Environmental regulation of individual body size contributes to geographic variation in clonal life cycle expression

Clonal behavior has been hypothesized to provide an escape from allometric metabolic scaling that limits the maximum mass achieved by a single individual. Here, we demonstrate the capacity of a wide-spread, non-native sea anemone to buffer its colony biomass accumulation rate across environments by modulating ramet body size through environmentally dependent growth, fission, and catabolism. In 2015, thermal reaction norms for growth and fission behavior were constructed using clonal lines of the sea anemone Diadumene lineata. In 2018, variation in growth patterns under a factorial cross of temperature level and oxygen availability was examined to test the hypothesis that individual ramet size is regulated by oxygen limitation in accordance with optimal size theory. Across a wide range of temperatures, colonies accumulated a similar amount of biomass despite a radical shift from unitary to clonal growth, supporting fission as a mechanism to buffer growth rates over a range of conditions. Individual body size appears to be regulated by the environment with increased temperature and reduced oxygen modifying fission and mass-specific growth patterns, leading to the production of smaller-bodied ramets in warm conditions. However, whether anemones in common garden conditions reduce individual body size through catabolism or fission depends on the region of origin and may relate to differences in seasonal temperature patterns among coastlines, which influence the energetic benefits of fission rate plasticity

Chemical combination effects predict connectivity in biological systems

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured

An empirical study of software reuse by experts in object-oriented design

This paper presents an empirical study of the software reuse activity by expert designers in the context of object-oriented design. Our study focuses on the three following aspects of reuse : (1) the interaction between some design processes, e.g. constructing a problem representation, searching for and evaluating solutions, and reuse processes, i.e. retrieving and using previous solutions, (2) the mental processes involved in reuse, e.g. example-based retrieval or bottom-up versus top-down expanding of the solution, and (3) the mental representations constructed throughout the reuse activity, e.g. dynamic versus static representations. Some implications of these results for the specification of software reuse support environments are discussed

Therapeutic effect of hyperbaric oxygen in psoriasis vulgaris: two case reports and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Psoriasis is an inflammatory and immunological cutaneous disease. The high morbidity in patients with psoriasis results from severe clinical manifestations and/or adverse effects of treatment. The Undersea and Hyperbaric Medical Society and Federal Medicare and Medicaid Services have approved the use of hyperbaric oxygen (HBO₂) for more than 15 indications, including wound healing, infections and late effects of radiation, which are largely unresponsive to conventional treatments. Accumulated data show that HBO₂ has anti-inflammatory effects and other positive influences on the immune system, making it a rational treatment in the management of psoriasis plaques and arthritis.</p> <p>Case presentation</p> <p>We present the cases of two patients with long histories of psoriasis vulgarus who exhibited marked improvement with use of HBO_2. The first patient was 40 years old and had pustular psoriasis and psoriatic arthritis. He was treated with six sessions of HBO₂ (at 2.8 atmospheres of pressure for 60 minutes), which successfully controlled his symptoms. At the 18-month post-treatment follow up, the patient exhibited complete remission of psoriasis and marked improvement in psoriatic arthritis without medication. The second patient was 55 years old with extensive psoriatic lesions, and exhibited marked improvement within 15 sessions of HBO₂. No adverse effects of HBO₂ were identified.</p> <p>Conclusions</p> <p>HBO₂ may possess potential therapeutic efficacy in the management of psoriasis. We outline the pathogenesis of psoriasis and the selective anti-inflammatory and immunosuppressive effects of HBO₂. We hope that this will provide a basis for elucidating the mechanisms of action and consequently pave the way for further controlled studies.</p

Cancer risk in hospitalised psoriasis patients: a follow-up study in Sweden

We examined overall and specific cancer risks among Swedish subjects who had been hospitalised one or more times for psoriasis. A database was created by identifying such patients from the Swedish Hospital Discharge Register and linking them with the Cancer Registry. Follow-up of patients was carried out from the last hospitalisation through 2004. A total of 15 858 patients were hospitalised for psoriasis during 1965–2004, of whom 1408 developed cancer, giving an overall standardised incidence ratios (SIRs) of 1.33. A significant excess was noted for squamous cell skin cancer, and for cancers of the upper aerodigestive tract, oesophagus, stomach, liver, pancreas, lung, kidney and bladder as well as non-Hodgkin lymphoma. Many of these may reflect the effects of alcohol drinking and tobacco smoking. Patients with multiple hospitalisations showed high risk, particularly for oesophageal (SIR 6.97) and skin (SIR 4.76) cancers

Hybrid SPECT/CT for the assessment of a painful hip after uncemented total hip arthroplasty

Background The diagnosis of hip pain after total hip replacement (THR) represents a highly challenging question that is of increasing concern to orthopedic surgeons. This retrospective study assesses bone scintigraphy with Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of patients. Methods Bone SPECT/CT datasets of 23 patients (mean age 68.9 years) with a painful hip after THR were evaluated. Selection of the patients required an inconclusive radiograph, normal serum levels of inflammatory parameters (CRP and ESR) or a negative aspiration of the hip joint prior to the examination. The standard of reference was established by an interdisciplinary adjudication-panel using all imaging data and clinical follow-up data (>12 month). Pathological and physiological uptake patterns were defined and applied. Results The cause of pain in this study group could be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5), spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1), septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n = 5) cases the cause of hip pain could not be identified. SPECT/CT imaging correctly identified the cause of pain in (n = 13) cases, in which the integrated CT-information led to the correct diagnosis in (n = 4) cases, mainly through superior anatomic correlation. Loosening was correctly assessed in all cases with a definite diagnosis. Conclusions SPECT/CT of THA reliably detects or rules out loosening and provides valuable information about heterotopic ossifications. Furthermore differential diagnoses may be detected with a whole-body scan and mechanical or osseous failure is covered by CT- imaging. SPECT/CT holds great potential for imaging-based assessment of painful prostheses

Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1

The wogonin-containing herb Scutellaria baicalensis has successfully been used for curing various diseases in traditional Chinese medicine. Wogonin has been shown to induce apoptosis in different cancer cells and to suppress growth of human cancer xenografts in vivo. However, its direct targets remain unknown. In this study, we demonstrate for the first time that wogonin and structurally related natural flavones, for example, apigenin, chrysin and luteolin, are inhibitors of cyclin-dependent kinase 9 (CDK9) and block phosphorylation of the carboxy-terminal domain of RNA polymerase II at Ser2. This effect leads to reduced RNA synthesis and subsequently rapid downregulation of the short-lived anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) resulting in apoptosis induction in cancer cells. We show that genetic inhibition of Mcl-1 or CDK9 expression by siRNA is sufficient to mimic flavone-induced apoptosis. Pull-down and in silico docking studies demonstrate that wogonin directly binds to CDK9, presumably to the ATP-binding pocket. In contrast, wogonin does not inhibit CDK2, CDK4 and CDK6 at doses that inhibit CDK9 activity. Furthermore, we show that wogonin preferentially inhibits CDK9 in malignant compared with normal lymphocytes. Thus, our study reveals a new mechanism of anti-cancer action of natural flavones and supports CDK9 as a therapeutic target in oncology

Comparing estimates of influenza-associated hospitalization and death among adults with congestive heart failure based on how influenza season is defined

<p>Abstract</p> <p>Background</p> <p>There is little consensus about how the influenza season should be defined in studies that assess influenza-attributable risk. The objective of this study was to compare estimates of influenza-associated risk in a defined clinical population using four different methods of defining the influenza season.</p> <p>Methods</p> <p>Using the Studies of Left Ventricular Dysfunction (SOLVD) clinical database and national influenza surveillance data from 1986–87 to 1990–91, four definitions were used to assess influenza-associated risk: (a) three-week moving average of positive influenza isolates is at least 5%, (b) three-week moving average of positive influenza isolates is at least 10%, (c) first and last positive influenza isolate are identified, and (d) 5% of total number of positive isolates for the season are obtained. The clinical data were from adults aged 21 to 80 with physician-diagnosed congestive heart failure. All-cause hospitalization and all-cause mortality during the influenza seasons and non-influenza seasons were compared using four definitions of the influenza season. Incidence analyses and Cox regression were used to assess the effect of exposure to influenza season on all-cause hospitalization and death using all four definitions.</p> <p>Results</p> <p>There was a higher risk of hospitalization associated with the influenza season, regardless of how the start and stop of the influenza season was defined. The adjusted risk of hospitalization was 8 to 10 percent higher during the influenza season compared to the non-influenza season when the different definitions were used. However, exposure to influenza was not consistently associated with higher risk of death when all definitions were used. When the 5% moving average and first/last positive isolate definitions were used, exposure to influenza was associated with a higher risk of death compared to non-exposure in this clinical population (adjusted hazard ratios [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.29 and adjusted HR, 1.19; 95% CI, 1.06 to 1.33, respectively).</p> <p>Conclusion</p> <p>Estimates of influenza-attributable risk may vary depending on how influenza season is defined and the outcome being assessed.</p

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal