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The summer of 2022 has been the so far hottest summer on record in Central Europe. High temperatures negatively affect the physiology of plants and cause considerable thermal stress in particular on the leaf level. The assessment of the temperature-dependent decline of the quantum use efficiency of the photosystem II (Fv/Fm) has gained much popularity to quantify the leaf-level sensitivity to thermal stress. An open question is whether leaves heat to those in vitro estimated threshold temperatures on hot days or if plants can avoid heat stress through transpirational cooling. Therefore, leaf temperatures were monitored on a non-native Austrian oak (Quercus cerris) during a heatwave in July 2022 and compared to observed air temperature and leaf thermal traits assessed with a chlorophyll fluorometer. The highest air temperature recorded during the heatwave was 42.5 °C and surpassed the breaking point temperature (temperature at 5% decline of Fv/Fm; T5) by 0.3 °C, but was 6.1 °C lower than T50 (temperature at 50% decline of Fv/Fm). However, during the hottest day, the maximum leaf temperature was significantly below the air temperature. Even the directly illuminated leaf facing south reached a maximum temperature of only 38.7 °C but reached 39.8 °C on the second hottest day when the air temperature went up to 39.6 °C. All leaves showed a certain degree of homeothermy as the slope between leaf temperature and air temperature was 0.83 (P < 0.05). In conclusion, Austrian oak can buffer thermal stress during heatwaves to a certain degree, however, leaf temperatures are only marginally below critical threshold temperatures. [ABSTRACT FROM AUTHOR]

Spinal dural arteriovenous fistulas (SDAVFs) constitute the most common type of spinal vascular malformations. Their diagnosis requires spinal digital subtraction angiography (DSA), which is time-consuming, requires catheterizing many vessels, and exposes patient to a high radiation and contrast doses. This study aims to evaluate the usefulness of time-resolved MR angiography (TR–MRA) in SDAVF diagnosis. We performed a systematic review of the PubMed and EMBASE databases followed by a meta-analysis. TR–MRA was an index test, and spinal DSA was a reference. Of the initial 324 records, we included 4 studies describing 71 patients with SDAVFs. In 42 cases, TR–MRA was true positive, and in 21 cases, it was true negative. We found 7 false-positive cases and 1 false negative. TR–MRA allowed for shunt level identification in 39 cases. Of these, the predicted level was correct in 23 cases (59%), to within 1 level in 38 cases (97.4%) and to within 2 levels in 39 cases (100%). The diagnostic odds ratio was 72.73 (95% CI [10.30; 513.35]), z = 4.30, p value < 0.0001. The pooled sensitivity was 0.98 (95% CI [0.64; 1.00]), and the pooled specificity was 0.79 (95% CI [0.10; 0.99]). The AUC of the SROC curve was 0.9. TR–MRA may serve as a preliminary study to detect SDAVFs and localize the shunt level with sensitivity and specificity as high as 98% and 79%, respectively. Unless the TR–MRA result is unequivocal, it should be followed by a limited spinal DSA. [ABSTRACT FROM AUTHOR]

For the detection of food adulteration, sensitive and reproducible analytical methods are required. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) is a highly sensitive method that can be used to obtain analytical fingerprints consisting of a variety of different components. Since the comparability of measurements carried out with different devices and at different times is not given, specific adulterants are usually detected in targeted analyses instead of analyzing the entire fingerprint. However, this comprehensive analysis is desirable in order to stay ahead in the race against food fraudsters, who are constantly adapting their adulterations to the latest state of the art in analytics. We have developed and optimized an approach that enables the separate processing of untargeted LC‑HRMS data obtained from different devices and at different times. We demonstrate this by the successful determination of the geographical origin of honey samples using a random forest model. We then show that this approach can be applied to develop a continuously learning classification model and our final model, based on data from 835 samples, achieves a classification accuracy of 94% for 126 test samples from 6 different countries. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary (CHO) cells are popular in the pharmaceutical industry for their ability to produce high concentrations of antibodies and their resemblance to human cells in terms of protein glycosylation patterns. Current data indicate the relevance of CHO cells in the biopharmaceutical industry, with a high number of product commendations and a significant market share for monoclonal antibodies. To enhance the production capabilities of CHO cells, a deep understanding of their cellular and molecular composition is crucial. Genome sequencing and proteomic analysis have provided valuable insights into the impact of the bioprocessing conditions, productivity, and product quality. In our investigation, we conducted a comparative analysis of proteomic profiles in high and low monoclonal antibody–producing cell lines and studied the impact of tunicamycin (TM)-induced endoplasmic reticulum (ER) stress. We examined the expression levels of different proteins including unfolded protein response (UPR) target genes by using label-free quantification techniques for protein abundance. Our results show the upregulation of proteins associated with protein folding mechanisms in low producer vs. high producer cell line suggesting a form of ER stress related to specific protein production. Further, Hspa9 and Dnaja3 are notable candidates activated by the mitochondria UPR and play important roles in protein folding processes in mitochondria. We identified significant upregulation of Nedd8 and Lgmn proteins in similar levels which may contribute to UPR stress. Interestingly, the downregulation of Hspa5/Bip and Pdia4 in response to tunicamycin treatment suggests a low-level UPR activation. Key points: • Proteome profiling of recombinant CHO cells under mild TM treatment. • Identified protein clusters are associated with the unfolded protein response (UPR). • The compared cell lines revealed noticeable disparities in protein expression levels. [ABSTRACT FROM AUTHOR]

Background: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy. Patients: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed. Results: The median age was 63, with a median of 3 prior treatments. Twenty patients (69%) were refractory to any systemic therapy before CAR-T cell treatment. Following leukapheresis, 25 patients (86%) received bridging therapy with the majority undergoing chemotherapy (52%) or combined modality therapy (32%). Radiotherapy (RT) was part of the bridging strategy in 44%, with moderately hypofractionated involved site RT (30.0 Gy/2.5 Gy) being applied most frequently (64%). Post-CAR-T infusion, the objective response rate at 30 days was 83%, with 55% achieving complete response. Twelve-month progression-free (PFS) and overall survival (OS) were 60% and 74%, respectively, with a median follow up of 11.1 months for PFS and 17.9 months for OS. Factors significantly associated with PFS were chemotherapy sensitivity pre-leukapheresis and response to bridging. Conclusion: The study underscores the importance of minimal tumor burden at CAR-T initiation, emphasizing the need for suitable bridging regimens. The findings advocate for clinical trials and further real-world analyses to optimize CAR-T cell therapy outcomes by identifying the most effective bridging strategies. [ABSTRACT FROM AUTHOR]

The multi-messenger detection of the gravitational-wave signal GW170817, the corresponding kilonova AT2017gfo and the short gamma-ray burst GRB170817A, as well as the observed afterglow has delivered a scientific breakthrough. For an accurate interpretation of all these different messengers, one requires robust theoretical models that describe the emitted gravitational-wave, the electromagnetic emission, and dense matter reliably. In addition, one needs efficient and accurate computational tools to ensure a correct cross-correlation between the models and the observational data. For this purpose, we have developed the Nuclear-physics and Multi-Messenger Astrophysics framework NMMA. The code allows incorporation of nuclear-physics constraints at low densities as well as X-ray and radio observations of isolated neutron stars. In previous works, the NMMA code has allowed us to constrain the equation of state of supranuclear dense matter, to measure the Hubble constant, and to compare dense-matter physics probed in neutron-star mergers and in heavy-ion collisions, and to classify electromagnetic observations and perform model selection. Here, we show an extension of the NMMA code as a first attempt of analyzing the gravitational-wave signal, the kilonova, and the gamma-ray burst afterglow simultaneously. Incorporating all available information, we estimate the radius of a 1.4M⊙ neutron star to be R = 11.9 8 − 0.40 + 0.35 km. The Nuclear-physics and Multi-Messenger Astrophysics framework, NMMA, combines multiple information from neutron stars and neutron star mergers. Here, the authors show an update of the NMMA framework to constrain neutron star equation of state by simultaneously analyzing multi-messenger observations. [ABSTRACT FROM AUTHOR]

Spinal dural arteriovenous fistulas (SDAVFs) constitute the most common type of spinal vascular malformations. Their diagnosis requires spinal digital subtraction angiography (DSA), which is time-consuming, requires catheterizing many vessels, and exposes patient to a high radiation and contrast doses. This study aims to evaluate the usefulness of time-resolved MR angiography (TR–MRA) in SDAVF diagnosis. We performed a systematic review of the PubMed and EMBASE databases followed by a meta-analysis. TR–MRA was an index test, and spinal DSA was a reference. Of the initial 324 records, we included 4 studies describing 71 patients with SDAVFs. In 42 cases, TR–MRA was true positive, and in 21 cases, it was true negative. We found 7 false-positive cases and 1 false negative. TR–MRA allowed for shunt level identification in 39 cases. Of these, the predicted level was correct in 23 cases (59%), to within 1 level in 38 cases (97.4%) and to within 2 levels in 39 cases (100%). The diagnostic odds ratio was 72.73 (95% CI [10.30; 513.35]), z = 4.30, p value < 0.0001. The pooled sensitivity was 0.98 (95% CI [0.64; 1.00]), and the pooled specificity was 0.79 (95% CI [0.10; 0.99]). The AUC of the SROC curve was 0.9. TR–MRA may serve as a preliminary study to detect SDAVFs and localize the shunt level with sensitivity and specificity as high as 98% and 79%, respectively. Unless the TR–MRA result is unequivocal, it should be followed by a limited spinal DSA. [ABSTRACT FROM AUTHOR]

The oil gland secretion of the oribatid mite Nothrus palustris is known to show the phenomenon of juvenile–adult polymorphism, i.e., juvenile instars produce secretions predominated by geranial, whereas adults secrete dehydrocineole along with a number of chemically unidentified compounds. We here re-analyzed the secretions of adult N. palustris by GC–MS and NMR spectroscopy, eventually identifying the unknown compounds as p-menthane monoterpenoids. The major components were two isomeric 6-isopropenyl-3-methyl-cyclohex-3-en-1-yl formates (= p-1,8-menthadien-5-yl formates), which accounted for about 75% of the secretion. These were accompanied by five additional, only partly identified p-menthanes (or p-methane-derivatives), all of which represented minor or trace components. In addition, adult secretions contained two C21-hydrocarbons, 1,12-heneicosadiene (major) and a heneicosatriene (minor). Menthane monoterpenoids represent a novel sub-class of terpene compounds in the oil gland secretions of Oribatida. In case of N. palustris, we assume that both geranial and p-menthane monoterpenoids arise via the mevalonate pathway which obviously shows a split at the level of geranyl pyrophosphate, leading to geranial in juveniles and to p-menthanes in adults. The significance of methane occurrence in oil glands as well as the taxonomic distribution of juvenile–adult polymorphism in oribatid oil gland secretions is discussed. The latter phenomenon—i.e., "chemo-metamorphosis" of secretions—is not known from early- and middle-derivative Oribatida nor from Astigmata, but appears to be more common in some derivative desmonomatan and brachypyline oribatid groups. [ABSTRACT FROM AUTHOR]

Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen. Here we have used the hetero-bifunctional zero-length reagent 1-Ethyl-3-(3-Dimethylaminopropyl)-Carbodiimide (EDC) to cross-link two soluble Env trimers, selected well-folded trimer species using antibody affinity, and transferred this process to good manufacturing practice (GMP) for experimental medicine use. Cross-linking enhanced trimer stability to biophysical and enzyme attack. Cryo-EM analysis revealed that cross-linking retained the overall structure with root-mean-square deviations (RMSDs) between unmodified and cross-linked Env trimers of 0.4–0.5 Å. Despite this negligible distortion of global trimer structure, we identified individual inter-subunit, intra-subunit, and intra-protomer cross-links. Antigenicity and immunogenicity of the trimers were selectively modified by cross-linking, with cross-linked ConS retaining bnAb binding more consistently than ConM. Thus, the EDC cross-linking process improves trimer stability whilst maintaining protein folding, and is readily transferred to GMP, consistent with the more general use of this approach in protein-based vaccine design. [ABSTRACT FROM AUTHOR]

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Mesozoic oceanic anoxic events are recognized as widespread deposits of marine organic-rich mudrocks temporally associated with mass extinctions and large igneous province emplacement. The Toarcian Oceanic Anoxic Event is one example during which expanded ocean anoxia is hypothesized in response to environmental perturbations associated with emplacement of the Karoo–Ferrar igneous province. However, the global extent of total seafloor anoxia and the relative extent of euxinic (anoxic and sulfide-rich) and non-euxinic anoxic conditions during the Toarcian Oceanic Anoxic Event are poorly constrained. Here we present estimates of the global total anoxic and euxinic seafloor areas before and during the Toarcian Oceanic Anoxic Event based on rhenium and molybdenum enrichments, respectively, in organic-rich mudrocks of the Fernie Formation (British Columbia, Canada). We find that mass balance models depict an expansion of up to ~7% total seafloor anoxia, which was dominated by euxinia, at the onset of the Toarcian Oceanic Anoxic Event, followed by a contraction before the end of the event. The global ocean redox trends revealed by the rhenium data mirrors the collapse and recovery patterns of global ammonite and foraminiferal biodiversity. Geochemical modeling shows that just a several percent expansion of O2-free areas with toxic sulfide build-up likely contributed to biodiversity loss or reorganization during the Toarcian mass extinction 183 million years ago. [ABSTRACT FROM AUTHOR]

Climate change is causing more frequent and severe climatic events, such as extreme heat and co-occurring drought, potentially accelerating tree mortality. Which tree species will cope better with those extreme events is still being researched. This study focuses on heat as a physiological stress factor and interspecific variation of thermal tolerance and sensitivity traits in 15 temperate coniferous and broad-leaved tree species. We investigate (1) whether thermal tolerance and sensitivity traits correlate with a drought-related physiological trait, particularly the leaf turgor loss point (πtlp, wilting point), and (2) how thermal tolerance and sensitivity traits co-vary within different tree-functional types classified by morphological and physiological traits of the leaf, i.e., leaf mass per area (LMA) and percentage loss of area (PLA). The study was carried out in the Traunstein Forest Dynamics Plot of the ForestGEO network in Germany. The temperature response of the maximum quantum yield of photosystem II (Fv/Fm) on leaf discs was determined, from which various physiological leaf traits were estimated, one of which is the breaking point temperature (T5), the temperature at which Fv/Fm declines by 5%. Additionally, the temperature of 50% (T50) and 95% (T95) decline in Fv/Fm was evaluated. The decline width between T50 and T5 (DWT50−T5) was taken as an indicator of the species' thermal sensitivity. The breaking point temperature ranged from 35.4 ± 3.0 to 47.9 ± 3.9 °C among the investigated tree species and T50 ranged between 46.1 ± 0.4 and 53.6 ± 0.7 °C. A large interspecific variation of thermal tolerance and sensitivity was found. European ash (Fraxinus excelsior L.) was the most heat-sensitive species, while Wild cherry (Prunus avium L.) was the least heat-sensitive species. Species with a more negative πtlp tended to have a higher breaking point temperature than species with a less negative πtlp. A lower thermal sensitivity characterized species with a higher LMA, and high PLA was found in species with low thermal sensitivity. Accordingly, species with thicker and tougher leaves have lower thermal sensitivity which coincides with a lower wilting point. We conclude that species that develop drought-adapted foliage can cope better with heat stress. Further, they might be able to maintain transpirational cooling during combined heat and drought stress, which could lessen their mortality risk during climatic extremes. [ABSTRACT FROM AUTHOR]

Background: Radioguided surgery (RGS) has recently emerged as a valuable new tool in the management of recurrent prostate cancer (PCa). After preoperative injection of a 99mTc-labeled prostate-specific membrane antigen (PSMA) inhibitor, radioguided intraoperative identification and resection of lesions is facilitated by means of suitable γ-probes. First clinical experiences show the feasibility of RGS and suggest superiority over conventional lymph node dissection in recurrent PCa. However, commonly used [99mTc]Tc-PSMA-I&S exhibits slow whole-body clearance, thus hampering optimal tumor-to-background ratios (TBR) during surgery. We therefore aimed to develop novel 99mTc-labeled, PSMA-targeted radioligands with optimized pharmacokinetic profile to increase TBR at the time of surgery. Methods: Three 99mTc-labeled N4-PSMA ligands were preclinically evaluated and compared to [99mTc]Tc-PSMA-I&S. PSMA affinity (IC50) and internalization were determined on LNCaP cells. Lipophilicity was assessed by means of the distribution coefficient logD7.4 and an ultrafiltration method was used to determine binding to human plasma proteins. Biodistribution studies and static µSPECT/CT-imaging were performed at 6 h p.i. on LNCaP tumor-bearing CB17-SCID mice. Results: The novel N4-PSMA tracers were readily labeled with [99mTc]TcO4− with RCP > 95%. Comparable and high PSMA affinity was observed for all [99mTc]Tc-N4-PSMA-ligands. The ligands showed variable binding to human plasma and medium to low lipophilicity (logD7.4 − 2.6 to − 3.4), both consistently decreased compared to [99mTc]Tc-PSMA-I&S. Biodistribution studies revealed comparable tumor uptake among all [99mTc]Tc-N4-PSMA-ligands and [99mTc]Tc-PSMA-I&S, while clearance from most organs was superior for the novel tracers. Accordingly, increased TBR were achieved. [99mTc]Tc-N4-PSMA-12 showed higher TBR than [99mTc]Tc-PSMA-I&S for blood and all evaluated tissue. In addition, a procedure suitable for routine clinical production of [99mTc]Tc-N4-PSMA-12 was established. Labeling with 553 ± 187 MBq was achieved with RCP of 98.5 ± 0.6% (n = 10). Conclusion: High tumor accumulation and favorable clearance from blood and non-target tissue make [99mTc]Tc-N4-PSMA-12 an attractive tracer for RGS, possibly superior to currently established [99mTc]Tc-PSMA-I&S. Its GMP-production according to a method presented here and first clinical investigations with this novel radioligand is highly recommended. [ABSTRACT FROM AUTHOR]

In recent years, various depth sensors that are small enough to be used with mobile hardware have been introduced. They provide important information for use cases like 3D reconstruction or in the context of augmented reality where tracking and camera data alone would be insufficient. However, depth sensors may not always be available due to hardware limitations or when simulating augmented reality applications for prototyping purposes. In these cases, different approaches like stereo matching or depth estimation using neural networks may provide a viable alternative. In this paper, we therefore explore the imitation of depth sensors using deep neural networks. For this, we use a state-of-the-art network for depth estimation and adapt it in order to mimic a Structure Sensor as well as an iPad LiDAR sensor. We evaluate the network which was pre-trained on NYU V2 directly as well as several variations where transfer learning is applied in order to adapt the network to different depth sensors while using various data preprocessing and augmentation techniques. We show that a transfer learning approach together with appropriate data processing can enable an accurate modeling of the respective depth sensors. [ABSTRACT FROM AUTHOR]

Mixed species forests are known to have a higher gross primary productivity (GPP) and net primary productivity (NPP) than forests containing only one single tree species. Trees growing in mixtures are characterized by higher autotrophic respiration (Ra), this results in a lower carbon use efficiency of mixed species forests compared to monocultures. The pathway responsible for the high quantities of carbon lost through respiratory pathways is still unclear. Here, we present the only existing measurements evaluating tree mixture effects based on stem CO2 efflux (Estem), scaled to woody respiration (Rw) on stand level. We conducted predawn Estem measurements on five tree species in an experimental tree plantation in Central Panama. Estem was scaled to the entire plot level woody respiration (Rw). Annual Rw was on average 0.25 ± 0.08 Mg C ha− 1 in the monocultures and 0.28 ± 0.10 Mg C ha− 1 in mixed species stands. In mixtures, annual Ra was more than three times higher than in monocultures. As mean Rw was almost constant across the mixture types and Ra varied largely, leads to the conclusion that mixed species plots allocate a higher amount of carbon toward respiratory processes in leaves and roots. This was supported by no significant differences in the mixture effects on the growth respiration relationship. [ABSTRACT FROM AUTHOR]

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Main conclusion: Using virus-induced gene silencing, we demonstrated that the enzymes GES, ISY, and MLPL are responsible for nepetalactone biosynthesis in Nepeta cataria. Nepetalactone is the main iridoid that is found in the Nepeta genus and is well-known for its psychoactive effect on house cats. Moreover, there is a burgeoning interest into the effect of nepetalactone on insects. Although the enzymes for nepetalactone biosynthesis have been biochemically assayed in vitro, validation of the role that these enzymes have in planta has not been demonstrated. Virus-induced gene silencing (VIGS) is a silencing method that relies on transient transformation and is an approach that has been particularly successful when applied to a variety of non-model plants. Here, we use a recently designed visual-marker dependent VIGS system to demonstrate that the nepetalactone biosynthetic enzymes GES, ISY, and MLPL impact nepetalactone biosynthesis in Nepeta cataria. [ABSTRACT FROM AUTHOR]

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Thousands of natural products are derived from the fused cyclopentane-pyran molecular scaffold nepetalactol. These natural products are used in an enormous range of applications that span the agricultural and medical industries. For example, nepetalactone, the oxidized derivative of nepetalactol, is known for its cat attractant properties as well as potential as an insect repellent. Most of these naturally occurring nepetalactol-derived compounds arise from only two out of the eight possible stereoisomers, 7S-cis-trans and 7R-cis-cis nepetalactols. Here we use a combination of naturally occurring and engineered enzymes to produce seven of the eight possible nepetalactol or nepetalactone stereoisomers. These enzymes open the possibilities for biocatalytic production of a broader range of iridoids, providing a versatile system for the diversification of this important natural product scaffold. Iridoid compounds are an important class of natural products. Here, the authors report on the discovery and engineering of nepetalactol-related short chain reductases and their application for the biosynthesis of nepetalactol or nepetalactone stereoisomers, as a versatile system for the production of the iridoid natural product scaffold. [ABSTRACT FROM AUTHOR]

Key message: Calmodulin-like-proteins (CML) belong to a family of calcium-sensing proteins that are unique for plants and involved in many different developmental and stress-related reactions. In defense against herbivory, some pathogens and drought, CML37 acts as a positive and CML42 as a negative regulator, respectively. We provide evidence that both CMLs act antagonistically in the regulation of induced defense responses. A double knock-out line, cml37 x cml42, thus shows wild-type phenotypes upon all kind of stresses we used. A transient increase in the cytosolic calcium concentration is one of the first reactions that can be measured in plant cells upon abiotic as well as biotic stress treatments. These calcium signals are sensed by calcium binding proteins such as calmodulin-like proteins (CMLs), which transduce the sensed information into appropriate stress responses by interacting with downstream target proteins. In previous studies, CML37 has been shown to positively regulate the plants' defense against both the insect herbivore Spodoptera littoralis and the response to drought stress. In contrast, CML42 is known to negatively regulate those two stress responses. Here, we provide evidence that these two CMLs act antagonistically in the regulation of induced responses directed against drought and herbivory stress as well as in the defense against the necrotrophic pathogen Alternaria brassicicola. Both CMLs shape the plant reactions by altering the phytohormone signaling. Consequently, the phytohormone-regulated production of defensive compounds like glucosinolates is also antagonistically mediated by both CMLs. The finding that CML37 and CML42 have antagonistic roles in diverse stress-related responses suggests that these calcium sensor proteins represent important tools for the plant to balance and fine-tune the signaling and downstream reactions upon environmental stress. [ABSTRACT FROM AUTHOR]

Cerebral arteries (CAs) are prone to the saccular aneurysm formation. Since aneurysms may be considered as balloon-like dilations of the locally weakened arterial wall, it should be determined whether the presence of intracranial aneurysm is related to the generalized weakening of CAs. Among 184 consecutive forensic autopsies, eight brains with a single unruptured saccular aneurysm were identified. Aneurysms with adjacent CAs and specific CA segments were excised, namely: the anterior communicating artery complex, and bifurcations of the basilar artery, internal carotid arteries, and middle cerebral arteries. Then, aneurysm and CA specimens were subjected to pressure-inflation tests until rupture occurred at the arterial bifurcation or at the wall of the CA or aneurysm. The same protocol was applied to the control group composed of CAs excised from eight brains without aneurysm. No significant differences were noted between the experimental and control groups, depending on the mean rupture pressure (1054 vs. 1048 mmHg) and rupture site (bifurcation vs. wall) of the analyzed specimens. These findings indicate that the presence of unruptured saccular aneurysm is not related to generalized weakening of CAs among autopsy subjects. Moreover, the CA bifurcations do not represent regions of decreased wall strength. [ABSTRACT FROM AUTHOR]

Baker's yeast (Saccharomyces cerevisiae) is a model organism for studying the morphology that emerges at the scale of multi-cell colonies. To look at how morphology develops, we collect a dataset of time-lapse photographs of the growth of different strains of S. cerevisiae. We discuss the general statistical challenges that arise when using time-lapse photographs to extract time-dependent features. In particular, we show how texture-based feature engineering and representative clustering can be successfully applied to categorize the development of yeast colony morphology using our dataset. The Local binary pattern (LBP) from image processing is used to score the surface texture of colonies. This texture score develops along a smooth trajectory during growth. The path taken depends on how the morphology emerges. A hierarchical clustering of the colonies is performed according to their texture development trajectories. The clustering method is designed for practical interpretability; it obtains the best representative colony image for any hierarchical cluster. Measurement(s) Yeast colony morphology Technology Type(s) Time-lapse photographs Factor Type(s) Genotype Sample Characteristic - Organism Saccharomyces cerevisiae [ABSTRACT FROM AUTHOR]

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Suboccipital decompression with duraplasty is a widely accepted method for treating patients with Chiari malformation type I. However, important details of the duraplasty technique are still controversial. This retrospective study analyzes clinical and radiological outcomes after surgery depending upon the type of graft and methods of graft fixation. Seventy consecutive decompressions with duraplasty were analyzed. Two types of grafts, nonautologous (Non-AutoG; 60.0%) and autologous (AutoG; 40.0%), and two methods of graft fixation, suturing (S; 67.1%) and gluing (G; 32.9%), were used in four different combinations: (Non-AutoG+S: 31.4%; Non-AutoG+G: 28.6%; AutoG+S: 35.7%; AutoG+G: 4.3%) according to surgeon preference. The mean follow-up was 63.4 months. According to gestalt and Chicago Chiari Outcome Scales, satisfactory results were obtained in 72.9% and 78.6% of cases, respectively, in the long term. The outcomes were not related to the kind of graft (p = 0.44), fixation method (p = 0.89) or duraplasty pattern (p = 0.32). Decreased syringomyelia was observed in 88.9% of cases, and no associations with the kind of graft (p = 0.84), fixation method (p = 1) or duraplasty pattern were found (p = 0.96). Pseudomeningocele occurred 5 times more often in the Non-AutoG group than in the AutoG group (52.4% vs. 10.7%; p < 0.05), whereas their formations were not related to the fixation method (p = 0.34). Three cases (12.0%) required reoperation with reduraplasty. Autologous and nonautologous dural grafts can be sutured or glued with similar clinical results; however, the use of nonautologous grafts is linked with a much higher risk of pseudomeningocele formation. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of practical surgical training is characterised by an inherent learning curve. Decisive are individual initial starting capabilities, learning speed, ideal learning plateaus, and resulting learning potentials. The quantification of learning curves requires reproducible tasks with varied levels of difficulty. The hypothesis of this study is that the use of three-dimensional (3D) vision is more advantageous than two-dimensional vision (2D) for the learning curve in laparoscopic training. Methods: Forty laparoscopy novices were recruited and randomised to a 2D Group and a 3D Group. A laparoscopy box trainer with two standardised tasks was used for training of surgical tasks. Task 1 was a positioning task, while Task 2 called for laparoscopic knotting as a more complex process. Each task was repeated at least ten times. Performance time and the number of predefined errors were recorded. 2D performance after 3D training was assessed in an additional final 2D cycle undertaken by the 3D Group. Results: The calculated learning plateaus of both performance times and errors were lower for 3D. Independent of the vision mode the learning curves were smoother (exponential decay) and efficiency was learned faster than precision. The learning potentials varied widely depending on the corresponding initial values and learning plateaus. The final 2D performance time of the 3D-trained group was not significantly better than that of the 2D Group. The final 2D error numbers were similar for all groups. Conclusions: Stereoscopic vision can speed up laparoscopic training. The 3D learning curves resulted in better precision and efficiency. The 3D-trained group did not show inferior performance in the final 2D cycle. Consequently, we encourage the training of surgical competences like suturing and knotting under 3D vision, even if it is not available in clinical routine. [ABSTRACT FROM AUTHOR]

Background: Most currently used surgical robots have no force feedback; the next generation displays forces visually. A novel single-port robotic surgical system called FLEXMIN has been developed. Through an outer diameter of 38 mm, two instruments are teleoperated from a surgeon's control console including true haptic force feedback. One additional channel incorporates a telescope, another is free for special instrument functions.Methods: This randomized cross-over study analyzed the effect of haptic feedback on the application of intracorporeal forces. In a standardized experiment setup, the subjects had to draw circles with the surgical robot as gently as possible. The applied forces, the required time spans, and predefined error rates were measured.Results: Without haptic feedback, the maximum forces (median/IQR) were 6.43 N/2.96 N. With haptic feedback, the maximum forces were lower (3.57 N/1.94 N, p < 0.001). Also, the arithmetic means of the force progression (p < 0.001) and their standard deviations (p < 0.001) were lower. Not significant were the shorter durations and lower error rates. No sequence effect of force or duration was detected. No characteristic learning or fatigue curve was observed.Conclusions: In the experiment setup, the true haptic force feedback can reduce the applied intracorporeal robotic force to one-half when considering the aspects maximum, means, and standard deviation. Other test tasks are needed to validate the influence of force feedback on surgical efficiency and safety. [ABSTRACT FROM AUTHOR]

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Crossover designs are called for in situations when several subjects undergo a sequence of treatments. Though, usually, the model contains the direct effects of treatments as well as the carryover effects, the primary interest lies in the estimation of direct effects of the treatment. Most results in the literature on crossover designs are available for the situations where either the number of periods or the number of subjects is a multiple of the number of treatments. In this article, we consider crossover designs for the non-regular settings, that is, the situations when the number of treatments divides neither the number of periods nor the number of subjects. We provide a construction method to obtain highly E-efficient crossover designs for non-regular settings, while also providing a crude lower bound to E-efficiency of the designs constructed through our construction method. In a table, we provide E-efficiencies of a constructed design for the number of treatments up to 10 and the number of subjects up to 50. [ABSTRACT FROM AUTHOR]

A shift toward the endovascular treatment of ophthalmic segment aneurysms is noticeable. However, it is not clear if the long-term treatment results improve with the development of endovascular methods. The aim of this study was to present the outcomes of the treatment of unruptured ophthalmic aneurysms using flow diverting devices (FDD) with or without coiling. This retrospective study included 52 patients with 65 UIAs treated in 2009–2016. The mean aneurysm size was 8.8 mm. Eight aneurysms were symptomatic. Therapeutic procedures included: 5 failed attempts, 55 first sessions with FDD deployment (bilateral procedures in 3) and 3 retreatment procedures. To cover 55 ICAs, 25 Silk, 26 Pipeline, 9 Fred and 1 Surpass FDD were used. FDD with coiling was applied in 19(29.2%), mainly for symptomatic and larger aneurysms. Mean radiological and clinical follow-up was 12 and 61 months, respectively. Postprocedural deterioration was noted in 3(5.8%) patients, but in long-term the modified Rankin Scale grades 0–2 were achieved in 98.1% of patients. One patient died from the treated aneurysm rupture (annual risk—0.07%). Raymond–Roy occlusion classification class I or II was achieved in 98.5% in the long term, with similar results in both groups. Complications occurred in 40.4% of patients and the most frequent were: imperfect FDD deployment (15%), failed attempt of FDD deployment (9.6%) and late FDD stenosis (9.6%). Flow-diverting devices, with additional coiling in selected cases, may offer a very high proportion of satisfactory outcomes. However, in our experience the high risk of complications remains. [ABSTRACT FROM AUTHOR]

The ectomycorrhizospheric habitat contains a diverse pool of organisms, including the host plant, mycorrhizal fungi, and other rhizospheric microorganisms. Different signaling molecules may influence the ectomycorrhizal symbiosis. Here, we investigated the potential of the basidiomycete Tricholoma vaccinum to produce communication molecules for the interaction with its coniferous host, Norway spruce (Picea abies). We focused on the production of volatile organic compounds and phytohormones in axenic T. vaccinum cultures, identified the potential biosynthesis genes, and investigated their expression by RNA-Seq analyses. T. vaccinum released volatiles not usually associated with fungi, like limonene and β-barbatene, and geosmin. Using stable isotope labeling, the biosynthesis of geosmin was elucidated. The geosmin biosynthesis gene ges1 of T. vaccinum was identified, and up-regulation was scored during mycorrhiza, while a different regulation was seen with mycorrhizosphere bacteria. The fungus also released the volatile phytohormone ethylene and excreted salicylic and abscisic acid as well as jasmonates into the medium. The tree excreted the auxin, indole-3-acetic acid, and its biosynthesis intermediate, indole-3-acetamide, as well as salicylic acid with its root exudates. These compounds could be shown for the first time in exudates as well as in soil of a natural ectomycorrhizospheric habitat. The effects of phytohormones present in the mycorrhizosphere on hyphal branching of T. vaccinum were assessed. Salicylic and abscisic acid changed hyphal branching in a concentration-dependent manner. Since extensive branching is important for mycorrhiza establishment, a well-balanced level of mycorrhizospheric phytohormones is necessary. The regulation thus can be expected to contribute to an interkingdom language. [ABSTRACT FROM AUTHOR]

Overpopulation of domestic pigeons is considered to be one of the major problems of urban centers, as these birds are responsible for the dissemination of relevant pathogens to animal and human health. The aim of this study was to detect potentially pathogenic Escherichia coli and Salmonella spp. in domestic pigeons captured in areas near silos used for grain and feed storage, analyzing the antimicrobial sensitivity and the presence of virulence-associated genes. We evaluated 41 pigeons. From each bird, cecal contents and a pool of viscera (heart, spleen, and liver) were collected. Fifty strains of E. coli and three strains of S. Typhimurium were isolated. The antimicrobial susceptibility assay showed that 2% of the isolates of E. coli were resistant to chloramphenicol and the combination of sulfamethoxazole + trimethoprim and 4% to tetracycline, doxycycline, and sulfonamide. The three S. Typhimurium strains were sensitive to all antimicrobials tested. The pathogenicity profile demonstrated that no E. coli isolates showed a STEC compatible profile. Regarding the APEC pathotype, all genes were observed in 8% of E. coli, 6% had only the iss gene and 4% presented ompT, hlyF, and iutA genes. invA, hilA, avrA, and lpfA genes were detected in 100% of Salmonella isolates. The sitC and pefA genes were only present in one strain and the remaining genes were detected in two. In conclusion, it was found that pigeons living in the vicinity of silos are carriers of important pathogens, and control measures should be taken to minimize animal and human health risks. [ABSTRACT FROM AUTHOR]

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Background: During laparoscopic operations, the trocars are often out of the viewing field of the laparoscope. Blind insertion of laparoscopic instruments is potentially dangerous especially when they are pointed or hot. A guidance of the instrument to the target point has the potential to improve the safety of instrument insertion.Methods: In this study, the effect of a mechanical and an optical tool for guided instrument insertion into the abdominal cave was evaluated. The controlled prospective randomized study measured safety and efficiency of instrument insertion by 60 novices in an inanimate standardized box trainer. A post-test questionnaire based on the NASA Task Load Index prompted for the subjective impressions of the subjects.Results: Instrument insertion with optical guidance showed a shorter (p = 0.002) insertion time (median 87.5 s for nine insertions) compared with blind insertion (median 112.0 s for nine insertions). The error number with optical guidance (median 0.5) was lower (p = 0.064) compared with blind insertion (median 1.0). The mechanical guidance showed a shorter (p = 0.001) insertion time (median 89.0 s for nine insertions) and less (p = 0.044) touch errors (median 0) compared with blind insertion. The results of the two guidance tools (mechanical vs. optical guidance) showed no significant difference. In the questionnaire, 89% of the novices subjectively judged the mechanical guidance tool better than blind insertion. The assessments of optical compared to mechanical guidance turned out quite similar.Conclusions: In the experimental setup, instrument insertion with a guidance tool performed faster and safer compared with blind insertion. The subjective assessments confirmed the benefit of instrument guidance. [ABSTRACT FROM AUTHOR]

The horseradish flea beetle Phyllotreta armoraciae exclusively feeds on Brassicaceae, which contain glucosinolates as characteristic defense compounds. Although glucosinolates are usually degraded by plant enzymes (myrosinases) to toxic isothiocyanates after ingestion, P. armoraciae beetles sequester glucosinolates. Between and within brassicaceous plants, the glucosinolate content and composition can differ drastically. But how do these factors influence sequestration in P. armoraciae? To address this question, we performed a five-day feeding experiment with three Arabidopsis thaliana lines that differ four-fold in glucosinolate content and the composition of aliphatic and indolic glucosinolates. We quantified the amounts of ingested, sequestered, and excreted glucosinolates, and analyzed the changes in glucosinolate levels and composition in beetles before and after feeding on Arabidopsis. P. armoraciae accumulated almost all ingested glucosinolate types. However, some glucosinolates were accumulated more efficiently than others, and selected glucosinolates were modified by the beetles. The uptake of new glucosinolates correlated with a decrease in the level of stored glucosinolates so that the total glucosinolate content remained stable at around 35 nmol/mg beetle fresh weight. Beetles excreted previously stored as well as ingested glucosinolates from Arabidopsis, which suggests that P. armoraciae regulate their endogenous glucosinolate level by excretion. The metabolic fate of ingested glucosinolates, i.e. the proportions of sequestered and excreted glucosinolates, depended on glucosinolate type, content, and composition in the food plant. Overall, P. armoraciae sequestered and excreted up to 41% and 31% of the total ingested aliphatic and indolic glucosinolates from Arabidopsis, respectively. In summary, we show that glucosinolate variability in Brassicaceae influences the composition but not the level of sequestered glucosinolates in P. armoraciae beetles. [ABSTRACT FROM AUTHOR]

In this work, the influence of a partial introduction of bromide (x = 0–0.33) into MA0.75FA0.15PEA0.1Sn(BrxI1−x)3 (MA: methylammonium, FA: formamidinium, PEA: phenylethylammonium) triple cation tin perovskite on the material properties and photovoltaic performance is investigated and characterized. The introduction of bromide shifts the optical band gap of the perovskite films from 1.29 eV for the iodide-based perovskite to 1.50 eV for the perovskite with a bromide content of x = 0.33. X-ray diffraction measurements reveal that the size of the unit cell is also gradually reduced based on the incorporation of bromide. Regarding the photovoltaic performance of the perovskite films, it is shown that already small amounts of bromide (x = 0.08) in the perovskite system increase the open circuit voltage, short circuit current density and fill factor. The maximum power conversion efficiency of 4.63% was obtained with a bromide content of x = 0.25, which can be ascribed to the formation of homogeneous thin films in combination with higher values of the open circuit voltage. Upon introduction of a higher amount of bromide (x = 0.33), the perovskite absorber layers form pinholes, thus reducing the overall device performance. [ABSTRACT FROM AUTHOR]

Leaf traits have been shown to explain a great fraction of differences in growth rates in trees. With this study, we evaluate if differences in growth performance of different species mixtures in a tropical tree plantation can be attributed to the plasticity of the specific leaf area index. We compare the specific leaf area of five native Panamanian tree species growing in monospecific stands, stands containing two or three tree species and stands containing all five tree species. We could confirm the commonly observed interspecific linear relationship between leaf dry mass per leaf area. Despite the general relationship, a plasticity of the specific leaf area was detected for certain species in different mixture types. In general, the plasticity was lower for sun leaves than for shade leaves and the expression of leaf trait plasticity depended largely on the species. We performed an additive partitioning of mixture effects and the analysis resulted in strong complementarity effects on plot level. We speculate that leaf plasticity might increase the ability of certain tree species to use light more efficiently in mixed species stands. The resulting complementarity between species allows mixed stands an optimized light resource use and higher productivity. Accordingly, relative growth rate on plot level scaled linearly with specific leaf area of a given stand. Establishing mixed reforestation stands covering a wider range of tree leaf functional traits, such as assembling tree species characterized by different specific leaf area, might favor the expression of the trait plasticity and thus the overall plantation performance. [ABSTRACT FROM AUTHOR]

Evolutionary-based predictions imply that the premenstrual syndrome (PMS) affects women who failed to conceive while in biosocial conditions that allow immediate reproduction. We investigated how the PMS is related to the heart rate variability (HRV), a marker of general fitness and well-being. The HRV indices (SDNN and rMSSD) were calculated using resting ECGs of 113 physiologically fertile women and 64 women using hormonal contraception (HC users, HCu). The intensity of PMS symptoms was self-assessed (Shortened Premenstrual Assessment Form). Analyses were conducted using parametric and nonparametric tests and general linear modelling (GLM). In HC non-users (HCnu), a greater intensity of PMS symptoms was significantly associated with higher values of HRV. Similar relations were not present in HCu. Post-hoc GLM confirmed that the relation between the PMS intensity and HRV indices varies as a function of the HCu status. A positive association between the PMS intensity and high HRV indices in women who did not use HC may confirm that the PMS affects fertile women who did not conceive, despite being in conditions favorable to pregnancy. The absence of a similar link in HCu women implies that synthetic steroids may disturb the link between the PMS and functioning of the autonomic nervous system. [ABSTRACT FROM AUTHOR]

The fibroblast growth factor (FGF) 23/Klotho axis is a principal regulator of phosphate hemostasis and vitamin D metabolism, but limited data is available on its role in the central nervous system. Here, we investigate soluble α-Klotho (sKlotho) and C-terminal as well as intact FGF23 in cerebrospinal fluid (CSF) and plasma and their relationship to mineral metabolism parameters in humans. In 39 children aged 0.3-16.8 years undergoing lumbar puncture for the exclusion of inflammatory neurological disease, sKlotho and FGF23 were investigated by Western blot analysis, followed by ELISA quantification in CSF and plasma. The percentage of intrathecal synthesis of both proteins was calculated by measuring both the expected and observed CSF/plasma ratios of sKlotho and FGF23. The secreted (KL1) and cleaved (KL1+KL2) isoforms of sKlotho, and FGF23 were clearly detected in CSF in all subjects, although protein levels were lower compared to those of plasma samples (each p < 0.01). The intrathecal percentage of CSF sKlotho and FGF23 synthesis amounted to 98 and 99 %, respectively. CSF sKlotho levels were higher in boys than in girls (p < 0.01), and correlated positively with plasma C-terminal FGF23 concentrations (p < 0.05) and standardized height (p < 0.01). Importantly, there were no significant correlations between plasma and CSF levels of sKlotho or FGF23. Plasma sKlotho as well as C-terminal and intact FGF23, respectively, were associated with parameters of mineral metabolism These results provide evidence that cleaved and secreted sKlotho and FGF23 are present in CSF, mainly derived from brain and affected by sex, height, and mineral metabolism parameters in children. Nevertheless, the absence of significant associations between plasma and CSF levels of Klotho and FGF23, respectively, suggest that the regulation of Klotho and FGF23 may be different between organs secreting these hormones into blood and CSF. [ABSTRACT FROM AUTHOR]

The production potential of recombinant monoclonal antibody (mAb) expressing cell lines depends, among other factors, on the intrinsic antibody structure determined by the amino acid sequence. In this study, we investigated the influence of somatic mutations in the V(D)J sequence of four individual, mature model mAbs on the expression potential. Therefore, we defined four couples, each consisting of one naturally occurring mAb (2G12, Ustekinumab, 4B3, and 2F5) and the corresponding germline-derived cognate mAb (353/11, 554/12, 136/63, and 236/14). For all eight mAb variants, recombinant Chinese hamster ovary (CHO) cell lines were developed with mAbs expressed from a defined chromosomal locus. The presented workflow investigates critical parameters including productivity, intra- and extracellular product profile, XBP1 splicing, thermal stability, and in silico hydrophobicity. Significant differences in productivity were even observed between the germline-derived mAbs which did not undergo somatic mutagenesis. Accordingly, back-to-germline mutations of mature mAbs are not necessarily reflecting improved expression and stability but indicate opportunities and limits of mAb engineering. From our studies, we conclude that germinalization represents a potential to improve mAb properties depending on the antibody's germline family, highlighting the fact that mAbs should be treated individually. [ABSTRACT FROM AUTHOR]

Lead halide perovskites have proved to be exceptionally efficient absorber materials for photovoltaics. Besides improving the properties of the perovskite absorbers, device engineering and the optimization of interfaces will be equally important to further the advancement of this emerging solar cell technology. Herein, we report a successful modification of the interface between the NiOx hole transport layer and the perovskite absorber layer using 4-bromobenzylphosphonic acid based self-assembled monolayers leading to an improved photovoltaic performance. The modification of the NiOx layer is carried out by dip coating which allows sufficient time for the self-assembly. The change in the surface free energy and the non-polar nature of the resulting surface is corroborated by contact angle measurements. X-ray photoelectron spectroscopy confirms the presence of phosphor and bromine on the NiOx surface. Furthermore, the resultant solar cells reveal increased photovoltage. For typical devices without and with modification, the photovoltage improves from 0.978 V to 1.029 V. The champion VOC observed was 1.099 V. The increment in photovoltage leads to improved power conversion efficiencies for the modified cells. The maximum power point tracking measurements of the devices show stable power output of the solar cells. [ABSTRACT FROM AUTHOR]

Copyright of Psychotherapie Forum is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)