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Paez and Estaeban70 also noted the resistance of vaccinia virus to interferon but obtained evidence that resistance was related to inhibition of the 2-5A system by intervention of a vaccinia viral ATPase (that would block production of 2-5A from the synthetase) and a viral phosphatase that would 50 -dephosphorylate biologically active 2-5A 50 -mono-, di-, and triphosphates Similarly, novel oligoadenylates of unknown structure and unable to activate RNase L accumulate in interferon-treated SV-40 virus-infected monkey CV-1 cells71 Some of the 20 ,50 -oligoadenylates corresponded to nonphosphorylated cores, (A20 p)nA, but a considerable amount eluted in the HPLC at retention times intermediate between ppp(A20 p)3A and cores The unknown peaks did not seem to be changed upon digestion with alkaline phosphatase, implying the lack of terminal phosphate residues Poly(I) poly(C) addition to interferon-treated CV-1 cells gave high levels of authentic biologically active 2-5A.

What is reproductive toxicity Reproductive toxicity refers to any adverse effect on any aspect of male or female sexual structure, function, and lactation including effects on the reproductive potential and viability of the offspring. This concept may also include the following: Organ toxicity. Can interfere with normal system function. Teratogenicity. Ability to cause dysmorphogenesis in the developing fetus. Behavioral teratogenicity. Ability to adversely affect the mental development of the fetus. Developmental toxicity. Includes both teratogenicity terms above and abnormal postnatal development. This chapter discusses both male and female reproductive toxicity and provides an overview of reproductive physiology.

In the following we summarize related work in the area of using heavy-tailed distributions in traf c modeling.

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Fig. 15.14 (a) Histogram (empirical density function) for interarrival times during two hours of the AT&T WorldNet modem user trace. (b) Histogram of Weibull shape parameter c for the AT&T WorldNet modem user trace over 12 minute time periods.

The anterior pituitary is stimulated by the hypothalamus (via the gonadotrophic hormone releasing hormone) to release gonadotrophic hormones (leutenizing hormone LH; and follicle stimulating hormone FSH). In addition to LH and FSH, prolactin is released by the anterior pituitary. The target of LH and FSH in the male is the testis. While LH stimulates steroidogenesis, FSH has its primary effects on the sertoli cells. The role of prolactin (which is inhibited by dopamine) is to modulate the effects of LH in the testicular tissue. Critical points within the hypothalamic pituitary gonadal axis (Figure 20.1) may be susceptible to alterations by xenobiotics, leading to altered reproductive function and pathology.

In yet another apparent virus-related evasion of the 2-5A pathway, Cayley et al56 noted that in human Chang cells herpes simplex viruses 1 and 2 (HSV-1 and HSV2) were much more resistant to interferon s antiviral action than was encephalomyocarditis virus In all the above cases of interferon virus (HSV-1, HSV-2 or EMCV)-infected cells, similar amounts of 20 ,50 -oligoadenylates were synthesized, but in the instances of HSV-1 and HSV-2 infections, these oligoadenylates did not produce the characteristic RNase L activation footprints of ribosomal RNA cleavage HPLC analysis of extracts from interferon, virus-infected cells showed that while RNase L-activating trimer ppp(A20 p)2A and tetramer ppp(A20 p)3A were present, there were also present apparent 20 ,50 -oligoadenylates that competed with the above 2-5A activators, but themselves were only weak activators of RNase L.

Bolotin [6] studied a year's worth of complete call records for phone calls and found that their call duration is better described by a mixture of lognormal distributions than exponential distributions Duffy et al [12] suggest that heavytailed distributions with possibly in nite variance=mean might be best suited for describing the durations of phone calls Marshall and Morgan [29] note that the empirical statistical distributions of localarea network traf c have longer tails than an exponential distribution They observe that some of the interarrival time histograms look as if they could be well tted by a lognormal distribution or a mixture of two lognormal ones Fowler and Leland [17] showed that local-area network traf c has a high level of variability on every time scale that they measured Such observations are inconsistent with the assumption of exponential distributions As mentioned earlier, Willinger et al.

A Textbook of Modern Toxicology, Third Edition, edited by Ernest Hodgson ISBN 0-471-26508-X Copyright 2004 John Wiley & Sons, Inc.

[42] explain the self-similar nature of Ethernet traf c as the result of superposition of many on=off sources where the length of the on and off periods are heavy tailed Fractal-like behavior has also been observed in VBR video traf c [20] Paxson and Floyd [35] nd that for wide-area traf c Poisson processes are only valid for modeling the arrival of user sessions (TELNET and FTP connections) and that they fail to model other arrival processes Traf c processes that are better modeled using self-similar processes include FTP data connection arrivals, FTPDATA bytes, and TELNET packet interarrival times Paxson [33, 34] examines the behavior of TELNET, NNTP, SMTP, and FTP wide-area TCP connections His results show that lognormal, Pareto, and extreme distributions yield statistically better models for the tails of a variety of parameters.

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