Search

To describe the technique and outcomes of the closure of maxillary lip defects using a buccal transposition flap and to identify potential routes of vascular supply to the flap.Five dogs treated clinically and 1 cadaveric dog head.Short case series and cadaveric study.A left maxillary labial defect and a buccal transposition flap were created on a cadaver head. Iodinated contrast was injected into the left common carotid artery and computed tomography was performed to assess the vascular supply. Medical records were reviewed for all dogs that underwent tumor excision with maxillary lip resection, reconstructed with a buccal transposition flap.The buccal transposition flap was perfused by branches of the angularis oris artery and superior labial artery. Five dogs were included in this study. All flaps survived. Three dogs developed postoperative complications, including oronasal fistula (n = 2) and partial flap dehiscence (n = 1). The cosmetic and functional outcomes were considered satisfactory in all cases.Buccal transposition flaps for the closure of large maxillary lip defects provided adequate functional and cosmetic outcomes. The buccal transposition flap had vascular contributions from the angularis oris artery and the superior labial artery.

This multi-institutional study assessed the efficacy of Enterococcus faecium NRRL B-2354 as a nonpathogenic Salmonella surrogate for thermal processing of nonfat dry milk powder, peanut butter, almond meal, wheat flour, ground black pepper, and date paste. Each product was analyzed by two laboratories (five independent laboratories total), with the lead laboratory inoculating (E. faecium or a five-strain Salmonella enterica serovar cocktail of Agona, Reading, Tennessee, Mbandaka, and Montevideo) and equilibrating the product to the target water activity before shipping. Both laboratories subjected samples to three isothermal treatments (between 65 and 100°C). A log-linear and Bigelow model was fit to survivor data via one-step regression. On the basis of D80°C values estimated from the combined model, E. faecium was more thermally resistant (P0.05) than Salmonella in nonfat dry milk powder (DEf-80°C, 100.2 ± 5.8 min; DSal-80°C, 28.9 ± 1.0 min), peanut butter (DEf-80°C, 133.5 ± 3.1 min; DSal-80°C, 57.6 ± 1.5 min), almond meal (DEf-80°C, 34.2 ± 0.4 min; DSal-80°C, 26.1 ± 0.2 min), ground black pepper (DEf-80°C, 3.2 ± 0.8 min; DSal-80°C, 1.5 ± 0.1 min), and date paste (DEf-80°C, 1.5 ± 0.0 min; DSal-80°C, 0.5 ± 0.0 min). Although the combined laboratory D80°C for E. faecium was lower (P0.05) than for Salmonella in wheat flour (DEf-80°C, 9.4 ± 0.1 min; DSal-80°C, 10.1 ± 0.2 min), the difference was ∼7%. The zT values for Salmonella in all products and for E. faecium in milk powder, almond meal, and date paste were not different (P0.05) between laboratories. Therefore, this study demonstrated the impact of standardized methodologies on repeatability of microbial inactivation results. Overall, E. faecium NRRL B-2354 was more thermally resistant than Salmonella, which provides support for utilizing E. faecium as a surrogate for validating thermal processing of multiple low-moisture products. However, product composition should always be considered before making that decision.

The structure and function of mitochondria have been characterized with increasing precision. How the protein inventory defines the characteristics of the organelle remains insufficiently understood, however. Recently we devised a quantitative proteomic approach to estimate the copy numbers of proteins in a single plant mitochondrion, as physical operational unit in the cell. We illustrate how such a simple thought experiment can give fascinating insights into how a mitochondrion works.

Recent revisions to U.S. Department of Agriculture, Food Safety and Inspection Service (FSIS) compliance and safe harbor guidelines for ready-to-eat meat and poultry products addressed process humidity requirements. Given the lack of prior data for impingement-cooked products, the present study was conducted to evaluate the impact of process humidity on Salmonella lethality at the product core and surface and compliance of the results with FSIS lethality performance standards. Whole muscle beef strips, ground beef patties, whole muscle chicken breast fillets, and breaded ground chicken patties were inoculated with an eight-serovar cocktail of Salmonella. Beef and chicken samples were cooked in a pilot-scale moist-air impingement oven to a core temperature of 70.0 and 72.8°C, respectively, immediately quenched in liquid nitrogen, and dissected to obtain core and surface samples. Variables included oven temperature (218 and 232°C), air velocity (0.7 and 2.8 m/s), and oven humidity (0.7, 15, 30, or 70% moisture by volume [%, v/v]). Additional treatments were performed to examine the impact of supplemental critical control processes such as increased endpoint temperature, postoven carryover time, and pre- or postoven steam treatments. Salmonella reductions of7 log units were reliably achieved in chicken patties regardless of the processing variables; however, none of the treatments reliably ensured6.5-log reductions of Salmonella in ground beef. A majority of whole-muscle samples failed to meet the required performance lethality when processed at 0.7% (v/v) humidity; however, Salmonella inactivation was significantly improved (P0.05) at oven humidities of ≥30% (v/v). Dry oven conditions achieved greater Salmonella lethality at the core than at the surface for multiple products (P0.05). The efficacies of minimal and supplemental critical controls were dependent on product, process, and humidity (P0.05). Overall, process humidity and product variability should be considered in regulatory requirements and process validations.

The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy.This double-blinded study tested 32 healthy males (age: 25.4 ± 7.3 years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration.There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference = 0.280 mM [0.075 to 0.485], p = .026) and mI (mean difference = 0.662 mM [0.203 to 1.122], p = .026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change = -0.201 mM [-0.335 to -0.067], p = .003) and no change in mI (mean change = -0.327 mM [-0.737 to 0.083], p = .118) in the TNS group; conversely, there was no change in tCr (mean change = -0.100 mM [-0.074 to 0.274], p = .259) and an increase in mI (mean change = 0.347 mM [0.106 to 0.588], p = .005) in the sham group.These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

Field trials were conducted to assess the impact of aminocyclopyrachlor on green ash (Fraxinus pennsylvanica Marshall) and honey locust (Gleditsia triacanthos L.) trees in an urban environment. Aminocyclopyrachlor is a relatively new, selective, plant-growth-regulator herbicide in the pyrimidine carboxylic acid family. Treatments were applied to Kentucky bluegrass (Poa pratensis L.) sod growing with and without trees present. Evaluations included determination of a safe spraying distance from target trees and the effect of application timing on tree response. This multi-year study showed that green ash was highly tolerant to aminocyclopyrachlor while honey locust developed severe injury in trees closest to applications. Honey locust trees up to 7 m (23 ft) from the tree trunk to the edge of the application displayed moderate to severe injury symptoms and fall treatment in October and November had the lowest tree injury compared to all other application timings. Honey locust trees exhibiting moderate to severe cosmetic injury would not be acceptable to landowners; recovery over time was minimal. Trees located 13 m (43 ft) away displayed no injury for any treatment timing. Soil analysis demonstrated that aminocyclopyrachlor dissipation was the same underneath green ash and honey locust trees, and that dissipation was faster in the presence of growing trees. Taken together, these results provide a basic groundwork necessary for improving aminocyclopyrachlor labels, and a better understanding of this herbicide's effect on certain woody species.Index words: Herbicide injury, aminocyclopyrachlor, herbicide fate, tree safety.Species used in this study: Green ash, Fraxinus pennsylvanica Marshall, honey locust, Gleditsia triacanthos L.Chemicals used in this study: Aminocyclopyrachlor.

Isothermal inactivation experiments often are used to investigate the thermal resistance of pathogens, such as Salmonella, in foods; however, little is known about the reproducibility of such experimental methodologies. The objective of this study was to quantify the reproducibility of Salmonella isothermal resistance results via a six-laboratory comparison. Inoculation was performed at a single location and then distributed to each laboratory for isothermal analysis. Salmonella Agona 447967 was inoculated into oat flour, re-equilibrated to a water activity (aw) of 0.45, and then packaged and distributed to each laboratory. Before conducting the inactivation trials, each laboratory was required to verify the inoculated product's aw, enumerate Salmonella population levels, and verify that the isothermal treatment medium was at the target temperature (80°C). All laboratories were required to process at least three replications, collect at least six sample time points with three subsamples at each sampling point, enumerate survivors using an identical plating methodology and media, and verify that the temperature did not substantially change during isothermal treatment. The log-linear model was fit to the Salmonella survivor data, and the resultant D-values were statistically compared via Welch's t test (α = 0.05). Two significant differences in thermal inactivation kinetics were identified as potentially resulting from suspected methodology deviations. Two of the inoculated batches distributed for analysis yielded significantly lower D-values, which likely resulted from a deviation in the inoculation procedures. One laboratory yielded significantly lower D-values, which was likely the result of temperature deviations. Overall, excluding the D-values resulting from deviations, the inactivation results were reproducible, yielding D-values of 30.2 ± 3 min. These results indicate that isothermal inactivation results can be reproducible but that even minor methodology deviations can substantially affect measured Salmonella thermal resistance. HIGHLIGHTS

BACKGROUND: Gadolinium retention after repeated gadolinium-based contrast agent (GBCA) exposure has been reported in subcortical gray matter. However, gadolinium retention in the cerebral cortex has not been systematically investigated. PURPOSE: To determine whether and where gadolinium is retained in rat and human cerebral cortex. MATERIALS AND METHODS: The cerebral cortex in Sprague-Dawley rats treated with gadopentetate dimeglumine (three doses over 4 weeks; cumulative gadolinium dose, 7.2 mmol per kilogram of body weight; n = 6) or saline (n = 6) was examined with antemortem MRI. Two human donors with repeated GBCA exposure (three and 15 doses; 1 and 5 months after exposure), including gadopentetate dimeglumine, and two GBCA-naive donors were also evaluated. Elemental brain maps (gadolinium, phosphorus, zinc, copper, iron) for rat and human brains were constructed by using laser ablation inductively coupled plasma mass spectrometry. RESULTS: Gadopentetate dimeglumine–treated rats showed region-, subregion-, and layer-specific gadolinium retention in the neocortex (anterior cingulate cortex: mean gadolinium concentration, 0.28 µg ∙ g(−1) ± 0.04 [standard error of the mean]) that was comparable (P > .05) to retention in the allocortex (mean gadolinium concentration, 0.33 µg ∙ g(−1) ± 0.04 in piriform cortex, 0.24 µg ∙ g(−1) ± 0.04 in dentate gyrus, 0.17 µg ∙ g(−1) ± 0.04 in hippocampus) and subcortical structures (0.47 µg ∙ g(−1) ± 0.10 in facial nucleus, 0.39 µg ∙ g(−1) ± 0.10 in choroid plexus, 0.29 µg ∙ g(−1) ± 0.05 in caudate-putamen, 0.26 µg ∙ g(−1) ± 0.05 in reticular nucleus of the thalamus, 0.24 µg ∙ g(−1) ± 0.04 in vestibular nucleus) and significantly greater than that in the cerebellum (0.17 µg ∙ g(−1) ± 0.03, P = .01) and white matter tracts (anterior commissure: 0.05 µg ∙ g(−1) ± 0.01, P = .002; corpus callosum: 0.05 µg ∙ g(−1) ± 0.02, P = .001; cranial nerve: 0.02 µg ∙ g(−1) ± 0.01, P = .004). Retained gadolinium colocalized with parenchymal iron. T1-weighted MRI signal intensification was not observed. Gadolinium retention was detected in the cerebral cortex, pia mater, and pia-ensheathed leptomeningeal vessels in two GBCA-exposed human brains but not in two GBCA-naive human brains. CONCLUSION: Repeated gadopentetate dimeglumine exposure is associated with gadolinium retention in specific regions, subregions, and layers of cerebral cortex that are critical for higher cognition, affect, and behavior regulation, sensorimotor coordination, and executive function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kanal in this issue.

Triazoles are privileged heterocycles for a variety of applications. The synthesis of 1H-triazoles can be accomplished by the Banert cascade from propargylic azides. Depending on the substrate and conditions, the Banert cascade can proceed by either a sigmatropic or prototropic mechanism. This report describes the first detailed kinetic analysis of the Banert cascade proceeding by both pathways including substituent effects and KIE. The analysis identified the inflection point in the divergent pathways, allowing future work to predict which Banert products are accessible.

Canary structures being used as early warning indicators represent an important tool for condition and health monitoring of electronic components and systems. In this paper, printed circuit boards (PCBs) with canary structures based on surface mounted device (SMD)-2512 ceramic chip resistors with reduced solder pad sizes were studied. Focus of these investigations was set on thermomechanical and mechanical stresses caused by passive thermal cycling as well as by vibrational loads. For this purpose, experimental methods such as deformation analysis and accelerated aging tests as well as finite element (FE) based methods were applied. In addition, an outlook on the implementation of these canary structures into dual inverter electronic control boards for electrical powertrain applications will be given.

The MEG experiment at the Paul Scherrer Institut (PSI) represents the state of the art in the search for the charged Lepton Flavor Violating μ+→e+γ decay, setting the most stringent upper limit on the BR(μ+→e+γ)≤4.2×10^-13 (90% C.L.). An upgrade of MEG, MEG II, was designed, commissioned and recently started the physics data taking. Its goal is to reach a sensitivity level of . In order to 6×10^-14 reconstruct the positron momentum vector a Cylindrical Drift CHamber (CDCH) with unprecedented peculiarities was built, featuring angular and momentum resolutions at the 6.5 mrad and 100 keV/c level. The CDCH is a 2-meter long, 60 cm in diameter, low-mass, single volume detector with high granularity: 9 layers of 192 drift cells, few mm wide, defined by wires in a stereo configuration for longitudinal hit localization. The filling gas mixture is Helium:Isobutane 90:10. The total radiation length is 1.5×10^-3 X0, thus minimizing the Multiple Coulomb Scattering and allowing for a single-hit resolution

Mitochondria host vital cellular functions, including oxidative phosphorylation and co-factor biosynthesis, which are reflected in their proteome. At the cellular level plant mitochondria are organized into hundreds of discrete functional entities, which undergo dynamic fission and fusion. It is the individual organelle that operates in the living cell, yet biochemical and physiological assessments have exclusively focused on the characteristics of large populations of mitochondria. Here, we explore the protein composition of an individual average plant mitochondrion to deduce principles of functional and structural organisation. We perform proteomics on purified mitochondria from cultured heterotrophic Arabidopsis cells with intensity-based absolute quantification and scale the dataset to the single organelle based on criteria that are justified by experimental evidence and theoretical considerations. We estimate that a total of 1.4 million protein molecules make up a single Arabidopsis mitochondrion on average. Copy numbers of the individual proteins span five orders of magnitude, ranging from >40 000 for Voltage-Dependent Anion Channel 1 to sub-stoichiometric copy numbers, i.e. less than a single copy per single mitochondrion, for several pentatricopeptide repeat proteins that modify mitochondrial transcripts. For our analysis, we consider the physical and chemical constraints of the single organelle and discuss prominent features of mitochondrial architecture, protein biogenesis, oxidative phosphorylation, metabolism, antioxidant defence, genome maintenance, gene expression, and dynamics. While assessing the limitations of our considerations, we exemplify how our understanding of biochemical function and structural organization of plant mitochondria can be connected in order to obtain global and specific insights into how organelles work.

New dates from culturally modified red pine rediscovered in the Boundary Waters Canoe Area Wilderness in northern Minnesota provide an opportunity to merge tree-ring records of human land use with archaeological records, historical travel accounts, and traditional knowledge to enhance understanding of Anishinaabeg land tenure in the Wilderness. Records from 244 culturally modified trees (CMTs) demonstrate varying intensities of human use along historical water routes, notably the Border Route that connected Grand Portage to Rainy Lake and Lake of the Woods during the North American fur trade. Crossdated modification years from 119 CMTs provide direct evidence of human-landscape interaction along historical travel routes utilized by Anishinaabeg and Euro-American traders from the mid-1700s to the early 1900s. This CMT network preserves a fading biological record of fur-trade-era cultural history that contributes to a growing cross-cultural conversation on the storied traditional use of a cultural landscape that is now the most visited federal wilderness area in the United States.

Iron–sulfur (Fe–S) clusters are ubiquitous cofactors in all life and are used in a wide array of diverse biological processes, including electron transfer chains and several metabolic pathways. Biosynthesis machineries for Fe–S clusters exist in plastids, the cytosol, and mitochondria. A single monothiol glutaredoxin (GRX) is involved in Fe–S cluster assembly in mitochondria of yeast and mammals. In plants, the role of the mitochondrial homolog GRXS15 has only partially been characterized. Arabidopsis (Arabidopsis thaliana) grxs15 null mutants are not viable, but mutants complemented with the variant GRXS15 K83A develop with a dwarf phenotype similar to the knockdown line GRXS15amiR. In an in-depth metabolic analysis of the variant and knockdown GRXS15 lines, we show that most Fe–S cluster-dependent processes are not affected, including biotin biosynthesis, molybdenum cofactor biosynthesis, the electron transport chain, and aconitase in the tricarboxylic acid (TCA) cycle. Instead, we observed an increase in most TCA cycle intermediates and amino acids, especially pyruvate, glycine, and branched-chain amino acids (BCAAs). Additionally, we found an accumulation of branched-chain α-keto acids (BCKAs), the first degradation products resulting from transamination of BCAAs. In wild-type plants, pyruvate, glycine, and BCKAs are all metabolized through decarboxylation by mitochondrial lipoyl cofactor (LC)-dependent dehydrogenase complexes. These enzyme complexes are very abundant, comprising a major sink for LC. Because biosynthesis of LC depends on continuous Fe–S cluster supply to lipoyl synthase, this could explain why LC-dependent processes are most sensitive to restricted Fe–S supply in grxs15 mutants.

Background: In the past few years, several randomized trials have clearly shown that endovascular treatment (ET) in addition to intravenous thrombolysis (IVT) is superior to IVT alone in patients with proximal cerebral arterial occlusions. However, the effectiveness of ET in pre-stroke dependent patients (modified Rankin Scale ≥3) is uncertain. Methods: Using our prospectively obtained stroke database, we analyzed the impact of pre-stroke dependence on the rates of poor outcome (discharge mRS 5–6), in-hospital death, infarct sizes, and symptomatic intracranial hemorrhage (SICH) in patients with distal intracranial carotid artery M1 and M2 occlusions during two time periods. Results: From 1/2008 to 10/2012, a total of 544 patients (455 without and 89 with dependence) were treated with IVT, and from 11/2012 to 12/2019 a total of 1,061 patients (919 without and 142 with dependence) received ET (with or without IVT). Irrespective of the treatment modality, the dependent patients had significantly higher rates of poor outcome (55 vs. 32%, p < 0.001), death (24 vs. 11%; p < 0.001), or SICH (8.2 vs. 3.6%, p < 0.01) than independent patients. In dependent patients, ET significantly reduced the rates of poor outcome (49 vs. 64%, p < 0.01) and led to smaller infarcts, whereas the rates of in-hospital death (25 vs. 22%; p = 0.6) or SICH (8.5 vs. 7.9%, p = 0.9) were comparable between both treatment modalities. Conclusions: Compared with IVT, ET avoids poor outcome and leads to smaller infarcts in dependent patients. However, the overall high rates of poor outcome in this patient population stress the importance to perform decisions based on a case-by-case basis. © Copyright © 2021 Kastrup, Roth, Politi, Alexandrou, Hildebrandt, Schröter and Papanagiotou.

The adaptation of plant metabolism to abiotic stress involves profound changes in amino acid metabolism. Unfavorable environmental conditions often lead to an impairment of photosynthesis. In response to the resulting lack of energy, plants activate respiratory pathways that use amino acids as alternative substrates. This review highlights recent progress in understanding these amino acid oxidation pathways, their regulation during stress, and the role of amino acids as signaling molecules. We present an updated map of the degradation pathways for lysine and the branched-chain amino acids including the last missing step in plant lysine catabolism, which has recently been identified, and several new steps involved in the degradation of leucine, isoleucine, and valine. The adaptation of amino acid metabolism to energy deprivation is mediated by the balance between TOR and SnRK signaling. The coordinated induction of several catabolic pathways during starvation is achieved by SnRK1 kinase via formation of a ternary complex including bZIP transcription factors. Recent findings indicate that some amino acids might act as TOR activators and thus promote a shift from catabolic to anabolic pathways. The metabolism of the sulfur containing amino acid cysteine is highly interconnected with TOR and SnRK signaling. Mechanistic details have recently been elucidated for cysteine signaling during the abscisic acid dependent drought response. Local cysteine synthesis triggers abscisic acid production and in addition, cysteine degradation produces the gaseous messenger hydrogen sulfide, which promotes stomatal closure via protein persulfidation. Amino acid signaling in plants is still an emerging topic with potential for fundamental discoveries.

Canary structures being used as early warning indicators represent an important tool for condition and health monitoring of electronic components and systems. In this paper, printed circuit boards with canary structures based on SMD 2512 ceramic chip resistors with reduced solder pad sizes were studied. Focus of these investigations was set on thermo-mechanical and mechanical stresses caused by passive thermal cycling as well as by vibrational loads. For this purpose, experimental methods such as deformation analysis and accelerated ageing tests as well as finite element based methods were applied. In addition, an outlook on the implementation of these canary structures into dual inverter electronic control boards for electrical powertrain applications will be given.

During drought stress, cellular proteostasis on the one hand and amino acid homeostasis on the other hand are severely challenged, because the decrease in photosynthesis induces massive proteolysis, leading to drastic changes in both the proteome and the free amino acid pool. Thus, we selected progressive drought stress in Arabidopsis (Arabidopsis thaliana) as a model to investigate on a quantitative level the balance between protein and free amino acid homeostasis. We analyzed the mass composition of the leaf proteome based on proteomics datasets, and estimated how many protein molecules are present in a plant cell and its subcellular compartments. In addition, we calculated stress-induced changes in the distribution of individual amino acids between the free and protein-bound pools. Under control conditions, an average Arabidopsis mesophyll cell contains about 25 billion protein molecules, of which 80% are localized in chloroplasts. Severe water deficiency leads to degradation of more than 40% of the leaf protein mass, and thus causes a drastic shift in distribution toward the free amino acid pool. Stress-induced proteolysis of just half of the 340 million RubisCO hexadecamers present in the chloroplasts of a single mesophyll cell doubles the cellular content of free amino acids. A major fraction of the amino acids released from proteins is channeled into synthesis of proline, which is a compatible osmolyte. Complete oxidation of the remaining fraction as an alternative respiratory substrate can fully compensate for the lack of photosynthesis-derived carbohydrates for several hours.

Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood. Conclusions: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.

During dehydration cellular proteostasis as well as amino acid homeostasis are severely challenged, since the decrease in photosynthesis induces massive proteolysis. Thus, we selected progressive drought stress in Arabidopsis thaliana as a model to investigate the balance between protein and free amino acid homeostasis on a quantitative level. We analyze the mass protein composition of rosette leaves and estimate, how many protein molecules are present in a plant cell and its subcellular compartments. Under control conditions, an average Arabidopsis mesophyll cell contains about 25 billion protein molecules and 80% of them are localized in the chloroplasts. Severe water deficiency leads to degradation of more than 40% of the leaf proteome and thus causes a drastic shift towards the free amino acid pool. Stress induced proteolysis of half of the 400 million RubisCO hexadecamers present in the chloroplasts of an individual mesophyll cell alone doubles the cellular content in free amino acids. A major fraction of the amino acids released from proteins is channeled into the synthesis of proline as a compatible osmolyte. Complete oxidation of the remaining part as an alternative respiratory substrate can fully compensate the lack of carbohydrates derived from photosynthesis for several hours.

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors in all life and are used in a wide array of diverse biological processes, including electron transfer chains and several metabolic pathways. Biosynthesis machineries for Fe-S clusters exist in plastids, the cytosol and mitochondria. A single monothiol glutaredoxin (GRX) has been shown to be involved in Fe-S cluster assembly in mitochondria of yeast and mammals. In plants, the role of the mitochondrial homologue GRXS15 has only partially been characterized. Arabidopsisgrxs15null mutants are not viable, but mutants complemented with the variantGRXS15 K83Adevelop with a dwarf phenotype. In an in-depth metabolic analysis, we show that most Fe-S cluster-dependent processes are not affected, including biotin biosynthesis, molybdenum cofactor biosynthesis and the electron transport chain. Instead, we observed an increase in most TCA cycle intermediates and amino acids, especially pyruvate, 2-oxoglutarate, glycine and branched-chain amino acids (BCAAs). The most pronounced accumulation occurred in branched-chain α-keto acids (BCKAs), the first degradation products resulting from deamination of BCAAs. In wild-type plants, pyruvate, 2-oxoglutarate, glycine and BCKAs are all metabolized through decarboxylation by four mitochondrial lipoyl cofactor-dependent dehydrogenase complexes. Because these enzyme complexes are very abundant and the biosynthesis of the lipoyl cofactor depends on continuous Fe-S cluster supply to lipoyl synthase, this could explain why lipoyl cofactor-dependent processes are most sensitive to restricted Fe-S supply inGRXS15 K83Amutants.One-sentence summaryDeficiency in GRXS15 restricts protein lipoylation and causes metabolic defects in lipoyl cofactor-dependent dehydrogenase complexes, with branched-chain amino acid catabolism as dominant bottleneck.

Tracking systems for modern particle physics experiments, both for the search of extremely rare processes, which require high momentum resolutions in ranges dominated by multiple scattering, and for the next generation of high luminosity lepton colliders, which require large active volumes and high granularity, make use of light drift chambers able to withstand high rates and, therefore, made of large numbers of closely spaced wires. For such chambers, the use of the classical feed-through technique, as wire anchoring system, cannot be implemented and it is necessary to develop an automatic system (wiring robot) to locate the wires with high accuracy and under a well monitored and uniform mechanical tension with fast and reliable operations.

The MEG experiment at the Paul Scherrer Institut searches for the charged-Lepton-Flavor-Violating mu+ -> e+ gamma decay. MEG has already set the world best upper limit on the branching ratio: BR, 11 pages, 8 figures, 1 table, proceeding at INSTR'20 conference, accepted for publication in JINST

An automatic target monitoring method based on photographs taken by a CMOS photo-camera has been developed for the MEG II detector. The technique could be adapted for other fixed-target experiments requiring good knowledge of their target position to avoid biases and systematic errors in measuring the trajectories of the outcoming particles. A CMOS-based, high resolution, high radiation tolerant and high magnetic field resistant photo-camera was mounted inside the MEG II detector at the Paul Scherrer Institute (Switzerland). MEG II is used to search for lepton flavour violation in muon decays. The photogrammetric method's challenges, affecting measurements of low momentum particles' tracks, are high magnetic field of the spectrometer, high radiation levels, tight space constraints, and the need to limit the material budget in the tracking volume. The camera is focused on dot pattern drawn on the thin MEG II target, about 1 m away from the detector endcaps where the photo-camera is placed. Target movements and deformations are monitored by comparing images of the dots taken at various times during the measurement. The images are acquired with a Raspberry board and analyzed using a custom software. Global alignment to the spectrometer is guaranteed by corner cubes placed on the target support. As a result, the target monitoring fulfils the needs of the experiment., Comment: 10 pages, 14 figures. This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing