UGT76B1, a promiscuous hub of small molecule-based immune signaling, glucosylates N-hydroxypipecolic acid, and balances plant immunity.

Glucosylation modulates the biological activity of small molecules and frequently leads to their inactivation. The Arabidopsis thaliana glucosyltransferase UGT76B1 is involved in conjugating the stress hormone salicylic acid (SA) as well as isoleucic acid (ILA). Here, we show that UGT76B1 also glucosylates N-hydroxypipecolic acid (NHP), which is synthesized by FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1) and activates systemic acquired resistance (SAR). Upon pathogen attack, Arabidopsis leaves generate two distinct NHP hexose conjugates, NHP-O-ß-glucoside and NHP glucose ester, whereupon only NHP-O-ß-glucoside formation requires a functional SA pathway. The ugt76b1 mutants specifically fail to generate the NHP-O-ß-glucoside, and recombinant UGT76B1 synthesizes NHP-O-ß-glucoside in vitro in competition with SA and ILA. The loss of UGT76B1 elevates the endogenous levels of NHP, SA, and ILA and establishes a constitutive SAR-like immune status. Introgression of the fmo1 mutant lacking NHP biosynthesis into the ugt76b1 background abolishes this SAR-like resistance. Moreover, overexpression of UGT76B1 in Arabidopsis shifts the NHP and SA pools toward O-ß-glucoside formation and abrogates pathogen-induced SAR. Our results further indicate that NHP-triggered immunity is SA-dependent and relies on UGT76B1 as a common metabolic hub. Thereby, UGT76B1-mediated glucosylation controls the levels of active NHP, SA, and ILA in concert to balance the plant immune status.

Signal Enhancement of a Differential Photoacoustic Cell by Connecting the Microphones via Capillaries.

Differential photoacoustic spectroscopy (DPAS) cells are usually excited on the first longitudinal ring mode, with a microphone situated in the middle of each of the two resonator tubes. However, it is known from other photoacoustic spectroscopy cell designs that connecting the microphones via a capillary can lead to signal enhancement. By means of finite element method (FEM) simulations, we compared such a photoacoustic spectroscopy (PAS) cell with a capillary to a DPAS cell with a capillary attached to each of the two resonators and showed that the behavior of both systems is qualitatively the same: In both the PAS and the DPAS cell, in-phase and anti-phase oscillations of the coupled system (resonator-capillary) can be excited. In the DPAS cell, capillaries of suitable length also increase the pressure signal at the microphones according to the FEM simulations. For different capillary diameters (1.2 mm/1.7 mm/2.2 mm), the respective optimal capillary length (36-37.5 mm) and signal amplification was determined (94%, 70%, 53%). According to the results of these FEM simulations, a significant increase in sensitivity can, therefore, also be achieved in DPAS cells by expanding them with thin tubes leading to the microphones.

Pipecolic acid synthesis is required for systemic acquired resistance and plant-to-plant-induced immunity in barley.

Defense responses in plants are based on complex biochemical processes. Systemic acquired resistance (SAR) helps to fight infections by (hemi-)biotrophic pathogens. One important signaling molecule in SAR is pipecolic acid (Pip), accumulation of which is dependent on the aminotransferase ALD1 in Arabidopsis. While exogenous Pip primes defense responses in the monocotyledonous cereal crop barley (Hordeum vulgare), it is currently unclear if endogenous Pip plays a role in disease resistance in monocots. Here, we generated barley ald1 mutants using CRISPR/Cas9, and assessed their capacity to mount SAR. Endogenous Pip levels were reduced after infection of the ald1 mutant, and this altered systemic defense against the fungus Blumeria graminis f. sp. hordei. Furthermore, Hvald1 plants did not emit nonanal, one of the key volatile compounds that are normally emitted by barley plants after the activation of SAR. This resulted in the inability of neighboring plants to perceive and/or respond to airborne cues and prepare for an upcoming infection, although HvALD1 was not required in the receiver plants to mediate the response. Our results highlight the crucial role of endogenous HvALD1 and Pip for SAR, and associate Pip, in particular together with nonanal, with plant-to-plant defense propagation in the monocot crop barley.

Metabolomic adjustments in the orchid mycorrhizal fungus Tulasnella calospora during symbiosis with Serapias vomeracea.

All orchids rely on mycorrhizal fungi for organic carbon, at least during early development. In fact, orchid seed germination leads to the formation of a protocorm, a heterotrophic postembryonic structure colonized by intracellular fungal coils, thought to be the site of nutrient transfer. The molecular mechanisms underlying mycorrhizal interactions and metabolic changes induced by this symbiosis in both partners remain mostly unknown. We studied plant-fungus interactions in the mycorrhizal association between the Mediterranean orchid Serapias vomeracea and the basidiomycete Tulasnella calospora using nontargeted metabolomics. Plant and fungal metabolomes obtained from symbiotic structures were compared with those obtained under asymbiotic conditions. Symbiosis induced substantial metabolomic alterations in both partners. In particular, structural and signaling lipid compounds increased markedly in the external fungal mycelium growing near the symbiotic protocorms, whereas chito-oligosaccharides were identified uniquely in symbiotic protocorms. This work represents the first description of metabolic changes occurring in orchid mycorrhiza. These results - combined with previous transcriptomic data - provide novel insights on the mechanisms underlying the orchid mycorrhizal association and open intriguing questions on the role of fungal lipids in this symbiosis.

The isoleucic acid triad: distinct impacts on plant defense, root growth, and formation of reactive oxygen species.

Isoleucic acid (ILA), a branched-chain amino acid-related 2-hydroxycarboxylic acid, occurs ubiquitously in plants. It enhances pathogen resistance and inhibits root growth of Arabidopsis. The salicylic acid (SA) glucosyltransferase UGT76B1 is able to conjugate ILA. Here, we investigate the role of ILA in planta in Arabidopsis and reveal a triad of distinct responses to this small molecule. ILA synergistically co-operates with SA to activate SA-responsive gene expression and resistance in a UGT76B1-dependent manner in agreement with the observed competitive ILA-dependent repression of SA glucosylation by UGT76B1. However, ILA also shows an SA-independent stress response. Nitroblue tetrazolium staining and pharmacological experiments indicate that ILA induces superoxide formation of the wild type and of an SA-deficient (NahG sid2) line. In contrast, the inhibitory effect of ILA on root growth is independent of both SA and superoxide induction. These effects of ILA are specific and distinct from its isomeric compound leucic acid and from the amino acid isoleucine. Leucic acid and isoleucine do not induce expression of defense marker genes or superoxide production, whereas both compounds inhibit root growth. All three responses to ILA are also observed in Brassica napus.

Exploiting the aiming beam to increase the safety of laser lithotripsy: Experimental evaluation of light reflection and fluorescence.

BACKGROUND AND OBJECTIVES: In Holmium laser lithotripsy, usually, the surgeon is guided by a visible beam superimposing the infrared (IR) treatment radiation. It has been shown that a green aiming beam excites stone autofluorescence. This fluorescence signal can be used for calculi detection to check the correct fiber position before triggering the IR laser, thus preventing damage to soft tissue and application devices. However, also the directly reflected green light from the fiber tip gives valuable information on fiber position and its surface condition. MATERIALS AND METHODS: An external fiber-fiber-coupling-box (fiber core diameter 365 µm) for pulsed holmium laser radiation (2.1 µm) was set up containing a green diode laser module (520 nm, average power on the sample <0.5 mW) and optics and detectors for measuring the reflected light of this aiming beam as well as the fluorescence excited with it. Measurements were done via a lock-in technique with more than 20 human calculi samples and porcine calix in vitro. After the implementation of automatic data storage signals during ongoing in vitro lithotripsy procedures were recorded with the fiber positioned on tissue, stone, or in/on medical equipment (working channel of an endoscope, stone retrieval basket). RESULTS: Stone fluorescence signals measured were a factor of 7 to >100 higher than those of tissue. Stone fluorescence was detectable in "non-contact mode" with a linear signal decrease over a distance up to ~1 mm in front of the fiber tip (core diameter 365 µm) and with severely damaged fibers (max. decrease: 75% with pinched off fiber). Reflection signals of the fiber tip surface in air and water surrounding decreased significantly when the fiber was damaged; measured ratios of intact to damaged fiber found in the air were (5-17):1 and in water (1.6-3.7):1. Surfaces in front of the fiber aggravated the evaluation of fiber condition due to reflections but enabled to detect, for example, the working channel of a flexible endoscope in combination with the (missing) fluorescence signal. CONCLUSIONS: Autofluorescence induced by a green aiming beam can be exploited for stone detection in laser lithotripsy. A reflection measurement can give further information on fiber condition and position. Implementing this kind of safety features for an automatic block of IR laser emission in case of weak or missing fluorescence and un-normal reflections can assist the surgeon by avoiding tissue perforation, and damage to medical devices such as endoscopes. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Pipecolic Acid Is Induced in Barley upon Infection and Triggers Immune Responses Associated with Elevated Nitric Oxide Accumulation.

Pipecolic acid (Pip) is an essential component of systemic acquired resistance, priming resistance in Arabidopsis thaliana against (hemi)biotrophic pathogens. Here, we studied the potential role of Pip in bacteria-induced systemic immunity in barley. Exudates of barley leaves infected with the systemic immunity-inducing pathogen Pseudomonas syringae pv. japonica induced immune responses in A. thaliana. The same leaf exudates contained elevated Pip levels compared with those of mock-treated barley leaves. Exogenous application of Pip induced resistance in barley against the hemibiotrophic bacterial pathogen Xanthomonas translucens pv. cerealis. Furthermore, both a systemic immunity-inducing infection and exogenous application of Pip enhanced the resistance of barley against the biotrophic powdery mildew pathogen Blumeria graminis f. sp. hordei. In contrast to a systemic immunity-inducing infection, Pip application did not influence lesion formation by a systemically applied inoculum of the necrotrophic fungus Pyrenophora teres. Nitric oxide (NO) levels in barley leaves increased after Pip application. Furthermore, X. translucens pv. cerealis induced the accumulation of superoxide anion radicals and this response was stronger in Pip-pretreated compared with mock-pretreated plants. Thus, the data suggest that Pip induces barley innate immune responses by triggering NO and priming reactive oxygen species accumulation.

Stone/tissue differentiation for Holmium laser lithotripsy using autofluorescence: Clinical proof of concept study.

BACKGROUND AND OBJECTIVES: Holmium laser lithotripsy is the gold standard for intracorporeal fragmentation of urinary calculi. Usually, a visible beam is superimposed on the IR treatment laser as an aiming beam to guide the surgeon. In vitro tests showed that this aiming beam (532 nm, power <1 mW) excites strong fluorescence on human calculi. Tissue, in contrast, emitted much weaker fluorescence. If this is verified in vivo, the fluorescence signal induced by the aiming beam could be used to implement a feedback loop, preventing the Holmium laser being fired on tissue. MATERIALS AND METHODS: Fluorescence signals of 67 tissue and 68 stone spots were measured in a clinical proof of concept study with eight patients. For this, a modulated excitation/detection scheme (lock-in technique) was implemented. A frequency-doubled, diode-pumped solid-state laser module (532 nm, modulation frequency 66 Hz, average power 0.3 mW) was coupled via a dichroic mirror with the Holmium lithotripsy laser into the treatment fiber. The fluorescence signal entering the treatment fiber was detected via another dichroic mirror with a photodiode and a lock-in amplifier. RESULTS: In most instances (94%), the calculus of a patient gave a signal which was at least twice the maximum signal of ureteral tissue. CONCLUSION: The results of our proof of concept study indicate that measuring the fluorescence signal of a green aiming beam could be used to implement a feedback loop for Holmium laser lithotripsy. Preventing the laser being fired on tissue, this would increase the safety of the procedure. Lasers Surg. Med. 49:361-365, 2017. © 2016 Wiley Periodicals, Inc.

Characterization of the pivotal carbon metabolism of Streptococcus suis serotype 2 under ex vivo and chemically defined in vitro conditions by isotopologue profiling.

Streptococcus suis is a neglected zoonotic pathogen that has to adapt to the nutritional requirements in the different host niches encountered during infection and establishment of invasive diseases. To dissect the central metabolic activity of S. suis under different conditions of nutrient availability, we performed labeling experiments starting from [(13)C]glucose specimens and analyzed the resulting isotopologue patterns in amino acids of S. suis grown under in vitro and ex vivo conditions. In combination with classical growth experiments, we found that S. suis is auxotrophic for Arg, Gln/Glu, His, Leu, and Trp in chemically defined medium. De novo biosynthesis was shown for Ala, Asp, Ser, and Thr at high rates and for Gly, Lys, Phe, Tyr, and Val at moderate or low rates, respectively. Glucose degradation occurred mainly by glycolysis and to a minor extent by the pentose phosphate pathway. Furthermore, the exclusive formation of oxaloacetate by phosphoenolpyruvate (PEP) carboxylation became evident from the patterns in de novo synthesized amino acids. Labeling experiments with S. suis grown ex vivo in blood or cerebrospinal fluid reflected the metabolic adaptation to these host niches with different nutrient availability; however, similar key metabolic activities were identified under these conditions. This points at the robustness of the core metabolic pathways in S. suis during the infection process. The crucial role of PEP carboxylation for growth of S. suis in the host was supported by experiments with a PEP carboxylase-deficient mutant strain in blood and cerebrospinal fluid.

Stone/tissue differentiation for holmium laser lithotripsy using autofluorescence.

BACKGROUND AND OBJECTIVES: Holmium laser lithotripsy is a safe and effective method to disintegrate urinary stones of all compositions in an endoscopic procedure. However, handling and safety could be improved by a real-time feedback system permanently monitoring the position of the treatment fiber. The laser is fired only when the fiber is identified as being placed in front of stone. This work evaluates the potential of fluorescence detection with an excitation wavelength of 532 nm for this purpose. MATERIALS AND METHODS: A fiber-based fluorescence measurement was set-up to acquire autofluorescence signals from several human renal calculi, artificial stones, and porcine tissue samples (renal calix and ureter). Three different approaches were investigated. First, experiments were performed with a pulsed laser source with a wavelength of 532 nm, pulse energy 36.5 ± 1 µJ, pulse duration 1.2 ± 0.5 nanoseconds, and a repetition rate of 1 kHz with 15 urinary concretions. In the second step, a series of measurements on 42 human urinary calculi samples was carried out using low power continuous wave excitation of 0.4 ± 0.1 mW. Fluorescence was also measured simultaneously to stone fragmentation by holmium laser pulses (pulse energy 240 ± 50 mJ, repetition rate 10 Hz). Finally, a modulated excitation/detection scheme (lock-in technique) was implemented to render fluorescence detection insensitive to white background light. RESULTS: Unlike porcine renal calix, ureter, and artificial stone human urinary calculi show a strong fluorescence signal when excited with 532 nm. With pulsed excitation on urinary stone (20,000 ± 11,000) counts were registered at 587 nm with the CCD-array of a grating spectrometer in an integration time of 50 milliseconds. Tissue gave lower count rates of ≤(5,500 ± 1,100) even with longer integration times (500 milliseconds/1 second). With a cw excitation power of 0.4 mW (13,000 ± 11,000) counts were registered in an integration time of 200 milliseconds at 587 nm (porcine renal calix: (770 ± 340)). Modulated excitation (66 Hz) with an average power of 0.3 mW and detection with a photodiode resulted in a lock-in amplifier signal of 1.5-4.3V on stone (background and skin: <0.5V). CONCLUSION: With the lock-in technique, autofluorescence from stones can be detected with only the average excitation power of a green aiming beam overlaid to the Ho:YAG-laser beam (power ≤ 1 mW). Since tissue shows very little autofluorescence when excited with 532 nm, this fluorescence signal enables monitoring of the correct position of the treatment fiber during ureteroscopic procedures.

Metabolic and transcriptional activities of Staphylococcus aureus challenged with high-doses of daptomycin.

Treatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully (13)C-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 min and 3 h after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful toward the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology.

Stone/tissue differentiation during intracorporeal lithotripsy using diffuse white light reflectance spectroscopy: In vitro and clinical measurements.

BACKGROUND AND OBJECTIVE: Holmium laser lithotripsy is the 'gold standard' for intracorporeal fragmentation of stones. However, there is a risk of damaging and perforating the ureter wall when the laser is accidentally fired while the fiber is in contact with tissue. The aim of this study was to evaluate if white illumination light, diffusely reflected back into the treatment fiber and spectrally analyzed, can be used for differentiating between stone and tissue. STUDY DESIGN/MATERIALS AND METHODS: Firstly, in vitro reflectance spectra (Xenon light source, wavelength range λ = 350-850 nm) of 38 human kidney stones, porcine renal calix and ureter tissue were collected. Secondly, in an in vivo study with 8 patients, 72 ureter and 49 stone reflectance signals were recorded during endourological interventions. The spectra were analyzed to discriminate between stone and tissue by the absence or presence of minima due to hemoglobin absorption at λ1 = 542nm and λ3 = 576nm. RESULTS: In vitro, all stone and tissue signals could correctly be identified by calculating the ratio R = I (λ1 = 542 nm)/I (λ2 = 475 nm): Because of the hemoglobin absorption at λ1 , R is smaller for tissue than for calculi. In vivo, only 75% tissue spots could correctly be identified utilizing this method. Using the more sophisticated evaluation of looking for minima in the diffuse reflectance spectra at λ1 = 542 nm and λ3 = 576 nm, 62 out of 64 tissue spots were correctly identified (sensitivity 96.9%). This was also the case for 39 out of 43 stone spots. Taking into account the number of measured spectra, a tissue detection probability of 91% and a stone detection probability of 77% was achieved (significance level 5%). CONCLUSION: White light diffusely reflected off the treatment zone into the fiber can be used to strongly improve the safety of Holmium laser lithotripsy by implementing an automatic feedback control algorithm that averts mispositioning the fiber.

Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence.

OBJECTIVE: It has been shown that optical coherence tomography (OCT) can identify brain tumor tissue and potentially be used for intraoperative margin diagnostics. However, there is limited evidence on its use in human in vivo settings, particularly in terms of its applicability and accuracy of residual brain tumor detection (RTD). For this reason, a microscope-integrated OCT system was examined to determine in vivo feasibility of RTD after resection with automated scan analysis. METHODS: Healthy and diseased brain was 3D scanned at the resection edge in 18 brain tumor patients and investigated for its informative value in regard to intraoperative tissue classification. Biopsies were taken at these locations and labeled by a neuropathologist for further analysis as ground truth. Optical OCT properties were obtained, compared, and used for separation with machine learning. In addition, two artificial intelligence-assisted methods were utilized for scan classification, and all approaches were examined for RTD accuracy and compared to standard techniques. RESULTS: In vivo OCT tissue scanning was feasible and easily integrable into the surgical workflow. Measured backscattered light signal intensity, signal attenuation, and signal homogeneity were significantly distinctive in the comparison of scanned white matter to increasing levels of scanned tumor infiltration (p < 0.001) and achieved high values of accuracy (85%) for the detection of diseased brain in the tumor margin with support vector machine separation. A neuronal network approach achieved 82% accuracy and an autoencoder approach 85% accuracy in the detection of diseased brain in the tumor margin. Differentiating cortical gray matter from tumor tissue was not technically feasible in vivo. CONCLUSIONS: In vivo OCT scanning of the human brain has been shown to contain significant value for intraoperative RTD, supporting what has previously been discussed for ex vivo OCT brain tumor scanning, with the perspective of complementing current intraoperative methods for this purpose, especially when deciding to withdraw from further resection toward the end of the surgery.

The neurosurgical benefit of contactless in vivo optical coherence tomography regarding residual tumor detection: A clinical study.

Purpose: In brain tumor surgery, it is crucial to achieve complete tumor resection while conserving adjacent noncancerous brain tissue. Several groups have demonstrated that optical coherence tomography (OCT) has the potential of identifying tumorous brain tissue. However, there is little evidence on human in vivo application of this technology, especially regarding applicability and accuracy of residual tumor detection (RTD). In this study, we execute a systematic analysis of a microscope integrated OCT-system for this purpose. Experimental design: Multiple 3-dimensional in vivo OCT-scans were taken at protocol-defined sites at the resection edge in 21 brain tumor patients. The system was evaluated for its intraoperative applicability. Tissue biopsies were obtained at these locations, labeled by a neuropathologist and used as ground truth for further analysis. OCT-scans were visually assessed with a qualitative classifier, optical OCT-properties were obtained and two artificial intelligence (AI)-assisted methods were used for automated scan classification. All approaches were investigated for accuracy of RTD and compared to common techniques. Results: Visual OCT-scan classification correlated well with histopathological findings. Classification with measured OCT image-properties achieved a balanced accuracy of 85%. A neuronal network approach for scan feature recognition achieved 82% and an auto-encoder approach 85% balanced accuracy. Overall applicability showed need for improvement. Conclusion: Contactless in vivo OCT scanning has shown to achieve high values of accuracy for RTD, supporting what has well been described for ex vivo OCT brain tumor scanning, complementing current intraoperative techniques and even exceeding them in accuracy, while not yet in applicability.

Theoretical and experimental evaluation of the distance dependence of fiber-based fluorescence and reflection measurements for laser lithotripsy.

Objectives. In laser lithotripsy, a green aiming beam overlying the infrared (IR) treatment radiation gives rise to reflection and fluorescence signals that can be measured via the treatment fiber. While stone autofluorescence is used for target detection, the condition of the fiber can be assessed based on its Fresnel reflection. For good applicability, fluorescence detection of stones should work even when the stone and fiber are not in direct contact. Fiber breakage detection, on the other hand, can be falsified if surfaces located in front of the fiber reflect light from the aiming laser back into it. For both applications, therefore, a fundamental investigation of the dependence of the signal amplitude on the distance between fiber and surface is important.Methods. Calculations of the signal drop of fluorescence or diffuse and specular reflection with increasing fiber distance were performed using ray tracing based on a simple geometric model for different fiber core diameters. Reflection signals from a mirror, diffuse reflector, human calculi, and porcine renal tissue placed in water were measured at varying distances (0-5 mm). For human calculi, fluorescence signals were recorded simultaneously.Results. The calculations showed a linear signal decrease down to ∼60% of the maximum signal (fiber in contact). The distancezat which the signal drops to for example 50% depends linearly on the diameter of the fiber core. For fibers used in lithotripsy and positioned in water,z50%ranges from 0.55 mm (200µm core diameter) to 2.73 mm, (1 mm core diameter). The calculations were in good agreement with the experimental results.Conclusions. The autofluorescence signals of stones can be measured in non-contact mode. Evaluating the Fresnel signal of the end face of the fiber to detect breakage is possible unless the fiber is situated less than some millimeters to reflecting surfaces.

Registration of histological brain images onto optical coherence tomography images based on shape information.

Identifying tumour infiltration zones during tumour resection in order to excise as much tumour tissue as possible without damaging healthy brain tissue is still a major challenge in neurosurgery. The detection of tumour infiltrated regions so far requires histological analysis of biopsies taken from at expected tumour boundaries. The gold standard for histological analysis is the staining of thin cut specimen and the evaluation by a neuropathologist. This work presents a way to transfer the histological evaluation of a neuropathologist onto optical coherence tomography (OCT) images. OCT is a method suitable for real timein vivoimaging during neurosurgery however the images require processing for the tumour detection. The method demonstrated here enables the creation of a dataset which will be used for supervised learning in order to provide a better visualization of tumour infiltrated areas for the neurosurgeon. The created dataset contains labelled OCT images from two different OCT-systems (wavelength of 930 nm and 1300 nm). OCT images corresponding to the stained histological images were determined by shaping the sample, a controlled cutting process and a rigid transformation process between the OCT volumes based on their topological information. The histological labels were transferred onto the corresponding OCT images through a non-rigid transformation based on shape context features retrieved from the sample outline in the histological image and the OCT image. The accuracy of the registration was determined to be 200 ± 120µm. The resulting dataset consists of 1248 labelled OCT images for each of the two OCT systems.

Differentiation of different stages of brain tumor infiltration using optical coherence tomography: Comparison of two systems and histology.

The discrimination of tumor-infiltrated tissue from non-tumorous brain tissue during neurosurgical tumor excision is a major challenge in neurosurgery. It is critical to achieve full tumor removal since it directly correlates with the survival rate of the patient. Optical coherence tomography (OCT) might be an additional imaging method in the field of neurosurgery that enables the classification of different levels of tumor infiltration and non-tumorous tissue. This work investigated two OCT systems with different imaging wavelengths (930 nm/1310 nm) and different resolutions (axial (air): 4.9 µm/16 µm, lateral: 5.2 µm/22 µm) in their ability to identify different levels of tumor infiltration based on freshly excised ex vivo brain samples. A convolutional neural network was used for the classification. For both systems, the neural network could achieve classification accuracies above 91% for discriminating between healthy white matter and highly tumor infiltrated white matter (tumor infiltration >60%) .This work shows that both OCT systems with different optical properties achieve similar results regarding the identification of different stages of brain tumor infiltration.

Continuous generation of single photons with controlled waveform in an ion-trap cavity system.

The controlled production of single photons is of fundamental and practical interest; they represent the lowest excited quantum states of the radiation field, and have applications in quantum cryptography and quantum information processing. Common approaches use the fluorescence of single ions, single molecules, colour centres and semiconductor quantum dots. However, the lack of control over such irreversible emission processes precludes the use of these sources in applications (such as quantum networks) that require coherent exchange of quantum states between atoms and photons. The necessary control may be achieved in principle in cavity quantum electrodynamics. Although this approach has been used for the production of single photons from atoms, such experiments are compromised by limited trapping times, fluctuating atom-field coupling and multi-atom effects. Here we demonstrate a single-photon source based on a strongly localized single ion in an optical cavity. The ion is optimally coupled to a well-defined field mode, resulting in the generation of single-photon pulses with precisely defined shape and timing. We have confirmed the suppression of two-photon events up to the limit imposed by fluctuations in the rate of detector dark counts. The stream of emitted photons is uninterrupted over the storage time of the ion, as demonstrated by a measurement of photon correlations over 90 min.

Corrigendum: The Defense-Related Isoleucic Acid Differentially Accumulates in Arabidopsis Among Branched-Chain Amino Acid-Related 2-Hydroxy Carboxylic Acids.

[This corrects the article DOI: 10.3389/fpls.2018.00766.].