Variable Size Research Articles

Weakly supervised detection of pheochromocytomas and paragangliomas in CT using noisy data

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors that have metastatic potential. Management of patients with PPGLs mainly depends on the makeup of their genetic cluster: SDHx, VHL/EPAS1, kinase, and sporadic. CT is the preferred modality for precise localization of PPGLs, such that their metastatic progression can be assessed. However, the variable size, morphology, and appearance of these tumors in different anatomical regions can pose challenges for radiologists. Since radiologists must routinely track changes across patient visits, manual annotation of PPGLs is quite time-consuming and cumbersome to do across all axial slices in a CT volume. As such, PPGLs are only weakly annotated on axial slices by radiologists in the form of RECIST measurements. To ameliorate the manual effort spent by radiologists, we propose a method for the automated detection of PPGLs in CT via a proxy segmentation task. Weak 3D annotations (derived from 2D bounding boxes) were used to train both 2D and 3D nnUNet models to detect PPGLs via segmentation. We evaluated our approaches on an in-house dataset comprised of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. On a test set of 53 CT volumes, our 3D nnUNet model achieved a detection precision of 70% and sensitivity of 64.1%, and outperformed the 2D model that obtained a precision of 52.7% and sensitivity of 27.5% (p< 0.05). SDHx and sporadic genetic clusters achieved the highest precisions of 73.1% and 72.7% respectively. Our state-of-the art findings highlight the promising nature of the challenging task of automated PPGL detection.

Effect of sintering temperature, additive ratios, and reinforcement of boron and boron carbide particle sizes on the mechanical and tribological properties of the synthesized Cu-Cr hybrid composites

In this study, hybrid composites were generated by combining Copper (Cu) powder with Chromium (Cr) powder at a fixed weight of 1 %, as well as Boron (B) and Boron carbide (B4C) powders at specific weight ratios (1 %, 2 %, 3 %, and 4 %), with variable particle sizes (1 µm and 44 µm). Powder metallurgy production parameters were employed to produce two sets of samples at sintering temperatures of 750 °C and 850 °C. Analysis of the microstructure of the samples was performed, as well as hardness and abrasion tests. A variety of B/B4C ratios and particle diameters were employed to characterize Cu-based hybrid composites using SEM-EDS and XRD. Weight loss graphs and coefficient of friction values were generated for each sample subsequent to wear tests. The results of the tests indicated a 76.25 % increase in hardness values with B reinforcement and a 60.71 % increase with B4C reinforcement in comparison to a pure Cu sample. As the sintering temperature increased and the size of the reinforcement particles decreased, the hardness of the material increased, resulting in identical results in the wear testing. A tribo-layer was observed to have formed between the wear pin and the samples in the new hybrid composites with Boron matrix in the SEM images taken after wear. The wear resistance properties of Cu matrix hybrid composites were found to be enhanced by this tribolayer.

Meningkatkan Kualitas Laba Melalui Corporate Governance

This study aims to examine the effect of independent commissioners, audit committees, and managerial ownership on earnings quality. This study uses three control variables, namely firm size, profitability, and leverage. The population in this study are manufacturing companies listed on the Indonesia Stock Exchange (IDX) in 2019-2021. Sampling using purposive sampling technique produces 182 data. The results obtained indicate that managerial ownership has a significant positive effect on earnings quality. Ownership of shares owned by directors is considered capable of providing oversight of performance between agents and management. In contrast, independent commissioners and audit committees have no effect on earnings quality. This is because the supervision carried out by independent commissioners and audit committees is considered less than optimal. For the variable firm size, profitability, and leverage have a significant positive effect on earnings quality.

The components of an electrical synapse as revealed by expansion microscopy of a single synaptic contact.

Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as 'chemical' and 'electrical' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a 'gap junction' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact's surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.

A novel A-stable method of order of accuracy three, based on optimization for solving initial value problems

This paper presents a novel A-stable nonlinear method of order of accuracy three, based on optimization for solving the first-order initial value problems. The A-stability is proven and the consistency of order three is investigated as well. The convergence of the method is established under certain assumptions. Additionally, a second-order method is derived based on this approach, and a variable step size formulation is implemented using the second and third-order methods to enhance efficiency. Numerical examples provided in the paper demonstrate the validity of the theory and underscore the advantages of the method compared to three other A-stable methods of order three, including an implicit RK method, a Rosenbrock method, and an explicit (nonstandard) method.

O-017 Swim-up versus density gradients for sperm preparation in intrauterine insemination: a multi-centre randomised clinical trial

Abstract Study question What is the effectiveness of swim-up (SU) and density gradients (DG) for sperm preparation in infertile couples undergoing intrauterine insemination (IUI)? Summary answer In couples undergoing IUI, there is no significant difference in the treatment outcomes between SU and DG. What is known already Swim-up (SU) and density gradients (DG) are the most two commonly used techniques for sperm preparation in intrauterine insemination (IUI). The latest Cochrane review concluded that there is uncertainty about the effectiveness of SU versus DG and no studies reported on live birth. Study design, size, duration This open-label, multi-centre randomised clinical trial was conducted on 912 infertile couples at a tertiary IVF center, Ho Chi Minh City, Vietnam from August 2020 to June 2023. Couples were randomly asigned to two groups, SU and DG using computerized randomisation on the day of IUI with variable block size of 2, 4 or 6. Primary outcome was live birth rate. Participants/materials, setting, methods Infertile couples were eligible if aged ≥18, indicated for IUI with ≤2 IUI prior attempts and husbands’ sperm concentration ≥5x106/ml, progressive motility (PR) ≥32% and total PR sperm count &amp;gt;5x106 before sperm preparation (WHO 2010 criteria). Couples using frozen semen, or high viscosity semen were not eligible. Women had ovulation induction using hMG. Sperm preparation was performed within one hour after ejaculation. IUI was performed once at 36 to 40 hours after hCG trigger. Main results and the role of chance Between August 2020 and June 2023, 912 couples were randomly assigned to SU (n = 456) or DG (n = 456). Baseline characteristics were comparable between the two groups (mean female age of 31.3 ± 0.4 years; total sperm count: 86.2 [52.9;137.6] million; sperm motility: 44.8 ± 8.2%). Live birth occurred in 55 (12.1%) couples in the SU group and 71 (15.7%) couples in the DG group (RR 0.77; 95% CI 0.56-1.07). Ongoing pregnancy and multiple pregnancy were also comparable between the two groups. There were no statistically significant differences between the SU and DG groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications. Pre-planned subgroup analysis showed that the live birth rate was not materially affected by the IUI indications, total motile sperm after preparation (&amp;lt;1, ≥1 and &amp;lt;5, ≥5 and &amp;lt;10 and ≥10 million). Limitations, reasons for caution The main limitation of the study was its open-label design, due to the nature of the interventions. Wider implications of the findings Our study suggests that in couples undergoing IUI with progressive motility (PR) ≥32% and total PR sperm count &amp;gt;5x106 before sperm preparation, SU or DG can both be used for sperm preparation, with a preference for density gradients. Trial registration number NCT04477356

Development of a sectionalizing method for simulation of large-scale complicated natural gas pipeline networks

By 2025, the total mileage of natural gas pipelines in China is expected to reach 163,000 km, placing urgent demands on the simulation technology for increasingly large-scale and more complicated pipeline networks. This paper describes the development of a new sectionalizing method, which is based on optimization strategy, for simulating large-scale and complicated natural gas pipeline networks. Based on analysis of the topological structures, the entire pipeline networks are decomposed into multiple sub-networks according to the connecting nodes between the adjoined pipelines. The sectionalizing method is then implemented by minimizing the residuals of conservation for continuity and momentum at the connecting nodes in isothermal mode. The hydraulic variables in each sub-network are obtained after the hydraulic variables at connecting nodes are updated. The calculation accuracy and efficiency of this sectionalizing method are demonstrated by comparison with a commercial software through three different test cases. It is shown that the maximum relative deviation of pressure of the method developed is within 2.5% of that calculated using the commercial software. In a 5 × 104 km test case with variable spatial step sizes, the computational efficiency is 2.1 to 3.2 times of that of the commercial software. The results of the three case studies suggest that this sectionalizing method is promising and suitable for application to large-scale complicate natural gas network simulation.

Enhanced thermal cycle stability and shape memory effect in NiTiHf shape memory alloys fabricated by laser powder bed fusion

We report on the fabrication of NiTiHf high temperature shape memory alloys (SMAs) via laser powder bed fusion (LPBF), which are almost free of micro-pores and display (Ti, Hf)2Ni nanoprecipitates with variable size and volume fraction. The effect of variable laser powers of 50 W, 60 W and 70 W on the martensite variant microstructures and mechanical properties of the LPBFed SMAs was investigated. Interestingly, all LPBFed NiTiHf samples display enhanced thermal cycle stability of transformation temperatures with a temperature eviation of −3°C, which is attributed to the lack of dislocation slip originated from the habit plane configuration characteristic with multidomain (001) martensite compound twins. Meanwhile, all LPBFed NiTiHf samples exhibit trained one-way and two-way shape memory effects due to the dislocation slip upon compression deformation at room temperature.

