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This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: The odds of erectile dysfunction (ED) are thrice more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to PDE5 inhibitors. However, bone morphogenetic protein 2 (BMP2) is known to be involved in angiogenesis. Objective: To assess the efficacy of BMP2 stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction. Methods: The induction of diabetes mellitus was done by streptozotocin (STZ, 50 mg/kg daily) administered intraperitoneally for five successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post inductions, animals were allocated to one of five groups: a control group, an STZ-induced diabetic mouse group receiving two intra-cavernous 20 μL PBS injections, or one of three BMP2 groups administered two injections of BMP2 protein (1μg, 5 μg, or 10 μg) diluted in 20 μL of PBS with three days interval between the first and second injection. The erectile functions were assessed two weeks after PBS or BMP2 protein injections by recording the ICP (intracavernous pressure) through cavernous nerve electrical stimulation. Angiogenic activities also nerve regenerating effects of BMP2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured MCECs (mouse cavernous endothelial cells). Moreover, fibrosis-related factors protein expressions were evaluated by western blot. Results: Erectile function recovery to 81% of the control value in diabetic mice was found with intra-cavernous BMP2 injection (5 μg/20 μL). Pericytes and also endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with BMP2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of MCECs. BMP2 protein enhanced cell proliferation and reduced apoptosis in MCECs and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, BMP2 suppressed fibrosis by reducing MCEC fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions. Conclusions: BMP2 modulates neurovascular regeneration and inhibits fibrosis to revive the mice's erection function in diabetic conditions. Our findings propose that the BMP2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction (ED). Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: The odds of erectile dysfunction (ED) are thrice more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to PDE5 inhibitors. However, bone morphogenetic protein 2 (BMP2) is known to be involved in angiogenesis. Objective: To assess the efficacy of BMP2 stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction. Methods: The induction of diabetes mellitus was done by streptozotocin (STZ, 50 mg/kg daily) administered intraperitoneally for five successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post inductions, animals were allocated to one of five groups: a control group, an STZ-induced diabetic mouse group receiving two intra-cavernous 20 μL PBS injections, or one of three BMP2 groups administered two injections of BMP2 protein (1μg, 5 μg, or 10 μg) diluted in 20 μL of PBS with three days interval between the first and second injection. The erectile functions were assessed two weeks after PBS or BMP2 protein injections by recording the ICP (intracavernous pressure) through cavernous nerve electrical stimulation. Angiogenic activities also nerve regenerating effects of BMP2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured MCECs (mouse cavernous endothelial cells). Moreover, fibrosis-related factors protein expressions were evaluated by western blot. Results: Erectile function recovery to 81% of the control value in diabetic mice was found with intra-cavernous BMP2 injection (5 μg/20 μL). Pericytes and also endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with BMP2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of MCECs. BMP2 protein enhanced cell proliferation and reduced apoptosis in MCECs and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, BMP2 suppressed fibrosis by reducing MCEC fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions. Conclusions: BMP2 modulates neurovascular regeneration and inhibits fibrosis to revive the mice's erection function in diabetic conditions. Our findings propose that the BMP2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction (ED). Disclosure: No. [ABSTRACT FROM AUTHOR]

Decellularized extracellular matrix (dECM) is a versatile functional biomaterial that has a structure and composition specific to the organ and is involved differently in the functional properties of cells, tissues and organs. The remaining cells or nucleic acid fragments must be completely removed during the decellularization process that removes cells while preserving biological properties in the tissue, which is essential because it can cause immune resistance reactions and inflammation. Methods for decellularization are diverse and widely studied, but there is still no definitive method for decellularization due to the conditions for successful decellularization and the pathological and structural differences of each organ. This study identified customized decellularization method for porcine-derived organs. Porcine-derived biological tissues were decellularized in a mixture of 0.5% SDS, 1% Triton X-100, and dECM was extracted by physical, chemical, and enzymatic methods including Pepsin. Finally, sterilization is performed by irradiating 1 kGy of electron beam. Components such as dsDNA, GAGs, and collagen were analyzed, and decellularization was evaluated by scanning electron microscope (SEM) and electrophoresis. To evaluate the safety of the cells, HT-22 and Hep G2 cells were cultured with various concentrations of dECM added to the culture medium to observe cell proliferation. The results showed that the dsDNA content in porcine-derived dECM was significantly reduced by more than 99% by keeping it below 10 ng/mg (dry weight) (p<0.0001). In addition, the content of GAG and collagen was mostly maintained, and the size of DNA fragments was smaller than 100 bp. No visible macroscopic nuclear material was observed, and at the same time, collagen fibers and elastic fibers were also identified. In cell culture, the proliferation rate of cells with dECM added to the culture medium was significantly increased. In conclusion, it has been proven that dECM can be effectively extracted through an organ-specific customized decellularization method. Furthermore, it is believed that it can be widely used as a material for cell and basic experiments using dECM through cell safety experiments. [ABSTRACT FROM AUTHOR]

Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR. This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy. Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8-11.7 months). The median progression-free survival was 7.1 months (95% confidence interval, 3.6-10.6 months), and the median overall survival was 14.2 months (95% confidence interval, 9.3-19.1 months). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment. We conclude that ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and constitute a population with unmet needs. • Combination of ceralasertib and durvalumab had a tolerable safety profile in patients with metastatic melanoma. • Combination treatment resulted in median progression-free survival of 7.1 months and median overall survival of 14.2 months. • Our data suggest that this combination could be used to salvage patients with immunotherapy-resistant melanoma. • Ceralasertib plus durvalumab is worthy of further investigation for melanoma after failure of frontline immunotherapy. [ABSTRACT FROM AUTHOR]

Air pollution poses a serious threat to human health in Asia. This study analyzes the association of air pollutants and greenness with incidence rates of allergic rhinitis in Seoul at the administrative district level to gain insight into district-level urban policies to improve public health. A spatial regression model is constructed to investigate the correlation between allergic rhinitis incidence rates and five air pollutants measured at 128 air pollution monitoring stations around Seoul: sulfur dioxide (SO2), particulate matter less than 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO). The allergic rhinitis incidence data are derived from the National Health Insurance Service's database that includes the number of allergic rhinitis-related clinic visits by the patients over 20 years of age and living in Seoul. A kriging geostatistical interpolation was used to estimate average air pollution level of 423 administrative districts. To assess pollen concentrations that can affect allergic rhinitis, the average normalized difference vegetation index (NDVI) is measured based on the urban greenness. The model, controlling for built environment and socio-economic attributes, identifies the possibility of a weak association between allergic rhinitis incidence rates and carbon monoxide levels. The NDVI value is negatively correlated with allergic rhinitis incidence rates, implying a complicated aspect in relation to the effect of urban greenness. [ABSTRACT FROM AUTHOR]

Examine the number densities and energies for the desorption of gas molecules on solid surfaces. Details of the application of Langmuir recoil force measurements and numerical modeling; Analysis of desorption processes by laser-induced thermal means; Evaluation of recoil forces using a torsion balance.

This Letter addresses the missing value prediction problem in data. Existing missing value prediction studies apply their algorithms after replacing missing values with a constant value, which does not represent the missing values clearly and has disadvantages in processing data with a high missing rate. The authors propose a model that generalises a single data sample from its observations and predicts the value of a query feature. The authors' model can deal with an incomplete data sample independently of missing values. In this process, the feature embedding matrix and feature importance weights are introduced to represent each feature and learned jointly with the proposed model. Through experiments, they verify that the proposed model effectively predicts the missing values of data. [ABSTRACT FROM AUTHOR]

This Letter addresses the missing value prediction problem in data. Existing missing value prediction studies apply their algorithms after replacing missing values with a constant value, which does not represent the missing values clearly and has disadvantages in processing data with a high missing rate. The authors propose a model that generalises a single data sample from its observations and predicts the value of a query feature. The authors' model can deal with an incomplete data sample independently of missing values. In this process, the feature embedding matrix and feature importance weights are introduced to represent each feature and learned jointly with the proposed model. Through experiments, they verify that the proposed model effectively predicts the missing values of data. [ABSTRACT FROM AUTHOR]

Arctic sea ice area (SIA) during late summer and early fall decreased substantially over the last four decades, and its decline accelerated beginning in the early 2000s. Statistical analyses of observations show that enhanced poleward moisture transport from the North Pacific to the Arctic Ocean contributed to the accelerated SIA decrease during the most recent period. As a consequence, specific humidity in the Arctic Pacific sector significantly increased along with an increase of downward longwave radiation beginning in 2002, which led to a significant acceleration in the decline of SIA in the Arctic Pacific sector. The resulting sea ice loss led to increased evaporation in the Arctic Ocean, resulting in a further increase of the specific humidity in mid-to-late fall, thus acting as a positive feedback to the sea ice loss. The overall set of processes is also found in a long control simulation of a coupled climate model. [ABSTRACT FROM AUTHOR]

