François Hollande will require a more detailed and far-reaching economic strategy if he is to turn France’s ailing economy around

Like many countries across Europe, France has suffered economically since the beginning of the financial crisis. As Andy Langenkamp writes, French President François Hollande’s recent ‘responsibility pact’ outlined a number of reforms designed to restructure the economy, making it more competitive in the long-term. He argues that while Hollande has the political resources required to implement bold reforms, his current plan is too vaguely stated to turn France’s economy around

The U.S. has made it through shutdowns before, but a lengthy fight over the debt ceiling could cause unprecedented market chaos

The U.S. government has been in a state of shutdown since last Tuesday, and there seems little likelihood of Republicans and Democrats coming to an agreement on funding the government in the next few days. While the government has made it through the previous 17 shutdowns that have occurred since 1977, Andy Langenkamp argues that the threat of the U.S. reaching its debt ceiling in less than two weeks’ time should be of even greater concern. The 2011 debt ceiling fight cost the country billions, and previous technical defaults have also been responsible for recessions and higher borrowing costs. While the markets are still relatively calm for now, if Congress does not come to an agreement on the debt ceiling soon, the country’s economic recovery will be severely at risk

Immunorecognition of leukemic stem cells by NK cells : the role of HDAC inhibitors in NKG2D ligand-mediated anti-tumor responses in acute myeloid leukemia

The diagnosis of acute myeloid leukemia (AML) is associated to a poor long-term outcome due to frequent relapse despite intensive chemotherapy, radiation and hematopoietic stem cell transplantation (HSCT) as well as continuous advances in treatment modalities. Relapses might be caused by leukemic stem cells (LSC). According to a recently emerging concept, LSC display many features of normal hematopoietic stem cells (HSC) like quiescence and self renewal capacity and therefore are poorly accessible for conventional therapies which primarily reach the rapidly proliferating cells. Additionally, LSC are apparently able to escape from immunorecognition and thereby sustain the disease. NK cells, as the main innate immune effectors against tumor cells, are able to recognize and kill malignant cells when triggered by cell surface expression of a multitude of activating ligands. The best-described receptor-ligand pair in humans is NKG2D and its ligands, ULBP and MICA/B. Furthermore, NCR is an important family of activating receptors on NK cells, whose ligands are not yet known. The regulation of NK cells is completed by several inhibitory receptors (KIR) specific for different HLA class I molecules on potential target cells. While preceding work in our lab was describing the interaction between NK cells and leukemic blasts of AML, there is no information available on the recognition of LSC by NK cells. In this study we aimed to elucidate the interaction of NK cells with LSC of AML. The cell surface expression of ligands for activating and inhibitory NK cell receptors on LSC was in focus of these studies. Moreover, we applied a pharmacological approach to treat the patient-derived primary AML leukemic cells and examined the consequences for cell surface expression of NK cell-specific ligands. By employing hematopoietic colony forming assays, cytotoxicity assays as well as in vivo NOD/SCID xenotransplantation we aimed to functionally assess the implications of the upregulation of activating ligands for NK cell immunorecognition of LSC. In initial experiments, we demonstrated that activating ligands for the NKG2D receptor and NCR receptors on NK cells are absent or only weakly expressed on the surface of patient derived AML blasts. This expression could be increased by pharmacological means applying bryostatin-1, a modulator of PKC activity. Upregulation of cell surface expression of NKG2D ligands on AML blasts led to increased immunorecognition by NK cells in cytotoxicity assays. Subsequently, we demonstrated that similarly to total blasts, LSC of AML as judged by the phenotype CD45dimCD34+CD38-, did not express ULBP and MICA/B on their surface. To pharmacologically increase their expression, we employed the HDAC inhibitor valproic acid (VA), a drug acting through epigenetic modification of gene expression and having long-term records in different clinical applications. This treatment with VA proved to be of importance for the immunorecognition by NK cells. In the functional assays we employed NK cells selected for the KIR-HLA class I mismatch in order to circumvent inhibitory signals inactivating the NK cells. Serial replating colony forming unit (CFU) assays with LSC after treatment with VA and after coincubation with KIR-HLA mismatched NK cells demonstrated an efficient reduction in colony formation capacity upon this synergistic treatment. The cytotoxicity assays with VA-treated LSC as targets and KIR-HLA mismatched NK cells as effectors revealed interindividual differences among patient samples, reflecting a complex regulation of NK cell activation and immunorecognition. Altogether, a direct interaction of NK cells and LSC could be demonstrated in vitro. In the in vivo setting, by transplantation of AML cells intrafemurally into NOD/SCID mice with consecutive treatment of VA and HLA-mismatched NK cells, we were able to achieve a stable engraftment of human AML in the mouse bone marrow. However, the combined treatment with VA and NK cells was not influencing the content of malignant cells as compared to untreated mice. The ongoing studies aim at optimization of AML treatment with NK cell-based immunotherapy in the preclinical NOD/SCID transplantation model. Taken together, these results showed the potential of VA as an applicable anti-neoplastic drug to enhance immunorecognition of LSC of AML by NK cells, mediated by increased cell surface expression of activating ligands. The functional consequences of an enhanced immunorecognition by NK cells in abolishing the colony forming capacity of patient derived LSC are promising beneficial effects for innovative AML treatments in future

Evaluating the impact of deep-water channel architecture on the probability of correct facies classification using 3D synthetic seismic data

2021 Fall.Includes bibliographical references.Modeling studies of bed-to geobody-scale architecture in deep-water channel deposits reveal that channel element stacking patterns and internal architecture strongly control connectivity. This architecture is critical to understanding hydrocarbon flow and recovery but is unresolvable in exploration-scale seismic-reflection profiles. Forward seismic reflectivity modeling of a digital outcrop models is commonly used to explore how depositional architecture is interpretable in a filtered seismic response. One limitation of forward seismic reflectivity modeling studies is that they often stop short of qualitatively assessing the link between underlying depositional architecture and seismic response. This study addresses the gap between qualitative interpretation and quantitative evaluation by calculating the prediction reliability of inverted seismic data. Specifically, this study uses synthetic 3D seismic modeling and inversion of a 3D outcrop model of deepwater channels in the Tres Pasos Formation of the Magallanes Basin of southern Chile. The model includes outcrop- (bed and geobody) to seismic- (reservoir to basin) scale architecture. The primary objective is to quantify where and when channel architecture is accurately predicted by seismic facies classification. Bayesian classification is used to test the probability of correct facies classification from P-impedance and if the classification results are dependent upon architectural styles (e.g., channel element stacking patterns). Model sensitivity variables include seismic frequency (ranging from 15 to 180 Hz) and deep versus shallow rock properties. Results show that prediction reliability increased for both channel element axis sandstone and mass transport deposits with increasing frequency. Deep reservoirs or faster seismic velocities more accurately predict facies than shallow reservoirs or slower seismic velocities due to the increasing contrast between sandstone and shale velocities. Channel axis sandstone is less easily interpreted where channel elements are vertically aggraded, reducing acoustic impedance contrasts with background shale. When channel elements are laterally stacked or disorganized, facies can be predicted from seismic attributes with a higher confidence, due to a strong contrast between channel element sandstone and background shale. This study highlights that architectural information strongly impacts 3D inverted seismic data and highlights conditions that either hinder or aid accurate interpretation from facies classification

Finding Fundamental Fairness: Protecting the Rights of Homosexuals under European Union Accession Law

In tackling the issue of sexual orientation discrimination, the European Union must make significant efforts to conform or, perhaps, eradicate incongruous legislation within Applicant Countries. The difficulty of this endeavor is two-fold: first, in terms of the number and complexity of the laws of each Applicant Country; and, second, in the absence of any detailed and systematic documentation of sexual orientation discrimination within those same Applicant Countries. Compounding, if not confounding, such legitimate endeavors are the inconsistent anti-gay legislation prevalent within the present Member States. The stakes are high for Member States and Applicant Countries alike. Thus, the European Union\u27s enlargement process may serve as proper method to end sexual orientation discrimination and provide protections for homosexuals within the European Union and in those countries that wish to become part of the European Union

Latinx/White Differences in Postsecondary Trajectories: The Role of Parents’ Preferences

As postsecondary schooling expands, stratification in attainment persists along ethnoracial lines. We build on current research investigating ethnoracial differences in the transition to college by interrogating parents’ preference for their child’s residence during college. We extend research in two ways. First, we predict whether parents’ live-at-home preference is associated with behavior at multiple points in the college-going pipeline. Second, we investigate whether the effect of parents’ live-at-home preference differs by ethnoracial group. Results suggest that students whose parents prefer that they live at home are less likely to apply to four-year universities, less likely to attend four-year universities, less likely to enroll full-time among those who are attending four-year universities, and more likely to live with their parents or elsewhere off campus during college. Results also suggest that parents’ live-at-home preference has less of an impact on Latinx students’ likelihood of applying to and attending four-year universities than white students