Allometry and ecology shape eye size evolution in spiders

Eye size affects many aspects of visual function, but eyes are costly to grow and maintain. The allometry of eyes can provide insight into this trade-off, but this has mainly been explored in species that have two eyes of equal size. By contrast, animals possessing larger visual systems can exhibit variable eye sizes within individuals. Spiders have up to four pairs of eyes whose sizes vary dramatically, but their ontogenetic, static, and evolutionary allometry has not yet been studied in a comparative context. We report variable dynamics in eye size across 1,098 individuals in 39 species and 8 families, indicating selective pressures and constraints driving the evolution of different eye pairs and lineages. Supplementing our sampling with a recently published phylogenetically comprehensive dataset, we confirmed these findings across more than 400 species; found that ecological factors such as visual hunting, web building, and circadian activity correlate with eye diameter; and identified significant allometric shifts across spider phylogeny using an unbiased approach, many of which coincide with visual hunting strategies. The modular nature of the spider visual system provides additional degrees of freedom and is apparent in the strong correlations between maximum/minimum investment and interocular variance and three key ecological factors. Our analyses suggest an antagonistic relationship between the anterior and posterior eye pairs. These findings shed light on the relationship between spider visual systems and their diverse ecologies and how spiders exploit their modular visual systems to balance selective pressures and optical and energetic constraints.

First report—parotid tissue choristomas within and adjacent to TMJ ligaments

PurposeTo report the first examples of ectopic salivary glands of TMJ ligaments & capsules. Methods and MaterialsNine subjects with chronic TMJ disorders were found incidentally to have ectopic salivary glands (choristomas) within or near damaged TMJ ligaments and capsules. Clinicopathologic characteristics of 12 TMJs are summarized. ResultsThe 9 subjects were ages 22-64 years (average = 43.0); 6 were female. Microscopic examination revealed major, almost complete ligament replacement by dense, avascular fibrous scar tissue in all but 1 sample. Chronic inflammatory cells were present in the stroma of 3 samples. A total of 33 lobular, independent salivary structures of variable sizes where embedded in or near ligaments and/or capsules. Half were multiple in the same joint; 13 were bilaterally located in the joints of a single subject, with 8 small glandular lobules in one TMJ. All glands consisted of histologically normal serous acini except 1 which showed a focal lobule of mucus acini and another comprised only of mucus acini. Serial sections showed no connection to parotid glands. Some choristomas showed the aging phenomena of fatty infiltrates (n = 7) and oncocytosis (n = 7). Additionally, 3 of the 12 TMJ samples contained preauricular lymph nodes, with 3 nodes in 1 joint and bilateral involvement in 1 subject. Of the 5 identified nodes, all but one was hyperplastic, with nonspecific inflammatory histiocytosis. ConclusionsWe report, for the first time, independent salivary gland choristomas (n = 33) within the soft tissues of the TMJ (n = 12), with one joint containing 8 such choristomas. All consisted of normal serous tissue except one, a mucus gland. Additionally, a fourth of TMJ surgical samples contained hyperplastic preauricular lymph nodes.

Pengaruh Volatilitas Penjualan, Ukuran Perusahaan dan Arus Kas Operasional Terhadap Persistensi Laba

Earnings persistence has a crucial role in reflecting the quality that refers to the earnings of a related company. This has a probability in the future while avoiding a number of risks related to liquidation. This study has a specific purpose in conducting tests on sales volatility, which is then related to company size as well as operating cash flow, which has an influence on earnings persistence, specifically referring to companies in the property and real estate sectors during the 2020–2022 period. The sample of this research includes 177 data points originating from 67 companies in the sector that are officially listed on the IDX. This research method involves a descriptive method involving a quantitative-based approach. The technique is to use purposive sampling. Then, data analysis is realized by multiple linear regression analysis methods utilizing software, namely SPSS for version 2018. The findings of this research explain the partial effect that leads to operational cash flow, which has a negative and significant effect on earnings persistence in companies engaged in the realm of property and real est ate. As for the sales volatility variable and company size, they do not have a significant influence on earnings persistence in the company.

Structure, Evolution, and Mitochondrial Genome Analysis of Mussel Species (Bivalvia, Mytilidae).

