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Structural proteomics techniques are useful for identifying the binding sites of proteins. The surface of a target protein with and without a bound binding partner is artificially labeled using a hydroxy radical, deuterium, or a low-molecular-weight chemical, and the difference in the label strength with and without the bound partner is determined. Label strength maps are then prepared on the Protein Data Bank (PDB) structure to identify the binding surface. However, the surface-accessible sites determined using such structural proteomics methods are frequently inconsistent with those calculated based on PDB structures, speculating that the measurement determines chemical accessibility rather than solvent accessibility. In this study, the solvent-accessible surface of human serum albumin was analyzed using covalent protein labeling with varying concentrations of CH

With its complicated pathobiology and pathophysiology, heart failure (HF) remains an increasingly prevalent epidemic that threatens global human health. Ferroptosis is a form of regulated cell death characterized by the iron-dependent lethal accumulation of lipid peroxides in the membrane system and is different from other types of cell death such as apoptosis and necrosis. Mounting evidence supports the claim that ferroptosis is mainly regulated by several biological pathways including iron handling, redox homeostasis, and lipid metabolism. Recently, ferroptosis has been identified to play an important role in HF induced by different stimuli such as myocardial infarction, myocardial ischemia reperfusion, chemotherapy, and others. Thus, it is of great significance to deeply explore the role of ferroptosis in HF, which might be a prerequisite to precise drug targets and novel therapeutic strategies based on ferroptosis-related medicine. Here, we review current knowledge on the link between ferroptosis and HF, followed by critical perspectives on the development and progression of ferroptotic signals and cardiac remodeling in HF.

/Objectives: Postoperative pancreatic fistula (POPF) is a serious complication after pancreaticoduodenectomy (PD). Thus, identification of the risk factors for POPF is urgently needed. In this study, we aimed to identify whether arterial lactate (LCT) levels following PD might be a marker of the potential risk of POPF.Between September 2009 and December 2020, 151 patients who underwent elective PD were retrospectively enrolled. Patient characteristics, perioperative clinicopathological variables, postoperative blood biochemistry data were analyzed in univariable and multivariable analyses. Pancreatic fistula of Grade B and C was considered as POPF.Patients were divided into the POPF group (n = 33, 21.9%) and non-POPF group (n = 118, 78.1%). Higher body mass index (p = 0.017), increased estimated blood loss (p = 0.047), soft textured pancreas (p = 0.007), smaller main pancreatic duct (p = 0.016), higher LCT levels (p 0.001), higher aspartate aminotransferase levels (p = 0.023) and higher procalcitonin levels (p = 0.024) were significantly associated with POPF. Receiver operating characteristic curve analysis revealed that 2.1 mmol/L was the optimal cut-off value of LCT (sensitivity = 78.8%, specificity = 61.2%) for predicting POPF occurrence. Univariate and multivariate analyses confirmed that an LCT of ≥2.1 mmol/L was independently associated with the risk of POPF following PD (odds ratio = 6.78, 95% confidence interval = 2.22-20.74; p = 0.001).Higher LCT is a predictive marker for POPF following PD.

Shotgun proteomics is a powerful method for comprehensively identifying and quantifying tryptic peptides, but it is difficult to analyze proteolytic events. One-dimensional gel and liquid chromatography-tandem mass spectrometry (GeLC-MS/MS) enables the separation of proteolytic fragments using SDS-PAGE followed by identification using LC-MS/MS. GeLC-MS/MS is thus an excellent method for identifying fragmentation. However, the lower reproducibility of gel extraction and nano flow LC-MS/MS can produce inaccurate results in comparative analyses of protein quantification among samples. In this study, a novel GeLC-MS/MS method coupled with stable isotope dimethyl labeling was developed. In the method, a mixture of light- and heavy-labeled samples is loaded onto an SDS-PAGE gel, and proteins with different isotopes in one extracted band are quantitatively analyzed by one-shot injection. This procedure enables accurate determination of the abundance ratio of peptides between two samples, even in cases of low peptide abundance, and it is not affected by the reproducibility of the gel extraction or LC-MS procedures. Therefore, our new GeLC-MS/MS method coupled with stable isotope dimethyl labeling provides high accuracy and comprehensive peptide comparisons, enabling the detection of proteolysis events caused by disease or physiological processes.

Encapsulation of guest molecules into the vacant space of biomacromolecular crystals has been utilized for various purposes including functioning as a protein container to protect against physical stress and structural determination of the guest. Todarodes pacificus hemocyanin (TpHc) is a hollow cylindrical decameric protein complex with an inner space 110 A in diameter and 160 A in height. In the crystal, TpHc forms a straw-like bundle and contains one reactive Cys (Cys3246) in the inner domain of each protomer. Here, we conjugated biotin onto Cys3246 of TpHc followed by incubation with streptavidin. The streptavidin was immobilized into the inner space of TpHc due to its interaction with biotin. Moreover, the complex containing TpHc and streptavidin was crystallized under the same conditions used for unmodified TpHc. In order to expand this methodology for a variety of proteins, we conjugated the ligand nitrilotriacetic acid (NTA) chelated to a Ni2+ ion (Ni2+-NTA) to TpHc. We found that His-tagged green fluorescent protein (GFP) was encapsulated into the Ni2+-NTA-conjugated TpHc via the interaction between the His-tag and the Ni2+-NTA group. X-ray crystallography demonstrated that the crystal packing of the complex containing TpHc and GFP was identical to that of the unmodified TpHc. Our guest immobilization method is distinct from previous approaches that are dependent on diffusion of the guest into the host crystal. Thus, our findings may accelerate the development of proteinaceous crystal engineering.

