Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe_(49.7)Cr_(17.7)Mn_(1.9)Mo_(7.4)W_(1.6)B_(15.2)C_(3.8)Si_(2.4). The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

A Stability Indicating HPLC Assay Method for Analysis of Rivastigmine Hydrogen Tartrate in Dual-Ligand Nanoparticle Formulation Matrices and Cell Transport Medium

The objective of this study was to develop and validate a method for quantitative analysis of rivastigmine hydrogen tartrate (RHT) in dual-ligand polymeric nanoparticle formulation matrices, drug release medium, and cellular transport medium. An isocratic HPLC analysis method using a reverse phase C 18 column and a simple mobile phase without buffer was developed, optimised, and fully validated. Analyses were carried out at a flow rate of 1.5 mL/min at 50°C and monitored at 214 nm. This HPLC method exhibited good linearity, accuracy, and selectivity. The recovery (accuracy) of RHT from all matrices was greater than 99.2%. The RHT peak detected in the samples of a forced degradation study, drug loading study, release study, and cellular transport study was pure and free of matrix interference. The limit of detection (LOD) and limit of quantification (LOQ) of the assay were 60 ng/mL and 201 ng/mL, respectively. The method was rugged with good intra- and interday precision. This stability indicating HPLC method was selective, accurate, and precise for analysing RHT loading and its stability in nanoparticle formulation, RHT release, and cell transport medium

Pseudorapidity Window Size Dependence of Multiplicity Fluctuations in High-Energy Collisions with System Size and Beam Energies

An investigation of the critical behavior of strongly interacting QCD matter has been performed by analyzing fluctuation observables on event-by-event (ebe) basis measured in high-energy collision experiments. The fluctuation analysis is performed using nuclear interactions at different target sizes and at different colliding beam energies as a function of varying width of pseudorapidity interval. For the sake of comparison, event-by-event multiplicity fluctuations in hadronic and heavy-ion collisions (p-H, p-A and A-B) are studied within the framework of the Lund Monte Carlo based FRITIOF model. Charged particle multiplicity and the variance of the multiplicity distribution are estimated for the interactions involving different target sizes and beam momenta i.e., p-H, p-CNO, p-AgBr at 200A GeV/c and $^{16}$O-AgBr collisions at 14.6, 60 and 200A GeV/c. Further, multiplicity fluctuations are quantified in terms of intensive quantity, the scaled variances $\omega$ and the strongly intensive quantity $\Sigma_{FB}$ derived from the charged particle multiplicity and the width of the multiplicity distribution. Strongly intensive quantity $\Sigma_{FB}$ is a quantity of great significance to extract information about short and long-range multiplicity correlations. Furthermore, the collision centrality and centrality bin width dependent behavior of the multiplicity fluctuation have been examined in the framework of Lund Monte Carlo based FRITIOF model. Results based on the fluctuation analysis carried out in the present study are interpreted in terms of dynamics of collision process and the possibility of related QCD phase transition.Comment: 33 pages, 14 figures, published in Int. J. Mod. Phy. E Vol. 31, 2250056 (2022

Challenges in cyto-diagnosis: a report of 2 interesting cases of pseudomyxoma peritonei

Diffuse intra-abdominal gelatinous or mucinous ascites is commonly known as pseudomyxoma peritonei (PMP). It is a clinical entity rather than a histological diagnosis and usually results from peritoneal dissemination of mucus producing neoplasms most frequently from the appendix and rarely other GIT tumours. Since ascites may be the first symptom, cytologists may face diagnostic challenges in mucinous ascites. We present two cases of mucinous ascites in elderly females, in which thick, sticky, gelatinous fluid was received for cytological examination. After correlation of cytological examination findings with clinical and radiological features, diagnosis of disseminated peritoneal adenomucinosis was made which was later confirmed by fluid cell block with IHC studies

Role of visual inspection of cervix with acetic acid and high risk human papilloma virus DNA testing in screening for cervical cancer

Background: To evaluate the role of VIA alone and in combination with high risk Human Papilloma virus DNA testing as a screening test for cervical dysplasia and cancer.Methods: 400 symptomatic patients from the gynecology outpatient department were screened using Pap smear and VIA. HPV DNA testing was done for 62 VIA positive and 100 VIA negative women. Colposcopy was done for all women. Those found positive on any or all of the screening tests were subjected to cervical biopsy. The results were analysed for PAP, VIA, HPV and a combined test using VIA and HPV both.Results: VIA had the highest sensitivity (91%) to detect any grade of dysplasia. The sensitivity of the combination test (VIA + HPV) was 80.6% which was lower than that of VIA (91%) and also lower than that of HR HPV DNA detection (86%). The specificity of the combination test (VIA + HPV) was 68.3 % which was significantly higher than that of VIA alone (39%) (p = 0.000) and also higher than that for HPV DNA detection when used alone (56%). Pap smear had the highest specificity (95.12 %) but sensitivity was much lower at 52.7 %.Conclusions: VIA is a highly sensitive screening test. The main disadvantage is its low specificity. However the combination test of VIA + HR HPV testing overcomes this and at the same time maintains a high sensitivity. Thus a test which combines VIA plus HR HPV testing is better screening method than either of the three tests (VIA, HPV, PAP) done alone

Failure rates and factors associated with infrazygomatic crestal orthodontic implants:A prospective study

Objective: Infrazygomatic crestal (IZC) implants have gained increased popularity over the past few years. Hardly any studies have been done to assess the rate and reasons for failure of IZCs. This prospective study was planned and designed with the primary objective of assessing the rate of failure of bone-screws (BS) placed in the infrazygomatic crest. In continuation, the secondary objective was to assess the factors that were associated with the failure. Materials and methods: The study was carried out by taking a detailed case history, (age, gender, vertical skeletal pattern, medical history), photographic records, radiographs, and clinical examination of a total of 32 randomly selected. patients of south indian origin who required infrazygomatic implants bilaterally as the choice of anchorage conservation to retract their incisors. All selected subjects were required to take a PA Cephalogram after the implant placement. The age of the patients ranged from 18 to 33 with an average age of 25 years. The patient log was maintained which included the treatment mechanics, status of oral hygiene, stability of implants, time of loading of the implant, presence of inflammation and time of failure of implant. The angulation of implant was measured on a digital PA cephalogram using Nemoceph software. These parameters were examined to evaluate independent and dependent variables using the Chi-Square test and Fischer's exact test. Result: A failure rate 28.1% for IZC placed in the infrazygomatic crest region was observed. Patients with a high mandibular plane angle, poor oral hygiene, immediately loaded implant, peri-implantitis, and severe clinical mobility showed higher failure rates. Variables such as age, gender, sagittal skeletal pattern, length of the implant, type of movement, occluso-gingival position, method of force application, and angle of placement were not significantly associated with implant failure. Conclusion: Oral hygiene and peri-screw inflammation must be controlled to minimize the failure of bone screws placed in the infrazygomatic crest region. Loading of the implant should be done after a latent period of two weeks. A higher failure rate was observed in patients with vertical growth pattern

Role of the Arabidopsis PIN6 auxin transporter in auxin homeostasis and auxin-mediated development

Plant-specific PIN-formed (PIN) efflux transporters for the plant hormone auxin are required for tissue-specific directional auxin transport and cellular auxin homeostasis. The Arabidopsis PIN protein family has been shown to play important roles in developmental processes such as embryogenesis, organogenesis, vascular tissue differentiation, root meristem patterning and tropic growth. Here we analyzed roles of the less characterised Arabidopsis PIN6 auxin transporter. PIN6 is auxin-inducible and is expressed during multiple auxin–regulated developmental processes. Loss of pin6 function interfered with primary root growth and lateral root development. Misexpression of PIN6 affected auxin transport and interfered with auxin homeostasis in other growth processes such as shoot apical dominance, lateral root primordia development, adventitious root formation, root hair outgrowth and root waving. These changes in auxin-regulated growth correlated with a reduction in total auxin transport as well as with an altered activity of DR5-GUS auxin response reporter. Overall, the data indicate that PIN6 regulates auxin homeostasis during plant development.Christopher I. Cazzonelli, Marleen Vanstraelen, Sibu Simon, Kuide Yin, Ashley Carron-Arthur, Nazia Nisar, Gauri Tarle, Abby J. Cuttriss¤, Iain R. Searle, Eva Benkova, Ulrike Mathesius, Josette Masle, Jiří Friml, Barry J. Pogso

Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: A genome-wide association study

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: We did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p-8 when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p-12). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest from this analysis. PKN2 inhibitors are currently in development and signify a potential novel therapeutic approach for IPF. FUNDING: Action for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, and National Institutes of Health National Heart, Lung, and Blood Institute. Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.https://doi.org/10.1016/s2213-2600(22)00251-

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

The prevalence of heteroresistant Acinetobacter baumannii is increasing. Infections due to these resistant pathogens pose a global treatment challenge. Here, the pharmacodynamic activities of polymyxin B (PMB) (2–20 mg/L) and tigecycline (0.15–4 mg/L) were evaluated as monotherapy and in combination using a 4 × 4 concentration array against two carbapenem-resistant and polymyxin-heteroresistant A. baumannii isolates. Time Kill Experiments was employed at starting inocula of 106 and 108 CFU/mL over 48 h. Clinically relevant combinations of PMB (2 mg/L) and tigecycline (0.90 mg/L) resulted in greater reductions in the bacterial population compared with polymyxin alone by 8 h (ATCC 19606, −6.38 vs. −3.43 log10 CFU/mL; FADDI AB115, −1.38 vs. 2.08 log10 CFU/mL). At 10× the clinically achievable concentration (PMB 20 mg/L in combination with tigecycline 0.90 mg/L), there was bactericidal activity against FADDI AB115 by 4 h that was sustained until 32 h, and against ATCC 19606 that was sustained for 48 h. These studies show that aggressive polymyxin-based dosing in combination with clinically achievable tigecycline concentrations results in early synergistic activity that is not sustained beyond 8 h, whereas combinations with higher tigecycline concentrations result in sustained bactericidal activity against both isolates at both inocula. These results indicate a need for optimised front-loaded polymyxin-based combination regimens that utilise high polymyxin doses at the onset of treatment to achieve good pharmacodynamic activity whilst minimising adverse events