Central Nervous System Essay -- Biology, Cells, Retinogenesis

SPECIFIC AIMS The neural progenitor cells give rise to myriad cell types of the central nervous system during development [1]. However, the molecular basis of generation of diverse cell types from a single pool of progenitors is largely unknown. As a part of the central nervous system, the neural retina is an ideal model system to comprehend this mechanism because its cellular diversity also results from multipotent progenitors, the retinal progenitor cells (RPCs) [2-4]. During retinogenesis, RPCs pass through different competent stages, each characterized largely by a unique set of transcription factors and defining RPCs’ ability to generate specific cell types during sequential cell divisions [5-7]. This study is an attempt to further our understanding of how transcription factors direct RPCs to differentiate into retinal ganglion cells (RGCs), the cell that connect retina to the brain. It is known that the basic helix-turn-helix transcription factor Math-5 renders RPCs the competence to adopt an RGC fate [8-10]. It essentially acts by turning on the expression of the POU domain factor Pou4f2 and the LIM homeobox factor Isl1, both critical for RGC differentiation and survival [11-12]. However, not all Math5-expressing progenitors become RGCs [13]. Nor can Pou4f2 and Isl1 be the only factors governing the terminal differentiation of RGCs as a large proportion of Math-5 controlled genes is not regulated by them [12]. What factors specify RGC fate? What are those non-Pou4f2/Isl1 factors that take part in RGC differentiation? If we are to set a milestone in medicine by using cell replacement therapy to treat neurodegenerative diseases, such fundamental questions like these must be answered. Available evidences suggest that the tra... ...OC factors in RGC development. In the developing liver, OC factors control TGF-ÃŽ ² signaling [18, 21], which is pro-apoptotic in RGCs [23]. Therefore, an Inquiry into the retinal onecut/TGF-ÃŽ ² connection and its downstream consequences may further our understanding of the regulation of RGC apoptosis, which is disturbed in several degenerative diseases. Using qPCR, Western blot, and reporter assay, I will first assess if retinal TGF-ÃŽ ² signaling is enhanced in the absence of OC factors. Then using a rescue experiment, I will see if increased TGF-ÃŽ ² signaling accounts for the retinal phenotype seen in onecut-null mice. Finally, using in situ hybridization, IF staining and reporter assay, I will look into the relationship of OC factors with Math5, Pouf42, and Isl1 to establish their tentative position in the hierarchy of transcription factors that control RGC development.

Case Review: Linear Technology Essay

Linear Technology was based out of Silicon Valley and founded in 1981. The company specialized in design, manufacture and marketing of analog integrated circuits. Linear enjoyed a diversified customer base, with 33% of its business coming from the communications sector, 27% from computers, 6% from automotive, and 34% from various other applications. With their focus on the analog segment of the IC sector, which was characterized by custom designed products, it was imperative that Linear hires and retains talented people who were accustomed to out-of-the-box thinking and who could readily develop innovative techniques and products that would keep them competitive. Going IPO in 1986, Linear operated with a modest CAPEX. Additionally they enjoyed low obsolescence of equipment and techniques. This combined with their low R&D expenses led to margins that exceeded that of competing digital IC products. This is supported by Linear’s 7th seat positioning on the Philadelphia Stock Exchange Semiconductor Index (SOX). Linear’s net income was at its highest in 2001, when global technology spending was at its highest, and its lowest sales the following year. They still maintained positive cash flows and strong margins; this was accomplished through various mechanisms such as cost cutting aided by their variable cost structure. As of 2003 Q3, Linear was emerging out of the recession with strong financials. However, top line sales and net income remained lower than their high point in 2001. Due to political unrest throughout the World, the future of the tech industry remained unclear. Year over year growth in 2003 when compared to 2002 was good, but the company didn’t see a clear path to reaching 2001 levels. At the same time, they didn’t want to sacrifice margins in new markets like Asia. By 1992 Linear’s management was comfortable in their ability to sustain future cash flows, having been cash flow positive since IPO, and began issuing dividends of $.00625 per share (payout ratio: 15%). In 2002 LLTC  continued issuing dividends, despite the higher payout ratio (27.24%), as they didn’t want to lose favor with investors. It is likely that Linear viewed dividends as a way to stay in the portfolio of mutual funds and EU investors who strongly favored dividend-paying stocks. Simultaneously, Linear also began to buy back shares when interest rates were low or/and when market valuation of Linear stock was low. They were skeptical about paying out all or more of their cash in dividends as this could signal lack of growth potential. It is notable that many institutional investors held Linear stock, largest among which was Janus Capital. Linear wanted to be sure to send positive signals to their investors. With a large cash balance ($1.5 billion) and no debt, Linear was at a crossroads – they needed to know what to do with their cash. Their options were: 1) Invest in new projects, 2) Payout via dividends and/or repurchases, and 3) Save it for future investments in innovation and diversification. In this p per, we will analyze three different approaches in deciding Linear’s payout for Q3. Approach – 1 Cent Dividend Increase The analysis below assumes the decision to repurchase 165.7 million in stock will not be adjusted. The decision to be made is to either raise our dividend by one cent per share, or leave the third quarter dividend of .05 per share intact. Payout Decision Historically Linear has not increased dividends in Q3, so a conservative approach for the board would be to approve the continuation of the dividend policy from Q2. Continuing the status quo of .05 per share, the payout ratio would adjust to 27.48 percent of Net Income. Increasing dividend by one cent per share would increase the YTD payout ratio to approximately 29.31 percent for the three quarters (Exhibit 1), a modest increase. At $0.06 dividend per share, the total Q3 dividend payout will be $18.7 million, which will still be considered small by our institutional investors, given our large cash position. The adoption of the 1-cent increase will provide a full offering of 215.70 million dollars back to our investors in the form of dividends and stock repurchases as shown below: Paying the additional 1-cent would still be consistent with our long-term dividend strategy, but the total package will not be aligned with the requests of some of our largest investors. Available Cash to Distribute At this point it is important to note that the firm will be paying out more to the shareholders via share buybacks and dividends, than the firm has available to the equity holders through its operations. This overpayment holds true if the firm holds the dividend at .05, or increases it to .06. The firm has generated a total of 207.5 million FCFE dollars, but would be choosing to payout a total of 215.7 million given the decision to increase the dividend by one cent. Staying committed to the .05 dividend reduces this figure by only three million. Cash Needs and Agency issues Surplus cash to address any unforeseen needs will readily be available by adopting the conservative one-cent increase plan. Increasing the dividend to .06 includes holding on to almost 100 percent of a very large cash position, and therefore provides little pressure to identify such future cash needs. Signaling Linear’s sales are trending upward since the 2002 decline, but the immediate future is still not clear. The adoption of this conservative plan would continue their strategy of consistently signaling a message of safety and consistency of cash flows to their investors, yet provide options for our turbulent times. Other uses for this cash such as improved employee incentives, training, and workplace improvements should also be considered. Other Considerations The drawback for adopting the conservative plan without addressing the concerns of Janus and other like-minded investors could signal that they are not quite ready to suggest that their recent troubles are behind them. If we do choose this plan, a carefully crafted message to address investor concerns should be communicated to investors as quickly as possible. Additionally, other approaches such as one-time share buybacks and special dividends should be considered to address the concerns of Janus and other firms that share their view on Linear’s current cash position. We address these in Approach 2, 3 outlined in the sections that follow. Approach – 2 Payout all of Linear Technology’s Cash 1 In this section, we consider an alternate payout strategy in which Linear returns all of its 1.5 billion to its shareholders, by either (a) Paying a special dividend of $5.01 per share, or (b) Repurchasing about 50 million shares. (a) Special Dividend of $5.01 per share One goal of the special dividend will be to show investors that Linear is in a good position and to buy shares from Linear Technology is not comparable with the risk normally associated with the purchase of shares from technology companies. Additionally it signals to the market that Linear is serious about sharing its wealth with its shareholders. With these higher overall payouts, Linear Technology can reach investors that have specific income goals. Share price In case of a dividend announcement, demand for shares will rise. If investors know that a certain dividend amount will be paid, the share price increases by that amount (Law of One price). In this case, the current share price is $30.87 and dividend announced will be $5.01; hence the share price cum dividend can be expected to increase to $35.88. 1 Exhibit 4 shows calculations for numbers presented in this section Firm value Depending on the time until the dividend is paid, not the whole amount of dividend is added to the share price. If there is still a certain period of time until the dividend is paid, only the net present value of the dividend will be added to the share price. It also can be said that the closer the payment of the dividend gets, the more the amount of the total dividend payment is added to the normal share price. That also means that consequently the market value of equity also will rise. At the day ex-dividend day the share price will drop below the level of the pre-announcement day because the dividend as driver of the rising demand had been paid. The additional value of $5.01 that was is not part of the share value any more. The dividend, as part of the equity, is paid to the shareholder. Therefore, the dividend policy as a whole will not be a decisive factor in the firm’s value. Payout ratio However, in this scenario the payout ratio becomes a ridiculously