<i>In vivo</i> accumulation of T cells in response to IL‐2/anti‐IL‐2 mAb complexes is dependent in part on the TNF family ligand 4‐1BBL

Lin, Gloria H Y,Stone, John C,Surh, Charles D,Watts, Tania H Nature Publishing Group 2012 Immunology and cell biology Vol.90 No.7

<P>Immune complexes combining IL‐2 with particular anti‐IL‐2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL‐2 with anti‐IL‐2 (Clone S4B6) greatly enhances the biological potency of IL‐2 <I>in vivo</I> leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that <I>in vivo</I> administration of IL‐2/anti‐IL‐2 mAb (IL‐2/mAb) complexes induces 4‐1BB expression on both adoptively transferred antigen‐specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following <I>in vivo</I> IL‐2/mAb‐complex treatment was found to be dependent in part on the presence of 4‐1BBL in the host. These effects were independent of IL‐2‐induced cell division, suggesting that 4‐1BBL‐induced survival signals contribute to IL‐2/mAb‐complex‐induced T‐cell accumulation <I>in vivo</I>.</P>

Effects of Anteromedial Portal versus Transtibial ACL Tunnel Preparation on Contact Characteristics of the Graft and the Tibial Tunnel Aperture

Akshay Mehta,Charles C. Lin,Ronald A. Campbell,Garwin Chin,Michelle H. McGarry,Thay Q. Lee,Gregory J. Adamson 대한정형외과학회 2019 Clinics in Orthopedic Surgery Vol.11 No.1

Background: The purpose of this study was to compare the tibial tunnel aperture contact characteristics simulating an anteromedial and transtibial anterior cruciate ligament (ACL) tunnel preparation. Methods: Seven matched pairs of cadaveric knees were tested. From each knee, a 10-mm quadriceps ACL graft was prepared. The native ACL was arthroscopically removed and tibial tunnels were drilled. In one knee, a transtibial technique was performed with femoral tunnel drilling approached through the tibial tunnel. For the anteromedial technique on the contralateral knee, the posterior tibial tunnel was chamfered with a rasp. The knees were then disarticulated and tibial tunnel aperture geometry was measured. A pressure sensor was placed between the graft and the posterior aspect of the tibial tunnel and the graft was secured with an interference screw. Contact force, contact area, contact pressure, peak contact pressure, hysteresis and stiffness were measured at cyclic loads of 50 N, 100 N, 150 N, and 200 N. Results: Tibial tunnel aperture area, diameter and deviation from a circle were significantly larger with the transtibial technique (p < 0.05). There was no significant difference in hysteresis, stiffness, contact area, contact force and mean contact pressure. The peak contact pressure between the ACL graft and the tibial tunnel was significantly higher with the anteromedial technique for 100 N (p = 0.04), 150 N (p = 0.01), and 200 N (p = 0.002) cyclic loading. Conclusions: Increased peak contact pressure on the graft at the tibial aperture with the anteromedial technique may increase the stress on the graft and possibly lead to failure following ACL reconstruction.

Probabilistic Constrained Approach for Distributed Robust Beamforming Design in Cognitive Two-way Relay Networks

( Xueyan Chen ),( Li Guo ),( Chao Dong ),( Jiaru Lin ),( Xingwang Li ),( Charles C. Cavalcante ) 한국인터넷정보학회 2018 KSII Transactions on Internet and Information Syst Vol.12 No.1

In this paper, we propose the distributed robust beamforming design scheme in cognitive two-way amplify-and-forward (AF) relay networks with imperfect channel state information (CSI). Assuming the CSI errors follow a complex Gaussian distribution, the objective of this paper is to design the robust beamformer which minimizes the total transmit power of the collaborative relays. This design will guarantee the outage probability of signal-to- interference-plus-noise ratio (SINR) beyond a target level at each secondary user (SU), and satisfies the outage probability of interference generated on the primary user (PU) above the predetermined maximum tolerable interference power. Due to the multiple CSI uncertainties in the two-way transmission, the probabilistic constrained optimization problem is intractable and difficult to obtain a closed-form solution. To deal with this, we reformulate the problem to the standard form through a series of matrix transformations. We then accomplish the problem by using the probabilistic approach based on two sorts of Bernstein-type inequalities and the worst-case approach based on S-Procedure. The simulation results indicate that the robust beamforming designs based on the probabilistic method and the worst-case method are both robust to the CSI errors. Meanwhile, the probabilistic method can provide higher feasibility rate and consumes less power.

The anterolateral ligament of the knee joint: a review of the anatomy, biomechanics, and anterolateral ligament surgery

( Ji Hyun Ahn ),( Nilay A. Patel ),( Charles C. Lin ),( Thay Q. Lee ) 대한슬관절학회 2019 대한슬관절학회지 Vol.31 No.1

Residual knee instability and low rates of return to previous sport are major concerns after anterior cruciate ligament (ACL) reconstruction. To improve outcomes, surgical methods, such as the anatomical single-bundle technique or the double-bundle technique, were developed. However, these reconstruction techniques failed to adequately overcome these problems, and, therefore, new potential answers continue to be of great interest. Based on recent anatomical and biomechanical studies emphasizing the role of the anterolateral ligament (ALL) in rotational stability, novel surgical methods including ALL reconstruction and anterolateral tenodesis have been introduced with the possibility of resolving residual instability after ACL reconstruction. However, there is still little consensus on many aspects of the ALL, including: several anatomical issues, appropriate indications for ALL surgery, and the optimal surgical method and graft choice for reconstruction surgery. Therefore, further studies are necessary to advance our knowledge of the ALL and its contribution to knee stability.

Does Knee Arthroscopy for Treatment of Meniscal Damage with Osteoarthritis Delay Knee Replacement Compared to Physical Therapy Alone?

Ronald A. Navarro,Annette L. Adams,Charles C. Lin,John Fleming,Ivan A. Garcia,Janet Lee,Mary Helen Black 대한정형외과학회 2020 Clinics in Orthopedic Surgery Vol.12 No.3

Background: To determine patient factors that lead to treatment of meniscal tears with osteoarthritis (OA) with knee arthroscopy (KA) or physical therapy only (PT-only); and to assess differences in clinical outcomes including the time to knee arthroplasty. Methods: Patients aged ≥ 45 years with OA at meniscal tear diagnosis were followed up from the date of surgery (KA) or first PT visit (PT-only) until partial/total knee replacement surgery, death, disenrollment, or end of study. Demographic and clinical characteristics were compared and used to derive propensity scores. A Cox proportional hazards model was used to estimate the risk of knee replacement surgery and greater healthcare utilization associated with KA vs. PT-only. Results: Among 7,026 patients (KA, 69%; PT-only, 31%), 27% had partial or total knee replacement surgery during follow-up. PT-only patients were older and more likely to be women and had more comorbidities. After accounting for differences between groups, the cumulative incidence of knee replacement was modestly but significantly higher for those who received KA than those who underwent PT-only (hazard ratio, 1.30; 95% confidence interval, 1.17–1.44; p < 0.001), although there was no significant difference in health service utilization, narcotic medication dispenses, or knee injections after initiating treatment. Conclusions: For patients with meniscal damage complicated by OA, those who underwent KA were 30% more likely to have partial or total knee replacement surgery at any given time than those who had PT alone.

Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription

Josefowicz, Steven Z.,Shimada, M.,Armache, A.,Li, Charles H.,Miller, Rand M.,Lin, S.,Yang, A.,Dill, Brian D.,Molina, H.,Park, H.S.,Garcia, Benjamin A.,Taunton, J.,Roeder, Robert G.,Allis, C. Cell Press 2016 Molecular cell Vol.64 No.2

<P>The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide. Using pharmacological and genetic approaches, we identified mitogen-and stress-activated protein kinases (MSKs) as primary mediators of H3S28ph in macrophages. Cell-free transcription assays demonstrated that H3S28ph directly promotes p300/CBP-dependent transcription. Further, MSKs can activate both signal-responsive transcription factors and the chromatin template with additive effects on transcription. Specific inhibition of MSKs in macrophages selectively reduced transcription of stimulation-induced genes. Our results suggest that MSKs incorporate upstream signaling inputs and control multiple downstream regulators of inducible transcription.</P>