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Symptomatic vasospasm (SVS) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), and serum sodium frequently decreases before SVS. Serum sodium changes might be regulated by sodium metabolism-related hormones. This multi-institutional prospective cohort study therefore investigated the measurement of sodium metabolism-related hormones to elucidate the pathophysiology of serum sodium changes in SAH.SAH patients were treated with clipping or coiling from September 2017 to August 2020 at five hospitals. The laboratory data of 133 SAH patients were collected over 14 days and correlations between changes in serum sodium, sodium metabolism-related hormones (plasma adrenocorticotropic hormone (ACTH), serum cortisol, plasma arginine vasopressin (AVP)), and SVS were determined. Serum sodium concentrations were measured every day and serum sodium levels135 mEq/L were maintained until day 14.Of the 133 patients, 18 developed SVS within 14 days of subarachnoid hemorrhage onset (SVS group) and 115 did not suffer from SVS (non-SVS group). Circulating AVP, ACTH, and cortisol concentrations were significantly higher on day 1 in the SVS group compared with the non-SVS group. Fluctuations in serum sodium in the SVS group were significantly higher than those in the non-SVS group. There were antiparallel fluctuations in serum sodium and potassium from days 2 to 14.Elevated levels of ACTH/cortisol and AVP on day 1 may be predictive markers for the occurrence of SVS. Multiple logistic regression analysis showed that serum sodium fluctuations were associated with SVS occurrence. Serum sodium fluctuations were associated with stress-related hormonal dynamics. (249 words).

The treatment strategy for ruptured brain arteriovenous malformations (bAVMs) in the acute phase is still controversial. We describe five consecutive cases of successful emergent endoscopic evacuation (EEE) of intracerebral hematoma (ICH) caused by ruptured bAVMs with the electromagnetic (EM)-neuronavigation system to avoid damage to the bAVMs intended to save valuable time in the emergent phase. A single-institution retrospective analysis was performed in patients with ruptured bAVMs treated by the EM-navigated EEE as part of the strategic multimodality therapy. EM-navigated EEE was performed as follows: 1) obtaining three-dimensional computed tomography to identify the location of the nidus, large draining vein, feeding artery, and hematoma; 2) using a supine position without rigid head fixation for both supra- and infratentorial hematoma; 3) planning the entry point and trajectory of the endoscope as far as possible from the location of the nidus using the EM-navigation system; 4) designing a linear skin incision line suitable for the endoscopic surgery as well as possible decompressive craniectomy; and 5) performing EM-navigated endoscopic partial evacuation of ICH. EM-navigated EEE of ICH was successfully performed for all 5 patients, resulting in partial removal of the ICH without rebleeding from bAVMs. The mean surgical time was 37 min. Subsequent strategic endovascular embolization and curative resection of bAVMs could be performed for all patients, achieving Glasgow Coma Scale score of 15. EM-navigated EEE of partial ICH may be valuable in the emergent phase of ruptured bAVMs with massive life-threatening ICH to reduce the intracranial pressure and to obtain better prognosis.

We have developed MMDAgent (a fully open-source toolkit for voice interaction systems), which runs on a variety of platforms such as personal computers and smartphones. From this, the editing environment of the dialog scenario also needs to be operated on various platforms. So, we develop a scenario editor that is implemented on a Web browser. The purpose of this paper also includes making it easy to edit the scenario. Experiments were conducted for subjects using the proposed scenario editor. It was found that our proposed system provides better readability of a scenario and allows easier editing. Keywords: Spoken dialog system, Scenario editor, Web browser, MMDAgent

Introduction. Although Fisher syndrome and LEMS are classified into autoimmune neuromuscular diseases, we cannot find the coincidence of them in a single patient in the previous literature. Results. A 70-year-old female was admitted to our hospital because of bilateral hand numbness, double vision and unsteadiness which had developed 2 weeks. She had no history of preceding infection and/or related illness. On admission, her condition was characterized by mydriasis, extraocular muscle weakness, mild proximal muscle weakness and truncal ataxia. In addition, the tendon reflexes were absent at rest, and improved with brief exercise. Motor nerve conduction studies showed significantly low compound muscle action potentials (CMAPs) and increments of more than 200% after brief exercise (post-exercise facilitation) in several nerves. Sensory nerve conduction studies showed significantly low sensory nerve action potential (SNAPs) of median and ulnar nerves, and normal SNAPs of sural nerves. We also demonstrated the impairment of neuromuscular transmission in several muscles based on abnormal decrements in the repetitive nerve stimulation (RNS) test and abnormal jitter in the single-fiber electromyography (SFEMG). Both anti-GQ1b and GT1a ganglioside antibodies and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in her sera. Her conditions improved spontaneously. She accomplished walking alone in six weeks, and paralysis of the eye muscles recovered in five months. Median and ulnar SNAPs returned to normal in accordance with recovery of clinical findings. On the other hand, low CMAPs with post-exercise facilitation remained after complete recovery. Positron emission tomography and gastrointestinal endoscopy did not show any malignancy. Conclusion. Some electrophysiological studies revealed the impairment of neuromuscular transmission using RNS and/or SFEMG in patients with Fisher syndrome. Also, it has been known that autoimmune neurological phenotypes are diverse among patients with P/Q-type VGCC antibodies. This may be the first case who showed clinical and laboratory characteristics of Fisher syndrome and LEMS simultaneously.

