Large Inclusions Research Articles

A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report.

Chediak-Higashi syndrome (CHS) is a life-threatening autosomal recessive immunodeficiency disease presenting with recurrent infections, hypopigmentation, progressive neurodegeneration, and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated stage. Two-thirds of patients experience a fatal accelerated phase. CHS is caused by lysosomal transport regulator (LYST) gene mutations. We report the case of CHS, who was born with pale skin and silver hair. Bone marrow aspirate revealed large inclusions in granulocytes, monocytes, and lymphocytes. Genetic analysis revealed a new nonsense mutation in the LYST gene: c.8186G > A (W2729Ter). The child presented with fever, hepatosplenomegaly, and lymphadenectasis. Laboratory tests showed pancytopenia, hypofibrinogenemia, and high serum ferritin, indicating an accelerated phase of CHS. She underwent allogeneic hematopoietic stem cell transplantation (HCST) combined with umbilical cord blood transplantation (UCBT) after HLH-related chemotherapy. The patient has been alive for nine months without recurrence. We have identified a novel nonsense mutation in the LYST gene that correlates with a severe phenotype, and HSCT combined with UCBT is an effective treatment.

Statistical Thermodynamic Description of Self-Assembly of Large Inclusions in Biological Membranes.

Recent studies revealed anomalous underscreening in concentrated electrolytes, and we suggest that the underscreened electrostatic forces between membrane proteins play a significant role in the process of self-assembly. In this work, we assumed that the underscreened electrostatic forces compete with the thermodynamic Casimir forces induced by concentration fluctuations in the lipid bilayer, and developed a simplified model for a binary mixture of oppositely charged membrane proteins with different preference to liquid-ordered and liquid-disordered domains in the membrane. In the model, like macromolecules interact with short-range Casimir attraction and long-range electrostatic repulsion, and the cross-interaction is of the opposite sign. We determine energetically favored patterns in a system in equilibrium with a bulk reservoir of the macromolecules. Different patterns consisting of clusters and stripes of the two components and of vacancies are energetically favorable for different values of the chemical potentials. Effects of thermal flutuations at low temperature are studied using Monte Carlo simulations in grand canonical and canonical ensembles. For fixed numbers of the macromolecules, a single two-component cluster with a regular pattern coexists with dispersed small one-component clusters, and the number of small clusters depends on the ratio of the numbers of the molecules of the two components. Our results show that the pattern formation is controlled by the shape of the interactions, the density of the proteins, and the proportion of the components.

Molecular consequences of SCA5 mutations in the spectrin-repeat domains of β-III-spectrin.

Spinocerebellar ataxia type 5 (SCA5) mutations in the protein β-III-spectrin cluster to the N-terminal actin-binding domain (ABD) and the central spectrin-repeat domains (SRDs). We previously reported that a common molecular consequence of ABD-localized SCA5 mutations is increased actin binding. However, little is known about the molecular consequences of the SRD-localized mutations. It is known that the SRDs of β-spectrin proteins interact with α-spectrin to form an α/β-spectrin dimer. In addition, it is known that SRDs neighbouring the β-spectrin ABD enhance actin binding. Here, we tested the impact of the SRD-localized R480W and the E532_M544del mutations on the binding of β-III-spectrin to α-II-spectrin and actin. Using multiple experimental approaches, we show that both the R480W and E532_M544del mutants can bind α-II-spectrin. However, E532_M544del causes partial uncoupling of complementary SRDs in the α/β-spectrin dimer. Further, the R480W mutant forms large intracellular inclusions when co-expressed with α-II-spectrin in cells, supporting that R480W mutation grossly disrupts the α-II/β-III-spectrin physical complex. Moreover, actin-binding assays show that E532_M544del, but not R480W, increases β-III-spectrin actin binding. Altogether, these data support that SRD-localized mutations alter key interactions of β-III-spectrin with α-II-spectrin and actin.

Impact and erosion dynamics of inclusion-enriched dry granular flows on rigid barriers with basal clearance: Numerical insights from hybrid MP-DEM simulations

Rigid barriers with basal openings are often installed along predicted flow paths to protect downstream facilities from dry granular flows containing large boulders. However, current design practices do not consider the effects of these inclusions during impact, discharge, overflow, and bed erosion. We conducted hybrid MP-DEM simulations to study the dynamics of dry sand flow with inclusions impacting a rigid barrier with a basal opening. Our findings show that accounting for large inclusions is crucial for barrier design, as they alter dry granular flow regimes, delay dead zone formation, and affect overflow dynamics. Current analytical solutions may overestimate velocity attenuation by up to 60% if inclusions are not considered. A 10% increase in inclusion volume fraction leads to 6%-28% increases in internal energy dissipation during overflow, resulting in an overflow distance 20% lower than existing predictions. Additionally, channel bed erosion due to landing flow with inclusions creates a flow depth up to 3.5 times thicker than at the first barrier location. This suggests that using the initial flow depth for impact force assessment on a second barrier may not be conservative for erodible channel beds and inclusion-enriched flows.

Effect of hot rolling reduction process on macro-inclusion in high silicon steel plates: A numerical study

Inclusions inevitably exist in steel plate, whose behaviour during rolling severely affects the quality of product. In this article, a finite element method was used to simulate the hot rolling behaviour of hard and soft inclusions in high silicon steel plates at different sizes, positions and shapes (circle and square) when the adhesion to the matrix were weak. The shape, relative position and dimensions around the inclusions after rolling were obtained. When the inclusions are hard, cracks are produced around the inclusions after rolling. When inclusions are soft, there are no cracks around the inclusions. Large hard inclusions are more likely to move to the plate surface. When the inclusions are in the position of 1/16 of the sheet, the relative distance between the inclusions and the surface of the sheets is significantly reduced, from 0.062 at the beginning to less than 0.02. Furthermore, the effect of the size and location of hard inclusions on the microscopic defects produced after rolling is discussed. The microscopic defects around the inclusions increase with increasing size and decreasing distance of the inclusions.

Large and Extensive Multilocular Peritoneal Inclusion Cysts Lack Genomic Alterations and Follow an Indolent Clinical Course Despite Rare Recurrences.

Peritoneal inclusion cysts (PICs) are unilocular or multilocular cystic lesions lined by bland mesothelial cells. While most are small and localized, rare examples may be large or multifocal with diffuse peritoneal involvement, causing clinical and even pathologic concern for malignancy. We examined 20 PIC, including 8 large solitary and 12 multifocal lesions. Solitary PIC were found in 7 female and 1 male patients ranging from 19 to 55 (median: 37) years. Expanded collagenous (n=2) or edematous (n=1) areas were occasionally seen in the septae, and 1 had microscopic foci of myxoid stroma. Four had hobnail cells, and 1 had minor areas of papillary mesothelial hyperplasia. Multifocal PICs occurred in 9 female and 3 male patients ranging from 26 to 80 (median: 53) years. Three showed extensive associated fibrosis with entrapment of preexisting adipose tissue, 2 had areas resembling granulation tissue, and 3 had scattered foci of myxoid stroma. Hobnail cells were present in 9, papillary mesothelial hyperplasia in 2, entrapped single cells in 1, and 2 had areas resembling adenomatoid tumors. Two of the multifocal PICs had limited local recurrences at 18 and 21 months. No patients died of disease. Clonal alterations were not identified in any of the tested PICs (mutational and fusion analysis in 5, chromosomal microarray in 1). Despite limited local recurrences, we demonstrate that even large and multifocal PICs may lack identifiable genomic alterations and are associated with benign outcomes.

