Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.Subject terms: Chemotaxis, Bone, Ion channel signalling, Rheumatoid arthritis, Drug development     

The consensus string problem for a metric is NP-complete

Given a set S of strings, a consensus string of S based on consensus error is a string w that minimizes the sum of the distances between w and all the strings in S. In this paper, we show that the problem of finding a consensus string based on consensus error is NP-complete when the penalty matrix is a metric.     

Elements of the Lagrangian Whitney trick

We investigate the possibility of a Lagrangian Whitney trick, a process to remove a pair of intersection points of a self-transverse Lagrangian immersion by a homotopy through Lagrangian immersions. There is a model for which a Lagrangian Whitney trick with compact support works assuming the model satisfies an area-capacity condition. Reduction of more general cases to the model, not necessarily fulfilling the area-capacity requirement, is possible if the given pair of double points admits a suitable symplectic disc and a certain Maslov-Viterbo index is 1. We look into an example to see the actualities of the Maslov-Viterbo index and the area-capacity conditions. The authors would like to thank the anonymous referee whose suggestions improved remarkably the exposition of the paper. This work was supported by the grant no.R01-2000-000-00004-0 from Korea Science & Engineering Foundation.     

Exact self-gravitating N-body motion in the CGHS model

In the asymptotically flat two-dimensional dilaton gravity, we present an N-body particle action which has a dilaton coupled mass term for the exact solubility. This gives nonperturbative exact solutions for the N-body self-gravitating system, so the infalling particles form a black hole and their trajectories are exactly described. In our two-dimensional case, the critical mass for the formation of black holes does not exist, so even a single particle forms a black hole. The infalling particles give additional time-like singularities in addition to the space-like black hole singularity. However, the latter singularities can be properly cloaked by the future horizons within some conditions.     

Dynamical Invariant and Exact Mechanical Analyses for the Caldirola–Kanai Model of Dissipative Three Coupled Oscillators

We study the dynamical invariant for dissipative three coupled oscillators mainly from the quantum mechanical point of view. It is known that there are many advantages of the invariant quantity in elucidating mechanical properties of the system. We use such a property of the invariant operator in quantizing the system in this work. To this end, we first transform the invariant operator to a simple one by using a unitary operator in order that we can easily manage it. The invariant operator is further simplified through its diagonalization via three-dimensional rotations parameterized by three Euler angles. The coupling terms in the quantum invariant are eventually eliminated thanks to such a diagonalization. As a consequence, transformed quantum invariant is represented in terms of three independent simple harmonic oscillators which have unit masses. Starting from the wave functions in the transformed system, we have derived the full wave functions in the original system with the help of the unitary operators.     

Using Gd-EOB-DTPA-enhanced 3-T MRI for the differentiation of infiltrative hepatocellular carcinoma and focal confluent fibrosis in liver cirrhosis

Purpose

The purpose of the study was to determine significant imaging features to differentiate between infiltrative hepatocellular carcinoma (HCC) and confluent fibrosis (CF) in liver cirrhosis using Gd-EOB-DTPA-enhanced 3-T magnetic resonance imaging.

Material and methods

Nineteen infiltrative HCCs and eight CFs were included. We evaluated the difference in imaging findings and apparent diffusion coefficient (ADC) between the two entities. We compared T2-weighted image (WI) and hepatobiliary phase (HBP) in terms of the clarity of the lesion outer margin.

Results

Seventeen infiltrative HCCs showed lobulated margin, while focal CFs showed either straight (n = 3) or irregular margins (n = 5) (P = .001). All infiltrative HCCs had intact or bulging contours, and all focal CFs showed capsular retraction (P = .001). Fourteen infiltrative HCCs and two focal CFs showed arterial enhancement (P = .035). The ADC of infiltrative HCCs was significantly lower than that of CFs (P = .001). Satellite nodules were noted in 10 infiltrative HCCs. In terms of outer margin clarity, infiltrative HCCs showed a more distinct margin on HBP than on T2-WI (P = .005), while these two sequences were not significantly different in focal CFs (P = 1.000).

Conclusion

HBP improved the imaging characteristics of infiltrative HCC, allowing it to be distinguished from focal CF. Infiltrative HCC showed lower ADC values than focal CF. Lobular configuration, contour bulging, enhancement pattern, associated satellite nodules and portal vein thrombosis were still found to be highly suggestive MR findings for infiltrative HCC.