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3,4-Methylenedioxy-N-methamphetamine (MDMA, ecstasy) is an amphetamine derivative and is a popular type of drug that is abused due to its effects on the central nervous system (CNS), including alertness and euphoria. However, life-threatening (brain edema, heart failure, and coma) and fatal hyperthermia sometimes occur in some individuals taking MDMA. In a one-generation reproductive toxicity study, the potential toxicity of chronic exposure of MDMA was investigated on the reproductive capabilities of parental mice (F0), as well as the survival/development of their subsequent offspring (F1). Male and female C57BL/6 mice were administered orally MDMA at 0, 1.25, 5 or 20 mg/kg body weight (b.w.) throughout the study, beginning at the premating period, through mating, gestation, and lactation periods. MDMA did not produce any apparent clinical signs in F0 or F1 mice, and produced no significant changes in body weight, feed/water intake, or organ weights. In contrast, administration of MDMA produced external abnormalities in fetuses, stillbirth and labored delivery, and diminished viability and weaning indices in offspring, but these data were not significant. In addition, physical development of F1 mice was not markedly influenced by MDMA treatment. Nonetheless, serum biochemistry markers showed that levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) were markedly elevated in a dose-dependent manner from 5 mg and higher MDMA/kg b.w., whereas levels of triglycerides (TG), potassium (K), and uric acid (UA) were reduced. Data suggest that MDMA may exert a weak reproductive and developmental toxicity, and the no-observed-adverse-effect level (NOAEL) of MDMA is estimated to be 1.25 mg/kg b.w./d.

Exposure and risk assessment was performed by evaluating levels of volatile organic compounds (VOC) benzene, toluene, ethylbenzene, and xylene (BTEX) in 207 consumer products. The products were categorized into 30 different items, consisting of products of different brands. Samples were analyzed for BTEX by headspace-gas chromatography/mass spectrometry (headspace-GC/MS) with limit of detection (LOD) of 1 ppm. BTEX were detected in 59 consumer products from 18 item types. Benzene was detected in whiteout (ranging from not detected [ND] to 3170 ppm), glue (1486 ppm), oil-based ballpoint pens (47 ppm), and permanent (marking) pens (2 ppm). Toluene was detected in a leather cleaning product (6071 ppm), glue (5078 ppm), whiteout (1130 ppm), self-adhesive wallpaper (15-1012 ppm), shoe polish (806 ppm), permanent pen (609 ppm), wig adhesive (372 ppm), tapes (2-360 ppm), oil-based ballpoint pen (201 ppm), duplex wallpaper (12-52 ppm), shoes (27 ppm), and air freshener (13 ppm). High levels of ethylbenzene were detected in permanent pen (ND-345,065 ppm), shoe polish (ND-277,928 ppm), leather cleaner (42,223 ppm), whiteout (ND-2,770 ppm), and glue (ND-792 ppm). Xylene was detected in permanent pen (ND-285,132 ppm), shoe polish (ND-87,298 ppm), leather cleaner (12,266 ppm), glue (ND-3,124 ppm), and whiteout (ND-1,400 ppm). Exposure assessment showed that the exposure to ethylbenzene from permanent pens ranged from 0 to 3.11 mg/kg/d (men) and 0 to 3.75 mg/kg/d (women), while for xylene, the exposure ranges were 0-2.57 mg/kg/d and 0-3.1 mg/kg/d in men and women, respectively. The exposure of women to benzene from whiteout ranged from 0 to 0.00059 mg/kg/d. Hazard index (HI), defined as a ratio of exposure to reference dose (RfD), for ethylbenzene was 31.1 (3.11 mg/kg/d/0.1 mg/kg/d) and for xylene (2.57 mg/kg/d/0.2 mg/kg/d) was 12.85, exceeding 1 for both compounds. Cancer risk for benzene was calculated to be 3.2 × 10(-5) based on (0.00059 mg/kg/d × 0.055 mg/kg-d(-1), cancer potency factor), assuming that 100% of detected levels in some products such as permanent pens and whiteouts were exposed in a worst-case scenario. These data suggest that exposure to VOC via some consumer products exceeded the safe limits and needs to be reduced.

We retrospectively compared the treatment outcomes of localized prostate cancer between radical prostatectomy (RP) and external beam radiotherapy (EBRT). We retrospectively analyzed 738 patients with localized prostate cancer who underwent either RP (n = 549) or EBRT (n = 189) with curative intent at our institution between March 2001 and December 2011. Biochemical failure was defined as a prostate-specific antigen (PSA) level of ≥ 0.2 ng/ml in the RP group and the nadir of + ≥ 2 ng/ml in the EBRT group. The median (range) follow-up duration was 48.8 months (0.7–133.2 months) and 48.7 months (1.0–134.8 months) and the median age was 66 years (45–89 years) and 71 years (51–84 years; p

Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has neurobiological effects including antidepressant activity, antibiotic potency, anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin activates transient receptor potential conical channel-6 (TRPC6), a nonselective cation channel. To elucidate the roles of hyperforin and TRPC6 in neuroinflammation in vivo, we investigated the effect of hyperforin on neuroinflammatory responses and its related events in the rat piriform cortex (PC) following status epilepticus (SE). Hyperforin attenuated microglial activation, p65-serine 276 NFκB phosphorylation, and suppressed TNF-α expression in the PC following SE. Hyperforin also effectively alleviated SE-induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction and blood-derived monocyte infiltration. Our findings suggest that hyperforin may effectively attenuate microglia-mediated neuroinflammation in the TRPC6-independent manner.

The purpose of this study was to evaluate the dosimetric benefit of magnetic resonance imaging (MRI)-based dose adaptation in intracavitary brachytherapy (ICR) for cervical cancer. Dose-volume histograms were compared between matched conventional and optimized plans in 22 patients who were treated by MRI-based ICR. Doses to organs-at-risk (OAR) and dose covering 90% of high-risk clinical target volume (HR-CTV) were evaluated to compare OAR sparing and target coverage, respectively. The probability of RTOG rectal toxicity grade of ≥2 in the 22 patients was estimated based on the prediction model generated from previous three-dimensional CT-based ICR data. After optimization, doses to OAR showed a statistically significant decrease. The reduction percentage (reduced dose by optimization × 100/dose in the conventional plan) was higher in patients with HR-CTV >20 cc than in patients with HR-CTV ≤20 cc in the rectum. In patients with HR-CTV ≤20 cc, the mean probability of RTOG rectal toxicity grade ≥2 was 67.6% for the conventional plan and 47.8% for the optimized plan, based on the prediction model. In conclusion, dose adaptation by MRI-based ICR for cervical cancer resulted in significant dose reduction to the rectum, especially in patients with HR-CTV ≤20 cc.

This study investigates the impact of economic statecraft on the North Korean Government. As a totalitarian regime, which is characterized by a controlled mass media, the North Korean Government tries to contain potential problems caused by sanctions by using three types of political rhetoric: appeasement , backlash , and surveillance . Using time-series data from 1949 to 2010 derived from a content analysis of the New Year's Day addresses by Kim Il Sung, Kim Jong Il, and Kim Jong Un, the empirical results suggests that the North Korean Government does alter its rhetorical strategies in response to external economic sanctions. Negative sanctions cause the regime to use appeasement strategies (or calls for reforms and internal changes). It tends to use backlash rhetoric (or blaming the sanctioning powers) in response to, interestingly, positive sanctions. Surveillance rhetoric, or the call for internal vigilance against enemies, on the other hand, does not have any statistical connection with sanctions, rather driven by other factors, such as the Korean War, external instability, and so on.

To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50–66 GyE) in 20–22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p

452 Background: To evaluate the long-term clinical outcome of respiratory-gatedconformal radiotherapy in combination withtransarterial chemoembolization (TACE)asafirst-line treatment foradvanced hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Methods: This was a retrospective analysis of patientswho were diagnosed with HCC showing MVI who received TACE plus radiotherapy as their initial treatment between 2010 and 2015. Inclusion criteria were Child-Pugh A or B hepatic function and Eastern Cooperative Oncology Group performance score 0–2. None of the patients had a previous history of radiotherapy to the liver or extrahepatic metastasis. Results: A total of 467 patients were included in the study. Patients were between 34 and 87 years of age, and 89.3% were male. The median maximum tumor diameter was 9.8 cm and 297 patients (63.6%) had Child-Pugh A hepatic function. Two hundred and eighty (60%) patients had multiple tumors; 45% of tumors showed bilobar involvement. Unilateral portal vein invasion was observed in 206 (44.1%) patients and main/bilateral portal veinor multiple vascular invasion were observed in 261 (55.9%) patients. The median overall survival was 12.5 months, with one- and two-year survival rates of 52% and 28%, respectively. Larger tumor size, multiple tumors, infiltrative tumor type, Child-Pugh class B, and alpha-fetoprotein ≥ 200 ng/ml were independent predictors of overall survival. Grade ≥ 3 hepatic and gastrointestinal toxicities were observed in 3 (0.6%) and 5 (1.1%) patients, respectively. Conclusions: Radiotherapy combined with TACE as an initial treatment was a safe and effective modality for advanced HCC patients with MVIand could be considered as first-line therapy in patients with liver-confined HCC showing MVI.

The recombinant clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas system has opened a new era for mammalian genome editing. Here, we constructed pX330 plasmids expressing humanized Cas9 (hCas9) and single guide RNAs (sgRNAs) against mouse genes and validated them both in vitro and in vivo. When we randomly chose 291 target sequences within protein coding regions of 73 genes, an average number of off-target candidates (exact match 13 nucleotides from 3' target and NGG) found by Bowtie software was 9.2 ± 21.0 (~1.8 times more than the estimated value, 5.2). We next validated their activity by observing green fluorescence reconstituted by homology dependent repair (HDR) of an EGFP expression cassette in HEK293T cells. Of the pX330 plasmids tested, 81.8% (238/291) were found to be functional in vitro. We finally injected the validated pX330 plasmids into mouse zygotes in its circular form against 32 genes (including two genes previously tested) and obtained mutant mice at a 52.9 ± 22.3% (100/196) mutation frequency. Among the pups carrying mutations on the autosomes, 43.6% (47/96) carried the mutations in both alleles. When off-target candidate sites were examined in 63 mutant mice, 0.8% (3/382) were mutated. We conclude that our method provides a simple, efficient, and cost-effective way for mammalian gene editing that is applicable for large scale mutagenesis in mammals.

In the present study, we addressed the question of whether the distinct patterns of heat shock protein (HSP) 70 and HSP90 expressions in the brain region represents the regional specific responses to status epilepsticus (SE) in an effort to better understand the role of HSPs in epileptogenic insult. HSP70 immunoreactivity was increased in CA3 pyramidal cells as well as dentate granule cells at 12h-1week after SE. HSP70 immunoreactivity was transiently increased in neurons within the piriform cortex (PC) following SE. Linear regression analysis showed no correlation between the intensity of NeuN and that of HSP70. In contrast to HSP70, HSP90 immunoreactivity was decreased in CA1-3 pyramidal cells at 4days-4weeks after SE. In addition, HSP90 immunoreactivity was decreased in PC neurons at 12h-4weeks after SE. linear regression analysis showed a direct proportional relationship between the intensity of NeuN and that of HSP90. Therefore, these findings suggest that HSP90 degradation may be closely related to neuronal vulnerability to SE insult.

We investigate on the technological potential and issues of non-woven separator as an alternative to conventional separator in terms of various evaluation points. Thus, optimal evaluation systems for new nonwoven polyacrylonitrile (PAN) separator are proposed to compare with commercialized polyethylene (PE) separator, and corresponding stacking-type pouch batteries are used as an evaluation tool. Cell performance, electrochemical stability, and thermal stability for both separators are compared. Based on the comparison results, each separator’s effects are discussed in detail. In comparison to PE separator, the non-woven separator exhibits distinct advantage in microporous structure, leading to superior reliability of cell. Based on the understanding of non-woven separator, cell performances of the separator at different charge/discharge conditions are discussed in terms of ion transport of the separator and AC impedance of the cell. Moreover, the problems of nonwoven separator to be solved are clearly stated through the phenomenological analyses. The overall evaluation results indicate that the non-woven PAN separator has many advantages over the PE separator, which, in turn, contribute to superior cell performances. Therefore, the PAN nonwoven membrane can be the most promising candidate for separators of the next generation of lithium-ion battery if the problems to be stated will be solved.

LiNi 0.5 Mn 1.5 O 4 , a cathode material for high potential applications, rapidly deteriorates at high temperatures. In this study, fluoride-containing additives are found to offer protection to the material in damaging temperature ranges. The results of investigations using a fluoride-rich pyrazole, fluoro-ethylene carbonate, trially cyanurate with multiple double bonds, and LiF explain the combined action of the protective layer and fluoride in promoting longer life cycles. Both fluoride in a protective film and free fluoride ions prevent LiF accumulation on the electrode, extending the life of the cathode material at high temperatures.

Summary The placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface are poorly understood. We identified an Epcam hi labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange.

Chordomas are rare, slow-growing tumors that arise from the remnant of the primitive notochord. They are characterized by a locally aggressive growth pattern and high recurrence rates. The most com...

