Japan and Taiwan in the wake of bio-globalization : drugs, race and standards

Thesis (Ph. D. in History and Social Study of Science and Technology (HASTS))--Massachusetts Institute of Technology, Program in Science, Technology and Society, 2005.Also issued in a 2 v. set, printed in leaves.MIT Dewey Library copy: 2 v. set.Includes bibliographical references (p. 518-545).This is a study of Japan and Taiwan's different responses to the expansion of the global drug industry. The thesis focuses on the problematic of "voicing," of how a state can make its interests heard in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH is a unique project that facilitates the formation of a single global market by creating universal standards for clinical trials and drug approvals. Tracing, through "slow motion" ethnography, step by step, why Japan claims a racial difference requires additional local clinical trials with "Asian bodies," this thesis rejects conventional interpretations of protectionism for Japan's resistance to globalization. It argues that more than protectionism is involved, and that a rich ethnographic understanding of Japan's medical infrastructure is required to understand the claim of biological, cultural, and national differences, as well as biostatistical arguments about the ambiguities of "extrapolation" of clinical data from one place to another.(cont.) The inherent ambiguities of efforts to create "bridging" studies as a temporary solution to these problematics created a deadlock in the ICH, and provided an opening for Taiwan, another Asian state, which does not enjoy formal recognition from the world, to speak for itself to this conference, and to create the fragile, but politically critical, possibility of becoming a clinical trial center for Asian populations. The language of genomics and biostatistics become in the more recent period the vehicles for both Japanese and Taiwanese efforts at "voicing" their concerns. Both genomics and biostatistics look different in these contexts than they do from the United States or European Union. In sum, (1) Japan's and Taiwan's response, as well as "global ethnographic objects" such as the ICH, provide important tools to rethink the comparative method as well as universalizing claims of harmonization. (2) Race, culture, and the nation-state are transformed as categories through the contemporary reworkings of genomics and biostatistics. (3) The thesis demonstrates that abstract accounts of the spread of clinical trials and resistance in various parts of the world are not to be trusted unless they include detailed probings of local understandings, identity issues, and problems of voicing.by Wen-Hua Kuo.Ph.D.in History and Social Study of Science and Technology (HAST

Lipid storage changes in human skeletal muscle during detraining

Exercise training is known to increase intramuscular triglyceride content in both trained and untrained legs. The purpose of the study was to determine the changes of intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) of both trained and untrained legs during detraining. We measured both IMCL and EMCL levels in previously trained vs. untrained legs during 4-weeks of detraining after 6-weeks of strength training. Eight young men (aged 21.4 + / - 1.4 years) trained their vastus lateralis muscle in one leg using a dynamometer, whereas the contralateral leg served as untrained control. Muscle cross-sectional area (CSA), IMCL, EMCL, total creatine (creatine + phophocreatine) of extensor (vastus lateralis) muscles were assessed using magnetic resonance imaging (MRI) and proton magnetic resonance spectra (H-1-MRS) before training, 3 days after and 28 days after the last bout of training. CSA was increased in both legs by Day 3 after training, and was still high at Day 28 post-training; IMCL increased in both legs by Day 3 after training, then decreased at Day 28 post-training only in the untrained leg; EMCL shows no significant change by Day 3 after training, but at Day 28 post-training has increased in the trained leg and decreased in the untrained leg; total creatine did not change significantly. Conclusion: Decreases of IMCL and EMCL storages in previously untrained leg during detraining indicates an ectopic influence on tissue lipid storage by different metabolic demand among tissues in the same human body

Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg·kg−1·bw−1, high dose (ANS-HD) 30 mg·kg−1·bw−1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery

Glycosylation variants of a β-glucosidase secreted by a Taiwanese fungus, Chaetomella raphigera, exhibit variant-specific catalytic and biochemical properties

Cellulosic biomass is an abundant and promising energy source. To make cellulosic biofuels competitive against conventional fuels, conversion of rigid plant materials into sugars must become efficient and cost-effective. During cellulose degradation, cellulolytic enzymes generate cellobiose (β-(1→4)-glucose dimer) molecules, which in turn inhibit such enzymes by negative feedback. β-Glucosidases (BGLs) cleave cellobiose into glucose monomers, assisting overall cellulolytic activities. Therefore, BGLs are essential for efficient conversion of cellulosic biomass into biofuels, and it is important to characterize newly isolated BGLs for useful traits. Here, we report our discovery that the indigenous Taiwanese fungus Chaetomella raphigera strain D2 produces two molecular weight variants of a single BGL, D2-BGL (shortened to "D2"), which differ in O-glycosylation. The more extensively O-glycosylated form of native D2 (nD2L) has increased activity toward the natural substrate, cellobiose, compared to the less O-glycosylated form (nD2S). nD2L is more stable at 60°C, in acidic pH, and in the presence of the ionic detergent sodium dodecyl sulfate than nD2S. Furthermore, unlike nD2S, nD2L does not display substrate inhibition by an artificial substrate p-nitrophenyl glucopyranoside (pNPG), and the glucose feedback inhibition kinetics of nD2L is competitive (while it is non-competitive for nD2S), suggesting that these two glycovariants of D2 bind substrates differently. Interestingly, D2 produced in a heterologous system, Pichia pastoris, closely mimics properties of nD2S. Our studies suggest that O-glycosylation of D2 is important in determining its catalytic and biochemical properties

THE EFFECT OF INSULIN AND CARBOHYDRATE SUPPLEMENTATION ON GLYCOGEN REPLENISHMENT AMONG DIFFERENT HINDLIMB MUSCLES IN RATS FOLLOWING PROLONGED SWIMMING

In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1) sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1), 2) sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1), 3) swimming without recovery, 4) swimming with 16 hours recovery and carbohydrate supplement, and 5) swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S), plantaris (P), quadriceps (Q) and gastrocnemius (G) were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05), and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05). In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05). We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity

Increasing fMRI Sampling Rate Improves Granger Causality Estimates

Estimation of causal interactions between brain areas is necessary for elucidating large-scale functional brain networks underlying behavior and cognition. Granger causality analysis of time series data can quantitatively estimate directional information flow between brain regions. Here, we show that such estimates are significantly improved when the temporal sampling rate of functional magnetic resonance imaging (fMRI) is increased 20-fold. Specifically, healthy volunteers performed a simple visuomotor task during blood oxygenation level dependent (BOLD) contrast based whole-head inverse imaging (InI). Granger causality analysis based on raw InI BOLD data sampled at 100-ms resolution detected the expected causal relations, whereas when the data were downsampled to the temporal resolution of 2 s typically used in echo-planar fMRI, the causality could not be detected. An additional control analysis, in which we SINC interpolated additional data points to the downsampled time series at 0.1-s intervals, confirmed that the improvements achieved with the real InI data were not explainable by the increased time-series length alone. We therefore conclude that the high-temporal resolution of InI improves the Granger causality connectivity analysis of the human brain

Single-crystalline δ-Ni2Si nanowires with excellent physical properties

[[abstract]]In this article, we report the synthesis of single-crystalline nickel silicide nanowires (NWs) via chemical vapor deposition method using NiCl2·6H2O as a single-source precursor. Various morphologies of δ-Ni2Si NWs were successfully acquired by controlling the growth conditions. The growth mechanism of the δ-Ni2Si NWs was thoroughly discussed and identified with microscopy studies. Field emission measurements show a low turn-on field (4.12 V/μm), and magnetic property measurements show a classic ferromagnetic characteristic, which demonstrates promising potential applications for field emitters, magnetic storage, and biological cell separation.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙

Ganoderma lucidum polysaccharides enhance CD14 endocytosis of LPS and promote TLR4 signal transduction of cytokine expression

We have previously reported that a well-characterized glycoprotein fraction containing fucose residues in an extract of Ganoderma lucidum polysaccharides (EORP) exerts certain immuno-modulation activity by stimulating the expression of inflammatory cytokines via TLR4. Continuing our studies, we have demonstrated that EORP increases the surface expression of CD14 and TLR4 within murine macrophages J774A.1 cells in vitro, and further promotes LPS binding and uptake by J774A.1 cells in a CD14-dependent fashion. Moreover, we observed the co-localization of internalized LPS with lysosome- and Golgi-apparatus markers within 5 min after J774A.1 cells stimulated with LPS. In addition, EORP pretreatment of J774A.1 cells and human blood-derived primary macrophages, followed by LPS stimulation, results in the super-induction of interleukin-1beta (IL-1) expression. Endocytosis inhibitors: such as cytochalasin D and colchicine effectively block EORP-enhanced LPS internalization by J774A.1 cells; yet they fail to decrease the LPS-induced phosphorylation of certain mitogen-activated protein kinases, and IL-1 mRNA and proIL-1 protein expression, indicating that LPS internalization by J774A.1 cells is not associated with LPS-dependent activation. Our current results could provide a potential EORP-associated protection mechanism for bacteria infection by enhancing IL-1 expression and the clearance of contaminated LPS by macrophages. J. Cell. Physiol. 212: 537–550, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56052/1/21050_ftp.pd