A distal enhancer of GATA3 regulates Th2 differentiation and allergic inflammation.

Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma-associated GATA3 enhancer region in experimental allergic airway inflammation, we first examined the correlation between GATA3 expression and the activation of the hG900 region was analyzed by flow cytometry and ChIP-qPCR. We found that The activation of enhancers in the hG900 region was strongly correlated to the levels of GATA3 in human peripheral T cell subsets. We next generated mice lacking the mG900 region (mG900KO mice) were generated by the CRISPR-Cas9 system, and the development and function of helper T cells and ILCs in mG900KO mice were analyzed in steady-state conditions and allergic airway inflammation induced by papain or house dust mite (HDM). The deletion of the mG900 did not affect the development of lymphocytes in steady-state conditions or allergic airway inflammation induced by papain. However, mG900KO mice exhibited reduced allergic inflammation and Th2 differentiation in the HDM-induced allergic airway inflammation. The analysis of the chromatin conformation around Gata3 by circular chromosome conformation capture coupled to high-throughput sequencing (4C-seq) revealed that the mG900 region interacted with the transcription start site of Gata3 with an influencing chromatin conformation in Th2 cells. These findings indicate that the mG900 region plays a pivotal role in Th2 differentiation and thus enhances allergic airway inflammation.

Sub-Tip-Radius Near-Field Interactions in Nano-FTIR Vibrational Spectroscopy on Single Proteins.

Tip-enhanced vibrational spectroscopy has advanced to routinely attain nanoscale spatial resolution, with tip-enhanced Raman spectroscopy even achieving atomic-scale and submolecular sensitivity. Tip-enhanced infrared spectroscopy techniques, such as nano-FTIR and AFM-IR spectroscopy, have also enabled the nanoscale chemical analysis of molecular monolayers, inorganic nanoparticles, and protein complexes. However, fundamental limits of infrared nanospectroscopy in terms of spatial resolution and sensitivity have remained elusive, calling for a quantitative understanding of the near-field interactions in infrared nanocavities. Here, we demonstrate the application of nano-FTIR spectroscopy to probe the amide-I vibration of a single protein consisting of ∼500 amino acid residues. Detection with higher tip tapping demodulation harmonics up to the seventh order leads to pronounced enhancement in the peak amplitude of the vibrational resonance, originating from sub-tip-radius geometrical effects beyond dipole approximations. This quantitative characterization of single-nanometer near-field interactions opens the path toward employing infrared vibrational spectroscopy at the subnanoscale and single-molecule levels.

Eosinophil-rich variant of nodal marginal zone lymphoma: a clinicopathological study of 11 cases.

AIMS: Tissue eosinophilia is commonly observed in T-cell and classic Hodgkin lymphomas, but rarely in B-cell lymphomas. Herein, we present the first report of a case series on nodal marginal zone lymphoma (NMZL) with tissue eosinophilia. METHODS AND RESULTS: All 11 patients in this study had nodal disease at primary presentation. The mean age at diagnosis was 64 years. The mean follow-up period was 39 months, and all patients were alive. Nine of the 11 patients (82%) showed no recurrence, but the other two patients experienced recurrence in the lymph nodes or skin. Marked eosinophilic infiltration was observed in all biopsied lymph nodes. Nine of the 11 patients had a preserved nodular architecture with expanded interfollicular areas. The other two patients showed diffuse lymphoma cell infiltration with effacement of nodal architecture. One of them was diagnosed as having diffuse large B-cell lymphoma transformed from NMZL because large cells accounted for >50% of the lymphoma cells and formed sheet-like patterns. Cells were positive for CD20 and BCL2 and negative for CD5, CD10, and BCL6. Some patients showed myeloid cell nuclear differentiation antigen (MNDA) positivity. All patients showed B-cell monoclonality via flow cytometry, southern blotting, and/or polymerase chain reaction (PCR). CONCLUSION: All patients showed distinctive morphological features and could be misdiagnosed with peripheral T-cell lymphoma due to their eosinophil-rich backgrounds. The predominance of B cells, absence of histiocytes, and high endothelial venules in the interfollicular areas are key factors for diagnosis. B-cell monoclonality is the most reliable evidence of differentiation. We designated this type of lymphoma as an eosinophil-rich variant of NMZL.

Charge Transfer-Mediated Dramatic Enhancement of Raman Scattering upon Molecular Point Contact Formation.

Charge-transfer enhancement of Raman scattering plays a crucial role in current-carrying molecular junctions. However, the microscopic mechanism of light scattering in such nonequilibrium systems is still imperfectly understood. Here, using low-temperature tip-enhanced Raman spectroscopy (TERS), we investigate how Raman scattering evolves as a function of the gap distance in the single C60-molecule junction consisting of an Ag tip and various metal surfaces. Precise gap-distance control allows the examination of two distinct transport regimes, namely tunneling regime and molecular point contact (MPC). Simultaneous measurement of TERS and the electric current in scanning tunneling microscopy shows that the MPC formation results in dramatic Raman enhancement that enables one to observe the vibrations undetectable in the tunneling regime. This enhancement is found to commonly occur not only for coinage but also transition metal substrates. We suggest that the characteristic enhancement upon the MPC formation is rationalized by charge-transfer excitation.

Nanoscale Heating of an Ultrathin Oxide Film Studied by Tip-Enhanced Raman Spectroscopy.

We report on the nanoscale heating mechanism of an ultrathin ZnO film using low-temperature tip-enhanced Raman spectroscopy. Under the resonance condition, intense Stokes and anti-Stokes Raman scattering can be observed for the phonon modes of a two-monolayer (ML) ZnO on an Ag(111) surface, enabling us to monitor local heating at the nanoscale. It is revealed that the local heating originates mainly from inelastic electron tunneling through the electronic resonance when the bias voltage exceeds the conduction band edge of the 2-ML ZnO. When the bias voltage is lower than the conduction band edge, the local heating arises from two different contributions, namely direct optical excitation between the interface state and the conduction band of 2-ML ZnO or injection of photoexcited electrons from an Ag tip into the conduction band. These optical heating processes are promoted by localized surface plasmon excitation. Simultaneous mapping of tip-enhanced Raman spectroscopy and scanning tunneling spectroscopy for 2-ML ZnO including an atomic-scale defect demonstrates visualizing a correlation between the heating efficiency and the local density of states, which further allows us to analyze the local electron-phonon coupling strength with ∼2 nm spatial resolution.

Atomic Point Contact Raman Spectroscopy of a Si(111)-7 × 7 Surface.

Tip-enhanced Raman scattering (TERS) has recently demonstrated the exceptional sensitivity to observe vibrational structures on the atomic scale. However, it strongly relies on electromagnetic enhancement in plasmonic nanogaps. Here, we demonstrate that atomic point contact (APC) formation between a plasmonic tip and the surface of a bulk Si sample can lead to a dramatic enhancement of Raman scattering and consequently the phonons of the reconstructed Si(111)-7 × 7 surface can be detected. Furthermore, we demonstrate the chemical sensitivity of APC-TERS by probing local vibrations resulting from Si-O bonds on the partially oxidized Si(111)-7 × 7 surface. This approach will expand the applicability of ultrasensitive TERS, exceeding the previous measurement strategies that exploit intense gap-mode plasmons, typically requiring a plasmonic substrate.

Dramatic Enhancement of Tip-Enhanced Raman Scattering Mediated by Atomic Point Contact Formation.

Tip-enhanced Raman scattering (TERS) in ångström-scale plasmonic cavities has drawn increasing attention. However, Raman scattering at vanishing cavity distances remains unexplored. Here, we show the evolution of TERS in transition from the tunneling regime to atomic point contact (APC). A stable APC is reversibly formed in the junction between an Ag tip and ultrathin ZnO or NaCl films on the Ag(111) surface at 10 K. An abrupt increase of the TERS intensity occurs upon APC formation for ZnO, but not for NaCl. This remarkable observation is rationalized by a difference in hybridization between the Ag tip and these films, which determines the contribution of charge transfer enhancement in the fused plasmonic junction. The strong hybridization between the Ag tip and ZnO is corroborated by the appearance of a new vibrational mode upon APC formation, whereas it is not observed for the chemically inert NaCl.

Silent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment-free remission.

This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D-STOP, after a 3-year follow-up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment-free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7-74.3] and 59.3% (95% CI: 45.0-71.0), respectively. CD3- CD56+ NK, CD16+ CD56+ NK, and CD57+ CD56+ NK large granular lymphocyte (NK-LGL), CD8+ CD4- cytotoxic T cell, and CD57+ CD3+ T-LGL cell numbers were relatively elevated throughout the 24-month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24-month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3- CD56+ NK >376 cells/µL, CD16+ CD56+ NK > 241 cells/µL, or CD57+ CD56+ NK-LGL >242 cells/µL during consolidation compared with others were 26.7% (8.3%-49.6%) vs 78.3% (55.4%-90.3%), HR 0.032 (0.0027-0.38; P = .0064), 31.2% (11.4%-53.6%) vs 85.0% (60.4%-94.9%), HR 0.039 (0.0031-0.48; P = .011), or 36.8% (16.5%-57.5%) vs 77.3% (53.7%-89.8%), HR 0.21 (0.065-0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D-STOP, NCT01627132).

Near-Field Manipulation in a Scanning Tunneling Microscope Junction with Plasmonic Fabry-Pérot Tips.

Near-field manipulation in plasmonic nanocavities can provide various applications in nanoscale science and technology. In particular, a gap plasmon in a scanning tunneling microscope (STM) junction is of key interest to nanoscale imaging and spectroscopy. Here we show that spectral features of a plasmonic STM junction can be manipulated by nanofabrication of Au tips using focused ion beam. An exemplary Fabry-Pérot type resonator of surface plasmons is demonstrated by producing the tip with a single groove on its shaft. Scanning tunneling luminescence spectra of the Fabry-Pérot tips exhibit spectral modulation resulting from interference between localized and propagating surface plasmon modes. In addition, the quality factor of the plasmonic Fabry-Pérot interference can be improved by optimizing the overall tip shape. Our approach paves the way for near-field imaging and spectroscopy with a high degree of accuracy.

Resolving the Correlation between Tip-Enhanced Resonance Raman Scattering and Local Electronic States with 1 nm Resolution.

Low-temperature tip-enhanced Raman spectroscopy (TERS) enables chemical identification with single-molecule sensitivity and extremely high spatial resolution even down to the atomic scale. The large enhancement of Raman scattering obtained in TERS can originate from physical and/or chemical enhancement mechanisms. Whereas physical enhancement requires a strong near-field through excitation of localized surface plasmons, chemical enhancement is governed by resonance in the electronic structure of the sample, which is also known as resonance Raman spectroscopy. Here we report on tip-enhanced resonance Raman spectroscopy (TERRS) of ultrathin ZnO layers epitaxially grown on a Ag(111) surface, where both enhancement mechanisms are operative. In combination with scanning tunneling spectroscopy (STS), it is demonstrated that the TERRS intensity strongly depends on the local electronic resonance of the ZnO/Ag(111) interface. We also reveal that the spatial resolution of TERRS is dependent on the tip-surface distance and reaches nearly 1 nm in the tunneling regime, which can be rationalized by strong-field confinement resulting from an atomic-scale protrusion on the tip apex. Comparison of STS and TERRS mapping clearly shows a correlation between resonantly enhanced Raman scattering and the local electronic states at near-atomic resolution. Our results suggest that TERRS is a new approach for the atomic-scale optical characterization of local electronic states.

Elucidating the Nuclear Quantum Dynamics of Intramolecular Double Hydrogen Transfer in Porphycene.

We address the double hydrogen transfer (DHT) dynamics of the porphycene molecule, a complex paradigmatic system in which the making and breaking of H-bonds in a highly anharmonic potential energy surface require a quantum mechanical treatment not only of the electrons but also of the nuclei. We combine density functional theory calculations, employing hybrid functionals and van der Waals corrections, with recently proposed and optimized path-integral ring-polymer methods for the approximation of quantum vibrational spectra and reaction rates. Our full-dimensional ring-polymer instanton simulations show that below 100 K the concerted DHT tunneling pathway dominates but between 100 and 300 K there is a competition between concerted and stepwise pathways when nuclear quantum effects are included. We obtain ground-state reaction rates of 2.19 × 1011 s-1 at 150 K and 0.63 × 1011 s-1 at 100 K, in good agreement with experiment. We also reproduce the puzzling N-H stretching band of porphycene with very good accuracy from thermostated ring-polymer molecular dynamics simulations. The position and line shape of this peak, centered at around 2600 cm-1 and spanning 750 cm-1, stem from a combination of very strong H-bonds, the coupling to low-frequency modes, and the access to cis-like isomeric conformations, which cannot be appropriately captured with classical-nuclei dynamics. These results verify the appropriateness of our general theoretical approach and provide a framework for a deeper physical understanding of hydrogen transfer dynamics in complex systems.

Efficacy and Safety of a Weekly Cyclophosphamide-Bortezomib-Dexamethasone Regimen as Induction Therapy Prior to Autologous Stem Cell Transplantation in Japanese Patients with Newly Diagnosed Multiple Myeloma: A Phase 2 Multicenter Trial.

We assessed the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction prior to autologous stem cell transplantation (ASCT) in newly diagnosed Japanese patients with multiple myeloma (MM). This regimen consisted of four 28-day cycles of once-weekly oral cyclophosphamide (300 mg/m2), subcutaneous bortezomib (1.3 mg/m2), and oral dexamethasone (40 mg). Responding patients underwent stem cell collection followed by ASCT. The primary endpoint was the postinduction rate of achieving a near complete response (nCR) or better. Among the 38 enrolled patients, a complete response (CR), an nCR, a very good partial response (VGPR), and a partial response (PR) were achieved in 10.5, 2.6, 23.7, and 36.8% of cases, respectively. A grade 4 hematological adverse event (AE) was observed in 1 patient. Grade 3-4 infection, including febrile neutropenia, was observed in 4 patients (10.5%). Although 2 patients dropped out due to AE, 94.7% of the patients completed the induction phase. However, because of a poor response to induction chemotherapy (

Real-space observation of far- and near-field-induced photolysis of molecular oxygen on an Ag(110) surface by visible light.

Dissociation of molecular oxygen is an important elementary process in heterogeneous catalysis. Here, we report on a real-space observation of oxygen photolysis on the Ag(110) surface at 78 K by far- and near-field excitation in the ultraviolet-near-infrared range using a low-temperature scanning tunneling microscope (STM) combined with wavelength-tunable laser excitation. The photolysis of isolated oxygen molecules on the surface occurs even by visible light with the cross section of ∼10-19 cm2. Time-dependent density functional theory calculations reveal optical absorption of the hybridized O2-Ag(110) complex in the visible and the near-infrared range which is associated with the oxygen photolysis. We suggest that the photolysis mechanism involves a direct charge transfer process. We also demonstrate that the photolysis can be largely enhanced in plasmonic STM junctions, and the cross section is estimated to be ∼10-17 cm-2 in the visible and the near-infrared range, which appears to be an interesting feature of plasmon-induced reactions from the perspective of photochemical conversion with the aid of solar energy.

Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial).

BACKGROUND: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). METHODS: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib. RESULTS: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis. CONCLUSIONS: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.

Near-Field Enhanced Photochemistry of Single Molecules in a Scanning Tunneling Microscope Junction.

Optical near-field excitation of metallic nanostructures can be used to enhance photochemical reactions. The enhancement under visible light illumination is of particular interest because it can facilitate the use of sunlight to promote photocatalytic chemical and energy conversion. However, few studies have yet addressed optical near-field induced chemistry, in particular at the single-molecule level. In this Letter, we report the near-field enhanced tautomerization of porphycene on a Cu(111) surface in a scanning tunneling microscope (STM) junction. The light-induced tautomerization is mediated by photogenerated carriers in the Cu substrate. It is revealed that the reaction cross section is significantly enhanced in the presence of a Au tip compared to the far-field induced process. The strong enhancement occurs in the red and near-infrared spectral range for Au tips, whereas a W tip shows a much weaker enhancement, suggesting that excitation of the localized plasmon resonance contributes to the process. Additionally, using the precise tip-surface distance control of the STM, the near-field enhanced tautomerization is examined in and out of the tunneling regime. Our results suggest that the enhancement is attributed to the increased carrier generation rate via decay of the excited near-field in the STM junction. Additionally, optically excited tunneling electrons also contribute to the process in the tunneling regime.

[Chronic myeloid leukemia harboring T315I and F317L mutations successfully treated with interferon-α and ponatinib].

Our patient was diagnosed with chronic myeloid leukemia (CML) in chronic phase (CP) when he was 40 years old. Although dasatinib (DAS) was prescribed during his clinical course, he was poorly compliant with the treatment. In November 20XX, at 65 years of age, he visited our hospital with leukocytosis. He was diagnosed with CML in CP and recommenced DAS at 50 mg/day, achieving a complete hematological response after 2 months. However, DAS was increased to 100 mg/day because only minimum cytogenetic response was evident even after 9 months, but CML progressed to the accelerated phase after 18 months. The ABL kinase domain mutations T315I and F317L were detected. Ponatinib (PON) was not yet approved, and he declined allogeneic stem cell transplantation therapy. He commenced interferon-α (IFN-α) in addition to DAS, and the F317L mutation (only) disappeared after 7 months; the patient achieved a major cytogenetic response. In January 20XX＋4, he commenced PON monotherapy (the drug was approved by this time) and achieved a major molecular response after 8 months. The T315I mutation disappeared during PON therapy. Although IFN-α is rarely used in the treatment of CML, this case suggests that IFN-α should be re-considered in patients with CML who exhibit tyrosine kinase inhibitor resistance.

Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation.

Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation. Peripheral lymphocyte profiles were analyzed by flow cytometry. The estimated 12-month treatment-free survival (TFS) was 62.9% (95% confidence interval: 48.5%-74.2%). During dasatinib consolidation, the percentage of total lymphocytes and numbers of CD3- CD56+ natural killer (NK) cells, CD16+ CD56+ NK cells and CD56+ CD57+ NK-large granular lymphocytes (LGL) were significantly higher in patients with molecular relapse after discontinuation but remained unchanged in patients without molecular relapse for >7 months. At the end of consolidation, patients whose total lymphocytes comprised <41% CD3- CD56+ NK cells, <35% CD16+ CD56+ NK cells, or <27% CD56+ CD57+ NK-LGL cells had higher TFS relative to other patients (77% vs 18%; P < .0008; 76% vs 10%; P < .0001; 84% vs 46%; P = .0059, respectively). The increase in the number of these NK cells occurred only during dasatinib consolidation. In patients with DMR, dasatinib discontinuation after 2-year consolidation can lead to high TFS. This outcome depends significantly on a smaller increase in NK cells during dasatinib consolidation.

Plasmon-Assisted Resonant Electron Tunneling in a Scanning Tunneling Microscope Junction.

We report plasmon-assisted resonant electron tunneling from a Ag or Au tip to field emission resonances (FERs) of a Ag(111) surface induced by cw laser excitation of a scanning tunneling microscope (STM) junction at visible wavelengths. As a hallmark of the plasmon-assisted resonant tunneling, we observe a downshift of the first peak in the FER spectra by a fixed amount equal to the incident photon energy. STM-induced luminescence measurement for the Ag and Au tip reveals the clear correlation between the laser-induced change in the FER spectra and the plasmonic properties of the junction. Our results clarify a novel resonant electron transfer mechanism in a plasmonic nanocavity.

How Structural Defects Affect the Mechanical and Electrical Properties of Single Molecular Wires.

We report how individual defects affect single graphene nanoribbons by scanning tunneling and atomic force microscopy pulling experiments simultaneously accessing their electrical and mechanical properties. The on-surface polymerization of the graphene nanoribbons is controlled by cooperative effects as theoretically suggested. Further, we find, with the help of atomistic simulations, that defects substantially vary the molecule-substrate coupling and drastically increase the flexibility of the graphene nanoribbons while keeping their desirable electronic properties intact.

Quantum tunneling in real space: Tautomerization of single porphycene molecules on the (111) surface of Cu, Ag, and Au.

Tautomerization in single porphycene molecules is investigated on Cu(111), Ag(111), and Au(111) surfaces by a combination of low-temperature scanning tunneling microscopy (STM) experiments and density functional theory (DFT) calculations. It is revealed that the trans configuration is the thermodynamically stable form of porphycene on Cu(111) and Ag(111), whereas the cis configuration occurs as a meta-stable form. The trans → cis or cis → trans conversion on Cu(111) can be induced in an unidirectional fashion by injecting tunneling electrons from the STM tip or heating the surface, respectively. We find that the cis ↔ cis tautomerization on Cu(111) occurs spontaneously via tunneling, verified by the negligible temperature dependence of the tautomerization rate below ∼23 K. Van der Waals corrected DFT calculations are used to characterize the adsorption structures of porphycene and to map the potential energy surface of the tautomerization on Cu(111). The calculated barriers are too high to be thermally overcome at cryogenic temperatures used in the experiment and zero-point energy corrections do not change this picture, leaving tunneling as the most likely mechanism. On Ag(111), the reversible trans ↔ cis conversion occurs spontaneously at 5 K and the cis ↔ cis tautomerization rate is much higher than on Cu(111), indicating a significantly smaller tautomerization barrier on Ag(111) due to the weaker interaction between porphycene and the surface compared to Cu(111). Additionally, the STM experiments and DFT calculations reveal that tautomerization on Cu(111) and Ag(111) occurs with migration of porphycene along the surface; thus, the translational motion couples with the tautomerization coordinate. On the other hand, the trans and cis configurations are not discernible in the STM image and no tautomerization is observed for porphycene on Au(111). The weak interaction of porphycene with Au(111) is closest to the gas-phase limit and therefore the absence of trans and cis configurations in the STM images is explained either by the rapid tautomerization rate or the similar character of the molecular frontier orbitals of the trans and cis configurations.