In this study, the optimization of gas and processing time of atmospheric pressure plasma cleaning was performed for successful ultrasonic direct bonding of electroplated Au flip chip bump. The ...plasma cleaning conditions strongly affected bondability of the Au flip chip bumps. The plasma cleaning with Ar gas for 1 s effectively removed contaminants from the surface without the surface oxidation, thereby improving the joint strength.
Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ ...dysfunction, age, genetics) and extrinsic (e.g., drug–drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision‐making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool.
Clinical Pharmacology & Therapeutics (2011) 89 2, 259–267. doi:10.1038/clpt.2010.298
Flavonoids are present in fruits, vegetables and beverages derived from plants (tea, red wine), and in many dietary supplements or herbal remedies including Ginkgo Biloba, Soy Isoflavones, and Milk ...Thistle. Flavonoids have been described as health-promoting, disease-preventing dietary supplements, and have activity as cancer preventive agents. Additionally, they are extremely safe and associated with low toxicity, making them excellent candidates for chemopreventive agents. The cancer protective effects of flavonoids have been attributed to a wide variety of mechanisms, including modulating enzyme activities resulting in the decreased carcinogenicity of xenobiotics. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzymes involved in the activation of procarcinogens and phase II enzymes, largely responsible for the detoxification of carcinogens.
A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction of specific CYP isozymes, and the activation or inhibition of these enzymes. Some flavonoids alter CYPs through binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acting as either AhR agonists or antagonists. Inhibition of CYP enzymes, including CYP 1A1, 1A2, 2E1 and 3A4 by competitive or mechanism-based mechanisms also occurs. Flavones (chrysin, baicalein, and galangin), flavanones (naringenin) and isoflavones (genistein, biochanin A) inhibit the activity of aromatase (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic effects, important in breast and prostate cancers. Activation of phase II detoxifying enzymes, such as UDP-glucuronyl transferase, glutathione
S-transferase, and quinone reductase by flavonoids results in the detoxification of carcinogens and represents one mechanism of their anticarcinogenic effects. A number of flavonoids including fisetin, galangin, quercetin, kaempferol, and genistein represent potent non-competitive inhibitors of sulfotransferase 1A1 (or P-PST); this may represent an important mechanism for the chemoprevention of sulfation-induced carcinogenesis.
Importantly, the effects of flavonoids on enzymes are generally dependent on the concentrations of flavonoids present, and the different flavonoids ingested. Due to the low oral bioavailability of many flavonoids, the concentrations achieved in vivo following dietary administration tend to be low, and may not reflect the concentrations tested under in vitro conditions; however, this may not be true following the ingestion of herbal preparations when much higher plasma concentrations may be obtained. Effects will also vary with the tissue distribution of enzymes, and with the species used in testing since differences between species in enzyme activities also can be substantial. Additionally, in humans, marked interindividual variability in drug-metabolizing enzymes occurs as a result of genetic and environmental factors. This variability in xenobiotic metabolizing enzymes and the effect of flavonoid ingestion on enzyme expression and activity can contribute to the varying susceptibility different individuals have to diseases such as cancer. As well, flavonoids may also interact with chemotherapeutic drugs used in cancer treatment through the induction or inhibition of their metabolism.
Observations of the Failed Eruption of a Filament Ji, Haisheng; Wang, Haimin; Schmahl, Edward J ...
Astrophysical journal/The Astrophysical journal,
10/2003, Volume:
595, Issue:
2
Journal Article
Umbilical cord blood (UCB) is well known to be a rich source of hematopoietic stem cells with practical and ethical advantages, but the presence of mesenchymal stem cells (MSCs) in UCB has been ...disputed and it remains to be validated. In this study, we examined the ability of cryopreserved UCB harvests to produce cells with characteristics of MSCs. We were able to obtain homogeneous plastic adherent cells from the mononuclear cell fractions of cryopreserved UCB using our culture conditions. These adherent cell populations exhibited fibroblast-like morphology and typical mesenchymal-like immunophenotypes (CD73
+, CD105
+, and CD166
+, etc.). These cells presented the self-renewal capacity and the mesenchymal cell-lineage potential to form bone, fat, and cartilage. Moreover, they expressed mRNAs of multi-lineage genes including SDF-1, NeuroD, and VEGF-R1, suggesting that the obtained cells had the multi-differentiation capacity as bone marrow-derived MSCs. These results indicate that cryopreserved human UCB fractions can be used as an alternative source of MSCs for experimental and therapeutic applications.
This paper discusses a near real-time approach to solar active-region monitoring and flare prediction using the Big Bear Solar Observatory Active Region Monitor (ARM). Every hour, ARM reads, ...calibrates, and analyses a variety of data including: full-disk Hα images from the Global Hα Network; EUV, continuum, and magnetogram data from the Solar and Heliospheric Observatory (SOHO); and full-disk magnetograms from the Global Oscillation Network Group (GONG). For the first time, magnetic gradient maps derived from GONG longitudinal magnetograms are now available on-line and are found to be a useful diagnostic of flare activity. ARM also includes a variety of active-region properties from the National Oceanic and Atmospheric Administration's Space Environment Center, such as up-to-date active-region positions, GOES 5-min X-ray data, and flare-to-region identifications. Furthermore, we have developed a Flare Prediction System which estimates the probability for each region to produce C-, M-, or X-class flares based on nearly eight years of NOAA data from cycle 22. This, in addition to BBSO's daily solar activity reports, has proven a useful resource for activity forecasting.PUBLICATION ABSTRACT
In this study we have made a forecast evaluation of geoeffective coronal mass ejections (CMEs) by using frontside halo CMEs and the magnetospheric ring current index, Dst. This is the first time, to ...our knowledge, that an attempt has been made to construct contingency tables depending on the geoeffectiveness criteria as well as to estimate the probability of CME geoeffectiveness depending on CME location and/or speed. For this, we consider 7742 CMEs observed by SOHO/LASCO and select 305 frontside halo CMEs with their locational information from 1997 to 2003 using SOHO/EIT images and GOES data. To select CME‐geomagnetic storm (Dst < −50 nT) pairs, we adopt a CME propagation model for estimating the arrival time of each CME at the Earth and then choose the nearest Dst minimum value within the window of ±24 hours. For forecast evaluation, we present contingency tables to estimate statistical parameters such as probability of detection yes (PODy) and false alarm ratio (FAR). We examine the probabilities of CME geoeffectiveness according to their locations, speeds, and their combination. From these studies, we find that (1) the total probability of geoeffectiveness for frontside halo CMEs is 40% (121/305); (2) PODys for the location (L < ∣50°∣) and the speed (>400 km s−1) are estimated to be larger than 80% but their FARs are about 60%; (3) the most probable areas (or coverage combinations) whose geoeffectiveness fraction is larger than the mean probability (∼40%), are 0° < L < +30° for slower speed CMEs (≤800 km s−1), and −30° < L < +60° for faster CMEs (>800 km s−1); (4) when the most probable area is adopted as the new criteria, the PODy becomes slightly lower, but all other statistical parameters such as FAR and bias are significantly improved. Our results can give us some criteria to select geoeffective CMEs with the probability of geoeffectiveness depending on the location, speed, and their combination.
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