Evolution of inclusions in DH36 grade ship plate steel during high heat input welding

In this paper, the solid solution and precipitation behavior of inclusions on the surface and 1/2 thickness of the tested steel plate under the condition of welding heat input of 400 kJ/cm is investigated by using laser confocal experiments with hot-rolled state DH36 ship plate steel as the research object, and the mechanism of the effect of inclusions on the phase transformation of an acicular ferrite is revealed. The results show that the inclusions of the tested steel are mainly composed of Oxide-MnS, MnS, Oxide, TiN, Spinel, etc. The amount of inclusions on the surface of the tested steel plate is significantly higher than that at the 1/2 thickness position. During the heating stage, the small inclusions on the surface immediately disappeared, and the large inclusions gradually solidified in the matrix; atomic diffusion occurred at the bond between the inclusions and the matrix; while the small inclusions at the 1/2 thickness position gradually disappeared at the beginning of the heating stage, and the inclusions began to precipitate and grow when the temperature was increased to 990 °C. The acicular ferrite preferentially nucleates and grows near the boundary of the inclusions during the post-weld cooling stage, and its growth ends when two acicular ferrites cross.

Experimental study on single value fluctuation of impact work in 700 MPa low-alloy tempering plate

The single value fluctuation of impact work occurs frequently in high strength steel, especially for medium or super thick plates. With respect to the single value fluctuation of impact work in 700 MPa low alloy thin tempered plate, the present study carried out a comprehensive and comparative analysis through metallographic microstructure, second-phase precipitated particle and inclusion distribution. The results show that the microstructure type, grain boundary ratio of HAGBs/LAGBs, grain size and orientation of the specimens with 37 J and 7 J impact work are basically the same. The two specimens show excellent process-microstructure consistency, which fully indicate that the temperature fields of the two specimens are consistent. Since the temperature field is basically the same, the (Ti, Nb, Mo)C compound precipitated particles in the two specimens maintain a good Baker-Nutting relationship with the matrix, and the interface between the precipitated particles and the matrix maintain a stable coherent/semi-coherent relationship. The main reason for the decrease of impact work of tempered plate is related to the distribution of inclusions. There are more spherical and square large size inclusion particles and microcracks in the specimen with lower impact work. Among them, the large square inclusion particles dominate mostly. And with the increase of the plastic deformation degree of the metal matrix, the large square inclusion has an obvious evolution by separation from the matrix to forming microcracks, and then to fracture.

Effect of Cerium on Inclusion Evolution and Pitting Corrosion of Nb-Microalloyed Steel.

Nb-microalloyed steels are widely used in construction engineering fields due to their excellent mechanical properties, but they face serious corrosion problems in service environments. Pitting corrosion is the severest form of corrosion, and the types of inclusions are the leading cause to induce pitting corrosion. A new strategy is proposed to enhance the corrosion resistance of steels by achieving a beneficial transformation of inclusions with Ce treatment. In this paper, two types of Nb-microalloyed steels (0% Ce and 0.0058% Ce steel) were prepared to study the modification effect on inclusions in industrial production. The spherical CaS•C12A7 inclusions were modified to smaller ellipsoidal Ce2O2S inclusions, and the proportion of inclusions (0-2 μm) increased significantly from 27 to 66%, while large inclusions (>6 μm) disappeared. A kinetic model of inclusion evolution was established. The results of electrochemical tests indicated that the corrosion potential was positively shifted, and the corrosion current was reduced after Ce treatment. Additionally, the number of defects in the passivation film was decreased, and the corrosion resistance of the steel was significantly improved. The addition of Ce changed the types of inclusions and reduced the number of pitting nucleation points, which led to a remarkable reduction in the number and size of pitting pits. The mechanism of pitting corrosion induced by different types of inclusions was further investigated, and a pitting corrosion model was modeled based on the immersion experiments. Research results provide theoretical support for enhancing the corrosion resistance of steel.

