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Aim: Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L‐FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L‐FABP increase using a more severe mouse model with histone‐induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L‐FABP as a preliminary study. Methods: Human L‐FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L‐FABP, we used heparin and rolipram. Results: The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L‐FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L‐FABP levels significantly decreased. Conclusion: Histone is one of the causative agents for the increase of urinary L‐FABP at an early stage of AKI. In addition, it suggested that urinary L‐FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L‐FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor. Summary at a glance: Histone is one of the causative agents for urinary L‐FABP increase at an early stage of AKI. Urinary L‐FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Urinary L‐FABP reflected the degree of damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor. [ABSTRACT FROM AUTHOR]

Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 ([T.sub.H]2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants., Since the first report of its adjuvant activity in 1926 (ref. 1), it has been widely believed that alum creates an immunologically inert 'depot' that prolongs antigen exposure or facilitates [...]

Background: The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. Methods: Eight-week-old SDT fatty rats (n = 12) and Sprague-Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise 4 times a week from ages 8–16 weeks. Results: The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. Conclusion: Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels. [ABSTRACT FROM AUTHOR]

This paper presents the design and performance of 60-GHz-band coplanar monolithic microwave integrated circuit (MMIC) active filters. To compensate for the loss of the passive filter, a resonator composed of a quarter-wavelength line is terminated by a circuit with a constant negative resistance over a wide frequency band. Cross-coupling is introduced to make the attenuation poles on both sides of the passband. We develop two types of two-stage filter: one with medium bandwidth and the other with narrow bandwidth. The former shows an insertion loss of 3.0 dB with a 3-dB bandwidth of 2.6 GHz and a rejection of larger than 20 dB at a 3-GHz separation from a center frequency of 65.0 GHz. This filter also shows a noise figure of 10.5 dB. The latter filter shows an insertion loss of 2.8 dB with a 10-dB bandwidth of 2.1 GHz at a center frequency of 65.0 GHz. It also shows an output power of 5.0 dBm at a 1-dB compression point, The loss variation due to temperature variation is successfully compensated using a gate bias control circuit. The size of the MMIC filters is 2.5 mm x 1.1 mm. Index Terms--Active filters, bandpass filters, coplanar wave-guides, negative-resistance circuits.

This paper describes the development, along with detailed phase-noise analysis, of V-band monolithic-microwave integrated-circuit (MMIC) dielectric-resonator oscillators (DROs) achieving state-of-the-art performances. A T[E.sub.01[delta]]-mode Ba(Mg,Ta)[O.sub.3] cylindrical dielectric resonator (DR) is directly placed on a MMIC GaAs substrate to avoid the loss and uncertainty of bonding wires. A 0.15-[micro]m AlGaAs-InGaAs heterojunction field-effect transistor with optimized structure is developed as an active device. A design procedure proposed by the authors is employed, which allows us to analyze and optimize circuits in consideration for the output power, phase noise, and temperature stability. A developed DRO co-integrated with a buffer amplifier exhibits a low phase noise of -90 dBc/Hz at 100-kHz offset, a high output power of 10.0 dBm, and an excellent frequency stability of 1.6 ppm/[degrees]C at an oscillation frequency of 59.6 GHz, all of which are state-of-the-art performances reported for MMIC DROs above V-band. An experimental and theoretical analysis for the phase-noise-reduction effect of a DR is also addressed. Index Terms--Dielectric resonator oscillators (DROs), dielectric resonators (DRs), field-effect transistors (FETs), millimeter wave, monolithic microwave integrated circuits (MMICs), oscillators.

This paper describes a systematic approach to the design and analysis for dielectric resonator oscillators (DROs). The approach features a temperature- and structural-parameters-independent dielectric resonator (DR) model and a newly developed temperature-dependent nonlinear FET model. The implementation of these models on a harmonic-balance circuit simulator allows prediction for mechanical tuning characteristics, coupling strength dependencies, and temperature-dependent performance of oscillation frequency, output power, and phase noise of DROs. V-band heterojunction FET monolithic-microwave integrated-circuit DROs utilizing a [TE.sub.01[sigma]]-mode cylindrical DR were designed and fabricated based on the proposed procedure. Good agreement between the predicted and measured characteristics indicates the validity of our design technique featuring the proposed DR and FET models. Index Terms--Dielectric resonator oscillators (DROs), dielectric resonators (DRs), FETs, millimeter wave, monolithic microwave integrated circuits (MMICs), oscillators, temperature.

