Investigating the Effects of Psilocybin on Models of Anxiety, Recognition Memory, and Depression-Like Behavior and the Role of the 5-HT2A Receptor in Mediating Psilocybin’s Impact on Behavioral Despair

Psychedelics are a class of hallucinogenic substances that exert their effects through serotonin (5-HT) receptor agonism, particularly at the 5-HT2 receptor, which is further characterized into the 2A, 2B, and 2C subtypes. While some research studies indicate that psychedelics mediate their effects via 5-HT2A receptor agonism, others show that it is not necessary to induce these effects. Recently, there has been a growing interest in psychedelic-assisted therapy as a promising alternative for treatment of anxiety and depression, two of the most common psychiatric disorders worldwide associated with significant morbidity. Although antidepressants and pharmacological interventions for anxiety have revolutionized management, they often have mixed efficacy and fail to provide satisfactory emotional relief. Clinical studies show that psychedelics like psilocybin and LSD produce antidepressant and anxiolytic effects, but there is still an active debate on whether or not these effects are mediated via action at the 5-HT2A receptor. In this study, my first aim was to examine psilocybin’s effects on the following behavioral assays in male WT C57BL/6 mice: head-twitch response (HTR), a 5-HT2A-specific rodent model of hallucinogenic action; locomotor activity, a model of anxiety; novel object recognition (NOR), to assess recognition memory; light-dark box preference, an additional model of anxiety; and forced swim test (FST), a model of depression-like behavior. HTR assessed the acute effects of psilocybin, while the remaining assays measured psilocybin’s post-acute effects (i.e. 24 hrs following administration). Second, I aimed to determine whether or not psilocybin’s post-acute antidepressant-like effects are mediated by the 5-HT2A receptor by conducting FST assays using the 5-HT2A-specific antagonist volinanserin (M100,907). Acutely, psilocybin evoked a greater HTR relative to the vehicle group, but post-acutely it did not produce a significant difference in locomotion, NOR, or light-dark exploratory behavior. However, mice given psilocybin in the first FST had both lower immobility and higher climbing times relative to controls. In the second FST, mice administered M100,907 shortly before injection with psilocybin exhibited no significant difference in immobility and climbing times compared to controls. Interestingly, in the third FST, mice given M100,907 alone had a significantly lower climbing time, while immobility and swimming times between the vehicle and experimental groups were nonsignificant. The results of this study suggest that the 5-HT2A receptor may indeed play a central role in mediating psychedelics’ post-acute effects, and that antagonizing it impairs these effects. These findings highlight the need for additional studies that examine the post-acute effects of a variety of psychedelics and further investigate the level of involvement of the 5-HT2A receptor using genetically modified animal models

Capture of manufacturing uncertainty in turbine blades through probabilistic techniques

Efficient designing of the turbine blades is critical to the performance of an aircraft engine. An area of significant research interest is the capture of manufacturing uncertainty in the shapes of these turbine blades. The available data used for estimation of this manufacturing uncertainty inevitably contains the effects of measurement error/noise. In the present work, we propose the application of Principal Component Analysis (PCA) for de-noising the measurement data and quantifying the underlying manufacturing uncertainty. Once the PCA is performed, a method for dimensionality reduction has been proposed which utilizes prior information available on the variance of measurement error for different measurement types. Numerical studies indicate that approximately 82% of the variation in the measurements from their design values is accounted for by the manufacturing uncertainty, while the remaining 18% variation is filtered out as measurement error

Solar PV parameter estimation using multi-objective optimisation

The estimation of the electrical model parameters of solar PV, such as light-induced current, diode dark saturation current, thermal voltage, series resistance, and shunt resistance, is indispensable to predict the actual electrical performance of solar photovoltaic (PV) under changing environmental conditions. Therefore, this paper first considers the various methods of parameter estimation of solar PV to highlight their shortfalls. Thereafter, a new parameter estimation method, based on multi-objective optimisation, namely, Non-dominated Sorting Genetic Algorithm-II (NSGA-II), is proposed. Furthermore, to check the effectiveness and accuracy of the proposed method, conventional methods, such as, ‘Newton-Raphson’, ‘Particle Swarm Optimisation, Search Algorithm, was tested on four solar PV modules of polycrystalline and monocrystalline materials. Finally, a solar PV module photowatt PWP201 has been considered and compared with six different state of art methods. The estimated performance indices such as current absolute error matrics, absolute relative power error, mean absolute error, and P-V characteristics curve were compared. The results depict the close proximity of the characteristic curve obtained with the proposed NSGA-II method to the curve obtained by the manufacturer’s datasheet

