Advanced electronics for fourier-transform ion cyclotron resonance mass spectrometry

With the development of mass spectrometry (MS) instruments starting in the late 19th century, more and more research emphasis has been put on MS related subjects, especially the instrumentation and its applications. Instrumentation research has led modern mass spectrometers into a new era where the MS performance, such as resolving power and mass accuracy, is close to its theoretical limit. Such advanced performance releases more opportunities for scientists to conduct analytical research that could not be performed before. This thesis reviews general MS history and some of the important milestones, followed by introductions to ion cyclotron resonance (ICR) technique and quadrupole operation. Existing electronic designs, such as Fourier-transform ion cyclotron resonance (FT-ICR) preamplifiers (for ion signal detection) and radio-frequency (RF) oscillators (for ion transportation/filtering) are reviewed. Then the potential scope for improvement is discussed. Two new FT-ICR preamplifiers are reported; both preamplifiers operate at room temperature. The first preamplifier uses an operational amplifier (op amp) in a transimpedance configuration. When a 18-k feedback resistor is used, this preamplifier delivers a transimpedance of about 85 dB , and an input current noise spectral density of around 1 pA/ p Hz. The total power consumption of this circuit is around 310 mW when tested on the bench. This preamplifier has a bandwidth of fi3 kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61k at 12 T for FT-ICR MS. The transimpedance and the bandwidth can be adjusted by replacing passive components such as the feedback resistor and capacitor. The feedback and bandwidth limitation of the circuit is also discussed. When using an 0402 type surface mount resistor, the maximum possible transimpedance, without sacrificing its bandwidth, is approximated to 5.3 M . Under this condition, the preamplifier is estimated to be able to detect ~110 charges. The second preamplifier employs a single-transistor design using a different feedback arrangement, a T-shaped feedback network. Such a feedback system allows ~100-fold less feedback resistance at a given transimpedance, hence preserving bandwidth, which is beneficial to applications demanding high gain. The single-transistor preamplifier yields a low power consumption of ~5.7 mW, and a transimpedance of 80 dB in the frequency range between 1 kHz and 1 MHz (m/z of around 180 to 180k for a 12-T FT-ICR system). In trading noise performance for higher transimpedance, an alternative preamplifier design has also been presented with a transimpedance of 120 dB in the same frequency range. The previously reported room-temperature FT-ICR preamplifier had a voltage gain of about 25, a bandwidth of around 1 MHz when bench tested, and a voltage noise spectral density of ~7.4 nV/ p Hz. The bandwidth performance when connecting this preamplifier to an ICR cell has not been reported. However, from the transimpedance theory, the transimpedance preamplifiers reported in this work will have a bandwidth wider by a factor of the open-loop gain of the amplifier. In a separate development, an oscillator is proposed as a power supply for a quadrupole mass filter in a mass spectrometer system. It targets a stabilized output frequency, and a feedback control for output amplitude stabilization. The newly designed circuit has a very stable output frequency at 1 MHz, with a frequency tolerance of 15 ppm specified by the crystal oscillator datasheet. Within this circuit, an automatic gain control (AGC) unit is built for output amplitude stabilisation. A new transformer design is also proposed. The dimension of the quadrupole being used as a mass filter will be determined in the future. This circuit (in particular the transformer and the quadrupole connection/mounting device) will be finalised after the design of the quadrupole. Finally, this thesis concludes with a discussion between the gain and the noise performance of an FT-ICR preamplifier. A brief analysis about the correlation between the gain, cyclotron frequency, and input capacitance is performed. Future work is also suggested for extending this research

Adult morphology and redescription of Lestidiops indopacificus (Ege, 1953), with comments on the features of related species (Teleostei, Aulopiformes, Paralepididae)

Two specimens representing the first known adults of Lestidiops indopacificus (Ege, 1953) are reported and described from Taiwan, and the validity and generic assignment of this species are confirmed. The origin of the pelvic fin directly below the dorsal-fin base shows that L. indopacificus belongs to the L. mirabilis species complex. It can be separated from its congeners by the position of the nostrils above the posterior end of the maxilla, the light body color with unevenly distributed melanophores in adults, and a distinct combination of meristic values and other morphological characteristics. New geographic records are reported for the two other current members of this species complex, L. mirabilis (Ege, 1933) and L. extremus (Ege, 1953). The diagnostic features that separate these three very similar species are discussed

Enhancing momentum profits in the Taiwan Stock Market: The role of extreme absolute strength

Abstract(#br)We show that stocks with extreme absolute strength are highly volatile and thus attenuate the profitability of momentum in Taiwan, a market that has been widely documented as an exception of the momentum phenomenon. An enhanced momentum strategy that removes these stocks from the winner and loser portfolios generates significant profitability in the intermediate term. A major advantage of the enhanced momentum strategy is its robust profitability over time. More importantly, it is free from the momentum crashes. We provide further evidence to show that return dispersion and information uncertainty are closely related to momentum profitability in the cross-section when stocks with extreme absolute strength are removed

Use of top-down and bottom-up fourier transform ion cyclotron resonance mass spectrometry for mapping calmodulin sites modified by platinum anticancer drugs

Calmodulin (CaM) is a highly conserved, ubiquitous, calcium-binding protein; it binds to and regulates many different protein targets, thereby functioning as a calcium sensor and signal transducer. CaM contains 9 methionine (Met), 1 histidine (His), 17 aspartic acid (Asp), and 23 glutamine acid (Glu) residues, all of which can potentially react with platinum compounds; thus, one-third of the CaM sequence is a possible binding target of platinum anticancer drugs, which represents a major challenge for identification of specific platinum modification sites. Here, top-down electron capture dissociation (ECD) was used to elucidate the transition metal–platinum(II) modification sites. By using a combination of top-down and bottom-up mass spectrometric (MS) approaches, 10 specific binding sites for mononuclear complexes, cisplatin and [Pt(dien)Cl]Cl, and dinuclear complex [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] on CaM were identified. High resolution MS of cisplatin-modified CaM revealed that cisplatin mainly targets Met residues in solution at low molar ratios of cisplatin–CaM (2:1), by cross-linking Met residues. At a high molar ratio of cisplatin:CaM (8:1), up to 10 platinum(II) bind to Met, Asp, and Glu residues. [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] forms mononuclear adducts with CaM. The alkanediamine linker between the two platinum centers dissociates due to a trans-labilization effect. [Pt(dien)Cl]Cl forms {Pt(dien)}2+ adducts with CaM, and the preferential binding sites were identified as Met51, Met71, Met72, His107, Met109, Met124, Met144, Met145, Glu45 or Glu47, and Asp122 or Glu123. The binding of these complexes to CaM, particularly when binding involves loss of all four original ligands, is largely irreversible which could result in their failure to reach the target DNA or be responsible for unwanted side-effects during chemotherapy. Additionally, the cross-linking of cisplatin to CaM might lead to the loss of the biological function of CaM or CaM–Ca2+ due to limiting the flexibility of the CaM or CaM–Ca2+ complex to recognize target proteins or blocking the binding region of target proteins to CaM

Effect of Antrodia

Antrodia camphorata is a rare Taiwanese medicinal mushroom. Antrodia camphorata extract has been reported to exhibit antioxidant, anti-inflammation, antimetastasis, and anticancer activities and plays a role in liver fibrosis, vasorelaxation, and immunomodulation. Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Platelet activation plays a crucial role in intravascular thrombosis, which is involved in a wide variety of cardiovascular diseases. However, the effect of Antrodia camphorata on platelet activation remains unclear. We examined the effects of Antrodia camphorata on platelet activation. In the present study, Antrodia camphorata treatment (56–224 μg/mL) inhibited platelet aggregation induced by collagen, but not U46619, an analogue of thromboxane A2, thrombin, and arachidonic acid. Antrodia camphorata inhibited collagen-induced calcium (Ca2+) mobilization and phosphorylation of protein kinase C (PKC) and Akt. In addition, Antrodia camphorata significantly reduced the aggregation and phosphorylation of PKC in phorbol-12, 13-dibutyrate (PDBu) activated platelets. In conclusion, Antrodia camphorata may inhibit platelet activation by inhibiting of Ca2+ and PKC cascade and the Akt pathway. Our study suggests that Antrodia camphorata may be a potential therapeutic agent for preventing or treating thromboembolic disorders