Controlling organization and forces in active matter through optically defined boundaries.

Living systems are capable of locomotion, reconfiguration and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, 'active' molecules that create and manipulate non-equilibrium structures and force fields of up to millimetre length scales1-3. Experimental active-matter systems of biological or synthetic molecules are capable of spontaneously organizing into structures4,5 and generating global flows6-9. However, these experimental systems lack the spatiotemporal control found in cells, limiting their utility for studying non-equilibrium phenomena and bioinspired engineering. Here we uncover non-equilibrium phenomena and principles of boundary-mediated control by optically modulating structures and fluid flow in an engineered system of active biomolecules. Our system consists of purified microtubules and light-activatable motor proteins that crosslink and organize the microtubules into distinct structures upon illumination. We develop basic operations-defined as sets of light patterns-to create, move and merge the microtubule structures. By combining these operations, we create microtubule networks that span several hundred micrometres in length and contract at speeds up to an order of magnitude higher than the speed of an individual motor protein. We manipulate these contractile networks to generate and sculpt persistent fluid flows. The principles of boundary-mediated control that we uncover may be used to study emergent cellular structures and forces and to develop programmable active-matter devices.

Corticosteroid-induced drug reaction with eosinophilia and systematic symptoms successfully treated with a tumor necrosis factor alpha inhibitor.

BACKGROUND: Despite recent advances in the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS), the mainstay of treatment involves discontinuing the culprit drugs and administering topical or systemic corticosteroid. OBJECTIVE: The clinical use of a tumor necrosis factor (TNF)-alpha inhibitor was rarely explored in treatment of DRESS. METHODS: We present a case of corticosteroid-induced DRESS that was successfully treated with a TNF-alpha inhibitor without sequalae. RESULTS: This is the first case report that showed the clinical use of a TNF alpha inhibitor in treating corticosteroids- induced DRESS and immediate hypersensitivity reactions. The HLA-B*5801 was identified as a possible genetic factor associated with a corticosteroid-induced DRESS. CONCLUSIONS: A TNF-alpha inhibitor could be a primary option in treating DRESS, especially in patients with hypersensitivity reaction to corticosteroids.

Effect of Tranexamic Acid Administration on Postoperative Ecchymosis and Edema in Excision of Lipomas.

BACKGROUND: Previous studies have shown that systemic tranexamic acid reduces bleeding during soft tissue surgeries and reduces postoperative ecchymosis and edema experienced by surgical patients. OBJECTIVE: To evaluate the effect of postoperative tranexamic acid administration on the reduction of ecchymosis and edema after lipoma surgery. MATERIALS AND METHODS: A total of 40 patients who underwent lipoma excision were included in the comparative analysis. In the tranexamic acid group (n = 20), 1 g of tranexamic acid was administered daily for 5 consecutive postoperative days. Tranexamic acid was not administered to the control group (n = 20). The severity of ecchymosis and edema at the first visit after surgery was rated on a 4-point scale by 2 blinded dermatologists. RESULTS: The mean interval of the initial visit after surgery was 1.1 ± 0.5 (range: 1-4) days. Mean ecchymosis scores were significantly lower in the tranexamic acid group (0.5 ± 0.8) than in the control group (1.2 ± 1.0) (p < .05). No statistical difference was seen in mean edema scores between groups (0.5 ± 0.6 in tranexamic acid vs 0.7 ± 0.8 in control). CONCLUSION: We observed that postoperative administration of tranexamic acid significantly decreased ecchymosis in lipoma excision.

Connecting the Dots between Mechanosensitive Channel Abundance, Osmotic Shock, and Survival at Single-Cell Resolution.

Rapid changes in extracellular osmolarity are one of many insults microbial cells face on a daily basis. To protect against such shocks, Escherichia coli and other microbes express several types of transmembrane channels that open and close in response to changes in membrane tension. In E. coli, one of the most abundant channels is the mechanosensitive channel of large conductance (MscL). While this channel has been heavily characterized through structural methods, electrophysiology, and theoretical modeling, our understanding of its physiological role in preventing cell death by alleviating high membrane tension remains tenuous. In this work, we examine the contribution of MscL alone to cell survival after osmotic shock at single-cell resolution using quantitative fluorescence microscopy. We conducted these experiments in an E. coli strain which is lacking all mechanosensitive channel genes save for MscL, whose expression was tuned across 3 orders of magnitude through modifications of the Shine-Dalgarno sequence. While theoretical models suggest that only a few MscL channels would be needed to alleviate even large changes in osmotic pressure, we find that between 500 and 700 channels per cell are needed to convey upwards of 80% survival. This number agrees with the average MscL copy number measured in wild-type E. coli cells through proteomic studies and quantitative Western blotting. Furthermore, we observed zero survival events in cells with fewer than ∼100 channels per cell. This work opens new questions concerning the contribution of other mechanosensitive channels to survival, as well as regulation of their activity.IMPORTANCE Mechanosensitive (MS) channels are transmembrane protein complexes which open and close in response to changes in membrane tension as a result of osmotic shock. Despite extensive biophysical characterization, the contribution of these channels to cell survival remains largely unknown. In this work, we used quantitative video microscopy to measure the abundance of a single species of MS channel in single cells, followed by their survival after a large osmotic shock. We observed total death of the population with fewer than ∼100 channels per cell and determined that approximately 500 to 700 channels were needed for 80% survival. The number of channels we found to confer nearly full survival is consistent with the counts of the numbers of channels in wild-type cells in several earlier studies. These results prompt further studies to dissect the contribution of other channel species to survival.

Evaluation of a novel device, high-intensity focused ultrasound with a contact cooling for subcutaneous fat reduction.

BACKGROUND: Non-invasive devices for fat reduction involving high-intensity focused ultrasound (HIFU) are attracting attention. HIFU can deliver energy to the desired depth and can ablate subcutaneous adipose tissue (SAT), but purpura and pain may still limit its use. OBJECTIVES: The aim of this study was to investigate the effects of a novel HIFU device for fat destruction with a contact cooling system compared to HIFU without contact cooling. METHODS: A group of three pigs were administered a series of four HIFU treatments with or without contact cooling over a period of 12 weeks. Energy fluence parameters ranged from 60 to 300 J/cm2 . Immediately after the treatment and at 1, 4, and 12 weeks, the tissue was studied by hematoxylin and eosin (H&E), Masson-trichrome, toluidine blue, CD68 staining, and transmission electron microscopy. Three human volunteers also received treatment with this HIFU device with cooling and were evaluated subjectively and objectively by computed tomography (CT). RESULTS: HIFU treatment with a contact cooling decreased the skin surface temperature and prevented epidermal damage. Ecchymosis was observed on the non-cooled area immediately after HIFU treatment, but not on the cooled area. Histological analyses on both areas (cooled and non-cooled) revealed disrupted adipocytes in the treatment area immediately, at 1 and 4 weeks following treatment. Lipophagic histiocytic fat necrosis was evident at 4 weeks. Finally, at 12 weeks all inflammation subsided, and the lobules were markedly atrophied with reduced SAT thickness. The human volunteers experienced reduction of a few centimeter-range reduction in waist circumference after 4 weeks and pain was tolerable without bruising. CONCLUSIONS: HIFU treatment with a cooling system efficiently destroyed adipocytes. This novel HIFU device with an added contact cooling system may provide an effective, safe and less painful treatment as a non-invasive device for fat reduction. Lasers Surg. Med. 48:878-886, 2016. © 2016 Wiley Periodicals, Inc.

Genetic landscape of open chromatin in yeast.

Chromatin regulation underlies a variety of DNA metabolism processes, including transcription, recombination, repair, and replication. To perform a quantitative genetic analysis of chromatin accessibility, we obtained open chromatin profiles across 96 genetically different yeast strains by FAIRE (formaldehyde-assisted isolation of regulatory elements) assay followed by sequencing. While 5∼10% of open chromatin region (OCRs) were significantly affected by variations in their underlying DNA sequences, subtelomeric areas as well as gene-rich and gene-poor regions displayed high levels of sequence-independent variation. We performed quantitative trait loci (QTL) mapping using the FAIRE signal for each OCR as a quantitative trait. While individual OCRs were associated with a handful of specific genetic markers, gene expression levels were associated with many regulatory loci. We found multi-target trans-loci responsible for a very large number of OCRs, which seemed to reflect the widespread influence of certain chromatin regulators. Such regulatory hotspots were enriched for known regulatory functions, such as recombinational DNA repair, telomere replication, and general transcription control. The OCRs associated with these multi-target trans-loci coincided with recombination hotspots, telomeres, and gene-rich regions according to the function of the associated regulators. Our findings provide a global quantitative picture of the genetic architecture of chromatin regulation.

The rate of osmotic downshock determines the survival probability of bacterial mechanosensitive channel mutants.

Mechanosensitive (MS) channels allow cells to sense and respond to environmental changes. In bacteria, these channels are believed to protect against an osmotic shock. The physiological function of these channels has been characterized primarily by a standardized assay, where aliquots of batch-cultured cells are rapidly pipetted into a hypotonic medium. Under this method, it has been inferred many types of MS channels (MscS homologs in Escherichia coli) demonstrate limited effectiveness against shock, typically rescuing less than 10% of the cells when expressed at native levels. We introduce a single-cell-based assay which allows us to control how fast the osmolarity changes, over time scales ranging from a fraction of a second to several minutes. We find that the protection provided by MS channels depends strongly on the rate of osmotic change, revealing that, under a slow enough osmotic drop, MscS homologs can lead to survival rates comparable to those found in wild-type strains. Further, after the osmotic downshift, we observe multiple death phenotypes, which are inconsistent with the prevailing paradigm of how cells lyse. Both of these findings require a reevaluation of our basic understanding of the physiology of MS channels.

A genome-wide association study of copy-number variation identifies putative loci associated with osteoarthritis in Koreans.

BACKGROUND: OA is a complex disease caused by environmental and genetic risk factors. The purpose of this study is to identify candidate copy number variations (CNVs) associated with OA. METHODS: We performed a genome-wide association study of CNV to identify potential loci that confer susceptibility to or protection from OA. CNV genotyping was conducted using NimbleGen HD2 3 × 720K comparative hybridization array and included samples from 371 OA patients and 467 healthy controls. The putative CNV regions identified were confirmed with a TaqMan assay. RESULTS: We identified six genomic regions associated with OA encompassing CNV loci. None of six loci had previously been reported in genome-wide association studies with OA, although a genetic analysis suggested that they have functional effects. The protein product of a candidate risk gene for obesity, TNKS, targets Wnt inhibition, and this gene was significantly associated with hand and knee OA. Copy number deletion on TNKS was associated with a 1.37-fold decreased risk for OA. In addition, CA10, which shows a strong association with osteoporosis, was also significant in our study. Copy number deletion on this gene was associated with a 1.69-fold decreased risk for OA. CONCLUSION: We identified several CNV loci that may contribute to OA susceptibility in Koreans. Further functional investigations of these genes are warranted to fully characterize their putative association.

Genome-wide copy number variation study reveals KCNIP1 as a modulator of insulin secretion.

Copy number variations (CNVs) have emerged as another important genetic marker in addition to SNP for understanding etiology of complex diseases. In light of this, we performed a genome-wide CNV study to identify type 2 diabetes (T2D)-associated CNV using an array comparative genomic hybridization from 3180 subjects for T2D cases (n=863) and controls (n=2,317). Thus, five CNV regions having a p-value threshold ≤0.05 were identified and evaluated by validation with quantitative PCR and comparison with previously reported CNV regions in the Database of Genomic Variants. Furthermore, we performed a functional experiment to assess the biological significance of a gene encompassing a CNV region. The inhibition of KCNIP1 led to increased insulin secretion in a glucose-dependent manner, but had no effect on insulin gene transcription as well as cell apoptosis. Taken together, these data indicate that KCNIP1 from CNV study might function as a T2D-susceptibility gene whose dysregulation alters insulin production.

Hesperidin, A Popular Antioxidant Inhibits Melanogenesis via Erk1/2 Mediated MITF Degradation.

Regulation of melanogenesis has been the focus of treatment for hyperpigmentary skin disorders. Although hesperidin is one of the most well-known, naturally occurring flavonoids with antioxidant and anti-inflammatory effect, its anti-melanogenic effect is not known. The present study aims to determine the anti-melanogenic effect of hespiridin as well as its underlying molecular mechanisms. Melanin contents were measured in normal human melanocytes and B16F10 melanoma cells. Protein and mRNA levels of tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1) and TRP-2 were determined. Melanogenesis-regulating signals were examined. In results, hesperidin strongly inhibited melanin synthesis and tyrosinase activity. Hesperidin decreased tyrosinase, TRP-1, and TRP-2 protein expression but increased phospho-extracellular signal-regulated kinase 1/2 (p-Erk1/2) expression. Specific inhibitor of Erk1/2 or proteasome inhibitor reversed the inhibition of melanogenesis induced by hesperidin. Taken together, hesperidin, a popular antioxidant, stimulated Erk1/2 phosphorylation which subsequently degraded MITF which resulted in suppression of melanogenic enzymes and melanin synthesis.

Associations between blood mercury levels and subclinical changes in liver enzymes among South Korean general adults: analysis of 2008-2012 Korean national health and nutrition examination survey data.

INTRODUCTION: We herein used data from the Korean National Health and Nutritional Examination Survey (KNHANES) 2008-2012 to examine the associations between blood mercury levels and subclinical changes of liver function in a representative sample of the adult Korean population. METHODS: This study was based on data obtained from KNHANES, in which a rolling sampling design was used to perform a complex, stratified, multistage probability cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. The associations between subclinical hepatic changes and blood mercury levels were assessed after adjustment for various demographic and lifestyle factors. RESULTS: Multivariate linear regression analyses revealed that each doubling of blood mercury increased serum aspartate transaminase (AST) by 0.676U/L and serum alanine transaminase (ALT) by 1.067U/L. The mean differences (95% CI) in serum AST and ALT between the lowest and highest quartiles were statistically significant at 1.249 (0.263-2.235)U/L and 2.248 (0.648-3.848), respectively. Logistic regression analysis showed that the odd ratios for having serum AST and ALT levels above the median were statistically significant in both the models according to the increase of blood mercury. The risks of having serum AST and ALT levels higher than the median among subjects in 4th quartile of blood mercury were 1.524 and 1.947, respectively. DISCUSSION: The present findings show that subclinical changes of liver function are associated with blood mercury levels. This is the first study to show an association between blood mercury levels and mild liver dysfunction, as a possible proxy measure of nonalcoholic fatty liver disease (NAFLD), in Asian population.

Iron deficiency increases blood lead levels in boys and pre-menarche girls surveyed in KNHANES 2010-2011.

INTRODUCTION: We present data from the Korean National Health and Nutritional Examination Survey (KNHANES) 2010-11 on the distribution of blood lead levels, and examine their association with iron deficiency in a representative sample of the adolescent Korean population. METHODS: This study was based on data obtained from KNHANES, in which a rolling sampling design was used to perform a complex, stratified, multistage probability cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Serum ferritin was categorized into three levels: low (serum ferritin <15.0µg/L), low normal (serum ferritin 15.0-30.0µg/L for girls and 15.0-50.0 for boys), and normal (serum ferritin ≥30.0µg/L for girls and ≥50.0 for boys), and its association with blood lead levels was assessed after adjustment for various demographic and lifestyle factors. RESULTS: The geometric mean (GM) of blood lead in the low serum ferritin group was significantly higher than that in the normal group among boys but not girls. After controlling for covariates, multiple regression analysis showed that blood lead was inversely correlated with serum ferritin levels in boys and pre-menarche girls only. DISCUSSION: The present study shows that iron deficiency increases blood lead levels in a representative sample of the male and pre-menarche female adolescent population, as evaluated in KNHANES. The confounding effect of estrogen on blood lead levels should be considered.

Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells.

Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous origin in replicating cells included sub-telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with γ-H2AX of endogenous origin. γ-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous γ-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Sub-telomeres were less responsive to external DNA damage than to endogenous stress. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy.

Motor processivity and speed determine structure and dynamics of microtubule-motor assemblies.

Active matter systems can generate highly ordered structures, avoiding equilibrium through the consumption of energy by individual constituents. How the microscopic parameters that characterize the active agents are translated to the observed mesoscopic properties of the assembly has remained an open question. These active systems are prevalent in living matter; for example, in cells, the cytoskeleton is organized into structures such as the mitotic spindle through the coordinated activity of many motor proteins walking along microtubules. Here, we investigate how the microscopic motor-microtubule interactions affect the coherent structures formed in a reconstituted motor-microtubule system. This question is of deeper evolutionary significance as we suspect motor and microtubule type contribute to the shape and size of resulting structures. We explore key parameters experimentally and theoretically, using a variety of motors with different speeds, processivities, and directionalities. We demonstrate that aster size depends on the motor used to create the aster, and develop a model for the distribution of motors and microtubules in steady-state asters that depends on parameters related to motor speed and processivity. Further, we show that network contraction rates scale linearly with the single-motor speed in quasi-one-dimensional contraction experiments. In all, this theoretical and experimental work helps elucidate how microscopic motor properties are translated to the much larger scale of collective motor-microtubule assemblies.

Fixed Drug Eruption in a Patient Taking Valacyclovir without Cross-Reactivity to Acyclovir.

Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.

Effects of a supportive workplace environment on the success rate for smoking cessation camp.

Background: This study was conducted to identify the success rate for smoking cessation over time after participation in a therapeutic smoking cessation camp, and to identify how participant characteristics, including a supportive workplace environment for smoking cessation (SWESC), affect the success rate for smoking cessation. Methods: In all, 296 participants at smoking cessation camps in Ulsan between 2015 and 2020 were investigated. The success rates of smoking cessation after weeks 4, 6, 12, and 24 at camp were investigated. The participants were grouped as workers with an SWESC, and workers without an SWESC, and variables (age, education, household income, marital status, drinking, exercise, body mass index, morbidity, job, number of counseling sessions, cigarettes smoked per day and smoking initiation age) were investigated. Multiple logistic regression analysis was conducted at each time point. In addition, Cox regression analysis was performed to evaluate the variables affecting the success rate for smoking cessation over time. Results: The smoking cessation success rate of workers with an SWESC at week 24 (90.7%) was higher than that for workers without an SWESC (60.5%). Multiple logistic regression was performed to determine the relationship between each variable and the success rates for smoking cessation at week 6, 12, and 24. SWESC was confirmed as significant (p < 0.05) variables for increased success rate for smoking cessation at all 3 time points. After adjusting for all variables, the Cox proportional hazards survival analysis showed a hazard ratio of 6.17 for SWESC (p < 0.001,; 95% confidence interval: 3.08-12.38). Conclusions: At a professional treatment smoking cessation camp, participants with an SWESC showed a significantly higher success rate for smoking cessation. Supportive workplace environment for workers' health is expected to be an important factor for smoking cessation projects as well as other health promotion projects at workplace.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models.

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing-related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant (P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

MD-2 as the target of nonlipid chalcone in the inhibition of endotoxin LPS-induced TLR4 activity.

Myeloid differentiation 2 (MD-2) recognizes endotoxin lipopolysaccharide (LPS), which is required for Toll-like receptor 4 (TLR4) activity. MD-2 represents a more attractive therapeutic target than TLR4 for intervention in severe inflammatory disorders due to microbial infection. Here, we suggest MD-2 as a molecular target of nonlipid chalcone in the inhibition of LPS-induced cellular inflammation. A chalcone derivative, 2',4-dihydroxy-6'-isopentyloxychalcone (JSH) competitively displaced LPS from MD-2, and was fitted into the ligand-binding site on the crystal structure of MD-2 under the most energetically favorable simulation. JSH nullified TLR4 activation mechanism and sequentially inhibited nuclear factor-κB (NF-κB) activation that involves the phosphorylation and degradation of inhibitory κBs and the nuclear import and transcriptional activity of NF-κB in LPS-activated macrophages. Moreover, JSH suppressed NF-κB-target inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1ß (IL-1ß) and IL-6. Taken together, this study assigns the chalcone structure as an LPS antagonist binding to MD-2 with therapeutic potential against inflammatory conditions.

Nickel dust-induced occupational contact dermatitis by welding and grinding work in shipyard workers: a report of nine cases.

Background: Occupational skin diseases are skin conditions that occur or worsen in relation to work and known to be the second most common type of occupational disease affecting individuals in the United States. In Korea, epidemiological reports related to occupational skin diseases are rare. But, no cases of occupational contact dermatitis caused by welding and grinding work have been reported previously. Case presentation: Nine male workers working in the production department for liquefied natural gas (LNG) ships in Ulsan complained of erythematous papules/patches and itching in various areas of the body after welding and grinding work. The work environment monitoring report revealed that the amount of nickel dust exceeded the time weighted average (TWA) and poor local ventilation status. Based on the symptoms and the overall results of surveys, several tests, and work environment monitoring report, the 2 workers who had positive patch-test reactions to nickel were diagnosed with nickel dust-induced allergic contact dermatitis. The other 7 workers were diagnosed that there was a high probability that they had nickel dust-induced irritant contact dermatitis. The 2 workers who had nickel dust-induced allergic contact dermatitis were recommended to switch their jobs. Conclusions: Nickel is one of the most common cause of allergic contact dermatitis. In this case, the dust was assumed to be created by welding work with a high nickel content new welding rod and subsequent grinding work, and the concentration of this dust exceeded the time weighted average. Thus, it is thought that the nickel dust may have caused contact dermatitis through continuous contact with the workers' exposed skin in a poorly ventilated space. Currently, several domestic shipbuilding companies are manufacturing LNG tankers using a new construction method. Consequently, it is highly likely that similar cases will occur in the future, which makes this case report meaningful.

Comparison and calibration of different reporters for quantitative analysis of gene expression.

Absolute levels of gene expression in bacteria are observed to vary over as much as six orders of magnitude. Thermodynamic models have been proposed as a tool to describe the expression levels of a given transcriptional circuit. In this context, it is essential to understand both the limitations and linear range of the different methods for measuring gene expression and to determine to what extent measurements from different reporters can be directly compared with one aim being the stringent testing of theoretical descriptions of gene expression. In this article, we compare two protein reporters by measuring both the absolute level of expression and fold-change in expression using the fluorescent protein EYFP and the enzymatic reporter ß-galactosidase. We determine their dynamic and linear range and show that they are interchangeable for measuring mean levels of expression over four orders of magnitude. By calibrating these reporters such that they can be interpreted in terms of absolute molecular counts, we establish limits for their applicability: autofluorescence on the lower end of expression for EYFP (at ∼10 molecules per cell) and interference with cellular growth on the high end for ß-galactosidase (at ∼20,000 molecules per cell). These qualities make the reporters complementary and necessary when trying to experimentally verify the predictions from the theoretical models.