Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Acceptable compression ratio of full-field digital mammography using JPEG 2000.

AIM: To estimate the acceptable compression ratio of full-field digital mammography (FFDM) using the Joint Photographic Experts Group (JPEG) 2000 compression algorithm. MATERIALS AND METHODS: Eighty cases that included images of 40 masses (20 benign, 20 malignant) and 40 microcalcifications (20 benign, 20 malignant) were collected. The images were compressed to five different lossy ratios: 20:1, 40:1, 60:1, 80:1, and 100:1, and four radiologists independently determined whether the compressed group was distinguishable from the control group. The ratio of the compressed group that was rated indistinguishable from the control group was compared for each reviewer, and the results were analysed for agreements of three or more reviewers. RESULTS: The ability to distinguish the compressed image from the control group is given as a range across the four reviewers: 0-1.3% (0/80 to 1/80) of the 20:1, 0-2.5% (0/80 to 2/80) of the 40:1, 5-7.5% (4/80 to 6/80) of the 60:1, 10-37.5% (8/80 to 30/80) of the 80:1, and 30-87.5% (24/80 to 70/80) of the 100:1. For three compression groups (20:1, 40:1, and 60:1), three or more reviewers agreed that there was a distinguishable difference for 0/80, 0/80, and 3/80 images, respectively. Thus, the compressed images do not differ significantly from the control group (p>0.05). However, the 80:1 and 100:1 compressed images were different for 9/80 and 29/80 images, respectively, which is significantly different from the control group (p<0.05). CONCLUSION: The lossy 60:1 compression ratio for FFDM is visually identical to the control image and, therefore, potentially acceptable for primary interpretation.

Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice.

Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.

Increased expression of Toll-like receptor 5 during progression of cervical neoplasia.

The purpose of this study was to determine whether Toll-like receptor 5 (TLR5) expression was associated with disease progression in cervical neoplasia. TLR5 expression was evaluated by immunohistochemistry (IHC) in 55 formalin-fixed paraffin-embedded cervical tissues; 10 normal cervical specimens, 9 low-grade cervical intraepithelial neoplasias (CINs), 12 high-grade CINs, and 24 invasive squamous cell carcinomas (ISCCs). TLR5 expression was also evaluated at the RNA level, in fresh, frozen cervical carcinoma tissues by real-time quantitative RT-PCR. TLR5 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathologic grade in the following order: low-grade CIN less than high-grade CIN less than ISCC (P < 0.001). Immunohistochemical staining showed that TLR5 expression was undetectable (80%) or weak (20%) in normal cervical squamous epithelial tissues. However, moderate expression was detected in 33.3% of low-grade CIN (3/9), 41.7% of high-grade CIN (5/12), and 45.8% of ISCC (11/24). Strong expression was detected in as much as 33.3% of high-grade CIN (4/12) and 50% of ISCC (12/24). Contrary to IHC results, real-time quantitative RT-PCR revealed that TLR5 expression in tumors was not statistically different compared to normal cervical tissues (P = 0.1452). The IHC result suggests that TLR5 may play a significant role in tumor progression of cervical neoplasia and may represent a useful marker for malignant transformation of cervical squamous cells.

Stable microwave coaxial cavity plasma system at atmospheric pressure.

We present a systematic study of the development of a novel atmospheric microwave plasma system for material processing in the pressure range up to 760 torr and the microwave input power up to 6 kW. Atmospheric microwave plasma was reliably produced and sustained by using a cylindrical resonator with the TM(011) cavity mode. The applicator and the microwave cavity, which is a cylindrical resonator, are carefully designed and optimized with the time dependent finite element Maxwell equation solver. The azimuthal apertures are placed at the maximum magnetic field positions between the cavity and the applicator to maximize the coupling efficiency into the microwave plasma at a resonant frequency of 2.45 GHz. The system consists of a magnetron power supply, a circulator, a directional coupler, a three-stub tuner, a dummy load, a coaxial cavity, and a central cavity. Design and construction of the resonant structures and diagnostics of atmospheric plasma using optical experiments are discussed in various ranges of pressure and microwave input power for different types of gases.

Spatio-temporal analysis of molecular delivery through the blood-brain barrier using focused ultrasound.

The deposition of gadolinium through ultrasound-induced blood-brain barrier (BBB) openings in the murine hippocampus was investigated. First, wave propagation simulations through the intact mouse skull revealed minimal beam distortion while thermal deposition simulations, at the same sonication parameters used to induce BBB opening in vivo, revealed temperature increases lower than 0.5 degrees C. The simulation results were validated experimentally in ex vivo skulls (m = 6) and in vitro tissue specimens. Then, in vivo mice (n = 9) were injected with microbubbles (Optison; 25-50 microl) and sonicated (frequency: 1.525 MHz, pressure amplitudes: 0.5-1.1 MPa, burst duration: 20 ms, duty cycle: 20%, durations: 2-4 shots, 30 s per shot, 30 s interval) at the left hippocampus, through intact skin and skull. Sequential, high-resolution, T1-weighted MRI (9.4 Tesla, in-plane resolution: 75 microm, scan time: 45-180 min) with gadolinium (Omniscan; 0.5 ml) injected intraperitoneally revealed a threshold of the BBB opening at 0.67 MPa and BBB closing within 28 h from opening. The contrast-enhancement area and gadolinium deposition path were monitored over time and the influence of vessel density, size and location was determined. Sonicated arteries, or their immediate surroundings, depicted greater contrast enhancement than sonicated homogeneous brain tissue regions. In conclusion, gadolinium was delivered through a transiently opened BBB and contained to a specific brain region (i.e., the hippocampus) using a single-element focused ultrasound transducer. It was also found that the amount of gadolinium deposited in the hippocampal region increased with the acoustic pressure and that the spatial distribution of the BBB opening was determined not only by the ultrasound beam, but also by the vasculature of the targeted brain region.

Taste and odour issues in South Korea's drinking water industry.

This paper reviews taste and odour (T&O) issues of South Korea's water industry. For this purpose, an overview of the water supply systems and drinking water standards is presented and some results from citizen surveys for customer satisfaction are included. A case study is presented in which the water intake was shifted from inside a main reservoir to a downstream location due to T&O problems. It is true that the South Korean water industry has long relied on the tolerance of consumers for periodic T&O events. Recently the South Korean water industry has become aware that the T&O problems are at the centre of consumers' concerns and has taken several positive approaches. These include monitoring T&O events using sensory and instrumental methods, installation of a baffled-channel PAC contactor and application of advanced water treatment processes.

Developing new automated alternation flicker using optic disc photography for the detection of glaucoma progression.

PurposeTo evaluate a progression-detecting algorithm for a new automated matched alternation flicker (AMAF) in glaucoma patients.MethodsOpen-angle glaucoma patients with a baseline mean deviation of visual field (VF) test>-6 dB were included in this longitudinal and retrospective study. Functional progression was detected by two VF progression criteria and structural progression by both AMAF and conventional comparison methods using optic disc and retinal nerve fiber layer (RNFL) photography. Progression-detecting performances of AMAF and the conventional method were evaluated by an agreement between functional and structural progression criteria. RNFL thickness changes measured by optical coherence tomography (OCT) were compared between progressing and stable eyes determined by each method.ResultsAmong 103 eyes, 47 (45.6%), 21 (20.4%), and 32 (31.1%) eyes were evaluated as glaucoma progression using AMAF, the conventional method, and guided progression analysis (GPA) of the VF test, respectively. The AMAF showed better agreement than the conventional method, using GPA of the VF test (κ=0.337; P<0.001 and κ=0.124; P=0.191, respectively). The rates of RNFL thickness decay using OCT were significantly different between the progressing and stable eyes when progression was determined by AMAF (-3.49±2.86 µm per year vs -1.83±3.22 µm per year; P=0.007) but not by the conventional method (-3.24±2.42 µm per year vs -2.42±3.33 µm per year; P=0.290).ConclusionsThe AMAF was better than the conventional comparison method in discriminating structural changes during glaucoma progression, and showed a moderate agreement with functional progression criteria.

Overexpression of the thymosin beta-10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis.

To understand the molecular changes during ovarian cancer development, we profiled differentially expressed genes in five paired normal and cancerous ovarian tissues. Among the genes that showed differential expression, thymosin beta-10 expression was decreased in four of five cancer tissues. The decreased level of expression was confirmed by Northern. To investigate the gene's functional role in ovarian cancers, we constructed an adenovirus vector expressing thymosin beta-10 and used it to infect ovarian cancer cell lines PA-I and SKOV3. The infected cells showed disrupted F-actin stress fibers, markedly decreased cell growth, and a high rate of apoptosis. Thus, because loss of thymosin beta-10 expression may contribute to the development of a subset of ovarian cancers, restoration of thymosin beta-10 expression may be a new strategy for ovarian cancer treatment.

Identification of a variant estrogen receptor lacking exon 4 and its coexpression with wild-type estrogen receptor in ovarian carcinomas.

By means of reverse transcription-PCR we have identified an alternatively spliced mRNA coding for a variant estrogen receptor (ER) that lacks exon 4 (ERDelta4) and is coexpressed with the wild-type ER mRNA in ovarian carcinomas. Furthermore, Western blot analysis revealed the expression of the ERDelta4 protein in normal as well as neoplastic ovarian tissues along with the wild-type ER, although the relative amounts of the wild-type ER and ERDelta4 proteins varied. The trans-activational properties of this variant were studied in ER-negative COS1 cell lines by cotransfection of the ERDelta4 expression vector and a reporter gene containing the estrogen response element. The ERDelta4 protein was not able to activate transcription of a reporter gene. However, it inhibited estrogen-dependent transcriptional activation in a dominant negative fashion when it was cotransfected with the wild-type ER and reporter plasmid. Because it has been shown that ERDelta4 is not able to bind to its response element, the observed inhibitory effect probably occurs through protein-protein interactions. Although several variants of the ER have been described from cancerous cells, none has been identified in ovarian tissues, and ERDelta4 is the only isoform detected in normal tissues. These results may have implications for understanding the physiological role of ERDelta4 in normal cells, because it may affect the function of the wild-type ER, depending on the level of the variant ER protein relative to that of the wild-type ER.

Aberration correction by nonlinear beam mixing: generation of a pseudo point sound source.

Nonlinear beam mixing with microbubbles was explored to create a pseudo point source for aberration correction of therapeutic ultrasound. A damping coefficient for a bubble driven by a dual frequency sound field was derived by revisiting Prosperetti's linearized damping model. As a result, the overall damping term for dual frequency was obtained by linear summation of two damping terms for each frequency. The numerical simulation based on the bubble model suggests that the most efficient size range to generate a 1 MHz frequency from 4 MHz and 5 MHz sound sources is 2.6 to 3.0 microm. Furthermore, this size range constitutes the primary distribution of a specific ultrasound contrast agent. When a chamber of 0.1% of the diluted agent is sonified by 4 MHz and 5 MHz sound beams with 80 degrees incident angle between them, an approximately 100 Pa, 1 MHz difference frequency signal can be measured approximately 10 cm away. In addition, the received 1 MHz difference frequency signal shows omni-directional characteristics, even though the overlap zone of the two sound beams is on the order of the difference frequency wavelength. Therefore, the induced sound source can be considered as a pseudo point source and is expected to be useful for aberration correction for therapeutic ultrasound.

Ciclopirox prevents peroxynitrite toxicity in astrocytes by maintaining their mitochondrial function: a novel mechanism for cytoprotection by ciclopirox.

Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely prevents the increased death in glucose-deprived astrocytes exposed to 3-morpholinosydnonimine (SIN-1, a peroxynitrite-releasing reagent). The increased vulnerability was in good correlation with the peroxynitrite-evoked decrease of mitochondrial transmembrane potential (MTP) in astrocytes. A simultaneous exposure to glucose deprivation and SIN-1 rapidly depolarized MTP and depleted ATP in astrocytes. Inclusion of ciclopirox initially increased the MTP, maintained it high, and blocked the ATP depletion in glucose-deprived SIN-1-treated astrocytes. However, ciclopirox did not prevent the depletion of reduced glutathione in glucose-deprived SIN-1-treated astrocytes. Consistently, ciclopirox did not scavenge various kinds of oxidants including peroxynitrite, nitric oxide, superoxide anion, hydrogen peroxide and hydroxyl radical. Ciclopirox has been experimentally used as a cell cycle G1/S phase transition blocker (Hoffman et al., Cytometry 12 (1991) 26). Flow cytometry analysis, however, showed that the cytoprotective effect of ciclopirox was not attributed to its inhibition of the cell cycle progression. The present results indicate that ciclopirox protects astrocytes from peroxynitrite cytotoxicity by attenuating peroxynitrite-induced mitochondrial dysfunction.

Immunostimulated glial cells potentiate glucose deprivation-induced death of cultured rat cerebellar granule cells.

The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation-induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-gamma (200 U/ml) and lipopolysaccharides (1 microg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose-deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons in part through the expression of inducible NOS but not through NMDA receptor activation. Potentiation of glucose-deprived CGC death by immunostimulated glial cells may be clinically implicated in the tendency of recurrent ischemic insults to be more severe and fatal than an initial ischemic insult.

Purification and properties of Aquifex aeolicus DNA polymerase expressed in Escherichia coli.

The gene encoding Aquifex aeolicus (Aae) DNA polymerase was expressed under the control of the trp promoter on a high-copy plasmid, pTRPNS, in Escherichia coli. The expressed enzyme was purified 11-fold with a 13.8% yield and a specific activity of 2268.3 U mg(-1). The optimum pH of the enzyme was 6.8-7.2. The optimal concentrations of KCl and Mg(2+) were 20-30 mM and 4-5 mM, respectively. Aae DNA polymerase contained a double-strand-dependent 3'-->5' proofreading exonuclease activity but lacked any detectable 5'-->3' exonuclease activity.

Cloning and analysis of the DNA polymerase-encoding gene from Thermus filiformis.

The gene encoding Thermus filiformis (Tfi) DNA polymerase was cloned and its nucleotide sequence was determined. The primary structure of Tfi DNA polymerase was deduced from its nucleotide sequence. Tfi DNA polymerase is comprised of 833 amino acid residues and its molecular mass was determined to be 93,890 Da. The deduced amino acid sequence of Tfi DNA polymerase showed a high sequence homology to E. coli DNA polymerase I-like DNA polymerases: 78.5% homology to Taq DNA polymerase, 78.4% to Tca DNA polymerase, and 41.8% to E. coli DNA polymerase I. An extremely high sequence identity was observed in the region containing polymerase activity. The G + C content of the coding region for the Tfi DNA polymerase gene was 68.5%, which was higher than that of the chromosomal DNA (65%). The G + C contents in the first, second, and third positions of the codons used were 71.8%, 40.9%, and 92.7% respectively. Codon usage in Tfi DNA polymerase was heavily biased towards the use of G + C in the third position. Rare codons with U or A as the third base were sometimes used to avoid using GA(A/T) TC and TCGA sequences, as they are recognition sites for the restriction endonucleases TfiI and TaqI.

Proliferation-dependent vulnerability of glucose-deprived astrocytes to nitric oxide-induced cytotoxicity.

The present study investigated the vulnerability of glucose-deprived astrocytes to nitric oxide (NO)-induced cytotoxicity. Primary murine cortical astrocyte cultures of different ages were deprived of glucose in the presence of the NO-releasing reagent 3-morpholinosydnonimine. Glucose-deprived astrocytes displayed an age-dependent vulnerability to NO cytotoxicity. However, this difference in vulnerability with age was found to be dependent on initial plating density. The augmented deaths of astrocyte cultures were consistent with the [3H]thymidine incorporation pattern. Thus, rapidly dividing astrocytes were much more susceptible to NO cytotoxicity under glucose-deprived conditions. The data indicate that the vulnerability of glucose-deprived astrocytes to NO cytotoxicity depends on the proliferative state rather than age in vitro.

Enhancement of intestinal glucose transport following chronic parathion poisoning.

Chronic administration of parathion to male rats stimulated glucose (p less than 0.05) but not calcium (p greater than 0.05) transport in the everted duodenal gut sac preparation. Chronic parathion stimulation was not reduced by concurrent administered of atropine. Acutely applied parathion or paraoxon, its active metabolite, did not increase glucose transport in this preparation.

Effect of topically applied 0.1% dexamethasone on endothelial healing and aqueous composition during the repair process of rabbit corneal alkali wounds.

PURPOSE: The effects of topical dexamethasone on the endothelial healing and the change of aqueous compositions were investigated during the repair process of alkali-wounded rabbit cornea. METHODS: A central corneal alkali wound was produced by a 60 sec application of a 5.5 mm round filter paper soaked in 1N NaOH onto one eye of each rabbit. The eyes subsequently were treated topically with either 0.1% dexamethasone or a balanced salt solution (BSS) 4 times per day for 8 weeks. Endothelial wound morphometry was performed after alizarin red and trypan blue staining. The concentrations of ascorbic acid, glucose, and the ions, Na+, K+, Ca2+ and Mg2+, were measured in the aqueous humor. RESULTS: Endothelial healing in control (alkali-wounded but not treated with dexamethasone) corneas showed a biphasic pattern of healing: an initial short-term healing for the first week and then a late long-term healing following the secondary endothelial breakdown. Topical administration of 0.1% dexamethasone deterred endothelial healing during the early period and prevented the secondary endothelial breakdown. However, the total repair process of endothelium was accelerated by the dexamethasone-treatment. Among the various components of the aqueous humor examined, ascorbic acid seemed the most sensitive to change caused by the alkali injury and dexamethasone treatment. CONCLUSIONS: The present data indicate that dexamethasone may have a therapeutic potential in the management of endothelial healing after corneal alkali injury.

Query-based learning applied to partially trained multilayer perceptrons.

An approach is presented for query-based neural network learning. A layered perceptron partially trained for binary classification is considered. The single-output neuron is trained to be either a zero or a one. A test decision is made by thresholding the output at, for example, one-half. The set of inputs that produce an output of one-half forms the classification boundary. The authors adopted an inversion algorithm for the neural network that allows generation of this boundary. For each boundary point, the classification gradient can be generated. The gradient provides a useful measure of the steepness of the multidimensional decision surfaces. Conjugate input pairs are generated using the boundary point and gradient information and presented to an oracle for proper classification. These data are used to refine further the classification boundary, thereby increasing the classification accuracy. The result can be a significant reduction in the training set cardinality in comparison with, for example, randomly generated data points. An application example to power system security assessment is given.