Density Of Granules Research Articles

Integrating granular computing with density estimation for anomaly detection in high-dimensional heterogeneous data

Detecting anomalies in complex data is crucial for knowledge discovery and data mining across a wide range of applications. While density-based methods are effective for handling varying data densities and diverse distributions, they often struggle with accurately estimating densities in heterogeneous, uncertain data and capturing interdependencies among features in high-dimensional spaces. This paper proposes a fuzzy granule density-based anomaly detection algorithm (GDAD) for heterogeneous data. Specifically, GDAD first partitions high-dimensional attributes into subspaces based on their interdependencies and employs fuzzy information granules to represent data. The core of the method is the definition of fuzzy granule density, which leverages local neighborhood information alongside global density patterns and effectively characterizes anomalies in data. Each object is then assigned a fuzzy granule density-based anomaly factor, reflecting its likelihood of being anomalous. Through extensive experimentation on various real-world datasets, GDAD has demonstrated superior performance, matching or surpassing existing state-of-the-art methods. GDAD's integration of granular computing with density estimation provides a practical framework for anomaly detection in high-dimensional heterogeneous data.

FEATURES OF STRUCTURAL REORGANISATION OF THE HYPOTHALAMIC SUPRAOPTIC NUCLEUS IN RATS DURING THE EARLY STAGES OF DIABETES DEVELOPMENT

The objective of the study – to ascertain the structural organisation of the hypothalamicsupraoptic nucleus in rats with streptozotocin- induced diabetes.Materials and Methods. Mature rats, modelled with streptozotocin- induced diabetes,were used in the experiment. On the 14th day of the experimental diabetes developmentin rats, quantitative cyto-myeloarchitecture parameters, histological and ultrastructuralchanges in the anterior hypothalamic supraoptic nucleus were determined.Results. After 14 days of the experiment modelling, the histological structure of thehypothalamic supraoptic nucleus remains practically unchanged and identical to the intactanimals. However, occasional occurrences of central chromatolysis were observed in thelight neurons of the supraoptic nucleus. The perikarya of the dark neurons were denselyfilled with Nissl substance. The ultrastructural feature of the dark neurosecretory cellsis the presence of highly developed granular endoplasmic reticulum in their peripheralzone, which was represented by flat elongated cisterns. These cisterns had a large numberof ribosomes on their surface. Additionally, free ribosomes and polysomes were present inthe hyaloplasm between the cisterns. A similar pattern has been observed in light neurons.Furthermore, an increase in the volumetric density of neurosecretory granules comparedto intact indicators of up to 2.36 ± 0.12 % (p ≤ 0.01) has been detected. In the neuropil of the hypothalamus, most of the axons were filled with neurosecretory granules (NG)of moderate electron density. Alongside axons that were expanded and filled withneurosecretory granules, axons of neurosecretory cells with usual structure containingmitochondria, synaptic vesicles, neurotubules, and neurofilaments have been observed.Conclusions. 1. The hypothalamic supraoptic nucleus contained light and darkneurosecretory cells with a well-developed protein synthesis apparatus. 2. Ultrastructuralchanges of the neuro-glio-capillary complexes in the investigated hypothalamic nuclei weredetected on the 14th day of the experimental streptozotocin- induced diabetes, indicatingthe activation of neurosecretion synthesis and the transport to the neurohypophysis. Anincrease in the volumetric density of neurosecretory granules compared to intact animalswas found to be 2.36±0.12 % (p≤0.01).

Spatial-temporal patterns of ecological-environmental attributes within different geological-topographical zones: a case from Hailun District, Heilongjiang Province, China