We report a case of moyamoya disease (MMD), which developed after non-herpetic acute limbic encephalitis (NHALE) associated with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody. The patient's mother had a history of MMD. No vascular lesions were identified at the time of the NHALE. Nine years later, the patient visited our hospital due to memory disturbances and repeated transient ischemic attacks affecting the right limb. Diffusion-weighted magnetic resonance imaging revealed scattered areas of signal hyperintensity, and the patient was ultimately diagnosed with MMD based on angiography. Revascularization surgery was performed on the left side, where cerebral blood flow was impaired on 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography. Postoperatively, the patient was discharged with a normal neurological examination. NHALE associated with LGI1 antibodies is an autoimmune disease. Although autoimmune disease is the most frequent finding other than atherosclerosis in quasi-MMD, this is the first report of NHALE associated with anti-LGI1 antibodies mimicking quasi-MMD. Inflammation and angiogenesis may contribute to the development of MMD, in addition to genetic background.

A series of four Tin(IV)porphyrins with different substituents on meso-phenyl groups, trans-dihydroxy-5,10,15,20-tetra(p-tolyl)porphyrinatetin(IV) (Sn(IV)TTP(OH)2), trans-dihydroxy-tetra(2,4,6-trimethyl)phenylporphyrinatetin(IV) (Sn(IV)TMP(OH)2), trans-dihydroxy-5,10,15,20-tetra(p-carboxyphenyl)porphyrinatetin(IV) (Sn(IV)TCPP), and trans-dihydroxy-5,10,15,20-tetra(N-methyl-4′-pyridiniumyl)porphyrinatetin(IV) (Sn(IV)TMPyP(OH)2) have been prepared and characterized focusing on their protolytic behavior of the axial ligands, hydroxy groups, both in the ground and excites states as well as their electrochemical oxidation behavior. The two axially ligating hydroxy groups on each Tin(IV)-porphyrins exhibit protonations and deprotpnations in five steps. The pKa value of each protolytic equilibrium in the ground states was spectrophotometrically determined, while fluorescence decay time profiles indicate that the protolytic processes are sufficiently slower than the intrinsic fluorescence decay rates to lead to non-protolysis in the excited states. The oxidation peak potentials were determined by cyclic voltammetric analysis. Pourbaix diagram of each protolytic species of Sn(IV)TMPyP in water indicated that the one-electron oxidation of fully deprotonated Sn(IV)TMPyP(O−)2 is not a proton-coupled process, while the doubly hydroxy coordinated species Sn(IV)TMPyP(OH)2 has a proton-coupled one. Tin(IV)-porphyrins exhibit efficient catalytic currents on the first oxidation wave in their cyclic voltammetry and the saturated catalytic currents were high enough in a wide range of pH to be promising as water oxidation catalysts. This is the first detailed study on Tin(IV)-porphyrins to examine water oxidation ability of the one-electron oxidized form against twenty kinds of species (five protolytic species for each of the four Tin(IV)-porphyrins).

We report here a new class of co-catalysts for hydrogen evolution on TiO2 particles upon photo-irradiation. TiO2 particles prepared by sol/gel method was allowed to graft metal ion by a simple treatment with metal salts (Pt (IV), Rh (III), Cu (II), Fe(III), Al (III) ions) in water. The metal ion surface-grafted particles of TiO2(sol/gel) exhibit excellent photochemical hydrogen evolution compared to Pt (0) cluster loaded particles of TiO2(sol/gel) under the UV light irradiation of λ > 290 nm. XPS analysis shows that the valence states of the metal ions grafted on the TiO2 particles are the same with the parent metal ion salts and no metal (0) clusters were detected. DFT calculation of the simple model of metal ion/TiO2 indicated that an injected electron mostly localized on the metal ion sites, but not on Ti sites, which rationalizes the metal ion serve as the hydrogen evolution sites. Earth abundant metal ions, Cu (II), Fe (III), and Al (III) thus can provide new class of hydrogen evolution sites for artificial photosynthetic systems. To explore the possibility of utilizing semiconductor as an electron relay in the future system of molecular-catalyst-sensitized water splitting into hydrogen and hydrogen peroxide, the stability of hydrogen peroxide on various TiO2 surfaces was examined. Hydrogen peroxide was found to be pretty stable on Rh (III), Fe (III), and Al (III) ions surface-grafted TiO2, while Pt (IV) and Cu (II) ion grafted one similarly caused decomposition of hydrogen peroxide as Pt (0) cluster loaded TiO2 (Pt(0)/TiO2).

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Deterioration progress and performance reduction were experimentally evaluated in 40-year-old corroded reinforced concrete (RC) beams. The corrosion process was natural, without acceleration by current application, admixture inclusion, or exposure to an artificial chloride environment. The mechanical performance of the beams was evaluated through a four-point bending test. The corroded steel reinforcing bars were extracted for corrosion evaluation and tensile testing. A good correlation was established between crack width and cross-section loss, as well as between cross-section loss and ultimate capacity loss. Furthermore, the relationship between deterioration progress and performance degradation with the exposure period for each deterioration stage was elucidated.

Summary Wolbachia , endosymbiotic bacteria prevalent in invertebrates, manipulate their hosts in a variety of ways: they induce cytoplasmic incompatibility, male lethality, male-to-female transformation, and parthenogenesis. However, little is known about the molecular basis for host manipulation by these bacteria. In Drosophila melanogaster , Wolbachia infection makes otherwise sterile Sex - lethal ( Sxl ) mutant females capable of producing mature eggs. Through a functional genomic screen for Wolbachia genes with growth-inhibitory effects when expressed in cultured Drosophila cells, we identified the gene WD1278 encoding a novel protein we call toxic manipulator of oogenesis (TomO), which phenocopies some of the Wolbachia effects in Sxl mutant D. melanogaster females. We demonstrate that TomO enhances the maintenance of germ stem cells (GSCs) by elevating Nanos (Nos) expression via its interaction with nos mRNA, ultimately leading to the restoration of germ cell production in Sxl mutant females that are otherwise without GSCs.

