Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. ...However, the ubiquitous non-genetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. Some are pushed into nearby, latent attractor states of the gene regulatory network which resemble evolutionary ancient or early developmental gene expression programs that confer stemness and resilience. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering non-genetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.
Much theoretical and experimental attention has been focused on the electrical switching of the antiferromagnetic (AFM) Néel vector via spin-orbit torque. Measurements employing multiterminal ...patterned structures of Pt/AFM show recurring signals of the supposedly planar Hall effect and magnetoresistance, implying AFM switching. We show in this Letter that similar signals have been observed in structures with and without the AFM layer, and of an even larger magnitude using different metals and substrates. These may not be the conclusive evidence of spin-orbit torque switching of AFM, but the thermal artifacts of patterned metal structure on substrate. Large current densities in the metallic devices, beyond the Ohmic regime, can generate unintended anisotropic thermal gradients and voltages. AFM switching requires unequivocal detection of the AFM Néel vector before and after SOT switching.
Atmospheric blocking due to anomalous, persistent meandering of the jet stream often causes weather extremes in the midlatitudes. Despite its ubiquity, the onset mechanism of blocking is not well ...understood. Here we demonstrate with meteorological data that there exists a close analogy between blocking and traffic congestion on a highway, and that they can be described by a common mathematical theory. The theory predicts that the jet stream has a capacity for the flux of wave activity (a measure of meandering), just as the highway has traffic capacity, and when it is exceeded, blocking manifests as congestion. Stationary waves modulate the jet stream's capacity for transient waves and localize block formation. Climate change likely affects blocking frequency by modifying the jet stream's proximity to capacity.
The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for γ-ray astronomy, but the overall spectrum of the EBL ...between 0.1 and 1000 μm has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4, combined with a determination of galaxy-SED-type fractions. These are based on fitting Spitzer Wide-Area Infrared Extragalactic Survey (SWIRE) templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and active galactic nucleus (AGN) galaxies in that redshift range are estimated, and two alternative extrapolations of SED types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the ultraviolet (UV) to the infrared (IR), the evolving star formation rate density of the Universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, another observationally based model and observational data. The EBL uncertainties in our modelling based directly on the data are quantified, and their consequences for attenuation of very-high-energy γ-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from IR and γ-ray astronomy are needed in order to reduce the uncertainties in the far-IR.
The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we ...systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction.
Zilverstand et al. find that behaviors in drug addiction are closely tied to brain impairments underlying drug cue reactivity, decision making, inhibitory control, and social-emotional processing. Neuroimaging biomarkers can also be used to predict initiation and progression of drug addiction.
The study aimed to determine the long-term Staphylococcus aureus colonization patterns and strain relatedness, and the association between maternal and infant colonization in infancy.
A birth cohort ...study was conducted from January 2012 to November 2014. Nasopharyngeal swabs for S. aureus detection were collected from infants at the age of 1, 2, 4, 6 and 12 months and from mothers when their children were 1-month-old.
In total, 254 samples were collected at each planned visit during the first 12-month study. The prevalence of S. aureus colonization decreased in the first year of life, ranging from 61.0% (155/254) at the age of 1 month to 12.2% (31/254) at 12 months. Persistent colonization, defined as a positive culture on four or five occasions, was detected in only 13.8% (35/254) of carriers. Most of the persistent carriers were colonized with methicillin-resistant S. aureus (MRSA) only, and among persistent MRSA carriers, 61.1% (11/18) had indistinguishable genotypes. Of the mothers with MRSA colonization, 77.1% (27/35) had infants who were concomitantly colonized at the age of 1 month; 70.4% (19/27) of the infant–mother paired isolates belonged to indistinguishable or related subtypes, which suggests that surrounding carriers, probably their mothers, may be the possible source for MRSA acquisition in early infancy.
Staphylococcus aureus colonization including MRSA was commonly observed in our cohort. Strains of persistent MRSA among infant–mother pairs were usually of indistinguishable genotypes. Therefore, horizontal spread within households is possibly an important factor related to infant MRSA colonization.
One-shot image semantic segmentation poses a challenging task of recognizing the object regions from unseen categories with only one annotated example as supervision. In this article, we propose a ...simple yet effective similarity guidance network to tackle the one-shot (SG-One) segmentation problem. We aim at predicting the segmentation mask of a query image with the reference to one densely labeled support image of the same category. To obtain the robust representative feature of the support image, we first adopt a masked average pooling strategy for producing the guidance features by only taking the pixels belonging to the support image into account. We then leverage the cosine similarity to build the relationship between the guidance features and features of pixels from the query image. In this way, the possibilities embedded in the produced similarity maps can be adopted to guide the process of segmenting objects. Furthermore, our SG-One is a unified framework that can efficiently process both support and query images within one network and be learned in an end-to-end manner. We conduct extensive experiments on Pascal VOC 2012. In particular, our SG-One achieves the mIoU score of 46.3%, surpassing the baseline methods.
During regulatory review of clinical pharmacology data in new drug applications and biologics license applications, questions are routinely asked about how intrinsic factors (e.g., organ dysfunction, ...age, and genetics) and extrinsic factors (e.g., drug–drug interactions) might influence dose–response and exposure–response and about the impact of these individual factors on the efficacy and safety of the candidate compound. Physiologically based pharmacokinetic (PBPK) modeling and simulation is one of the tools that can be used to address these critical questions.
Clinical Pharmacology & Therapeutics (2012); 91 3, 542–549. doi:10.1038/clpt.2011.320
The objective of this study was to determine the usefulness of augmented reality (AR) in teaching. An experiment was conducted to examine children's learning performances, which included the number ...of errors they made, their ability to remember the content of what they had read and their satisfaction with the three types of teaching materials, including a picture book, physical interactions and an AR graphic book. The three teaching materials were aimed to respectively demonstrate the characteristics of six bacteria with 2D graphics, 3D physical objects, and 3D virtual objects. Seventy‐two fifth‐grade children were randomly selected to participate in the study, and they were divided into three groups, each of which used the assigned teaching material to learn the name of the six different bacteria in intervals of 1, 2 and 3 min. Results showed that the AR graphic book offers a practical and hands‐on way for children to explore and learn about the bacteria. Follow‐up interviews indicated that the children liked the AR graphic book the most, and they preferred it to the other materials.
Lay Description
What is currently known about Augmented Reality and learning?
Augmented reality (AR) provides a new perspective for learning by allowing learners to visualize complex spatial relationships and concepts.
What the paper adds to the subject matter?
AR improves learning performances to a similar extent as the most used teaching materials (both picture books and physical interactions) do.
AR not only facilitates learning but also increases learning motivations better than conventional teaching materials do.
The implications of study findings for practitioners.
If children feel bored about reading textbooks, give them AR (because AR effectively enhances learning and children are more motivated when using AR).
AR teaching material is a good alternative to conventional picture book and physical interactions.
Multiferroics have attracted strong interest for potential applications where electric fields control magnetic order. The ultimate speed of control via magnetoelectric coupling, however, remains ...largely unexplored. Here, we report an experiment in which we drove spin dynamics in multiferroic TbMnO3 with an intense few-cycle terahertz (THz) light pulse tuned to resonance with an electromagnon, an electric-dipole active spin excitation. We observed the resulting spin motion using time-resolved resonant soft x-ray diffraction. Our results show that it is possible to directly manipulate atomic-scale magnetic structures with the electric field of light on a sub-picosecond time scale.
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