Based on the nucleotide sequences of the mitochondrial genome (mitogenome) of specimens taken from two mussel species (Arcuatula senhousia and Mytilus coruscus), an investigation was performed by means of the complex approaches of the genomics, molecular phylogenetics, and evolutionary genetics. The mitogenome structure of studied mussels, like in many other invertebrates, appears to be much more variable than in vertebrates and includes changing gene order, duplications, and deletions, which were most frequent for tRNA genes; the mussel species' mitogenomes also have variable sizes. The results demonstrate some of the very important properties of protein polypeptides, such as hydrophobicity and its determination by the purine and pyrimidine nucleotide ratio. This fact might indirectly indicate the necessity of purifying natural selection for the support of polypeptide functionality. However, in accordance with the widely accepted and logical concept of natural cutoff selection for organisms living in nature, which explains its action against deleterious nucleotide substitutions in the nonsynonymous codons (mutations) and its holding of the active (effective) macromolecules of the polypeptides in a population, we were unable to get unambiguous evidence in favor of this concept in the current paper. Here, the phylogeny and systematics of mussel species from one of the largest taxons of bivalve mollusks are studied, the family known as Mytilidae. The phylogeny for Mytilidae (order Mytilida), which currently has no consensus in terms of systematics, is reconstructed using a data matrix of 26-27 mitogenomes. Initially, a set of 100 sequences from GenBank were downloaded and checked for their gender: whether they were female (F) or male (M) in origin. Our analysis of the new data confirms the known drastic differences between the F/M mitogenome lines in mussels. Phylogenetic reconstructions of the F-lines were performed using the combined set of genetic markers, reconstructing only protein-coding genes (PCGs), only rRNA + tRNA genes, and all genes. Additionally, the analysis includes the usage of nucleotide sequences composed of other data matrices, such as 20-68 mitogenome sequences. The time of divergence from MRCA, estimated via BEAST2, for Mytilidae is close to 293 Mya, suggesting that they originate in the Silurian Period. From all these data, a consensus for the phylogeny of the subfamily of Mytilinae and its systematics is suggested. In particular, the long-debated argument on mussel systematics was resolved as to whether Mytilidae, and the subfamily of Mytilinae, are monophyletic. The topology signal, which was strongly resolved in this paper and in the literature, has refuted the theory regarding the monophyly of Mytilinae.

A double sampling ridge penalized likelihood ratio control charting method with variable sample size for Phase II monitoring of high-dimensional covariance matrix

Today, manufacturers face two challenges: the financial limitation of sampling and the large number of study quality characteristics. In such situations, the problem dimension is usually larger than the sample size, which is known in the literature of statistical quality control as a high dimensional process. The use of conventional multivariate charts to monitor the covariance matrix of such processes is not possible for two reasons: (1) the non-reversibility of the sample covariance matrix, (2) the possibility of the occurrence of sparse shifts in which only a few elements of the covariance matrix are affected. This paper focuses on Phase II monitoring of the covariance matrix of high-dimensional processes based on integrating the ridge penalized likelihood ratio (RPLR) statistic and the combined DS-VSS sampling method, in which DS and VSS features are used concurrently. The performance of the proposed DS-VSS RPLR control chart is compared with the RPLR one in terms of three metrics of the average run length, standard deviation of the run length, and expected value of sample size under three types of joint diagonal/off-diagonal, diagonal and off-diagonal shift patterns. The results show that the DS-VSS scheme is more sensitive than the RPLR in detecting both sparse and non- sparse changes.

Compositional differences of near-critical petroleum from closed pores to wellhead in Gulong shale oil play, Songliao Basin, NE China

The Gulong shale oil play located in northern Songliao Basin is a promising exploration target in China. Member 1 of Qingshankou Formation (Well H) with high thermal maturity was preferred to obtain pressure-retained cores, long-time exposed cores, and produced petroleum (crude oil and gas). The selected samples were subjected to sequential extraction, GC, GC-MS, thermal desorption–gas chromatography (TD-GC) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis. The compositional differences of in-situ fluids, residual bitumen trapped in open, confined, and closed pores, as well as wellstream, were systematically investigated. (1) In-situ fluid compositions, with a 30.8% proportion of nC1−5 in n-alkanes, were studied by TD-GC analysis on pressure-retained cores. Interestingly, limited amounts of C8- compounds were detected in long-time exposed bulk cores but were almost absent in exposed powder. Primally poor pore connectivity and partially adsorption or absorption of organic matter contribute to the retention of gaseous hydrocarbons. (2) Sequential extraction is a best method for obtaining compositions of fluid in pores with variable sizes. Aliphatic compounds of residual bitumen trapped in open pores are similar to those in confined pores, while polar compounds are more enriched in confined and closed pores. Originally connected pores in early oil window, has turned into confined or closed pores by compaction and cementation with increasing depth. (3) Wellstream compositions are significantly different from in-situ fluid compositions, especially in shale oil extraction. The proportion of gaseous hydrocarbons in the wellstream (76.2%) is considerably higher than that of in-situ fluids (34.1%). Comparison of aromatic hydrocarbons indicated that the wellstream is sourced from free fluids and partially adsorbed hydrocarbons in open pores. (4) Nitrogen and oxide compounds with a higher degree of condensation (higher DBE value) have poor movability, leading to extremely low content or even absence in crude oil. The compositional differences from in-situ fluids to the wellbore through the stimulated fractures are caused by selective adsorption of pore walls, confinement effect of nanopores and fluid phase changing. This study provides a window to the compositional differences of fluids released from different occurrence spaces and confirms compounds heterogeneity.

A new pair of block techniques for direct integration of third-order singular IVPs

This paper proposes a new pair of block techniques (NPBT) for the direct solution of third-order singular initial-value problems (IVPs). The proposed method uses a polynomial and two intermediate points to approximate the theoretical solution of third-order singular IVPs, resulting in a reasonable approximation within the integration interval. The method's essential features, including stability and convergence order, are analyzed. The proposed NPBT method is improved by using an embedding-like strategy that allows it to be executed in a variable step size mode in order to gain better efficiency. The effectiveness of the proposed method is assessed using various model problems. The approximate solution provided by the proposed NPBT method is more accurate than that of the existing methods utilized for comparison. This efficient solution positions NPBT as a good numerical method for integrating third-order singular IVP models in the fields of applied sciences and engineering.

"Cap polyposis", refractory to drug treatment, including infliximab.

Cap polyposis is a rare disease characterized by the presence of inflammatory polyps with an adherent fibrin sheath ("cap"), in variable number and size, in the rectum and sigmoid. It presents with tenesmus, mucous stools and rectorrhagia. There is currently no standardized treatment, having been treated empirically with aminosalicylates, oral or rectal steroids, metronidazole, H. pylori eradication therapy and infliximab with variable results. In refractory cases, endoscopic resection of polyps may be used and surgery may even be necessary. We present the case of a 36-year-old patient diagnosed in our center with cap polyposis, refractory to both pharmacological and endoscopic treatment, and therefore treatment with infliximab was decided out of indication. The case we present is the fourth case of cap polyposis treated with infliximab available in the current literature and highlights the difficulty of achieving a clinical response with pharmacological treatment, including biologic drugs such as infliximab.

Dual frequency ultrasonic liquid phase exfoliation method for the production of few layer graphene in green solvents

In this work, we implement a dual frequency (24 kHz and 1174 kHz) ultrasonic assisted liquid phase exfoliation (ULPE) technique in deionized water (DIW) and other eco-friendly solvents, to produce a variety of high-quality few-layer graphene (FLG) solutions under controlled ultrasonication conditions. The resulting FLG dispersions of variable sizes (∼0.2–1.5 μm2) confirmed by characterisation techniques comprising UV–Vis spectroscopy, Raman spectroscopy and high-resolution transmission electron microscopy (HR-TEM). For the first time we demonstrate that high yield of FLG flakes with minimal defects, stable for 6 + months in a solution (stability ∼ 70 %), can be obtained in less than 1-hour of treatment in either water/ethanol (DIW:EtOH) or water/isopropyl alcohol (DIW:IPA) eco-friendly mixtures.We also scrutinized the underlying mechanisms of cavitation using high-speed imaging synchronized with acoustic pressure measurements. The addition of ethanol or IPA to deionized water is proposed to play a central role in exfoliation as it regulates the extend of the cavitation zone, the intensity of the ultrasonic field and, thus, the cavitation effectiveness. Our study revealed that lateral sizes of the obtained FLG depend on the choice of exfoliating media and the diameter of a sonotrode used. This variability offers flexibility in producing FLG of different sizes, applicable in a wide spectrum of size-specific applications.