A double ring-shaped GroEL consisting of 14 ATPase subunits assists protein folding, together with co-chaperonin GroES. The dynamic GroEL–GroES interaction is actively involved in the chaperonin reaction. Therefore, revealing this dynamic interaction is a key to understanding the operation principle of GroEL. Nevertheless, how this interaction proceeds in the reaction cycle has long been controversial. Here, we directly imaged GroEL–GroES interaction in the presence of disulfide-reduced α-lactalbumin as a substrate protein using high-speed atomic force microscopy. This real-time imaging revealed the occurrence of primary, symmetric GroEL:GroES2 and secondary, asymmetric GroEL:GroES1 complexes. Remarkably, the reaction was observed to often branch into main and side pathways. In the main pathway, alternate binding and release of GroES occurs at the two rings, indicating tight cooperation between the two rings. In the side pathway, however, this cooperation is disrupted, resulting in the interruption of alternating rhythm. From various properties observed for both pathways, we provide mechanistic insight into the alternate and non-alternate operations of the two-engine system. © 2016 Elsevier Ltd, Embargo Period 12 months

Aluminium(III)-tetramesitylporphyrin, with the Earth’s the most abundant metal and the third most abundant element as the Al(III) ion, induces the photochemical oxygenation of cyclohexene in deaerated aqueous acetonitrile to form the corresponding epoxide and alcohol with water as both electron and oxygen atom donor upon visible light irradiation. The Al(III) should be the most available and meaningful element to be utilized in the artificial photosynthetic unit. The excited triplet state of the water-coordinated porphyrin is responsible for the photochemical oxygenation.

Silicon as the second most abundant element on Earth was effectively utilized as the central atom in the porphyrin to induce photochemical oxygenation of alkenes as the first example of photocatalytic reaction through activation of water molecule in the presence of K2PtCl6 as an electron acceptor. Oxygen atom of water was confirmed to be incorporated in the oxygenated product by the photoreaction with H218O. The excited triplet state of silicon porphyrin was revealed to be responsible for the photochemical oxygenation. The one-electron oxidized silicon porphyrin was predicted by DFT calculation to have its spin population mostly on the axially ligated hydroxyl oxygen atom. The oxyl radical character of the axial ligand could rationalize the oxygenation reaction.

In certain scenarios, seawater may be the only mixing/curing agent available; hence, it is necessary to optimize conditions for its application in concrete structures. In this study, the applicability of seawater as a mixing and curing agent in 4-year-old mortar cement specimens is evaluated. Unlike previous studies, we focused on evaluating the long-term performance of reinforced mortar specimens exposed to seawater. Specimens comprised ordinary Portland cement (OPC), grand granulated blast furnace slag (GGBFS), and reinforced concrete with plain steel, epoxy-coated, or stainless-steel bars; they were subjected to wetting–drying cycles (mimicked for tidal/splash zones) in the laboratory, and the corrosion was evaluated through electrochemical techniques. The results indicate that the effect of seawater on corrosion activity is considerably higher as a curing agent than that as a mixing agent. Further, GGBFS exhibited better performance than OPC; similarly, epoxy-coated and stainless-steel bars exhibited better corrosion resistance than plain steel bars. The results obtained in this study highlight the need to study the application of seawater in concrete mixing.

Introduction. The aim of this study is to elucidate the impairment of excitation-contraction (E-C) coupling in ICU-acquired weakness (ICUAW) using a unique electrophysiologic method in patients received the intensive care in ICU. Methods. We examined 13 patients with ICUAW and 11 normal controls. We performed successive recordings of electrophysiological tests after ICU admission. First, CMAPs of abductor hallucis muscle (AH) and sural SNAPs were recorded using a conventional method. In addition, the tibial nerve was stimulated at the popliteal fossa using a supramaximal rectangular pulse to record CMAPs from soleus muscle (SOL). Simultaneously, movement- related potential (MRP) was recorded using an accelerometer (SV1101; NEC, Tokyo Japan) taped at the base of hallux and calculated E-C coupling time (ECCT) based on the latency differences between soleus CMAP and MRP. Results. We recorded significantly decreased CMAP amplitudes in 6 AHs and 8 SOLs and significantly longer CMAP durations in 2 SOLs. Also, we recorded significantly decreased MRPs in 9 patients and significantly prolonged ECCTs in 10 patients. These abnormal findings were detected even in very short durations of ICU stay such as 2-3 days. The durations of ICU stay seemed to be correlated with involvement of CMAP amplitudes of AH/SOL, MRPs and ECCTs. Ten patients showed decreased SOL-CMAP amplitude concomitant with decreased MRP and/or prolonged ECCT in spite of preservation of SOL-CMAP duration. In addition, CMAP amplitudes of AH/SOL and MRP were significantly smaller in patients than in controls. Furthermore, CMAP durations of AH and ECCTs were significantly longer in patients than in controls. Conclusion. The E-C coupling may be impaired in the very early stages of CIM. Noninvasive measurement of MRP and ECCT is easy to perform, and may be useful to detect the impairment of E-C coupling in the early stages of ICUAW.

Transverse sinus-sigmoid sinus (TS-SS) dural arteriovenous fistula (dAVF) is common type of dAVF, on the other hand, anterior condylar confluence (ACC) dAVF is relatively rare. There has been no report presenting patients with TS-SS dAVF and ACC dAVF identified simultaneously yet. We present a case of TS-SS dAVF and ACC dAVF that developed subcortical hemorrhage of left temporal lobe. A 66-year-old woman with no past history was transferred to our hospital for sudden-onset consciousness disturbance, and was urgently admitted after the detection of a subcortical hemorrhage in the left temporal lobe. We suspected a dAVF based on magnetic resonance angiography and performed digital subtraction angiography (DSA). DSA revealed that the left occipital artery, left ascending pharyngeal artery, left middle meningeal artery, left tentorial artery, and posterior meningeal artery flowed into the TS-SS and ACC. DSA also showed outflow from the TS-SS to the brain surface through the vein of Labbe and the vein of Trolard. We performed transvenous embolization to prevent re-bleeding, she was then discharged from our hospital and her remaining sensory aphasia gradually improved. In the present study, the active investigation to determine the cause of subcortical hemorrhage led to a definitive diagnosis. The combination of ACC dAVF and TS-SS dAVF has not been reported thus far and this is considered a valuable case.

Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20 μM and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2-signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.

PROP1 mutation causes combined pituitary hormone deficiency (CPHD). Several mutations are located in a transactivation domain (TAD) of Prop1, and the loss of TAD binding to cofactors is likely the cause of CPHD. PROP1 cofactors have not yet been identified. In the present study, we aimed to identify the PROP1-interacting proteins from the human brain cDNA library. Using a yeast two-hybrid assay, we cloned nine candidate proteins that may bind to PROP1. Of those nine candidates, amino-terminal enhancer of split (AES) was the most abundant, and we analyzed the AES function. AES dose-dependently decreased the PROP1-induced Pit-1 reporter gene expression. An immunoprecipitation assay revealed the relationship between AES and PROP1. In a mammalian two-hybrid assay, a leucine zipper-like motif of the AES Q domain was identified as a region that interacted with TAD. These results indicated that AES was a corepressor of PROP1.

The photocatalytic hydrogen production with aid of simultaneous metal deposition using TiO2 was investigated in biomass glucose solution. Because the hydrogen production was very trace with pure TiO2, the simultaneous metal deposition was applied into the glucose solution. The photocatalytic H2 production activity with TiO2 was significantly enhanced by simultaneous metal deposition for Au and Pd. The experimental factors such as glucose concentration, metal ion concentration and reaction temperature were investigated. The photocatalytic hydrogen production increased with increasing the concentration of glucose, and it followed Langmuir–Hinshelwood mechanism. Under the optimal conditions, the photocatalytic hydrogen generations from aqueous glucose solution with in-situ Au and Pd deposited TiO2 were about 203 and 362 times larger compared with those observed with pure TiO2. The enhanced photocatalytic activity could be explained in terms of reduced electron hole recombination via electron transfer from conductance band of TiO2 to metal.

Although there have been some reports regarding body mass index (BMI) and subtypes of stroke, there have been few concerning the relationship between BMI and location of spontaneous intracerebral hemorrhage (ICH). Determining the location of spontaneous ICH is important because outcome is thought to be affected by its location. The aim of this study was to determine whether location of spontaneous ICH varied according to BMI level.In this retrospective study, 463 patients with spontaneous ICH were divided into 3 groups according to BMI (kg/m(2)):18.5 (underweight), 18.5 to 24.0 (normal weight), 24.0 to 29 (overweight), and29.0 (obesity). We compared the clinical characteristics among patients with putaminal, thalamic, lobar, pontine, or cerebellar hemorrhage on univariate and multinominal logistic regression analysis.Among the 5 locations, BMI level was lowest in patients with lobar hemorrhage and highest in those with pontine hemorrhage. Compared to patients with nonlobar hemorrhage, patients with lobar hemorrhage showed a higher proportion of individuals who were underweight, female, and age70 years and a lower proportion who were hypertensive. Compared with patients with nonpontine hemorrhage, those with pontine hemorrhage showed a higher proportion of individuals who were obese.Our findings indicate that BMI can affect the location of spontaneous ICH.

Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)-induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% L-isoleucine, 45.8% L-leucine, and 27.6% L-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy.

Objective Some studies have investigated the relationship between anatomic location and outcome in patients with cerebellar hemorrhage (CH), but not as yet the relationship between location of CH, as categorized according to vascular territory, and outcome. Furthermore, other studies have shown that taking antithrombotics was related to having CH; however, there have been no studies assessing the relationship between antithrombotics and the location of CH. The aim of this study was to determine whether the outcome of patients with CH at 1-year after onset differed depending on antithrombotic use and lesion location. Methods A retrospective, single-institution study involving 53 patients with CH was conducted. Location of the CH, categorized by vascular territory, was classified as either superior cerebellar artery hemorrhage (SCAH), anterior inferior cerebellar artery hemorrhage, or posterior inferior cerebellar artery hemorrhage. Outcome was evaluated using the modified Rankin scale (mRS) and mRS was divided into good (mRS ≤2) or poor (mRS ≥3). Results Thirty-four patients had SCAH, 5 had anterior inferior cerebellar artery hemorrhage, and 14 had posterior inferior cerebellar artery hemorrhage. Patients with poor outcome had higher proportions of Glasgow coma scale score ≤8, SCAH, intraventricular bleeding, hydrocephalus, and maximal transverse diameter ≥30 mm by univariate analysis. After multivariate analysis, Glasgow coma scale score ≤8 and SCAH showed a significant association with poor outcome. Conclusions Outcome at 1-year after onset differed by location of the CH lesion as categorized according to vascular territory. SCAH was related to poor outcome by a larger maximal transverse diameter of hematoma and hydrocephalus.

