Showing papers by "University of Tokyo published in 2006"

Global variation in copy number in the human genome

Abstract: Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

Doping a Mott insulator: Physics of high-temperature superconductivity

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.

Global Hydrological Cycles and World Water Resources

Abstract: Water is a naturally circulating resource that is constantly recharged. Therefore, even though the stocks of water in natural and artificial reservoirs are helpful to increase the available water resources for human society, the flow of water should be the main focus in water resources assessments. The climate system puts an upper limit on the circulation rate of available renewable freshwater resources (RFWR). Although current global withdrawals are well below the upper limit, more than two billion people live in highly water-stressed areas because of the uneven distribution of RFWR in time and space. Climate change is expected to accelerate water cycles and thereby increase the available RFWR. This would slow down the increase of people living under water stress; however, changes in seasonal patterns and increasing probability of extreme events may offset this effect. Reducing current vulnerability will be the first step to prepare for such anticipated changes.

Transcriptional regulatory networks in cellular responses and tolerance to dehydration and cold stresses.

Abstract: Plant growth and productivity are greatly affected by environmental stresses such as drought, high salinity, and low temperature. Expression of a variety of genes is induced by these stresses in various plants. The products of these genes function not only in stress tolerance but also in stress response. In the signal transduction network from perception of stress signals to stress-responsive gene expression, various transcription factors and cis-acting elements in the stress-responsive promoters function for plant adaptation to environmental stresses. Recent progress has been made in analyzing the complex cascades of gene expression in drought and cold stress responses, especially in identifying specificity and cross talk in stress signaling. In this review article, we highlight transcriptional regulation of gene expression in response to drought and cold stresses, with particular emphasis on the role of transcription factors and cis-acting elements in stress-inducible promoters.

Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

Abstract: Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.

Photocatalyst releasing hydrogen from water

Abstract: Enhancing catalytic performance holds promise for hydrogen production by water splitting in sunlight.

Gene networks involved in drought stress response and tolerance

Abstract: Plants respond to survive under water-deficit conditions via a series of physiological, cellular, and molecular processes culminating in stress tolerance. Many drought-inducible genes with various functions have been identified by molecular and genomic analyses in Arabidopsis, rice, and other plants, including a number of transcription factors that regulate stress-inducible gene expression. The products of stress-inducible genes function both in the initial stress response and in establishing plant stress tolerance. In this short review, recent progress resulting from analysis of gene expression during the drought-stress response in plants as well as in elucidating the functions of genes implicated in the stress response and/or stress tolerance are summarized. A description is also provided of how various genes involved in stress tolerance were applied in genetic engineering of dehydration stress tolerance in transgenic Arabidopsis plants.

Stereotactic Radiosurgery Plus Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery Alone for Treatment of Brain Metastases: A Randomized Controlled Trial

Abstract: ContextIn patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.ObjectiveTo determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.Design, Setting, and PatientsRandomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.InterventionsPatients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).Main Outcome MeasuresThe primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.ResultsThe median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.ConclusionsCompared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.Trial Registrationumin.ac.jp/ctr Identifier: C000000412

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation

Abstract: While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor (GPCR) TGR5 and activate nuclear hormone receptors such as farnesoid X receptor alpha (FXR-alpha; NR1H4). FXR-alpha regulates the enterohepatic recycling and biosynthesis of BAs by controlling the expression of genes such as the short heterodimer partner (SHP; NR0B2) that inhibits the activity of other nuclear receptors. The FXR-alpha-mediated SHP induction also underlies the downregulation of the hepatic fatty acid and triglyceride biosynthesis and very-low-density lipoprotein production mediated by sterol-regulatory-element-binding protein 1c. This indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators. Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2-/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption. These effects are independent of FXR-alpha, and instead are mediated by increased cAMP production that stems from the binding of BAs with the G-protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism because they coexpress D2 and TGR5. The BA-TGR5-cAMP-D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control.

Klotho converts canonical FGF receptor into a specific receptor for FGF23

Abstract: FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.

Insights into social insects from the genome of the honeybee Apis mellifera

Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

GeV electron beams from a centimetre-scale accelerator

Abstract: Gigaelectron volt (GeV) electron accelerators are essential to synchrotron radiation facilities and free-electron lasers, and as modules for high-energy particle physics. Radiofrequency-based accelerators are limited to relatively low accelerating fields (10–50 MV m−1), requiring tens to hundreds of metres to reach the multi-GeV beam energies needed to drive radiation sources, and many kilometres to generate particle energies of interest to high-energy physics. Laser-wakefield accelerators1,2 produce electric fields of the order 10–100 GV m−1 enabling compact devices. Previously, the required laser intensity was not maintained over the distance needed to reach GeV energies, and hence acceleration was limited to the 100 MeV scale3,4,5. Contrary to predictions that petawatt-class lasers would be needed to reach GeV energies6,7, here we demonstrate production of a high-quality electron beam with 1 GeV energy by channelling a 40 TW peak-power laser pulse in a 3.3-cm-long gas-filled capillary discharge waveguide8,9.

IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis

Abstract: IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17−/− murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17−/− mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17−/− mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17−/− CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-γ−/− cells, while IFN-γ-producing cells were increased in IL-17−/− cells, suggesting that IL-17 and IFN-γ mutually regulate IFN-γ and IL-17 production. These observations indicate that IL-17 rather than IFN-γ plays a crucial role in the development of EAE.

Widespread amphibian extinctions from epidemic disease driven by global warming

Abstract: As the Earth warms, many species are likely to disappear, often because of changing disease dynamics. Here we show that a recent mass extinction associated with pathogen outbreaks is tied to global warming. Seventeen years ago, in the mountains of Costa Rica, the Monteverde harlequin frog (Atelopus sp.) vanished along with the golden toad (Bufo periglenes). An estimated 67% of the 110 or so species of Atelopus, which are endemic to the American tropics, have met the same fate, and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis) is implicated. Analysing the timing of losses in relation to changes in sea surface and air temperatures, we conclude with 'very high confidence' (> 99%, following the Intergovernmental Panel on Climate Change, IPCC) that large-scale warming is a key factor in the disappearances. We propose that temperatures at many highland localities are shifting towards the growth optimum of Batrachochytrium, thus encouraging outbreaks. With climate change promoting infectious disease and eroding biodiversity, the urgency of reducing greenhouse-gas concentrations is now undeniable.

IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.

Abstract: The interferon-regulatory factor (IRF) family of transcription factors was initially found to be involved in the induction of genes that encode type I interferons. IRFs have now been shown to have functionally diverse roles in the regulation of the immune system. Recently, the crucial involvement of IRFs in innate and adaptive immune responses has been gaining much attention, particularly with the discovery of their role in immunoregulation by Toll-like receptors and other pattern-recognition receptors.

Cosmological constraints from the SDSS luminous red galaxies

Abstract: We measure the large-scale real-space power spectrum P(k) using luminous red galaxies (LRGs) in the Sloan Digital Sky Survey (SDSS) and use this measurement to sharpen constraints on cosmological parameters from the Wilkinson Microwave Anisotropy Probe (WMAP). We employ a matrix-based power spectrum estimation method using Pseudo-Karhunen-Loeve eigenmodes, producing uncorrelated minimum-variance measurements in 20 k-bands of both the clustering power and its anisotropy due to redshift-space distortions, with narrow and well-behaved window functions in the range 0.01h/Mpc 0.1h/Mpc and associated nonlinear complications, yet agree well with more aggressive published analyses where nonlinear modeling is crucial.

Constraining the Evolution of the Ionizing Background and the Epoch of Reionization with z~6 Quasars II: A Sample of 19 Quasars

Abstract: We study the evolution of the ionization state of the intergalactic medium (IGM) at the end of the reionization epoch using moderate-resolution spectra of a sample of 19 quasars at 5.74 5.7: the GP optical depth evolution changes from τ ~ (1 + z)4.3 to (1 + z)11, and the average length of dark gaps with τ > 3.5 increases from 80 comoving Mpc. The dispersion of IGM properties along different lines of sight also increases rapidly, implying fluctuations by a factor of 4 in the UV background at z > 6, when the mean free path of UV photons is comparable to the correlation length of the star-forming galaxies that are thought to have caused reionization. The mean length of dark gaps shows the most dramatic increase at z ~ 6, as well as the largest line-of-sight variations. We suggest using dark gap statistics as a powerful probe of the ionization state of the IGM at yet higher redshift. The sizes of H II regions around luminous quasars decrease rapidly toward higher redshift, suggesting that the neutral fraction of the IGM has increased by a factor of 10 from z = 5.7 to 6.4, consistent with the value derived from the GP optical depth. The mass-averaged neutral fraction is 1%-4% at z ~ 6.2 based on the GP optical depth and H II region size measurements. The observations suggest that z ~ 6 is the end of the overlapping stage of reionization and are inconsistent with a mostly neutral IGM at z ~ 6, as indicated by the finite length of the dark absorption gaps.

Functional liquid-crystalline assemblies: self-organized soft materials.

Abstract: In the 21st century, soft materials will become more important as functional materials because of their dynamic nature. Although soft materials are not as highly durable as hard materials, such as metals, ceramics, and engineering plastics, they can respond well to stimuli and the environment. The introduction of order into soft materials induces new dynamic functions. Liquid crystals are ordered soft materials consisting of self-organized molecules and can potentially be used as new functional materials for electron, ion, or molecular transporting, sensory, catalytic, optical, and bio-active materials. For this functionalization, unconventional materials design is required. Herein, we describe new approaches to the functionalization of liquid crystals and show how the design of liquid crystals formed by supramolecular assembly and nano-segregation leads to the formation of a variety of new self-organized functional materials.

Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

Abstract: In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)-γ remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation.

Avian flu: influenza virus receptors in the human airway.

Abstract: Avian and human flu viruses seem to target different regions of a patient's respiratory tract.

Why some interfaces cannot be sharp

Abstract: A central goal of modern materials physics and nanoscience is the control of materials and their interfaces to atomic dimensions. For interfaces between polar and nonpolar layers, this goal is thwarted by a polar catastrophe that forces an interfacial reconstruction. In traditional semiconductors, this reconstruction is achieved by an atomic disordering and stoichiometry change at the interface, but a new option is available in multivalent oxides: if the electrons can move, the atoms do not have to. Using atomic-scale electron energy loss spectroscopy, we have examined the microscopic distribution of charge and ions across the (001) LaAlO3/SrTiO3 interface. We find that there is a fundamental asymmetry between the ionically compensated AlO2/SrO/TiO2 interface, and the electronically compensated AlO2/LaO/TiO2 interface, both in interfacial sharpness and charge density. This suggests a general strategy to design sharp interfaces, remove interfacial screening charges, control the band offset and, hence, markedly improve the performance of oxide devices.

Critical features of colossal magnetoresistive manganites

Abstract: Colossal magnetoresistance (CMR) phenomena are observed in the perovskite-type hole-doped manganites in which the double-exchange ferromagnetic metal phase and the charge–orbital ordered antiferromagnetic phase compete with each other. The quenched disorder arising from the inherent chemical randomness or the intentional impurity doping may cause major modifications in the electronic phase diagram as well as in the magnetoelectronic properties near the bicritical point that is formed by such a competition of the two phases. One is the phase separation phenomenon on various time-scales (from static to dynamic) and on various length-scales (from glass-like nano to grain-like micron). The other is the enhanced phase fluctuation with anomalous reduction in the transition temperatures of the competing phases (and hence in the bicritical-point temperature). The highly effective suppression of such a phase fluctuation by an external magnetic field is assigned here to the most essential ingredient of the CMR physics. Such profound and dramatic features as appearing in the bicritical region are extensively discussed in this paper with ample examples of the material systems specially designed for this purpose. The unconventional phase-controls over the competing phases in terms of magnetic/electric fields and photo-excitations are also exemplified.

The fourth data release of the Sloan Digital Sky Survey

Abstract: This paper describes the Fourth Data Release of the Sloan Digital Sky Survey (SDSS), including all survey-quality data taken through 2004 June. The data release includes five-band photometric data for 180 million objects selected over 6670 deg2 and 673,280 spectra of galaxies, quasars, and stars selected from 4783 deg2 of those imaging data using the standard SDSS target selection algorithms. These numbers represent a roughly 27% increment over those of the Third Data Release; all the data from previous data releases are included in the present release. The Fourth Data Release also includes an additional 131,840 spectra of objects selected using a variety of alternative algorithms, to address scientific issues ranging from the kinematics of stars in the Milky Way thick disk to populations of faint galaxies and quasars.

An Improved Mellor–Yamada Level-3 Model: Its Numerical Stability and Application to a Regional Prediction of Advection Fog

Abstract: This note describes a numerically stable version of the improved Mellor–Yamada (M–Y) Level-3 model proposed by Nakanishi and Niino [Nakanishi, M and Niino, H: 2004, Boundary-Layer Meteorol 112, 1–31] and demonstrates its application to a regional prediction of advection fog In order to ensure the realizability for the improved M–Y Level-3 model and its numerical stability, restrictions are imposed on computing stability functions, on L/q, the temperature and water-content variances, and their covariance, where L is the master length scale and q 2/2 the turbulent kinetic energy per unit mass The model with these restrictions predicts vertical profiles of mean quantities such as temperature that are in good agreement with those obtained from large-eddy simulation of a radiation fog In a regional prediction, it also reasonably reproduces the satellite-observed horizontal distribution of an advection fog

Diels-Alder in Aqueous Molecular Hosts: Unusual Regioselectivity and Efficient Catalysis

Abstract: Self-assembled, hollow molecular structures are appealing as synthetic hosts for mediating chemical reactions. However, product binding has inhibited catalytic turnover in such systems, and selectivity has rarely approached the levels observed in more structurally elaborate natural enzymes. We found that an aqueous organopalladium cage induces highly unusual regioselectivity in the Diels-Alder coupling of anthracene and phthalimide guests, promoting reaction at a terminal rather than central anthracene ring. Moreover, a similar bowl-shaped host attains efficient catalytic turnover in coupling the same substrates (although with the conventional regiochemistry), most likely because the product geometry inhibits the aromatic stacking interactions that attract the planar reagents to the host.