Pester Power as a Diasporic Dilemma:A Study on the Expatriate Indians in Bahrain

With the changes in the notion of family structure, movement from joint-family to nuclear family, children started acquiring unique stake in family decision making. It ranges from purchasing a semi-durable cloth to automobile, which have long durability. Sometimes their pattern of intervention is transformed into nagging, which is technically called pester power. This study explores the influencing role of children in consumer buying decisions focusing on the expatriate Indians in Bahrain

Photodegradation of Selected PCBs in the Presence of Nano-TiO2 as Catalyst and H2O2 as an Oxidant

Photodegradation of five strategically selected PCBs was carried out in acetonitrile/water 80:20. Quantum chemical calculations reveal that PCBs without any chlorine on ortho-positions are closer to be planar, while PCBs with at least one chlorine atoms at the ortho-positions causes the two benzene rings to be nearly perpendicular. Light-induced degradation of planar PCBs is much slower than the perpendicular ones. The use of nano-TiO2 speeds up the degradation of the planar PCBs, but slows down the degradation of the non-planar ones. The use of H2O2 speeds up the degradation of planar PCBs greatly (by >20 times), but has little effect on non-planar ones except 2,3,5,6-TCB. The relative photodegradation rate is: 2,2′,4,4′-TCB > 2,3,5,6-TCB > 2,6-DCB ≈ 3,3′,4,4′-TCB > 3,4′,5-TCB. The use of H2O2 in combination with sunlight irradiation could be an efficient and “green” technology for PCB remediation

Einfluss der Verarbeitungstechnologie und Werkstoffzusammensetzung auf die Struktur-Eigenschafts-Beziehungen von thermoplastischen Nanoverbundwerkstoffen

Die Einarbeitung von nanoskaligen Füllstoffen zur Steigerung von polymeren Eigenschaftsprofilen ist sehr viel versprechend und stößt daher heutzutage sowohl in der Forschung als auch in der Industrie auf großes Interesse. Bedingt durch ausgeprägte Oberflächen und hohe Anziehungskräfte, liegen Nanopartikel allerdings nicht singulär sondern als Partikelanhäufungen, so genannten Agglomeraten oder Aggregaten, vor. Zur Erzielung der gewünschten Materialverbesserungen gilt es, diese aufzuspalten und homogen in der polymeren Matrix zu verteilen. Bei thermoplastischen Kunststoffen ist die gleichläufige Doppelschneckenextrusion eines der gängigsten Verfahren zur Einarbeitung von Additiven und Füllstoffen. Aus diesem Grund war es Ziel dieser Arbeit, mittels dieses Verfahrens verbesserte Verbundwerkstoffe mit Polyamid 66- und Polyetheretherketon-Matrix, durch Einarbeitung von nanoskaligem Titandioxid (15 und 300 nm), zu generieren. In einem ersten Schritt wurden die verfahrenstechnischen Parameter, wie Drehzahl und Durchsatz, sowie die Prozessführung und damit deren Einfluss auf die Materialeigenschaften beleuchtet. Der spezifische Energieeintrag ist ausschlaggebend zur Deagglomeration der Nanopartikel. Dieser zeigte leichte Abhängigkeiten von der Drehzahl und dem Durchsatz und verursachte bei der Einarbeitung der Partikel keine wesentlichen Unterschiede in der Aufspaltung der Partikel sowie gar keine in den resultierenden mechanischen Eigenschaften. Die Prozessführung wurde unterteilt in Mehrfach- und Einfachextrusion. Die Herstellung eines hochgefüllten Masterbatches, dessen mehrfaches Extrudieren und anschließendes Verdünnen, führte zu einer sehr guten Deagglomeration und stark verbesserten Materialeigenschaften. Mittels Simulation des Extrusionsprozesses konnte festgestellt werden, dass das Vorhandensein von ungeschmolzenem Granulat in der Verfahrenszone zu einer Schmelze/Nanopartikel/ Feststoffreibung führt, die die Ursache für eine sehr gute Aufspaltung der Partikel zu sein scheint. Durch Modifikation des Extrusionsprozesses erreichte die Einfachextrusion annähernd den Grad an Deagglomeration bei Mehrfachextrusion, wobei die Materialien bei letzterem Verfahren die besten Eigenschaftsprofile aufwiesen. In einem zweiten Schritt wurde ein Vergleich der Einflüsse von unterschiedlichen Partikelgrößen und –gehalten auf die polymeren Matrizes vollzogen. Die 15 nm Partikel zeigten signifikant bessere mechanische Ergebnisse auf als die 300 nm Partikel, und die Wirkungsweise des 15 nm Partikels auf Polyetheretherketon war stärker als auf Polyamid 66. Es konnten Steigerungen in Steifigkeit, Festigkeit und Zähigkeit erzielt werden. Rasterelektronenmikroskopische Aufnahmen bestätigten diese Ergebnisse. Eine Berechnung der Plan-Selbstkosten von einem Kilogramm PEEK-Nanoverbundwerkstoff im Vergleich zu einem Kilogramm unverstärktem PEEK verdeutlichte, dass ein Material kreiert wurde, welches deutlich verbesserte Eigenschaften bei gleichem Preis aufweist. Zusammenfassend konnte in dieser Arbeit ein tieferes Verständnis des Extrusionsvorganges zur Herstellung von kostengünstigen und verbesserten Thermoplasten durch das Einbringen von Nanopartikeln gewonnen werden

Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants

The rapid spread of SARS-CoV-2 required immediate actions to control the transmission of the virus and minimize its impact on humanity. An extensive mutation rate of this viral genome contributes to the virus’ ability to quickly adapt to environmental changes, impacts transmissibility and antigenicity, and may facilitate immune escape. Therefore, it is of great interest for researchers working in vaccine development and drug design to consider the impact of mutations on virus-drug interactions. Here, we propose a multitarget drug discovery pipeline for identifying potential drug candidates which can efficiently inhibit the Receptor Binding Domain (RBD) of spike glycoproteins from different variants of SARS-CoV-2. Eight homology models of RBDs for selected variants were created and validated using reference crystal structures. We then investigated interactions between host receptor ACE2 and RBDs from nine variants of SARS-CoV-2. It led us to conclude that efficient multi-variant targeting drugs should be capable of blocking residues Q(R)493 and N487 in RBDs. Using methods of molecular docking, molecular mechanics, and molecular dynamics, we identified three lead compounds (hesperidin, narirutin, and neohesperidin) suitable for multitarget SARS-CoV-2 inhibition. These compounds are flavanone glycosides found in citrus fruits – an active ingredient of Traditional Chinese Medicines. The developed pipeline can be further used to (1) model mutants for which crystal structures are not yet available and (2) scan a more extensive library of compounds against other mutated viral proteins

Investigation of cannabidiol’s potential targets in limbic seizures. <i>In-silico</i> approach

Even though the vast armamentarium of FDA-approved antiepileptic drugs is currently available, over one-third of patients do not respond to medication, which arises a need for alternative medicine. In clinical and preclinical studies, various investigations have shown the advantage of specific plant-based cannabidiol (CBD) products in treating certain groups of people with limbic epilepsy who have failed to respond to conventional therapies. This work aims to investigate possible mechanisms by which CBD possesses its anticonvulsant properties. Molecular targets for CBD’s treatment of limbic epilepsy, including hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), gamma-aminobutyric acid aminotransferase (GABA-AT), and gamma-aminobutyric acid type A receptor (GABAA), were used to evaluate its binding affinity. Interactions with the CB1 receptor were initially modeled as a benchmark, which further proved the efficiency of proposed here approach. Considering the successful benchmark, we further used the same concept for in silico investigation, targeting proteins of interest. As a result of molecular docking, molecular mechanics, and molecular dynamics simulations models of CBD-receptor complexes were proposed and evaluated. While CBD possessed decently high affinity and stability within the binding pockets of GABA-AT and some binding sites of GABAA, the most effective binding was observed in the CBD complex with HCN1 receptor. 100 ns molecular dynamics simulation revealed that CBD binds the open pore of HCN1 receptor, forming a similar pattern of interactions as potent Lamotrigine. Therefore, we can propose that HCN1 can serve as a most potent target for cannabinoid antiepileptic treatment. Communicated by Ramaswamy H. Sarma</p

Ultra Bright Near‐Infrared Sulfonate‐Indolizine Cyanine‐ and Squaraine‐Albumin Chaperones: Record Quantum Yields and Applications

The design of bright, high quantum yield (QY) materials in the near-infrared (NIR) spectral region in water remains a significant challenge. A series of cyanine and squaraine dyes varying water solubilizing groups and heterocycles are studied to probe the interactions of these groups with albumin in water. Unprecedented, \u27ultra bright\u27 emission in water is observed for a sulfonate indolizine squaraine dye (61.1% QY) and a sulfonate indolizine cyanine dye (46.7% QY) at NIR wavelengths of \u3e700 nm and \u3e800 nm, respectively. The dyes presented herein have a lower limit of detection than the most sensitive dyes known in the NIR region for albumin detection by at least an order of magnitude, which enables more sensitive diagnostic testing. Additionally, biotinylated human serum albumin complexed with the dyes reported herein was observed to function as an immunohistochemical reagent enabling high resolution imaging of cellular α-tubulin at low dye concentrations

A Remote Longitudinal Observational Study of Individuals at Genetic Risk for Parkinson Disease: Baseline Results.

Background and objectivesTo recruit and characterize a national cohort of individuals who have a genetic variant (LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials.MethodsIn partnership with 23andMe, Inc., a personal genetics company, LRRK2 G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study. We examined concordance between self-reported and clinician-determined PD diagnosis. We applied the Movement Disorder Society Prodromal Parkinson's Disease Criteria and asked investigators to identify concern for parkinsonism to distinguish participants with probable prodromal PD. We compared baseline characteristics of LRRK2 G2019S carriers with PD, with prodromal PD, and without PD.ResultsOver 15 months, we enrolled 277 LRRK2 G2019S carriers from 34 states. At baseline, 60 had self-reported PD (mean [SD] age 67.8 years [8.4], 98% White, 52% female, 80% Ashkenazi Jewish, and 67% with a family history of PD), and 217 did not (mean [SD] age 53.7 years [15.1], 95% White, 59% female, 73% Ashkenazi Jewish, and 57% with a family history of PD). Agreement between self-reported and clinician-determined PD status was excellent (κ = 0.94, 95% confidence interval 0.89-0.99). Twenty-four participants had prodromal PD; 9 met criteria for probable prodromal PD and investigators identified concern for parkinsonism in 20 cases. Compared with those without prodromal PD, participants with prodromal PD were older (63.9 years [9.0] vs 51.9 years [15.1], p &lt; 0.001), had higher modified Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor scores (5.7 [4.3] vs 0.8 [2.1], p &lt; 0.001), and had higher Scale for Outcomes in PD for Autonomic Symptoms scores (11.5 [6.2] vs 6.9 [5.7], p = 0.002). Two-thirds of participants enrolled were new to research, 97% were satisfied with the overall study, and 94% of those without PD would participate in future preventive clinical trials.DiscussionAn entirely remote national cohort of LRRK2 G2019S carriers was recruited from a single site. This study will prospectively characterize a large LRRK2 G2019S cohort, refine a new model of clinical research, and engage new research participants willing to participate in future therapeutic trials

Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease

Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. clinicaltrials.gov Identifier: NCT00833690