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Transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of cation channels, is broadly expressed in sensory neural pathways, including the trigeminal neurons innervating the nasal cavity and vagal neurons innervating the trachea and the lung. TRPA1 acts as a detector of various irritant chemicals as well as hypoxia and hyperoxia. For the past 15 years, we have characterised its role in respiratory and behavioural modulation in vivo using Trpa1 knockout (KO) mice and wild‐type (WT) littermates. Trpa1 KO mice failed to detect, wake up from sleeping, and escape from formalin vapour and a mild hypoxic (15% O2) environment. Respiratory augmentation induced by mild hypoxia was absent in either Trpa1 KO mice or WT mice treated with a TRPA1 antagonist. Irritant gas introduced into the nasal cavity inhibited respiratory responses in WT mice but not in the KO mice. The effect of TRPA1 on the olfactory system seemed minimal because olfactory bulbectomized WT mice reacted similarly to the intact mice. Immunohistological analyses using a cellar activation marker, the phosphorylated form of extracellular signal‐regulated kinase, confirmed activation of trigeminal neurons in WT mice but not in Trpa1 KO mice in response to irritant chemicals and mild hypoxia. These data collectively show that TRPA1 is necessary for multiple chemical‐induced protective responses in respiration and behaviour. We propose that TRPA1 channels in the airway may play a sentinel role for environmental threats and prevent incoming damage. [ABSTRACT FROM AUTHOR]

Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long‐term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor‐specific CTLs could play a role in long‐term survival (5 years or longer) in patients with recurrence and/or distant metastases. Therefore, we aimed to obtain Abs that specifically bind to cancer cells by using serum samples from patients with a good prognosis. A phage library was prepared using PBMC mRNA of the patients, and cell panning was carried out using an esophageal cancer cell line. Results showed the presence of an epidermal growth factor receptor (EGFR) Ab, KT112, that specifically bound to the cancer cell line. Notably, KT112 bound to only EGFR‐positive cancer cells but failed to bind to normal esophageal cells. Furthermore, KT112 was characterized by responses to EGFR expressed on cancer cells but not to the recombinant extracellular domain of EGFR. Immunohistochemical analysis showed that KT112 reacted with 17.4% of esophageal squamous cell carcinoma tissue but not with any other cancer or normal tissue, suggesting that the Ab recognizes cancer‐specific forms of EGFR and might have contributed to tumor suppression in patients with esophageal cancer. Furthermore, because of its high cancer specificity, KT112 could be a promising therapeutic option (e.g., in Ab‐drug conjugates) for esophageal cancer. [ABSTRACT FROM AUTHOR]

In recent years, several studies have been performed on methods of investigating the periphery of power lines using remote sensing. Among the survey methods using unmanned aerial vehicles (UAVs), those methods are being studied wherein the environment around power lines is photographed by a UAV, and separation measurements are performed by reconstructing the three‐dimensional (3D) point cloud between power lines and the vegetation. Such methods currently rely on reconstructing the power line, making it necessary to acquire images from a position close to the power line. However, by using information available from the power company on the position and structure of pylons and the sag of power lines, it is possible to calculate the position of the power line without 3D reconstruction. In this study, time series management of vegetation around power lines was enabled using the data obtained by UAVs at different times and information on the transmission equipment. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

IgG2 subclass antibodies have unique properties that include low effector function and a rigid hinge region. Although some IgG2 subclasses have been clinically tested and approved for therapeutic use, they have a higher propensity than IgG1 for aggregation, which can curtail or abolish their biological activity and enhance their immunogenicity. In this regard, acid‐induced aggregation of monoclonal antibodies during purification and virus inactivation must be prevented. In the present study, we replaced the constant domain of IgG2 with that of IgG1, using anti‐2,4‐dinitrophenol (DNP) IgG2 as a model antibody, and investigated whether that would confer greater stability. While the anti‐DNP IgG2 antibody showed significant aggregation at low pH, this was reduced for the IgG2 antibody containing the IgG1 CH2 domain. Substituting three amino acids within the CH2 domain—namely, F300Y, V309L, and T339A (IgG2_YLA)—reduced aggregation at low pH and increased CH2 transition temperature, as determined by differential scanning calorimetric analysis. IgG2_YLA exhibited similar antigen‐binding capacity to IgG2, low affinity for FcγRIIIa, and low binding ability to C1q. The same YLA substitution also reduced the aggregation of panitumumab, another IgG2 antibody, at low pH. Our engineered human IgG2 antibody showed reduced aggregation during bioprocessing and provides a basis for designing improved IgG2 antibodies for therapeutic applications. [ABSTRACT FROM AUTHOR]

Human IgG comprises four subclasses with different biological functions. The IgG3 subclass has a unique character, exhibiting high effector function and Fab arm flexibility. However, it is not used as a therapeutic drug owing to an enhanced susceptibility to proteolysis. Antibody aggregation control is also important for therapeutic antibody development. To date, there have been few reports of IgG3 aggregation during protein expression and the low pH conditions needed for purification and virus inactivation. This study explored the potential of IgG3 antibody for therapeutics using anti‐CD20 IgG3 as a model to investigate aggregate formation. Initially, anti‐CD20 IgG3 antibody showed substantial aggregate formation during expression and low pH treatment. To circumvent this phenomenon, we systematically exchanged IgG3 constant domains with those of IgG1, a stable IgG. IgG3 antibody with the IgG1 CH3 domain exhibited reduced aggregate formation during expression. Differential scanning calorimetric analysis of individual amino acid substitutions revealed that two amino acid mutations in the CH3 domain, N392K and M397V, reduced aggregation and increased CH3 transition temperature. The engineered human IgG3 antibody was further improved by additional mutations of R435H to obtain IgG3KVH to achieve protein A binding and showed similar antigen binding as wild‐type IgG3. IgG3KVH also exhibited high binding activity for FcγRIIIa and C1q. In summary, we have successfully established an engineered human IgG3 antibody with reduced aggregation during bioprocessing, which will contribute to the better design of therapeutic antibodies with high effector function and Fab arm flexibility. [ABSTRACT FROM AUTHOR]

BACKGROUND Cocoa contains biologically active ingredients that have broad-spectrum antimicrobial activity, which includes an inhibitory effect on influenza virus infection. RESULTS A cocoa extract ( CE) was prepared by treating defatted cocoa powder with boiling water. The extract demonstrated dose-dependent inhibition of infection in Madin-Darby canine kidney ( MDCK) cells infected with human influenza virus A ( H1N1, H3N2), human influenza virus B and avian influenza viruses ( H5N1, H5N9). CE inhibited viral adsorption to MDCK cells. Animal experiments showed that CE significantly improved survival in mice after intra-nasal administration of a lethal dose of influenza virus. In human intervention trials, participants were allocated to two groups, one in which the participants ingested cocoa for 3 weeks before and after vaccination against A( H1N1)pdm2009 influenza virus and another in which the participants did not ingest cocoa. Neutralizing antibody titers against A( H1N1)pdm2009 influenza virus increased significantly in both groups; however, the extent of the increase was not significantly different between the two groups. Although natural killer cell activity was also elevated in both groups, the increase was more substantial in the cocoa intake group. CONCLUSION Drinking cocoa activates natural immunity and enhances vaccination-induced immune response, providing stronger protection against influenza virus infection and disease onset. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

We demonstrated that indium tribromide effectively functioned as a single catalyst for two successive steps in a one-pot procedure. First, the hydroamination of alkynes with anilines took place to give the Markovnikov product. Then, hydrosilylation of the imine intermediates by treatment with a hydrosilane substrate afforded the corresponding secondary amines. [ABSTRACT FROM AUTHOR]

We previously reported that 3′-sulfoquinovosyl-1′-monoacylglycerol ( SQMG) effectively suppresses the growth of solid tumors, likely via its anti-angiogenic activity. To investigate how SQMG affects angiogenesis, we performed DNA microarray analysis and quantitative real-time polymerase chain reaction. Consequently, upregulation of thrombospondin 1 ( TSP-1) in SQMG-treated tumors in vitro and in vivo was confirmed. To address the mechanisms of TSP-1 upregulation by SQMG, we established stable TSP-1-knockdown transformants ( TSP1- KT) by short hairpin RNA induction and performed reporter assay and in vivo assessment of anti-tumor assay. On the reporter assay, transcriptional upregulation of TSP-1 in TSP1- KT could not be induced by SQMG, thus suggesting that TSP-1 upregulation by SQMG occurred via TSP-1 molecule. In addition, growth of TSP1- KT xenografted tumors in vivo was not inhibited by SQMG, thus suggesting that anti-angiogenesis via TSP-1 upregulation induced by SQMG did not occur, as the SQMG target molecule TSP-1 was knocked down in TSP1- KT transformants. These data provide that SQMG is a promising candidate for the treatment of tumor-induced angiogenesis via TSP-1 upregulation. ( Cancer Sci 2012; 103: 1546-1552) [ABSTRACT FROM AUTHOR]

The article investigates the improvement of poly(vinyl alcohol) (PVA) properties by the addition of magnesium nitrate. The authors prepared composites of PVA and magnesium nitrate hexadydrate and found that the composites were very soft and rubber-like. By using wide-angle X-ray diffraction and small-angle X-ray scattering, it was found that the crystallites of PVA were destroyed by the additive.

We previously reported that 3′-sulfoquinovosyl-1′-monoacylglycerol (SQMG) was effective in suppressing the growth of solid tumors due to hemorrhagic necrosis in vivo. In the present study, we investigated the antiangiogenic effect of SQMG. In vivo assessment of antitumor assays showed that some tumor cell lines, but not others, were sensitive to SQMG. Microscopic study suggested that in SQMG-sensitive tumors, but not SQMG-resistant tumors, angiogenesis was reduced. We next investigated gene expression relating to angiogenesis in tumor tissues by quantitative real-time polymerase chain reaction. Consequently, although vascular endothelial growth factor gene expression was not detected with significant differences among the cases, significant downregulation of Tie2 gene expression was observed in all SQMG-sensitive tumors as compared with controls, but not in SQMG-resistant tumors. These data suggested that the antitumor effects of SQMG could be attributed to antiangiogenic effects, possibly via the downregulation of Tie2 gene expression in SQMG-sensitive tumors. ( Cancer Sci 2008; 99: 1063–1070) [ABSTRACT FROM AUTHOR]

This paper proposes a realization of first- and second-order switched-capacitor (SC) all-pass filters (APF) with a low amplitude sensitivity and a parasitic capacitor insensitivity. Kato and Takebe have proposed a first-order SC APF where the peak group delay for the zero angular frequency can be defined by means of a programmable capacitor array, as well as a second-order SC APF with the first-order SC APF as a partial subcircuit, where the peak value of the bandpass group delay and the corresponding angular frequency (peak angular frequency) can be defined independently. Their second-order SC APF has the problem that the amplitude element sensitivity is large and the response is sensitive to parasitic capacitance. The SC APFs proposed in this paper are insensitive to parasitic capacitance, and the absolute value sum of the amplitude sensitivities is very small, being 0 in the first-order SC APF and less than 2 in the second-order SC APF. Further, the number of operational amplifiers is reduced by 1 and the number of capacitors is halved in the proposed second-order SC APF, compared to the already proposed circuits. The proposed circuit is experimentally constructed by discrete components, and a satisfactory result is obtained. © 2000 Scripta Technica, Electron Comm Jpn Pt 3, 84(1): 84–94, 2001 [ABSTRACT FROM AUTHOR]

Alteration of the p53 tumor suppressor gene is a common, if not general, observation in human malignant tumors. p73 Is a novel member of the p53 family at chromosome 1p36.3, at which locus frequent defects are seen in many tumors including neuroblastoma. Besides structural similarities, the fact that p73 functions in the regulation of the cell cycle and apoptosis promotes the expansion of the research field concerning p53-associated tumor progression. In this paper, we review the structure and function of p73 as well as the mutational status in various human tumors. In addition, possibilities for new therapeutic applications with p73 for cancer cell control are discussed. [ABSTRACT FROM AUTHOR]

This paper proposes an adaptive second-order IIR bandpass decimation filter for detecting a single sinusoid with an unknown frequency embedded in noise. The purpose is to realize a filter with high Q (selectivity) and less output amplitude fluctuation after convergence. As the first step, the adaptive second-order IIR bandpass filter with the variable center frequency is outlined. Then, we present a new method that derives the decimation filter function with a small amount of computation. The filter is derived from the above filter with the denominator coefficient made variable, and with the polynomial of z-M as the denominator, where M (integer) is the decimation ratio. A method is shown to design the adaptive signal generator and the coefficient update circuit for a single sinusoid detection adaptive filter based on the proposed method. Lastly, the convergence and the output error characteristics of the proposed adaptive decimation filter are examined by a computer simulation example. © 2000 Scripta Technica, Electron Comm Jpn Pt 3, 83(7): 91–101, 2000 [ABSTRACT FROM AUTHOR]

This paper proposes a method of constructing first- and second-order switched-capacitor variable all-pass circuits that have small total capacitance and are parasitic-insensitive. A first-order circuit, in which the peak group delay at zero angular frequency can be specified by using a programmable capacitor array, and a second-order circuit that has a first-order subcircuit, in which the peak bandpass group delay and the corresponding angular frequency (peak angular frequency) can be specified independently, have already been presented. Those constructions, however, have the problem that the capacitance spread is generally enlarged in the first-order circuit (defined here as the maximum capacitance when the minimum capacitance is normalized to 1). This increases the total capacitance in both the first- and second-order circuits and makes the second-order circuit parasitic-sensitive. This paper, on the other hand, proposed circuits that are parasitic-insensitive and have smaller total capacitances than the circuits proposed in the past. The second-order circuit proposed in the past also has the problem that the peak angular frequency cannot be set higher than half the Nyquist angular frequency, but this is possible in the proposed second-order circuit. Another point is that the number of operational amplifiers is reduced by one in the proposed circuit. The calculated amplitude element-sensitivities of the first- and second-order circuits are smaller than the past values. The proposed circuit was experimentally constructed using discrete components, and a satisfactory result was obtained. © 1999 Scripta Technica, Electron Comm Jpn Pt 3, 82(10): 50–62, 1999 [ABSTRACT FROM AUTHOR]

The filter on monolithic LSI for communication and measurement is realized by the digital signal processor (DSP) or the switched capacitor (SC) circuit. In the analog-digital interface, high-speed processing, applications requiring low power consumption operations, and low cost, SC circuits will be superior to the DSP circuits. The authors devised the SC circuit called parallel cyclic-type, which can further enhance the high-frequency and low power-consumption operation. The single-rate FIR and IIR filters have been proposed using the circuit. In this paper, the high frequency and low power-consumption FIR and IIR decimation filters using the SC parallel cyclic-type circuits are proposed. The effects of the finite gain bandwidth (GB product) of the operational amplifier and of the parasitic capacitance on the filter characteristics are analyzed. The proposed filters and the decimation filter by Franca et al. are constructed using discrete elements and the characteristics are examined. The characteristics are compared with the computer simulations. It is verified as a result that the proposed decimation filter has a much better performance than the filter by Franca et al. [ABSTRACT FROM AUTHOR]

In this paper, a new algorithm for the detection of a single sinusoid corrupted by Gaussian noise using IIR adaptive bandpass/notch filter is presented. As the first step, the relation between the convergence speed and the filter Q-factor in IIR adaptive bandpass filter is analyzed. Based on the result of analysis, an algorithm is derived in which the filter Q-factor and the adaptive control signal generator Q-factor are made continuously variable so that they are inversely proportional to the distance between the filter center frequcncy f0 and the frequency f of the sinusoid to be detected. This makes both the convergence speed of f0 and f and the resolution high. Then it Is found that limiting the maximum amplitude response of the adaptive control signal generator to a value proportional to sin 2&pie;f can suppress the coefficient fluctuation after convergence effectively. By this approach, an IIR adaptive filter with a high Q can easily be realized. As the next step, an additional high-speed and highly stable adaptive algorithm is proposed in which the step size of the filter coefficient update is made to vary inversely with the fitter Q-factor. A realization of the IIR adaptive notch filter is also presented. Finally, the usefulness of the proposed adaptive algorithm is verified by a computer simulation. [ABSTRACT FROM AUTHOR]

