Precision Spectroscopy of Negative-Ion Resonances in Ultralong-Range Rydberg Molecules.

The level structure of negative ions near the electron detachment limit dictates the low-energy scattering of an electron with the parent neutral atom. We demonstrate that a single ultracold atom bound inside a Rydberg orbit forming an ultralong-range Rydberg molecule provides an atomic-scale system that is highly sensitive to electron-neutral scattering and thus allows for detailed insights into the underlying near-threshold anion states. Our measurements reveal the so-far unobserved fine structure of the ^{3}P_{J} triplet of Rb^{-} and allows us to extract parameters of the associated p-wave scattering resonances that deviate from previous theoretical estimates. Moreover, we observe a novel alignment mechanism for Rydberg molecules mediated by spin-orbit coupling in the negative ion.

Ionic Impurity in a Bose-Einstein Condensate at Submicrokelvin Temperatures.

Rydberg atoms immersed in a Bose-Einstein condensate interact with the quantum gas via electron-atom and ion-atom interaction. To suppress the typically dominant electron-neutral interaction, Rydberg states with a principal quantum number up to n=190 are excited from a dense and tightly trapped micron-sized condensate. This allows us to explore a regime where the Rydberg orbit exceeds the size of the atomic sample by far. In this case, a detailed line shape analysis of the Rydberg excitation spectrum provides clear evidence for ion-atom interaction at temperatures well below a microkelvin. Our results may open up ways to enter the quantum regime of ion-atom scattering for the exploration of charged quantum impurities and associated polaron physics.

Observation of Rydberg Blockade Induced by a Single Ion.

We study the long-range interaction of a single ion with a highly excited ultracold Rydberg atom and report on the direct observation of an ion-induced Rydberg excitation blockade mediated over tens of micrometer distances. Our hybrid ion-atom system is directly produced from an ultracold atomic ensemble via near-threshold photoionization of a single Rydberg excitation, employing a two-photon scheme that is specifically suited for generating a very low-energy ion. The ion's motion is precisely controlled by small electric fields, which allows us to analyze the blockade mechanism for a range of principal quantum numbers. Finally, we explore the capability of the ion as a high-sensitivity, single-atom-based electric field sensor. The observed ion-Rydberg-atom interaction is of current interest for entanglement generation or studies of ultracold chemistry in hybrid ion-atom systems.

Photoassociation of Trilobite Rydberg Molecules via Resonant Spin-Orbit Coupling.

We report on a novel method for the photoassociation of strongly polar trilobite Rydberg molecules. This exotic ultralong-range dimer, consisting of a ground-state atom bound to the Rydberg electron via electron-neutral scattering, inherits its polar character from the admixture of high-angular-momentum electronic orbitals. The absence of low-L character hinders standard photoassociation techniques. Here, we show that for suitable principal quantum numbers the resonant coupling of the orbital motion with the nuclear spin of the perturber, mediated by electron-neutral scattering, hybridizes the trilobite molecular potential with the more conventional S-type molecular state. This provides a general path to associate trilobite molecules with large electric dipole moments, as demonstrated via high-resolution spectroscopy. We find a dipole moment of 135(45) D for the trilobite state. Our results are compared to theoretical predictions based on a Fermi model.

Estimates of Water Consumption of Growing Pigs under Practical Conditions Based on Climate and Performance Data.

The water consumption of fattening pigs was recorded under practical conditions and compared with calculated water consumption. The experiment was carried out in the summer of 2020 with 79 fattening pigs. Data loggers were used to record the climate data, such as temperature and relative humidity. These data were used to calculate the temperature-humidity index (THI). It was found that there were sometimes considerable discrepancies between the measured and the calculated water consumption. One possible reason for this discrepancy could be the age of the existing water requirement equations, as in recent decades there has been a clear breeding development and thus a strong increase in pig performance. Based on these deviations, six new water consumption equations were established, which considered the variables body weight (BW), temperature, THI and feed consumption. It was found that the THI and BW should be included in one equation as predictor variables and the evaluation also showed good results. Its use, in practice, should also be considered. Overall, it became apparent that there is still a need for further research to make water consumption equations more precise. This would require a larger database.

