Parallel Events Research Articles

Evaluating the Representation and Responsiveness of the United Nations Commission on the Status of Women (CSW) to Diverse Women Populations Worldwide.

The United Nations Commission on the Status of Women (CSW) is “the principal global intergovernmental body exclusively dedicated to the promotion of gender equality and the empowerment of women.” The continued success of the CSW's mission is critical. Under the guise of needing competent male leaders to protect them, women and girls in many countries nonetheless suffer dire consequences from international conflict and war. While females may send mostly male loved ones into armed conflict, women and girls themselves face economic sanctions, poverty, displacement, and heightened risk of sexual violence, in an environment that already fails to respect their equal human rights with men. It is no accident that in most countries, females are de facto excluded from positions of power where they could try to prevent such conflict (Enloe, 2014), and the CSW is actively working to overcome this reality. In this article, we use a mixed-method approach to evaluate the level of United Nations Commission on the Status of Women (CSW) representation and responsiveness to diverse women populations as reflected in (a) state delegations' participation in formal session, (b) NGO participation, and (c) NGO priorities. We find that the CSW displays a high level of representation and responsiveness to diverse state delegations across UN regions in terms of their speaking time in formal session. The CSW is at best moderately representative of women's NGOs through regional advance consultations, and the level of responsiveness to women's NGOs is low. This is due to: costly barriers to entry to gain ECOSOC status, large underrepresentation of some UN Regions, and the fact that during formal session, women's NGOs participate primarily at parallel off-site events. Although the CSW passed important resolutions, its representation and responsiveness to women's NGO priorities is lower than it should be. We base our evaluation by comparing our surveys of attending and non-attending women's NGOs that showed top priorities that the 2010 CSW did not discuss or pass resolutions on such as: land rights, sex trafficking, internet access for women, and the effects of climate change on women. We contend that during 1970–1994, when World Conferences on Women occurred, parallel transnational advance consultations among women's NGOs in tandem with CSW regional consultations created a broadening of the CSW's agenda. The CSW rationally anticipated different kinds of feminism beyond liberal feminism and a broader set of priority issues for diverse women populations. We therefore argue for a Fifth World Conference on Women to increase the representativeness and responsiveness of the CSW.

Trefoil factor 2 activation of CXCR4 requires calcium mobilization to drive epithelial repair in gastric organoids.

Determining the signalling cascade of epithelial repair, using murine gastric organoids, allows definition of regulatory processes intrinsic to epithelial cells, at the same time as validating and dissecting the signalling cascade with more precision than is possible in vivo Following single cell damage, intracellular calcium selectively increases within cells adjacent to the damage site and is essential for promoting repair. Trefoil factor 2 (TFF2) acts via chemokine C-X-C receptor 4 and epidermal growth factor receptor signalling, including extracellular signal-regulated kinase activation, to drive calcium mobilization and promote gastric repair. Sodium hydrogen exchanger 2, although essential for repair, acts downstream of TFF2 and calcium mobilization. The gastric mucosa of the stomach is continually exposed to environmental and physiological stress factors that can cause local epithelial damage. Although much is known about the complex nature of gastric wound repair, the stepwise process that characterizes epithelial restitution remains poorly defined. The present study aimed to determine the effectors that drive gastric epithelial repair using a reductionist culture model. To determine the role of trefoil factor 2 (TFF2) and intracellular calcium (Ca2+ ) mobilization in gastric restitution, gastric organoids were derived from TFF2 knockout (KO) mice and yellow Cameleon-Nano15 (fluorescent calcium reporter) transgenic mice, respectively. Inhibitors and recombinant protein were used to determine the upstream and downstream effectors of gastric restitution following photodamage (PD) to single cells within the gastric organoids. Single cell PD resulted in parallel events of dead cell exfoliation and migration of intact neighbouring cells to restore a continuous epithelium in the damage site. Under normal conditions following PD, Ca2+ levels increased within neighbour migrating cells, peaking at ∼1min, suggesting localized Ca2+ mobilization at the site of cell protrusion/migration. TFF2 KO organoids exhibit delayed repair; however, this delay can be rescued by the addition of exogenous TFF2. Inhibition of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK)1/2 or a TFF2 receptor, chemokine C-X-C receptor 4 (CXCR4), resulted in significant delay and dampened Ca2+ mobilization. Inhibition of sodium hydrogen exchanger 2 (NHE2) caused significant delay but did not affect Ca2+ mobilization. A similar delay was observed in NHE2 KO organoids. In TFF2 KO gastric organoids, the addition of exogenous TFF2 in the presence of EGFR or CXCR4 inhibition was unable to rescue repair. The present study demonstrates that intracellular Ca2+ mobilization occurs within gastric epithelial cells adjacent to the damage site to promote repair by mechanisms that involve TFF2 signalling via CXCR4, as well as activation of EGFR and ERK1/2. Furthermore NHE2 is shown to be important for efficient repair and to operate via a mechanism either downstream or independent of calcium mobilization.

The Fine Tuning of Drp1-Dependent Mitochondrial Remodeling and Autophagy Controls Neuronal Differentiation.

Mitochondria play a critical role in neuronal function and neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington diseases and amyotrophic lateral sclerosis, that show mitochondrial dysfunctions associated with excessive fission and increased levels of the fission protein dynamin-related protein 1 (Drp1). Our data demonstrate that Drp1 regulates the transcriptional program induced by retinoic acid (RA), leading to neuronal differentiation. When Drp1 was overexpressed, mitochondria underwent remodeling but failed to elongate and this enhanced autophagy and apoptosis. When Drp1 was blocked during differentiation by overexpressing the dominant negative form or was silenced, mitochondria maintained the same elongated shape, without remodeling and this increased cell death. The enhanced apoptosis, observed with both fragmented or elongated mitochondria, was associated with increased induction of unfolded protein response (UPR) and ER-associated degradation (ERAD) processes that finally affect neuronal differentiation. These findings suggest that physiological fission and mitochondrial remodeling, associated with early autophagy induction are essential for neuronal differentiation. We thus reveal the importance of mitochondrial changes to generate viable neurons and highlight that, rather than multiple parallel events, mitochondrial changes, autophagy and apoptosis proceed in a stepwise fashion during neuronal differentiation affecting the nuclear transcriptional program.

Parallel colonization of subalpine habitats in the central European mountains by Primula elatior

The island-like distribution of subalpine habitats across mountain ranges can trigger the parallel evolution of locally adapted ecotypes. Such naturally replicated scenarios allow testing hypotheses on how elevational differentiation structures genetic diversity within species. Nevertheless, the parallel colonization of subalpine habitats across different mountain ranges has only rarely been documented with molecular data. We chose Primula elatior (Primulaceae), naturally spanning entire elevation range in multiple mountain regions of central Europe, to test for the origin of its scattered subalpine populations. Nuclear microsatellite variation revealed three genetic groups corresponding with the distinct study regions. We found that genetic differentiation between foothill and subalpine populations within each region was relatively low, suggesting that the colonization of subalpine habitats occurred independently within each mountain range. Furthermore, the strongest differentiation was usually found between the subalpine populations suggesting that mountain ridges may act as migration barriers that can reduce gene flow more strongly than elevational differences between foothill and subalpine populations. Finally, we found that subalpine colonization did not result in a loss of genetic diversity relative to foothill populations in agreement with the high migration rates that we document here between the subalpine and the foothill populations. In summary, our study shows subalpine Primula elatior populations are genetically diverse and distinct results of parallel colonization events from multiple foothill gene pools.

A modular hybrid simulation framework for complex manufacturing system design

For complex manufacturing systems, the current hybrid Agent-Based Modelling and Discrete Event Simulation (ABM–DES) frameworks are limited to component and system levels of representation and present a degree of static complexity to study optimal resource planning. To address these limitations, a modular hybrid simulation framework for complex manufacturing system design is presented. A manufacturing system with highly regulated and manual handling processes, composed of multiple repeating modules, is considered. In this framework, the concept of modular hybrid ABM–DES technique is introduced to demonstrate a novel simulation method using a dynamic system of parallel multi-agent discrete events. In this context, to create a modular model, the stochastic finite dynamical system is extended to allow the description of discrete event states inside the agent for manufacturing repeating modules (meso level). Moreover, dynamic complexity regarding uncertain processing time and resources is considered. This framework guides the user step-by-step through the system design and modular hybrid model. A real case study in the cell and gene therapy industry is conducted to test the validity of the framework. The simulation results are compared against the data from the studied case; excellent agreement with 1.038% error margin is found in terms of the company performance. The optimal resource planning and the uncertainty of the processing time for manufacturing phases (exo level), in the presence of dynamic complexity is calculated.

Transcriptional regulators and regulatory pathways involved in prostate gland adaptation to a hypoandrogen environment.

Anti-androgen therapies, including orchiectomy, are effective at promoting prostate cancer remission, but are followed by progression to the more aggressive castration-resistant prostate cancer (CRPC). Castration promotes gland and tumor shrinkage. However, prostate adaptation to androgen deprivation involves striking parallel events, all requiring changes in gene expression. We hypothesized that transcription factors (TF) and other transcription-related genes are needed to orchestrate those changes. In this work, downstream analysis using bioinformatic tools and published microarray data allowed us to identify sixty transcriptional regulators (including 10 TF) and to integrate their function in physiologically relevant networks. Functional associations revealed a connection between Arnt, Bhlhe41 and Dbp circadian rhythm genes with the Ar circuitry and a small gene network centered in Pex14, which might indicate a previously unanticipated metabolic shift. We have also identified human homologs and mapped the corresponding genes to human chromosome regions commonly affected in prostate cancer, with particular attention to the PTEN/HHEX/MXI1 cluster at 10q23-25 (frequently deleted in PCa) and to MAPK1 at 22q11.21 (delete in intermediate risk but not in high risk PCa). Twenty genes were found mutated or with copy number alterations in at least five percent of three cancer cohorts and six of them (PHOX2A, NFYC, EST2, EIF2S1, SSRP1 and PARP1) associated with impacted patient survival. These changes are specific to the adaptation to the hypoandrogen environment and seem important for the progression to CRPC when mutated.

Welcome, Orientation, Language Training: a project at the Charité for new international medical students.

Objective: A comprehensive, integrated support programme for new international students of medicine has been developed, implemented and evaluated at the Charité. The objectives of the programme were improved social integration, orientation on the study program and Charité campus, as well as qualification in medical specialist language.Project outline: The “Charité Orientation Module for International Students” (ChOIS) was designed by a working group with a variety of expertise in the field of international students. The programme has three stages: Recruitment (specific invitation on matriculation); Orientation week before semester start; and Parallel events during the first semester. ChoOIS was piloted in the Winter Semester 2015/16 and, following evaluation, continued in a modified form in the Summer Semester 2016. Key features were: Welcome and social integration by faculty welcome-events and student group activities; Orientation on the study program, on teaching infrastructures at the Charité and on student life in Berlin by senior medical students; and Training in language for medical communication and bedside teaching by professional lecturers. Results: Results of evaluations conducted after the orientation weeks, at the end of the semester and retrospectively in the 3rd semester produced high approval ratings of the individual features of the ChOIS-programme and of the programme as a whole by participating students. Discussion: A comprehensive, integrated support programme for new international students of medicine has been developed and implemented. The ChOIS-programme can serve as a practice model to guide other medical faculties. In future, a programme that goes beyond the start of the course and includes more involvement by senior students would be desirable.

Enhancing Drought Monitoring and Early Warning for the United Kingdom through Stakeholder Coinquiries

Abstract Drought is widely written about as a complex, multifaceted phenomenon, with complexity arising not just from biophysical drivers, but also human understanding and experiences of drought and its impacts. This has led to a proliferation of different drought definitions and indicators, creating a challenge for the design of drought monitoring and early warning (MEW) systems, which are a key component of drought preparedness. Here, we report on social learning workshops conducted in the United Kingdom aimed at improving the design and operation of drought MEW systems as part of a wider international project including parallel events in the United States and Australia. We highlight key themes for MEW design and use: “types” of droughts, indicators and impacts, uncertainty, capacity and decision-making, communications, and governance. We shed light on the complexity of drought through the multiple framings of the problem by different actors, and how this influences their needs for MEW. Our findings suggest that MEW systems need to embrace this complexity and strive for consistent messaging while also tailoring information for a wide range of audiences in terms of the drought characteristics, temporal and spatial scales, and impacts that are important for their particular decision-making processes. We end with recommendations to facilitate this approach.

Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans.

In the human fungal pathogen Cryptococcus neoformans, sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. Cryptococcus sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear. Here, we show the spatiotemporal coordination of meiosis and basidial maturation by visualizing event-specific molecules in developing basidia defined by a quantitative approach. Monitoring of gene induction timing together with genetic analysis reveals co-regulation of the coordinated events by a shared regulatory program. Two RRM family regulators, Csa1 and Csa2, are crucial components that bridge meiosis and basidial maturation, further determining sporulation. We propose that the regulatory coordination of meiosis and basidial development serves as a determinant underlying the production of infectious meiospores in C. neoformans.

