Entkopplung und Integration von Arbeit und Technik : industriesoziologische Leitbilder im Spiegel betrieblicher Praxis

"Auf der Basis der empirischen Ergebnisse des NIFA-Panels ("Neue Informationstechnologien und Flexible Arbeitssysteme") beleuchtet der Beitrag den Stellenwert von zwei zentralen industriesoziologischen Rationalisierungsleitbildern im deutschen Maschinenbau. Dabei werden stellvertretend für das technikzentrierte Leitbild der Stand der Technikanwendung und deren Bedeutung für die Qualifizierung und Beschäftigung in der Branche untersucht. Die Verbreitung und Umsetzung von Gruppenarbeit sowie deren Zusammenhang mit der Qualifizierung der Beschäftigten des Maschinenbaus bilden die Basis für die Analyse der Relevanz eines humanorientierten Rationalisierungsleitbildes. Dabei zeigt sich, dass die fertigungsstrukturellen Bedingungen des Maschinenbaus ursächlich dafür sind, dass die Branche weder als Hochburg tayloristischer Arbeitsorganisation noch als eine Metropole der qualifizierten Gruppenarbeit betrachtet werden kann. Die Fertigungsanforderungen bewirken einerseits den geringen Verbreitungsgrad des Taylorismus und hemmen andererseits eine flächendeckende Umsetzung anthropozentrischer Gruppenarbeit. Aus diesem Grund gehen im deutschen Maschinenbau die zunehmende Bedeutung von Gruppenarbeit und der hohe Stellenwert von Qualifizierung einher mit zunehmendem Technikeinsatz in den Betrieben und sind mit der Gegenüberstellung technikzentriert/anthropozentrisch nicht zu erfassen. Vielmehr wird die Arbeitsorganisation in der Fertigung des Maschinenbaus auch Ende der 90er Jahre von den traditionellen Fertigungsorganisationsformen der Werkstattfertigung und Werkbankfertigung dominiert, wobei sich die Werkstatt (bislang) immer noch als die effizienteste Form der Bewältigung von nicht-standardisierten Prozessen erweist." (Autorenreferat, IAB-Doku)Maschinenbau, Arbeitsorganisation, Gruppenarbeit, Fertigungstechnik, Produktionsorganisation, Rationalisierung, Qualifizierung

Three layers of energy law for examining CO2 transport for carbon-capture and storage

This research is a legal analysis concerning four scenarios for cross-border carbon dioxide (CO2) transport that could increase the deployment of carbon-capture and storage (CCS) deployment in Europe. The legal analysis categorizes the law into three levels—international, national and local—and considers the four scenarios in light of these three levels of energy law. Upon reviewing the four scenarios, it is clear that the Rotterdam Nucleus (referred to as the ‘Pilot Case’) is the leading scenario and as a result it is explored in more detail. The potential Pilot Case is based on the development of Rotterdam (in the Netherlands) as a southern North Sea hub. Under this Rotterdam Nucleus scenario, captured CO2 will be transported through the Port of Rotterdam to depleted gas fields offshore the Netherlands. CO2 will also be transported through further links using CCS infrastructure to facilitate the processing of undeveloped gas fields offshore UK. The Pilot case contemplates further expansion opportunities, increasing the capture clusters through additional pipelines, expanding to further gas fields and using the port of Rotterdam for CO2 shipping—hence the analysis of the other scenarios may be invaluable in the future development of CO2 networks in the EU. Finally, and an original contribution of this article is that it employs the three lawyers of energy law theoretical framework to an energy problem that was examined by an interdisciplinary research team. Furthermore, this research was developed further through two key industry stakeholder meetings with CCS experts in the EU

463 Vibostolimab plus pembrolizumab with/without docetaxel vs docetaxel in NSCLC after platinum chemotherapy and immunotherapy

BackgroundAgents blocking interactions between the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) and its ligands (CD112, CD155) have demonstrated preclinical antitumor activity. Anti-TIGIT humanized monoclonal antibody vibostolimab (MK-7684) showed promising antitumor activity and manageable toxicity in heavily pretreated patients across multiple tumor types, particularly when combined with the PD-1 inhibitor pembrolizumab (NCT02964013). Pembrolizumab has significantly improved OS versus chemotherapy in PD-L1–positive advanced non–small-cell lung cancer (NSCLC). However, many patients present with primary or acquired resistance to immunotherapy. This phase 2 study (NCT04725188) evaluates efficacy and safety of MK-7684A, a co-formulation of vibostolimab plus pembrolizumab, administered with/without docetaxel versus docetaxel alone in patients with previously treated metastatic NSCLC.MethodsThis randomized, placebo- and active-controlled, multicenter, partial-blind study is enrolling adults with histologically/cytologically confirmed metastatic NSCLC with PD after platinum-doublet chemotherapy and 1 prior anti–PD-(L)1 therapy. Patients must have measurable disease per RECIST v1.1, ECOG PS of 0–1, and no known active CNS metastases (previously treated brain metastases allowed if radiologically/clinically stable). Tumor tissue from archival or newly-obtained core or excisional biopsies are evaluated centrally for PD-L1 expression before randomization, and local documentation of the absence of EGFR mutations or ALK/ROS1 gene rearrangements must be provided. Patients are randomized 1:1:1 to receive intravenous vibostolimab (200 mg) plus pembrolizumab (200 mg) Q3W (open-label), vibostolimab plus pembrolizumab plus docetaxel (standard-of-care dose) Q3W (blinded), or docetaxel plus placebo Q3W (blinded). Randomization is stratified by ECOG PS (0/1), prior anti–PD-(L)1 therapy (immediate/no immediate prior therapy), and PD-L1 tumor proportion score (<50%/≥50%). Treatment continues for up to 35 cycles (approximately 2 years) of vibostolimab plus pembrolizumab, and per locally approved label for docetaxel, or until PD, unacceptable AEs, intercurrent illness, or investigator decision. Patients with SD/PR/CR may be eligible for up to 17 additional rechallenge cycles of vibostolimab plus pembrolizumab following BICR-verified radiographic PD by RECIST v1.1 after initial treatment or first course is completed or stopped for confirmed CR. Primary endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, ORR and DOR per RECIST v1.1 by BICR, and safety. Radiographic imaging occurs at baseline, Q6W through week 36, Q9W through week 54, and then Q12W until PD, start of new anticancer treatment, withdrawal of consent, or death. AEs are assessed by NCI CTCAE v5.0. Approximately 240 patients will be randomized. Enrollment began in April of 2021, and is ongoing at 42 sites in 10 countries.AcknowledgementsMedical writing assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials.gov, NCT04725188Ethics ApprovalAn independent institutional review board or ethics committee approved the protocol at each study site, and the trial is being conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients are required to provide informed consent prior to participation in the study

MatriGrid® based biological morphologies: tools for 3D cell culturing

Recent trends in 3D cell culturing has placed organotypic tissue models at another level. Now, not only is the microenvironment at the cynosure of this research, but rather, microscopic geometrical parameters are also decisive for mimicking a tissue model. Over the years, technologies such as micromachining, 3D printing, and hydrogels are making the foundation of this field. However, mimicking the topography of a particular tissue-relevant substrate can be achieved relatively simply with so-called template or morphology transfer techniques. Over the last 15 years, in one such research venture, we have been investigating a micro thermoforming technique as a facile tool for generating bioinspired topographies. We call them MatriGrid ® s. In this research account, we summarize our learning outcome from this technique in terms of the influence of 3D micro morphologies on different cell cultures that we have tested in our laboratory. An integral part of this research is the evolution of unavoidable aspects such as possible label-free sensing and fluidic automatization. The development in the research field is also documented in this account

Community compensation in the context of Carbon Capture and Storage: Current debates and practices

Societal opposition has the potential to slow down the implementation of Carbon Capture and Storage (CCS). One of the difficulties is that the perceived benefits associated with a CCS facility for local communities tend to be low compared to its perceived burdens. As is the case for other low carbon technologies, community compensation (or community benefits) has been suggested as a way to restore this perceived imbalance. A diverse literature has looked into the role of community compensation across various land uses and research fields. Synthesis is limited, while at the same time, the provision of community compensation in practice is moving from an ad hoc to a more institutionalized approach. Therefore, it is important to take stock of the literature. This paper provides a review of the community compensation literature in the form of four debates, drawing together environmental social science research on different low carbon technologies (e.g. CCS, renewable energy). In addition, current practices in community compensation for four European countries are discussed. The two parts of this paper are brought together in a set of lessons for the provision of community compensation for future CCS projects; in turn, suggestions for further research are made to address remaining knowledge gaps

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes:findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease