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The Bioconjugation and Radiosynthesis of critical systems, 89 Zr-DFO-labeled Antibodies. The exceptional affinity, specificity, and selectivity of antibodies make them extraordinarily attractive vectors for tumor-targeted PET radiopharmaceuticals. Due to their multi-day biological half-life, antibodies must be labeled with positron-emitting radionuclides with relatively long physical decay half-lives. Traditionally, the positron-emitting isotopes 124 I (t 1/2 = 4.18 d), 86 Y (t 1/2 = 14.7 hr), and 64 Cu (t 1/2 = 12.7 hr) have been used to explain how to an entire essay, label antibodies for PET imaging. More recently, however, the field has witnessed a dramatic increase in thinking the use of the positron-emitting radiometal 89 Zr in antibody-based PET imaging agents. 89 Zr is a nearly ideal radioisotope for PET imaging with immunoconjugates, as it possesses a physical half-life (t 1/2 = 78.4 hr) that is paragraph essay outline compatible with the in vivo pharmacokinetics of antibodies and emits a relatively low energy positron that produces high resolution images. Systems Thinking! Furthermore, antibodies can be straightforwardly labeled with 89 Zr using the siderophore-derived chelator desferrioxamine (DFO). In this protocol, the prostate-specific membrane antigen targeting antibody J591 will be used as a model system to illustrate (1) the bioconjugation of the on totalitarianism, bifunctional chelator DFO-isothiocyanate to an antibody, (2) the radiosynthesis and purification of a 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in critical systems vivo PET imaging with an third point research, 89 Zr-DFO-mAb radioimmunoconjugate in a murine model of cancer. Due to their remarkable sensitivity, affinity, and selectivity, antibodies have long been considered promising vectors for the delivery of radioisotopes to cancer cells. Critical Systems Thinking! However, their application in positron emission tomography (PET) imaging has been hampered by explain movie essay, the lack of a suitable positron-emitting radioisotope for thinking their labeling. 1-3 One of the explain movie essay, most critical considerations in the design of radioimmunoconjugates is matching the physical decay half-life of the radioisotope to the in vivo pharmacokinetics of the critical thinking, antibody. Ng Paggawa! More specifically, antibodies often have relatively long, multi-day biological half-lives and therefore must be labeled with radioisotopes with comparable physical half-lives. For PET imaging applications, antibodies have traditionally been radiolabeled with 64 Cu (t 1/2 = 12.7 hr), 86 Y (t 1/2 = 14.7 hr), or 124 I (t 1/2 = 4.18 d). 4,5 However, each of these radioisotopes possesses significant limitations that hamper their suitability for thinking clinical imaging. While radioimmunoconjugates labeled with 86 Y and 64 Cu have proven promising in preclinical investigations, both isotopes possess physical half-lives that are too short to be effective for imaging in humans. Case Study Of Advertising! 124 I, in contrast, has a nearly ideal physical half-life for imaging with antibodies, but it is critical systems thinking expensive and third has suboptimal decay characteristics that lead to relatively low resolution clinical images. Furthermore, 124 I-labeled radioimmunoconjugates can be subject to dehalogenation in critical vivo , a process which can lower tumor-to-background activity ratios. 6,7. The drive to find a positron-emitting radioisotope to supplant 64 Cu, 86 Y, and person paper 124 I in radioimmunoconjugates has fueled the recent surge in research on 89 Zr-labeled antibodies. 8-12 The reason for the advent of 89 Zr is thinking straightforward: the radiometal possesses near-ideal chemical and case of advertising physical properties for critical systems use in diagnostic PET radioimmunoconjugates. 13 89 Zr is produced via the 89 Y( p,n ) 89 Zr reaction on a cyclotron using a commercially available and 100% naturally abundant 89 Y target. 14,15 The radiometal has a positron yield of 23%, decays with a half-life of 78.4 hr, and third person point of view research paper emits positrons with the relatively low energy of 395.5 keV ( Figure 1 ). 13,16,17 It is systems important to note that 89 Zr also emits a high energy, 909 keV γ-ray with 99% efficiency. While this emission does not interfere energetically with the emitted 511 keV photons, it does require extra consideration with regard to transport, handling, and dosimetry. Help! Despite this caveat, these decay characteristics ultimately mean that 89 Zr not only has a more favorable half-life for imaging with antibodies than 86 Y and critical thinking 64 Cu but can also produce higher resolution images than 124 I, which emits positrons with higher energies of 687 and 975 keV as well as a number of photons with energies within 100-150 keV of the 511 keV positron-created photons. 13 Moreover, 89 Zr is also safer to handle, less expensive to of view research paper, produce, and residualizes in tumors more effectively than its radioiodine counterpart. Critical! 18,19 One potential limitation of an entire movie, 89 Zr is critical systems thinking that it does not have a therapeutic isotopologue, e.g. , 86 Y (PET) vs. 90 Y (therapy). This precludes the construction of chemically identical, surrogate imaging agents that can be employed as dosimetric scouts for their therapeutic counterparts. 1984 Essays! That said, investigations suggest that 89 Zr-labeled antibodies do have potential as imaging surrogates for 90 Y- and 177 Lu-labeled immunoconjugates. 20,21. From a chemical standpoint, as a Group IV metal, 89 Zr exists as a +4 cation in aqueous solution. The Zr 4+ ion is thinking highly charged, relatively large (effective ionic radius = 0.84 Å), and can be classified as a “hard” cation. As such, it exhibits a preference for ligands bearing up to of advertising campaign, eight hard, anionic oxygen donors. Easily the most common chelator used in 89 Zr-labeled radioimmunoconjugates is desferrioxamine (DFO), a siderophore-derived, acyclic chelator bearing three hydroxamate groups. The ligand stably coordinates the Zr 4+ cation quickly and cleanly at critical, RT at biologically relevant pH levels, and the resulting Zr-DFO complex remains stable over the course of multiple days in saline, blood serum, and whole blood. 22 Computational studies strongly suggest that DFO forms a hexacoordinate complex with Zr 4+ in which the metal center is point of view research paper coordinated to the three neutral and three anionic oxygen donors of the ligand as well as two exogenous water ligands( Figure 2 ). 23,24 The in vivo behavior of radioimmunoconjugates employing the systems, 89 Zr-DFO conjugation scaffold has generally been excellent. However, in some cases, imaging and acute biodistribution studies have revealed elevated activity levels in paraan the bones of mice injected with 89 Zr-labeled antibodies, data that suggests that the critical systems, osteophilic 89 Zr 4+ cation is released from the chelator in vivo and subsequently mineralizes in the bone. 25 Recently, a number of investigations into compare and contrast essay the development of novel 89 Zr 4+ chelators particularly ligands with eight oxygen donors have appeared in the literature. 24,26,27 Nevertheless, at present, DFO is the most widely employed chelator in 89 Zr-labeled radioimmunoconjugates by a wide margin. A variety of different bioconjugation strategies have been employed to attach DFO to antibodies, including bioorthogonal click chemistry, the reaction of thiol-reactive DFO constructs with cysteines in the antibody, and the reaction of activated ester-bearing DFO constructs with lysines in thinking the antibody. 4,28-30 Easily the most common strategy, however, has been the use of an isothiocyanate-bearing derivative of 1984 essays on totalitarianism, DFO, DFO-NCS ( Figure 2 ). 22 This commercially available bifunctional chelator robustly and reliably forms stable, covalent thiourea linkages with the systems thinking, lysines of the antibody ( Figure 3 ). Over the past few years, a wide variety of 89 Zr-DFO-labeled radioimmunoconjugates have been reported in the literature. Preclinical investigations have been especially abundant, featuring antibodies ranging from the more well-known cetuximab, bevacizumab, and person of view research paper trastuzumab to more esoteric antibodies such as the CD105-targeting TRC105 and fPSA-targeting 5A10. 30-36 More recently, a small number of early-phase clinical trials using 89 Zr-DFO-labeled antibodies have emerged in the literature. Specifically, groups in the Netherlands have published trials employing 89 Zr-DFO-cmAb U36, 89 Zr-DFO-ibritumomab tiuxetan, and 89 Zr-DFO-trastuzumab. 21,32,37 In addition, a range of other clinical trials with 89 Zr-labeled radioimmunoconjugates are currently underway, including investigations here at Memorial Sloan Kettering Cancer Center using the PSMA-targeting 89 Zr-DFO-J591 for prostate cancer imaging and the HER2-targeting 89 Zr-DFO-trastuzumab for breast cancer imaging. 23,30 In addition, while radiolabeled antibodies remain the most common 89 Zr-labeled radiopharmaceuticals, the systems, radiometal has also increasingly been employed with other vectors, including peptides, proteins, and nanomaterials. Case Study Of Advertising! 38-43. The modularity of this 89 Zr-DFO labeling methodology is a tremendous asset. The repertoire of biomarker-targeting antibodies is ever-expanding, and the interest in performing in vivo PET imaging using these constructs is critical systems thinking growing apace. As a result, we believe that the development of more standardized practices and protocols could benefit the field. An excellent written experimental protocol for DFO-NCS conjugation and 89 Zr radiolabeling has already been published by and contrast essay outline, Vosjan, et al. 22 We feel that the visual demonstration provided by this work could further help investigators new to these techniques. In the protocol at hand, the prostate-specific membrane antigen targeting antibody J591 will be used as a model system to illustrate (1) the thinking, bioconjugation of the bifunctional chelator DFO-isothiocyanate to an antibody, (2) the radiosynthesis and purification of the 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in third point research paper vivo PET imaging with a 89 Zr-DFO-mAb radioimmunoconjugate in thinking a murine model of cancer. 23,44,45. All of the in vivo animal experiments described were performed according to an approved protocol and under the ethical guidelines of the Memorial Sloan Kettering Cancer Center Institutional Animal Care and Use Committee (IACUC). 2. Radiolabeling J591-DFO with 89 Zr. CAUTION: This step of the protocol involves the handling and manipulation of radioactivity. Of Advertising Campaign! Before performing these steps or performing any other work with radioactivity researchers should consult with their home institution’s Radiation Safety Department. All possible steps should be taken to minimize exposure to critical systems, ionizing radiation.   NOTE: In the interest of proper radiochemical note-keeping, the amount of radioactivity in essay the sample should be measured using a dose calibrator and recorded before and after Steps 2.2-2.13 in the protocol below. This will help with the accurate determination of radiochemical yields and specific activities. 3. In Vivo PET Imaging with 89 Zr-DFO-J591. CAUTION: As in Protocol Section 2, this step of the systems, protocol involves the handling and manipulation of radioactivity. Before performing these steps researchers should consult with their home institution’s Radiation Safety Department. All possible steps should be taken to minimize exposure to ionizing radiation. The first step in dissertation this protocol the conjugation of DFO-NCS to the antibody is typically quite robust and reliable. Generally, the purified, chelator-modified immunoconjugate can be obtained in critical systems > 90% yield, and using 3 molar equivalents of DFO-NCS in the initial conjugation reaction will yield a degree-of-labeling of the chelator of approximately 1.0-1.5 DFO/mAb. The 89 Zr radiolabeling and purification steps of the procedure are likewise straightforward. At the concentrations outlined in the protocol above, radiolabeling yields of > 80% and thus specific activities of > 2.0 mCi/mg are typical after 60 min at RT. The radio-TLC chromatogram of the crude radiolabeling mixture will likely reveal some DTPA-bound 89 Zr 4+ that elutes at the solvent front ( Figure 4A ). However, after quenching the reaction with DTPA and purifying the 89 Zr-DFO-mAb construct via size exclusion chromatography, the radiochemical purity of the purified, isolated 89 Zr-DFO-mAb conjugate should be > 95% ( Figure 4B ). In the event that the radiochemical purity of the isolated 89 Zr-DFO-mAb conjugate is less than 95%, the purification procedure should be repeated prior to performing any in vitro or in vivo experiments. Moving on to the in vivo experiments, in the protocol described above, athymic nude mice bearing PSMA-expressing, LNCaP prostate cancer xenografts were employed to investigate the in vivo behavior of 89 Zr-DFO-J591. Both acute biodistribution and PET imaging experiments revealed that 89 Zr-DFO-J591 clearly delineates the prostate cancer xenografts with excellent image contrast and high tumor-to-background activity ratios ( Figure 5 ). The uptake of the radioimmunoconjugate in third person the tumor is evident as early as 24 hr (20.9% ± 5.6% ID/g), and the activity concentration in the tumor increases to critical systems, a maximum of 57.5% ± 5.3% ID/g at 96 hr post-injection. Case Campaign! As is typical for radioimmunoconjugates, a relatively high concentration of radiotracer is present in the blood at early time points (9.1% ± 5.3% ID/g at 24 hr), followed by a slow decrease in the amount of radioactivity in the blood over the course of the thinking, experiment. The non-target tissue with the highest activity concentration was the bone, which displayed uptake values around 10% ID/g throughout the experiment, presumably as a result of the in vivo release of the osteophilic cation 89 Zr 4+ . All other organs including heart, lung, liver, spleen, stomach, large and small intestine, kidney, and muscle displayed relatively low activity concentrations, often well below 5% ID/g. As a control, an five and contrast outline, additional cohort of mice were injected co-injected 300 µg unlabeled DFO-J591 in order to saturate the antigen and thus illustrate selective blocking. Critically, the blocking experiment lowered uptake of the critical systems, radioimmunoconjugate in the tumor from 48.9% ± 9.3% ID/g to 23.5% ± 11.1% ID/g at case, 72 hr post-injection, clearly indicating that 89 Zr-DFO-J591 selectively targets its antigen. Figure 1. ( A ) A simplified decay scheme and ( B ) some salient decay characteristics of 89 Zr. Critical Systems! 13,16,17 IT = isomeric transition; EC = electron capture. Modified and reprinted with permission from third of view research paper Deri, et al. Nuclear Medicine and Biology . 40 , 3-14 (2013). Please click here to critical, view a larger version of this figure. Figure 2. ( A ) The structure of DFO-NCS with the coordinating oxygen atoms colored red; ( B ) A DFT-derived structure of the Zr-DFO coordination complex. Ng Paggawa! Modified and reprinted with permission from Deri, et al. Journal of Medicinal Chemistry. 57, 4849-4860 (2014). Systems! Copyright 2014 American Chemical Society. Please click here to view a larger version of this figure. Figure 4. Representative radio-TLC chromatograms of the case of advertising, crude radiolabeling mixture (A) and purified product (B) of 89 Zr-DFO-J591. Radio-TLCs were run on silica strips using an eluent of critical systems thinking, 50 mM DTPA, pH 5.0. Please click here to view a larger version of paraan ng paggawa ng thesis, this figure. Figure 5. Coronal PET images of 89 Zr-DFO-J591 (11.1-12.9 MBq [300-345 μCi] injected via tail vein in thinking 200 μl 0.9% sterile saline) in athymic nude mice bearing subcutaneous, PSMA-expressing LNCaP prostate cancer xenografts (white arrows) between 24 and 120 hr post-injection. 1984! Modified and reprinted with permission from Zeglis, et al. Bioconjugate Chemistry . 24 , 1057-1067 (2013). Copyright 2013 American Chemical Society. Critical Systems! Please click here to view a larger version of this figure. While the construction, radiolabeling, and imaging of 89 Zr-DFO-labled radioimmunoconjugates is generally a rather straightforward procedure, it is important to keep a few key considerations in mind during each step of the explain how to an entire movie, process. For example, perhaps the most likely cause for critical concern during the conjugation step of the procedure is the aggregation of the help dissertation, antibody during the conjugation reaction. This problem is most often a product of poor mixing of the conjugation reaction after the addition of the DFO-NCS stock solution. 22 When this happens, the non-homogenous distribution of the DFO-NCS can cause excessively high levels of critical systems thinking, local reaction with the ng thesis, antibody, which can in turn lead to critical systems, aggregation. This issue can be relatively easily circumvented by adding the DFO-NCS stock solution in small aliquots (< 5 µl), thoroughly mixing the paraan ng paggawa, reaction mixture after the addition of the DFO-NCS, and critical systems thinking agitating the reaction mixture on a temperature-controlled shaker. Third Person Point Of View Research! In addition, after the conjugation and purification of the DFO-mAb construct, it is important to precisely determine the critical systems thinking, number of DFO conjugated to each mAb. The full characterization of the five, number of DFO chelates per antibody can be achieved using radiometric isotopic dilution experiments similar to those performed by Holland, et al. and Anderson, et al. , though MALDI-TOF mass spectrometry is a viable alternative. 14,23,30,51,52 During the radiolabeling step, easily the most common problem is lower-than-expected radiolabeling yields. If unexpectedly low yields occur despite assiduously following the critical systems, protocol above, three different troubleshooting strategies are available: (1) incubating the dissertation, radiolabeling reaction for longer amounts of time ( e.g., 2-3 hr); (2) repeating the radiolabeling reaction using a higher concentration of critical systems, antibody; or (3) repeating the initial DFO-NCS conjugation reaction using a higher molar excess of the bifunctional chelator. While the DFO-NCS conjugation is facile and compare and contrast essay outline robust, one of its undeniable weaknesses is that it is not site-specific: DFO-NCS forms thiourea linkages with available lysines in the antibody regardless of their position. As a result, it is possible that the chelators may become appended to the antigen-binding region of the critical thinking, antibody, thereby adversely affecting the immunoreactivity of the 89 Zr-DFO-labeled conjugate. Therefore, a fine balance must be struck in the construction of 89 Zr-labeled radioimmunoconjugates: higher numbers of chelators per antibody facilitate higher specific activities, but higher degrees of labeling also increase the risk of compromising the immunoreactivity of the construct. In the end, the dissertation, goal is simple: attach as many chelators as necessary without compromising immunoreactivity. After obtaining the purified 89 Zr-DFO-mAb radioimmunoconjugate, it is critical to determine the in vitro immunoreactivity of the construct prior to any in vivo experimentation. To this end, we recommend using the in vitro methods published by critical, Lindmo, et al. 53,54 If the immunoreactivity of the construct is lower than 80-90%, it may be necessary to return to the conjugation reaction and append fewer DFO moieties per antibody. Alternatively, if the immunoreactivity of the purified 89 Zr-DFO-mAb is high (> 90%) and higher specific activities are desired, it may be possible to attach more chelators to person research paper, the antibody without decreasing immunoreactivity. Finally, the in vivo behavior of a 89 Zr-DFO-labeled antibody is, of course, highly dependent on both the identity of the antibody and the tumor model employed. In the model system presented here, the maximum uptake value in the tumor reaches approximately 60% ID/g; however, reports in the literature for maximum tumor uptake values range from as low as 15-20% ID/g to as high as 80-90% ID/g. 33,44,55-57 Likewise, the amount of uptake in non-target tissues — in particular the liver and spleen — can vary widely depending on the antibody/antigen system being studied. Critical! The specific activity of the 89 Zr-DFO-labeled antibody is an important consideration for in vivo experiments. Literature values for person the specific activities of critical systems thinking, 89 Zr-DFO-mAbs typically range from 1984 essays 1-6 mCi/mg (37-222 mBq/mg). Systems! 8,10 Generally, higher specific activities are preferable, as they decrease the likelihood of the inadvertent saturation of the antigen ( i.e., self-blocking). This becomes especially true in systems with lower levels antigen expression. Ng Thesis! Regardless of the antibody/antigen system, no in systems vivo investigation of a 89 Zr-DFO-labeled imaging agent is complete without a demonstration of selectivity. 1984 On Totalitarianism! This can be achieved via blocking experiments using large amounts of systems, unlabeled biomolecule or the 1984 on totalitarianism, use of a cell line that does not express the antigen in question. In the procedure described herein, the former was employed, but the systems thinking, selectivity of third person point of view research, 89 Zr-DFO-J591 has also been demonstrated using PSMA-negative PC3 prostate cancer xenografts. 23. It is important to critical systems, note that despite its clear advantages, this DFO-NCS-based synthetic methodology is not perfect. As we have discussed, DFO is compare essay not an ideal chelator for 89 Zr 4+ , and the non-site-specific nature of the systems, conjugation reaction can prove cumbersome. Analyze An Entire! To circumvent these issues, exciting efforts to develop new chelators for 89 Zr 4+ and site-specific radiolabeling methodologies are currently underway, yet these new technologies still need to be optimized and validated in both the laboratory and clinic. Systems Thinking! 24,26,27,29,44 Ultimately, the DFO-NCS methodology for the construction of ng paggawa, 89 Zr-DFO-labeled antibodies has proven to be an critical systems thinking, extremely powerful tool for the synthesis of radioimmunoconjugates and has the potential to be used to help dissertation, create a wide variety of clinically useful radiopharmaceuticals. The authors have nothing to disclose. The authors thank Prof. Thomas Reiner, Dr. Critical Systems Thinking! Jacob Houghton, and Dr. Serge Lyaschenko for helpful conversations. 

books a dying art dont believe it essay

Los Angeles Times Magazine. September 22, 1991, Sunday. LENGTH: 5408 words. HEADLINE: THE DEATH OF READING ; WILL A NATION THAT STOPS READING EVENTUALLY STOP THINKING? BYLINE: B y Mitchell Stephens , Mitchell Stephens, a journalism professor at New York University and the author of A History of News, read 2 books on his recent vacation. WHAT'S MISSING FROM THESE PICTURES? * THREE PEOPLE SIT in systems thinking, a doctor's waiting room. One stares at the television that rests on an end table, the second fiddles with a hand-held video game; the head of the third is wrapped in earphones. * A couple of kids, waiting for bedtime, lie on the floor of third point of view research paper, a brightly painted room, busily manipulating the controls of a video game. * Two hundred people sit in an airplane. Critical? Some have brought their own tapes, some doze, most stare up at a small movie screen. What is missing from these pictures, and increasingly from our lives, is the activity through which most of us learned much of what we know of the wider world. What's missing is the analyze essay, force that, according to a growing consensus of critical systems, historians, established our patterns of thought and, in an important sense, made our civilization. What's missing is the venerable, increasingly dated activity that you -- what's the matter? bored with all your CDs and videotapes? -- are engaged in explain essay, right now. Ironically, but not coincidentally, reading has begun fading from critical systems thinking, our culture at the very moment that its importance to that culture is 1984 essays finally being established. Thinking? Its decline, many theorists believe, is explain movie as profound as, say, the fall of communism, and some have taken to prophesying that the systems, downturn in reading could result in the modern world's cultural and political decline. "A mode of thinking is being lost," laments Neil Postman, whose book, "Amusing Ourselves to Death," is a warning about the consequences of a falloff in person point paper, reading. "We are losing a sort of psychic habit, a logic, a sense of complexity, an ability to critical systems spot contradictions and even falsity." Postman, a professor of communication arts at New York University, believes this loss is now being felt in our cultural activities and in our politics, as well as in our children's SAT scores, and that it could get worse. But of course such prophecies are delivered in print, so no one pays much heed. The anecdotal evidence that reading is in decline is copious and compelling. "When I go out socially in Washington," confides Daniel Boorstin, a historian and former librarian of Congress, "I'm careful not to embarrass my dinner companions by asking what they have read lately. Help Dissertation? Instead I say, 'I suppose you don't have much time to read books nowadays.' " That is a courtesy, alas, for which most of us would be grateful. The fact is that few of us, and few of our friends and few of our children, have the time to read as much as we would like. We're too busy working or working out or playing or -- OK, let's admit it -- watching TV. * Our homes barely make room for reading. Those old islands of critical thinking, quiet -- libraries, studies and dens -- long ago were invaded by flat screens and dissertation, Nintendos. Systems? Now they are called "family rooms" or, more accurately, "television rooms." And our architects seem to have given up providing us with bookshelves; instead they busy themselves designing "entertainment centers." So we haven't quite gotten around to Stephen M. Paraan Ng Paggawa? Hawking's "A Brief History of Time," yet. We're saving Amy Tan's latest novel for vacation, maybe. And that pile of critical, unread New Yorkers or Rolling Stones or Los Angeles Times Magazines keeps growing, each unread issue an additional piece of anecdotal evidence. * Those whose livelihoods depend on our reading suggest, optimistically, that the person research, widespread notion that it is in critical systems thinking, decline is an oversimplification. Essays On Totalitarianism? "I believe that people who used to read a lot of books read less now," concedes Alberto Vitale, chairman of Random House, the nation's largest publisher of trade (nontext) books. "But in systems thinking, my opinion, there are many more people reading books." The optimists do have some statistics on their side. An Entire Movie? Books, the oldest form of print, seem to be doing reasonably well. Critical Systems Thinking? Publishers, in fact, are churning out more and explain an entire movie essay, more of them: 133,196 new titles listed in critical systems thinking, "Books in Print" in the past year. That is about 16 times the number of titles printed 40 years ago (one of the reasons "keeping up" may seem so much harder for us than it did for third person point of view paper our parents and critical systems, grandparents). Paraan Ng Paggawa Ng Thesis? And publishers are selling more, too: about 2 billion books in 1990, an critical thinking 11% increase over 1985. Reports of the death of the book seem greatly exaggerated. Ah, but are those books actually being read? Not, in many cases, from cover to cover. A recent Gallup Poll found many more people in 1984 on totalitarianism, 1990 than in 1957 who say they are currently reading a book or novel, but many fewer now than in critical systems, 1975 who say they have completed a book in the past week. In a society where professional success now requires acquaintance with masses of esoteric information, books are often purchased to be consulted, not read. Campaign? About 15% of the new titles in critical thinking, "Books in case study of advertising, Print" are scientific or technical books. Fiction and general-interest nonfiction works would seem to be designed to be read, but lately these books also serve other functions. Their authors often employ them as routes to movie contracts or to tenure or to the intellectual renown that apparently comes with having catalogued definitively, in two or three dense volumes, how George Bernard Shaw, say, spent each of his evenings. Their publishers increasingly see these books not as collections of thinking, sentences and paragraphs that might be clarified and sharpened but as product that must be publicized and marketed so the balance sheets of the large conglomerates they now work for might tilt in paraan ng paggawa ng thesis, the right direction. Given the pace of modern life, the readers of these books, too, may have other purposes in mind -- a quick, conversation-enhancing skim perhaps. Critical Systems Thinking? "People tend to read too rapidly," moans Russell Jacoby, author of explain how to an entire movie essay, "The Last Intellectual." "They tend to read while commuting, watching a game on critical systems, TV or playing Nintendo." Jacoby, who recently taught history at UC Riverside, keeps threatening to open "slow-reading centers." And books increasingly have another function for those who purchase them. They have begun replacing the bottle of Scotch or the third person point of view research paper, tie as gifts -- giving them about the same chance of being opened as those ties had of being worn. The number of bookstores in the United States has been growing in systems thinking, recent decades, at a rate second only to that of paraan, fast-food restaurants, but according to statistics supplied by the American Booksellers Assn., more than one quarter of all their sales are in November and December -- for the holidays. In 1985, Michael Kinsley of the New Republic conducted an experiment. Thinking? Notes offering a $5 reward to anyone who saw them and called the magazine were hidden about three-quarters of the way through 70 copies of the hottest nonfiction books in Washington, D.C., bookstores. Paraan? These were the books that all of systems, Washington seemed to be talking about. "Washington" was apparently basing its comments on ng paggawa, the reviews and maybe a quick skim. No one called. "Fortunately for critical systems booksellers," Kinsley wrote, "their prosperity depends on people buying books, not on people actually reading the bulky things." (Kinsley's advice to authors who would like their words actually to 1984 on totalitarianism be read: "Cut out the middleman, and just write the critical, review.") Those of ng paggawa ng thesis, us with less disposable income, or less inclination to dispose of it in bookstores, can still get our books from systems, libraries. Study Campaign? "You can't say people take books out of the library just to put them on critical systems thinking, the coffee table," says Simon Michael Bessie, chairman of the Center for the Book at the Library of Congress. And library use is up. Public-library circulation in the United States has grown from explain how to movie essay, 4.7 "units" per capita per year in 1980 to 6.1 in 1989, according to a study by the Library Research Center at the University of critical systems, Illinois. However, the "units" we are checking out of the library now include not only lots of school and study of advertising, business readings but also cassettes, CDs and systems thinking, videotapes. Here is perhaps the most frightening of the statistics on five and contrast, books: According to systems the Gallup Poll, the number of Americans who admitted to having read no books during the help dissertation, past year -- and this is critical systems not an easy thing to admit to a pollster -- doubled from dissertation, 1978 to thinking 1990, from 8% to 16%. "I cannot live without books," Thomas Jefferson, whose collection helped start the Library of Congress, told John Adams. More and more of us apparently can. MAGAZINES WOULD APPEAR TO BE BETTER suited to our hectic lives, if for no other reason than that they require much less of five paragraph compare outline, a time commitment than do books. Gathering evidence to confirm or deny this surmise, however, is not easy. There are too many different kinds of critical systems, magazines and too many individual variations in their popularity. We do know that the magazine business has been in case study campaign, dire straits lately, but this has been caused by a falloff in advertising, not necessarily in critical systems, circulation. The best indicator of whether we are spending more or less time with magazines may be "time-use" studies such as those compiled at the University of Maryland. These show that the proportion of the 1984 essays on totalitarianism, population that reads a magazine on critical systems thinking, a typical day dropped from 38% in 1946 to 28% in 1985. Magazine publishers, however, can take some encouragement from the fact that most of that drop had occurred by the 1950s. The statistics on newspaper readership are much less ambiguous and much grimmer. Paraan? According to the University of Maryland time-use studies, the share of the adult population that "read a newspaper yesterday" has declined from 85% in 1946 to systems thinking 73% in how to an entire movie essay, 1965 to critical systems thinking 55% in 1985. The numbers on per capita newspaper circulation and the percentage of American homes that receive a daily newspaper form similar graphs -- graphs you could ski down. "What has changed is the strength of the habit of reading a newspaper," notes Al Gollin of the Newspaper Advertising Bureau. "It used to be one of those things that almost everybody did." No more. Americans on average now read newspapers much less frequently than they did 30 years ago, 20 years ago, even 10 years ago. And young people have been losing the dissertation, newspaper habit even faster than their parents. Systems Thinking? "We are developing a generation that has no interest in case campaign, reading except insofar as it is assigned in school," concludes Daniel Kevles, professor of humanities at Caltech. "They don't read newspapers or magazines. I sense a general lack of interest in public affairs among my students." A recent Times Mirror survey found that only systems thinking 30% of Americans under the age of 35 said they had read a newspaper the previous day, compared to 67% in 1965. The Gulf War provided further evidence of how far the newspaper has fallen. According to a survey by Birch/Scarborough, a grand total of 8.9% of us said we kept up with war news primarily through newspapers. The days when we found most of our news set in type on a page are long gone. Those time-use studies actually discovered a slight increase from 1965 to 1985 in the amount of time people said they spend reading books and third person of view, magazines: from 1.7 to 1.9 hours a week. Critical? But if you throw in newspapers, the help dissertation, total time people spent with reading as their primary activity has dropped more than 30% in those years, from 4.2 hours a week to 2.8. And this drop has occurred at the same time that the amount of education Americans obtain has been rising dramatically. The percentage of Americans who have completed four years of high school has more than tripled since 1940, according to the Bureau of the Census Current Population Survey, and the percentage of Americans completing four years of college has more than quadrupled. If education still stimulated the desire to read, all the statistics on reading would be shooting up. That they are not may say something about the quality of critical systems thinking, our educational system and 1984 essays on totalitarianism, about the interests of the students it now attracts. It certainly says something about reading and critical, its future. If dramatically increased exposure to an educational system based on the printed word cannot get us to read, what will? READING'S TROUBLES ARE NOT DIFFICULT to explain. A hundred years ago, on days when no circus was in town, people looking for ng thesis entertainment had three alternatives: fulfilling biological needs, talking or reading. Those looking for information were restricted to the latter two. Many of our ancestors, to be sure, were unable to read, but those who could relied upon it, as Thomas Jefferson did, with a desperation that is difficult for us to critical imagine. Books, in help, those days, had a unique power to transport. "There is no Frigate like a Book," wrote 19th-Century poet Emily Dickinson, "To take us Lands away." Now, of course, there are many easier ways of getting there. "Our society is particularly ingenious at thinking up alternatives to the book," notes Boorstin. Critical Systems Thinking? Indeed, we have thought up an explain how to analyze an entire essay entire communications revolution, and there have not been many of those in systems, human history. The first such revolution was the development of help dissertation, language hundreds of thousands of years ago; the second, the systems thinking, development of explain how to analyze an entire movie essay, reading and systems thinking, writing in the Middle East about 5,000 years ago; the third, the invention of the printing press 500 years ago. The fourth communications revolution -- ours -- began, perhaps, with the experiments of Samuel Morse, Guglielmo Marconi and Thomas Edison in the 19th Century, and it has been picking up steam ever since. Movies, recordings, radio, telephones, computers, photocopiers and third point of view research, fax machines are all part of it. But, of course, the most powerful product of thinking, this revolution, so far, and the one that has posed the largest threat to reading, has been television. Some print lovers have taken heart from the recent troubles of the TV networks or from the fact that the amount of time the average American family keeps the TV on each day, as measured by Nielsen, finally leveled off in the mid-1980s -- at study, about seven hours a day. But, of course, we have since supplemented broadcast and even cable TV with other equally diverting forms of systems thinking, programming. The first television wave washed over us in the 1950s and outline, '60s. But then, while we were still getting used to having this perky new friend in our bedrooms, a second wave hit. In 1982, only 5.5% of American homes had videocassette recorders. Now 72.5% of them do, and, according to Nielsen, videotapes keep the set on an average of an thinking extra half-hour each day in those homes. Add still more minutes for video games. So much for that leveling-off. Russell Jacoby and his wife have found a sure way to five paragraph protect themselves and their two children from the siren songs of the tube: When their set was stolen a number of years ago, they simply didn't replace it. But most of the rest of us now share our homes with one or more TV sets, which we turn on more than we would like to admit. "Everyone lies about critical systems how much time they and an entire, their families spend watching TV," Jacoby asserts. It is systems a wonder that we manage to find the time to read even as much as we do. "There are only so many hours in the day," says Alberto Vitale of Random House, wistfully. AS A YOUTH, ABRAHAM LINCOLN IS REPORTed to have spent so many hours buried in his books that the neighbors labeled him lazy. When Lincoln arrived in Congress, his fellow congressmen, by one account, dismissed him as a "bookworm." That insult is not heard much nowadays, nor are readers disparaged as lazy. Instead, the more dedicated parents among us feel guilty if we don't manage to read to our children each evening, hoping the kids will pick up the habit we parents are rapidly losing. The First Lady campaigns for dissertation literacy. We end TV shows with pleas to read books. And, according to the Gallup Poll, 61% of us proclaim reading "more rewarding" than watching television; 73% lament that we read too few books; 92% attest that reading is systems thinking a "good use" of our time. Third Point Research Paper? And 45% of the poll's respondents believe, against all the evidence, that they will be "reading more in critical, the months and years ahead." Reading certainly is well loved now that it is in decline. Yet it is no longer something that we ache to do. Explain Analyze Movie Essay? How many kids today surreptitiously finish books by flashlight under the covers? Instead, reading, like eating broccoli, has now become something that we feel we should do (always a bad sign). Some teen-agers and -- says Michael Silverblatt, host of KCRW's "Bookworm" show -- some Southern Californians actually find it hip to pretend to read less than they really do, but the vast majority of us sincerely, vigorously and guiltily genuflect in front of the printed page. Never in critical thinking, human history has reading been more respected. This is not surprising. One of the characteristics of any technological revolution is nostalgia for the old order. Socrates, who lived a few hundred years after the invention of the Greek alphabet, when writing was transforming Greek culture, strenuously argued the superiority of the oral culture it was replacing. 1984? According to Plato's (written) account, Socrates predicted that the use of writing would weaken memories and deprive "learners" of the chance to question what they were being taught. Such nostalgia for critical the methods of oral tradition -- memorization, rhetoric, recital -- kept them alive in the schools well into 1984 essays this century. Critical Systems Thinking? Now similar calls are going out to defend the schools against case of advertising, the incursions of the new information technologies so that our educational institutions can serve as repositories of another fading tradition -- reading. WE DID NOT REALIZE THAT WE WERE LIVING in the age of print until it began to end. Only then did we gain the perspective to systems see the effects of reading on our thoughts. Those effects are profound, as anthropological studies of societies without reading have begun to show. For example, the following statements were presented to members of a mostly preliterate tribe in a remote area of the Soviet Union: "In the essay outline, far north, where there is snow, all bears are white. Critical? Novaya Zembla is in the far north, and there is always snow there." Then these people were asked what color the bears are in and contrast essay, Novaya Zembla. Thinking? A typical response, as reported by Father Walter Ong in his book "Orality and Literacy": "I don't know. Five Paragraph Compare Essay Outline? I've seen a black bear. Critical Systems? I've never seen any others. Each locality has its own animals." These people could not solve this simplest of logical problems. It is not that such preliterate people are less intelligent than we are. They simply think differently -- "situationally." When words are written down, not just enunciated, they are freed from the subjective situations and experiences ("I've seen a black bear") in which they were imbedded. Dissertation? Written words can be played with, analyzed, rearranged and critical thinking, organized into categories (black bears, white bears, places where there is always snow). The correspondences, connections or contradictions among various statements can be carefully examined. As investigators such as Ong and third person point research, anthropologist Jack Goody have explained, our system of thinking, logic -- our ability to third person of view research paper find principles that apply independently of situations -- is a product of literacy. This logic, which goes back to the Egyptians, Hebrews and Greeks, led to mathematics and philosophy and history. Among its accomplishments is our culture. And when written words are set in print, they gain additional powers. Our sentences grow even less connected to our persons as they are spelled out in the interchangeable letters of movable type. Our thoughts grow more abstract, more removed from the situations in which we happen to critical find ourselves. Superstitions, biases and ng thesis, legendary characters like dragons and critical systems thinking, kings have difficulty fitting into these straight, precise lines of type. Charts, maps and columns of figures can be duplicated exactly for the first time. According to seminal media theorist Marshall McLuhan and historian Elizabeth Eisenstein, the scientific revolution and the Enlightenment were both products of the printing press. "Reading is 1984 on totalitarianism central to our culture," states Ong, a professor of humanities at Saint Louis University. "It is connected to virtually all the forces that shaped our culture." Among those who ponder such matters, there is no longer much controversy about that. The question, as we leave the age of print for the uncharted waters of critical thinking, this new electronic age, is whether we risk losing much of what reading enabled us to gain. Neil Postman, for one, fears that the answer is yes. Outline? "New communications technologies giveth," he proclaims, "and they taketh away." On the critical systems thinking, debit side Postman would place recent developments in on totalitarianism, art, education, religion, journalism and politics -- all of which, in critical systems, his view, are losing the seriousness and intellectual content print gave them as they are transformed into "show business" to meet the needs of electronic media. Reading demands that we sit still, be quiet and concentrate hard enough to decode a system of symbols and case study, follow extended arguments. This is an injunction that increasingly is systems falling on of advertising campaign, earphone-plugged ears. Television and its electronic brethren are much less strict. We can be cleaning, daydreaming or half-dozing; they don't seem to care. All television demands is our gaze. Critical Systems? Dazzling collages of case study, imagery and rhythm are assembled just to get us to open our eyelids a bit wider. Kings used to turn thumbs down on spectacles that bored them; we simply press thumb to remote control, zapping any scene, exposition or argument that takes much more than a fraction of a minute to unfold. Critical Systems Thinking? "Thinking," Postman writes, "does not play well on TV." Our entertainers, pundits, professors, ministers and leaders, therefore, are judged not so much on their ability to reason but on their ability to project a diverting image. Amuse us or we'll change the channel. Whether or not the points being made are valid is of less importance. Somehow this does not seem what Jefferson and the other founders had in mind when they entrusted us with governing a country. Pessimists like Postman do not have much difficulty convincing us that life on a late-20th-Century couch can be frivolous and vegetable-like. Explain How To An Entire? We already feel guilty that we are watching "the boob tube" rather than reading. However, making the critical thinking, case that life in help, that supposed golden age of reading was really much more noble than life today is more difficult. As his example of political discourse before TV, Postman chooses those astoundingly literate, three-hour-long debates between Lincoln and Stephen A. Douglas in 1858. But 18th- and 19th-Century American politics was not all conducted on this level. The slogans with which William Henry Harrison made his case for the presidency in 1840, for example -- "Log Cabin and Hard Cider," "Tippecanoe and Tyler, too" -- are as vacuous as anything concocted by Ronald Reagan's media wizards. The arguments against TV are based on a certain amount of such false nostalgia. People then did not read quite so much, and their reading material was not quite so exemplary as those pining for a lost golden age suggest. "We have no figures on how much or how well books were read in the past," Ong notes. "All we have are the comments of bibliophiles. There is no evidence, for example, that all the copies of the critical systems, books printed in the 16th and 17th centuries were read. There is plenty of evidence that a lot of them were not read." Nevertheless, the doomsayers do have some harder evidence on their side. There is, to begin with, the decline in study campaign, writing skills, much fretted over by educators in critical thinking, recent years. Written language demands stricter rules of syntax and grammar than spoken language, and these are the rules, first codified in printed dictionaries and five, grammar books, that we learn (or now fail to critical systems thinking learn) in school. The sentences of the electronic age, because they are supplemented by images, can get away with playing by looser rules. Try, sometime, to diagram the sentences of a TV-football "analyst." It is not surprising, therefore, that students who watch and listen more and read less are losing command of their writing. As anyone who has seen that rare thing, a letter written by a student, knows, young people today often have considerable difficulty filling a page with clear, exact sentences. Their performance on recent SATs raises the question of paraan ng paggawa, whether they also have difficulty producing clear, exact thought. The average score on systems, the SAT verbal test, taken by a large number of college-bound high school students, was 466 (on a scale of 200 to 800) in paraan ng paggawa ng thesis, 1968. Then, as the first TV generation began taking the test, scores began tumbling. The average score leveled off from critical systems thinking, 1978 to 1984 essays 1987, but now, with the arrival of the MTV kids, it has begun skidding again -- down to 422 this year. The College Boards do not test a representative sample of American teen-agers. Critical? More -- and perhaps less qualified -- students are now going to college and therefore taking the test, which may be driving scores down. Still, the correspondence between verbal scores and the two waves of TV's assault upon reading is hard to overlook. "The decline in SAT scores has a lot to do with not reading," asserts College Board President Donald M. Stewart. Why? "The ability to read is linked to the ability to process, analyze and 1984 on totalitarianism, comprehend information," Stewart explains. "I guess that's called thinking." Michael Silverblatt of "Bookworm" uses an analogy that young people might find more persuasive: "Just as people who don't work out critical thinking, can't do certain things with their bodies, people who don't read can't do certain things with their minds." Boorstin puts the five paragraph compare essay, problem even more bluntly. He calls people who do not read "self-handicapped" and says, "A person who doesn't read books is only half-alive." And if the members of a society stop reading? "Then you have a half-alive society." FROM THE PERSPECTIVE OF enthusiasts of the new culture of videos, videotapes, video games and critical, CDs, all this must sound like the outline, whining of a ragged, nearly defeated old order. Not everyone is critical systems convinced that all that is deep and serious in case study campaign, our society is in fact under siege. "I know a number of extremely intelligent adults who don't read more than a book or two a year but still remain healthy, active contributors to systems society," says Wendy Lesser, editor of Three Penny Review, a respected Berkeley literary publication. "I think if you can get people to learn to discriminate between good and bad TV programs, you've done more for them than you would by simply forcing them to read a book, however trashy." And even those who believe that the decline in reading does herald some profound cultural changes are not convinced those changes will necessarily be for the worse. Perhaps, they might argue, the logic inculcated by writing and compare and contrast essay, print is not the only way of processing information about the world. Perhaps an immersion in critical systems thinking, electronic forms of communication might lead to different but equally valid ways of being smart -- forms of intelligence that go unrecognized by SAT tests. Five Compare Outline? "I'm listening to that argument with more and thinking, more sympathy," concedes Stewart of the College Boards. It is possible, moreover, that electronic forms of communication have more potential than is currently being expressed in either the dissertation, vapid fantasies of Madonna videos or the static talk shows and costume dramas of public television. These media might be capable, given time, of creating a culture as profound and deep as that of critical systems, reading. These technologies might, in other words, have more to "giveth" than we can yet imagine. It took 2,000 years of writing before an third of view paper alphabet was developed. It took a century and a half of printing before someone thought to critical thinking print a novel or a newspaper. New communications technologies do not arrive upon third research paper the scene fully grown; they need time to systems develop the methods and forms that best exploit their potential. Our communications revolution, from this perspective, is still quite young. TV has been around for only half a century. Most of its programming is still recycled theater -- mini-dramas and comedies; its more stylistically adventurous forms -- commercials and music videos -- are little more than demonstrations of the visual capabilities of the an entire movie essay, medium. Television's technicians have mastered the art of mating laugh track to quip; they can make everything from cats to toothbrushes dance. But TV still may not have stumbled upon the grammar and syntax of video -- the patterns and relations of images and critical thinking, sounds that will enable us to third point of view research communicate complex ideas with clarity and exactness. Television may not yet have discovered the forms that will do for that medium what the novel and the newspaper did for critical systems print. TV today grapples with difficult subjects only by getting slow and boring. It is possible to imagine a television program that would be difficult for the opposite case reason: because it is too fast, too busy, too full of information. Perhaps such super-dense television would be able to plumb depths quickly enough to fit the critical systems thinking, video generation's short attention spans, or perhaps this TV would be stimulating enough to stretch those attention spans. Does television really have such potential? Does a whole culture's worth of new perspectives, new ideas, new creations in fact lie slumbering in our television sets, just waiting for programming capable of awakening them? "Possibly," Daniel Kevles comments with some skepticism, "but I think any more intelligent programming will still have to coexist with MTV and action dramas." Still, if the case study campaign, electronic media can, even intermittently, transform themselves into systems thinking vehicles for ideas with the 1984, reach and capacity of print, it would be good news for our society. Systems? The Postmans of the world could rest easy: We would not go giggling off into of view research decadence and dictatorship. But such a development would represent still more bad news for reading. IS READING LIKELY TO survive the electronic age? Of course, Daniel Boorstin says. He scoffs at the notion that books, magazines or newspapers are going to disappear any time soon. Critical Systems Thinking? Boorstin calls this the "displacement fallacy" and points out case of advertising, that radio survived and prospered after the introduction of TV, despite many gloomy predictions to the contrary. "New technologies tend to discover unique opportunities for the old," Boorstin maintains. Not every outdated communication technology succeeds in finding such an systems opportunity. Help? Consider smoke signals, for example, or town criers or the telegram. Critical? Nevertheless, Boorstin has a point. Books already have found some new functions for themselves -- as reference manuals, for example. Magazines have survived in part by discovering audiences too small and specialized for TV to reach. And newspapers? Well, maybe USA Today, with its brief, snappy stories, is responding to a new opportunity presented by the TV generation's shortened attention spans. Or maybe newspapers are still searching for analyze movie essay their niche in the electronic age. Print and electronics also collaborate more than is generally recognized. According to the preliminary results of a study by Robert Kubey, a communications professor at Rutgers University, words appear in critical thinking, about 20% of the images in a sample of 30 channels available on cable. And the person point paper, alphabet has recently found a new life for itself on thinking, the keyboards of computers. "I'm using about 20 times as much paper since I started using a computer," Ong adds. "A new technology does not wipe out what went before; it transforms and enhances it. Case Study Campaign? When people started writing, they didn't quit talking." Indeed, they probably spoke more logically. However, the introduction of writing undoubtedly did cause people to spend less time talking -- because of the old not-enough-hours-in-the-day problem. Critical Systems Thinking? And it probably did cause them to rely less on speech for communicating important information. So, whatever new forms print may assume in paraan ng paggawa, response to electronics, it is unlikely that print will regain its position as our major source of information or entertainment. Reading still plays and, for the foreseeable future, will continue to systems play, a crucial role in our society. Nevertheless, there is no getting around the fact that reading's role has diminished and likely will continue to shrink. This does not mean we should begin turning first-grade classes over to video lessons. Until the new technologies grow up a bit, it would not hurt any of us to read more to our children or take a book with us the next time we must sit and wait. And perhaps it was not a bad idea that you chose, instead of watching the Rams game or renting "Dances With Wolves," to make it through this article.