Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of intensity- and spatial-based image descriptors to characterise and quantify neoplastic lesions in positron emission tomography

Intra-tumour biological heterogeneity is a characteristic shared by all cancers and is thought to contribute to treatment failure. Within-lesion spatial heterogeneity can be qualitatively visualised in Positron Emission Tomography (PET) imaging. Quantifying the variability of the biological processes and the complexity of the signal being measured in PET oncology is essential. The aim of this thesis was to develop and validate intensityand spatial-based metrics to quantitatively account for the complexity of radiotracer uptake and to annotate intra-tumour PET heterogeneity. Texture analysis was employed to characterise the in vivo tumour heterogeneity of cell proliferation in breast tumours using 18 F-fluorothymidine ( 18 F-FLT) PET. The repeatability of the feature measurements was assessed in patients who had two PET scans prior to therapy. Associations between features at baseline and clinical response measured after three cycles of chemotherapy were explored. Associations between feature changes at one week after the start of chemotherapy and clinical response were also explored. Furthermore, the influence of analysis parameters and imaging protocols were studied. A subset of textural features produced reliable measurements and were associated with treatment response. A technique based on multifractal analysis was also developed for characterising the space-filling properties of an object of interest in PET imaging. The derived spatial index was further combined with intensity metrics and the technique was shown to correct for partial volume effects. The method was illustrated on mathematical objects, validated on test-retest 18 F-FLT PET clinical data and applied to realistic PET simulations. This work contributes to the demonstration that intensityand spatial-based image analysis methods can supplement existing methods in PET quantification studies. These techniques provide some improvements on existing methods to derive classical quantitative PET indices and permit extraction of additional information to further characterise patient populations in the clinical setting and in relation to therapy.
Phytochelatin synthase OsPCS1 plays a crucial role in reducing arsenic levels in rice grains

Reduction of the level of arsenic (As) in rice grains is an important challenge for agriculture. A recent study reported that the OsABCC1 transporter prevents the accumulation of As in grains by sequestering As-phytochelatin complexes into vacuoles in the upper nodes. However, how phytochelatins are provided in response to As remains unclear. Here, we show that the phytochelatin synthase OsPCS1 plays a crucial role in reducing As levels in rice grains. Using a forward genetic approach, we isolated two rice mutants (has1 and has2) in which As levels were much higher in grains but significantly lower in node I compared with the wild type. Map-based cloning identified the genes responsible as OsABCC1 in has1 and OsPCS1 in has2. The levels of As in grains and node I were similar between the two mutants, suggesting that OsABCC1 preferentially cooperates with OsPCS1 to sequester As, although rice has another phytochelatin synthase, OsPCS2. An in vitro phytochelatin synthesis assay indicated that OsPCS1 was more sensitive to activation by As than by cadmium, whereas OsPCS2 was more weakly activated by As than by cadmium. Transgenic plants highly expressing OsPCS1 showed significantly lower As levels in grains than did wild-type plants. Our results provide new knowledge of the relative contribution of rice PCS paralogs to As sequestration and suggest a good candidate tool to reduce As levels in rice grains.
Peer Observation : An Exploration of a Cross-Discipline Observation Project

In this article the authors compare two phases of an ongoing, annual online peer observation project at the Open University. Adopting a non-managerialist approach, the project aims to give teachers a renewed sense of collegiality, allowing them to take responsibility for aspects of their professional development and share practice points. While the first phase focused on a single discipline group in languages, the second brought together teachers in languages with teachers of Math, Computing, and Technology, all employing Elluminate Live as their online teaching platform. The authors comment on congruent and divergent gains emerging from the two phases.
Neonatal Brain Metabolite Concentrations: An In Vivo Magnetic Resonance Spectroscopy Study with a Clinical MR System at 3 Tesla

Brain metabolite concentrations change dynamically throughout development, especially during early childhood. The purpose of this study was to investigate the brain metabolite concentrations of neonates (postconceptional age (PCA): 30 to 43 weeks) using single-voxel magnetic resonance spectroscopy (MRS) and to discuss the relationships between the changes in the concentrations of such metabolites and brain development during the neonatal period. A total of 83 neonatal subjects were included using the following criteria: the neonates had to be free of radiological abnormalities, organic illness, and neurological symptoms; the MR spectra had to have signal-to-noise ratios ≥ 4; and the estimated metabolite concentrations had to display Cramér-Rao lower bounds of ≤ 30%. MRS data (echo time/repetition time, 30/5000 ms; 3T) were acquired from the basal ganglia (BG), centrum semiovale (CS), and the cerebellum. The concentrations of five metabolites were measured: creatine, choline, N-acetylaspartate, myo-inositol, and glutamate/glutamine complex (Glx). One hundred and eighty-four MR spectra were obtained (83 BG, 77 CS, and 24 cerebellum spectra). Creatine, N-acetylaspartate, and Glx displayed increases in their concentrations with PCA. Choline was not correlated with PCA in any region. As for myo-inositol, its concentration decreased with PCA in the BG, whereas it increased with PCA in the cerebellum. Quantitative brain metabolite concentrations and their changes during the neonatal period were assessed. Although the observed changes were partly similar to those detected in previous reports, our results are with more subjects (n = 83), and higher magnetic field (3T). The metabolite concentrations examined in this study and their changes are clinically useful indices of neonatal brain development.
Hybrid crosses and the genetic basis of interspecific divergence in lifespan in Pristionchus nematodes

Characterizing the genetic basis of among‐species variation in lifespan is a major goal of evolutionary gerontology research, but the very feature that defines separate species – the inability to interbreed – makes achieving this goal impractical, if not impossible, for most taxa. Pristionchus nematodes provide an intriguing system for tackling this problem, as female lifespan varies among species that can be crossed to form viable (although infertile) hybrids. By conducting reciprocal crosses among three species – two dioecious (long‐lived Pristionchus exspectatus and short‐lived Pristionchus arcanus) and one androdioecious (short‐lived Pristionchus pacificus) – we found that female lifespan was long for all hybrids, consistent with the hypothesis that the relatively short lifespans seen for P. pacificus hermaphrodites and P. arcanus females are caused by independent, recessive alleles that are masked in hybrid genomes. Cross‐direction had a small effect on survivorship for crosses involving P. exspectatus, indicating that nuclear–mitochondrial interactions may also influence Pristionchus longevity. Our findings suggest that long lifespan in P. exspectatus reflects the realization of an ancestral potential for extended longevity in the P. pacificus species complex. This work demonstrates the utility of interspecific hybrids for ageing research and provides a foundation for future work on the genetic architecture of interspecific lifespan variation.
Regulation of p53 during senescence in normal human keratinocytes

p53, the guardian of the genome, is a tumor suppressor protein and critical for the genomic integrity of the cells. Many studies have shown that intracellular level of p53 is enhanced during replicative senescence in normal fibroblasts, and the enhanced level of p53 is viewed as the cause of senescence. Here, we report that, unlike in normal fibroblasts, the level of intracellular p53 reduces during replicative senescence and oncogene‐induced senescence (OIS) in normal human keratinocytes (NHKs). We found that the intracellular p53 level was also decreased in age‐dependent manner in normal human epithelial tissues. Senescent NHKs exhibited an enhanced level of p16INK4A, induced G2 cell cycle arrest, and lowered the p53 expression and transactivation activity. We found that low level of p53 in senescent NHKs was due to reduced transcription of p53. The methylation status at the p53 promoter was not altered during senescence, but senescent NHKs exhibited notably lower level of acetylated histone 3 (H3) at the p53 promoter in comparison with rapidly proliferating cells. Moreover, p53 knockdown in rapidly proliferating NHKs resulted in the disruption of fidelity in repaired DNA. Taken together, our study demonstrates that p53 level is diminished during replicative senescence and OIS and that such diminution is associated with H3 deacetylation at the p53 promoter. The reduced intracellular p53 level in keratinocytes of the elderly could be a contributing factor for more frequent development of epithelial cancer in the elderly because of the loss of genomic integrity of cells.
Stability in ATM networks

We address the issues of stability in ATM networks. A network is stable if and only if all the packets have a bounded delay. We first consider ATM networks with an FCFS scheduling policy. We then study networks with a priority driven scheduling policy. For each network, we develop criteria for testing the stability of an ATM network and methods of deriving delay bounds in a stable network. In previous work, the Cruz-Gallager-Parekh (1991, 1992) ring has been a "benchmark" architecture to study the stability problem. For example, Gallager and Parerkh (1993) claimed that the ring with a size of no more than four switches is stable when the total utilization of the links is less than 100%. We validated this result. Furthermore, we find that a ring with large number of switches is stable if the utilization of each link is less than or equal to 73%.
Reactive Ion Etching of Columnar Nanostructured ${\rm TiO}_{2}$ Thin Films for Modified Relative Humidity Sensor Response Time

A CF4 dry etch recipe for TiO2 was optimized for nanostructured thin films. The impact of our etching process and ultraviolet irradiation of nanostructured relative humidity (RH) sensors was studied. Reactive ion etching of titanium dioxide decreased device adsorption response time by opening high diffusivity channels while retaining the high surface area and high dynamic range of the interdigitated electrode device. The full electrical response (impedance and phase) and response time of our sensors was studied as a function of etch duration. Using a TiO2 etch recipe consisting of CF4 produced large changes to RH sensor electrical response and introduced a large hysteresis. As a result of significant microstructural change, the adsorption response time of the RH sensors is greatly improved from ap 150 ms to an instrument-limited 50 ms. The adsorption times are at least six times faster than previous, thinner sensors. However, the current sensors do not recover as well as previous sensors, possibly due to nodular defects observed here and which are absent in previous devices. Although sensor step desorption times improved from an unetched ap 130 ms to the instrument limit of 50 ms, full recovery times increased beyond ap 3 s. When the etch treatment was followed by a 48 h ultraviolet treatment, the hysteresis introduced by the CF4 etch was significantly reduced, without reducing the improvement in response time.
Cadmium-induced apoptosis in oyster hemocytes involves disturbance of cellular energy balance but no mitochondrial permeability transition

SUMMARY Exposure to environmentally prevalent heavy metals such as cadmium can have detrimental effects on a variety of commercially and ecologically important species such as oysters. Since Cd2+ is known to induce apoptosis in immune cells of vertebrates, we have investigated the effects of this metal on isolated oyster hemocytes, the main cellular immune defense in mollusks. Enhanced apoptosis of these cells could conceivably create immunosuppressed conditions in these organisms and result in reduced disease resistance and increased opportunistic infection, resulting in decline of their populations. Cd2+ exposure induced apoptosis in oyster hemocytes in a dose-dependent manner in the range of 10-100 μmol l-1, as indicated by the translocation of phosphatidylserine to the outer leaflet of the plasma membrane. At higher concentrations (200-1000 μmol l-1), there was no further increase in apoptosis but a significant increase in the level of necrosis. In stark contrast to vertebrate immune cells, there was no decrease in the mitochondrial membrane potential or activation of caspases in response to Cd2+ in the apoptotic range. Surprisingly, Cd2+ exposure in this range did cause a significant decrease in intracellular ATP levels, indicating a severe disturbance of energy metabolism. Similarly, Cd2+ exposure of isolated mitochondria resulted in partial uncoupling of mitochondria but no difference in mitochondrial membrane potential. The results demonstrate that the important environmental pollutant Cd2+ induces apoptosis in oyster immune cells and does so through a mitochondria/caspase-independent pathway, suggesting that a novel, perhaps ancient, apoptotic pathway is active in these cells. Furthermore, it appears that the observed decrease in ATP production during apoptosis is not due to the loss of the mitochondrial proton-motive force but is more likely to be due to inhibition of the F0/F1-ATPase and/or mitochondrial ADP/ATP or substrate transport.
Modeling tracer kinetics in dynamic Gd‐DTPA MR imaging

Three major models (from Tofts, Larsson, and Brix) for collecting and analyzing dynamic MRI gadolinium‐diethylenetriamine penta‐acetic acid (Gd‐DTPA) data are examined. All models use compartments representing the blood plasma and the abnormal extravascular extracellular space (EES), and they are intercompatible. All measure combinations of three parameters: (1) kpsρ is the influx volume transfer constant (min−1), or permeability surface area product per unit volume of tissue, between plasma and EES; (2) ve is the volume of EES space per unit volume of tissue (0 < ve < 1); and (3) kep, the efflux rate constant (min−1), is the ratio of the first two parameters (kep = kpsρ/ve). The ratio kep is the simplest to measure, requiring only signal linearity with Gd tracer concentration or, alternatively, a measurement of T1 before injection of Gd (T10). To measure the physiologic parameters kpsρ and ve separately requires knowledge of T10 and of the tissue relaxivity R1 (≈︁ in vitro value).
Two histological markers reveal a similar photoperiodic difference in the volume of the high vocal center in male European starlings

Most studies of seasonal changes in the avian song control system have used Nissl stains to characterize the nuclei. More recent work has indicated that changes in nucleus volume evident in Nissl‐stained tissue are not always apparent when investigated with other histochemical criteria. In this experiment, we used two different markers (Nissl stain and α2‐adrenergic receptor autoradiography) to characterize changes in the song system of European starlings (Sturnus vulgaris). Fluctuating levels of circulating testosterone (T) appear to be causally related to seasonal changes in the song system. Therefore, we used photoperiod manipulations to place male starlings into different physiological conditions. Photosensitive male starlings were placed on 11L:13D or 16L:8D photoperiods for at least 5 months. Birds on 11L:13D have enlarged gonads and circulating T. In contrast, starlings maintained on 16L:8D initially show marked gonadal growth. However, after about 6–8 weeks the birds are photorefractory (i.e., the gonads are regressed and T falls to undetectable levels). The volume of the high vocal center (HVC) was 44% larger in the 11L:13D than in 16L:8D birds in Nissl‐stained tissue. The density of α2‐adrenergic receptors as determined by in vitro receptor autoradiography with [3H]p‐amino‐lonidine (PAC) is higher in HVC than in the surrounding neostriatum, clearly delineating the boundaries of the nucleus. We reconstructed the volume of HVC using PAC autoradiography on adjacent sections. The results were identical to those from the Nissl‐stained tissue. Thus, two histochemical markers indicate a photoperiodic difference in HVC volume of male starlings. © 1995 Wiley‐Liss, Inc.
Trade and the Global Recession

We develop a dynamic multi-country general equilibrium model to investigate forces acting on the global economy during the Great Recession and ensuing recovery. Our multi-sector framework accounts completely for countries' trade, investment, production, and GDPs in terms of different sets of shocks. Applying the model to 21 countries, we investigate the 29 percent drop in world trade in manufactures during 2008-2009. A shift in final spending away from tradable sectors, largely caused by declines in durables investment efficiency, account for most of the collapse in trade relative to GDP. Shocks to trade frictions, productivity, and demand play minor roles.
Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish.
Fluorescence Lifetime Imaging of Apoptosis

