TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.

The transcription factor TRPS1 is a context-dependent oncogene in breast cancer. In the mammary gland, TRPS1 activity is restricted to the luminal population and is critical during puberty and pregnancy. Its function in the resting state remains however unclear. To evaluate whether it could be a target for cancer therapy, we investigated TRPS1 function in the healthy adult mammary gland using a conditional ubiquitous depletion mouse model where long-term depletion does not affect fitness. Using transcriptomic approaches, flow cytometry and functional assays, we show that TRPS1 activity is essential to maintain a functional luminal progenitor compartment. This requires the repression of both YAP/TAZ and SRF/MRTF activities. TRPS1 represses SRF/MRTF activity indirectly by modulating RhoA activity. Our work uncovers a hitherto undisclosed function of TRPS1 in luminal progenitors intrinsically linked to mechanotransduction in the mammary gland. It may also provide new insights into the oncogenic functions of TRPS1 as luminal progenitors are likely the cells of origin of many breast cancers.

A comprehensive transcriptome signature of murine hematopoietic stem cell aging.

We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally "young-like" HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively.

A Study on Focused Ion Beam (FIB) Milling Machining and Fabrication Technology of Nano-Scale Diamond Tool for Machining Fine-Patterns in a Free-Form Surfaces.

Recently, the technology of the industry has been increasing for diffractive optical elements, holograms, optical components, and next-generation display components. The advanced high value-added industry is designing fine patterns on ultra-precision optical components and applying them to various industries. In the case of the ultra-fine pattern, a contact-type machining technique is required because it requires a precise pattern in nano-scale units. In this paper, the fabrication technology of ultra-precision diamond which is essential in the ultra-precision processing technology was suggested. The material used in the experiment was a single-crystal diamond tool (SCD), and the equipment for machining the SCD used a focused ion beam (FEI COMPANY, system Nova 600) equipment. The back fire method was applied without metal coating in order to carry out the process study and the focused beam of 30 keV Ga+ ions were carried out processing for various fabrication of diamond cutting tools. As a result of applying the backfire method through the process experiment, the cutting edge width of the ultra-precision diamond tool was verified 275 nm.

Reciprocal Sliding Friction Model for an Electro-Deposited Coating and Its Parameter Estimation Using Markov Chain Monte Carlo Method.

This paper describes a sliding friction model for an electro-deposited coating. Reciprocating sliding tests using ball-on-flat plate test apparatus are performed to determine an evolution of the kinetic friction coefficient. The evolution of the friction coefficient is classified into the initial running-in period, steady-state sliding, and transition to higher friction. The friction coefficient during the initial running-in period and steady-state sliding is expressed as a simple linear function. The friction coefficient in the transition to higher friction is described with a mathematical model derived from Kachanov-type damage law. The model parameters are then estimated using the Markov Chain Monte Carlo (MCMC) approach. It is identified that estimated friction coefficients obtained by MCMC approach are in good agreement with measured ones.

The Contact Ageing Effect on Fretting Damage of an Electro-Deposited Coating against an AISI52100 Steel Ball.

This article investigates the effect of contact ageing on fretting damage of an epoxy-based cathodic electro-deposited coating for use on automotive seat slide tracks (made of cold-rolled high strength steel). Static normal load was induced at the contact between the coating and an AISI52100 ball for a certain duration. It was identified that plastically deformed contact area increased logarithmically as a function of time when the contact was under static normal load. Fretting tests after various durations of static contact were conducted using a ball-on-flat plate apparatus. All fretting tests were halted when the friction coefficient reached a critical value of 0.5, indicating complete coating failure. The total number of fretting cycles to the critical friction coefficient was found to vary with the duration of static contact before fretting. It was identified that the number of cycles to the critical friction coefficient decreased with the increased duration of static contact. Meanwhile, the friction coefficient at steady-state sliding was not greatly affected by the duration of static contact before fretting. Finally, the relation between coating thickness after indentation creep and the number of cycles to the critical friction coefficient was found to be linear. Obtained results show that the duration of static contact before fretting has an influence on the fretting lifetime of an electro-deposited coating.

High-Efficiency Polymer LEDs with Fast Response Times Fabricated via Selection of Electron-Injecting Conjugated Polyelectrolyte Backbone Structure.

Imidazolium ionic side-group-containing fluorene-based conjugated polyelectrolytes (CPEs) with different π-conjugated structures, poly[(9,9-bis(8'-(3″-methyl-1″-imidazolium)octyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] dibromide (F8im-Br) and poly[(9,9-bis(8'-(3″-methyl-1″-imidazolium)octyl)-2,7-fluorene)-alt-(benzo(2,1,3)thiadiazol-4,8-diyl) dibromide (F8imBT-Br), are synthesized and utilized as an electron injection layer (EIL) in green-emitting F8BT polymer light-emitting diodes (PLEDs). Both CPE EIL devices significantly outperform Ca cathode devices; 17.9 cd A(-1) (at 3.8 V) and 16.6 lm W(-1) (at 3.0 V) for F8imBT-Br devices, 11.1 cd A(-1) (at 4.2 V) and 9.1 lm W(-1) (at 3.4 V) for F8im-Br devices, and 7.2 cd A(-1) (at 3.6 V) and 7.0 lm W(-1) (at 3.0 V) for Ca devices. Importantly, unlike the F8im-Br EIL devices, F8imBT-Br PLEDs exhibit much faster electroluminescence turn-on times (<10 µs) despite both EILs possessing the same tethered imidazolium and mobile bromide ions. The F8imBT-Br devices represent, to the best of our knowledge, the highest efficiency in thin (70 nm) single-layer F8BT PLEDs in conventional device architecture with the fastest EL response time using CPE EIL with mobile ions. Our results clearly indicate the importance of an additional factor of EIL materials, specifically the conjugated backbone structure, to determine the device efficiency and response times.

Evaluation and Description of Friction between an Electro-Deposited Coating and a Ceramic Ball under Fretting Condition.

This article describes fretting behavior of zirconia and silicon nitride balls on an electro-deposited coating. Fretting tests are performed using a ball-on-flat configuration. The evolution of the kinetic friction coefficient is determined, along with slip ratio. Experimental results show that the steady-state friction coefficient between ceramic balls (Si3N4 and ZrO2) and an electro-deposited coating is about 0.06, lower than the value between AISI 52100 ball and the coating. After a steady-state sliding, the transition of the friction coefficient is varied with a ball. The friction coefficient for ZrO2 balls became a critical value after higher fretting cycles than those for Si3N4 and AISI 52100 balls. In addition, it is identified that two parameters can describe the transition of the friction coefficient. Finally, the evolution of the friction coefficient is expressed as an exponential or a power-law form.

Method for the synthesis of amine-functionalized fullerenes involving SET-promoted photoaddition reactions of α-silylamines.

A novel method for the preparation of structurally diverse fullerene derivatives, which relies on the use of single electron transfer (SET)-promoted photochemical reactions between fullerene C60 and α-trimethylsilylamines, has been developed. Photoirradiation of 10% EtOH-toluene solutions containing C60 and α-silylamines leads to high-yielding, regioselective formation of 1,2-adducts that arise through a pathway in which sequential SET-desilylation occurs to generate α-amino and C60 anion radical pair intermediates, which undergo C-C bond formation. Protonation of generated α-aminofullerene anions gives rise to formation of monoaddition products that possess functionalized α-aminomethyl-substituted 1,2-dihydrofullerene structures. Observations made in this effort show that the use of EtOH in the solvent mixture is critical for efficient photoproduct formation. In contrast to typical thermal and photochemical strategies devised previously for the preparation of fullerene derivatives, the new photochemical approach takes place under mild conditions and does not require the use of excess amounts of substrates. Thus, the method developed in this study could broaden the scope of fullerene chemistry by providing a simple photochemical strategy for large-scale preparation of highly substituted fullerene derivatives. Finally, the α-aminomethyl-substituted 1,2-dihydrofullerene photoadducts are observed to undergo photoinduced fragmentation reactions to produce C60 and the corresponding N-methylamines.

Crack simulation of nano-bioceramic composite microstructures with cohesive failure law: effects of sintering, loads and time.

Crack behaviour of zirconia toughened alumina (ZTA) microstructures are simulated with a two-dimensional finite element simulation. Finite element models are developed using actual microstructure images of zirconia toughened alumina and a bilinear cohesive zone law. Simulation conditions are similar to those found at frictional contact between a femoral head and an acetabular cup of hip prosthesis. Effects of microstructures and contact stresses are investigated in terms of crack generation. Moreover, fatigue behaviour of a microstructure is determined by performing simulations under cyclic loading conditions. It is identified that total crack length observed in a microstructure increases with increasing the magnitude of applied contact stress. Cyclic simulation results show that progressive crack growth occurs with respect to number of fatigue cycles. In addition, it is demonstrated that zirconia grains resist crack growth in microstructures.