Aging and Clonal Behavior of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging.     

Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.     

The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.     

Delamination growth mechanisms in woven glass fiber reinforced polymer composites under Mode II fatigue loading at cryogenic temperatures

The purpose of this research is to characterize the cryogenic delamination growth behavior in woven glass fiber reinforced polymer (GFRP) composite laminates subjected to Mode II fatigue loading. Mode II fatigue delamination tests were performed at room temperature, liquid nitrogen temperature (77 K) and liquid helium temperature (4 K) using the four-point bend end-notched flexure (4ENF) test method, and the delamination growth rate data for the woven GFRP laminates were obtained. The energy release rate range was determined by the finite element method. Microscopic examinations of the specimen sections and fracture surfaces were also carried out. The present results are discussed to obtain an understanding of the fatigue delamination growth mechanisms in the woven GFRP laminates under Mode II loading at cryogenic temperatures.     

Pipe Heating System with Underground Water Tank for Snow Thawing and Ice Prevention on Roads and Bridge Decks

In order to prevent traffic accidents on snow-covered bridge decks, the writers developed a new pipe heating system that uses only groundwater stored in a large underground tank. The underground tank provides geothermal energy, i.e., groundwater of constant temperature, through heating pipes embedded in concrete pavements with no electric heater or fuel boiler. The pipe heating system was constructed at approximately 50% of the cost of comparable systems. In addition, there is a reduction of 10% in operating costs compared with the previous system. The present paper outlines its design and construction and provides fundamental data for the developed system. The piped heating system has kept the road conditions safe during the winter season by always removing the snow and ice from the heated road and bridge sections earlier than the surrounding roads. According to long-term temperature measurements, this system has prevented the road temperature from decreasing below 0°C, even through nighttime and morning periods. This report presents the system as an economical and effective solution for snow thawing and ice prevention.     

各种引气剂以及抑泡剂对混凝土经时变化状态等的影响

众所周知,采用粉煤灰制备混凝土,因粉煤灰成分中含有未燃炭等微粒子,容易造成阴离子型引气剂吸附在这些微粒子上,导致含气量经时损失.同时在混凝土的制备、运输过程中,因受采用的材料、拌和状态等物理因素影响,还会发生含气量经时增加的现象.所以在制备、管理混凝土时,如何保证出机初期一定的含气量、缓解含气量的经时损失或经时增加,是一项极其关键的技术.本文将就采用能改善上述状态的引气剂、抑泡剂拌和混凝土,对混凝土的经时变化以及抗冻融性等特征产生的影响进行论述.     

Application of SPRT to an image data sequence for a remote monitoring system

Recently, remote monitoring camera systems have been widely used for security. In such systems, one important function is that the system automatically detects any change in the scenes from the monitoring cameras. In wireless remote monitoring camera systems, the images of the scenes are generally transmitted as compressed data (e.g., JPEG file), because of the capacity of the wireless channel. This article shows the automated detection of the change point in time-series data of compressed JPEG file quantity (Kbytes) from the monitoring camera by applying the sequential probabilistic ratio test (SPRT) and the Chow test, which is well known as a standard method for detecting structural change in time-series data.     

Providing scalable NH-diverse iBGP route re-distribution to achieve sub-second switch-over time

The role of BGP inside an AS is to disseminate the routes learned from external peers to all routers of the AS. A straightforward, but not scalable, solution, is to resort to a full-mesh of iBGP sessions between the routers of the domain. Achieving scalability in the number of iBGP sessions is possible by using Route Reflectors (RR). Relying on a sparse iBGP graph using RRs however has a negative impact on routers’ ability to quickly switch to an alternate route in case of a failure. This stems from the fact that routers do not often know routes towards distinct next-hops, for any given prefix.In this paper, we propose a solution to build sparse iBGP topologies, where each BGP router learns two routes with distinct next-hops (NH) for each prefix. We qualify such iBGP topologies as NH-diverse. We propose to leverage the “best-external” option available on routers. By activating this option, and adding a limited number of iBGP sessions to the existing iBGP topology, we obtain NH-diverse iBGP topologies that scale, both in number of sessions and routing table sizes. We show that NH diversity enables to achieve sub-second switch-over time upon the failure of an ASBR or interdomain link. The scalability of our approach is confirmed by an evaluation on a research and a Service Provider network.     

Fabrication and operation limit of lead-free PTCR ceramics using BaTiO3–(Bi1/2Na1/2)TiO3 system

The electric properties of BaTiO₃–(Bi_1/2Na_1/2)TiO₃ (BT–BNT) solid solution ceramics were studied as a lead-free PTCR (positive temperature coefficient of resistivity) thermistor material usable over 130°C. For determining the maximum switching temperature T _s, the phase diagram of BT–BNT binary system was clarified. Two semiconductorization processes and their electric properties are described. The lanthanum(La)-doped BBNT ceramics sintered in air still showed dielectric behaviors, but the niobium(Nb)-doped ones had a low resistivity at room temperature, ρ _RT, on the order of 10³ Ωcm and showed a PTC behavior. Sintering under a low O₂ atmosphere produces BT–BNT ceramics with less than 10² Ωcm compared to those prepared in air. Our current research produced the BBNT ceramics with T _s values around 210°C by increasing the (Bi_1/2Na_1/2) content in the ceramics.