XePhIR: the zebrafish xenograft phenotype interactive repository.

Zebrafish xenografts are an established model in cancer biology, with a steadily rising number of models and users. However, as of yet, there is no platform dedicated to standardizing protocols and sharing data regarding zebrafish xenograft phenotypes. Here, we present the Xenograft Phenotype Interactive Repository (XePhIR, https://www.xephir.org) as an independent data-sharing platform to deposit, share and repurpose zebrafish xenograft data. Deposition of data and publication with XePhIR will be done after the acceptation of the original publication. This will enhance the reach of the original research article, enhance visibility and do not interfere with the publication or copyrights of the original article. With XePhIR, we strive to fulfill these objectives and reason that this resource will enhance reproducibility and showcase the appeal and applicability of the zebrafish xenograft model. Database URL: https://www.xephir.org.

Does the Implementation of an Animal Welfare Programme on a Farm Yield a Demonstrable Improvement in Fattening Pig Welfare?

In the course of social criticism of fattening pig farming, an animal welfare programme called "Initiative Animal Welfare" (ITW) was founded to increase animal welfare in pig farming in Germany. Furthermore, there is a legal obligation to record animal welfare parameters as a self-monitoring measure. The "German Association for Technology and Structures in Agriculture" published a guideline on the applicable animal welfare criteria. This guide formed the basis of this study's data collection. The aim was to apply the animal welfare parameters on farms by comparing the results between farms participating in ITW with those not participating. A cumulative score was calculated by evaluating the collected data. In addition, the relative risk was calculated in order to estimate the risk of finding a negative expression of a parameter. Our data show that ITW farms did not perform significantly better than the farms without ITW in terms of both the cumulative score and the relative risk. Overall, it must be considered that in both farm variants the occurrence of negative evaluations was very rare and the visited farms thus certainly can be considered to be well-managed farms. Climate parameters were recorded in each compartment and showed no significant differences in most cases.

Calcium supplementation of bioinks reduces shear stress-induced cell damage during bioprinting.

During bioprinting, cells are suspended in a viscous bioink and extruded under pressure through small diameter printing needles. The combination of high pressure and small needle diameter exposes cells to considerable shear stress, which can lead to cell damage and death. Approaches to monitor and control shear stress-induced cell damage are currently not well established. To visualize the effects of printing-induced shear stress on plasma membrane integrity, we add FM 1-43 to the bioink, a styryl dye that becomes fluorescent when bound to lipid membranes, such as the cellular plasma membrane. Upon plasma membrane disruption, the dye enters the cell and also stains intracellular membranes. Extrusion of alginate-suspended NIH/3T3 cells through a 200µm printing needle led to an increased FM 1-43 incorporation at high pressure, demonstrating that typical shear stresses during bioprinting can transiently damage the plasma membrane. Cell imaging in a microfluidic channel confirmed that FM 1-43 incorporation is caused by cell strain. Notably, high printing pressure also impaired cell survival in bioprinting experiments. Using cell types of different stiffnesses, we find that shear stress-induced cell strain, FM 1-43 incorporation and cell death were reduced in stiffer compared to softer cell types and demonstrate that cell damage and death correlate with shear stress-induced cell deformation. Importantly, supplementation of the suspension medium with physiological concentrations of CaCl2greatly reduced shear stress-induced cell damage and death but not cell deformation. As the sudden influx of calcium ions is known to induce rapid cellular vesicle exocytosis and subsequent actin polymerization in the cell cortex, we hypothesize that calcium supplementation facilitates the rapid resealing of plasma membrane damage sites. We recommend that bioinks should be routinely supplemented with physiological concentrations of calcium ions to reduce shear stress-induced cell damage and death during extrusion bioprinting.

Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain.

