UV-Vis and FTIR spectroscopy of gamma irradiated polymethyl methacrylate

The effect of gamma irradiation on the UV-Vis and FTIR spectroscopy of polymethyl methacrylate (PMMA) foils has been studied. A new absorption band has been observed in the visible spectral range due to color centers induced in the gamma irradiated PMMA. This band shows maximum absorption (low transmission) for 10 kGy irradiation, which decreases and saturates after 50 kGy followed by a further increase at 500 kGy. The FTIR peaks show an increased absorption up to ~100 kGy irradiation, which reverses for higher doses. Broad band absorption has been observed in FTIR spectra around 1600 and 3600 cm-1 due to absorption of moisture in the irradiated samples. The reduction in the absorption intensity at 1718 cm-1 in the irradiated PMMA (> 100 kGy) has been found associated with the dimerization of the carbonyl groups. An initial increase in the absorption of FTIR peaks with increase in the doses of irradiation is due to increased cross linking in the PMMA structure that is induced by the absorption of moisture. The dimerization of carbonyl groups becomes dominant at higher doses of irradiation (~500 kGy)

Synthesis of (S)-(–)di-O-methyl-M5032

1172-117

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Molecular modeling for the design of novel performance chemicals and materials

xvi, 382 p. : ill. (chiefly col.) ; 27 cm

Molecular modeling for the design of novel performance chemicals and materials

Molecular modeling (MM) tools offer significant benefits in the design of industrial chemical plants and material processing operations. While the role of MM in biological fields is well established, in most cases MM works as an accessory in novel products/materials development rather than a tool for direct innovation. As a result, MM engineers and practitioners are often seized with the question: ""How do I leverage these tools to develop novel materials or chemicals in my industry?"" Molecular Modeling for the Design of Novel Performance Chemicals and Materials answers this important questi

A molecular modeling approach towards engineering of polymer nanogels for controlled drug delivery

Traditionally, a drug is administered initially at a higher dosage so as to repeat the next dose after several hours or days. This, besides being un-economical, results in side effects. Recently, there has been an increased attention on the methods of continuous administration of drugs in a controlled fashion. One of the promising methods of accomplishing this is to incorporate a drug in the polymer matrix. Cross-linked polymeric gels like hydrogels are currently being evaluated as carriers in controlled delivery system: The cross-linking density is an important parameter to engineer a given hydrogel. Experimental estimation of cross-linking density is expensive and time consuming. Several theoretical models have also been developed to model the diffusion of molecules in hydrogels. However, application of these theoretical relations is limited. MoltecW&f dynamics (MD) simulations offer a paradigm to explore various phenomena occurring at pico/nanosecond time scales. MD simulations also possess an inherent advantage over continuum modeling in addressing nano-scale interactions between drug and polymer networks which are crucial for designing customized gels. In this paper we report on the effect of cross-linking ratio on diffusivity of drug molecules in polymeric hydrogels as studied through MD simulations

In Silico Design of Peptides with Binding to the Receptor Binding Domain (RBD) of the SARS-CoV-2 and Their Utility in Bio-Sensor Development for SARS-CoV-2 Detection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people across the globe and created not only a health emergency but also a financial crisis. This virus attacks on the angiotensin-converting enzyme 2 (ACE2) receptor situated on the surface of the host cell membrane. The spike protein of the virus binds to this receptor which is a critical step of infection. A molecule which can specifically stop this binding could be a potential therapeutic. In this study, we have tested 12 potential peptides which can bind to the receptor binding domain (RBD) of the spike protein of the virus and thus can potentially inhibit the binding of the latter on ACE2 receptor. These peptides are screened based on their binding with RBD of the spike protein and aqueous stability, obtained using several atomistic molecular dynamic simulations. The potential of mean force calculation of two most promising peptides confirmed their binding to the RBD of the spike protein. Furthermore, these two potential peptides were tested for their use in a biosensing application for SARS-CoV-2 detection. Two types of biosensing platforms, a graphene sheet and a carbon nano tube (CNT), were tested. The peptides were modified in order to functionalize the graphene and CNT. Based on the interaction between the substrate, peptide and spike protein, the utility of screened peptide for a given bio sensing platform is discussed and recommended. </p