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Objective. ETS1 and ETS2, the main ETS family of transcription factors, have been found to act as downstream effectors of the RAS/MAPK pathway. This study explores the expression and prognostic values of ETS1 and ETS2 across cancers. We also aimed to explore the significance of ETS1 and ETS2 expression in normal immune cells with relation to tumorigenesis. Methods. The expression of ETS1 and ETS2 was examined in the HPA and GEPIA2 databases. The KM plotter was applied to examine prognostic value of ETS1 and ETS2. Correlation between ETS1/ETS2 and infiltrating immune cells and immune checkpoints was assessed using TIMER2.0. The mutation landscape of ETS1/ETS2 was explored using the cBioPortal. STRING and GEPIA2 were used to screen ETS1/ETS2 binding and correlated genes. Enrichr was applied to perform GO and KEGG enrichment analyses. Results. ETS1 showed enhanced expression in lymphoid tissue, while ETS2 showed low tissue specificity. ETS1 was increased in 12 and decreased in 6 cancers, while ETS2 was increased in 4 and decreased in 13 cancers. Both ETS1 and ETS2 were favorable prognostic markers in LIHC and KIRC, while they showed different prognostic roles in more cancers. ETS1 showed stronger correlation with several infiltrating immune cells and immune checkpoints compared with ETS2. Both ETS1 and ETS2 harbored low mutation ratio. ETS1 interacting and correlated genes were enriched in GO terms in response to cadmium ion and response to oxidative stress, while those of ETS2 were enriched in transcription regulation. Conclusion. ETS1 and ETS2 showed different patterns in expression, prognostic values, correlation with immune infiltrating, and immune checkpoints. ETS1 and ETS2 play distinct roles across cancer.

Background: Non-attendance with scheduled postoperative follow-up visits remains a common problem in orthopaedic clinical researches. The goal of this study was to determine the risk factors for loss to follow-up of hip-fracture patients postoperatively. Methods: A 1-year postoperatively retrospective analysis was conducted on patients who underwent surgery for hip-fractures between January 2017 and December 2018. According to whether they finished the appointed follow-up schedule, the patients were divided into two groups: LTFU Group (Follow-up loss group) and FU Group (Follow-up group). Patients’ clinical outcomes were evaluated by Functional Recovery Score (FRS) questionnaires. Telephone interviews were attempted on those lost to follow-up to determine the reasons. The baseline characteristics between the two groups were compared and the statistical differences were analyzed by logistic regression. Results: 1,041 patients met the inclusion criteria were included in this study, of which 212 (20.37%) patients were lost to follow-up at 1 year postoperatively. The mean age in LTFU Group was 76.70±12.78 and 71.31±13.87 in FU Group (PConclusions: Loss to follow-up was common in patients with hip-fracture postoperatively. Our study suggested advanced age, difficult transport, long distance, fracture type and surgical procedures were risk factors for noncompliance. Key Words Hip Fracture, Orthopaedic surgery, Replacement, Internal fixation, Loss, Follow-up

The plant parasitic nematode

Biodegradable shape-memory polymers (SMPs) which are functional materials with applicability for medicine devices are designed to acquire their therapeutically relevant shape and drug release after implantation. In the work, an amphiphilic polymer (PVAD) is synthesized by using polytetrahydrofuran (PTMG), vinyl acetate (VAc), acrylic acid (AA), tetramethyltetravinylcyclotetrasiloxane (D

The metal wear debris generated by wear during the operation of the mechanical equipment can reflect the fault status of the equipment, and the online monitoring of the metal wear debris in the oil can timely understand the operation information of the equipment. Aiming at the effective response of metal wear debris under symmetrical magnetic excitation, an online monitoring system for metal wear debris with dual-coil balanced magnetic excitation was developed. Based on the spatial magnetic field distribution of the current-carrying element, an analytical model of the magnetic field intensity distribution of a single-turn current-carrying ring is designed, and it is optimized as a single set of coils made of a current-carrying ring, and the coupling of the magnetic excitation of the symmetrical double coil is deduced. The magnetic field distribution model is simulated and analyzed by numerical method. The flow channel of the system is 8 mm. After the semi-physical simulation test with the wear debris speed of 3.03-5.25 m/s, the sensor can realize the detection of 100 μm ferromagnetic metal and 1000 μm non-ferromagnetic metal. The experiment verifies the correctness of the simulation model of the coupled magnetic field distribution. This research provides technical support for the detection of hydraulic oil contaminants, which is of great significance for preventing hydraulic system failures and extending the working life of hydraulic equipment.

Background: S100 family members(S100s) are small molecular EF hand calcium binding proteins and widely expressed in many tissues and organs. S100s are shown to be biomarkers of disease progression and prognosis in various types of cancers. Nevertheless, the expression patterns, function, prognostic values of S100s and its association with tumor-infiltrating immune cells in Pancreatic Adenocarcinoma(PAAD) patients have not been systematically clarified. Methods: we explored that the expression and roles of the entire twenty S100s in PAAD patients by using the following public databases: Oncomine, GEPIA, cBioPortal, Metascape, STRING, TIMER and GeneMANIA.Results: The S100A2/A3/A4/A6/A8/A9/A10/A11/A13/A14/A16/B/P mRNA expression were significantly upregulated in PAAD patients. The mRNA expression of S100A3/A4/A5/A6/A10/A11/A14/A16/Z were significantly negatively related with the tumor stage in PAAD patients. We found that the S100A2/A3/A5/A10/A11/A14/A16 were significantly correlated with poor OS, whereas the increased levels of S100A1/B/G/Z were strongly associated with good OS. We found significant correlations among S100s and Tumor-Infiltrating Immune Cells. Cox proportional risk models revealed that B cells, Dendritic cells and S100A1/A5/A6/A8/A9/A13/A14 were significantly related with outcomes in PAAD patients. Conclusions: S100A2/A3/A10/A11/A14/A16 may serve as new diagnostic and prognostic biomarkers for PAAD patients and provide new clues for immunotherapy in PAAD patients.

Background: Research suggests that circRNAs play important roles in non-small cell lung cancer (NSCLC). The function of hsa_circ_0068252 in NSCLC, especially in cisplatin (DDP) resistance and the mechanisms, was explored in this study. Methods: NSCLC patient samples and two NSCLC cell lines along with corresponding DDP-resistant cell lines were used. Expression levels of circ_0068252 were detected. SiRNA for circ_0068252 and inhibitor for miRNA were used in all functional analyses. A co-culture system of NSCLC cells with CD8+ T cells was used. The cellular location of circ_0068252 was detected and its target miRNA was predicted and verified. Finally, the mechanism responsible for circ_0068252 function on PD-L1 was analyzed using luciferase reporter assay in the two DDP-resistant cell lines, as well as in the co-culture system. The cytotoxicity of T cells was detected by lactate dehydrogenase assay. Results: Our findings revealed that a high level of circ_0068252 was correlated with poor prognosis of NSCLC and DDP resistance. Knockdown of circ_0068252 could promote the sensitivity of DDP-resistant NSCLC cells to DDP. Moreover, knockdown of circ_0068252 could regulate the immune microenvironment which was mediated via CD8+ T cells. Finally, circ_0068252 could up-regulate PD-L1 expression by adsorbing miR-1304-5p. Conclusion: The circ_0068252/miR-1304-5p/PD-L1 signal axis participates in the regulation of DDP resistance and immune escape of NSCLC cells. Our results suggest that circ_0068252 may be a potential diagnostic marker and therapeutic target for DDP-resistant NSCLC.

Central nervous system infectious disease caused by the multidrug-resistant

Thermo-responsive shape memory polymers which are a class of important smart materials can recover permanent shape from temporary shape by simple thermal stimulus, but most of the polymers lack of biodegradability and biocompatibility. Poly(L-lactide) (PLLA) is a green degradable thermoplastic, however, only limited studies involve controlling its shape change. In the work, a new x-shaped copolymer with defined architecture has been devised by using tetramethyltetravinylcyclotetrasiloxane (D4vi) as centronucleus and polytetrahydrofuran-co-poly(e-caprolactone) (PTMG-co-PCL) as branch to achieve PLLA shape memory. When the weight ratio of DAPP and PLLA is 50/50, the composite exhibits good thermo-responsive shape memory capacity because a balance between Tm of the x-shaped polymer rand Tg of PLLA is kept. The shape fixation ratio is 84% at 15 °C, and the recovery ratio 94% at 55 °C. And the shape memory capability does not change evidently after the reversible spiral transition is repeated for 30 times. At the same time, the composite shows great flexibility. So the obtained composite is promising for medical and bionic devices, self-healing systems, self-assembly structures.

A rotating machine such as inductor motor has highly distorted elliptical magnetic flux densities in its stator core. The iron loss estimation taking into account the rotating magnetic field is significant not only for the design but also for the performance analysis of electrical machines. A rotational hysteresis loss formula is also proposed to improve the computation accuracy especially when the magnetic flux density is high or the axis ration of a rotational magnetic flux density is big. For an induction motor core model, iron losses are experimentally measured on the top sheet of the core by using a self-developed B–H vector sensor. The proposed iron loss model is validated through comparisons of the calculated iron losses with experimentally measured ones.

To solve the problem of the hard and brittle mechanical properties of poly(l-lactide) (PLLA), a novel pectinate polymethylphenylsilane-co-poly(e-caprolactone) (PCL-PMPS-PCL) has been designed to modify PLLA via the hydrolysis polycondensnsation of methylphenyldimethoxysilane and ring-opening polymerization of e-caprolactone. The triblock copolymer is characterized with 1HNMR and GPC. It is harmonized with PLLA in chloroform to make smooth blending film. Incorporation of PCL-PMPS-PCL lowers Tg of PLLA, enhances the macromolecular mobility, and facilitates PLLA to form defective crystals. Compared to the brittle PLLA, the cross section of blends is rough and uneven. With the blending amount of PCL-PMPS-PCL going up, the tensile strength curve has a downward glacis, while the elongation at a break climbs upward, and reaches 25% at 10 wt%, exhibiting that the typical characteristics of ductile material. At the same time, the tensile strength for 10 wt% PCL-PMPS-PCL/PLLA reserve about 60 MPa, so PCL-PMPS-PCL can serve as a candidate of plasticizing PLLA.

International audience; An original two-step organocatalytic syn- thesis of optically active glutarimides from 2- oxocyclobutane carboxamides is described featuring an isothiourea-catalyzed two-atom ring-expansive rearrangement.

Background: Non-attendance with scheduled postoperative follow-up visits remains a common problem in orthopaedic clinical researches. The goal of this study was to determine the risk factors for loss to follow-up of hip-fracture patients postoperatively. Methods: A 1-year postoperatively retrospective analysis was conducted on patients who underwent surgery for hip-fractures between January 2017 and December 2018. According to whether they finished the appointed follow-up schedule, the patients were divided into two groups: LTFU Group (Follow-up loss group) and FU Group (Follow-up group). Electronic Medical Records (EMR) was examined to identify the patients’ variables of interest and telephone or text message interviews were attempted on those who didn’t return for follow-up to determine the reasons for loss to follow-up. The baseline characteristics between the 2 groups were compared and the statistical differences were analyzed by logistic regression. Results: 1041 patients met the inclusion criteria were included in this study, of which 212 (20.37%) were lost to follow-up at 1 year postoperatively. The logistic regression analysis showed that old age at surgery, fracture type, distance to hospital, HA surgery and patients transport to hospital by urban-rural public traffic or bus were found to be risk factors for noncompliance with the follow-up visit. As for the reasons for loss to follow-up in in LTFU Group, 75 patients (35.4%) claimed symptoms improvement, 43 (20.3%) cited difficulties of transportation to hospital, 23 (10.8%) chose other health care institutions, and 57 (26.9%) couldn’t travel to hospital alone. Other reasons including thinking follow-up was unnecessary (n=4, 1.8%), no spare time (n=5, 2.4%) and financial problems (n=5, 2.4%). Conclusion: Loss to follow-up was common in patients with hip-fracture postoperatively. Our study suggested advanced age, difficult transport, long distance, fracture type and surgical procedures were risk factors for noncompliance.

The complex dynamic characteristics of Floating Offshore Wind Turbines (FOWTs) have raised wider consideration, as they are likely to experience harsher environments and higher instabilities than the bottom fixed offshore wind turbines. Safer design of a mooring system is critical for floating offshore wind turbine structures for station keeping. Failure of mooring lines may lead to further destruction, such as significant changes to the platform’s location and possible collisions with a neighbouring platform and eventually complete loss of the turbine structure may occur. The present study focuses on the dynamic responses of the National Renewable Energy Laboratory (NREL)’s OC3-Hywind spar type floating platform with a NREL offshore 5-MW baseline wind turbine under failed mooring conditions using the fully coupled numerical simulation tool FAST. The platform motions in surge, heave and pitch under multiple scenarios are calculated in time-domain. The results describing the FOWT motions in the form of response amplitude operators (RAOs) and spectral densities are presented and discussed in detail. The results indicate that the loss of the mooring system firstly leads to longdistance drift and changes in platform motions. The natural frequencies and the energy contents of the platform motion, the RAOs of the floating structures are affected by the mooring failure to different degrees.

Tension leg platform (TLP) is a cost-effective and high-performance support structure for floating offshore wind turbine (FOWT) because of its small responses in heave, pitch, and roll with the constraint of the tendons. China, as the largest market of offshore wind energy, has shown a demand for developing reliable, viable floating platform support structures, especially aiming at the intermediate water depth. The present paper described a newly proposed 10-MW Braceless-TLP FOWT designed for a moderate water depth of 60 m. The numerical simulations of the FOWT are carried out using the coupled aero-hydro-servo-elastic-mooring calculation tool FAST. The measured wind and wave data of the target site close to the Fujian Province of China were used to evaluate the performance of the FOWT under the 100-, 50-, 5-, and 2-year-return stochastic weather conditions. The natural periods of the platform in surge, sway, heave, pitch, roll, and yaw were found to be within the range recommended by the design standard DNV-RP-0286 Coupled Analysis of Floating Wind Turbines. The largest surge of the water depth ratio among all the load cases was 15%, which was smaller than the admissible ratio of 23%. The tower top displacements remained between −1 m and 1 m, which were at a similar order to those of a 10-MW monopile-supported offshore wind turbine. The six tendons remained tensioned during the simulation, even under the operational and extreme (parked) environmental conditions. The Braceless-TLP FOWT showed an overall satisfying performance in terms of the structural stability and illustrates the feasibility of this type of FOWT at such a moderate water depth.

This paper presents the design and dynamic analysis of a multi-column tension leg platform floating offshore wind turbine (TLP FOWT) with broken tendons. The proposed concept is based on a conventional Tri-Floater platform configuration but is especially optimized for an intermediate water depth of 60 m. Tendons are simulated to be broken at a specific time of interest. The hydrodynamic parameters and motion responses of the TLP FOWT have been calculated using the hydrodynamic analysis software WAMIT and ANSYS/AQWA. These parameters are then used in the simulation of coupled responses of the FOWT by the National Renewable Energy Laboratory's analysis suite of tool, FAST. The tendon failure has been investigated to examine the system performance under the accidental limit states (ALS) described in the design code DNV-RP-0286.A series of dynamic analysis under operational and extreme environmental conditions (with 12 different load cases) are carried out with the combination of wind and waves. The results demonstrate that the turbine is able to remain highly stable during the 3-h simulations conducted. The platform's response amplitude operators (RAOs) evaluated show good stability in heave and pitch. The tendon failures affected the FOWT's heave, pitch and roll motions, hence its natural frequencies, and the tension in the non-broken tendons. The average tensile force in the line adjacent to the broken line is found to be doubled, while the safety factors as specified in DNV-OS-E301 are remained within the recommended value. This paper provides further insights into the hydrodynamics of the multi-column TLP FOWT, with the aim to provide new information to the offshore wind research community.

Electrospun biodegradable fiber mesh is a promising alternative scaffold for delivering progenitor cells for repairing damaged or diseased tissue, but its cripple mechanical stability has not met the requirement of tissue engineering yet. In this work, the well-defined poly(e-caprolactone)-branched poly(methyl methacrylate-co-hydroxyethylmethacrylate) (PCL-PMH) has been successfully synthesized to toughen electrospun poly(l-lactide) (PLLA) fiber membrane. Characterization of the obtained nanofibrous meshes indicates that PCL-PMH and PLLA can be well blended to make smooth fibers, and fibrous diameter vary little with blending PCL-PMH. The aggregation state of two macromolecules is closely correlated with blend ratio, molecular structure, and molecular weight of PCL-PMH, and only when PCL-PMH and PLLA form good interfacial adhesion can PMH give full play to its potential for toughening the fiber membrane. The tensile strength and elongation at break of the blend are 6.20 MPa and 63.40% under the optimal conditions, respectively, and it also exhibits the representative feature of toughness materials. The blending fiber membrane is as no cytotoxic as original PLLA. This work will provide a new way for toughness of electrospun fiber membrane in practice.

Mg-doped sialon ceramics with the composition of M0.4Si10.2Al1.8O1N15 were fully densified by hot pressing at 1850 °C for 1 h, using 0.5 wt.% MgF2 or CaF2 as a sintering additive. Densification behavior, phase assemblage, microstructure, and mechanical and optical properties were investigated in detail. The addition of fluorides, especially MgF2, not only resulted in more high-temperature liquid by promoting the dissolution of more N and other constituents but also reduced the viscosity of liquid due to the terminal effect of fluorine. Consequently, the densification was effectively improved. Additionally, the fluoride addition facilitated the formation of a small amount of β-sialon. Both the samples possessed high hardness (∼20 GPa) and fracture toughness (∼4.2 MPa m1/2). The CaF2-added sample exhibited higher infrared transmittance than its counterpart due to less residual glass phase. The present work implies that fluorides are also very effective sintering additives for densifying α-sialon.

To create novel materials of skin tissue engineering, the blends of tannin-grafted poly(ɛ-caprolactone) (TA-g-PCL) and poly(l-lactic acid) (PLLA) have been prepared by electrospinning, and their corresponding characteristics are evaluated such as morphology, FTIR, thermodynamics, mechanics, wettability, as well as biocompatibility. TA-g-PCL and PLLA can be well blended to make smooth fibers, and fibrous diameter turns thinner with blending TA-g-PCL. At 15 wt%, the fibrous membrane shows higher tensile strength and elongation at a break than the other samples due to its best crystallinity. Membranous wettability drops with blending TA-g-PCL, but it increases sharply after incorporating PF108. At the same time, PLLA/TA-g-PCL fiber membrane is biocompatible. The biodegradable PLLA/TA-g-PLLA membrane is a promising candidate as skin tissue engineering.

A new strategy for surface treatment of hematite nanoplates for efficient photoelectrochemical (PEC) performances is proposed. Silver orthophosphate (Ag 3 PO 4 ) has been adopted to mediate the formation of α-Fe 2 O 3 films. Phosphate ions in Ag 3 PO 4 is found to cause a significant morphology change during annealing process, from β-FeOOH nanorod arrays to hematite nanoplates. Meanwhile, Ag ions is doped into α-Fe 2 O 3 film. The obtained nanoplate structured Fe 2 O 3 –Ag–P films demonstrate much higher photoelectrochemical performance as photoanodes than the bare Fe 2 O 3 nanorod thin films. The effects of phosphate and silver ions on the morphology, surface characteristics and the PEC properties of the photoanodes are investigated.

Tannin and biodegradable polyester have attracted increasing interest for biomedical applications. To improve their compatibility, a novel tannin grafted polycaprolactone (TA-g-PCL) has been synthesized via ring-opening polymerization reaction. The structure of the product is characterized with FTIR, (1)H NMR and GPC. GPC results show that the experimental molecular weight is far less than the theoretical due to complicated stereo structure and large steric hindrance of tannic molecule, but the polydispersity of the product is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL are closely related to its molecular weight. With PCL molecular chain grows, TA-g-PCL changes from amorphous form to crystalline structure, and its dissolubility in chloroform is also enhanced significantly.

Poly(L-lactide) (PLLA) was one of the most well-known biodegradable polyesters. Although its thermo-responsive shape memory (SM) function has been studied by proper program, high transformation temperature is not suitable in some biomedical applications. Water-responsive SM polymer is an alternative choice and exhibits great potential because it is harmless to the cells and tissues of organisms. In the work, a novel PCL-(PMVS-s-PAA)-PCL-PTMG-PCL-(PMVS-s-PAA)-PCL copolymer was devised as an additive to endow PLLA with water-responsive SM capability. The incorporated PLLA was characterized by cross-section, water contact angle, differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). Inserted PTMG segment and assisted ambient temperature were contributed to its SM behaviors. The shape fixation ratio and shape recovery ratio were 92.0% and 94.2%, respectively. The schematic diagram between internal microstructures and macroscopic properties was proposed. At the same time, the incorporated PLLA showed excellent toughness. So the obtained SM material would be promising for medical and biomimetic fields.

