Ultrafast spin-lasers.

Lasers have both ubiquitous applications and roles as model systems in which non-equilibrium and cooperative phenomena can be elucidated1. The introduction of novel concepts in laser operation thus has potential to lead to both new applications and fundamental insights2. Spintronics3, in which both the spin and the charge of the electron are used, has led to the development of spin-lasers, in which charge-carrier spin and photon spin are exploited. Here we show experimentally that the coupling between carrier spin and light polarization in common semiconductor lasers can enable room-temperature modulation frequencies above 200 gigahertz, exceeding by nearly an order of magnitude the best conventional semiconductor lasers. Surprisingly, this ultrafast operation of the resultant spin-laser relies on a short carrier spin relaxation time and a large anisotropy of the refractive index, both of which are commonly viewed as detrimental in spintronics3 and conventional lasers4. Our results overcome the key speed limitations of conventional directly modulated lasers and offer a prospect for the next generation of low-energy ultrafast optical communication.

Uncovering epigenetic and transcriptional regulation of growth in Douglas-fir: identification of differential methylation regions in mega-sized introns.

Tree growth performance can be partly explained by genetics, while a large proportion of growth variation is thought to be controlled by environmental factors. However, to what extent DNA methylation, a stable epigenetic modification, contributes to phenotypic plasticity in the growth performance of long-lived trees remains unclear. In this study, a comparative analysis of targeted DNA genotyping, DNA methylation and mRNAseq profiling for needles of 44-year-old Douglas-fir trees (Pseudotsuga menziesii (Mirb.) Franco) having contrasting growth characteristics was performed. In total, we identified 195 differentially expressed genes (DEGs) and 115 differentially methylated loci (DML) that are associated with genes involved in fitness-related processes such as growth, stress management, plant development and energy resources. Interestingly, all four intronic DML were identified in mega-sized (between 100 and 180 kbp in length) and highly expressed genes, suggesting specialized regulation mechanisms of these long intron genes in gymnosperms. DNA repetitive sequences mainly comprising long-terminal repeats of retroelements are involved in growth-associated DNA methylation regulation (both hyper- and hypomethylation) of 99 DML (86.1% of total DML). Furthermore, nearly 14% of the DML was not tagged by single nucleotide polymorphisms, suggesting a unique contribution of the epigenetic variation in tree growth.

In-vitro effects of novel periodontal scalers with a planar ultrasonic piezoelectric transducer on periodontal biofilm removal, dentine surface roughness, and periodontal ligament fibroblasts adhesion.

OBJECTIVES: To compare ultrasonic scaler prototypes based on a planar piezoelectric transducer with different working frequencies featuring a titanium (Ti-20, Ti-28, and Ti-40) or stainless steel (SS-28) instrument, with a commercially available scaler (com-29) in terms of biofilm removal and reformation, dentine surface roughness and adhesion of periodontal fibroblasts. MATERIALS AND METHODS: A periodontal multi-species biofilm was formed on specimens with dentine slices. Thereafter specimens were instrumented with scalers in a periodontal pocket model or left untreated (control). The remaining biofilms were quantified and allowed to reform on instrumented dentine slices. In addition, fibroblasts were seeded for attachment evaluation after 72 h of incubation. Dentine surface roughness was analyzed before and after instrumentation. RESULTS: All tested instruments reduced the colony-forming unit (cfu) counts by about 3 to 4 log10 and the biofilm quantity (each p < 0.01 vs. control), but with no statistically significant difference between the instrumented groups. After 24-hour biofilm reformation, no differences in cfu counts were observed between any groups, but the biofilm quantity was about 50% in all instrumented groups compared to the control. The attachment of fibroblasts on instrumented dentine was significantly higher than on untreated dentine (p < 0.05), with the exception of Ti-20. The dentine surface roughness was not affected by any instrumentation. CONCLUSIONS: The planar piezoelectric scaler prototypes are able to efficiently remove biofilm without dentine surface alterations, regardless of the operating frequency or instrument material. CLINICAL RELEVANCE: Ultrasonic scalers based on a planar piezoelectric transducer might be an alternative to currently available ultrasonic scalers.

Correction: Lay et al. Ultrasonic Quality Assurance at Magnesia Shotcrete Sealing Structures. Sensors 2022, 22, 8717.

The authors wish to correct the following errors in the original paper [...].

Ultrasonic Quality Assurance at Magnesia Shotcrete Sealing Structures.

Engineered barriers are a key element to enable safe nuclear waste disposal. One method currently under research for their construction is magnesia concrete applied in a shotcrete procedure. In this study, the ultrasonic echo method is evaluated as a means for quality assurance. Imaging of internal structures (backwall, boreholes) and defects, such as delamination, has successfully been achieved in the shotcrete. Additionally, detailed information about the potential cause of selected reflectors are obtained by phase analysis. In several test blocks of various sizes, no consistent concrete section boundaries have been found by ultrasonic imaging, which was verified by subsequent drilling and complementary tests. An experiment with artificial defects imitating cracks, air-filled voids, and material with lower density has been challenging and shows the limitations of the current methods. Although significant defects, such as a large delamination, are reliably identified, several smaller defects are not identified. Generally, ultrasonic imaging provides a suitable base as a mean for quality assurance during and after the construction of sealing structures. However, further developments are required to enhance the reliability of the method and a full validation is still pending. Still, the method has potential to increase the safety of nuclear waste repositories.

Femtosecond pulse generation from external cavity diode laser based on self-mode-locking.

In this Letter, we report optical pulse generation from a single-section diode gain chip, employed in an external cavity geometry based on the self-mode-locking regime. The gain chip emits light at 1550 nm wavelength range. The external cavity is operated at various repetition rates, ranging from 1 to 2.5 GHz. An optical pulse width of approximately 650 fs is obtained by fitting a Lorentzian distribution. A low RF spectral width of 78.875 kHz is measured corresponding to a low pulse-to-pulse RMS timing jitter of 1.273 ps. This system paves the way towards ultra-compact, cost-effective, and chirp-compensated femtosecond laser pulse sources with adjustable repetition rates.

Characterization of intracalyceal pressure during ureteroscopy.

PURPOSE: To provide the first report of measuring intracalyceal pressures during ureteroscopy (URS). METHODS: A prospective single-center clinical study using a cardiac pressure guidewire to measure intracalyceal pressure during flexible URS was performed. Eight patients (45 calyces) undergoing URS for nephrolithiasis were included. A Verrata® pressure guide wire was passed through the working channel of a dual lumen flexible ureteroscope and into the calyces while irrigation was maintained at 150 mmHg. Pressure was measured in the renal pelvis, upper pole, interpolar, and lower pole calyces both with and without a ureteral access sheath (UAS). The pressure in each location with and without a UAS was compared. The correlation between calyceal pressure and infundibular dimensions (width, length) was determined. RESULTS: Intracalyceal pressure was significantly lower in each region when a UAS was used. Compared to patients with a 12/14Fr UAS, those with a 14/16Fr UAS had significantly lower pressure in the interpolar (25.3 ± 13.1 vs. 44.0 ± 27.5 mmHg, p = 0.03) and lower pole (16.2 ± 3.5 vs. 49.2 ± 40.3 mmHg, p = 0.004) calyces. Interpolar calyceal pressure in the presence of a UAS was significantly higher than the renal pelvis pressure (RPP) (30.8 ± 19.6 vs. 17.9 ± 11.0 mmHg, p = 0.004). CONCLUSIONS: During flexible URS, RPP strongly correlates with, but does not uniformly represent, the intracalyceal pressure. With a 14/16Fr UAS and an inflow pressure of 150 mmHg, RPP and intracalyceal pressure never exceed the threshold for renal backflow.

Digital holography for spatially resolved analysis of the semiconductor optical response.

We present spatially resolved measurements of the below-band-gap carrier-induced absorption and concurrent phase change in a semiconductor with the help of transmission digital holography. The application is demonstrated for a bulk GaAs sample, while the holograms are recorded with a conventional CMOS sensor. We show that the phase information enables spatially resolved monitoring of excess carrier distributions. Based on that, we discuss a phase-based approach for separation of carrier and heat related effects in the semiconductor optical response.

Confocal laser scanning holographic microscopy of buried structures.

In this paper, we present a confocal laser scanning holographic microscope for the investigation of buried structures. The multimodal system combines high diffraction limited resolution and high signal-to-noise-ratio with the ability of phase acquisition. The amplitude and phase imaging capabilities of the system are shown on a test target. For the investigation of buried integrated semiconductor structures, we expand our system with an optical beam induced current modality that provides additional structure-sensitive contrast. We demonstrate the performance of the multimodal system by imaging the buried structures of a microcontroller through the silicon backside of its housing in reflection geometry.

Two-photon polymerization with diode lasers emitting ultrashort pulses with high repetition rate.

In this Letter, we investigate the resolution of two-photon polymerization (2PP) with an amplified mode-locked external cavity diode laser with adjustable pulse length and a high repetition rate. The experimental results are analyzed with a newly developed 2PP model. Even with low pulse peak intensity, the produced structural dimensions are comparable to those generated by traditional 2PP laser sources. Thus, we show that a compact monolithic picosecond laser diode without amplification and with a repetition rate in the GHz regime can also be applied for 2PP. These results show the high application potential of compact mode-locked diode lasers for low-cost and compact 2PP systems.

Monitoring of photochemically induced changes in phase-modulating samples with digital holographic microscopy.

This paper analyzes the performance of single-shot digital holographic microscopy for rapid characterization of static step-index structures in transparent polymer materials and for online monitoring of the photoinduced polymerization dynamics. The experiments are performed with a modified Mach-Zehnder transmission digital holographic microscope of high stability (phase accuracy of 0.69°) and of high magnification (of ≈90×). Use of near-infrared illumination allows both nondestructive examination of the manufactured samples and monitoring of optically induced processes in a photosensitive material concurrently with its excitation. The accuracy of the method for a precise sample's topography evaluation is studied on an example of microchannel sets fabricated via two-photon polymerization and is supported by reference measurements with an atomic force microscope. The applicability of the approach for dynamic measurements is proved via online monitoring of the refractive index evolution in a photoresin layer illuminated with a focused laser beam at 405 nm. High correlation between the experimental results and a kinetics model for the photopolymerization process is achieved.

High-resolution 3D light fluence mapping for heterogeneous scattering media by localized sampling.

We demonstrate an innovative concept for three-dimensional optical fluence mapping in heterogeneous highly scattering media as, e.g., biomedical tissues. We propose to use the relative light extinction analysis principle together with a miniaturized collection fiber in a direct fluence measurement setup as a method to obtain the spatially resolved light intensity distribution under transversally inhomogeneous light propagation conditions and provide local characterization of the transport medium. System performance is validated in two extreme conditions: an optically thin scattering medium and an absorption-dominated light transport. Both extremes demonstrate good agreement to theoretical expectations. Finally, we successfully prove the ability of the system to deliver high-resolution fluence maps through a model study of the light distribution induced in a scattering medium by a vertical diode laser stack with individual bars pitched only 500 µm apart.

Depth-filtering in common-path digital holographic microscopy.

We demonstrate a method to select different layers in a sample using a low coherent gating approach combined with a stable common-path quantitative phase imaging microscopy setup. The depth-filtering technique allows us to suppress the negative effects generated by multiple interference patterns of overlaying optical interfaces in the sample. It maintains the compact and stable common-path setup, while enabling images with a high phase sensitivity and acquisition speed. We use a holographic microscope in reflective geometry with a non-tunable low coherence light source. First results of this technique are shown by imaging the hardware layer of a standard micro-controller through its thinned substrate.

Femtosecond semiconductor laser system with resonator-internal dispersion adaptation.

We present a femtosecond laser diode system that is capable of autonomously adjusting itself to compensate for the external dispersion in an arbitrary application. The laser system contains a spatial light modulator inside the cavity which is controlled by an evolutionary algorithm in order to allow for phase and amplitude shaping of the laser emission. The cavity-internal dispersion control is shown to be much more efficient than an external control with a pulse shaper.

A Recombinant Bispecific CD20×CD95 Antibody With Superior Activity Against Normal and Malignant B-cells.

Monoclonal antibodies directed to the B-cell-specific CD20-antigen are successfully used for the treatment of lymphomas and autoimmune diseases. Here, we compare the anti-B-cell activity of three different antibodies directed to CD20: (i) a chimeric, monospecific antibody, (ii) an Fc-optimized variant thereof, and (iii) a bispecific CD20×CD95-antibody in a newly developed recombinant format, termed Fabsc. The bispecific antibody specifically triggers the CD95 death receptor on malignant, as well as activated, normal B-cells. We found that the capability of this antibody to suppress the growth of malignant B-cells in vitro and in vivo and to specifically deplete normal, activated B-cells from peripheral blood mononuclear cell (PBMC) cultures was superior to that of the Fc-optimized monospecific antibody. This antibody in turn was more effective than its nonoptimized variant. Moreover, the bispecific antibody was the only reagent capable of significantly suppressing antibody production in vitro. Our findings imply that the bispecific CD20×CD95-antibody might become a new, prototypical reagent for the treatment of B-cell-mediated autoimmune disease.

Reduction of Minimal Residual Disease in Pediatric B-lineage Acute Lymphoblastic Leukemia by an Fc-optimized CD19 Antibody.

Prognosis of primary refractory and relapsed pediatric B-lineage acute lymphoblastic leukemia (ALL) is very poor. Relapse rates significantly correlate with persistent minimal residual disease (MRD). In MRD, favorable effector-target ratios prevail and thus this situation might be optimally suited for immunotherapy with antibodies recruiting immunological effector cells. We here report on the generation, preclinical characterization and first clinical application in B-lineage ALL of an Fc-optimized CD19 antibody. This third-generation antibody (4G7SDIE) mediated enhanced antibody-dependent cellular cytotoxicity (ADCC) against leukemic blasts with effector cells from healthy volunteers and B-lineage ALL patients. The antibody was produced in a university-owned production unit and was applied on a compassionate use basis to 14 pediatric patients with refractory and relapsed B-lineage ALL at the stage of MRD. In 10/14 patients, MRD was reduced by ≥ 1 log or below the patient-individual detection limit, and 5/14 patients have achieved ongoing complete molecular remission with a median leukemia-free survival of 428 days. Two additional patients died in complete molecular remission due to complications not related to antibody therapy. Besides profound in vivo B-cell depletion, side effects were negligible. A clinical phase 1/2 study to further assess the therapeutic activity of 4G7SDIE is in preparation.

Preoperative Computed Tomography Assessment for Perinephric Fat Invasion: Comparison With Pathological Staging.

OBJECTIVE: The aim of this study was to assess the accuracy of computed tomography (CT) imaging in diagnosing perinephric fat (PNF) invasion in patients with renal cell carcinoma. METHODS: We retrospectively reviewed the medical records and preoperative CT images of 161 patients (105 men and 56 women) for pT1-pT3a renal cell carcinoma. We analyzed the predictive accuracy of CT criteria for PNF invasion stratified by tumor size. We determined the predictive value of CT findings in diagnosing PNF invasion using logistic regression analysis. RESULTS: The overall accuracy of perinephric (PN) soft-tissue stranding, peritumoral vascularity, increased density of the PNF, tumoral margin, and contrast-enhancing soft-tissue nodule to predict PNF invasion were 56%, 59%, 35%, 80%, and 87%, respectively. Perinephric soft-tissue stranding and peritumoral vascularity showed high sensitivity but low specificity regardless of tumor size. A contrast-enhancing soft-tissue nodule showed low sensitivity but high specificity in predicting PNF invasion. Among tumors 4 cm or less, PN soft-tissue stranding showed 100% sensitivity and 70% specificity, and tumor margin showed 100% sensitivity and 98% specificity. Among CT criteria for PNF invasion, PN soft-tissue stranding was chosen as the only significant factor for assessing PNF invasion by logistic regression analysis. CONCLUSIONS: Computed tomography does not seem to reliably predict PNF invasion. However, PN soft-tissue stranding was shown to be the only significant factor for predicting PNF invasion, which showed good accuracy with high sensitivity and high specificity in tumors 4 cm or less.

Heterogeneous antigenic properties of the porcine reproductive and respiratory syndrome virus nucleocapsid.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus responsible for a widespread contagious disease of domestic pigs with high economic impact. Switzerland is one of the rare PRRSV-free countries in Europe, although sporadic outbreaks have occurred in the past. The PRRSV isolate IVI-1173 from the short outbreak in Switzerland in 2012 was entirely sequenced, and a functional full-length cDNA clone was constructed. Genetic and antigenic characterization of IVI-1173 revealed the importance of amino acid 90 of the nucleocapsid protein N as part of a conformational epitope. IVI-1173 was not detected by SDOW17, a monoclonal antibody against N widely used to detect PRRSV-infected cells. Substitution of alanine at position 90 of N [N(A90)] with a threonine [N(T90)] restored reactivity of vIVI1173-N(T90) to SDOW17 completely. The relevance of this amino acid for the conformational SDOW17 epitope of PRRSV N was further confirmed by the opposite substitution in a functional cDNA clone of the genotype 2 isolate RVB-581. Finally, N proteins from ten genotype 1 strains differing from threonine at position 90 were analysed for reactivity with SDOW17. N(A90) totally disrupted or severely affected the epitope in 7 out of 8 strains tested. Based on these findings, 225 genotype 1 strains were screened for the prevalence of N(A90). N(A90) is rare in classical subtype 1 and in subtype 3 strains, but is frequent in Russian subtype 1 (70%) and in subtype 2 (45%) isolates. In conclusion, this study highlights the variable antigenic properties of N among genotype 1 PRRSV strains.

Characterization of a bispecific FLT3 X CD3 antibody in an improved, recombinant format for the treatment of leukemia.

FLT3 is a receptor-tyrosine-kinase that is expressed on leukemic cells of the myeloid and lymphoid lineage rather specifically. We here report on the construction and selection of bispecific FLT3 X CD3 antibodies in a new recombinant format, termed Fabsc, that resembles the normal antibody structure more closely than the well-established bispecific single chain (bssc)-format. Our preferred antibody, which emerged from an initial selection procedure utilizing different FLT3- and CD3-antibodies, contains the FLT3-antibody 4G8 and the CD3-antibody UCHT1. The 4G8 X UCHT1 Fabsc-antibody was found to be superior to a bssc-antibody with identical specificities with respect to (i) affinity to the target antigen FLT3, (ii) production yield by transfected cells, and (iii) the diminished formation of aggregates. T-cell activation in the presence and absence of cultured leukemic cells and killing of these cells was comparable for both molecules. In addition, the 4G8 X UCHT1 Fabsc-antibody was found to induce T-cell activation and efficient killing of leukemic blasts in primary peripheral blood mononuclear cell (PBMC) cultures of acute myeloid leukemia (AML) patients. In these experiments, the bispecific molecule was clearly superior to an Fc-optimized monospecific FLT3-antibody described previously, indicating that within PBMC of AML patients the recruitment of T cells is more effective than that of natural killer cells.