Klotho mice: a novel wound model of aged skin.

BackgroundAs the elderly population continues to expand, it becomes increasingly important to develop treatments to improve wound healing in the elderly. One problem limiting the research is the lack of appropriate animal models for wound healing in elderly patients. We hypothesized that the Klotho mouse of premature aging is a suitable animal model to shed light on many of the biological processes involved in aging skin.MethodsKlotho mice (kl/kl), Klotho-heterozygous mice (kl/+), and wild-type mice (+/+) were wounded, and the area of the wound was measured every 3 days until the wound was healed. To compare the klotho phenotype with wild-type mice, wounds were also harvested at 4 and 7 days after wounding. For histological examination, paraffin-embedded sections were stained with hematoxylin and eosin and Masson trichrome. Collagen expression in the wound was also studied by analyzing messenger RNA using real-time polymerase chain reaction.ResultsKlotho mice showed a significantly slower rate of wound closure compared with Klotho-heterozygous mice and wild-type mice. Histology showed substantial less healing and collagen deposition in the wounds of the Klotho mice. The expression of collagen messenger RNA in Klotho mice was also less than that in heterozygous and wild-type mice. The Klotho mice exhibited significant phenotypic similarities with aged skin, such as atrophy and delayed wound healing.ConclusionThese preliminary data suggest that the Klotho mouse may be a model to further investigate wound healing in the elderly

QCD Correction to Neutralino Annihilation Process and Dark Matter Density in Supersymmetric Models

We calculate QCD correction to the neutralino annihilation cross section into quark anti-quark final state and discuss its implications to the calculation of neutralino relic density. We see that the QCD correction enhances the pair-annihilation cross section by O(10 %) when final-state quarks are non-relativistic. Consequently, when the lightest neutralinos dominantly annihilate into a t\bar{t} pair, the relic density of the lightest neutralino is significantly affected by the QCD correction, in particular when the lightest-neutralino mass is close to the top-quark mass.Comment: 19 pages, 5 figure

Big-Bang Nucleosynthesis with Unstable Gravitino and Upper Bound on the Reheating Temperature

We study the effects of the unstable gravitino on the big-bang nucleosynthesis. If the gravitino mass is smaller than \sim 10 TeV, primordial gravitinos produced after the inflation are likely to decay after the big-bang nucleosynthesis starts, and the light element abundances may be significantly affected by the hadro- and photo-dissociation processes as well as by the p n conversion process. We calculate the light element abundances and derived upper bound on the reheating temperature after the inflation. In our analysis, we calculate the decay parameters of the gravitino (i.e., lifetime and branching ratios) in detail. In addition, we performed a systematic study of the hadron spectrum produced by the gravitino decay, taking account of all the hadrons produced by the decay products of the gravitino (including the daughter superparticles). We discuss the model-dependence of the upper bound on the reheating temperature.Comment: 32 pages, 11 figure

Crucial Dependence of ``Precarious'' and ``Autonomous'' phi^4s Upon the Normal-ordering Mass

Using the Gaussian wave-functional approach with the normal-ordering renormalization prescription, we show that for the (3+1)-dimensional massive lambda phi^4 theory, ``precarious'' and ``autonomous'' phi^4s can exist if and only if the normal-ordering mass is equal to the classical masses at the symmetrc and asymmetric vacua, respectively.Comment: 6 pages, no figures, Revtex file, accepted for publication in Mod. Phys. Lett.

Bi-directional of a Built-in Test Circuit for Interconnect Defects in Assembled PCBs

Bi-directional of a built-in test circuit is proposed to detect open defects at inputs and output interconnects between ICs and a PCB. The test circuit is based on an electrical characteristic of an inverter gate. A test method is related to supply current which flows to the inverter by providing a test signal to the test circuit. The test signal is generated by an AC voltage signal with a DC offset voltage. The open defects which occur at the interconnects will be detected by the large supply current flows to the inverter. On the other hand, if the defects don't occur, the supply current of the inverter is almost zero. Testability of the test circuit is examined using a Spice simulation. The results show that the open defects at the interconnects can be detected and located

Reconstructing Dark Matter Density with e^+e^- Linear Collider in Focus-Point Supersymmetry

It has been known that, in the focus point scenario of supersymmetry, the thermal relic of the lightest superparticle (LSP) is known to be a good candidate of the cold dark matter. Assuming that the LSP in the focus-point scenario be the cold dark matter, we address a question how and how well the relic density of the LSP can be determined once the superparticles are found at future e^+e^- linear collider. We will see that the determinations of the mass of the LSP as well as those of the Higgsino-like chargino and neutralinos, which will be possible by a study of the decay kinematics of the chargino or by threshold scan, will give us important information to theoretically reconstruct the relic density. Even if the Higgsino-like superparticles and the LSP are the only superparticles which are kinematically accessible, relic density of the LSP may be calculated with the accuracy of factor \sim 2; by adopting a mild theoretical assumption or by determining the masses of the Wino-like superparticles, uncertaintiy can be reduced to \sim 10 % or smaller.Comment: 13 pages, 4 figure

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space

Immunodominant T cell epitopes preferentially targeted in multiple individuals are the critical element of successful vaccines and targeted immunotherapies. However, the underlying principles of this “convergence” of adaptive immunity among different individuals remain poorly understood. To quantitatively describe epitope immunogenicity, here we propose a supervised machine learning framework generating probabilistic estimates of immunogenicity, termed “immunogenicity scores,” based on the numerical features computed through sequence-based simulation approximating the molecular scanning process of peptides presented onto major histocompatibility complex (MHC) by the human T cell receptor (TCR) repertoire. Notably, overlapping sets of intermolecular interaction parameters were commonly utilized in MHC-I and MHC-II prediction. Moreover, a similar simulation of individual TCR-peptide interaction using the same set of interaction parameters yielded correlates of TCR affinity. Pathogen-derived epitopes and tumor-associated epitopes with positive T cell reactivity generally had higher immunogenicity scores than non-immunogenic counterparts, whereas thymically expressed self-epitopes were assigned relatively low scores regardless of their immunogenicity annotation. Immunogenicity score dynamics among single amino acid mutants delineated the landscape of position- and residue-specific mutational impacts. Simulation of position-specific immunogenicity score dynamics detected residues with high escape potential in multiple epitopes, consistent with known escape mutations in the literature. This study indicates that targeting of epitopes by human adaptive immunity is to some extent directed by defined thermodynamic principles. The proposed framework also has a practical implication in that it may enable to more efficiently prioritize epitope candidates highly prone to T cell recognition in multiple individuals, warranting prospective validation across different cohorts

タソウ ハイセン LSI ノ ダンセン コショウ ケンサ ニ カンスル ケンキュウ

Open faults are difficult to test since the floating wire occurred by an open fault has unstable voltage. In this work, the effect of adjacent lines around an open fault in multi-layered wiring LSIs is discussed. To observe the relation between an open fault and the adjacent lines, a 0.35μm CMOS IC is designed and fabricated. The open fault macros with a transmission gate and with an intentional break are included in the IC. The adjacent lines in the same layer and the different layers are placed in the test chip. The simulation and experimental results show that the voltage at the floating wire is affected by the adjacent lines

Incidence of sexually transmitted hepatitis C virus infection among men who have sex with men in Japan from 2009 to 2023

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct-acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty-two cases were newly confirmed to be HCV infection in 2009-2019 and a total of 9 cases in 2020-2023, with an incidence rate of 5.04 per 1000 person-years in 2009-2019 and 5.55 per 1000 person-years in 2020-2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non-HIV-infected persons, may be much higher