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Papers by Steven Kim

Molecular Cancer Therapeutics

A high-throughput screen for Ras–mitogen-activated protein kinase (MAPK) signaling inhibitors ide... more A high-throughput screen for Ras–mitogen-activated protein kinase (MAPK) signaling inhibitors identified two series (class 1 and 2) of substituted 4-anilino-3-quinolinecarbonitriles as potent (IC50s <10 nmol/L) mitogen-activated protein/extracellular signal-regulated kinase 1 (MEK1) kinase inhibitors. These compounds had cyanoquinoline cores, but differed in their respective aniline groups [1a, 1b: 4-phenoxyphenylaniline; 2a, 2b: 3-chloro-4-(1-methylimidazol-2-sulfanyl)aniline]. These compounds were competitive inhibitors of ATP binding by MEK1 kinase, and they had minimal or no effect on Raf, epidermal growth factor receptor (EGFR), Akt, cyclin-dependent kinase 4 (CDK4), or MK2 kinases at concentrations >100-fold higher than those that inhibited MEK1 kinase. Both class 1 and 2 compounds inhibited in vitro growth of human tumor cell lines. A class 2 compound (2b) was the most potent inhibitor of human tumor cell growth in vitro, and this effect was linked to distinct suppressi...

PLOS ONE

Background Untreated latent tuberculosis infection (LTBI) is a major source of active tuberculosi... more Background Untreated latent tuberculosis infection (LTBI) is a major source of active tuberculosis disease in the United States. In 2016, the United States Preventive Services Task Force (USPSTF) recommended that screening for latent tuberculosis infection among individuals at increased risk be performed as routine preventive care. Traditionally, LTBI management–including both testing and treatment–has been conducted by specialists in the United States. It is believed that knowledge gaps among primary care team members and discomfort with LTBI treatment are significant barriers to LTBI management being conducted in primary care. Methods and objectives This qualitative study sought to evaluate the knowledge, attitudes, and skills of primary care team members regarding the LTBI care cascade, and to identify each stepwise barrier limiting primary care teams in following the USPSTF recommendations. Results We conducted 24 key informant interviews with primary care providers and nurses i...

International Journal of Cardiology, 2021

The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation... more The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately. Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (<0.5 mV with area > 5 cm2) were defined as sites by omnipolar Vmax, bipolar HD wave map, conventional bipolar electrograms acquired from electrode pairs along to and across to the catheter shaft. The primary end point was the first documented recurrence of any AF during follow-ups. PVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001). LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

JACC: Clinical Electrophysiology, 2018

OBJECTIVES This study sought to evaluate the relation between bipolar electrode spacing and far-a... more OBJECTIVES This study sought to evaluate the relation between bipolar electrode spacing and far-and near-field electrograms. BACKGROUND The detailed effects of bipolar spacing on electrograms (EGMs) is not well described. METHODS With a HD-Grid catheter, EGMs from different bipole pairs could be created in each acquisition. This study analyzed the effect of bipolar spacing on EGMs in 7 infarcted sheep. A segment was defined as a 2-mm center-to-center bipole. In total, 4,768 segments (2,020 healthy, 1,542 scar, and 1,206 in border areas, as defined by magnetic resonance imaging [MRI]) were covered with an electrode pair of spacing of 2 mm (Bi-2), 4 mm (Bi-4), and 8 mm (Bi-8). RESULTS A total of 3,591 segments in Bi-2 were free from local abnormal ventricular activities (LAVAs); 1,630 segments were within the MRI-defined scar and/or border area. Among them, 172 (10.6%) segments in Bi-4 and 219 (13.4%) segments in Bi-8 showed LAVAs. In contrast, LAVAs were identified in 1,177 segments in Bi-2; 1,118 segments were within the MRI-defined scar and/or border area. Among them, LAVAs were missed in 161 (14.4%) segments in Bi-4 and in 409 (36.6%) segments in Bi-8. In segments with LAVAs, median far-field voltage increased from 0.09 mV (range: 0.06 to 0.14 mV) in Bi-2, to 0.16 mV (range: 0.10 to 0.24 mV) in Bi-4, and to 0.28 mV (range: 0.20 to 0.42 mV) in Bi-8 (p < 0.0001). Median near-field voltage increased from 0.14 mV (range; 0.08 to 0.25 mV) in Bi-2, to 0.21 mV (range: 0.12 to 0.35 mV) in Bi-4, and to 0.32 mV (range: 0.17 to 0.48 mV) in Bi-8 (p < 0.0001). The median near-/far-field voltage ratio decreased from 1.67 in Bi-2, to 1.43 in Bi-4, and 1.23 in Bi-8 (p < 0.0001). CONCLUSIONS Closer spacing better discriminates surviving tissue from dead scar area. Although far-field voltage systematically increases with spacing, near-field voltages were more variable, depending on local surviving muscular bundles. Near-field EGMs are more easily observed with smaller spacing, largely due to the reduction of the far-field effect.

Nephrology Dialysis Transplantation, 2015

EP Europace, 2016

Background: Endocardial voltage and late-gadolinium enhancement (LGE) are utilised as surrogate m... more Background: Endocardial voltage and late-gadolinium enhancement (LGE) are utilised as surrogate markers of fibrosis. Ablation of low voltage regions in PsAF has shown promising results, and LGE-CMRI defined scar guided ablation will be investigated in DECAAFII. We have reported the lack of correlation between AF voltage mapped over 1-2 AF cycles and LGE-scar. We hypothesised that increasing the sampling duration of AF voltage mapping allows for more accurate representation of the underlying structural substrate defined by LGE CMRI. Methods: Ten patients undergoing PsAF ablation underwent pre-procedural LGE-CMRI. Intra-procedural bipolar voltage mapping in AF was performed over 8s during 2 different AF epochs, where the mean peak-to-peak voltage (AF-V) at each site evaluated offline. A subset of patients underwent SR voltage (SR-V) mapping. Only data from the posterior LA wall as analysed as they represent best fidelity. The AF-V and SR-V in areas of LGE-scar, and areas of overlap of low voltage (LVA) (MPV ,0.4mV) and LGE-scar, were quantified. Reproducibility of the AF-V (with varying sampling durations) over 2 distinct AF epochs was also evaluated. Results: The AF-V in areas of LGE and non-LGE was 0.25 þ /-0.18 mV & 0.59 þ /-0.36 mV respectively (l2 norm 0.51). The mean SR-V was 2.19 þ /-1.90 mV & 3.21 þ /-2.43 respectively (l2 norm 0.13) (Fig. 1A&1B). Surface overlap analysis was performed at thresholds 0.1-3.0 mV to detect for LGE. According to the ROC curve, the AF-V map detected for the presence of LGE with a sensitivity(Ss) of 74.7% and a specificity(Sp) of 63.4% at a threshold of 0.4 mV. The SR-V map had a Ss of 60.1% & Sp of 62.2% at a threshold of 2.0 mV. Acquired over 2 different AF epochs, increasing sampling durations increase ICCs (Fig 2A). Conclusion: AF-V is highly variable but increasing its sampling window allows for meaningful consistent spatial differentiation. AF-V, over 8s, may provide a more accurate reflection of underlying atrial fibrosis due to its inherent nature reflecting multiple rapid wavefront activations, as compared to SR, in recruiting the underlying substrate.

Progress Report Item No: 0001AA Title of the Project: Optimization of Properties of a New Materia... more Progress Report Item No: 0001AA Title of the Project: Optimization of Properties of a New Material for Electronic and Magnetic Applications Topic No.: Contract No.: Contract Starting Date: Contract Ending Date: Contractor: BMDO 97-014 BMDO N00014-97-C-0209 May 14, 1997 ...

Video force microscopy (VFM) is a technique that takes segmented time-lapse images as input and m... more Video force microscopy (VFM) is a technique that takes segmented time-lapse images as input and makes least-squares estimates for the cell-edge tensions and cell-internal pressures needed to drive observed changes in cell shape. VFM has previously been used to estimate the cell-level forces that drive invagination during Drosophila gastrulation. Doing so required time-lapse images containing entire cross-sections of the embryo. Here, we extend video force microscopy to in-plane images of epithelia-including examples in which the images cover only a small region of a larger epithelium. This extension requires imposition of constraints on the average cell-internal pressure and the average stress external to the observed patch. We will demonstrate successful estimation of forces in exact models, as well as anomalous cases that prevent successful force estimation. We will then show applications of this technique for inferring the forces driving Drosophila germband retraction and wound healing.

Clinical and Diagnostic Virology, 1995

Existing phenotypic tests of antiretroviral susceptibility in clinical isolates of human immunode... more Existing phenotypic tests of antiretroviral susceptibility in clinical isolates of human immunodeficiency virus (HIV) are expensive and slow, and require passage of virus in cell culture with the possible consequence of selecting variants. We sought to develop a rapid 14-day assay for zidovudine susceptibility of cell-associated HIV performed directly in patient blood samples. Twenty-three tests were performed prospectively in 21 children, and the results were compared with those of the AIDS Clinical Trials Group/Department of Defense consensus drug susceptibility assay (DSA) as well as certain clinical parameters. Five strains from ZDV-naive children were sensitive by the rapid test. Three were tested by DSA, and all were sensitive. Six strains from children who had received &amp;gt;/=24 months of ZDV were resistant by the rapid assay. Four of these strains were tested by the DSA, and all were shown resistant. The viral strains from children who received &amp;lt;24 months of therapy or who had switched from ZDV to other antiviral therapy exhibited variable sensitivity by both tests. Changes in CD4 cells in the subsequent 6 months, as well as weight gain during this time were both correlated to the results of the rapid test. The syncytium-inducing capacity of the virus strains was analyzed similarly. The rapid intracellular virus susceptibility assay is a test of drug sensitivity performed on HIV growing in cells obtained directly from an infected patient. The test has a two-week turn-around time and, in this preliminary report, gives results which correlate with both time on zidovudine and also subsequent CD4 cell changes.

MRS Proceedings, 2001

Negative Electron Affinity (NEA) of Diamond-like-Carbon (DLC) films has made DLC films a favorabl... more Negative Electron Affinity (NEA) of Diamond-like-Carbon (DLC) films has made DLC films a favorable candidate for field emission display (FED). It was suggested that triple-junction type structure could enhance the field emission characteristics. A triple junction is defined as the intersection of a semiconductor surface with a metal substrate in vacuum. In this study, field emission enhancement in triple junction type structures was investigated. As a metal substrate 5000 of Mo films were deposited. Then, 3000–4000 of DLC film was deposited as a semiconductor material. Thin film layers were made using a negative ion beam source. After the deposition, using an excimer laser, we removed the DLC layer and made circular shaped triple junction trenches with a diameter of 25–250 μm. The field emission characteristics such as I–V characteristics turn on voltage and emission lifetime data were obtained for a diode type field emission measurement system. Overall results show significantly en...

Surface and Coatings Technology, 2002

We produced indium tin oxide (ITO) films on glass substrates by DMIBD technology and investigated... more We produced indium tin oxide (ITO) films on glass substrates by DMIBD technology and investigated the effect of secondary ion beam energy and oxygen partial pressure on the surface morphology, crystallinity and optical property of ITO films. During deposition, substrate ...