Temperature-dependent THz properties and emission of organic crystal BNA.

As high-average power ultrafast lasers become increasingly available for nonlinear conversion, the temperature dependence of the material properties of nonlinear crystals becomes increasingly relevant. Here, we present temperature-dependent THz complex refractive index measurements of the organic crystal BNA over a wide range of temperatures from 300 K down to 80 K for THz frequencies up to 4 THz for the first time. Our measurements show that whereas the temperature-dependent refractive index has only minor deviation from room temperature values, the temperature-dependent absorption coefficient decreases at low temperature (-24% from 300 K to 80 K). We additionally compare these measurements with conversion efficiency and spectra observed during THz generation experiments using the same crystal actively cooled in the same temperature range, using an ultrafast Yb-laser for excitation. Surprisingly, the damage threshold of the material does not improve significantly upon active cooling, pointing to a nonlinear absorption mechanism being responsible for damage. However, we observe a significant increase in THz yield (+23%) at lower temperatures, which is most likely due to the reduced THz absorption. These first findings will be useful for future designs of high-average power pumped organic-crystal based THz-TDS systems.

Spectral broadening of 2-mJ femtosecond pulses in a compact air-filled convex-concave multi-pass cell.

Multi-pass cell (MPC) based temporal pulse compressors have emerged in recent years as a powerful and versatile solution to the intrinsic issue of long pulses from Yb-based high-power ultrafast lasers. The spectral broadening of high-energy (typically more than 100 µJ) pulses has only been realized in gas-filled MPCs due to the significantly lower nonlinear coefficient of gases compared with solid-state media. Whereas these systems reach impressive performance in terms of spectral broadening with very low spatiotemporal couplings, they are typically complex setups, i.e., large and costly pressure-controlled vacuum chambers to avoid strong focusing, ionization, and damage to the mirrors. Here, we present spectral broadening of 2-mJ pulses in a simple and compact (60-cm-long) multi-pass cell operated in ambient air. Instead of the traditional Herriott cell with concave-concave (CC/CC) mirrors, we use a convex-concave (CX/CC) design, where the beam stays large at all times, both minimizing damage and allowing operation in ambient air. We demonstrate spectral broadening of 2.1-mJ pulses at 100 kHz repetition rate (200 W of average power) from 2.1 nm (pulse duration of 670 fs) to a spectral bandwidth of 24.5 nm, supporting 133-fs pulses with 96% transmission efficiency. We show the compressibility of these pulses down to 134 fs and verify that the spectral homogeneity of the beam is similar to previously reported CC/CC designs. To the best of the authors' knowledge, this is the first report of a CX/CC MPC compressor operated at high pulse energies in air. Because of its simplicity, small footprint, and low cost, we believe this demonstration will have significant impact in the ultrafast laser community.

Associations of GHR, IGF-1 and IGFBP-3 expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children.

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP), regulate growth and metabolic pathways. Here, we asked if serum levels of these factors are altered with overweight/obesity and if this is related to adipose tissue (AT) expression and/or increased fat mass. Furthermore, we hypothesized that expression of GHR, IGF-1 and IGFBP-3 is associated with AT function. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio obesity-related elevations were detectable until early puberty. Circulating levels did not correlate with AT expression of these factors, which was decreased with overweight/obesity. Independent from obesity, expression of GHR, IGF-1 and IGFBP-3 was related to AT dysfunction,and increased insulin levels. Serum GHBP was associated with liver fat percentage and transaminase levels. We conclude that obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased AT mass and elevations in GHBP are more closely related to liver status in children. The diminished AT expression of these factors with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

Average power scaling of THz spintronic emitters efficiently cooled in reflection geometry.

Metallic spintronic terahertz (THz) emitters have become well-established for offering ultra-broadband, gapless THz emission in a variety of excitation regimes, in combination with reliable fabrication and excellent scalability. However, so far, their potential for high-average-power excitation to reach strong THz fields at high repetition rates has not been thoroughly investigated. In this article, we explore the power scaling behavior of tri-layer spintronic emitters using an Yb-fiber excitation source, delivering an average power of 18.5 W (7 W incident on the emitter after chopping) at 400 kHz repetition rate, temporally compressed to a pulse duration of 27 fs. We confirm that a reflection geometry with back-side cooling is ideally suited for these emitters in the high-average-power excitation regime. In order to understand limiting mechanisms, we disentangle the effects on THz power generation by average power and pulse energy by varying the repetition rate of the laser. Our results show that the conversion efficiency is predominantly determined by the incident fluence in this high-average-power, high-repetition-rate excitation regime if the emitters are efficiently cooled. Using these findings, we optimize the conversion efficiency and reach highest excitation powers in the back-cooled reflection geometry. Our findings provide guidelines for scaling the power of THz radiation emitted by spintronic emitters to the milliwatt-level by using state-of-the-art femtosecond sources with multi-hundred-Watt average power to reach ultra-broadband, strong-field THz sources with high repetition rate.

Milliwatt average power, MHz-repetition rate, broadband THz generation in organic crystal BNA with diamond substrate.

We demonstrate a 13.3 MHz repetition rate, broadband THz source with milliwatt- average power, obtained by collinear optical rectification of a high-power Yb-doped thin-disk laser in the organic crystal BNA (N-benzyl-2-methyl-4-nitroaniline). Our source reaches a maximum THz average power of 0.95 mW with an optical-to-THz efficiency of 4×10-4 and a spectral bandwidth spanning up to 6 THz at -50 dB, driven by 2.4 W average power (after an optical chopper with duty cycle of 10%), 85 fs-pulses. This high average power excitation was possible without damaging the crystal by using a diamond-heatsinked crystal with significantly improved thermal properties. To the best of our knowledge, this result represents the highest THz average power reported so far using the commercially available organic crystal BNA, showing the potential of these crystals for high average power, high repetition rate femtosecond excitation. The combination of high power, high dynamic range, high repetition rate and broadband spectrum makes the demonstrated THz source highly attractive to improve various time-domain spectroscopy applications. Furthermore, we present a first exploration of the thermal behavior of BNA in this excitation regime, showing that thermal effects are the main limitation in average power scaling in these crystals.

Engineering a Copper@Polypyrrole Nanowire Network in the Near Field for Plasmon-Enhanced Solar Evaporation.

Harvesting solar energy for vapor generation is an appealing technology that enables substantial eco-friendly applications to overcome the long-standing global challenge of water and energy crisis. Nonetheless, an undesirable low light utilization efficiency and large heat losses impede their practical use. Here, we demonstrate a typical design paradigm capable of achieving superb nonconvective flow assisted water collecting rates of 2.09 kg/m2h under 1 sun irradiation with a high photothermal conversion efficiency of up to 97.6%. The high performance is ensured by an elaborately constructed coaxial copper@polypyrrole nanowire aerogel with surpassing photons acquisition and thermal localization capabilities. Using state-of-the-art micro-/nanoscale measurements and multiphysics calculations, we show that the metallic copper nanowire core can effectively excite surface plasmon resonance, which induces swift relaxation dynamics to achieve a highly efficient light-to-heat conversion process. A thin polypyrrole layer dramatically enhances broadband light absorption with minimized infrared radiation and low thermal conduction, leading to an impressive local heat concentration as high as 220 °C under 4 sun irradiation. Engineered empty space inside aerogel assembly of building blocks further facilitates large light penetration depth, smooth mass transfer, and robust mechanical capacity for synergistically boosting actual presentation. This work provides not only a rational design principle to create sophisticated solar-thermal materials but also critical information that complements insights about heat generation and temperature confinement in a scale-span system during strong light-matter interaction processes.

Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values.

BACKGROUND: Obesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes. METHODS: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020). FINDINGS: Children with obesity were significantly taller than normal-weight peers, differing at maximum by 7·6 cm (1·4 height, standard deviation scores or SDS) at age 6-8 years. Already at birth, children with obesity were slightly taller and thereafter had increased growth velocities by up to 1·2 cm/year. This growth acceleration was unrelated to parental height, but was accompanied by increased levels of insulin-like growth factor-1 (IGF-1), insulin and leptin. During puberty, children with obesity showed a catch-down in height SDS. The reduction in pubertal growth velocity by up to 25% coincided with a decrease in levels of IGF-1 (by 17%) and testosterone (by 62%) in boys and estradiol (by 37%) in girls. We confirmed these alterations in growth in the independent CrescNet cohort and furthermore provide height reference values for children with obesity for open access. INTERPRETATION: Dynamics of linear growth are altered distinctively in different developmental phases in children with obesity. Early emergence before other profound comorbidities implies predisposition, environmental, and/or endocrine factors affecting growth in early life. Height reference values for children with obesity may enhance the precision of clinical health surveillance. FUNDING: German Research Foundation, German Diabetes Association, EU, ESF, ERDF, State of Saxony, ESPE, Hexal, Novo Nordisk, Pfizer Pharma.

A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment.

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.

Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein-Self Interaction Using a Luciferase Complementation Assay.

The current number of drugs available for the treatment of Alzheimer's disease (AD) is strongly limited and their benefit for therapy is given only in the early state of the disease. An effective therapy should affect those processes which mainly contribute to the neuronal decay. There have been many approaches for a reduction of toxic Aß peptides which mostly failed to halt cognitive deterioration in patients. The formation of neurofibrillary tangles (NFT) and its precursor tau oligomers have been suggested as main cause of neuronal degeneration because of a direct correlation of their density to the degree of dementia. Reducing of tau aggregation may be a viable approach for the treatment of AD. NFT consist of hyperphosphorylated tau protein and tau hyperphosphorylation reduces microtubule binding. Several protein kinases are discussed to be involved in tau hyperphosphorylation. We developed novel inhibitors of three protein kinases (gsk-3ß, cdk5, and cdk1) and discussed their activity in relation to tau phosphorylation and on tau⁻tau interaction as a nucleation stage of a tau aggregation in cells. Strongest effects were observed for those inhibitors with effects on all the three kinases with emphasis on gsk-3ß in nanomolar ranges.

BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking.

Bardet-Biedl Syndrome (BBS) is a pleiotropic and genetically heterozygous disorder caused independently by numerous genes (BBS1-BBS17). Seven highly conserved BBS proteins (BBS1, 2, 4, 5, 7, 8 and 9) form a complex known as the BBSome, which functions in ciliary membrane biogenesis. BBS7 is both a unique subunit of the BBSome and displays direct physical interaction with a second BBS complex, the BBS chaperonin complex. To examine the in vivo function of BBS7, we generated Bbs7 knockout mice. Bbs7(-/-) mice show similar phenotypes to other BBS gene mutant mice including retinal degeneration, obesity, ventriculomegaly and male infertility characterized by abnormal spermatozoa flagellar axonemes. Using tissues from Bbs7(-/-) mice, we show that BBS7 is required for BBSome formation, and that BBS7 and BBS2 depend on each other for protein stability. Although the BBSome serves as a coat complex for ciliary membrane proteins, BBS7 is not required for the localization of ciliary membrane proteins polycystin-1, polycystin-2, or bitter taste receptors, but absence of BBS7 leads to abnormal accumulation of the dopamine D1 receptor to the ciliary membrane, indicating that BBS7 is involved in specific membrane protein localization to cilia.

Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.

Bardet-Biedl syndrome (BBS) is a heterogeneous disorder characterized by obesity, retinopathy, polydactyly, and congenital anomalies. The incidence of hypertension and diabetes are also increased in BBS patients. Mutation of 16 genes independently causes BBS, and seven BBS proteins form the BBSome that promotes ciliary membrane elongation. BBS3 (ARL6), an ADP ribosylation factor-like small GTPase, is not part of the BBSome complex. The in vivo function of BBS3 is largely unknown. Here we developed a Bbs3 knockout model and demonstrate that Bbs3(-/-) mice develop BBS-associated phenotypes, including retinal degeneration, male infertility, and increased body fat. Interestingly, Bbs3(-/-) mice develop some unique phenotypes not seen in other BBS knockout models: no overt obesity, severe hydrocephalus, and elevated blood pressure (shared by some but not all BBS gene knockout mice). We found that endogenous BBS3 and the BBSome physically interact and depend on each other for their ciliary localization. This finding explains the phenotypic similarity between Bbs3(-/-) mice and BBSome subunit knockout mice. Loss of Bbs3 does not affect BBSome formation but disrupts normal localization of melanin concentrating hormone receptor 1 to ciliary membranes and affects retrograde transport of Smoothened inside cilia. We also show that the endogenous BBSome and BBS3 associate with membranes and the membrane association of the BBSome and BBS3 are not interdependent. Differences between BBS mouse models suggest nonoverlapping functions to individual BBS protein.