Study of 2D kinetics and force regulation in T cell recognition

T cell activation and thymic selection are thought to be determined by the binding propensity (avidity or affinity) of the T cell receptor (TCR) to its ligands. However, binding propensity quantified by previous 3D TCR–pMHC kinetics such as using tetramer staining or surface plasmon resonance (SPR) under estimate TCR–pMHC interaction due to neglecting physiological conditions. Recent studies considering membrane contribution in TCR–pMHC interaction reported 2D kinetics and force regulated bond dissociation kinetics have better prediction to biological responses in CD8+ T cells. In this study, we further tested the findings in CD4+ T cells and CD4+ CD8+ (double-positive, DP) thymocytes. We analyzed TCR–pMHC interaction for a well-characterized panel of altered peptide ligands (APLs) on multiple transgenic mouse TCR systems. Using ultrasensitive 2D mechanical assays, in situ 2D kinetic measurements show better sensitivity than the SPR 3D kinetic measurements in gauging the ligand potency and thymic selection. Furthermore, force-regulated bond lifetime of TCR–pMHC interaction amplifies the discrimination in recognition of APLs and thymic selection. When force was applied to TCR–pMHC–CD4/8 bonds, two distinct patterns emerged: agonist/negative selecting ligands formed CD4/8-dependent catch-slip bonds where lifetime first increased, reached a maximum, then decreased with increasing force, whereas antagonist/positive selecting ligands formed slip-only bonds where lifetime monotonically decreases with increasing force. Our results highlight an important role of mechanical force in ligand discrimination and suggest a new mechanism for T cell activation and thymic selection that is distinct from previous models based on 3D measurements.Ph.D

Formation of Warped Disks by Galactic Fly-by Encounters. I. Stellar Disks

Warped disks are almost ubiquitous among spiral galaxies. Here we revisit and test the `fly-by scenario' of warp formation, in which impulsive encounters between galaxies are responsible for warped disks. Based on N-body simulations, we investigate the morphological and kinematical evolution of the stellar component of disks when galaxies undergo fly-by interactions with adjacent dark matter halos. We find that the so-called `S'-shaped warps can be excited by fly-bys and sustained for even up to a few billion years, and that this scenario provides a cohesive explanation for several key observations. We show that disk warp properties are governed primarily by the following three parameters; (1) the impact parameter, i.e., the minimum distance between two halos, (2) the mass ratio between two halos, and (3) the incident angle of the fly-by perturber. The warp angle is tied up with all three parameters, yet the warp lifetime is particularly sensitive to the incident angle of the perturber. Interestingly, the modeled S-shaped warps are often non-symmetric depending on the incident angle. We speculate that the puzzling U- and L-shaped warps are geometrically superimposed S-types produced by successive fly-bys with different incident angles, including multiple interactions with a satellite on a highly elongated orbit.Comment: 16 pages, 13 figures, 3 tables. Accepted for publication in Ap

Multisensor Fusion of Landsat Images for High-Resolution Thermal Infrared Images Using Sparse Representations

Land surface temperature (LST) is an important parameter in the analysis of climate and human-environment interactions. Landsat Earth observation satellite data including a thermal band have been used for environmental research and applications; however, the spatial resolution of this thermal band is relatively low. This study investigates an efficient method of fusing Landsat panchromatic and thermal infrared images using a sparse representation (SR) technique. The application of SR is used for the estimation of missing details of the available thermal infrared (TIR) image to enhance its spatial features. First, we propose a method of building a proper dictionary considering the spatial resolution of the original thermal image. Second, a sparse representation relation between low- and high-resolution images is constructed in terms of the Landsat spectral response. We then compare the fused images created with different sampling factors and patch sizes. The results of both qualitative and quantitative evaluation show that the proposed method improves spatial resolution and preserves the thermal properties of basic LST data for use with environmental problems

Simple Use of the Suppository Type Povidone-Iodine Can Prevent Infectious Complications in Transrectal Ultrasound-Guided Prostate Biopsy

Purpose. To determine the effect of simple use of suppository povidone-iodine on infectious complications after transrectal ultrasonography-guided biopsy of the prostate. Methods. All 481 patients are included and received antibiotic prophylaxis. Among them, 360 patients received povidone-iodine suppository (Gynobetadine; 200 mg) immediately prior to biopsy and 121 patients did not. Infectious complications were classified. To evaluate bactericidal effects, we counted bacterial colonies in the rectum, harvested from a rectal swab before insertion of the suppository and after biopsy. Aliquots of the suspended bacterial strains were added to Mueller-Hinton agar medium for incubation. Colony counts were determined. Results. Infectious complications developed in 1 case (0.3%) in the rectal preparation group (Group 1) and in 8 cases (6.6%) in the nonrectal preparation group (Group 2). One in Group 1 had a fever without sepsis. Two patients had sepsis and six had fever without sepsis in Group 2. Rectal preparation was a statistically significant risk factor influencing the development of infectious complications. In vitro experiments, the mean number of colony-forming units decreased 99.9% after the rectal povidone-iodine preparation. Conclusions. All through the biopsy, povidone-iodine melted into the rectum and decreased the bacterial colony count. Simple use of povidone-iodine suppository before prostate biopsy minimizes the risk of infectious complications

Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

Excess cost of non-remission among outpatients with major depressive disorder

Background: The purpose of this study was to assess the economic benefit of achieving remission among outpatients with major depressive disorder (MDD) who are currently employed in Korea. Methods: Cross-sectional observational study. A total of 337 outpatients with MDD with paid jobs were recruited from 14 psychiatric clinics in Korea and were then divided into three groups as follows: new visit group (n = 128), remitted group (n = 100) and non-remitted group (n = 109). The 17-item Hamilton Depression Rating Scale (HAM-D) was used to decide whether a patient should be assigned to the remitted or non-remitted group. Direct medical and non-medical costs were measured via interview with the subjects. The World Health Organization Health and Work Performance Questionnaire (HPQ) were applied in order to measure the lost productive time (LPT) and related productivity costs. Results: The three groups did not show a significant difference in direct medical cost. However, the difference between the remitted group and non-remitted group was statistically significant (25.49 ± 52.99 vs. 44.79 ± 126.55, χ2 = 12.99, p = 0.0015). The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = −3.29, p = 0.001). Although the non-remitted group received treatment at psychiatric clinics similar to the remitted group, it lost 33 more working hours per month, which is compatible to $332 per month. Conclusion: These results suggest the economic importance of achieving remission in treating depression