47 research outputs found
Generic Role Model for the Systematic Development of Internal AI-based Services in Manufacturing
Latest research has shown that one challenge for the development and implementation of Industrial AI-based services is uncertainty of roles and responsibilities. To address this challenge, we developed a generic role model for the systematic development of AI-based services in manufacturing. The role model describes which roles are necessary within the development process of an Industrial AI-based service. Thereby, a distinction is made whether the roles are assigned to the âcore teamâ, the âextended teamâ or participate in âsupporting rolesâ. Furthermore, the model shows whether the roles are involved in the âIdeationâ phase, the âRequirements and designâ phase, the âTestâ phase or the âImplementation and roll-outâ phase. Based on desktop research, semi-structured interviews and expert workshops we identified 22 roles that are relevant to the development and implementation of Industrial AI-based services
Predictors of graft survival at diagnosis of antibodyâmediated renal allograft rejection: a retrospective singleâcenter cohort study
Antibody-mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy-proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24 months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P = 0.018 and HR 1.57; P = 0.045) and eGFR slope (beta 0.46; P < 0.001). Cyclophosphamide treatment (6x 15 mg/m²) plus high-dose intravenous immunoglobulins (IVIG) (1.5 g/kg) was superior compared with single-dose rituximab (1x 500 mg) plus low-dose IVIG (30 g) (HR 0.10; P = 0.008 and beta 10.70; P = 0.017) and one cycle of bortezomib (4x 1.3 mg/m(2)) plus low-dose IVIG (HR 0.16; P = 0.049 and beta 11.21; P = 0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome
Development and Technical Validation of an Immunoassay for the Detection of APP669â711 (Aβâ3â40) in Biological Samples
The ratio of amyloid precursor protein (APP)669â711 (Aβâ3â40)/Aβ1â42 in blood plasma was reported to represent a novel Alzheimerâs disease biomarker. Here, we describe the characterization of two antibodies against the N-terminus of Aβâ3âx and the development and âfit-for-purposeâ technical validation of a sandwich immunoassay for the measurement of Aβâ3â40. Antibody selectivity was assessed by capillary isoelectric focusing immunoassay, Western blot analysis, and immunohistochemistry. The analytical validation addressed assay range, repeatability, specificity, between-run variability, impact of pre-analytical sample handling procedures, assay interference, and analytical spike recoveries. Blood plasma was analyzed after Aβ immunoprecipitation by a two-step immunoassay procedure. Both monoclonal antibodies detected Aβâ3â40 with no appreciable cross reactivity with Aβ1â40 or N-terminally truncated Aβ variants. However, the amyloid precursor protein was also recognized. The immunoassay showed high selectivity for Aβâ3â40 with a quantitative assay range of 22 pg/mLâ7.5 ng/mL. Acceptable intermediate imprecision of the complete two-step immunoassay was reached after normalization. In a small clinical sample, the measured Aβ42/Aβâ3â40 and Aβ42/Aβ40 ratios were lower in patients with dementia of the Alzheimerâs type than in other dementias. In summary, the methodological groundwork for further optimization and future studies addressing the Aβ42/Aβâ3â40 ratio as a novel biomarker candidate for Alzheimerâs disease has been set
Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccinationâspecific humoral and cellular immunity in kidney transplant recipients
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses. counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27(++)CD38(+) plasmablasts. Whereas overall proportions of spike-reactive CD4(+) T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67(+) and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients
A Dual-Species Atom Interferometer Payload for Operation on Sounding Rockets
We report on the design and the construction of a sounding rocket payload capable of performing atom interferometry with Bose-Einstein condensates of 41 K and 87 Rb. The apparatus is designed to be launched in two consecutive missions with a VSB-30 sounding rocket and is qualified to withstand the expected vibrational loads of 1.8 g root-mean-square in a frequency range between 20â2000 Hz and the expected static loads during ascent and re-entry of 25 g. We present a modular design of the scientific payload comprising a physics package, a laser system, an electronics system and a battery module. A dedicated on-board software provides a largely automated process of predefined experiments. To operate the payload safely in laboratory and flight mode, a thermal control system and ground support equipment has been implemented and will be presented. The payload presented here represents a cornerstone for future applications of matter wave interferometry with ultracold atoms on satellites
Effective hematopoietic stem cell-based gene therapy in a murine model of hereditary pulmonary alveolar proteinosis
Hereditary pulmonary alveolar proteinosis due to GM-CSF receptor deficiency (herPAP) constitutes a life-threatening lung disease characterized by alveolar deposition of surfactant protein secondary to defective alveolar macrophage function. As current therapeutic options are primarily symptomatic, we have explored the potential of hematopoietic stem cell-based gene therapy. Using Csf2rbâ/â mice, a model closely reflecting the human herPAP disease phenotype, we here demonstrate robust pulmonary engraftment of an alveolar macrophage population following intravenous transplantation of lentivirally corrected hematopoietic stem and progenitor cells. Engraftment was associated with marked improvement of critical herPAP disease parameters, including bronchoalveolar fluid protein, cholesterol and cytokine levels, pulmonary density on computed tomography scans, pulmonary deposition of Periodic Acid-Schiff+ material as well as respiratory mechanics. These effects were stable for at least nine months. With respect to engraftment and alveolar macrophage differentiation kinetics, we demonstrate the rapid development of CD11c+/SiglecF+ cells in the lungs from a CD11câ/SiglecF+ progenitor population within four weeks after transplantation. Based on these data, we suggest hematopoietic stem cell-based gene therapy as an effective and cause-directed treatment approach for herPAP
Ultracold atom interferometry in space
Bose-Einstein condensates (BECs) in free fall constitute a promising source for space-borne interferometry. Indeed, BECs enjoy a slowly expanding wave function, display a large spatial coherence and can be engineered and probed by optical techniques. Here we explore matter-wave fringes of multiple spinor components of a BEC released in free fall employing light-pulses to drive Bragg processes and induce phase imprinting on a sounding rocket. The prevailing microgravity played a crucial role in the observation of these interferences which not only reveal the spatial coherence of the condensates but also allow us to measure differential forces. Our work marks the beginning of matter-wave interferometry in space with future applications in fundamental physics, navigation and earth observation
Space-borne Bose-Einstein condensation for precision interferometry
Space offers virtually unlimited free-fall in gravity. Bose-Einstein
condensation (BEC) enables ineffable low kinetic energies corresponding to
pico- or even femtokelvins. The combination of both features makes atom
interferometers with unprecedented sensitivity for inertial forces possible and
opens a new era for quantum gas experiments. On January 23, 2017, we created
Bose-Einstein condensates in space on the sounding rocket mission MAIUS-1 and
conducted 110 experiments central to matter-wave interferometry. In particular,
we have explored laser cooling and trapping in the presence of large
accelerations as experienced during launch, and have studied the evolution,
manipulation and interferometry employing Bragg scattering of BECs during the
six-minute space flight. In this letter, we focus on the phase transition and
the collective dynamics of BECs, whose impact is magnified by the extended
free-fall time. Our experiments demonstrate a high reproducibility of the
manipulation of BECs on the atom chip reflecting the exquisite control features
and the robustness of our experiment. These properties are crucial to novel
protocols for creating quantum matter with designed collective excitations at
the lowest kinetic energy scales close to femtokelvins.Comment: 6 pages, 4 figure
MBoC | ARTICLE Identification of a Rab GTPase-activating protein cascade that controls recycling of the Rab5
ABSTRACT Transport within the endocytic pathway depends on a consecutive function of the endosomal Rab5 and the late endosomal/lysosomal Rab7 GTPases to promote mem-brane recycling and fusion in the context of endosomal maturation. We previously identified the hexameric BLOC-1 complex as an effector of the yeast Rab5 Vps21, which also recruits the GTPase-activating protein (GAP) Msb3. This raises the question of when Vps21 is inacti-vated on endosomes. We provide evidence for a Rab cascade in which activation of the Rab7 homologue Ypt7 triggers inactivation of Vps21. We find that the guanine nucleotide ex-change factor (GEF) of Ypt7 (the Mon1-Ccz1 complex) and BLOC-1 both localize to the same endosomes. Overexpression of Mon1-Ccz1, which generates additional Ypt7-GTP, or over-expression of activated Ypt7 promotes relocalization of Vps21 from endosomes to the endo-plasmic reticulum (ER), which is indicative of Vps21 inactivation. This ER relocalization is prevented by loss of either BLOC-1 or Msb3, but it also occurs in mutants lacking endo-someâvacuole fusion machinery such as the HOPS tethering complex, an effector of Ypt7. Importantly, BLOC-1 interacts with the HOPS on vacuoles, suggesting a direct Ypt7-depen-dent cross-talk. These data indicate that efficient Vps21 recycling requires both Ypt7 and endosomeâvacuole fusion, thus suggesting extended control of a GAP cascade beyond Rab interactions