The self-discharge of Zn anode material is identified as a main factor that can limit the energy density of alkaline Zn–air batteries. Al 2 O 3 has most positive effect on controlling the hydrogen evolution reaction accompanied by corroding Zn anode among various additives. The overpotential for hydrogen evolution is measured by potentio-dynamic polarization analysis. Al-oxide with high overpotential for hydrogen evolution reaction is uniformly coated on the surface of Zn powders via chemical solution process. The morphology and composition of the surface-treated and pristine Zn powders are characterized by SEM, EDS, XRD and XPS analyses. Aluminum is distributed homogeneously over the surface of modified Zn powders, indicating uniform coating of Al-oxide, and O1s and Al2 p spectra further identified surface coating layer to be the Al-oxide. The Al-oxide coating layer can prevent Zn from exposing to the KOH electrolyte, resulting in minimizing the side reactions within batteries. The 0.25 wt.% aluminum oxide coated Zn anode material provides discharging time of more than 10 h, while the pristine Zn anode delivers only 7 h at 25 mA cm −2 . Consequently, a surface-treated Zn electrode can reduce self-discharge which is induced by side reaction such as H 2 evolution, resulting in increasing discharge capacity.

Styela (S.) clava (Korean name: miduduk) tunic is produced as a by-product after processing of S. clava. For utilizing this tunic, a konjac containing the tunic extracts was prepared and the qualities evaluated for their color, textural properties, and sensory attributes. The tunic extract was prepared by boiling tunic with water, followed by filtration through filter paper. Significant 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity was found in the tunic extract. Increasing the concentration of tunic extract in the konjac tended to decrease lightness (L) and increase the redness (a) and the yellowness (b) of the konjac. The strength and hardness of the konjac increased with increasing concentrations of the tunic extract. All test samples with a 3 mm thickness had good flexibility and did not break even after 4 times folds. In sensory evaluations, the konjac containing 25% S. clava tunic extracts acquired a relatively higher score. The results suggest that S. clava tunic can be applied to konjac products to improve their quality and functionality.

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca(2+), which express in many cell types, including neurons. However the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 in neuronal death and vasogenic edema within the rat piriform cortex (PC) following SE. In non-SE animals, TRPC3 immunoreactivity was abundantly detected in the PC. Following SE, TRPC3 immunoreactivity was increased in neurons. Furthermore, TRPC3 expression was detected in endothelial cells that did not contain it in non-SE animals. Loss of SMI-71 (a blood-brain barrier antigen) immunoreactivity was also observed in TRPC3 positive endothelial cells. In addition, FJB positive neurons and vasogenic edema were noticeably detected in the PC. To directly determine whether TRPC3 activation is correlated to SE-induced vasogenic edema formation and neuronal damages in the PC, the effect of Pyr-3 (a TRPC3 antagonist) on SE-induced insults were investigated. Pyr-3 infusion effectively attenuated vasogenic edema in the PC as compared to the vehicle. Therefore, our findings indicate that TRPC3 activation/overexpression induced by SE may involve BBB disruption and neuronal damages in the rat PC following SE. Therefore, the present study was TRPC3 may play an important role in SE-induced vasogenic edema formation through BBB disruptions in the rat PC.

Purpose To analyze the toxicities and dose–volume histogram parameters of external-beam and magnetic resonance imaging–based intracavitary brachytherapy in cervical cancer patients. Methods and Materials Acute and late toxicities were assessed in 135 patients divided into four groups: group 1, grade 0; group 2, grades 1–4; group 3, grades 0–1; and group 4, grades 2–4. The doses at the International Commission on Radiation Units and Measurements (D ICRU ) and minimum doses to the most exposed 0.1, 1, 2, and 5 cc (D 0.1cc , D 1cc , D 2cc , and D 5cc ) of normal organs were calculated as equivalent doses in 2 Gy (α/β = 3). Results The median follow-up was 35.2 months. For rectum, D ICRU , D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 0.1cc , and D 1cc between groups 3 and 4. For bladder, D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 1cc , D 2cc , and D 5cc between groups 3 and 4. Grade 2–4 bladder toxicity occurred in fewer patients with D 2cc ≤ 95 Gy than those with D 2cc > 95 Gy (7% vs. 22%, p = 0.014). Conclusions D ICRU , D 0.1cc , D 1cc , and D 2cc are relevant for predicting late rectal toxicities. The patients with bladder D 2cc > 95 Gy are required to be in close observation for severe late toxicities.

