Search

Glycyrrhizin (GL), the well-known sweet saponin of licorice, has been used as a food-additive and as a medicine. Its aglycone, glycyrrhetic acid (GA) showed antiinflamatory, antiulcer and antiviral properties. GA is now produced form GL by acid hydrolysis. However, it is difficult to obtain GA in a good yield by using this method, because many by-productsare also produced. Screening of different microorganisms (13 bacteria, 2 yeasts and 23 fungi) for production of GA from GL revealed that Aspergillus niger NRRL 595 produced the highest yield of GA. The bioconversion of GL by A. niger NRRL 595 for 96 h, followed by isolation and purification of the transformation products led to the separation of two conversion products, namely: GA and 3-oxo-GA. Confirmation of the identity of these products was established by determination of their Rf values, m.p., and IR, UV, MS and NMR spectra. The conditions for cultivation of this fungus with the maximum hydrolytic activity for the maximum yield of GA were investigated. Based on the results, A. niger NRRL 595 was cultivated with a medium composed of 1.75 % GL, 0.5 % glucose, 0.8 % corn steep liquor at pH 6.5 at 32 °C for 96 h. The cultivation of fungal cells under the latter conditions afforded GA and 3-oxo-GA in a yield of 65 % and 22 %, respectively.

Among seven fungi (three Aspergilli and four Penicilli) have been screened for production of glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) from glycyrrhizin (GL), Aspergillus terreus was found to be the most potent GAMG producer. This strain was capable of expressing two intracellular β-D-glucuronidase forms, one responsible for partial hydrolysis of GL to GAMG and the other one for hydrolysis of GL to glycyrrhetic acid (GA). The highest yield of GAMG was achieved when the reaction mixture was incubated at pH 6 at 40 °C for 1 h using GL (0.1%, w/v) as a substrate. The maximum hydrolytic activity for production of GAMG (396 U/mL) was obtained using production medium composed of (g%, w/v): corn steep liquor 2.5, soybean flour 3.5, glucose 0.5 and CaCO3 0.5; pH 6.0. The medium was inoculated with 15% (v/v) inoculum and incubated at 27 °C for 3 days. Under these optimal conditions, GAMG yield became about 2 times higher than GA yield and the cells bioconversion efficiency increased from 24.6 to 78.3%.

While other works use segments of nonlinear crystal to compensate for walk-off, this work utilizes a quantum dot (QD) nanostructure for such compensation. Such nanocrystal structures allow two benefits: the high nonlinear susceptibility in these nanocrystals and the high surface density of QDs in the structure. Good results are obtained for pre-chirping and modulation parameters. The results are computed at 10 and 100 kV/cm applied electric fields. Compared to ordinary nonlinear crystals, the pulse width, intensity, and efficiency of the second harmonic (SH) pulse are all higher in QD nanocrystals, even with a low electric field applied. Higher applied fields give higher results.

Background Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a subset of cancers and have been shown to confer sensitivity to immune checkpoint inhibition (ICI); however, there is a lack of prospective data in urothelial carcinoma (UC).Methods and analysis We performed a systematic review to estimate the prevalence of dMMR and MSI-H in UC, including survival and clinical outcomes. We searched for studies published up to 26 October 2022 in major scientific databases. We screened 1745 studies and included 110. Meta-analyses were performed if the extracted data were suitable.Results The pooled weighted prevalences of dMMR in bladder cancer (BC) and upper tract UC (UTUC) were 2.30% (95% CI 1.12% to 4.65%) and 8.95% (95% CI 6.81% to 11.67%), respectively. The pooled weighted prevalences of MSI-H in BC and UTUC were 2.11% (95% CI 0.82% to 5.31%) and 8.36% (95% CI 5.50% to 12.53%), respectively. Comparing localised versus metastatic disease, the pooled weighted prevalences for MSI-H in BC were 5.26% (95% CI 0.86% to 26.12%) and 0.86% (95% CI 0.59% to 1.25%), respectively; and in UTUC, they were 18.04% (95% CI 13.36% to 23.91%) and 4.96% (95% CI 2.72% to 8.86%), respectively. Cumulatively, the response rate in dMMR/MSI-H metastatic UC treated with an ICI was 22/34 (64.7%) compared with 1/9 (11.1%) with chemotherapy.Conclusion Both dMMR and MSI-H occur more frequently in UTUC than in BC. In UC, MSI-H occurs more frequently in localised disease than in metastatic disease. These biomarkers may predict sensitivity to ICI in metastatic UC and resistance to cisplatin-based chemotherapy.

