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Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G‐patch domain and a Forkhead‐associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross‐sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme‐linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen‐6 (KL‐6) levels, C‐reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL‐6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis. [ABSTRACT FROM AUTHOR]

This article presents a case report of a 38-year-old female with nodular scleroderma (NS) successfully treated with tocilizumab (TCZ). NS is a rare variant of scleroderma characterized by multiple sclerotic nodules and keloidal plaques. The patient had cutaneous sclerosis, joint stiffness, and difficulty breathing. After treatment with TCZ, the nodules and plaques softened and flattened, and the patient reported an improvement in skin tightness. The article discusses the immunological profiles of NS and its similarities to morphea, as well as the potential triggers for NS, such as pregnancy and delivery. The treatment of NS is often challenging, but TCZ has shown promise in alleviating cutaneous fibrosis. Further research is needed to understand the underlying pathophysiology of NS. [Extracted from the article]

Objectives: An interim analysis of post-marketing surveillance data to assess the safety and effectiveness of sarilumab in Japanese patients with rheumatoid arthritis refractory to previous treatment. Methods: The interim analysis included patients who initiated sarilumab therapy between June 2018 and January 2021. The primary objective of this surveillance was safety. Results: In total, 1036 patients were enrolled and registered by 12 January 2021 (interim cut-off date). Of these, 678 were included in the safety analysis [75.4% female; mean age (± standard deviation) 65.8 ± 13.0 years]. Adverse drug reactions, defined as adverse events classified as possibly or probably related to sarilumab, were reported in 170 patients (incidence: 25.1%), with white blood cell count decreased (4.4%) and neutrophil count decreased (1.6%) most frequently reported. Serious haematologic disorders (3.4%) and serious infections (including tuberculosis) (2.5%) were the most frequently reported priority surveillance items. No malignant tumour was reported. An absolute neutrophil count (ANC) below the minimum standard value did not increase the incidence of serious infections. Conclusions: Sarilumab was well tolerated, and no new safety signals were noted in this analysis. There was no difference in the frequency of serious infections between patients with an ANC below or above normal. [ABSTRACT FROM AUTHOR]

Objectives: To assess clinical features in patients with polymyalgia rheumatica (PMR) in Japan by the International Classification of Disease (ICD)-10 code assignment. Methods: Demographics, treatment patterns, and concomitant diseases (identified using ICD-10 code only) in patients who were assigned the PMR ICD-10 code M35.3 at least once between 1 January 2015 and 31 December 2020 were aggregated from a nationwide medical information database owned by the Health, Clinic, and Education Information Evaluation Institute. Results: The cumulative number of patients with PMR was 6325 (mean [standard deviation] age, 74.3 [11.4] years; male:female, 1:1.3). Most patients were >50 years (96.5%) with >33% between 70 and 79 years. Glucocorticoids were prescribed in ∼54% of patients within 30 days of PMR code assignment. All other drug types were prescribed in <5% of patients. Hypertension, diabetes mellitus, rheumatoid arthritis, and osteoporosis were noted in >25% and giant cell arteritis in 1% of patients. During the study period, 4075 patients were newly assigned the PMR code and 62% were prescribed glucocorticoids within 30 days. Conclusions: This is the first retrospective real-world data analysis describing the clinical features of PMR in a large patient population from Japan. Further studies of prevalence, incidence, and clinical features are warranted in patients with PMR. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence‐based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG. [ABSTRACT FROM AUTHOR]

Simple Summary: LL-37 contributes the vertical invasion of tumor cells in melanoma. Indeed, the ratio of LL-37-expressing cells correlated positively to T stage severity. Moreover, LL-37 induced pro-angiogenic factors in both human and mouse systems. Our results suggested that LL-37 stimulates both tumor cells and macrophages to promote melanoma invasion by the induction of pro-angiogenic factors. LL-37 can stimulate various skin-resident cells to contribute to tumor development. Since tumor (T) stage is determined by the vertical invasion of tumor cells in melanoma, we hypothesized that the LL-37 expression level is correlated with the T stage in melanoma patients. Immunohistochemical staining of LL-37 was performed in each stage of melanoma (Tis-T4), suggesting the ratio of LL-37-expressing cells correlate positively to T stage severity. Next, to examine pro-angiogenetic factors induced by LL-37 stimulation, the B16F10 melanoma model was used. Intra-tumorally administered CRAMP, the mouse ortologe of LL-37, significantly increased the mRNA expression of CXCL5, IL23A, MMP1a, and MMP9 in B16F10 melanoma. To confirm the induction of pro-angiogenic factors, A375 human melanoma cells were stimulated by LL-37 in vitro. The mRNA expression of CXCL5, IL23A, and MMP9, but not MMP1, were significantly increased by LL-37 stimulation. Moreover, LL-37-stimulated A375 culture supernatant promoted tube networks, suggesting that these tumor-derived factors promote the pro-angiogenic effect on tumor development. In contrast to melanoma cell lines, M2 macrophages stimulated by LL-37 in vitro significantly increased their expression and secretion of MMP-1, but not MMP-9 expression. Collectively, these results suggest that LL-37 stimulates both tumor cells and macrophages to promote melanoma invasion by the induction of pro-angiogenic factors. [ABSTRACT FROM AUTHOR]

An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare variant of cutaneous T cell lymphoma (CTCL) characterized by CD30-expressing large atypical cells with kidney-shaped nuclei called hallmark cells. Since PCALCL is a rare variant of CTCL, the treatment of PCALCL is still controversial. In this report, a case of PCALCL successfully treated with denileukin diftitox as second-line therapy is described. Interestingly, the administration of denileukin diftitox decreased CD8+ T cells, CD25+ cells, granulysin-bearing lymphocytes, and CD163+ macrophages. The present case suggests that denileukin diftitox might induce an anti-lymphoma effect as well as modulate the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic disease centered on tumor necrosis factor (TNF), interleukin (IL)‐23, and IL‐17 axis. While psoriasis patients benefit from biologics targeting TNF, IL‐17s, and IL‐23 nowadays, suppression of these molecules could modulate the balances of immune systems. However, the incidence of autoimmune disease and T‐helper 2 reaction during biologic treatments for psoriasis patients is not well documented. We retrospectively examined antinuclear antibody (ANA), eosinophil counts, and immunoglobulin E (IgE) levels for psoriasis patients who underwent biologic treatments in our dermatology clinic from June 10, 2010 to January 29, 2020. A cumulative total of 199 biologic treatments were performed for a total of 128 psoriasis patients. Compared to the non‐biologic group of 109 psoriasis patients who received non‐biologic treatment, patients treated with infliximab showed more incidents of high ANA (14%, p = 0.039) and high eosinophils (14%, p = 0.021). The use of brodalumab increased incidents of high eosinophils (21%, p = 0.005) but did not affect increase in ANA and IgE. The increase in high IgE level was observed significantly more during the use of risankizumab (15%, p = 0.011). Methotrexate was the most frequently used concomitant systemic treatment, but methotrexate did not affect ANA, eosinophil counts, and IgE levels. Since the biologics for psoriasis treatment modulate the balance of T‐helper cells, careful observation is required to detect unexpected changes of systemic immune conditions under biologic treatments. [ABSTRACT FROM AUTHOR]

Biologics has had a great impact on psoriasis treatment as well as the life of psoriasis patients. Infliximab (IFX), one of the biologics targeting tumor necrosis factor (TNF), is the first of the biologics introduced to Japanese psoriasis patients. Many patients had benefits of IFX from initial applications and sustained remission of skin lesions and arthritis. Some, however, fall into so‐called secondary failure, in which patients become less responsive to IFX when the treatment is repeated. The mechanism of secondary failure and the background of patients with secondary failure have not been completely elucidated. To address this issue, we retrospectively evaluated psoriasis patients treated with IFX in our department. In this retrospective, single‐center, case‐control study based on the clinical record, a total of 34 patients were enrolled. We excluded 7 patients who discontinued IFX because of adverse events of IFX. We divided other 27 patients into two groups; 16 patients who kept using IFX (Continuance group); and 11 patients who switched to other treatments (Discontinuance group). Among various clinical features, body mass index (BMI), HbA1c, and serum CRP level were significantly higher in the Discontinuance group than the Continuance group. The results indicated that these three clinical features of BMI, HbA1c and serum CRP level before treatment are the predictors of successful IFX treatment and suggest that improvement of metabolic conditions contributes to avoiding secondary failure and discontinuance of IFX. [ABSTRACT FROM AUTHOR]

We have reported that the IL-2 Luc assay can detect the effects of chemicals on IL-2 promoter activity by using a dual reporter cell line, 2H4 cells that measure IL-2 promoter-driven luciferase activity (IL2LA) and GAPDH promoter-driven luciferase activity (GAPLA). Since the IL-2 Luc assay cannot detect immunosuppressive drugs that are antimitotic towards rapidly proliferating cells, we attempted to establish a new assay to detect these chemicals by taking advantage of the dual reporter cell properties of 2H4 cells. We first determined the optimal incubation time with drugs and the seeding cell density, and confirmed that the change in GAPLA and IL2LA levels reflects the change in cell count and IL-2 production of 2H4 cells after drug treatment. We designed the IL-2 luciferase lymphotoxicity test (IL-2 Luc LTT) to detect the antimitotic effects of chemicals by modifying the protocol and criteria of the IL-2 Luc assay. To determine the performance of the IL-2 Luc LTT and that of the combination of the IL-2 Luc LTT and the IL-2 Luc assay, we examined 46 drugs: 19 immunosuppressive drugs with different mechanisms of action, 12 anti-cancer drugs, and 15 non-immunosuppressive drugs. The performances of the IL-2 Luc LTT, the IL-2 Luc assay and their combination were 43.3%, 61.3%, and 93.3%, respectively, for sensitivity, 84.6%, 53.3%, and 50.0%, respectively, for specificity, and 55.8%, 58.7%, and 79.5%, respectively, for accuracy. These results demonstrated that the combination of these two assays is promising for the detection of immunosuppressive drugs with different mechanisms of action. [ABSTRACT FROM AUTHOR]

A 66‐year‐old man with a 2‐year history of suspected scalp eczema with excessive dandruff developed painful swollen joints in the extremities. Four months after developing polyarthritis and polydactylitis, eczema gradually spread to the face. He was referred to our hospital for intractable scalp and facial eczema and polyarthritis. Based on the appearance of the head and facial skin lesions, psoriasis was suspected. Treatment with apremilast (a phosphodiesterase‐4‐inhibitor) was initiated, which swiftly alleviated the skin lesions. The joint deformities persisted, but the pain in the joints disappeared. This case implies that psoriatic arthritis should be suspected even if psoriatic skin lesions are localized to the scalp. [ABSTRACT FROM AUTHOR]

Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17. [ABSTRACT FROM AUTHOR]

Perifolliculitis capitis abscedens et suffodiens (PCAS) or dissecting cellulitis is a rare condition presenting deep follicular occlusions, follicular ruptures and follicular infections in the scalp area with unknown etiology, which consequently cause primary neutrophilic cicatricial alopecia by the repeated follicular inflammation. PCAS is categorized as one of the "follicular occlusion tetrad" along with hidradenitis suppurativa, acne conglobata and pilonidal cyst. In the pathogenesis of the follicular occlusion tetrad, the involvement of neutrophils and its activator tumor necrosis factor (TNF) have been discussed. Here, we report a case of PCAS that was successfully treated with adalimumab, a human anti‐TNF monoclonal antibody. This is the first Asian case of PCAS that was improved by a TNF inhibitor. [ABSTRACT FROM AUTHOR]

We established a luciferase reporter assay system, the Multi-ImmunoTox Assay (MITA), which can evaluate the effects of chemicals on the promoter activities of four cytokines: IL-2, IFN-γ, IL-1β, and IL-8. We previously reported that MITA correctly reflected the change in mRNA of human whole-blood cells treated with dexamethasone, cyclosporine, FK506, or several other immunosuppressive drugs. In this study, we combined MITA with the IL-8 Luc assay to detect skin sensitization chemicals (OECD 442E) (modified MITA: mMITA) and established a data set of 60 chemicals examined by mMITA. Using the mMITA results, chemicals can be classified based on the lowest observed effect level (LOEL) of chemicals in suppressing or augmenting the promoter activities of the four cytokines. Moreover, we demonstrated that K-means clustering and hierarchical clustering of the 60 chemicals based on the LOEL for their effects on IL-2 and IL-8 promoter activities and the judgment by the IL-8 Luc assay resulted in the same 6-cluster solution: cluster 1 with preferential suppression of IL-8, cluster 2 with suppression of IL-2 and a positive IL-8 Luc assay result, cluster 3 with suppression of both IL-2 and IL-8, cluster 4 with no effects on IL-2 or IL-8 and a negative IL-8 Luc assay result, cluster 5 with suppression of both IL-2 and IL-8 and a negative IL-8 Luc assay result, and cluster 6 with preferential suppression of IL-8. These data suggest that mMITA is a promising novel high-throughput approach for detecting unrecognized immunological effects of chemicals and for profiling their immunotoxic effects. [ABSTRACT FROM AUTHOR]

The efficacy and safety of biologic treatments have been established in patients with moderate to severe psoriasis, but there are few reports on biologic therapy for patients with psoriasis complicated by end-stage renal failure on hemodialysis ( HD). In this report, we demonstrated the efficacy and safety of adalimumab for patients with severe psoriasis on HD. A 46-year-old Japanese man with a 14-year history of psoriasis was referred to our clinic in September 2009. He had developed hypertension and renal failure during a 7-year history of cyclosporin treatment. With the infliximab treatment, he achieved 75% improvement of the Psoriasis Area and Severity Index ( PASI) score within 3 months from the PASI of 42.3 before the treatment. However, his renal failure gradually deteriorated, and HD was initiated at 1 year after the introduction of infliximab. Because of hydration during the i.v. injection of infliximab, he developed pulmonary edema with every infliximab treatment after starting HD. We switched to ustekinumab treatment, but his psoriasis was not improved. Then, we switched to adalimumab and achieved a PASI-100 response within 2 months. The patient received adalimumab treatment for more than a year without any adverse effects. In addition to our case, five articles reported cases of psoriasis patients with renal failure on HD who were treated with biologics. The psoriatic lesions were improved by biologics in these cases, and no severe adverse effects on the renal function were reported. Thus, biologics are a reasonable treatment option for patients with severe psoriasis with renal failure on HD. [ABSTRACT FROM AUTHOR]

Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1–derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance. [ABSTRACT FROM AUTHOR]

In order to search for the α condensed state in 16O, we have performed the decay particle measurement via the $^{12} {\rm C} (^{16}{\rm O}, ^{16}{\rm O}^* [\alpha + ^{12}{\rm C} ({\rm g.s.}, 2_1^+, 0_2^+)])^{12}{\rm C}$ reaction. Although the decay branching ratio of the α + 12C channel was predicted to be small, the branching ratio between the α + 12C and $\alpha + ^{12}{\rm C}(2_1^+)$ channels was obtained to be 7:3 by using the result of a simple simulation. [ABSTRACT FROM AUTHOR]

This paper describes the experimental evaluation of a cooperative distance learning method, which can be utilized on narrow-band Internet. In this method, students in a group learning environment perform a series of study tasks several times, then create an online report, communicating through a chat facility about a given topic. They try to gain a benefit from their study through a more cooperative attitude. The teacher gives a short lecture at the first stage, and then gives supplementary explanations after ascertaining the degree of understanding by the students at the middle stage of the study. Teaching materials are distributed to the students' PCs beforehand and the lecture can be carried out in a narrow-band environment by transmitting commands. The teacher analyzes the students' communication logs and gives advice for the next study session. This paper describes the result of an evaluation of the proposed method involving a simulated installation of the environment within the campus, which simulated a trial of cooperative distance learning in the periphery of an overseas desert environment. © 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 93(4): 36–49, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10139 [ABSTRACT FROM AUTHOR]

Background: EUV lithography is making substantial progress in optimizing (i) tool, (ii) mask blanks, and (iii) resist materials to support the next generation EUV imaging performance. EUV masks use a variety of absorbers and capping layers fabricated on mirroring multi-layer (ML) stacks. Aim: The highly conformal e-beam resist-patterning process needs to understand the absorbed intensity distribution spread from the electron scattering in the resist/substrate stack, as well as the consecutive radiation-chemical effects induced by the electron energy spread together with the dissolution behavior of the resist. Approach: We present the results of resist response to 50-keV electron multi-beam exposure based on statistical numerical simulation on different EUV absorbers and reflecting ML stacks directly compared with the numerical lithographic parameters extracted from the experimental resist screening. The experiments were performed with the IMS Nanofabrication Multi-Beam Mask Writer (MBMW) ALPHA tool in a positive Chemically Amplified Resist provided by FUJIFILM, coated on experimental EUV masks with different stack compositions prepared by HOYA. Results: All input parameters for MBMW corrections were precisely specified to the corresponding absorbed energy distribution signature of the specific EUV stack. Experiments confirmed the necessity to match the model calibration values to each small change in the mask stack composition. Conclusions: The method was successfully implemented into leading-edge mask writing and resist/substrate/tool testing for achieving the sub-7-nm node at different EUV-mask stacks. [ABSTRACT FROM AUTHOR]

A high-throughput high-sensitivity optical technique for measuring magnetostriction of thin-film composition-spread samples has been developed. It determines the magnetostriction by measuring the induced deflection of micromachined cantilever unimorph samples. Magnetostriction measurements have been performed on as-deposited Fe–Ga and Fe–Ga–Al thin-film composition spreads. The thin-film Fe–Ga spreads display a similar compositional variation of magnetostriction as bulk. A previously undiscovered peak in magnetostriction at low Ga content was also observed and attributed to a maximum in the magnetocrystalline anisotropy. Magnetostrictive mapping of the Fe–Ga–Al ternary system reveals the possibility of substituting up to 8 at. % Al in Fe70Ga30 without significant degradation of magnetostriction. [ABSTRACT FROM AUTHOR]

Psoriasis is a systemic inflammatory disease caused by crosstalk between various cells such as T cells, neutrophils, dendritic cells, and keratinocytes. Antimicrobial peptides (AMPs) such as β-defensin, S100, and cathelicidin are secreted from these cells and activate the innate immune system through various mechanisms to induce inflammation, thus participating in the pathogenesis of psoriasis. In particular, these antimicrobial peptides enhance the binding of damage-associated molecular patterns such as self-DNA and self-RNA to their receptors and promote the secretion of interferon from activated plasmacytoid dendritic cells and keratinocytes to promote inflammation in psoriasis. Neutrophil extracellular traps (NETs), complexes of self-DNA and proteins including LL-37 released from neutrophils in psoriatic skin, induce Th17. Activated myeloid dendritic cells secrete a mass of inflammatory cytokines such as IL-12 and IL-23 in psoriasis, which is indispensable for the proliferation and survival of T cells that produce IL-17. AMPs enhance the production of some of Th17 and Th1 cytokines and modulate receptors and cellular signaling in psoriasis. Inflammation induced by DAMPs, including self-DNA and RNA released due to microinjuries or scratches, and the enhanced recognition of DAMPs by AMPs, may be involved in the mechanism underlying the Köbner phenomenon in psoriasis. [ABSTRACT FROM AUTHOR]

Extreme ultraviolet (EUV) lithographic exposure is performed in a vacuum environment. The Mo/Si multilayers used as imaging optics and a mask can be contaminated by carbon, which is originally an outgassing species of the hydrocarbons that decompose from the resist materials during EUV exposure. This carbon contamination reduces the total reflectivity of the imaging optics and mask, and affects the lithographic performance, including the throughput and resist pattern replication resolution. This contamination should be reduced to maintain the lithographic performance; thus, the relationship between the carbon contamination and the outgassing species should be clarified. We therefore developed a novel tool for in situ contamination layer thickness evaluation. The distinctive features of this tool are as follows: 1) exposure using a total power of in-band EUV light (267 mW/cm2) that is as high as that required for high-volume manufacturing (>100 mW/cm2), 2) the visible light beam of the in situ spectroscopic ellipsometry is focused on the Mo/Si multilayer witness sample to obtain the detection limit for measured thickness and that the limit was found to be 0.03 nm, and 3) the witness and 8-in. resist wafer sample stages have extremely low outgassing characteristics. Using this tool, a starting adhesion point was observed and the carbon contamination layer thickness was evaluated during the resist exposure. For 90 min resist exposure, no contamination adhered onto the Mo/Si witness sample until the exposure time reached 25 min, and after which, the contamination started to adhere to the witness sample. [ABSTRACT FROM AUTHOR]