Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.open0

Performance of a Distributed Simultaneous Strain and Temperature Sensor Based on a Fabry-Perot Laser Diode and a Dual-Stage FBG Optical Demultiplexer

A simultaneous strain and temperature measurement method using a Fabry-Perot laser diode (FP-LD) and a dual-stage fiber Bragg grating (FBG) optical demultiplexer was applied to a distributed sensor system based on Brillouin optical time domain reflectometry (BOTDR). By using a Kalman filter, we improved the performance of the FP-LD based OTDR, and decreased the noise using the dual-stage FBG optical demultiplexer. Applying the two developed components to the BOTDR system and using a temperature compensating algorithm, we successfully demonstrated the simultaneous measurement of strain and temperature distributions under various experimental conditions. The observed errors in the temperature and strain measured using the developed sensing system were 0.6 °C and 50 με, and the spatial resolution was 1 m, respectively

Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses

Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress. Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs. Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility

Should HLA-B*5701 Screening Be Performed in Every Ethnic Group before Starting Abacavir?

Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans.Saag M, 2008, CLIN INFECT DIS, V46, P1111, DOI 10.1086/529382Mallal S, 2008, NEW ENGL J MED, V358, P568*PAN ANT GUID AD A, 2008, GUID US ANT AG HIV 1Waters LJ, 2007, AIDS, V21, P2533Sun HY, 2007, J ANTIMICROB CHEMOTH, V60, P599, DOI 10.1093/jac/dkm243Rauch A, 2006, CLIN INFECT DIS, V43, P99Phillips EJ, 2006, CLIN INFECT DIS, V43, P103Martin AM, 2005, TISSUE ANTIGENS, V65, P571, DOI 10.1111/j.1399-0039.2005.00401.xLee KW, 2005, TISSUE ANTIGENS, V65, P437, DOI 10.1111/j.1399-0039.2005.00386.xMiddleton D, 2004, TISSUE ANTIGENS, V63, P555Phillips EJ, 2002, AIDS, V16, P2223Saito S, 2000, TISSUE ANTIGENS, V56, P522Park MH, 1999, TISSUE ANTIGENS, V53, P3861

Clinical Features, Risk Factors and Outcomes of Bacteremia due to Enterococci with High-Level Gentamicin Resistance: Comparison with Bacteremia due to Enterococci without High-Level Gentamicin Resistance

High-level gentamicin resistance (HLGR) in enterococci has increased since the 1980s, but the clinical significance of the resistance and its impact on outcome have not been established. One hundred and thirty-six patients with bacteremia caused by enterococci with HLGR (HLGR group) were compared with 79 patients with bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and monomicrobial bacteremia were more common in the HLGR group than the non-HLGR group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia, monomicrobial infection, stay in intensive care at culture, and use of 3rd generation cephalosporin, were independent risk factors for acquisition of HLGR enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001; 50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for mortality due to enterococcal bacteremia in multivariate analysis. Therefore, HLGR enterococcal bacteremia is associated with more severe comorbid conditions and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself does not contribute significantly to mortality

Salvage Treatment for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Efficacy of Linezolid With or Without Carbapenem

Background. Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia. Methods. All adult patients with persistent MRSA bacteremia for >= 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin. Results. Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P = .006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate (P < .001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P = .030). Conclusions. Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.Jenkins TC, 2008, CLIN INFECT DIS, V46, P1000, DOI 10.1086/529190Falagas ME, 2008, LANCET INFECT DIS, V8, P53, DOI 10.1016/S1473-3099(07)70312-2Hawkins C, 2007, ARCH INTERN MED, V167, P1861Kollef MH, 2007, CLIN INFECT DIS, V45, pS191, DOI 10.1086/519470Micek ST, 2007, CLIN INFECT DIS, V45, pS184, DOI 10.1086/519471*CLIN LAB STAND I, 2007, M100S17 CLIN LAB STAHidayat LK, 2006, ARCH INTERN MED, V166, P2138Howden BP, 2006, ANTIMICROB AGENTS CH, V50, P3039, DOI 10.1128/AAC.00422-06Hageman JC, 2006, CLIN INFECT DIS, V43, pE42Jacqueline C, 2006, ANTIMICROB AGENTS CH, V50, P2547, DOI 10.1128/AAC.01501-05Sakoulas G, 2006, CLIN INFECT DIS, V42, pS40Jones RN, 2006, CLIN INFECT DIS, V42, pS13Khatib R, 2006, SCAND J INFECT DIS, V38, P7, DOI 10.1080/00365540500372846Wu VC, 2006, CLIN INFECT DIS, V42, P66Jacqueline C, 2005, ANTIMICROB AGENTS CH, V49, P45, DOI 10.1128/AAC.49.1.45-51.2005*CDCP, 2005, CA MRSA CLIN FAQS CDFowler VG, 2004, J INFECT DIS, V190, P1140Wisplinghoff H, 2004, CLIN INFECT DIS, V39, P309, DOI 10.1086/421946Khosrovaneh A, 2004, CLIN INFECT DIS, V38, P1328Howden BP, 2004, CLIN INFECT DIS, V38, P521KIM SH, 2004, 42 ANN M INF DIS SOC, P142Fowler VG, 2003, ARCH INTERN MED, V163, P2066Kim SH, 2003, CLIN INFECT DIS, V37, P794Moise PA, 2002, J ANTIMICROB CHEMOTH, V50, P1017, DOI 10.1093/jac/dkf215Li JS, 2000, CLIN INFECT DIS, V30, P633You I, 2000, DIAGN MICR INFEC DIS, V36, P37Lowy FD, 1998, NEW ENGL J MED, V339, P520Hiramatsu K, 1997, LANCET, V350, P1670LIBMAN H, 1984, ARCH INTERN MED, V144, P5411

Millimeter-Wave/Sub-Terahertz CMOS Transceivers for High-Speed Wireless Communications

Millimeter-wave and sub-terahertz frequency bands are available for wideband applications such as high data-rate communication systems. As the respective wavelength is on the order of a millimeter, a compact on-chip antenna can be designed, thereby reducing the overall form factor and obviating expensive off-chip packaging. However, the channel propagation loss increases significantly with the frequency. Although CMOS technology is prevalent in digital processing and data communication, CMOS devices are lossy and inefficient at such high frequencies. Thus, it is challenging to implement an efficient and wideband transceiver at sub-terahertz frequencies using CMOS technology.The aim of this dissertation is to demonstrate sub-terahertz wireless links for high-speed chip-to-chip communication in CMOS. First, transceiver architectures and building blocks are discussed to address the challenges and limitations of the CMOS process. Two fully integrated CMOS transceivers, a 260 GHz OOK transceiver and a 240 GHz QPSK/BPSK transceiver, are then demonstrated using on-chip antennas. Frequency multiplication and mixer-first design are employed to operate beyond the cut-off frequency. In the QPSK modulation, a maximum data rate of 16 Gbps is realized with an energy efficiency of 30 pJ/bit.These demonstrations show that millimeter-wave/sub-terahertz wireless communication can be a promising solution for high-speed chip-to-chip communication. Improvements in the energy efficiency and silicon area of these wireless links can result in replacing or complementing existing wired links

Millimeter-Wave/Sub-Terahertz CMOS Transceivers for High-Speed Wireless Communications

