Best Effort and Practice Activation Codes

Activation Codes are used in many different digital services and known by many different names including voucher, e-coupon and discount code. In this paper we focus on a specific class of ACs that are short, human-readable, fixed-length and represent value. Even though this class of codes is extensively used there are no general guidelines for the design of Activation Code schemes. We discuss different methods that are used in practice and propose BEPAC, a new Activation Code scheme that provides both authenticity and confidentiality. The small message space of activation codes introduces some problems that are illustrated by an adaptive chosen-plaintext attack (CPA-2) on a general 3-round Feis- tel network of size 2^(2n) . This attack recovers the complete permutation from at most 2^(n+2) plaintext-ciphertext pairs. For this reason, BEPAC is designed in such a way that authenticity and confidentiality are in- dependent properties, i.e. loss of confidentiality does not imply loss of authenticity.Comment: 15 pages, 3 figures, TrustBus 201

Efficient algorithms for pairing-based cryptosystems

We describe fast new algorithms to implement recent cryptosystems based on the Tate pairing. In particular, our techniques improve pairing evaluation speed by a factor of about 55 compared to previously known methods in characteristic 3, and attain performance comparable to that of RSA in larger characteristics.We also propose faster algorithms for scalar multiplication in characteristic 3 and square root extraction over Fpm, the latter technique being also useful in contexts other than that of pairing-based cryptography

Shifts in doctor-patient communication between 1986 and 2002: a study of videotaped General Practice consultations with hypertension patients

BACKGROUND: Departing from the hypotheses that over the past decades patients have become more active participants and physicians have become more task-oriented, this study tries to identify shifts in GP and patient communication patterns between 1986 and 2002. METHODS: A repeated cross-sectional observation study was carried out in 1986 and 2002, using the same methodology. From two existing datasets of videotaped routine General Practice consultations, a selection was made of consultations with hypertension patients (102 in 1986; 108 in 2002). GP and patient communication was coded with RIAS (Roter Interaction Analysis System). The data were analysed, using multilevel techniques. RESULTS: No gender or age differences were found between the patient groups in either study period. Contrary to expectations, patients were less active in recent consultations, talking less, asking fewer questions and showing less concerns or worries. GPs provided more medical information, but expressed also less often their concern about the patients' medical conditions. In addition, they were less involved in process-oriented behaviour and partnership building. Overall, these results suggest that consultations in 2002 were more task-oriented and businesslike than sixteen years earlier. CONCLUSION: The existence of a more equal relationship in General Practice, with patients as active and critical consumers, is not reflected in this sample of hypertension patients. The most important shift that could be observed over the years was a shift towards a more businesslike, task-oriented GP communication pattern, reflecting the recent emphasis on evidence-based medicine and protocolized care. The entrance of the computer in the consultation room could play a role. Some concerns may be raised about the effectiveness of modern medicine in helping patients to voice their worries

The bacterial DNA binding protein matp involved in linking the nucleoid terminal domain to the divisome at midcell interacts with lipid membranes

© 2019 Monterroso et al. Division ring formation at midcell is controlled by various mechanisms in Escherichia coli, one of them being the linkage between the chromosomal Ter macrodomain and the Z-ring mediated by MatP, a DNA binding protein that organizes this macrodomain and contributes to the prevention of premature chromosome segregation. Here we show that, during cell division, just before splitting the daughter cells, MatP seems to localize close to the cytoplasmic membrane, suggesting that this protein might interact with lipids. To test this hypothesis, we investigated MatP interaction with lipids in vitro. We found that, when encapsulated inside vesicles and microdroplets generated by microfluidics, MatP accumulates at phospholipid bilayers and monolayers matching the lipid composition in the E. coli inner membrane. MatP binding to lipids was independently confirmed using lipid-coated microbeads and biolayer interferometry assays, which suggested that the recognition is mainly hydrophobic. Interaction of MatP with the lipid membranes also occurs in the presence of the DNA sequences specifically targeted by the protein, but there is no evidence of ternary membrane/protein/DNA complexes. We propose that the association of MatP with lipids may modulate its spatiotemporal localization and its recognition of other ligands. IMPORTANCE The division of an E. coli cell into two daughter cells with equal genomic information and similar size requires duplication and segregation of the chromosome and subsequent scission of the envelope by a protein ring, the Z-ring. MatP is a DNA binding protein that contributes both to the positioning of the Z-ring at midcell and the temporal control of nucleoid segregation. Our integrated in vivo and in vitro analysis provides evidence that MatP can interact with lipid membranes reproducing the phospholipid mixture in the E. coli inner membrane, without concomitant recruitment of the short DNA sequences specifically targeted by MatP. This observation strongly suggests that the membrane may play a role in the regulation of the function and localization of MatP, which could be relevant for the coordination of the two fundamental processes in which this protein participates, nucleoid segregation and cell division

The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology:A Systematic Review

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients

Data-driven prioritization and preclinical evaluation of therapeutic targets in glioblastoma

Background: Patients with glioblastoma (GBM) have a dismal prognosis, and there is an unmet need for new therapeutic options. This study aims to identify new therapeutic targets in GBM. Methods: mRNA expression data of patient-derived GBM (n = 1279) and normal brain tissue (n = 46) samples were collected from Gene Expression Omnibus and The Cancer Genome Atlas. Functional genomic mRNA profiling was applied to capture the downstream effects of genomic alterations on gene expression levels. Next, a class comparison between GBM and normal brain tissue was performed. Significantly upregulated genes in GBM were further prioritized based on (1) known interactions with antineoplastic drugs, (2) current drug development status in humans, and (3) association with biologic pathways known to be involved in GBM. Antineoplastic agents against prioritized targets were validated in vitro and in vivo. Results: We identified 712 significantly upregulated genes in GBM compared to normal brain tissue, of which 27 have a known interaction with antineoplastic agents. Seventeen of the 27 genes, including EGFR and VEGFA, have been clinically evaluated in GBM with limited efficacy. For the remaining 10 genes, RRM2, MAPK9 (JNK2, SAPK1a), and XIAP play a role in GBM development. We demonstrated for the MAPK9 inhibitor RGB-286638 a viability loss in multiple GBM cell culture models. Although no overall survival benefit was observed in vivo, there were indications that RGB-286638 may delay tumor growth. Conclusions: The MAPK9 inhibitor RGB-286638 showed promising in vitro results. Furthermore, in vivo target engagement studies and combination therapies with this compound warrant further exploration

Physical education at preschools: practitioners’ and children’s engagements with physical activity and health discourses

This is an Accepted Manuscript of an article published by Taylor & Francis in British Journal of Sociology of Education on December 2013, available online: http://wwww.tandfonline.com/10.1080/01425692.2013.848780This paper focuses on one aspect of a qualitative study concerned with investigating the place and meaning of ‘physical education’ to practitioners and children at three preschools in Scotland. We examine the ways in which the participants engaged with discourses related to physical activity and health in order to construct their subjectivities. Fourteen practitioners and 70 children participated. Research methods employed were observations, interviews with adults, a group drawing and discussion activity with children, and interviews with children. Both the adults’ and children’s talk illustrated the dominance of neoliberal, healthism meanings which position individuals as responsible for their own health. While the children’s talk primarily centred on health as a corporeal notion, the practitioners tended to talk about physical activity and health in both corporeal terms and in relation to the self more holistically. The practitioners also talked about physical activity as a means of regulating children’s behaviour

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro. Abou El Hassan MA, Verheul HM, Jorna AS, Schalkwijk C, van Bezu J, van der Vijgh WJ, Bast A. Department of Medical Oncology, Free University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected] Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 micro M monoHER. Resting (confluent) HUVECs were incubated with (0.5-25 micro M) doxorubicin with(out) monoHER (0.2-1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC(50)=60.0+/-20.8 nM) than resting cells (LC(50)=4.0+/-0.3 micro M). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of > or =0.4 micro M (P=0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (< or =25 micro M, P<0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in viv