high 945% (Exhibit-4), which is very high compared to peers. (Exhibit 2) Signaling By deploying capital through an increased dividend versus a share repurchase, management is signaling that Linear’s stock is fairly valued in the market. However, If Linear increases its dividend too much say by giving out all the cash as dividends, management could signal to the market that it believes the company’s growth is slowing and there are no new positive NPV projects for the company to invest in. However, this may help send a positive signal that the company is confident about generating positive cash flows for its operational and investment needs. Since profits of Linear Technology this quarter was far lower than that last year, a huge special dividend may help the investors regain faith in the company. Agency problems Increasing dividend is also a good way to reduce agency costs. With large amount of cash balance in hand, managers’ control over the capital becomes larger. Paying dividend to the investors is an efficient way to get additional monitoring of the capital, and thus make it less attractive to managers to invest the money in projects that will reduce the benefits of the shareholders. Tax Clientele With this very high dividend, the company may attract more European and/or mutual fund investors, but it may generally upset Institutional investors who do not have tax exemptions. Also, the announcement of a dividend may prompt older and poorer investors to buy more of Linear’s stock. (b) Share repurchase Share price and Shares outstanding Linear can repurchase 50.7 (16.23% of common shares) million common shares by spending all of its cash. When they do that, the number of outstanding shares will be 261.7 million. Historically, the stock price of companies has risen following a share  repurchase announcement as it can boost EPS. In this case EPS increases to $0.65. (Exhibit-4) Signaling By deploying all of its capital towards share repurchases, management can signal the market that its stock very undervalued. Linear has had a positive cash flow over the years and they have an opportunity with a net cash of $1.5 billion to bridge the supposed valuation disconnect by accelerating share repurchases. In summary, if the company goes out with a big stock buyback or special dividend, it will send a signal to investors that the company, is no longer a growth company, and stock value may decrease Approach – 3 Payout 50% of Linear Technology’s Cash2 Considering that management does not have a good line of sight into the future at this point, paying out all of Linear’s cash may be a risky move. Hence, in this section we look at a less aggressive approach that lies between preserving their cash balance (Approach 1) and paying out all of their cash (Approach 2). In evaluating this approach, we have assumed that Linear will need to keep up its quarterly dividend at $0.05, and the remainder of the cash after accounting for this quarterly dividend is available for either a special dividend or a share repurchase. The following section analysis the effect of paying out 50% of the remaining cash reserves either in the form of a special dividend of $2.51 or by repurchasing 25.35 million shares. EPS and Share Price If we were to repurchase shares using 50% of the cash, the EPS will increase from 0.55 to 0.59 close to the 2002 numbers of 0.62. Using a price/earnings ratio of 56.53 in 2003 (Exhibit-3), we can estimate the share price to increase to 33.65 with this increased EPS, cum dividend. If we were to pay out a special dividend of $2.51 per share instead, the share price cum dividend could be estimated to be a closely comparable $33.38 (Exhibit-5). EPS will be 0.55, very close to Q2 levels (0.54). Payout Ratio The dividend payout ratio in the case of the special dividend will be close to 486.3% (Exhibit-4) which is once again much higher than all of Linear’s peers (Exhibit-2). In contrast, with a share repurchase, the payout ratio remains at level consistent with previous quarters at 27.5%. 2 Exhibit 4 shows the calculations for numbers presented in this section Firm value and Shareholder wealth Repurchases will help alleviate some of the dilution of the EPS arising out of options awarded to employees and managers, considering that Linear’s incentives for all employees include stock options. On the other hand, dividends will help distribute the wealth more evenly among all investors, while repurchases cause an uneven distribution as the shareholders who do not sell will see a drop in book value of the shares, from $5.01 to $3.23 (rough approximation based solely on cash assets – Exhibit 5. Tax Clientele With the new rules that stipulate equal taxation rate of 15% for Capital gains and OIC, there are no quantifiable advantages one way or the other with respect to the decision to payout either in the form of a special dividend or repurchases. There may however, be some psychological impacts to be considered depending on preferences of the shareholders. For example, if the vast majority of shareholders belong to the older demographic, they may prefer it if the stock paid dividends. Signaling Linear’s investors are used to getting a dividend, and seeing periodic repurchases. Additional payouts of cash help increase ROE and reduce shareholders’ risk premium. At current low interest rates on cash (as of 2003), paying out at least some of the cash balance appears to be in the best interests of the shareholders. Though high payouts may signal that the company is lacking growth potential, it helps send a positive message that the company is keen on sharing its wealth. This message of being a â€Å"cash-cow† is better compared to the image of a company that is hoarding its wealth. Peers A quick look at Maxim’s financials indicates that they have started sharing their cash with their shareholders – in 2002 their cash returned was over 200% of their FCFE (Exhibit-2), and their cash reserves reduced by 455 million. They appear to have used that cash in repurchases in an effort to concentrate their wealth among a smaller number of shareholders, at the same  time they managed to increase their top line numbers significantly, even compared to 2000. By sharing half their cash with their shareholders, Linear will be able to put itself on par with this close competitor. Agency issues and other considerations One time special dividends don’t need to be kept up, so are essentially similar to repurchases in that respect. However, repurchases help boost EPS and prevent dilution, both of which have longer-lasting effects. In this respect a repurchase may be better than a dividend. As far as agency issues go, retaining 50% of the cash position may not provide as much incentive to work harder on identifying positive NPV projects, as expending 100% of the cash, but will work much better than retaining almost all of the cash as in Approach 1. Our Recommendation for Linear Our recommendation to Linear is to maintain status quo with respect to dividends – pay the quarterly dividend of $0.05 per share, and to buy back 25.35 million shares using half the cash balance. Dividends consistent with previous quarters of 2003, are recommended to avoid any adverse market reactions, while the company works on figuring out their strategy to increase top line sales and earnings to the 2000-2001 levels or better. Cancelling the dividend altogether or paying less than last quarter is not an option, as this would be perceived very negatively by the market. Historically, Linear has never increased dividends in the Q3 compared to Q2; hence it is safe to maintain a dividend of 5 cents per share as in Q3. Additionally, as shown in Exhibit-2, Linear already pays more dividends compared to peers, including their close competitor Maxim. Paying out all of the cash may deprive the company of the required levels of liquidity. Given that the analog semiconductor industry requires constant innovation and considering opportunities for new ventures such as entering the Asian market, it is safe to assume that the company should keep some cash reserves to account for unknowns. Linear is well aware that they need to expand their business and find ways to increase top line numbers, so keeping some cash, and supplementing it with capital from debt or/and equity markets is worth looking into. This forms the basis of our reasoning for recommending the use of only 50% of the cash balance to repurchase shares. Additionally, by repurchasing shares, Linear will be able to still sufficiently signal to the market that the stock is undervalued. At the same time, by maintaining some of the cash balance, they additionally signal the existence of profitable positive NPV projects for Linear to pursue. Considering the industry characteristics, and the stagnation reached in top line revenues, Linear will need to look at innovation and new markets, both of which could bring dramatic increases in growth. In light of this, we are convinced that the EPS boosting effect of a share repurchase is more valuable to Linear at this point, than the effects of an equitable distribution of shareholder wealth via special dividends.

Long Term Management Plan After 45min Consultation

We would like to consider this patient as a whole instead of 2 different illnesses. This patient is chronically depressed and recently being diagnosed with stage 3a Non Small Cell Lung Cancer. It is very difficult to formulate long term management plan after 45min consultation because information available about patient expectations and concerns are limited. In order to arrange patient centered management , patient participation is very important, because patient had stopped antidepressant and counselling prematurely, it could have been due to lack of patient involvement during the treatment choices and poor therapeutic relationship with the physician. Firs all, It is very important to establish a good rapport with the patient , because this patients doesn’t have pleasant experience with the conventional medical treatment, considering severity of his condition and available treatment modalities, conventional treatments are the first line options to be considered. Alternativ e treatments can be considered as an adjuvant therapies to conventional plan to minimize adverse effects or improve the quality of life. So, this long term plan is just a hypothetical sketch, which addresses key challenges, most appropriate therapeutic choices for best outcome of the patient health.The most difficult challenge in this patient is lack of time; How long you can wait to improve patients depression and energy level? ; Because waiting might have injurious to his health, and jeopardizeShow MoreRelatedA Project Study on ‚Äà ²Recruitment and Selection in Ims Learning Resources Pvt. Ltd‚Äà ´11571 Words   |  47 Pagesmost important thing is that enterprise grows, diversifies, and takes over other units-all necessitating hiring of new men and women. In fact recruitment functions stop only when the organization ceases to exist. To understand recruitment in simple terms it is understood as process of searching for obtaining applications of job from among from whom the right people can be selected. To define recruitment we can define it formally as it is a process of finding and attracting capable applicants for employment