Wideband Direct Detection Constraints on Hidden Photon Dark Matter with the QUALIPHIDE Experiment

We report direction detection constraints on the presence of hidden photon dark matter with masses between 20-30 ueV using a cryogenic emitter-receiver-amplifier spectroscopy setup designed as the first iteration of QUALIPHIDE (QUantum LImited PHotons In the Dark Experiment). A metallic dish sources conversion photons from hidden photon kinetic mixing onto a horn antenna which is coupled to a C-band kinetic inductance traveling wave parametric amplifier, providing for near quantum-limited noise performance. We demonstrate a first probing of the kinetic mixing parameter "chi" to just above 10^-12 for the majority of hidden photon masses in this region. These results not only represent stringent constraints on new dark matter parameter space but are also the first demonstrated use of wideband quantum-limited amplification for astroparticle applicationsComment: 6 Pages, 5 figures

Role of Exosomes in Tumor Induced Neo-Angiogenesis

Exosomes are the nanovesicles, belonging to the type of extracellular vesicles (EVs), produced by normal as well as tumor cells and function as a mode in cell-to-cell communication. Tumor cells utilize various approach to communicate with neighboring cells for facilitating tumor invasion and progression, one of these approaches has been shown through the release of exosomes. Tumor-derived exosomes (TEX) have the ability to reprogram/modulate the activity of target cells due to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment (TME) to promote angiogenesis which is an important element for solid tumor growth and metastasis. So, exosomes play a vital role in cancer invasiveness and progression by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their role in different cancer models. Then, we will emphasis on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular importance on the underlying mechanisms in various cancer origins. In the end, we will unveil the therapeutic potential of tumor derived exosomes as drug delivery vehicles against angiogenesis

Tumor reversion: a dream or a reality.

Reversion of tumor to a normal differentiated cell once considered a dream is now at the brink of becoming a reality. Different layers of molecules/events such as microRNAs, transcription factors, alternative RNA splicing, post-transcriptional, post-translational modifications, availability of proteomics, genomics editing tools, and chemical biology approaches gave hope to manipulation of cancer cells reversion to a normal cell phenotype as evidences are subtle but definitive. Regardless of the advancement, there is a long way to go, as customized techniques are required to be fine-tuned with precision to attain more insights into tumor reversion. Tumor regression models using available genome-editing methods, followed by in vitro and in vivo proteomics profiling techniques show early evidence. This review summarizes tumor reversion developments, present issues, and unaddressed challenges that remained in the uncharted territory to modulate cellular machinery for tumor reversion towards therapeutic purposes successfully. Ongoing research reaffirms the potential promises of understanding the mechanism of tumor reversion and required refinement that is warranted in vitro and in vivo models of tumor reversion, and the potential translation of these into cancer therapy. Furthermore, therapeutic compounds were reported to induce phenotypic changes in cancer cells into normal cells, which will contribute in understanding the mechanism of tumor reversion. Altogether, the efforts collectively suggest that tumor reversion will likely reveal a new wave of therapeutic discoveries that will significantly impact clinical practice in cancer therapy

A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Indian patients

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare multi-organ cancer syndrome and understanding its genetic basis may help comprehend the molecular mechanism of familial cancer. A number of germ line mutations in the STK11 gene, encoding a serine threonine kinase have been reported in these patients. However, STK11 mutations do not explain all PJS cases. An earlier study reported absence of STK11 mutations in two Indian families and suggested another potential locus on 19q13.4 in one of them. METHODS: We sequenced the promoter and the coding region including the splice-site junctions of the STK11 gene in 16 affected members from ten well-characterized Indian PJS families with a positive family history. RESULTS: We did not observe any of the reported mutations in the STK11 gene in the index patients from these families. We identified a novel pathogenic mutation (c.790_793 delTTTG) in the STK11 gene in one index patient (10%) and three members of his family. The mutation resulted in a frame-shift leading to premature termination of the STK11 protein at 286(th )codon, disruption of kinase domain and complete loss of C-terminal regulatory domain. Based on these results, we could offer predictive genetic testing, prenatal diagnosis and genetic counselling to other members of the family. CONCLUSION: Ours is the first study reporting the presence of STK11 mutation in Indian PJS patients. It also suggests that reported mutations in the STK11 gene are not responsible for the disease and novel mutations also do not account for many Indian PJS patients. Large-scale genomic deletions in the STK11 gene or another locus may be associated with the PJS phenotype in India and are worth future investigation

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis