71 research outputs found
AstroGrid-D: Grid Technology for Astronomical Science
We present status and results of AstroGrid-D, a joint effort of
astrophysicists and computer scientists to employ grid technology for
scientific applications. AstroGrid-D provides access to a network of
distributed machines with a set of commands as well as software interfaces. It
allows simple use of computer and storage facilities and to schedule or monitor
compute tasks and data management. It is based on the Globus Toolkit middleware
(GT4). Chapter 1 describes the context which led to the demand for advanced
software solutions in Astrophysics, and we state the goals of the project. We
then present characteristic astrophysical applications that have been
implemented on AstroGrid-D in chapter 2. We describe simulations of different
complexity, compute-intensive calculations running on multiple sites, and
advanced applications for specific scientific purposes, such as a connection to
robotic telescopes. We can show from these examples how grid execution improves
e.g. the scientific workflow. Chapter 3 explains the software tools and
services that we adapted or newly developed. Section 3.1 is focused on the
administrative aspects of the infrastructure, to manage users and monitor
activity. Section 3.2 characterises the central components of our architecture:
The AstroGrid-D information service to collect and store metadata, a file
management system, the data management system, and a job manager for automatic
submission of compute tasks. We summarise the successfully established
infrastructure in chapter 4, concluding with our future plans to establish
AstroGrid-D as a platform of modern e-Astronomy.Comment: 14 pages, 12 figures Subjects: data analysis, image processing,
robotic telescopes, simulations, grid. Accepted for publication in New
Astronom
Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non–Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection
Importance: Patients with brain metastases from non-small cell lung cancer (NSCLC) have regularly been excluded from prospective clinical trials that include therapy with immune checkpoint inhibitors (ICIs). Clinical data demonstrating benefit with ICIs, specifically following neurosurgical brain metastasis resection, are scarce.
Objective: To evaluate and compare the association of radiation therapy with ICIs vs classic therapy involving radiation therapy and chemotherapy regarding overall survival in a cohort of patients who underwent NSCLC brain metastasis resection.
Design, setting and participants: This single-center 1:1 propensity-matched comparative effectiveness study at the largest neurosurgical clinic in Germany included individuals who had undergone craniotomy with brain metastasis resection from January 2010 to December 2021 with histologically confirmed NSCLC. Of 1690 patients with lung cancer and brain metastasis, 480 were included in the study. Key exclusion criteria were small-cell lung cancer, lack of tumor cells by means of histopathological analysis on brain metastasis resection, and patients who underwent biopsy without tumor resection. The association of overall survival with treatment with radiation therapy and chemotherapy vs radiation therapy and ICI was evaluated.
Exposures: Radiation therapy and chemotherapy vs radiation therapy and ICI following craniotomy and microsurgical brain metastasis resection.
Main outcomes and measures: Median overall survival.
Results: From the whole cohort of patients with NSCLC (N = 384). 215 (56%) were male and 169 (44%) were female. The median (IQR) age was 64 (57-72) years. The 2 cohorts of interest included 108 patients (31%) with radiation therapy and chemotherapy and 63 patients (16%) with radiation therapy and ICI following neurosurgical metastasis removal (before matching). Median (IQR) follow-up time for the total cohort was 47.9 (28.2-70.1) months with 89 patients (23%) being censored and 295 (77%) dead at the end of follow-up in December 2021. After covariate equalization using propensity score matching (62 patients per group), patients receiving radiation therapy and chemotherapy after neurosurgery had significantly lower overall survival (11.8 months; 95% CI; 9.1-15.2) compared with patients with radiation therapy and ICIs (23.0 months; 95% CI; 20.3-53.8) (P < .001).
Conclusions and relevance: Patients with NSCLC brain metastases undergoing neurosurgical resection had longer overall survival when treated with radiation therapy and ICIs following neurosurgery compared with those receiving platinum-based chemotherapy and radiation. Radiation and systemic immunotherapy should be regularly evaluated as a treatment option for these patients
Functional Implications of LH/hCG Receptors in Pregnancy-Induced Cushing Syndrome
Context: Elevated human choriogonadotropin (hCG) may stimulate aberrantly
expressed luteinizing hormone (LH)/hCG receptor (LHCGR) in adrenal glands,
resulting in pregnancy-induced bilateral macronodular adrenal hyperplasia and
transient Cushing syndrome (CS). Objective: To determine the role of LHCGR in
transient, pregnancy-induced CS. Design, Setting, Patient, and Intervention:
We investigated the functional implications of LHCGRs in a patient presenting,
at a tertiary referral center, with repeated pregnancy-induced CS with
bilateral adrenal hyperplasia, resolving after parturition. Main Outcome
Measures and Results: Acute testing for aberrant hormone receptors was
negative except for arginine vasopressin (AVP)–increased cortisol secretion.
Long-term hCG stimulation induced hypercortisolism, which was unsuppressed by
dexamethasone. Postadrenalectomy histopathology demonstrated steroidogenically
active adrenocortical hyperplasia and ectopic cortical cell clusters in the
medulla. Quantitative polymerase chain reaction showed upregulated expression
of LHCGR, transcription factors GATA4, ZFPM2, and proopiomelanocortin (POMC),
AVP receptors (AVPRs) AVPR1A and AVPR2, and downregulated melanocortin 2
receptor (MC2R) vs control adrenals. LHCGR was localized in subcapsular, zona
glomerulosa, and hyperplastic cells. Single adrenocorticotropic
hormone–positive medullary cells were demonstrated in the zona reticularis.
The role of adrenal adrenocorticotropic hormone was considered negligible due
to downregulated MC2R. Coexpression of CYP11B1/CYP11B2 and AVPR1A/AVPR2 was
observed in ectopic cortical cells in the medulla. hCG stimulation of the
patient’s adrenal cell cultures significantly increased cyclic adenosine
monophosphate, corticosterone, 11-deoxycortisol, cortisol, and androstenedione
production. CTNNB1, PRKAR1A, ARMC5, and PRKACA gene mutational analyses were
negative. Conclusion: Nongenetic, transient, somatic mutation-independent,
pregnancy-induced CS was due to hCG-stimulated transformation of LHCGR-
positive undifferentiated subcapsular cells (presumably adrenocortical
progenitors) into LHCGR-positive hyperplastic cortical cells. These cells
respond to hCG stimulation with cortisol secretion. Without the ligand, they
persist with aberrant LHCGR expression and the ability to respond to the same
stimulus
The genomic and transcriptional landscape of primary central nervous system lymphoma
Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations
The genomic and transcriptional landscape of primary central nervous system lymphoma
Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations
Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein.
Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes
Using Probability Distributions for Projecting Changes in Travel Behavior
Mobility is a must for human life on this planet, because important activities like working or shopping cannot be done from home for everyone. Present modes of transports contributes significantly to green house gas emissions while the efforts to reduce these emissions can be improved in many countries. Pathways to a more sustainable form of mobility can be modelled using travel demand models to aid decision makers. However, to project human behavior into the future one should analyze the changes in the past to understand the drivers in mobility change. Mobility surveys provide sets of activity diaries, which show changes in travel behavior over time. Those activity diaries are one of the inputs in activity-based demand generation models like travel activity pattern simulation (TAPAS). This paper shows a method of using probability distributions between person and diary groups. It offers an opportunity for an increased heterogeneity in travel behavior without sacrificing too much accuracy. Additionally it will present the use case of temporal back- and forecasting of changes in activity choices of existing mobility survey data. The results show the possibilities within this approach together with its limits and pitfalls
Linux SMP
Vortrag UNIX-Stammtisch 09/9
Monetary Policy and Climate Change
Abstract Without a doubt, climate change will have a strong impact on both the European and the global economy. This report examines to what extent this requires action from central banks such as the ECB. While it is not contested that central banks need to undertake necessary steps to ensure price and financial stability within their mandates, some commentators suggested that central banks should also actively support the transition to a low-carbon economy through their impact on financial markets. Our report draws a rather pessimistic conclusion regarding the effectiveness and desirability of such active policies. Even if the discussion around the central bank’s primary mandate is excluded, existing research shows that using monetary policy instruments to support the green transition might involve sizeable adverse side effects and is moreover much less effective than fiscal policy instruments
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