Publications by authors named "Jason Ku"

6 Publications

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Simple parameters of synthetic MRI for assessment of bone density in patients with spinal degenerative disease.

J Neurosurg Spine 2021 Oct 15:1-8. Epub 2021 Oct 15.

1Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Objective: Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements.

Methods: This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine.

Results: There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = -0.565 and -0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = -0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ -1.0) and osteoporosis (T-score ≤ -2.5) with PD (both p < 0.001).

Conclusions: PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.
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http://dx.doi.org/10.3171/2021.6.SPINE21666DOI Listing
October 2021

Correlation of bone density to screw loosening in dynamic stabilization: an analysis of 176 patients.

Sci Rep 2021 09 1;11(1):17519. Epub 2021 Sep 1.

Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Beitou District, Taipei, 112, Taiwan, ROC.

Although osteoporosis has negative impacts on lumbar fusion, its effects on screw loosening in dynamic stabilization remain elusive. We aimed to correlate bone mineral density (BMD) with screw loosening in Dynesys dynamic stabilization (DDS). Consecutive patients who underwent 2- or 3-level DDS for spondylosis, recurrent disc herniations, or low-grade spondylolisthesis at L3-5 were retrospectively reviewed. BMD was assessed by the Hounsfield Unit (HU) in vertebral bodies (VB) and pedicles with and without cortical bone (CB) on pre-operative computed tomography (CT). Screw loosening was assessed by radiographs and confirmed by CT. HU values were compared between the loosened and intact screws. 176 patients and 918 screws were analyzed with 78 loosened screws found in 36 patients (mean follow-up: 43.4 months). The HU values of VB were similar in loosened and intact screws (p = 0.14). The HU values of pedicles were insignificantly less in loosened than intact screws (including CB: 286.70 ± 118.97 vs. 297.31 ± 110.99, p = 0.45; excluding CB: 238.48 ± 114.90 vs. 240.51 ± 108.91, p = 0.88). All patients had clinical improvements. In conclusion, the HU values, as a surrogate for BMD, were unrelated to screw loosening in DDS. Therefore, patients with compromised BMD might be potential candidates for dynamic stabilization rather than fusion.
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http://dx.doi.org/10.1038/s41598-021-95232-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410763PMC
September 2021

Metabolic Engineering Design Strategies for Increasing Acetyl-CoA Flux.

Metabolites 2020 Apr 23;10(4). Epub 2020 Apr 23.

Department of Biological Science and Technology, National Chiao Tung University, Hsinchu City 300, Taiwan.

Acetyl-CoA is a key metabolite precursor for the biosynthesis of lipids, polyketides, isoprenoids, amino acids, and numerous other bioproducts which are used in various industries. Metabolic engineering efforts aim to increase carbon flux towards acetyl-CoA in order to achieve higher productivities of its downstream products. In this review, we summarize the strategies that have been implemented for increasing acetyl-CoA flux and concentration, and discuss their effects. Furthermore, recent works have developed synthetic acetyl-CoA biosynthesis routes that achieve higher stoichiometric yield of acetyl-CoA from glycolytic substrates.
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http://dx.doi.org/10.3390/metabo10040166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240943PMC
April 2020

A balanced ATP driving force module for enhancing photosynthetic biosynthesis of 3-hydroxybutyrate from CO.

Metab Eng 2018 03 17;46:35-42. Epub 2018 Feb 17.

Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan. Electronic address:

Using engineered photoautotrophic microorganisms for the direct chemical synthesis from CO is an attractive direction for both sustainability and CO mitigation. However, the behaviors of non-native metabolic pathways may be difficult to control due to the different intracellular contexts between natural and heterologous hosts. While most metabolic engineering efforts focus on strengthening driving forces in pathway design to favor biochemical production in these organisms, excessive driving force may be detrimental to product biosynthesis due to imbalanced cellular intermediate distribution. In this study, an ATP-hydrolysis based driving force module was engineered into cyanobacterium Synechococcus elongatus PCC 7942 to produce 3-hydroxybutyrate (3HB), a valuable chemical feedstock for the synthesis of biodegradable plastics and antibiotics. However, while the ATP driving force module is effective for increasing product formation, uncontrolled accumulation of intermediate metabolites likely led to metabolic imbalance and thus to cell growth inhibition. Therefore, the ATP driving force module was reengineered by providing a reversible outlet for excessive carbon flux. Upon expression of this balanced ATP driving force module with 3HB biosynthesis, engineered strain produced 3HB with a cumulative titer of 1.2 g/L, a significant increase over the initial strain. This result highlighted the importance of pathway reversibility as an effective design strategy for balancing driving force and intermediate accumulation, thereby achieving a self-regulated control for increased net flux towards product biosynthesis.
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http://dx.doi.org/10.1016/j.ymben.2018.02.004DOI Listing
March 2018

Renewable synthesis of -butyraldehyde from glucose by engineered .

Biotechnol Biofuels 2017 4;10:291. Epub 2017 Dec 4.

Department of Biological Science and Technology, National Chiao Tung University, 1001 Daxue Road, Hsinchu, 300 Taiwan.

Background: -Butyraldehyde is a high-production volume chemical produced exclusively from hydroformylation of propylene. It is a versatile chemical used in the synthesis of diverse C4-C8 alcohols, carboxylic acids, esters, and amines. Its high demand and broad applications make it an ideal chemical to be produced from biomass.

Results: An strain was engineered to produce -butyraldehyde directly from glucose by expressing a modified CoA-dependent -butanol production pathway with mono-functional Coenzyme A-acylating aldehyde dehydrogenase (Aldh) instead of the natural bifunctional aldehyde/alcohol dehydrogenase. Aldh from outperformed the other tested homologues. However, the presence of native alcohol dehydrogenase led to spontaneous conversion of -butyraldehyde to -butanol. This problem was addressed by knocking out native alcohol dehydrogenases, significantly improving the butyraldehyde-to-butanol ratio. This ratio was further increased reducing media complexity from Terrific broth to M9 media containing 2% yeast extract. To increase production titer, in situ liquid-liquid extraction using dodecane and oleyl alcohol was investigated. Results showed oleyl alcohol as a better extractant, increasing the titer of -butyraldehyde produced to 630 mg/L.

Conclusion: This study demonstrated -butyraldehyde production from glucose. Through sequential strain and condition optimizations, butyraldehyde-to-butanol ratio was improved significantly compared to the parent strain. Results from this work may serve as a basis for further development of renewable -butyraldehyde production.
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http://dx.doi.org/10.1186/s13068-017-0978-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713646PMC
December 2017

Closed-loop learning control of bio-networks.

J Comput Biol 2004 ;11(4):642-59

Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.

A general goal of systems biology is to acquire a detailed quantitative understanding of the life-sustaining interactions between genes and proteins. There arises an interesting question of whether these network dynamics can be controlled externally. In the open-loop approach to experimental biology, a control design would be chosen based on a desired target response and modeling with all the available knowledge about the system. If the system is not completely understood or disturbances occur, then unexpected deviations from the desired response can arise. A means to circumvent this difficulty is to optimize the controls in a closed-loop operation by modifying successive input controls based on the performance of previous controls. This paper presents a simulation of closed-loop learning control applied to biological systems in order to generate a desired response. The most powerful advantage of this technique is that the controls are deduced based on experimental results and the process can operate without a model for the underlying biochemical network. This feature eliminates the problem of faulty predictions as well as the need for a detailed understanding of the underlying molecular pathways, suggesting that biological systems can be controlled even before the post-systems biology era.
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http://dx.doi.org/10.1089/cmb.2004.11.642DOI Listing
January 2005
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