The climate change and extension of human activities are shedding more stresses on ecosystems. Ecological zoning could help manage the ecosystem and deal with environmental problems more effectively. Geology and topography could affect the ecology primarily and are vital perspectives on ecological zoning. It is worth preliminarily understanding the spatial-temporal patterns of ecological-environmental attributes within various geological-topographical ecological zones (GTEZs). The objective of this study was to delineate GTEZs and present a spatial-temporal analysis on soil and land surface parameters within GTEZs. Firstly, Landsat imageries, high resolution satellite imagery products, digital elevation model, regional geological map, black soil thickness, soil bulk density, meteorological data, and ground survey were collected and conducted. Secondly, GTEZs in Hailun District were delineated according to geological and topographical background. Thirdly, soil composition, and monthly land surface temperature (LST), enhanced vegetation index (EVI), net primary productivity (NPP) were derived from ground survey and Landsat imageries. Finally, spatial-temporal patterns of various ecological-environmental attributes within different GTEZs were preliminarily revealed and analyzed. Results show that sand alluvial plain zone and silt-clay undulating plain zone mainly possess thick soil with fine-medium granule and higher bulk density, and are mainly covered by crops and grass, vegetation flourish the most in August with the highest monthly EVI and NPP. While the sand-conglomerate hill zone, sandstone hill zone, and granite hill zone possess relatively thin soil with medium-coarse granule and lower bulk density, and are mainly covered by forest, vegetation flourish the most in June and July, and has the highest yearly total NPP. With thinner soil thickness and higher NPP, hill zones tend to have more vulnerability to disturbance and more contribution to carbon neutrality target.

The Effects and Mechanism of ATM Kinase Inhibitors in Toxoplasma gondii.

Toxoplasma gondii, an important opportunistic pathogen, underscores the necessity of developing novel therapeutic drugs and identifying new drug targets. Our findings indicate that the half-maximal inhibitory concentrations (IC50) of KU60019 and CP466722 (abbreviated as KU and CP) against T. gondii are 0.522 μM and 0.702 μM, respectively, with selection indices (SI) of 68 and 10. Treatment with KU and CP affects the in vitro growth of T. gondii, inducing aberrant division in the daughter parasites. Transmission electron microscopy reveals that KU and CP prompt the anomalous division of T. gondii, accompanied by cellular enlargement, nuclear shrinkage, and an increased dense granule density, suggesting potential damage to parasite vesicle transport. Subsequent investigations unveil their ability to modulate the expression of certain secreted proteins and FAS II (type II fatty acid synthesis) in T. gondii, as well as including the dot-like aggregation of the autophagy-related protein ATG8 (autophagy-related protein 8), thereby expediting programmed death. Leveraging DARTS (drug affinity responsive target stability) in conjunction with 4D-Label-free quantitative proteomics technology, we identified seven target proteins binding to KU, implicated in pivotal biological processes such as the fatty acid metabolism, mitochondrial ATP transmission, microtubule formation, and Golgi proteins transport in T. gondii. Molecular docking predicts their good binding affinity. Furthermore, KU has a slight protective effect on mice infected with T. gondii. Elucidating the function of those target proteins and their mechanism of action with ATM kinase inhibitors may potentially enhance the treatment paradigm for toxoplasmosis.

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats.

The cerebellum has a long, protracted developmental period that spans from the embryonic to postnatal periods; as a result, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is crucial for foetal and early postnatal brain development; however, its effects on cerebellar growth and development are unknown. The aim of this study was to examine the effects of maternal folate intake on the histomorphology and cell density of the developing cerebellum. Twelve adult female rats (rattus norvegicus) were randomly assigned to one of four premixed diet groups: standard (2mg/kg), folate-deficient (0mg/kg), folate-supplemented (8mg/kg) or folate supra-supplemented (40 mg/kg). The rats started their diets 14 days before mating and consumed them throughout pregnancy and lactation. On postnatal days 1, 7, 21 and 35, five pups from each group were sacrificed, and their brains were processed for light microscopic analysis. Histomorphology and cell density of the external granule, molecular, Purkinje and internal granule layers were obtained. The folate-deficient diet group had smaller, dysmorphic cells and significantly lower densities of external granule, molecular, Purkinje and internal granule cells. Although the folate-enriched groups had greater cell densities than the controls, the folate-supplemented group had considerably higher cell densities than the supra-supplemented group. The folate supra-supplemented group had ectopic Purkinje cells in the internal granule cell layer. These findings imply that a folate-deficient diet impairs cellular growth and reduces cell density in the cerebellar cortex. On the other hand, folate supplementation increases cell densities, but there appears to be an optimal dose of supplementation since excessive folate levels may be detrimental.

Influence of Infrared Dry Heat Treatment on the Structure and Properties of Potato Starch

AbstractThe current study presents a novel approach to starch modification using infrared dry heat treatment (IR‐DHT). IR‐heating at 200 °C allows one to reduce the processing time to 15 min and does not lead to irreversible amorphization of starch structure. Upon IR‐DHT, an increase in density of starch granules from 1.4888 ± 0.0005 to 1.5038 ± 0.0005 g cm−3 is observed. The crystallinity degree of the starch exposed in water at 20 °C after IR‐DHT does not change compared to the crystallinity of native starch hydrated at the same temperature. However, the exposure in excess of water of native potato starch at 45 °C induces an increase of crystallinity up to 81% (along with a significant increase in the intensity of the d100 reflection), while heat‐treated starch exposed in water at the same temperature has reduced crystallinity (RC = 39%). In addition, the concentration of soluble carbohydrates released during the exposure process (45 °C, excess of water) increases by an order of magnitude for heat‐treated starch compared to the native sample. Hence, IR‐DHT may become a promising way to influence the processes of acid and enzymatic hydrolysis and control starch properties, such as pasting, solubility, and digestibility.

Comparative Evaluation of Formulations Designed using Chemically Modified Pectin and Eudragit for Sustained Release of Nateglinide

The present work was proposed to chemically modified Pectin with its hydrophilicity reduced and potential for being an universal excipient. The Bulk densities of NTGT granules were found to be 0.3473 which indicate good packing capacity. Carr’s index of NTGT granules were found to be 5.88 which indicate excellent flow properties. Hausner ratio of NTGT granules were found to be 1.0621. Angle of repose of NTGT granules were excellent flow properties. The formulations MP1P2 after optimization to limit the release in the first 3 hrs could also be equally effective. Comparative evaluation of the designed formulations, the release of nateglinide from tablets coated with eudragit RL100 was progressively prolonged, as concentration of eudragit in the coating solution was increased about 63.91% at 12hr of NTGEUD3 batch. The formulated batches gives a clear indication that once daily formulations of nateglinide as oral hypoglycemics drug can be designed using this approach and subsequent release at a consistently uniform rate for sustained action has been achieved.

Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene.

We recently reported that phogrin, also known as IA-2β or PTPRN2, forms a complex with the insulin receptor in pancreatic β cells upon glucose stimulation and stabilizes insulin receptor substrate 2. In β cells of systemic phogrin gene knockout (IA-2β-/-) mice, impaired glucose-induced insulin secretion, decreased insulin granule density, and an increase in the number and size of lysosomes have been reported. Since phogrin is expressed not only in β cells but also in various neuroendocrine cells, the precise impact of phogrin expressed in β cells on these cells remains unclear. In this study, we performed a comprehensive analysis of morphological changes in RIP-Cre+/-Phogrinflox/flox (βKO) mice with β cell-specific phogrin gene knockout. Compared to control RIP-Cre+/- Phogrin+/+ (Ctrl) mice, aged βKO mice exhibited a decreased density of insulin granules, which can be categorized into three subtypes. While no differences were observed in the density and size of lysosomes and crinosomes, organelles involved in insulin granule reduction, significant alterations in the regions of lysosomes responding positively to carbohydrate labeling were evident in young βKO mice. These alterations differed from those in Ctrl mice and continued to change with age. These electron microscopic findings suggest that phogrin expression in pancreatic β cells plays a role in insulin granule homeostasis and crinophagy during aging, potentially through insulin autocrine signaling and other mechanisms.

Cytodifferentiation of pituitary tumors influences pathogenesis and cavernous sinus invasion.

Pituitary tumors (PTs) continue to present unique challenges given their proximity to the cavernous sinus, whereby invasive behavior can limit the extent of resection and surgical outcome, especially in functional tumors. The aim of this study was to elucidate patterns of cavernoinvasive behavior by PT subtype. A total of 169 consecutive first-time surgeries for PTs were analyzed; 45% of the tumors were functional. There were 64 pituitary transcription factor-1 (PIT-1)-expressing, 62 steroidogenic factor-1 (SF-1)-expressing, 38 T-box transcription factor (TPIT)-expressing, and 5 nonstaining PTs. The gold standard for cavernous sinus invasion (CSI) was based on histopathological examination of the cavernous sinus medial wall and intraoperative exploration. Cavernous sinus disease was present in 33% of patients. Of the Knosp grade 3 and 4 tumors, 12 (19%) expressed PIT-1, 7 (11%) expressed SF-1, 8 (21%) expressed TPIT, and 2 (40%), were nonstaining (p = 0.36). PIT-1 tumors had a significantly higher predilection for CSI: 53% versus 24% and 18% for TPIT and SF-1 tumors, respectively (OR 6.08, 95% CI 2.86-13.55; p < 0.001). Microscopic CSI-defined as Knosp grade 0-2 tumors with confirmed invasion-was present in 44% of PIT-1 tumors compared with 7% and 13% of TPIT and SF-1 tumors, respectively (OR 11.72, 95% CI 4.35-35.50; p < 0.001). Using the transcavernous approach to excise cavernous sinus disease, surgical biochemical remission rates for patients with acromegaly, prolactinoma, and Cushing disease were 88%, 87%, and 100%, respectively. The granule density of PIT-1 tumors and corticotroph functional status did not influence CSI. The likelihood of CSI differed by transcription factor expression; PIT-1-expressing tumors had a higher predilection for invading the cavernous sinus, particularly microscopically, compared with the other tumor subtypes. This elucidates a unique cavernoinvasive behavior absent in cells from other lineages. Innovative surgical techniques, however, can mitigate tumor behavior and achieve robust, reproducible biochemical remission and gross-total resection rates. These findings can have considerable implications on the surgical management and study of PT biology and behavior.

Optimization of freeze granulation and sintering behavior of MgO granules for thermal interface materials

Heat management of high-performance secondary batteries, used in various applications that require high charging and discharging rates, such as electric vehicles and electronic devices, has recently been attracting increased attention. One of the most popular heat management technologies involves the use of thermal interface materials (TIMs) for heat dissipation. TIMs are composites of thermally conductive granulated fillers uniformly dispersed in a polymer matrix. In this study, the freeze granulation process is optimized to prepare MgO granules with high thermal conductivity as an alternative to commercial alumina fillers for TIMs. The heat dissipation characteristics of TIMs are directly related to their thermal properties, size distribution, shape, density, and filler content. Therefore, a suspension is optimized with high solid content and low viscosity for proper spraying. The size distribution and sintered granule density are analyzed for various spraying distances and pressures to optimize the process for producing high-quality TIMs. Finally, a TIM with MgO granules formed by freeze granulation dispersed in silicone-based resin is fabricated, with a high thermal conductivity exceeding 5.425 W/m∙K (with an interfacial thermal resistance of 0.343 K∙ cm2/W) and low density of 2.78 g/cm3.

Identification of Climate-Smart Bread Wheat Germplasm Lines with Enhanced Adaptation to Global Warming.

Bread wheat (Triticum aestivum L.) is widely grown in sub-tropical and tropical areas and, as such, it is exposed to heatstress especially during the grain filling period (GFP). Global warming has further affected its production and productivity in these heat-stressed environments. We examined the effects of heatstress on 18 morpho-physiological and yield-related traits in 96 bread wheat accessions. Heat stress decreased crop growth and GFP, and consequently reduced morphological and yield-related traits in the delayed sown crop. A low heat susceptibility index and high yield stability were used for selecting tolerant accessions. Under heatstress, the days to 50% anthesis, flag-leaf area, chlorophyll content, normalized difference vegetation index (NDVI), thousand grain weight (TGW), harvest index and grain yield were significantly reduced both in tolerant and susceptible accessions. The reduction was severe in susceptible accessions (48.2% grain yield reduction in IC277741). The plant height, peduncle length and spike length showeda significant reduction in susceptible accessions, but a non-significant reduction in the tolerant accessions under the heatstress. The physiological traits like the canopy temperature depression (CTD), plant waxiness and leaf rolling were increased in tolerant accessions under heatstress. Scanning electron microscopy of matured wheat grains revealed ultrastructural changes in endosperm and aleurone cells due to heat stress. The reduction in size and density of large starch granules is the major cause of the yield and TGW decrease in the heat-stress-susceptible accessions. The most stable and high-yielding accessions, namely, IC566223, IC128454, IC335792, EC576707, IC535176, IC529207, IC446713 and IC416019 were identified as the climate-smart germplasm lines. We selected germplasm lines possessing desirable traits as potential parents for the development of bi-parent and multi-parent mapping populations.

Down-regulation of peptidylarginine deiminase type 1 in reconstructed human epidermis disturbs nucleophagy in the granular layer and affects barrier function

Deimination is a post-translational modification catalyzed by a family of enzymes named peptidylarginine deiminases (PADs). PADs transform arginine residues of protein substrates into citrulline. Deimination has been associated with numerous physiological and pathological processes. In human skin, three PADs are expressed (PAD1-3). While PAD3 is important for hair shape formation, the role of PAD1 is less clear. To decipher the main role(s) of PAD1 in epidermal differentiation, its expression was down-regulated using lentivirus-mediated shRNA interference in primary keratinocytes and in three-dimensional reconstructed human epidermis (RHE). Compared to normal RHEs, down-regulation of PAD1 caused a drastic reduction in deiminated proteins. Whereas proliferation of keratinocytes was not affected, their differentiation was disturbed at molecular, cellular and functional levels. The number of corneocyte layers was significantly reduced, expression of filaggrin and cornified cell envelope components, such as loricrin and transglutaminases, was down-regulated, epidermal permeability increased and trans-epidermal-electric resistance diminished drastically. Keratohyalin granule density decreased and nucleophagy in the granular layer was disturbed. These results demonstrate that PAD1 is the main regulator of protein deimination in RHE. Its deficiency alters epidermal homeostasis, affecting the differentiation of keratinocytes, especially the cornification process, a special kind of programmed cell death.

Attribute transmission and effects of diluents and granulation liquids on granule properties and tablet quality for high shear wet granulation and tableting process

This study aims to examine (i) the effect of diluent types (lactose monohydrate, corn starch, and microcrystalline cellulose) and granulation liquids (20% polyvinylpyrrolidone K30, 65% alcohol, and dispersion containing 40% model drug– Pithecellobium clypearia Benth extracted powder) on granule properties and tablet quality for high shear wet granulation and tableting (HSWG-T) and, more importantly, (ii) the attribute transmission in the process. In general, the impact of diluents on granule properties and tablet quality was more dominant than that of granulation liquids. Attribute transmission patterns were revealed as follows. The granules’ ISO. Roundness and density correlated with raw material (i.e., model drug, diluent, and/or granulation liquid) properties such as density and viscosity. The granules’ compressibility parameter a correlated with the granules’ Span, and parameter y0 correlated with the granules’ flowability and friability. Compactibility parameters ka and kb correlated mainly with granules' flowability and density, and parameter b correlated significantly and positively with tablet tensile strength. The compressibility correlated negatively with tablet solid fraction (SF) and friability, while the compactibility correlated positively with tablet disintegration time. Moreover, the rearrangement and elasticity of granules correlated positively with SF and friability, respectively. Overall, this study provides some guides for achieving high-quality tablets via HSWG-T.

A novel dry granule preparation technology and comparison of granule properties with conventional wet system for ceramic tiles production

The ceramic tile manufacturing process uses a lot of energy, mainly thermal energy, and to a lesser extent electric energy. Total energy costs account for between 50% and 55% of average direct manufacturing costs. Fossil fuel combustion, such as natural gas combustion, produces carbon dioxide emission. Therefore, energy consumption and emissions issues are vitally important for both environmental effects and process costs in ceramic tile manufacturing. The wet process of granule production systems including wet grinding and spray drying is widely used for the production of granules. Although there is high energy consumption for the water evaporation in the spray dryer, it ensures to produce high quality tile for many years. In this study, important granule properties were introduced for a novel dry granule production system. In the successful application of a dry granulation system, the conformity of produced granules is vitally important such as particle size distribution, bulk density, flow properties, and moisture of granules and conformity for the pressing process. This paper includes the comparative studies for properties of granules produced in spray dryer and new dry granule preparation systems and the full results of the industrial trials with these granules. The cost comparison of both granule production systems was also made for the same raw material usage. The natural gas consumption and water consumption were reduced respectively from 46 to 15 m3/ton and from 540 to 95 liters/ton in the new dry granulation system while electricity consumption and maintenance costs remain almost the same in both systems.

Sustainable Use of Biochar, Poultry and Cattle Manure for the Production of Organic Granular Fertilizers

In agricultural activities, there is an increasing need for organic fertilizers to use nature-friendly materials used to fertilize the soil. Farmers have been using granular organic fertilizers made from composted or dried manure of cattle, poultry, pigs, ash, bone meal, and other materials for some time, but the quantities of these organic fertilizers are not large. Biochar is also being intensively studied as a material to improve soil quality and plant growth and reduce greenhouse gas emissions from soil. The suitability of cattle manure compost, poultry manure, biochar, and their combinations for granular fertilizers was analyzed in this work. The preparation of biochar for granulation may have differences compared to other organic materials due to the moisture content, fractional composition, bulk density, and other parameters of the granulated material, so this work examines the physical–mechanical and chemical properties of cattle and poultry manure and biochar raw material and the final granulated product. Research has found that the fractional composition of raw materials under investigation manure and biochar was up to 2 mm. The moisture content of the studied raw material varied from 8.97% in the case of poultry manure to 25.11% in the case of cattle manure compost. The lowest moisture content was obtained due to additional drying. The addition of biochar reduces the granule density in investigated cases. Poultry manure granules were the most mechanically stable, with a semi-static stability of 382.6 ± 78.08 N. After the addition of biochar, weaker binding properties were determined in the experimental granules. Analysis of the composition of elements shows that these granules can be used for fertilization or soil improvement. High concentrations of nitrogen (N), phosphorus (P), and potassium (K) were detected in the granules. The obtained results showed that it is appropriate to enrich the manure granules with biochar.

Application of unsupervised and supervised learning to a material attribute database of tablets produced at two different granulation scales

The purpose of this study is to demonstrate the usefulness of machine learning (ML) for analyzing a material attribute database from tablets produced at different granulation scales. High shear wet granulators (scale 30 g and 1000 g) were used and data were collected according to the design of experiments at different scales. In total, 38 different tablets were prepared, and the tensile strength (TS) and dissolution rate after 10 min (DS10) were measured. In addition, 15 material attributes (MAs) related to particle size distribution, bulk density, elasticity, plasticity, surface properties, and moisture content of granules were evaluated. By using unsupervised learning including principal component analysis and hierarchical cluster analysis, the regions of tablets produced at each scale were visualized. Subsequently, supervised learning with feature selection including partial least squares regression with variable importance in projection and elastic net were applied. The constructed models could predict the TS and DS10 from the MAs and the compression force with high accuracy (R2= 0.777 and 0.748, respectively), independent of scale. In addition, important factors were successfully identified. ML can be used for better understanding of similarity/dissimilarity between scales, for constructing predictive models of critical quality attributes, and for determining critical factors.

Structural and proteomic repercussions of growth hormone receptor deficiency on the pituitary gland: Lessons from a translational pig model.

Growth hormone receptor deficiency (GHRD) results in low serum insulin-like growth factor 1 (IGF1) and high, but non-functional serum growth hormone (GH) levels in human Laron syndrome (LS) patients and animal models. This study investigated the quantitative histomorphological and molecular alterations associated with GHRD. Pituitary glands from 6 months old growth hormone receptor deficient (GHR-KO) and control pigs were analyzed using a quantitative histomorphological approach in paraffin (9 GHR-KO [5 males, 4 females] vs. 11 controls [5 males, 6 females]), ultrathin sections tissue sections (3 male GHR-KO vs. 3 male controls) and label-free proteomics (4 GHR-KO vs. 4 control pigs [2 per sex]). GHR-KO pigs displayed reduced body weights (60% reduction in comparison to controls; p < .0001) and decreased pituitary volumes (54% reduction in comparison to controls; p < .0001). The volume proportion of the adenohypophysis did not differ in GHR-KO and control pituitaries (65% vs. 71%; p = .0506) and GHR-KO adenohypophyses displayed a reduced absolute volume but an unaltered volume density of somatotrophs in comparison to controls (21% vs. 18%; p = .3164). In GHR-KO pigs, somatotroph cells displayed a significantly reduced volume density of granules (23.5%) as compared to controls (67.7%; p < .0001). Holistic proteome analysis of adenohypophysis samples identified 4660 proteins, of which 592 were differentially abundant between the GHR-KO and control groups. In GHR-KO samples, the abundance of somatotropin precursor was decreased, whereas increased abundances of proteins involved in protein production, transport and endoplasmic reticulum (ER) stress were revealed. Increased protein production and secretion as well as significantly reduced proportion of GH-storing granules in somatotroph cells of the adenohypophysis without an increase in volume density of somatotroph cells in the adenohypophysis could explain elevated serum GH levels in GHR-KO pigs.

