Zaheer, Mohd Moonis;Hasan, Syed Danish;Islam, Nazrul;Aslam, Moazzam
Ocean Systems Engineering
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v.11
no.1
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pp.17-42
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2021
Articulated loading platforms (ALPs) belongs to a class of offshore structures known as compliant. ALP motions have time periods falling in the wind excitation frequency range due to their compliant behaviour. This paper deals with the dynamic behavior of a double hinged ALP subjected to low-frequency wind forces with random waves. Nonlinear effects due to variable submergence, fluctuating buoyancy, variable added mass, and hydrodynamic forces are considered in the analysis. The random sea state is characterized by the Pierson-Moskowitz (P-M) spectrum. The wave forces on the submerged elements of the platform's shaft are calculated using Morison's Equation with Airy's linear wave theory ignoring diffraction effects. The fluctuating wind load has been estimated using Ochi and Shin wind velocity spectrum for offshore structures. The nonlinear dynamic equation of motion is solved in the time domain by the Wilson-θ method. The wind-structure interactions, along with the effect of various other parameters on the platform response, are investigated. The effect of offset of aerodynamic center (A.C.) with the center of gravity (C.G.) of platform superstructure has also been investigated. The outcome of the analyses indicates that low-frequency wind forces affect the response of ALP to a large extent, which otherwise is not enhanced in the presence of only waves. The mean wind modifies the mean position of the platform surge response to the positive side, causing an offset. Various power spectral densities (PSDs) under high and moderate sea states show that apart from the significant peak occurring at the two natural frequencies, other prominent peaks also appear at very low frequencies showing the influence of wind on the response.
You, Eunae;Jeong, Jangho;Lee, Jieun;Keum, Seula;Hwang, Ye Eun;Choi, Jee-Hye;Rhee, Sangmyung
BMB Reports
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v.55
no.4
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pp.192-197
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2022
Cell signals for growth factors depend on the mechanical properties of the extracellular matrix (ECM) surrounding the cells. Microtubule acetylation is involved in the transforming growth factor (TGF)-β-induced myofibroblast differentiation in the soft ECM. However, the mechanism of activation of α-tubulin acetyltransferase 1 (α-TAT1), a major α-tubulin acetyltransferase, in the soft ECM is not well defined. Here, we found that casein kinase 2 (CK2) is required for the TGF-β-induced activation of α-TAT1 that promotes microtubule acetylation in the soft matrix. Genetic mutation and pharmacological inhibition of CK2 catalytic activity specifically reduced microtubule acetylation in the cells cultured on a soft matrix rather than those cultured on a stiff matrix. Immunoprecipitation analysis showed that CK2α, a catalytic subunit of CK2, directly bound to the C-terminal domain of α-TAT1, and this interaction was more prominent in the cells cultured on the soft matrix. Moreover, the substitution of alanine with serine, the 236th amino acid located at the C-terminus, which contains the CK2-binding site of α-TAT1, significantly abrogated the TGF-β-induced microtubule acetylation in the soft matrix, indicating that the successful binding of CK2 and the C-terminus of α-TAT1 led to the phosphorylation of serine at the 236th position of amino acids in α-TAT1 and regulation of its catalytic activity. Taken together, our findings provide novel insights into the molecular mechanisms underlying the TGF-β-induced activation of α-TAT1 in a soft matrix.
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.
Surveillance and reconnaissance intelligence in the space domain will become increasingly important in future battlefield environments. Moreover, to assimilate the military provocations and trends of hostile countries, imagery intelligence of the highest possible resolution is required. There are many methods for improving the resolution of optical satellites when observing the ground, such as designing satellite optical systems with a larger diameter and lowering the operating altitude. In this paper, we propose a method for improving ground observation resolution by using an optical system for a previously designed low orbit satellite and lowering the operating altitude of the satellite. When the altitude of a satellite is reduced in a circular orbit, a large amount of thrust fuel is required to maintain altitude because the satellite's altitude can decrease rapidly due to atmospheric drag. However, by using the critical inclination, which can fix the position of the perigee in an elliptical orbit to the observation area, the operating altitude of the satellite can be reduced using less fuel compared to a circular orbit. This method makes it possible to obtain a similar observational resolution of a medium-sized satellite with the same weight and volume as a small satellite. In addition, this method has the advantage of reducing development and launch costs to that of a small-sized satellite. As a result, we designed an elliptical orbit. The perigee of the orbit is 300 km, the apogee is 8,366.52 km, and the critical inclination is 116.56°. This orbit remains at its lowest altitude to the Korean peninsula constantly with much less orbit maintenance fuel compared to the 300 km circular orbit.
Vibrations in the pipe system trigger fatigue-related issues and lead to fatal other problems caused by pipe damage. There are numerous studies to analyze and reduce the cause of pipe vibration, among which a small number of studies are being conducted on pipe vibration reduction using friction supports. The study of friction supports, however, focused only on predicting and evaluating the performance of the friction supports and seldomly considered the design perspective of the install location of the supports. Therefore, this study intends to suggest the optimization process for finding the best installation region of friction support to attenuate the vibration of entire piping system. The optimal position of the friction support is predicted only by linear analysis to guarantee optimization efficiency in the design process. The designed friction support location is verified by time domain analysis.
Objectives: This study was designed to assess the change of heart rate variability (HRV) at resting, upright, and psychological stress in anxiety disorder patients. Methods: HRV was measured at resting, upright, and psychological stress states in 60 anxiety disorder patients. We used visual analogue scale (VAS) score to assess tension and stress severity. Beck depression inventory (BDI) and state trait anxiety inventories I and II (STAI-I and II) were used to assess depression and anxiety severity. Differences between HRV indices were evaluated using paired t-tests. Gender difference analysis was accomplished with ANCOVA. Results: SDNN (Standard deviation of normal RR intervals) and low frequency/high frequency (LF/HF) were significantly increased, while NN50, pNN50, and normalized HF (nHF) were significantly decreased in the upright position compared to resting state (p < 0.01). SDNN, root mean square of the differences of successive normal to normal intervals, and LF/HF were significantly increased, while nHF was significantly decreased in the psychological stress state compared to resting state (p < 0.01). SDNN, NN50, pNN50 were significantly lower in upright position compared to psychological stress and nVLF, nLF, nHF, and LF/HF showed no significant differences between them. Conclusion: The LF/HF ratio was significantly increased after both physical and psychological stress in anxiety disorder, but did not show a significant difference between these two stresses. Significant differences of SDNN, NN50, and pNN50 without any differences of nVLF, nLF, nHF, and LF/HF between two stresses might suggest that frequency domain analysis is more specific than time domain analysis.
Fertilized egg, by successive cell divisions, differentiates into different tissues and organs with various structures and functions. Different cells and tissues contain different proteins, products of selective gene expression. Not all the genes in any genomes are equally active, temporal and spatial gene expression being the general rule. Present paper attempts to review the tanscriptional mechanisms or the initiations of transcription from several angles. In some of the organisms the genes in the process of transcription or the genes in the inactive state can be seen under the light microscope. Some bands of Drosophila polytene chromosomes may exhibit a swollen or puff appearance under certain conditions. A puff, unfolded or decondensed form of chromomere, represents sets of intense transcriptional activity or RNA synthesis. The heterochromatic X chromosome whose genes remain inactive in the female mammals can be visualized as a dark staining structure called Barr body, Configuration of chromatin differs between transcribed and nontranscribed chromatin. Modification to the chromatin facilitates RNA synthesis. The movement of large polymerase molecule along the DNA would probably be facilitated if some modifications of the chromatin configuration is effected. Methylation of cytosines in CG sequences is associated with inactive genes. Methylation can play a role in determination of mammalian cells during embryogenesis. Demethylation is necessary for the gene to be expressed during development A histone modification that is also known to be correlated with transcriptional capacity of chromatin is acetylation of the lysine residues of the core histones. Chromatin containing a high