Three-dimensional topology optimization model to simulate the external shapes of bone.

Elucidation of the mechanism by which the shape of bones is formed is essential for understanding vertebrate development. Bones support the body of vertebrates by withstanding external loads, such as those imposed by gravity and muscle tension. Many studies have reported that bone formation varies in response to external loads. An increased external load induces bone synthesis, whereas a decreased external load induces bone resorption. This relationship led to the hypothesis that bone shape adapts to external load. In fact, by simulating this relationship through topology optimization, the internal trabecular structure of bones can be successfully reproduced, thereby facilitating the study of bone diseases. In contrast, there have been few attempts to simulate the external structure of bones, which determines vertebrate morphology. However, the external shape of bones may be reproduced through topology optimization because cells of the same type form both the internal and external structures of bones. Here, we constructed a three-dimensional topology optimization model to attempt the reproduction of the external shape of teleost vertebrae. In teleosts, the internal structure of the vertebral bodies is invariable, exhibiting an hourglass shape, whereas the lateral structure supporting the internal structure differs among species. Based on the anatomical observations, we applied different external loads to the hourglass-shaped part. The simulations produced a variety of three-dimensional structures, some of which exhibited several structural features similar to those of actual teleost vertebrae. In addition, by adjusting the geometric parameters, such as the width of the hourglass shape, we reproduced the variation in the teleost vertebrae shapes. These results suggest that a simulation using topology optimization can successfully reproduce the external shapes of teleost vertebrae. By applying our topology optimization model to various bones of vertebrates, we can understand how the external shape of bones adapts to external loads.

Rise and fall of Landau's quasiparticles while approaching the Mott transition.

Landau suggested that the low-temperature properties of metals can be understood in terms of long-lived quasiparticles with all complex interactions included in Fermi-liquid parameters, such as the effective mass m⋆. Despite its wide applicability, electronic transport in bad or strange metals and unconventional superconductors is controversially discussed towards a possible collapse of the quasiparticle concept. Here we explore the electrodynamic response of correlated metals at half filling for varying correlation strength upon approaching a Mott insulator. We reveal persistent Fermi-liquid behavior with pronounced quadratic dependences of the optical scattering rate on temperature and frequency, along with a puzzling elastic contribution to relaxation. The strong increase of the resistivity beyond the Ioffe-Regel-Mott limit is accompanied by a 'displaced Drude peak' in the optical conductivity. Our results, supported by a theoretical model for the optical response, demonstrate the emergence of a bad metal from resilient quasiparticles that are subject to dynamical localization and dissolve near the Mott transition.

Commensurability of the spin-density-wave state of (TMTSF)2PF6 observed by 13C-NMR.

A spin-density-wave (SDW) for (TMTSF)(2)PF(6) has been reported to appear below T(SDW) (=/~12 K), with a subphase transition at T* (=/~4 K). To determine the structure of the subphase, we synthesized (TMTSF)(2)PF(6), in which one side of the central carbon bond in each TMTSF molecule was replaced by (13)C, and utilized this compound in (13)C nuclear magnetic resonance measurements. Below T(SDW), the spectrum became broad and T(1)(-1) decreased, in agreement with previous results. Below T*, fine structures emerged in the center of the spectrum and T(1)(-1) decreased exponentially. These phenomena were attributed to the emergence of commensurability at T*.

Antiferromagnetic fluctuations in the organic superconductor kappa-(BEDT-TTF)2Cu(NCS)_{2} under pressure.

We measured the 13C-NMR spectrum and T1 of the quasi-two-dimensional organic superconductor kappa-(BEDT-TTF)2Cu(NCS)_{2} under pressure. This material was thought to show a relationship between T_{c} and the effective cyclotron mass m_{c};{*}, obtained from the Shubnikov-de Haas (SdH) effect. We found that kappa-(BEDT-TTF)2Cu(NCS)_{2} behaved as a Fermi liquid at low temperature under all pressures, and antiferromagnetic fluctuations were expected. The pressure dependence of the Korringa factor is similar to that of the effective cyclotron mass m_{c};{*}, suggesting that antiferromagnetic fluctuations contribute to the superconductivity of this material. We also found that, under pressure, T;{*} was shifted to 150 K, the temperature characteristic of the shift from bad metal to good metal.

2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants.

One of the formidable challenges in therapy of infections by human immunodeficiency virus (HIV) is the emergence of drug-resistant variants that attenuate the efficacy of highly active antiretroviral therapy (HAART). We have recently introduced 4'-ethynyl-nucleoside analogs as nucleoside reverse transcriptase inhibitors (NRTIs) that could be developed as therapeutics for treatment of HIV infections. In this study, we present 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine (EFdA), a second generation 4'-ethynyl inhibitor that exerted highly potent activity against wild-type HIV-1 (EC50 approximately 0.07 nM). EFdA retains potency toward many HIV-1 resistant strains, including the multi-drug resistant clone HIV-1A62V/V75I/F77L/F116Y/Q151M. The selectivity index of EFdA (cytotoxicity/inhibitory activity) is more favorable than all approved NRTIs used in HIV therapy. Furthermore, EFdA efficiently inhibited clinical isolates from patients heavily treated with multiple anti-HIV-1 drugs. EFdA appears to be primarily phosphorylated by the cellular 2'-deoxycytidine kinase (dCK) because: (a) the antiviral activity of EFdA was reduced by the addition of dC, which competes nucleosides phosphorylated by the dCK pathway, (b) the antiviral activity of EFdA was significantly reduced in dCK-deficient HT-1080/Ara-Cr cells, but restored after dCK transduction. Further, unlike other dA analogs, EFdA is completely resistant to degradation by adenosine deaminase. Moderate decrease in susceptibility to EFdA is conferred by a combination of three RT mutations (I142V, T165R, and M184V) that result in a significant decrease of viral fitness. Molecular modeling analysis suggests that the M184V/I substitutions may reduce anti-HIV activity of EFdA through steric hindrance between its 4'-ethynyl moiety and the V/I184 beta-branched side chains. The present data suggest that EFdA, is a promising candidate for developing as a therapeutic agent for the treatment of individuals harboring multi-drug resistant HIV variants.

Telemedicine system using a cellular telephone for continuous ambulatory peritoneal dialysis patients.

We developed a new telemedicine system to monitor the condition of continuous ambulatory peritoneal dialysis (CAPD) patients by using a cellular telephone and an Internet Web site. All data for the CAPD patients--blood pressure, heart rate, body weight, ultrafiltration volume, and urine volume--are collected and sent directly by cellular telephone to a data server that was constructed at the NTT DoCoMo Company data center. The system is directly connected to Internet by application service provider (ASP) technology. Anywhere, at any time, each patient can confirm changes in their data in graph form by using a cellular telephone or a computer connection to an Internet Web site. The average of each type of data is calculated and shown at the Web site. All data collected by cellular telephone are calculated and, in real time, sent directly to the treating physician's office over the Internet. Abnormal data are sent directly to the treating physician's office and shown in the host computer with an emergency signal (emergency alarm system). In addition, CAPD patients can easily contact the medical staff in the Kidney and Dialysis Center of Saitama Medical School (main hospital) using the same telemedicine system. We are using this telemedicine system for 46 CAPD patients being treated by Saitama Medical School. The cost of using the system is just US$3.00 or less per month for each patient. This newly developed system has great advantages for CAPD patients, especially elderly and handicapped patients. The system can be expanded into a network that serves all CAPD patients and all hospitals in Japan.