BACKGROUND AND AIMS: Liver metastases are the leading cause of death in colorectal cancer. To gain better insight into the biology of metastasis and possibly identify new therapeutic targets we systematically investigated liver-metastasis-specific molecular aberrations. METHODS: Primary colorectal cancer (pCRC) and matched liver metastases (LMs) from the same patients were analysed by microarray-based comparative genomic hybridisation in 21 pairs and gene expression profiling in 18 pairs. Publicly available databases were used to confirm findings in independent datasets. RESULTS: Chromosome aberration patterns and expression profiles of pCRC and matched LMs were strikingly similar. Unsupervised cluster analysis of genomic data showed that 20/21 pairs were more similar to each other than to any other analysed tumour. A median of only 11 aberrations per patient was found to be different between pCRC and LM, and expression of only 16 genes was overall changed upon metastasis. One region on chromosome band 11p15.5 showed a characteristic gain in LMs in 6/21 patients. This gain could be confirmed in an independent dataset of LMs (n=50). Localised within this region, the growth factor IGF2 (p=0.003) and the intestinal stem cell specific transcription factor ASCL2 (p=0.029) were found to be over-expressed in affected LM. Several ASCL2 target genes were upregulated in this subgroup of LM, including the intestinal stem cell marker OLFM4 (p=0.013). The correlation between ASCL2 expression and four known direct transcriptional targets (LGR5, EPHB3, ETS2 and SOX9) could be confirmed in an independent expression dataset (n=50). CONCLUSIONS: With unprecedented resolution a striking conservation of genomic alterations was demonstrated in liver metastases, suggesting that metastasis typically occurs after the pCRC has fully matured. In addition, we characterised a subset of liver metastases with an ASCL2-related stem-cell signature likely to affect metastatic behaviour of tumour cells.

Designing of spider silk proteins for human induced pluripotent stem cell-based cardiac tissue engineering.

Materials made of recombinant spider silk proteins are promising candidates for cardiac tissue engineering, and their suitability has so far been investigated utilizing primary rat cardiomyocytes. Herein, we expanded the tool box of available spider silk variants and demonstrated for the first time that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes attach, contract, and respond to pharmacological treatment using phenylephrine and verapamil on explicit spider silk films. The hiPSC-cardiomyocytes contracted for at least 14 days on films made of positively charged engineered Araneus diadematus fibroin 4 (eADF4(κ16)) and three different arginyl-glycyl-aspartic acid (RGD)-tagged spider silk variants (positively or negatively charged and uncharged). Notably, hiPSC-cardiomyocytes exhibited different morphologies depending on the spider silk variant used, with less spreading and being smaller on films made of eADF4(κ16) than on RGD-tagged spider silk films. These results indicate that spider silk engineering is a powerful tool to provide new materials suitable for hiPSC-based cardiac tissue engineering.

Animal Welfare Assessment of Fattening Pigs: A Case Study on Sample Validity.

A guide for animal welfare assessment of fattening pigs recommends recording some of the indicators for a sample of the animals from a herd. However, it is not certain whether the herd's level of welfare can be correctly judged using a random sample. Therefore, both the true prevalences of welfare indicators in a full census and the estimated prevalences of the indicators based upon simulated samples taken according to five strategies (termed S1 to S5) were determined. Deviations from the true level of animal welfare in the herd due to the sampling were recorded and analyzed. Depending on the strategy, between 12% and 43% of the samples over- or underestimated the true prevalences by more than 50%. The validity of the sampling strategies was evaluated using the normalized root-mean-squared error (NRMSE) and the relative bias (RB). In terms of accuracy, the strategies differed only slightly (between NRMSE = 0.13 for S2 and NRMSE = 0.19 for S4). However, the strategies varied more obviously regarding the bias (between RB = -0.0002 for S1 and RB = -0.0370 for S5). The described results are the outcome of an initial case study on the sample validity of the indicators and have to be verified using the data of more herds.

Acceptance and Feasibility of a Guideline for the Animal Welfare Assessment of Fattening Pigs from Farmers' Point of View.

The welfare of farm animals is being increasingly discussed in society and politics. To evaluate animal welfare, indicator systems are often used. Such a system has been developed by the German Association for Technology and Structures in Agriculture and suggested in the publication "Animal Welfare Indicators: Practical Guide-Pigs". The association's aim is to provide farmers with a useful method for recording the welfare of pigs. Crucial for the acceptance of the guide by farmers is a high degree of feasibility of the recommended indicators as well as the proposed methods for their recording. To evaluate this, 40 farmers keeping fattening pigs were interviewed. The guided semi-structured interview was conducted on the farms after the farmers evaluated the welfare of their fattening pigs according to the guide. The results are: Apart from the indicators faecal soiling and tail length, all the other eleven indicators are accepted for the assessment of fattening pig welfare by a majority of the interviewed farmers (between 57.5% and 90% acceptance per indicator). Furthermore, the feasibility of the individual indicators was assessed as being positive. The relationship between time expenditure and benefit was rated on a five-point scale at an average of 3.1 (medium), which clearly shows that there is a need for further development of this guide. Some possible changes with a potential for improvement could be identified; for example, the aggregation of the results after the collection of the individual indicators to an overall result that can be compared and interpreted.

Determination of the Moisture Content and the Generation of Airborne Particulate Matter From Various Types of Footing From Indoor Riding Arenas Considered to Have Optimal Rideability.

It has been known for some years now that the occurrence of lameness in horses is closely related to the characteristics of the riding surface and that respiratory tract diseases can be induced by airborne particles. To ensure both optimal rideability (e.g., grip, elasticity, etc.) and low dust production, riding surfaces have to be regularly attended to, which also includes watering the floor. However, at present, it is not known what the individual moisture content of the various types of riding surface should be to ensure optimal rideability or what their potential for releasing dust is at the time of optimal rideability. The aim of the present study was to determine the moisture content, the density as weight/liter, particle size distribution and the release of airborne particulate matter (APM) with a diameter <10 µm (PM10) of the footing material from three types of indoor riding arena surfaces considered to have optimal rideability. Loose footing material samples were taken from the surfaces of 25 indoor riding arenas [5 pure sand (S), 10 sand-wood chips (SW), and 10 sand-fibre (SF)] and investigated under standardized conditions. The evaluation of the surface's rideability was carried out subjectively by the respective facility manager. The ambient particulate monitor TEOM 1400a was used to measure the PM10 production from the footing samples. Although, according to the facility managers, all of the investigated riding surfaces had optimal rideability at the time of sampling; obvious differences could be found with respect to their moisture content, density, particle size distribution, and release of APM, both between and within the 25 indoor arenas. The moisture content of SW (14.96 ± 4.00%) was significantly higher than that of SF (8.99 ± 2.95%; P = .0046), but the S moisture content (10.82 ± 2.65%) was not significantly different to either of them (S vs. SW: P = .0982 and S vs. SF: P = .2446). With respect to the release of APM, it could be shown that the average release from SF was 2.50-5.47 times higher than either for the S or SW (CSum-S: 12.81 mg/m³air, SW: 5.86 mg/m³air, and SF: 32.06 mg/m³air; t-test-S vs. SW: P = .3882, S vs. SF: P = .2560, and SW vs. SF: P = .0031). The reason for this was the extremely high APM release in three of the ten investigated SF samples. In addition, significant differences were also observed in the APM release within the three individual types of footing. Although no factors significantly affected the release of APM in either the S or SW footings, the density of the SF footing was found to have a significant influence on its APM production: the higher the density, the lower the APM release. The density itself was related to both the footing's moisture content and fiber content. The reason why SF footings with a low density (associated with a high fibrous material content) and a high moisture content tended to cause a greater release of APM is that there was a segregation of the fibrous material caused by the measuring technique used. This led to the fibrous material rising to the top of the sample resulting in a release of APM directly from this material. To prevent such a high release of particles from SF footings with a high fiber content occurring in practice, such footings should be regularly and adequately watered, and any segregation of the fibrous material should be prevented using suitable arena grooming techniques.

Enterobacteria associated with houseflies (Musca domestica) as an infection risk indicator in swine production farms.

Houseflies (Musca domestica) spend part of their life development on animal or human manure. Manure is high in pathogenic microbes; thus, houseflies have been known as a mechanical vector for various important zoonotic diseases. Therefore, the present study showcases captured houseflies from intensive swine production regions (which are areas of high manure concentration) in Southern Brazil, and analyses their bodies' to the presence of Escherichia coli and Salmonella sp. and the sensitivity of these bacteria to various antibiotics. Additionally, Quantitative Microbiology Risk Assessment was performed simulating the contamination of lettuce by flies' bacteria and subsequent lettuce consumption by an adult human being. Houseflies were captured in swine buildings and farm houses from five farms. E. coli quantification values ranged from 104 to 106 CFU/20 flies, and all sampling sites had positive results from bacteria presence in the collected houseflies. On the other hand, Salmonella sp. presence was observed in only three farms, where the quantification ranged from 102 to 105 CFU/20 flies. The bacteria showed to be resistant to at least two from the four tested antibiotics (ampicillin, Cefalotin, Ciprofloxacin and Norfloxacin) antibiotics used in human or veterinary medicine. Infection probability analyses showed risk of human infection by E.coli, indicating possible transmission of zoonotic pathogens through flies. In this context, it was possible to conclude that there is a need for flies control, especially in swine farms where zoonotic pathogens can be abundant, to minimize the health impact of the vectorization of enteric bacteria.

[Leukocytoclastic vasculitis with severe renal involvement following Parvovirus B19 primary infection]. / Vasculite leucocytoclasique compliquée d'une atteinte rénale grave au décours d'une primo-infection à Parvovirus B19.

BACKGROUND: Leukocytoclastic vasculitis following Parvovirus B19 primary infection has occasionally been reported in children but it occurs rarely in adults. We present an original case report with severe renal complications. PATIENTS AND METHODS: A 33-year-old man presented with fever and eruption of the abdomen and members. Papules and vesiculopustules were associated with oral and genital ulcerations. These lesions subsequently became purpuric and necrotic. Histological analysis confirmed the diagnosis of pustulous leukocytoclastic vasculitis with IgA deposits. Laboratory investigations showed elevated sedimentation rate, hepatic cytolysis and renal impairment (hematuria, leucocyturia and proteinuria 1.5 g/24 hours). Anti-parvovirus B19 IgM were positive. Three months after the eruption resolved, IgM were undetectable while anti-parvovirus B19 IgG appeared. Renal injury progressively worsened: elevation of proteinuria (5 g/24 hours) and diminution of creatinine clearance (51 ml/min). Renal biopsy showed glomerulonephritis with mesangial IgA deposits. Major proteinuria persisted one year after the disappearance of dermatological lesions in spite of ACE inhibitor treatment. DISCUSSION: The role of Parvovirus B19 has been suspected as an aetiological agent in many kinds of vasculitis, e.g. polyarteritis nodosa, Wegener's disease and leucocytoclastic vasculitis. In this case report, the detection of specific IgM and the absence of other factors associated with vasculitis are consistent with a causal role of Parvovirus B19. In previously published cases, the prognosis of parvovirus B19-associated vasculitis does not seem to differ from that of idiopathic vasculitis. To our knowledge, this is the first case exhibiting concomitant and persistent severe renal involvement.

Novel PGS/PCL electrospun fiber mats with patterned topographical features for cardiac patch applications.

Nano- and micro-scale topographical features play a critical role in the induction and maintenance of various cellular properties and functions, including morphology, adhesion, gene regulation, and cell-to-cell communication. In addition, recent studies have indicated that the structure and function of heart tissue are also sensitive to mechanical cues at the nano- and micro-scale. Although fabrication methods exist for generating topographical features on polymeric scaffolds for cell culture, current techniques, especially those with nano-scale resolution, are typically complex, prohibitively expensive and not accessible to most biology laboratories. Here, we present a simple and tunable fabrication method for the production of patterned electrospun fibers that simulate the complex anisotropic and multi-scale architecture of cardiac tissue, to promote cardiac cell alignment. This method is based on the combination of electrospinning and soft lithography techniques, in which electrospun fibers, based on a blend of poly(glycerol sebacate) and poly(caprolactone), were collected on a patterned Teflon-coated silicon wafer with imprinted topographical features. Different surface topographies were investigated, such as squares and grooves, with constant or different interspatial distances. In vitro cell culture studies successfully demonstrated the alignment of both C2C12 myoblasts and neonatal rat cardiomyocytes on fabricated electrospun patterned surfaces. C2C12 cells were cultured over a period of 72h to study the effect of topographical cues on cell morphology. Cells attached within the first 8h after seeding and after 24h most of the cells started to align responding to the topographical cues. Similarly, cardiomyocytes responded to the topographical features by aligning themselves and by expressing Connexin 43 along cellular junctions. Summarizing, we have developed a new method with the potential to significantly promote cardiac tissue engineering by fabricating electrospun fibers with defined topographical features to guide and instruct donor and/or host cells.

[Diffuse sebaceous hyperplasia of the face induced by cyclosporine]. / Hyperplasies sébacées profuses du visage induites par la ciclosporine.

INTRODUCTION: Many cutaneous complications have been reported in patients treated with cyclosporine. Alterations of the pilosebaceous follicle are particularly frequent. Hypertrichosis, follicular keratosis, acne and folliculitis are very common. Nevertheless, the occurrence of sebaceous hyperplasia is exceptional. OBSERVATION: A 27 year-old man consulted in February 2003 for a papulous eruption of the face. He was treated by cyclosporine and prednisone since his renal transplantation in 1993. The lesions flowed together on the cheeks, forehead and temples. The histological analysis confirmed the diagnosis of sebaceous hyperplasia. There was a perceptible improvement of the cutaneous state after one month of isotretinoin treatment. DISCUSSION: Sebaceous hyperplasia appears in about 10 p. 100 of patients treated with cyclosporine. This side effect occurs only in men of a mean age of 40 years. An increase in sebaceous gland size is often described, but profuse forms are uncommon. Our case report is exceptional because of the young age of the patient, and the occurrence of diffuse sebaceous hyperplasia that appeared a long time after the introduction of cyclosporine.

Phenotypic changes of rabbit mandibular condylar cartilage cells in culture.

The present study describes the behavior of mandibular condylar cartilage (MCC) cells as a function of time in primary culture, since it is not yet clear whether these cells maintain their phenotype in culture. MCC cells from New Zealand white rabbits were seeded at high density and cultured in DMEM containing 50 micrograms/mL ascorbic acid and 10% fetal bovine serum. These cells appeared as a heterogeneous population and changed their shape, size, and refractivity as cultures aged. Cartilage-like cells, which always dominated the culture, were infiltrated with a minority of fibroblast-like cells. Cell number increased progressively, and cultures reached confluence at nine days. Antibody activity for cartilage-specific glycosaminoglycan was determined by ELISA assay. This reaction reached a maximum at six days and decreased thereafter. Cultures stained with Alcian blue (pH 1.0) supported these results. Cytoplasmic mRNA analysis indicated that the transcription of type II collagen gene was present at all time points. Type I collagen and alkaline phosphatase mRNA levels showed progressive increases from 12 h to nine days, with significantly higher values in cells cultured for six, nine, and 12 days than in cells collected from earlier time points. These results suggest that in our present culture system, MCC cells undergo phenotypic changes that resemble their maturation processes in vivo.

Determination of the impurity profile of ethyl-2-(4-[(5R)-3[4-(methoxycarboxamidoiminomethyl)-phenyl]-2- oxo-5-oxazolidinylmethyl]-1-piperazinyl) acetate, citrate, a highly active platelet aggregation inhibitor, by liquid chromatography-mass spectrometry.

Ethyl-2-(4-[(5R)-3-[4-(methoxycarboxamidoiminomethyl)-phenyl] -2-oxo-5-oxazolidinylmethyl]-1-piperazinyl) acetate, a glycoprotein IIb/IIIa antagonist, is a drug substance of the oxazolidinone type from Merck's research to be developed for the chronic oral treatment of thrombotic disorders. For the separation of the byproducts in the bulk drug substance, a reversed-phase HPLC gradient separation was developed. The eluent consisting of a nonvolatile phosphate buffer system had to be changed to a volatile acetate buffer system in order to perform on-line LC-MS coupling. With a triple quadrupole system it was possible to characterize most of the unknown byproducts occuring during synthesis and during scale-up to kg amounts of the bulk drug substance.