level of histone acetylation is very sensitive to DNase 1. For the transcription to occur TBP must first bind to the TATA box. Another TF, TF IIB, then binds to the promoter-TBP complex, facilitating the access of RNA polymerase to the transcription initiation site. As recently as eight years ago researchers assumed that histones were irrelevant to the regulation of gene expression. Histones combine with the DNA to form nucleosome of the chromatin. Histones are vital participant in gene regulation. Histone and basal factors compete for access to TATA box. When DNA is exposed to basal factors before histones are introduced, the basal factors assemble on TATA boxes preventing the access of histones, allowing transcription to occur, for transcription to begin, activator protein at the upstream activation sequence or enhancer must interact with the tail of histone H4 at TATA box and cause the histone role particle to dissociate from the TATA box leading to partial breakup of the histone core particle and allowing the basal factors to bind to the TATA box. New concept of genomic flux in contrast to the old concept of static genome has been developed based on the powerful new molecular techniques. Genomic changes such as repetitive DNAs and transposable elements, it is assumed but not yet proved, may affect some of the developmental patterns that characterize particular cells, tissues, organs, and organisms. In the last decade or so remarkable achievement have been made in the researches of the structures and functions of TFs and the specific target sequences located in promoters or enhancers where these TFs bind. TFs have independent domains that bind DNA and that activate transcription. DNA binding domain of TFs serves to bring the protein into the right location. There are many types of DNA binding domains. Common types of motifs can be found that are responsible for binding to DNA. The motifs are usually quite short and comprise only a small part of the protein structure. Steroid receptors have domains for hormone binding, DNA binding, and activating transcription. The zinc finger motif comprises a DNA binding domain. Leucine zipper consist of a stretch of amino acids with a leucine residue in every seventh position Two proteins form a dimer because they interact by means of leucine zippers on similar α-helical domain. This positions their DNA binding basic domains for interaction with the two halves of a DNA sequence with dyad symmetry of TGACTCA, ACTGAGT.
Recently, transport parameters of conservative solutes such as KCl in a porous medium have been successfully determined using time domain reflectometry (TDR) . This study was initiated to Investigate the applicability of TDR technique to monitoring the fate of a heavy metal ion in a sandy soil and the distribution of its concentration along travel distance with time. A column test was conducted in a laboratory that consists of monitoring both resident and flux concentrations of $ZnCl_2$in a sandy soil under a breakthrough condition. A tracer of $ZnCl_2$(10 g/L) was injected onto the top surface of the sample as pulse type as soon as a steady-state condition was achieved. Time-series measurements of resistance and electrical conductivity were performed at 10 cm and 20 cm of distances from the inlet boundary by horizontal-positioning of parallel TDR metallic rods and using an EC-meter for the effluent exiting the bottom boundary respectively. In addition. Zn ions of the effluent were analyzed by ICP-AES. Since the mode and position of concentration detected by TDR and effluent were different, comparison between ICP analysis and TDR-detected concentration was made by predicting flux concentration using CDE model accommodating a decay constant with the transport parameters obtained from the resident concentrations. The experimental results showed that the resident concentration resulted in earlier and higher peak than the flux concentration obtained by EC-meter, implying the homogeneity of the packed sandy soil. A close agreement was found between the predicted from the transport parameters obtained by TDR and the measured $ZnCl_2$concentration. This indicates that TDR technique can also be applied to monitoring heavy metal concentrations in the soil once that a decay constant is obtained for a given soil.
The objectives of this study are to identify the actual educational contents of management for head nurse and to propose the educational subjects according to identity the needs of head, charge, and staff nurses. The subjects were investigated the actual Management Development Programs and educational needs of head nurses and prospective nurse manager(charge nurse, staff nurse with a lot of clinical experiences) in general hospitals. The tools were composed of two questionnaires: One was developed from the literature review for making items to measure actual situation. The other was revised Katz's model for measurement of educational needs. The first respondents of actual situation were 27 general hospitals with over 400 beds in Seoul and the second respondents were 89 head nurses, 67 charge nurses and 136 nurses at 3 hospitals by convenient sampling out of 27 general hospitals. Data were collected by telephone interview, mail questionnaire and visiting from 7th of October through 30th of November in 1997. In data analysis, general characteristics of the respondents and actual status of Management Development Programs were analyzed by frequency and percentage. Educational needs according to general characteristics were analyzed by ANOVA The results were as follows: 1. Actual situation of Management Development Program 1) Seven hospitals(26%) had Management Development Program for prospective managers and 14 hospitals (52%) for head nurses. 2) Education Department existed in 14 hospitals (52%). 3) One hospital(4%) had top level managers took part in the Management Development. 4) Two hospitals selected head nurse, who had finished courses of Management Development. Eight hospitals(30%) assessed educational needs. The assessment tools consisted of making a question via questionnaire(75%), determining at department meeting(12%) and interview(13%). 5) Educational programs had 3 types: 10 lecture type, 7 discussion type and 4 role play type programs. 6) One hospital evaluated the change of learner's attitude. 7) Four hospitals scored educational point, but that was measured only by attending. 8) Actual Management Development Programs were as follows. parenthesis indicates the number of hospitals. (1) Management Development Programs for Prospective manager. Role perception of Middle level Manager (1) . Role reconstruction of Nurse Manager (1). Workshop for Charge Nurse (1). Nursing Delivery System and Nursing Process (1). Communication (1). Motivation (1) (2) Management Development Programs for Head nurse.. Head nurse's Role (5). Administrative Work (7). Service Education (4). Prevention and Countermeasure of Nursing Incidence (3). Appraisal (3) 2. The results of needs on Management Development subject 1) The educational needs of all respondents on 3 skill domains showed positive agreement to strongly positive agreement. 2) High priority(more than 4.5) items were 12 of 24 Human skill items(50%), 1 of 6 Technical skill items(16%), and 2 of 13 Conceptual skill items (15%). 3) Out of high priority items, 8 items were instituted. 4) All respondents showed high needs on 3 skill domains regardless of 3 positions (head nurse, charge nurse, and nurse). Educational needs of Human skill domain, according to position were 108. S, 108.7, 106.8 (mean score = 72) , needs of Technical skill domain were 26.5, 26.6, 26.I(mean score=18), and needs of Conceptual skill domains were 56.9,56.7, 55.1(mean score=39). 5) Needs of 3 skill domains according to clinical career showed significant difference. Out of respondents, nurses with career of over 16years showed lowest degree of needs in Human skill domains(F=4.47, P=.004) and Conceptual skill domain(F=2.93, P=.034). 6) Educational needs according to educational background were not significant difference. But out of respondents, nurses educated at 3-year junior college relatively showed lowest needs in all of the 3 skill domains. With the above-mentioned findings, further study is necessary for generalization of this study at hospitals with different bed size and location. Also it is needed to study about management skill of nurse and charge nurse, and effective educational method.
Beta-asarone is the well-known active ingredient of Rhizoma acori graminei. In this study, we investigated and compared the binding affinity of mosquito oviposition pheromone (MOP; (5R,6S)-6-acetoxy-5-hexadecanolide) and beta-asarone on the A domain of the mosquito odorant binding protein 1 (CquiOBP1) by in silico computational docking studies. The three-dimensional crystallographic structure of CquiOBP1 was obtained from the PDB database (PDB ID: 3OGN). In silico computational auto-docking analysis was performed using PyRx, Autodock Vina, Discovery Studio Version 4.5, and the NX-QuickPharm option based on scoring functions. The beta-asarone showed optimum binding affinity (docking energy) with CquiOBP1 as -6.40 kcal/mol as compared to the MOP (-6.00 kcal/mol). Among the interacting amino acids (LEU76, LEU80, ALA88, MET89, HIS111, TRP114, and TYR122), tryptophan 114 in the CquiOBP1 active site significantly interacted with both MOP and beta-asarone. Amino acids substitution (mutation) from non-polar groups to the polar (or charged) groups of the CquiOBP1 dramatically changed the X, Y, Z grid position and binding affinity of both ligands. These results significantly indicated that beta-asarone could be a more potent ligand to the CquiOBP1 than MOP. Therefore, the extract of Rhizoma acori graminei or beta-asarone can be applied to the fields of insecticidal and repellant biomaterial development.
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