The braking system of hybrid electric vehicle (HEV) is composed of friction and regenerative braking system, meaning that braking torque is generated by the collaboration of the friction and regenerative braking system. With the attributes, there are two problems in the HEV braking system. First, rapid deceleration occurs due to dynamic characteristic difference when shifting the friction and regenerative braking systems. Second, the friction braking torque alters with temperature because the friction coefficient changes with the temperature. These problems cause the vehicle to be unstable. In this paper, the concurrence control and compensation control were proposed to solve these problems. And also, the concurrence control and compensation control were combined for the stability of the braking system. In order to confirm the effect of these control algorithms, the experiment and simulation were conducted. Consequently, it was confirmed that the control algorithm of this study improved the vehicle safety and stability. [ABSTRACT FROM AUTHOR]

We demonstrate |W〉 state encoding of multiatom ensemble qubits. Using optically trapped Rb atoms, the T2 coherence time is 2.6(3) ms for N=7.6 atoms and scales approximately inversely with the number of atoms. Strong Rydberg blockade between two ensemble qubits is demonstrated with a fidelity of 0.89(1), and with a fidelity of ~1.0 when postselected on a control ensemble excitation. These results are a significant step towards deterministic entanglement of atomic ensembles. [ABSTRACT FROM AUTHOR]

Objectives Postoperative surgical site infection ( SSI) is a frequent postoperative complication in patients with oral cancer and significantly affects patient recovery and medical expenses. The aim of this study was to examine the predictors of SSI in patients undergoing major surgery for oral or oropharyngeal squamous cell carcinoma ( OSCC) and to determine the relationship between perioperative albumin and the development of SSI. Subjects and methods In 337 consecutive patients who underwent clean-contaminated surgery for OSCC, serum albumin, glucose, and hemoglobin levels were perioperatively measured. Differences between the groups were examined using Fisher's exact test, Mann-Whitney U-test, and multiple logistic regression analysis. Results Surgical site infection was detected in 88 (26.1%) patients with median time to development of 10 (2-25) days. Multiple logistic regression analysis showed that only postoperative serum albumin < 2.5 g dl−1 was an independent variable predictive of SSI ( P = 0.003). The duration of hospital stay was negatively correlated with postoperative albumin ( R2 = -0.302, P < 0.001). Conclusion Early postoperative hypoalbuminemia <2.5 g dl−1 is an independent risk factor for the development of SSI in patients undergoing oral cancer surgery. Clinicians should be aware of the implications of postoperative hypoalbuminemia and consider more intensive postoperative care in these patients. [ABSTRACT FROM AUTHOR]

This study showed that one or more comorbidities, tumor recurrence, and second primary cancer occurrence were independent predictors of both noncancer health events (NCHE) and noncancer mortality (NCM) in 600 patients with advanced-stage head and neck squamous cell carcinomas. Patients with respiratory NCHE had a particularly high risk of NCM.Background The survival of patients with head and neck squamous cell carcinoma (HNSCC) can be affected by noncancer health events (NCHE) as well as by index cancer progression and second primary cancer (SPC). This study aimed to investigate the risk factors for NCHE and noncancer mortality (NCM) in patients with advanced-stage HNSCC. Patients and methods This cohort study involved 600 consecutive patients with overall stage III to IV HNSCC who were treated between 2001 and 2010 at our tertiary referral hospital. NCHE was defined as re-admission (i.e. after the primary treatments for the index tumors) due to noncancer-related causes. The incidences of NCHE and NCM and their risk factors were analyzed by using cumulative incidence and cause-specific hazard functions. Results During a median follow-up period of 54 months, 224 (37.3%) and 55 (9.2%) of the 600 patients had NCHE and NCM, respectively. The 5-year index cancer mortality, SPC mortality, and NCM rates were 23.8%, 4.2%, and 8.9%, respectively. Multivariate analyses revealed that body mass index <20 kg/m2 (P = 0.018), Charlson comorbidity index (CCI) ≥1 (P < 0.001), tumor recurrence (P < 0.001), SPC occurrence (P < 0.001), and initial chemotherapy (P = 0.049) were independent NCHE predictors. Older age (P < 0.001), CCI ≥1 (P = 0.008), tumor recurrence (P < 0.001), and SPC occurrence (P = 0.047) were independent NCM predictors. Patients with respiratory NCHE were at a higher risk of NCM than patients with other NCHE types (P < 0.001). Conclusions One or more comorbidities, tumor recurrence, and SPC occurrence were independent predictors of both NCHE and NCM. Patients with respiratory NCHE had a particularly high risk of NCM. [ABSTRACT FROM PUBLISHER]

Single-unit umbilical cord blood (CB) SCT is limited by low total nucleated cell (TNC) dose. Co-infusion of CD34+ cells from a third party HLA-mismatched donor, known as dual or haplo-cord transplant, reduces the period of post-transplant neutropenia and related complications. The aim of this study was to analyze the value of early post-transplant peripheral blood (PB) and T cell chimerism after 28 dual transplants regarding CB engraftment. Cumulative incidence of myeloid engraftment at 30 days was 93% with a median time to engraftment of 14 days (10-29). Patients who developed CB graft failure (n=5) showed very low percentages of CB cells on days +14, +21 and +28 with decreasing dynamics. On the other hand, percentages of CB cells in patients who achieved CB engraftment increased over time. Interestingly, such patients showed two distinct chimerism dynamics in PB, but all of them showed a predominance of CB T cells early after SCT with increasing dynamics over time. Early post-transplant chimerism dynamics in PB and T cells predicts CB graft failure enabling rapid therapeutic measures to be applied. On the other hand, early increasing percentages of CB T cells correlates with ultimate CB engraftment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the neuromuscular mechanisms of the involved muscles that contribute to the greater positional variability at the ankle joint in older adults compared with young adults. Eleven young adults (25.6±4.9 years) and nine older adults (76.9±5.9 years) were asked to accurately match and maintain a horizontal target line with 5° dorsiflexion of their ankle for 20 s. The loads were 5 and 15% of the one repetition maximum load (1 RM). The visual gain was kept constant at 1° for all trials. Positional variability was quantified as the standard deviation (SD) of the detrended position signal. The neural activation of the tibialis anterior and soleus muscles was quantified as the normalized EMG amplitude, power spectrum density (PSD; EMG oscillations) and coactivation of the two muscles. As expected, positional variability was greater in older adults (older: 0.11±0.06° vs. young: 0.04±0.02°; p=.003). The only significant neural difference occurred for the PSD of the tibialis anterior muscle, where young adults exhibited significantly greater power than older adults from 30-60 Hz. The amplified positional variability of ankle joint in older adults was associated with lower power from 30-60 Hz oscillations in the tibialis anterior muscle (r(2)=.3, p=.01). These results provide novel evidence that older adults exhibit greater positional variability with the ankle joint relative to young adults likely due to their inability to activate the tibialis anterior muscle from 30-60 Hz. [ABSTRACT FROM AUTHOR]

Background:CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.Methods and results:The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.Conclusion:CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer. [ABSTRACT FROM AUTHOR]

Summary Introduction: Nucleated red blood cell (NRBC) count is closely associated with the prognosis of neonates. The analysis of NRBC has traditionally been measured manually. Recently, a newly developed automated hematology analyzer, the UniCel DxH 800 (DxH 800), was released. The goal of our study was to evaluate the performance of the DxH 800 NRBC method in neonates with the reference manual method and against previous generation hematology analyzers. Methods: NRBCs were counted in 162 neonatal blood samples using the DxH 800, LH 750, and ADVIA 2120 vs. the reference manual technique. The concordance rate, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained. Results: The DxH 800 showed an R2 value of 0.945 and the concordance rate of 93.8%. Further assessment revealed 85.3% sensitivity, 96.1% specificity, 85.3% PPV, and 96.1% NPV, resulting in the highest area under the curve (0.961). The LH 750 and ADIVA 2120 demonstrated R2 values of 0.851 and 0.529, respectively. Conclusion: The results obtained indicate the UniCel DxH 800 to be an excellent test on neonatal blood and superior to the other analyzers. Therefore, the DxH 800 is an effective and highly sensitive system for the analysis of NRBCs on newborns. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that glucocorticoid (Gc) can induce neuronal cell toxicity in the hippocampus. In addition, we examined that serum Gc increased by restraint stress aggravated kainic acid (KA)-induced neuronal death in hippocampal CA3 region. However, the effect of other stressful stimulus like lipopolysaccharide (LPS) increasing serum Gc on KA-induced neuronal death was not elucidated until now. Thus, we examined the time course effect of LPS on KA-induced neuronal death in the hippocampal CA3 region of mice, especially to address the role of Gc and inflammatory mediators. In the present study, we found that an aggravating effect of LPS on KA-induced neuronal death was correlated with an alteration of hippocampal IL-1β mRNA level at all time points, and the serum Gc and hippocampal IL-1β mRNA level was peak at 90 min after LPS treatment (LPS 90 min) when the aggravating effect of LPS on KA-induced neuronal death was maximum. In addition, RU38486 (glucocorticoid receptor antagonist) decreased the hippocampal IL-1β mRNA level and abolished the aggravating effect of LPS on KA-induced neuronal death at LPS 90 min and 24 h. In the immunohistochemical study, we found activated and ramified microglia (OX-42) and astrocyte (GFAP) at 24 h after LPS treatment (LPS 24 h) in the hippocampus. These results suggest that Gc itself, cytokines triggered by Gc, or both appears to be involved in the LPS effect depending on LPS pretreatment time. [Copyright &y& Elsevier]

