Computational Docking Simulations of Nitroanisole and Nitrophenol with CYP2E1

Studies have shown that CYP2E1, a cytochrome P450 enzyme containing two primary binding sites, plays a substantial role in the oxidative metabolism of many foreign substances, including the detoxification reaction of 4-nitroanisole to 4-nitrophenol. Through the advancements of the computational docking software Tripos Sybyl7.2, it has been possible to investigate the mechanism of oxidation of 4-nitroanisole. Docking modules of Sybyl7.2 software, including Surflext and molecular dynamics, have created the ability to ascertain the likely binding configurations of 4-nitranisole and its constitutional isomers in either the distal or proximal binding sites of CYP2E1. Knowing the relative binding relationships of 4-nitroanisole to the heme of the CYP2E1 plays in human oxidative metabolism of xenobiotic substances. The goal in this research was to observe the configuration of nitroanisole and its derivatives in relation to the heme of the enzyme and possibly determine a cause for the unconventional reaction kinetics of CYP2E1

Efektivitas Penggunaan Aplikasi Wordwall dalam Pembelajaran IPS Secara Daring (Online) di Kelas Tinggi Sekolah Dasar

Situasi pandemi Covid-19 mengubah pembelajaran tatap muka di kelas menjadi pembelajaran daring (online). Media pembelajaran online yang menjamin keutuhan kegiatan pembelajaran serta mengangkat motivasi dan fokus peserta didik adalah aplikasi Wordwall. Masalah penelitian adalah ‘Bagaimana efektivitas penggunaan media wordwall pada kegiatan pembelajaran IPS secara daring di kelas tinggi SD?”, Penelitian bertujuan melihat efektivitas penggunaan media wordwall pada kegiatan pembelajaran IPS secara daring di kelas tinggi SD. Penelitian ini adalah jenis Mixed Method. Analisis data menggunakan analisis kuantitatif pada angket dan tes, analisis kualitatif pada wawancara. Subjek penelitian adalah peserta didik  kelas tinggi SDK Canosa. Hasil penelitian menunjukan rata-rata kelas hasil belajar IPS peserta didik  kelas tinggi adalah sebesar  79.99. Ditinjau dari KKM 70, maka diketahui 55 dari 58 (94.83%) orang peserta didik  tuntas, 3 orang (5.20%) tidak tuntas. Angket menunjukkan tingkat capaian responden (peserta didik ) sebesar 91.90% atau sangat efektif, hasil wawancara kepala sekolah dan guru mengindikasikan peserta didik  terlibat secara aktif dalam pembelajaran dan antusias mengerjakan kuis-kuis, menggabungkan kata, menemukan kata, dan melakukan game

A plan for the development of superconducting Undulator prototypes for LCLS-II and future FELs

Undulators serve as the primary source of radiation for modern storage rings, and more recently for the advent of Free-Electron Lasers (FELs). The performance of future FELs can be greatly enhanced using the much higher magnetic fields of superconducting undulators (SCU) [1]. For example, the LCLS-II hard x-ray undulator can be shortened by up to 70 m using an SCU in place of a PMU (permanent magnet undulator), or its spectral performance can be critically improved when using a similar length. In addition, SCUs are expected to be orders of magnitude less sensitive to radiation dose; a major issue at LCLS-II with its 1-MHz electron bunch rate. We present a funded R&D collaboration between SLAC, ANL, and LBNL, which aims to demonstrate the viability of superconducting undulators for FELs by building, testing, measuring, and tuning two 1.5-m long planar SCU prototypes using two different technologies: NbTi at ANL and Nb Sn at LBNL. Our goal is to review and reassess the LCLS-II HXR baseline plans (PMU) in July of 2015, after the development and evaluation of both prototypes, possibly in favor of an SCU for LCLS-II.

β-Amyloid 25-35 Peptide Reduces the Expression of Glutamine Transporter SAT1 in Cultured Cortical Neurons

β-Amyloid (Aβ) peptides may cause malfunction and death of neurons in Alzheimer’s disease. We investigated the effect of Aβ on key transporters of amino acid neurotransmission in cells cultured from rat cerebral cortex. The cultures were treated with Aβ(25-35) at 3 and 10 μM for 12 and 24 h followed by quantitative analysis of immunofluorescence intensity. In mixed neuronal–glial cell cultures (from P1 rats), Aβ reduced the concentration of system A glutamine transporter 1 (SAT1), by up to 50% expressed relative to the neuronal marker microtubule-associated protein 2 (MAP2) in the same cell. No significant effects were detected on vesicular glutamate transporters VGLUT1 or VGLUT2 in neurons, or on glial system N glutamine transporter 1 (SN1). In neuronal cell cultures (from E18 rats), Aβ(25-35) did not reduce SAT1 immunoreactivity, suggesting that the observed effect depends on the presence of astroglia. The results indicate that Aβ may impair neuronal function and transmitter synthesis, and perhaps reduce excitotoxicity, through a reduction in neuronal glutamine uptake

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

Background: Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Methods: Using cognitive testing data and data on functional limitations from Wave A (2001–2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. Results: Our algorithm had a cross-validated predictive accuracy of 88% (86–90), and an area under the curve of 0.97 (0.97–0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3–4) in individuals 70–79, 11% (9–12) in individuals 80–89 years old, and 28% (22–35) in those 90 and older. Conclusions: Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys

Global mortality from dementia: Application of a newmethod and results from the global burden of disease study 2019

INTRODUCTION: Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. METHODS: We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. RESULTS: We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41–4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27–2.71]) than men (0.56 million [0.14–1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10–1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1–117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. DISCUSSION: Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally