Five-Branes in Heterotic Brane-World Theories

The effective action for five-dimensional heterotic M-theory in the presence of five-branes is systematically derived from Horava-Witten theory coupled to an M5-brane world-volume theory. This leads to a five-dimensional N=1 gauged supergravity theory on S^1/Z_2 coupled to four-dimensional N=1 theories residing on the two orbifold fixed planes and an additional bulk three-brane. We analyse the properties of this action, particularly the four-dimensional effective theory associated with the domain-wall vacuum state. The moduli Kahler potential and the gauge-kinetic functions are determined along with the explicit relations between four-dimensional superfields and five-dimensional component fields.Comment: 19 pages, Latex, typos corrected, reference adde

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

Macrophages (MF) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MF. We found that infection of both subsets with RV resulted in a low TNF-a and a high interferon (IFN, type I and type III) release whereby M-MF produced far more IFNs than GM-MF. Thus, TNF-a production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MF compared to the addition of LPS to the uninfected cells the TNF-a response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-b one putative priming stimulus induced by RV. Small amounts of IFN-b were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MF to RV and LPS revealed an increased phosphorylation of NFkB (MMF), but different to uninfected MF a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-b can prime MF to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MF defense to viral infection is modulated by a following exposure to a bacterial infection

Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND/AIM:mmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT). PATIENTS AND METHOD:We retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0-40% vs. 41-100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated. RESULTS:Median OS was 14 months (range: 3-167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively. CONCLUSION:Assessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT

An analysis of MRI derived cortical complexity in premature-born adults : regional patterns, risk factors, and potential significance

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain’s basic geometry of cortical organization in prematurity

Sequelae of premature birth in young adults

Background and Purpose Qualitative studies about the abnormalities appreciated on routine magnetic resonance imaging (MRI) sequences in prematurely born adults are lacking. This article aimed at filling this knowledge gap by (1) qualitatively describing routine imaging findings in prematurely born adults, (2) evaluating measures for routine image interpretation and (3) investigating the impact of perinatal variables related to premature birth. Methods In this study two board-certified radiologists assessed T1-weighted and FLAIR-weighted images of 100 prematurely born adults born very preterm (VP <32 weeks) and/or at very low birth weight (VLBW <1500 g) and 106 controls born at full term (FT) (mean age 26.8 ± 0.7 years). The number of white matter lesions (WML) was counted according to localization. Lateral ventricle volume (LVV) was evaluated subjectively and by measurements of Evans’ index (EI) and frontal-occipital-horn ratio (FOHR). Freesurfer-based volumetry served as reference standard. Miscellaneous incidental findings were noted as free text. Results The LVV was increased in 24.7% of VP/VLBW individuals and significantly larger than in FT controls. This was best identified by measurement of FOHR (AUC = 0.928). Ventricular enlargement was predicted by low gestational age (odds ratio: 0.71, 95% CI 0.51–0.98) and presence of neonatal intracranial hemorrhage (odds ratio: 0.26, 95% CI 0.07–0.92). The numbers of deep and periventricular WML were increased while subcortical WMLs were not. Conclusion Enlargement of the LVV and deep and periventricular WMLs are typical sequelae of premature birth that can be appreciated on routine brain MRI. To increase sensitivity of abnormal LVV detection, measurement of FOHR seems feasible in clinical practice

POST-TRAUMATIC STRESS DISORDER AFTER COVID-19 INTENSIVE CARE ADMISSION: CHARACTERISTICS AND PERSPECTIVES

An increase of psychopathology such as post-traumatic stress disorder (PTSD) is described in patients affected with COVID- 19 that stayed at an intensive care unit (ICU). However, data on follow-up and on impact of contextual factors are limited. In a single-center, observational study, PTSD symptomatology was prevalent among 38% of participants (n=8), persisting in clinical PTSD in 2 participants after one year. In patients with initial PTSD symptoms, scores on depression, anxiety and insomnia sca les were significantly higher. A higher mental burden due to avoidance of contact and a reduced quality of life was also retained in patients with PTSD symptoms

Industrial Data Science: Developing a Qualification Concept for Machine Learning in Industrial Production

The advent of Industry 4.0 and the availability of large data storage systems lead to an increasing demand for specially educated data-oriented professionals in industrial production. The education of these specialists should combine elements from three fields: Industrial engineering, data analysis and data administration. However, a comprehensive education program incorporating all three elements has not yet been established in Germany. The aim of the acquired research project, titled “Industrial Data Science” is to develop and implement a qualification concept for Machine Learning based on demands coming up in industrial environments. The concept is targeted at two groups: Advanced students from any of the three mentioned fields (Mechanical Engineering, Statistics, Computer Science) and industrial professionals. In the qualification concept the needs of industrial companies are considered. Therefore, a survey was created to inquire the use and potentials of Machine Learning and the requirements for future Data Scientists in industrial production. The evaluation of the survey and the resulting conclusions affecting the qualification concept are presented in this paper

Evidence of a dynamic ice sheet system in Filchner Trough until the early Holocene

The past ice sheet conditions in the southern Weddell Sea Embayment (WSE) are only poorly known. Studies from this area have led to two contradicting scenarios of maximum ice extent during the Last Glacial Maximum (LGM). The first scenario is mainly based on terrestrial data indicating only very limited ice sheet thickening in the hinterland and suggests a grounding-line position on the inner shelf. The alternative scenario is based on marine geological and geophysical data and concludes that the LGM grounding line was located on the outer shelf, about 650 km further offshore than in the other scenario. Three hypotheses have been brought forward to explain these two apparently contradictory scenarios. A) An ice plain was present on the shelf that enabled a large ice extent while maintaining little ice thickness in the hinterland. B) The maximum grounded ice advance lasted for a short period only and was probably caused by a short-termed touch down of an ice shelf on the outer shelf, which did not cause sufficient ice sheet thickening in the hinterland to be traced today. C) Due to an ice flow switch, Filchner Trough was fed by an area further to the west where ice had thickened at the LGM. Besides the poorly constrained LGM ice extent, studies suggest a complex development of its retreat speed and drainage pattern in succession of the LGM that needs to be further constraint. For example, radar data from ice rises in the southwestern hinterland of the WSE suggest that ice flow switches occurred as late as the Mid-Holocene and cosmogenic exposure ages indicate an early Holocene ice sheet thickness in the Ellsworth Mountains comparable to that of the LGM. We investigated multibeam bathymetry data (ATLAS Hydrosweep DS3), acoustic sub-bottom profiles (ATLAS Parasound P-70) and marine sediment cores collected from Filchner Trough during RV “Polarstern” expedition PS96 in Dec 2015-Feb 2016. Our key finding is a previously unknown stacked grounding zone wedge (GZW) located on the outer shelf. This GZW shows that the Filchner palaeo-ice stream stabilized at this position at least two times. Two sediment cores were recovered seaward of the GZW and on top of the lower part of the GZW, respectively. Radiocarbon dates from these cores indicate that (i) the GZW was formed in the Early Holocene and (ii) grounded ice did not extend seaward of the GZW at the LGM. Hence, our data provide evidence that the grounding line in Filchner Trough experienced dynamic changes in the Holocene and that no linear ice sheet retreat occurred within this trough after the LGM