Tissue stem cells are the cell of origin for many malignancies. Metabolites regulate the balance between self-renewal and differentiation, but whether endogenous metabolic pathways or nutrient ...availability predispose stem cells towards transformation remains unknown. Here, we address this question in epidermal stem cells (EpdSCs), which are a cell of origin for squamous cell carcinoma. We find that oncogenic EpdSCs are serine auxotrophs whose growth and self-renewal require abundant exogenous serine. When extracellular serine is limited, EpdSCs activate de novo serine synthesis, which in turn stimulates α-ketoglutarate-dependent dioxygenases that remove the repressive histone modification H3K27me3 and activate differentiation programmes. Accordingly, serine starvation or enforced α-ketoglutarate production antagonizes squamous cell carcinoma growth. Conversely, blocking serine synthesis or repressing α-ketoglutarate-driven demethylation facilitates malignant progression. Together, these findings reveal that extracellular serine is a critical determinant of EpdSC fate and provide insight into how nutrient availability is integrated with stem cell fate decisions during tumour initiation.
We extend the black hole (BH) feedback models of Ciotti, Ostriker, and Proga to two dimensions. In this paper, we focus on identifying the differences between the one-dimensional and two-dimensional ...hydrodynamical simulations. We examine a normal, isolated L * galaxy subject to the cooling flow instability of gas in the inner regions. Allowance is made for subsequent star formation, Type Ia and Type II supernovae, radiation pressure, and inflow to the central BH from mildly rotating galactic gas which is being replenished as a normal consequence of stellar evolution. The central BH accretes some of the infalling gas and expels a conical wind with mass, momentum, and energy flux derived from both observational and theoretical studies. The galaxy is assumed to have low specific angular momentum in analogy with the existing one-dimensional case in order to isolate the effect of dimensionality. The code then tracks the interaction of the outflowing radiation and winds with the galactic gas and their effects on regulating the accretion. After matching physical modeling to the extent possible between the one-dimensional and two-dimensional treatments, we find essentially similar results in terms of BH growth and duty cycle (fraction of the time above a given fraction of the Eddington luminosity). In the two-dimensional calculations, the cool shells forming at 0.1-1 kpc from the center are Rayleigh-Taylor unstable to fragmentation, leading to a somewhat higher accretion rate, less effective feedback, and a more irregular pattern of bursting compared with the one-dimensional case.
Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. We investigated whether and to what consequence stem cells possess and ...accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we found that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis, and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory is distinct, separable, and has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue-regenerating tasks relative to their naïve counterparts.
Two-dimensional integral field surveys such as ATLAS3D are producing rich observational data sets yielding insights into galaxy formation. These new kinematic observations have highlighted the need ...to understand the evolutionary mechanisms leading to a spectrum of fast rotators and slow rotators in early-type galaxies. We address the formation of slow and fast rotators through a series of controlled, comprehensive hydrodynamical simulations, sampling idealized galaxy merger scenarios constructed from model spiral galaxies. Idealized and controlled simulations of this sort complement the more ‘realistic’ cosmological simulations by isolating and analysing the effects of specific parameters, as we do in this paper. We recreate minor and major binary mergers, binary merger trees with multiple progenitors, and multiple sequential mergers. Within each of these categories of formation history, we correlate progenitor gas fraction, mass ratio, orbital pericentre, orbital ellipticity, and spin with remnant kinematic properties. We create kinematic profiles of these 95 simulations comparable to ATLAS3D data. By constructing remnant profiles of the projected specific angular momentum (
$\lambda _R= \langle R|V|\rangle / \langle R \sqrt{V^2+\sigma ^2}\rangle$
), triaxiality, and measuring the incidences of kinematic twists and kinematically decoupled cores, we distinguish between varying formation scenarios. We find that binary mergers nearly always form fast rotators. Slow rotators can be formed from zero initial angular momentum configurations and gas-poor mergers, but are not as round as the ATLAS3D galaxies. Remnants of binary merger trees are triaxial slow rotators. Sequential mergers form round slow rotators that most resemble the ATLAS3D rotators.
Poly-ether-ether-ketone (PEEK) is a high-performance, temperature-resistance polymer that is finding an increasing range of applications. In order to even enhance PEEK׳s mechanical and tribological ...properties particles of different compositions, shapes and sizes are added into its matrix. PEEK has already been combined with many different particles; however, very rarely MoS2 and WS2 – two state-of-the-art solid-lubricants – were added into the PEEK matrix. Furthermore, a comprehensive tribological study combining MoS2 and WS2 particles of different sizes and concentrations has not yet been reported. In this investigation we looked at the effect of micro- and nanosized MoS2 and WS2 particles in PEEK on the dry-sliding tribological behaviour against stainless steel (100Cr6). A non-conventional technique, i.e., the sintering of dry-pressed compacts, was used to prepare the PEEK composites. The results show that all the particles, irrespective of their composition and size, reduce the friction (up to 30%); however, the nanoscale particles require a higher concentration to form an effective low-friction tribofilm. The formation of a tribofilm is necessary to reduce the wear of all the composites (up to 51%); this is strongly promoted by the addition of nano- or microparticles of both the MoS2 and WS2 materials. In addition, the hardness, which is greatly increased by the addition of all the particles, significantly improves the wear behaviour. The results of XPS analyses showed that the oxidation occurs during tribological sliding, which reduces particles beneficial wear behaviour effects.
•The effect of MoS2 and WS2 particles on tribological behaviour of PEEK was studied.•Micro- and nano-sized particles in four concentrations were used.•The coefficients of friction for composites were decreased for all particles.•The wear rates were lower when nanoparticles were used.•Oxidation rate of WS2 particles is higher compared to MoS2 particles.
The silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC) composite system for fusion applications has seen a continual evolution from development a fundamental understanding of the ...material system and its behavior in a hostile irradiation environment to the current effort which is directed at a broad-based program of technology maturation program. In essence, over the past few decades this material system has steadily moved from a laboratory curiosity to an engineering material, both for fusion structural applications and other high performance application such as aerospace. This paper outlines the recent international scientific and technological achievements towards the development of SiC/SiC composite material technologies for fusion application and discusses future research directions. It also reviews the materials system in the larger context of progress to maturity as an engineering material for both the larger nuclear community and broader engineering applications.
The problem of evaluating the accuracy of Poisson approximation to the distribution of a sum of independent integer-valued random variables has attracted a lot of attention in the past six decades. ...From a practical point of view, it has important applications in insurance, reliability theory, extreme value theory, etc.; from a theoretical point of view, the topic provides insights into Kolmogorov’s problem. The task of establishing an estimate with the best possible constant at the leading term remained open for decades. The paper presents a solution to that problem. A first-order asymptotic expansion is established as well. We generalise and sharpen the corresponding inequalities of Prokhorov, LeCam, Barbour, Hall, Deheuvels, Pfeifer, and Roos. A new result is established for the intensively studied topic of Poisson approximation to the binomial distribution.
In 2010, the iPrEx trial demonstrated that oral antiretroviral pre-exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk men who have sex with men (MSM). The impact of iPrEx ...on PrEP knowledge and actual use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP awareness, interest and experience among at-risk MSM before and after iPrEx, and to determine demographic and behavioral factors associated with these measures.
Cross-sectional, national, internet-based surveys were administered to U.S. based members of the most popular American MSM social networking site 2 months before (n = 398) and 1 month after (n = 4 558) publication of iPrEx results. Comparisons were made between these samples with regards to PrEP knowledge, interest, and experience. Data were collected on demographics, sexual risk, and experience with post-exposure prophylaxis (PEP). Regression analyses were performed to identify factors associated with PrEP awareness, interest, and experience post-iPrEx. Most participants were white, educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited pre- and post-iPrEx (13% vs. 19%), whereas interest levels after being provided with a description of PrEP remained high (76% vs. 79%). PrEP use remained uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI 1.52-36.6) and PEP experience (OR 34.2; CI 13.3-88.4). PrEP interest was associated with older age (OR 1.01; CI 1.00-1.02), unprotected anal intercourse with ≥1 male partner in the prior 3 months (OR 1.40; CI 1.10-1.77), and perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13-1.27).
Among MSM engaged in online networking, awareness of PrEP was limited 1 month after the iPrEx data were released. Utilization was low, although some MSM who reported high-risk behaviors were interested in using PrEP. Studies are needed to understand barriers to PrEP utilization by at-risk MSM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Concern exists that a constellation of negative maternal emotions during pregnancy generates persistent negative consequences for child development. Maternal reports of anxiety, pregnancy-specific ...and nonspecific stress, and depressive symptoms were collected during mid-pregnancy and at 6 weeks and 24 months after birth in a sample of healthy women with low risk pregnancies. Developmental assessment and cardiac vagal tone monitoring were administered to 94 children at age 2. Higher levels of prenatal anxiety, nonspecific stress, and depressive symptoms were associated with more advanced motor development in children after postnatal control for each psychological measure; anxiety and depression were also significantly and positively associated with mental development. Mild to moderate levels of psychological distress may enhance fetal maturation in healthy populations.
The present article reports the results of a systematic review on the potential benefits of the combined use of virtual reality (VR) and non-invasive brain stimulation (NIBS) as a novel approach for ...rehabilitation. VR and NIBS are two rehabilitation techniques that have been consistently explored by health professionals, and in recent years there is strong evidence of the therapeutic benefits of their combined use. In this work, we reviewed research articles that report the combined use of VR and two common NIBS techniques, namely transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Relevant queries to six major bibliographic databases were performed to retrieve original research articles that reported the use of the combination VR-NIBS for rehabilitation applications. A total of 16 articles were identified and reviewed. The reviewed studies have significant differences in the goals, materials, methods, and outcomes. These differences are likely caused by the lack of guidelines and best practices on how to combine VR and NIBS techniques. Five therapeutic applications were identified: stroke, neuropathic pain, cerebral palsy, phobia and post-traumatic stress disorder, and multiple sclerosis rehabilitation. The majority of the reviewed studies reported positive effects of the use of VR-NIBS. However, further research is still needed to validate existing results on larger sample sizes and across different clinical conditions. For these reasons, in this review recommendations for future studies exploring the combined use of VR and NIBS are presented to facilitate the comparison among works.
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