Applications of inertial navigation and modern control theory to the all weather landing problem

Inertial navigation and automatic landing control theory applied to instrument landing proble

Some applications of mathematical optimization to automatic landing systems

Algorithms applied to vertical trajectory control syste

Computer-Aided Histopathological Characterisation of Endometriosis Lesions.

Endometriosis is a common gynaecological condition characterised by the growth of endometrial tissue outside the uterus and is associated with pain and infertility. Currently, the gold standard for endometriosis diagnosis is laparoscopic excision and histological identification of endometrial epithelial and stromal cells. There is, however, currently no known association between the histological appearance, size, morphology, or subtype of endometriosis and disease prognosis. In this study, we used histopathological software to identify and quantify the number of endometrial epithelial and stromal cells within excised endometriotic lesions and assess the relationship between the cell contents and lesion subtypes. Prior to surgery for suspected endometriosis, patients provided menstrual and abdominal pain and dyspareunia scores. Endometriotic lesions removed during laparoscopic surgery were collected and prepared for immunohistochemistry from 26 patients. Endometrial epithelial and stromal cells were identified with Cytokeratin and CD10 antibodies, respectively. Whole slide sections were digitised and the QuPath software was trained to automatically detect and count epithelial and stromal cells across the whole section. Using this classifier, we identified a significantly larger number of strongly labelled CD10 stromal cells (p = 0.0477) in deeply infiltrating lesions (99,970 ± 2962) compared to superficial lesions (2456 ± 859). We found the ratio of epithelial to stromal cells was inverted in deeply infiltrating endometriosis lesions compared to superficial peritoneal and endometrioma lesions and we subsequently identified a correlation between total endometrial cells and abdominal pain (p = 0.0005) when counted via the automated software. Incorporating histological software into current standard diagnostic pipelines may improve endometriosis diagnosis and provide prognostic information in regards to severity and symptoms and eventually provide the potential to personalise adjuvant treatment decisions

A conformational variant of p53 (U-p53AZ) as blood-based biomarker for the prediction of the onset of symptomatic Alzheimer\u27s disease

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer\u27s disease (AD). OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years. DESIGN: Retrospective Longitudinal Prognostic biomarker study. SETTING: Single-center study based on the AIBL cohort. PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses. MEASUREMENTS: The AlzoSure® Predict test, consisting of immunoprecipitation (IP) followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS), was performed to quantify the AZ 284® peptide as readout of U-p53AZ and compared with an independent neuropsychological diagnosis. The amyloid load via amyloid β-positron emission tomography (Aβ-PET) and supporting clinical information were included where possible. RESULTS: U-p53AZ diagnostic and prognostic performance was assessed in both time-independent and time-dependent (36, 72 and 90 months following initial sampling) analyses. Prognostic performance of Aβ-PET and survival analyses with different risk factors (gender, Aβ-PET and APOE ε4 allele status) were also performed. U-p53AZ differentiated neuropsychologically graded AD from non-AD samples, and its detection at intermediate/high levels precisely identified present and future symptomatic AD. In both time-independent and time-dependent prognostic analyses U-p53AZ achieved area under the curve (AUC) \u3e98%, significantly higher than Aβ-PET AUCs (between 84% and 93%, P respectively \u3c0.0001 and \u3c0.001). As single factor, U-p53AZ could clearly determine the risk of AD neuropsychological diagnosis over time (low versus intermediate/high U-p53AZ hazard ratio=2.99). Proportional hazards regression analysis identified U-p53AZ levels as a major independent predictor of AD onset. CONCLUSIONS: These findings support use of U-p53AZ as blood-based biomarker predicting whether individuals would reach neuropsychologically-defined AD within six years prior to AD diagnosis. Integration of U-p53AZ in screening processes could support refined participant stratification for interventional studies

Economic footprint of California wildfires in 2018

Recent increases in the frequency and scale of wildfires worldwide have raised concerns about the influence of climate change and associated socioeconomic costs. In the western United States, the hazard of wildfire has been increasing for decades. Here, we use a combination of physical, epidemiological and economic models to estimate the economic impacts of California wildfires in 2018, including the value of destroyed and damaged capital, the health costs related to air pollution exposure and indirect losses due to broader economic disruption cascading along with regional and national supply chains. Our estimation shows that wildfire damages in 2018 totalled $148.5 (126.1–192.9) billion (roughly 1.5$27.7 billion (19%) in capital losses, $32.2 billion (22$88.6 billion (59%) in indirect losses (all values in US$). Our results reveal that the majority of economic impacts related to California wildfires may be indirect and often affect industry sectors and locations distant from the fires (for example, 52% of the indirect losses—31% of total losses—in 2018 were outside of California). Our findings and methods provide new information for decision makers tasked with protecting lives and key production sectors and reducing the economic damages of future wildfires

Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors

Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells. Transient expression led to increased multilineage hematopoietic engraftment in in vivo competitive repopulation assays without the side effects reported in constitutive overexpression models. Adult stem cell fate has not been programmed previously using IdLVs, but we demonstrate that these transient gene expression tools can produce clinically relevant alterations or be applied to investigate basic biology

Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility.

Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility

Dendritic and T Cell Response to Influenza is Normal in the Patients with X-Linked Agammaglobulinemia

Introduction Influenza virus is a potential cause of severe disease in the immunocompromised. X-linked agammaglobu-linemia (XLA) is a primary immunodeficiency characterized by the lack of immunoglobulin, B cells, and plasma cells, secondary to mutation in Bruton’s tyrosine kinase (Btk) gene