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Focused ultrasound (FUS) is a non-invasive and non-ionizing technique which deploys ultrasound waves to induce bio-effects. When paired with acoustically active particles such as microbubbles (MBs), it can open the blood brain barrier (BBB) to facilitate drug delivery otherwise inhibited due to the presence of BBB. One of the parameters that affects the FUS beam propagation is the beam incidence angle on the skull. Prior work by our group has shown that, as incidence angles deviate from 90°, FUS focal pressures attenuate and result in a smaller BBB opening volume. The incidence angles calculated in our prior studies were in 2D and used skull information from CT. The study presented herein develops methods to calculate incidence angle in 3D in non-human primate (NHP) skull fragments using harmonic ultrasound imaging without using ionizing radiation. Our results show that ultrasound harmonic imaging is capable of accurately depicting features such as sutures and eye-sockets of the skull. Furthermore, we were able to reproduce previously reported relationships between the incidence angle and FUS beam attenuation. We also show feasibility of performing ultrasound harmonic imaging in in-vivo non-human primates. The all-ultrasound method presented herein combined with our neuronavigation system stands to increase more widespread adoption of FUS and render it accessible by eliminating the need for CT cranial mapping.

The strength in nanostructured bainitic steels primarily arises from the fine platelets of bainitic ferrite embedded in carbon-enriched austenite. However, the toughness is dictated by the shape and volume fraction of the retained austenite. Therefore, the exact determination of processing–morphology relationships is necessary to design stronger and tougher bainite. In the current study, the morphology of bainitic ferrite in Fe-0.89C-1.59Si-1.65Mn-0.37Mo-1Co-0.56Al-0.19Cr (wt pct) bainitic steel has been investigated as a function of the prior austenite grain size (AGS). Specimens were austenitized at different temperatures ranging from 900 °C to 1150 °C followed by isothermal transformation at 300 °C. Detailed microstructural characterization has been carried out using scanning electron microscopy and X-ray diffraction. The results showed that the bainitic laths transformed in coarse austenite grains are finer resulting in higher hardness, whereas smaller austenite grains lead to the formation of thicker bainitic laths with a large fraction of blocky type retained austenite resulting in lower hardness.

Background Acinetobacter baumannii has emerged as a predominant cause of hospital-acquired infections worldwide, posing a significant challenge due to its extraordinary ability to acquire resistance to multiple antibiotics. According to recent data, infections caused by multidrug-resistant A. baumannii lead to increased morbidity, longer hospital stays, and higher healthcare costs. Carbapenems and tigecycline have historically provided reliable treatment for A. baumannii infections; however, recent global trends indicate a significant increase in carbapenem and tigecycline resistance among circulating isolates. Objectives The study aimed to determine the prevalence and genetic characterization of tigecycline resistance in A. baumannii (TRAB) among carbapenem-resistant isolates and to assess the transferability of carbapenem and tetracycline resistance genes between isolates. Methods All 160 clinical isolates were obtained from admitted patients in SGPGIMS, Lucknow (India). Identification of the isolates was performed using MALDI-TOF MS, followed by antimicrobial susceptibility testing (AST), determination of minimum inhibitory concentrations (MICs), and PCR-based detection of carbapenem and tetracycline resistance genes. The transferability of resistance genes was further assessed through conjugation assays, and the AST of transconjugant isolates was evaluated accordingly. Results A total of 32 out of 160 isolates (20%) were resistant to both carbapenem and tigecycline. All these isolates were multidrug-resistant (MDR), exhibiting resistance to more than three classes of antibiotics. Genetic screening showed the blaNDM and blaOXA-48 carbapenemase genes in 25% and 18.75% of the respective isolates; blaKPC was not detected. Among tetracycline resistance genes, only tet(B) was present in 15.63% (5/32) of the isolates; other genes such as tet(A) , tet(K) , tet(M) , and tet(S) were absent. Both carbapenemase and tetracycline resistance genes were plasmid-mediated, and often co-existed in the same isolates. However, only the carbapenemase genes were transferable by conjugation; the tetracycline resistance genes were not transferable. Conclusions The increasing prevalence of carbapenem and tigecycline-resistant A. baumannii is primarily linked to plasmid-mediated carbapenemase genes, which facilitate their spread. In contrast, tigecycline resistance, although present, appears to be non-transferable under the conditions studied.

In the present work, we have developed a polymer based gas sensor. The polymer nanocomposites are synthesized by the chemical oxidative polymerization of aniline with ammonium persulfate and sulfuric acid. The fabricated sensor is able to achieve a sensing response of 4.56% for PANI/MMT-rGO at 2 ppm of hydrogen cyanide (HCN) gas. The sensitivity of the sensors PANI/MMT and PANI/MMT-rGO are 0.89 ppm −1 and 1.1174 ppm −1 respectively. The increase in the sensitivity of the sensor may be due to an increase in the surface area provided by MMT and rGO which provided more binding sites for the HCN gas. The sensing response of the sensor increases as the concentration of the gas exposed increases but saturates after 10 ppm. The sensor recovers automatically. The sensor is stable and can work for 8 months.

The blood–brain barrier (BBB) prevents harmful toxins from entering brain but can also inhibit therapeutic molecules designed to treat neurodegenerative diseases. Focused ultrasound (FUS) combined with microbubbles can enhance permeability of BBB and is often performed under MRI guidance. We present an all-ultrasound system capable of targeting desired regions to open BBB with millimeter-scale accuracy in two dimensions based on Doppler images. We registered imaging coordinates to FUS coordinates with target registration error of 0.6 ± 0.3 mm and used the system to target microbubbles flowing in cellulose tube in two in vitro scenarios (agarose-embedded and through a rat skull), while receiving echoes on imaging transducer. We created passive acoustic maps from received echoes and found error between intended location in imaging plane and location of pixel with maximum intensity after passive acoustic maps reconstruction to be within 2 mm in 5/6 cases. We validated ultrasound-guided procedure in three in vivo rat brains by delivering MRI contrast agent to cortical regions of rat brains after BBB opening. Landmark-based registration of vascular maps created with MRI and Doppler ultrasound revealed BBB opening inside the intended focus with targeting accuracy within 1.5 mm. Combined use of power Doppler imaging with passive acoustic mapping demonstrates an ultrasound-based solution to guide focused ultrasound with high precision in rodents.

Background Amaryllidaceae alkaloids (AAs) are a large group of plant-specialized metabolites displaying an array of biological and pharmacological properties. Previous investigations on AA biosynthesis have revealed that all AAs share a common precursor, norbelladine, presumably synthesized by an enzyme catalyzing a Mannich reaction involving the condensation of tyramine and 3,4-dihydroxybenzaldehyde. Similar reactions have been reported. Specifically, norcoclaurine synthase (NCS) which catalyzes the condensation of dopamine and 4-hydroxyphenylacetaldehyde as the first step in benzylisoquinoline alkaloid biosynthesis. Results With the availability of wild daffodil ( Narcissus pseudonarcissus ) database, a transcriptome-mining search was performed for NCS orthologs. A candidate gene sequence was identified and named norbelladine synthase ( NBS ). NpNBS encodes for a small protein of 19 kDa with an anticipated pI of 5.5. Phylogenetic analysis showed that Np NBS belongs to a unique clade of PR10/Bet v1 proteins and shared 41% amino acid identity to opium poppy NCS1. Expression of NpNBS cDNA in Escherichia coli produced a recombinant enzyme able to condense tyramine and 3,4-DHBA into norbelladine as determined by high-resolution tandem mass spectrometry. Conclusions Here, we describe a novel enzyme catalyzing the first committed step of AA biosynthesis, which will facilitate the establishment of metabolic engineering and synthetic biology platforms for the production of AAs.

A continuous and dependable energy supply is essential for maintaining a nation’s economic stability. Globally, coal ranks as the second largest fossil fuel resource after oil and gas, leading to the establishment of coal-fired power infrastructure. Nonetheless, the pyrolysis and “burn-out” reactions of High-ash coal impose fundamental limitations that hinder its efficient use and exacerbate environmental degradation. Coal pyrolysis processes is significantly influenced by numerous experimental factors, including the, chemical concentration, operating temperature, process time. A significant weight loss was seen for periods of up to 30 min at 510 °C; yet, the change in responsiveness reduced after this time. It was found that as an increasing the concentration of SnCl 2 causes a remarkable burn-out increase, up to 9%, whilst at lower concentrations a consistent temperature and pyrolysis time shows a considerable decrease. At 610 and 710 °C, 9% SnCl 2 -impregnated coal. In present investigation Artificial Neural Networks and Response Surface Methodology employed to envisage the percentage of burn-out of High-ash coal. The sensitivity analyses indicated that the pyrolysis temperature stands out as the most significant input parameter, with pyrolysis time and catalyst concentration following closely behind. The ANN and RSM techniques were employed to forecast the burn-out percentage of High-ash coal. The ANN (R 2  = 0.9965) indicates superior predictability compared to RSM.