Abstract: Since Korea joined ITER as Korea was developing a fully super-conducting tokamak, KSTAR, the national plan for developing fusion energy was renewed and focused on a clear mission – developing a technological self-reliant program for a fusion demonstration device. A new technical roadmap was developed toward self-reliant technologies for constructing a fusion power plant in a similar time window as in the EU, Japan and the US. This looks tough and formidable but Korea could take advantage of their well-established nuclear technologies in power plant design, construction, and operation. The government and the legislature recognized the importance of this effort by establishing a special law for supporting it practically and for giving it a high priority in their R&D agenda. Under this favorable environment, various scenarios for finding the most effective and efficient path to achieve the goal were reviewed and some of the features of this review will be presented. [Copyright &y& Elsevier]

Abstract: In the present study, we characterized differential expressions of phosphorylated Ca2+/calmodulin-dependent protein kinase IIα (pCaMKIIα) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1 β) significantly increased pCaMKIIα expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-α, and IL-1β but not by s.c. injections of formalin or i.p. injections of acetic acid. In an immunohistochemical study, we found that increased pCaMKIIα and pERK expressions were mainly located at CA3 or the dentate gyrus of the hippocampus. In a behavioral study, we assessed the effects of PD98059 (a MEK 1/2 inhibitor) and KN-93 (a CaMKII inhibitor) following i.c.v. administration on the nociceptive behaviors induced by i.t. injections of glutamate, pro-inflammatory cytokines (TNF-α or IL-1β), and i.p. injections of acetic acid. PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERKα and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKIIα in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner. [Copyright &y& Elsevier]

Haemophilia B (HB) is a rare X-linked recessive bleeding disorder caused by a mutation in the F9 gene. The aims of this study were to characterize the mutation spectrum of F9 in Korean patients with HB to establish the optimal molecular diagnostic strategy and to find genotype–phenotype correlations. Study subjects consisted of 33 unrelated Korean patients with HB. We performed polymerase chain reaction (PCR) amplification and direct sequencing of all exons and flanking sequences of F9. When large deletion was suspected from PCR failure, exon dosage test using multiplex ligation-dependent probe amplification (MLPA) was performed. We identified disease-causing mutations in 32 out of 33 patients by direct sequencing analyses (mutation detection rate, 97%). A total of 28 unique mutations were detected, including 7 novel ones. Six mutations were recurrent but observed in no more than two patients. In the remaining one patient, exon 1 was not amplified, and MLPA analysis confirmed a large deletion involving exon 1. The genotype–phenotype correlations between the type of mutation and the severity of factor deficiency were not consistent, as has been previously reported. One patient developed inhibitor, and he was the patient with exon 1 deletion. Based on our results from 33 Korean patients with HB, which showed no hotspot for mutations, direct sequencing of all exons with flanking sequences is needed as the first-line test. MLPA can be a feasible platform at clinical laboratories to detect large deletion mutations in suspected cases. [ABSTRACT FROM AUTHOR]

Abstract: Nicotine is attractive as an analgesic component despite that its antinociceptive mechanism is not well known until now. In the present study, we examined the antinociceptive effect of nicotine administered supra-spinally on acetic acid–induced visceral pain induction (writhing test), and found that the antinociceptive effect of nicotine was abolished by mu-, delta-, and kappa-opioid receptor antagonist administered i.c.v. In addition, s.c. 5% formalin pretreatment at 5 h, 20 h, 40 h, and 1 week prior to i.c.v. nicotine injection abolished the antinociceptive effect of nicotine in the writhing test, suggesting that s.c. formalin pretreatment induced tolerance to the antinociceptive effect of nicotine in the supra-spinal region. Furthermore, neuronal loss of the hippocampal cornus ammonis (CA) 3 region reduced nicotine-induced an antinociceptive effect in the writhing test. In Western blot assay, we examined s.c. formalin injection down-regulated mu-opioid receptor in the hippocampus after 40 h, and its effect was maintained for 1 week. However, various acetylcholine receptor subunits and delta-, and kappa-opioid receptors were not altered. These results suggest that s.c. formalin pretreatment can contribute to induce tolerance on nicotine-induced antinociception as down-regulating mu-opioid receptor in the hippocampus, especially 40 h after s.c. formalin injection. [Copyright &y& Elsevier]

Abstract: We examined proopiomelanocortin (POMC) mRNA and β-endorphin expression in the hypothalamus of mice after various nociceptive stimuli. The time-course study (10 min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly increases from 1 h after s.c. formalin injection and returns to the control level at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection did not affect the hypothalamic POMC gene expression at all time points. We found that the POMC mRNA after s.c. formalin injection was located in the arcuate nucleus of the hypothalamus. In the same manner, β-endorphin immunoreactivity was also increased in the hypothalamic arcuate nucleus. The expression of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2), phosphorylated calcium/calmodulin-dependent protein kinase-IIα (pCaMK-IIα) protein and phosphorylated IκB (pIκB) protein was increased by s.c. formalin injection at various time points. We also found that increased pERK1/2, pCaMKIIα and pIκB protein after s.c. formalin injection was mainly located in the arcuate nucleus of hypothalamus in which cells containing β-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIα and pIκB immunoreactivity. In addition, formalin-induced POMC mRNA expression was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen-activated protein kinase (MAPK) pathways inhibitor; 6.6 μg) and KN93 (pCaMK-II inhibitor; 20 μg). In conclusion, POMC mRNA expression in the arcuate nucleus of the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2, pCaMK-IIα and NFκB may play an important role in the expression of the hypothalamic POMC gene and β-endorphin expression. [Copyright &y& Elsevier]

Alginate bead containing calcium carbonate particle were prepared by dropping the suspension of alginate/calcium carbonate (4/1, w/w) into aqueous solution of CaCl2 (0.1 M). The pH-dependent release property of the bead was observed for 12 h using blue dextran as a model drug. The release increased up to 4 h in a saturation manner. When no calcium carbonate was contained, the release exhibited no marked variation with pH and the values were 27-39%. On the other hand, in case calcium carbonate was included in the matrix of alginate beads, intensive release(40-50%) was achieved in acidic and neutral conditions and the degrees of release were suppressed in alkali conditions and the values were ∼20%. The pH-sensitive release property is possibly because the particles of calcium carbonate embedded in the matrix of beads were leached out in acidic and neutral conditions, leaving cavities in the matrix. The cavities are likely to be main pathways for the release of blue dextran. [ABSTRACT FROM AUTHOR]

Abstract: The effect of single or repeated restraint stress on several signal molecules in the hypothalamus was studied in ICR mice. Single restraint stress was induced for 30, 60, and 120 min. A repeated restraint stress was induced for 2 h daily during four consecutive days, and then induced in the same time course on the fifth day. In the immunoblot assay, we observed that the signal molecules c-Fos, phosphorylated extracellular cell-regulated protein kinase (pERK), phosphorylated calcium/calmodulin dependent protein kinase II (pCaMKII) and phosphorylated cyclic-AMP response element binding protein (pCREB) in the hypothalamus were increased by single restraint, and the increased c-Fos and pERK levels were attenuated by repeated restraint stress. However, pCaMKII and pCREB levels were increased by both single and repeated restraint stress. We also observed in the immunohistochemistry study that immunoreactivities (IR) of these signal molecules were changed in paraventricular (PVN) and arcuate nuclei (ArcN) of the hypothalamus in accordance with immunoblot results. Furthermore, in confocal immunofluorescence, the pCaMKII and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of PVN and ArcN. In addition, we found that c-Fos and pCaMKII IR in locus coeruleus (LC) were increased by single restraint, and were attenuated by repeated restraint stress. However, the pERK and pCREB IR were increased by both single and repeated restraint stress. The confocal study revealed that pERK and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of LC. Our results suggest that single and repeated restraint stress differentially triggers the induction and phosphorylation of several signal molecules in the PVN, ArcN, and LC. In addition, single and repeated stress stimuli elicited the brain-region specific changes of signal molecules examined. Furthermore, the upstream signal molecule activating CREB may be also brain-region specific, especially in repeated stress stimuli. [Copyright &y& Elsevier]

A letter to the editor on "Effects of precursors in the ethanol-based sol-gel synthesis of Zn2SiO4:Mn phosphor," by C. J. Kim, and M. S. Kwon in the August 2006 issue is presented.

The Korea Superconducting Tokamak Advanced Research (KSTAR) is a medium size, fully superconducting tokamak, which is scheduled to begin operation in year 2006. The control system of KSTAR consists of a supervisory system, plasma control system, and local control systems for various subsystems. Modular system, high reliability, flexibility and long time maintainability are major factors for the system design. The EPICS is the first choice for the distributed system control and the MDSPlus will be utilized for the data handling and analysis. The reflective memory network will be used for the real time plasma control. A pilot system has been being developed with VME and Compact PCI buses. Current status of the development of KSTAR control system will be presented. [Copyright &y& Elsevier]

The article reports that three basic forms of ordering, i.e., CuAu, chalcopyrite, and CuPt, have been reported widely in various III-V ternary semiconductors grown by molecular beam epitaxy and organometallic vapor phase epitaxy. Ordering was reported to reduce the energy band gap of a III-V alloy with respect to that for the disordered alloy. Relatively little work has been done on II-VI/III-V mixed heterostructures probably due to possible cross-doping effects resulting from inter-diffusion or due to strain effects as a consequence of the lattice mismatch between II-VI active layers and the III-V substrates.

In brain magnetic resonance (MR) images, image segmentation and 3D visualization are very useful tools for the diagnosis of abnormalities. Segmentation of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is the basic process for 3D visualization of brain MR images. Of the many algorithms, the fuzzy c-means (FCM) technique has been widely used for segmentation of brain MR images. However, the FCM technique does not yield sufficient results under radio frequency (RF) nonuniformity. We propose a hierarchical FCM (HFCM), which provides good segmentation results under RF nonuniformity and does not require any parameter setting. We also generate Talairach templates of the brain that are deformed to 3D brain MR images. Using the deformed templates, only the cerebrum region is extracted from the 3D brain MR images. Then, the proposed HFCM partitions the cerebrum region into WM, GM, and CSF. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol 13, 115–125, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10035 [ABSTRACT FROM AUTHOR]

Presents a study which introduced a longitudinal feedback system (LFS) to cure longitudinal coupled bunch mode instabilities in the Pohang Light Source (PLS) storage ring. Description of the PLS; Design and properties of the LFS kicker; Measurement setups and results; Conclusion.

Formaldehyde is one of the toxic volatile organic compounds and is known to be a carcinogen and a major cause of sick building syndrome. In this study, polystyrene (PS)/polyaniline (PANI) core-shell type microparticles with narrow size distributions were prepared by applying the Swelling-Diffusion-Interfacial Polymerization Method (SDIPM). The PANI shell was uniformly coated on the PS core and the PANI loading efficiency estimated by gravimetric reaction yield analysis was 98.69%. A formaldehyde sensor device was fabricated by a solution casting of the PS/PANI core-shell type microparticles on the Interdigitated Electrodes (IDEs). The PS/PANI coated IDE sensor showed an excellent sensitivity for formaldehyde in range of 1–50 ppm at room temperature as follows: −9.9% of response for 1 ppm and −37.6% of response for 50 ppm. In addition, it showed a clear reversibility indicating that the sensor could be reused at least 3 times for the detection of formaldehyde. Image 1 • Polystyrene/polyaniline core-shell microparticles showing narrow size distribution and uniform shell thickness. • Formaldehyde sensor device via a solution casting of the PS/PANI core-shell microparticles on the interdigitated electrodes. • PS/PANI coated IDE formaldehyde sensor showing high sensitivity, practical controllability, and clear reversibility. • PS/PANI coated IDE formaldehyde sensor applicable to the application area requiring a bendable form. [ABSTRACT FROM AUTHOR]

The attractive force between two conducting electrodes, one charged and the other at nominally zero potential, has been measured using a modified torsion balance whose deflection is monitored by a linear rotary differential capacitance (LRDC) transducer. This device has a resolution of 10[sup -7] tad and is simple to operate. The results for different electrode geometries as a function of separation distance and voltage on the charged conductor agree to ± 20% or better with theoretical results, in most cases. In the case of aluminum electrodes, the attractive force is not stable; rather, it varies periodically as the result of an unknown discharge process. [ABSTRACT FROM AUTHOR]

B TYPE: b Abstract Publication B TOPIC: b Cardiothoracic Surgery B PURPOSE: b Prior left pneumonectomy in a patient undergoing coronary artery bypass grafting (CABG) is a highly infrequent comorbidity. B METHODS: b This is the case report of a 76 year old man who had undergone left pneumonectomy 7 years previously for left upper lobe Stage IIIA squamous cell carcinoma followed by chemoradiotherapy who presented with non ST elevation myocardial infarction. Chest computed tomography (CT) showed characteristic post-pneumonectomy changes with significant displacement of mediastinum (including the heart) to the left, fluid filled left pleural cavity and hypertrophic right lung. [Extracted from the article]

A letter to the editor is presented in response to the article about the loss of the Y chromosome in leukocyte lineages of donor origin after stem cell transplantation is presented.

We demonstrate high fidelity two-qubit Rydberg blockade and entanglement on a pair of sites in a large two-dimensional qubit array. The qubit array is defined by a grid of blue detuned lines of light with 121 sites for trapping atomic qubits. Improved experimental methods have increased the observed Bell state fidelity to FBell=0.86(2). Accounting for errors in state preparation and measurement we infer a fidelity of F-SPAMBell=0.88. Accounting for errors in single qubit operations we infer that a Bell state created with the Rydberg mediated CZ gate has a fidelity of FCZBell=0.89. Comparison with a detailed error model based on quantum process matrices indicates that finite atom temperature and laser noise are the dominant error sources contributing to the observed gate infidelity. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about sol-gel synthesis and green luminescence of nanocrystalline Zn2SiO4:manganese phosphor.

Introduction: Radical prostatectomy for prostate cancer not only induces cavernous nerve injury but also causes cavernous angiopathy, which is responsible for poor responsiveness to phosphodiesterase-5 inhibitors. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. Objective: To investigate the effectiveness of IGFBP5 knockdown at improving erectile function in a mouse model of cavernous nerve injury. Methods: Eight-week-old C57BL/6 mice were used to prepare cavernous nerve injury model. Mice were divided into 4 groups: a sham operation group and three cavernous nerve injury (CNI) groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. One week later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. Results: IGFBP5 expression in cavernous tissues were significantly increased in CNI mice compare to sham mice. CNI mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements. Furthermore, in CNI mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment. Conclusions: Knockdown of IGFBP5 improved erectile function in CNI mice by enhancing neurovascular regeneration. Local inhibition of IGFBP5 expression may provide a new treatment strategy for the treatment of neurovascular diseases. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Radical prostatectomy for prostate cancer not only induces cavernous nerve injury but also causes cavernous angiopathy, which is responsible for poor responsiveness to phosphodiesterase-5 inhibitors. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. Objective: To investigate the effectiveness of IGFBP5 knockdown at improving erectile function in a mouse model of cavernous nerve injury. Methods: Eight-week-old C57BL/6 mice were used to prepare cavernous nerve injury model. Mice were divided into 4 groups: a sham operation group and three cavernous nerve injury (CNI) groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. One week later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. Results: IGFBP5 expression in cavernous tissues were significantly increased in CNI mice compare to sham mice. CNI mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements. Furthermore, in CNI mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment. Conclusions: Knockdown of IGFBP5 improved erectile function in CNI mice by enhancing neurovascular regeneration. Local inhibition of IGFBP5 expression may provide a new treatment strategy for the treatment of neurovascular diseases. Disclosure: No. [ABSTRACT FROM AUTHOR]

The conceptual design and theory of diagnostics to measure electron temperature and density fluctuations using electron cyclotron emission (ECE) was proposed and a new, single-sightline ECE system with the heterodyne radiometer has been built for TEXT-U. This ECE system was designed to employ auto- and cross-correlation techniques. Calculations indicate that fluctuations as small as 0.2% in amplitude can be achieved from auto-correlation of the ECE signal. The cross-correlation technique, however, must be used to resolve the fluctuations in frequency. Auto- and cross-correlation between optically thick ECE channels will be used for our initial approach to electron temperature fluctuation measurement with the single-sightline ECE system. A description of the TEXT-U ECE system, investigation of the feasibility of this measurement, and the initial results of test, calibration, and operation are presented. [ABSTRACT FROM AUTHOR]

A multi-purpose experimental instrument, called as KoBRA (Korea Broad acceptance Recoil spectrometer and Apparatus), has been constructed for low-energy nuclear physics experiments at RAON (Rare Isotope Accelerator complex for ON-line experiments), and is being prepared in order to produce rare isotope beams at an energy of about 20 MeV/nucleon during the first beam commissioning phase. A test was performed to measure the positions of 4 He ions at the dispersive and achromatic foci of KoBRA using an 241 Am α -source placed at the production target position, so as to examine the momentum dispersion and ion beam transport. We report on the results of the test and the detailed design of KoBRA including ion optics, together with the status of detectors for particle identification of rare isotopes. [ABSTRACT FROM AUTHOR]

An abstract of the study "Quantitative Analysis of Tetracycline-Inducible Expression of the Green Fluorescent Protein Gene in Transgenic Chickens," by B. Koo and colleagues is presented.