Mitigating uncertainty: A risk informed approach for deploying hydrogen refueling stations

Regulatory gaps and safety concerns induce uncertainty amongst stakeholders, increases investment risk and impedes the deployment of hydrogen refueling stations (HRS). In this study, a risk-informed approach was employed on a potential HRS in Canada, to optimize separation distances, and identify regulatory gaps. This risk assessment improves upon previous ones that assumed uniform hydrogen leak sizes throughout the entire HRS. This analysis considers variable leak sizes based on the varying pipe flow area in different parts of the HRS like the tube-trailer area, hydrogen system area and the dispenser area. For each area, the potential leak sizes of 0.1%, 1%, 10%, and 100% of the pipe flow area were evaluated to cover a range of possible leaks. Leak frequency for 1% and 10% leak sizes were found to be 2.38E-02/year and 2.68E-03/year indicating relatively smaller difference as compared to other leak sizes. Leak frequency and consequence distances were assessed using HyRAM+ (V5.0) and Safeti (V8.9) respectively. Separation distances, which refer to the required spacing measured from the hydrogen process areas beyond which the risks are considered tolerable, were assessed for the tube-trailer area, storage area, and dispenser area at 350 bar and 700 bar dispensing pressures. Results indicated that 700 bar scenario requires substantially larger separation distances up to 39.1 m due to extended harm distances at lower temperatures. This study proposes safety barriers which reduced jet and flash fire frequencies by 100 and 20 events/year, respectively, that enables decreasing separation distances for each area. The comprehensive evaluation of separation distances generates important insights into separation distance criteria and guidelines, addressing the identified gap in existing codes and standards. While the study focuses on a potential HRS in Canada, the methodology, approach, and results presented are broadly applicable and transferable to similar contexts globally.

The ric-8b protein (resistance to inhibitors of cholinesterase 8b) is key to preserving contractile function in the adult heart

Resistance to inhibitors of cholinesterases (ric-8 proteins) are involved in modulating G-protein function, but little is known of their potential physiological importance in the heart. In the present study, we assessed the role of resistance to inhibitors of cholinesterase 8b (Ric-8b) in determining cardiac contractile function. We developed a murine model in which it was possible to conditionally delete ric-8b in cardiac tissue in the adult animal after the addition of tamoxifen. Deletion of ric-8b led to severely reduced contractility as measured using echocardiography days after administration of tamoxifen. Histological analysis of the ventricular tissue showed highly variable myocyte size, prominent fibrosis, and an increase in cellular apoptosis. RNA sequencing revealed transcriptional remodeling in response to cardiac ric-8b deletion involving the extracellular matrix and inflammation. Phosphoproteomic analysis revealed substantial downregulation of phosphopeptides related to myosin light chain 2. At the cellular level, the deletion of ric-8b led to loss of activation of the L-type calcium channel through the β-adrenergic pathways. Using fluorescence resonance energy transfer-based assays, we showed ric-8b protein selectively interacts with the stimulatory G-protein, Gαs. We explored if deletion of Gnas (the gene encoding Gαs) in cardiac tissue using a similar approach in the mouse led to an equivalent phenotype. The conditional deletion of the Gαs gene in the ventricle led to comparable effects on contractile function and cardiac histology. We conclude that ric-8b is essential to preserve cardiac contractile function likely through an interaction with the stimulatory G-protein and downstream phosphorylation of myosin light chain2.

THE EFFECT OF BANK-SPECIFIC AND BANK RISK ON BANK STABILITY AS MEASURED BY NPL OF THE BANGLADESHI COMMERCIAL BANK

This paper analyzed the effects of bank-specific and bank-risk drivers on bank stability as measured by non-performing loans(NPL) of commercial banks in Bangladesh from 2011 to 2021.This study used panel linear regression, and panel corrected standard error (PCSEs) to estimate the model. The main objective of the study was to analysed the effects of bank specific and bank risk on bank stability of conventional banks in Bangladesh. Capital adequacy, asset quality, income diversification, bank competition, managerial efficiency, and profitability (ROE) are used as proxies for bank-specific and liquidity risk; Sensitivity to marketing risk is used as proxies for bank risk, while control variable is used as bank size and non-performing loan (NPL) are used as a proxy for measurement of bank stability. The main results show that capital adequacy and profitability (ROE) are negative, but asset quality, income diversification, bank competition, and managerial efficiency are positively related to the NPL. The results further evaluate those determinants of bank risk, liquidity risk, and marketing risk have a positive impact on the NPL. The control variable bank size has a negative impact on the NPL. Based on our results, authorities in Bangladesh may develop rules for managing operations and ensuring bank stability as measured by NPLs.