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Earlier sum frequency generation (SFG) experiments involve one infrared and one visible laser, and a measurement of the intensity of the response, yielding data on the surface sensitive properties of the sample. Recently, both the real and imaginary components of the susceptibility were measured in two different sets of experiments. In one set, a broadband infrared laser was used, permitting observations at very short times, while in another set the infrared laser was narrowband, permitting higher spectral resolution. The differences in the spectrum obtained by the two will be most evident in studying narrow absorption bands, e.g., the band due to dangling OH bonds at a water interface. The direct comparisons in the integrated amplitude (sum rule) of the imaginary part of the dangling OH bond region differ by a factor of 3. Due to variations in experimental setup and data processing, corrections were made for the quartz reference, Fresnel factors, and the incident visible laser wavelength. After the corrections, the agreement differs now by the factors of 1.1 within broadband and narrowband groups and the two groups now differ by a factor of 1.5. The 1.5 factor may arise from the extra heating of the more powerful broadband laser system on the water surface. The convolution from the narrowband SFG spectrum to the broadband SFG spectrum is also investigated and it does not affect the sum rule. Theory and narrowband experiments are compared using the sum rule and agree to a factor of 1.3 with no adjustable parameters.
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In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.
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The experimental sum frequency generation (SFG) spectrum is the response to an infrared pulse and a visible pulse and is a highly surface-sensitive technique. We treat the surface dangling OH bonds at the air/water interface and focus on the absolute SFG intensities for the resonant terms, a focus that permits insight into the consequences of some approximations. For the polarization combinations, the calculated linewidths for the water interface dangling OH SFG band at 3,700 [Formula: see text] are, as usual, too large, because of the customary neglect of motional narrowing. The integrated spectrum is used to circumvent this problem and justified here using a Kubo-like formalism and theoretical integrated band intensities rather than peak intensities. Only relative SFG intensities are usually reported. The absolute integrated SFG intensities for three polarization combinations for sum frequency, visible, and infrared beams are computed. We use molecular dynamics and the dipole and the polarizability matrix elements obtained from infrared and Raman studies of [Formula: see text]O vapor. The theoretical expressions for two of the absolute susceptibilities contain only a single term and agree with experiment to about a factor of 1.3, with no adjustable parameters. The Fresnel factors are included in that comparison. One of the susceptibilities contains instead four positive and negative terms and agrees less well. The expression for the SFG correlation function is normally derived from a statistical mechanical formulation using a time-evolving density matrix. We show how a derivation based on a two-field relaxation leads to the same final result.
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A method is proposed for analyzing fast (10 µs) single-molecule rotation trajectories in F1 adenosinetriphosphatase ([Formula: see text]-ATPase). This method is based on the distribution of jumps in the rotation angle that occur in the transitions during the steps between subsequent catalytic dwells. The method is complementary to the "stalling" technique devised by H. Noji et al. [Biophys. Rev. 9, 103-118, 2017], and can reveal multiple states not directly detectable as steps. A bimodal distribution of jumps is observed at certain angles, due to the system being in either of 2 states at the same rotation angle. In this method, a multistate theory is used that takes into account a viscoelastic fluctuation of the imaging probe. Using an established sequence of 3 specific states, a theoretical profile of angular jumps is predicted, without adjustable parameters, that agrees with experiment for most of the angular range. Agreement can be achieved at all angles by assuming a fourth state with an â¼10 µs lifetime and a dwell angle about 40° after the adenosine 5'-triphosphate (ATP) binding dwell. The latter result suggests that the ATP binding in one ß subunit and the adenosine 5'-diphosphate (ADP) release from another ß subunit occur via a transient whose lifetime is â¼10 µs and is about 6 orders of magnitude smaller than the lifetime for ADP release from a singly occupied [Formula: see text]-ATPase. An internal consistency test is given by comparing 2 independent ways of obtaining the relaxation time of the probe. They agree and are â¼15 µs.
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ATPases Translocadoras de Prótons/química , ATPases Translocadoras de Prótons/metabolismo , Imagem Individual de Molécula/métodos , Hidrólise , Modelos Moleculares , RotaçãoRESUMO
The Drude-Smith equation is widely used for treating the frequency-dependent electrical conductivity of materials in the terahertz region. An attractive feature is its sparsity of adjustable parameters. A significant improvement over Drude theory for these materials, the theory includes backscattering of the charge carriers. It has nevertheless been criticized, including by Smith himself, because of the arbitrariness of a step in the derivation. We recall a somewhat similar behavior of back scattering in fluids observed in molecular dynamics computations and discussed in terms of memory functions. We show how theories such as Drude-Smith and Cocker etâ al. are examples of a broader class of theories by showing how they also arise as particular cases of a memory function formalism that divides the interactions into short and long range.
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The front cover artwork is provided by Wei-Chen Chen and Rudolph A. Marcus. The image shows an electron undergoing backscattering in a disordered solid, a phenomenon commonly described using the Drude-Smith equation represented by the damping curve. Read the full text of the Article at 10.1002/cphc.202100299.
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Experimental studies on single-molecule junctions are typically in need of a simple theoretical approach that can reproduce or be fitted to experimentally measured transport data. In this context, the single-level variant of the Landauer approach is most commonly used, but methods based on Marcus theory are also gaining popularity. Recently, a generalized theory unifying these two approaches has also been developed. In the present work, we extend this theory so that it includes entropic effects (which can be important when polar solvents are involved but are likely minor for solid-state systems). We investigate the temperature-dependence of the electric current and compare it to the behavior predicted by the Landauer and the conventional Marcus theory. We argue that this generalized theory provides a simple yet effective framework for understanding charge transport through molecular junctions. Furthermore, we explore the role of the entropic effects in different transport regimes and suggest experimental criteria for detecting them in solvated molecular junctions. Finally, in order to account for nuclear tunneling effects, we also demonstrate how lifetime broadening can be introduced into the Marcus-Levich-Dogonadze-Jortner-type description of electron transport.
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A Nomarski polarizing prism has been used in conjunction with a focused laser differential interferometer to measure the phase velocity of a density disturbance at sampling frequencies ≥10MHz. Use of this prism enables the simultaneous measurement of density disturbances at two closely spaced points that can be arbitrarily oriented about the instrument's optical axis. The orientation is prescribed by rotating the prism about this axis. Since all four beams (one beam pair at each measurement point) propagate parallel to one another within the test volume, any bias imparted by density fluctuations away from the measurement plane on the disturbance phase velocity is minimized. A laboratory measurement of a spark-generated shock wave and a wind tunnel measurement of a second-mode instability wave on a cone model in a Mach 6 flow are presented to demonstrate the performance of the instrument. High-speed schlieren imaging is used in both cases to verify the results obtained with the instrument.
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The theory of elastic group transfer for the binding and release rate constants for nucleotides in F1-ATPase as a function of the rotor angle is further extended in several respects. (i) A method is described for predicting the experimentally observed lifetime distribution of long binding events in the controlled rotation experiments by taking into account the hydrolysis and synthesis reactions occurring during these events. (ii) A method is also given for treating the long binding events in the experiments and obtaining the rate constants for the hydrolysis and synthesis reactions occurring during these events. (iii) The theory in the previous paper is given in a symmetric form, an extension that simplifies the application of the theory to experiments. It also includes a theory-based correction of the reported "on" and "off" rates by calculating the missed events. A near symmetry of the data about the angle of -40° and a "turnover" in the binding rate data vs. rotor angle for angles greater than [Formula: see text]40° is also discussed.
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Difosfato de Adenosina/química , ATPases Translocadoras de Prótons/química , Trifosfato de Adenosina/química , Hidrólise , Transporte de Íons , Cinética , Nucleotídeos/química , Ligação Proteica , RotaçãoRESUMO
The rising incidence of infection among youth in sub-Saharan Africa makes HIV-related research among younger people a top priority. There remains, however, a lack of consistent and unambiguous ethical principles and guidance for researchers wishing to conduct HIV studies with adolescents. The overarching aim of our research was to better understand youths' experiences with HIV studies. The present study explored four questions: (1) What strategies are effective for recruiting youth for HIV studies? (2) What motivates youth to participate in these studies? (3) How do study participants perceive HIV testing within the context of a research study? (4) What do participants understand about the risks of study participation? These data are essential to inform guidelines for the responsible conduct of research with young people. We interviewed 82 adolescents (aged 15-19) in Kenya taking part in a study examining ethical issues pertaining to their involvement in HIV-related research. Pursuant to our research questions, we found that direct study recruitment combined with encouragement from female relatives was the greatest facilitator to study enrolment among young people. Most young participants expressed that they were motivated to join the study in order to (1) learn their HIV status (n = 49) and (2) receive HIV-related education (n = 26), even though both are already free and widely available. Participants largely preferred testing in a place they deemed "private," although both the health clinic and home were regarded by adolescents as locations with greater privacy. Adolescents largely did not accurately perceive risks of the study two months after baseline, although they could remember the benefits with great clarity. This work can inform researchers, policymakers, and ethics review committees on approaches to maximize efficiency in recruitment and data collection, and to enhance understanding of risks and benefits in HIV-related research among adolescents. While further research is needed, these data may be used by others conducting HIV research in this region to improve recruitment strategies and more effectively engage and appeal to young people.
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We summarize the different types of single molecule experiments on the F1 component of FOF1-ATP Synthase and what has been learned from them. We also describe results from our recent studies on interpreting the experiments using a chemical-mechanical theory for these biological motors.
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Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , ATPases Translocadoras de Prótons/química , ATPases Translocadoras de Prótons/metabolismo , Trifosfato de Adenosina/metabolismo , CinéticaRESUMO
A recently proposed chemomechanical group transfer theory of rotary biomolecular motors is applied to treat single-molecule controlled rotation experiments. In these experiments, single-molecule fluorescence is used to measure the binding and release rate constants of nucleotides by monitoring the occupancy of binding sites. It is shown how missed events of nucleotide binding and release in these experiments can be corrected using theory, with F1-ATP synthase as an example. The missed events are significant when the reverse rate is very fast. Using the theory the actual rate constants in the controlled rotation experiments and the corrections are predicted from independent data, including other single-molecule rotation and ensemble biochemical experiments. The effective torsional elastic constant is found to depend on the binding/releasing nucleotide, and it is smaller for ADP than for ATP. There is a good agreement, with no adjustable parameters, between the theoretical and experimental results of controlled rotation experiments and stalling experiments, for the range of angles where the data overlap. This agreement is perhaps all the more surprising because it occurs even though the binding and release of fluorescent nucleotides is monitored at single-site occupancy concentrations, whereas the stalling and free rotation experiments have multiple-site occupancy.
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Difosfato de Adenosina/química , Trifosfato de Adenosina/química , Modelos Químicos , ATPases Translocadoras de Prótons/química , Sítios de Ligação , Carbocianinas/química , Elasticidade , Corantes Fluorescentes/química , Hidrólise , Transporte de Íons , Cinética , Ligação Proteica , Rotação , Imagem Individual de Molécula/métodosRESUMO
Experimental measurements were performed on a swept flat-plate model with an airfoil leading edge and imposed chordwise pressure gradient to determine the effects of a backward-facing step on transition in a low-speed stationary crossflow-dominated boundary layer. Detailed hot-wire measurements were performed for three step heights ranging from 36 to 49% of the boundary-layer thickness at the step and corresponding to subcritical, nearly critical, and critical cases. In general, the step had a small localized effect on the growth of the stationary crossflow vortex, whereas the unsteady disturbance amplitudes increased with increasing step height. Intermittent spikes in instantaneous velocity began to appear for the two larger step heights. A physical explanation was provided for the mechanism leading to transition and the sudden movement in the transition front due to the critical steps. The large localized velocity spikes, which ultimately led to an intermittent breakdown of the boundary layer, were the result of nonlinear interactions of the different types of unsteady instabilities with each other and with the stationary crossflow vortices. Thus, the unsteady disturbances played the most important role in transition, but the stationary crossflow vortices also had a significant role via the modulation and the increased amplitude of the unsteady disturbances.
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Tick-borne Babesia parasites are responsible for costly diseases worldwide. Improved control and prevention tools are urgently needed, but development of such tools is limited by numerous gaps in knowledge of the parasite-host relationships. We hereby used atomic force microscopy (AFM) and frequency-modulated Kelvin probe potential microscopy (FM-KPFM) techniques to compare size, texture, roughness and surface potential of normal and infected Babesia bovis, B. bigemina and B. caballi erythrocytes to better understand the physical properties of these parasites. In addition, AFM and FM-KPFM allowed a detailed view of extraerythrocytic merozoites revealing shape, topography and surface potential of paired and single parasites. B. bovis-infected erythrocytes display distinct surface texture and overall roughness compared to noninfected erythrocytes. Interestingly, B. caballi-infected erythrocytes do not display the surface ridges typical in B. bovis parasites. Observations of extraerythrocytic B. bovis, B. bigemina and B. caballi merozoites using AFM revealed differences in size and shape between these three parasites. Finally, similar to what was previously observed for Plasmodium-infected erythrocytes, FM-KPFM images reveal an unequal electric charge distribution, with higher surface potential above the erythrocyte regions that are likely associated with Babesia parasites than over its remainder regions. In addition, the surface potential of paired extraerythrocytic B. bovis Mo7 merozoites revealed an asymmetric potential distribution. These observations may be important to better understand the unique cytoadhesive properties of B. bovis-infected erythrocytes, and to speculate on the role of differences in the distribution of surface charges in the biology of the parasites.
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Babesia bovis/fisiologia , Eritrócitos/parasitologia , Merozoítos/fisiologia , Microscopia de Força Atômica/métodos , Animais , Bovinos , Interações Hospedeiro-Parasita , Imageamento Tridimensional/métodosRESUMO
A theoretical model of elastically coupled reactions is proposed for single molecule imaging and rotor manipulation experiments on F1-ATPase. Stalling experiments are considered in which rates of individual ligand binding, ligand release, and chemical reaction steps have an exponential dependence on rotor angle. These data are treated in terms of the effect of thermodynamic driving forces on reaction rates, and lead to equations relating rate constants and free energies to the stalling angle. These relations, in turn, are modeled using a formalism originally developed to treat electron and other transfer reactions. During stalling the free energy profile of the enzymatic steps is altered by a work term due to elastic structural twisting. Using biochemical and single molecule data, the dependence of the rate constant and equilibrium constant on the stall angle, as well as the Børnsted slope are predicted and compared with experiment. Reasonable agreement is found with stalling experiments for ATP and GTP binding. The model can be applied to other torque-generating steps of reversible ligand binding, such as ADP and Pi release, when sufficient data become available.
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Difosfato de Adenosina/química , Trifosfato de Adenosina/química , Guanosina Trifosfato/química , Modelos Químicos , Simulação de Dinâmica Molecular , ATPases Translocadoras de Prótons/química , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Guanosina Trifosfato/metabolismo , Ligação Proteica , ATPases Translocadoras de Prótons/metabolismo , TermodinâmicaRESUMO
A swept flat plate model with an imposed pressure gradient was experimentally investigated in a low-speed flow to determine the effect of a backward-facing step on transition in a stationary crossflow-dominated flow. Detailed hotwire measurements of boundary-layer flow were performed to investigate the upstream shift in transition due to a step height of 49% of the local unperturbed boundary-layer thickness. Increasing the initial stationary crossflow amplitude caused an upstream movement of the transition front for the backward-facing step case. The step caused a local increase in the growth of the stationary crossflow instabilities, but the stationary crossflow amplitude at transition was sufficiently low (<0.04Ue ) so that stationary crossflow was not solely responsible for transition. The unsteady velocity spectra downstream of the step were rich with unsteady disturbances in the 80- to 1500-Hz range. Three distinct families of disturbances were identified based on phase speed and wave angle, namely, a highly oblique disturbance (possibly traveling-crossflow-like), a Tollmien-Schlichting-wave-like disturbance, and a shear-layer instability. The stationary crossflow disturbances caused a modulation of the unsteady disturbances, resulting in spatially concentrated peaks in unsteady disturbance amplitude. This modulation of the unsteady disturbances is believed to be the reason for the upstream movement of the transition front with increasing stationary crossflow amplitude.
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Supersonic boundary-layer receptivity to freestream acoustic disturbances is investigated by solving the Navier-Stokes equations for Mach 3.5 flow over a 7 deg half-angle cone. The freestream disturbances are generated from a wavy wall placed at the nozzle wall. The freestream acoustic disturbances radiated by the wavy wall are obtained by solving the linearized Euler equations. The results show that no noticeable instability modes are generated when the acoustic disturbances impinge the cone obliquely. The results show that the perturbations generated inside the boundary layer by the acoustic disturbances are the response of the boundary layer to the external forcing. The amplitude of the forced disturbances inside the boundary layer are about 2.5 times larger than the incoming field for zero azimuthal wave number, and they are about 1.5 times for large azimuthal wave numbers.
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OBJECTIVES: Although the postnatal physiology of D-loop transposition of the great arteries with intact ventricular septum (D-TGA/IVS) is well established, little is known about fetal D-TGA/IVS. In the normal fetus, the pulmonary valve (PV) is larger than the aortic valve (AoV), there is exclusive right-to-left flow at the foramen ovale (FO) and ductus arteriosus (DA), and the left ventricle (LV) ejects 40% of combined ventricular output (CVO) through the aorta, primarily to the brain. In D-TGA/IVS, the LV ejects oxygen-rich blood to the pulmonary artery, theoretically leading to pulmonary vasodilation, increased branch pulmonary artery flow and reduced DA flow. In this study, we tested the hypothesis that D-TGA/IVS anatomy results in altered cardiac valve sizes, ventricular contribution to CVO, and FO and DA flow direction. METHODS: Seventy-four fetuses with D-TGA/IVS that underwent fetal echocardiography at our institution between 2004 and 2015 were included in the study. AoV, PV, mitral valve and tricuspid valve sizes were measured and Z-scores indexed to gestational age were generated. Ventricular output was calculated using Doppler-derived velocity-time integral, and direction of flow at the FO and DA shunts was recorded in each fetus using both color Doppler and flap direction. Measurements in the D-TGA/IVS fetuses were compared with data of 222 controls, matched for gestational-age range, from our institutional normal fetal database. RESULTS: The LV component of CVO was higher in D-TGA/IVS fetuses than in controls (50.7% vs 40.2%; P < 0.0001), with no difference in the total CVO. Flow was bidirectional at the FO in 56 (75.7%) and at the DA in 24 (32.4%) D-TGA/IVS fetuses. Only 21.6% fetuses had normal right-to-left flow at both shunts. Bidirectional shunting was more common in third-trimester fetuses than in second-trimester ones (P < 0.03). AoV and PV diameters were nearly identical in D-TGA/IVS in contrast to control fetuses, hence AoV Z-score was higher than PV Z-score (1.13 vs -0.65, P < 0.0001) in D-TGA/IVS. CONCLUSIONS: In fetuses with D-TGA/IVS there is loss of the normal right-sided dominance, as each ventricle provides half of the CVO, with a relatively large AoV diameter and a small PV diameter, and high incidence of bidirectional FO and DA flow. This may support the theory that high pulmonary artery oxygen content reduces pulmonary vascular resistance, thereby increasing branch pulmonary artery flow and venous return, which results in increased LV preload and output. Pulmonary sensitivity to oxygen is thought to increase later in gestation, which may explain the higher incidence of bidirectional shunting. Consequences of these flow alterations include increased aortic and, most likely, brain flow, perhaps in an attempt to compensate for the substrate deficiency observed in D-TGA/IVS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
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Débito Cardíaco/fisiologia , Coração Fetal/fisiopatologia , Fluxo Pulsátil/fisiologia , Transposição dos Grandes Vasos/fisiopatologia , Septo Interventricular/fisiopatologia , Adulto , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/embriologia , Valva Aórtica/fisiopatologia , Ecocardiografia/métodos , Feminino , Coração Fetal/diagnóstico por imagem , Coração Fetal/embriologia , Idade Gestacional , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/embriologia , Ventrículos do Coração/fisiopatologia , Humanos , Gravidez , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/embriologia , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/embriologia , Ultrassonografia Pré-Natal/métodos , Septo Interventricular/diagnóstico por imagem , Septo Interventricular/embriologiaRESUMO
UV-B absorption by the photoreceptor UV resistance locus 8 (UVR8) consisting of two identical protein units triggers a signal chain used by plants in connection with protection and repair of UV-B induced damage. X-ray structural analysis of the purified protein [Christie JM, et al. (2012) Science 335(6075):1492-1496] [Wu D, et al. (2012) Nature 484(7393): 214-220] has revealed that the dimer is held together by arginine-aspartate salt bridges. In this paper we address the initial processes in the signal chain. On the basis of high-level quantum-chemical calculations, we propose a mechanism for the photodissociation of UVR8 that consists of three steps: (i) In each monomer, multiple tryptophans form an extended light-harvesting system in which the La excited state of Trp233 experiences strong electrostatic stabilization by the protein environment. The strong stabilization singles out this tryptophan to be an efficient exciton acceptor that accumulates the excitation energy from the entire protein subunit. (ii) A fast decay of the locally excited state by charge separation generates the radical ion pair Trp285(+)-Trp233(-) with a dipole moment of â¼18 D. (iii) Key to the proposed mechanism is that this large dipole moment drives the breaking of the salt bridges between the two monomer subunits. The suggested mechanism for the UV-B-driven dissociation of the dimer that rests on the prominent players Trp233 and Trp285 explains the experimental results obtained from mutagenesis of UVR8.