Millimeter-wave and sub-terahertz frequency bands are available for wideband applications such as high data-rate communication systems. As the respective wavelength is on the order of a millimeter, a compact on-chip antenna can be designed, thereby reducing the overall form factor and obviating expensive off-chip packaging. However, the channel propagation loss increases significantly with the frequency. Although CMOS technology is prevalent in digital processing and data communication, CMOS devices are lossy and inefficient at such high frequencies. Thus, it is challenging to implement an efficient and wideband transceiver at sub-terahertz frequencies using CMOS technology.The aim of this dissertation is to demonstrate sub-terahertz wireless links for high-speed chip-to-chip communication in CMOS. First, transceiver architectures and building blocks are discussed to address the challenges and limitations of the CMOS process. Two fully integrated CMOS transceivers, a 260 GHz OOK transceiver and a 240 GHz QPSK/BPSK transceiver, are then demonstrated using on-chip antennas. Frequency multiplication and mixer-first design are employed to operate beyond the cut-off frequency. In the QPSK modulation, a maximum data rate of 16 Gbps is realized with an energy efficiency of 30 pJ/bit.These demonstrations show that millimeter-wave/sub-terahertz wireless communication can be a promising solution for high-speed chip-to-chip communication. Improvements in the energy efficiency and silicon area of these wireless links can result in replacing or complementing existing wired links

MEKK-3 Acts Cooperatively with NSY-1 in SKN-1-Dependent Manner against Oxidative Stress and Aging in Caenorhabditis elegans

Oxidative stress resulting from reactive oxygen species and other toxic metabolites is involved in human diseases, and it plays an important role in aging. In Caenorhabditis elegans, SKN-1 is required for protection against oxidative stress and aging. As p38 mitogen-activated protein kinase signaling is activated in response to oxidative stress, SKN-1 accumulates in intestinal nuclei and induces phase II detoxification genes. However, NSY-1, a well-known mitogen-activated protein kinase kinase kinase (MAPKKK) of C. elegans, acts as a partial regulator of the SKN-1-induced oxidative stress signaling pathway, suggesting that the regulator for optimal activation of SKN-1 remains unknown. Here, we report a MAPKKK, MEKK-3, as a new regulator required for full activation of SKN-1-mediated resistance against oxidative stress and aging. In RNA-interference-based screening, we found that the simultaneous knockdown of mekk-3 and nsy-1 significantly decreased the oxidative stress resistance and survival of SKN-1 transgenic worms. MEKK-3 was induced in response to oxidative stress. Mechanistic analysis revealed that double knockdown of mekk-3 and nsy-1 completely suppressed the nuclear localization of SKN-1. These results were reproduced in mutant worms in which SKN-1 is constitutively localized to intestinal nuclei. In addition, mekk-3 and nsy-1 were required for optimal induction of SKN-1 target genes such as gcs-1 and trx-1. These data indicate that MEKK-3 plays an essential role in the SKN-1-dependent signaling pathway involved in oxidative stress resistance and longevity by cooperating with NSY-1

Risk Assessment Method Combining Independent Protection Layers (IPL) of Layer of Protection Analysis (LOPA) and RISKCURVES Software: Case Study of Hydrogen Refueling Stations in Urban Areas

The commercialization of eco-friendly hydrogen vehicles has elicited attempts to expand hydrogen refueling stations in urban areas; however, safety measures to reduce the risk of jet fires have not been established. The RISKCURVES software was used to evaluate the individual and societal risks of hydrogen refueling stations in urban areas, and the F–N (Frequency–Number of fatalities) curve was used to compare whether the safety measures satisfied international standards. From the results of the analysis, it was found that there is a risk of explosion in the expansion of hydrogen refueling stations in urban areas, and safety measures should be considered. To lower the risk of hydrogen refueling stations, this study applied the passive and active independent protection layers (IPLs) of LOPA (Layer of Protection Analysis) and confirmed that these measures significantly reduced societal risk as well as individual risk and met international standards. In particular, such measures could effectively reduce the impact of jet fire in dispensers and tube trailers that had a high risk. Measures employing both IPL types were efficient in meeting international standard criteria; however, passive IPLs were found to have a greater risk reduction effect than active IPLs. The combination of RISKCURVES and LOPA is an appropriate risk assessment method that can reduce work time and mitigate risks through protective measures compared to existing risk assessment methods. This method can be applied to risk assessment and risk mitigation not only for hydrogen facilities, but also for hazardous materials with high fire or explosion risk