Characterization of Rectifying and Sphere Curves in R^3

Studies of curves in 3D-space have been developed by many geometers and it is known that any regular curve in 3D space is completely determined by its curvature and torsion, up to position. Many results have been found to characterize various types of space curves in terms of conditions on the ratio of torsion to curvature. Under an extracondition on the constant curvature, Y.L. Seo and Y. M. Oh found the series solution when the ratio of torsion to curvature is a linear function. Furthermore, this solution is known to be a rectifying curve by B. Y. Chen’s work. This project, uses a different approach to characterize these rectifying curves

A rapid review of integrated primary care centres and polyclinics

Integration within primary health care and with secondary care is a major policy concern in many countries, with integrated primary health care centres (IPHCs) often seen as a part of the solution. IPHCs in Australia include GP Super Clinics and Aboriginal Community Controlled Health Services (national), HealthOne NSW (NSW) and GP Plus (SA) in Australia. Proposed national reforms recommend their broader establishment. This review examines what is known about the use and effectiveness of IPHCs in Australia and elsewhere and identifies what Australia can learn from this.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

SMaSH: A Benchmarking Toolkit for Human Genome Variant Calling

Motivation: Computational methods are essential to extract actionable information from raw sequencing data, and to thus fulfill the promise of next-generation sequencing technology. Unfortunately, computational tools developed to call variants from human sequencing data disagree on many of their predictions, and current methods to evaluate accuracy and computational performance are ad-hoc and incomplete. Agreement on benchmarking variant calling methods would stimulate development of genomic processing tools and facilitate communication among researchers. Results: We propose SMaSH, a benchmarking methodology for evaluating human genome variant calling algorithms. We generate synthetic datasets, organize and interpret a wide range of existing benchmarking data for real genomes, and propose a set of accuracy and computational performance metrics for evaluating variant calling methods on this benchmarking data. Moreover, we illustrate the utility of SMaSH to evaluate the performance of some leading single nucleotide polymorphism (SNP), indel, and structural variant calling algorithms. Availability: We provide free and open access online to the SMaSH toolkit, along with detailed documentation, at smash.cs.berkeley.edu

Diabetes and Tooth Loss in a National Sample of Dentate Adults Reporting Annual Dental Visits

IntroductionPeriodontal disease has been associated with tooth loss and reported as more prevalent among people with diabetes than among those without diabetes. Having an annual dental examination is a national goal of Healthy People 2010. Our objective was to examine whether an association exists between diabetes and tooth loss among a population reporting an annual dental visit.MethodsWe used data from the 2004 Behavioral Risk Factor Surveillance System to examine the association between self-reported diabetes and tooth removal due to decay or periodontal disease among 155,280 respondents reporting a dental visit within the past year. We calculated prevalence estimates, odds ratios, and 95% confidence intervals. Multiple logistic regression allowed for adjustment.ResultsThe overall prevalence of tooth removal among the people in the study was 38.3%. People with diabetes had a significantly higher prevalence of tooth removal. In a multivariable model adjusting for selected covariates, respondents with diabetes were 1.46 times as likely (95% CI, 1.30–1.64) to have at least one tooth removed than respondents without diabetes. A stronger association between diabetes and tooth loss was observed among people in the younger age groups than among those in the older age groups.ConclusionEven among people reporting a recent dental visit, diabetes was independently associated with tooth loss. Multidisciplinary efforts are needed to raise awareness of the risk of tooth loss among younger people with diabetes. Good oral hygiene as well as annual dental examinations are important for preventing tooth loss

Discovery of ram-pressure stripped gas around an elliptical galaxy in Abell 2670

Studies of cluster galaxies are increasingly finding galaxies with spectacular one-sided tails of gas and young stars, suggestive of intense ram-pressure stripping. These so-called "jellyfish" galaxies typically have late-type morphology. In this paper, we present MUSE observations of an elliptical galaxy in Abell 2670 with long tails of material visible in the optical spectra, as well as blobs with tadpole-like morphology. The spectra in the central part of the galaxy reveals a stellar component as well as ionized gas. The stellar component does not have significant rotation, while the ionized gas defines a clear star-forming gas disk. We argue, based on deep optical images of the galaxy, that the gas was most likely acquired during a past wet merger. It is possible that the star-forming blobs are also remnants of the merger. In addition, the direction and kinematics of the one-sided ionized tails, combined with the tadpole morphology of the star-forming blobs, strongly suggests that the system is undergoing ram pressure from the intracluster medium. In summary, this paper presents the discovery of a post-merger elliptical galaxy undergoing ram pressure stripping.Comment: 6 pages, 5 figures, accepted for publication in ApJ

Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.

How pathogenic cluster of differentiation 4 (CD4) T cells in rheumatoid arthritis (RA) develop remains poorly understood. We used Nur77-a marker of T cell antigen receptor (TCR) signaling-to identify antigen-activated CD4 T cells in the SKG mouse model of autoimmune arthritis and in patients with RA. Using a fluorescent reporter of Nur77 expression in SKG mice, we found that higher levels of Nur77-eGFP in SKG CD4 T cells marked their autoreactivity, arthritogenic potential, and ability to more readily differentiate into interleukin-17 (IL-17)-producing cells. The T cells with increased autoreactivity, nonetheless had diminished ex vivo inducible TCR signaling, perhaps reflective of adaptive inhibitory mechanisms induced by chronic autoantigen exposure in vivo. The enhanced autoreactivity was associated with up-regulation of IL-6 cytokine signaling machinery, which might be attributable, in part, to a reduced amount of expression of suppressor of cytokine signaling 3 (SOCS3)-a key negative regulator of IL-6 signaling. As a result, the more autoreactive GFPhi CD4 T cells from SKGNur mice were hyperresponsive to IL-6 receptor signaling. Consistent with findings from SKGNur mice, SOCS3 expression was similarly down-regulated in RA synovium. This suggests that despite impaired TCR signaling, autoreactive T cells exposed to chronic antigen stimulation exhibit heightened sensitivity to IL-6, which contributes to the arthritogenicity in SKG mice, and perhaps in patients with RA

Awareness, Accuracy, and Predictive Validity of Self-reported Cholesterol in Women

Background: Although current guidelines emphasize the importance of cholesterol knowledge, little is known about accuracy of this knowledge, factors affecting accuracy, and the relationship of self-reported cholesterol with cardiovascular disease (CVD). Methods: The 39,876 female health professionals with no prior CVD in the Women’s Health Study were asked to provide self-reported and measured levels of total and high-density lipoprotein (HDL) cholesterol. Demographic and cardiovascular risk factors were considered as determinants of awareness and accuracy. Accuracy was evaluated by the difference between reported and measured cholesterol. In addition, we examined the relationship of self-reported cholesterol with incident CVD over 10 years. Results: Compared with women who were unaware of their cholesterol levels, aware women (84%) had higher levels of income, education, and exercise and were more likely to be married, normal in weight, treated for hypertension and hypercholesterolemia, nonsmokers, moderate drinkers, and users of hormone therapy. Women underestimated their total cholesterol by 9.7 mg/dL (95% CI: 9.2–10.2); covariates explained little of this difference (R$^2$ < .01). Higher levels of self-reported cholesterol were strongly associated with increased risk of CVD, which occurred in 741 women (hazard ratio 1.23/40 mg/dL cholesterol, 95% CI: 1.15–1.33). Women with elevated cholesterol who were unaware of their level had particularly increased risk (HR=1.88, P < .001) relative to aware women with normal measured cholesterol. Conclusion: Women with obesity, smoking, untreated hypertension, or sedentary lifestyle have decreased awareness of their cholesterol levels. Self-reported cholesterol underestimates measured values, but is strongly related to CVD. Lack of awareness of elevated cholesterol is associated with increased risk of CVD

Ex vivo MRI facilitates localization of cerebral microbleeds of different ages during neuropathology assessment

Cerebral microbleeds (CMBs) identified by in vivo magnetic resonance imaging (MRI) of brains of older persons may have clinical relevance due to their association with cognitive impairment and other adverse neurologic outcomes, but are often not detected in routine neuropathology evaluations. In this study, the utility of ex vivo MRI in the neuropathological identification, localization, and frequency of CMBs was investigated. The study included 3 community dwelling elders with Alzheimer’s dementia, and mild to severe small vessel disease (SVD). Ex vivo MRI was performed on the fixed hemisphere to identify CMBs, blinded to the neuropathology diagnoses. The hemibrains were then sliced at 1 cm intervals and 2, 1 or 0 microhemorrhages (MH) were detected on the cut surfaces of brain slabs using the routine neuropathology protocol. Ex vivo imaging detected 15, 14 and 9 possible CMBs in cases 1, 2 and 3, respectively. To obtain histological confirmation of the CMBs detected by ex vivo MRI, the 1 cm brain slabs were dissected further and MHs or areas corresponding to the CMBs detected by ex vivo MRI were blocked and serially sectioned at 6 µm intervals. Macroscopic examination followed by microscopy post ex vivo MRI resulted in detection of 35 MHs and therefore, about 12 times as many MHs were detected compared to routine neuropathology assessment without ex vivo MRI. While microscopy identified previously unrecognized chronic MHs, it also showed that MHs were acute or subacute and therefore may represent perimortem events. Ex vivo MRI detected CMBs not otherwise identified on routine neuropathological examination of brains of older persons and histologic evaluation of the CMBs is necessary to determine the age and clinical relevance of each hemorrhage

Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up NewWays of Inhibiting HIV-1 Fusion

Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijms23052794/s1.Acknowledgments: M.C.-M. acknowledges a grant from Youth Employment Operative Program of the Andalusia Government and the European Social Fund (ESF). S.C. acknowledges an exchange studentship from the ERASMUS+ program of the European Union. The results shown are included as part of M.C.-M. doctoral thesis.Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region.Grants BIO2016-76640-R and PID2019.107515RB.C21 from the Spain’s State Research AgencySRA/10.13039/501100011033, co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future

Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3 + 2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e