Deep Random based Key Exchange protocol resisting unlimited MITM

We present a protocol enabling two legitimate partners sharing an initial secret to mutually authenticate and to exchange an encryption session key. The opponent is an active Man In The Middle (MITM) with unlimited computation and storage capacities. The resistance to unlimited MITM is obtained through the combined use of Deep Random secrecy, formerly introduced and proved as unconditionally secure against passive opponent for key exchange, and universal hashing techniques. We prove the resistance to MITM interception attacks, and show that (i) upon successful completion, the protocol leaks no residual information about the current value of the shared secret to the opponent, and (ii) that any unsuccessful completion is detectable by the legitimate partners. We also discuss implementation techniques.Comment: 14 pages. V2: Updated reminder in the formalism of Deep Random assumption. arXiv admin note: text overlap with arXiv:1611.01683, arXiv:1507.0825

Minimum Information about a Biosynthetic Gene cluster

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.Netherlands Organization for Scientific Research (NWO)/Rubicon/825.13.001EU/FP7/Joint Call OCEANBiotechnology and Biological Sciences Research Council (BBSRC)Natural Environment Research Council (UK)National Institute for Energy Ethics and Society (NIEeS; UK)Gordon and Betty Moore FoundationNational Science Foundation (NSF; US)US Department of EnergyEngineering and Physical Sciences Research Council (EPSRC

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Radiotherapy prolongs the survival of advanced non-small-cell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)

Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) â¤1 vs > 1: 4+/-5.389 (95%CI,0-14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P:0.049)] and central-memory-T-cells (CD3+CD8+CD45RA-CCR7+) [FBV â¤1 vs > 1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P:0.045]

Free-ocean CO2 enrichment (FOCE) systems: present status and future developments

Free-ocean CO2 enrichment (FOCE) systems are designed to assess the impact of ocean acidification on biological communities in situ for extended periods of time (weeks to months). They overcome some of the drawbacks of laboratory experiments and field observations by enabling (1) precise control of CO2 enrichment by monitoring pH as an offset of ambient pH, (2) consideration of indirect effects such as those mediated through interspecific relationships and food webs, and (3) relatively long experiments with intact communities. Bringing perturbation experiments from the laboratory to the field is, however, extremely challenging. The main goal of this paper is to provide guidelines on the general design, engineering, and sensor options required to conduct FOCE experiments. Another goal is to introduce xFOCE, a community-led initiative to promote awareness, provide resources for in situ perturbation experiments, and build a user community. Present and existing FOCE systems are briefly described and examples of data collected presented. Future developments are also addressed as it is anticipated that the next generation of FOCE systems will include, in addition to pH, options for oxygen and/or temperature control. FOCE systems should become an important experimental approach for projecting the future response of marine ecosystems to environmental change

Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case–control studies using two primary-care databases

Background: Bisphosphonates are the most commonly prescribed osteoporosis drugs but long-term effects are unclear, although antitumour properties are known from preclinical studies. Methods: Nested case–control studies were conducted to investigate bisphosphonate use and risks of common nongastrointestinal cancers (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and cervical). Patients 50 years and older, diagnosed with primary cancers between 1997 and 2011, were matched to five controls using the UK practice-based QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases were analysed separately and the results combined. Results: A total of 91 556 and 88 845 cases were identified from QResearch and CPRD, respectively. Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.87–0.97), prostate (OR: 0.87, 95% CI: 0.79–0.96) and pancreatic (OR: 0.79, 95% CI: 0.68–0.93) cancers in the combined analyses, but no significant trends with duration. For alendronate, reduced risk associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI: 0.70–0.93) and combined (OR: 0.84, 95% CI: 0.75–0.93) analyses (trend with duration P-values 0.009 and 0.001). There were no significant associations from any of the other analyses. Conclusion: In this series of large population-based case–control studies, bisphosphonate use was not associated with increased risks for any common non-gastrointestinal cancers

(Micro)evolutionary changes and the evolutionary potential of bird migration

Seasonal migration is the yearly long-distance movement of individuals between their breeding and wintering grounds. Individuals from nearly every animal group exhibit this behavior, but probably the most iconic migration is carried out by birds, from the classic V-shape formation of geese on migration to the amazing nonstop long-distance flights undertaken by Arctic Terns Sterna paradisaea. In this chapter, we discuss how seasonal migration has shaped the field of evolution. First, this behavior is known to turn on and off quite rapidly, but controversy remains concerning where this behavior first evolved geographically and whether the ancestral state was sedentary or migratory (Fig. 7.1d, e). We review recent work using new analytical techniques to provide insight into this topic. Second, it is widely accepted that there is a large genetic basis to this trait, especially in groups like songbirds that migrate alone and at night precluding any opportunity for learning. Key hypotheses on this topic include shared genetic variation used by different populations to migrate and only few genes being involved in its control. We summarize recent work using new techniques for both phenotype and genotype characterization to evaluate and challenge these hypotheses. Finally, one topic that has received less attention is the role these differences in migratory phenotype could play in the process of speciation. Specifically, many populations breed next to one another but take drastically different routes on migration (Fig. 7.2). This difference could play an important role in reducing gene flow between populations, but our inability to track most birds on migration has so far precluded evaluations of this hypothesis. The advent of new tracking techniques means we can track many more birds with increasing accuracy on migration, and this work has provided important insight into migration's role in speciation that we will review here

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK