lecture8(资源分配)

Lecture 8:Cell-Surface Interactions: Host Responses to Biomaterials2. Immune Response: Complement Alternative PathwayfibroblastsCell Activity time hrs days weeks • Endothelial cellsenzymesplasma protein C3 ⇒ cleavedC3b fragmentC3b attaches to biomtl or injurious agent surface ⇒ insoluble ligand for leukocyte receptors (also adsorbed IgG ) C3b catalyzes C5 cleavage to C5a ⇒ soluble ligand for leukocyteIMMUNE CELLRECRUITMENTNeutrophils (PMN’s, polymorphonuclear leukocytes, 3-5M/cc): bind C5a Associated with acute inflammatory response (minutes→1-2 days)¾become hyperadherent by ↑ CR3 (integrin CD11b/CD18) surface expression – attach to vasculature via endothelial ICAMs ¾chemotactic to C5a: migrate to inflammation site¾On site,neutrophils bind to C3b, catalyzing release of cytotoxic species: H2O2, O2−•(superoxide radical), OH•,enzymes⇒ attack/engulf/degrade invading microbes ¾Released products from neutrophils, activated platelets and endothelial cells, along with fibrin, form the provisional matrix(structural & biochemical functions)Monocytes (0.2-0.6M/cc): bind C5a⇒ follow the course of neutrophils Evolve to macrophages(days→ weeks/months)¾Macrophages: secrete reactive species, enzymes, cytokines (immune cell regulators, ex. IL-1), fibronectin, growth factors(ex. fibroblast growth factor), coagulation factors Monocytes & macrophages associated with chronic inflammationMacrophage response depends on foreign material properties…a) fluids or small particles (micron-sized) – engulfed & degraded“phagocytosis”foreign materialb) smooth, inert implants – FBGCs absent (nothing to engulf)⇒ macrophage layer surrounds implant¾Macrophage/FBGC products (FN, FGF) recruit fibroblasts¾Fibroblasts deposit collagen—pink “granulation tissue” (3-5 days), accompanied by capillary sprouting (angiogenesis)⇒wound healing histologyForeign body reaction: presence of FBGCs/macrophages,granulation tissue, and capillaries at tissue/material interface¾Connective tissue remodeling ⇒ thin, encapsulating fibrous layer (fibrosis) isolates implant and foreign body rxn (weeks) Cell Regeneration CapabilityCategory Normalreplic. rate Response toinjuryExamplesrenewing/ labile High;via stem celldifferentiationmodest ↑skin, intenstinalmucosa, bonemarrowExpanding/ stable Low large ↑endothelium,fibroblasts,hepatocytes,osteoblastsStatic/ permanent None Noreplication;replaced by scartissueheart musclecells, nerve cellsImplant biocompatibility is assessed largely by intensity & duration of the inflammatory response.Materials Class Inflammatory responseMetals very severe in absenceof passive oxidesOxides minimalProcessed naturalpolymersseveresynthetic polymers mild, unless particulatemorphology; additivescan give responseBiomaterial Biocompatibility Concerns1. Chronic inflammation•prolonged local chemical or physical irritation—delayed healing •often due to moving parts, debris, roughness•proliferation of connective tissue, or tissue necrosis(2 extremes of macrophage response)ex. PE cup liners in hip replacement implants3.051/BE.340 6 2. Toxicity•classical toxicity: from corrosion, degradation or wear products;cytotoxicity increases with amount present•immune system toxicity:i) immunogenic substances: proteins, carbohydrates, lipidsex. collagenii) small molecules (metals, degradation products, drugs) bind onhost proteins/cells, making an innocuous substance antigenicex. hypersensitivity to metals, acrylics, silicone3. Bacterial Infection•Bacteria compete with cells to adhere to surface¾similar mechanisms; better adapted to nonviable surfaces¾resistant to antibiotics (different surface expression) •Most common bacterial infections:¾polymeric biomaterials: S. epidermidis¾metallic biomaterials: S. aureus¾have receptors for fibronectin & collagenex. artificial hearts, synthetic vessels, joint replacementimplants, fixation devices, IV catheters, urologic devices,contact lensesNote: ~60,000 U.S. deaths/yr from device-related infectionsurinary catheters, central venous catheters ⇒ pathway into body3.051/BE.340 74. Tumorigenesis•rarely observed•morphology dependent vs. chemistry dependent(ex. asbestos – needle-like particulates, aspect ratio>100:1) •requires fibrous encapsulation (not seen at chronic inflammation sites)•implant role unclear—foreign body reaction may stimulatematuration & proliferation of precancerous cells•chemical carcinogens: little supportive data¾metal implant debris (Cr, Co, Ni) ⇒ carcinogenic in rodents¾polymer impurities/additives: monomers, solvents,plasticizers, antioxidants5. Blood Incompatibility•blood-¾may compromise device by occlusionex. small (<4 mm dia.) vascular grafts, stents, IV catheters¾may detach (embolize) & create vessel occlusion downstreamex. emboli to brain from mechanical heart valves ⇒ stroke¾susceptible devices require use of anti-coagulation drugs(heparin) ⇒bleeding riskImage removed due to copyright considerations3.051/BE.340 8•complement activation by extracorpeal therapies¾C3b adsorption to material ⇒C5a activation of neutrophils& monocytes (WBCs) to hyperadherent state¾WBCs stick in lungs⇒ neutropenia, respiratory distress,hypoxemia (O2 deficiency—similar symptoms to altitudesickness), tachycardia, cardiac arrestex. hemodialysis membranes, cardiopulmonary bypass (CPB)devicesReferences:M.A. Horton, Ed., Molecular Biology of Cell Adhesion Molecules, John Wiley &Sons: NY, 1996.D.A. Hammer and M. Tirrell, “Biological Adhesion at Interfaces”, Annu. Rev.Mater. Sci. 1996, 26: 651-691.K.M. Yamada, “Cell Adhesion Molecules”, in Encyclopedia of Molecular Biology,T.E. Creighton, Ed., John Wiley & Sons: NY, 1999, pp. 361-366.J.M. Anderson, “Biological Responses to Materials”, Annu. Rev. Mater. Res. 2001,31: 81-110.。

Similarity of regulation between eukaryotes and prokaryote1、Principles are the same: signals, activators and repressors, recruitment and allostery （变构）, cooperative binding2、Expression of a gene can be regulated at the similar steps, and the initiation of transcription is the most pervasively regulated step.Difference in regulation between eukaryotes and prokaryote1. Pre-mRNA splicing adds an important stepfor regulation.2. The eukaryotic transcriptional machineryis more elaborate than its bacterial counterpart.3. Nucleosomesand their modifiers influenceaccess to genes.4. Many eukaryotic genes have more regulatory binding sites and are controlled by more regulatory proteins than are bacterial genes.cis-regulatory elementA cis-regulatory element or cis-element is aregion of DNA or RNA that regulates the expression of Genes located on that same strand. This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites of one or more trans-acting factors. A cis-element may be located in the promoter region 5' to the gene it controls, in an intron, or in the 3'untranslated region. Trans-regulatory elementsTrans-regulatory elements are species which may modify the expression of genes distant from the gene that was originally transcribedto create them. To demonstrate the concept (this is not a specific example), a transcription factor which regulates a geneon chromosome 6 might itself have been transcribed from a gene on chromosome 11. This term is constructed from the Latin root -trans, which means "across from". Expound the general mechanism of control of gene expression of Eukaryotes。

Lecture 8 Long Lived AssetsScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-2What is a long term asset?Definition of Asset: have probably future economic benefits as a result of past transactions. LT asset: future economic benefit more than one year.FA-10/30/20098-3Why important?Long-term assets is the most important investments for many companies. Research shows that investments in LT assets returns more than those in short term assets Long term assets are less liquidFA-10/30/20098-4PPE of Selected Companies$44 millione-Bay Wal-Mart Anheuser-Busch McDonald's 0%29%$32,839 million47%$7,965 million63%$16,325 million78% 20% 40% 60% 80%As a percent of total assetsFA-10/30/20098-5Classification of LT assets:– Tangible assets（固定资产）: Property, plant and equipment (i.e. Land, building, machinery, etc.) – Intangible assets(无形资产）: (acquired) patents, brands, etc.FA-10/30/20098-6ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-7Acquisition CostThe acquisition value of an asset is either:– The fair value of what was given up in exchange for the asset (such as cash), or – The fair value of what was received whichever is more easily determined.FA-10/30/20098-8Acquisition CostThe acquisition value is all inclusive– invoice price plus costs necessary to bring asset to condition and location for intended use Add: (there is never a complete list) - search cost - legal cost - transportation and installation - Other costs related to the purchase.FA-10/30/2009 8-9Lump-Sum Asset PurchaseThe total cost of a combined purchase of land and building is separated on the basis of their relative market values.On January 1, UpCo purchased land and building for $200,000 cash. How much of the purchase price will be charged to the building and land accounts? The appraised values are building, $162,500, and land, $87,500.FA-10/30/2009 8-10Lump-Sum Asset PurchaseAsset Land Building Total Appraised Value $ $ a 87,500 162,500 250,000 % of Value b* Purchase Price Apportioned Cost c b × c 35% × $ 200,000 = $ 70,000 65% × 200,000 = 130,000 100% $ 200,000* $87,500 ÷ $250,000 = 35%$162,500 ÷ $250,000 = 65%Journal Entry?FA-10/30/2009 8-11Issues in Accounting for Plant AssetsDecline in asset value over its useful li feAcquisition 1. Compute costUse 2. Allocate cost to periods benefitedDisposal 3. Record disposalFA-10/30/20098-12Repairs and improvements (修理和改良）Repairs generally restore usefulness. As such, repairs are expensed in the period they occur. Improvements generally increase usefulness. As such, improvements can either – Increase the useful life of the asset – Increase the output of the asset.FA-10/30/20098-13ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-14DepreciationDepreciation: a process to allocate acquisition costs. Issues in depreciation accounting1. Measuring the depreciable basis of the asset 2. Estimating its useful service life 3. Deciding on the pattern of expiration of asset costFA-10/30/2009 8-15南方航空2004年報（百万元）Southern airline 31,334 LTA out of 39,371 Total assetFA-10/30/2009 8-16DepreciationDepreciation basis （折旧基础） – Acquisition cost less salvage value – Estimating salvage value （a market price into the distant future）. Useful years: – A difficult task – Therefore, accountants reconsider assets’ estimated service lives every few yearsFA-10/30/2009 8-17The effects of depreciationIncome Statement Revenues COGS Depreciation expenses … … Net Income Balance Sheet AssetsCash A/R Inventory PPE-original -Accumulated Dep.…Net Book value of PPE = Original BV- Accu. DepreciationFA-10/30/20098-18ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-19Depreciation method for financial reporting purpose1. Straight-line method 2. Units of production 3. Accelerated method - Sum-of-the-years’-digits method 年限总和法- Double-declining method (DDB) 余额递减法FA-10/30/20098-20Depreciation methodMarkam Corp acquires a new machine costing $20,000. The firm expects to use the machine for 5 years and that the salvage value will be $2,000.Depreciation base = $20,000 - $2,000 = $18,000FA-10/30/20098-21Straight Line DepreciationAllocate the depreciation base equally among the years of useful life, in this case, it is five years. The straight line rate would be 1/( 5 years) or 20% per yearbeginning net book balance $20,000 16,400 12,800 9,200 5,600 depreciation ending charge accum.depr. net book 20% of basis after charge balance $3,600 $3,600 $16,400 3,600 7,200 12,800 3,600 10,800 9,200 3,600 14,400 5,600 3,600 18,000 2,0008-22year 1 2 3 4 5FA-10/30/2009basis $18,000 18,000 18,000 18,000 18,000百聯股份2008年報FA-10/30/20098-23ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-24Units of Production DepreciationMarkam Corp acquires a new machine costing $20,000. Engineers say the machine should run for 24,000 hours and that the salvage value will be $2,000. 1. The basis to be depreciated is cost minus salvage or $18,000 2. The per hour unit rate would be $18,000/( 24,000 hours) or $0.75 per hour 3. During the five years, the running hours are 5000, 4000, 6000, 5000, 4000 hours respectively. Then depreciation expense in each year will be…FA-10/30/2009 8-25ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-26Accelerated depreciation:Sum of Years’ Digits MethodDepreciation charge is calculated as a variable depreciation rate times depreciation base. – The depreciation rate is equal to the number of years remaining (including the current year) divided by the sum of the years’ digits – The sum of the years’ digits is the sum of the numbers 1, 2, 3, …, up to and including the last year of useful life. – For a 5 year useful life, the sum is 1+2+3+4+5 = 15; therefore depreciation rate for first year is 5/15=1/3FA-10/30/2009 8-27Accelerated depreciation:Sum of Years’ Digits Method Use the example of Markam, depreciation expense will be:Depreciation Charge (rate*basis)remaining years 5 4 3 2 1 accum.depr. after charge (rate * basis) $6,000 4,800 3,600 2,400 1,200 ending net book balance $14,000 9,200 5,600 3,200 2,0008-28year 1 2 3 4 5FA-10/30/2009rate basis 5/15 $18,000 4/15 18,000 3/15 18,000 2/15 18,000 1/15 18,000Accelerated depreciation:Double declining balance method1. 2. The straight line rate would be 1/( 5 years) or 20% Double declining balance uses a fixed rate of twice the straight line rate, or 40% (the last two years change to SL)year 1 2 3 4 5FA-10/30/2009beginning ending net book depreciation accum.depr. net book balance charge after charge balance $20,000 $8,000 * $8,000 $12,000 12,000 4,800 * 12,800 7,200 7,200 2,880 * 15,680 4,320 4,320 1,160 16,840 3,160 3,160 1,160 18,000 2,000* 40% of net book value8-29ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-30Depreciation - the accounting process using SL1. When purchase the machine, Dr. Machine 20,000 Cr. Cash 20,000 2. Dec. 31 of year 1 Dr. Depreciation expense 3,600 Cr. Accumulated depreciation 3,600 3. Dec. 31 of year 2 Dr. Depreciation expense 3,600 Cr. Accumulated depreciation 3,600FA-10/30/2009 8-31Impact of different methods on I/S and B/SYear Dep. Exp.-SL Dep. Exp.Sum-of-digits Ending net asset book value - SL Ending net asset book value –sumof-digits1 2 3 4 5 TotalsFA-10/30/2009$3,600 3,600 3,600 3,600 3,600$6,000 $16,400 $14,000 4,800 3,600 2,400 1,200 12,800 9,200 5,600 2,000 9,200 5,600 3,200 2,000$18,000 $18,0008-32EAcquisition cost - salvageDDep. expenseS A NTimeE-immediate expensing; N-no depreciation; S-straight line depreciation; A-accelerated depreciation; D-decelerated depreciation;FA-10/30/2009 8-33格力电器2008年报FA-10/30/20098-34ScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-35Intangible Assets and AmortizationAssets may provide future benefits without having physical form. Intangible assets may have a limited life.– Patents expire after 20 years in the U.S.Intangible assets are reduced in value in recognition of this limited life.– The revaluation is similar to depreciation but is called amortization.FA-10/30/2009 8-36Intangible Assets and AmortizationAccountants face two key issues with regards to intangible assets: – Have the expenditures made to acquire or develop the intangible asset generated sufficient future benefits that the expenditures should be capitalized? – Have the expenditures produced benefits so hard to measure that the the expenditures should be expensed.FA-10/30/2009 8-37Intangibles Investment“As the embodiment of ideas, intangibles are what drive growth in an information economy. Baruch Lev, an accounting professor at New York University, reckons that in the late 1990s, businesses invested approximately $1 trillion per year in such assets”FA-10/30/20098-38Intangibles InvestmentAn intangibles investment rate of $1 trillion suggests that U.S. businesses are investing nearly as much in intangibles as they are in plant and equipment.If we are investing $1 trillion a year in intangibles…then the long-run equilibrium value of intangibles is $6 trillion.Lev 2002FA-10/30/2009 8-39R&D and advertisingResearch and development are expenditures for knowledge that may increase the competitiveness in the future. Advertising is expenditures to inform potential customers about the product or services of the firmGAAP requires expensing.FA-10/30/2009 8-40Lev, Nissim and Thomas (2005)BVDIST: The distortion effect on market value caused by the difference between the R&D adjusted book value and the reported book value.FA-10/30/2009 8-41PatentsA patent is a right granted by a government for exclusive use and benefits for and invention for a limited time. The U.S. has been extending the definition of what qualifies as an invention to include what are called intellectual property rights. Patents in the U.S. are generally amortized over 20 years using a straight line method.FA-10/30/2009 8-42CopyrightsCopyrights are similar to patent but are not inventions, rather they are rights given for exclusive use of an artistic design or words.– Music, photographs, and famous people are sometimes copyrighted. Trademarks, TM, are similar but are specific identifiers for firms.Copyrights give the owner the exclusive right to reproduce and sell artistic or published work. Copyrights extend for the life of the creator plus 50 years.FA-10/30/2009 8-43Italian Renaissance artist Leonardo da Vinci died in 1519 therefore, anyone can copy MONA LISA or his other paintings without receiving permission or paying a fee.FA-10/30/20098-44Anyone can change the picture in anyway he/she wants.FA-10/30/20098-45Goodwill(商誉）Occurs when one company buys another company. Only purchased goodwill is an intangible asset.The amount by which the purchase price exceeds the fair market value of net assets acquired. Goodwill is not amortized.FA-10/30/2009 8-46GoodwillEddy Company paid $1,000,000 to purchase James Company. The acquired assets were appraised at a fair value of $900,000 and liabilities are $200,000. What amount of goodwill should be recorded on Eddy Company books?FMV of Assets Debt Assumed FMV of Net Assets Purchase Price GoodwillFA-10/30/2009$ $900,000 200,000700,000 1,000,000 $ 300,0008-47If the firm has a patent? If the FMV>purchase priceScheduleThe importance of Long-term Assets Initial Valuation Depreciation– – – – Straight Line Depreciation Units of Production Accelerated depreciation Impact of different methodsIntangibles Earnings management through long-lived assetsFA-10/30/2009 8-48Earnings management through long-lived assets1. Through Choosing depreciation method 2. Through estimating useful life and salvage value before use or in the middle of use 3. Through taking impairment charges 4. Retirement of AssetsFA-10/30/20098-49Through Choosing depreciation methodEM through switching between depreciation methods is difficult. 1) If a firm is using accelerated depreciation method, and want to switch to straight-line method to boost earnings, then it must choose timing. 2) Auditors won’t allow firms to switch often.FA-10/30/2009 8-50。