For x- and gamma- irradiations delivering entrance doses from 2- up to 1000 Gy to commercial 1.0 mm thick borosilicate glass microscope slides, study has been made of their thermoluminescence yield. With an effective atomic number of 10.6 (approximating bone equivalence), photon energy dependency is apparent in the low x-ray energy range, with interplay between the photoelectric effect and attenuation. As an example, over the examined dose range, at 120 kVp the photon sensitivity has been found to be some 5× that of 60Co gamma irradiations, also with repeatability to within ~1%. The glow-curves, taking the form of a single prominent broad peak, have been deconvolved yielding at best fit a total of five peaks, the associated activation energies and frequency factors also being obtained. The results indicate borosilicate glass slides to offer promising performance as a low-cost passive radiation dosimeter, with utility for both radiotherapy and industrial applications.
We explore the utility of controlled low-doses (0.2-100 Gy) of photon irradiation as initiators of structural alteration in carbon-rich materials. To-date our work on carbon has focused on β-, x- and γ-irradiations and the monitoring of radiotherapeutic doses (from a few Gy up to some tens of Gy) on the basis of the thermoluminescence (TL) signal, also via Raman and X-ray photo-spectroscopy (XPS), providing analysis of the dose dependence of single-walled carbon nanotubes (SWCNT). The work has been extended herein to investigate possibilities for analysis of structural alterations in graphite-rich mixtures, use being made of two grades of graphite-rich pencil lead, 8H and 2B, both being in the form produced for mechanical pencils (propelling or clutch pencils). 2B has the greater graphite content (approaching 98 wt %), 8H being a mixture of C, O, Al and Si (with respective weight percentages 39.2, 38.2, 9.8 and 12.8). Working on media pre-annealed at 400 °C, both have subsequently been irradiated to penetrating photon-mediated doses. Raman spectroscopy analysis has been carried out using a 532 nm laser Raman spectrometer, while for samples irradiated to doses from 1 to 40 Gy, XPS spectra were acquired using Al Kα sources (hv ∼1400 eV); carbon KLL Auger peaks were acquired using 50 eV Pass Energy. At these relatively low doses, alterations in order-disorder are clearly observed, defect generation and internal annealing competing as dominating effects across the dose range.
The present study continues research into the utilisation of carbonaceous media for medical radiation dosimetry, focusing on the effects of surface area-to-volume ratio and carbon content on structural interaction alterations and dosimetric properties in sheet- and bead-type graphitic materials (with the respective carbon content of ∼98 wt% and ∼90 wt%). Using 60Co gamma-rays and doses from 0.5 Gy to 20 Gy, the study has been made of the response of commercially available graphite in the form of 0.1 mm, 0.2 mm, 0.3 mm and 0.5 mm thick sheets, also of activated carbon beads. Confocal Raman and photoluminescence spectroscopy have been employed, examining radiation-induced structural interaction alterations. Dose-dependent variation in the Raman intensity ratio ID/IG relates to the varying dominance of defect generation and dose-driven defect annealing. Of the various thickness graphite sheets, the 0.1 mm thick medium possesses the greatest surface area-to-volume ratio. Perhaps unsurprisingly, it also exhibits the greatest thermoluminescence (TL) yield compared to that of the other carbonaceous sheet foils used herein. Moreover, the second greatest mass-normalised TL yield has been observed to be that of the porous beads, reflected in the greater defect density (ID/IG > 2) when compared to the other media, due in part to their inherent feature of large internal surface area. Considering the challenge posed in matching skin thickness with skin dose, the near tissue equivalent graphite sheets show particular promise as a skin dosimeter, sensitive as a function of depth.
Epithelial-mesenchymal transition (EMT) is increasingly explored in cancer progression. Considering that triple negative (TN) breast cancer has the poorest survival among molecular subtypes, we investigated 49 TN, 45 luminal and 25 HER2-enriched female breast carcinomas for EMT expression (using E-cadherin and vimentin immunohistochemistry) against lymphovascular and/or lymph node invasion. E-cadherin and vimentin expressions were semi-quantitated for positive- cancer cells (0=0-<1%, 1=1-10%, 2 =11-50%, 3=>50%) and staining intensity (0=negative, 1=weak, 2=moderate, 3=strong), with final score (low=0-4 and high=6-9) derived by multiplying percentage and intensity scores for each marker. Low E-cadherin and/or high vimentin scores defined EMT positivity. Low E-cadherin co-existing with high vimentin defined "complete" (EMT-CV), while low E-cadherin (EMT-C) or high vimentin (EMT-V) occurring independently defined "partial" subsets. 38 (31.9%) cancers expressed EMT, while 59.2 % TN, 13.3% luminal and 12% HER2-enriched cancers expressed EMT (p<0.05). Among the cancers with lymphovascular and/or lymph node invasion, EMT positivity by molecular types were 66.7% TN, 7.4% luminal and 11.8% HER2-enriched (p<0.05). Although EMT-V, associated with stem-cell properties was the dominant TN EMT profile, EMT-CV, a profile linked to vascular metastases, was encountered only in TN. EMT appears important in TN cancer and different EMT profiles may be associated with its aggressive nature.
The sensitivity of a novel silica-based fibre-form thermoluminescence dosimeter was tested off-site of a rare-earths processing plant, investigating the potential for obtaining baseline measurements of naturally occurring radioactive materials. The dosimeter, a Ge-doped collapsed photonic crystal fibre (PCFc) co-doped with B, was calibrated against commercially available thermoluminescent dosimetry (TLD) (TLD-200 and TLD-100) using a bremsstrahlung (tube-based) x-ray source. Eight sampling sites within 1 to 20 km of the perimeter of the rare-earth facility were identified, the TLDs (silica- as well as TLD-200 and TLD-100) in each case being buried within the soil at fixed depth, allowing measurements to be obtained, in this case for protracted periods of exposure of between two to eight months. The values of the dose were then compared against values projected on the basis of radioactivity measurements of the associated soils, obtained via high-purity germanium gamma-ray spectrometry. Accord was found in relative terms between the TL evaluations at each site and the associated spectroscopic results. Thus said, in absolute terms, the TL evaluated doses were typically less than those derived from gamma-ray spectroscopy, by ∼50% in the case of PCFc-Ge. Gamma spectrometry analysis typically provided an upper limit to the projected dose, and the Marinelli beaker contents were formed from sieving to provide a homogenous well-packed medium. However, with the radioactivity per unit mass typically greater for smaller particles, with preferential adsorption on the surface and the surface area per unit volume increasing with decrease in radius, this made for an elevated dose estimate. Prevailing concentrations of key naturally occurring radionuclides in soil,226Ra,232Th and40K, were also determined, together with radiological dose evaluation. To date, the area under investigation, although including a rare-earth processing facility, gives no cause for concern from radiological impact. The current study reveals the suitability of the optical fibre based micro-dosimeter for all-weather monitoring of low-level environmental radioactivity.
At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9th and 10th order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.
Study has been made of the thermoluminescence yield of various novel tailor-made silica fibres, 6 and 8 mol % Ge-doped, with four differing outer dimensions, comprised of flat and cylindrical shapes, subjected to electron irradiation. Main thermoluminescence dosimetric characteristics have been investigated, including the glow curve, dose response, energy dependence, minimum detectable dose, effective atomic number, linearity of index and sensitivity of the fibres. The studies have also established the uncertainties involved as well as the stability of response in terms of fading effect, reproducibility and annealing. In addition, dose-rate dependence was accounted for as this has the potential to be a significant factor in radiotherapy applications. The 6 and 8 mol % fibres have been found to provide highly linear dose response within the range 1 to 4 Gy, the smallest size flat fibre, 6 mol% Ge-doped, showing the greatest response by a factor of 1.1 with respect to the highly popular LiF phosphor-based medium TLD100. All of the fibres also showed excellent reproducibility with a standard deviation of < 2% and < 4% for 6 and 8 mol % Ge-doped fibres respectively. For fading evaluation, the smallest 6 mol% Ge-doped dimension flat fibre, i.e., 85 × 270 μm displayed the lowest signal loss within 120 days post-irradiation, at around 26.9% also showing a response superior to that of all of the other fibres. Moreover, all the fibres and TLD-100 chips showed independence with respect to electron irradiation energy and dose-rate. Compared with the 8 mol% Ge-doped optical fibres, the 6 mol% Ge-doped flat optical fibres have been demonstrated to possess more desirable performance features for passive dosimetry, serving as a suitable alternative to TLD-100 for medical irradiation treatment applications.
Amyloidosis is a deleterious condition caused by abnormal amyloid fibril build-up in living tissues. To date, 42 proteins that are linked to amyloid fibrils have been discovered. Amyloid fibril structure variation can affect the severity, progression rate, or clinical symptoms of amyloidosis. Since amyloid fibril build-up is the primary pathological basis for various neurodegenerative illnesses, characterization of these deadly proteins, particularly utilising optical techniques have been a focus. Spectroscopy techniques provide significant non-invasive platforms for the investigation of the structure and conformation of amyloid fibrils, offering a wide spectrum of analyses ranging from nanometric to micrometric size scales. Even though this area of study has been intensively explored, there still remain aspects of amyloid fibrillization that are not fully known, a matter hindering progress in treating and curing amyloidosis. This review aims to provide recent updates and comprehensive information on optical techniques for metabolic and proteomic characterization of β-pleated amyloid fibrils found in human tissue with thorough literature analysis of publications. Raman spectroscopy and SAXS are well established experimental methods for study of structural properties of biomaterials. With suitable models, they offer extended information for valid proteomic analysis under physiologically relevant conditions. This review points to evidence that despite limitations, these techniques are able to provide for the necessary output and proteomics indication in order to extrapolate the aetiology of amyloid fibrils for reliable diagnostic purposes. Our metabolic database may also contribute to elucidating the nature and function of the amyloid proteome in development and clearance of amyloid diseases.
The central dogma of molecular biology was no longer "central" after ground-breaking discoveries conveyed gene expression involves more complex physiological functions in cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are short non-coding RNA that regulate gene expression, affecting key molecular pathways involved in sustaining the proliferative signalling for tumour development, evasion of cellular death, invasion, angiogenesis, as well as metastasis in a plethora of cancer types. MiRNA expression is dysregulated in human cancer through a number of processes, including miRNA gene amplification or deletion, faulty miRNA transcriptional regulation, dysregulated epigenetic alterations, and flaws in the miRNA biogenesis machinery. As a result, the current progress of treatment intervention focuses on modifying the miRNA levels in cancer therapeutics. Nevertheless, the mode of delivery and current management of miRNA therapies remains one of the many questions that need to be addressed. Here, we provided a comprehensive mini-review outlining the role of miRNA in cancer as well as its mode of delivery which includes liposomes, viral vectors, inorganic material-based nanoparticles, and cell-derived membrane vesicles. Likewise, the regulation of miRNA in other diseases and their challenges in translational research was also thoroughly discussed.
Trace and minor elements play crucial roles in a variety of biological processes, including amyloid fibrils formation. Mechanisms include activation or inhibition of enzymatic reactions, competition between elements and metal proteins for binding positions, also changes to the permeability of cellular membranes. These may influence carcinogenic processes, with trace and minor element concentrations in normal and amyloid tissues potentially aiding in cancer diagnosis and etiology. With the analytical capability of the spectroscopic technique X-ray fluorescence (XRF), this can be used to detect and quantify the presence of elements in amyloid characterization, two of the trace elements known to be associated with amyloid fibrils. In present work, involving samples from a total of 22 subjects, samples of normal and amyloid-containing tissues of heart, kidney, thyroid, and other tissue organs were obtained, analyzed via energy-dispersive X-ray fluorescence (EDXRF). The elemental distribution of potassium (K), calcium (Ca), arsenic (As), and iron (Fe) was examined in both normal and amyloidogenic tissues using perpetual thin slices. In amyloidogenic tissues the levels of K, Ca, and Fe were found to be less than in corresponding normal tissues. Moreover, the presence of As was only observed in amyloidogenic samples; in a few cases in which there was an absence of As, amyloid samples were found to contain Fe. Analysis of arsenic in amyloid plaques has previously been difficult, often producing contradictory results. Using the present EDXRF facility we could distinguish between amyloidogenic and normal samples, with potential correlations in respect of the presence or concentration of specific elements.
Amyloid diseases are characterized by the accumulation of misfolded protein aggregates in human tissues, pose significant challenges for both diagnosis and treatment. Protein aggregations known as amyloids are linked to several neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, and systemic amyloidosis. The key goal of this research is to employ Small-Angle X-ray Scattering (SAXS) to examine the supramolecular structures of amyloid aggregates in human tissues. We present the structural analysis of amyloid using SAXS, which is employed directly to analyze thin tissue samples without damaging the tissues. This technique provides size and shape information of fibrils, which can be used to generate low-resolution 2D models. The present study investigates the structural changes in amyloid fibril axial d-spacing and scattering intensity in different human tissues, including kidney, heart, thyroid, and others, while also accounting for the presence of triglycerides in these tissues. Tissue structural components were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. The d-spacing is a critical parameter in SAXS that provides information about the periodic distances between structures within a sample. From the supramolecular SAXS patterns, the axial d-spacing of fibrils in amyloid tissues is prominent and exists within the 3rd to 10th order, compared to that of healthy tissues which do not have notable peak orders. The axial period of fibrils in amyloid tissues is within the scattering vector range 57.40-64.64 nm-1 while in normal tissues the range is between 60.68 and 61.41 nm-1, which is 3.0 nm-1 smaller than amyloid-containing tissues. Differences in d-spacing are often correlate with distinct pathological mechanisms or stages of disease progression. The application of SAXS to investigate amyloid structures in human tissues has enormous potential to further knowledge of amyloid disorders. This work will open the path for novel diagnostic instruments and therapeutic strategies meant to reduce the burden of amyloid-related diseases by offering a thorough structural examination of amyloid aggregates.
Using irradiated doped-silica preforms from which fibres for thermoluminescence dosimetry applications can be fabricated we have carried out a range of luminescence studies, the TL yield of the fibre systems offering many advantages over conventional passive dosimetry types. In this paper we investigate such media, showing emission spectra for irradiated preforms and the TL response of glass beads following irradiation to an 241Am-Be neutron source located in a tank of water, the glass fibres and beads offering the advantage of being able to be placed directly into liquid. The outcomes from these and other lines of research are intended to inform development of doped silica radiation dosimeters of versatile utility, extending from environmental evaluations through to clinical and industrial applications.
Accidents resulting in widespread dispersal of radioactive materials have given rise to a need for materials that are convenient in allowing individual dose assessment. The present study examines natural Dead Sea salt adopted as a model thermoluminescence dosimetry system. Samples were prepared in two different forms, loose-raw and loose-ground, subsequently exposed to 60Co gamma-rays, delivering doses in the range 2-10 Gy. Key thermoluminescence (TL) properties were examined, including glow curves, dose response, sensitivity, reproducibility and fading. Glow curves shapes were found to be independent of given dose, prominent TL peaks for the raw and ground samples appearing in the temperature ranges 361-385 ºC and 366-401 ºC, respectively. The deconvolution of glow curves has been undertaken using GlowFit, resulting in ten overlapping first-order kinetic glow peaks. For both sample forms, the integrated TL yield displays linearity of response with dose, the loose-raw salt showing some 2.5 × the sensitivity of the ground salt. The samples showed similar degrees of fading, with respective residual signals 28 days post-irradiation of 66% and 62% for the ground and raw forms respectively; conversely, confronted by light-induced fading the respective signal losses were 62% and 80%. The effective atomic number of the Dead Sea salt of 16.3 is comparable to that of TLD-200 (Zeff 16.3), suitable as an environmental radiation monitor in accident situations but requiring careful calibration in the reconstruction of soft tissue dose (soft tissue Zeff 7.2). Sample luminescence studies were carried out via Raman and Photoluminescence spectroscopy as well as X-ray diffraction, ionizing radiation dependent variation in lattice structure being found to influence TL response.
In clinical settings, standard dosimeters might miss radiation mishaps. Retrospective dosimeters could help to track personnel (such as patients and other staff who don't wear dosimeters) exceeding safe limits and assess long-term exposure trends. This study has investigated key thermoluminescence (TL) dosimetric characteristics, including the glow curve structure, dose-response, energy dependence, sensitivity and fading of various safety glasses that are used as screen protectors of smartphones subjected to photon irradiation. Among the studied glasses, the HD Anti-Peep safety glass for iPhone has been found to exhibit a linear dose-response with a regression coefficient of 99% within the dose range of 2-10 Gy. Moreover, all the safety glasses showed independence with respect to photon energy of 6 MV and 10 MV. The TL glow curves of the samples showed a broad glow peak between 125 °C and 325 °C at 10 Gy. The TL kinetic parameters of the safety glasses were also studied by analyzing the glow curves using the peak shape and initial rise method. The geometric factor (μg) is found to be within the range of 0.43-0.53, which indicates the suitability of applying Chen's general-order formula to calculate the kinetic parameters such as activation energy, frequency factor and trap lifetime. The activation energy (E) and frequency factor (s) are found in the range of 0.31-0.54 eV and 4.55 × 103 to 2.12 × 106 s-1 respectively obtained via the peak shape method. The relatively long trap lifetime and observed thermoluminescence features indicate that the HD Anti-Peep safety glass offers a better option to estimate dose retrospectively to ensure the safety of human health.