The main purpose of this work is studying the linear Susceptibility in the hybrid nanostructure that composed of a dual quantum dot (DQD) and metal nanoparticle (MNP) hybrid system under a standing-wave field. In our model, we used density matrix equations by taking into our account the interaction between excitons and surface plasmons. The proposed DQD is composed of two QDs. Each QD contains an InAs QD with a disk shape. The interaction between the QD and the wetting layer (WL) is taken into consideration. The application of the standing wave field on DQD-MNP hybrid system was modeled and examined. The susceptibility of thehybridDQD-MNPsystem reduced by the pump field under a standing-wave field. The high susceptibility obtained with a wide MNP radius. An interesting result was shown in the inversion of the grating period with the tunneling component in the conduction band. The smaller size of DQD gave us high susceptibility due to the quantization effect.

Summary: Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

The use of steel beams with variable sections along their length is getting more attention in recent years. These variable sections can vary gradually along the beam or change abruptly as a drop or a step. The current study investigates the lateral torsional buckling (LTB) of stepped steel beams with flanged I section subjected to uniformly distributed pressure on the top flange. The studied parameters are the step height, the step length, and the boundary conditions of the beam. The finite element method is used to carry out a linear buckling analysis of the beams’ models. The results show significant degradation in beams LTB strength due to the jump of the beam's section. Reducing the simply supported beam depth by 25 % reduces LTB strength by about 40–50 %, while reducing the fixed beam depth by 25 % reduces LTB strength by about 30–40 %. Further reduction in depth showed no significant additional reduction in simply supported beams strength, while the fixed beams showed another 30–40 % reduction in strength with another 25 % reduction in beam total depth. The step made the compressive stress transfer between the two flange parts through the web.

Background Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce.Methods In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT).Results Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58–74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7–3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4–3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS.Conclusions Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

Multi-objective design optimization problems offer a set of solution alternatives within a Pareto-front. In structural design, the design variables are typically the section properties. The outcomes of these design variables are usually used in selecting standard sections. However, the properties of the selected standard sections normally have different values from the determined design variables. Accordingly, the values of the objective functions for these solutions will change after selecting standard sections. This change may be different among these solutions. Thus far, only Pareto-optimal solutions have been standardized in the literature. The effects of the inclusion of non-Pareto solutions in the standardization process have never been examined. In this paper, the differences between including the near-optimal solutions and not including them in the final structural design optimization set are explored. The paper investigates the impact of selecting standard sections on both Pareto-front solutions and near-optimal solutions, and it studies the importance of keeping track of the near-optimal solutions. A modified version of a multiple-objective particle swarm optimization method, enhanced with a proposed computationally efficient section standardization algorithm, is used to solve multi-objective system-reliability design optimization problems. The concepts of the paper are applied to examples of bridge structures. The results demonstrate the efficiency of the proposed technique in capturing final design solutions that would have been otherwise missed due to standardization.

The energy consumption levels of buildings in the United Arab Emirates (UAE) are among the highest in the world. One of the main reasons for this energy consumption is the need to cool buildings due to the hot climate of the UAE. As a large part of the heat accumulated inside buildings comes from windows, in this study, the effects of window size and direction in a typical building in the UAE on energy consumption and thermal performance are investigated through numerical modeling. The modeling process includes thermal conductivity, thermal convection, and solar radiation simulation. The energy performance of any building at any location can be obtained based on local weather data and the computational thermal characteristics of the building elements, such as its walls, roofs, windows, and doors. The study covered all different seasons of the year and different orientations for the windows, allowing the daily and yearly energy consumption associated with the windows to be obtained. Furthermore, the energy consumption was obtained for solar radiation and heat gain separately for both single- and double-glazed windows. It was found that north-facing windows consume significantly less annual energy (36% less), when compared with windows facing in the other three directions. Furthermore, the east- and west-facing windows consumed about 41% and 35% more daily cooling energy in August, when compared to north- and south-facing windows, respectively. The use of a window with a height equal to that of the wall can cause a clear greenhouse effect; hence, it is recommended to limit the window’s height to two-thirds of the wall height, which can save about one-third of the associated yearly cooling energy. This study should be considered as a general guideline, as the thermal performance of any specific building will be affected by its own thermal characteristics.

Abstract Gain spectra of CdxZn1−xTe/AlGaN undoped and doped quantum dot (QD) structures are studied under the inhomogeneous broadening assumption at four Cd mole fractions (x=0.25,0.5,0.75,0.95). For the Cd0.25Zn0.75Te QD structure, two peaks appear due to the excited state (ES) and ground state (GS) transitions. The gain for the doped structures doubles the undoped ones. The gain increases while the wavelength is reduced with increasing Cd content due to the broader band discontinuity between the QD states. The discontinuity of the bands for each structure (mole fraction) is calculated, which is one of the merits of this work. While the structure Cd0.25Zn0.75Te offers the peak wavelengths 470 and 630 nm, other mole fractions offer the wavelengths between them. These visible bands are essential in different applications. The effect of QD size effect is also examined. The wavelength is extended by 20 nm for each 1 nm QD height increment.