A planar dielectric waveguide filter with coplanar waveguide (CPW) I/O ports suitable for flip-chip bonding is proposed and is demonstrated for 60-GHz-band applications. The filter is formed incorporating metallized through holes in an alumina substrate. In order to improve stopband rejection, short-circuited CPW resonators with a half-wavelength are added to waveguide-to-CPW transitions. A fabricated four-resonator filter exhibits an insertion loss of 3.2 dB with a 3-dB bandwidth of 3.0 GHz and rejection of 35 dB at 3-GHz lower separation from a center frequency of 59.5 GHz. The filter is mounted by using flip-chip bonding in a multilayer ceramic package with structures to suppress parasitically propagating electromagnetic waves. No degradation of the stopband rejection is observed from 50 to 80 GHz. Index Terms--Bandpass filters, coplanar waveguides, dielectric waveguides, flip-chip devices, millimeter-wave filters, waveguide filters.

This paper presents a 60-GHz-band GaAs heterojunction FET (HJFET) low-noise amplifier (LNA) operating with a single bias supply. A diode-regulated self-bias circuit was incorporated for suppressing the FET drain-current variations due to threshold voltage nonuniformities. The effect of the bias circuit on the drain - current distribution is carefully discussed based on the FET dc characteristics. A developed three-stage monolithic microwave integrated circuit (MMIC) LNA exhibited an average noise figure of 3.3 dB with 18-dB gain from 58 to 62 GHz. The LNA could operate over 2-5 V with a constant noise figure. The LNA chip size is 1.85 mm x 1.07 mm. Index Terms - Amplifier noise, millimeter-wave amplifiers, millimeter-wave integrated circuits, MMIC's, MODFET amplifiers.

The development of 60 GHz-band ultra-miniature FM/frequency-shift keying (FM/FSK) transmitter/receiver modules fabricated with a complete monolithic-microwave integrated circuits (MMIC) chip set, including dielectrically stabilized fundamental-frequency oscillators for multimedia wireless communication systems, is reported. The 0.9 cc transmitter module, which consists of a voltage controlled oscillator (VCO) and two power amplifiers, exhibits 11.5 MHz/V modulation sensitivity, 10.2 dBm output power, and -2.4 ppm/[degrees] C frequency stability. With the receiver module, which consists of low noise amplifier (LNA), a mixer, and a local oscillator (LO), 5.4 dB double-side band (DSB) noise figure with 10.8 dB downconversion gain has been achieved. The 60 GHz-band monolithic dielectric-resonator (DR) stabilized oscillators offer a practical approach to ultra-miniature transmitter/receiver modules for high-speed wireless LAN systems with data rates greater than 10 Mbps and for video-signal and compressed HDTV-signal (MUSE) transmission systems.

This paper describes design consideration and performance of a Ka-band monolithic phase shifter utilizing nonresonant FET switches. The switches show broad-band on/off characteristics up to 60 GHz without using inductors; thus, robust circuit design is possible for a switched-line phase shifter. To determine circuit topology, we introduce a schematic design approach. As a result, desired phase shift as well as good matching characteristics can be realized. The developed 4-bit monolithic phase shifter demonstrates an overall phase deviation less than 5 [degrees] rms and an insertion loss variation less than 0.65 dB rms from 33 to 35 GHz. For all 16 states, the insertion loss is measured to be 13.14 [+ or -] 1.1 dB and the VSWR is less than 1.6. The chip size of the monolithic phase shifter is 2.5 mm x 2.2 mm. Index Terms--Millimeter-wave phase shifter, MMIC's, MMIC phase shifters, MODFET switches.