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The detection of solar induced chlorophyll fluorescence (SIF) in the field with spectrometers is based on the depth of the solar Fraunhofer or oxygen absorption lines in the upwelling radiance compared to that in the downwelling irradiance. This relative depth enables the differentiation of SIF from the reflected radiation. Recent studies have shown that if oxygen bands are used to retrieve SIF from tower-based measurements, then atmospheric correction is required. This study presents a band shape fitting (BSF) approach to retrieve both the relative optical path length (deepening) and SIF (infilling) from field measurements at the same time, using information in the measured spectral shape of the O2 feature. This approach is an alternative to using radiative transfer process models for estimating atmospheric transmittance. The method was applied to measurements taken from 100 m elevation above a forest, yielding plausible results for SIF in the O2A and O2B bands. The sensitivity to combined atmospheric and instrument characteristics prohibits application at much greater distances from the surface.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, synthesized by two isoforms of glutamate decarboxylase (GAD): GAD65 and GAD67. GABA may act as a trophic factor during brain development, but its contribution to the development and maturation of cerebellar neural circuits is not known. To understand the roles of GABA in cerebellar organization and associated functions in motor coordination and balance, we examined GAD65 conventional knock out (KO) mice and mice in which GAD67 was eliminated in parvalbumin-expressing neurons (PV-Cre; GAD67flox/flox mice). We found aberrant subcellular localization of the Shaker-type K channel Kv1.1 in basket cell collaterals of PV-Cre; GAD67 flox/flox mice and abnormal projections from basket cells to Purkinje cells in both mouse strains. We also found that altered synaptic properties of basket cell terminals to Purkinje cells in PV-Cre; GAD67flox/flox mice. Furthermore, PV-Cre; GAD67 flox/flox mice exhibited abnormal motor coordination in the rotarod test. These results indicate that GABA signaling in the cerebellum is critical for establishing appropriate connections between basket cells and Purkinje cells and is associated with motor coordination in mice.

Background GATA6, a transcription factor expressed in cholangiocytes, has been implicated in the response to liver injury. In biliary atresia, a disease characterized by extrahepatic bile duct obstruction, liver expression of GATA6 increases with pathological bile duct expansion and decreases after successful Kasai portoenterostomy. The aim of this study was to garner genetic evidence that GATA6 is involved in ductular formation/expansion. Methods The murine Gata6 gene was conditionally deleted using Alb-cre, a transgene expressed in hepatoblasts (the precursors of hepatocytes and cholangiocytes) and mature hepatocytes. Bile duct ligation (BDL) was used to model biliary obstruction. Results Alb-Cre;Gata6(flox/flox) mice were viable and fertile. Cre-mediated recombination of Gata6 in hepatocytes had little impact on cellular structure or function. GATA6 immunoreactivity was retained in a majority of biliary epithelial cells in adult Alb-Cre;Gata6(flox/flox) mice, implying that surviving cholangiocytes were derived from hepatoblasts that had escaped biallelic Cre-mediated recombination. Although GATA6 immunoreactivity was preserved in cholangiocytes, Alb-cre;Gata6(flox/flox) mice had a demonstrable biliary phenotype. A neutrophil-rich infiltrate surrounded newly formed bile ducts in neonatal Alb-Cre;Gata6(flox/flox) mice. Foci of fibrosis/necrosis, presumed to reflect patchy defects in bile duct formation, were observed in the livers of 37% of adult Alb-cre;Gata6(flox/flox) mice and 0% of controls (p

Background Blood coagulation protease activity is proposed to drive hepatic fibrosis through activation of protease‐activated receptors (PARs). Whole‐body PAR‐1 deficiency reduces experimental hepatic fibrosis, and in vitro studies suggest a potential contribution by PAR‐1 expressed by hepatic stellate cells. However, owing to a lack of specific tools, the cell‐specific role of PAR‐1 in experimental hepatic fibrosis has never been formally investigated. Using a novel mouse expressing a conditional PAR‐1 allele, we tested the hypothesis that PAR‐1 expressed by hepatic stellate cells contributes to hepatic fibrosis. Methods PAR‐1flox/flox mice were crossed with mice expressing Cre recombinase controlled by the lecithin retinol acyltransferase (LRAT) promoter, which induces recombination in hepatic stellate cells. Male PAR‐1flox/flox/LRATCre and PAR‐1flox/flox mice were challenged twice weekly with carbon tetrachloride (CCl4, 1 mL/kg i.p.) for 6 weeks to induce liver fibrosis. Results PAR‐1 mRNA levels were reduced (>95%) in hepatic stellate cells isolated from PAR‐1flox/flox/LRATCre mice. Hepatic stellate cell activation was evident in CCl4‐challenged PAR‐1flox/flox mice, indicated by increased α‐smooth muscle actin labeling and induction of several profibrogenic genes. CCl4‐challenged PAR‐1flox/flox mice displayed robust hepatic collagen deposition, indicated by picrosirius red staining and type I collagen immunolabeling. Notably, stellate cell activation and collagen deposition were significantly reduced (>30%) in PAR‐1flox/flox/LRATCre mice. Importantly, the reduction in liver fibrosis was not a consequence of reduced acute CCl4 hepatotoxicity in PAR‐1flox/flox/LRATCre mice. Conclusions The results constitute the first direct experimental evidence that PAR‐1 expressed by stellate cells directly promotes their profibrogenic phenotype and hepatic fibrosis in vivo.

Wt1 gene encodes a nuclear transcription factor which is specifically expressed in ovarian granulosa cells and testicular Sertoli cells. Our previous studies demonstrated that Wt1 is required for the lineage specification of supporting cells and inactivation of Wt1 results in Sertoli cells to Leydig-like cells transformation. To test whether Wt1 is also involved in lineage maintenance of granulosa cells during ovary development, Wt1 was specifically deleted in pre-granulosa cells using Foxl2-cre. We found that the female Wt1−/flox; Foxl2-cre mice were infertile with atrophic ovaries and no growing follicles with multiple layers of granulosa cells were observed. A large number of 3β-HSD-positive steroidogenic cells were detected in ovaries of Wt1−/flox; Foxl2-cre mice during embryonic stage and these cells were derived from Foxl2-expressing pre-granulosa cells. The quantitative results showed the expression of granulosa cell marker genes (Foxl2, Follistatin) was downregulated and steroidogenic cell marker genes (3β-HSD, Cyp11a1, Star and Sf1) was dramatically increased in Wt1−/flox; Foxl2-cre ovaries. We also found that the meiosis of germ cells in Wt1−/flox; Foxl2-cre ovaries was delayed but not arrested. This study demonstrates that Wt1 is required for lineage maintenance of granulosa cells and inactivation of Wt1 results in pre-granulosa cells to steroidogenic cells transformation which in turn causes the defect of ovary development.

The upcoming Fluorescence Explorer (FLEX) satellite mission aims to provide high quality radiometric measurements for subsequent retrieval of sun-induced chlorophyll fluorescence (SIF). The combination of SIF with other observations stemming from the FLEX/Sentinel-3 tandem mission holds the potential to assess complex ecosystem processes. The calibration and validation (cal/val) of these radiometric measurements and derived products are central but challenging components of the mission. This contribution outlines strategies for the assessment of in situ radiometric measurements and retrieved SIF. We demonstrate how in situ spectrometer measurements can be analysed in terms of radiometric, spectral and spatial uncertainties. The analysis of more than 200 k spectra yields an average bias between two radiometric measurements by two individual spectrometers of 8%, with a larger variability in measurements of downwelling radiance (25%) compared to upwelling radiance (6%). Spectral shifts in the spectrometer relevant for SIF retrievals are consistently below 1 spectral pixel (up to 0.75). Found spectral shifts appear to be mostly dependent on temperature (as measured by a temperature probe in the instrument). Retrieved SIF shows a low variability of 1.8% compared with a noise reduced SIF estimate based on APAR. A combination of airborne imaging and in situ non-imaging fluorescence spectroscopy highlights the importance of a homogenous sampling surface and holds the potential to further uncover SIF retrieval issues as here shown for early evening acquisitions. Our experiments clearly indicate the need for careful site selection, measurement protocols, as well as the need for harmonized processing. This work thus contributes to guiding cal/val activities for the upcoming FLEX mission.

The impact of elevated $[\text{CO}_{2}](\mathrm{e}[\text{CO}_{2}])$ in on yield, biomass (BM) and chlorophyll fluorescence (ChlF) was analyzed in three genotypes of common beans (Phaseolus vulgaris L.), a key food-security crop. Active- and passive-sensed ChlF traits acquired by the Light-Induced-Fluorescence-Transient (LIFT), Moni-Pulse-Amplitude-Modulation (MoniPAM), and Fluorescence Box $(\text{FloX})$ instruments were compared. Total biomass increased for all genotypes under $\mathrm{e}[\text{CO}_{2}]$ , but their biomass partitioning significantly differed. The highest yielding genotype under $\mathrm{e}[\text{CO}_{2}]$ also showed the highest photosynthetic activity according to different active-sensed ChlF methods. Furthermore, $\mathrm{e}[\text{CO}_{2}]$ resulted in earlier senescence, which was detected by either satellite- or FloXderived Normalized Difference Vegetation Index (NDVI). Moreover, we observed a significant agreement between MoniPAM- and LIFT-measured ChlF data $(\mathrm{R}^{2}=0.89, p= 0.02)$ , as well as between SIF and FloX measurements $(\mathrm{R}^{2}= 0.62,p=0.03)$ .

PURPOSE Conversion chemotherapy is often used for borderline or unresectable (B/U) liver metastases from colorectal cancer (CRC) with the aim of achieving resectability. Although intensive and costly regimens are often used, the best regimen in this scenario remains unclear. We aimed to evaluate the outcomes of patients with B/U liver metastases from CRC treated with conversion chemotherapy with the modified fluorouracil, leucovorin, and oxaliplatin (mFLOX) regimen followed by metastasectomy. METHODS We performed a single-center retrospective analysis of patients with B/U liver metastases from CRC treated with chemotherapy with the mFLOX regimen followed by surgery. B/U disease was defined as at least one of the following: more than four lesions, involvement of hepatic artery or portal vein, or involvement of biliary structure. RESULTS Fifty-four consecutive patients who met our criteria for B/U liver metastases were evaluated. Thirty-five patients (64%) had more than four liver lesions, 16 (29%) had key vascular structure involvement, and 16 (29%) had biliary involvement. After chemotherapy, all patients had surgery and 42 (77%) had R0 resection. After a median follow-up of 37.2 months, median progression-free survival (PFS) was 16.9 months and median overall survival (OS) was 68.3 months. R1-R2 resections were associated with worse PFS and OS compared with R0 resection (PFS: hazard ratio, 2.65; P = .007; OS: hazard ratio, 2.90; P = .014). CONCLUSION Treatment of B/U liver metastases from CRC with conversion chemotherapy using mFLOX regimen followed by surgical resection was associated with a high R0 resection rate and favorable survival outcomes. On the basis of our results, we consider mFLOX a low-cost option for conversion chemotherapy among other options that have been proposed.

Acute kidney injury (AKI) is the rapid loss of renal function after an insult, and renal proximal tubule cells (RPTCs) are central to the pathogenesis of AKI. The β2-adrenergic receptor (β2AR) agonist formoterol accelerates the recovery of renal function in mice after ischemia-reperfusion injury (IRI) with associated rescue of mitochondrial proteins; however, the cell type responsible for this recovery remains unknown. The role of RPTCs in formoterol-induced recovery of renal function was assessed in a proximal tubule–specific knockout of the β2AR (γGT-Cre:ADRB2Flox/Flox). These mice and wild-type controls (ADRB2Flox/Flox) were subjected to renal IRI, followed by once-daily dosing of formoterol beginning 24 hours post-IRI and euthanized at 144 hours. Compared with ADRB2Flox/Flox mice, γGT-Cre:ADRB2Flox/Flox mice had decreased renal cortical mRNA expression of the β2AR. After IRI, formoterol treatment restored renal function in ADRB2Flox/Flox but not γGT-Cre:ADRB2Flox/Flox mice as measured by serum creatinine, histopathology, and expression of kidney injury marker-1 (KIM-1). Formoterol-treated ADRB2Flox/Flox mice exhibited recovery of mitochondrial proteins and DNA copy number, whereas γGT-Cre:ADRB2Flox/Flox mice treated with formoterol did not. Analysis of mitochondrial morphology by transmission electron microscopy demonstrated that formoterol increased mitochondrial number and density in ADRB2Flox/Flox mice but not in γGT-Cre:ADRB2Flox/Flox mice. These data demonstrate that proximal tubule β2AR regulates renal mitochondrial homeostasis. Formoterol accelerates the recovery of renal function after AKI by activating proximal tubule β2AR to induce mitochondrial biogenesis and demonstrates the overall requirement of RPTCs in renal recovery.

The use of biogas has currently two disadvantages. First, processing biogas to natural gas quality for feeding into the natural gas grid is a rather energy-consuming process. Second, the conversion into electricity directly in biogas plants produces waste heat, which largely cannot be used. Therefore, a feed-in of the desulfurized and dry biogas to local biogas grids would be preferable. Thus, the biogas could be used directly at the end consumer for heat and power production. As biogas varies in its methane (CH4) and carbon dioxide (CO2) content, respectively, this paper studies the influence of different biogas mixtures compared to natural gas on the combustion in a flameless oxidation (FLOX®)-based six nozzle combustor. The single staged combustor is suitable for use in a micro gas turbine (MGT) based combined heat and power (CHP) system with an electrical power output of 3 kW. The combustor is studied in an optically accessible atmospheric test rig, as well as integrated into the MGT system. This paper focuses on the influence of the admixture of CO2 to natural gas on the NOx and CO emissions. Furthermore, at atmospheric conditions, the shape and location of the heat release zone are investigated using OH* chemiluminescence (OH* CL). The combustor could be stably operated in the MGT within the complete stationary operating range with all fuel mixtures.

Increased global demand for cleaner energy production and growing concern about using fossil fuels have urged many researchers to focus their work on developing more efficient and flexible combustion processes. In this regard, a FLOX®-based liquid fuel single-nozzle burner is investigated for use in a Capstone C30 micro gas turbine (MGT). The main advantages of FLOX®-based combustor systems are their decreased NOx emissions and increased fuel flexibility. An atmospheric test rig is set up to investigate the behavior of the FLOX®-based liquid fuel burner under the influence of the hot gas. The circulating gas in the C30 annular combustion chamber is emulated by hot cross-flow gas generated by a 20-nozzle FLOX®-based natural gas burner operated on a separate horizontal test rig. The variation and combination of the process parameters of both burners are done systematically according to Design of Experiments (DOE) as a statistical design methodology. DOE methodology is adopted rather than the conventional one-factor-at-a-time (OFAT) strategy, as DOE considers any possible interaction between the factors and reduces the number of experiments. Employing statistical design of experiments allows determining which input variables are responsible for the observed changes in the response, developing a model relating the response to the important input variables, and using this model for improving the combustor system. The results are subsequently run through the Analysis of Variance (ANOVA) in order to allow for an objective conclusion about the effect of the factors on the selected responses, which include mass flow rate (·fuel) and global air equivalence ratio (λ) of both of the liquid and natural gas burners. The hot gas cross-flow interaction with the liquid fuel burner is assessed through analyzing exhaust gas emissions and averaged flame OH*-chemiluminescence images. The models developed by the DOE method can be used to estimate the emissions and the flame geometrical properties of any other operating points that are not explicitly tested.

BACKGROUND: Discoidin domain receptor 2 (Ddr2) is a rate-limiting factor in articular cartilage degeneration, a condition which normally leads to joint destruction. In human osteoarthritic tissues and mouse models of osteoarthritis (OA), the expression of Ddr2 increases and interacts with collagen type II, inducing the expression of matrix metalloproteinase 13 (MMP-13) and the receptor itself in chondrocytes. Moreover, conditional deletion of Ddr2 can significantly delay the progression of articular cartilage degeneration in post-traumatic OA mouse models. However, the biological effect of the conditional removal of Ddr2 in aging-related OA is still unknown. Therefore, this investigation was to determine whether the conditional removal of Ddr2 in articular cartilage could delay the cartilage degeneration in an aging-related mouse model (Col11a1(+/−)) of OA. METHODS: Mice Acan(+/CreERT2) were bred with Ddr2(flox/flox) mice to generate Acan(+/CreERT2);Ddr2(+/flox) mice. Acan(+/CreERT2);Ddr2(+/flox) mice were crossed with Ddr2(flox/flox) mice to produce Acan(+/CreERT2);Ddr2(flox/flox) mice. A similar breeding procedure was used to generate Col11a1(+/−);Ddr2(flox/flox) mice, in which Acan(+/CreERT2) mice were replaced by Col11a1(+/−) mice. Acan(+/CreERT2);Ddr2(flox/flox) mice were bred with Col11a1(+/−);Ddr2(flox/flox) mice to produce Acan(+/CreERT2);Ddr2(flox/flox);Col11a1(+/−) mice that were then treated with tamoxifen or oil at the age of 10 weeks. Knee joints from oil- and tamoxifen-treated Acan(+/CreERT2);Ddr2(flox/flox);Col11a1(+/−) mice, and Acan(+/CreERT2);Ddr2(flox/flox) mice at the ages of 3, 9 and 15 months were collected for histology and immunohistochemistry analyses. The protein expressions of Ddr2 and Mmp-13 and the degraded collagen type II were examined. RESULTS: The cartilage degeneration was significantly delayed in tamoxifen-treated Acan(+/CreERT2);Ddr2(flox/flox);Col11a1(+/−) mice. The scores, representing the severity of the cartilage damage, between oil- and tamoxifen-treated mice were: (mean ± SD) 1.33±0.47 vs. 1.29±0.45 (P>0.05) at the age of 3 months, 3.50±0.50 vs. 2.14±0.35 (P

The generation of conditional knockout mice using the Cre-loxP system is advantageous for the functional analysis of genes. Flanked by two loxP sites (floxed) mice can be directly obtained from fertilized eggs by the CRISPR/Cas9 genome editing system. We previously reported that sequential knock-in (KI) of each loxP site by electroporation (EP) at the 1- and 2-cell embryonic stages increases the number of mice with floxed alleles compared with simultaneous KI. However, EP at the 2-cell stage frequently induced blastomere fusion. These fused embryos cannot develop to term because they are tetraploidized. In this study, we examined the following three conditions to inhibit blastomere fusion by EP at the 2-cell stage: (1) hypertonic treatment, (2) Calcium (Ca2+)-free treatment, and (3) actin polymerization inhibition. Hypertonic treatment of 2-cell stage embryos prevented blastomere fusion and facilitated blastocyst development, however, KI efficiency was decreased. Ca2+-free treatment and actin polymerization inhibition by cytochalasin B (CB) reduced fusion rate, and did not have negative effects on development and KI efficiency. These results suggest that Ca2+-free and CB treatment at the 2-cell stage is effective to generate floxed mice in combination with a sequential EP method.

It has recently been shown that the loss of the Hippo signaling effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in adrenocortical steroidogenic cells impairs the postnatal maintenance of the adrenal gland. To further explore the role of Hippo signaling in mouse adrenocortical cells, we conditionally deleted the key Hippo kinases large tumor suppressor homolog kinases 1 and -2 (Lats1 and Lats2, two kinases that antagonize YAP and TAZ transcriptional co-regulatory activity) in steroidogenic cells using an Nr5a1-cre strain (Lats1flox/flox;Lats2flox/flox;Nr5a1-cre). We report here that developing adrenocortical cells adopt characteristics of myofibroblasts in both male and female Lats1flox/flox;Lats2flox/flox;Nr5a1-cre mice, resulting in a loss of steroidogenic gene expression, adrenal failure and death by 2 to 3 weeks of age. A marked accumulation of YAP and TAZ in the nuclei of the myofibroblast-like cell population with an accompanying increase in the expression of their transcriptional target genes in the adrenal glands of Lats1flox/flox;Lats2flox/flox;Nr5a1-cre animals suggested that the myofibroblastic differentiation could be attributed in part to YAP and TAZ. Taken together, our results suggest that Hippo signaling is required to maintain proper adrenocortical cell differentiation and suppresses their differentiation into myofibroblast-like cells.

Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro–activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19(Cre)Ppp2r1a(fl/fl) (flox/flox) mouse which lacks functional PP2A only in B cells. Flox/flox mice displayed reduced spontaneous germinal center formation and decreased responses to T cell-dependent and T-independent antigens, while their B cells responded poorly in vitro to stimulation with an anti-CD40 antibody or CpG in the presence of IL-4. Transcriptome and metabolome studies revealed altered nicotinamide adenine dinucleotide (NAD) and purine/pyrimidine metabolism and increased expression of purine nucleoside phosphorylase in PP2A-deficient B cells. Our results demonstrate that PP2A is required for optimal B cell function and may contribute to increased B cell activity in systemic autoimmunity.

Die thermische Vergasung ermöglicht die Nutzung fester Biomasse für die Kraft-Wärme-Kopplung. Bislang konnte sich die Technologie noch nicht etablieren, da eine Wirtschaftlichkeit dieser Anlagen häufig nicht erreicht wird. Die schwankende Zusammensetzung des erzeugten Brenngases sowie die darin enthaltenen Verunreinigungen verursachen hohe Wartungskosten und erschweren die Zuverlässigkeit der Anlagen. Da Mikrogasturbinen als brennstoffflexibel und wartungsarm gelten, stellen sie eine mögliche Alternative zu den mit Vergasern überwiegend eingesetzten Verbrennungsmotoren dar. Allerdings sind die auf dem Markt erhältlichen Mikrogasturbinen zumeist für konventionelle Brennstoffe wie Erdgas ausgelegt, weshalb sich die vorhandenen Brennkammersysteme nicht für das niederkalorische Brenngas eignen. Bei letzteren ist aufgrund des niedrigen Heizwerts ein erheblich größerer Brennstoffmassenstrom für die gleiche thermische Leistung erforderlich. Weiterhin unterscheiden sich die Verbrennungseigenschaften von dem aus der Vergasung stammenden Holzgas deutlich gegenüber Erdgas. Daher ist das Ziel der vorliegenden Arbeit die Entwicklung eines neuen Brennkammersystems, das den Einsatz von Holzgas in der Mikrogasturbine Turbec T100 ermöglicht. Dabei soll ein schadstoffarmer und zuverlässiger Betrieb bei schwankenden Gasqualitäten gewährleistet werden. Hierfür wird in der Arbeit ein Konzept erstellt und bis zur Erprobung eines Prototypen in realer Einsatzumgebung entwickelt. Ein Schwerpunkt bildet die Untersuchung der Brennstoffflexibilität des Systems. Zudem wird das Betriebsverhalten der Turbec T100 mit niederkalorischem Brenngas umfangreich charakterisiert sowie Optimierungspotentiale identifiziert. Das gewählte Konzept enthält zwei Brennerstufen, die unterschiedliche Techniken der Flammenstabilisierung verwenden. Die Geometrie der Hauptstufe, in der mehr als 90 % des Brennstoffs eingebracht werden, ist abgeleitet von dem als schadstoffarm und brennstoffflexibel geltenden FLOX®-Brenner. Als Pilotstufe hingegen dient ein für Holzgas ebenfalls neu entwickelter Drallbrenner, der konzentrisch zur Hauptstufe stromaufwärts angeordnet ist. Die experimentelle Untersuchung des Prototypen erfolgt in vier Schritten. Das Verbrennungsverhalten wird zuerst in einem atmosphärischen Prüfstand durch Messung der OH*-Chemolumineszenz, der Schadstoffemissionen sowie des Druckverlustes analysiert. Die hierfür relevanten Betriebsparameter werden mit einem stationären Mikrogasturbinen-Simulationsprogramm ermittelt und auf atmosphärische Bedingungen skaliert. Durch getrennte Variation der Parameter Luftverhältnis, thermische Leistung, 13Brennstoffzusammensetzung, Lufteintrittstemperatur und Brennstoffstufung erfolgt die Auswahl eines geeigneten Betriebsbereichs für die Mikrogasturbine. Im zweiten Schritt charakterisiert die Arbeit das Betriebsverhalten der mit dem Brennkammersystem ausgerüsteten Turbec T100 unter Verwendung synthetisch gemischter Brenngase. Die Messungen legen ein erfolgreiches Anfahren sowie ein stabiles Betriebsverhalten bei verschiedenen Gaszusammensetzungen und Lastpunkten dar. Am Prüfstand zeigen sich Betriebsgrenzen der Turbec T100 beim Einsatz niederkalorischer Brenngase, da sich durch den enormen Brennstoffmassenstrom die Betriebspunkte von Luftverdichter und Leistungselektronik im Vergleich zum Erdgasbetrieb bedeutend verschieben. Trotzdem erreicht die Turbec T100 elektrische Leistungen von 50 kW bis 100 kW bei deutlicher Unterschreitung der Schadstoffemissionsgrenzwerte. Anhand der Messdaten und numerischen Simulationen werden die Optimierungspotentiale der Turbec T100 für die Nutzung von niederkalorischen Brenngasen aufgezeigt. Zur Untersuchung des Verbrennungsverhaltens des entwickelten Brennkammersystems und zur näheren Betrachtung der Brennstoffflexibilität dient eine an die Turbec T100 angeflanschte optische Brennkammer. Diese ermöglicht die Messung der OH*-Chemolumineszenz sowie der OH-PLIF in einer Ebene durch die Düsen der Hauptstufe. Die damit gewonnenen Ergebnisse belegen das robuste Verhalten, da sich die Position und Form der Flammen in der Hauptstufe für verschiedene Leistungen vernachlässigbar gering verändern. Die Reduktion des Wasserstoffanteils im Brenngas weit unter die in Holzgas üblichen Konzentrationen zeigt eine deutlich veränderte Flammenstabilisierung für Brenngasmischungen, die keinen oder nur geringe Konzentrationen von Wasserstoff aufweisen. Hierbei wird die Bedeutung des Wasserstoffs und der Einfluss der durch den Wasserstoffanteil beeinflussten Zündverzugszeit ersichtlich. Die positiven Ergebnisse aus den Prüfständen werden durch die Erprobung der entwickelten Brennkammer in einer Demonstrationsanlage, bei der eine bestehende Holzvergaseranlage mit einem neu aufgebauten MikrogasturbinenBHKW gekoppelt wird, bestätigt. Zwar zeigen sich beim gekoppelten Betrieb Probleme im Anfahrvorgang mit Heizwerten geringer als 3 MJ/kg, dies beruht jedoch darauf, dass sich der Vergaser dieser Anlage im Fackelbetrieb nicht ausreichend aufheizen lässt. Im stationären Betrieb belegen die Ergebnisse das robuste Verhalten der Mikrogasturbine bei schlagartig schwankenden Gasqualitäten. Mit Abschluss der Arbeit liegt ein Brennkammersystem vor, dass die Kopplung der Mikrogasturbine mit Festbettvergasern ermöglicht. Ein stabiler Betrieb wird von 50 kWel bis 100 kWel erreicht, wobei die gesetzlichen Grenzwerte der Schadstoffemissionen im gesamten Bereich weit unterschritten werden. Die hohe Brennstoffflexibilität des Brennkammersystems gewährleistet zum einen den stabilen Betrieb mit Vergasern zum anderen bietet es auch Potentiale zur Nutzung anderer niederkalorischer Brenngase. Neben den technischen Errungenschaften demonstriert die Arbeit eine erfolgreiche Vorgehensweise zur Auslegung und Implementierung eines Brennkammersystems für Mikrogasturbinen.

This is chapter 1 of the State of Environmental Science in Svalbard (SESS) report 2019 (https://sios-svalbard.org/SESS_Issue2). Svalbard’s climate is undergoing dramatic changes, but how this will influence plant productivity is largely unknown. Understanding these changes at the ecosystem level requires that we use data from different sources – including satellites – to assess climate-induced effects on plant vitality and productivity. However, measuring plant productivity is a challenging task. For the Adventdalen area we use radar satellite data to map snow and ice in the melting season and optical satellite data to map the start and peak of the growing season. The satellite data can be related to plant productivity, but must be interpreted based on measurements done in the field. An observation system for continuous field monitoring of vegetation was established in Adventdalen in Svalbard in 2015. This system consists of field-based racks with various sensors and cameras, which are placed in different vegetation types. The system has successfully recorded the timings of green-up, plant growth and senescence since its establishment. To further increase the usefulness of the observation system, we need to develop methods to validate the satellite data with data from the sensors and cameras on the racks in Adventdalen. This would allow more accurate estimates of plant productivity over broader regions and scaling up to all of Svalbard. The most advanced instrument in this observation system is a state-of-the-art spectrometer that measures radiances and sun-induced fluorescence; it was deployed in Adventdalen in the summer of 2019. This expensive instrument can give even better estimates of plant productivity and can also be used to calibrate the other measurements and the satellite data. However, the observation system as currently configured in Adventdalen does not provide sufficient data on bryophytes (mosses).

The use of biogas has currently two disadvantages. Firstly, processing biogas to natural gas quality for feeding into the natural gas grid is a rather energy consuming process. Secondly, the conversion into electricity directly in biogas plants produces waste heat, which largely cannot be used. Therefore, a feed-in of the desulfurized and dry biogas to local biogas grids would be preferable. Thus, the biogas could be used directly at the end consumer for heat and power production. As biogas varies in its methane (CH4) and carbon dioxide (CO2) content, respectively, this paper studies the influence of different biogas mixtures compared to natural gas on the combustion in a FLOX®-based six nozzle combustor. The single staged combustor is suitable for the use in a micro gas turbine (MGT) based combined heat and power (CHP) system with an electrical power output of 3 kW. The combustor is studied in an optically accessible atmospheric test rig, as well as integrated into the MGT system. This paper focuses on the influence of the admixture of CO2 to natural gas on the NOX and CO emissions. Furthermore, at atmospheric conditions the shape and location of the heat release zone is investigated using OH* chemiluminescence (OH* CL). The combustor could be stably operated in the MGT within the complete stationary operating range with all fuel mixtures.

As an alternative to the commonly used swirl burners in micro gas turbines (MGT), the FLOX®-based combustion concept promises great potential for the nitric oxide emission reduction and increased fuel flexibility. Previous research on FLOX®-based MGT combustors mainly addressed gaseous fuels and there is limited knowledge available on liquid fuel FLOX®-based MGT combustors. Despite having to deal with a new set of challenges while utilizing liquid fuel in the burner, first steps are taken to gain more information on the influencing operational parameters. In this regard, a FLOX®-based liquid fuel burner is developed to fit into a newly designed combustor for the Capstone C30 MGT. The C30 combustor operates with three burners arranged tangentially to an annular combustion chamber and provides a total thermal power of 115 kW. In this work, operational properties of merely one of the three C30 liquid fuel burners are investigated and the rest of the two burners are emulated in form of hot cross–flow. As for the liquid burners, the experiments are conducted with three geometrically different single–nozzle burners at atmospheric pressure. The studied FLOX®-based burners consist of an air nozzle with a coaxially arranged fuel pressure atomizer. The cross–flow is realized by utilizing a 20–nozzle FLOX®-based natural gas combustor. Measurements include visualization of the reaction zone and analysis of the exhaust gas emissions. By detecting the hydroxyl radical chemiluminescence (OH*-CL) emissions, the position of the heat release zone within the combustion chamber is attained. Correspondingly, the flame height above burner and the flame length are calculated. The investigated design parameters include air preheat temperature up to 733 K, equivalence ratio, burner geometry, and thermal power. The work presented in this paper aims to deepen the understanding of the design parameter interactions involved within the single–nozzle liquid–FLOX®-based burners. The cross–flow is set at a constant operating point to take the influence of the circulating hot gases on the flame into account. Through variation of thermal power the effect of liquid fuel preparation, i.e., atomization, evaporation, and mixing on combustion properties and exhaust gas emissions are examined. Analyses of measurements of different burner configurations are shown. The results show that the burners with the medium diameter consistently performed remarkably at different flame temperatures and thermal powers. The lowest NOx and CO emissions for the medium diameter burner lied between 5–7 ppm and 8–10 ppm, respectively. The collected data sets can be used for the validation of numerical simulations as well.

In frame of the European Space Agency’s (ESA) “FLEXSense Campaign 2018” and the Copernicus Marine Environment Monitoring Service (CMEMS) project, the Global Ocean Satellite monitoring and marine ecosystem study group (GOS) of the Italian National Research Council (CNR) organized the oceanographic cruise “FLEX 2018”. The CNR research vessel “Dallaporta” provided a ground station for several bio-optical instruments to investigate the coastal waters of the Tyrrhenian Sea (central Italy) in June 2018. The field measurements were performed in time synchrony with spaceborne (i.e. Sentinel 3A and Sentinel 3B satellites) and airborne (i.e. HyPlant airborne imaging spectrometer) observations, with the intent to contribute to calibration/validation activities for existing and future space mission developments. Particularly, active and passive fluorescence were investigated at different scales in aquatic ecosystems, to support preparatory activities of the FLuorescence EXplorer (FLEX) satellite mission to be launched in 2022. Results provide new insight on the sensitivity of Solar Induced Fluorescence (SIF) retrievals for atmospheric disturbances and other scale related aspects, and will eventually facilitate the implementation of robust retrieval schemes for the FLEX mission products. In addition, active fluorescence signals acquired from a LIDAR fluorosensor show a good agreement with SIF pattern retrieved by HyPlant and Sentinel-3 Ocean and Land Colour Instrument (OLCI). Our results demonstrate that the combination of active and passive fluorescence, together with the synergistic measurements from integrated platforms, is a promising approach to support the retrieval and interpretation of SIF in aquatic environments.

OBJECTIVE This study aimed to clarify the underlying mechanism of pathognomonic angiogenesis between the temporal muscle and neocortex after indirect bypass for moyamoya disease by shedding light on the role of platelet-derived growth factor receptor–α (PDGFRα) in angiogenesis. METHODS The gene for PDGFRα was systemically inactivated in adult mice (α-KO mice). The Pdgfra-preserving mice (Flox mice) and α-KO mice were exposed to bilateral common carotid artery stenosis (BCAS) by using microcoils. One week later the animals underwent encephalomyosynangiosis (EMS) on the right side. Cerebral blood flow (CBF) was serially measured using a laser Doppler flowmeter. Histological analysis was performed on the distribution of CD31-positive vessels and collagen deposit at 28 days after BCAS. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of collagen mRNA in the skin fibroblasts derived from Flox and α-KO mice. RESULTS BCAS significantly reduced CBF up to approximately 70% of the control level at 28 days after the onset. There was no significant difference in CBF between Flox and α-KO mice. EMS significantly enhanced the improvement of CBF on the ipsilateral side of Flox mice, but not α-KO mice. EMS significantly induced the development of CD31-positive vessels in both the neocortex and temporal muscle on the ipsilateral side of Flox mice, but not α-KO mice. Deposition of collagen was distinctly observed between them in Flox mice, but not α-KO mice. Expression of mRNA of collagen type 1 alpha 1 (Col1a1) and collagen type 3 alpha 1 (Col3a1) was significantly downregulated in the skin fibroblasts from α-KO mice. CONCLUSIONS This is the first study that denotes the role of a specific growth factor in angiogenesis after EMS for moyamoya disease by inactivating its gene in mice. The findings strongly suggest that PDGFRα signal may play an important role in developing spontaneous angiogenesis between the temporal muscle and neocortex after EMS in moyamoya disease.

Wnt4 and Wnt5a have well-established roles in the embryonic development of the female reproductive tract, as well as in implantation, decidualization, and ovarian function in adult mice. Although these roles appear to overlap, whether Wnt5a and Wnt4 are functionally redundant in these tissues has not been determined. We addressed this by concomitantly inactivating Wnt4 and Wnt5a in the Mullerian mesenchyme and in ovarian granulosa cells by crossing mice bearing floxed alleles to the Amhr2cre strain. Whereas fertility was reduced by ∼50% in Wnt4flox/flox; Amhr2cre/+ and Wnt5aflox/flox; Amhr2cre/+ females, Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice were either nearly or completely sterile. Loss of fertility was not due to an ovarian defect, as serum ovarian hormone levels, follicle counts, and ovulation rates were comparable to controls. Conversely, the uterus was abnormal in Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice, with thin myometrial and stromal layers, frequent fibrosis and a >90% reduction in numbers of uterine glands, suggesting redundant or additive roles of Wnt4 and Wnt5a in uterine adenogenesis. Loss of fertility in Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ mice was attributed to defects in decidualization, implantation, and placental development, the severity of which were proportional to the extent of gland loss. Furthermore, a third of Wnt4flox/flox; Wnt5aflox/flox; Amhr2cre/+ females had a partial agenesis of Mullerian duct-derived structures, but with normal oviducts and ovaries. Together, our results suggest that Wnt4 and Wnt5a play redundant roles in the development of the female reproductive tract, and may provide insight into the etiology of certain cases of Mullerian agenesis in women.

Purpose While the normal cornea has limited innervation by the lymphatic system, chronic immune-inflammatory disorders such as dry eye (DE) can induce lymphangiogenesis in the ocular surface. Using a conditional knock-down murine model, Lyve-1 Cre ;VEGFR2 flox mice, this study investigated the role of lymphangiogenesis in the pathophysiology of DE. Methods DE was induced in both wild type (WT) B6 and Lyve-1 Cre ;VEGFR2 flox mice. Tissue immunostaining and volumetric gross measurements were used to assess changes in the ocular surface, skin, and lymph nodes (LNs). The expression of lymphangiogenic factors (TNF-α, IL-6/-8/-12/-17, VEGF-C/-D, IFN-γ, VEGFR-2/-3, Lyve-1, and podoplanin) and the frequency of immune cells (CD4, CD11b, and CD207) on the ocular surface and lacrimal glands were quantified by real-time polymerase chain reaction and flow cytometry. Results Compared to WT mice, there were fewer lymphatic vessels and a reduction in lymphangiogenic markers in the ocular surface and skin of Lyve-1 Cre ;VEGFR2 flox mice. After DE induction, mRNA levels of TNF-α, IL-8, and IFN-γ were significantly reduced in Lyve-1 Cre ;VEGFR2 flox mice compared to WT mice ( p Cre ;VEGFR2 flox mice with DE were significantly smaller and populated by fewer dendritic cells and effector T cells than those from WT mice ( p Cre ;VEGFR2 flox mice were notably intact like in the naive condition. Conclusions Inhibition of lymphangiogenesis in the cornea effectively attenuates not only the inflammatory response including trafficking of immune cells but also preserves corneal nerves under desiccating stress. Corneal lymphangiogenesis might be a contributing factor in deterioration on the ocular surface homeostasis.

Deficiencies in pancreatic β-cell mass contribute to both type 1 and type 2 diabetes. We investigated the role of the glucose-regulated protein (GRP) 94, an endoplasmic reticulum protein abundantly expressed in the pancreatic acini and islets, in β-cell development, survival, and function. We used a conditional knockout (KO) mouse in which the GRP94 gene, Hsp90b1, was specifically deleted in pancreatic and duodenal homeobox 1 (Pdx1)–expressing cells. These Hsp90b1 flox/flox;Pdx1Cre KO mice exhibited pancreatic hypoplasia at embryonic day (E) 16.5 to E18.5 and had significantly reduced β-cell mass at 4 weeks after birth. Further mechanistic studies showed that deletion of GRP94 reduced β-cell proliferation with increased cell apoptosis in both Pdx1+ endocrine progenitor cells and differentiated β cells. Although Hsp90b1 flox/flox;Pdx1Cre KO mice remained euglycemic at 8 weeks of age, they exhibited impaired glucose tolerance. In aggregate, these findings indicate that GRP94 is an essential regulator of pancreatic β-cell development, mass, and function.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway. They act as major regulators of stem cell maintenance, cell growth, and differentiation. To characterize their roles in the adrenal cortex, we generated a mouse model in which Yap and Taz were conditionally deleted in steroidogenic cells (Yapflox/flox;Tazflox/flox;Nr5a1cre/+). Male Yapflox/flox;Tazflox/flox;Nr5a1cre/+ mice were characterized by an age-dependent degeneration of the adrenal cortex associated with an increase in apoptosis and a progressive reduction in the expression levels of steroidogenic genes. Evaluation of the expression levels of stem and progenitor cell population markers in the adrenal glands of Yapflox/flox;Tazflox/flox;Nr5a1cre/+ mice also showed the downregulation of sonic hedgehog (Shh), a marker of the subcapsular progenitor cell population. Gross degenerative changes were not observed in the adrenal glands of Yapflox/flox;Tazflox/flox;Nr5a1cre/+ females, although steroidogenic capacity and Shh expression were reduced, suggesting that mechanisms of adrenocortical maintenance are sex specific. These results define a crucial role for YAP and TAZ in the maintenance of the postnatal adrenal cortex.

Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop anewstrategy for improving fertility in older women prior to menopause. In the ovary of 6-month-old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor-positive endocrine cells and (ii) actin-rich fibrotic cells expressing collagen. Both the endocrine and fibrotic cells disappeared following long-term treatment with a GnRH antagonist, indicating that the high levels of serum LH induced the survival of both cell types and the abnormal endocrine profile to reduce fertility. Moreover, follicular development to the antral stages was observed with reduced LH and the disappearance of the abnormal stromal cells. Mice treated with the GnRH antagonist regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months. We conclude that endocrine and matrix alternations occur within the ovarian stroma with increasing age and that abolishing these alternations resets the cyclical release of LH. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause., This work was supported in part by The Japan Society for the Promotion of Science (JSPS) KAKENHI, JP24688028, JP 16H05017 (to MS) and JP15J05331 (to TU), by Japan Agency for Medical Research and Development (AMED) 16gk0110015 h0001 (to MS), and by National Institute of Health (NIH)-HD-076980 (to JSR).

This paper presents the experimental results on flameless oxidation of light fuel oil in a reverse-flow cooled combustion chamber. NOX and CO emissions as well as temperatures in the combustion chamber are used to determine combustion performance of the cold air flameless oxidation (FLOX®) burner. Five different twin fluid atomizers with varying spray angles between 0° and 80° and different bore diameters have been used and the influence of atomizing air pressure between 4 and 6 bar on the combustion performance was investigated. In the tests air stoichiometry ratios ranged from 1.1 to 1.9 and thermal inputs were varied between 50 and 150 kW. Results show that good combustion performance in flameless mode was achieved. Low NOX emissions combined with low CO emissions which meet strictest CO (according to DIN EN 267 class 3 burners, 60 mg/kWhth) and NOX regulations (according to 1. BImSchV, 110 mg/kWhth) were obtained at an air ratio of 1.1.

Rac signaling impacts a relatively large number of downstream targets; however, few studies have established an association between Rac pathways and pathological conditions. In the present study, we generated mice with double knockout of Rac1 and Rac3 (Atoh1-Cre;Rac1(flox/flox);Rac3(-/-)) in cerebellar granule neurons (CGNs). We observed impaired tangential migration at E16.5, as well as numerous apoptotic CGNs at the deepest layer of the external granule layer (EGL) in the medial cerebellum of Atoh1-Cre; Rac1(flox/flox);Rac3(-/-) mice at P8. Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) CGNs differentiated normally until expression of p27(kip1) and NeuN in the deep EGL at P5. Primary CGNs and cerebellar microexplants from Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) mice exhibited impaired neuritogenesis, which was more apparent in Map2-positive dendrites. Such findings suggest that impaired tangential migration and final differentiation of CGNs have resulted in decreased cerebellum size and agenesis of the medial internal granule layer, respectively. Furthermore, Rac depleted/deleted cells exhibited decreased levels of Mid1 and impaired mTORC1 signaling. Mid1 depletion in CGNs produced mild impairments in neuritogenesis and reductions in mTORC1 signaling. Thus, a novel Rac-signaling pathway (Rac1Mid1-mTORC1) may be involved in medial cerebellar development.

BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.METHODS: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.RESULTS: Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.CONCLUSIONS: Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.

Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signalling in the brainstem. We investigated how long-term loss of cholinergic signalling from mesopontine nuclei influence motor behaviours. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChTEn1-Cre-flox/flox). VAChTEn1-Cre-flox/flox mice did not show any gross health or neuromuscular abnormality on metabolic cages, wire-hang and grip-force tests. Young VAChTEn1-Cre-flox/flox mice (2-5 months-old) presented motor learning/coordination deficits on the rotarod; moved slower, and had smaller steps on the catwalk, but showed no difference in locomotor activity on the open field. Old VAChTEn1-Creflox/flox mice (13-16 months-old) showed more pronounced motor learning/balance deficits on the rotarod, and more pronounced balance deficits on the catwalk. Furthermore, old mutants moved faster than controls, but with similar step length. Additionally, old VAChT-deficient mice were hyperactive. These results suggest that dysfunction of cholinergic neurons from mesopontine nuclei, which is commonly seen in PD, has causal roles in motor functions. Prevention of mesopontine cholinergic failure may help to prevent/improve postural instability and falls in PD patients. This article is protected by copyright. All rights reserved.

Premixed methane–air turbulent flame is generated in a single-nozzle jet-stabilized combustor designed based on the FLOX ® concept 1 . Confinement-induced, self-sustained jet oscillation is observed. Its influence on combustion stability near lean blow-out (LBO) is investigated using simultaneous particle imaging velocimetry (PIV), planar laser-induced fluorescence of OH radicals (OH PLIF), and OH chemiluminescence imaging at 5-kHz repetition rate. Via proper orthogonal decomposition (POD) of the velocity field and extended POD of the scalar fields, pronounced variations in the flame shape are observed during a cycle of jet oscillation. In extreme cases, flame is partially blown out in the combustor due to jet impingement on the wall during the first half of its oscillation cycle. In the subsequent half cycle following jet detachment, flame is restabilized after robust flashback and re-light. Statistical analysis shows that such pattern is by far the most prevalent mechanism for blow-out and restabilization to take place at the operating condition. Additionally, these events are found with much higher probability during slow-paced jet oscillations.

Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redundancy within the Iroquois family. However, global loss of both Irx3 and Irx5 in mice leads to significant skeletal malformations and embryonic lethality from cardiac defects. Here, we study the bone-specific functions of Irx3 and Irx5 using Osx-Cre to drive osteoblast lineage–specific deletion of Irx3 in Irx5−/− mice. Although we found that the Osx-Cre transgene alone could also affect craniofacial mineralization, newborn Irx3flox/flox/Irx5−/−/Osx-Cre+ mice displayed additional mineralization defects in parietal, interparietal, and frontal bones with enlarged sutures and reduced calvarial expression of osteogenic genes. Newborn endochondral long bones were largely unaffected, but we observed marked reductions in 3–4-week old bone mineral content of Irx3flox/flox/Irx5−/−/Osx-Cre+ mice. Our findings indicate that IRX3 and IRX5 can work together to regulate mineralization of specific cranial bones. Our results also provide insight into the causes of the skeletal changes and mineralization defects seen in Hamamy syndrome patients carrying mutations in IRX5., Highlights • Osteoblast-specific deletion of Irx3 and Irx5 causes mineralization defects in parietal, interparietal, and frontal bones of newborn mice. • 3–4 week old Irx3flox/flox/Irx5−/−/Osx-Cre+ mice show similar bone fragility to Hamamy syndrome patients who have mutations in IRX5. • Osx-Cre transgene alone causes an early bone mineralization phenotype that recovers later.