Use of mammalian target of rapamycin inhibitors after failure of tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma undergoing hemodialysis: A single‐center experience with four cases

We retrospectively identified patients with end‐stage renal disease undergoing hemodialysis treated with the mammalian target of rapamycin inhibitors as a second‐ and/or third‐line targeted therapy after treatment failure with the tyrosine kinase inhibitors for metastatic renal cell carcinoma. Patient medical records were reviewed to evaluate the response to therapies and treatment‐related toxicities. Four patients were identified. All patients had undergone nephrectomy, and one had received immunotherapy before targeted therapy. Two patients had clear cell histology, and the other two had papillary histology. All patients were classified into the intermediate risk group according to the Memorial Sloan‐Kettering Cancer Center risk model. All patients were treated with everolimus as a second‐ or third‐line therapy, and two patients were treated with temsirolimus as a second‐ or third‐line therapy after treatment failure with sorafenib or sunitinib. The median duration of everolimus therapy was 6.7 months, whereas that of temsirolimus was 9.5 months. All patients had stable disease as the best response during each period of therapy. There were no severe adverse events. The use of mammalian target of rapamycin inhibitors in patients who previously failed to respond to tyrosine kinase inhibitors appears to be feasible in patients with end‐stage renal disease requiring hemodialysis.     

Proposal of flux‐lock‐type fault current limiter with high‐TC superconducting element

This paper proposes a new type of fault current limiter (FCL), which consists of a high‐T_C superconducting (HTS) element and two coils wound on the same core without any leakage magnetic flux. In this FCL, either the limiting impedance or the initial limiting current level can be controlled by adjusting the inductances and the winding direction of the coils. Therefore, this FCL could relax the material restrictions on high‐T_C superconducting FCL. A current‐limiting experiment by a model FCL was carried out, and the limiting performance was observed. The initial limiting current level of the model FCL was 1.7 times higher than the critical current of the HTS element, and the fault current is suppressed to 52% immediately after the short‐circuit in the test. Considering voltage–current characteristics of a high‐T_C superconductor in a computer simulation, the calculated results almost agreed with the experimental results. © 1999 Scripta Technica, Electr Eng Jpn, 127(1): 31–38, 1999     

Forced convective boiling of subcooled water at high velocity

This paper deals with heat transfer and critical heat flux (CHF) in subcooled flow boiling offering a fundamental study aimed at high heat flux cooling. Experiments with water at 0.12 MPa were conducted in a mass velocity range from 500 kg/m²s to 15,000 kg/m²s (velocity from 0.5 m/s to 15 m/s) and subcooling from 20 K to 60 K. A sheet of stainless steel (80 mm in heated length, 10 mm wide, and 0.2 mm thick) was mounted flush with a sidewall of a vertical rectangular channel (cross-section 20 mm by 30 mm) and heated directly using direct current. It was found that mass velocity and subcooling strongly affect CHF and heat transfer in non-boiling convection and partial nucleate boiling regimes. These two parameters have no appreciable influence in the fully developed nucleate boiling regime. In the parameter range used, CHF reached 15 MW/m². Boiling bubble behavior just prior to reaching CHF was found to vary depending on mass velocity and subcooling. 1998 Scripta Technica, Heat Trans Jpn Res, 27(5): 376–389, 1998     

The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells

Persistent cell shrinkage, called apoptotic volume decrease (AVD), is a pivotal event of apoptosis. Activation of the volume-sensitive outwardly rectifying Cl(-) channel (VSOR) is involved in the AVD induction. On the other hand, activation of the MAP kinase (MAPK) cascade is also known to play a critical role in apoptosis. In the present study, we investigated the relationship between the AVD induction and the stress-responsive MAPK cascade activation during the apoptosis process induced by staurosporine (STS) in HeLa cells. STS was found to induce AVD within 2-5 min and phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK after over 20-30 min. VSOR blockers suppressed not only STS-induced AVD but also phosphorylation of JNK and p38 as well as activation of caspase-3/7. Moreover, a p38 inhibitor, SB203580, and a JNK inhibitor, SP600125, failed to affect STS-induced AVD, whereas these compounds reduced STS-induced activation of caspase-3/7. Also, treatment with ASK1-specific siRNA suppressed STS-induced caspase-3/7 activation without affecting the AVD induction. Furthermore, sustained osmotic cell shrinkage per se was found to trigger phosphorylation of JNK and p38, caspase activation, and cell death. Thus, it is suggested that activation of p38 and JNK is a downstream event of AVD for the STS-induced apoptosis of HeLa cells.     

Self—Induced Oscillation of Supersonic Jet During Impingement on Cylindrical Body

INTaoDUCTIONThephenomenaoftheinteractionbetweenthesu-personicjetandanobstaclearerelatedtotheproblemSoftheaeronauticalengineeringsuchasthedesignoftherocketlaunchersysteml1]andillterestinginrela-tiontotheindustrialengineerings.Thefiowisshowntobethehsocomplexthreedimensionalwavpat-terncolit~shodwavesduetotheimpingemelltofasuPersonicjetonanobstacle,ManystudiesontheinteractionbrtweenthesuPersonicjetandanobstaclehavebeenreportedconcerningtheinteractionsoftheshodwaves[l]-I5l,theflowcharacteristi…     

Repair system where the repairmen change depending on the failed machines

In this study, the repair system of the machines having multi-input sources is analyzed in the steady state by assuming that the repairmen change is dependent on the failed machines. In the cases of two and three repairmen, it is assumed that the service abilities of each repairman differ. The mean number of failed machines and the mean waiting failed machines are derived as the characteristic values of the system.     

Estimation of endotoxin-like substances in deep seawater by using bioassay.

Deep seawater has recently been under trial as a fundamental material for mineral water, food, face lotion and an efficacious reagent for the cure of atopic dermatitis in Japan. However, little is known about the biologically effective substances, including toxic compounds in deep seawater. In this study, we investigated the effects of deep seawater on the function of murine macrophages in vitro, and examined the endotoxin-like substances in seawater. Mitochondrial activity and NO production in macrophage cells cultured with stimulants were enhanced in a depth dependent manner by pretreatment with deep seawater. In addition, fractions from deep seawater, enriched by hydrophobic column chromatography, activated the macrophage cells much more than the corresponding fractions from surface seawater. Furthermore, the effects of the fractions on macrophage cells remained significant, even with the addition of polymyxin B. which is a specific inhibitor of endotoxins. These results indicate that endotoxins and unknown substances, which affect macrophage functions, exist in a depth dependent manner in seawater.     

Novel FePBNbCr glassy alloys “SENNTIX” with good soft-magnetic properties for high efficiency commercial inductor cores

According to a recent study, Fe-based glassy alloys are expected good soft-magnetic properties such as high saturation magnetization and lower coercive force. We focused on Fe-based glassy alloys and have succeeded in developing novel glassy Fe_97?x?yP_xB_yNb₂Cr₁ (x = 5–13, y = 7–15) alloys for an inductor material. The glassy alloy series of Fe_97?x?yP_xB_yNb₂Cr₁ (x = 5–13, y = 7–15) have high glass-forming ability with the large critical thickness of 110–150 μm and high B_s of 1.25–1.35 T. The glassy alloy powder with chemical composition Fe₇₇P_10.5B_9.5Nb₂Cr₁ exhibits an excellent spherical particle shape related to the lower melting point and liquid phase point. In addition, Fe–P–B–Nb–Cr powder/resin composite core has much lower core loss of 653–881 kW/m³, which is approximately 1/3 lower than the conventional amorphous Fe–Si–B–Cr powder/resin composite core and 1/4 lower than the conventional crystalline Fe–Si–Cr powder/resin composite core due to the lower coercive force of 2.5–3.1 A/m. Based on above results, the glassy Fe₇₇P_10.5B_9.5Nb₂Cr₁ alloy powder enable to achieve ultra-high efficient and high quality products in a commercial inductor. In fact, the surface mounted inductor using Fe–P–B–Nb–Cr powder/resin exhibits the high efficiency of approximately 2.0% compared with the conventional inductors made of the crystalline Fe–Si–Cr powder/resin composite core.     

Comparison of Monte Carlo calculation methods for effective delayed neutron fraction

Monte Carlo calculation methods to estimate the effective delayed neutron fraction β_eff are investigated: one is proposed by Meulekamp et al. and the other is by Nauchi et al. It is revealed that both the methods calculate the delayed neutron fraction weighted with the importance functions defined by Kobayashi. The accuracy of the methods are also examined for several simple benchmark systems. Consequently, it is found that Meulekamp’s method causes ∼5% discrepancies in the β_eff values for fast systems; Nauchi’s method gives good results for fast bare systems but ∼10% discrepancies for fast reflected systems. Both the methods calculate the β_eff values approximately within the accuracy of ∼2% for thermal systems.