Search

Glutamine synthetase (GS) is a decameric enzyme that plays a key role in nitrogen metabolism. Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N-degron is not essential for GS decamer formation. It is also shown that the N-degron can be exposed to a solvent region through a series of conformational adjustments upon ligand binding. In summary, this study elucidated the dynamic movement of the N-degron and the possible effect of glutamine in enhancing the acetylation process.

α-Glucosidase (EC 3.2.1.20) is a carbohydrate-hydrolyzing enzyme which generally cleaves α-1,4-glycosidic bonds of oligosaccharides and starch from the nonreducing ends. In this study, the novel α-glucosidase from Weissella cibaria BBK-1 (WcAG) was biochemically and structurally characterized. WcAG belongs to glycoside hydrolase family 13 (GH13) and to the neopullanase subfamily. It exhibits distinct hydrolytic activity towards the α-1,4 linkages of short-chain oligosaccharides from the reducing end. The enzyme prefers to hydrolyse maltotriose and acarbose, while it cannot hydrolyse cyclic oligosaccharides and polysaccharides. In addition, WcAG can cleave pullulan hydrolysates and strongly exhibits transglycosylation activity in the presence of maltose. Size-exclusion chromatography and X-ray crystal structures revealed that WcAG forms a homodimer in which the N-terminal domain of one monomer is orientated in proximity to the catalytic domain of another, creating the substrate-binding groove. Crystal structures of WcAG in complexes with maltose, maltotriose and acarbose revealed a remarkable enzyme active site with accessible +2, +1 and −1 subsites, along with an Arg–Glu gate (Arg176–Glu296) in front of the active site. The −2 and −3 subsites were blocked by Met119 and Asn120 from the N-terminal domain of a different subunit, resulting in an extremely restricted substrate preference.

A new type of the acoustic black hole beam—a helix-acoustic black hole—is proposed to overcome the spatial restriction on modular acoustic black hole structures. The modular acoustic black hole structure, consisted of a base and several number of acoustic black hole beams, has potential to apply into real engineering world. There are two main sections in an acoustic black hole beam: (1) a uniform thickness part and (2) an acoustic black hole region of which the thickness decreases according to the power-law profile. Conventional acoustic black hole beams can be ultimately assembled as 8–10 acoustic black hole beams on a modular acoustic black hole structure. In this article, a different shape of an acoustic black hole beam is newly designed to allow the assembly of more acoustic black hole beams on the modular acoustic black hole structure. The shape of the helix-acoustic black hole is such that the thickness of the acoustic black hole region smoothly decreases, just like a conventional acoustic black hole beam, as well as twisting along the longitudinal direction. The normal direction of the bottom surface in the uniform thickness is the same along the longitudinal axis in the conventional acoustic black hole beam. However, the normal direction of the helix-acoustic black hole of the bottom surface in the acoustic black hole region is different along the longitudinal direction. It is necessary to use numerical simulations to explore the performance of the helix-acoustic black hole beam because the shape of acoustic black hole region is different from the conventional one. Two types of numerical simulations were conducted: transient analysis and modal frequency analysis. From the transient analysis, the acoustic black hole effect was investigated by comparing the travel time which is dependent on the variation of the thickness. Using modal frequency analysis, the reflection coefficients between the conventional acoustic black hole beam and helix-acoustic black hole beam are also compared. It is noted that reflection coefficients were additionally compared depending on how “sharply” or “smoothly” they were twisted in the acoustic black hole region of the helix-acoustic black hole. Those results demonstrate that the helix-acoustic black hole has a dynamic characteristic similar to that of conventional acoustic black hole beams, which means that more helix-acoustic black holes can be assembled on the modular acoustic black hole structure by resolving the spatial restriction and leading to expectations of better performance.

We present a new approach to the design of the signal generated locally to enhance the performance in tracking of the time-multiplexed binary offset carrier (TMBOC) signal. Considering that the advantages of the TMBOC signal such as a high degree resistance to noise and multipath result from its BOC(6,1) segments, we propose to design the local signal with exploiting only BOC(6,1) segments, which is different from the conventional design approach using both BOC(6,1) and BOC(1,1) segments of the TMBOC signal. Separating and re-grouping the components composing the BOC(6,1) segments, we produce a local signal set and develop a special correlation procedure tailored to the local signal set. Numerical results indicate that the proposed approach achieves the TMBOC signal tracking with a higher degree of robustness to noise and multipath influences over that of the conventional approach in various urban canyon environments.

Vesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone.

This paper documents a tight connection between long run consumption risks (LRRs), currency excess returns and traditional global currency risk factors. We adopt a novel identification strategy that estimates country level LRRs using asset market data alone. With this identification strategy in hand, we find that: (1) currencies that suffer a bad relative LRR shock appreciate on impact before depreciating over the long run, (2) the High-Minus-Low (HML) carry trade sorts currencies on the basis of global LRR exposures, (3) the dollar carry trade outperforms on impact before underperforming over the long run in response to positive US relative LRR shocks, (4) US relative LRR shocks drive global currency risk factors. We interpret these facts as evidence in favour of an international LRR model where US LRRs drive global shocks to the world economy.

I study the link between the US wealth share, the dollar and international risk sharing. Motivating this study are novel stylised facts regarding the US wealth share uncovered in this paper. Using aggregate portfolio holdings data, I find that: i) the US wealth share is countercyclical: the US gains relative wealth vis-a-vie the rest of the world (ROW) during global recessions, ii) these countercyclical wealth share dynamics are driven by valuation forces headlined by US equities: the US stock market outperforms the ROW during global recessions, iii) bond valuation forces associated with countercyclical convenience yields play a limited role in driving this valuation channel. I show that these wealth share dynamics along with traditional dollar dynamics can be rationalised using a simple two country recursive model of international risk sharing.

We address the identification and generation of the discrete-time chaotic system (DTCS) with a two-layered recurrent neural network (RNN). First, we propose an identification procedure of the DTCS in which the RNN is required to have less layers than in the conventional procedures. Next, based on Li–Yorke theorem, we propose a generation procedure which enables us to predict a range of chaotic behavior of the DTCS in advance. Simulation results demonstrate that the proposed identification procedure, employing the Levenberg–Marquardt algorithm and a two-layered RNN, requires lower computational complexity than the conventional identification procedures at comparable performance.

An index mapping algorithm that efficiently associates the subcarrier activation pattern (SAP) or constellation mode pattern (CMP) sequences with the index selecting bit (ISB) sequences is proposed to improve the error performances of two OFDM-`index modulation' (IM) variants, OFDM-`in-phase/quadrature' (IQ)-IM and `coordinate interleaving' (CI)-`multiple-mode' (MM)-OFDM-IM. If the Hamming distances between every combinational pair of the Gray-coded ISB sequences are written in a 2-dimensional Hamming distance table, the minimum Hamming distances (i.e., 1's) are located in an X-shaped cross. In the proposed index mapping algorithm, the selection and ordering of the SAP or CMP sequences is determined by a mapping strategy of locating the minimum Hamming distances (i.e., 2's) of the SAP or CMP sequences in the same X-shaped cross as that of the minimum Hamming distances (i.e., 1's) of the Gray-coded ISB sequences. A pseudo-code is provided to reify the proposed index mapping algorithm. We show by numerical simulation that the proposed index mapping algorithm can provide substantial performance improvement for various IM schemes such as OFDM-IQ-IM, CI-MM-OFDM-IM, and OFDM-IM, especially when an error correction code is applied simultaneously.

The reduction of vibration by acoustic black holes (ABHs) with damping treatments can be achieved in two stages: energy focalization and energy dissipation. The energy focalization is mainly due to changes of the local thickness by slowing down the flexural wave speed and energy dissipation can be achieved by using viscoelastic damping materials. In structures with embedded ABHs, the damping effectiveness can depend significantly on the types of damping treatments. In this paper, 4 different damping treatments according to the types of attached region are considered in order to estimate the effectiveness of damping treatments as 1) a fully-covered unconstrained damping treatment, 2) a fully-covered constrained damping treatment, 3) a partially-covered unconstrained damping treatment and 4) a partially- covered constrained damping treatment as well as no damping treatment as reference data. In this study, the performance of damping treatments is explored using numerical simulations of three-dimensional thin plate embedded truncated ABH(s). The wave energy in the ABH, the normalized total energy and the focalization ratio are introduced to compare the effectiveness of the damping treatments. The numerical results show that the fully-covered constrained damping treatment provides the most effective configuration in terms of the wave energy in ABH and the normalized total energy.

In dynamic systems, numerous structural components, such as mounts, bushings, and tires, deteriorate over time due to environmental conditions. In these elastomers, the typical environmental factor of aging is manifested by the oxidation of polymer chains due to exposure to air. The amount of oxidation in elastomers heavily depends on temperature. Elastomer components under thermal degradation show different dynamic characteristics over time. Predicting the mechanical properties of aged elastomers is crucial in structural design for enduring high-quality noise and vibration. In this work, we propose a procedure for predicting the dynamic properties of elastomers undergoing thermal degradation. This process is divided into 1) an inter-variability analysis in specific degradation states caused by uncertainties in the operational temperature environment, variation in the manufacturing process, and error of the material property model and 2) an analysis of the degradation variability caused by uncertainties in the degradation environment and the degradation model. The degradation variability includes the inter-variability and thus becomes a distribution of distributions. Therefore, the double-loop eigenvector dimension reduction method is proposed to predict degradation variability. The time–temperature superposition principle and an equivalent degradation time are introduced to accumulate the degradation states in case of thermal degradation at various temperatures. The proposed method is applied to a circular mount problem. The numerical results illustrate that the proposed method effectively predicts the aging of the dynamic elastomer properties that is due to the thermal environment.

Summary Biodegradable polyester polyhydroxyalkanoate (PHA) is a promising bioplastic material for industrial use as a replacement for petroleum-based plastics. PHA synthase PhaC forms an active dimer to polymerize acyl moieties from the substrate acyl-coenzyme A (CoA) into PHA polymers. Here we present the crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, bound to CoA. The structure reveals an asymmetric dimer, in which one protomer adopts an open conformation bound to CoA, whereas the other adopts a closed conformation in a CoA-free form. The open conformation is stabilized by the asymmetric dimerization and enables PhaC to accommodate CoA and also to create the product egress path. The bound CoA molecule has its β-mercaptoethanolamine moiety extended into the active site with the terminal SH group close to active center Cys291, enabling formation of the reaction intermediate by acylation of Cys291., Graphical Abstract, Highlights • Crystal structure of PhaCCs-CAT bound to coenzyme A • A unique asymmetric open-closed dimer • Restructuring of the CAP subdomain provides a cleft toward the active site • The cleft enables the substrate entry and the product egress, Polymer Chemistry; Biocatalysis; Structural Biology

AKT/PKB is downregulated by the ubiquitin-proteasome system (UPS), which plays a key role in cell survival and tumor progression in various types of cancer. The objective of this study was to determine the relationship between the sequential ubiquitination of lysine residues K284 to K214 in AKT and R-HSPA5 (the arginylated form of HSPA5), which contribute to the autophagic/lysosomal degradation of AKT when impaired proteasomal activity induces cellular stress. Results show that proteasome inhibitors (PIs) increased ATE1 (arginyltransferase 1)-mediated R-HSPA5 levels in a reactive oxygen species (ROS)-dependent manner. Further, binding of fully ubiquitinated AKT with R-HSPA5 induced AKT degradation via the autophagy-lysosome pathway. Specifically, the K48 (Lys48)-linked ubiquitinated form of AKT was selectively degraded in the lysosome with R-HSPA5. The deubiquitinase, USP7 (ubiquitin specific peptidase 7), prevented AKT degradation by inhibiting AKT ubiquitination via interaction with AKT. MUL1 (mitochondrial ubiquitin ligase activator of NFKB 1) also played a vital role in the lysosomal degradation of AKT by sequentially ubiquitinating AKT residues K284 to K214 for R-HSPA5-mediated autophagy. Consistent with this finding, despite HSPA5 arginylation, AKT was not degraded in mul1 KO cells. These results suggest that MUL1-mediated sequential ubiquitination of K284 to K214 may serve as a novel mechanism by which AKT is designated for lysosomal degradation. Moreover, binding of R-HSPA5 with fully ubiquitinated AKT is required for the autophagic/lysosomal degradation of AKT. Thus, modulating the MUL1-mediated non-proteasomal proteolysis mechanisms, such as sequential ubiquitination, may prove to be a novel therapeutic approach for cancer treatment. Abbreviations: AKT1: thymoma viral proto-oncogene 1; ATE1: arginyltransferase 1; ATG5: autophagy related 5; CASP3: caspase 3; EGFP: enhanced green fluorescent protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3B; glycogen synthase kinase 3 beta; HA: hemagglutinin; HSPA5/GRP78/BIP: heat shock protein 5; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; MUL1: mitochondrial ubiquitin ligase activator of NFKB1; NAC: N-acetylcysteine; NEK2: NIMA (never in mitosis gene a)-related expressed kinase 2; NH4Cl: ammonium chloride; PARP1: poly(ADP-ribose) polymerase family, member 1; PI: proteasome inhibitor; R-HSPA5: arginylated HSPA5; ROS: reactive oxygen species; SQSTM1: sequestome 1; Ub: ubiquitin; USP7: ubiquitin specific peptidase 7.

SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.

Background and Purpose The outcomes of acute internal carotid artery (ICA) terminus occlusions are poor. We classified ICA terminus occlusions into 2 groups according to the occlusion pattern of the circle of Willis and hypothesized that clinical outcomes would significantly differ between them. Methods Consecutive patients with acute ICA terminus occlusions evaluated by baseline computed tomographic angiography were enrolled. We investigated the occlusion patterns in the circle of Willis, retrospectively classified patients into simple ICA terminus occlusion (STO; with good Willisian collaterals from neighboring cerebral circulation) and complex ICA terminus occlusion (CTO; with one or more of A2 anterior cerebral artery, fetal posterior cerebral artery occlusion, or hypoplastic/absent contralateral A1; or with poor collaterals from anterior communicating artery) groups, and compared their baseline characteristics and outcomes. Results The STO group (n=58) showed smaller infarct volumes at 72 hours than the CTO group (n=34) (median, 81 mL [interquartile range, 38-192] vs. 414 mL [193-540], P

The GST pull-down assay is an intuitive and fast in vitro method for analyzing protein-protein or protein-ligand interactions and is comprised of a "bait" which is a GST-fused protein expressed in E. coli host or a baculovirus expression system and a "prey" which comprises putative binding partner protein(s) or other ligand molecule(s). This method is suitable for examining the direct interaction between two purified proteins and estimating the extent of the affinity.

The GST pull-down assay is an intuitive and fast in vitro method for analyzing protein-protein or protein-ligand interactions and is comprised of a "bait" which is a GST-fused protein expressed in E. coli host or a baculovirus expression system and a "prey" which comprises putative binding partner protein(s) or other ligand molecule(s). This method is suitable for examining the direct interaction between two purified proteins and estimating the extent of the affinity.

By virtue of the critical roles of Akt in vascular endothelial cell (EC) survival and function, cigarette smoke-induced Akt reduction may contribute to EC death and dysfunction in smokers' lungs. One of the negative Akt regulatory mechanisms is K48-linked Akt ubiquitination and subsequent proteasomal degradation. Here, we assessed the involvement of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), recently revealed as a novel Akt ubiquitin E3 ligase, in cigarette smoke-induced Akt ubiquitination and its contribution to pulmonary EC death and dysfunction. In human lung microvascular ECs (HLMVECs), cigarette smoke extract (CSE) noticeably elevated MUL1 expression and K48-linked Akt ubiquitination, whereas Akt, p-Akt, eNOS, and p-eNOS levels were decreased. MUL1 knockdown suppressed CSE-induced Akt ubiquitination/degradation and cytoplasmic reductions of Akt and p-Akt. Furthermore, MUL1 knockdown attenuated reductions of eNOS and p-eNOS and alleviated EC survival, migration, and tube formation in the presence of CSE exposure. In addition, overexpression of K284R Akt, a mutant for a MUL1-ubiquitination site, produced similar effects. In HLMVECs exposed to CSE, Akt-MUL1 interaction was increased in coimmunoprecipitation and in situ proximity ligation assays. Similarly, the proximity ligation assay signals were elevated in rat lungs exposed to cigarette smoke for 3 months, during which Mul1 levels were noticeably increased. Finally, we found that CSE-mediated MUL1 induction in HLMVECs is mediated by retinoic acid receptor-related orphan receptor α. Taken together, these data suggest that cigarette smoke-induced MUL1 elevation mediates Akt ubiquitination/degradation, potentially leading to pulmonary EC death and functional impairment.

An unambiguous tracking scheme is proposed for CBOC(6,1,1/11) signal.The proposed scheme combines the partial correlations in a specially designed way.The autocorrelation side-peaks are completely removed by the proposed scheme.Better TESD and MEE performances are achieved over those of the conventional schemes. This paper proposes a novel unambiguous correlation function for composite binary offset carrier (CBOC) signal tracking based on partial correlations. In the proposed scheme, first, we partition sub-carriers of the CBOC signal into partial sub-carriers, and subsequently, we obtain partial correlations by correlating the partial sub-carriers with the received CBOC signal. Finally, a novel unambiguous correlation function with no side-peak is constructed by combining the partial correlations in a specially designed way. Unlike the conventional schemes, the proposed scheme does not require any auxiliary signal and from numerical results, it is found to offer a better tracking performance than those of the conventional schemes in terms of the tracking error standard deviation (TESD) and multipath error envelope (MEE).

Background and Purpose The goal of stent retriever–based thrombectomy is removal of embolic clots in patients with intracranial large artery occlusion. However, outcomes of stent retrieval may differ between acute arterial occlusions due to intracranial atherosclerotic disease (IAD) and those due to embolism. This case series describes the outcomes of stent retriever–based thrombectomy and rescue treatments in 9 patients with IAD-related occlusion. Methods Among patients who underwent endovascular treatment for acute intracranial large artery occlusion, those in whom stent retrieval was attempted as first-line treatment were included in this review. IAD was defined as significant fixed focal stenosis at the occlusion site, which was evident on final angiographic assessment or observed during endovascular treatment. Results Median number of stent retriever passes was 2 (range, 1-3), and temporary bypass was seen in all patients. Immediate partial recanalization (arterial occlusive lesion grade 2-3) was observed in 7 patients. Immediate modified thrombolysis in cerebral infarction grade 2b-3 was seen in 6 patients, but the lesions often required rescue treatment due to reocclusion or flow insufficiency. In terms of rescue treatments, angioplasty and intra-arterial tirofiban infusion seemed to be effective. Conclusions Our findings suggest that stent retrieval can effectively remove thrombi from stenotic lesions and achieve partial recanalization despite the tendency toward reocclusion in most patients with IAD-related occlusion. Further research into the use of rescue treatments, such as tirofiban infusion and angioplasty, is warranted.

Based on grouping the pulses that compose the sub-carrier of the time-multiplexed binary offset carrier (TMBOC), we present an unambiguous correlation function that has no side-peaks causing the ambiguity in the TMBOC signal tracking, and also, that has a higher degree of the sharpness of the main-peak (DSM) over those of the conventional unambiguous correlation functions. Splitting the pulses composing the TMBOC sub-carrier into 12 groups, and, subsequently, forming the 12 group correlations corresponding to the 12 groups, we investigate the contribution of each of the 12 group correlations to the side peaks and main peak of the TMBOC autocorrelation function. Then, we propose a combining method of the 12 group correlations based on the investigation to remove the side peaks while improving the DSM. Numerical results demonstrate that the proposed unambiguous correlation function not only has no side-peaks, but also has a higher DSM, and, consequently, has a better tracking error performance than those of the conventional unambiguous correlation functions.

Recent research on non-thermal plasma (NTP, an ionized gas) has identified it as a novel cancer therapeutic tool. However, the molecular mechanism remains unclear. In this study, we demonstrated NTP induced cell death of head and neck cancer (HNC) through the AKT ubiquitin-proteasome system. NTP increased the gene expression of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), an E3 ligase for AKT, and NTP-induced HNC cell death was prevented by MUL1 siRNA. We also showed that MUL1 inhibited the level of AKT and p-AKT and MUL1 expression was increased by NTP-induced ROS. Furthermore, we optimized and manufactured a new type of NTP, a liquid type of NTP (LTP). In syngeneic and xenograft in vivo tumor models, LTP inhibited tumor progression by increasing the MUL1 level and reducing p-AKT levels, indicating that LTP also has an anti-cancer effect through the same mechanism as that of NTP. Taken together, our results suggest that NTP and LTP have great potential for HNC therapy.

Although obesity is clearly identified as a risk factor for diabetes, the relationship between diabetes and metabolically healthy status of obesity is less clear. This study was aimed to evaluate the incidental risk of diabetes according to metabolically healthy status of obesity. 31,834 Korean men without diabetes categorized into six groups according to their metabolically healthy status stratified by degree of obesity were followed up for 5 years: metabolically healthy normal weight (MH-NW), metabolically healthy overweight (MH-OW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MU-NW), metabolically unhealthy overweight (MU-OW), and metabolically unhealthy obese (MUO). Cox proportional hazards analysis was used to measure the risk for diabetes according to their categories. While overall incidence was 9.0 %, incidence of diabetes was in proportion to the degree of obesity and metabolically healthy status (MH-NW: 6.3 %, MH-OW: 7.5 %, MHO: 9.2 %, MU-NW: 11.8 %, MU-OW: 14.9 %, MUO: 20.1 %). When MH-NW was set as reference, the adjusted HRs (95 % CI) for diabetes of the MH-OW, MHO, MU-NW, MU-OW, MUO compared to MH-NW were 1.18 (1.06-1.32), 1.58 (1.03-2.41), 1.81 (1.61-2.04), 2.36 (2.11-2.63), and 3.47 (2.84-4.24), respectively. In conclusion, risk for diabetes was in proportion to the degree of obesity in both metabolically healthy and unhealthy group. Metabolically healthy status was more significant determinant for incident diabetes than obesity itself.

A time-reversal (TR)-based transmission using pre-distortion of the transmitted waveforms for intersymbol interference (ISI) alignment is proposed. This scheme differs from the previous TR-based pre-filtering schemes in that it uses distinctively designed pre-distorted waveforms that are based on the transmitted symbol information. In the proposed pre-distortion scheme, the successively received waveforms carrying adjacent transmitted symbols are aligned so that the received symbol power can be intensified. Since the overlapped portions of the successively transmitted waveforms from the proposed pre-distortion scheme are correlated, the power of the overall transmitted signal that is formed by time-shifting and adding the pre-distorted waveforms becomes larger than the sum of the individual pre-distorted waveform powers. In order to adjust the pre-distorted waveform power without measuring the actual power of the overall transmitted signal, an upper bound on the average power of the overall transmitted signal was derived analytically under a low SNR assumption. Simulation showed that the proposed pre-distortion scheme outperformed both conventional TR and the minimum mean square error (MMSE)-based pre-filtering when the ISI was serious with a high transmission rate.

AKT (also known as protein kinase B, PKB) plays an important role in cell survival or tumor progression. For these reasons, AKT is an emerging target for cancer therapeutics. Previously our studies showed that mitochondrial E3 ubiquitin protein ligase 1 (MUL1, also known as MULAN/GIDE/MAPL) is suppressed in head and neck cancer (HNC) and acts as negative regulator against AKT. However, the MUL1 regulatory mechanisms remain largely unknown. Here we report that cisplatin (CDDP) induces thyroid cancer cell death through MUL1-AKT axis. Specifically, CDDP-induced MUL1 leads to ubiquitylation of active form of AKT. We also observed that the role of forkhead box O3 (FOXO3) is pivotal in CDDP-induced MUL1 regulation. FOXO3 knock-downed cells show resistance against CDDP-mediated MUL1-AKT axis. CDDP-mediated intracellular ROS increment plays an important role in FOXO3-MUL1-AKT signal pathway. The data provide compelling evidence to support the idea that the regulation of FOXO3-MUL1-AKT axis can be a novel strategy for the treatment of HNC with CDDP.

Background and purpose This study was to evaluate the diagnostic value of improved motion-sensitized driven-equilibrium (iMSDE)-prepared 3D T1-weighted magnetic resonance imaging (MRI) (iMSDE-3DMRI) in intracranial vertebrobasilary dissection (VBD) and to compare iMSDE-3DMRI images with those obtained using 2D high-resolution (HR) MRI with respect to their diagnostic performance in VBD. Materials and methods We retrospectively reviewed 105 lesions from 102 patients who underwent multimodal imaging and contrast-enhanced iMSDE-3DMRI (CE-iMSDE-3DMRI). The 2D-HRMRI protocol comprised four axial HR images. The CE-iMSDE-3DMRI images were reformatted in the axial, coronal, and sagittal planes. The 2D-HRMRI-based diagnosis was compared with the final diagnosis. The 2D-HRMRI and CE-iMSDE-3DMRI images were examined independently for the diagnosis performance of dissection. Results VBD was confirmed in 66 lesions in 63 patients; 17 patients had confirmed atherosclerosis, and 22 had no lesions in the vertebrobasilar artery. Diagnostic performances of 2D-HRMRI (AUC, 0.839 ± 0.04; sensitivity, 94.0; specificity, 79.5; diagnostic accuracy, 88.6) CE-iMSDE-3DMRI (AUC, 0.847 ± 0.04; sensitivity, 84.8; specificity, 84.6; diagnostic accuracy, 84.7) and 2D-HRMRI + CE-iMSDE-3DMRI (AUC, 0.893 ± 0.03; sensitivity, 97.0; specificity, 85.0; diagnostic accuracy, 92.5) were good. Comparisons of the diagnostic performance of 2D-HRMRI andCE-iMSDE-3DMRI showed that combined interpretation of 2D-HRMRI and iMSDE-3DMRI yields a significantly higher diagnostic performance than that of 2D-HRMRI (P = 0.042). Conclusions CE-iMSDE-3DMRI showed good diagnostic performance for the diagnosis of intracranial VBD. These results suggest that CE-iMSDE-3DMRI can be used in combination with 2D-HRMRI for the diagnosis of intracranial VBD.

Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase PhaC is poor due to the paucity of available three-dimensional structural information. Here we present a high-resolution crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, PhaC Cs -CAT. The structure shows that PhaC Cs -CAT forms an α/β hydrolase fold comprising α/β core and CAP subdomains. The active site containing Cys291, Asp447 and His477 is located at the bottom of the cavity, which is filled with water molecules and is covered by the partly disordered CAP subdomain. We designated our structure as the closed form, which is distinct from the recently reported catalytic domain from Cupriavidus necator (PhaC Cn -CAT). Structural comparison showed PhaC Cn -CAT adopting a partially open form maintaining a narrow substrate access channel to the active site, but no product egress. PhaC Cs -CAT forms a face-to-face dimer mediated by the CAP subdomains. This arrangement of the dimer is also distinct from that of the PhaC Cn -CAT dimer. These findings suggest that the CAP subdomain should undergo a conformational change during catalytic activity that involves rearrangement of the dimer to facilitate substrate entry and product formation and egress from the active site.

To investigate the impacts of climate change on environmental conditions and pelagic biodiversity, spatial patterns in pelagic ciliate communities were studied at 18 stations from five habitats in the Amundsen Sea (western Antarctic) during austral summer from December 2010 to January 2011. Clear spatial patterns were observed in community structure, and significant differences were found among the various habitats. The species number, abundance, biomass and biodiversity indices (Shannon diversity H′, Pielou’s evenness J′, and Margalef richness D) also showed clear spatial trends. Pelagic ciliate community structure accurately reflected environmental variability. Alone or in combination, several primary environmental variables were found to affect community spatial patterns in specific habitats. Shannon H′ and Margalef D showed strong relationships with spatial changes in chlorophyll a and might be better predictors in future Antarctic studies. This study presents the first detailed description of spatial patterns in pelagic ciliate communities and their correlations with environmental variability in habitats in the Amundsen Sea during early austral summer. Our findings provide detailed and basic data on the composition, distribution, and variation of ciliate communities in the Amundsen Sea, and will help answer important questions about polar ecosystems.