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Showing papers by "Massachusetts Institute of Technology published in 2006"


Journal ArticleDOI
TL;DR: An automated labeling system for subdividing the human cerebral cortex into standard gyral-based neuroanatomical regions is both anatomically valid and reliable and may be useful for both morphometric and functional studies of the cerebral cortex.

9,940 citations


Journal ArticleDOI
TL;DR: Solar energy is by far the largest exploitable resource, providing more energy in 1 hour to the earth than all of the energy consumed by humans in an entire year, and if solar energy is to be a major primary energy source, it must be stored and dispatched on demand to the end user.
Abstract: Global energy consumption is projected to increase, even in the face of substantial declines in energy intensity, at least 2-fold by midcentury relative to the present because of population and economic growth. This demand could be met, in principle, from fossil energy resources, particularly coal. However, the cumulative nature of CO2 emissions in the atmosphere demands that holding atmospheric CO2 levels to even twice their preanthropogenic values by midcentury will require invention, development, and deployment of schemes for carbon-neutral energy production on a scale commensurate with, or larger than, the entire present-day energy supply from all sources combined. Among renewable energy resources, solar energy is by far the largest exploitable resource, providing more energy in 1 hour to the earth than all of the energy consumed by humans in an entire year. In view of the intermittency of insolation, if solar energy is to be a major primary energy source, it must be stored and dispatched on demand to the end user. An especially attractive approach is to store solar-converted energy in the form of chemical bonds, i.e., in a photosynthetic process at a year-round average efficiency significantly higher than current plants or algae, to reduce land-area requirements. Scientific challenges involved with this process include schemes to capture and convert solar energy and then store the energy in the form of chemical bonds, producing oxygen from water and a reduced fuel such as hydrogen, methane, methanol, or other hydrocarbon species.

7,076 citations


PatentDOI
27 Jan 2006-Science
TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
Abstract: In certain aspects, the invention relates to methods for identifying compounds which modulate Akt activity mediated by the rictor-mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activity.

5,430 citations


Journal ArticleDOI
TL;DR: In this article, the authors considered seven slip mechanisms that can produce a relative velocity between the nanoparticles and the base fluid and concluded that only Brownian diffusion and thermophoresis are important slip mechanisms in nanofluids.
Abstract: Nanofluids are engineered colloids made of a base fluid and nanoparticles (1-100 nm) Nanofluids have higher thermal conductivity' and single-phase heat transfer coefficients than their base fluids In particular the heat transfer coefficient increases appear to go beyond the mere thermal-conductivity effect, and cannot be predicted by traditional pure-fluid correlations such as Dittus-Boelter's In the nanofluid literature this behavior is generally attributed to thermal dispersion and intensified turbulence, brought about by nanoparticle motion To test the validity of this assumption, we have considered seven slip mechanisms that can produce a relative velocity between the nanoparticles and the base fluid These are inertia, Brownian diffusion, thermophoresis, diffusioplwresis, Magnus effect, fluid drainage, and gravity We concluded that, of these seven, only Brownian diffusion and thermophoresis are important slip mechanisms in nanofluids Based on this finding, we developed a two-component four-equation nonhomogeneous equilibrium model for mass, momentum, and heat transport in nanofluids A nondimensional analysis of the equations suggests that energy transfer by nanoparticle dispersion is negligible, and thus cannot explain the abnormal heat transfer coefficient increases Furthermore, a comparison of the nanoparticle and turbulent eddy time and length scales clearly indicates that the nanoparticles move homogeneously with the fluid in the presence of turbulent eddies so an effect on turbulence intensity is also doubtful Thus, we propose an alternative explanation for the abnormal heat transfer coefficient increases: the nanofluid properties may vary significantly within the boundary layer because of the effect of the temperature gradient and thermophoresis For a heated fluid, these effects can result in a significant decrease of viscosity within the boundary layer, thus leading to heat transfer enhancement A correlation structure that captures these effects is proposed

5,329 citations


Journal ArticleDOI
21 Apr 2006-Cell
TL;DR: It is proposed that bivalent domains silence developmental genes in ES cells while keeping them poised for activation, highlighting the importance of DNA sequence in defining the initial epigenetic landscape and suggesting a novel chromatin-based mechanism for maintaining pluripotency.

5,131 citations


Journal ArticleDOI
TL;DR: The first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler is described, which can address a variety of biological questions quantitatively.
Abstract: Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens and functional genomics (for example, using RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler. CellProfiler can address a variety of biological questions quantitatively, including standard assays (for example, cell count, size, per-cell protein levels) and complex morphological assays (for example, cell/organelle shape or subcellular patterns of DNA or protein staining).

4,578 citations


Journal ArticleDOI
29 Sep 2006-Science
TL;DR: The first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules is created, and it is demonstrated that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs.
Abstract: To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.

4,429 citations


Journal ArticleDOI
TL;DR: Fibroblasts are a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
Abstract: Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. Their production of growth factors, chemokines and extracellular matrix facilitates the angiogenic recruitment of endothelial cells and pericytes. Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.

4,232 citations


Journal ArticleDOI
Gerald A. Tuskan1, Gerald A. Tuskan2, Stephen P. DiFazio3, Stephen P. DiFazio1, Stefan Jansson4, Joerg Bohlmann5, Igor V. Grigoriev6, Uffe Hellsten6, Nicholas H. Putnam6, Steven G. Ralph5, Stephane Rombauts7, Asaf Salamov6, Jacquie Schein, Lieven Sterck7, Andrea Aerts6, Rishikeshi Bhalerao4, Rishikesh P. Bhalerao8, Damien Blaudez9, Wout Boerjan7, Annick Brun9, Amy M. Brunner10, Victor Busov11, Malcolm M. Campbell12, John E. Carlson13, Michel Chalot9, Jarrod Chapman6, G.-L. Chen1, Dawn Cooper5, Pedro M. Coutinho14, Jérémy Couturier9, Sarah F. Covert15, Quentin C. B. Cronk5, R. Cunningham1, John M. Davis16, Sven Degroeve7, Annabelle Déjardin9, Claude W. dePamphilis13, John C. Detter6, Bill Dirks17, Inna Dubchak6, Inna Dubchak18, Sébastien Duplessis9, Jürgen Ehlting5, Brian E. Ellis5, Karla C Gendler19, David Goodstein6, Michael Gribskov20, Jane Grimwood21, Andrew Groover22, Lee E. Gunter1, Björn Hamberger5, Berthold Heinze, Yrjö Helariutta8, Yrjö Helariutta23, Yrjö Helariutta24, Bernard Henrissat14, D. Holligan15, Robert A. Holt, Wenyu Huang6, N. Islam-Faridi22, Steven J.M. Jones, M. Jones-Rhoades25, Richard A. Jorgensen19, Chandrashekhar P. Joshi11, Jaakko Kangasjärvi23, Jan Karlsson4, Colin T. Kelleher5, Robert Kirkpatrick, Matias Kirst16, Annegret Kohler9, Udaya C. Kalluri1, Frank W. Larimer1, Jim Leebens-Mack15, Jean-Charles Leplé9, Philip F. LoCascio1, Y. Lou6, Susan Lucas6, Francis Martin9, Barbara Montanini9, Carolyn A. Napoli19, David R. Nelson26, C D Nelson22, Kaisa Nieminen23, Ove Nilsson8, V. Pereda9, Gary F. Peter16, Ryan N. Philippe5, Gilles Pilate9, Alexander Poliakov18, J. Razumovskaya1, Paul G. Richardson6, Cécile Rinaldi9, Kermit Ritland5, Pierre Rouzé7, D. Ryaboy18, Jeremy Schmutz21, J. Schrader27, Bo Segerman4, H. Shin, Asim Siddiqui, Fredrik Sterky, Astrid Terry6, Chung-Jui Tsai11, Edward C. Uberbacher1, Per Unneberg, Jorma Vahala23, Kerr Wall13, Susan R. Wessler15, Guojun Yang15, T. Yin1, Carl J. Douglas5, Marco A. Marra, Göran Sandberg8, Y. Van de Peer7, Daniel S. Rokhsar6, Daniel S. Rokhsar17 
15 Sep 2006-Science
TL;DR: The draft genome of the black cottonwood tree, Populus trichocarpa, has been reported in this paper, with more than 45,000 putative protein-coding genes identified.
Abstract: We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

4,025 citations


Journal ArticleDOI
TL;DR: A minimum-redundancy code is one constructed in such a way that the average number of coding digits per message is minimized.
Abstract: An optimum method of coding an ensemble of messages consisting of a finite number of members is developed. A minimum-redundancy code is one constructed in such a way that the average number of coding digits per message is minimized.

3,528 citations


Journal ArticleDOI
TL;DR: This work highlights recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for biomedical and biological applications and shows how such systems' intelligent behavior can be used in sensors, microarrays, and imaging.
Abstract: Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

Journal ArticleDOI
TL;DR: In this paper, a review of the physics of high-temperature superconductors from the point of view of the doping of a Mott insulator is presented, with the goal of putting the resonating valence bond idea on a more formal footing.
Abstract: This article reviews the physics of high-temperature superconductors from the point of view of the doping of a Mott insulator. The basic electronic structure of cuprates is reviewed, emphasizing the physics of strong correlation and establishing the model of a doped Mott insulator as a starting point. A variety of experiments are discussed, focusing on the region of the phase diagram close to the Mott insulator (the underdoped region) where the behavior is most anomalous. The normal state in this region exhibits pseudogap phenomenon. In contrast, the quasiparticles in the superconducting state are well defined and behave according to theory. This review introduces Anderson's idea of the resonating valence bond and argues that it gives a qualitative account of the data. The importance of phase fluctuations is discussed, leading to a theory of the transition temperature, which is driven by phase fluctuations and the thermal excitation of quasiparticles. However, an argument is made that phase fluctuations can only explain pseudogap phenomenology over a limited temperature range, and some additional physics is needed to explain the onset of singlet formation at very high temperatures. A description of the numerical method of the projected wave function is presented, which turns out to be a very useful technique for implementing the strong correlation constraint and leads to a number of predictions which are in agreement with experiments. The remainder of the paper deals with an analytic treatment of the $t\text{\ensuremath{-}}J$ model, with the goal of putting the resonating valence bond idea on a more formal footing. The slave boson is introduced to enforce the constraint againt double occupation and it is shown that the implementation of this local constraint leads naturally to gauge theories. This review follows the historical order by first examining the U(1) formulation of the gauge theory. Some inadequacies of this formulation for underdoping are discussed, leading to the SU(2) formulation. Here follows a rather thorough discussion of the role of gauge theory in describing the spin-liquid phase of the undoped Mott insulator. The difference between the high-energy gauge group in the formulation of the problem versus the low-energy gauge group, which is an emergent phenomenon, is emphasized. Several possible routes to deconfinement based on different emergent gauge groups are discussed, which leads to the physics of fractionalization and spin-charge separation. Next the extension of the SU(2) formulation to nonzero doping is described with a focus on a part of the mean-field phase diagram called the staggered flux liquid phase. It will be shown that inclusion of the gauge fluctuation provides a reasonable description of the pseudogap phase. It is emphasized that $d$-wave superconductivity can be considered as evolving from a stable U(1) spin liquid. These ideas are applied to the high-${T}_{c}$ cuprates, and their implications for the vortex structure and the phase diagram are discussed. A possible test of the topological structure of the pseudogap phase is described.

Journal ArticleDOI
TL;DR: A novel scheme that first selects the best relay from a set of M available relays and then uses this "best" relay for cooperation between the source and the destination and achieves the same diversity-multiplexing tradeoff as achieved by more complex protocols.
Abstract: Cooperative diversity has been recently proposed as a way to form virtual antenna arrays that provide dramatic gains in slow fading wireless environments. However, most of the proposed solutions require distributed space-time coding algorithms, the careful design of which is left for future investigation if there is more than one cooperative relay. We propose a novel scheme that alleviates these problems and provides diversity gains on the order of the number of relays in the network. Our scheme first selects the best relay from a set of M available relays and then uses this "best" relay for cooperation between the source and the destination. We develop and analyze a distributed method to select the best relay that requires no topology information and is based on local measurements of the instantaneous channel conditions. This method also requires no explicit communication among the relays. The success (or failure) to select the best available path depends on the statistics of the wireless channel, and a methodology to evaluate performance for any kind of wireless channel statistics, is provided. Information theoretic analysis of outage probability shows that our scheme achieves the same diversity-multiplexing tradeoff as achieved by more complex protocols, where coordination and distributed space-time coding for M relay nodes is required, such as those proposed by Laneman and Wornell (2003). The simplicity of the technique allows for immediate implementation in existing radio hardware and its adoption could provide for improved flexibility, reliability, and efficiency in future 4G wireless systems.

Journal ArticleDOI
27 Mar 2006
TL;DR: The ability to use standard Bluetooth-enabled mobile telephones to measure information access and use in different contexts, recognize social patterns in daily user activity, infer relationships, identify socially significant locations, and model organizational rhythms is demonstrated.
Abstract: We introduce a system for sensing complex social systems with data collected from 100 mobile phones over the course of 9 months. We demonstrate the ability to use standard Bluetooth-enabled mobile telephones to measure information access and use in different contexts, recognize social patterns in daily user activity, infer relationships, identify socially significant locations, and model organizational rhythms.

Journal ArticleDOI
TL;DR: This work presents a distributed random linear network coding approach for transmission and compression of information in general multisource multicast networks, and shows that this approach can take advantage of redundant network capacity for improved success probability and robustness.
Abstract: We present a distributed random linear network coding approach for transmission and compression of information in general multisource multicast networks. Network nodes independently and randomly select linear mappings from inputs onto output links over some field. We show that this achieves capacity with probability exponentially approaching 1 with the code length. We also demonstrate that random linear coding performs compression when necessary in a network, generalizing error exponents for linear Slepian-Wolf coding in a natural way. Benefits of this approach are decentralized operation and robustness to network changes or link failures. We show that this approach can take advantage of redundant network capacity for improved success probability and robustness. We illustrate some potential advantages of random linear network coding over routing in two examples of practical scenarios: distributed network operation and networks with dynamically varying connections. Our derivation of these results also yields a new bound on required field size for centralized network coding on general multicast networks

Journal ArticleDOI
TL;DR: This paper found evidence consistent with managers manipulating real activities to avoid reporting annual losses, such as price discounts to temporarily increase sales, overproduction to report lower cost of goods sold, and reduction of discretionary expenditures to improve reported margins.

Journal ArticleDOI
TL;DR: This work analyzes the averaging problem under the gossip constraint for an arbitrary network graph, and finds that the averaging time of a gossip algorithm depends on the second largest eigenvalue of a doubly stochastic matrix characterizing the algorithm.
Abstract: Motivated by applications to sensor, peer-to-peer, and ad hoc networks, we study distributed algorithms, also known as gossip algorithms, for exchanging information and for computing in an arbitrarily connected network of nodes. The topology of such networks changes continuously as new nodes join and old nodes leave the network. Algorithms for such networks need to be robust against changes in topology. Additionally, nodes in sensor networks operate under limited computational, communication, and energy resources. These constraints have motivated the design of "gossip" algorithms: schemes which distribute the computational burden and in which a node communicates with a randomly chosen neighbor. We analyze the averaging problem under the gossip constraint for an arbitrary network graph, and find that the averaging time of a gossip algorithm depends on the second largest eigenvalue of a doubly stochastic matrix characterizing the algorithm. Designing the fastest gossip algorithm corresponds to minimizing this eigenvalue, which is a semidefinite program (SDP). In general, SDPs cannot be solved in a distributed fashion; however, exploiting problem structure, we propose a distributed subgradient method that solves the optimization problem over the network. The relation of averaging time to the second largest eigenvalue naturally relates it to the mixing time of a random walk with transition probabilities derived from the gossip algorithm. We use this connection to study the performance and scaling of gossip algorithms on two popular networks: Wireless Sensor Networks, which are modeled as Geometric Random Graphs, and the Internet graph under the so-called Preferential Connectivity (PC) model.

Journal ArticleDOI
TL;DR: It is shown that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolongedRapamycin treatment reduces the levels of m TORC2 below those needed to maintain Akt/PKB signaling.

Journal ArticleDOI
TL;DR: The importance of miRNA-directed gene regulation during plant development is now particularly clear and typically at the cores of gene regulatory networks, targeting genes that are themselves regulators, such as those encoding transcription factors and F-box proteins.
Abstract: MicroRNAs (miRNAs) are small, endogenous RNAs that regulate gene expression in plants and animals. In plants, these approximately 21-nucleotide RNAs are processed from stem-loop regions of long primary transcripts by a Dicer-like enzyme and are loaded into silencing complexes, where they generally direct cleavage of complementary mRNAs. Although plant miRNAs have some conserved functions extending beyond development, the importance of miRNA-directed gene regulation during plant development is now particularly clear. Identified in plants less than four years ago, miRNAs are already known to play numerous crucial roles at each major stage of development-typically at the cores of gene regulatory networks, targeting genes that are themselves regulators, such as those encoding transcription factors and F-box proteins.

Journal ArticleDOI
18 May 2006-Nature
TL;DR: It is shown that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation, and dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development.
Abstract: The mechanisms by which embryonic stem (ES) cells self-renew while maintaining the ability to differentiate into virtually all adult cell types are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that help to maintain cellular identity during metazoan development by epigenetic modification of chromatin structure. PcG proteins have essential roles in early embryonic development and have been implicated in ES cell pluripotency, but few of their target genes are known in mammals. Here we show that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation. Using genome-wide location analysis in murine ES cells, we found that the Polycomb repressive complexes PRC1 and PRC2 co-occupied 512 genes, many of which encode transcription factors with important roles in development. All of the co-occupied genes contained modified nucleosomes (trimethylated Lys 27 on histone H3). Consistent with a causal role in gene silencing in ES cells, PcG target genes were de-repressed in cells deficient for the PRC2 component Eed, and were preferentially activated on induction of differentiation. Our results indicate that dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development.

Journal ArticleDOI
28 Sep 2006-Nature
TL;DR: A comprehensive set of experiments giving compelling evidence for BEC of polaritons of bosonic quasi-particles are detailed, which indicate the spontaneous onset of a macroscopic quantum phase.
Abstract: Phase transitions to quantum condensed phases—such as Bose–Einstein condensation (BEC), superfluidity, and superconductivity—have long fascinated scientists, as they bring pure quantum effects to a macroscopic scale. BEC has, for example, famously been demonstrated in dilute atom gas of rubidium atoms at temperatures below 200 nanokelvin. Much effort has been devoted to finding a solid-state system in which BEC can take place. Promising candidate systems are semiconductor microcavities, in which photons are confined and strongly coupled to electronic excitations, leading to the creation of exciton polaritons. These bosonic quasi-particles are 109 times lighter than rubidium atoms, thus theoretically permitting BEC to occur at standard cryogenic temperatures. Here we detail a comprehensive set of experiments giving compelling evidence for BEC of polaritons. Above a critical density, we observe massive occupation of the ground state developing from a polariton gas at thermal equilibrium at 19 K, an increase of temporal coherence, and the build-up of long-range spatial coherence and linear polarization, all of which indicate the spontaneous onset of a macroscopic quantum phase. Bose–Einstein condensation (BEC), a form of matter first postulated in 1924, has famously been demonstrated in dilute atomic gases at ultra-low temperatures. Much effort is now being devoted to exploring solid-state systems in which BEC can occur. In theory semiconductor microcavities, where photons are confined and coupled to electronic excitations leading to the creation of polaritons, could allow BEC at standard cryogenic temperatures. Kasprzak et al. now present experiments in which polaritons are excited in such a microcavity. Above a critical polariton density, spontaneous onset of a macroscopic quantum phase occurs, indicating a solid-state BEC. BEC should also be possible at higher temperatures if coupling of light with solid excitations is sufficiently strong. Demokritov et al. have achieved just that, BEC at room temperature in a gas of magnons, which are a type of magnetic excitation. This paper presents a comprehensive set of experiments in which polaritons are excited in a semiconductor microcavity. Above a critical density of polaritons, massive occupation of the ground state at 19 K is observed and various pieces of experimental evidence point to a spontaneous onset of a macroscopic quantum phase.


Journal ArticleDOI
17 Feb 2006-Science
TL;DR: By modifying its crystal structure, lithium nickel manganese oxide is obtained unexpectedly high rate-capability, considerably better than lithium cobalt oxide (LiCoO2), the current battery electrode material of choice.
Abstract: New applications such as hybrid electric vehicles and power backup require rechargeable batteries that combine high energy density with high charge and discharge rate capability. Using ab initio computational modeling, we identified useful strategies to design higher rate battery electrodes and tested them on lithium nickel manganese oxide [Li(Ni 0.5 Mn 0.5 )O 2 ], a safe, inexpensive material that has been thought to have poor intrinsic rate capability. By modifying its crystal structure, we obtained unexpectedly high rate-capability, considerably better than lithium cobalt oxide (LiCoO 2 ), the current battery electrode material of choice.

Posted Content
TL;DR: In this article, a positive theory of accounting is proposed to explore the factors influencing management's attitudes on accounting standards that are likely to affect a firm's cashflows and in turn are affected by accounting standards.
Abstract: This article provides the beginning of a positive theory of accounting by exploring those factors influencing management's attitudes on accounting standards that are likely to affect a firm's cashflows and in turn are affected by accounting standards. These factors are taxes, regulation, management compensation plans, bookkeeping costs and political costs, and they are combined into a model that predicts that large firms that experience reduced earnings due to changed accounting standards favor the change. All other firms oppose the change if the additional bookkeeping costs justify the cost of lobbying. This prediction was tested using the corporate submissions to the FASB's Discussion Memorandum on General Price Level Adjustments. The empirical results are consistent with the theory.

Journal ArticleDOI
TL;DR: Some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment are discussed, and the methods for implementing them are discussed.
Abstract: The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.

Journal ArticleDOI
TL;DR: In this paper, the authors review the properties and behavior of 20 X-ray binaries that contain a dynamically confirmed black hole, 17 of which are transient systems, during the past decade, many of these transien...
Abstract: We review the properties and behavior of 20 X-ray binaries that contain a dynamically-confirmed black hole, 17 of which are transient systems. During the past decade, many of these transien...

Journal ArticleDOI
TL;DR: Photodynamic therapy uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system.
Abstract: Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.

Journal ArticleDOI
11 May 2006-Nature
TL;DR: It is proposed that Orai1 is an essential component or regulator of the CRAC channel complex, which contains four putative transmembrane segments and is based on a novel protein that was identified in SCID patients.
Abstract: Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels, promoting the immune response to pathogens by activating the transcription factor NFAT. We have previously shown that cells from patients with one form of hereditary severe combined immune deficiency (SCID) syndrome are defective in store-operated Ca2+ entry and CRAC channel function. Here we identify the genetic defect in these patients, using a combination of two unbiased genome-wide approaches: a modified linkage analysis with single-nucleotide polymorphism arrays, and a Drosophila RNA interference screen designed to identify regulators of store-operated Ca2+ entry and NFAT nuclear import. Both approaches converged on a novel protein that we call Orai1, which contains four putative transmembrane segments. The SCID patients are homozygous for a single missense mutation in ORAI1, and expression of wild-type Orai1 in SCID T cells restores store-operated Ca2+ influx and the CRAC current (I(CRAC)). We propose that Orai1 is an essential component or regulator of the CRAC channel complex.

Journal ArticleDOI
TL;DR: This paper developed a theory of prosocial behavior that combines heterogeneity in individual altruism and greed with concerns for social reputation or self-respect, and analyzed the socially optimal level of incentives and how monopolistic or competitive sponsors depart from it.
Abstract: We develop a theory of prosocial behavior that combines heterogeneity in individual altruism and greed with concerns for social reputation or self-respect. Rewards or punishments (whether material or imagerelated) create doubt about the true motive for which good deeds are performed and this “overjustification effect” can induce a partial or even net crowding out of prosocial behavior by extrinsic incentives. We also identify the settings that are conducive to multiple social norms and more generally those that make individual actions complements or substitutes, which we show depends on whether stigma or honor is (endogenously) the dominant reputational concern. Finally, we analyze the socially optimal level of incentives and how monopolistic or competitive sponsors depart from it. Sponsor competition is shown to potentially reduce social welfare.

Journal ArticleDOI
27 Jul 2006-Nature
TL;DR: Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.
Abstract: Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.