Computer Screen Research Articles

Evaluation of Anti-vitiligo properties through an In-silico Computational screening of Selected Herbal Bioactive Components with the target protein Tyrosinase

Background: Vitiligo is one of the most hypopigmented disorders of the skin, it can be correlated with Swetha kuttam or ven kuttam or ven pulli mentioned in Siddha classical literature. Current therapeutic management available for vitiligo is only moderately effective in controlling further severity of symptoms. Hence in recent times, people rely most on alternative complementary treatments for the management of vitiligo. The research articles have shown the following bio-active compounds present in the selected herbs Kaempferol, Quercetin, Anacardic acid, Glabridin, Isovitexin, Aristolochic acid and Hydnocarpin which is already mentioned in the Siddha literature for the management of vitiligo(venkuttam). Objective: This research article attempts to carry out the molecular docking analysis of the chosen herbal bioactive components against the target enzyme Tyrosinase in Vitiligo. Methods: Docking calculations were done for the obtained bio-active compounds including Kaempferol from Indigofera aspalathoides(Vahl.), Quercetin from Smilax china(Linn.), Tinosporide from Tinospora cordifolia(Willd.)Hook.f.&Thoms, Anacardic acid from Semecarpus anacardium (Linn.), Glabridin from Glycyrrhiza glabra(Linn.), Isovitexin from Psoralea corylifolia (Linn.), Oleic acid from Nigella sativa(Linn.), Aristolochic acid from Aristolochia bracteolata (Lam.) & Hydnocarpin from Hydnocarpus laurifolia (Dennst.) Sleumer against Tyrosinase(PDB)-1WX3, the intended protein. Results: Nine bioactive compounds have been screened in total, the following leads as Quercetin, Glabridin, Isovitexin and Hydnocarpin which interact with target to form four interactions with 70–100% binding effectiveness with the protein – Tyrosinase enzyme. Conclusion: The computational analysis led to the conclusion that the bioactive molecules present in the chosen herbals had significant binding efficacy and may exert promising anti-vitiligo properties.

Design, synthesis, biological and computational screening of novel pyridine-based thiadiazole derivatives as prospective anti-inflammatory agents

In this study, a novel series of pyridine-based thiadiazole derivatives (NTD1-NTD5) were synthesized as prospective anti-inflammatory agents by combining substituted carboxylic acid derivatives of 5-substituted-2-amino-1,3,4-thiadiazole with nicotinoyl isothiocyanate in the presence of acetone. The newly synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, and mass spectrometry. First, the compounds underwent rigorous in vivo testing for acute toxicity and anti-inflammatory activity and the results revealed that three compounds-NTD1, NTD2, and NTD3, displayed no acute toxicity and significant anti-inflammatory activity, surpassing the efficacy of the standard drug, diclofenac. Notably, NTD3, which featured benzoic acid substitution, emerged as the most potent anti-inflammatory agent among the screened compounds. To further validate these findings, an in silico docking study was carried out against COX-2 bound to diclofenac (PDB ID: 1pxx). The computational analysis demonstrated that NTD2, and NTD3, exhibited substantial binding affinity, with the lowest binding energies (−8.5 and −8.4, kcal/mol) compared to diclofenac (−8.4 kcal/mol). This alignment between in vivo and in silico data supported the robust anti-inflammatory potential of these derivatives. Moreover, molecular dynamics simulations were conducted, extending over 100 ns, to examine the dynamic interactions between the ligands and the target protein. The results solidified NTD3's position as a leading candidate, showing potent inhibitory activity through strong and sustained interactions, including stable hydrogen bond formations. This was further confirmed by RMSD values of 2-2.5 Å and 2-3Ǻ, reinforcing NTD3's potential as a useful anti-inflammatory agent. The drug likeness analysis of NTD3 through SwissADME indicated that most of the predicted parameters including Lipinski rule were within acceptable limits. While these findings are promising, further research is necessary to elucidate the precise relationships between the chemical structures and their activity, as well as to understand the mechanisms underlying their pharmacological effects. This study lays the foundation for the development of novel anti-inflammatory therapeutics, potentially offering improved efficacy and safety profiles.

IoT Based Smart E-Mirror using OpenCV with Raspberry PI

This paper describes the design, construction and working of an IoT based smart mirror. Every morning our day begins by watching ourselves at least once in mirror before leaving our homes. We interact with it psychological to find out how we look and how our attire is. Smart Mirror or Magic Mirror is one of the applications of Raspberry Pie. A computer screen embedded in mirror looks very futuristic. The Raspberry Pie stays at back scenes and controls the data displayed on mirror. While looking at mirror you can look at various notifications from social sites as well news, weather forecast and more things. Such mirrors can be programmed to work as AI and control home appliances by voice input or touch screen. The Raspberry Pi is connected to monitor via HDMI as well as it also has inbuilt Wi-Fi and Bluetooth interfaces so we can just swipe music and videos to mirror

Investigation of the effect of laser technology on the color of polyester fabrics

Purpose The purpose of this study is to determine the effect of laser treatment on disperse dye-uptake and fastness values of polyester fabrics. Furthermore, it was aimed to evaluate colors directly over the photos of fabric samples instead of color measuring with spectrophotometer which is thought to be useful in terms of online digital color assessment.Design/methodology/approach In this study, 100% polyester (150 denier) single jersey knitted fabrics (weight: 145 g/m2, course density: 15 loops/cm, wale density: 24 loops/cm) were used in the trials. The effect of laser treatments before and after dyeing on color was investigated. Laser treatments were applied to fabrics at different resolutions (20, 25 and 30 dpi) and pixel times (60, 80 and 100 µs) before dyeing. The power of the laser beam was 210 W and the wavelength was 10.6 µm. In order to determine the effect of laser treatment on polyester; FTIR analysis, SEM-EDX analysis and bursting strength tests were applied to untreated and treated fabric samples.Findings It was found that treatments with laser have a significant effect on disperse dye-uptake of polyester fibers, and for this reason laser-treated fabrics were dyed in darker shade. Furthermore, it was determined that the samples treated at 30 dpi started to melt and the fabric was damaged considerably, but the fabrics treated at 20 and 25 dpi were not affected at all. Another result obtained regarding the use of laser technology in polyester fabrics is that if some areas of fabrics are not treated with laser and some other areas are treated with laser at 20 dpi 60 µs and 25 dpi 60 µs, it will be possible to obtain patterns containing three different shades of the same color on the fabric.Originality/valueWhen the literature is examined, it is seen that there are various studies on the dyeability and patterning of polyester fabrics with disperse dyes by laser technology. As it is known, today color measurement is done digitally using a spectrophotometer. However, when we look at a photograph on computer screens, the colors we see are defined by RGB (red-green-blue) values, while in the spectrophotometer they are defined by L*a*b* (L*: lightness-darkness, a*: redness-greenness, b*: yellowness-blueness) values. Especially when it is desired to produce various design products by creating patterns with laser technology, it would be more useful to show the color directly to the customer on the computer screen and to be able to speak over the same values on the color. For this reason, in this study, the color measurement of the fabric samples was not made with a spectrophotometer, instead, the RGB values obtained from the photographs of the samples were converted into L*a*b* values with MATLAB and interpreted, that is, a digital color evaluation was made on the photographs. Therefore, it is believed that this study will contribute to the literature.

Systems and Computational Screening identifies SRC and NKIRAS2 as Baseline Correlates of Risk (CoR) for Live Attenuated Oral Typhoid Vaccine (TY21a) associated Protection

AimWe investigated the molecular underpinnings of variation in immune responses to the live attenuated typhoid vaccine (Ty21a) by analyzing the baseline immunological profile. We utilized gene expression datasets obtained from the Gene Expression Omnibus (GEO) database (accession number: GSE100665) before and after immunization. We then employed two distinct computational approaches to identify potential baseline biomarkers associated with responsiveness to the Ty21a vaccine. Main methodsThe first pipeline (knowledge-based) involved the retrieval of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network construction, and topological network analysis of post-immunization datasets before gauging their pre-vaccination expression levels. The second pipeline utilized an unsupervised machine learning algorithm for data-driven feature selection on pre-immunization datasets. Supervised machine-learning classifiers were employed to computationally validate the identified biomarkers. Key findingsBaseline activation of NKIRAS2 (a negative regulator of NF-kB signalling) and SRC (an adaptor for immune receptor activation) was negatively associated with Ty21a vaccine responsiveness, whereas LOC100134365 exhibited a positive association. The Stochastic Gradient Descent (SGD) algorithm accurately distinguished vaccine responders and non-responders, with 88.8%, 70.3%, and 85.1% accuracy for the three identified genes, respectively. SignificanceThis dual-pronged novel analytical approach provides a comprehensive comparison between knowledge-based and data-driven methods for the prediction of baseline biomarkers associated with Ty21a vaccine responsiveness. The identified genes shed light on the intricate molecular mechanisms that influence vaccine efficacy from the host perspective while pushing the needle further towards the need for development of precise enteric vaccines and on the importance of pre-immunization screening.

Computational Design of Photosensitive Polymer Templates To Drive Molecular Nanofabrication.

Molecular electronics promises the ultimate level of miniaturization of computers and other machines as organic molecules are the smallest known physical objects with nontrivial structure and function. But despite the plethora of molecular switches, memories, and motors developed during the almost 50-years long history of molecular electronics, mass production of molecular computers is still an elusive goal. This is mostly due to the lack of scalable nanofabrication methods capable of rapidly producing complex structures (similar to silicon chips or living cells) with atomic precision and a small number of defects. Living nature solves this problem by using linear polymer templates encoding large volumes of structural information into sequence of hydrogen bonded end groups which can be efficiently replicated and which can drive assembly of other molecular components into complex supramolecular structures. In this paper, we propose a nanofabrication method based on a class of photosensitive polymers inspired by these natural principles, which can operate in concert with UV photolithography used for fabrication of current microelectronic processors. We believe that such a method will enable a smooth transition from silicon toward molecular nanoelectronics and photonics. To demonstrate its feasibility, we performed a computational screening of candidate molecules that can selectively bind and therefore allow the deterministic assembly of molecular components. In the process, we unearthed trends and design principles applicable beyond the immediate scope of our proposed nanofabrication method, e.g., to biologically relevant DNA analogues and molecular recognition within hydrogen-bonded systems.

Computational screening of damaging nsSNPs in human SOD1 genes associated with amyotrophic lateral sclerosis identifies destabilising effects of G38R and G42D mutations through in silico evaluation.

Amyotrophic lateral sclerosis (ALS), a complicated neurodegenerative disorder affected by hereditary and environmental variables, is a condition. In this study, the genetic makeup of ALS is investigated, with a focus on the SOD1 gene's single-nucleotide polymorphisms (SNPs) and their ability to affect disease risk. Eleven high-risk missense variations that may impair the functionality of the SOD1 protein were discovered after a thorough examination of SNPs in the SOD1 gene. These mutations were chosen using a variety of prediction approaches, highlighting their importance in the aetiology of ALS. Notably, it was discovered that the stability of the SOD1 wild-type protein structure was compromised by the G38R and G42D SOD1 variants. Additionally, Edaravone, a possible ALS medication, showed a greater affinity for binding mutant SOD1 structures, pointing to potential personalised treatment possibilities. The high-risk SNPs discovered in this investigation seem to have functional effects, especially on the stability of proteins and their interactions with other molecules. This study clarifies the complex genetics of ALS and offers insights into how these genetic variations may affect the effectiveness of therapeutic interventions, particularly in the context of edaravone. In this study advances our knowledge of the genetic mechanisms causing ALS vulnerability and prospective therapeutic strategies. Future studies are necessary to confirm these results and close the gap between individualised clinical applications and improved ALS care.

Difference of effectiveness between educational video media and PowerPoint on sedentary lifestyle on students’ knowledge

Living a sedentary lifestyle entails engaging in minimal physical activity and getting insufficient exercise. One of the common repercussions of sedentary habits among adolescents is obesity. With the onset of the COVID-19 pandemic, students often studied online, spending prolonged hours in front of computer screens. This shift to remote learning exacerbated the sedentary behavior already prevalent among adolescents, potentially worsening the risk of obesity and other associated health issues. To mitigate the detrimental effects of a sedentary lifestyle, this research aimed to enhance students' comprehension of relevant information on a sedentary lifestyle. A quasi-experimental pre-test and post-test design was used in this kind of study. Using the purposive sampling technique, the study sample consisted of 72 students from class X: 36 respondents from class X-1 were assigned to the instructional video media group, while 36 respondents from class X-2 were assigned to the PowerPoint group. A pre-test questionnaire was distributed to each group, followed by interventions and a post-test questionnaire. The Mann-Whitney test was used to analyze the data between groups, while the Wilcoxon test was used to analyze each group's data. After using PowerPoint and video media as an intervention, there was a significant difference in the respondents' knowledge level, with p values being the same (p value=0.000). The treatment group that used educational video media and the group that used PowerPoint media differed in effectiveness (p value=0.015). After receiving an intervention using a PowerPoint and video, the respondents' level of knowledge increased. Compared to PowerPoint presentations, educational videos are a more effective way to enhance understanding of inactive lifestyles. A remarkable opportunity exists to enhance adolescents' understanding of the importance of leading an active lifestyle by harnessing the potential of video media as an instrumental tool.

Pentecostalism and the Eucharist in a digital age: A theological reflection on Bill Johnson’s praxis

ABSTRACT During the Covid-19 pandemic most, if not all, Christian denominations moved their worship services online. While this may have been satisfactory in some respects, it caused problems for many liturgical traditions because of the centrality of the Eucharist as an act of worship. They struggled to decide whether it was legitimate to celebrate the sacrament online. However, Pentecostals and independent charismatic churches simply moved their eucharistic services online without too many obvious problems. Individuals sat at home with bread and fruit juice in front of their computer screens. Since the pandemic has passed, many people continue to sit in front of their computer screens or smartphones in order to participate in the Eucharist. But these practices raise some important and interesting theological questions from a Pentecostal perspective. This paper explores Pentecostal eucharistic theology using the example of Bill Johnson’s teaching praxis, as posted on the social medial platform YouTube. It offers a theological reflection on Pentecostal scholarship and makes suggestions as to how the discussion of Pentecostal eucharistic praxis may be developed.

Principal’s Leadership of School in Empowering Computer-Based Teachers at SD Surakarta

In the era of the Industry 5.0 revolution, learning is transformed by the digitalization of education. The background of this research is the very rapid development of computing in education, which requires the use of educational software and human resources (SDM). This involvement will have an impact on students in learning at Madrasah Tsanawiyah Surakarta. Qualitative research methods were used with a case study approach by subject research teachers and students of the Seventh Grade Madrasah Tsanawiyah Surakarta. Data collection techniques include documentation, observations, and interviews. Analysis techniques using triangulation of sources, methods, and techniques. Research results show that students are involved through technology in digital classroom collaboration by creating teaching materials using applications, viewing students on computer screens, and making computational-based questions. Implementation of digital use to maintain teachers currently has not been collaborative. Teacher understanding with discussions, workshops using innovative LCD learning processes with facilities, Flip Books, and one-month workshop positions inside the school. The researchers’ findings show that the use of digital media is very helpful in developing student understanding; students are more actively following learning as well. Contributing to teachers’ creation of Flip Books as a learning module.

Understanding large scale sequencing datasets through changes to protein folding.

The expansion of high-quality, low-cost sequencing has created an enormous opportunity to understand how genetic variants alter cellular behaviour in disease. The high diversity of mutations observed has however drawn a spotlight onto the need for predictive modelling of mutational effects on phenotype from variants of uncertain significance. This is particularly important in the clinic due to the potential value in guiding clinical diagnosis and patient treatment. Recent computational modelling has highlighted the importance of mutation induced protein misfolding as a common mechanism for loss of protein or domain function, aided by developments in methods that make large computational screens tractable. Here we review recent applications of this approach to different genes, and how they have enabled and supported subsequent studies. We further discuss developments in the approach and the role for the approach in light of increasingly high throughput experimental approaches.

Protein-engineered leaf and branch compost cutinase variants using computational screening and IsPETase homology

Polyethylene terephthalate (PET) is a popular material used in plastic products, particularly in food-packaging. However, its waste is environmentally hazardous and current industrial recycling methods are energy-intensive and can cycle mechanically weaker plastic products over time. A green solution is to employ PET-hydrolyzing enzymes (PHE). Leaf and branch compost cutinase (LCC) has been identified as the best-performing naturally occurring PHE at temperatures above the glass transition temperature, Tg of PET while PETase, identified from Ideonella sakaiensis 201-F6 (IsPETase), has exhibited the best performance at moderate temperatures (< 45 °C). Using a high-throughput computational approach, we have screened for single-substitution variants for improved hydrolysis activity against PET using Rosetta interface energy scores as a target metric. Homology alignment of IsPETase was employed to generate an LCC variant that possessed a double cysteine mutation, characteristic of a unique disulfide bond in IsPETase, to study the impact on moderate temperature hydrolysis. A resulting point-mutation variant from our computational screening method and the IsPETase homology variant of LCC led to improved hydrolysis activity at 70 °C while the latter also possessed improved hydrolysis activity at moderate temperatures of 30 °C – 50 °C, demonstrating that a computational screening workflow and homology alignment between high-performing PHEs are promising strategies to improve hydrolysis activity.

Abstract 1098: Identification of SUMO2 as a novel therapeutic target for synovial sarcoma

Abstract Synovial Sarcoma (SySa) is a rare soft tissue sarcoma that accounts for 5 - 10% of all soft tissue sarcomas. It disproportionately affects children, adolescents and young adults with tumors emerging in muscles, tendons, nerve tissue and joints. Current treatment involves radiation and radical surgery including limb amputation with overall survival around 50% highlighting the urgent need to develop targeted therapies for these patients. In this study, we hypothesized that the fusion SS18-SSX protein found in SySa transcriptionally rewires the tumor cells creating a dependence on specific genes that if uncovered can be exploited therapeutically. To study genes that are selectively essential to SySa, we analyzed the dependency maps (DepMap) whole genome RNAi and CRISPR screening datasets consisting of ~1750 human cancer cell lines including 9 SySa cell lines. We identified 368 target genes that specifically impact the proliferation of SySa when compared to other tumor cell lines. To interrogate these genes systematically, we designed pooled CRISPR libraries and conducted in vitro as well as in vivo screens in SySa cell line HS-SY-II. Our screens revealed that Small Ubiquitin like-modifier 2 (SUMO2) was one of the most significant dependencies in both the in vitro as well as in vivo screens. We tested the SUMO2 inhibitor, TAK-981, a clinical stage small molecule inhibitor specific for E1 SUMO-activating enzyme (SAE), against a panel of SySa cell lines with HS-SY-II and SYO1 showing an EC50 in the low nanomolar range. Furthermore, TAK-981 treatment potently induced apoptosis and reduced the proportion of cycling cells in both HS-SY-II as well as SYO1 cell lines. Strikingly, transcriptomic studies on HS-SY-II and SYO1 cell lines showed that TAK-981 treatment substantially altered the oncogenic signatures of SySa. This was evident both in the HS-SY-II cell line expressing the SS18-SSX1 fusion as well as the SYO1 cell line expressing the SS18-SSX2 fusion protein. These data strongly indicate that SUMO2 is critical for the transcriptional activity of the different SS18-SSX chimeric oncoproteins. In addition, TAK-981 treatment showed a highly significant downregulation of genes associated with cell cycle progression as well as a modulation of genes of the BAF and PRC1/PRC2 complexes that have been implicated in SySa pathogenesis. Taken together, we developed an integrated computational and experimental screening approach to prioritize and validate selective dependencies in synovial sarcoma. Our studies identify SUMO2 as a novel, selective vulnerability in this cancer and since SUMO2 inhibitors are currently in Phase 1/2 clinical trials for other malignancies, our findings present a novel potential avenue for targeted treatment of synovial sarcoma. Citation Format: Rema Iyer, Pramod Akula Bala, Rabi Murad, Aniruddha J. Deshpande. Identification of SUMO2 as a novel therapeutic target for synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1098.

Abstract 6001: Repurposing dihydroergotamine mesylate as a potential MCL-1 inhibitor and its antitumor effect in pancreatic cancer cells

Abstract Background: Myeloid cell leukemia 1 (MCL-1) is an anti-apoptotic member of the BCL-2 protein family which is involved in intrinsic (mitochondrial) pathway of apoptosis and is deregulated in several cancers. Current MCL-1 specific inhibitors have limitations in terms of efficiency, tolerability, and off-target effects and challenges associated with shallow binding groove of MCL-1. In this study, dihydroergotamine mesylate (DHE), an approved anti-migraine drug, was found as a potential ligand of the MCL-1 BH3-binding pocket and was further evaluated for its potential MCL-1 inhibition and effect on pancreatic cancer cells. Methods: PubChem Database was used for library preparation and virtual screening (OpenBabel and AutoDock Vina). The 55 crystal structures available for MCL-1 in Protein Data Bank (PDB) were clustered using principal component analysis with Bio3D R-package to select representative PDBs for further screening. Consensus voting and k-means clustering was used to shortlist compounds for Molecular dynamics (MD) simulations. MD simulations (100 nanoseconds) by GROMACS were employed to measure stability of ligands in MCL-1 binding pocket. DHE efficacy on cell proliferation was evaluated with MTS and clonogenic assays and on apoptosis using the FITC/Annexin V flow cytometry assay in MiaPaCa-2 and PANC-1 pancreatic cancer cell lines. Effect of DHE treatment on MCL-1 gene and protein expression was analyzed using qRT-PCR and western blotting, respectively. Results: Computational screening identified DHE (PubChem ID: 12308974) as a top hit exhibiting consistent interactions within the MCL-1 BH3-binding pocket. Notably, DHE displayed stable RMSD and formed four hydrogen bonds throughout MD simulations. In vitro results showed that DHE significantly reduced viability of MiaPaCa-2 and PANC-1 pancreatic cancer cells with IC50 values of 31 μM and 47 μM, respectively. DHE significantly (P&amp;lt;0.001) suppressed colony formation by pancreatic cancer cells in a dose-dependent (10μM, 20μM, and 40μM) manner. The percentage of Annexin V-positive and Propidium iodide-negative fraction in MiaPaCa-2 cells treated with DHE also increased in a dose-dependent manner. DHE did not have significant effect on MCL-1 mRNA expression. However, western blotting demonstrated MCL-1 protein levels were significantly reduced in both pancreatic cancer cell lines upon DHE treatment. Conclusion: Our findings showed DHE suppresses the pancreatic cancer cells viability and proliferation, and significantly increased early apoptotic cells. DHE treatment had no effect on MCL-1 at the transcription level but significantly reduced the protein, suggesting posttranslational modifications, and thus future mechanism of action studies is required. The present study reports that the anti-migraine drug DHE might be a novel therapeutic agent for pancreatic cancer and needs to be explored further. Citation Format: Pooja Mittal, Jae Ho Lo, Shivani Soni, Francesca Battaglin, Shradheya RR Gupta, Lesly Torres-Gonzalez, Yan Yang, Sandra Algaze, Priya Jayachandran, Karam Ashouri, Alexandra Wong, Wu Zhang, Jian Yu, Lin Zhang, Joshua Millstein, Indrakant Kumar Singh, Heinz Josef Lenz. Repurposing dihydroergotamine mesylate as a potential MCL-1 inhibitor and its antitumor effect in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6001.

Abstract 174: Cholesterol efflux protein ABCA1 skews macrophages towards an anti-tumor phenotype and consequently impacts breast cancer progression

Abstract With a lifetime risk of approximately 1 in 8, breast cancer maintains in its position as the most prevalent form of cancer and ranks second in terms of cancer-related fatalities in women. The primary cause of mortality is often attributed to the recurrence of metastatic breast cancer. While immune therapy shows some effectiveness, many patients do not exhibit meaningful responses, likely due to immune-suppressive factors present within the tumor microenvironment. These factors include myeloid cells such as Macrophages(MΦ), therefore, there is a strong need to devise strategies to shift (MΦ) from a pro-tumor to an anti-tumor phenotype. Our previous research has uncovered the susceptibility of MΦs to disruptions in cholesterol metabolic balance. Considering these findings, coupled with epidemiological evidence linking elevated plasma cholesterol to unfavorable prognosis, the impact of cholesterol homeostasis in tumor associated MΦs on breast cancer becomes evident. An in-depth computational screen helped us identify ABCA1—a cholesterol efflux protein with elevated mRNA expression associated with increased survival. Beyond cholesterol efflux, ABCA1 also facilitates the movement of cholesterol from the inner membrane layer to the outer layer. Previous work has shown that cholesterol within the inner membrane layer can directly interact with and activate various receptors on the membrane's surface, initiating downstream signaling events. Consequently, the activities of ABCA1 in cholesterol efflux and translocation likely hold substantial regulatory implications. Underscoring the clinical significance of ABCA1 are our findings that heightened ABCA1 expression within breast tumors correlates with augmented levels of cytotoxic T cells, T cell effector enzymes (Prf-1 and Gzmb), and improved survival rates. Crucially, our in vitro investigations indicate that ABCA1 modulates multiple functions of MΦs to adopt an anti-cancer phenotype, encompassing: (1) the ability to infiltrate tumor spheroids, (2) angiogenesis, (3) efferocytosis—an immune-suppressive phagocytic process devoid of antigen presentation, and (4) the expansion, migration, and activity of cytotoxic T cells. ABCA1 transports cholesterol from macrophages to a lipid poor ApoA1 protein and facilitates the formation of nascent HDL via reverse cholesterol transport. We leveraged this mechanism to therapeutically target ABCA1 using ApoA1 mimetics 5A and 4F. Our data so far indicates that these ApoA1 phenocopy ABCA1 overexpression in MΦs. Together, our data provides compelling evidence for the involvement of ABCA1 in the pathophysiology of breast tumors. The anticipated outcomes of this research will establish the basis for the future utilization of ABCA1 and its downstream effects for therapeutic purposes. Citation Format: Shruti V. Bendre, Natalia Krawczynska, Shaunak Bhogale, Erin Weisser, Simon Han, Basel Hajyousif, Avni Singh, Rajendra K C, Yu Wang, Claire P. Schane, Adam T. Nelczyk, Anasuya DasGupta, Hashni E. Gamage, Kevin T. VanBortle, Emad Tajkhorshid, Saurabh Sinha, Wohnwa Cho, Erik R. Nelson. Cholesterol efflux protein ABCA1 skews macrophages towards an anti-tumor phenotype and consequently impacts breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 174.

An exploration of the influence of animal and object categories on recall of item location following an incidental learning task.

The current study explores the role of attention in location memory for animals and objects. Participants completed an incidental learning task where they rated animals and objects with regard to either their ease of collection to win a scavenger hunt (Experiments 1a and b) or their distance from the centre of the computer screen (Experiment 2). The images of animals and objects were pseudo-randomly positioned on the screen in both experiments. After completing the incidental learning task (and a reverse counting distractor task), participants were then given a surprise location memory recall task. In the location memory recall task, items were shown in the centre of the screen and participants used the mouse to indicate the position the item had been shown during the incidental encoding task. The results of both experiments show that location memory for objects was more accurate than for animals. While we cannot definitively identify the mechanism responsible for the difference in the location memory of objects and animals, we propose that differences in the influence of object-based attention at encoding affect location memory when tested at recall.

Repurposing of Compounds from Streptomyces spp. as Potential Inhibitors of Aminoacyltransferase FemA: An Essential Drug Target against Drug-resistant Staphylococcus aureus.

Drug-resistant Staphylococcus aureus represents a substantial healthcare challenge worldwide, and its range of available therapeutic options continues to diminish progressively. Thus, this study aimed to identify potential inhibitors against FemA, a crucial protein involved in the cell wall biosynthesis of S. aureus. The screening process involved a comprehensive structure-based virtual screening on the StreptomDB database to identify ligands with potential inhibitory effects on FemA using AutoDock Vina. The most desirable ligands with the highest binding affinity and pharmacokinetic properties were selected. Two ligands with the highest number of hydrogen bonds and hydrophobic interactions were further analyzed by molecular dynamics (MD) using the GROMACS version 2018 simulation package. Six H-donor conserved residues were selected as protein active sites, including Arg- 220, Tyr-38, Gln-154, Asn-73, Arg-74, and Thr-24. Through virtual screening, a total of nine compounds with the highest binding affinity to the FemA protein were identified. Frigocyclinone and C21H21N3O4 exhibited the highest binding affinity and demonstrated favorable pharmacokinetic properties. Molecular dynamics analysis of the FemA-ligand complexes further indicated desirable stability and reliability of complexes, reinforcing the potential efficacy of these ligands as inhibitors of FemA protein. Our findings suggest that Frigocyclinone and C21H21N3O4 are promising inhibitors of FemA in S. aureus. To further validate these computational results, experimental studies are planned to confirm the inhibitory effects of these compounds on various S. aureus strains. Combining computational screening with experimental validation contributes valuable insights to the field of drug discovery in comparison to the classical drug discovery approaches.

Exploring the Potential of Metal-Organic Frameworks for Cryogenic Helium-Based Gas Gap Heat Switches via High-Throughput Computational Screening.

With the advantages of a long lifetime and high reliability, gas gap heat switches (GGHSs) are attractive in many thermal management applications, especially in space-borne cryogenic systems. The performance of a GGHS is significantly affected by the adsorption characteristics of the adsorbent in the sorption pump. Compared with the commonly used adsorbent in the GGHSs (activated carbon), metal-organic frameworks (MOFs) have larger surface areas, higher pore volumes, and exceptional tunability, which motivates this study to explore their potential for application in cryogenic GGHSs. To this end, two performance metrics, the required volume of adsorbent (vsor) and total input heat (qtot), were computed for about 6000 MOFs via molecular simulations and compared with those of activated carbon. It is found that over 2300 MOFs possess a smaller vsor than activated carbon, and the smallest vsor of MOFs is about 12.7% of that of activated carbon. vsor and qtot generally change in the same direction, which implies it is possible to reduce both parameters simultaneously by choosing a suitable MOF. Structure-performance analysis reveals that 1/vsor consistently increases first and then decreases with pore limiting diameter, largest cavity diameter, available pore volume, accessible surface area, helium void fraction, and bulk density. Descriptor ranges corresponding to high-performing MOFs were identified based on Precision-Recall analysis. Notably, Zr-containing MOFs are particularly likely to have smaller vsor values than activated carbon. It is anticipated that the promising MOFs identified by this study will motivate further experimental investigations, and the insights into structure-performance relationships can serve to guide the rational design of novel MOF candidates for GGHSs.

Culture and self-construal in the age of globalization: an empirical inquiry based on multiple approaches.

There are three main types of culture in human society, namely, individual-oriented, relationship-oriented and social-oriented cultures. In history, there are two main positions on the relationship between culture and self-construal: the cultural determinist position and the interaction position. After analyzing literature critically, we propose that the interaction position is more persuasive than the cultural determinist position. A self-construal model was constructed from an interactionist and polycultural perspective, pointing out the relationship between three cultures and self-construal. We argue that individuals interacting with cultures in the context of globalization can develop a more integrated self-construal. The present study proposes the existence of polycultural self-construal, and aimed to explore how self-construal factors relate to cultures. Three approaches-psychological tests, priming with cultural icons and content analysis-were used to explore mechanisms between cultures (individual-oriented, relationship-oriented, and social-oriented cultures) and self-construal. In Study 1, we recruited 460 undergraduate students as participants through campus advertising to complete three psychological tests, namely, the Cultural Identity Scale (CIS), the Marlowe-Crowne Social Approval Scale (MC-SDS), and the Polycultural Self-construal Scale (PSCS). In Study 2, we created icon materials that could prime the three cultures. The experimental process was divided into two stages: priming and measurement. First, 165 participants were presented with icon materials on the computer screen to activate the corresponding culture, and then they were asked to complete the PSCS. In Study 3, the experimental procedures were followed as for Study 2. Then the Ten Statements Test (TST) was used. Each of the 178 participants gave 10 different responses to the question of "Who am I?." Each participant's "I am …" narratives were qualitatively processed using content analysis. The individual-oriented culture mainly affects the individuality and equality factor of self-construal. The relationship-oriented culture mainly impacts the relationality factor of self-construal, while the social-oriented culture mainly affects the collectivity and equality factors of self-construal. There were no significant differences in the effects of the three cultures on the autonomy factor of self-construal. The multi-components of the polycultural self-construal are difficult to interpret based on one culture type. All three cultures have specific and shared effects on human self-construal.

Halide Superionic Conductors with Non‐Close‐Packed Anion Frameworks

AbstractHalide superionic conductors (SICs) are drawing significant research attention for their potential applications in all‐solid‐state batteries. A key challenge in developing such SICs is to explore and design halide structural frameworks that enable rapid ion movement. In this work, we show that the close‐packed anion frameworks shared by traditional halide ionic conductors face intrinsic limitations in fast ion conduction, regardless of structural regulation. Beyond the close‐packed anion frameworks, we identify that the non‐close‐packed anion frameworks have great potential to achieve superionic conductivity. Notably, we unravel that the non‐close‐packed UCl3‐type framework exhibit superionic conductivity for a diverse range of carrier ions, including Li+, Na+, K+, and Ag+, which are validated through both ab initio molecular dynamics simulations and experimental measurements. We elucidate that the remarkable ionic conductivity observed in the UCl3‐type framework structure stems from its significantly more distorted site and larger diffusion channel than its close‐packed counterparts. By employing the non‐close‐packed anion framework as the key feature for high‐throughput computational screening, we also identify LiGaCl3 as a promising candidate for halide SICs. These discoveries provide crucial insights for the exploration and design of novel halide SICs.