FIR transversal filters have been proposed using a parallel cycling-type circuit configuration which alleviates the performance degradation at higher frequencies due to the finite gain-bandwidth product of op amps in switched capacitor filters. A parallel cyclic-type circuit realizes the delay and weighting of the input signal with switches and capacitors without op amps. It is also of low-power consumption because it requires only one op amp for its adder. This paper describes a method to implement direct form I IIR filters using a parallel cyclic-type circuit. The performance degradation caused by the finite gain bandwidth product of the op amp and by parasitic capacitances is analyzed, both for the canonical circuit with the delay element using op amps and for the parallel cyclic-type circuit. Also, a parallel cyclic-type circuit is proposed for high-frequency operations containing multiple adders. This circuit incorporates a novel feedback scheme using the "Look Ahead" calculation method. Finally, through experiments, the performance improvement by the parallel cyclic-type circuits over the canonical and biquad circuits is demonstrated. [ABSTRACT FROM AUTHOR]

The high-frequency performance of switched-capacitor filters is bounded mainly by the finite gain bandwidth product of operational amplifiers. In this paper, the effects of finite gain bandwidth product of operational amplifiers on the performance of FIR (transversal) filters using such amplifiers as delay elements (canonical circuit) is analyzed. Next, a new low-power consumption FIR switched-capacitor circuit for high frequencies, which we call a parallel cyclic-type circuit (PCTC), is proposed. The proposed circuit does not use operational amplifiers as delay elements. Instead, switches and capacitors are used for both the delaying and the weighting operations. We present a basic circuit using subblocks, a circuit with reduced number of capacitors, and a modified circuit having plural operational amplifiers for higher- frequency use. We thee show the design of a fourth- order FIR filter employing PCTC. Under the condition that sampling frequency is one-half of unity gain frequency of operational amplifier, computer simulations of fourth-order transversal switched-capacitor filters with canonical circuit and that with parallel cyclic-type circuit are performed and the experimental results of these circuits using discrete components are also given. Both demonstrate that the parallel cyclic-type circuit has significantly better performance than the canonical circuit. [ABSTRACT FROM AUTHOR]

The second-order recursive fundamental section up to now, has larger coefficient sensitivities of the amplitude at the filter central frequency and the central angular frequency itself. This makes it difficult to realize high-Q bandpass characteristics. This paper proposes a new structure with a feedback loop containing sampled-data filter with medium-Q bandpass filter and a long-time delay element. When a second-order bandpass filter is used as the feedback filter, the transfer function of the new structure is a pseudo-second-order function. Then the approximate relation is derived between Q of the feedback filter and Q of the new structure filter. The validity of the expression is verified by numerical calculations. It is shown also that when realizing a bandpass filter of the same Q, to what extent the new structure is superior to the traditional second-order structure from the viewpoints of coefficient sensitivity and round-off noise. The design procedure for the new structure is shown also. In the digital filter, the long-time delay can be realized by using a register or a memory. In the analog sampled-data filter, it is realized by a charge-transfer device. Thus, the new structure can be realized by a digital filter, or by combining switched capacitor circuits and a charge-transfer device. Finally, an experimental example of a high-Q filter by the latter method is shown. [ABSTRACT FROM AUTHOR]

High-frequency responses of switched-capacitor filters deteriorated mostly as a result of the finite gain bandwidth product of an operational amplifier. The authors previously proposed a type of FIR and IIR switched-capacitor filter using a parallel cyclic-type circuit in order to improve high-frequency performance. In the parallel cyclic-type circuit, an operational amplifier is not used as a delay element. Instead, both delay and weighting operations are implemented with switches and a coefficient capacitor simultaneously. Only one operational amplifier is used for a summing operation. Consequently, the maximum operational frequency of the filter is extended up to the unity gain frequency of the operational amplifier. This paper proposes a new type of FIR and IIR switched-capacitor interpolation filter that can be operated in a high-frequency region by using the parallel cyclic-type circuit. Effects of both the finite gain band-width of the operational amplifier and parasitic capacitances on fitter performance are analyzed by applying the analysis method of periodically time-varying digital filter. These effects are found to be very few in number below the unity gain frequency of the operational amplifier. Third-order FIR and biquadratic IIR interpolation filters are constructed with discrete components and verified to have good frequency performance that coincides with the analyzed one. [ABSTRACT FROM AUTHOR]

In a first hydroamination step the Markovnikov product is generated followed by hydrosilylation of the corresponding imine intermediate. [ABSTRACT FROM AUTHOR]