Combined use of wavelength division multiplexing (WDM) and mode division multiplexing (MDM) attracts a lot of attention for expanding transmission capacity. For WDM/MDM transmission, a broadband mode multi/demultiplexer (MUX/DEMUX) is necessary. In this work, we propose a silica-PLC-based Mach–Zehnder (MZ) interferometer mode MUX. The MZ filter for mode and wavelength is composed of bus and add waveguides, and it can be constructed by newly designed broadband 3dB-mode-divider. Furthermore, the size of the chip can be drastically reduced compared with that of silica-PLC by using Si/silica hybrid PLC platform (1/20), and the wavelength dependence of free-spectral range (FSR) is suppressed by using the platform with the bus-tapered waveguide, and Si/silica hybrid PLC platform in both of bus and add waveguides.

OBJECTIVES To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. METHODS We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014. Exclusion criteria were that the paper was a review, concerned surgical techniques themselves (without follow-up), and included patients treated non-surgically. Using Stata 14, we performed aggregate data and individual data meta-analysis using random-effect and Cox multilevel models respectively. RESULTS We collected data on 3501 patients from 17 studies. The overall median survival was 43 months. In aggregate data meta-analysis, the hazard ratio for patients with previous liver metastases was 1.19 (95% CI 0.90-1.47), with low heterogeneity (I2 4.3%). In individual data meta-analysis, the hazard ratio for these patients was 1.37 (95% CI 1.14-1.64; p

We investigated the air hole structure in hole-assisted fiber (HAF) with the aim of terminating fiber fuse propagation. We focused on two structural parameters c/MFD and S1/S2, which are related respectively to the position and area of the air holes, and mapped their appropriate values for terminating fiber fuse propagation. Here, MFD is the mode field diameter, c is the diameter of an inscribed circle linking the air holes, S1 is the total area of the air holes, and S2 is the area of a circumscribed circle linking the air holes. On the basis of these results, we successfully realized a compact fiber fuse terminator consisting of a 1.35 mm-long HAF, which can terminate fiber fuse propagation even with a 22 W input. In addition, we observed fiber fuse termination using a high-speed camera. We additionally confirmed that the HAF-based fiber fuse terminator is effective under various input power conditions. The penetration length of the optical discharge in the HAF was only less than 300 μm when the input power was from 2 to 22 W.

A simple and efficient method for estimating modal amplitude and phase of multimode near field patterns (NFPs) based on artificial-neural-network (ANN) with the help of the optimization method is proposed. The inferred amplitude and phase of measured NFPs based on ANN are refined by using a grey-wolf optimizer (GWO). By using the proposed method, the image correlation between reproduced and measured NFPs is improved without re-training of ANN, which is the most time-consuming part of ANN-based numerical modal decomposition technique. Numerical examples of three and six mode cases are presented for the estimation using simple ANN. For six-mode case, the correlation is greatly improved by using the optimizer. Finally, the estimation of the measured NFPs from three-mode exchanger and six-mode mode conversion grating is implemented, and 5% improvement in the correlation value is observed for six-mode case. The proposed method offers alternative way to improve the correlation without using elaborated ANN.

Recently developed PLC-based mode multi/demultiplexers (MUX/DEMUXs) for mode division multiplexing (MDM) transmission are reviewed. We firstly show the operation principle and basic characteristics of PLC-based MUX/DEMUXs with an asymmetric directional coupler (ADC). We then demonstrate the 3-mode (2LP-mode) multiplexing of the LP01, LP11a, and LP11b modes by using fabricated PLC-based mode MUX/DEMUX on one chip. In order to excite LP11b mode in the same plane, a PLC-based LP11 mode rotator is introduced. Finally, we show the PLC-based 6-mode (4LP-mode) MUX/DEMUX with a uniform height by using ADCs, LP11 mode rotators, and tapered waveguides. It is shown that the LP21a mode can be excited from the LP11b mode by using ADC, and the two nearly degenerated LP21b and LP02 modes can be (de)multiplexed separately by using tapered mode converter from E13 (E31) mode to LP21b (LP02) mode.

Three new acylphloroglucinols, baeckenones A–C ( 1 – 3 ), were isolated from the chloroform extract of the leaves of Baeckea frutescens together with three known compounds 4 – 6 . The structures of the isolated compounds were determined using extensive spectroscopic analyses including IR, NMR, and HRMS. Baeckenone B ( 2 ) exhibited a moderate antibacterial activity against Bacillus subtilis with an MIC value of 40 μM.

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased.

We propose a novel connector for a multi-core fiber (MCF) that employs a V-groove ferrule. The proposed connector achieves rotational angle alignment by the insertion of a V-groove ferrule into a split sleeve with a pin. The proposed mechanism enables us to align cores directly in MCF not only in the vertical, horizontal and longitudinal directions but also in the rotational direction. With the proposed technique there is no need to control the clearance of the connector components because the rotational axis of the plug is directly aligned with the adaptor when we fit the pin into the V-groove. Moreover, the floating structure can remain unchanged since currently available connector parts can be employed. We show that this technique can precisely align the rotational angle for MCF with an arbitrary core structure. We also show that a more stable connection can be realized if we take account of the tolerance of the V-groove and pin.

The acylalkylpyrone synthase CsyB from Aspergillus oryzae catalyzes the one-pot formation of the 3-acyl-4-hydroxy-6-alkyl-α-pyrone scaffold from acetoacetyl-CoA, fatty acyl-CoA, and malonyl-CoA. This is the first type III polyketide synthase that performs not only the polyketide chain elongation but also the condensation of two β-ketoacyl units. The crystal structures of wild-type CsyB and its I375F and I375W mutants were solved at 1.7-, 2.3-, and 2.0-Å resolutions, respectively. The crystal structures revealed a unique active site architecture featuring a hitherto unidentified novel pocket for accommodation of the acetoacetyl-CoA starter in addition to the conventional elongation/cyclization pocket with the Cys-His-Asn catalytic triad and the long hydrophobic tunnel for binding the fatty acyl chain. The structures also indicated the presence of a putative nucleophilic water molecule activated by the hydrogen bond networks with His-377 and Cys-155 at the active site center. Furthermore, an in vitro enzyme reaction confirmed that the (18)O atom of the H2(18)O molecule is enzymatically incorporated into the final product. These observations suggested that the enzyme reaction is initiated by the loading of acetoacetyl-CoA onto Cys-155, and subsequent thioester bond cleavage by the nucleophilic water generates the β-keto acid intermediate, which is placed within the novel pocket. The second β-ketoacyl unit is then produced by polyketide chain elongation of fatty acyl-CoA with one molecule of malonyl-CoA, and the condensation with the β-keto acid generates the final products. Indeed, steric modulation of the novel pocket by the structure-based I375F and I375W mutations resulted in altered specificities for the chain lengths of the substrates.

FtsZ is a prokaryotic homolog of tubulin and is a key molecule in bacterial cell division. FtsZ with bound GTP polymerizes into tubulin-like protofilaments. Upon polymerization, the T7 loop of one subunit is inserted into the nucleotide-binding pocket of the second subunit, which results in GTP hydrolysis. Thus, the T7 loop is important for both polymerization and hydrolysis in the tubulin/FtsZ family. Although x-ray crystallography revealed both straight and curved conformations of tubulin, only a curved structure was known for FtsZ. Recently, however, FtsZ from Staphylococcus aureus has been shown to have a very different conformation from the canonical FtsZ structure. The present study was performed to investigate the structure of FtsZ from Staphylococcus aureus by mutagenesis experiments; the effects of amino acid changes in the T7 loop on the structure as well as on GTPase activity were studied. These analyses indicated that FtsZ changes its conformation suitable for polymerization and GTP hydrolysis by movement between N- and C-subdomains via intermolecular interactions between bound nucleotide and residues in the T7 loop.

We investigated the measurement conditions for measuring multipath interference (MPI) occurring between fundamental and higher order modes. We considered the sampling interval as a function of the free spectral range (FSR) as a measurement condition. We also investigated the effect of randomized polarization states when measuring the MPI characteristics. We then confirmed the MPI characteristic, which we measured using three methods with a suitable sampling interval over FSR value and a suitable number of repetitions of randomized polarization states. Furthermore, we describe the MPI characteristic of bending loss insensitive fibers (BIFs) with offset connections and tight bends. We discuss the MPI degradation factor in an access network employing BIF.

We investigate the design and characteristics of a single-mode and low bending loss HAF both numerically and experimentally. An air filling fraction S is introduced to enable us to design a HAF with desired characteristics more easily. We show that we can expect to realize a single-mode and low bending loss HAF by considering the S dependence of the bending loss α b and cutoff wavelength λ c as well as their relative index difference Δ dependence. We also show that the mode-field diameter (MFD) and chromatic dispersion characteristics of the single-mode and low bending loss HAF can be tailored by optimizing the distance between the core and the air holes. We also investigate the usefulness of the fabricated HAFs taking the directly modulated transmission and multipath interference (MPI) characteristics into consideration. We show that the designed HAF has sufficient applicability to both analog and digital transmission systems. Our results reveal that the single-mode and low bending loss HAF is beneficial in terms of developing a future fiber to the home (FTTH) network as well as for realizing flexible optical wiring.

Besides mast cells and basophils, the high-affinity IgE Fc receptor (FcepsilonRI) is exclusively expressed on certain FcalphaR (IgA Fc receptor)-expressing immune cells such as neutrophils in allergic patients. Transfected rat basophilic leukemia cell line (RBL-2H3) co-expressing FcepsilonRI and FcalphaR was analyzed for effects of simultaneous receptor engagement by their specific antibodies on degranulation and signaling. Whereas supraoptimal FcepsilonRI engagement decreased degranulation, which is known as a bell-shaped dose-response curve, such inhibitory effect was not observed with FcalphaR engagement. However, simultaneous engagement of FcepsilonRI and FcalphaR showed that supraoptimal FcepsilonRI engagement down-regulates FcalphaR-mediated degranulation. This inhibition was associated with extensive phosphorylation of inositol polyphosphate 5'-phosphatase SHIP1 and FcepsilonRIbeta, and reversed by adding actin-depolymerizing drug, latrunculin B. The results suggest an endogenous mechanism by which FcalphaR functionality is down-regulated in an 'allergic environment' where FcepsilonRI is co-expressed and extensively cross-linked on FcalphaR-expressing effector cells.

In this paper, we describe Raman amplification characteristics and the potential for distributed Raman amplification (DRA) transmission in silica core photonic crystal fiber (PCF). We measured the Raman gain spectra of PCFs at different pump wavelengths, and confirmed that the pump wavelength dependence of the Raman gain coefficient of PCF agrees well with that of silica glass. DRA transmission performance in the 850 and 1580 nm wavelength regions was also examined individually using 6.0 and 12.7 km long PCFs. Finally, we clarified numerically that the signal-to-noise ratio (SNR) can be improved over a wide wavelength region by using silica core PCF and DRA. Our results show that silica core PCF has potential as a DRA transmission medium over an arbitrary wavelength region.

Background Anti-endothelial cell antibodies (AECA) are circulating antibodies that bind to endothelial antigens and induce endothelial cell damage. These antibodies have been detected in patients with collagen vascular disease and systemic vasculitis. Sarcoidosis is a multiple granulomatous disorder of unknown etiology, and its clinical presentation, organ involvement, and prognosis are highly diverse. In this study, we aimed to investigate the expression of AECA in patients with sarcoidosis. We also examined whether these antibodies could serve as a marker for the activity, severity, and prognosis of sarcoidosis. Methods Forty sarcoidosis patients, whose diagnosis was established by clinicoradiologic findings and histologic confirmation of noncaseating epithelioid cell granulomas, were studied. Serum and BAL samples were examined for AECA by cellular enzyme-linked immunosorbent assay (ELISA) using human umbilical vein endothelial cells. The findings were expressed in terms of an ELISA ratio (ER). Fifty-seven subjects without any clinical, radiologic, or serologic evidence of pulmonary disease or autoimmune disorders served as the reference population to judge the positivity of AECA. Results Patients with sarcoidosis had a significantly higher positivity rate for and levels of AECA in both serum and BAL fluid than the reference population. In addition, the ER of AECA was significantly elevated in patients with multiple lesions or who required corticosteroid therapy compared with that in patients without multiple lesions or who did not need corticosteroid therapy. Conclusion Expression of AECA might be a useful marker to predict the course of sarcoidosis.

This paper describes the transmission characteristics of a hole assisted fiber (HAF), which has a conventional germanium-doped core surrounded by several air holes. We report the design principle of the HAF in terms of both bending loss and mode-field diameter characteristics. We also discuss both numerically and experimentally the splicing characteristics of the bending loss optimized HAF when it is spliced with conventional 1.3 μm zero-dispersion single-mode fiber. In addition, we clarify the transmission performance of HAF based optical cord in both digital and analog transmission systems. These results show that bending loss optimized HAF will be useful for constructing a flexible optical network.

Nucleocapsid protein of HIV, containing two CCHC-type zinc fingers connected by a linker, is a multi-functional protein involved in many critical steps of the HIV life cycle. Several in vitro investigations demonstrated that the reactivities of the first zinc finger flanked by the linker of HIV-1 NCp7 and HIV-2 NCp8 were essential for binding to viral RNA, however, that of the second zinc finger flanked by the linker of NCp7 was very weak and non-specific, whereas the part of NCp8 called NCp8-f2, interacted strongly and specifically with viral RNA. In this study, the three-dimensional structure of NCp8-f2 was determined for the first time. Furthermore, we established that NCp8-f2 specifically binds to the stem-loop SD in viral RNA, and that the hydrophobic cleft and the basic residues close to the cleft were essential for specific binding to SD. We discuss the functional significance of NCp8-f2 for NCp8 being a multi-functional protein.

Bimetallic Pd–Pt catalysts are used industrially to saturate aromatics in industrial feedstocks under mild reaction conditions to bypass the thermodynamic limitations. A considerable amount of research effort has been focused on elucidating the structural and electronic properties of bimetallic Pd–Pt particles, generally supported on acidic supports, to correlate their properties with their sulfur tolerance as well as with their catalytic activity/selectivity. However, the properties of bimetallic Pd–Pt particles under these characterization conditions are still partly unknown, particularly what happens during hydrotreating. We therefore prepared bimetallic Pd–Pt catalysts (Pd/Pt atomic ratio of 4/1) using the same precursors of noble metals and various supports, such as acidic and non-acidic ultra-stable Y-type (USY) zeolites, SiO2–Al2O3, SiO2 and Al2O3, and then investigated the structural and electronic properties of the supported bimetallic Pd–Pt particles. These properties that appeared under liquid-phase hydrotreating conditions were correlated with reaction selectivity for tetralin hydrogenation and in 4,6-dimethyldibenzothiophene hydrodesulfurization, as well as with Fourier-transform analyses of adsorbed CO, dispersion and EXAFS data of reduced/sulfided catalysts. The effects of several parameters involved – such as calcination/activation conditions and the presence of extra-framework alumina and chlorine in the zeolite supports – on the sulfur tolerance of the bimetallic Pd–Pt catalysts were also investigated. In addition to sulfur poisoning, agglomeration of the Pd–Pt particles and inhibitory effects caused by nitrogen-containing compounds and aromatics were also investigated to develop measures to minimize the agglomeration of Pd–Pt particles under hydrotreating conditions for real feedstocks.

To achieve selective hydrodesulfurization (HDS) of fluid catalytic-cracked (FCC) gasoline for producing sulfur-free gasoline (S

We aimed to reveal the usefulness of and problematic points with the Criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft fourth edition) proposed by the UTI Subcommittee of the Clinical Evaluation Guidelines Committee, Japan Society of Chemotherapy, for evaluating antimicrobial agents for complicated urinary tract infections. We conducted a multicenter trial involving 159 patients with complicated urinary tract infections without indwelling urinary catheters. The antimicrobial agents used were cefcapene pivoxil and levofloxacin. "Early evaluation" took place the day after completion of 7 days of therapy; "late evaluation" took place 5-9 days after the end of treatment, and "follow-up evaluation" was done 4-6 weeks after treatment. In the early evaluation, overall clinical efficacy was judged as excellent in 52.9% of the patients, moderate in 26.1%, and poor in 21.0%, and the bacteriological response was judged as "eradicated" for 86.4% of the 198 bacterial strains isolated. Of 96 patients included in the "late evaluation" category in accordance with the draft fourth edition, the clinical outcome was judged as "cured" in 68.4% and the microbiological outcome was judged as "eradicated" in 59.4%. These rates may be low, because 25 patients in whom clinical efficacy was evaluated as "poor" at the end of treatment were separately classified as "failed" at the late evaluation. Of the 49 patients with an excellent clinical response at the end of treatment, symptoms were exacerbated in 18 at the follow-up evaluation. Overall, the draft fourth edition, with some modifications of the third edition criteria, such as the addition of a follow-up evaluation 7 days after the cessation of drug administration, has the potential to play a role in the international standards for evaluating antimicrobial drug efficacy for complicated urinary tract infections.

Monodisperse platinum nanoparticles were successfully fabricated on the porous structure of carbon gel microspheres with a narrow pore size distribution. The size of the platinum nanoparticles supported on the carbon gel microspheres was almost coincident with the pore size of the carbon gel microspheres. The results indicated the potential for controlling the size distribution of the supported platinum nanoparticles using the carbon gel microspheres with different pore size distributions.

Supported Pd–Pt catalysts are efficient for hydrodesulfurization (HDS) and hydrodearomatization (HDA) reactions of diesel fuel and their activity varied with the kinds of supports. Concerning HDA, alumina supported catalysts showed four times higher TOF (turn over frequency) than silica supported one. In order to elucidate the difference in activity, the structural analysis of the active phase was performed. After reduction pretreatment, relatively uniform and large metallic alloy Pd–Pt particles were formed on SiO 2 , whereas, Pd and Pt atoms formed rather segregated particles on Al 2 O 3 . Subsequent X-ray absorption of fine structure (XAFS) analysis under HDS conditions showed no contribution of sulfur for SiO 2 supported catalyst, whereas, formation of sulfided metal species was observed in XAFS spectra for the Al 2 O 3 supported catalyst. It is suggested that on Pd–Pt/SiO 2 , thin sulfide layer on the metal cluster surface blocked the active sites and lowered the HDA activity. Presence of partially sulfided phase originated from rather segregated structure like Pd–Pt/Al 2 O 3 is thought to be requisite for high HDA activity.

The effects of coexistence of nitrogen compounds on the catalytic activity of the Pd and Pt monometallic catalysts supported on amorphous silica and high-silica USY zeolite (SiO2/Al2O3 = 390) were investigated using a high-pressure fixed-bed continuous flow reactor operating at 3.9 MPa and 553 K. Types of catalytic activity studied included the tetralin hydrogenation activity and the 4,6-dimethyldibenzothiophene (4,6-DMDBT) hydrodesulfurization activity. The Pd/USY zeolite catalyst showed the highest tetralin hydrogenation activity with feedstock containing only 4,6-DMDBT (S = 300 ppm) without nitrogen compounds. However, its hydrogenation activity was strongly inhibited by the addition of n-butylamine (N = 20 ppm). Significant inhibitory effects by nitrogen compounds were also observed for the Pd/SiO2 catalyst. The Pt/USY zeolite catalyst showed lower hydrogenation activity than the Pd/USY zeolite, while the Pt/SiO2 catalyst showed higher activity than the Pd/SiO2 catalysts. The inhibitory effects of nitrogen compounds on these Pt catalysts were less pronounced than on Pd catalysts. On the other hand, with respect to hydrodesulfurization, Pt catalysts showed higher activity in 4,6-DMDBT hydrodesulfurization than Pd catalysts, irrespective of the support species, due to the latter's higher hydrogenolytic ability to cleave the C S bond even in the presence of nitrogen compounds. On the other hand, Pd catalysts were subject to a decrease in 4,6-DMDBT hydrodesulfurization resulting from a loss in hydrogenation activity in the presence of nitrogen compounds. We conclude that Pt catalysts are superior to Pd catalysts with respect to both hydrogenation and hydrodesulfurization for the hydrotreatment of industrial feedstocks containing sulfur and nitrogen compounds.

The sulfur tolerance of monometallic Pd, Pt and bimetallic Pd–Pt catalysts supported on slightly acidic ultra-stable Y (USY) zeolite (SiO 2 /Al 2 O 3 = 390) and on non-acidic silica, having mesopores with a pore diameter of 3 or 10 nm, were investigated using the CO adsorption method and the extended X-ray adsorption fine structure (EXAFS) method. Well-dispersed noble metal particles supported on USY zeolite and silica with an average pore diameter of 3 nm showed high surface sulfur tolerance and high catalytic hydrogenation activity, although bulk phase sulfidation simultaneously occurred. The synergistic effects of sulfur tolerance were significant in the bimetallic Pd–Pt particles supported on USY zeolite and silica with an average pore diameter of 3 nm. On the other hand, on silica with an average pore diameter of 10 nm, the surface sulfur tolerance of low dispersed noble metals was the lowest, although its bulk phase sulfur tolerance was the highest. The Pd K-edge and Pt L III -edge EXAFS spectra indicated a strong interaction between the well-dispersed noble metal particles and the supports of the USY zeolite and silica with an average pore diameter of 3 nm. This distorted structure may increase the sulfur tolerance of noble metals, though some surface and bulk phase sulfidation simultaneously occurred.

The size effect of monometallic Pd and Pt clusters was investigated for the sulfur tolerance of these noble metal catalysts supported on high-silica USY zeolite, using the CO adsorption method and the extended X-ray adsorption fine structure (EXAFS) method. Both Pd and Pt particles show the highest surface sulfur tolerance in the form of 25 A in diameter, the bulk phases of the Pd and the Pt particles approach that of the metallic structure. With increased cluster size, the surface sulfur tolerance of Pt particles decreases gradually, while that of Pd particles decreases rapidly. For large noble metal particles >50 A in diameter, EXAFS spectra show that sulfidation in the bulk phase of the noble metal particles is suppressed for Pt but promoted for Pd.

The high-resolution absorption cross-section measurements of O2 in the extreme ultraviolet region have been carried out using a 0.0008 nm resolution and at temperatures of 295 and 535 K. The photon wavelength regions were selected to coincide with the most prominent EUV solar emission features, namely, the N II 108.5 nm, the N II 91.7 nm, the O I 91.1 nm, the O II 83.4 nm, and the He II 30.4 nm. The absorption features of O2 in the extreme ultraviolet region are known to be quite diffuse, therefore the cross-section values of O2 in this spectral region will not critically depend upon the resolution. As the temperature increases from 295 to 535 K we observed that the cross-section value can increase by as much as 60% and decrease by as much as 35% in the presently selected wavelength regions.

In order to achieve selective hydrodesulfurization (HDS) of fluid catalytic cracked (FCC) gasoline for producing S

Photonic crystal fibers (PCF) with a silica–air microstructure have received increasing attention in recent years. In this paper, we analyze the loss properties of PCF and report our progress on low loss PCF. We show that the loss performance of PCF is dominated by scattering loss and OH− absorption loss. We show that the PCF scattering loss depends on both the roughness of the hole interior surface and the power distribution in the fiber cross-section. By employing appropriate polishing, etching and dehydration processes, we succeeded in obtaining a PCF with an OH− absorption loss as low as 0.4 dB/km at 1.38 μm and another PCF with a loss of 0.28 dB/km at a wavelength of 1.55 μm, which are the lowest values to the best of our knowledge.

Objectives We investigated the effects of erbB2 inhibition by anti-erbB2 antibody on cardiomyocyte survival and mitochondrial function. Background ErbB2 is an important signal integrator for the epidermal growth factor family of receptor tyrosine kinases. Herceptin, an inhibitory antibody to the erbB2 receptor, is a potent chemotherapeutic but causes cardiac toxicity. Methods Primary cultures of neonatal rat ventricular myocytes were exposed to anti-erbB2 antibody (Ab) (7.5 μg/ml) for up to 24 h. Cell viability, mitochondrial function, and apoptosis were measured using multiple complementary techniques. Results ErbB2 inhibition was associated with a dramatic increase in expression of the pro-apoptotic Bcl-2 family protein Bcl-xS and decreased levels of anti-apoptotic Bcl-xL. There was a time-dependent increase in mitochondrial translocation and oligomerization of bcl-associated protein (BAX), as indicated by 1,6-bismaleimidohexane crosslinking. The BAX oligomerization was associated with cytochrome c release and caspase activation. These alterations induced mitochondrial dysfunction, a loss of mitochondrial membrane potential (ψ) (76.9 ± 2.4 vs. 51.7 ± 0.1; p Conclusions Anti-erbB2 activates the mitochondrial apoptosis pathway through a previously undescribed modulation of Bcl-xL and -xS, causing impairment of mitochondrial function and integrity and disruption of cellular energetics.

Akt activation reduces cardiomyocyte death and induces cardiac hypertrophy. To help identify effector mechanisms, gene expression profiles in hearts from transgenic mice with cardiac-specific expression of activated Akt (myr-Akt) were compared with littermate controls. 40 genes were identified as differentially expressed. Quantitative reverse transcription-PCR confirmed qualitative results of transcript profiling for 9 of 10 genes examined, however, there were notable quantitative discrepancies between the quantitative reverse transcription-PCR and microarray data sets. Interestingly Akt induced significant up-regulation of insulin-like growth factor-binding protein-5 (IGFBP-5), which could contribute to its anti-apoptotic effects in the heart. In addition, Akt-mediated down-regulation of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 (PGC-1) and PPAR-alpha may shift myocytes toward glycolytic metabolism shown to preserve cardiomyocyte function and survival during transient ischemia. IGFBP-5 transcripts also increased after adenoviral gene transfer of myr-Akt to cultured cardiomyocytes, suggesting that this represents a direct effect of Akt activation. In contrast, substantial induction of growth differentiation factor-8 (GDF-8), a highly conserved inhibitor of skeletal muscle growth, was observed in transgenic hearts but not after acute Akt activation in vitro, suggesting that GDF-8 induction may represent a secondary effect perhaps related to the cardiac hypertrophy seen in these mice. Thus, microarray analysis reveals previously unappreciated Akt regulation of genes that could contribute to the effects of Akt on cardiomyocyte survival, metabolism, and growth.

To uncover conformational changes in biomolecules accompanied with biochemical events remains challenging, even though the atomic structures and the kinetics of the biomolecules are revealed. F1-ATPase is a rotary molecular motor in which a central γ subunit rotates against hexagonally arranged subunits α3β3, hydrolyzing ATP sequentially in three β subunits. Previous study using a single-molecule fluorescence polarization method has proposed sets of the β subunit conformations during the rotation (Masaike et al., Nat. Struct. Mol. Biol. 2008). However, further information is indispensable for identifying the ATP-waiting form of which the atomic structure has not been revealed. Here we performed single-pair FRET measurement to detect distance changes between two β subunits. Time trajectories of FRET efficiency showed two-state transitions between high (0.8) and low (0.5). Given the crystal structures, low FRET efficiency indicates one β subunit in the open form but another in the closed form. On the other hand, high FRET efficiency indicates both of the β subunits in the closed form. Next, we performed a simultaneous measurement of FRET between two fluorescently labeled β subunits and the rotation of the γ subunit. High FRET efficiency was occurred in one of the three catalytic dwells. In the remaining five dwells, other two catalytic dwells and three ATP-waiting dwells, FRET efficiency was lower. These results suggest that in the ATP-waiting dwell two of three β subunits would not take the closed form as in the catalytic dwell. We are performing further experiments with a magnetic tweezers.

Chemokines such as the monocyte chemol attractant protein-1 (MCP-1) convert monocyte rolling to firm arrest under physiological flow conditions via integrin activation and simultaneously activate phosphoinositide 3-kinase (PI3K). Here we used adenoviral gene transfer and biochemical inhibitors to manipulate PI3K-dependent pathways in human monocytes. In in vitro lipid kinase assays from purified human monocytes, we showed that MCP-1 activates the “classical” PI3Kα pathway and not PI3Kγ, a PI3K isoform thought to be activated only by the βγ complex of heterotrimeric G proteins. The activity of PI3Kα in purified human monocytes was evident within 30 s. MCP-1-induced monocyte arrest was significantly inhibited both by wortmannin (n = 4; p < 0.01) and LY294002 (n = 4; p < 0.01) with restoration of the rolling phenotype (p < 0.05 for both inhibitors, compared with rolling of control monocytes after MCP-1 treatment). To test the hypothesis that activation of PI3K is sufficient to induce monocyte adhesion, we transduced the monocytic THP-1 cell line with a recombinant adenovirus (Ad) carrying a constitutively active mutant of PI3K (Ad.BD110). We examined the ability of these cells to adhere to human vascular endothelium (HUVEC) transduced with adenoviruses carrying E-selectin, intercellular adhesion molecule-1 (ICAM-1), and VCAM-1. Under flow conditions, ICAM-1- and VCAM-1-dependent firm adhesion of Ad.BD110-transduced THP-1 cells was enhanced compared with THP-1 cells infected with control Ad (n = 4; p < 0.01 for both). Adhesion augmented by constitutive PI3K activation was entirely abrogated by pretreatment with wortmannin (n= 3; p < 0.01). In contrast, a constitutively active Akt construct had no effect on THP-1 adhesion (n = 3;p = NS). We conclude that PI3K activation is necessary and sufficient to enhance monocytic adhesion under physiological flow conditions. BD110-expressing THP-1 cells should provide a useful tool for identifying the signaling pathways downstream of PI3K that are necessary for monocyte recruitment relevant to a variety of human vascular pathologies.

There is a growing need to understand the impact of environmental sulfhydryl group-reactive heavy metals on the immune system. Here we show that Ag(+) induces mast cell degranulation, as does the aggregation of the high affinity immunoglobulin E receptor (FcepsilonRI). Micromolar quantities of Ag(+) specifically induced degranulation of mast cell model rat basophilic leukemia (RBL-2H3) cells without showing cytotoxicity. The Ag(+)-mediated degranulation could be observed as rapidly as 5 min after the addition of the ions. Ag(+) also induced a rapid change in tyrosine phosphorylation of multiple cellular proteins including the focal adhesion kinase but not Syk kinase. The Syk-selective inhibitor piceatannol and the Src family-selective tyrosine kinase inhibitor PP1 dose-dependently inhibited FcepsilonRI-mediated degranulation, whereas neither compound inhibited the Ag(+)-mediated degranulation. Furthermore, likewise FcepsilonRI aggregation, Ag(+) also induced leukotriene secretion. These results show that Ag(+) activates RBL-2H3 mast cells through a tyrosine phosphorylation-linked mechanism, which is distinct from that involved in FcepsilonRI-mediated activation.

A concept of microstructural control named “directional grain growth” (DGG) has been proposed. In this method, local phase transition and grain growth are utilized for controlling grain shape and grain orientation in a restricted region for an inhomogeneous material in chemical composition which is given directionality by plastic deformation. In heat treatment for DGG, a seed grain grows preferentially in a shaped region without precipitates by being held at a relatively low temperature and then enlarges further by encroaching the surrounding region where precipitates vanish gradually with temperature elevating at a slow rate. Such a DGG heat treatment was applied to a Ti–45.6at %Al–1.7at.%Mn alloy fabricated by reactive sintering of an extruded mixture of elemental powders and contained inevitably directional inhomogeneity. As a result, a structure was obtained consisting of giant columnar grains of Al-bearing αTi phase of several mm in length, 6.0–7.0 in aspect ratio and a preferred orientation. The axis of the columnar grains was approximately perpendicular to [0001]α.

Mast cells play a central role in immediate allergic reactions mediated by immunoglobulin E. It has recently been reported that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. However, the physiological role of ROS is poorly understood. Here we demonstrate that mast cell model rat basophilic leukemia (RBL-2H3) cells generate ROS in response to antigen and the calcium-ionophore A23187 via activation of diphenyleneiodonuim (DPI)-sensitive enzyme and that blockade of ROS generation by DPI suppresses histamine release induced by either stimulant. Increased tyrosine phosphorylation of pp125(FAK) and a 77-kDa protein coprecipitating specifically with the kinase occurred in parallel with the secretion, and blockade of ROS generation by DPI also suppressed the tyrosine phosphorylation of both proteins. These findings suggest that ROS generated by a flavoenzyme-dependent mechanism may be involved in histamine release through the pp125(FAK) pathway.

An overexpression of inflammatory cytokines has been found in the lesional skin as well as peripheral blood in patients with psoriasis, although its etiological significance is not yet understood. In order to evaluate the cell type responsible for the elevated cytokines in the peripheral blood, we investigated cytokine profiles of the fractionated peripheral blood mononuclear cells (PBMCs) in 30 patients with psoriasis and 27 healthy controls. Without stimulation, higher levels of interleukin (IL)-1β, IL-6, and IL-8 were produced by freshly isolated PBMCs from the patients than those from the controls. In the fractionated PBMCs, the monocyte-rich fractions were mainly responsible for the production of these cytokines and mRNA. The elevated levels of monocyte-derived cytokine mRNAs decreased following successful treatment with cyclosporin A. Although no correlation was found between the cytokine levels and the psoriasis area and severity index (PASI) scores, patients with arthropathy showed significantly high production levels of IL-1β, IL-6, and IL-8. These findings suggest that monocytes are the major cell source producing inflammatory cytokines in the peripheral blood of psoriasis, and the increased cytokine levels are related to the coexistent arthropathy rather than the severity of cutaneous lesions.