Development, evaluation and optimization of baclofen oral floating tablet

The present investigation concerns the development of a floating matrix tablet, which after oral administration prolong the gastric residence time and increases bioavailability of drugs, which are predominantly absorbed from gastric region .With this aim, floating dosage form containing baclofen as drug, and different grades of HPMC as release retarding polymer was prepared. Sodium bicarbonate and citric acid were used as gas generating agents. Some factors were investigated concerning the effect of release retarding polymer on drug release behaviors like t50% and t90%. A 32 factorial design was applied to optimize the drug release profile. The amounts of HPMC K4M(X1) and HPMC K100M (X2) were selected as independent variables. The time required for 50% (t50%) and 90% (t90%) drug dissolution were selected as dependent variables. The results of full factorial design indicates that moderate amount of both the release retardant polymer, controlled the release behavior. It can be concluded from release kinetic models that the release followed Higuchi model, as the correlation coefficient (R2 value) was high in all the evaluated models. The release mechanism followed non-fickian diffusion as the release exponent (n-value) was >0.5 in all the optimized formulations.Colegio de Farmacéuticos de la Provincia de Buenos Aire

SN 2018gj: A Short-plateau Type II Supernova with Persistent Blue-shifted H-alpha Emission

We present an extensive, panchromatic photometric (UV, Optical, and NIR) and low-resolution optical spectroscopic coverage of a Type IIP supernova SN 2018gj that occurred on the outskirts of the host galaxy NGC 6217. From the V-band light curve, we estimate the plateau length to be ~ 70 +- 2 d, placing it among the very few well-sampled short plateau supernovae (SNe). With V-band peak absolute magnitude Mv < -17.0 +- 0.1 mag, it falls in the middle of the luminosity distribution of the Type II SNe. The colour evolution is typical to other Type II SNe except for an early elbow-like feature in the evolution of V-R colour owing to its early transition from the plateau to the nebular phase. Using the expanding photospheric method, we present an independent estimate of the distance to SN 2018gj. We report the spectral evolution to be typical of a Type II SNe. However, we see a persistent blue shift in emission lines until the late nebular phase, not ordinarily observed in Type II SNe. The amount of radioactive nickel (56Ni) yield in the explosion was estimated to be 0.026 +- 0.007 Msol. We infer from semi-analytical modelling, nebular spectrum, and 1-D hydrodynamical modelling that the probable progenitor was a red supergiant with a zero-age-main-sequence mass < 13 Msol. In the simulated hydrodynamical model light curves, reproducing the early optical bolometric light curve required an additional radiation source, which could be the interaction with the proximal circumstellar matter (CSM).Comment: Accepted for publication in ApJ (31 pages, 23 figures and 7 tables

Machine learning-derived baseline visual field patterns predict future glaucoma onset in the Ocular Hypertension Treatment Study

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. RESULTS: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (\u3e95th percentile or \u3c75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. CONCLUSIONS: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting

Syntax-guided synthesis

The classical formulation of the program-synthesis problem is to find a program that meets a correctness specification given as a logical formula. Recent work on program synthesis and program optimization illustrates many potential benefits of allowing the user to supplement the logical specification with a syntactic template that constrains the space of allowed implementations. Our goal is to identify the core computational problem common to these proposals in a logical framework. The input to the syntax-guided synthesis problem (SyGuS) consists of a background theory, a semantic correctness specification for the desired program given by a logical formula, and a syntactic set of candidate implementations given by a grammar. The computational problem then is to find an implementation from the set of candidate expressions so that it satisfies the specification in the given theory. We describe three different instantiations of the counter-example-guided-inductive-synthesis (CEGIS) strategy for solving the synthesis problem, report on prototype implementations, and present experimental results on an initial set of benchmarks.National Science Foundation (U.S.) (Expeditions in Computing Project ExCAPE Award CCF 1138996

Al and Autonomous Systems: An Experiment in Industry 5.0 Transformation

Important practical consequences are shown in this experimental study of AI and autonomous systems integration in the context of Industry 5.0. AI optimization of the product manufacturing process resulted in a 35% decrease in the real faulty rate and a significant 20% rise in production rates, reaching an actual rate of 1440 units per hour. The actual defective rate was just 1.3%. Since autonomous robots were introduced, work completion rates have increased by 18%, totaling 2,520 tasks completed, and maintenance expenses have decreased by 9%, amounting to a $450 real cost savings. Furthermore, with an actual faulty rate of 2.6%, the AI-driven quality control method showed an astounding 35% decrease in defective goods. Ultimately, significant 15% energy consumption decrease was accomplished using AI-based energy optimization solutions, translating into real energy savings of 1,500 kWh. These results highlight the real advantages of combining AI and Autonomous Systems in Industry 5.0, such as increased productivity, lower costs, better product quality, and sustainability

Microbial beta glucosidase enzymes: recent advances in biomass conversation for biofuels application

The biomass to biofuels production process is green, sustainable, and an advanced technique to resolve the current environmental issues generated from fossil fuels. The production of biofuels from biomass is an enzyme mediated process, wherein β-glucosidase (BGL) enzymes play a key role in biomass hydrolysis by producing monomeric sugars from cellulose-based oligosaccharides. However, the production and availability of these enzymes realize their major role to increase the overall production cost of biomass to biofuels production technology. Therefore, the present review is focused on evaluating the production and efficiency of β-glucosidase enzymes in the bioconversion of cellulosic biomass for biofuel production at an industrial scale, providing its mechanism and classification. The application of BGL enzymes in the biomass conversion process has been discussed along with the recent developments and existing issues. Moreover, the production and development of microbial BGL enzymes have been explained in detail, along with the recent advancements made in the field. Finally, current hurdles and future suggestions have been provided for the future developments. This review is likely to set a benchmark in the area of cost effective BGL enzyme production, specifically in the biorefinery area

Far-Ultraviolet to Near-Infrared Observations of SN 2023ixf: A high energy explosion engulfed in complex circumstellar material

We present early-phase panchromatic photometric and spectroscopic coverage spanning far-ultraviolet (FUV) to the near-infrared (NIR) regime of the nearest hydrogen-rich core-collapse supernova in the last 25 years, SN~2023ixf. We observe early `flash' features in the optical spectra due to a confined dense circumstellar material (CSM). We observe high-ionization absorption lines Fe II, Mg II in the ultraviolet spectra from very early on. We also observe a multi-peaked emission profile of H-alpha in the spectrum beginning ~16 d, which indicates ongoing interaction of the SN ejecta with a pre-existing shell-shaped CSM having an inner radius of ~ 75 AU and an outer radius of ~140 AU. The shell-shaped CSM is likely a result of enhanced mass loss ~ 35 - 65 years before the explosion assuming a standard Red-Supergiant wind. Spectral modeling of the FUV, NUV, and the optical spectra during 9-12 d, using the radiative transfer spectrum synthesis code TARDIS indicates that the supernova ejecta could be well represented by a progenitor elemental composition greater than solar abundances. Based on early light curve models of Type II SNe, we infer that the nearby dense CSM confined to ~7+-3e14~cm(~45 AU) is a result of enhanced mass loss ~1e-(3.0+-0.5) Msol/yr two decades before the explosion.Comment: Submitted to AAS Journals, 4 figures, 2 table

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV