Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions. We use LipocyteProfiler to identify known and novel cellular mechanisms altered by polygenic risk of metabolic disease, including insulin resistance, fat distribution, and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse deep phenotypic profiling in lipocytes and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.

A single-cell atlas of human and mouse white adipose tissue.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

Impact of Preparation of Titanium Alloys on Their Abrasive Water Jet Machining.

Several titanium alloys, i.e., grade 2 Ti, Ti6Al4V and NiTi alloy, prepared by selected deformation procedures were subjected to abrasive water jet (AWJ) cutting and subsequently analysed. The study describes samples' preparations and respective material structures. The impact of deformation processing of the selected alloys on the declination angle during cutting, and the results of measurements of surface wall quality performed for the selected samples at the Department of Physics of Faculty of Electrical Engineering and Computer Science at VSB-Technical University of Ostrava, are presented and discussed, as are also the influences of structural features of the processed titanium alloys on surface qualities of the investigated samples. The results showed that the highest resistance to AWJ machining exhibited the Ti6Al4V alloy prepared by forward extrusion. Its declination angle (recalculated to the thickness 10 mm to compare all the studied samples) was 12.33° at the traverse speed of 100 mm/min, pumping pressure of 380 MPa, and abrasive mass flow rate of 250 g/min.

Investigation of Significant Parameters during Abrasive Waterjet Turning.

This paper presents an investigation of abrasive waterjet turning (AWJT). The purpose of the article was to investigate significant parameters of the turning process and to evaluate their impact on the turning product. The influence of the traverse speed, the rotational speed, and the relative position of the jet to the specimen (lateral jet shift) were investigated. Based on the previous research done in this field, the multi-pass tangential turning method was selected. Rotational speed does not seem to have a significant impact on the AWJ turning process. However, the relative position of the jet is a key parameter for improving the efficiency of the process. Increasing the lateral jet shift causes the volume of the material removed to increase until the optimal impact angle is reached. These findings need to be extended in order to adjust AWJT. Without these improvements, a comparison of jet to traditional technologies is inappropriate.

Abrasive Waterjet (AWJ) Forces-Potential Indicators of Machining Quality.

The necessity of monitoring the abrasive waterjet (AWJ) processes increases with the spreading of this tool into the machining processes. The forces produced on the workpiece during the abrasive waterjet machining can yield some valuable information. Therefore, a special waterjet-force measuring device designed and produced in the past has been used for the presented research. It was tested during the AWJ cutting processes, because they are the most common and the best described up-to-date AWJ applications. Deep studies of both the cutting process and the respective force signals led to the decision that the most appropriate indication factor is the tangential-to-normal force ratio (TNR). Three theorems concerning the TNR were formulated and investigated. The first theorem states that the TNR strongly depends on the actual-to-limit traverse speed ratio. The second theorem claims that the TNR relates to the cutting-to-deformation wear ratio inside the kerf. The third theorem states that the TNR value changes when the cutting head and the respective jet axis are tilted so that a part of the jet velocity vector projects into the traverse speed direction. It is assumed that the cutting-to-deformation wear ratio increases in a certain range of tilting angles of the cutting head. This theorem is supported by measured data and can be utilized in practice for the development of a new method for the monitoring of the abrasive waterjet cutting operations. Comparing the tilted and the non-tilted jet, we detected the increase of the TNR average value from 1.28 ± 0.16 (determined for the declination angle 20° and the respective tilting angle 10°) up to 2.02 ± 0.25 (for the declination angle 30° and the respective tilting angle of 15°). This finding supports the previously predicted and published assumptions that the tilting of the cutting head enables an increase of the cutting wear mode inside the forming kerf, making the process more efficient.

Abrasive Waterjet (AWJ) Forces-Indicator of Cutting System Malfunction.

Measurements enabling the online monitoring of the abrasive waterjet (AWJ) cutting process are still under development. This paper presents an experimental method which can be applicable for the evaluation of the AWJ cutting quality through the measurement of forces during the cutting process. The force measuring device developed and patented by our team has been used for measurement on several metal materials. The results show the dependence of the cutting to deformation force ratio on the relative traverse speed. Thus, the force data may help with a better understanding the interaction between the abrasive jet and the material, simultaneously impacting the improvement of both the theoretical and empirical models. The advanced models could substantially improve the selection of suitable parameters for AWJ cutting, milling or turning with the desired quality of product at the end of the process. Nevertheless, it is also presented that force measurements may detect some undesired effects, e.g., not fully penetrated material and/or some product distortions. In the case of a proper designing of the measuring device, the force measurement can be applied in the online monitoring of the cutting process and its continuous control.

Influence of Material Structure on Forces Measured during Abrasive Waterjet (AWJ) Machining.

Material structure is one of the important factors influencing abrasive waterjet (AWJ) machining efficiency and quality. The force measurements were performed on samples prepared from two very similar steels with different thicknesses and heat treatment. The samples were austenitized at 850 °C, quenched in polymer and tempered at various temperatures between 20 °C and 640 °C. The resulting states of material substantially differed in strength and hardness. Therefore, samples prepared from these material states are ideal for testing of material response to AWJ. The force measurements were chosen to test the possible influence of material structure on the material response to the AWJ impact. The results show that differences in material structure and respective material properties influence the limit traverse speed. The cutting to deformation force ratio seems to be a function of relative traverse speed independently on material structure.

Functionalized Chiral Bambusurils: Synthesis and Host-Guest Interactions with Chiral Carboxylates.

Bambusurils are a class of macrocyclic anion receptors that exhibit notable anion recognition properties, able to bind various inorganic anions as well the carboxylates or sulfonates. Recently, we reported enantioselective recognition of chiral carboxylates using non-functionalized chiral bambusuril derivatives. Herein, we report the synthesis and host-guest properties of two new representatives of chiral bambusuril macrocycles bearing ester functional groups, differing by the substituents attached to their portals. Their supramolecular properties in terms of carboxylate binding were studied by means of NMR in DMSO-d6 . The reported bambusurils bind selected chiral carboxylates with enantioselectivity factors up to 3.1. The results indicated that the selectivity towards different carboxylates is governed by the steric constraint of the substituents surrounding bambusuril portals. No clear trend in the binding affinities and their enantioselectivities was found.