Scanning the internet for liveness

Internet-wide scanning depends on a notion of liveness: does a target IP address respond to a probe packet? However, the interpretation of such responses, or lack of them, is nuanced and depends on multiple factors, including: how we probed, how different protocols in the network stack interact, the presence of filtering policies near the target, and temporal churn in IP responsiveness. Although often neglected, these factors can significantly affect the results of active measurement studies. We develop a taxonomy of liveness which we employ to develop a method to perform concurrent IPv4 scans using ICMP, five TCP-based, and two UDP-based protocols, comprehensively capturing all responses to our probes, including negative and cross-layer responses. Leveraging our methodology, we present a systematic analysis of liveness and how it manifests in active scanning campaigns, yielding practical insights and methodological improvements for the design and the execution of active Internet measurement studies.</jats:p

Chromosomal radiosensitivity of lymphocytes in South African breast cancer patients of different ethnicity: An indirect measure of cancer susceptibility

Background. Breast cancer is the leading cancer among South African (SA) women. SA has citizens from diverse ethnic groups, and the lifetime risk of breast cancer differs according to ethnicity. Candidate genes for increased breast cancer risk are those involved in DNA damage repair pathways, and mutations in these genes are characterised by increased chromosomal radiosensitivity. Several European studies have shown that breast cancer patients are more sensitive to ionising radiation than healthy individuals.Objectives. To investigate the in vitro chromosomal radiosensitivity of SA women with breast cancer and the possible influence of ethnicity and clinical parameters on chromosomal radiosensitivity.Methods. Chromosomal radiosensitivity was analysed with the micronucleus assay using lymphocytes of breast cancer patients and healthy individuals of different ethnic groups. Lymphocytes were irradiated in vitro with 2 Gy or 4 Gy, and micronuclei (MN) were scored 70 hours after irradiation. These MN frequencies were correlated with the ethnicity and clinical parameters of the breast cancer patients.Results. MN values were higher in breast cancer patients than in healthy controls. This was noted for black and white breast cancer patients at the different radiation doses. No correlations could be demonstrated between MN values and clinical parameters of the breast cancer, except that MN values were significantly higher in oestrogen receptor (ER)-positive breast cancers.Conclusion. SA breast cancer patients have elevated chromosomal radiosensitivity compared with healthy controls. ER positivity also influences chromosomal radiosensitivity

Imaging of 3D tissue-engineered models of oral cancer using 890 and 1300 nm optical coherence tomography

© 2015, Nizhny Novgorod State Medical Academy. All rights reserved. Optical coherence tomography (OCT) generates its primary form of contrast from elastic backscatter. It is now the gold standard technique for retinal screening and is emerging rapidly in cardiovascular research however it remains a research goal to establish it to the same degree in epithelial cancer detection and diagnosis. In this report we compare two different OCT systems: an 890 nm spectrometer-based OCT system with 2.5 µm axial resolution and a 1300 nm swept-source OCT system with 7.5 µm axial resolution to determine the effect of these different OCT parameters on the endogenous backscatter contrast of dysplastic/malignant oral mucosa models relative to normal mucosa models. Tissueengineered oral mucosa models constructed with a dysplastic cell line (DOK), a malignant cell line (Cal27) and normal cell were imaged with both of these OCT platforms and comparisons made with regard to apparent epithelial thickness and the visibility of the epithelium relative to the underlying stroma. For the Cal27’s, hematoxylin and eosin staining confirmed the formation of a keratinized layer superficial to a thickened layer of viable cells on top of the stroma. The keratinized layer presented as a hyperreflective thickened layer superficial to a darker region on both OCT platforms. The keratinized layer caused a steep fall in signal at 890 nm, making it difficult to visualise underlying structures, whereas 1300 nm OCT clearly visualized both the epithelial cells and the stroma lying beneath. For the DOK cells, hematoxylin and eosin staining confirmed the formation of an epithelial layer frequently presenting an abnormal morphology especially at the epidermal/stromal junction, with features such as infiltrating, bulbous rete pegs. These were more clearly visualized under 890 nm OCT. These observations show that 890 nm OCT retains some of its known advantages of higher contrast between anatomical tissue layers when used to observe dysplastic and malignant 3D oral mucosa constructs. However 1300 nm OCT is confirmed to possess a greater ability to image the full thickness of the model epithelia and in particular it is more suited to imaging through the keratinized layer

Corticosteroid delivery using oral mucosa equivalents for the treatment of inflammatory mucosal diseases

Oral lichen planus (OLP) is an immune‐mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T‐cells, to examine corticosteroid potency and delivery of clobetasol‐17‐propionate from a novel electrospun mucoadhesive patch. The OMEs displayed tight junctions, desmosomes, hemidesmosomes, and an efficient permeability barrier. Following application of corticosteroids to cells cultured as monolayers, the degree of cytotoxicity measured correlated to the level of potency recognized for each corticosteroid; by contrast, OMEs were largely unaffected by corticosteroid treatment. Permeation of clobetasol‐17‐propionate into and through the OMEs was time‐ and dose‐dependent, regardless of whether this corticosteroid was delivered in liquid form or from a mucoadhesive patch, and both liquid‐ and patch‐delivered clobetasol‐17‐propionate significantly reduced the secretion of interleukin‐2 by activated T‐cells. This study confirms that OMEs are more suitable models than cell monolayers for evaluating toxicity and drug delivery. After topical exposure, clobetasol‐17‐propionate accumulated in OMEs at a higher level than betamethasone‐17‐valerate and hydrocortisone‐17‐valerate, and exerted its immunosuppressive actions following application via the patch delivery system, highlighting the efficacy of this mode of drug delivery to treat OLP

Management of chronic conditions in resource limited settings: multi stakeholders’ perception and experiences with receiving and providing integrated HIV, diabetes and hypertension services in Tanzania

Background: The rising prevalence of non-communicable diseases (NCDs) alongside the continuing high burden of HIV poses a serious challenge to middle- and low-income countries’ healthcare systems. Pilot studies of integrated models of service delivery for HIV, hypertension and diabetes have demonstrated that they are feasible and acceptable among patients and care providers. This study assessed multi-stakeholders’ perspectives of the delivery and receipt of integrated care in Tanzania. Methods: A qualitative process evaluation was conducted in Dar es Salaam region of Tanzania where the integrated service delivery model was implemented from July to November 2021. In-depth interviews were held with seven key informants at the national, regional and district levels, eight healthcare providers, two researchers working at the integrated clinic and forty patients benefiting from integrated services at a large hospital. Three focus group discussions were held with community leaders and residents of the hospital’s catchment area, and clinic level observations were conducted. Thematic analysis was conducted followed by the use of Bronfenbrenner’s ecological model to identify factors pertinent to sustaining and scaling up of the integrated model. Results: Participants of the study at all levels were aware of the increased prevalence of NCDs specifically for hypertension and diabetes and were concerned about the trend of increasing co-morbid conditions among people living with HIV (PLHIV). The integrated service delivery model was positively perceived by stakeholders because of its multiple benefits for both patients and the healthcare system. These include stigma and discrimination reduction, improved quality of care, efficient use of limited resources, cost and time saving, reduced duplication of services and fostering of early detection for undiagnosed conditions. The organisation of the clinic was critical in increased satisfaction. Several challenges were observed, which included costs for NCD services relative to free care for HIV and inconsistent availability of NCD medications. Conclusion: Stakeholders reported numerous benefits of the integrated service delivery model that are fundamental in improving the health of many Tanzanians living with NCDs and HIV. These benefits highlight the need for policy and decision-makers to sustain and expand the integrated service delivery model as a solution to many challenges facing the health system especially at the primary care level

High resolution infrared absorption spectra, crystal field, and relaxation processes in CsCdBr_3:Pr^3+

High resolution low-temperature absorption spectra of 0.2% Pr^3+ doped CsCdBr_3 were measured in the spectral region 2000--7000 cm-1. Positions and widths of the crystal field levels within the 3H5, 3H4, 3F2, and 3F3 multiplets of the Pr^3+ main center have been determined. Hyperfine structure of several spectral lines has been found. Crystal field calculations were carried out in the framework of the semiphenomenological exchange charge model (ECM). Parameters of the ECM were determined by fitting to the measured total splittings of the 3H4 and 3H6 multiplets and to the observed in this work hyperfine splittings of the crystal field levels. One- and two-phonon relaxation rates were calculated using the phonon Green's functions of the perfect (CsCdBr_3) and locally perturbed (impurity dimer centers in CsCdBr_3:Pr^3+) crystal lattice. Comparison with the measured linewidths confirmed an essential redistribution of the phonon density of states in CsCdBr_3 crystals doped with rare-earth ions.Comment: 16 pages, 5 tables, 3 figure

Resolving the extragalactic hard X-ray background

The origin of the hard (2-10 keV) X-ray background has remained mysterious for over 35 years. Most of the soft (0.5-2 keV) X-ray background has been resolved into discrete sources, which are primarily quasars; however, these sources do not have the flat spectral shape required to match the X-ray background spectrum. Here we report the results of an X-ray survey 30 times more sensitive than previous studies in the hard band and four times more sensitive in the soft band. The sources detected in our survey account for at least 75 per cent of the hard X-ray background. The mean X-ray spectrum of these sources is in good agreement with that of the background. The X-ray emission from the majority of the detected sources is unambiguously associated with either the nuclei of otherwise normal bright galaxies or optically faint sources, which could either be active nuclei of dust enshrouded galaxies or the first quasars at very high redshifts.Comment: Nature article in pres

Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

Optical coherence tomography (OCT) is a noninvasive imaging methodology that is able to image tissue to depths of over 1 mm. Many epithelial conditions, such as melanoma and oral cancers, require an invasive biopsy for diagnosis. A noninvasive, real-time, point of care method of imaging depth-resolved epithelial structure could greatly improve early diagnosis and long-term monitoring in patients. Here, we have used tissue-engineered (TE) models of normal skin and oral mucosa to generate models of melanoma and oral cancer. We have used these to determine the ability of OCT to image epithelial differences in vitro. We report that while in vivo OCT gives reasonable depth information for both skin and oral mucosa, in vitro the information provided is less detailed but still useful. OCT can provide reassurance on the development of TE models of skin and oral mucosa as they develop in vitro. OCT was able to detect the gross alteration in the epithelium of skin and mucosal models generated with malignant cell lines but was less able to detect alteration in the epithelium of TE models that mimicked oral dysplasia or, in models where tumor cells had penetrated into the dermis

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass