Adjustment Methods for Planimetric Observations and Co-Ordinates in Survey Networks

Correction and adjustment of observed angles and sides in geodetic networks are necessary for the purpose of the correct location of coordinated points. Correction equations are usually in the form of linear overdetermined (observation) or underdetermined (condition) equations which are solved by the least squares theorem. The introduction of the electro-magnetic methods of linear measurement requires the adjustment of sides as well as the adjustment of angles necessary in classical triangulation nets. For the simultaneous adjustment of angles and sides two new sets of conditions have been introduced: (i) the area misfit condition, where the area obtained from distances and angles has to satisfy a special condition, and (ii) that the sum of the projections of the three sides of a triangle on the coordinate axes have to satisfy a zero condition. A special study has been made into the adjustment of the braced geodetic quadrilateral, as being one of the most favourable figures from the adjustment point of view. The different apices of this quadrilateral have been investigated to allow a choice to be made as to which of them shall be introduced in an angle misfit condition during adjustment. This gives rise to the conclusion that all apices will introduce the same corrections for all practical purposes. Since observed angles and sides are different physical quantities, the question of relative weighting has been given special attention and recommendations have been made in the light of various theoretical and practical investigations. The Systematic relaxation method for adjusting survey nets has been theoretically derived by Professors Southwell and Black based on the minimum strain-energy conserved in an elastic frame-work at the position of equilibrium. Using this theory mechanical analogues have been designed and constructed for the first time to carry out the adjustment of the triangulation net directly from field observations, without the necessity of forming and solving a set of linear equations. An analogue for the adjustment of angles was found to be excessively complicated mechanically and difficult to use in practice. Through the use of a direction adjustment method these limitations have been overcome. The final model constructed achieved comparable results to those obtained numerically by a least squares solution. Suggestions for a more highly developed version are made and the situations favourable to mechanical analogue computations are discussed. The use of an electrical analogue as suggested by Su using a D.C. circuit has been thoroughly investigated from both the theoretical and practical points of view, which showed that such a solution will be simple only for certain limited cases. As an alternative the possibilities of the more general purpose electronic analogue computer have been investigated via the solution of correction equations. Various examples have been solved on this computer which proved to have several advantages over other computation methods. Finally equivalent problems have been solved numerically on a digital computer for a comparison of the relative merits of analogue and digital methods for the particular case of adjustment of geodetic networks. The relative merits of these solutions are discussed in the light of different problems and circumstances

Allostatic load and depressive symptoms in older adults: An analysis of 12-year panel data

BACKGROUND: Whether changes in allostatic load (AL) and depressive symptoms relate over time has not been yet fully explored. This study evaluated the association between AL and depressive symptoms over 12 years among community-dwelling older adults. METHODS: Panel data from 8291 participants in the English Longitudinal Study of Ageing were analysed. Depressive symptoms were assessed with the 8-item Centre for Epidemiologic Studies Depression Scale (CES-D). The AL score was derived from nine metabolic, cardiovascular and immune biomarkers. The association between AL and depressive symptoms was modelled in a linear hybrid model adjusting for time-invariant (sex, ethnicity) and time-variant confounders (age, marital status, education, wealth, physical activity, smoking status, alcohol intake, limitations in daily living, comorbidities). RESULTS: The mean AL score was 3.1 (SD: 2.1), 3.5 (2.3), 3.2 (2.3) and 3.3 (2.5) whereas the mean CES-D score was 1.4 (SD: 1.8), 1.2 (1.8), 1.2 (1.8) and 1.2 (1.7) in waves 2, 4, 6 and 8, respectively. In the adjusted model, the between-person differences (coefficient: 0.02, 95% CI: 0.01, 0.04) but not the within-individual differences (0.01; 95% CI: −0.01, 0.03) in the AL score were associated with CES-D score. The between-person coefficient indicates that participants with greater AL scores also had slightly higher CES-D scores. The within-person coefficient indicates that changes in the AL score were not associated with changes in the CES-D score. CONCLUSION: AL was associated with depressive symptoms. However, most of the association was driven by differences in AL between individuals rather than changes in AL over time

tt*-geometry on the big phase space

The big phase space, the geometric setting for the study of quantum cohomology with gravitational descendents, is a complex manifold and consists of an infinite number of copies of the small phase space. The aim of this paper is to define a Hermitian geometry on the big phase space. Using the approach of Dijkgraaf and Witten, we lift various geometric structures of the small phase space to the big phase space. The main results of our paper state that various notions from tt*-geometry are preserved under such liftings

Cosmic ray short burst observed with the Global Muon Detector Network (GMDN) on June 22, 2015

We analyze the short cosmic ray intensity increase ("cosmic ray burst": CRB) on June 22, 2015 utilizing a global network of muon detectors and derive the global anisotropy of cosmic ray intensity and the density (i.e. the omnidirectional intensity) with 10-minute time resolution. We find that the CRB was caused by a local density maximum and an enhanced anisotropy of cosmic rays both of which appeared in association with Earth's crossing of the heliospheric current sheet (HCS). This enhanced anisotropy was normal to the HCS and consistent with a diamagnetic drift arising from the spatial gradient of cosmic ray density, which indicates that cosmic rays were drifting along the HCS from the north of Earth. We also find a significant anisotropy along the HCS, lasting a few hours after the HCS crossing, indicating that cosmic rays penetrated into the inner heliosphere along the HCS. Based on the latest geomagnetic field model, we quantitatively evaluate the reduction of the geomagnetic cut-off rigidity and the variation of the asymptotic viewing direction of cosmic rays due to a major geomagnetic storm which occurred during the CRB and conclude that the CRB is not caused by the geomagnetic storm, but by a rapid change in the cosmic ray anisotropy and density outside the magnetosphere.Comment: accepted for the publication in the Astrophysical Journa

Racial Discrimination and Uptake of Dental Services among American Adults

This study examined the relationship between racial discrimination and use of dental services among American adults. We used data from the 2014 Behavioral Risk Factor Surveillance System, a health-related telephone cross-sectional survey of a nationally representative sample of adults in the United States. Racial discrimination was indicated by two items, namely perception of discrimination while seeking healthcare within the past 12 months and emotional impact of discrimination within the past 30 days. Their association with dental visits in the past year was tested in logistic regression models adjusting for predisposing (age, gender, race/ethnicity, income, education, smoking status), enabling (health insurance), and need (missing teeth) factors. Approximately 3% of participants reported being discriminated when seeking healthcare in the past year, whereas 5% of participants reported the emotional impact of discrimination in the past month. Participants who experienced emotional impact of discrimination were less likely to have visited the dentist during the past year (Odds Ratios (OR): 0.57; 95% CI 0.44–0.73) than those who reported no emotional impact in a crude model. The association was attenuated but remained significant after adjustments for confounders (OR: 0.76, 95% CI 0.58–0.99). There was no association between healthcare discrimination and last year dental visit in the fully adjusted model. Emotional impact of racial discrimination was an important predictor of use of dental services. The provision of dental health services should be carefully assessed after taking account of racial discrimination and its emotional impacts within the larger context of social inequalities

Identifying a causal link between prolactin signaling pathways and COVID-19 vaccine-induced menstrual changes

COVID-19 vaccines have been instrumental tools in the fight against SARS-CoV-2 helping to reduce disease severity and mortality. At the same time, just like any other therapeutic, COVID-19 vaccines were associated with adverse events. Women have reported menstrual cycle irregularity after receiving COVID-19 vaccines, and this led to renewed fears concerning COVID-19 vaccines and their effects on fertility. Herein we devised an informatics workflow to explore the causal drivers of menstrual cycle irregularity in response to vaccination with mRNA COVID-19 vaccine BNT162b2. Our methods relied on gene expression analysis in response to vaccination, followed by network biology analysis to derive testable hypotheses regarding the causal links between BNT162b2 and menstrual cycle irregularity. Five high-confidence transcription factors were identified as causal drivers of BNT162b2-induced menstrual irregularity, namely: IRF1, STAT1, RelA (p65 NF-kB subunit), STAT2 and IRF3. Furthermore, some biomarkers of menstrual irregularity, including TNF, IL6R, IL6ST, LIF, BIRC3, FGF2, ARHGDIB, RPS3, RHOU, MIF, were identified as topological genes and predicted as causal drivers of menstrual irregularity. Our network-based mechanism reconstruction results indicated that BNT162b2 exerted biological effects similar to those resulting from prolactin signaling. However, these effects were short-lived and didn’t raise concerns about long-term infertility issues. This approach can be applied to interrogate the functional links between drugs/vaccines and other side effects

Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction

BACKGROUND: It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS). Methods: Patients meeting Framingham criteria for HF with EF\u3c50% were enrolled (n=1017) and plasma underwent SOMAscan® profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and N-Terminal pro-B-Type Natriuretic Peptide (NTproBNP), then was tested in the validation cohort. Risk stratification improvement was evaluated by C-statistic, integrated discrimination index (IDI), continuous net reclassification index (NRI), and median improvement in risk score (MIRS) for 1-year and 3-year mortality. Results: Participants\u27 mean age was 68 years, 48% identified as African American, 35% were female and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio (HR) =2.27 [95% Confidence interval (95%CI) 1.84-2.82], p=6.3x10(-14)), Kaplan-Meier curves differed significantly between HFrEF-PRS quartiles (p=2.2x10(-6)), and it remained significant after adjustment for clinical score and NTproBNP (HR=1.37, 95%CI 1.05-1.79, p=0.021). The HFrEF-PRS improved metrics of risk stratification (C-statistic change=0.009, p=0.612; IDI=0.041, p=0.010; NRI=0.391, p=0.078; MIRS=0.039, p=0.016) and associated with cardiovascular death and HF phenotypes (e.g. 6-minute walk distance, EF change). Most HFrEF-PRS proteins had little known connection to HFrEF. Conclusions: A plasma multi-protein score improved risk stratification in HFrEF patients and identified novel candidates

Target identification of Mycobacterium tuberculosis phenotypic\textit{Mycobacterium tuberculosis phenotypic} hits using a concerted chemogenomic, biophysical and structural approach

Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the treatment of tuberculosis. However, the absence of defined molecular targets and modes of action could lead to failure in drug development. Therefore, a combination of ligand-based and structure-based chemogenomic approaches followed by biophysical and biochemical validation have been used to identify targets for Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA as targets for several hits, with some showing dual activity against these proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50 μM against M. tuberculosis EthR and three were confirmed to be also simultaneously active against InhA. Further hit validation was performed using X-ray crystallography yielding eight new crystal structures of EthR inhibitors. Although the EthR inhibitors attain their activity against M. tuberculosis by hitting yet undefined targets, these results provide new lead compounds that could be further developed to be used to potentiate the effect of EthA activated pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.GM is grateful to the European Molecular Biology Laboratory and Marie Sklodowska-Curie Actions for funding this work. VM and MB acknowledge Bill & Melinda Gates Foundation [subcontract by the Foundation for the National Institutes of Health (NIH)] (OPP1024021). VM and MS acknowledge the European Community’s Seventh Framework Programme [grant number 260872]. GP would like to acknowledge the Wellcome Trust and the European Molecular Biology Laboratory for funding. JPO was funded by the member nation states of the European Molecular Biology Laboratory. TLB acknowledges The Wellcome Trust for funding and support (grant number 200814/Z/16/Z)

Singularities and Topology of Meromorphic Functions

We present several aspects of the "topology of meromorphic functions", which we conceive as a general theory which includes the topology of holomorphic functions, the topology of pencils on quasi-projective spaces and the topology of polynomial functions.Comment: 21 pages, 1 figur

Knockout of ACE-N facilitates improved cardiac function after myocardial infarction

Angiotensin-converting enzyme (ACE) hydrolyzes N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) into inactive fragments through its N-terminal site (ACE-N). We previously showed that Ac-SDKP mediates ACE inhibitors\u27 cardiac effects. Whether increased bioavailability of endogenous Ac-SDKP caused by knocking out ACE-N also improves cardiac function in myocardial infarction (MI)-induced heart failure (HF) is unknown. Wild-type (WT) and ACE-N knockout (ACE-NKO) mice were subjected to MI by ligating the left anterior descending artery and treated with vehicle or Ac-SDKP (1.6 mg/kg/day, s.c.) for 5 weeks, after which echocardiography was performed and left ventricles (LV) were harvested for histology and molecular biology studies. ACE-NKO mice showed increased plasma Ac-SDKP concentrations in both sham and MI group compared to WT. Exogenous Ac-SDKP further increased its circulating concentrations in WT and ACE-NKO. Shortening (SF) and ejection (EF) fractions were significantly decreased in both WT and ACE-NKO mice post-MI, but ACE-NKO mice exhibited significantly lesser decrease. Exogenous Ac-SDKP ameliorated cardiac function post-MI only in WT but failed to show any additive improvement in ACE-NKO mice. Sarcoendoplasmic reticulum calcium transport ATPase (SERCA2), a marker of cardiac function and calcium homeostasis, was significantly decreased in WT post-MI but rescued with Ac-SDKP, whereas ACE-NKO mice displayed less loss of SERCA2 expression. Our study demonstrates that gene deletion of ACE-N resulted in improved LV cardiac function in mice post-MI, which is likely mediated by increased circulating Ac-SDKP and minimally reduced expression of SERCA2. Thus, future development of specific and selective inhibitors for ACE-N could represent a novel approach to increase endogenous Ac-SDKP toward protecting the heart from post-MI remodeling