The conformational property of ethoxybenzene has been investigated by means of the laser-jet spectroscopy and the theoretical calculations. The quantum-mechanical analysis of the two-dimensional potential surfaces for the S 0 and S 1 states that have been obtained from the DFT and TDDFT calculations, respectively, has been carried out. Its result suggested the existence of the second conformer ( gauche ) in addition to the main conformer ( trans ) in the both states, and it was predicted that the 0–0 band of the gauche conformer would appear at about 400 cm −1 lower than that of the trans conformer. The S 1 ← S 0 fluorescence excitation spectrum of jet-cooled ethoxybenzene has been measured. The peak that is assignable to the 0–0 band of the second conformer has been observed, whose spectral position (red-shifted from that of the trans conformer by about 229 cm −1 ) is qualitatively consistent with the theoretical prediction.

The purpose of this study was to develop a computerized method for detection of multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images. We have proposed a new false positive reduction scheme, which consisted of a rule-based method, a level set method, and a support vector machine. We applied the proposed method to 49 slices selected from 6 studies of three MS cases including 168 MS lesions. As a result, the sensitivity for detection of MS lesions was 81.5% with 2.9 false positives per slice based on a leave-one-candidate-out test, and the similarity index between MS regions determined by the proposed method and neuroradiologists was 0.768 on average. These results indicate the proposed method would be useful for assisting neuroradiologists in assessing the MS in clinical practice.

Senile systemic amyloidosis and familial amyloid polyneuropathy are caused by oxidative deposition of conformationally altered transthyretin (TTR). We identified oxidative modification of the 10th cysteine of TTR through S-sulfonation in vitro. Based on mass spectrometric analysis, we determined the spectrophotometric, western blotting, and fluorescent microscopic properties of TTR incubated with and without cysteine-S-sulfonate in acidic (pH 4) and alkaline (pH 8) conditions at 37 degrees. The absorption of the aggregated TTR molecules increased more with incubation time and the concentration of cysteine-S-sulfonate at pH 4 than at pH 8. The Congo red binding to the S-sulfonated TTR at pH 4 was saturated with an apparent Bmax of 2.01 mol per mole of the S-sulfonated TTR and apparent KD of 7.75x10(-6) M. On the other hand, the Bmax of cysteinyl TTR was 1.38, and its KD was 3.52x10(-6) M while the Bmax of reduced TTR was 0.86, and its KD was 2.86x10(-6) M. Moreover, we detected positive amyloid fibril staining using Thioflavin T and Congo red with the S-sulfonated TTR but not with untreated or reduced TTR by microscopic fluorescent analysis. After modification of TTR in vitro, oligomers resisted reduction and denaturation was irreversibly induced, and which contributed differences in the Western blotting patterns obtained with four anti-TTR antibodies. In conclusion, this study showed that the formation of S-sulfonation of TTR through oxidative modifications of the thiol residue on the 10th cysteine of TTR is an important trigger step in the formation of transthyretin-related amyloid fibril.

The application of field effect transistor (FET) to chiral discrimination was investigated. An Au film vapor-deposited on a self-assembled monolayer (SAM) of (3-mercaptopropyl)trimethoxysilane, which was formed on the SiO2 gate of FET as an adhesive and insulating layer, stabilizes the drain current–gate voltage (Id–Vg) property of FET. The modification by homocysteine (Hcy) SAM on the surface of Au-coated gate makes it possible for the FET to distinguish between the enantiomers of alanine (Ala). Namely, after the sequential addition of Ala and Cu(II) to a K2SO4 solution in this system, it was confirmed that the lateral shift of Id–Vg curves for the FET corresponded to the chirality of Ala. With the l -Hcy SAM-modified gate, a notable negative shift was observed for l -Ala, whereas the shift observed with d -Ala was much smaller. In contrast, opposite results were obtained with d -Hcy SAM. Results of quartz crystal microbalance measurement suggested that such an FET response was originated from the enantioselective formation of diastereomeric Cu complexes with Ala molecules on the Hcy SAM. This system was demonstrated to respond quantitatively to one enantiomeric form of Ala in mixed solutions of two enantiomers as well as in pure enantiomeric solutions.

Peripheral neuropathy often occurs in hereditary spinocerebellar ataxia (hSCA), but the features of nerve involvement have not been fully investigated. We evaluated the prevalence of peripheral neuropathy in hSCAs and classified the underlying pathologies into length-dependent axonopathy and neuronopathy based on sural/radial amplitude ratio (SRAR). SRAR has been reported as a sensitive indicator to differentiate the pathology of peripheral neuropathy. In this study, we defined SRAR less than 0.3 as length-dependent axonopathy, and SRAR more than 0.3 as neuronopathy. We evaluated 22 patients with hSCA (2 patients with SCA1, 1 with SCA2, 12 with SCA3, 2 with SCA6, and 5 with unknown genotypes) and 9 patients with sporadic SCA. Peripheral neuropathy was observed in 13 patients with hSCA (1 SCA1, 1 SCA2, 10 SCA3 and 1 with unknown genotypes). Ten of 13 patients (77%) showed less than SRAR 0.3, which coincided with length-dependent axonopathy. Furthermore, during follow-up for 3 years, three of 5 patients turned into the feature of length-dependent axonopathy from that of neuronopathy. These results indicate that the sural SNAPs might decrease earlier than the radial SNAPs in hSCAs. In conclusion, the length-dependent axonopathy is the dominant form of peripheral neuropathy in patients with hSCA.

Although defective neuromuscular transmission is known to be a cause of muscle weakness in myasthenia gravis (MG), previous studies have shown the possible roles of other processes, the failure of which may also cause muscle weakness in MG. Especially, excitation-contraction (E-C) coupling may be defective in patients with MG. Some investigators have applied the post-tetanic potentiation and/or the staircase phenomenon to elucidate the impairment of E-C coupling in MG. Recently, we reported a new method to assess E-C coupling of masseter and abductor pollicis brevis muscles using an accelerometer. In this method, compound muscle action potentials (CMAP) in the belly-tendon fashion and movement-related potentials (MRP) of jaw and finger movements were simultaneously recorded following nerve stimulation. The E-C coupling time (ECCT) was obtained from the difference in onset latencies between CMAP and MRP. The impairment of E-C coupling was assessed by prolonged ECCT and/or low MRP amplitude. In this lecture, I will discuss our data in MG, (1) correlation of bite force with ECCT of the masseter, (2) correlation between anti-ryanodine receptor antibody and ECCT, (3) early effect of tacrolimus in improving ECCT, (4) impairment of post-tetanic potentiation of muscle twitch, (5) effect of local cooling on E-C coupling.

金沢大学理工研究域数物科学系, Elucidating origin, composition, size, and lifetime of microdomains in biological membranes remains a major issue for the understanding of cell biology. For lipid domains, the lack of a direct access to the behaviour of samples at the mesoscopic scale has constituted for long a major obstacle to their characterization, even in simple model systems made of immiscible binary mixtures. By its capacity to image soft surfaces with a resolution that extends from the molecular to the microscopic level, in air as well as under liquid, atomic force microscopy (AFM) has filled this gap and has become an inescapable tool in the study of the surface topography of model membrane domains, the first essential step for the understanding of biomembranes organization. In this review we mainly focus on the type of information on lipid microdomains in model systems that only AFM can provide. We will also examine how AFM can contribute to understand data acquired by a variety of other techniques and present recent developments which might open new avenues in model and biomembrane AFM applications. © 2009 Elsevier B.V. All rights reserved.

Flat substrate surfaces are a key to successful imaging of biological macromolecules by atomic force microscopy (AFM). Although usable substrate surfaces have been prepared for still imaging of immobilized molecules, surfaces that are more suitable have recently been required for dynamic imaging to accompany the progress of the scan speed of AFM. In fact, the stateof-the-art high-speed AFM has achieved temporal resolution of 30 ms, a capacity allowing us to trace molecular processes played by biological macromolecules. Here, we characterize three types of streptavidin two-dimensional crystals as substrates, concerning their qualities of surface roughness, uniformity, stability, and resistance to nonspecific protein adsorption. These crystal surfaces are commonly resistant to nonspecific protein adsorption, but exhibit differences in other properties to some extent. These differences must be taken into consideration, but these crystal surfaces are still useful for dynamic AFM imaging, as demonstrated by observation of calcium-induced changes in calmodulin, GroES binding to GroEL, and actin polymerization on the surfaces. © 2009 by the Biophysical Society.

{4-[4,5-Bis(methylsulfanyl)-1,3-dithiol-2-ylidene]cyclohexa-2,5-dien-1-ylidene}malononitrile (BMDCM) is designed toward a highly amphoteric and polar molecule (HAPM). Its electron donating and accepting abilities in the solid state were examined from the measurements of its electronic structure using ultraviolet photoemission spectroscopy (UPS) and inverse photoemission spectroscopy (IPES): The threshold ionization energy I s th and electron affinity A s th in the solid state were determined to be 5.1 ± 0.1 5 and 3.5 ± 0.4 eV, respectively. These values turn out to be comparable to the corresponding values of typical donor or acceptor compounds, indicating high abilities in both electron donating and accepting nature of BMDCM. The origin of such a nature of BMDCM is discussed in terms of aromatic stabilization in its ionic states.

The molecular structure of trans -cinnamaldehyde (( E )-3-phenyl-2-propenal) was determined by means of gas electron diffraction. The nozzle temperature was 165 °C. The results of B3LYP calculations with the 6-31G ∗∗ basis set were used as Supporting information . It was found that this molecule has two stable conformers, s- cis and s- trans , which differ in the orientation of the CH O group. Their abundances at 165 °C were determined to be 25 ± 19% and 75%, for the s- cis and s- trans , respectively. This conformational composition is consistent with the prediction by the theoretical calculations. The determined structural parameters ( r g and ∠ α ) of the more abundant conformer, s- trans , of trans -cinnamaldehyde are as follows: r (C C) ring > = 1.398(1) A; r (C C) = 1.348 (←) A; r (C 1 C) = 1.470(8) A; r (C C( O)) = 1.473(←) A; r (C O) = 1.225(6) A; r (C H)> = 1.116(6) A; ∠C 6 C 1 C 2 = 118.6(3)°; ∠C 1 C 2 C = 121.0(←)°; ∠C C 6 C 1 = 121.4(←)°; ∠C 2 C 1 C( C) = 122.0(26)°; ∠C 1 C C = 128.3(26)°; ∠C C CO = 115.3(27)°; ∠C C O = 126.6(19)°. The C 1 , C 2 and C 6 atoms are on the ring with the C 1 attached to the CH CH CHO group, and the C 2 and C 6 are on the cis and trans sides to the C C bond, respectively. Angle brackets denote average values; parenthesized values are the estimated limits of error (3 σ ) referring to the last significant digit; left arrows in the parentheses mean that the differences to the preceding parameters are fixed.

The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed atrogin-1 and MuRF1 mRNA levels (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for atrogin-1 mRNA. However, glutamine failed to reduce atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.

Strain-driven bending process proposed for the fabrication of small and precise cantilevers is reported. The process starts from the multi-layer structure grown by molecular beam epitaxy (MBE). The cantilevers consist of the two parts imitating the beam and the tip, each of which has different bending direction and radius. The shape determined by location of strained layer in multi-layer structure controlled with layer design and fabrication process including selective etching technique. We demonstrated cantilevers having a rolling up beam with 5 – 20 μ m length and a rolling down thinner tip with 3 μ m length. However the tips showed tortuous shape. The complex shape might originate from inhomogeneity dissolving of extra compounds generated in sacrifice layer etching process. Moreover, we measured resonant frequencies of the fabricated cantilevers by optical lever method. We obtained high resonant frequency of 2 MHz for the cantilever with 5 μ m length, 1 μ m width, and 100 nm thickness. This frequency seems suitable for video-rate scanning in dynamic mode atomic force microscopy (AFM). These results suggest that the strain-driven bending process is applicable to three-dimensional (3D) micro-cantilevers for video-rate scanning in dynamic AFM.

Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [ d -Lys 3 ]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and MuRF1 mRNA levels through ghrelin receptors in myocytes.

Catalytic properties of three-dimensional zeolites, Y (FAU), Beta (BEA), and CIT-1 (CON) zeolites were examined in the alkylation, isopropylation, sec-butylation, and tert-butylation, of biphenyl (BP), and compared to those of H-mordenite (MOR). The selectivities for 4,4′-dialkylbiphenyl (4,4′-DABP) varied with the types of zeolite and of alkylating agent. FAU, BEA, and CON gave only low selectivities for 4,4′-diisopropylbiphenyl (4,4′-DIPB) in the isopropylation, and predominant isomers were bulky and thermodynamically unstable 2,x′-DIPB (2,2′-, 2,3′-, and 2,4′-) at lower temperatures, and bulky and thermodynamically stable 3,4′- and 3,3′-DIPB at higher temperatures: this is quite different from catalytic features over MOR, which gave 4,4′-DIPB with high selectivities at moderate temperatures. These results suggest that FAU, BEA, and CON have no shape-selective nature in the isopropylation, and that the reaction is principally controlled kinetically at lower temperatures, and thermodynamically at higher temperatures. The sec-butylation gave similar results to the isopropylation. Although the selectivities for 4,4′-di-sec-butylbiphenyl (4,4′-DSBB) were higher than those in the isopropylation, predominant isomers were 2,x′-DSBB (2,2′-, 2,3′-, and 2,4′-) at lower temperatures, and 3,4′- and 3,3′-DSBB at higher temperatures. The tert-butylation gave 4,4′-di-tert-butylbiphenyl (4,4′-DTBB) in moderate to high selectivities over all zeolites at moderate temperatures: the selectivity for 4,4′-DTBB was higher than 80% over BEA and CON; however, it still remained at 50% over FAU. FAU channels with super cages are too large for selective formation of 4,4′-DTBB. From these results, it is concluded that the selectivity for 4,4′-DABP in the alkylation over MOR, FAU, BEA, and CON is determined by the exclusion of bulky isomers at their transition states, and that the exclusion is caused by the steric restriction at the transition states of bulky isomers by the zeolite channels.

To investigate the inhibitory specificity of angiotensin converting enzyme (ACE) inhibitors to matrix metalloproteinase (MMP)-9, we predicted molecular interactions between an ACE inhibitor imidapril and MMP-9 active site based on recent X-ray structural analyses. Two binding modes differing in the orientation of imidapril on the active site were identified, and its hydrophobic group appeared to preferentially interact with the S1 site compared with the S1' site. Compared with the lisinopril-MMP-9 model in our previous study, imidapril was stabilized effectively on the active site with less of molecular distortions. We also measured ACE and MMP-9 inhibitory activities of imidapril and lisinopril after myocardial infarction. Imidapril had a stronger inhibitory activity against MMP-9 than lisinopril. These findings show that imidapril inhibits MMP-9 directly like lisinopril and its hydrophobic interactions with the S1 site of MMP-9 would be important for enhancing inhibitory activity.

Matrix metalloproteinase-9 activity is dramatically increased during the acute phase after myocardial infarction. However, the relationship between matrix metalloproteinase-9 activity and cardiac dysfunction is unclear. In 1-day post-myocardial infarction hamsters, matrix metalloproteinase-9 activity was significantly increased, while matrix metalloproteinase-2 activity was not increased. A selective matrix metalloproteinase inhibitor, [2S,4S]-N-Hydroxy-5-ethoxymethyloxy-2-methyl-4-[4-phenoxybenzoyl] aminopentanamide (ONO-4817), significantly suppressed matrix metalloproteinase-9 activity 1 day after myocardial infarction. ONO-4817 also significantly prevented the development of cardiac dysfunction and left-ventricular dilatation. Matrix metalloproteinase-9 might play a crucial role in cardiac dysfunction and left-ventricular dilatation during the very acute phase after myocardial infarction.

Immune responses against heat shock protein 60 (HSP60) of pathogen-origin are thought to be defensive events which, due to molecular mimicry, misdirect to a human counterpart. Therefore, atherosclerosis may be serologically predicted by anti-HSP60 antibodies (Abs). In the present study, we analyzed the clinical prevalence of the serum IgG Abs against Helicobacter pylori (Hp)-derived HSP60 (Hp-HSP60) or its peptide fragments in patients with cardiovascular disease (CVD; n = 250), as compared to those in age- and gender-matched non-CVD patients ( n = 293). Anti-Hp cell lysate Abs frequently appeared in Hp-infected patients who were not associated with CVD. In contrast, Abs against the particular amino acid sequence Hp-HSP60 II3 (II3 region, Glu 141 –Leu 160 , in Hp-HSP60) predominantly appeared in CVD patients, as well as IgG anti-human HSP60 (Hu-HSP60 w ). Furthermore, neither titer of anti-Hp-HSP60 II3 nor anti-Hu-HSP60 w Abs was correlated with the levels of high sensitivity C-reactive protein (hsCRP). This data strongly suggested that IgG anti-Hp-HSP60 II3 Abs cross-reacted with Hu-HSP60 w were independent diagnostic markers relevant to CVD. Further, the 20 amino acid residues (Glu 141 –Leu 160 ) might be predominant CVD-associated epitopes that induce anti-Hu-HSP60 auto-Abs, whose location was predicted in the tertiary structure of Hu-HSP60.

Phenol in water was degraded by simultaneous use of ozone and silica-gel or zeolite. When Al 2 O 3 -supported silica-gel or TiO 2 -supported silica-gel was conjugated with ozonation, the phenol degradation was significantly enhanced, although raw silica-gel did not show such effect. When zeolite was conjugated with ozonation, phenol degradation was significantly enhanced as well. The ion-exchange of Na + in zeolite by Ni 2+ or Co 2+ and supporting metallic Ni or Co thereon did not show significant influence on this effect.

Pinellic acid from the tuber of Pinellia ternate, an active herbal component of the traditional Japanese herbal (Kampo) medicine Sho-seiryu-to, is a C18 trihydroxy fatty acid whose absolute stereochemistry has now been determined. All stereoisomers of pinellic acid were synthesized via regioselective asymmetric dihydroxylation, regioselective inversion, and stereoselective reduction in order to determine their absolute stereochemistries and adjuvant activities. Among this series of isomers, the (9S,12S,13S)-compound, which is a natural product, exhibited the most potent adjuvant activity. Spectral data for all of the stereoisomers of the 1,2-allylic diols were compared and related to their stereochemistries.

A three-component Mannich reaction of 3a-hydroxyfuroindoline (3), β-ketoester and formaldehyde was employed as an efficient and concise method to synthesize naturally-occurring (+)-Madindolines A (1) and B (2). The scope and limitations of the Mannich reaction with 3 are described.

A research program is under way to develop a series of madindoline-based inhibitors targeting interleukin 6. Such inhibitors will have potential use in fighting a variety of diseases for which no effective therapeutic drugs currently exist. Madindoline is no longer available from natural sources. Consequently, we have developed a purely synthetic route to ensure a supply of the compound. The synthesis of a range of analogues is described, all of which were evaluated for their inhibitory activity against the growth of IL-6-dependent 7TDI cells. From these assays, several synthetic madindoline analogues were identified as highly promising candidates for further development.

In this report, we describe an efficient, highly convergent, stereocontrolled first total synthesis and a second-generation synthesis of madindolines A 1 and B 2, potent selective inhibitors of interleukin 6. The key steps include (1) asymmetric oxidative ring-closure reaction of tryptophol 3 to construct a chiral 3a-hydroxyfuroindoline 4 using the modified Sharpless asymmetric epoxidation condition, (2) highly diastereoselective acylation to build up the quaternary carbon center, and (3) intramolecular acylation of ester 32 with allylsilanes to produce the full substituted cyclopentenedione units. Our first synthetic route defines for the first time both their relative and absolute configurations. Moreover, a more efficient second-generation synthesis was designed, which is suitable for gram-scale preparation of these compounds.

A vertical wetted-wall corona discharge reactor was used for removal of acetaldehyde in air. The reactor consists of a wire cathode sustained at the center of a cylindrical anode. Acetaldehyde laden air was fed either upward or downward through the wetted-wall reactor, in which water was circulated as a falling thin film on the inner wall of the anode. Ozone and short-lived species such as ions and radicals were generated in the reactor by gas corona. When some of these short-lived radicals drifted and reached the water film, reactive OH radical was produced in the water. Since gaseous acetaldehyde was readily absorbed into the water before the gas mixture entered the corona zone, decomposition of aqueous acetaldehyde by OH radical was considered as the main mechanism. O 3 oxidation did not play a significant role in the present condition. It was found that there are a minimum current and a maximum inlet concentration of gaseous acetaldehyde for highly effective decomposition of aqueous acetaldehyde and TOC, resulting in steady state operation. It was calculated that one electron removed approximately 13 molecules of acetaldehyde. In comparison with the deposition type, the wetted-wall type exhibited clearly higher removal efficiency and lower byproduct formation. In addition, the effect of gas flow direction was discussed.

The influence of dissolved several inorganic contaminants into water was examined on the decomposition of aqueous organic compounds by direct contact of gas corona discharge. It was found that addition of 0.01 mol l −1 NaOH into water significantly improves the decomposition of aqueous phenol while the addition of HCl of the same concentration inhibits the decomposition rate. As it is known that phenol is converted to stable acetic acid during the decomposition process in the reactor, the influence of NaOH, HCl, H 3 PO 4 and NaCl was examined on the degradation of acetic acid. As a result, dissolved Cl − inhibits its decomposition efficiency. It is also found that this decomposition rate is significantly improved by raised pH which is higher than 11.

This paper describes the development of a miniature abrasion-detecting device for a small precision lathe. The device works by detecting the amplitude of the first natural frequency of the cutting tool, which increases with abrasion. By employing a small unimorph piezoelectric vibrator as a sensor and using an electric power control with an analog switch, a miniature, low power device for detecting abrasion is developed. The 30 mm by 30 mm device does not need a regulator in the electrical circuit and runs continuously for more than a week on a coin-sized battery.

We previously demonstrated that FAK-transfected HL-60 (HL-60/FAK) cells exhibit anti-apoptotic capacity. Here, we report that HL-60/FAK cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. This observation prompted us to investigate the mechanism of how HL-60/FAK cells augment cell proliferation. Since a protein kinase C (PKC) inhibitor, chelerythrine, or a PI3-kinase inhibitor, LY294002, suppressed cell proliferation effectively, both PKC and PI-3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, particularly PKCalpha, beta and eta isoforms were activated and directly associated with FAK in HL-60/FAK cells. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity.