Higher-Order Allan Variance for Atomic Clocks of Arbitrary Order

In this paper, we perform a time-domain analysis of the higher-order Allan variance for atomic clock models of arbitrary order. Adopting a standard atomic clock model where the time series of the clock reading deviation is expressed as a Wiener or integrated Wiener process, we define the higher-order Allan variance as the mean squared higher-order difference of the clock reading deviation. The main results of this paper are threefold. First, we prove that the higher-order difference operation of the clock reading deviation, which can be interpreted as a linear aggregation with binomial coefficients, is not only sufficient, but also necessary for a resulting aggregated time series to be an independent and identically distributed Gaussian process. Second, we derive a complete analytical expression of the higher-order Allan variance, which consists of both time-dependent and time-independent terms. Third and finally, we prove that the higher-order Allan variance is time-independent if and only if the order of difference operation is greater than or equal to the order of the atomic clock model

Preparation of Corrosion-Resistant Films on Magnesium Alloys by Steam Coating

This chapter introduces a novel, chemical-free “steam coating” method for preparing films on magnesium (Mg) alloys and assesses their effectiveness in improving the corrosion resistance of two different Mg alloys. A film composed of crystalline Mg(OH)2 and Mg-Al layered double hydroxide (LDH) was successfully formed on AZ31 Mg alloy, and its corrosion resistance was evaluated through electrochemical measurements and immersion tests in an aqueous solution containing 5 wt.% NaCl. An anticorrosive film was also formed on Ca-added flame-resistant AM60 (AMCa602) Mg alloy via the same steam coating method and found to be composed of crystalline Mg(OH)2 and Mg-Al layered double hydroxide (LDH). Its corrosion resistance was also investigated, and the effectiveness of the steam coating method for improving the corrosion resistance of Mg was fully explored

CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact

The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.Instituto de BiotecnologíaFil: Ishizaki, Takahiro. Umeå University. Department of Molecular Biology; SueciaFil: Ishizaki, Takahiro. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Hernandez, Sophia. Umeå University. Department of Molecular Biology; SueciaFil: Hernandez, Sophia. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paoletta, Martina. Umeå University. Department of Molecular Biology; SueciaFil: Paoletta, Martina. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Sanderson, Theo. Francis Crick Institute; Reino UnidoFil: Bushell, Ellen S. C. Umeå University. Department of Molecular Biology; SueciaFil: Bushell, Ellen S. C. The Laboratory for Molecular Infection Medicine Sweden (MIMS); Sueci

Nanometer-thin TiO2 enhances skeletal muscle cell phenotype and behavior

Ken Ishizaki*, Yoshihiko Sugita*, Fuminori Iwasa, Hajime Minamikawa, Takeshi Ueno, Masahiro Yamada, Takeo Suzuki, Takahiro OgawaLaboratory for Bone and Implant Sciences, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA*Authors contributed equally to this workBackground: The independent role of the surface chemistry of titanium in determining its biological properties is yet to be determined. Although titanium implants are often in contact with muscle tissue, the interaction of muscle cells with titanium is largely unknown. This study tested the hypotheses that the surface chemistry of clinically established microroughened titanium surfaces could be controllably varied by coating with a minimally thin layer of TiO2 (ideally pico-to-nanometer in thickness) without altering the existing topographical and roughness features, and that the change in superficial chemistry of titanium is effective in improving the biological properties of titanium.Methods and results: Acid-etched microroughened titanium surfaces were coated with TiO2 using slow-rate sputter deposition of molten TiO2 nanoparticles. A TiO2 coating of 300 pm to 6.3 nm increased the surface oxygen on the titanium substrates in a controllable manner, but did not alter the existing microscale architecture and roughness of the substrates. Cells derived from rat skeletal muscles showed increased attachment, spread, adhesion strength, proliferation, gene expression, and collagen production at the initial and early stage of culture on 6.3 nm thick TiO2-coated microroughened titanium surfaces compared with uncoated titanium surfaces.Conclusion: Using an exemplary slow-rate sputter deposition technique of molten TiO2 nanoparticles, this study demonstrated that titanium substrates, even with microscale roughness, can be sufficiently chemically modified to enhance their biological properties without altering the existing microscale morphology. The controllable and exclusive chemical modification technique presented in this study may open a new avenue for surface modifications of titanium-based biomaterials for better cell and tissue affinity and reaction.Keywords: nanotechnology, orthopedic implants, molten TiO2 nanoparticles, surface chemistr

Distinct effects on the secretion of MTRAP and AMA1 in Plasmodium yoelii following deletion of acylated pleckstrin homology domain-containing protein

Plasmodium, the causative agents of malaria, are obligate intracellular organisms. In humans, pathogenesis is caused by the blood stage parasite, which multiplies within erythrocytes, thus erythrocyte invasion is an essential developmental step. Merozoite form parasites released into the blood stream coordinately secrets a panel of proteins from the microneme secretory organelles for gliding motility, establishment of a tight junction with a target naive erythrocyte, and subsequent internalization. A protein identified in Toxoplasma gondii facilitates microneme fusion with the plasma membrane for exocytosis; namely, acylated pleckstrin homology domain-containing protein (APH). To obtain insight into the differential microneme discharge by malaria parasites, in this study we analyzed the consequences of APH deletion in the rodent malaria model, Plasmodium yoelii, using a DiCre-based inducible knockout method. We found that APH deletion resulted in a reduction in parasite asexual growth and erythrocyte invasion, with some parasites retaining the ability to invade and grow without APH. APH deletion impaired the secretion of microneme proteins, MTRAP and AMA1, and upon contact with erythrocytes the secretion of MTRAP, but not AMA1, was observed. APH-deleted merozoites were able to attach to and deform erythrocytes, consistent with the observed MTRAP secretion. Tight junctions were formed, but echinocytosis after merozoite internalization into erythrocytes was significantly reduced, consistent with the observed absence of AMA1 secretion. Together with our observation that APH largely colocalized with MTRAP, but less with AMA1, we propose that APH is directly involved in MTRAP secretion; whereas any role of APH in AMA1 secretion is indirect in Plasmodium

Household income relationship with health services utilization and healthcare expenditures in people aged 75 years or older in Japan: A population-based study using medical and long-term care insurance claims data

Background: This study aimed to determine whether there are disparities in healthcare services utilization according to household income among people aged 75 years or older in Japan.Methods: We used data on medical and long-term care (LTC) insurance claims and on LTC insurance premiums and needs levels for people aged 75 years or older in a suburban city. Data on people receiving public welfare were not available. Participants were categorized according to household income level using LTC insurance premiums data. The associations of low income with physician visit frequency, length of hospital stay (LOS), and medical and LTC expenditures were evaluated and adjusted for 5-year age groups and LTC needs level.Results: The study analyzed 12,852 men and 18,020 women, among which 13.3% and 41.5%, respectively, were categorized as low income. Participants with low income for both genders were more likely to be functionally dependent. In the adjusted analyses, lower income was associated with fewer physician visits (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI], 0.87–0.92 for men and IRR 0.97; 95% CI, 0.95–0.99 for women), longer LOS (IRR 1.98; 95% CI, 1.54–2.56 and IRR 1.42; 95% CI, 1.20–1.67, respectively), and higher total expenditures (exp(β) 1.09; 95% CI, 1.01–1.18 and exp(β) 1.09; 95% CI, 1.05–1.14, respectively).Conclusions: This study suggests that older people with lower income had fewer consultations with physicians but an increased use of inpatient services. The income categorization used in this study may be an appropriate proxy of socioeconomic status

cAMP-dependent protein kinase regulates secretion of apical membrane antigen 1 (AMA1) in Plasmodium yoelii

Malaria remains a heavy global burden on human health, and it is important to understand the molecular and cellular biology of the parasite to find targets for drug and vaccine development. The mouse malaria model is an essential tool to characterize the function of identified molecules; however, robust technologies for targeted gene deletions are still poorly developed for the widely used rodent malaria parasite, Plasmodium yoelii. To overcome this problem, we established a DiCre-loxP inducible knockout (iKO) system in P. yoelii, which showed more than 80% excision efficacy of the target locus and more than 90% reduction of locus transcripts 24 h (one cell cycle) after RAP administration. Using this developed system, cAMP-dependent protein kinase (PKAc) was inducibly disrupted and the phenotypes of the resulting PKAc-iKO parasites were analyzed. We found that PKAc-iKO parasites showed severe growth and erythrocyte invasion defects. We also found that disruption of PKAc impaired the secretion of AMA1 in P. yoelii, in contrast to a report showing no role of PKAc in AMA1 secretion in P. falciparum. This discrepancy may be related to the difference in the timing of AMA1 distribution to the merozoite surface, which occurs just after egress for P. falciparum, but after several minutes for P. yoelii. Secretions of PyEBL, Py235, and RON2 were not affected by the disruption of PKAc in P. yoelii. PyRON2 was already secreted to the merozoite surface immediately after merozoite egress, which is inconsistent with the current model that RON2 is injected into the erythrocyte cytosol. Further investigations are required to understand the role of RON2 exposed on the merozoite surface