Novel Insights into Adult and Cancer Stem Cell Biology.

Adult tissues are thought to harbor two populations of "dormant" and "actively dividing" stem cells. Quiescent stem cells undergo rare asymmetric cell divisions (ACDs) through which they self-renew and give rise to tissue-committed "progenitors" of distinct fate and "progenitors" in turn undergo symmetric cell divisions (SCDs) and clonal expansion. However, quiescent stem cells have not been demonstrated in adult tissues such as skin, testis, liver, and brain. After surgical removal of part of liver and pancreas-adult differentiated cells divide and regenerate and a possible role of stem cells remains doubtful. Long-term repopulating hematopoietic stem cells are quiescent in nature but ACD has not been convincingly demonstrated even among them. Attempts by various groups to identify a common stemness program that ensures self-renewal among different kinds of stem cells have also remained futile. Uncontrolled self-renewal and compromised differentiation of stem cells possibly initiate leukemia/cancer, but the identity of leukemic stem cells and whether cancer stem cells arise by epithelial-mesenchymal transition (EMT) in solid tumors are all open-ended questions that need greater clarity. Acceptance of the presence of very small embryonic-like stem cells (VSELs) in adult tissues could clarify several of these existing dilemmas in the field. Data are compiled showing that VSELs undergo ACD in the hematopoietic system, testis, ovary, uterus, and pancreas, whereas tissue-committed progenitors undergo SCD and clonal expansion. VSELs possess similar overlapping stemness program as in embryonic stem cells, embryonic carcinoma cells, embryonic germ cells, induced pluripotent stem cells, and primordial germ cells. VSELs and leukemic and cancer cells express overlapping embryonic markers. Uncontrolled proliferation of VSELs and compromised differentiation possibly initiate leukemia. Process of EMT and initiation of solid tumor from VSELs (located among the epithelial cells) are indeed two distinct and parallel events. To conclude, VSELs provide explanation to several confounding aspects of adult stem cell biology.

Brain region-dependent gene networks associated with selective breeding for increased voluntary wheel-running behavior.

Mouse lines selectively bred for high voluntary wheel-running behavior are helpful models for uncovering gene networks associated with increased motivation for physical activity and other reward-dependent behaviors. The fact that multiple brain regions are hypothesized to contribute to distinct behavior components necessitates the simultaneous study of these regions. The goals of this study were to identify brain-region dependent and independent gene expression patterns, regulators, and networks associated with increased voluntary wheel-running behavior. The cerebellum and striatum from a high voluntary running line and a non-selected control line were compared. Neuropeptide genes annotated to reward-dependent processes including neuropeptide S receptor 1 (Npsr1), neuropeptide Y (Npy), and proprotein convertase subtilisin/kexin type 9 (Pcsk9), and genes implicated in motor coordination including vitamin D receptor (Vdr) and keratin, type I cytoskeletal 25 (Krt25) were among the genes exhibiting activity line-by-region interaction effects. Genes annotated to the Parkinson pathway presented consistent line patterns, albeit at different orders of magnitude between brain regions, suggesting some parallel events in response to selection for high voluntary activity. The comparison of gene networks between brain regions highlighted genes including transcription factor AP-2-delta (Tfap2d), distal-less homeobox 5 gene (Dlx5) and sine oculis homeobox homolog 3 (Six3) that exhibited line differential expression in one brain region and are associated with reward-dependent behaviors. Transcription factors including En2, Stat6 and Eomes predominated among regulators of genes that differed in expression between lines. Results from the simultaneous study of striatum and cerebellum confirm the necessity to study molecular mechanisms associated with voluntary activity and reward-dependent behaviors in consideration of brain region dependencies.

Orchid colonization: multiple parallel dispersal events and mosaic genetic structure in Dactylorhiza majalis ssp. lapponica on the Baltic island of Gotland.

The island of Gotland in the Baltic Sea has had no contact with surrounding continental areas since the withdrawal of the Weichselian ice sheet at approx. 17 ka BP. Plants present on Gotland must have arrived by long-distance dispersal, so populations are expected to exhibit reduced levels of genetic diversity compared with populations on surrounding mainlands. However, orchids have very small seeds, which appear well adapted to long-distance dispersal, and they should therefore be less affected than other plant species by colonization bottlenecks. The aim of this study was to analyse the genetic structure of orchids colonizing isolated islands, using the marsh orchid Dactylorhiza majalis ssp. lapponica as a case study. More than 500 samples from 27 populations were analysed for 15 plastid and eight nuclear marker loci. Population diversity and differentiation patterns were compared for nuclear and plastid marker systems and analysed in relation to geographical location. We found high genetic diversity but no clear geographical structure of genetic differentiation between populations on Gotland. However, the between-population differentiation in plastid and nuclear markers were correlated and the greatest diversity was found at sites at comparatively high elevations, which were the first to emerge above the water after the Ice Age. The regional population on Gotland has been established by a minimum of four dispersal events from continental regions. Subsequent gene flow between sites has not yet homogenized the differentiation pattern originating from initial colonization. We conclude that long-distance seed dispersal in orchids has a strong impact on structuring genetic diversity during periods of expansion and colonization, but contributes less to gene flow between populations once a stable population structure has been achieved.

Synthesis of Chlorotrifluoromethylated Pyrrolidines by Electrocatalytic Radical Ene-Yne Cyclization.

The stereoselective synthesis of chlorotrifluoromethylated pyrrolidines was achieved using anodically coupled electrolysis, an electrochemical process that combines two parallel oxidative events in a convergent and productive manner. The bench-stable and commercially available solids CF3 SO2 Na and MgCl2 were used as the functional group sources to generate CF3. and Cl. , respectively, via electrochemical oxidation, and the subsequent reaction of these radicals with the 1,6-enyne substrate was controlled with an earth-abundant Mn catalyst. In particular, the introduction of a chelating ligand allowed for the ene-yne cyclization to take place with high stereochemical control over the geometry of the alkene group in the pyrrolidine product.

Neopterygian phylogeny: the merger assay.

The phylogenetic relationships of the recently described genus †Ticinolepis from the Middle Triassic of the Monte San Giorgio are explored through cladistic analyses of the so far largest morphological dataset for fossil actinopterygians, including representatives of the crown-neopterygian clades Halecomorphi, Ginglymodi and Teleostei, and merging the characters from previously published systematic studies together with newly proposed characters. †Ticinolepis is retrieved as the most basal Ginglymodi and our results support the monophyly of Teleostei and Holostei, as well as Halecomorphi and Ginglymodi within the latter clade. The patterns of relationships within these clades mostly agree with those of previous studies, although a few important differences require future research. According to our results, ionoscopiforms are not monophyletic, caturids are not amiiforms and leptolepids and luisiellids form a monophyletic clade. Our phylogenetic hypothesis confirms the rapid radiation of the holostean clades Halecomorphi and Ginglymodi during the Early and Middle Triassic and the radiation of pholidophoriform teleosts during the Late Triassic. Crown-group Halecomorphi have an enormous ghost lineage throughout half of the Mesozoic, but ginglymodians and teleosts show a second radiation during the Early Jurassic. The crown-groups of Halecomorphi, Ginglymodi and Teleostei originated within parallel events of radiation during the Late Jurassic.

Anodically Coupled Electrolysis for the Heterodifunctionalization of Alkenes.

The emergence of new catalytic strategies that cleverly adopt concepts and techniques frequently used in areas such as photochemistry and electrochemistry has yielded a myriad of new organic reactions that would be challenging to achieve using orthodox methods. Herein, we discuss the strategic use of anodically coupled electrolysis, an electrochemical process that combines two parallel oxidative events, as a complementary approach to existing methods for redox organic transformations. Specifically, we demonstrate anodically coupled electrolysis in the regio- and chemoselective chlorotrifluoromethylation of alkenes.

Revealing the selection history of adaptive loci using genome-wide scans for selection: an example from domestic sheep

BackgroundOne of the approaches to detect genetics variants affecting fitness traits is to identify their surrounding genomic signatures of past selection. With established methods for detecting selection signatures and the current and future availability of large datasets, such studies should have the power to not only detect these signatures but also to infer their selective histories. Domesticated animals offer a powerful model for these approaches as they adapted rapidly to environmental and human-mediated constraints in a relatively short time. We investigated this question by studying a large dataset of 542 individuals from 27 domestic sheep populations raised in France, genotyped for more than 500,000 SNPs.ResultsPopulation structure analysis revealed that this set of populations harbour a large part of European sheep diversity in a small geographical area, offering a powerful model for the study of adaptation. Identification of extreme SNP and haplotype frequency differences between populations listed 126 genomic regions likely affected by selection. These signatures revealed selection at loci commonly identified as selection targets in many species (“selection hotspots”) including ABCG2, LCORL/NCAPG, MSTN, and coat colour genes such as ASIP, MC1R, MITF, and TYRP1. For one of these regions (ABCG2, LCORL/NCAPG), we could propose a historical scenario leading to the introgression of an adaptive allele into a new genetic background. Among selection signatures, we found clear evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. We confirmed this allelic heterogeneity in one case by resequencing the MC1R gene in three black-faced breeds.ConclusionsOur study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations.

Abstract LB-A03: Allele specific HLA loss and immune escape in lung cancer evolution

Abstract Cancer cells adopt a variety of mechanisms to evade the immune system and avoid T-cell recognition. Disruption of human leukocyte antigen (HLA), which may lead to reduced neoantigen presentation, has been proposed as an immune escape strategy in many cancers, including lung cancer. Mutations in HLA class I genes are infrequent in early stage non-small cell lung cancers (NSCLC), suggesting alternative mechanisms of HLA disruption may be common. To date, the polymorphic nature of the locus has precluded copy number analysis and exploration of HLA loss. To investigate the prevalence and importance of HLA disruption, we present LOHHLA (Loss Of Heterozygosity in Human Leukocyte Antigen), a computational tool to determine HLA allele-specific copy number from sequencing data. Building upon previous work imputing HLA haplotypes from sequencing data (Shukla, 2015; Szolek, 2014) and utilizing previously published datasets (Jamal-Hanjani, 2017; Brastianos, 2015), we endeavored to address the prevalence and timing of HLA LOH in lung cancer and its impact on tumor evolution and neoantigen presentation. Using LOHHLA, we find HLA LOH occurs in 40% of NSCLCs and is associated with a high subclonal neoantigen burden, APOBEC mediated-mutagenesis, upregulation of cytolytic activity and PD-L1 positivity. The focal nature of these alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggest that HLA LOH is an immune escape mechanism, selected later in NSCLC tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for immunotherapeutic approaches targeting neoantigens. Citation Format: Nicholas McGranahan, Rachel Rosenthal, Crispin T. Hiley, Andrew J. Rowan, Thomas B.K. Watkins, Gareth A. Wilson, Nicolai J. Birkbak, Selvaraju Veeriah, Peter Van Loo, Javier Herrero, Charles Swanton. Allele specific HLA loss and immune escape in lung cancer evolution [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A03.

L'inferno e il rifugio di Arbe. Slavi ed ebrei in un campo di concentramento italiano, tra fascismo, Resistenza e Shoah

In the context of the Nazi-Fascist occupation of Yugoslavia, this paper examines two parallel events that concerned Italy as an occupying nation: the repressive internment of Slavic civilians in Slovenian and Croatian areas; and the internment of Jews in Croatian areas annexed or submitted to Italian occupation. The paper analyses the establishment of Arbe/Rab. In 1943, Slavs and Jews were interned in two separate sections of the camp. The Slavs defined their experience as hell on earth, while the Jews saw it as a fortunate shelter. The first passed to history as one of the harshest episodes of Fascist persecution of minorities and war crimes, the second as an example of humanitarian intervention. Based on both witnesses and historiographical sources, this paper examines different types of internment practiced by the Italian Fascist regime in Yugoslavia: the repressive, the precautionary and the protective ones. Internment policies in Arbe, and the second occupation zone, and the treatment of some Jews as distinct from that of other groups of Slavs and Jews are analysed within three contexts: the policy of rejection of Jews at the Italian Croatian border; the creation of the clandestine Slovenian organization, Osvonodilna Fronta and its offspring, the Rabska Brigade, joined also by Croatian and Jewish internees; and the controversial death of Arbe’s commander.

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

SummaryImmune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens.Video

Tracking patent transfers in different European countries: methods and a first application to medical technologies

Drawing on more than half a million granted patents in all technological sectors filed at EPO between 1998 and 2012 we gather information on 300,000 inscriptions affecting changes in their ownership at the EPO and top national registers (France, Germany, Switzerland, Spain). After grouping parallel legal events in different European validation countries, we find that more than 30% of EPO patents in all fields change ownership at least once. For the field of medical technologies, we exploit additional information on corporate structures to further distinguish between "intragroup" and "bare" changes of ownership thanks. Our results indicate that more than two-thirds of the transfers happen "intragroup", that is between related corporate entities. Using regressions analyses, we finally explore and discuss relations between the occurrence and types of these transfers of patent and proxies for patent quality.