• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

• Parasites, Hosts and Diseases
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• v.45 no.4
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• pp.255-266
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• 2007

The protective effect of the Synadenium carinatum latex lectin (ScLL), and the possibility of using it as an adjuvant in murine model of vaccination against American cutaneous leishmaniasis, were evaluated. BALB/c mice were immunized with the lectin ScLL (10, 50, 100$[\mu}g$/animal) separately or in association with the soluble Leishmania amazonensis antigen (SLA). After a challenge infection with $10^6$ promastigotes, the injury progression was monitored weekly by measuring the footpad swelling for 10 weeks. ScLL appeared to be capable of conferring partial protection to the animals, being most evident when ScLL was used in concentrations of 50 and 100${\mu}g$/animal. Also the parasite load in the interior of macrophages showed significant reduction (61.7%) when compared to the control group. With regard to the cellular response, ScLL 50 and 100 ${\mu}g$/animal stimulated the delayed-type hypersensitivity (DTH) reaction significantly (P < 0.05) higher than SLA or SLA plus ScLL 10 weeks after the challenge infection. The detection of high levels of IgG2a and the expression of mRNA cytokines, such as IFN-$\gamma$, IL-12, and TNF-$\alpha$ (Th1 profiles), corroborated the protective role of this lectin against cutaneous leishmaniasis. This is the first report of the ScLL effect on leishmaniasis and shows a promising role for ScLL to be explored in other experimental models for treatment of leishmaniasis.

• Journal of Korean Society for Quality Management
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• v.47 no.3
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• pp.615-630
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• 2019

Purpose: Based on the theory of "Stimulus-Organism-Response" (S-O-R), this thesis takes customer forgiveness as a medium variable to explore the impact of merchant service remedy on customer behavior intention in the context of online shopping service failure. This thesis divides the merchant service remedy into two dimensions: spiritual recovery and material recovery, and reveals the influence difference of different merchant service remedy methods on customer behavior intention and the mediating role of customer forgiveness. Methods : 325 questionnaires were distributed and 307 valid questionnaires were collected for data analysis. The relationship between potential variables is proposed by using Structural Equations Modeling. Results : The two dimensions of service recovery have significant positive impact on customer forgiveness, and physical recovery has greater impact on customer forgiveness. In the influence of physical recovery on customer behavior intention, customer forgiveness is a partial mediating effect. However, in the influence of spiritual recovery on customer behavior intention, customer forgiveness is a complete mediating effect. Conclusion : In case of service faults, merchants should take the initiative to provide appropriate physical recovery and provide spiritual recovery sincerely and patiently. Only in this way can they regain good impression in the hearts of consumers and promote them to improve the quality of service recovery, so as to increase their willingness to repurchase Intention and positive word of mouth.

• Structural Engineering and Mechanics
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• v.59 no.1
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• pp.37-57
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• 2016

Reservoir geomechanics can play an important role in hydrocarbon recovery mechanism. In $CO_2$-EOR process, reservoir geomechanics analysis is concerned with the simultaneous study of fluid flow and the mechanical response of the reservoir under $CO_2$ injection. Accurate prediction of geomechanical effects during $CO_2$ injection will assist in modeling the Carbon dioxide recovery process and making a better design of process and production equipment. This paper deals with the implementation of a program (FORTRAN 90 interface code), which was developed to couple conventional reservoir (ECLIPSE) and geomechanical (ABAQUS) simulators, using a partial coupling algorithm. A geomechanics reservoir partially coupled approach is presented that allows to iteratively take the impact of geomechanics into account in the fluid flow calculations and therefore performs a better prediction of the process. The proposed approach is illustrated on a realistic field case. The reservoir geomechanics coupled models show that in the case of lower maximum bottom hole injection pressure, the cumulative oil production is more than other scenarios. Moreover at the high injection pressures, the production rates will not change with the injection bottom hole pressure variations. Also the FEM analysis of the reservoir showed that at $CO_2$ injection pressure of 11000 Psi the plastic strain has been occurred in the some parts of the reservoir and the related stress path show a critical behavior.

• Smart Structures and Systems
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• v.19 no.1
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• pp.21-31
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• 2017

To control the stochastic vibration of a vibration-sensitive instrument supported on a beam, the beam is designed as a sandwich structure with magneto-rheological visco-elastomer (MRVE) core. The MRVE has dynamic properties such as stiffness and damping adjustable by applied magnetic fields. To achieve better vibration control effectiveness, the optimal bounded parametric control for the MRVE sandwich beam with supported mass under stochastic and deterministic support motion excitations is proposed, and the stochastic and shock vibration suppression capability of the optimally controlled beam with multi-mode coupling is studied. The dynamic behavior of MRVE core is described by the visco-elastic Kelvin-Voigt model with a controllable parameter dependent on applied magnetic fields, and the parameter is considered as an active bounded control. The partial differential equations for horizontal and vertical coupling motions of the sandwich beam are obtained and converted into the multi-mode coupling vibration equations with the bounded nonlinear parametric control according to the Galerkin method. The vibration equations and corresponding performance index construct the optimal bounded parametric control problem. Then the dynamical programming equation for the control problem is derived based on the dynamical programming principle. The optimal bounded parametric control law is obtained by solving the programming equation with the bounded control constraint. The controlled vibration responses of the MRVE sandwich beam under stochastic and shock excitations are obtained by substituting the optimal bounded control into the vibration equations and solving them. The further remarkable vibration suppression capability of the optimal bounded control compared with the passive control and the influence of the control parameters on the stochastic vibration suppression effectiveness are illustrated with numerical results. The proposed optimal bounded parametric control strategy is applicable to smart visco-elastic composite structures under deterministic and stochastic excitations for improving vibration control effectiveness.

• Microbiology and Biotechnology Letters
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• v.49 no.2
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• pp.181-191
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• 2021

The present study addresses isolation, optimization, partial purification, and characterization of a haloalkaline serine protease from a newly isolated haloarchaeal strain isolated from Wadi El Natrun in Egypt. We expected that a two-step sequential statistical approach (one variable at a time, followed by response surface methodology) might maximize the production of the haloalkaline serine protease. The enzyme was partially purified using Hiprep 16/60 sephacryl S-100 HR gel filtration column. Molecular identification revealed the newly isolated haloarchaeon to be Natrialba hulunbeirensis strain WNHS14. Among several tested physicochemical determinants, casamino acids, KCl, and NaCl showed the most significant effects on enzyme production as determined from results of the One-Variable-At-A-time (OVAT) study. The BoxBehnken design localized the optimal levels of the three key determinants; casamino acids, KCl, and NaCl to be 0.5% (w/v), 0.02% (w/v), and 15% (w/v), respectively, obtaining 62.9 U/ml as the maximal amount of protease produced after treatment at 40℃, and pH 9 for 9 days with 6-fold enhancement in yield. The enzyme was partially purified after size exclusion chromatography with specific activity, purification fold, and yield of 1282.63 U/mg, 8.9, and 23%, respectively. The enzyme showed its maximal activity at pH, temperature, and NaCl concentration optima of 10, 75℃, and 2 M, respectively. Phenylmethylsulfonyl fluoride (PMSF, 5 mM) completely inhibited enzyme activity.

• The Korean Journal of Applied Statistics
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• v.31 no.6
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• pp.733-749
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• 2018

Sample selection arises as a result of the partial observability of the outcome of interest in a study. Heckman introduced a sample selection model to analyze such data and proposed a full maximum likelihood estimation method under the assumption of normality. Recently sample selection models for binomial and Poisson response variables have been proposed. Based on the theory of symmetry-modulated distribution, we extend these to a model for overdispersed count data. This type of data with no sample selection is often modeled using negative binomial distribution. Hence we propose a sample selection model for overdispersed count data using the negative binomial distribution. A real data application is employed. Simulation studies reveal that our estimation method based on profile log-likelihood is stable.

• Journal of Korean Academy of Nursing
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• v.49 no.4
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• pp.495-504
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• 2019

Purpose: Nursing students experience a high degree of perceived stress during skills training. The resulting academic sentiment is worthy of research. This study examined the learning motivation as a mediator in the association between perceived stress and positive deactivating academic emotions in nursing students undergoing skills training. Methods: A survey was conducted on 386 third-year undergraduate nursing students at a university in Changchun, China, in 2017. The survey included the items on perceived stress, learning motivation during nursing skill training, and general academic emotion. There were 381 valid responses (response rate=98.7%). Based on the results of partial correlation and stepwise multiple regression equations, the study examined the mediation model between perceived stress, learning motivation and positive-deactivating academic emotions using process 2.16 (a plug-in specifically used to test mediation or moderation effect in SPSS). Results: There was a significant negative correlation between students' perceived stress and learning motivation during nursing skills training and positive-deactivating academic emotions. Nervousness, loss of control, and interest in developing reputation had significant predictive effects on positive-deactivating academic emotions. The mediating model was well supported. Conclusion: Learning motivation during nursing skills training lessened the damage of perceived stress on positive-deactivating academic emotions. Improving students' motivation to learn could reduce their perceived stress and build more positive emotions. Positive emotions during learning played an important role in helping nursing students improve skills and enhance their nursing competence.

• Acute and Critical Care
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• v.33 no.4
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• pp.222-229
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• 2018

Background: The diagnosis of pediatric acute respiratory distress syndrome (PARDS) is a pragmatic decision based on the degree of hypoxia at the time of onset. We aimed to determine whether reclassification using oxygenation metrics 24 hours after diagnosis could provide prognostic ability for outcomes in PARDS. Methods: Two hundred and eighty-eight pediatric patients admitted between January 1, 2010 and January 30, 2017, who met the inclusion criteria for PARDS were retrospectively analyzed. Reclassification based on data measured 24 hours after diagnosis was compared with the initial classification, and changes in pressure parameters and oxygenation were investigated for their prognostic value with respect to mortality. Results: PARDS severity varied widely in the first 24 hours; 52.4% of patients showed an improvement, 35.4% showed no change, and 12.2% either showed progression of PARDS or died. Multivariate analysis revealed that mortality risk significantly increased for the severe group, based on classification using metrics collected 24 hours after diagnosis (adjusted odds ratio, 26.84; 95% confidence interval [CI], 3.43 to 209.89; P=0.002). Compared to changes in pressure variables (peak inspiratory pressure and driving pressure), changes in oxygenation (arterial partial pressure of oxygen to fraction of inspired oxygen) over the first 24 hours showed statistically better discriminative power for mortality (area under the receiver operating characteristic curve, 0.701; 95% CI, 0.636 to 0.766; P<0.001). Conclusions: Implementation of reclassification based on oxygenation metrics 24 hours after diagnosis effectively stratified outcomes in PARDS. Progress within the first 24 hours was significantly associated with outcomes in PARDS, and oxygenation response was the most discernable surrogate metric for mortality.