Signal estimation and threshold optimization using an array of bithreshold elements

We consider the problem of optimizing signal transmission through multi-channel noisy devices. We investigate an array of bithreshold noisy devices which are connected in parallel and convergent on a summing center. Utilizing the concept of noise-induced linearization we derive an analytical approximation of the normalized power norm and clarify the relation between the optimum threshold and the standard deviation of noises. We show that the optimum threshold value is 0.63 times the standard deviation of the noises. This relation is applicable to both subthreshold and suprathreshold inputs.Comment: 14 pages, 6 figure

Macrophage Migration Inhibitory Factor: A Multifunctional Cytokine in Rheumatic Diseases

Macrophage migration inhibitory factor (MIF) was originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibited the random migration of macrophages. MIF is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses. Moreover, the pivotal nature of its involvement highlights the importance of MIF to the pathogenesis of various inflammatory disorders and suggests that blocking MIF may be a useful therapeutic strategy for treating these diseases. This paper discusses the function and expressional regulation of MIF in several rheumatic diseases and related conditions

フクブ ショクドウ チョウフクショウ ニ タイシ フククウキョウカ テキシュツジュツ オ シコウ シタ １レイ

A 9-year-old boy was admitted to the hospital for close exploration of cystic tumor of the esophagus ventral detected in the abdominal contrast CT scan during the investigation of hematuria. Upper gastrointestinal fluoroscopic and endoscopic examination with ultrasonography showed a cystic tumor with the diameter of 2cm and smooth surface in the abdominal esophagus. Laparoscopic surgery was performed under the diagnosis of abdominal esophageal duplication cyst. At surgery, the soft and well-defined mass was present in the abdominal esophagus ventral and continuous with the esophagus wall. Histopathological study showed the cystic wall was lined with the pseudostratified ciliated epithelium and subepithelial muscle layer. These findings indicated abdominal esophageal duplication cyst. He was discharged on postoperative day 8 with good postoperative course. Abdominal esophageal duplication cyst is a rare disease. Laparoscopic surgery, which has not seen attempted before this case, seems to be a useful treatment of abdominal esophageal duplication cyst

Involvement of CX3CL1/CX3CR1 axis in etanercept therapy for patients with active rheumatoid arthritis

Michihito Sato, Kumiko Ohtsuka, Ryo Takahashi, Kuninobu Wakabayashi, Tsuyoshi Odai, Takeo Isozaki, Nobuyuki Yajima, Yusuke Miwa, Tsuyoshi KasamaDivision of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, JapanObjective: To examine the relationship between serum chemokine levels and patient responsiveness in rheumatoid arthritis (RA) patients to etanercept (ETN) and the influence of ETN administration on serum chemokine levels.Methods: Serum levels of the chemokines CX3CL1, CXCL8, CXCL10, and CCL3 were quantified prior to (at baseline) and after 14 weeks of treatment with ETN in 20 patients using enzyme-linked immunosorbent assay. Disease status was assessed using the Disease Activity Score (DAS28). The response to ETN was classified according to the European League Against Rheumatism (EULAR) response criteria.Results: By 14 weeks, ETN produced a significant overall reduction in DAS28 among the 20 patients with RA; eight patients achieved a good response, and 10 patients achieved a moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was observed in the responsive group, although ETN treatment had no significant effect on the serum levels of the other three chemokines. In addition, the messenger ribonucleic acid expression of CX3CR1 in peripheral blood mononuclear cells and the cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells were both decreased after ETN treatment.Conclusions: Our results suggest that the CX3CL1 and CX3CR1 in patients with active RA may be sensitive to antitumor necrosis factor-α therapy and confirm that CX3CL1/CX3CR1 axis plays a crucial role in the pathogenesis of RA.Keywords: rheumatoid arthritis, chemokine, CX3CL1, CX3CR1, TNF antagonist, etanercep

Increased serum levels of macrophage migration inhibitory factor (MIF) in patients with microscopic polyangiitis

Hirohito Kanemitsu, Mizuho Matsunawa, Kuninobu Wakabayashi, Michihito Sato, Ryo Takahashi, Tsuyoshi Odai, Takeo Isozaki, Nobuyuki Yajima, Yusuke Miwa, Tsuyoshi KasamaDivision of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, JapanObjective: To test the hypothesis that macrophage migration inhibitory factor (MIF) is involved in the disease activity of systemic vasculitis.Methods: Patients with systemic vasculitis were divided into three groups based on the size of the affected vessels. Microscopic polyangiitis (MPA) was considered as small vessel vasculitis (SVV), polyarteritis nodosa as medium-sized vessel vasculitis (MVV), and giant cell arteritis and Takayasu arteritis as large vessel vasculitis (LVV). Sera from patients with systemic vasculitis and healthy individuals were collected, and MIF levels were measured using an enzyme-linked immunosorbent assay. Disease activity of vasculitis was assessed using the Birmingham Vasculitis Activity Score (BVAS).Results: Serum MIF levels were significantly higher in the vasculitis patients than in healthy individuals. Among the vasculitis patients, MIF levels were significantly higher in patients in the SVV group (median; 4161.7 pg/ml) than in the other groups (MVV; 1443.2 pg/ml and LVV; 1576.7 pg/ml). In patients with MPA, a positive correlation was observed between serum MIF levels and CRP levels and disease activity (BVAS). Notably, serum MIF levels were significantly diminished after clinical improvement.Conclusions: Our findings suggest that MIF may have an important role in small vessel vasculopathy and serve as a useful serologic marker of MPA disease activity.Keywords: macrophage migration inhibitory factor, systemic vasculitis, microscopic polyangiitis, cytokin

RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells

Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity(1,2). Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global pandemic. It is an urgent challenge to clarify the innate recognition mechanism to control this virus. Here we show that retinoic acid-inducible gene-I (RIG-I) sufficiently restrains SARS-CoV-2 replication in human lung cells in a type I/III interferon (IFN)-independent manner. RIG-I recognizes the 3 ' untranslated region of the SARS-CoV-2 RNA genome via the helicase domains, but not the C-terminal domain. This new mode of RIG-I recognition does not stimulate its ATPase, thereby aborting the activation of the conventional mitochondrial antiviral-signaling protein-dependent pathways, which is in accordance with lack of cytokine induction. Nevertheless, the interaction of RIG-I with the viral genome directly abrogates viral RNA-dependent RNA polymerase mediation of the first step of replication. Consistently, genetic ablation of RIG-I allows lung cells to produce viral particles that expressed the viral spike protein. By contrast, the anti-SARS-CoV-2 activity was restored by all-trans retinoic acid treatment through upregulation of RIG-I protein expression in primary lung cells derived from patients with chronic obstructive pulmonary disease. Thus, our findings demonstrate the distinctive role of RIG-I as a restraining factor in the early phase of SARS-CoV-2 infection in human lung cells

Fabrication of GaN nanowires containing n(+)-doped top layer by wet processes using electrodeless photo-assisted electrochemical etching and alkaline solution treatment

We attempted to fabricate GaN nanowires by electrodeless photo-assisted electrochemical (PEC) etching and successive alkaline solution treatment. The sample consisting of n(+)-doped and unintentionally doped GaN grown on a GaN substrate was selectively etched using a Ti mask in a mixed solution of K2S2O8 and KOH under UV light radiation. This specific layer structure required a relatively concentrated KOH solution for etching. The PEC etching resulted in the formation of a tapered cone structure of GaN with its top diameter determined by the mask size. Successive KOH treatment after PEC etching yielded GaN nanowires with diameters of about 220 nm

TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development

SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells

The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains