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As more of the patients with traumatic pelvic injuries survive, they desire an optimal quality of life, including normal sexual function, even after the most severe injuries. We present the case of a 31-year-old woman who had dyspareunia due to impaired vaginal penetration after severe pelvic injury. After excision of a disunited fragment of pelvic bone and an adhesion band at the vaginal wall, dyspareunia was considerably resolved and the patient resumed sexual function. In cases of severe pelvic injury, physicians used to be satisfied with the patient's survival alone, and tended to regard sexual dysfunction as a trivial outcome. However, restoration of sexual function is an important part of management of these patients. In selected cases, obstructive dyspareunia resulting from traumatic pelvic injury can be managed by planned surgical intervention.

This paper reports a low-loss RF MEMS silicon switch that employs reflowed glass as a structural material beneath a contact metal. The glass structure is inserted into a silicon substrate through the glass reflow process to reduce the insertion loss of the RF MEMS switch. To verify this enhancement in the loss characteristic, two types of RF MEMS switches were fabricated with two different structural materials underneath the contact metal: silicon or reflowed glass. The reference RF MEMS switch is totally made of silicon. In the frequency range of 5 to 30 GHz, S-parameter measurements of the fabricated switches were carried out and the insertion losses were measured as 0.12 ~ 0.33 dB and 0.38 ~ 0.53 dB for the proposed and the reference RF MEMS switch, respectively. The insertion loss was reduced as much as 0.26 dB for the proposed RF MEMS switch in the measured frequency range and it was shown that the insertion loss of the RF MEMS switch is effectively reduced by changing the structural material under the contact metal.

Adeno-associated virus (AAV) vectors can deliver transgenes to diverse cell types and are therefore useful for basic research and gene therapy. Although AAV has many advantages over other viral vectors, its relatively small packaging capacity limits its use for delivering large genes. The available transgene size is further limited by the existence of additional elements in the expression cassette without which the gene expression level becomes much lower. By using alternative combinations of shorter elements, we generated a series of AAV expression cassettes and systematically evaluated their expression efficiency in neurons to maximize the transgene size available within the AAV packaging capacity while not compromising the transgene expression. We found that the newly developed smaller expression cassette shows comparable expression efficiency with an efficient vector generally used for strong gene expression. This new expression cassette will allow us to package larger transgenes without compromising expression efficiency.

An expressed sequence tag (EST) analysis provideus portions of expressed genes. We have constructed cDNA library and determined randomly sequences from cDNA library clones of T. molitor injected with acholeplasma lysate. We identified the homologous to a galectin gene. As the result of cloning and characterization of novel, we found that the protein has an open reading frame (ORF) of 495 bp, with 164 amino acid residues and molecular weight of 18.5 kDa. To characterize the role of novel Tm-galectin in immune system, we quantified the mRNA level of galectin at different times after treatment with immune elicitors. The galectin mRNA was up-regulated about 7-folds within 18 hrs. This suggests that Tm-galectin is a novel member of animal lectins, and has a role in the process of pathogen recognition. Our study would be helpful for the study on immune defense system and signaling cascade., {"references":["Park, J. W., 2006. A synthetic peptidoglycan fragment as a competitive \ninhibitor of the melanization cascade. J. Biol. Chem. 281, 7747-55.","Yang, R., Rabinovich, G., Liu, F., 2008. Galectins: Structure, function \nand therapeutic potential. Expert Reviews in Molecular Medicine 10, \n1–24","Liu, F., Patterson, R.J., Wang, J.L., 2002. Intracellular functions of \ngalectins. Biochimica et Biophysica Acta 1572, 263–273.","Liu, F., 2010. \"Galectins: Regulators of acute and chronic inflammation\". \nAnnals of the New York Academy of Sciences 1183, 158–182.","Yang, R., Rabinovich, G., Liu, F., 2008. \"Galectins: Structure, function \nand therapeutic potential\". Expert Reviews in Molecular Medicine 10: \n1–24.","Fujita, T., 2002. Evolution of the lectin-complement pathway and its role \nin innate immunity. Nat. Rev. Immunol. 2, 346-353.","Revillard, J.P., 2002. Innate immunity. Eur. J. Dermatol. 12, 224-227.","Turner, M.W., 1996. Mannose-binding lectin: the pluripotent molecule of \nthe innate immune system. Immunol. Today 17, 532.","Jiang, R., Kim, E.H., Gong, J.H., Kwon, H.M., Kim, C.H., Ryu, K.H. et al. \n2009. Three pairs of protease-serpin complexes cooperatively regulate the \ninsect innate immune responses. J. Biol. Chem.284, 35652-35658. \n[10] Yu, F., Finley, R.L Jr., Raz, A., Kim, H.R., 2002. Galectin-3 translocates \nto the perinuclear membranes and inhibits cytochrome c release from the \nmitochondria. A role for synexin in galectin-3 translocation. J. Biol. \nChem. 277, 15819-15827."]}

Background Lowering blood pressure (BP) and reducing diurnal variation are important for the prevention of stroke in patients with hypertension. Objective This study was conducted to compare the BP-lowering and diurnal BP variation effects of amlodipine and losartan on acute stroke patients. Methods Seventy-seven hypertensive patients with acute stroke were enrolled in this randomized, double-blind, single-center clinical trial. They were randomly assigned to receive either amlodipine or losartan daily. To evaluate whether amlodipine was noninferior to losartan, ambulatory BP monitoring was performed before the drugs were first administered and at the end of week 8. BP variables analyzed included the mean awake, sleep, morning, evening, and prewake BP values; the nocturnal dipping status; and the morning surge. Results Thirty-nine patients in the amlodipine group and 38 patients in the losartan group completed the follow-up. In the baseline characteristics, mean age was 63.6 years, and 68.8% were male. In the intention-to-treat analysis, the mean (SD) systolic BP decreased 14.82 (11.71) mm Hg in the amlodipine group and 13.11 (12.69) mm Hg in the losartan group, and amlodipine proved noninferior to losartan (mean difference, 1.71 mm Hg [95% CI, –3.83 to 7.26]). However, in the per-protocol analysis, noninferiority was not proven (BP reduction, 16.06 [11.33] vs 17.17 [11.85] mm Hg; mean difference, –1.11 mm Hg [95% CI, –6.88 to 4.65]). Amlodipine had a greater tendency than losartan to produce a blunt morning surge. Conclusions The noninferiority of amlodipine was not confirmed by the per-protocol analysis. However, amlodipine showed a favorable effect on the morning surge. ClinicalTrials.gov identifier: NCT01830517.

A β-glucosidase gene bglX was cloned from Lactococcus sp. FSJ4 by the method of shotgun. The bglX open reading frame consisted of 1,437 bp, encoding 478 amino acids. SDS-PAGE showed a recombinant bglX monomer of 54 kDa. Substrate specificity study revealed that the enzyme exhibited multifunctional catalysis activity against pNPG, pNPX and pNPGal. This enzyme shows higher activity against aryl glycosides of xylose than those of glucose or galactose. The enzyme exhibited the maximal activity at 40 °C, and the optimal pH was 6.0 with pNPG and 6.5 with pNPX as the substrates. Molecular modeling and substrate docking showed that there should be one active center responsible for the mutifuntional activity in this enzyme, since the active site pocket was substantially wide to allow the entry of pNPG, pNPX and pNPGal, which elucidated the structure–function relationship in substrate specificities. Substrate docking results indicated that Glu180 and Glu377 were the essential catalytic residues of the enzyme. The CDOCKER_ENERGY values obtained by substrate docking indicated that the enzyme has higher activity against pNPX than those of pNPG and pNPGal. These observations are in conformity with the results obtained from experimental investigation. Therefore, such substrate specificity makes this β-glucosidase of great interest for further study on physiological and catalytic reaction processes.

The Segment Travel River Ecosystem Autograph Model ( stream ), which is a multiconstituent stream ecosystem model, was developed and applied to steep and shallow streams in this study. The formulation of stream was based on the moving segment approach in the cell-in-series (CIS) system where a stream is assumed to be a series of completely mixed flow reactors. Major constituents included in stream are dissolved oxygen (DO), 5-day biochemical oxygen demand (BOD5), suspended solids (SS), coliform bacteria, nitrogen species, phosphorus species, and phytoplankton. Dissolved oxygen change caused by sediment oxygen demand (SOD) and respiration and photosynthesis of periphyton and macrophytes are included in the model structure. stream was programmed in basic and can be executed on an ms-dos personal computer. stream was designed for implementation with EGA/VGA colour graphics. The model results and the data are displayed on the computer screen and the output device in a graphic format. A demonstration application is presented to validate the stream model. The results indicate that the stream model could effectively simulate water quality of steep and shallow streams where longitudinal dispersive transport is negligible.

For the robust practice of genomic medicine, sequencing results must be compatible, regardless of the sequencing technologies and algorithms used. Presently, genome sequencing is still an imprecise science and is complicated by differences in the chemistry, coverage, alignment, and variant-calling algorithms. We identified ~3.33 million single nucleotide variants (SNVs) and ~3.62 million SNVs in the SJK genome using SOLiD and Illumina data, respectively. Approximately 3 million SNVs were concordant between the two platforms while 68,532 SNVs were discordant; 219,616 SNVs were SOLiD-specific and 516,080 SNVs were Illumina-specific (i.e., platform-specific). Concordant, discordant, and platform-specific SNVs were further analyzed and characterized. Overall, a large portion of heterozygous SNVs that were discordant with genotyping calls of single nucleotide polymorphism chips were highly confident. Approximately 70% of the platform-specific SNVs were located in regions containing repetitive sequences. Such platform-specificity may arise from differences between platforms, with regard to read length (36 bp and 72 bp vs. 50 bp), insert size (~100-300 bp vs. ~1-2 kb), sequencing chemistry (sequencing-by-synthesis using single nucleotides vs. ligation-based sequencing using oligomers), and sequencing quality. When data from the two platforms were merged for variant calling, the proportion of callable regions of the reference genome increased to 99.66%, which was 1.43% higher than the average callability of the two platforms, representing ~40 million bases. In this study, we compared the differences in sequencing results between two sequencing platforms. Approximately 90% of the SNVs were concordant between the two platforms, yet ~10% of the SNVs were either discordant or platform-specific, indicating that each platform had its own strengths and weaknesses. When data from the two platforms were merged, both the overall callability of the reference genome and the overall accuracy of the SNVs improved, demonstrating the likelihood that a re-sequenced genome can be revised using complementary data.

A model for ethanol production from a glucose-maltose mixture has been proposed, which includes a term representing the glucose repression effect on maltose consumption. The model parameters were estimated from batch experimental data. Results of sensitivity analysis on the Monod constants for glucose and maltose, and the repression constant, showed that ±10% changes in these three parameters caused no significant effect on data fitting.

This paper seeks to enhance our understanding of financial analysts in assisting market investors’ use of accounting earnings in the Korean stock market. We examine whether stock returns differentially reflect earnings information for firms with analyst coverage. We propose that the role of analysts as external monitors as well as information intermediaries enhances the market investors’ valuation of earnings. We find that market valuation of earnings is higher for firms with analyst following. Furthermore, market investors’ valuation of earnings increases (or decreases) with the number of analysts (or with the dispersion of analysts’ forecasts). This suggests that the beneficial effect of analysts arises through the quantity and quality of analysts’ information. This study contributes to the literature by investigating the important role of analysts in emerging market.

Tomita's parsing method (GLR) is a practical and successful parsing method for natural language. However, one difficulty in the GLR is that interleaved constraint processing of syntax and semantics in parallel is not trivial during parsing, because it uses the precompiled table for a fast real-time parsing. In this paper, we present a method which makes the GLR adaptable to interleaved parsing while making some limitation on its generality. For interleaved parsing, the conflicts of the LR parsing table must be resolved at the parse time. The shift-reduce conflict among the above conflicts is the most serious one for interleaved parsing because of the lack of knowledge for the conflict resolution at the parse time. Therefore, we concentrate on resolving a shift-reduce conflict by introducing a grammar which is called a shift-first LR(k) grammar . Our method for this is that the conflict resolution is delayed by the shift-first strategy which makes an unconditional choice of shift actions in the case of a shift-reduce conflict.

Among the commercial anode materials, graphite isn`t suitable for high-power applications such as electric vehicles and large-scale energy storage due to formation of the solid-electrolyte interphase (SEI) leading to lithium irreversibly at about 0.8V and inactive high rate performance. Although, Li4Ti5O12 (LTO) are being pursued as alternatives to graphite electrodes due to high lithium storage voltages (1.0~2.0V) which are higher than the formation of SEI voltage and high rate capability, it has low theoretical capacity (~175mAhg-1). Recently titanium-niobium oxides (TNO) such as TiNb2O7, Ti2Nb10O29 with high redox potential range have been considered as interesting candidates for anode material of LIB. Because they have higher theoretical capacity of 380~396mAhg-1 due to multiple redox couples such as Ti4+/Ti3+, Nb5+/Nb4+, Nb4+/Nb3+ by compared with LTO having only Ti4+/Ti3+ redox couple. In addition, they have good stability, high rate capability. However, they are show limited reversible capacities (240~270mAhg-1) owing to low electronic conductivity and lithium diffusion coefficient. Chunfu Lin et al. presented that TiNb6O17 showed higher capacity, lithium diffusion coefficient and high rate performance than Ti2Nb10O29. Because it is consist of larger amount of Nb5+ ions with larger size (0.64A) than that of Ti4+ ions (0.605A). As a result, it has more open lithium insertion structure and lithium diffusion coefficient than Ti2Nb10O29. But this study not exactly proposed chemical properties such as oxidation state, lithium insertion behavior of TiNb6O17. Based on above study, we have compared physical properties and electrochemical performance of new compound TiNb6O17 and TiNb2O7 which were fabricated using a solid-state reaction method. In a typical synthesis, TiO2 and Nb2O5 in the molar ratio (1:2, 1:6) were mixed with ethanol in a ball mill at 300rpm for 4h. After drying, calcination treatment is carried at 1100°C for 10h in air atmosphere. The crystal structures were determined by X-ray diffraction (XRD), rietveld refinement in order to compare lattice parameters and unit cell volume. X-ray absorption spectroscopy (XAS) was measured to confirm variation of oxidation state and lithium insertion/extraction behavior after charge and discharge. The morphologies were observed by scanning electron microscope (SEM). Finally, we investigated electrochemical performance by measuring cyclic voltammetry, galvanostatic charge-discharge curve and C-rate. Also, electrochemical impedance spectroscopy (EIS) and slow scan rate cyclic voltammetry (SSCV) were measured to compare lithium diffusion coefficients of TiNb2O7 and TiNb6O17. As the result of, TiNb6O17 exhibited better electrochemical performance with lithium diffusion coefficient, charge-discharge capacities and high rate performance than TiNb2O7.

Background and Purpose— The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis. Methods— A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment. Results— Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018–1.049), male gender (OR, 3.399; 95% CI, 2.335–4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117–2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274–2.618; P =0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105–2.010; P =0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005–5.890; P =0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS ( P Conclusions— The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

Intracranial metastatic lesions arise through a number of routes. Therefore, they can involve any part of the central nervous system and their imaging appearances vary. Magnetic resonance imaging (MRI) plays a key role in lesion detection, lesion delineation, and differentiation of metastases from other intracranial disease processes. This article is a reasoned pictorial review illustrating the many faces of intracranial metastatic lesions based on the location - intra-axial metastases, calvarial metastases, dural metastases, leptomeningeal metastases, secondary invasion of the meninges by metastatic disease involving the calvarium and skull base, direct or perineural intracranial extension of head and neck neoplasm, and other unusual manifestations of intracranial metastases. We also review the role of advanced MRI to distinguish metastases from high-grade gliomas, tumor-mimicking lesions such as brain abscesses, and delayed post-radiation changes in radiosurgically treated patients.

Host cell pathology induced by nuclear targeting of bacterial proteins has recently been identified as a pathogenic mechanism of bacteria. However, very few bacterial proteins were identified to target the nuclei of host cells. This study was designed to screen nuclear targeting proteins with nuclear localization signals (NLSs) in Helicobacter pylori using a combination of bioinformatic analysis and the Gateway recombinational cloning system. Forty-nine functional or hypothetical proteins were predicted to carry the putative NLSs among 1570 open reading frames (ORFs) of H. pylori 26695. Entire sets of 49 H. pylori ORFs were cloned for the generation of green fluorescent protein-tagged proteins using the Gateway recombinational cloning system. Twenty-six H. pylori proteins with the putative NLSs were found to target in the nuclei of COS-7 cells, whereas 23 were localized in the cytoplasm of host cells. Deletion of NLS sequences from four selected nuclear targeting proteins, urease subunit A, Omp18, secreted protein involved in flagellar motility, and response regulator, resulted in cytoplasmic localization of these mutant proteins. In conclusion, a combination of bioinformatic analysis and the Gateway cloning system was shown to be a useful tool for large-scale screening of nuclear targeting proteins with NLSs in H. pylori, which can be used to better understand the H. pylori-directed host cell pathology.

Purpose: This study analyzed the type of acute urinary retention (AUR) and evaluated the treatments used, including trial without catheter (TWOC). Materials and Methods: This study was based on 299 patients who were treated for AUR from January 2007 to August 2009. The patients were classified into the spontaneous AUR group (group S) and the precipitated AUR group (group P), in which AUR was consecutive to triggering events. The treatment modalities including TWOC, the success rate of TWOC, age, prostate-specific antigen (PSA) levels, the volume of the prostate, and the drained volume at catheterization were analyzed in each group. Results: Of 299 men with AUR, 160 (54%) had spontaneous AUR and 139 (46%) had precipitated AUR. Compared with group P, patients in group S were more likely to be treated by surgery, either immediately (16.9% vs. 3.6%, p＜0.05) or after prolonged catheterization (42.2% vs. 29.1%, p＜0.05). The success rate of TWOC was lower in men of older ages (≥70 years) and in those with enlarged prostates (≥50 ml), higher PSA levels (≥3 ng/ml), and a large drained volume at catheterization (≥1,000 ml). Conclusions: In this group of AUR patients, there were slightly more patients with spontaneous AUR (54%) than with precipitated AUR (46%). The success rate of TWOC was more than 70% regardless of the type of AUR. Although TWOC is recommended primarily in the treatment of AUR, early surgical intervention should be considered if the patient has an enlarged prostate (≥50 ml) or a large drained volume at catheterization (≥1,000 ml).

We fabricated and characterized the magnetoelectric (ME) properties of 3-0 ME composite materials comprised of the high piezoelectric voltage coefficient material, 0.9Pb(Zr0.52Ti0.48)O3-0.1 Pb(Zn1/3Nb2/3)O3 + 0.005Mn (PZT-PZN), and the magnetostrictive material, Ni0.8Zn0.2Fe2O4 (NZF). As the ME effect is generated by the product coupling between the piezoelectric properties and the magnetostrictive properties, the NZF content should be optimized for a higher ME coefficient. The dielectric constant and spontaneous polarization (P) were decreased with increasing NZF content before the percolation of the NZF particulates. However, as the NZF content exceeded the percolation content, the dielectric loss was dramatically increased due to the low resistivity of NZF. While the piezoelectric constant was decreased with increasing NZF content, the maximum magnetization was linearly increased. When we combined the piezoelectric and magnetostrictive effects, the ME composite sintered at 1200 degrees C with 20% NZF showed a maximum dE/dH of 27 mV/cm x Oe at a magnetic bias of 1240 Oe.

Expressed sequence tags (ESTs) from the Antarctic green algae Pyramimonas gelidicola were analyzed to obtain molecular information on cold acclimation of psychrophilic microorganisms. A total of 2,112 EST clones were sequenced, generating 222 contigs and 219 singletons, and 200 contigs and 391 singletons from control (4 degrees C) and cold-shock conditions (-2 degrees C), respectively. The complete EST sequences were deposited to the DDBJ EST database (http:// www.ddbj.nig.ac.jp/index-e.html) and the nucleotide sequences reported in this study are available in the DDBJ/EMBL/ GenBank. These EST databases of Antarctic green algae can be used in a wide range of studies on psychrophilic genes expressed by polar microorganisms.

Background and Purpose— Predictors of progression of intracranial atherosclerotic stenosis have not been clearly identified. We investigated whether poststroke changes in lipid profiles would affect the prognosis of symptomatic intracranial atherosclerotic stenosis. Methods— This is a substudy of Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). From 10 centers we enrolled 230 subjects with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or basilar artery. At baseline and 7 months after stroke, subjects underwent MR angiogram and assessment of cardiovascular risk factors including lipoprotein levels. Progression of intracranial atherosclerotic stenosis was determined by comparing stenosis on the baseline and follow-up MR angiograms. Results— Cilostazol treatment was more frequently seen in the nonprogression group (109 of 198 [55.1%]) than in the progression group (11 of 32 [34.4%]). At 7 months after stroke when compared with baseline, low-density lipoprotein cholesterol and total cholesterol levels decreased in both groups. However, only nonprogressors showed increase in high-density lipoprotein cholesterol levels between baseline and follow-up. Changes in apolipoprotein B/apolipoprotein A-I levels were not different between the groups, although apolipoprotein B/A-I at 7 months was higher in progressors than in nonprogressors. Remnant lipoprotein cholesterol levels decreased in nonprogressors, whereas they did not change in progressors. In multivariable analyses, after adjusting for cilostazol treatment and remnant lipoprotein cholesterol reduction or apolipoprotein B/A-I at 7 months, high-density lipoprotein cholesterol elevation remained as a significant predictor for the nonprogression. Conclusions— This is the first prospective multicenter study to demonstrate that high-density lipoprotein cholesterol elevation, along with remnant lipoprotein cholesterol reduction and low apolipoprotein B/A-I, is associated with prevention of angiographic progression of symptomatic intracranial atherosclerotic stenosis. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00130039.

This paper suggests a complete solution for thermal isolation which hinders a stable fabrication of silicon micro-structures with a large proof mass and long springs when the device is released using silicon deep etching process. Comprehensive analysis on a thermal equivalent circuit and the implementation of thin metal layers have successfully reduced a temperature rise down to 6.16 °C whereas conventional fabrication method shows 217 °C temperature rise in simulation. The reduction of the temperature rise leads to an improved spring width of 34.2 μm (20 μm without the metal layer) in case of the designed width of 40 μm. As a result, the resonant frequency of a proposed model is improved to 678 Hz while a reference model shows 439 Hz, where the simulated frequency of design is 754 Hz.

Ethanol fermentation with Saccharomyces cerevisiae was carried out in a bioreactor equipped with a sintered stainless steel filter to obtain a high cell density as well as a high productivity. With a 100 g glucose/l feed, the maximum yeast concentration was 208 g/L similar to that obtained in external membrane cell recycle cultures. However, with tapioca hydrolysates, treated with activated carbon column, the yeast concentration attained was 42g/L.

To identify characteristics of the cell-mediated immune (CMI) response to human papillomavirus-16 (HPV) E7 viral peptide pools to help the formulation of therapeutic vaccines.Prospective study. Population. Korean women.University hospital.From December 2008 to August 2010, 33 HPV-16-positive patients, seven patients exhibiting a high-risk HPV infection other than HPV-16 with grade 2/3 cervical intraepithelial neoplasm (CIN2/3), and nine healthy control donors were enrolled.CMI response to synthetic HPV-16 E7 overlapping peptide pools using the IFN-γ ELISPOT assay.The E7 sequence comprising amino acids 16-55 was a major immunogenic region. The CMI response to HPV-16 E7 is highly type-specific. The follow-up CMI response may last longer than expected after the lesion is resected.We found that the E7 sequence comprising amino acids 16-55 is a major immunogenic region that is critical for the T-cell-mediated immune response with CIN2/3 or cervical cancer. The identification of CMI responses to HPV-16 E7 peptide pools may provide insight into therapeutic vaccine trials for the control of HPV-associated diseases.

Learning Objectives After completing this course, the reader will be able to: Compare the prognostic factors for hemoglobin level in ovarian cancer patients.Explain the prognostic relationship between the duration of anemia during chemotherapy and survival in patients with advanced epithelial ovarian cancer. This article is available for continuing medical education credit at CME.TheOncologist.com Objective. To propose a measure of anemia to be used as a prognostic factor for progression-free survival and overall survival in advanced epithelial ovarian cancer patients. Patients and Methods. Seventy-six patients with International Federation of Gynecology and Obstetrics stage III and stage IV epithelial ovarian cancer who had received at least six courses of platinum- and taxane-based systemic chemotherapy and achieved clinical or pathologic complete response were included. A novel prognostic factor based on the duration of anemia was proposed and the impact of anemia on progression-free and overall survival times was analyzed by a log-rank test and a Cox proportional hazards model. Results. We introduce a binary variable, Hb1020, that takes a value of 1 if the duration of a hemoglobin (Hb) level Conclusions. Hb1020, based on the duration of anemia, is a potential prognostic factor for epithelial ovarian cancer. Using Hb1020, we will be able to administer highly optimized treatment for anemia to improve patient survival. Further independent studies are needed to confirm its prognostic role.

GaN-based light-emitting diode (LED) was fabricated on the sapphire substrate with monolithic convex microstructures (CMs) array. Using confocal scanning electroluminescence (EL), we have directly observed the strong outcoupling phenomenon of the light confined in a LED via the CMs array. This outcoupled light could be efficiently converged on the convex center through consecutive reflections at the flat area and the curved slant area of the CMs array. Compared to the conventional LED, the ray tracing simulation and far field EL results of the LED with a CM array showed efficient light extraction toward the top surface, i.e., 0-5, 40-45 and 60-65 degree by the outcoupling effect. We conclude that the outcoupled optical path via CMs is the dominant factor of the enhanced light extraction in the LED with a CM array.

Dolichoectasia is a dilatation and elongation of the arteries, usually affecting intracranial basilar and vertebral arteries. It may cause posterior circulation stroke or transient ischemic attacks independent of atherosclerotic disease. Compression of cranial nerves or brainstem leads to hemifacial spasm, trigeminal neuralgia, or brainstem dysfunction (temporary or permanent). Intracranial bleeding is another possible manifestation. In general, the mortality and morbidity is higher in patients with dolichoectasia. Progression of arterial dilatation or elongation is an ominous sign for poor prognosis. Optimal treatment for vertebrobasilar dolichoectasia is uncertain. Adequate control of blood pressure may prevent ischemic or hemorrhagic stroke. In case of ischemic stroke, antiplatelet treatment is indicated for the prevention of recurrent stroke. However, the risk of hemorrhagic stroke should be considered in patients with severe forms of dolichoectasia. Close observation and follow-up neuroimaging is recommended to monitor the progression of the disease and appearance of new ischemic or hemorrhagic lesions. Surgical decompression may be reserved for the medically intractable patients with trigeminal neuralgia or hemifacial spasm.

All the nonpolar a‐plane GaN epilayers were grown on nominally on‐axis r‐plane sapphire substrate in metalorganic chemical vapor deposition reactor. The growth rate of a‐plane GaN epilayers was controlled by TMGa flow rate, f[TMGa]. The GaN epilayer grown at high growth mode reveals striated morphology with triangular‐shaped pits with sharp corner, suggesting a relatively higher growth rate on the (11_00) m‐plane facet than (112_0) a‐plane facet. In case of low growth rate, the reason for high difference of ω tilt offset was considered by higher compressive uniaxial strain of m‐axis. Room temperature photoluminescence measurement revealed that the band‐edge emission intensity increased at high TMGa flow rate, which consider reduction in the nonradiative recombination centers.

In this work, a defect‐selective etched nanoporous GaN was formed using electrochemical etching in oxalic acid and employed as a template for the overgrowth of high quality GaN epilayers by metalorganic chemical vapor deposition. To illustrate the influence of the nanoporous GaN on the subsequent overgrown GaN epilayer, high resolution x‐ray diffraction (XRD) and transmission electron microscopy (TEM) were measured. The line‐width values of the XRD rocking curve decreased both for the (002) symmetry plane and (102) asymmetry plane. TEM observations indicated that the GaN epilayers overgrown on the nanoporous GaN templates had fewer threading dislocations due to dislocation bending and annihilation in the form of dislocation loops. Results indicate that the use of nanoporous GaN as a template is an effective way to reduce the density of threading dislocations in GaN epilayers.

In this study, we have fabricated an integrated ZnO nanorods/GaN‐based light emitting diode (LED) to achieve enhanced light emission efficiency. By a hydrothermal method assisted by pre‐formed ZnO nanodots, ZnO nanorod arrays were successfully grown on GaN LED under 50 mM zinc acetate di‐hydrate for 60 min at 150 °C. As a result, we observed vertically aligned ZnO nanorod arrays on GaN LED by scanning electron microscopy. The diameter and length of the nanorods were formed 40 to 60 nm and ∼300 nm, respectively. Compared to conventional GaN LEDs, enhanced light output of GaN LEDs with the ZnO nanorod arrays was observed.

Background Delayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea. Methods A prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay. Results Among the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival. Conclusions In Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.

A gene encoding a beta-1,3-1,4-glucanase (CelA) belonging to family 5 of glycoside hydrolases was cloned and sequenced from the Bacillus subtilis A8-8. The open-reading-frame of celA comprised 1499 base pairs and the enzyme was composed of 500 amino acids with a molecular mass of 55 kDa. The recombinant beta-1,3-1,4 glucanase was purified by GST-fusion purification system. The pH and temperature optima of the enzyme were 8.0 and 60 degrees C, respectively. The enzyme was stable within pH 6.0-9.0. It was stable up to 60 degrees C and retained 30% of its original activity at 70 degrees C for 60 min. It hydrolyzed lichenan, CMC, xylan, laminarin, avicel and pNPC, but was inactive towards cellobiose. The enzyme activity was markedly activated by Co2+ and Mn2+, but was strongly inactivated by Fe3+. The truncated gene, devoid of cellulose-binding domain (CBD) showed 60% of activity and bound to avicel.

Background: Aspirin is a proven antiplatelet agent in acute ischemic stroke, and there are no current guidelines for other antiplatelet treatments. We aimed to compare the efficacy and safety of cilostazol with aspirin in acute stroke. Methods: Patients with measurable neurological deficits (NIHSS score ≤15) within 48 h of onset were randomly assigned to cilostazol (200 mg/day) or aspirin (300 mg/day) for 90 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0–2 at 90 days. Cardiovascular events, bleeding complications, and other functional outcomes were also assessed. Statistical analysis was carried out by intention-to-treat and per-protocol bases. This trial is registered with ClinicalTrials.gov (NCT00272454). Results: In total, 458 patients were enrolled (mean age of 63 years, median NIHSS of 3), and mRS at 90 days was obtained in 447 patients. The primary endpoint was achieved in 76% (173/228) of those randomized to cilostazol and in 75% (165/219) assigned to aspirin, which supported the pre-specified non-inferiority of cilostazol to aspirin (95% CI of proportion difference: –6.15 to 7.22%, p = 0.0004). These results were also supported by per-protocol analysis (p = 0.045). Cardiovascular events occurred in 6 patients (3%) treated with cilostazol, and in 9 patients (4%) treated with aspirin (p = 0.41). Adverse events were more common in cilostazol-treated patients during the trial (91 vs. 85%, p = 0.055), while the frequencies of bleeding complications (cilostazol 11%, aspirin 13%, p = 0.43) or drug discontinuation (cilostazol 10%, aspirin 7%, p = 0.32) were not different. Conclusion: Cilostazol is feasible in acute ischemic stroke, and comparable to aspirin in its efficacy and safety.

Purpose Transcranial Doppler sonography (TCD) is commonly used for the diagnosis of middle cerebral artery (MCA) stenosis. However, TCD indices to predict distal MCA (M2) stenosis have not yet been established. We compared TCD and magnetic resonance angiography (MRA) to validate a new index for the diagnosis of M2 stenosis. Methods Consecutive patients who underwent TCD and MRA were included. Based on MRA, M2 stenosis was defined as >50% narrowing beyond the bifurcation area. TCD index of the M2/M1 ratio was defined as the ratio between the mean flow velocity (MFV) obtained at a depth of 30–44 mm (M2) and a depth of 45–65 mm (M1). Sensitivity and specificity of the M2/M1 ratio were calculated from the receiver operating characteristic curve. The diagnostic yield of elevated MFV (>80 cm/s) and asymmetry index of >30% for M2 stenosis were also investigated. Results Among the consecutive patients, 105 with M2 stenosis were compared with 123 without MCA stenosis. The M2/M1 ratio was significantly higher in the M2 stenosis group (1.10 versus 0.86, p < 0.001). Sensitivity and specificity for M2 stenosis were most satisfying when the M2/M1 ratio of 0.97 was adopted as the cutoff value. Diagnostic yield of the M2/M1 ratio was better than MFV or asymmetry index. Conclusions The M2/M1 ratio may be a highly specific parameter for assessing M2 stenosis with TCD. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:420–425, 2010

When a system is developed, Requirements Document is generated by requirement analysts and then translated to formal specifications by specifiers. If a formal specification can be generated automatically from Natural Language Requirements Document, system development cost and system fault from experts' misunderstanding will be decreased. Also, if we would like to get the higher accuracy in analysis of Requirements Document automatically, antecedent decision of pronoun is very important for elicitation of formal requirements (i.e. component, action, statement and parameters etc.) automatically from Natural Language Requirements Document via Natural Language Processing. Pronoun can be classified in personal and demonstrative pronoun. In the Requirements Document, the personal pronoun is almost not occurred so we focused on antecedent decision for a demonstrative pronoun. The final goal of this research is to generate automatically formal specifications from natural language requirements document using natural language processing to develop systems. For this, This paper, based on previous research [1], proposes the Anaphora Resolution System to decide antecedent of pronoun using Natural Language Processing from Natural Language Requirements Document in Korean.

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Epidemiological studies have demonstrated an increased risk of subsequent cancer in the patients who are diagnosed with idiopathic venous thrombosis. Cancers of the breast, lung and ovary in women and adenocarcinomas of an unknown primary cancer are most strongly associated with thrombosis. Mucin-producing cancers are most often associated with VTE and the highest rates of VTE were found for cases of ovarian cancer, but the absolute risk of cancer after thrombosis is relatively low (about 2% over the first year) and so the benefit of screening for cancer in thrombosis patients seems limited. But as this case, the association between thrombosis and occult cancer shows the importance of this association for patients who have thrombosis that is unresponsive to anticoagulant therapy. Especially, we should recognize that such patients can undergo investigation for an underlying malignancy. Diagnostic laparoscopy of an adnexal mass for confirming cancer in the acute setting of deep vein thrombosis (DVT) was performed for our patient. We report here on a case of a patient with DVT in the upper and lower extremities before the diagnosis of ovarian cancer, and we briefly review of the relevant literature.

This paper presents the new concept of RF MEMS silicon contact switch and its verification for high isolation at 50–110 GHz. A high isolation is achieved by locating the floating top contact electrode 30 µm apart from the bottom coplanar waveguide (CPW) signal line in lateral direction at initial off-state. The switch contact is realized by the dual axis movement, namely a lateral movement by comb electrodes and a following vertical movement by a bottom electrode. The actuation voltages are measured for dual axis movement. The isolation of the switch was measured at 50–110 GHz to prove the concept of isolation improvement using dual axis movement.

Neurofibromatosis Type I (NF1) is a single-gene disorder characterized by a high incidence of complex cognitive symptoms, including learning disabilities, attention deficit disorder, executive function deficits, and motor coordination problems. Because the underlying genetic cause of this disorder is known, study of NF1 from a molecular, cellular, and systems perspective has provided mechanistic insights into the etiology of higher-order cognitive symptoms associated with the disease. In particular, studies of animal models of NF1 indicated that disruption of Ras regulation of inhibitory networks is critical to the etiology of cognitive deficits associated with NF1. Animal models of Nf1 identified mechanisms and pathways that are required for cognition, and represent an important complement to the complex neuropsychological literature on learning disabilities associated with this condition. Here, we review findings from NF1 animal models and human populations affected by NF1, highlighting areas of potential translation and discussing the implications and limitations of generalizing findings from this single-gene disease to idiopathic learning disabilities.

We evaluated the efficacy and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) using paclitaxel as consolidation therapy in patients with epithelial ovarian cancer.Between November 1999 and January 2004, 18 patients with a negative second-look and 1 patient with positive peritoneal cytology only with stage Ic-IIIc epithelial ovarian cancer received consolidation intra-operative HIPEC using paclitaxel. The HIPEC was performed with open-abdomen technique, using 6 L of lactated Ringer's solution containing paclitaxel 175 mg/m(2), for 90 min in hyperthermic phase (43-44 degrees C). The survival rates were compared with 24 patients treated with conventional therapy (control group).The 8-year progression-free survival rates were 63.16% in the HIPEC-paclitaxel group and 29.17% in the control group (P = 0.027). The 8-year overall survival rates were 84.21% in the HIPEC-paclitaxel group and 25.00% in the control group (P = 0.0004). The time interval between initial treatment and HIPEC was statistically significant with respect to progression-free and overall survival in the HIPEC-paclitaxel group.HIPEC with paclitaxel during 2nd-look laparotomy is feasible and relatively safe and showed a good effect on survival. In patients with epithelial ovarian cancer who have a complete pathologic response, HIPEC with paclitaxel should be considered as a consolidation treatment option.

We compared the incidence of vaginal cuff dehiscence and other surgical complications after different modes of suturing during total laparoscopic hysterectomy (TLH), and reviewed the characteristics of patients with complications.We enrolled 248 patients undergoing TLH for benign diseases at Daejeon St Mary's Hospital of Korea from March 2007 through February 2009. We evaluated the clinical outcomes of different vaginal cuff suture techniques during TLH: the widely used interrupted figure-of-eight suture and a two-layer running suture.All operations were completed successfully by laparoscopy. Three of 248 hysterectomies (1.2%) were complicated by vaginal cuff dehiscence. One of them belonged to the two-layer running suture group, and the others belonged to the interrupted figure-of-eight suture group. However, there was no statistically significant difference in outcomes between the suture methods. One case of trocar site incisional herniation occurred. No ureteral, bladder, or major vascular injury occurred. The overall major complication rate including vaginal bleeding was 2.0% (5/248).The two-layer running suture technique was safe and effective for vaginal cuff suture during TLH, but there was no statistically significant advantage over the widely used figure-of-eight suture method. Diabetes, cigarette smoking and pelvic adhesions produced statistically significant increased risks of complication.

We cloned 2-keto-3-deoxy-gluconate kinase (KDGK), which catalyzes the phosphorylation of 2-keto-3-deoxygluconate (KDG) to 2-keto-3-deoxy-6-phophogluconate (KDPG) from Serratia marcescens KCTC 2172. The nucleotide sequence revealed a single open reading frame containing 1,208 bp and encoding for 309 amino acids, with a molecular weight of 33,993 Da. The enzyme was purified via GST affinity chromatography. The putative KdgT binding site was detected upstream of the initial codon. The KDG kinase utilized 2-ketogluconate (KG) and KDG as substrates. The optimal temperature and pH for KDGK activity were 50ºC and 8.0, respectively.

Most molecular and cellular studies of cognitive function have focused on either normal or pathological states, but recent research with transgenic mice has started to address the mechanisms of enhanced cognition. These results point to key synaptic and nuclear signalling events that can be manipulated to facilitate the induction or increase the stability of synaptic plasticity, and therefore enhance the acquisition or retention of information. Here, we review these surprising findings and explore their implications to both mechanisms of learning and memory and to ongoing efforts to develop treatments for cognitive disorders. These findings represent the beginning of a fundamental new approach in the study of enhanced cognition.

Primary fallopian tube carcinoma (PFTC) is a rare tumor that histologically and clinically resembles epithelial ovarian cancer. PFTC has a worse prognosis than ovarian cancer as it is not routinely suspected and so treatment may be delayed. The early clinical manifestations and a prompt investigation can often lead to a correct diagnosis at an early stage. The preoperative diagnosis is usually difficult, and most patients with PFTC undergo laparotomy with the presumed diagnosis of ovarian carcinoma according to the presence of an adnexal mass. PFTC can present preoperatively as a tubo-ovarian abscess and it should be considered in the differential diagnosis of acute pelvic peritonitis. PFTC should be suspected by clinicians even if the presenting symptoms are atypical. We report here on two cases of PFTC along with a brief review of the literature.

Introduction: Memory can be divided into declarative and non-declarative processes. Declarative or explicit memory is the conscious recall of knowledge about facts and events and is particularly well developed in the vertebrate brain. Non-declarative or implicit memory is the non-conscious recall of skilled behavior and other tasks and includes simple associative forms such as classical conditioning and non-associative forms such as sensitization 12. During sensitization an animal learns about the properties of a single noxious stimulus enabling the formation of a learned fear response. The cellular and molecular mechanisms that underlie the storage of implicit memory have been most extensively analyzed in the gill- and siphon-withdrawal reflex of marine mollusk Aplysia. This organism offers several unique advantages for the study of learning and memory, such as a relatively simple and tractable central nervous system, large identified neurons, and well-characterized neural circuits related to specific behaviors that can be modified by learning 3. In Aplysia, sensitization of the gill- and siphon-withdrawal reflex is induced by a strong stimulus to its tail 4. Repetitive stimuli produce long-term sensitization that lasts days to several weeks whereas a single stimulus induces short-term sensitization lasting only minutes to a few hours 56. These two forms of memory can be reconstituted in dissociated sensory-motor neuron cultures by the modulatory neurotransmitter serotonin (5-HT) 7. A single pulse of 5-HT induces short-term facilitation (STF), whereas five applications of 5-HT induce long-term facilitation (LTF) 8. In contrast to the short-term synaptic changes, which involve covalent modifications of preexisting molecules leading to an alteration of preexisting synaptic connections, long-term synaptic changes require the synthesis of new macromolecules including mRNAs and proteins 891011. In addition, long-term changes are accompanied by structural modifications including the growth of new synaptic connections between the sensory neurons and their target motor neurons 1213. These features of long-term, learning-related synaptic plasticity, are highly conserved throughout evolution of the nervous system. A variety of experimental systems, ranging in complexity from Aplysia to rodents, have been used to examine the molecular mechanism underlying long-term synaptic changes 121011. In this review, we focus on the role of nuclear transcription factors in the presynaptic sensory neurons of Aplysia during LTF. A model system for examining the molecular biology of long-term memory – the Aplysia sensory to motor neuron synapse: In sensory-motor neuron cultures, STF and LTF can be induced by applying 5-HT. One pulse of 5-HT activates PKA and PKC, probably via the activation of different types of G proteins. Activated PKA phosphorylates a potassium channel (S channel), resulting in the elevated influx of calcium leading to an increase in membrane excitability and spike broadening. PKC facilitates the mobilization of synaptic vesicles to the presynaptic active zone. Together, these kinases enhance transmitter release by modifying preexisting molecules 14151617. LTF induced by repeated pulses of 5-HT requires the synthesis of both new proteins and RNAs. Inhibitors of protein or RNA synthesis selectively block LTF, but not STF when applied within a critical time window that encompasses the training protocol 8. Analogous to STF, cAMP-dependent protein phosphorylation is also involved in LTF and cAMP analogs induce LTF 18. Bacskai and colleagues first demonstrated that in response to repeated pulses of 5-HT the catalytic subunit of PKA translocates into the nucleus of the presynaptic sensory neuron to activate CREB-1 19. Repeated pulses of 5-HT also induce phosphorylation of MAPK and the activated MAPK also translocates into the nucleus of the sensory neuron where it removes the repressive influence of ApCREB-2 20. Dash et al. provided the first evidence of the involvement of cAMP-inducible genes expressed during LTF in Aplysia. Microinjection of CRE (cAMP-responsive element) oligonucleotides into the nucleus of sensory neurons selectively blocked 5-HT-induced LTF without affecting short-term changes 21. These data first suggested that LTF requires the activation of cAMP-inducible genes, and that CRE oligonucleotides prevent interactions between CRE-binding protein (CREB)-related transcription factors and these genes. Using a newly developed gene transfer technique, Kaang and colleagues next showed directly that four or more pulses of 5-HT stimulate CRE-mediated gene expression. Moreover, transcription induced by 5-HT requires the phosphorylation of CREB on Ser119 by PKA 22. Indeed Bartsch et al. went on to show that injection of phosphorylated CREB into the sensory neuron can by itself initiate the long-term process 23. Collectively these results suggested that a signaling axis composed of cAMP-PKA-CREB participates in the molecular cascade leading to the expression of LTF. Subsequent studies confirmed the involvement of a number of related downstream molecules in the induction of LTF, including CAMAP, ApC/EBP, and ApAF. ApCREBs – Central modulators of LTF: In Aplysia, ApCREB1a and ApCREB2 have been characterized as an activator and repressor of LTF, respectively. ApCREB2 is a homolog of mammalian CREB2/ATF4 which is also identified as a transcriptional repressor 2425. Inhibition of ApCREB2 by injecting antiserum or double-strand RNA (dsRNA) into sensory neurons allowed a single pulse of 5-HT to produce translation-dependent LTF and the growth of new synapses 2526. Conversely, injection of an anti-CREB1 antibody into sensory neurons selectively blocked LTF. Moreover, introduction of the phosphorylated transcriptional activator, ApCREB1a, was sufficient to induce LTF. 23. PKA-mediated activation of ApCREB1a stimulated the downstream transcription factor, ApC/EBP, via recruiting CBP and subsequently facilitating histone acetylation 27. For activation of downstream gene expression by ApCREB1a, the inhibitory constraint of ApCREB2 must be relieved. This de-repression is mediated by the phosphorylation of ApCREB2 by nuclear translocated MAPK 2028. Together these results suggest that LTF requires not only the activation of memory-enhancer genes but also the inactivation of memory-suppressor genes. Moreover, CREBs appear to play a critical role in maintaining the dynamic balance between these positive and negative factors. CREB, a basic leucine zipper transcription factor, is also reported to be involved in long-term plasticity in the nervous systems of other organisms, including fly and mouse. In transgenic Drosophila, expression of dCREB2b led to the blockage of long-term memory, whereas dCREB2a facilitated memory 2930. Similarly, CREB-deficient mice displayed impaired long-term potentiation (LTP) and long-term memory 31. The threshold for late phase LTP was lowered in the hippocampus from mice expressing the constitutively active form of CREB 32. ApC/EBP – A key downstream gene for LTF: In view of the critical roles of CREB in memory consolidation, characterization of its downstream effectors has been a major focus of research in both invertebrate and vertebrate learning models 333435. In Aplysia the CCAAT enhancer-binding protein (ApC/EBP), an immediate early gene during the consolidation phase of LTF, was found by Alberini et al. to be a downstream target of ApCREB1 36. The C/EBP family of transcription factors contains a basic leucine-zipper domain. Specifically, expression of ApC/EBP is rapidly induced in response to 5-HT treatment and this occurs to an immediate early gene in a translation-independent manner 36. Inhibition of ApC/EBP by injection of ERE oligonucleotides, ApC/EBP antiserum or dsRNA into the sensory neurons in sensory-to-motor neuron cultures during a critical time window blocked 5-HT-induced LTF 3637. Moreover, a single pulse of 5-HT which normally induces only STF, produces LTF when ApC/EBP is overexpressed in the sensory neuron 37. These findings support the idea that ApC/EBP is both necessary and sufficient to consolidate short-term memory into long-term memory. However, since overexpression of ApC/EBP alone does not induce LTF, an additional component must be required for converting STF to LTF. Lee and colleagues used the RNA interference technique designed to block the function of ApC/EBP and similarly found that this blocked LTF in Aplysia 2637. Moreover, in addition to these studies in Aplysia, C/EBPβ and -δ are induced in the rodent hippocampus after inhibitory avoidance learning, suggesting that C/EBPs are highly conserved molecular components of the CREB-dependent signal pathway involved in memory consolidation 38. ApC/EBP is also known to be induced by the neural activity. The depolarization-induced ApC/EBP induction appears to be mediated by transient induction of the nucleolar protein, ApLLP, which was recently characterized as a novel transcription factor induced by neural activity in Aplysia sensory neuron 39. Kim et al. also showed that a single pulse of 5-HT can produce LTF when the synapse is pretreated with high potassium solution. LTF induced by this protocol was completely blocked by the injection of anti-ApLLP or anti-ApC/EBP antibody 39. One important feature of immediate early genes such as ApC/EBP, is that their expression is tightly regulated within a specific and narrow time window. ApC/EBP mRNA displays a peak expression at 2 h after induction that rapidly returns to the basal levels 36. Recent studies have found that the ApC/EBP 3' UTR contains putative AU-rich element (ARE) sequences which are cis-acting regulatory elements commonly found in labile mRNAs 40. Different sets of ARE binding proteins may interact with ApC/EBP mRNA to regulate its stability and/or translatability 414243. Yim et al. found that an ARE binding protein, ApELAV binds to and stabilizes ApC/EBP mRNA, suggesting that post-transcriptional regulation of ApC/EBP may also play an important role during LTF 40. ApAF – A binding partner for both ApCREB2 and ApC/EBP: Both ApC/EBP and ApCREBs are transcription factors containing the basic leucine zipper (bZIP) domain in the C-terminus. This domain is involved in both DNA binding and multimerization 232544. Using the bZIP domain of ApC/EBP as bait, Bartsch and colleagues screened a cDNA library to identify additional transcription factors acting downstream of ApCREB1. In this fashion, they cloned a novel transcription factor ApAF, whose activity is regulated by PKA 45. In contrast to ApC/EBP, which is induced in response to 5-HT, ApAF is a constitutively expressed gene. Interestingly, an in vitro binding assay revealed that ApAF interacts with both ApCREB2 and ApC/EBP, but not ApCREB1. Inhibition of ApAF by injection of a specific antibody blocked LTF induced by repeated pulses of 5-HT, suggesting that ApAF is necessary for LTF. Previously, it had been found that injection of phosphorylated ApCREB1a by itself or anti-ApCREB2 antibody combined with a single pulse of 5-HT induced LTF that phenocopied 5 × 5-HT-induced LTF 2325. ApAF is involved in both forms of LTF: an anti-ApAF antibody blocked LTF induced by phosphorylated CREB1a as well as that by ApCREB2 antibody injection paired with one pulse of 5-HT. Moreover, overexpression of ApAF enhanced both LTF induced by 5 × 5-HT and ApCREB2 antibody with 1 × 5-HT 45. Thus, ApAF may be a potential memory enhancer gene downstream of ApCREB1 and ApCREB2. To determine whether ApC/EBP is the critical partner of ApAF, Lee and colleagues investigated the effects of silencing the ApAF gene on LTF induced by ApC/EBP overexpression paired with one pulse of 5-HT 46. ApAF inhibition by dsRNA completely blocked LTF induced by both ApC/EBP overexpression and 5 × 5-HT. In combination with a single pulse of 5-HT, the ApAF-ApC/EBP heterodimer produced LTF, even in the absence of CRE- and CREB-mediated gene expression. These results provide direct evidence that the ApAF-ApC/EBP heterodimer is a key downstream effecter of ApCREB. Furthermore, ApAF enhances ERE-mediated gene expression by cooperating with ApC/EBP and phosphorylation at Ser-266 of ApAF by PKA is required for activation of the ApAF-ApC/EBP heterodimer during 5-HT-induced LTF 46. These data explain why ApC/EBP overexpression in the absence of 5-HT could not convert STF to LTF. The single pulse of 5-HT in ApC/EBP-induced LTF possibly functions in triggering the phosphorylation of ApAF by activated PKA. Lee et al. also examined the role of Ser-266 phosphorylation of ApAF in the relief of ApCREB2 repression 46. Overexpression of a dominant negative mutant of ApAF which cannot be phosphorylated at Ser-266 completely blocked both LTF induced by 5 × 5-HT and that by the ApC/EBP overexpression combined with 1 × 5-HT. Moreover, this mutant restored ApCREB1-mediated gene expression and 5-HT-induced LTF repressed by ApCREB2 as efficiently as its wild type counterpart, suggesting that Ser-266 phosphorylation of ApAF is not required to relieve ApCREB2 repression 46. However, the precise signaling pathway that regulates the interactions between ApAF and ApCREB2 remains to be characterized. Taken together, these studies of ApAF indicate that transcriptional regulation of memory consolidation is quite diverse and can recruit both direct and indirect interactions between transcription factors. CAMAP – A retrograde signal from the membrane to the CRE promoter: Neurons display a distinct highly differentiated form which consists of three basic compartments: a cell body or soma which contains the nucleus harboring genomic information and two types of processes axons and dendrites. Dendrites are input elements of the neuron. Together with the cell body they receive synaptic contacts from other neurons. Axons are the output elements of the neuron. The branches of each axon form numerous synaptic connections with other neurons. It is well known that long-term synaptic plasticity requires the synthesis of both new RNAs and proteins. This raises three fundamental questions: 1) Does synaptic plasticity always occur in a cell-wide manner? 2) If not, how does the nucleus identify the correct synapses for delivery of gene products to achieve synapse-specific plasticity? 3) Is the nucleus the only site responsible for transcription and translation? To address the question of synapse specificity, Martin and her colleagues developed a new culture system in Aplysia consisting of a bifurcated Aplysia sensory neuron which makes synapses with two spatially separated motor neurons in culture 47. They found that 5-HT can induce branch-specific LTF that was dependent on CREB activation in the nucleus of presynaptic sensory neuron. Branch-specific LTF was also accompanied by synapse-specific growth of new sensory neuron synapses. These studies highlight the importance of a retrograde signal propagating from the stimulated synaptic site to the nucleus. The CREB-downstream molecules produced in the cell body can be captured by other synapses which have been tagged or marked. This synaptic mark is PKA-dependent; however, rapamycin-dependent local protein synthesis is required for LTF to persist for more than 72 h 4748. Further molecular studies have dissected the characteristics of the retrograde signal and the synaptic mark. An early step in the growth of new synaptic connections is the internalization of an NCAM immunoglobulin-related cell adhesion molecule – apCAM. In recent studies Lee et al. addressed the question: How does this internalization of apCAM relate to the activation of transcription? Lee found that CAMAP is an interacting partner of apCAM in the sensory neuron. CAMAP serves as a transcriptional co-activator that is also a crucial retrograde signaling molecule involved in the initiation phase of LTF 49. ApCAM is down-regulated upon application of 5-HT 50. Serotonin leads to clathrin-mediated endocytosis of the transmembrane isoform of apCAM (TM-ApCAM) from the surface membrane of sensory neurons and this internalization depends on phosphorylation of its cytoplasmic tail by MAPK 5152. When TM-apCAM was overexpressed in sensory neurons, five pulses of 5-HT failed to produce synaptic facilitation or enhancement of synaptic growth, suggesting that down-regulation of apCAM is required for both LTF and the presynaptic structural changes induced by 5-HT 53. Whereas MAPK is known to be involved in apCAM downregulation, the subcellular mechanisms responsible for apCAM internalization remain to be characterized. CAMAP (apCAM-Associated Protein) was cloned by yeast two-hybrid screening using the cytoplasmic tail of TM-ApCAM as bait 49. CAMAP is colocalized with apCAM at the surface of the plasma membrane in the basal state and is translocated to the nucleus of sensory neuron after treatment with 5-HT. Nuclear translocation and dissociation from apCAM are modulated by PKA-mediated phosphorylation of CAMAP. A phosphorylation-mimicking mutant of CAMAP can dissociate from apCAM and translocate to the nucleus in the absence of 5-HT stimulation 49. How does CAMAP translocate to the nucleus? Importins, which transport cargo molecules from the cytosol to nucleus, are critically involved in synaptic plasticity in both Aplysia and rodent brain 54. This raises the possibility that importin may transport CAMAP into the nucleus of the sensory neuron. In view of nuclear translocation of CAMAP from the plasma membrane, Lee et al. suggested that CAMAP acts as a retrograde signaling molecule in the induction of LTF. To act as a retrograde signal, a molecule must meet several criteria, specifically, 1) it should translocate into the nucleus from the synaptic site in response to stimuli that induce synaptic plasticity, such as LTF and LTP, 2) it should play a specific function in the nucleus, and 3) blockage of its translocation and function should inhibit the long-term synaptic change. CAMAP appears to fulfill all of the above requirements. First, CAMAP translocates to the nucleus following both cell-wide and synapse-specific applications of 5-HT. After 5-HT treatment, the mobility of CAMAP is significantly increased at the distal neurites of sensory neurons. Second, CAMAP binds to ApCREB1 in the nucleus, where it acts as a transcriptional co-activator that can induce ApC/EBP expression. Interestingly, the N-terminal region, but not full-length CAMAP displayed transcriptional activity. The C-terminus of CAMAP appears to act as an autoinhibitory domain. This inhibitory clamp is relieved by PKA phosphorylation of CAMAP. Details of the molecular mechanisms that underlie the co-activator function of CAMAP and the PKA phosphorylation-dependent restoration of transcriptional activity of the N-terminus of CAMAP are currently not known. Finally, blockage of CAMAP expression by dsRNA completely suppresses 5-HT-induced ApC/EBP upregulation and LTF. Moreover, CAMAP dsRNA blocks synapse-specific LTF induced by local application of 5-HT at the synapse. Taken together, these results indicate that CAMAP is a critical retrograde messenger in the initiation of LTF. The precise role of CAMAP in the internalization of apCAM remains unclear. We have recently found that overexpression of mutant CAMAP that cannot be phosphorylated by PKA impaired the 5-HT-induced internalization of apCAM 49. This finding suggests that CAMAP tethers apCAM to the plasma membrane in the basal state, and that the phosphorylation and nuclear translocation of CAMAP are necessary for the subsequent down-regulation of apCAM. Chromatin alteration and epigenetic changes in gene expression with memory storage: Although epigenetic mechanisms were widely known to be involved in the formation and long-term storage of cellular information in response to transient environmental signals, the discovery of their putative relavance in adult brain function is relatively recent 2755. The epigenetic marking of chromatin, such as histone modification, chromatin remodeling and the activity of retrotransposons, may have long-term consequences in the transcriptional regulation of specific loci involved for long-term synaptic changes 56. The contribution of histone tail acetylation, a modification that favors transcription and is associated with active loci, to LTF formation was first revealed by the study of Guan et al. in Aplysia neurons 27. This study found that both facilitatory and inhibitory stimuli bidirectionally alter the acetylation stage and structure of promoters driven by the expression of genes involved in the maintenance of LTF, such as ApC/EBP. It also demonstrated that enhancing histone acetylation with histone deacetylase (HDAC) inhibitors facilitates the induction of LTF (Guan et al. 2002). HDAC inhibitors have recently been shown to have similar effects during L-LTP in the Schaffer collateral pathway of mammals and to enhance memory formation in hippocampus-dependent tasks 5758596061. HDAC inhibitor, sodium butyrate, has been shown to induce the growth of new dendrites and synapses, which might be an underlying mechanism of its memory enhancing effects 61. Moreover, mice with reduced histone acetyltransferase activity, such as different mouse models for Rubinstein-Taybi mental retardation syndrome, have deficits in both long-lasting forms of memory and LTP 57586263. These results indicate that critical chromatin changes occur during the formation of long-term memory and that these changes are required for the stable maintenance of these memories. Perspectives During the last decade molecular studies have increased our understanding of the signaling and regulatory mechanisms that underlie LTF (Figure 1). Several research groups have generated a variety of cellular models of long-term memory by investigating 5-HT-induced LTF and other forms of long-term synaptic changes induced by different stimulation paradigms in Aplysia. Figure 1 Schematic model of signaling pathways underlying long-term facilitation in Aplysia sensory neuron Schematic model of signaling pathways underlying long-term facilitation in Aplysia sensory neuron. The repeated treatments with neurotransmitter 5-HT activate a G-protein coupled receptor that stimulates adenylyl cyclase, which in turn activates PKA. MAPK are also activated and translocates into the nucleus. At the synaptic site, PKA stimulates the nuclear translocation of the retrograde signal molecule CAMAP via phosphorylating its Ser148. This phosphorylation results in both the dissociation from TM-apCAM and the restoration of its transcriptional activity from autoinhibition. In the nucleus, MAPK phosphorylates CREB2 which represses CREB1 and ApAF in the absence of 5-HT. Once freed from CREB2 and stimulated by PKA, CREB1 forms a homodimer to activate the downstream target gene, ApC/EBP. Translocated CAMAP acts as a co-activator of CREB1. ApC/EBP interacts with ApAF that is activated by PKA to form a core downstream effector of CREB1. ApC/EBP-ApAF heterodimer induces the late genes which are critical for the consolidation and maintenance of LTF. Robust neural activity induces and activates the transcription factor, ApLLP in the nucleus in a calcium-dependent manner. ApLLP induces ApC/EBP expression and lowers the threshold for LTF induction. Elucidating the downstream molecule of ApC/EBP remains to be challenged. SNS, strong noxious stimulus. Recently, operant conditioning was demonstrated in the gill-withdrawal and feeding behavior in Aplysia and an electrophysiological study revealed that operant and classical conditioning of feeding behavior differentially modify the intrinsic excitability of an identified neuron 646566. PolyADP-ribose-polymerase 1 (PARP1) facilitates the transcription of long-term memory related genes by decondensing chromatin structure in neurons that mediate operant conditioning 67. However, the transcription factors involved in this behavioral modification are yet to be identified. Interestingly, ApC/EBP is the common downstream molecule of the novel transcription factors, ApLLP and CAMAP. ApC/EBP, which pairs with ApAF, could activate the transcription of effector genes critically involved in the consolidation and maintenance of long-term memory 36. Genes encoding structural proteins, such as clathrin light chain and the chaperon BiP were identified as late effector genes 6869. The elongation factor 1 alpha was also suggested to be essential for maintaining newly formed synapses 70. However, the number of late genes identified thus far represents only a beginning. Since the DNA-binding motifs of ApC/EBP and ApAF homodimer or heterodimer have been analyzed, completion of the ongoing Aplysia genome sequencing project should facilitate the identification of other novel late effector molecules 45. Recently, advances have also been made in clarifying the molecular mechanisms that contribute to learning-related synaptic plasticity in the mammalian brain, particularly those that underlie the induction and expression of LTP and LTD 7172. When it comes to transcriptional regulation, however, our current understanding is far from complete. Aplysia was the first organism in which cAMP was shown to play a critical role in learning-related synaptic plasticity 2873. Since signaling cascades that underlie the expression of long-term memory are surprisingly well conserved throughout the species, insights from the molecular studies of Aplysia should provide an important foundation for future studies into the transcriptional regulation of memory formation in the more complex mammalian brain. Authors' contributions: All authors participated in developing the ideas, the writing, discussion and integration of the information. All authors read and approved the final manuscript.

Search volume of cruising planktivorous fish was calculated based on its detailed behavior Th examine the factors influencing search volume, a series of experiments were conducted by varying ambient conditions, such as structural complexity light intensity and turbidity Pseudorasbora parva were used in experiment as predator and Daphnia pulex was selected as prey The shape of scanning area of P parva showed elliptic and the search volume changed drastically depending on ambient conditions. Compared with the results of previous foraging model, the search volumes of the fish under previous study were larger (1.2 to 2.4 times) than those from our study These results on the changes in feeding rate can be useful in determining microhabitat requirement of P parva and othercyprinids with a similar foraging behavior The calculated search volume is compared with other foraging model andthe effect of zooplankton-planktivore interactions on aquatic ecosystem is discussed.

Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) has demonstrated favorable clinical outcomes in a 3-6 h window in patients selected with perfusion/diffusion mismatch. However, the advantages of combined IV and intraarterial (IA) thrombolysis after 3 h of stroke onset are unexplored.Acute ischemic stroke patients with persistent occlusion of intracranial large arteries were screened prospectively for thrombolysis by evaluating perfusion/diffusion mismatch on MRI. The IV rt-PA was initiated within 3-6 h, and additional urokinase (UK) was then administered via the IA route after angiography.Four patients had middle cerebral artery occlusion and one patient had an internal carotid artery occlusion. The median time from the symptom onset to the initiation of IV therapy and to the initiation of IA treatment was 215 +/- 30 min and 292 +/- 41 min, respectively. The median National Institutes of Health Stroke Scale (NIHSS) scores were as follows: initial, 13; immediately after IA treatment, 8; at 24 h, 5; and at 7 days, 3. The Thrombolysis in Myocardial Infarction (TIMI) score after the completion of thrombolysis was 2-3. Four patients without intracerebral hemorrhage recovered completely or exhibited mild disability and one patient with hemorrhage also demonstrated a favorable outcome.This preliminary result suggests that if a significant perfusion/diffusion mismatch on MRI is identified, a sequential combination thrombolysis of IV rt-PA and IA UK is potentially beneficial in moderate to severe acute ischemic stroke patients who are treated within 3-6 h after symptom onset.