Invariant Distribution of Promoter Activities in Escherichia coli

Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy. This allows continuous tracking of promoter activity as cells change their growth rate from exponential to stationary phase in different media. We find a heavy-tailed distribution of promoter activities, with promoter activities spanning several orders of magnitude. While the shape of the distribution is almost completely independent of the growth conditions, the identity of the promoters expressed at different levels does depend on them. Translation machinery genes, however, keep the same relative expression levels in the distribution across conditions, and their fractional promoter activity tracks growth rate tightly. We present a simple optimization model for resource allocation which suggests that the observed invariant distributions might maximize growth rate. These invariant features of the distribution of promoter activities may suggest design constraints that shape the allocation of transcriptional resources

INVERSE SCATTERING TRANSFORM ANALYSIS OF STOKES-ANTI-STOKES STIMULATED RAMAN SCATTERING

Zakharov-Shabat--Ablowitz-Kaup-Newel-Segur representation for Stokes-anti-Stokes stimulated Raman scattering is proposed. Periodical waves, solitons and self-similarity solutions are derived. Transient and bright threshold solitons are discussed.Comment: 16 pages, LaTeX, no figure

Fundamental Concepts of Cyber Resilience: Introduction and Overview

Given the rapid evolution of threats to cyber systems, new management approaches are needed that address risk across all interdependent domains (i.e., physical, information, cognitive, and social) of cyber systems. Further, the traditional approach of hardening of cyber systems against identified threats has proven to be impossible. Therefore, in the same way that biological systems develop immunity as a way to respond to infections and other attacks, so too must cyber systems adapt to ever-changing threats that continue to attack vital system functions, and to bounce back from the effects of the attacks. Here, we explain the basic concepts of resilience in the context of systems, discuss related properties, and make business case of cyber resilience. We also offer a brief summary of ways to assess cyber resilience of a system, and approaches to improving cyber resilience.Comment: This is a preprint version of a chapter that appears in the book "Cyber Resilience of Systems and Networks," Springer 201

ALPs effective field theory and collider signatures

We study the leading effective interactions between the Standard Model fields and a generic singlet CP-odd (pseudo-) Goldstone boson. Two possible frameworks for electroweak symmetry breaking are considered: linear and non-linear. For the latter case, the basis of leading effective operators is determined and compared with that for the linear expansion. Associated phenomenological signals at colliders are explored for both scenarios, deriving new bounds and analyzing future prospects, including LHC and High Luminosity LHC sensitivities. Mono-Z, mono-W, W-photon plus missing energy and on-shell top final states are most promising signals expected in both frameworks. In addition, non-standard Higgs decays and mono-Higgs signatures are especially prominent and expected to be dominant in non-linear realisations

Dispositional and Psychosocial Variables as Longitudinal Predictors of Acculturative Stress

ABSTRACT: As societies become more multicultural, citizens need to develop selfregulatory mechanisms in order to successfully cope with the increasing levelsof psychosocial stress related to acculturation. In this study, a longitudinal theoretical model was tested in order to evaluate the role of implicit theories of cultural intelligence, causal attributions, perceived social support, and cultural identity as predictors of acculturative stress. The research was carried out in Spain across three consecutive years with a multicultural sample of 292 students (natives and immigrants). The results confirm the proposed theoretical model using multi-group structural equation modelling to test the equivalence of the longitudinal causal structure in immigrants and natives. Moreover, mediation analyses confirmed the mediating effect of cultural identity between the implicit theories of cultural intelligence and acculturative stress, as well as the mediating effect of perceived social support between causal attributions and acculturative stress. The model indicates the relevance of promoting psychosocial interventions with native and immigrant adolescents in intercultural contexts. In those interventions, it will be relevant to promote incremental implicit theories of cultural intelligence and internal causal attributions, as well as to highlight a more intercultural identity and to encourage greater social support networks.The data collection was financially supported by the Spanish Ministry of Science and Technology Grant number PSI 2009-0742

Medial unicompartmental knee arthroplasty in the ACL-deficient knee

Symptomatic osteoarthritis (OA) of the knee develops often in association with anterior cruciate ligament (ACL) deficiency. Two distinct pathologies should be recognised while considering treatment options in patients with end-stage medial compartment OA and ACL deficiency. Patients with primary ACL deficiency (usually traumatic ACL rupture) can develop secondary OA (typically presenting with symptoms of instability and pain) and these patients are typically young and active. Patients with primary end stage medial compartment OA can develop secondary ACL deficiency (usually degenerate ACL rupture) and these patients tend to be older. Treatment options in either of these patient groups include arthroscopic debridement, reconstruction of the ACL, high tibial osteotomy (HTO) with or without ACL reconstruction, unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). General opinion is that a functionally intact ACL is a fundamental prerequisite to perform a UKA. This is because previous reports showed higher failure rates when ACL was deficient, probably secondary to wear and tibial loosening. Nevertheless in some cases of ACL deficiency with end-stage medial compartment OA, UKA has been performed in isolation and recent papers confirm good short- to mid-term outcome without increased risk of implant failure. Shorter hospital stay, fewer blood transfusions, faster recovery and significantly lower risk of developing major complications like death, myocardial infarction, stroke, deep vein thrombosis (as compared to TKA) make the UKA an attractive option, especially in the older patients. On the other hand, younger patients with higher functional demands are likely to benefit from a simultaneous or staged ACL reconstruction in addition to UKA to regain knee stability. These procedures tend to be technically demanding. The main aim of this review was to provide a synopsis of the existing literature and outline an evidence-based treatment algorithm

A Wide Extent of Inter-Strain Diversity in Virulent and Vaccine Strains of Alphaherpesviruses

Alphaherpesviruses are widespread in the human population, and include herpes simplex virus 1 (HSV-1) and 2, and varicella zoster virus (VZV). These viral pathogens cause epithelial lesions, and then infect the nervous system to cause lifelong latency, reactivation, and spread. A related veterinary herpesvirus, pseudorabies (PRV), causes similar disease in livestock that result in significant economic losses. Vaccines developed for VZV and PRV serve as useful models for the development of an HSV-1 vaccine. We present full genome sequence comparisons of the PRV vaccine strain Bartha, and two virulent PRV isolates, Kaplan and Becker. These genome sequences were determined by high-throughput sequencing and assembly, and present new insights into the attenuation of a mammalian alphaherpesvirus vaccine strain. We find many previously unknown coding differences between PRV Bartha and the virulent strains, including changes to the fusion proteins gH and gB, and over forty other viral proteins. Inter-strain variation in PRV protein sequences is much closer to levels previously observed for HSV-1 than for the highly stable VZV proteome. Almost 20% of the PRV genome contains tandem short sequence repeats (SSRs), a class of nucleic acids motifs whose length-variation has been associated with changes in DNA binding site efficiency, transcriptional regulation, and protein interactions. We find SSRs throughout the herpesvirus family, and provide the first global characterization of SSRs in viruses, both within and between strains. We find SSR length variation between different isolates of PRV and HSV-1, which may provide a new mechanism for phenotypic variation between strains. Finally, we detected a small number of polymorphic bases within each plaque-purified PRV strain, and we characterize the effect of passage and plaque-purification on these polymorphisms. These data add to growing evidence that even plaque-purified stocks of stable DNA viruses exhibit limited sequence heterogeneity, which likely seeds future strain evolution

Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme