−2, λRange 450–480 nm). This photoinduced DNA damage and apoptosis in A549 cells was induced by reactive oxygen species (ROS) and occurred through up-regulation of apoptotic marker caspase-3. Control experiments under dark conditions revealed an insignificant cytotoxicity towards these cells for two photosensitive molecules
SMAR1 inhibits Wnt/β-catenin signaling and prevents colorectal cancer progression
No full textReduced expression of Scaffold/Matrix Attachment Region Binding Protein 1 (SMAR1) is associated with various cancers resulting in poor prognosis of the diseases. However, the precise underlying mechanism elucidating the loss of SMAR1 requires ongoing study. Here, we show that SMAR1 is highly downregulated during aberrant Wnt3a signaling due to proteasomal degradation and predicted poor prognosis of colorectal cancer. However, substitution mutation (Arginine and Lysine to Alanine) in the D-box elements of SMAR1 viz. “RCHL” and “RQRL” completely abrogated its proteasomal degradation despite Wnt3a activity. SMAR1 inhibited Wnt/β-catenin signaling by recruiting Histone deacetylase-5 to β-catenin promoter resulting in reduced cell migration and invasion. Consequently, reduced tumor sizes in in-vivo NOD-SCID mice were observed that strongly associated with suppression of β-catenin. However, loss of SMAR1 led to enriched H3K9 Acetylation in the β-catenin promoter that further increased Wnt/β-catenin signaling activities and enhanced colorectal cancer progression drastically. Using docking and isothermal titration calorimetric studies we show that small microbial peptides viz. AT-01C and AT-01D derived from Mycobacterium tuberculosis mask the D-box elements of SMAR1. These peptides stabilized SMAR1 expression that further inhibited metastatic SW480 colorectal cancer cell migration and invasion. Drastically reduced subcutaneous tumors were observed in in-vivo NOD-SCID mice upon administration of these peptides (25 mg/kg body weight) intraperitoneally. Taken together our structural studies, in-vitro and in-vivo results strongly suggest that the D-box elements of SMAR1 represent novel druggable targets, where the microbial peptides hold promise as novel colorectal cancer therapeutics
Travel burden and clinical presentation of retinoblastoma: Analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
No full textBackground: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral. © 2020 Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ
Крупные прорывы озёр антарктических оазисов: обобщение современных знаний
No full textIn recent decades, the importance of studying the outburst lakes of Antarctic oases has been increasing, which is associated with a number of applied and fundamental problems. First of all, because supraglacial, englacial, and glacier-dammed lakes are characterized by a quick response to the climate changes. In the applied aspect, active (unstable) lakes and seasonal streams are relevant for research since they often provoke catastrophic natural disasters. Monitoring and prevention of such events are primarily necessary in the areas of Antarctic stations, where many year-round and seasonal research programs are implemented. This article presents historical and the present- day data and descriptions of lake outbursts located in the oases of East Antarctica. The study is based on the generalization of both published and unpublished materials presented in the funds of the Arctic and Antarctic Research Institute (St. Petersburg), in scientific and technical reports of the Soviet Antarctic Expedition and Russian Antarctic Expedition, Information bulletins (newsletters) of the Soviet Antarctic expeditions, and foreign articles. In addition to that, the results of fieldwork carried out in 2017–2020 were used. Currently, the aforementioned materials are in different form and funds, so the proposed study is the first step of generalizing research on the potential outburst water bodies on the Antarctic Continent. Through to the ongoing work, albeit irregular, our understanding of functioning of the surface hydrological systems of Antarctic oases is steadily growing.В последние десятилетия изучение прорывоопасных озёр антарктических оазисов становится всё более актуальным. Основной предпосылкой к их исследованию послужил тот факт, что нестабильные водоёмы провоцируют катастрофические явления, нанося ущерб станциям, полевым базам и выносным лагерям. Приводятся исторические и современные данные о наиболее известных прорывах озёр, расположенных в оазисах Восточной Антарктиды. Основу работы составляет обобщение изданных и неопубликованных данных с целью объединения имеющегося материала в рамках одной публикации для удобства дальнейших исследований и анализа
