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Both an Al0.3Ga0.7As heterojunction in the p-type emitter and a bandgap-graded layer in the n-type light absorbing base were employed in the GaAs-based solar cells. The simulation by AFORS-HET (Helmholtz-Zentrum Berlin) confirmed that the Al0.3Ga0.7As heterojunction enhanced the open-circuit voltage (Voc) by ~2%, and the n-type bandgap grading increased the fill factor by ~1%, respectively. The increased power conversion efficiency by ~3% supported the simulation results. An additional efficiency gain was obtained by the shape optimization of the band bending in the 80-nm compositional profile, increasing Voc up to 1.103 V. The cell with the anti-reflective coating exhibited high performance with a power conversion efficiency of 28.7% under 1 sun illumination, close to the world record of 28.8%.

Urotensin II (UII) is a neural hormone that induces cardiac hypertrophy and may be involved in the pathogenesis of cardiac remodeling and heart failure. Hypertrophy has been linked to histone deacetylase 5 (HDAC5) phosphorylation and nuclear factor κB (NF-κB) translocation, both of which are predominantly mediated by G protein-coupled receptor kinase 5 (GRK5). In the present study, we found that UII rapidly and strongly stimulated nuclear export of HDAC5 and nuclear import of NF-κB in H9c2 cells overexpressing the urotensin II receptor (H9c2UT). Hence, we hypothesized that GRK5 and its signaling pathway may play a role in UII-mediated cellular hypertrophy. H9c2UT cells were transduced with a GRK5 small hairpin RNA interference recombinant lentivirus, resulting in the down-regulation of GRK5. Under UII stimulation, reduced levels of GRK5 in H9c2UT cells led to suppression of UII-mediated HDAC5 phosphorylation and activation of the NF-κB signaling pathway. In contrast, UII-mediated activations of ERK1/2 and GSK3α/β were not affected by down-regulation of GRK5. In a cellular hypertrophy assay, down-regulation of GRK5 significantly suppressed UII-mediated hypertrophy of H9c2UT cells. Furthermore, UII-mediated cellular hypertrophy was inhibited by amlexanox, a selective GRK5 inhibitor, in H9c2UT cells and neonatal cardiomyocytes. Our results suggest that GRK5 may be involved in a UII-mediated hypertrophic response via activation of NF-κB and HDAC5 at least in part by ERK1/2 and GSK3α/β-independent pathways.

It has been reported that good spinal sagittal alignment reduces the risk of fall and positive sagittal balance is the radiographic parameter that is most highly correlated with adverse health outcomes. However, no reports have demonstrated a change in risk of falling in patients with lumbar spinal stenosis (LSS) according to sagittal balance status.From September 2013 to October 2014, 141 patients who underwent lumbar spine surgery, including decompression and fusion in-situ for LSS, were enrolled in this study. Based on sagittal balance status, patients were divided into sagittal balance (SB) and sagittal imbalance (SI) groups. Four functional mobility tests were used to evaluate the risk of falling, and a fall diary, Oswestry disability index (ODI), and the Euro-QoL 5D(EQ-5D) visual analogue scale (VAS) were utilized to assess clinical improvement.The mean patient age was 70.1 years in the SB group (N=46) and 70.9 years in the SI group (N=95) (not significant). The mean C7PL was 7.9mm in the SB group and 66.1mm in the SI group preoperatively (p0.05). Among the four functional tests, only postoperative SMT and STS improved significantly in the SB group (p0.05). Patients in the SI group showed significantly improved scores for all four functional tests during postoperative follow-up (p0.05), but their performance was still worse than patients in the SB group. Average number of falls per individual during the follow-up period was 1.1±2.5 in the SB group and 1.9±3.2 in the SI group (p0.05). There was a significant difference in the distribution of non-fallers and fallers (single and multiple fallers) between the two groups postoperatively(p0.05). ODI and the EQ-5D VAS showed greater improvement in the SB group than the SI group. Multiple regression analysis revealed that sagittal balance during follow-up significantly affected ODI, EQ-VAS, functional mobility tests. (p0.05).Therefore, when fusion surgery is planned in patients with LSS, careful consideration of sagittal balance status might be important to attain better surgical and functional outcomes and decrease the incidence of actual falls after surgical treatment.

Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/ kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction.

We previously reported that murrayafoline-A (1-methoxy-3-methyl-9H-carbazole, Mu-A) increases the contractility of ventricular myocytes, in part, via enhancing Ca(2+) influx through L-type Ca(2+) channels, and that it increases the Ca(2+) transients by activation of protein kinase C (PKC). In the present study, we further examined the cellular mechanisms for the enhancement of contractility and L-type Ca(2+) current (ICa,L) by Mu-A. Cell shortening and ICa,L were measured in rat ventricular myocytes using a video edge detection method and perforated patch-clamp technique, respectively. We found that the positive inotropic effect of Mu-A was not affected by pre-exposure to the β-adrenoceptor antagonist propranolol, the protein kinase A (PKA) inhibitors KT5720 or H-89, or the phospholipase C inhibitor U73122. Interestingly, the Mu-A-mediated increases in cell shortening and in the rate of contraction were completely suppressed by pre-treatment with the PKC inhibitor GF109203X. The stimulatory effect of Mu-A on ICa,L was not altered by inhibition of PKA (KT5720), G-protein coupled receptors (suramin), or α1-adrenoceptor (prazosin). However, pre-exposure to the PKC inhibitor, GF109203X or chelerythrine, abolished the Mu-A-induced increase in ICa,L. Pre-exposure to the Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 slightly reduced the stimulatory effects on contraction and ICa,L by Mu-A. Phosphorylation of PKC was enhanced by Mu-A in ventricular myocytes. These data suggest that Mu-A increases contraction and ICa,L via PKC in rat ventricular myocytes, and that the PKC-mediated responses in the presence of Mu-A may be partly mediated by CaMKII.

Fumigants are used worldwide for control of biological agents that damage wooden cultural property. To establish a policy for fumigant use, biological evaluation of insects and microorganisms considering many factors is required. This study was performed to evaluate biological sensitivity and wood penetration of three fumigants applied for control of biological agents that damage wooden cultural properties in Korea. Among these, methyl bromide and ethylene oxide can control insects and fungi when exposed directly. However, they were unable to completely control biological agents within deeper parts of wood. Ethanedinitrile, which was developed as an alternative fumigant, exhibited outstanding wood penetration and biocidal efficacy. Further research involving various environmental conditions is warranted.

An organic-inorganic hybrid perovskite is considered as a next generation solar energy harvester due to the high power conversion efficiency. The starting precursor solution for the organolead halide perovskite is of significant interests because the ionic components in the precursor can critically affect the nanostructures and thereby the optoelectronic properties. In this work, the basic and well-known precursor solution for CH3NH3PbI3(Cl) comprised of CH3NH3I and PbCl2, is specifically analyzed to unravel the phenomena in the Cl-mediated solutions. The shift in equilibrium between lead-halide complex and the solvent results into the CH3NH3PbI3(Cl) grain evolution with Cl incorporation, which is confirmed through x-ray fluorescence and diffraction. The effects of Cl on the optoelectronic properties are further verified by conductive atomic force microscopy, and the existing Cl leads to the 30-times-increased and inhomogeneously distributed photocurrent for CH3NH3PbI3(Cl) grains compared with CH3NH3PbI3. Moreover, photocurrent noise from the mixed-halide perovskite is reduced than that from the triiodide perovskite phase. Combining the microstructural evolution with the optoelectronic properties of mixed-halide perovskite, it is concluded that additional Cl reduces the defects of recombination centers resulting high photocurrent.

Correspondence to: Byung-Ho LeeDepartment of Dental Hygiene, Youngsan University, 288 Junam-ro, Yangsan 50510, KoreaTel: +82-55-380-9436, Fax: +82-55-380-9305, E-mail: leebh@ysu.ac.krCopyright © 2016 by the Korean Society of Dental Hygiene Science This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The mandibular ramus is considered an appropriate choice for reconstruction of maxillofacial defects because of sufficient amounts of material and fewer donor site complications. Although bone harvesting from the mandibular ramus has many advantages, in rare cases it can result in pathologic fracture of the mandible. Here, we present a case of 59-year-old man who suffered a pathologic mandible fracture related to biting hard foods, such as crab shells, after a sinus bone lifting with ramal bone graft procedure performed 2 weeks prior. He underwent closed reduction by intermaxillary fixation with an arch bar over the course of 4 weeks. Three months later, the patients had a stable occlusion with normal mouth opening and sensation. To prevent this complication, the osteotomy should be performed in such a way that it is not too vertical during ramal bone harvesting. Furthermore, we wish to emphasize the importance of patients being instructed to avoid chewing hard foods for at least 4 weeks after ramal bone harvesting.

A dual readout assay based on fluorescence polarization (FP) and time-resolved fluorescence resonance energy transfer (TR-FRET) exhibits many advantages over single assay technology in terms of screening quality and efficiency. In this study, we developed a dual readout assay combining FP and TR-FRET to identify ribosomal S6 kinase 1 (RSK1) inhibitors. This dual readout assay can monitor both FP and TR-FRET signals from a single RSK1 kinase reaction by using the immobilized metal affinity for phosphochemical (IMAP)-based assay. The Z' value and signal to background (S/B) ratio were 0.85 and 4.0 using FP, and 0.79 and 10.6 using TR-FRET, which led to performance of a pilot library screening against the drug repositioning set consisting of 2320 compounds with a reasonable reproducibility. From this screening, we identified 16 compounds showing greater than 50% inhibition against RSK1 for both FP and TR-FRET; 6 compounds with greater than 50% inhibition only for FP; and 4 compounds with greater than 50% inhibition only for TR-FRET. In a cell-based functional assay to validate the hit compounds, 10 compounds identified only in a single assay had little effect on the RSK-mediated phosphorylation of liver kinase B1, whereas 5 compounds showing greater than 80% inhibition for both FP and TR-FRET reduced the phosphorylation of liver kinase B1. These results demonstrate that the dual readout assay can be used to identify hit compounds by subsequently monitoring both FP and TR-FRET signals from one RSK1 reaction.

The design and ratio of the cortico-cancellous composition of allograft spacers are associated with graft-related problems, including subsidence and allograft spacer failure. Methods: The study analyzed stress distribution and risk of subsidence according to three types (cortical only, cortical cancellous, cortical lateral walls with a cancellous center bone) and three lengths (11, 12, 14 mm) of allograft spacers under the condition of hybrid motion control, including flexion, extension, axial rotation, and lateral bending,. A detailed finite element model of a previously validated, three-dimensional, intact C3&ndash, 7 segment, with C5&ndash, 6 segmental fusion using allograft spacers without fixation, was used in the present study. Findings: Among the three types of cervical allograft spacers evaluated, cortical lateral walls with a cancellous center bone exhibited the highest stress on the cortical bone of spacers, as well as the endplate around the posterior margin of the spacers. The likelihood of allograft spacer failure was highest for 14 mm spacers composed of cortical lateral walls with a cancellous center bone upon flexion (PVMS, 270.0 MPa, 250.2%) and extension (PVMS: 371.40 MPa, 344.2%). The likelihood of allograft spacer subsidence was also highest for the same spacers upon flexion (PVMS, 4.58 MPa, 28.1%) and extension (PVMS: 12.71 MPa, 78.0%). Conclusion: Cervical spacers with a smaller cortical component and of longer length can be risk factors for allograft spacer failure and subsidence, especially in flexion and extension. However, further study of additional fixation methods, such as anterior plates/screws and posterior screws, in an actual clinical setting is necessary.

Rationale: Emphysematous osteomyelitis is a rare disease caused by gas-forming bacteria. But only 45 cases have been reported in the literature since then. Patient concerns: A 72-year-old female presented to our hospital with severe lower back pain that aggravated 4 days ago. Diagnoses: Computed tomography (CT) revealed intraosseous mottled air in the T12 and L1 vertebral bodies and epidural space. The enhanced T1 and T2 magnetic resonance imaging scans showed heterogeneous signal intensity of vertebral bodies, suggestive of emphysematous osteomyelitis. Interventions: Surgery was performed to identify culture strains and to remove emphysematous lesions of the vertebral body using extensive transpedicular irrigation. Outcomes: Escherichia coli (E coli) was identified in the surgical specimen, and intravenous antibiotic therapy was continued with cefotaxime. The patient had a significant decrease in lower back pain after the surgery and the final CT scan before discharge revealed significantly decreased air at T12 and L1 vertebral bodies and no air density in the epidural space. Lessons: We present a patient diagnosed with emphysematous osteomyelitis in vertebral bodies caused by E coli and successfully treated with surgical intervention.

Background Comparative studies of the biomechanical effects of plates of varying lengths and different screw insertion angles on allograft spacers are lacking. Methods Finite element model analysis of a previously validated, three-dimensional, intact cervical spinal segment model of C3–6 was conducted in the present study. On the C5–6 segment, anterior discectomy and fusion were performed using allograft spacers and different combinations of anterior plates and screws. The biomechanical characteristics of combinations of short, medium, and maximal length plates with screw insertion angles of 0°, 8°, 16°, and 32° were analyzed. Findings In flexion and extension, the risk of allograft spacer subsidence decreased as screw angles increased. Short plates with a screw insertion angle of 32° posed the lowest subsidence risk, similar to medium length plates with a screw insertion angle of 16°, in all motion conditions. The risk of bone yielding increased as plate length increased, but decreased as the screw insertion angle increased. Interpretation Short plates with a large screw insertion angle (32°) showed the highest mechanical stability and load sharing of allograft spacers and the lowest risk of screw loosening. Accordingly, we recommend the use of a short plate and large screw insertion angle for anterior cervical discectomy and fusion.

Pyogenic sacroiliitis is a relatively rare condition that often leads to surgical treatment, including debridement and arthrodesis. Here we introduce a new surgical technique using bilateral dual iliac screws to secure early ambulation and maximal fusion success rate for the treatment of pyogenic sacroiliitis. We retrospectively reported a case and technical reports of pyogenic sacroiliitis treated by a new bilateral dual iliac screw fixation arthrodesis technique using radiologic outcomes, including plain X-rays and MRI scans, as well as outcomes based on the visual analogue scale for pain measurement. This technique improved uncontrolled pyogenic sacroiliitis with immediate stability that enabled ambulation and secured firm fixation for extensive evacuation of infected debris and subsequent autograft bone arthrodesis. In conclusion, we recommend bilateral dual iliac screw fixation for the treatment of pyogenic sacroiliitis, as this technique can improve uncontrolled pyogenic sacroiliitis with immediate stability.

Inhibition of IKK-β (inhibitor of nuclear factor kappa-B kinase subunit beta) has been broadly documented as a promising approach for treatment of acute and chronic inflammatory diseases, cancer, and autoimmune diseases. Recently, we have identified a novel class of thiazolidine-2,4-diones as structurally novel modulators for IKK-β. Herein, we report a hit optimization study via analog synthesis strategy aiming to acquire more potent derivative(s), probe the structure activity relationship (SAR), and get reasonable explanations for the elicited IKK-β inhibitory activities though an in silico docking simulation study. Accordingly, a new series of eighteen thiazolidine-2,4-dione derivatives was rationally designed, synthesized, identified with different spectroscopic techniques and biologically evaluated as noteworthy IKK-β potential modulators. Successfully, new IKK-β potent modulators were obtained, including the most potent analog up-to-date 7m with IC50 value of 260 nM. A detailed structure activity relationship (SAR) was discussed and a mechanistic study for 7m was carried out indicating its irreversible inhibition mode with IKK-β (Kinact value = 0.01 (min−1). Furthermore, the conducted in silico simulation study provided new insights for the binding modes of this novel class of modulators with IKK-β.

Study design This was a retrospective cohort study. Objective To evaluate the sagittal alignment and T1 slope after multilevel posterior cervical fusion surgery depending on the distal fusion level; C7 or T1, and find out the appropriate distal fusion level. Summary of background data The sagittal balance of the cervical spine is known to be affected by cervical lordosis and T1 slope. However, T1 slope is not a constant parameter that can be frequently changed after the surgery. Furthermore, useful studies to help guide surgeons in decision-making as to the most appropriate distal level of fusion for cervical sagittal balance are very limited. Materials and methods From 2014 to 2015, 50 patients who underwent multilevel posterior cervical fusion surgery were evaluated and followed up for >2 years. Group 1 was composed of 29 patients whose distal fusion level was C7. Group 2 was composed of 21 patients whose distal fusion level was T1. C1-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1 slope were measured on preoperative and the last follow-up. Results In group 1, C2-C7 SVA (23.1→30.4 mm, P=0.043) was worsened, and T1 slope (22.3→32.9 degrees, P=0.001) was increased after the surgery. In group 2, no significant change occurred in C2-C7 SVA after the surgery (25.3 →23.6 mm, P=0.648). The last follow-up T1 slope was similar with preoperative T1 slope (22.7→21.8 degrees, P=0.04) in group 2. Conclusions This study showed that sagittal alignment became worse after the multilevel posterior cervical surgery when distal fusion level was stopped at C7, which was associated with increase of T1 slope. However, when we extended the distal fusion level to T1, T1 slope was not changed after the surgery. Therefore, sagittal alignment was maintained after the surgery. On the basis of the results of this study, we recommend distal fusion extends to T1. Level of evidence Level III.

The insecticidal activity of phosphine (PH3) and ethyl formate (EF) toward Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) and their phytotoxicity to asparagus were evaluated. Both the PH3 and EF fumigants showed higher lethal concentration and time (LCT) values at lower temperatures. The LCT99 values of PH3 and EF at 5°C in a 12 liters desiccator for 4 h showed the following ranking: eggs (64.69 mg·h/liter for PH3 and EF indicating phytotoxicity to asparagus), nymphs (5.54 and 17.48 mg·h/liter, respectively), and adults (3.83 and 14.67 mg·h/liter, respectively). The adsorption of PH3 was approximately 11% at 2°C and 13% at 5°C, whereas the adsorption of EF increased sharply to 88% at 2°C and 97% at 5°C. The hatching rate of F. occidentalis eggs was approximately 95% at all locations (top, middle, and bottom) in the presence of 4 mg/liter PH3 at 5°C in a 0.65-m3 fumigation chamber for 24 h. However, extension of the treatment to 48 h resulted in 100% inhibition of egg hatching. The atmospheric level of PH3 decreased below the threshold limit value after 80 min, and phytotoxicity was not observed. The results revealed that EF is highly absorbed by asparagus and is not suitable as a fumigant, but PH3 is a suitable alternative to the fumigant methyl bromide for the control of western flower thrips in asparagus.

DITMD (1, 3- Dioxolo[4,5-g] isoquinolinium 5, 6, 7, 8- tetrahydro- 4- methoxy- 6, 6- dimethyl- 5- [2- oxo- 2- (2-pyridinyl)ethyl] - iodide) is a natural product-like compound with a hydrocotarnine moiety. The aim of this study was to investigate the anticancer effects of DITMD including mitotic arrest, apoptosis, radiosensitization, and to further explore its possible mechanism. DITMD (3−30 µM) induced an obvious cell cycle delay at G2/M transition and apoptosis in HeLa cells. In a validation study, DITMD caused chromosome alignment defects and accumulation of mitotic markers such as polo-like kinase 1, cyclin B1, and phospho-histone H3. DITMD pre-treatment for 11 h also significantly decreased the cells’ survival after X-ray irradiation. In mechanism studies, DITMD inhibited the polo-box domain of polo-like kinase 1 but not the conserved kinase domain. Molecular modeling also suggests that DITMD binds at the phosphate group recognition site and inhibits the action on phospho-peptide ligands. In addition, DITMD was analyzed as a PLHSpT competitive inhibitor with an IC50 value of 2.1 μM and exhibited good selectivity against 105 distinct kinases. Taken together, these results indicate that DITMD induced chromosome alignment defects, apoptosis and radio-sensitization, and suggest that one mechanism underlying these anticancer effects involves inhibiting the polo-box domain-dependent functions of polo-like kinase 1.

In order to incorporate functionalization into synthesized DNA nanostructures, enhance their production yield, and utilize them in various applications, it is necessary to study their physical stabilities and dynamic characteristics. Although simulation-based analysis used for DNA nanostructures provides important clues to explain their self-assembly mechanism, structural function, and intrinsic dynamic characteristics, few studies have focused on the simulation of DNA supramolecular structures due to the structural complexity and high computational cost. Here, we demonstrated the feasibility of using normal mode analysis for relatively complex DNA structures with larger molecular weights, i.e., finite-size DNA 2D rings and 3D buckyball structures. The normal mode analysis was carried out using the mass-weighted chemical elastic network model (MWCENM) and the symmetry-constrained elastic network model (SCENM), both of which are precise and efficient modeling methodologies. MWCENM considers both the weight of the nucleotides and the chemical bonds between atoms, and SCENM can obtain mode shapes of a whole structure by using only a repeated unit and its connectivity with neighboring units. Our results show the intrinsic vibrational features of DNA ring structures, which experience inner/outer circle and bridge motions, as well as DNA buckyball structures having overall breathing and local breathing motions. These could be used as the fundamental basis for designing and constructing more complicated DNA nanostructures.

Sook Young Lee, Yun Yong Jeong, Byung Ho Lee, Ji Eun Kim Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Republic of Korea Purpose: Cough on anesthetic emergence should be prevented considering its dangerous complications. Target-controlled infusion (TCI) of remifentanil can reduce emergence cough effectively, and sex-related differences in effect-site concentration (Ce) of remifentanil have been evaluated in young patients. In this study, we determined the Ce of remifentanil for preventing emergence cough following extubation in male and female elderly patients and evaluated the sex-related difference.Patients and methods: Twenty-three male and 22 female elderly patients aged between 60 and 75 years were enrolled. Anesthesia was maintained with sevoflurane and remifentanil TCI. The Ce of remifentanil for preventing emergence cough was determined for each sex using isotonic regression method with a bootstrapping approach, following Dixon’s up-and-down method.Results: The Ce of remifentanil for preventing emergence cough in 50% (EC50) and 95% (EC95) of the population was significantly lower in females than in males. Isotonic regression revealed the EC50 (83% confidence interval [CI]) of remifentanil was 1.67 (1.55–1.83) ng/mL in females and 2.60 (2.29–2.91) ng/mL in males. The EC95 (95% CI) of remifentanil was 2.30 (2.02–2.62) ng/mL in females and 3.41 (3.27–3.58) ng/mL in males. Dixon’s up-and-down method indicated that the mean EC50 in females was lower than in males (1.56±0.26 ng/mL vs 2.56±0.37 ng/mL, P

Carbon nanotubes (CNTs) have been considered a prominent nano-channel in cell membranes because of their prominent ion-conductance and ion-selectivity, offering agents for a biomimetic channel platform. Using a coarse-grained molecular dynamics simulation, we clarify a construction mechanism of vertical CNT nano-channels in a lipid membrane for a long period, which has been difficult to observe in previous CNT-lipid interaction simulations. The result shows that both the lipid coating density and length of CNT affect the suitable fabrication condition for a vertical and stable CNT channel. Also, simulation elucidated that a lipid coating on the surface of the CNT prevents the CNT from burrowing into the lipid membrane and the vertical channel is stabilized by the repulsion force between the lipids in the coating and membrane. Our study provides an essential understanding of how CNTs can form stable and vertical channels in the membrane, which is important for designing new types of artificial channels as biosensors for bio-fluidic studies.

A 4-day-old, male Poodle dog was presented with dull, depressed and exhausted activity after the birth. On physical examination, the puppy showed arthrogryposis, muscular atrophy and no movement of hindlimbs. Palpation on dorsum revealed an absence of lumbar and sacral vertebrae. On prenatal and postnatal radiography, lumbar vertebrae, sacrum and coccygeal vertebrae were not visualized. On ultrasonography, bilateral kidney and urinary bladder were observed. On computed tomography, there were no apparent abnormalities in the forelimbs, cervical vertebrae or head, while lumbar vertebrae, sacrum and coccygeal vertebrae were not observed. At necropsy examination, the liver, stomach, intestine, kidney and urinary bladder were normal. This congenital anomaly was consistent with Perosomus elumbis. Perosomus elumbis in dogs is a rare condition of unknown etiology. In this report, Perosomus elumbis was evaluated with radiography, ultrasound and computed tomography.

The Al-doped ZnO (ZnO:Al) front transparent conducting oxide (TCO) for high efficiency Si thin-film solar cell has been developed using RF magnetron sputtering deposition and chemical wet etching. Microscopic surface roughness of the as-deposited ZnO:Al film estimated by spectroscopic ellipsometry is closely related to the compactness of the TCO film, and shown to be a straightforward and powerful tool to optimize the deposition conditions for the proper post-etched surface morphology. Wet-etching time is adjusted to form the U-shaped craters on the surface of the ZnO:Al film without sharp etch pits that can cause the crack-like defects in the overgrown microcrystalline Si-absorbing layers, and deteriorate the Voc and FF of the Si thin-film solar cells. That is to say, the nanoroughness control of the as-deposited TCO film with proper chemical etching is the key optimization factor for the efficiency of the solar cell. The a-Si:H/a-SiGe:H/μc-Si:H triple junction Si thin-film solar cells grown on the optimized ZnO:Al front TCO with anti-reflection coatings show higher than 14% conversion efficiency.

In a search for novel molecules to treat inflammatory disorders, we identified several compounds with inhibitory action against the IKK2 enzyme using in silico methods. Based on the virtual hit of compounds 1 and 2, a novel series of 2-phenylimino-5((5-phenylfuran-2-yl)methylene)thiazolidin-4-one derivatives was designed, synthesized, and evaluated for IKK2 inhibitory activity. Among the synthesized derivatives, compounds 17f and 19f showed good IKK2 inhibitory potency, which have 4-carboxaminophenyl on the 2-furan ring and a methoxy group on the phenylimino moiety at the 2-position of the core structure. The most potent compound was 2-(2,4-dimethoxyphenyl)imino-5((5(4-carboxaminophenyl)furan-2-yl)methylene)thiazolidin-4-one (19f, IC50 = 0.94 μM), which represents a synergic effect of the two virtual hit compounds against IKK2. We also identified compounds showing inhibitory activities against interleukin (IL)-17, CCK-8, and tumor necrosis factor-alpha (TNF-α), which are NF-κB-dependent pro-inflammatory cytokine mediators.

Regardless of the great importance of light trapping towards the breakthrough in the saturated photoconversion efficiencies of Si thin-film solar cells, much research on the surface texturing of transparent conducting oxides (TCOs) has been focused more on the nanostructural control during thin film growth. Herein, an organic acid for the surface texturing of ZnO:Al is introduced as an alternative to the conventional HCl etchant, making more efficient light scattering by TCO. The texturing behavior by oxalic acid is investigated in terms of vertical roughness and lateral correlation length, and a mass-transport model is developed to explain the etching evolution mechanisms. Texturing with oxalic acid results in superior light-scattering performance (by ~8% more haze at λ =1000 nm) with maintaining the transparency and resistance, compared to the etching with HCl. This fascinating behavior is explained by utilizing the light-scattering haze model with the extracted two surface parameters. Significantly, this straightforward and reproducible texturing tactic extends tunability for the desirable TCO morphology, enabling efficient light trapping, and therefore appears potentially applicable for the large-scale photovoltaic devices in industry.

SLPI acts as a modulator of the innate immune responses of macrophages, neutrophils and odontoblasts, and LPS-inducible anti-inflammatory cytokine to suppress the production of pro-inflammatory products by macrophages. Many studies have revealed the effects of light emitting diodes (LEDs) on the tissue repair and inflammatory responses. Although the anti-inflammatory mechanisms of irradiation with LEDs in gingival fibroblasts are known, the effects of 660 nm red LEDs on the inflammation remain unclear. Moreover, there is no report regarding the molecular mechanism for the relationship between SLPI and biological effects of LEDs. The effects of 660 nm red LEDs on inflammation with SLPI were investigated by examining the effects of 660 nm LED on the SLPI expression of RAW264.7 cells after LPS stimulation. This paper reports that the 660 nm red LED induced SLPI expression or reduced the LPS response, and inhibited NF-κB activation directly, leading to the suppression of pro-inflammatory cytokines, such as TNF-α and IL-1β, suggesting that it might be a useful wavelength LED for inflammation therapy.

Ethnopharmacological relevance Tripterygium wilfordii (lei gong teng; Thunder of God Vine), which belongs to the Celastraceae family, has long been used in traditional Chinese medicine to treat inflammation and rheumatoid arthritis. Celastrol is a bioactive compound isolated from T. wilfordii. Aim of the study We investigated whether celastrol suppressed binding of lipopolysaccharides (LPS) to myeloid differentiation factor 2 (MD2), thereby downregulating Toll-like receptor4 (TLR4) activation in mouse primary macrophages. Materials and methods Cytokine expression was determined by polymerase chain reaction analysis and enzyme-linked immunosorbent assay in bone marrow-derived primary macrophages (BMDMs). The kinase activity of tank-binding kinase 1 (TBK1) was examined by a luciferase reporter assay and an in vitro kinase assay. LPS binding to MD2 was examined by an in vitro binding assay and confocal microscopy analysis. Results Celastrol reduced LPS-induced expression of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12, and IL-1β, at both the mRNA and protein levels in BMDMs. Celastrol suppressed LPS binding to MD2, as shown by the in vitro binding assay, whereas it did not inhibit TBK1. In addition, co-localization of LPS with MD2 in BMDMs was blocked by celastrol. The inhibitory effects of celastrol on LPS binding to MD2 were reversed by thiol donors (N-acetyl- L -cysteine and dithiothreitol), suggesting that the thiol reactivity of celastrol contributes to its inhibitory effects on TLR4 activation in macrophages. Conclusion Our results demonstrate that celastrol suppresses TLR4 activation through the inhibition of LPS binding to the TLR4/MD2 complex. These results provide a novel mechanism of action by which celastrol contributes to the anti-inflammatory activity of T. wilfordii .

Titanium (Ti) is the most widely used implant material in dentistry and orthopedics but the release of metal ions from Ti implants results in increased bone resorption by enhancing the production of inflammatory cytokines from the macrophages and facilitating osteoclast differentiation. Thymosin β4 (Tβ4) has several biological activities, such as promoting wound healing, angiogenesis, cell proliferation and migration in mammalian cells. This study examined the role of Tβ4 in osteoblasts via focal adhesions (FAs) and ERK1/2 signaling related to cell adhesion and proliferation for cell survival on the Ti surface. As a result, cell adhesion and proliferation increased in the Tβ4 treated cells (Tβ4/MC3T3-E1) but was significantly lower in the Tβ4 knock-down cells by Tβ4-siRNA (si-Tβ4/MC3T3-E1) than that of the untreated cells. The levels of FAK phosphorylation, paxillin expression, and paxillin localization were higher in the Tβ4/IMC3T3-E1 cells than that of the untreated cells but lower in the si-Tβ4/MC3T3-E1 cells. In addition, the levels of cell proliferation, Grb2 and Ras protein expression and phosphorylation of ERK1/2 were higher in the Tβ4/MC3T3-E1 cells than in the untreated cells but lower in the si-Tβ4/IMC3T3-E1 cells. These results suggest that Tβ4 might be a good nanomolecule that promotes osteoblast survival by facilitating adhesion and proliferation on the Ti surface.

In the study of protein dynamics relevant to functions, normal mode analysis based on elastic network models (ENMs) has become popular. These models are usually validated by comparing the calculated atomic fluctuation for a single protein in a vacuum to experimental temperature factors in the crystal packing state. Without reflecting the crystal packing effect, in addition, their arbitrary assignment of spring constants leads to inaccurate simulation results, yielding a low correlation of the B-factor. To overcome this limitation, we propose a robust elastic network model (RENM) that not only considers the crystalline effect by using symmetric constraint information but also uses lumped masses and specific spring constants based on the type of amino acids and chemical interactions, respectively. Simulation results with more than 500 protein structures verify qualitatively and quantitatively that one can obtain the better correlation of the B-factor by RENM without additional computational burden. Moreover, an optimal spring constant in physical units (dyne/cm) is quantitatively determined as a function of the temperature at 100 and 290K, which enables us to predict the atomic fluctuations and vibrational density of states (VDOS) without a fitting process. The additional investigation of 80 high-resolution crystal structures with anisotropic displacement parameters (ADPs) indicates that RENM could give a full description of vibrational characteristics of individual residues in proteins.

An effective way of synthesizing densely-formed branched ZnO-nanowire arrays was developed by a straightforward conversion reaction of ZnS into ZnO. Hierarchically structured ZnO nanowires are utilized for quantum-dot-sensitized solar cells (QDSCs), having resulted in the conversion-efficiency enhancement by a factor of two compared to the bare ZnO nanowires. This is attributed to the increased CdS-quantum-dot sensitizer by ∼80% and decreased diffused transmittance by ∼17%, induced by the densely-formed branched nanowires. The correlations between the branched nanostructures and photovoltaic performances are systematically investigated in terms of light absorption, charge-transfer resistance, and carrier lifetime. This facile and controllable branched nanowire synthesis is anticipated to be applicable to other semiconductor photoanodes for efficient light harvesting and charge collecting properties.

Background and Purpose Blockade of the actions of urotensin-II (U-II) mediated by the urotensin (UT) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2-(6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1-yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). Experimental Approach Pharmacological properties of KR36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC) or myocardial infarction (MI). Key Results KR36676 displayed high binding affinity for the UT receptor (Ki: 0.7 nM), similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor (IC50: 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR36676 (≥0.01 μM). Oral administration of KR36676 (30 mg·kg−1) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac function and myocyte size in rats with MI-induced cardiac hypertrophy. Conclusions and Implications A highly potent UT receptor antagonist exerted anti-hypertrophic effects not only in infarcted rat hearts but also in pressure-overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U-II and UT receptors in cardiac hypertrophy.

A tandem dye-sensitized solar cell (tandem-DSSC) was synthesized on the basis of thin-film semiconductor electrodes. The nanoporous p-type NiO films were successfully obtained by simultaneous deposition of Al and Ni, followed by selective etching of Al and oxidation. Likewise, the n-type photoanode was made where Ag was etched in nitric acid after the initial formation of Ag/TiO2 nanocomposites. Such dye-sensitized photoelectrodes were combined to construct a tandem solar cell which exhibited an enhanced open-circuit voltage. Also, the tandem devices were subjected to various light fluxes to correlate the experimental cell parameters (open-circuit voltage, short-circuit current, fill factor, recombination shunt resistance, etc.) with the ideal one-diode model. Interestingly, impedance spectra of the tandem cell was well matched with the parameters from each of the n-type or p-type DSSC, indicative of successfully-designed tandem structure.

Our body’s immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-β-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.

Members of a series of benzo[b]thiophene-2-carboxamide derivatives, possessing an N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl) group, were synthesized and evaluated as urotensin-II receptor antagonists. The results show that these substances have potent UT binding affinities. Observations made in a systematic SAR investigation of the effects of a variety of substituents (R(1) and R(2)) at the 5- and 6-positions in the benzo[b]thiophene-2-carboxamide moiety on UT binding affinities led to identification of the 5-cyano analog 7f as a highly potent UT antagonist with an IC50 value of 25nM. Despite having a good metabolic stability, 7f is a potent inhibitor of CYP isozyme and displays an unsuitable PK profile.

This study investigated an alternative fumigant for imported sweet pumpkin. Laboratory fumigations with ethyl formate (EF) and phosphine (PH3) alone and in combination were conducted at different temperatures in 12-liter desiccators to determine their efficacy and synergism against adults and eggs of two-spotted spider mites (Tetranychus urticae Koch), a major pest of sweet pumpkins; larger scale fumigations with EF were also performed to evaluate the impact of EF fumigation on the postharvest quality of sweet pumpkin and EF absorption. EF fumigation of 4 h achieved 100% control of both adults and eggs at 10°C. Efficacy of EF also increased with temperature. Conversely, PH3 fumigation for 4 and 6 h was not effective against either adults or eggs, and no synergism between EF and PH3 was observed. In larger scale fumigation tests, EF at 60 g/m3 for 4 h resulted in 100% control of both adults and eggs at 10°C, without causing injury to the sweet pumpkins. These results suggest that EF has the potential to be a safe and effective alternative to methyl bromide fumigation for controlling two-spotted spider mites on sweet pumpkin.

The kinase known as IKK-β activates NF-κB signaling pathway leading to expression of several genes contributing to inflammation, immune response, and cell proliferation. Modulation of IKK-β kinase activity could be useful for treatment and management of such diseases. Starting from a discovered weakly active hit compound, twenty four thiazolidinedione-scaffold based chemical entities belonging to five series have been designed, synthesized and evaluated as potential IKK-β modulators. Among them, compounds 6q, 6r and 6u showed low micromolar IC50 values while compounds 6v, 6w, and 6x elicited submicromolar IC50 values equal to 0.4, 0.7 and 0.9 μM respectively. These submicromolar IC50 values are 243, 139 and 105 folds the value of the reported IC50 of the starting hit compound. Kinetic study of compounds 6v and 6w confirmed this class of modulators as irreversible inhibitors. LPS-treated RAW 264.7 macrophages proved the anti-inflammatory activity of compounds 6q and 6v. Assay of hERG inhibition demonstrated a safe profile of compound 6q suggesting it as a lead for further development of IKK-β modulators.

In recent years, Zika virus (ZIKV) caused a new pandemic due to its rapid spread and close relationship with microcephaly. As a result, ZIKV has become an obvious global health concern. Information about the fundamental viral features or the biological process of infection remains limited, despite considerable efforts. Meanwhile, the icosahedral shell structure of the mature ZIKV was recently revealed by cryo-electron microscopy. This structural information enabled us to simulate ZIKV. In this study, we analyzed the dynamic properties of ZIKV through simulation from the mechanical viewpoint. We performed normal mode analysis (NMA) for a dimeric structure of ZIKV consisting of the envelope proteins and the membrane proteins as a unit structure. By analyzing low-frequency normal modes, we captured intrinsic vibrational motions and defined basic vibrational properties of the unit structure. Moreover, we also simulated the entire shell structure of ZIKV at the reduced computational cost, similar to the case of the unit structure, by utilizing its icosahedral symmetry. From the NMA results, we can not only comprehend the putative dynamic fluctuations of ZIKV but also verify previous inference such that highly mobile glycosylation sites would play an important role in ZIKV. Consequently, this theoretical study is expected to give us an insight on the underlying biological functions and infection mechanism of ZIKV.

Although enzyme-linked immunosorbent assay (ELISA) technology has been widely accepted for binding assays against the polo-box domain (PBD) of polo-like kinase-1 (Plk1), these assays have a limitation-related heterogeneous procedure, such as multiple incubations and washing steps to apply high-throughput screenings (HTSs). In the present study, a Plk1-PBD binding assay based on time-resolved fluorescence energy transfer (TR-FRET) was developed for HTS of PBD-binding inhibitors. The TR-FRET-based Plk1-PBD binding assay is sensitive and robust and can be miniaturized into the 384-well plate-based format. Compared with the ELISA-based Plk1-PBD binding assay (Z' factor, 0.53; signal-to-background ratio, 4.19), the TR-FRET-based Plk1-PBD binding assay improved the Z' factor (0.72) and signal-to-background ratio (8.16). Using TR-FRET based Plk1-PBD binding assay, pilot library screening of 1019 natural compounds was conducted and five hit compounds such as haematoxylin, verbascoside, menadione, lithospermic acid and (1,3-dioxolo[4,5-g]isoquinolinium 5,6,7,8-tetrahydro-4-methoxy-6,6-dimethyl-5-[2-oxo-2-(2-pyridinyl)ethyl]-iodide) (DITMD) were identified as Plk1-PBD inhibitor. In a functional assay to validate the hit compounds, five hit compounds exhibited suppression of HeLa cells proliferation. These results suggest that TR-FRET-based Plk1-PBD binding assay can be applied for an efficient and less time-consuming HTS of compound libraries.

The p97 adapter p37 was known to regulate spindle orientation in human cells, but the mechanism was unknown. In this study, we show that it limits the cortical recruitment of NuMA in a PP1–Repo-Man–dependent manner. This study identifies a novel pathway controlling cortical NuMA localization., Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi–LGN–NuMA complex, which targets the force generator dynein–dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Gαi, the kinase Aurora A, and the phosphatase PP2A. Our data show that in anaphase, when the spindle elongates, PP1/Repo-Man promotes the accumulation of NuMA at the cortex. In metaphase, p37 negatively regulates this function of PP1, resulting in lower cortical NuMA levels and correct spindle orientation.

At the base of a flagellar motor, its rotational direction and speed are regulated by the interaction between rotor and stator proteins. A switching event occurs when the cytoplasmic rotor protein, called C-ring, changes its conformation in response to binding of the CheY signal protein. The C-ring structure consists of FliG, FliM, and FliN proteins and its conformational changes in FliM and FliG including HelixMC play an important role in switching the motor direction. Therefore, clarifying their dynamic properties as well as conformational changes is a key to understanding the switching mechanism of the motor protein. In this study, to elucidate dynamic characteristics of the C-ring structure, both harmonic (intrinsic vibration) and anharmonic (transition pathway) analyses are conducted by using the symmetry-constrained elastic network model. As a result, the first three normal modes successfully capture the essence of transition pathway from wild type to CW-biased state. Their cumulative square overlap value reaches up to 0.842. Remarkably, it is also noted from the transition pathway that the cascade of interactions from the signal protein to FliM to FliG, highlighted by the major mode shapes from the first three normal modes, induces the reorientation (∼100° rotation of FliGC5) of FliG C-terminal that directly interacts with the stator protein. Presumably, the rotational direction of the motor protein is switched by this substantial change in the stator-rotor interaction.

Study design This was a prospective cohort study. Objectives To find out any differences in clinical outcomes when adding an en bloc total uncinate process resection (TUPR) to conventional anterior cervical discectomy and fusion (ACDF) to relieve an impinged nerve root. Summary of background data There has been a long debate on the extent of cervical decompression needed when ACDF is done for patients with foraminal stenosis. Materials and methods We included 606 patients who underwent ACDF due to foraminal stenosis. Minimum follow-up was 2 years. Patients with a soft disk herniation, myelopathy, anterior-posterior combined surgery or revision surgery were excluded. There were 275 patients (group U) who underwent ACDF with TUPR and 331 patients (group N) who underwent ACDF without TUPR. Clinical outcome measures were neck pain and arm pain, both assessed using Visual Analog Scale (VAS). We also measured Neck Disability Index (NDI) and patient-reported subjective improvement rate (PRSIR) in percentage. These parameters were measured preoperatively, immediately postoperatively, at 6 weeks as well as 3, 6, 9, 12 and 24 months. Statistical analysis was performed using independent sample t test and paired sample t test. Results Preoperative neck and arm pain, and NDI were similar between the 2 groups. All 4 parameters in both groups improved significantly at 6 weeks follow-up and the improved outcomes were maintained up to the 24 month follow-up. There were no significant differences between the 2 groups in overall neck pain VAS, NDI, and PRSIR. There was a significant difference in arm pain VAS statistically all throughout the follow-up period, with group U having lesser arm pain. Conclusions Overall clinical outcomes were significantly improved after the ACDF whether an en bloc uncinate process resection was added or not. However, arm pain VAS was significantly less statistically in the uncinate resection group at all times.