Genetically encoded fluorescence resonance energy transfer (FRET) reporters are powerful tools for analyzing cell signaling and function at single-cell resolution in standard 2D cell cultures, but these reporters rarely have been applied to 3D environments. FRET interactions between donor and acceptor molecules typically are determined by changes in relative fluorescence intensities, but wavelength-dependent differences in light absorption complicate this analysis method in 3D settings. Herein we report fluorescence lifetime imaging microscopy (FLIM) with phasor analysis, a method that displays fluorescence lifetimes on a pixel-wise basis in real time to quantify apoptosis in breast cancer cells stably expressing a genetically encoded FRET reporter. This microscopic imaging technology allowed us to identify treatment-induced apoptosis in single breast cancer cells in environments ranging from 2D cell culture, spheroids with cancer and bone marrow stromal cells, and living mice with orthotopic human breast cancer xenografts. Using this imaging strategy, we showed that combined metabolic therapy targeting glycolysis and glutamine pathways significantly reduced overall breast cancer metabolism and induced apoptosis. We also determined that distinct subpopulations of bone marrow stromal cells control the resistance of breast cancer cells to chemotherapy, suggesting heterogeneity of treatment responses of malignant cells in different bone marrow niches. Overall, this study establishes FLIM with phasor analysis as an imaging tool for apoptosis in cell-based assays and living mice, enabling real-time, cellular-level assessment of treatment efficacy and heterogeneity.
Regulation of osmotic stress transcription factor 1 (Ostf1) in tilapia (Oreochromis mossambicus) gill epithelium during salinity stress

SUMMARY Mechanisms of induction of osmotic stress transcription factor 1 (Ostf1) were analyzed in gill epithelium of tilapia exposed to salinity stress. Experiments with primary cultures of gill epithelial cells revealed that hyperosmotic Ostf1 induction was independent of systemic factors. In addition, the synthetic glucocorticoid receptor agonist dexamethasone did not affect Ostf1 levels, arguing against cortisol being the signal for Ostf1 induction during hyperosmotic stress. Exposure of primary gill cell cultures to a hyperosmotic agent that is cell permeable and non-hypertonic (glycerol) did not trigger Ostf1 induction. However, when gill cells were exposed to hypertonicity (either in the form of NaCl or other forms) Ostf1 was rapidly and significantly induced. Analysis of hnRNA and mRNA levels revealed that Ostf1 upregulation in gill cells of intact fish and primary cultures of gill epithelial cells was mediated by transient mRNA stabilization. In addition to the initial transient mRNA stabilization a subsequent transcriptional induction of Ostf1 was observed. In cultured gill cells increase in Ostf1 mRNA synthesis was stable and very potent, whereas in gill cells of intact fish this increase was transient. This observation suggests positive feedback by Ostf1 or one of its targets and negative feedback by systemic factors on Ostf1 transcription. We conclude that Ostf1 induction in gill epithelial cells of tilapia exposed to salinity stress (1) is independent of cortisol or other systemic factors; (2) depends on hypertonicity as the signal; and (3) is based on transient mRNA stabilization. Moreover, our data on primary cell cultures show that systemic signals are necessary to prevent sustained transcriptional induction of Ostf1 during hyperosmotic stress, indicating feedback regulation and a high degree of complexity of osmosensing and signaling networks in euryhaline fishes.
Multielement and chlorinated hydrocarbon analysis of municipal sewage sludges of American cities

w An analytical survey of 68 elements, dieldrin, and polychlorinated biphenyls (PCB's) was conducted in municipal sewage sludges sampled during 1972-73 from 16 American cities using several instrumental methods. Unusually elevated concentrations of certain toxic elements were found in sludges from specific cities. Relatively high levels of gold and mercury in sludge from San Francisco possibly derived from geochemical sources. Fluorine was high in several cities which fluoridate their water. PCB's were highest in sludge from Schenectady. Municipal sewage sludges result from the treatment of city sewage wastes containing human excreta, residues from food, and sometimes lumber processing, and a galaxy of industrial chemicals. These latter chemicals may derive from the manufacture of paper, textiles, rubber, plastics, leather, paints, detergents, drugs, agricultural chemicals and electrical