Electricity subsidies targeting performance indicators in selected Latin American countries

ABSTRACT This document calculates targeting performance indicators of electricity subsidies in Mexico, Panama, the Dominican Republic, and Uruguay. To do this, beneficiary and benefit incidence indicators are calculated using official household survey data and administrative records on electricity tariffs. In addition, this paper calculates inclusion and exclusion errors in the targeting of electricity subsidies. The results show that the share of poor households that receive the subsidy is very large in Mexico, Panama, and the Dominican Republic. However, the distribution of the subsidy is regressive in absolute terms, which implies that most of every dollar spent on keeping electricity prices low will benefit the wealthiest households. This document also finds large inclusion errors suggesting that an important share of the non-poor is also benefiting from the subsidy. These results shed light on the evaluation of electricity subsidies in the region to improve targeting and optimisation of resources.

Анализ ОКТ-предикторов анатомических и функциональных результатов aнтиангиогенной терапии отслойки пигментного эпителия при неоваскулярной возрастной макулярной дегенерации

Abstract Analysis of OCT predictors of anatomical and functional results of anti-VEGF therapy of pigment epithelium detachment in neovascular age-related macular degeneration E.V. Kozina, S.N. Sakhnov, V.V. Myasnikova, E.V. Bykova S. Fyodorov Eye Microsurgery Federal State Institution, Krasnodar branch, Krasnodar, Russian Federation Kuban State Medical University Ministry of Health of Russia, Krasnodar, Russian Federation Purpose. Analysis of optical coherence tomography (OCT) biomarkers for anatomical results prediction of anti-angiogenic therapy (antiVEGF) of pigment epithelial detachments (PED) in neovascular macular degeneration (n-AMD). Material and methods. Primary tomograms of 260 patients with PED higher than 200 µm were analyzed. The shape, height, length of the detachment and subpigmentary space reflectivity were assessed. After anti-VEGF injections, reattachment of PED according to OCT was observed in 114cases (44%) – 1st group; in 111 cases (43%) OCT showed PED resistance – 2nd group; in 35 cases (13%), the pigment epithelium tear (RPET) of 3–4 degrees was happened – 3rd group. In each OCT were studied of the following biomarkers: the ellipsoidal zone and RPE integrity, intra – and subretinal fluid, the drusen under RPE around PED, hyperreflective foci in retina. Results. A statistically significant difference was revealed between 1st and 2nd groups in the height and length of pigment epithelium detachment: PED height (506.2±204.3 µm) and length (3206.2±722.1 µm) have a tendency to reattachment during anti-VEGF therapy (р<0.05). High PED with neuroepithelial detachment has a higher risk of RPET (р<0.05). Presence of RPE defects and large hyperreflective foci in the retina can be considered as a predictor of the PED reattachment (р<0.05). Low PED with reflectivity subpigmentary space is a predictor of PED resistance (р<0.05). Conclusion. Patients with high PED, with neuroepithelial detachment, should be given antiVEGF therapy with great caution. Lower PED with hyperreflectity under PED tend to be anatomically resistant to therapy. Biomarkers of the adherence of the PE can be RPE defects and large hyperreflective inclusions in the internal layers. Key words: retinal pigment epithelium detachment, pigment epithelium tear, OCT biomarkers, hyperreflective foci, antiangiogenic therapy

Fowl Aviadenovirus (FAdV-11) as the causative agent of a vertical outbreak of inclusion body hepatitis in commercial broiler breeders in Brazil

Inclusion body hepatitis (IBH), caused by Fowl Aviadenovirus (FAdV), is a significant disease affecting chickens worldwide. FAdV-11 associated with IBH was identified in 9-day-old commercial broiler breeders in Brazil. The chicks exhibited a sudden increase in daily mortality, accompanied by nonspecific clinical signs, in one house on the farm. The cumulative mortality rate reached 11.13 % by 15 days of age. Macroscopically, the liver was markedly enlarged and pale red with a distinct lobular pattern. Histologically, the liver showed mild to severe multifocal coalescent vacuolar degeneration and necrosis, with hepatocyte nuclei diffusely enlarged and containing large basophilic inclusion bodies. Additionally, the heart exhibited a diffuse, moderate infiltration of lymphocytes and plasma cells, with focal thrombosis in the epicardium. FAdV was detected in liver samples using specific primers for the hexon gene (52 K-fw and 52 K-rv) in a polymerase chain reaction (PCR) assay. Sequencing of the hypervariable region of this gene (Hex L1) for phylogenetic analysis revealed FAdV-D species serotype 11. To our knowledge, this is the first report of FAdV-D serotype 11 as the causative agent of a vertical outbreak of inclusion body hepatitis in broiler breeders in Brazil.

Fluid and solid inclusions in large halite veins in the Kłodawa Salt Dome (Central Poland) – insights into its development

Secondary rocks are often found in salt domes. Among these, large halite crystal (LHC) veins and nests are common, as in the Kłodawa Salt Dome of Poland. Mineralogical tests carried out on LHC here showed the presence of fluid and solid inclusions in the halite crystals. The halite itself commonly exhibits birefringence, suggesting lattice stresses. Among the solid inclusions, anhydrite is the most common. Three types of anhydrite crystals have been distinguished as regards their size and occurrence, while small, rounded inclusions of sylvite appear much less frequently. Fluid inclusions are generally rare and mostly of the secondary type. This type of fluid inclusion assemblage (FIA) comprises various kinds as regards their size and shape, as well as in their liquid-to-gas phase ratio. Primary FIAs are of two types: small, chevron-like inclusions containing sylvite daughter minerals, and large liquid-gas inclusions with carnallite and other daughter minerals. The melting temperature of sylvite ranged from 90 to 278°C, and for carnallite from 68 to 142°C. Complete homogenization of the inclusions took place at temperatures between 260 and 471.2°C. This indicates the high-temperature origin of the LHC and the presence of significant amounts of K+, Mg+2, Ca+2, and SO4-2 ions in the solutions.

Asparagopsis taxiformis inclusion in grass silage-based diets fed to Norwegian red dairy cows: Effects on ruminal fermentation, milk yield, and enteric methane emission

Efforts to mitigate enteric methane (CH4) emission from ruminants by using the red macroalgae Asparagopsis taxiformis (AT) have demonstrated promising results both in vitro and in vivo. We assessed the effects of wild harvested and freeze-dried AT inclusion in the grass silage-based diets of Norwegian Red dairy cows on feed intake, milk yield and composition, rumen fermentation and CH4 emission. Fifteen (9 rumen cannulated and 6 intact) multiparous cows with an average (±SD) covariate period milk yield (MY) of 33.0 (3.8) kg/day were used in the experiment. The cows were divided into three groups (n = 5) after blocking for cannulation, and initial MY. After feeding on a common diet for 21 days (i.e., Covariate period), the groups were randomly allocated to three treatments: Control (no seaweed), 0.125%AT (Control + 0.125%AT, on organic matter (OM) basis) and 0.25%AT (Control + 0.25%AT, on OM basis). The cows were adapted to their diets for 13 days, followed by 39 experimental days for data collection. Inclusion of AT at 0.125% level did not affect dry matter intake (DMI, kg/d) but signicantly reduced both MY and energy corrected milk yield (ECM, kg/d) (P < 0.05) with a tendency for lower CH4 production (g/d) relative to the control group. Dry matter intake, ECM and CH4 production were reduced (P < 0.05) by 0.25%AT inclusion relative to the Control group. Apparent total tract nutrient digestibility (%), ECM per kg DMI, CH4 yield (g CH4/kg DMI) and CH4 intensity (g CH4/kg ECM) were not affected by AT inclusion. Inclusion of AT, at both levels, significantly reduced (P < 0.05) ruminal fluid total short chain fatty acids and molar proportions of actate, while increasing (P < 0.05) the molar proportion of propionate and isovalerate. Inclusion of AT decreased contents (%) of milk fat (P = 0.018) and protein (P = 0.010) resulting in significanly lower fat and protein yields. Lactose content (%) was higher for the AT groups (P = 0.021) but this did not compensate for lower MY resulting in lower milk lactose yield. Milk iodine content increased in a dose dependent manner with AT inclusion. In conclusion, AT inclusion at 0.25% level reduced CH4 emission from dairy cows with a grass silage-based diets. However, the reduced DMI for the 0.25%AT group along with reduced MY and elevated milk iodine content for both AT groups, for this particular harvest of AT, would suggest possible constraints for large scale inclusion of AT in dairy cow production.

Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features.

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.

Visualization of inclusions in a water model for continuous casting of steel

With the water model, we experimentally confirmed the possibility of using a suspension to imitate the molten casting powder (slag) at the upper edge of the melt during the continuous casting of steel. The project requires that the slag particles do not leave the suspension layer during operation or that they return to it from the molten steel. It turns out that this is possible if the selected suspension particles mimic sufficiently large inclusions in the real system. The imitation of slag particles in a real system with suspension particles in water model is ensured by the equal terminal flotation velocities of both. Among the discussed polyethylene and cork particles, only cork particles, with a size of 0.2 mm to 0.5 mm, and a density of around 400 kg/m3, meet this condition. It was shown that the presented methodology could be used to estimate the proper position of the submerged entry nozzle.

Evolution of microstructure and defects in sintering of tape-cast alumina laminates observed by synchrotron X-ray multiscale tomography

Processing-induced defects affect the performance and reliability of multilayered ceramics. They are introduced from the raw powder, or during tape casting, drying, thermo-compression, binder burnout, and sintering. Using synchrotron X-ray multiscale tomography, we investigated how the microstructural heterogeneities and various defects evolve in the sintering of tape-cast alumina laminate. The strength-limiting defects were identified as large defects at the layer interface and peculiar crack-like defects formed around large inclusions contained in the raw powder. Although a slurry might be uniform in colloidal processing, the particle packing in the tape was heterogeneous. This heterogeneity determined the spatial distribution of pores and formed complex pores in later stages. Moreover, we found the formation of flake-like sheets in slurry due to the self-assembly of polyhedral alumina crystals. This phenomenon has the potential to be applied in the manufacture of 2D micro-sheets controlled to the thickness of a single particle.

Fabric and Fluid Inclusions Characterization of a Stalagmite from Eastern Spain: A Precondition for Noble Gas Analysis by Step-Crushing Methodology

Fluid inclusions in stalagmites are becoming increasingly important for paleoclimate research. Within this framework, noble gas thermometry, based on noble gases dissolved in water from fluid inclusions, provides quantitative estimations of cave air paleotemperature. Two major issues of Noble Gas Temperature (NGT) determination on speleothems are (1) the potential lack of enough water for the analysis and (2) the presence of trapped gas not dissolved in water that can be released during the analysis from biphasic or all-gas fluid inclusions, as its contribution to the bulk noble gas signal can hinder NGT results. Although the step-crushing method helps to reduce the second issue, it also decreases the amount of water available for the calculations. In order to obtain reliable NGT results with low uncertainties, a major challenge is still to reach a balance between sufficient water for analysis and a small amount of “atmospheric” gas. The difficulty is that the extraction process cannot be standardized since it strongly depends on the type of sample. The objective of this work is to investigate how the characteristics of the speleothem can determine the adequacy of the extraction process. For this purpose, we consider a stalagmite from a Mediterranean cave that consists of columnar elongated calcite and contains a significant quantity of fluid inclusions, which suggests good potential for NGT analysis. Results, however, were poorly satisfactory. Trying to understand the source of the problems, an integrated study of petrography and petrophysical features was performed. The samples were found to be different depending on the stage of coalescence of crystals and thus separated into “open” and “closed” fabrics. Classic petrographic analysis and non-destructive (nuclear magnetic resonance) techniques were used to characterize the type and amount of fluid inclusions present in both types of fabrics. The study indicates that the closed fabric (total coalescence of calcite crystals) has most water trapped in water-filled, small intracrystalline fluid inclusions that usually contain very little gas. This fabric is very suitable for NGT determination, but since the amount of water is quite small, the sample should be crushed in only one step with a large number of beats to break all the inclusions. In contrast, samples with open fabric (partial coalescence of calcite crystals) contain a higher amount of water and, also, gas-filled large intercrystalline fluid inclusions. For this fabric, step-crushing of the sample is necessary. However, the low amount of water left for the second and third crushings could lead to flawed NGT results. Thus, we suggest modifying the method to get rid of part of the gas in the first crushing while leaving enough water for the following steps. This work shows the importance of characterizing speleothems and fluid inclusions, including their petrography and petrophysical characteristics, before starting NGT analysis, allowing the selection of the most favorable samples and the customization of the step-crushing procedure.

Study on the Causes and Control Measures of Mg–Al Spinel Inclusions in U75V Heavy Rail Steel

U75V heavy rail steel production uses an aluminum-free deoxidation process; however, large particles of MgO–Al2O3 inclusions form in the steel, which has a great impact on product quality. In this paper, we try to explain how spinel inclusions, which affect the metallurgical quality of heavy rail steel, are produced by thermodynamic and experimental methods, and then determined measures for avoiding such inclusions. The formation mechanism of spinel inclusions in U75V heavy rail steel was determined through the analysis of nozzle clogging in the pouring process and typical inclusions in steel. The results show that there are two types of spinel inclusions in heavy rail steel: one is pure Mg–Al spinel inclusions and the other is Mg–Al spinel inclusions coated with calcium aluminate. The small, pure Mg–Al spinel inclusions were precipitated during the solidification of the molten steel, and the precipitation temperature was related to the composition of the molten steel. The large spinel inclusions were derived from clogging of the submersed nozzle. Mg–Al spinel inclusions coated with calcium aluminate were transformed from CaO–SiO2–Al2O3–MgO complex inclusions in the steel during cooling, and the formation temperature was related to the content of Al2O3 and MgO in the inclusions. The content of Al2O3 and MgO in the inclusions was the key to the formation of the Mg–Al spinel inclusions. Therefore, in order to control the production of spinel inclusions in steel, it is necessary to strictly control the content of impurity elements such as magnesium and aluminum in the alloy auxiliary materials, to reduce the secondary oxidation of liquid steel and to reduce the erosion of refractory materials.

CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly.

The presence of large protein inclusions is a hallmark of neurodegeneration, and yet the precise molecular factors that contribute to their formation remain poorly understood. Screens using aggregation-prone proteins have commonly relied on downstream toxicity as a readout rather than the direct formation of aggregates. Here, we combined a genome-wide CRISPR knockout screen with Pulse Shape Analysis, a FACS-based method for inclusion detection, to identify direct modifiers of TDP-43 aggregation in human cells. Our screen revealed both canonical and novel proteostasis genes, and unearthed SRRD, a poorly characterized protein, as a top regulator of protein inclusion formation. APEX biotin labeling reveals that SRRD resides in proximity to proteins that are involved in the formation and breakage of disulfide bonds and to intermediate filaments, suggesting a role in regulation of the spatial dynamics of the intermediate filament network. Indeed, loss of SRRD results in aberrant intermediate filament fibrils and the impaired formation of aggresomes, including blunted vimentin cage structure, during proteotoxic stress. Interestingly, SRRD also localizes to aggresomes and unfolded proteins, and rescues proteotoxicity in yeast whereby its N-terminal low complexity domain is sufficient to induce this affect. Altogether this suggests an unanticipated and broad role for SRRD in cytoskeletal organization and cellular proteostasis.