Maternal Western-style diet in nonhuman primates leads to offspring islet adaptations including altered gene expression and insulin hypersecretion.

Maternal overnutrition is associated with increased susceptibility to type 2 diabetes in the offspring. Rodent models have shown that maternal overnutrition influences islet function in offspring. To determine whether maternal Western-style diet (WSD) alters prejuvenile islet function in a model that approximates that of human offspring, we utilized a well-characterized Japanese macaque model. We compared islet function from offspring exposed to WSD throughout pregnancy and lactation and weaned to WSD (WSD/WSD) compared with islets from offspring exposed only to postweaning WSD (CD/WSD) at 1 yr of age. WSD/WSD offspring islets showed increased basal insulin secretion and an exaggerated increase in glucose-stimulated insulin secretion, as assessed by dynamic ex vivo perifusion assays, relative to CD/WSD-exposed offspring. We probed potential mechanisms underlying insulin hypersecretion using transmission electron microscopy to evaluate β-cell ultrastructure, qRT-PCR to quantify candidate gene expression, and Seahorse assay to assess mitochondrial function. Insulin granule density, mitochondrial density, and mitochondrial DNA ratio were similar between groups. However, islets from WSD/WSD male and female offspring had increased expression of transcripts known to facilitate stimulus-secretion coupling and changes in the expression of cell stress genes. Seahorse assay revealed increased spare respiratory capacity in islets from WSD/WSD male offspring. Overall, these results show that maternal WSD feeding confers changes to genes governing insulin secretory coupling and results in insulin hypersecretion as early as the postweaning period. The results suggest a maternal diet leads to early adaptation and developmental programming in offspring islet genes that may underlie future β-cell dysfunction.NEW & NOTEWORTHY Programed adaptations in islets in response to maternal WSD exposure may alter β-cell response to metabolic stress in offspring. We show that islets from maternal WSD-exposed offspring hypersecrete insulin, possibly due to increased components of stimulus-secretion coupling. These findings suggest that islet hyperfunction is programed by maternal diet, and changes can be detected as early as the postweaning period in nonhuman primate offspring.

RNA-mediated demixing transition of low-density condensates

Biomolecular condensates play a key role in organizing cellular reactions by concentrating a specific set of biomolecules. However, whether condensate formation is accompanied by an increase in the total mass concentration within condensates or by the demixing of already highly crowded intracellular components remains elusive. Here, using refractive index imaging, we quantify the mass density of several condensates, including nucleoli, heterochromatin, nuclear speckles, and stress granules. Surprisingly, the latter two condensates exhibit low densities with a total mass concentration similar to the surrounding cyto- or nucleoplasm. Low-density condensates display higher permeability to cellular protein probes. We find that RNA tunes the biomolecular density of condensates. Moreover, intracellular structures such as mitochondria heavily influence the way phase separation proceeds, impacting the localization, morphology, and growth of condensates. These findings favor a model where segregative phase separation driven by non-associative or repulsive molecular interactions together with RNA-mediated selective association of specific components can give rise to low-density condensates in the crowded cellular environment.

The effect of citrate plasticizers on the properties of nitrocellulose granules

AbstractNitrocellulose granules containing the proposed new eco‐friendly inert plasticizers, substitutes for phthalate derivatives, such as acetyl triethyl nitrate (ATEC) and tributyl citrate (TBC) were obtained. The single‐base propellants were obtained using safe granulation process (water method). Diethylene glycol dinitrate (DEGDN) was used as an energetic modifier in obtained propellants. It was found that the addition of citrate plasticizers reduced the heat of combustion and dynamic vivacity of powders. At the same time DEGDN increased the heat of combustion of tested materials. Citrate derivatives did not affect the density and thermal decomposition of granules. It was concluded based on pyrostatic analysis that the TBC plasticizer influenced the kinetics of nitrocellulose gelatinization by DEGDN. The kinetic model [nth order with autocatalysis (CnB) reaction] was adjusted based on the process of thermal decomposition. The presence of DEGDN in granules reduces the activation energy and increases the constant heat cumulative rate. The prepared propellants are characterized by excellent thermal stability in accordance with the STANAG 4582 standard. The obtained propellants can be potentially used in small calibre ammunition.