Explain the mechanism of ribosomal frameshifting.

. Explain the process of alternative splicing. What does this process achieve for the virus?

Explain the general structure and function of an IRES element. Explain the polyprotein expression strategy.

Explain the general process of cap-dependent translation (what is the role of the cap?).

on the AP voltage curve that you drew above mark the following with letters and a pointer if needed

a treshold

b the point at which the Na+ channels first open(on the AP curve)

c the point at which the K+ channels first open (on the AP curve)

d the point at which the Na+ channels beguin to close (on the AP curve

E the point at which the K+ channels begin to close (on the AP curve)

1. How is reproduction different in birds and humans?
2. Do you think genetics have anything to do with producing eggs you buy in the store?
3. Why don’t birds generally reproduce during winter?
4. If birds do not reproduce during winter, why are eggs always available in the grocery store?
5. Why are light and heat useful environmental factors for controlling reproduction?
6. Describe the hormones that control reproduction in males and females.
7. Why did it take some time for reproduction to be triggered?
8. What different characteristics and behaviors were changed in the quail?
9. Why is it necessary to have genes under various controls in a cell?
10. Would any negative effects result from artificially creating a year-round breeding environment for quail or chickens?

Explain why the Bohr effect is good news for active muscles during exercise. How does this mechanism allow for effective gas exchange?

Provide two examples of how the immune response to bacterial antigens or toxins can cause severe disease and pathology. For each example, name the disease, the bacterial species, the corresponding bacterial toxin or antigen associated with the disease, and the immune response driving the pathology.

The most likely explanation for the difference in the length of time spent in S phase by α and ß cells is:

ß requires more time to synthesize components of the mitotic spindle

α has an excess of G-cyclin

ß has more DNA in the genome

How do the innate and adaptive immune systems communicate?

125.

An epithelial in the respiratory tract disengages from fibronectin and other proteins in the extracellular matrix (ECM). The cell responds by initiating apoptosis, a cellular suicide pathway. The transmembrane protein that is no longer binding to fibronectin, and therefore, is no longer transmitting signals from the ECM to the cell is: A. Integrin B. alpha-keratin C. Cadherin D. beta-keratin

Answer parts a and b in regards to natural selection and variation within and between populations. Be clear about which part you are answering.

a. How does natural selection impact variation within a population?
b. How does natural selection impact variation between populations; be specific about this answer (Hint: there's more than one option here).

Discussion Questions

1. Using the common motives for cross-border deals discussed in this chapter, speculate as to the reasons Actavis acquired Forest Labs.

2. What alternatives to acquisition could Actavis have pursued? Speculate as to why a takeover was the preferred option?

3. Speculate as to how Actavis’s takeover of Forest Labs may have created shareholder value?

4. Do you believe firms should be allowed to engage in tax inversions?

5. Why is Actavis organized as a holding company in Ireland?

6. Speculate as to why investors for both firms responded so favorably when news of the deal was announced?

END OF CHAPTER CASE STUDY: IRELAND-BASED DRUG MAKER ACTAVIS BUYS U.S. PHARMACEUTICALS FIRM FOREST LABS

Case Study Objectives: To Illustrate • Alternative motives for cross-border acquisitions • How taxes impact cross-border deals and capital flows • How activist investors can impact corporate decisions.

Reflecting the escalating costs of developing blockbuster drugs (i.e., those with the potential to deliver more than $1 billion in annual revenue) and the loss of patent protection on many substantial revenue producing medications, the pharmaceutical industry has been undergoing a wave of consolidation for more than a decade. The takeover strategy in many instances appeared to be largely formulaic: acquire rivals, slash costs, and minimize taxes. While Valeant Pharmaceuticals and Endo Health Solutions have employed this strategy effectively, drug maker Actavis is perhaps the most successful, tripling its market value during the last 3 years. Actavis is a global, integrated specialty pharmaceutical company focused on developing, manufacturing, and distributing generic and branded products in more than 60 countries. Structured as a holding company, its global headquarters is located in Dublin, Ireland. The firm’s US administrative headquarters is in Parsippany, NJ. Actavis historically has focused on generic drugs, but in recent years it has expanded through acquisition into branded drugs. Actavis on February 18, 2014, announced that it had reached an agreement to buy Forest Laboratories for $25 billion in cash and stock to create a pharmaceuticals firm with substantial exposure to branded and generic drugs. Forest Labs is a fully integrated specialty pharmaceutical firm focused on the US market, with a portfolio of branded products. The combined revenues of the two specialty pharmaceutical companies are expected to be more than $15 billion in 2015. The new company announced that it would be increasing its annual budget for pharmaceutical research and development to more than $1 billion. Strategically, Forest Labs represented an opportunity for Actavis to diversify into branded drugs and for Forest Labs to penetrate foreign markets not currently survived. Forest Labs also has an impressive number of drugs in the pipeline. In 2012, US-based Watson Pharmaceuticals bought Actavis, then headquartered in Switzerland, for nearly $6 billion and adopted its name. In 2013, the firm bought Irish-based Warner Chilcott for about $5 billion expanding its presence in specialty pharmaceuticals and moved its headquarters to Ireland to take advantage of the country’s favorable corporate tax environment. The takeover of Forest Labs needed an assist from famed activist investor Carl Icahn. Icahn has a track record of investing in drug makers and profiting from their turnarounds or sales to larger companies. His previous investments included ImClone Systems which was sold to Eli Lilly & Co. in 2008 for $6.3 billion and in Genzyme Corp which was sold to Sanofi in 2011 for $19.4 billion. In 2012, Icahn investments that were later sold included Amylin Pharmaceuticals which was acquired by Bristol-Myers Squibb for $5.1 billion. Icahn, who owns 11% of Forest’s stock through his firm Icahn Enterprises, played a key role in making this deal happen by prodding Forest Labs to install a new CEO in 2013 who was more amenable to selling the firm. To avoid a third proxy fight in as many years, Forest added an Icahn representative to its board in 2013 increasing his influence on board decisions. Under the terms of the deal, Forest shareholders will receive $26.04 in cash and 0.3306 of a share of Actavis, equivalent to $89.48 per share. This represents a premium of 25% from Forest Lab’s closing price the prior day. Forest shareholders will own 35% of the combined firms. Forest Labs agreed to pay a termination fee of $875 million if it backs out of the agreement in favor of a competing takeover proposal or if the firm’s shareholders do not approve the deal. The acquisitive Actavis has completed seven deals since January 2013. Like those deals, the firm expects to realize substantial costs savings. However, in this case, the takeover of Forest Labs will be accretive to earnings immediately following closing. This is relatively unusual as cost savings in most deals in the first year are negated by a combination of severance expenses and other integration-related costs. Actavis announced that it expects to realize a combination of operating and tax savings of $1 billion annually to be realized beginning in the first full year of operation of the combined firms. Assuming a discount rate of 12%, the present value of these savings in perpetuity is $8.3 billion ($1 billion/0.12), well in excess of the $5 billion acquisition premium paid for Forest Labs. Not surprisingly, investors greeted news of the merger favorably. Shares of Forest rose 30% and those of Actavis were up 12%. The takeover of Warner Chilcott in 2012 allowed Actavis to complete a “tax inversion” in which it relocated its headquarters to Ireland to escape the higher American statutory corporate tax rate. A big advantage of a “tax inversion” besides the lower statutory tax rate is that acquisitions become more affordable. Cash held overseas because of the more favorable tax rates can be used to pay for a deal and the earnings from the acquired firm are also taxed at Actavis’s lower tax rate. Tax inversions are not viewed as tax evasion strategies by the US taxing authorities as long as they can be justified by good business reasons such as getting nearer to a firm’s customers or suppliers. Tax evasion is the avoidance of taxes through illegal means such as misrepresenting income on a tax return. The maximum corporate tax rate in Ireland is 12.5% compared to 35% in the United States. Forest Labs earnings which had been taxed at the higher US rate will be taxed at the lower Irish rate currently paid by Actavis. Annual tax savings are expected to amount to at least $100 million. This gave Actavis a huge advantage in bidding for Forest Labs over other potential suitors by enabling it to offer a larger premium. From a legal perspective, an inversion is simply the process by which a corporate entity, established in another country, “buys” an established American company. The transaction takes place when the overseas entity purchases either the shares or assets of a domestic corporation. The shareholders of the domestic company typically become shareholders of the new foreign parent company. In essence, the legal location of the company changes through a corporate inversion from the United States to another country. An inversion typically does not change the operational structure or location of a company. In most cases, an inversion simply means the addition of a small office in the company’s new foreign “home.” Therefore, a re-incorporation rarely, if ever, leads to the loss of American jobs. However, it does lead to a loss of tax revenue.

1. compare and contrast the classic and alternative pathway of complement activation. which pathway is most directly tied in with the immune response?
2. How is a person's susceptibility to infection altered by complement deficiencies?