Miracle-dz/UniFAR-FTUs huggingface dataset:
Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, ks, is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine ks for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.
Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol

Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies ∼70 eV, substantially lower than that of liquid water ∼78 eV. Monte Carlo simulations for 10–50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of ∼1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol.
Guidance for Antibiotic Selection: Tissue Distribution and Target Site Concentration

To be effective, antibacterials must be active against microorganism(s) and reach sufficient concentrations at the site of infection. Thus, antibacterial distribution and its subsequent tissue concentration are important determinants of antibiotic efficacy. Tissue distribution has many factors that contribute to an antibiotic reaching the target site of infection. This article reviews those factors (ie, basic biochemical and physiochemical properties of cell membranes, carrier-mediated transporters, plasma- and tissue-protein binding, blood flow, inflammation), and the role of impaired tissue distribution in therapeutic outcomes of patients with a variety of infections. Suboptimal target site concentrations may have important clinical implications in such infections, as they may help explain poor therapeutic outcomes. Therefore, we reviewed and summarized the literature for the concentrations of antibacterials as site to serum ratios, providing practical information as a guide for antibiotic selection.
Glucose‐activated RUNX2 phosphorylation promotes endothelial cell proliferation and an angiogenic phenotype

The runt‐related protein‐2 (RUNX2) is a DNA‐binding transcription factor that regulates bone formation, tumor cell metastasis, endothelial cell (EC) proliferation, and angiogenesis. RUNX2 DNA binding is glucose and cell cycle regulated. We propose that glucose may activate RUNX2 through changes in post‐translational phosphorylation that are cell cycle‐specific and will regulate EC function. Glucose increased cell cycle progression in EC through both G2/M and G1 phases with entry into S‐phase occurring only in subconfluent cells. In the absence of nutrients and growth factors (starvation), subconfluent EC were delayed in G1 when RUNX2 expression was reduced. RUNX2 phosphorylation, activation of DNA binding, and pRb phosphorylation were stimulated by glucose and were necessary to promote cell cycle progression. Glucose increased RUNX2 localization at focal subnuclear sites, which co‐incided with RUNX2 occupancy of the cyclin‐dependent kinase (cdk) inhibitor p21Cip1 promoter, a gene normally repressed by RUNX2. Mutation of the RUNX2 cdk phosphorylation site in the C‐terminal domain (S451A.RUNX2) reduced RUNX2 phosphorylation and DNA binding. Expression of this cdk site mutant in EC inhibited glucose‐stimulated differentiation (in vitro tube formation), monolayer wound healing, and proliferation. These results define a novel relationship between glucose‐activated RUNX2 phosphorylation, cell cycle progression, and EC differentiation. These data suggest that inhibition of RUNX2 expression or DNA binding may be a useful strategy to inhibit EC proliferation in tumor angiogenesis. J. Cell. Biochem. 113: 282–292, 2012. © 2011 Wiley Periodicals, Inc.
Spectral prior image constrained compressed sensing (spectral PICCS) for photon-counting computed tomography

Photon-counting computed tomography (PCCT) is an emerging imaging technique that enables multi-energy imaging with only a single scan acquisition. To enable multi-energy imaging, the detected photons corresponding to the full x-ray spectrum are divided into several subgroups of bin data that correspond to narrower energy windows. Consequently, noise in each energy bin increases compared to the full-spectrum data. This work proposes an iterative reconstruction algorithm for noise suppression in the narrower energy bins used in PCCT imaging. The algorithm is based on the framework of prior image constrained compressed sensing (PICCS) and is called spectral PICCS; it uses the full-spectrum image reconstructed using conventional filtered back-projection as the prior image. The spectral PICCS algorithm is implemented using a constrained optimization scheme with adaptive iterative step sizes such that only two tuning parameters are required in most cases. The algorithm was first evaluated using computer simulations, and then validated by both physical phantoms and in vivo swine studies using a research PCCT system. Results from both computer-simulation and experimental studies showed substantial image noise reduction in narrow energy bins (43–73%) without sacrificing CT number accuracy or spatial resolution.
Approaches to communication assessment with children and adults with profound intellectual and multiple disabilities

Abstract Communication assessment of people with profound intellectual and multiple disabilities (PIMD) has seldom been investigated. Here, we explore approaches and decision making in undertaking communication assessments in this group of people. A questionnaire was sent to UK practitioners. The questionnaire elicited information about assessment approaches used and rationales for assessment choices. Fifty‐five speech and language therapists (SLTs) responded. Findings revealed that the Preverbal Communication Schedule, the Affective Communication Assessment and the Checklist of Communication Competence were the most frequently used published assessments. Both published and unpublished assessments were often used. Rationales for assessment choice related to assessment utility, sensitivity to detail and change and their applicability to people with PIMD. Underpinning evidence for assessments was seldom mentioned demonstrating the need for more empirical support for assessments used. Variability in practice and the eclectic use of a range of assessments was evident, underpinned by practice‐focused evidence based on tacit knowledge.
Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS‐induced inflammatory responses via TLR4‐mediated NF‐κB inactivation in RAW 264.7 macrophages

As an attempt to search for bioactive natural products exerting anti‐inflammatory activity, we have evaluated the anti‐inflammatory effects of euscaphic acid (19α‐hydroxyursane‐type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)‐induced RAW 264.7 macrophages. EA concentration‐dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) protein and iNOS, COX‐2, TNF‐α, and IL‐1β mRNA were inhibited by EA in a concentration‐dependent manner. In addition, EA attenuated LPS‐induced DNA binding and transcriptional activity of nuclear factor‐kappa B (NF‐κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF‐κB. Pretreatment with EA significantly inhibited the LPS‐induced phosphorylation of IκB kinase β (IKKβ), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS‐induced clustering of TNF receptor‐associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor‐β‐activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS‐induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF‐κB activations. J. Cell. Biochem. 113: 1936–1946, 2012. © 2012 Wiley Periodicals, Inc.
Review of ultrasound image guidance in external beam radiotherapy part II: intra-fraction motion management and novel applications

Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al Phys. Med. Biol. 60 R77–114). The combination of rapid imaging and zero ionising radiation dose makes US highly suitable for estimating intra-fraction motion. The current paper (Part II of the review) covers this topic. The basic technology for US motion estimation, and its current clinical application to the prostate, is described here, along with recent developments in robust motion-estimation algorithms, and three dimensional (3D) imaging. Together, these are likely to drive an increase in the number of future clinical studies and the range of cancer sites in which US motion management is applied. Also reviewed are selections of existing and proposed novel applications of US imaging to RT. These are driven by exciting developments in structural, functional and molecular US imaging and analytical techniques such as backscatter tissue analysis, elastography, photoacoustography, contrast-specific imaging, dynamic contrast analysis, microvascular and super-resolution imaging, and targeted microbubbles. Such techniques show promise for predicting and measuring the outcome of RT, quantifying normal tissue toxicity, improving tumour definition and defining a biological target volume that describes radiation sensitive regions of the tumour. US offers easy, low cost and efficient integration of these techniques into the RT workflow. US contrast technology also has potential to be used actively to assist RT by manipulating the tumour cell environment and by improving the delivery of radiosensitising agents. Finally, US imaging offers various ways to measure dose in 3D. If technical problems can be overcome, these hold potential for wide-dissemination of cost-effective pre-treatment dose verification and in vivo dose monitoring methods. It is concluded that US imaging could eventually contribute to all aspects of the RT workflow.
ATF5, a possible regulator of osteogenic differentiation in human adipose‐derived stem cells

The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their “stem‐ness” are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose‐derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down‐regulated in a randomized time‐course study of osteogenically differentiated adipose‐derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose‐derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. J. Cell. Biochem. 113: 2744–2753, 2012. © 2012 Wiley Periodicals, Inc.
Physically based principles of cell adhesion mechanosensitivity in tissues

The minimal structural unit that defines living organisms is a single cell. By proliferating and mechanically interacting with each other, cells can build complex organization such as tissues that ultimately organize into even more complex multicellular living organisms, such as mammals, composed of billions of single cells interacting with each other. As opposed to passive materials, living cells actively respond to the mechanical perturbations occurring in their environment. Tissue cell adhesion to its surrounding extracellular matrix or to neighbors is an example of a biological process that adapts to physical cues. The adhesion of tissue cells to their surrounding medium induces the generation of intracellular contraction forces whose amplitude adapts to the mechanical properties of the environment. In turn, solicitation of adhering cells with physical forces, such as blood flow shearing the layer of endothelial cells in the lumen of arteries, reinforces cell adhesion and impacts cell contractility. In biological terms, the sensing of physical signals is transduced into biochemical signaling events that guide cellular responses such as cell differentiation, cell growth and cell death. Regarding the biological and developmental consequences of cell adaptation to mechanical perturbations, understanding mechanotransduction in tissue cell adhesion appears as an important step in numerous fields of biology, such as cancer, regenerative medicine or tissue bioengineering for instance. Physicists were first tempted to view cell adhesion as the wetting transition of a soft bag having a complex, adhesive interaction with the surface. But surprising responses of tissue cell adhesion to mechanical cues challenged this view. This, however, did not exclude that cell adhesion could be understood in physical terms. It meant that new models and descriptions had to be created specifically for these biological issues, and could not straightforwardly be adapted from dead matter. In this review, we present physical concepts of tissue cell adhesion and the unexpected cellular responses to mechanical cues such as external forces and stiffness sensing. We show how biophysical approaches, both experimentally and theoretically, have contributed to our understanding of the regulation of cellular functions through physical force sensing mechanisms. Finally, we discuss the different physical models that could explain how tissue cell adhesion and force sensing can be coupled to internal mechanosensitive processes within the cell body.
Review of laser-driven ion sources and their applications

For many years, laser-driven ion acceleration, mainly proton acceleration, has been proposed and a number of proof-of-principle experiments have been carried out with lasers whose pulse duration was in the nanosecond range. In the 1990s, ion acceleration in a relativistic plasma was demonstrated with ultra-short pulse lasers based on the chirped pulse amplification technique which can provide not only picosecond or femtosecond laser pulse duration, but simultaneously ultra-high peak power of terawatt to petawatt levels. Starting from the year 2000, several groups demonstrated low transverse emittance, tens of MeV proton beams with a conversion efficiency of up to several percent. The laser-accelerated particle beams have a duration of the order of a few picoseconds at the source, an ultra-high peak current and a broad energy spectrum, which make them suitable for many, including several unique, applications. This paper reviews, firstly, the historical background including the early laser–matter interaction studies on energetic ion acceleration relevant to inertial confinement fusion. Secondly, we describe several implemented and proposed mechanisms of proton and/or ion acceleration driven by ultra-short high-intensity lasers. We pay special attention to relatively simple models of several acceleration regimes. The models connect the laser, plasma and proton/ion beam parameters, predicting important features, such as energy spectral shape, optimum conditions and scalings under these conditions for maximum ion energy, conversion efficiency, etc. The models also suggest possible ways to manipulate the proton/ion beams by tailoring the target and irradiation conditions. Thirdly, we review experimental results on proton/ion acceleration, starting with the description of driving lasers. We list experimental results and show general trends of parameter dependences and compare them with the theoretical predictions and simulations. The fourth topic includes a review of scientific, industrial and medical applications of laser-driven proton or ion sources, some of which have already been established, while the others are yet to be demonstrated. In most applications, the laser-driven ion sources are complementary to the conventional accelerators, exhibiting significantly different properties. Finally, we summarize the paper.
Towards the identification of new physics through quark flavour violating processes

We outline a systematic strategy that should help in this decade to identify new physics (NP) beyond the standard model (SM) by means of quark flavour violating processes, and thereby extend the picture of short distance physics down to scales as short as 10−20 m and even shorter distance scales corresponding to energies of 100 TeV. Rather than using all of the possible flavour-violating observables that will be measured in the coming years at the LHC, SuperKEKB and in Kaon physics dedicated experiments at CERN, J-PARC and Fermilab, we concentrate on those observables that are theoretically clean and very sensitive to NP. Assuming that the data on the selected observables will be very precise, we stress the importance of correlations between these observables as well as of future precise calculations of non-perturbative parameters by means of lattice QCD simulations with dynamical fermions. Our strategy consists of twelve steps, which we will discuss in detail while illustrating the possible outcomes with the help of the SM, models with constrained minimal flavour violation (CMFV), MFV at large and models with tree-level flavour changing neutral currents mediated by neutral gauge bosons and scalars. We will also briefly summarize the status of a number of concrete models. We propose DNA charts that exhibit correlations between flavour observables in different NP scenarios. Models with new left-handed and/or right-handed currents and non-MFV interactions can be distinguished transparently in this manner. We emphasize the important role of the stringent CMFV relations between various observables as standard candles of flavour physics. The pattern of deviations from these relations may help in identifying the correct NP scenario. The success of this program will be very much facilitated through direct signals of NP at the LHC, even if the LHC will not be able to probe the physics at scales shorter than 4 × 10−20 m. We also emphasize the importance of lepton flavour violation, electric dipole moments, and (g − 2)e, μ in these studies.
Neurobiology of Violence

Neurobiology of Violence is a thoughtful, well-written, and user-friendly discussion of the factors contributing to violent behavior. Physicians in clinical practice, especially in the major cities of the United States, have become increasingly concerned about the level of violence prevalent in urban centers. This is a book with some answers about the etiology of violence. The author's wisdom is evident in his opening to chapter 1: "Everybody knows intuitively what violence is. Unfortunately, intuitions differ. " He thoughtfully reviews the literature and how various authors have done their studies and continues with his perception of "the consensus opinion of scientists working in a given field. " He then gives his own opinion, adding to our knowledge. At the beginning of the book are definitions, which are important to worthwhile research. How violence has been reported, for example, as a part of population surveys, arrest reports, and so on is discussed, with the