Possibilities for Misinterpretation in ASV-Speciation Studies of Natural Waters

Die Probleme, die bei Speciesuntersuchungen von Spurenelementen mit Hilfe der Differentialpuls Anodic Stripping Voltammetrie auftreten, werden zu-sammenfassend dargestellt. Neben den bei der eigentlichen Bestimmung auftretenden Problemen, werden auch solche erwähnt, die mit der Probennahme sowie der Lagerung und Vorbehandlung der Proben in Zusammenhang stehen

Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines?

The bioreductive drug tirapazamine (TPZ, SR 4233, WIN 59075) is a lead compound in a series of potent cytotoxins that selectively kill hypoxic rodent and human solid tumour cells in vitro and in vivo. Phases II and III trials have demonstrated its efficacy in combination with both fractionated radiotherapy and some chemotherapy. We have evaluated the generality of an enzyme-directed approach to TPZ toxicity by examining the importance of the one-electron reducing enzyme NADPH:cytochrome P450 reductase (P450R) in the metabolism and toxicity of this lead prodrug in a panel of seven human non-small-cell lung cancer cell lines. We relate our findings on TPZ sensitivity in these lung lines with our previously published results on TPZ sensitivity in six human breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150) and with the sensitivity of all these cell types to eight unrelated cancer chemotherapeutic agents with diverse modes of action. Our results demonstrate that P450R plays a significant role in the activation of TPZ in this panel of lung lines, which is consistent with previous observations in a panel of breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150; Patterson et al (1997) Br J Cancer 76: 1338–1347). However, in the lung lines it is likely that it is the inherent ability of these cells to respond to multiple forms of DNA damage, including that arising from P450R-dependent TPZ metabolism, that underlies the ultimate expression of toxicity. © 1999 Cancer Research Campaig

A shared frequency set between the historical mid-latitude aurora records and the global surface temperature

Herein we show that the historical records of mid-latitude auroras from 1700 to 1966 present oscillations with periods of about 9, 10-11, 20-21, 30 and 60 years. The same frequencies are found in proxy and instrumental global surface temperature records since 1650 and 1850, respectively and in several planetary and solar records. Thus, the aurora records reveal a physical link between climate change and astronomical oscillations. Likely, there exists a modulation of the cosmic ray flux reaching the Earth and/or of the electric properties of the ionosphere. The latter, in turn, have the potentiality of modulating the global cloud cover that ultimately drives the climate oscillations through albedo oscillations. In particular, a quasi 60-year large cycle is quite evident since 1650 in all climate and astronomical records herein studied, which also include an historical record of meteorite fall in China from 619 to 1943. These findings support the thesis that climate oscillations have an astronomical origin. We show that a harmonic constituent model based on the major astronomical frequencies revealed in the aurora records is able to forecast with a reasonable accuracy the decadal and multidecadal temperature oscillations from 1950 to 2010 using the temperature data before 1950, and vice versa. The existence of a natural 60-year modulation of the global surface temperature induced by astronomical mechanisms, by alone, would imply that at least 60-70% of the warming observed since 1970 has been naturally induced. Moreover, the climate may stay approximately stable during the next decades because the 60-year cycle has entered in its cooling phase.Comment: 18 pages, 11 figure

Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50–150 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 200 mg kg−1dose of cyclophosphamide. Tirapazamine (25 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 150 mg kg−1dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50–200 mg kg−1); AQ4N (50–200 mg kg−1) produced a more effective combination than tirapazamine (12.5–50 mg kg−1). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg−1) 6 h prior to cyclophosphamide (100 mg kg−1) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg−1). © 2000 Cancer Research Campaig

Far-Persons

I argue for the moral relevance of a category of individuals I characterize as far-persons. Following Gary Varner, I distinguish near-persons, animals with a " robust autonoetic consciousness " but lacking an adult human's " biographical sense of self, " from the merely sentient, those animals living "entirely in the present." I note the possibility of a third class. Far-persons lack a biographical sense of self, possess a weak autonoetic consciousness, and are able to travel mentally through time a distance that exceeds the capacities of the merely sentient. Far-persons are conscious of and exercise control over short-term cognitive states, states limited by their temporal duration. The animals in question, human and nonhuman, consciously choose among various strategies available to them to achieve their ends, making them subjects of what I call "lyrical experience:" brief and potentially intense pleasures and pains. But their ends expire minute-by-minute, not stretching beyond, I say metaphorically, the present hour. I conclude by discussing the moral status of far-persons

Studies of the decays D^0 \rightarrow K_S^0K^-\pi^+ and D^0 \rightarrow K_S^0K^+\pi^-

The first measurements of the coherence factor R_{K_S^0K\pi} and the average strong--phase difference \delta^{K_S^0K\pi} in D^0 \to K_S^0 K^\mp\pi^\pm decays are reported. These parameters can be used to improve the determination of the unitary triangle angle \gamma\ in B^- \rightarrow $\widetilde{D}K^-$ decays, where $\widetilde{D}$ is either a D^0 or a D^0-bar meson decaying to the same final state, and also in studies of charm mixing. The measurements of the coherence factor and strong-phase difference are made using quantum-correlated, fully-reconstructed D^0D^0-bar pairs produced in e^+e^- collisions at the \psi(3770) resonance. The measured values are R_{K_S^0K\pi} = 0.70 \pm 0.08 and \delta^{K_S^0K\pi} = (0.1 \pm 15.7)$^\circ$ for an unrestricted kinematic region and R_{K*K} = 0.94 \pm 0.12 and \delta^{K*K} = (-16.6 \pm 18.4)$^\circ$ for a region where the combined K_S^0 \pi^\pm invariant mass is within 100 MeV/c^2 of the K^{*}(892)^\pm mass. These results indicate a significant level of coherence in the decay. In addition, isobar models are presented for the two decays, which show the dominance of the K^*(892)^\pm resonance. The branching ratio {B}(D^0 \rightarrow K_S^0K^+\pi^-)/{B}(D^0 \rightarrow K_S^0K^-\pi^+) is determined to be 0.592 \pm 0.044 (stat.) \pm 0.018 (syst.), which is more precise than previous measurements.Comment: 38 pages. Version 3 updated to include the erratum information. Errors corrected in Eqs (25), (26), 28). Fit results updated accordingly, and external inputs updated to latest best known values. Typo corrected in Eq(3)- no other consequence

Updated Measurement of the Strong Phase in D0 --> K+pi- Decay Using Quantum Correlations in e+e- --> D0 D0bar at CLEO

We analyze a sample of 3 million quantum-correlated D0 D0bar pairs from 818 pb^-1 of e+e- collision data collected with the CLEO-c detector at E_cm = 3.77 GeV, to give an updated measurement of \cos\delta and a first determination of \sin\delta, where \delta is the relative strong phase between doubly Cabibbo-suppressed D0 --> K+pi- and Cabibbo-favored D0bar --> K+pi- decay amplitudes. With no inputs from other experiments, we find \cos\delta = 0.81 +0.22+0.07 -0.18-0.05, \sin\delta = -0.01 +- 0.41 +- 0.04, and |\delta| = 10 +28+13 -53-0 degrees. By including external measurements of mixing parameters, we find alternative values of \cos\delta = 1.15 +0.19+0.00 -0.17-0.08, \sin\delta = 0.56 +0.32+0.21 -0.31-0.20, and \delta = (18 +11-17) degrees. Our results can be used to improve the world average uncertainty on the mixing parameter y by approximately 10%.Comment: Minor revisions, version accepted by PR

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer

Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They are the aetiological agents of almost all cervical cancers as well as a sub-set of other anogenital and head and neck cancers. Hijacking of host cellular pathways is essential for virus pathogenesis; however, a major challenge remains to identify key host targets and to define their contribution to HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating the function of the transcription factor YAP. Increased YAP expression has been observed in cervical cancer but the mechanisms driving this increase remain unclear. We found significant down-regulation of the master Hippo regulatory kinase STK4 (also termed MST1) in cervical disease samples and cervical cancer cell lines compared with healthy controls. Re-introduction of STK4 inhibited the proliferation of HPV positive cervical cells and this corresponded with decreased YAP nuclear localization and decreased YAP-dependent gene expression. The HPV E6 and E7 oncoproteins maintained low STK4 expression in cervical cancer cells by upregulating the oncomiR miR-18a, which directly targeted the STK4 mRNA 3’UTR. Interestingly, miR-18a knockdown increased STK4 expression and activated the Hippo pathway, significantly reducing cervical cancer cell proliferation. Our results identify STK4 as a key cervical cancer tumour suppressor, which is targeted via miR-18a in HPV positive tumours. Our study indicates that activation of the Hippo pathway may offer a therapeutically beneficial option for cervical cancer treatment