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Tissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform to initiate cancer. Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophages and nascent blood stem cells in zebrafish embryos. Macrophage interactions frequently led to either removal of cytoplasmic material and stem cell division or complete engulfment and stem cell death. Stressed stem cells were marked by surface Calreticulin, which stimulated macrophage interactions. Using cellular barcoding, we found that Calreticulin knock-down or embryonic macrophage depletion reduced the number of stem cell clones that established adult hematopoiesis. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.

This study investigated the impact of boron and copper on the microstructure and mechanical properties of Spheroidal graphite Cast Iron (SCI). The addition of boron increased the ferrite content, while copper increased the stability of pearlite. The interaction between boron and copper significantly increased the ferrite content. Differential Scanning Calorimetry (DSC) revealed that boron decreased the enthalpy change of the α + Fe3C -> γ transformation and increased the enthalpy change of the α -> γ transformation. The addition of boron and copper reduced the tensile and yield strength but increased elongation and impact energy. The findings provide valuable insights into the effect of boron and copper on SCI, facilitating the design and development of high-performance SCI materials.

While sevoflurane and desflurane have been regarded as inhalation agents providing rapid induction and emergence, previous studies demonstrated the superiority of desflurane-anesthesia compared to sevoflurane-anesthesia in the postoperative recovery in obese and geriatric patients. We investigated whether a short-term switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia enhances patient postoperative recovery profile in non-obese patients. We randomly divide patients undergoing elective surgery (n = 60) into two groups: sevoflurane-anesthesia group (Group-S, n = 30 ) and sevoflurane-desflurane group (Group-SD, n = 30 ). In Group-S, patients received only sevoflurane-anesthesia until the end of surgery (for >2 hours). In Group-SD, sevoflurane was stopped and switched to desflurane-anesthesia before the completion of sevoflurane-anesthesia (for approximately 30 minutes). We assessed the intergroup differences in the times to get eye-opening, extubation, and a bispectral index of 80 (BIS-80). Group-SD showed significantly shorter times to get eye-opening ( 438 ± 101 vs. 295 ± 45 s; mean difference, 143 s; 95% confidence interval [CI], 101–183; p < 0.001 ), extubation ( 476 ± 108 vs. 312 ± 42 s; mean difference, 164 s; 95% CI, 116–220; p < 0.001 ), and BIS-80 ( 378 ± 124 vs. 265 ± 49 minutes; mean difference, 113 s; 95% CI, 58–168 p < 0.001 ) compared to Group-S. There was no between-group difference in postoperative nausea, vomiting, and hypoxia incidences. Our results suggested that the short-term (approximately 30 minutes) switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia can facilitate the speed of postoperative patient recovery.

Although the physiological function of receptor-interacting protein kinase (RIPK) 3 has emerged as a critical mediator of programmed necrosis/necroptosis, the intracellular role it plays as an attenuator in human lungs and human bronchial epithelia remains unclear. Here, we show that the expression of RIPK3 dramatically decreased in the inflamed tissues of human lungs, and moved from the nucleus to the cytoplasm. The overexpression of RIPK3 dramatically increased F-actin formation and decreased the expression of genes for pro-inflammatory cytokines (IL-6 and IL-1β), but not siRNA-RIPK3. Interestingly, whereas RIPK3 was bound to histone 1b without LPS stimulation, the interaction between them was disrupted after 15 min of LPS treatment. Histone methylation could not maintain the binding of RIPK3 and activated movement towards the cytoplasm. In the cytoplasm, overexpressed RIPK3 continuously attenuated pro-inflammatory cytokine gene expression by inhibiting NF-κB activation, preventing the progression of inflammation during Pseudomonas aeruginosa infection. Our data indicated that RIPK3 is critical for the regulation of the LPS-induced inflammatory microenvironment. Therefore, we suggest that RIPK3 is a potential therapeutic candidate for bacterial infection-induced pulmonary inflammation.

Background The family Staphylinidae is the most speciose beetle group in the world. The outbreaks of two staphylinid species, Paederus fuscipes and Aleochara (Aleochara) curtula, were recently reported in South Korea. None of research about molecular markers and genetic diversity have been conducted in these two species. Objective To develop microsatellite markers and analyze the genetic diversity and population structures of two rove beetle species. Methods NGS was used to sequence whole genomes of two species, Paederus fuscipes and Aleochara (Aleochara) curtula. Microsatellite loci were selected with flanking primer sequences. Specimens of P. fuscipes and A. curtula were collected from three localities, respectively. Genetic diversity and population structure were analyzed using the newly developed microsatellite markers. Results The number of alleles ranged 5.727–6.636 (average 6.242) and 2.182–5.364 (average 4.091), expected heterozygosity ranged 0.560–0.582 (average 0.570) and 0.368–0.564 (average 0.498), observed heterozygosity ranged 0.458–0.497 (average 0.472) and 0.418–0.644 (average 0.537) in P. fuscipes and A. curtula, respectively. Population structure indicates that individuals of A. curtula are clustered to groups where they were collected, but those of P. fuscipes are not. Conclusion Population structures of P. fuscipes were shallow. In A. curtula, however, it was apparent that the genetic compositions of the populations are different significantly depending on collection localities.

Magnetic nanofluid hyperthermia (MNFH) with pure superparamagnetic nanoparticles (P-SPNPs) has drawn a huge attraction for cancer treatment modality. However, the low intrinsic loss power (ILP) and attributable degraded-biocompatibility resulting from the use of a heavy dose of P-SPNP agents as well as low heat induction efficiency in biologically safe AC magnetic field (HAC,safe) are challenging for clinical applications. Here, we report an innovatively designed pseudo-single domain-SPNP (PSD-SPNP), which has the same translational advantages as that of conventional P-SPNPs but generates significantly enhanced ILP at HAC,safe. According to the analyzed results, the optimized effective relaxation time, τeff, and magnetic out-of-phase susceptibility, χ'', precisely determined by the particle size at the specific frequency of HAC,safe are the main reasons for the significantly enhanced ILP. Additionally, in vivo MNFH studies with colloidal PSD-SPNPs strongly demonstrated that it can be a promising agent for clinically safe MNFH application with high efficacy.

As the home-meal replacement food industry grows, there is an increasing need for smoky flavorings that can satisfy the diverse tastes of consumers. In particular, the industry requires chargrilled flavorings that complement Korean foods. In this study, chargrilled flavoring was applied to bulgogi (Korean barbecued beef) and its effects on consumer liking, sensory perception, familiarity, and flavor congruency with the bulgogi were investigated. Eight formulations (one control and seven flavorings) were tested by 78 Korean subjects. A rate-all-that-apply test was conducted to profile the sensory attributes of the food from the consumers' perspectives. The samples with weaker woody and smoky flavors were preferred; the samples with strong woody and smoky flavors were perceived as being artificial and Western-styled, as well as less familiar and incongruent with bulgogi. This study shows that flavorings that are congruent with a food system can improve consumer liking and the perception of familiarity.

In this study, the characteristics of the SKD61 material used for the stem of an extruder were analyzed through structural analysis, tensile testing, and fatigue testing. The extruder works by pushing a cylindrical billet into a die with a stem to reduce its cross-sectional area and increase its length, and it is currently used to extrude complex and diverse shapes of products in the field of plastic deformation processes. Finite element analysis was used to determine the maximum stress on the stem, which was found to be 1152 MPa, lower than the yield strength of 1325 MPa obtained from tensile testing. Fatigue testing was conducted using the stress–life (S–N) method, considering the characteristics of the stem, and statistical fatigue testing was employed to create an S–N curve. The predicted minimum fatigue life of the stem at room temperature was 424,998 cycles at the location with the highest stress, and the fatigue life decreased with increasing temperature. Overall, this study provides useful information for predicting the fatigue life of extruder stems and improving their durability.

The hematopoietic niche is a supportive microenvironment comprised of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses, we define a conserved gene expression signature and cis-regulatory landscape unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code involving members of the Ets, Sox and Nuclear Hormone Receptor families that is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) is highly desirable in cancer treatment because it can allow for diagnosis, therapeutics, and prognosis simultaneously. However, the application of currently developed iron-oxide based superparamagnetic nanoparticles (IOSPNPs) for an MRI-guided MNFH agent is technically limited by the low AC heat induction power at the physiologically tolerable range of AC magnetic field (

본 연구에서는 공유소비 환경에서 공유소비의도의 선행요인으로 신뢰 개념을 주목하고 3가지 중요한 신뢰차원인 플랫폼 신뢰, 판매자 신뢰, 커뮤니티 신뢰가 공유소비의도에 미치는 영향력을 공유상품유형(재화 vs. 서비스) 간에 비교분석하였다. 실증분석 결과 플랫폼 신뢰와 커뮤니티 신뢰는 공유소비의도에 유의한 영향을 미치는 것으로 나타났으며, 커뮤니티 신뢰의 영향력이 가장 큰 것으로 확인되고 있다. 공유상품유형(재화 vs. 서비스) 간 비교 분석결과 판매자 신뢰와 커뮤니티 신뢰가 공유소비의도에 미치는 영향력은 모두 재화 공유보다 서비스 공유의 경우에 더 큰 것으로 나타났다. 반면에 플랫폼 신뢰가 공유소비의도에 미치는 영향력은 재화 공유와 서비스 공유 간에 차이가 없는 것으로 나타났다. 이러한 연구결과를 바탕으로 공유소비활성화를 위한 공유상품유형에 따른 효과적인 마케팅 커뮤니케이션 전략에 대해 연구되고 논의되었다.

While neural cell transplantation represents a promising therapy for neurodegenerative diseases, the formation of functional networks of transplanted cells with host neurons constitutes one of the challenging steps. Here, we introduce a magnetic guidance methodology that controls neurite growth signaling via magnetic nanoparticles (MNPs) conjugated with antibodies targeting the deleted in colorectal cancer (DCC) receptor (DCC-MNPs). Activation of the DCC receptors by clusterization and subsequent axonal growth of the induced neuronal (iN) cells was performed in a spatially controlled manner. In addition to the directionality of the magnetically controlled axon projection, axonal growth of the iN cells assisted the formation of functional connections with pre-existing primary neurons. Our results suggest magnetic guidance as a strategy for improving neuronal connectivity by spatially guiding the axonal projections of transplanted neural cells for synaptic interactions with the host tissue.

To enhance mechanical properties through improvement of dispersion stability of carbon black (CB) in epoxy resins, fluorine functional groups were introduced on the CB surface by fluorination. The changes in the chemical properties and dispersion stabilities after fluorination were evaluated with different partial pressures of fluorine gas. The mechanical properties of the fluorinated CB/epoxy composites were evaluated by the test of tensile, impact strengths and creep behavior. The fluorinated CB/epoxy composites showed approximately 1.6 and 1.1 times enhancement in the tensile and impact strengths compared to that of neat epoxy, respectively. Moreover, when a constant load was applied at 323 K, the fluorinated CB/epoxy composites lasted longer and had smaller strain changes than those of the raw CB/epoxy composites. Thus, well-dispersed CB by fluorination in epoxy resins effectively transfers mechanical stress.

Background: This study assessed the effect of a single bolus administration of lidocaine on the prevention of tourniquet-induced hypertension (TIH) and compared the effect of lidocaine to that of ketamine in patients undergoing general anesthesia.Methods: This randomized, controlled, double-blind study included 75 patients who underwent lower limb surgery using a tourniquet. The patients were administered lidocaine (1.5 mg/kg, n = 25), ketamine (0.2 mg/kg, n = 25) or placebo (n = 25). The study drugs were administered intravenously 10 min before tourniquet inflation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before tourniquet inflation, after tourniquet inflation for 60 min at 10 min intervals, and immediately after tourniquet deflation. The incidence of TIH, defined as an increase of 30% or more in SBP or DBP during tourniquet inflation, was also recorded.Results: SBP, DBP, and HR increased significantly over time in the control group compared to those in the lidocaine and ketamine groups for 60 min after tourniquet inflation (P < 0.001, P < 0.001, and P = 0.007, respectively). The incidence of TIH was significantly lower in the lidocaine (n = 4, 16%) and ketamine (n = 3, 12%) group than in the control group (n = 14, 56%) (P = 0.001). Conclusion: Single-bolus lidocaine effectively attenuated blood pressure increase due to tourniquet inflation, with an effect comparable to that of bolus ketamine.

Although diesel airborne particulate matter (PM2.5) has been known to play a role in many human diseases, there is no direct evidence that therapeutic drugs or proteins can diminish PM2.5‐induced diseases. Nevertheless, studies examining the negative control mechanisms of PM2.5‐induced diseases are critical to develop novel therapeutic medications. In this study, the consensus PDZ peptide of ZO‐1 inhibited PM2.5‐induced inflammatory cell infiltration, pro‐inflammatory cytokine gene expression, and TEER in bronchoalveolar lavage (BAL) fluid and AM cells. Our data indicated that the PDZ domain in ZO‐1 is critical for regulation of the PM2.5‐induced inflammatory microenvironment. Therefore, the PDZ peptide may be a potential therapeutic candidate during PM‐induced respiratory diseases.

BACKGROUND: Although fine airborne particulate matter (PM) has been known to play a role in many human diseases, there is no direct evidence that therapeutic drugs or proteins can diminish PM-induced diseases. Nevertheless, studies examining the negative control mechanisms of PM-induced diseases are critical to develop novel therapeutic medications. RESULTS: We found that CLB2.0, a surrogate for PM, induced production of multiple cytokines that alter airway inflammation. Interestingly, deletion of each PDZ domain in the ZO-1 protein dramatically decreased F-actin formation and increased the expression of genes for pro-inflammatory cytokines. We also found that the consensus PDZ peptide in ZO-1 downregulates the expression of pro-inflammatory cytokine genes and F-actin formation; in contrast, the GG24,25AA mutant PDZ peptide upregulates them. Moreover, CLB2.0-induced F-actin formation in 2D and 3D matrix cultures was significantly inhibited by PDZ peptide, but not by the mutant peptide. Induction of IL-8 secretion by CLB2.0 activates CXCR2 signaling, while increased RGS12 controlled by the PDZ peptide inhibits IL-8/CXCR2 signaling. The consensus PDZ peptide also inhibited CLB2.0-induced inflammatory cell infiltration, pro-inflammatory cytokine gene expression, and TEER in bronchoalveolar lavage (BAL) fluid and AM cells. CONCLUSIONS: Our data indicated that the PDZ domain in ZO-1 is critical for regulation of the CLB2.0-induced inflammatory microenvironment. Therefore, we suggest that the PDZ peptide may be a potential therapeutic candidate during PM-induced respiratory diseases.

Since the power transmission line (PTL) passes through the high mountain and heavy snowfall region, it is necessary to keep the stability of the PTL. In this study, PTL is modeled as the mass-spring-damper system by using multi-body dynamics analysis program. In order to analyze the dynamic behavior of PTL, a damping coefficient for a multi-body model is derived by using the free vibration test and Rayleigh damping theory. The icing cross section of the transmission line is considered by ellipse and triangle shape. The aerodynamic coefficient for each cross sections are derived by using the commercial CFD program, ANSYS Fluent. The fluctuating wind velocity is regenerated with time history by using Kaimal spectrum. Galloping simulations are performed for the elliptical and triangular iced sections by using the generated fluctuating wind velocity. There is an attack angle which showed the maximum vertical displacement according to the icing section. As a results, the triangular icing shape on the fluctuating wind velocity is more dangerous for the galloping phenomenon. This results can be available to the tower design for the power transmission line.

When the power transmission line (PTL) passes through a region of high mountains and heavy snowfall, maintaining the stability of the PTL and avoiding sleet jump and galloping are necessary. In this study, PTL is modeled as the mass-spring-damper system by using the multi-body dynamics analysis program, RecurDyn. The lumped mass model is compared with the finite element model based on deflection. To analyze the dynamic behavior of the PTL under icing and wind conditions, we obtained a damping coefficient for a multibody model from the free vibration test and Rayleigh damping theory. The icing cross-section of the transmission line is assumed to have ellipse and triangle shapes. The aerodynamic coefficients for each cross-section are derived by using the commercial CFD program, ANSYS Fluent. The occurrence of galloping is simulated for each shape according to the attack angle. Results indicate that the dynamic behavior of the PTL and the galloping conditions such as the icing shape, thickness, and attack angle, can be analyzed. Furthermore, the effects of each factor are evaluated. In the elliptical icing section, the effect of icing thickness is high; whereas in the triangular icing section, the wind velocity highly affects galloping.

The ability to sense and manipulate the state of biological systems has been extensively advanced during the last decade with the help of recent developments in physical tools. Unlike standard genetic and pharmacological perturbation techniques – knockdown, overexpression, small molecule inhibition – that provide a basic on/off switching capability, these physical tools provide the capacity to control the spatial, temporal, and mechanical properties of the biological targets. Among the various physical cues, magnetism offers distinct advantages over light or electricity. Magnetic fields freely penetrate biological tissues and are already used for clinical applications. As one of the unique features, magnetic fields can be transformed into mechanical stimuli which can serve as a cue in regulating biological processes. However, their biological applications have been limited due to a lack of high-performance magnetism-to-mechanical force transducers with advanced spatiotemporal capabilities. In this account, we present recent developments in magnetic nano-tweezers (MNTs) as a high-performance tool for interrogating the spatiotemporal control of cells in living tissue. MNTs are comprised of force-generating magnetic nanoparticles and field generators. Through proper design and the integration of individual components, MNTs deliver controlled mechanical stimulation to targeted biomolecules at any desired space and time. We first discuss about MNT configuration with different force-stimulation modes. By modulating geometry of the magnetic field generator, MNTs exert pulling, dipole-dipole attraction, and rotational forces to the target specifically and quantitatively. We discuss the key physical parameters determining force magnitude, which include magnetic field strength, magnetic field gradient, magnetic moment of the magnetic particle, as well as distance between the field generator and the particle. MNTs also can be used over a wide range of biological time scales — By simply adjusting the amplitude and phase of the applied current, MNTs based on electromagnets allow for dynamic control of the magnetic field from microseconds to hours. Chemical design and the nanoscale effects of magnetic particles are also essential for optimizing MNT performance. We discuss key strategies to develop magnetic nanoparticles with improved force-generation capabilities with a particular focus on the effects of size, shape, and composition of the nanoparticles. We then introduce various strategies and design considerations for target-specific biomechanical stimulations with MNTs. One-to-one particle-receptor engagement for delivering a defined force to the targeted receptor and the small size of the nanoparticles are important. Finally, we demonstrate the utility of MNTs for manipulating biological functions and activities with various spatial (single molecule/cell to organisms) and temporal resolution (microseconds to days). MNTs have the potential to be utilized in many exciting applications across diverse biological systems spanning from fundamental biology investigations of spatial and mechanical signaling dynamics at the single-cell and systems levels to in vivo therapeutic applications.

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) is highly desirable in cancer treatment because it can allow for diagnosis, therapeutics, and prognosis simultaneously. However, the application of currently developed iron-oxide based superparamagnetic nanoparticles (IOSPNPs) for an MRI-guided MNFH agent is technically limited by the low AC heat induction power at the physiologically tolerable range of AC magnetic field (H AC,safe), and the low transverse r 2-relaxivity responsible for the insufficient heating of cancers, and the low resolution of contrast imaging, respectively. Here, pseudo single domain colloidal Ni x Zn1−x –γFe2O3 (x = 0.6) superparamagnetic nanoparticle (NiZn-γFe2O3 PSD-SPNP) physically and theoretically designed at the H AC,safe, specifically by the applied frequency, is proposed for a highly enhanced MRI-guided MNFH agent application. The NiZn-γFe2O3 PSD-SPNP showed the superparamagnetic characteristics, significantly enhanced AC heat induction performance (ILP = 6.3 nHm2 kg−1), highly improved saturation magnetization (M s = 97 emu g−1 Fe, 3.55 × 105 A m−1) and r 2-relaxivity (r 2 = 396 mM−1 s−1) that are desirable for highly efficient MRI-guided MNFH agent applications. According to the analyzed results, the remarkably enhanced effective relaxation time constant and its dependent out-of-phase magnetic susceptibility, as well as the DC/AC magnetic softness optimized by the PSD-SPNP at the H AC,safe were revealed as the main physical reason for the significance. All the fundamental in vitro and in vivo experimental results demonstrated that the physically designed NiZn-γFe2O3 PSD-SPNP is bio-technically feasible for a highly efficient MRI-guided MNFH agent for future cancer nanomedicine.

An automatic mackerel grader is a machine that automatically sorts mackerel according to size. The chute spreads the mackerel to allow the latter to enter each roller evenly. Sorting is simulated to confirm that the multibody dynamics model of the automatic grader correctly sorts the mackerel. This process is completed according to the shape of the chute to confirm the effect on performance. A new shape of the chute and the application are proposed and evaluated by a comparison with conventional chute shapes. RecurDyn, a multi-body dynamics program, is used for the sorting simulation. The contact parameters are defined by Hertzian contact theory using the material information of mackerel and C/S steel. A rigid-body mackerel model is used to express the behavior of mackerel. Sorting is simulated for each shape. The sorting accuracy and error of the new shape are compared with those of two existing shapes. The new shape shows a 0.29 mm sorting error and better sorting accuracy than the existing shapes.

One of the factors that influence the dynamic characteristics of machining systems is the cutting tool. Cutting tools are very diverse, and receptance coupling substructure analysis (RCSA) is essential for analyzing the dynamic characteristics of each tool. For RCSA, a full receptance matrix of the equipment and tools is essential. In this study, rotational degree-of-freedom receptance was estimated and analyzed using translational receptance. Displacement/moment receptance was analyzed according to the distance of the response point using the first-and second-order finite difference methods. The rotation/moment receptance was estimated according to the distance of the response point. Rotation/moment receptance was analyzed using Schmitz’s method and compensation strategies. The limitations of these strategies were analyzed, and the rotation/moment receptance for the beam under free-free boundary conditions was predicted using the second compensation strategy.

Based on the labor-intensive nature of construction tasks and high costs associated with labor operations, reliable estimation of construction labor productivity is crucial. However, owing to the dynamic nature and variety of tasks involved in a construction activity, obtaining accurate and reliable productivity data has proven to be difficult. Herein, a motion data-based modeling approach for estimating the labor productivity is proposed. The method consists of the following: estimating the standard motion time of the tasks, measuring the unit workload of an operation cycle using 3D models, and quantifying the production rates based on the cycle times and unit workloads. Motion-data analysis is also integrated into simulation modeling to incorporate the impact of jobsite conditions. To validate the proposed approach, a case study is applied for estimating the production rate of concrete placement operations. The results demonstrate that the proposed approach can reliably estimate the productivity of the operations.

Cell-based therapies are attractive for treating various degenerative disorders and cancer but delivering functional cells to the region of interest in vivo remains difficult. The problem is exacerbated in dense biological matrices such as solid tissues because these environments impose significant steric hindrances for cell movement. Here, we show that neural stem cells transfected with zinc-doped ferrite magnetic nanoparticles (ZnMNPs) can be pulled by an external magnet to migrate to the desired location in the brain. These magnetically labeled cells (Mag-Cells) can migrate because ZnMNPs generate sufficiently strong mechanical forces to overcome steric hindrances in the brain tissues. Once at the site of lesion, Mag-Cells show enhanced neuronal differentiation and greater secretion of neurotrophic factors than unlabeled control stem cells. Our study shows that ZnMNPs activate zinc-mediated Wnt signaling to facilitate neuronal differentiation. When implemented in a rodent brain stroke model, Mag-Cells led to significant recovery of locomotor performance in the impaired limbs of the animals. Our findings provide a simple magnetic method for controlling migration of stem cells with high therapeutic functions, offering a valuable tool for other cell-based therapies.

Spatiotemporal interrogation of signal transduction at the single-cell level is necessary to answer a host of important biological questions. This protocol describes a nanotechnology-based single-cell and single-molecule perturbation tool, termed mechanogenetics, that enables precise spatial and mechanical control over genetically encoded cell-surface receptors in live cells. The key components of this tool are a magnetoplasmonic nanoparticle (MPN) actuator that delivers defined spatial and mechanical cues to receptors through target-specific one-to-one engagement and a micromagnetic tweezers (μMT) that remotely controls the magnitude of force exerted on a single MPN. In our approach, a SNAP-tagged cell-surface receptor of interest is conjugated with a single-stranded DNA oligonucleotide, which hybridizes to its complementary oligonucleotide on the MPN. This protocol consists of four major stages: (i) chemical synthesis of MPNs, (ii) conjugation with DNA and purification of monovalent MPNs, (iii) modular targeting of MPNs to cell-surface receptors, and (iv) control of spatial and mechanical properties of targeted mechanosensitive receptors in live cells by adjusting the μMT-to-MPN distance. Using benzylguanine (BG)-functionalized MPNs and model cell lines expressing either SNAP-tagged Notch or vascular endothelial cadherin (VE-cadherin), we provide stepwise instructions for mechanogenetic control of receptor clustering and for mechanical receptor activation. The ability of this method to differentially control spatial and mechanical inputs to targeted receptors makes it particularly useful for interrogating the differential contributions of each individual cue to cell signaling. The entire procedure takes up to 1 week.

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.

Tools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive, despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e., selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically activated processes are localized in space and time yet additionally require mechanical loading to become activated. To address this challenge, we synthesized magnetoplasmonic nanoparticles that can image, localize, and mechanically load targeted proteins with high spatiotemporal resolution. We demonstrate their utility by investigating the cell-surface activation of two mechanoreceptors: Notch and E-cadherin. By measuring cellular responses to a spectrum of spatial, chemical, temporal, and mechanical inputs at the single-molecule and single-cell levels, we reveal how spatial segregation and mechanical force cooperate to direct receptor activation dynamics. This generalizable technique can be used to control and understand diverse mechanosensitive processes in cell signaling. VIDEO ABSTRACT.

The National Groundwater Monitoring Network (NGMN) of South Korea provides data since 1995 to monitor the water level and quality of groundwater on a national scale. Major ions such as Ca, Mg, Na, K, HCO 3 , Cl, SO 4 and NO 3 have been monitored since 2008 to assess groundwater quality. Hydrochemical data of bedrock groundwater samples collected from 299 monitoring stations in 2009 were examined using the Self-Organizing Map (SOM) approach. Based on hydrochemical characteristics, bedrock groundwater is clustered into two groups and six subgroups. Group I containing 70.2% of groundwater samples (and monitoring stations) is characterized by lower TDS values and NO 3 concentrations than Group II, indicating that Group I waters are less affected by contamination. Subgroup I-1 (39.1%) represents Ca–HCO 3 -type groundwater with relatively low pH, TDS and concentrations of most ions compared with groundwater of Subgroups I-2-1 (26.1%) and I-2-2 (5.0%). Subgroup I-2-2 represents a moderately alkaline, F-rich, Na–HCO 3 -type groundwater. Group II records either anthropogenic or natural processes. Subgroup II-1 (16.1%) contains groundwater with low values of TDS, HCO 3 and pH, and moderately high NO 3 concentrations due to nitrification, while groundwater of Subgroups II-2-1 and II-2-2 is characteristically high in Ca and Mg. Subgroup II-2-1 is also very high in SO 4 and HCO 3 but very low in NO 3 , while Subgroup II-2-2 is substantially enriched in Cl and NO 3 . The hydrochemistry of groundwater of Subgroup II-2-1 likely results from dissolution of carbonates and gypsum in clastic sedimentary rocks and is affected by dissolution of pyrite and/or S-bearing fertilizers in crystalline rocks. The enrichment of NO 3 , Cl, Ca and Mg in groundwater of Subgroup II-2-2 is the result of substantial contamination from agrochemicals and manure. Thus, about 20.5% (Subgroups II-1 and II-2-2) of bedrock groundwater in South Korea records anthropogenic contamination. This study shows that the SOM approach can be successfully used to classify and characterize the groundwater in terms of hydrochemistry and quality on a regional scale.

K-water Institute, Korea Water Resources Corporation근래 들어 환경에 대한 관심이 높아지면서 지표수 개발 여건은 불리해지고 있으며, 또한 양질의 수자원에 대한 욕구는 점차 증가함에 따라 정부는 지하수 개발 정책을 도모하게 되었다. 이와 같은 개발 정책을 추진하기 위해서는 보다 정확한 지하수 개발가능량과 지하수 이용량 파악이 중요하다. 본 연구에서는 양질의 지하수 이용량 자료를 확보하기 위해 전국(5개 도의 32개 시군)을 대상으로 수년간 모니터링을 실시하고, 통계분석을 통해 합리적인 지하수 이용량 산정방법을 제시하였다.생활용 지하수의 경우 전국을 도시지역, 도농복합지역, 농촌지역으로 구분하고, 지하수 용도를 가정용, 공동주택용, 간이상수도용, 학교용, 일반용 등 5가지로 분류하였다. 농업용 지하수의 경우 전국을 강수량에 따라 평균 강수량지역, 평균 강수량 미만지역, 평균 강수량 초과지역으로 구분하고, 지하수 용도를 전작용, 답작용, 원예용, 축산용-육우, 축산용-양돈, 축산용-양계로 분류하였다. 이로부터 모니터링 자료에 대한 군집분석과 회귀분석을 통해 지역별-용도별 지하수 이용량 추정식을 제시하였다. 향후 본 연구에서 제시한 기준을 적용하여 국가 지하수 이용량 통계의 신뢰도가 크게 향상될 것으로 기대된다.주요어

SEAWAT, a linked modeling program of Visual MODFLOW was used to analyze the change in groundwater levels and salinity related groundwater dam construction in Cheongsan island, Wando-Gun, Jeollanam-Do. The steady-state model results show the groundwater flow and salinity distribution of the studied area. The groundwater flows from north-west and south-east highlands into the river, located in the middle part of the basin, and is eventually discharged to the ocean. Part of the sea water infiltrates into the river; and through the estuary`s alluvium aquifer, the sea water intrusion takes place spreading to about 830 m from the ocean. The transient model results show that after the groundwater dam construction, groundwater levels will rise to a maximum of 2.0 m upstream, and the groundwater storage will increase 21,000 after 10 years. Meanwhile 31% of the total area affected by sea water intrusion will decrease. To conclude, the groundwater dam is a very useful method for a secure water resource in preparation for drought and water shortages in the island regions.

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.

In this study, the position of the hopper in an automatic mackerel grader is determined. The mackerel grader is used for the purpose of sorting the mackerels according to the mackerel size. Hoppers classify mackerels with 4 categories such as very small mackerel, small mackerel, middle mackerel and large mackerel. The multi-body dynamics techniques are employed to carry out the sorting simulation and RecurDyn program is used for the simulation. Solid-Solid contact is defined between the mackerel and grader. From the simulation results, it is noted that the position of the 2nd hopper, the 3rd hopper and the 4th hopper is 1,584 mm, 2,586 mm and 3,581 mm, and sorting error rate of very small, small, middle and large mackerels 0%, 8.33%, 5.88% and 6.67%, respectively when rollers are rotated with 150 rpm.

Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (1000 Hz); therefore, fast kinetic study of hair cells has been difficult, even though mammalians have sound perception of 20 kHz or higher. Here, we demonstrate that the magnetic force nanoprobe (MFN) has superb spatiotemporal capabilities to mechanically stimulate spatially-targeted individual hair cells with a temporal resolution of up to 9 μs, which is equivalent to approximately 50 kHz; therefore, it is possible to investigate avian hair cell biomechanics at different tonotopic regions of the cochlea covering a full hearing frequency range of 50 to 5000 Hz. We found that the variation of the stimulation frequency and amplitude of hair bundles creates distinct mechanical responsive features along the tonotopic axis, where the kinetics of the hair bundle recovery motion exhibits unique frequency-dependent characteristics: basal, middle, and apical hair bundles can effectively respond at their respective ranges of frequency. We revealed that such recovery kinetics possesses two different time constants that are closely related to the passive and active motilities of hair cells. The use of MFN is critical for the kinetics study of free-standing hair cells in a spatiotemporally distinct tonotopic organization.

The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn(0.4)Fe(2.6)O(4)), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.

The conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications such as drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this Letter, we demonstrate a significant increase in the efficiency of magnetic thermal induction by nanoparticles. We take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power, which is a gauge of the conversion efficiency. The optimized core-shell magnetic nanoparticles have specific loss power values that are an order of magnitude larger than conventional iron-oxide nanoparticles. We also perform an antitumour study in mice, and find that the therapeutic efficacy of these nanoparticles is superior to that of a common anticancer drug.

Nitrate and chloride are the most common contaminants in groundwater and their concentrations increase easily due to fertilizer consumption and urbanization. The number of time series data for groundwater quality at a single site was not sufficient to analyze trends on Jeju Island. Therefore rectangle grids were drawn for the whole island and single grid was determined to be after considering similar stream density, homogeneous hydraulic coefficients, geologic features of volcanic rock and low topographic slopes. All data within each lattice were collected and arranged in time series order and analyzed using Sen`s method. 10.6 % of the total lattices for chloride and 22.4% for nitrate showed upward trends from the early 1990`s to the early 2000`s. Especially, upward trends for nitrate concentration are distinct in the low mid-mountainous areas of western and southern watersheds. Many septic tanks and much domestic waste from the urbanization of the low mid-mountainous area have produced this upward trend. Additionally, the agricultural region has dramatically increased since the 1990`s and this has led to an increase of fertilizer consumption and, as a result, nitrate concentration. Therefore, the target of any management plan for groundwater quality on Jeiu Island needs to be focused on careful land use decisions in the mid-mountainous areas which are near Halla Mountain.

Jeju Island is a volcanic island composed predominantly of permeable basalts. The island is poor in surface water but abundant in groundwater. No actual perennial streams exist and the water resources on the island are dependent almost entirely on groundwater. The groundwater bodies on the island are classified into three general categories: high level, basal and parabasal groundwaters. The parabasal groundwater is further subdivided into lower and upper parabasal groundwaters due to the position of the Seogwipo Formation, which is made up of sedimentary rocks with a low permeability. The distribution of each groundwater type was evaluated through analyses of the spatial distribution of the Seogwipo Formation and the hydraulic gradient of the groundwater. Basal groundwater emerges extensively along the coast of the eastern sector, less commonly along the coast of the western sector. Parabasal groundwater occurs extensively over most of the island except for the southern sector, where it occurs only locally in the coastal area. This paper presents a summary of several studies on the occurrence and features of groundwater resources on Jeju Island, the largest island in Korea.

Jeju Island is a volcanic one composed predominantly of permeable basalts. The water resources of the island are dependent almost entirely on groundwater. It is essential to fully understand the hydrogeological conditions of the aquifer systems for proper and sustainable development of groundwater resources. Groundwater characteristics, including water levels and aquifer parameters in the island were evaluated using extensively collected hydrogeologic data. Groundwater levels on the island were located in a range between −26 and 282 m above sea level. Groundwater levels in the northern and southern basins are generally higher than those in the eastern and western basins. Fluctuation patterns of groundwater levels and ECs were classified into three types: sinusoidal fluctuations of both water level and EC, sinusoidal fluctuation of water level only, and no distinct fluctuation pattern. Generally, there were higher groundwater yields in coastal areas than inland areas. The groundwater was most productive in the trachybasalts and basal groundwater areas. This paper is providing a summary of several investigations on the hydrogeological characteristics of the aquifers in the island.

We introduce cubic magnetic nanoparticles as an effective tool for precise and ultrafast control of mechanosensitive cells. The temporal resolution of our system is ∼1000 times faster than previously used magnetic switches and is comparable to the current state-of-the-art optogenetic tools. The use of a magnetism-gated switch reported here can address the key challenges of studying mechanotransduction in biological systems. The cube-shaped magnetic nanoparticles are designed to bind to components of cellular membranes and can be controlled with an electromagnet to exert pico-Newtons of mechanical force on the cells. The cubic nanoparticles can thus be used for noncontact mechanical control of the position of the stereocilia of an inner ear hair cell, yielding displacements of tens of nanometers, with sub-millisecond temporal resolution. We also prove that such mechanical stimulus leads to the influx of ions into the hair cell. Our study demonstrates that a magnetic switch can yield ultrafast temporal resolution, and has capabilities for remote manipulation and biological specificity, and that such magnetic system can be used for the study of mechanotransduction processes of a wide range of sensory systems.