Oji, A., Noda, T., Fujihara, Y. et al. CRISPR/Cas9 mediated genome editing in ES cells and its application for chimeric analysis in mice. Sci Rep 6, 31666 (2016). https://doi.org/10.1038/srep31666, Targeted gene disrupted mice can be efficiently generated by expressing a single guide RNA (sgRNA)/CAS9 complex in the zygote. However, the limited success of complicated genome editing, such as large deletions, point mutations, and knockins, remains to be improved. Further, the mosaicism in founder generations complicates the genotypic and phenotypic analyses in these animals. Here we show that large deletions with two sgRNAs as well as dsDNA-mediated point mutations are efficient in mouse embryonic stem cells (ESCs). The dsDNA-mediated gene knockins are also feasible in ESCs. Finally, we generated chimeric mice with biallelic mutant ESCs for a lethal gene, Dnajb13, and analyzed their phenotypes. Not only was the lethal phenotype of hydrocephalus suppressed, but we also found that Dnajb13 is required for sperm cilia formation. The combination of biallelic genome editing in ESCs and subsequent chimeric analysis provides a useful tool for rapid gene function analysis in the whole organism.

Purpose This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. Materials and methods We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. Results A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. Conclusion We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

// Yeon Joo Kim 1 , Sang Jun Byun 1 , Hanjong Ahn 2 , Choung-Soo Kim 2 , Beom-Sik Hong 2 , Sangjun Yoo 2 , Jae-Lyun Lee 3 and Young Seok Kim 1 1 Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea 2 Urology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea 3 Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea Correspondence to: Young Seok Kim, email: // Keywords : muscle-invasive bladder cancer, radical cystectomy, trimodal therapy, radiotherapy, chemotherapy Received : July 14, 2016 Accepted : March 15, 2017 Published : March 25, 2017 Abstract Although radical cystectomy (RC) is considered as the standard therapy for muscle-invasive bladder cancer (MIBC), trimodal therapy (TMT) combining transurethral resection of the tumor with radiotherapy and chemotherapy is increasingly recommended as an alternative approach for bladder preservation. In the absence of randomized trials, we compared the clinical outcomes between RC and TMT using propensity score matching with 50 patients in the RC arm and 29 patients in the TMT arm. With respective median follow-up periods of 23 and 32 months for the RC and TMT groups, 5-year distant metastasis-free survival (58% vs. 67%), overall survival (56% vs. 57%), and cancer-specific survival (69% vs . 63%) rates between the RC and TMT groups, respectively, were similar. However, the 5-year local recurrence-free survival was significantly better in the RC group than in the TMT group (74% vs . 35%). Following TMT, acute grade 3 hematological ( n = 2) and late grade 3 genitourinary ( n = 1) toxicities were reported. These findings demonstrated that oncological outcomes of TMT were comparable with those of RC, except for poorer local control. Large-scale, randomized trials are warranted to confirm the findings of the present retrospective comparison and to guide toward best treatment options.

Dendritic spines are dynamic structures whose efficacies and morphologies are modulated by activity-dependent synaptic plasticity. The actin cytoskeleton plays an important role in stabilization and structural modification of spines. However, the regulatory mechanism by which it alters the plasticity threshold remains elusive. Here, we demonstrate the role of pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN), one of the cofilin-mediated F-actin regulators, in modulating synaptic plasticity in vivo. PLPP/CIN transgenic (Tg) mice had immature spines with small heads, while PLPP/CIN knockout (KO) mice had gigantic spines. Furthermore, PLPP/CIN Tg mice exhibited enhanced synaptic plasticity, but KO mice showed abnormal synaptic plasticity. The PLPP/CIN-induced alterations in synaptic plasticity were consistent with the acquisition and the recall capacity of spatial learning. PLPP/CIN also enhanced N-methyl-D-aspartate receptor (GluN) functionality by regulating the coupling of GluN2A with interacting proteins, particularly postsynaptic density-95 (PSD95). Therefore, these results suggest that PLPP/CIN may be an important factor for regulating the plasticity threshold.

PurposeWe identified the predictive factors for locoregional failure after definitive chemoradiation in patients with locally advanced cervical cancer.MethodsAltogether, 397 patients with locally advanced cervical cancer (stage IB2–IVA) were treated with definitive chemoradiation between June 2001 and February 2010. Platinum-based concurrent chemotherapy was given to all patients with median radiation dose of external beam radiotherapy 50.4 Gy in 28 fractions and intracavitary radiotherapy 30 Gy in 6 fractions. Competing risk regression analysis was used to reveal the predictive factors for locoregional failure.ResultsDuring the median follow-up of 7.2 years, locoregional failure occurred in 51 (12.9%) patients. The estimated 3-year rate of locoregional control was 89%, whereas the overall survival rate was 82%. After univariate and multivariate analyses, large tumor size (>5 cm), young age (≤40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage (III–IV) were identified as risk factors for locoregional failure (P = 0.003, P = 0.075, P = 0.005, P = 0.055, and P < 0.001, respectively). After risk grouping according to the coefficients from the multivariate model, we identified a high-risk group for locoregional failure after treatment with definitive chemoradiation as follows: (1) tumor size larger than 5 cm, and at least 1 other risk factor or (2) tumor size 5 cm or less, and at least 3 other risk factors. The cumulated estimated 3-year rate of locoregional failure of the high-risk group was 26%, which was significantly higher than that of the low-risk group (7%, P < 0.001). The 3-year overall survival rates of the 2 groups were also significantly different (57% vs 86%, P < 0.001).ConclusionsLarge tumor size (>5 cm), young age (≤40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage are all risk factors for locoregional failure after definitive platinum-based chemoradiation in patients with locally advanced cervical cancer. In the high-risk group, further clinical trials are warranted to improve the locoregional control rate.

Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-κB and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-κB and IRF3 induced by the overexpression of downstream signaling components of the MyD88- or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

Background and purpose The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. Material and methods We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). Results Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2months (range 6.8–102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT ( p =0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients ( p =0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT ( p =0.317), respectively. DFS was 100% for EFI and 70.7% for PRT ( p =0.018). Conclusion EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression.

EN 1788:2001 suggests defining the temperature range for the thermoluminescence (TL) heating unit to calculate the TL ratio (TL1/TL2). In the present study, practical temperature ranges were established by using well-characterized lithium fluoride (LiF, TLD-100®) at 4 different research institutes in Korea. Temperature ranges differed according to models of TLD heating unit, which were wide in the case of RISO (160–249°C) as compared with Harshaw (155–232°C) TLD readers. The silicate minerals separated from irradiated turmeric samples were measured to check these intervals on a practical basis. The X-ray diffraction (XRD) analysis of separated minerals showed that quartz and feldspar minerals were the main source of well-characterized TL glow curve following irradiation. The TL glow peaks from the separated minerals were narrower in Harshaw than RISO TLD readers. The TL ratios determined after re-irradiation (1 kGy) for the tested minerals, using the pre-defined temperature intervals, provided the satisfactory results.

Recently, the livestock industry in Korea was heavily affected by the outbreak of official livestock diseases such as foot and mouse disease, high pathogenic avian influenza, swine influenza, and so on. It has been established that these diseases are being spread through direct contact, droplet and airborne transmission. Among these transmissions, airborne transmission is very complex in conducting field investigation due to the invisibility of the pathogens and unstable weather conditions. In this study, the airborne transmission was thoroughly investigated inside a pig house by conducting tracer gas () experiment because experiment with real pathogen is limited and dangerous. This is possible as it can be assumed that the flow is similar pattern very fine particles and gas. In the experiment, the ventilation structure as well as the location of gas emission were varied. The detection sensors were installed at 0.5 and 1.3 m height from the floor surface. The tracer gas level was measured every second. Results revealed that the direction of spread can be determined by the response time. Response time refers to the time to reach 150 ppm from the gas emission source at each measuring points. The location of the main flow as well as the gas emission was also found to be very important factor causing the spread.

In this paper, we propose a dynamic tree formation protocol for multiple UAV which is gathering data or accomplishing a mission such as disaster monitoring, environment monitoring, and disaster relief. Especilly, we designed Hop-LQI Weight algorithm to form optimal tree in wireless dynamic environment applying situation of radio signal attenuation over distance and implemented our algorithm in MSP 430 K-mote sensor platform using TinyOS codes. We verified performance of our algorithm by comparing average link setup time by the number of nodes with minimum LQI, link cost calculation method in wireless communication.

Pegylated-interferon plus ribavirin is the standard treatment for chronic hepatitis C. Sustained virological response (SVR) rates of up to 80% are reported in genotype 2 and 3 chronic hepatitis C cases. Obesity, a modifiable risk factor, may have a deleterious effect on antiviral treatment. We performed this study to examine the efficacy and safety of pegylated-interferon and ribavirin therapy in Korean patients with genotype 2 and 3 chronic hepatitis C and to investigate the risk factors for nonresponse to antiviral treatment. A total of 121 patients were treated with peginterferon alpha-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks. The end-of-treatment virologic response (ETVR), the SVR, the end-of-treatment biochemical response (ETBR), the sustained biochemical response (SBR), and the adverse events were analyzed. The ETVR and SVR were 94.1% and 89.1%, respectively. The ETBR was 80.2% and the SBR was 96%. Multivariate analysis showed that a body mass index of 25 and over was the only independent factor that affected the SVR (odds ratio=10.5, 95% confidence interval: 2.006-54.948, p=0.005). Twenty patients (16.5%) dropped out at the end of treatment, and 7 (5.8%) patients discontinued treatment because of treatment-related adverse events. Our study showed that combination therapy with pegylated-interferon and ribavirin as an initial treatment for genotype 2 and 3 chronic hepatitis C is very effective and safe, and that body mass index is an independent risk factor for nonresponse to antiviral treatment in patients with genotype 2 and 3 chronic hepatitis C.

In this paper, short-range underwater wireless communication technique using visible LEDs is proposed. As an alternative to conventional acoustic system, visible LED communications show high qualityand high speed data transmission characteristics. We design a frequency modulation-based optical wireless audio transmission system. The CD4046B phase-locked loop device is applied to implement the frequencymodulation and demodulation. With a transmission modulation of 100 kHz, audio signal has successfully received at a transmission distance of 30 cm. Key words: optical wireless communications, frequency modulation, visible communications, underwater communications †교신저자(한국해양대학교 전자통신공학과, E-mail: krsohn@hhu.ac.kr, Tel: 051-410-4312)1 한국해양대학교 대학원 전자통신공학과 1. 서 론 최근에 들어 LED는 반도체 기술의 발전으로 인해 기존의 조명시설을 대체할 수 있는 친환경 기술로 주목받고 있다. 기존의 형광등에 비하여 4∼5 배의 긴 수명과 최소 30% 이상의 에너지 절감효과를 기대할 수 있게 되었다. 그러나 가격면에서는 기존 조명이 아직까지 10배 이상 저렴하여 LED 조명 보급이 활발하지 못한 실정이다. LED의 또 다른 원천적인 특징은 저 전력으로 스위칭 되는 디지털 소자이며 수백 kHz 이상의 빠른 응답특성을 보인다는 것이다. 이러한 특징은 LED를 조명뿐만 아니라 통신용 광원으로 활용할 수 있음을 보여준다[1-2]. 조명에 통신기능을 융합하여 서비스 할 수 있는 모델을 개발한다면 LED 조명보급이 활성화 될 수 있을 것으로 예측하고 있다. 현재 가시광 영역의 파장(400~700nm)을 가지는 백색 LED를 이용하여 눈이 감지하지 못할 정도의 속도인 100 Hz 이상으로 점멸시켜 정보를 보내는 가시광 통신기

In this study, the identification of the irradiated seafood cooking drips from Hizikia fusiformis, Enteroctopus dofleini and Thunnus thynnus was conducted. The physical detection methods used included photo-stimulated luminescence (PSL) and thermoluminescence (TL), and the chemical detection methods were hydrocarbons analysis. In the PSL study, all seafood cooking drip samples showed 260~510 photon counts; thus, the PSL method could not be used for the detection of irradiated seafood cooking drips. The TL method could be used for the detection of irradiated H. fusiformis and E. dofleini cooking drips. In both cooking drips, the shapes of the glow curves indicated a specific peak at 150~250, which made it possible to identify the irradiated samples. The hydrocarbons derived by gamma irradiation of T. thynnus cooking drip were not detected due to low concentration and inconsistent content of fatty acids in the untreated T. thynnus cooking drip.

Animal models using cell lines that are dual-labeled with luciferase and green fluorescent protein (GFP) are powerful tools for performing simultaneous quantitative and qualitative analysis of metastatic tumors. However, the applications of such dual-labeled tumor models have been limited due to the technical challenges associated with low bioluminescent signaling from tumor cells. Here, we used lentiviral vector (LV) encoding firefly luciferase and GFP and engineered a more sensitive and highly metastatic prostate cancer cell line (MLL-Luc/GFP cells), which allows simultaneous fluorescence and luminescence imaging. The light emission of MLL-Luc/GFP cells was 33.5 fold higher than that of PC-3-luc2-GFP prostate cancer cells which showed 750 p/s light emission per cell. Furthermore, the MLL-Luc/GFP cells showed 3.9 fold higher luciferase activities than did 4T1-luc2, which was previously recognized as exhibiting the highest luciferase activity. An in vivo evaluation with optical imaging showed pinpoint localization of GFP-positive cells in a metastatic lung as well as easy detection of early metastatic spreading. The newly engineered MLL-Luc/GFP cells provide an appropriate metastatic animal model system for future studies of metastasis and the testing of anti-metastatic therapies specifically aimed at prostatic cancer.

Purpose To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group ( p = 0.89). Local progression–free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group ( p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

Purpose Bacille Calmette-Guérin (BCG) vaccination has been reported to be an effective treatment for asthma in several animal models. This study investigated whether the response to BCG treatment in asthma depends on subject clinical characteristics. Methods Stable asthma patients were vaccinated with BCG. One month later, alterations in pulmonary function after vaccination and their relationships with subject clinical characteristics were determined. Results Of 149 patients with asthma, 54 (36.2%) showed a good or fair response to BCG. The ΔFEV1 after vaccination was significantly related to age (r=-0.348, P0.05). A good/fair response was highly prevalent in atopic females compared with atopic males, especially among those aged ≤50 years (90.9% vs. 40.0%, P=0.024). Age (P

Purpose The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. Materials and Methods A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next follow-up; arm swelling that persisted over two consecutive examinations was considered PLE. Results At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). Conclusion One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication.

To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50–72 CGE (cobalt gray equivalent) in 5–12 fractions was delivered. The median follow-up duration was 29 months (range 4–95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan–Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4–95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5–14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3–37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC.

Purpose: We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy. Materials and Methods: Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients. Results: During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size ≥3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (≥70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically. Conclusion: Clinical size ≥3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age ≥70 years.

Transient receptor potential canonical channel-6 (TRPC6) forms Ca(2+)-permeable non-selective cation channels in neurons. Although TRPC6 plays an important role in neurite outgrowth and neuronal survival during development, TRPC6 expression profiles available to identify distinctive hippocampal neuronal damage and hippocampal excitability in epilepsy are less defined. As compared to normal animals, TRPC6 expression was down-regulated in chronic epileptic rats showing spontaneous recurrent seizures. TRPC6 knockdown increased seizure susceptibility, excitability ratio and paired-pulse inhibition in the dentate gyrus (DG) of normal animals. Furthermore, TRPC6 knockdown promoted programmed neuronal necrosis in dentate granule cells, but prevented it in CA1 and CA3 neurons following status epilepticus. The present data suggest for the first time that TRPC6 may inhibit seizure susceptibility and neuronal vulnerability in the rat DG.

In the present study, we investigated the characteristics of drug efflux transporter expressions following status epilepticus (SE). In the hippocampus and piriform cortex (PC), vasogenic edema peaked 3-4 days after SE. The expression of breast cancer resistance protein (BCRP), multidrug resistance protein-4 (MRP4), and p-glycoprotein (p-GP) were decreased 4 days after SE when vasogenic edema was peaked, but subsequently increased 4 weeks after SE. Multidrug resistance protein-1 (MRP1) expression gradually decreased in endothelial cells until 4 weeks after SE. These findings indicate that SE-induced vasogenic edema formation transiently reduced drug efflux pump expressions in endothelial cells. Subsequently, during recovery of vasogenic edema drug efflux pump expressions were differentially upregulated in astrocytes, neuropils, and endothelial cells. Therefore, we suggest that vasogenic edema formation may be a risk factor in pharmacoresistent epilepsy. [BMB Reports 2015; 48(6): 348-353]

Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000-15,000 female births worldwide. The disease-causing gene has been identified as MECP2 (methyl-CpG-binding protein 2). In this study, we performed diagnostic mutational analysis of the MECP2 gene in RTT patients. Four exons and a putative promoter of the MECP2 gene were analyzed from the peripheral blood of 43 Korean patients with Rett syndrome by PCR-RFLP and direct sequencing. Mutations were detected in the MECP2 gene in approximately 60.5% of patients (26 cases/43 cases). The mutations consisted of 14 different types, including 9 missense mutations, 4 nonsense mutations and 1 frameshift mutation. Of these, three mutations (G161E, T311M, p385fsX409) were newly identified and were determined to be disease-causing mutations by PCR- RFLP and direct sequencing analysis. Most of the mutations were located within MBD (42.3%) and TRD (50%). T158M, R270X, and R306C mutations were identified at a high frequency. Additionally, an intronic SNP (IVS3+23C>G) was newly identified in three of the patients. IVS3+23C>G may be a disease-related and Korea-specific SNP for RTT. L100V and A201V are apparently disease-causing mutations in Korean RTT, contrary to previous studies. Disease-causing mutations and polymorphisms are important tools for diagnosing RTT in Koreans. The experimental procedures used in this study should be considered for clinical molecular biologic diagnosis.