With the symmetric cryptosystem based on error correcting codes and the concept of equivalent matrix, this paper puts forward a secure communication scheme based on linear block codes. The proposed scheme realizes the secure and reliable integrated communication by hiding and changing the coding matrix (parity check matrix or generator matrix) randomly and simultaneously without decreasing the error correction ability of linear block codes. And also, based on RDF (Random Difference Families), we propose a design method of QC-LDPC codes based on the proposed secure and reliable communication framework. The proposed QC-LDPC codes have a large number of performance equivalent parity check matrix with the same parameters. At the same time, the LDPC codes hold better reliability of transmission and flexibility of design. Finally, the security and reliability of the proposed LDPC codes are verified by analysis and simulations.

International audience; The combination of aminocatalysis with N-heterocyclic carbene catalysis has been extended to a switchable dual catalytic system, which allowed a direct enantioselective entry to bridged bicyclo[3.n.1] ring systems and the total synthesis of the natural product (1R)-suberosanone.

In order to avoid channel information feedback and improve the performance of the adaptive coded modulation (ACM) system in space communication, this paper proposes an improved rate compatible modulation (RCM) scheme to approach the channel capacity for the time-varying channel. RCM is a seamless rate adaptive technology, in which modulation signals are incrementally generated from information bits through weighted mapping. Rate adaptation is achieved through varying the number of modulated signals. The paper suggests an adaptive RCM based on construction of sub-block generation matrix of RCM in order to improve the performance of traditional RCM at different Signal-Noise Ratio (SNR), and simulations show that the improved scheme can provide a higher throughput than existing ones. Finally, a low complexity decoding algorithm is proposed.

Nitromethane, a volatile and toxic organic compound, is commonly used as solvent for organic and catalytic reactions. In order to find an alternative for this specific nitro-containing organic solvent, the performance of some nitro-functionalized imidazoli- um salts such as 1-methyl-3-(4-nitrobenzyl)imidazoli- um hexafluorophosphate, 1-methyl-3-(4-nitrobenz- A tetrafluoroborate, 1-methyl-3-(4-ni- trobenzyl)imidazolium bis(trifluoromethanesulfonyl)- A and 1,2-dimethyl-3-(4- nitrobenzyl)imidazoli- um hexafluorophosphate, was examined in some reactions including trimethylsilylation of alcohols with hexamethyldisilazane, ring-opening reactions of 2-aryl-3,4-dihydropyrans with thiophenols or thiols, and a copper- mediated oxidative coupling of al- kynes. As expected, these imidazolium salts can indeed replace nitromethane in these reactions. Par- ticularly, the imidazolium salt along with the metal catalyst, if involved, can be easily recovered and reused without significant loss of activity. The use of these nitro-functionalized imidazolium salts as alter- native solvents for nitromethane not only confers a green aspect to the reaction system, but also facili- tates a rational design of a catalytic system with the concept of green chemistry.

Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by PKC (protein kinase C) activation, and the K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In the present study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular N- and C-termini of Kv4.2 GST (glutathione transferase) tagged fusion protein revealed that the C-terminal of Kv4.2 was phosphorylated by PKC, whereas the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Ser447 and Ser537. A phospho-site-specific antibody showed that phosphorylation at the Ser537 site was increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that mutation to alanine of both Ser447 and Ser537 in order to block phosphorylation at both of the PKC sites increased surface expression compared with wild-type Kv4.2. Electrophysiological recordings of the wild-type and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 (Kv4 channel-interacting protein 3) revealed no significant difference in the half-activation or half-inactivation voltage of the channel. Interestingly, Ser537 lies within a possible ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.

Purpose: To develop a novel technique of percutaneous kyphoplasty (PKP) with effective biomechanical strength and lower radiation exposure. Methods: Thirty fresh lumbar vertebrae isolated from six hogs were decalcified and compressed to induce osteoporotic vertebral compression fractures. Kyphoplasty was performed using three different techniques (ten for each group): conventional unilateral approach (group A), conventional bilateral approach (group B) and novel unilateral approach (group C). Biomechanical indexes including Yield load and stiffness were tested before and after kyphoplasty. The anterior height of each vertebral body (AHVB) was measured before compression, after compression and after kyphoplasty. Frequency of C-arm use and volume of bone cement were also recorded in the process. Results: Compared with group A, our novel technique in group C can significantly improve the recovery of AHVB after compression fractures. However, there was no statistical difference between group B and group C. Values of Yield load in both group B and group C were statistically higher than that in group A, however, no significant difference was found between group B and C. Statistical results of stiffness were similar to Yield load. Regarding volume of bone cement and radiation exposure, the novel technique in group C needed more bone cement and fluoroscopy use than in group A but less than in group B. Conclusions: This novel device makes unilateral kyphoplasty feasible, safe and effective. In the premise of guaranteed biomechanical strength, the new technique significantly reduces risk of radiation exposure in kyphoplasty.

International audience; It was observed that the stable and commercially available N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropyl- phenyl)imidazol-2-ylidene, the so-called IDipp, catalyzes hydrogen/ deuterium exchange reactions between pseudoacids and chloroform- d1, while the analogous saturated NHC 1,3-bis(2,4,6-trimethyl- phenyl)imidazolin-2-ylidene, the so-called SIMes, is inefficient for the same transformation. Experimental and computational DFT studies allowed these differences of reactivity to be attributed to the relative stability of the corresponding azolium−trichloromethyl anion ion pairs: in the former case, the complex evolves toward dissociation of the ions to produce an aromatic azolium cation and a basic trichloromethyl anion, while in the latter case, it evolves by ion recombination to give the product of formal carbene C−H insertion into the C−H bond of chloroform. These results provide a rationale for some early intuitions and observations of Wanzlick, Arduengo, and others on the reactivity of NHCs with chloroform as well as a simple organocatalytic method for the deuteration of pseudoacids (pKa,DMSO = 14−19) with chloroform-d1.

Human proliferation-associated protein p120 has previously been shown to localize to the nucleolus, and several functional domains of p120 have been elucidated. By using a nitrocellulose filter binding assay and a Northwestern blotting procedure this study shows that recombinant p120 binds to an rRNA fragment in vitro with a dissociation constant of 4 nM. The specific RNA-binding region of p120 (residues 1–57) was identified with glutathione S-transferase-fused p120 deletion constructs and Northwestern blotting procedures. This RNA-binding region of p120, which includes the nucleolar localization signal of p120, is similar to the arginine-rich RNA-binding regions found in other RNA-binding proteins such as HIV Rev and Tat. Experiments in vivo with HeLa cell nucleolar extracts showed that p120 was associated with the 60–80 S pre-ribosomal particles. This association is disrupted by treatment with either RNase A or buffer of high ionic strength. These results suggest that p120 might be involved in rRNA/ribosome maturation, consistent with the role of the yeast homologue Nop2p in rRNA biogenesis.

Angiotensin converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, myocardial infarction, and congestive heart failure. They have a known adverse effect of unresponsiveness to vasoconstrictors resulting in hypotension for the patients undergoing cardiac surgery. We report a case of a 43-year-old female patient with preoperative lisinopril (2.5 mg per day for a week prior to cardiac surgery), who was diagnosed with severe mitral and tricuspid valve regurgitation. She underwent both a mitral and tricuspid valve replacement operation using cardiopulmonary bypass (CPB). To address her ACEI-associated hypotension on cardiopulmonary bypass, bypass flows were as high as cardiac index of greater than 3 (3.1 +/- .2) L/min/m2 to provide sufficient perfusion indicated by cerebral oxymetry monitoring and adequate urine on pump. In addition, due to unresponsiveness to regular concentration of neosynephrine (neo), boluses of higher concentrations up to 320 microg/mL of neo were administered to maintain the perfusion pressure on pump. The patient was weaned from CPB uneventfully and was discharged home on postoperative day 7. Additional therapeutic treatment to ACEI-associated hypotension and unresponsiveness to neo for the patients undergoing cardiac surgery using CPB is reviewed as well in this paper.

Extracelluar signal-regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down-regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho-ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole-cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A-current, which could lead to altered intrinsic membrane excitability during SE.

We evaluated a role for the nuclear factor-kappa B (NF-kappaB) pathway in the regulation of seizure susceptibility and transcriptional activation during prolonged, continuous seizures (status epilepticus). Using two functionally distinct NF-kappaB inhibitors we observed a decrease in latency to onset of kainate-induced seizures and status epilepticus. To assess NF-kappaB transcriptional activation, we evaluated inhibitor kappa B alpha (IkappaBalpha) and brain-derived neurotrophic factor (bdnf) gene targets. Inhibition of the NF-kappaB signaling pathway significantly attenuated the increases in IkappaBalpha and bdnf mRNA levels that occurred during prolonged seizure activity, suggesting that the NF-kappaB pathway was involved in the up-regulation of these transcripts during status epilepticus. DNA-binding studies and chromatin immunoprecipitation assays using hippocampal extracts from animals with status epilepticus revealed that NF-kappaB subunits were associated with the candidate kappaB-binding elements within promoter 1 of the bdnf gene. The pattern of association was different for the p50 and p65 subunits supporting complex NF-kappaB modifications within promoter 1. In summary, our findings provide additional insights into the role of NF-kappaB transcriptional regulation in hippocampus following status epilepticus and suggest that NF-kappaB pathway activation contributes to seizure susceptibility.

Small conductance, Ca2+-activated voltage-independent potassium channels (SK channels) are widely expressed in diverse tissues; however, little is known about the molecular regulation of SK channel subunits. Direct alteration of ion channel subunits by kinases is a candidate mechanism for functional modulation of these channels. We find that activation of cyclic AMP-dependent protein kinase (PKA) with forskolin (50 microm) causes a dramatic decrease in surface localization of the SK2 channel subunit expressed in COS7 cells due to direct phosphorylation of the SK2 channel subunit. PKA phosphorylation studies using the intracellular domains of the SK2 channel subunit expressed as glutathione S-transferase fusion protein constructs showed that both the amino-terminal and carboxyl-terminal regions are PKA substrates in vitro. Mutational analysis identified a single PKA phosphorylation site within the amino-terminal of the SK2 subunit at serine 136. Mutagenesis and mass spectrometry studies identified four PKA phosphorylation sites: Ser465 (minor site) and three amino acid residues Ser568, Ser569, and Ser570 (major sites) within the carboxyl-terminal region. A mutated SK2 channel subunit, with the three contiguous serines mutated to alanines to block phosphorylation at these sites, shows no decrease in surface expression after PKA stimulation. Thus, our findings suggest that PKA phosphorylation of these three sites is necessary for PKA-mediated reorganization of SK2 surface expression.

Kv4.2 is the primary pore-forming subunit encoding A-type currents in many neurons throughout the nervous system, and it also contributes to the transient outward currents of cardiac myocytes. A-type currents in the dendrites of hippocampal CA1 pyramidal neurons are regulated by activation of ERK/MAPK, and Kv4.2 is the likely pore-forming subunit of that current. We showed previously that Kv4.2 is directly phosphorylated at three sites by ERK/MAPK (T602, T607, and S616). In this study we determined whether direct phosphorylation of Kv4.2 by ERK/MAPK is responsible for the regulation of the A-type current observed in neurons. We made site-directed mutants, changing the phosphosite serine (S) or threonine (T) to aspartate (D) to mimic phosphorylation. We found that the T607D mutation mimicked the electrophysiological changes elicited by ERK/MAPK activation in neurons: a rightward shift of the activation curve and an overall reduction in current compared with wild type (WT). Surprisingly, the S616D mutation caused the opposite effect, a leftward shift in the activation voltage. K+ channel-interacting protein (KChIP)3 ancillary subunit coexpression with Kv4.2 was necessary for the T607D effect, as the T607D mutant when expressed in the absence of KChIP3 was not different from WT Kv4.2. These data suggest that direct phosphorylation of Kv4.2 at T607 is involved in the dynamic regulation of the channel function by ERK/MAPK and an interaction of the primary subunit with KChIP is also necessary for this effect. Overall these studies provide new insights into the structure-function relationships for MAPK regulation of membrane ion channels.