Meiosis produces haploid cells essential for sexual reproduction. In yeast, entry into meiosis activates transcription factors which trigger a transcriptional cascade that results in sequential co-expression of early, middle and late meiotic genes. However, these factors are not conserved, and the factors and regulatory mechanisms that ensure proper meiotic gene expression in multicellular eukaryotes are poorly understood. Here, we report that DUET/MMD1, a PHD finger protein essential for Arabidopsis male meiosis, functions as a transcriptional regulator in plant meiosis. We find that DUET-PHD binds H3K4me2 in vitro, and show that this interaction is critical for function during meiosis. We also show that DUET is required for proper microtubule organization during meiosis II, independently of its function in meiosis I. Remarkably, DUET protein shows stage-specific expression, confined to diplotene. We identify two genes TDM1 and JAS with critical functions in cell cycle transitions and spindle organization in male meiosis, as DUET targets, with TDM1 being a direct target. Thus, DUET is required to regulate microtubule organization and cell cycle transitions during male meiosis, and functions as a direct transcription activator of the meiotic gene TDM1. Expression profiling showed reduced expression of a subset comprising about 12% of a known set of meiosis preferred genes in the duet mutant. Our results reveal the action of DUET as a transcriptional regulator during male meiosis in plants, and suggest that transcription of meiotic genes is under stagewise control in plants as in yeast.

We propose a novel method to monitor bladder wall mechanical properties as a function of filling volume, with the potential application to bladder compliance assessment. The proposed ultrasound bladder vibrometry (UBV) method uses ultrasound to excite and track Lamb waves on the bladder wall from which its mechanical properties are derived by fitting measurements to an analytical model. Of particular interest is the shear modulus of bladder wall at different volumes, which we hypothesize, is similar to measuring the compliance characteristics of the bladder. Three experimental models were used: 1) an ex vivo porcine model where normal and aberrant (stiffened by formalin) bladders underwent evaluation by UBV; 2) an in vivo study to evaluate the performance of UBV on patients with clinically documented compliant and noncompliant bladders undergoing UDS; and 3) a noninvasive UBV protocol to assess bladder compliance using oral hydration and fractionated voiding on three healthy volunteers. The ex vivo studies showed a high correlation between the UBV parameters and direct pressure measurement (R2 = 0.84-0.99). A similar correlation was observed for 2 patients with compliant and noncompliant bladders (R2 = 0.89-0.99) undergoing UDS detrusor pressure-volume measurements. The results of UBV on healthy volunteers, performed without catheterization, were comparable to a compliant bladder patient. The utility of UBV as a method to monitor changes in bladder wall mechanical properties is validated by the high correlation with pressure measurements in ex vivo and in vivo patient studies. High correlation UBV and UDS in vivo studies demonstrated the potential of UBV as a bladder compliance assessment tool. Results of studies on healthy volunteers with normal bladders demonstrated that UBV could be performed noninvasively. Further studies on a larger cohort are needed to fully validate the use of UBV as a clinical tool for bladder compliance assessment.

Background: The shift of focus toward pandemic control had an impact on public health issues that need to be addressed. As the impact may vary in the different areas based on COVID-19 cases and strictness of measures to control the disease, studying the local situation and related factors is essential to strengthening the TB program. Objectives: The objective is to compare the TB care before and during the COVID-19 pandemic and to explore the challenges faced by stakeholders during the pandemic. Materials and Methods: A mixed method study was conducted in Puducherry with a quantitative phase involving data extraction from the National TB Elimination Programme (NTEP), followed by in-depth interviews to explore the challenges faced by stakeholders. Results: In 2020, there were 67% and 23% reductions in number of presumptive TB case and notified TB cases, respectively, while the decline was lesser in the year 2021 (reduction of 59% and 13%, respectively). The main challenges faced in providing and accessing TB care were social stigma, lockdown restrictions, fear of getting COVID-19, redeployment of staff to COVID-19-related activities and increased COVID-19 workload. Conclusions: There is a need to strengthen active case finding for the missed TB cases through the mobile vans equipped with diagnostics, combined testing for COVID-19 and TB, greater inclusion of private sector and dispensaries as well as community awareness for stigma prevention.