The current consensus is that galaxies begin as small density fluctuations in the early Universe and grow by in situ star formation and hierarchical merging. Stars begin to form relatively quickly in ...sub-galactic-sized building blocks called haloes which are subsequently assembled into galaxies. However, exactly when this assembly takes place is a matter of some debate. Here we report that the stellar masses of brightest cluster galaxies, which are the most luminous objects emitting stellar light, some 9 billion years ago are not significantly different from their stellar masses today. Brightest cluster galaxies are almost fully assembled 4-5 billion years after the Big Bang, having grown to more than 90 per cent of their final stellar mass by this time. Our data conflict with the most recent galaxy formation models based on the largest simulations of dark-matter halo development. These models predict protracted formation of brightest cluster galaxies over a Hubble time, with only 22 per cent of the stellar mass assembled at the epoch probed by our sample. Our findings suggest a new picture in which brightest cluster galaxies experience an early period of rapid growth rather than prolonged hierarchical assembly.
In patients with epilepsy, the potential to prevent seizure‐related injuries and to improve the unreliability of seizure self‐report have fostered the development and marketing of numerous seizure ...detection devices for home use. Understanding the requirements of users (patients and caregivers) is essential to improve adherence and mitigate barriers to the long‐term use of such devices. Here we reviewed the evidence on the needs and preferences of users and provided an overview of currently marketed devices for seizure detection (medically approved or with published evidence for their performance). We then compared devices with known needs. Seizure‐detection devices are expected to improve safety and clinical and self‐management, and to provide reassurance to users. Key factors affecting a device’s usability relate to its design (attractive appearance, low visibility, low intrusiveness), comfort of use, confidentiality of recorded data, and timely support from both technical and clinical ends. High detection sensitivity and low false alarm rates are paramount. Currently marketed devices are focused primarily on the recording of non–electroencephalography (EEG) signals associated with tonic‐clonic seizures, whereas the detection of focal seizures without major motor features remains a clear evidence gap. Moreover, there is paucity of evidence coming from real‐life settings. A joint effort of clinical and nonclinical experts, patients, and caregivers is required to ensure an optimal level of acceptability and usability, which are key aspects for a successful continuous monitoring aimed at seizure detection at home.
The chameleon gravity model postulates the existence of a scalar field that couples with matter to mediate a fifth force. If it exists, this fifth force would influence the hot X-ray emitting gas ...filling the potential wells of galaxy clusters. However, it would not influence the clusters weak lensing signal. Therefore, by comparing X-ray and weak lensing profiles, one can place upper limits on the strength of a fifth force. This technique has been attempted before using a single, nearby cluster (Coma, z = 0.02). Here we apply the technique to the stacked profiles of 58 clusters at higher redshifts (0.1 < z < 1.2), including 12 new to the literature, using X-ray data from the XMM Cluster Survey and weak lensing data from the Canada–France–Hawaii–Telescope Lensing Survey. Using a multiparameter Markov chain Monte Carlo analysis, we constrain the two chameleon gravity parameters (β and ϕ∞). Our fits are consistent with general relativity, not requiring a fifth force. In the special case of f(R) gravity (where
$\beta = \sqrt{1/6}$
), we set an upper limit on the background field amplitude today of |f
R0| < 6 × 10−5 (95 per cent CL). This is one of the strongest constraints to date on |f
R0| on cosmological scales. We hope to improve this constraint in future by extending the study to hundreds of clusters using data from the Dark Energy Survey.
BACKGROUND: Botanists, ecologists and evolutionary biologists are familiar with the astonishing species richness and endemism of the fynbos of the Cape Floristic Region and the ancient and unique ...flora of the kwongkan of south-western Australia. These regions represent old climatically-buffered infertile landscapes (OCBILs) that are the basis of a general hypothesis to explain their richness and endemism. However, few ecologists are familiar with the campo rupestre of central and eastern Brazil, an extremely old mountaintop ecosystem that is both a museum of ancient lineages and a cradle of continuing diversification of endemic lineages. SCOPE: Diversification of some lineages of campo rupestre pre-dates diversification of lowland cerrado, suggesting it may be the most ancient open vegetation in eastern South America. This vegetation comprises more than 5000 plant species, nearly 15 % of Brazil’s plant diversity, in an area corresponding to 0.78 % of its surface. Reviewing empirical data, we scrutinise five predictions of the OCBIL theory, and show that campo rupestre is fully comparable to and remarkably convergent with both fynbos and kwongkan, and fulfills the criteria for a classic OCBIL. CONCLUSIONS: The increasing threats to campo rupestre are compromising ecosystem services and we argue for the implementation of more effective conservation and restoration strategies.
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique ...physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.
Cancer development is a multistep process in which exosomes play important roles. Exosomes are small vesicles formed in vesicular bodies in the endosomal network. The major role of exosomes seems to ...be the transport of bioactive molecules between cells. Depending on the cell of origin, exosomes are implicated in the regulation of several cellular events, with phenotypic consequences in recipient cells. Cancer derived exosomes (CCEs) are important players in the formation of the tumour microenvironment by (i) enabling the escape of tumour cells to immunological system and help initiating the inflammatory response; (ii) acting in the differentiation of fibroblasts and mesenchymal cells into myofibroblasts; (iii) triggering the angiogenic process; and (iv) enhancing the metastatic evolution of the tumour by promoting epithelial to mesenchymal transformation of tumour cells and by preparing the tumour niche in the new anatomical location. Since the finding that exosomes content resembles that of the cell of origin, they may be regarded as suitable biomarkers for cancer diagnosis, allowing for diagnosis and prognosis via a minimal invasive procedure. Exosome involvement in cancer may open new avenues regarding therapeutics, such as vectors for targeted drug delivery.
Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is the most aggressive type and there is no existing endocrine or targeted therapy. Modulated ...electro-hyperthermia (mEHT) is a non-invasive complementary cancer therapy using an electromagnetic field generated by amplitude modulated 13.56 MHz frequency that induces tumor cell destruction. However, we have demonstrated a strong induction of the heat shock response (HSR) by mEHT, which can result in thermotolerance. We hypothesized that inhibition of the heat shock factor 1 (HSF1) can synergize with mEHT and enhance tumor cell-killing. Thus, we either knocked down the HSF1 gene with a CRISPR/Cas9 lentiviral construct or inhibited HSF1 with a specific small molecule inhibitor: KRIBB11 in vivo. Wild type or HSF1-knockdown 4T1 TNBC cells were inoculated into the mammary gland's fat pad of BALB/c mice. Four mEHT treatments were performed every second day and the tumor growth was followed by ultrasound and caliper. KRIBB11 was administrated intraperitoneally at 50 mg/kg daily for 8 days. HSF1 and Hsp70 expression were assessed. HSF1 knockdown sensitized transduced cancer cells to mEHT and reduced tumor growth. HSF1 mRNA expression was significantly reduced in the KO group when compared to the empty vector group, and consequently mEHT-induced Hsp70 mRNA upregulation diminished in the KO group. Immunohistochemistry (IHC) confirmed the inhibition of Hsp70 upregulation in mEHT HSF1-KO group. Demonstrating the translational potential of HSF1 inhibition, combined therapy of mEHT with KRIBB11 significantly reduced tumor mass compared to either monotherapy. Inhibition of Hsp70 upregulation by mEHT was also supported by qPCR and IHC. In conclusion, we suggest that mEHT-therapy combined with HSF1 inhibition can be a possible new strategy of TNBC treatment with great translational potential.
Abstract
Measured spectral shifts due to intrinsic stellar variability (e.g., pulsations, granulation) and activity (e.g., spots, plages) are the largest source of error for extreme-precision ...radial-velocity (EPRV) exoplanet detection. Several methods are designed to disentangle stellar signals from true center-of-mass shifts due to planets. The Extreme-precision Spectrograph (EXPRES) Stellar Signals Project (ESSP) presents a self-consistent comparison of 22 different methods tested on the same extreme-precision spectroscopic data from EXPRES. Methods derived new activity indicators, constructed models for mapping an indicator to the needed radial-velocity (RV) correction, or separated out shape- and shift-driven RV components. Since no ground truth is known when using real data, relative method performance is assessed using the total and nightly scatter of returned RVs and agreement between the results of different methods. Nearly all submitted methods return a lower RV rms than classic linear decorrelation, but no method is yet consistently reducing the RV rms to sub-meter-per-second levels. There is a concerning lack of agreement between the RVs returned by different methods. These results suggest that continued progress in this field necessitates increased interpretability of methods, high-cadence data to capture stellar signals at all timescales, and continued tests like the ESSP using consistent data sets with more advanced metrics for method performance. Future comparisons should make use of various well-characterized data sets—such as solar data or data with known injected planetary and/or stellar signals—to better understand method performance and whether planetary signals are preserved.
In the last two decades new noninvasive mobile electroencephalography (EEG) solutions have been developed to overcome limitations of conventional clinical EEG and to improve monitoring of patients ...with long‐term conditions. Despite the availability of mobile innovations, their adoption is still very limited. The aim of this study is to review the current state‐of‐the‐art and highlight the main advantages of adopting noninvasive mobile EEG solutions in clinical trials and research studies of people with epilepsy or suspected seizures. Device characteristics are described, and their evaluation is presented. Two authors independently performed a literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A combination of different digital libraries was used (Embase, MEDLINE, Global Health, PsycINFO and https://clinicaltrials.gov/). Twenty‐three full‐text, six conference s, and eight webpages were included, where a total of 14 noninvasive mobile solutions were identified. Published studies demonstrated at different levels how EEG recorded via mobile EEG can be used for visual detection of EEG abnormalities and for the application of automatic‐detection algorithms with acceptable specificity and sensitivity. When the quality of the signal was compared with scalp EEG, many similarities were found in the background activities and power spectrum. Several studies indicated that the experience of patients and health care providers using mobile EEG was positive in different settings. Ongoing trials are focused mostly on improving seizure‐detection accuracy and also on testing and assessing feasibility and acceptability of noninvasive devices in the hospital and at home. This review supports the potential clinical value of noninvasive mobile EEG systems and their advantages in terms of time, technical support, cost, usability, and reliability when applied to seizure detection and management. On the other hand, the limitations of the studies confirmed that future research is needed to provide more evidence regarding feasibility and acceptability in different settings, as well as the data quality and detection accuracy of new noninvasive mobile EEG solutions.
We use Chandra X-ray and Spitzer infrared (IR) observations to explore the active galactic nucleus (AGN) and starburst populations of XMMXCS J2215.9-1738 at z = 1.46, one of the most distant ...spectroscopically confirmed galaxy clusters known. The high-resolution X-ray imaging reveals that the cluster emission is contaminated by point sources that were not resolved in XMM-Newton observations of the system, and have the effect of hardening the spectrum, leading to the previously reported temperature for this system being overestimated. From a joint spectroscopic analysis of the Chandra and XMM-Newton data, the cluster is found to have temperature T = 4.1{sup +0.6}{sub -0.9} keV and luminosity L {sub X} = (2.92{sup +0.24} {sub -0.35}) x 10{sup 44} erg s{sup -1}, extrapolated to a radius of 2 Mpc. As a result of this revised analysis, the cluster is found to lie on the {sigma} {sub v}-T relation, but the cluster remains less luminous than would be expected from self-similar evolution of the local L {sub X}-T relation. Two of the newly discovered X-ray AGNs are cluster members, while a third object, which is also a prominent 24 {mu}m source, is found to have properties consistent with it being a high-redshift, highly obscured object in the background. We find a total of eight >5{sigma} 24 {mu}m sources associated with cluster members (four spectroscopically confirmed and four selected using photometric redshifts) and one additional 24 {mu}m source with two possible optical/near-IR counterparts that may be associated with the cluster. Examining the Infrared Array Camera colors of these sources, we find that one object is likely to be an AGN. Assuming that the other 24 {mu}m sources are powered by star formation, their IR luminosities imply star formation rates {approx}100 M{sub sun} yr{sup -1}. We find that three of these sources are located at projected distances of <250 kpc from the cluster center, suggesting that a large amount of star formation may be taking place in the cluster core, in contrast to clusters at low redshift.
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