Most empirical studies of the static CAPM assume that betas remain constant over time and that the return on the value-weighted portfolio of all stocks is a proxy for the return on aggregate wealth. The general consensus is that the static CAPM is unable to explain satisfactorily the cross-section of average returns on stocks. We assume that the CAPM holds in a conditional sense, i.e., betas and the market risk premium vary over time. We include the return on human capital when measuring the return on aggregate wealth. Our specification performs well in explaining the cross-section of average returns.A SUBSTANTIAL PART OF the research effort in finance is directed toward improving our understanding of how investors value risky cash flows. It is generally agreed that investors demand a higher expected return for investment in riskier projects, or securities. However, we still do not fully understand how investors assess the risk of the cash flow on a project and how they determine what risk premium to demand. Several capital asset-pricing models have been suggested in the literature that describe how investors assess risk and value risky cash flows. Among them, the Sharpe-Lintner-Black Capital Asset Pricing Model (CAPM)1 is the one that financial managers use most often for assessing the risk of the cash flow from a project and for arriving at the appropriate * Jagannathan is from thebaugh, as well as with participants at numerous finance workshops in the United States, Canada, and East Asia. Special thanks go to the anonymous referee and the managing editor of the journal for valuable comments. We are grateful to Eugene Fama for providing us with the Fama-French factors and Raymond A. Dragan for editorial assistance. All errors in this paper are the authors' responsibility. The views expressed herein are those of the authors and not necessarily those of the Federal Reserve Bank of Minneapolis or the Federal Reserve System. Ravi Jagannathan gratefully acknowledges financial support from the National Science Foundation (grant SBR-9409824). Zhenyu Wang gratefully acknowledges financial support from the Alfred P. Sloan Foundation (doctoral dissertation fellowship, grant DD-518). An earlier version of the paper appeared under the title, "The CAPM Is Alive and Well." The compressed archive of the data and the FORTRAN programs used for this paper can be obtained via anonymous FTP at ftp.socsci.umn.edu. The path is outgoing/wang/capm.tar.Z. 1 See Sharpe (1964), Lintner (1965), and Black (1972). 3 4The Journal of Finance discount rate to use in valuing the project. According to the CAPM, (a) the risk of a project is measured by the beta of the cash flow with respect to the return on the market portfolio of all assets in the economy, and (b) the relation between required expected return and beta is linear. Over the past two decades a number of studies have empirically examined the performance of the static version of the CAPM in explaining the crosssection of realized average returns. The results reported in these studies ...

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Spherical superparamagnetic iron oxide nanoparticles have been developed as T 2 -negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3±30 mM À 1 s À 1 ), indicating that these octapod iron oxide nanoparticles are much more effective T 2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic.

ObjectivesTo investigate the roles and regulatory mechanisms of synovial macrophages and their polarisation in the development of osteoarthritis (OA).MethodsSynovial tissues from normal patients and patients with OA were collected. M1 or M2-polarised macrophages in synovial tissues of patients with OA and OA mice were analysed by immunofluorescence and immunohistochemical staining. Mice with tuberous sclerosis complex 1 (TSC1) or Rheb deletion specifically in the myeloid lineage were generated and subjected to intra-articular injection of collagenase (collagenase-induced osteoarthritis, CIOA) and destabilisation of the medial meniscus (DMM) surgery to induce OA. Cartilage damage and osteophyte size were measured by Osteoarthritis Research Society International score and micro-CT, respectively. mRNA sequencing was performed in M1 and control macrophages. Mice and ATDC5 cells were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in OA.ResultsM1 but not M2-polarised macrophages accumulated in human and mouse OA synovial tissue. TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice. The results show that promoting the macrophage M1 polarisation leads to exacerbation of experimental OA partially through secretion of Rspo2 and activation of β-catenin signalling in chondrocytes.ConclusionsSynovial macrophage M1 polarisation exacerbates experimental CIOA partially through Rspo2. M1 macrophages and Rspo2 are potential therapeutic targets for OA treatment.

Without the assumption of conditional homoskedasticity, a general asymptotic distribution theory for the two-stage cross-sectional regression method shows that the standard errors produced by the Fama-MacBeth procedure do not necessarily overstate the precision of the risk premium estimates. When factors are misspecified, estimators for risk premiums can be biased, and the t-value of a premium may converge to infinity in probability even when the true premium is zero. However, when a beta-pricing model is misspecified, the t-values for firm characteristics generally converge to infinity in probability, which supports the use of firm characteristics in cross-sectional regressions for detecting model misspecification.LINEAR BETA-PRICING MODELS have received wide attention in finance literature. Although sophisticated econometric methods are available for evaluating linear beta-pricing models, it is difficult to interpret statistical rejections obtained from these methods. The two-stage cross-sectional regression method, which is used in the two classic studies of the CAPM-one by Black, Jensen, and Scholes~1972! and the other by Fama and MacBeth~1973!-is still preferred in many empirical studies. With the cross-sectional regression method, it is rather straightforward to interpret the results in economic terms. It is also convenient to examine model misspecification by checking whether firm characteristics such as relative size and book-to-market value explain any residual variation in average returns across firms. The method is intuitive and easy to implement. Because of this, empirical studies of linear beta-pricing models still use the cross-sectional regression method as a diagnostic tool. 1

The growing importance of applications based on machine learning is driving the need to develop dedicated, energy-efficient electronic hardware. Compared with von-Neumann architectures, brain-inspired in-memory computing uses the same basic device structure for logic operations and data storage 1 – 3 , thus promising to reduce the energy cost of data-centric computing significantly 4 . While there is ample research focused on exploring new device architectures, the engineering of material platforms suitable for such device designs remains a challenge. Two-dimensional materials 5 , 6 such as semiconducting MoS2 could stand out as a promising candidate to face this obstacle thanks to their exceptional electrical and mechanical properties 7 – 9 . Here, we explore large-area grown MoS2 as an active channel material for developing logic-in-memory devices and circuits based on floating-gate field-effect transistors (FGFET). The conductance of our FGFETs can be precisely and continuously tuned, allowing us to use them as building blocks for reconfigurable logic circuits where logic operations can be directly performed using the memory elements. After demonstrating a programmable NOR gate, we show that this design can be simply extended to implement more complex programmable logic and functionally complete sets of functions. Our findings highlight the potential of atomically thin semiconductors for the development of next-generation low-power electronics.

(E.H.).MAX2 (for MORE AXILLARY GROWTH2) has been shown to regulate diverse biological processes, including plant architecture, photomorphogenesis, senescence, and karrikin signaling. Although karrikin is a smoke-derived abiotic signal, a role for MAX2 in abiotic stress response pathways is least investigated. Here, we show that the max2 mutant is strongly hypersensitive to drought stress compared with wild-type Arabidopsis (Arabidopsis thaliana). Stomatal closure of max2 was less sensitive to abscisic acid (ABA) than that of the wild type. Cuticle thickness of max2 was significantly thinner than that of the wild type. Both of these phenotypes of max2 mutant plants correlate with the increased water loss and drought-sensitive phenotype. Quantitative real-time reverse transcriptionpolymerase chain reaction analyses showed that the expression of stress-responsive genes and ABA biosynthesis, catabolism, transport, and signaling genes was impaired in max2 compared with wild-type seedlings in response to drought stress. Double mutant analysis of max2 with the ABA-insensitive mutants abi3 and abi5 indicated that MAX2 may function upstream of these genes. The expression of ABA-regulated genes was enhanced in imbibed max2 seeds. In addition, max2 mutant seedlings were hypersensitive to ABA and osmotic stress, including NaCl, mannitol, and glucose. Interestingly, ABA, osmotic stress, and drought-sensitive phenotypes were restricted to max2, and the strigolactone biosynthetic pathway mutants max1, max3, and max4 did not display any defects in these responses. Taken together, these results uncover an important role for MAX2 in plant responses to abiotic stress conditions.