Effects Of Aberrations Research Articles

Effects of aberrations on isoSTED microscopy

Aberrations are inevitable in optical microscopes and affect the image quality. In STED microscopy, the optical resolution is especially dominated by the performance of depletion pattern. To quench fluorescence only in the periphery of the excitation focus, the depletion focus ideally has a zero-intensity point that is surrounded by a high-intensity crest. Otherwise, distortion of the depletion beam causes unwanted fluorescence inhibition. The influence of aberrations on isoSTED microscopy differs from that on STED microscopy because isoSTED microscopy generates a more complicated shape of the depletion focal spot with two opposing objectives which have different focusing properties. We present analysis that elucidates the effects on the shape, the central minimum intensity, and the peak intensity of the isoSTED pattern regarding primary aberrations such as astigmatism, coma, and spherical aberration when those aberrations are added in the shared beam path and each beam path in the 4Pi-cavity. The simulation results demonstrate significant resolution degradation (>160%; defined as the focal volume) for the aberrations with root mean square wavefront errors of 0.5 rad.

Wavefront error of PHI/HRT on Solar Orbiter at various heliocentric distances

Aims.We use wavefront sensing to characterise the image quality of the High Resolution Telescope (HRT) of the Polarimetric and Helioseismic Imager (SO/PHI) data products during the second remote sensing window of the Solar Orbiter (SO) nominal mission phase. Our ultimate aims are to reconstruct the HRT data by deconvolving with the HRT point spread function (PSF) and to correct for the effects of optical aberrations on the data.Methods.We use a pair of focused–defocused images to compute the wavefront error and derive the PSF of HRT by means of a phase diversity (PD) analysis.Results.The wavefront error of HRT depends on the orbital distance of SO to the Sun. At distances > 0.5 au, the wavefront error is small, and stems dominantly from the inherent optical properties of HRT. At distances < 0.5 au, the thermo-optical effect of the Heat Rejection Entrance Window (HREW) becomes noticeable. We develop an interpolation scheme for the wavefront error that depends on the thermal variation of the HREW with the distance of SO to the Sun. We also introduce a new level of image reconstruction, termed ‘aberration correction’, which is designed to reduce the noise caused by image deconvolution while removing the aberrations caused by the HREW.Conclusions.The computed PSF via phase diversity significantly reduces the degradation caused by the HREW in the near-perihelion HRT data. In addition, the aberration correction increases the noise by a factor of only 1.45 compared to the factor of 3 increase that results from the usual PD reconstructions.

Wavefront measurements using the Ronchi test for high-NA lithography projection lenses.

The Ronchi test is widely used for wavefront measurements in advanced lithography tools, and a physical optics explanation of the Ronchi test based on scalar diffraction theory can be found in numerous publications. However, for high-numerical aperture (high-NA) lithography projection lenses, the vector nature of light should be considered when performing wavefront measurements, especially the effect of polarization aberrations on the wavefront test results. In this paper, a vector model for describing shearing interferometry for high-NA lithography projection lenses is established. In addition to considering the vector nature of light, the vector model also calculates the Ronchigram on the screen of a detector at any distance from a diffraction grating, as opposed to the distance restriction for the Fraunhofer diffraction approximation used by the existing methods. Using the developed mathematical model of the Ronchi test, the Ronchigrams of high-NA lithography projection lenses under non-polarized illumination are simulated, and the effect of the distance between the diffraction grating and the detection screen on the wavefront measurement accuracy are discussed.

Stakekold ZXSY Brazil, Precision Medicine in Pediatric Clinic: Reward Deficiency Syndrome (RDS) Is Surprisingly Evolving and Found Everywhere: Is It “Blowing in the Wind”? Yes, but how Syndrome Z.

Much neurobiological and psychological knowledge about brain development and maturation in pregnancy and early childhood should be evaluated simultaneously, due to several underlying pathophysiological findings, because with proven clinical evidence, with time greater than twenty years, such as situations of Adverse Emotions in Childhood (ACE ), Post Traumatic Stress Disorder (PTSD), and recently the absence/deficit of oxytoninergic neurons responsible for family synchrony, cause a series of aberrant pathophysiological effects, with inflammatory, behavioral, cognitive, affective and social impairments [1].

Shadows of rotating black holes in plasma environments with aberration effects

The shadows of black holes encode significant information about the properties of black holes and the spacetime surrounding them. So far, the effects of dispersive media, such as plasma, and relativistic aberration on the propagation of light around compact objects have been treated separately in the literature. In this paper, we will employ the Konoplya, Stuchl\'{\i}k, and Zhidenko family of stationary, axially symmetric, and asymptotically flat metrics to describe the spacetime around rotating black holes. We will study how the parameters of the black hole, the chromatic effects resulting from the presence of a nonmagnetized, pressureless plasma environment, and the effects of relativistic aberration of a moving observer modify the morphology of the shadow.

Effect of Higher Order Aberrations and Intraocular Scatter on Optical Quality Based on an Optical Eye Model

The impact of intraocular scatter and higher order aberrations (HOAs) on ocular optical quality was investigated. An optical eye model was constructed using the measured ocular aberrations, corneal surfaces, axial length, and scatter fraction, and the impact of HOAs and scatter on modulation transfer functions (MTFs) was studied based on the newly established optical eye model. For uniform intraocular scatter, the monochromatic and polychromatic MTF decreased as the HOAs or scatter fractions increased independently at each spatial frequency, which implied that both were essential for visual quality. In addition, the scatter effect on MTF was more significant for the eye with less HOA. The combined deterioration effect of these two factors on the MTF was less than their summation, suggesting a potential compensatory mechanism between HOAs and scatter.

Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment.

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK and ERK in melanoma is largely unknown. We demonstrate the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin. Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.

Effects of primary aberrations on a dark-field microscopy imaging system with the sharper focusing lens

The effects of primary aberrations of the sharper focusing lens on the image quality is analyzed for a dark-field microscopy imaging system, which is illuminated by a left-circularly (LC) polarized Laguerre–Gaussian (LG) vortex beam. To confirm the aberration tolerance range of the sharper focusing lens for precise measurement, the analytical expression of the field distribution on the image plane is deduced. Then the dark-field image results corresponding to a defect with a scale of 6µm×6µm are simulated. The influence of the spherical error, coma, and astigmatism on the imaging quality is compared in detail. Then the verification test has been carried out to show the effects of different primary aberrations. Finally, both the simulation and experiment results help us to identify that the tolerance range of spherical aberration, astigmatism, and coma should be less than 1.5λ, 1λ, and 1.25λ, respectively.

Commissioning of the DESIR high-resolution mass separator

DESIR is, together with S3-LEB, the low-energy part of the SPIRAL2 ISOL facility at GANIL. The High-Resolution mass Separator (HRS) included in DESIR is a 180° symmetric online separator with two 90° magnetic dipole sections arranged with electrostatic quadrupoles, sextupoles and a 48-pole electrostatic multipole on the mid plane. The HRS is now completely mounted at LP2i Bordeaux and under commissioning for the next years before its transfer to the entrance of the DESIR facility. Optical aberrations, mainly introduced by the dipoles, must be corrected up to the highest possible order to guarantee an optimal resolution of the separator. They are measured with a pepperpot-type emittance-meter, analyzed then corrected with the multipole. Up to now, 2nd order (hexapolar) and part of 3rd order (octupolar) aberrations are under control and an optimal FWHM separation has been achieved for two identical beams with a relative energy difference of ΔE/E(≡ΔM/M)=1/23400.In this paper, we present the effects of optical aberrations on the beam and its emittance figure, as well as the effect of the associated corrections with the multipole. Finally, we will show the latest resolution measurements and associated methodology.

Chronic arsenic exposure induces ferroptosis via enhancing ferritinophagy in chicken livers

Arsenic (As) is a well-known pollutant in the environment, whose contamination in groundwater is a serious threat to animals and humans. Ferroptosis, a form of cell death caused by iron-dependent lipid peroxidation, is involved in various pathological processes. Ferritinophagy is the selective autophagy of ferritin and a crucial step in the induction of ferroptosis. However, the mechanism of ferritinophagy in poultry livers exposed to As remains unexplored. In this study, we investigated whether As-induced chicken liver injury is related to ferritinophagy-mediated ferroptosis at the cellular and animal levels. Our results showed that As exposure via drinking water induced hepatotoxicity in chickens, characterized by abnormal liver morphology and elevated liver function markers. Our data suggested chronic As exposure led to mitochondrial dysfunction, oxidative stress, and impaired cellular processes in chicken livers and LMH cells. Our results also showed that As exposure activated the AMPK/mTOR/ULK1 signaling pathway and significantly changed the levels of ferroptosis and autophagy-related proteins in chicken livers and LMH cells. Moreover, As exposure induced iron overload and lipid peroxidation in chicken livers and LMH cells. Interestingly, pretreatment with ferrostatin-1, chloroquine (CQ), and deferiprone alleviated these aberrant effects. Using CQ, we found that As-induced ferroptosis is autophagy-dependent. Our findings further suggested chronic As exposure induced chicken liver injury by promoting ferritinophagy-mediated ferroptosis, as evidence by activated autophagy, decreased mRNA expression of FTH1, increased intracellular iron content, and alleviation of ferroptosis through pretreatment with CQ. In conclusion, ferritinophagy-mediated ferroptosis is one of the critical mechanisms of As-induced chicken liver injury. Inhibiting ferroptosis may provide new insights for preventing and treating liver injury induced by environmental As exposure in livestock and poultry.

A homozygous EVC mutation in a prenatal fetus with Ellis-van Creveld syndrome.

Ellis-van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases. A Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole-exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied. WES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.-164_174del, which ultimately leads to a 337 bp deletion at the 3' end of exon 1 and loss of the start codon. This is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity.

Aberration-compensated supercritical lens for sub-diffractive focusing within 20° field of view.

The supercritical lens has shown a remarkable capability of achieving far-field sub-diffraction limited focusing through elaborating a modulated interference effect. Benefiting from the relative high energy utilization efficiency and weak sidelobe properties, the supercritical lens holds significant advantage in a series of application scenarios. However, all of the demonstrated supercritical lenses mainly work in the on-axis illumination condition, so the off-axis aberration effect will severely deteriorate its sub-diffraction limit focusing capability for the illuminating beam with an oblique angle. In this work, an aberration-compensated supercritical lens with single-layer configuration is proposed and experimentally demonstrated. Such a single-layer supercritical lens consists of multilevel phase configurations patterned with the two-photon polymerization lithography technique. The simulation and experimental recorded results show that the aberration-compensated supercritical lens with a numerical aperture value of 0.63 could achieve a far-field sub-diffraction limited focusing property within 20° field of view at a wavelength of λ = 633 nm. This monochromatic aberration-compensated supercritical lens with single-layer configuration indicates excellent potential in the development of laser scanning ultrahigh optical storage and label free super-resolution imaging.

Impacts of low-order aberrations on capacity of orbital-angular-momentum quantum states

We use Hypergeometric Gaussian-II (HyGG-II) modes to investigate the impacts of non-Kolmogorov atmospheric turbulence on the Holevo channel capacity of a quantum communication scheme. The capacity of HyGG-II modes can be higher than that of Laguerre–Gaussian modes via modulating the hollowness parameter. The influences of low-order turbulence aberrations including tilt, defocus, astigmatism, and coma on the capacity are also explored. Generally, tilt aberration dominates among all low-order aberrations and defocus and astigmatism aberrations are always negligible. By contrast, the effect of coma aberration can be enhanced to be non-negligible when the turbulence strength or the channel zenith angle is enhanced. We also show that only the total and tilt aberrations are sensitive to the non-Kolmogorov power-law exponent. Our results may contribute to the quantum optical communication as well as aberration compensation in turbulent channels utilizing the novel family of vortex beams.

Coma Off It: Regularizing Variable Point-spread Functions

We describe a rapid and direct method for regularizing, post facto, the point-spread function (PSF) of a telescope or other imaging instrument across its entire field of view (FOV). Imaging instruments in general blur point sources of light by local convolution with a PSF that varies slowly across the FOV, due to coma, spherical aberration, and similar effects. It is possible to regularize the PSF in post-processing, producing data with a homogeneous “effective PSF” across the entire FOV. In turn, the method enables seamless wide-field astronomical mosaics at higher resolution than would otherwise be achievable, and potentially changes the design trade space for telescopes, lenses, and other optical systems where data uniformity is important. For many kinds of optical aberration, simple and rapid convolution with a locally optimized “transfer PSF” produces extremely uniform imaging properties at low computational cost. PSF regularization does not require access to the instrument that obtained the data, and can be bootstrapped from existing data sets that include starfield images or other means of estimating the PSF across the field.

The Effects of Blue-Light Filtering Intraocular Implants on Glare Geometry

Purpose One common complaint with natural opacified lenses is the deleterious effects of higher-order ocular aberrations and intraocular scatter, such as halos and starbursts, which are not always remedied with surgery and intraocular lens (IOL) implantation. Blue-light filtering (BLF) IOL filter scatter-prone short-wave light. Here, we determine whether BLF IOL reduce halo and starburst size. Methods This study was a case-control design, between- and within-subjects (contralateral implantation). Sixty-nine participants with either the BLF IOL (n = 25; AlconSN60AT), clear IOL (n = 24; AlconSA60AT or WF), or both (n = 20) IOL participated. Participants were exposed to a point source of broadband simulated sunlight, which created the appearance of halos/starbursts. Dysphotopsia was measured as the diameter of broadband light-induced halos and starbursts. Results A case-control analysis. Halo size was significantly larger (t[35.05] = 2.98, p = 0.005) in participants with the clear control lens (M = 3°55′ ± 2°48′), compared to the BLF IOL (M = 1°84′ ± 1°34′). Starburst size was not significantly different between groups. Contralateral analysis. Halo size was significantly smaller (t = −3.89, p = .001) in test eyes with the BLF (M = 3°16′ ± 2°35′) compared to the fellow control eyes (M = 5°42′ ± 3°17′). Starburst size was also significantly smaller (t = −2.60, p < 0.018) in BLF test eyes (M = 9°57′ ± 4°25′) than the fellow eye with the clear IOL (M = 12°33′ ± 5°25′). Conclusions BLF IOL filter short-wave light and mimic retinal screening by the young, natural crystalline lens. Such filtering can reduce some deleterious effects of bright light by decreasing ocular diffusion/halos and starbursts.

Exploring X Chromosomal Aberrations in Ovarian Cells by using Fluorescence In Situ Hybridization.

Millions of people worldwide deal with issues concerning fertility. Reduced fertility, or even infertility, may be due to many different causes, including genetic disorders, of which chromosomal abnormalities are the most common. Fluorescence in situ hybridization (FISH) is a well-known and frequently used method to detect chromosomal aberrations in humans. FISH is mainly used for the analysis of chromosomal abnormalities in the spermatozoa of males with numerical or structural chromosomal aberrations. Furthermore, this technique is also frequently applied in females to detect X chromosomal aberrations that are known to cause ovarian dysgenesis. However, information on the X chromosomal content of ovarian cells from females with X chromosomal aberrations in lymphocytes and/or buccal cells is still lacking. The aim of this study is to advance basic research regarding X chromosomal aberrations in females, by presenting two methods based on FISH to identify the X chromosomal content of ovarian cells. First, a method is described to determine the X chromosomal content of isolated ovarian cells (oocytes, granulosa cells, and stromal cells) in non-grafted ovarian cortex tissue from females with X chromosomal aberrations. The second method is directed at evaluating the effect of chromosomal aberrations on folliculogenesis by determining the X chromosomal content of ovarian cells of newly formed secondary and antral follicles in ovarian tissue, from females with X chromosomal aberrations after long-term grafting into immunocompromised mice. Both methods could be helpful in future research to gain insight into the reproductive potential of females with X chromosomal aberrations.

Abstract 3542: A stem cell model dissects detrimental effects of neuroblastoma-linked chromosomal aberrations on cell differentiation during neural crest development

Abstract Early childhood malignancies are driven by sparse genetic aberrations in oncogenes that often co-occur with large copy number variants (CNVs). The combination of these mutations is thought to transform developmentally pliant embryonic cells to initiate tumorigenesis. However, the mechanistic interactions between CNVs, oncogenes, and differentiation have not been systematically studied due to several obstacles: (i) CNVs cannot be engineered efficiently yet; (ii) transient embryonic progenitors are absent in full-grown tumors; and (iii) inter-species differences in lineage specification limit the applicability of animal models. To overcome these challenges, we used isogenic human embryonic stem cell (hESC) lines carrying gains of chromosome 17q/1q, which are prevalent in the embryonal tumor neuroblastoma (NB). We differentiated these cells toward trunk neural crest (NC) and their sympathoadrenal derivatives, the putative cells-of-origin of NB, and performed single-cell RNA sequencing and cell-biological assays at key differentiation stages. We found that CNVs impaired the specification of sympathoadrenal cell types and instead potentiated early Schwann-cell-precursor-like phenotypes. Additional overexpression of the oncogene MYCN (which is frequently amplified together with CNVs in high-risk NB tumors) exacerbated these differentiation defects, enabled tumourigenic cell proliferation, and generated cell states in vitro that transcriptionally resembled NB tumor cells. Finally, using epigenome analysis, we connected these states to a stepwise disruption of gene-regulatory networks centered on developmental transcription factors. Together, our results chart a mechanistic route to NB tumorigenesis and provide a general framework for the CNV-driven initiation of embryonal tumors, in which CNVs ‘prime’ embryonic cells for oncogenic transformation. The tumor-like cells in our model may serve as proxies to experimentally test therapeutic interventions during tumorigenesis. Citation Format: Ingrid M. Saldana-Guerrero, Luis F. Montano-Gutierrez, Christoph Hafemeister, Dylan Stavish, Lisa E. Shaw, Irfete S. Fetahu, Andrea Wenninger-Weinzierl, Caterina Sturtzel, Celine Souilhol, Sophia Tarelli, Mohamed R. Shoeb, Marie Bernkopf, Polyxeni Bozatzi, Maria Guarini, Eva Bozsaky, Michelle C. Buri, Eva M. Putz, Peter W. Andrews, Ivana Barbaric, Helen E. Bryant, Martin Distel, Sabine Taschner-Mandl, Matthias Farlik, Anestis Tsakiridis, Florian Halbritter. A stem cell model dissects detrimental effects of neuroblastoma-linked chromosomal aberrations on cell differentiation during neural crest development. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3542.

Effects of Aberrations on Point Spread Function of Three Zone Aberrated Optical Imaging System with Variable Apodization

Effects of Aberrations on Point Spread Function of Three Zone Aberrated Optical Imaging System with Variable Apodization

Spectral Effects and Range of Focus in a Multizonal-Refractive Intraocular Lens Compared with a Standard Trifocal Diffractive Design.

This study was performed to compare the optical performance of a multizonal presbyopia-correcting intraocular lens (IOL) and a conventional trifocal model. The optical quality and simulated visual acuity (VA) of 570 Precizon Presbyopic NVA (OPHTEC BV) and AcrySof IQ PanOptix (Alcon) were compared. The Precizon features a refractive design consisting of alternating optical zones that converge the incident light into two principal foci and a transitional zone for intermediate vision. By contrast, the PanOptix applies a diffractive (non-apodized) profile to achieve trifocality. Simulated VA was derived from the modulation transfer function. Chromatic aberration effects were also studied. The diffractive and multizonal-refractive lenses yielded comparable simulated VAs at far focus (0.00 logMAR). All curves showed a reduction in expected VA with an increase in negative defocus. At -1.0 D, the multizonal-refractive IOL's VA dropped by 0.05 logMAR, but for the diffractive model, it was one line (0.11 logMAR). The multizonal-refractive lens's VA prediction at the secondary peak was 0.03 logMAR-minimally better than the 0.06 logMAR of the diffractive lens at -2.5 D. The refractive lens exhibited a 24% decrease in polychromatic optical quality due to material dispersion. The performance of PanOptix was more substantially affected, showing a 44% loss at 50 lp/mm at far, with minimal effects at other distances. The multizonal-refractive lens does not fall short of the established trifocal IOL, and it can be used to extend the visual range of pseudophakic patients. Although the multizonal-refractive lens has lower material dispersion, the diffractive model corrects chromatism beyond far focus.

Effect of larger corneal spherical aberration in improving the near visual acuity of eyes implanted with the TECNIS Symfony.

To explore the effect of corneal spherical aberration on the visual acuity and visual quality of eyes implanted with the TECNIS Symfony intraocular lens (IOL). A total of 43 patients with age-related cataract (60 eyes) undergoing phacoemulsification and TECNIS Symfony IOL implantation were enrolled in this study. The uncorrected distance (UDVA), intermediate (UIVA), near visual acuity (UNVA), corrected distance visual acuity (CDVA), contrast sensitivity, and ocular spherical aberration were recorded 3 months after surgery. Preoperative and postoperative corneal spherical aberration were also measured using the iTrace device. Objective scattering index (OSI), modulation transfer function cut-off frequency (MTF cut-off), and Strehl ratio (SR) were measured by the Optical Quality Analyzing System. Catquest-9SF questionnaire were applied too. Spearman's correlation analysis was used to evaluate the relationship between spherical aberration and visual quality parameters. Patients were satisfied with their postoperatively visual quality. And the postoperative logMAR UDVA, UIVA, UNVA, and CDVA was 0.05 ± 0.07, 0.04 ± 0.06, 0.15 ± 0.07, and 0.03 ± 0.05, respectively. The mean preoperative corneal spherical aberration was 0.24 ± 0.10 μm, which is the only factor influencing postoperatively UNVA, and it was negatively correlated with UNVA and glare contrast sensitivity under 18 cpd (cycle/degree, cpd) spatial frequency (r = -0.403, -0.300, -0.360; all P < 0.05). Additionally, the greater the residual spherical aberration of the cornea, the better the near vision after operation. The mean postoperative ocular spherical aberration was -0.03 ± 0.07 μm, it was not correlated with visual acuity, contrast sensitivity, and visual quality (all P > 0.05). Preoperative positive spherical aberration can benefit near vision while decrease contrast sensitivities at high spatial frequencies when implanted with the TECNIS Symfony IOL.