The effects of high-pass masking on stimulus rate changes in the auditory brainstem response

The auditory brainstem response (ABR) to tonal stimuli is routinely used in a clinical setting to obtain estimates of hearing sensitivity. The latency and amplitude of ABR waveforms vary with stimulus frequency, intensity, and rate. However, interactions among these stimulus parameters on the ABR have only recently been fully examined. A study measuring effects of all three stimulus parameters in the same subjects demonstrated a latency shift of ABR Wave V in response to an increase in stimulus rate that was significantly greater for low frequency, low intensity stimuli than for other stimulus conditions tested (Hess and Hood, 2012). The goal of the current study was to replicate these findings and assure frequency regions being tested were appropriately isolated through the use of a high-pass masking paradigm. The current study was designed to further evaluate the interactions among stimulus parameters on the ABR in normal hearing adults. The ABR was recorded from sixteen adults with normal hearing for eight stimulus parameter conditions. Results revealed a significantly greater rate-induced latency shift in Wave V of the ABR for the low frequency, low intensity condition, confirming the results of the Hess and Hood (2012) study. The new finding in this study was that the latencies for all conditions remained similar in relationship with the addition of high-pass masking. These results suggest a frequency effect for lower intensity signals; however, the mechanisms behind this finding remain unknown

LFRic: meeting the challenges of scalability and performance portability in weather and climate models

This paper describes LFRic: the new weather and climate modelling system being developed by the UK Met Office to replace the existing Unified Model in preparation for exascale computing in the 2020s. LFRic uses the GungHo dynamical core and runs on a semi-structured cubed-sphere mesh. The design of the supporting infrastructure follows object-oriented principles to facilitate modularity and the use of external libraries where possible. In particular, a `separation of concerns' between the science code and parallel code is imposed to promote performance portability. An application called PSyclone, developed at the STFC Hartree centre, can generate the parallel code enabling deployment of a single source science code onto different machine architectures. This paper provides an overview of the scientific requirement, the design of the software infrastructure, and examples of PSyclone usage. Preliminary performance results show strong scaling and an indication that hybrid MPI/OpenMP performs better than pure MPI

Net ecosystem exchange from two formerly afforested peatlands undergoing restoration in the Flow Country of northern Scotland

Northern peatlands are important in the global carbon (C) cycle as they help regulate local, regional and global C budgets through high atmospheric carbon dioxide (CO2) uptake and low net CO2 losses to the atmosphere. Since the 1900s (but particularly the 1950s) land-use change has affected many peatland areas, driven in part by attempts to improve their commercial value. During this period, many peatlands in the UK were drained and planted with non-native conifer plantations. Efforts are now underway to restore the ecosystem functioning of these peatlands to those characteristic of pristine peatlands, in particular C flux dynamics. A lack of ecosystem level measurements means that the timescales of restoration and the degree to which they are successful remains poorly determined. In this research, we present the first year-round study of net ecosystem CO2 exchange (NEE) from peatlands undergoing restoration from forestry. Annual NEE was measured from two sites between March 2014 and June 2015, where restoration commenced 10 years and 16 years prior to the start of this study, and the results were then compared to existing measurements from a near-pristine peatland. Existing NEE data (expressed as CO2-C) from the near-pristine peatland indicated a C sink of 114 g m-2 yr-1, and our estimates suggest that the older restored site (16 years) was also a NEE sink (71 g m-2 yr-1). In contrast, the younger site (10 years) was a NEE source (80 g m-2 yr-1). We critically assess the confidence of these measurements and also present these data in relation to other northern hemisphere peatlands to better understand the timeframe in which a peatland site can turn from a C source to a C sink after restoration

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Studies directed at establishing the structural features that control Pt/DNA interactions and the anticancer activity of Pt drugs are described. [1H, 15N]-HSQC 2D NMR spectroscopic studies of the reactions of cisplatin with oligonucleotides containing ApG and GpA binding sites reveal dramatic differences in the rates of formation of monofunctional adducts at the two sites. When the reactant is cis-[Pt(NH3)2(OH2)2]2+ no such differences are observed suggesting that outer-sphere interactions between the reactant and the oligonucleotide may play a substantial role in determining the rates. Rates of closure to the bifunctional adducts are similar to those observed for cisplatin. Studies of the adduct profiles formed by sterically bulky and/or optically active complexes reveal that steric interactions play a major role in mediating the binding of Pt(ll) to DNA but that hydrogen bonds play less of a role. In vitro cytotoxic activities for these complexes do not always follow the trends that would be expected on the basis of the adduct profiles

Endogenous production of IL-1B by breast cancer cells drives metastasis and colonisation of the bone microenvironment

Background: Breast cancer bone metastases are incurable highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL-1B by tumor cells drives metastasis and growth in bone. Methods: Tumor/stromal IL-B and IL-1R1 expression was assessed in patient samples and effects of the IL-1R antagonist, Anakinra or the IL-1B antibody Canakinumab on tumor growth and spontaneous metastasis were measured in a humanized mouse model of breast cancer bone metastasis. Effects of tumor cell-derived IL-1B on bone colonisation and parameters associated with metastasis were measured in MDA-MB-231, MCF7 and T47D cells transfected with IL-1B/control. Results: In tissue samples from >1300 patients with stage II/III breast cancer, IL-1B in tumor cells correlated with relapse in bone (hazard ratio 1.85; 95% CI 1.05-3.26; P=0.02) and other sites (hazard ratio 2.09; 95% CI 1.26-3.48; P=0.0016). In a humanized model of spontaneous breast cancer metastasis to bone, Anakinra or Canakinumab reduced metastasis and reduced the number of tumor cells shed into the circulation. Production of IL-1B by tumor cells promoted EMT (altered E-Cadherin, N-Cadherin and G-Catenin), invasion, migration and bone colonisation. Contact between tumor and osteoblasts or bone marrow cells increased IL-1B secretion from all three cell types. IL-1B alone did not stimulate tumor cell proliferation. Instead, IL-1B caused expansion of the bone metastatic niche leading to tumor proliferation. Conclusion: Pharmacological inhibition of IL-1B has potential as a novel treatment for breast cancer metastasis

Energy Intake and Expenditure of Professional Soccer Players of the English Premier League: Evidence of Carbohydrate Periodization.

In an attempt to better identify and inform the energy requirements of elite soccer players, we quantified the energy expenditure (EE) of players from the English Premier League (n=6) via the doubly labeled water method (DLW) over a 7-day in-season period. Energy intake (EI) was also assessed using food diaries, supported by the remote food photographic method and 24 h recalls. The 7-day period consisted of 5 training days (TD) and 2 match days (MD). Although mean daily EI (3186 ± 367 kcals) was not different from (P>0.05) daily EE (3566 ± 585 kcals), EI was greater (P<0.05) on MD (3789 ± 532 kcal; 61.1 ± 11.4 kcal.kg(-1) LBM) compared with TD (2956 ± 374 kcal; 45.2 ± 9.3 kcal.kg(-1) LBM, respectively). Differences in EI were reflective of greater (P<0.05) daily CHO intake on MD (6.4 ± 2.2 g.kg(-1)) compared with TD (4.2 ± 1.4 g.kg(-1)). Exogenous CHO intake was also different (P<0.01) during training sessions (3.1 ± 4.4 g.h(-1)) versus matches (32.3 ± 21.9 g.h(-1)). In contrast, daily protein (205 ± 30 g.kg(-1), P=0.29) and fat intake (101 ± 20 g.kg(-1), P=0.16) did not display any evidence of daily periodization. Although players readily achieve current guidelines for daily protein and fat intake, data suggest that CHO intake on the day prior to and in recovery from match play was not in accordance with guidelines to promote muscle glycogen storage

Resistance to amorphisation in Ca1-xLa2x/3TiO3 perovskites – a bulk ion-irradiation study

The changes induced from 1 MeV Kr+ and 5 MeV Au+ ion irradiation at room temperature have been utilised to determine the impact of cation vacancies on the radiation damage response of bulk Ca1-xLa2x/3TiO3 perovskite structured ceramics. Perovskite systems have long been considered as candidate waste forms for the disposition of actinide wastes, and doping with multi-valent elements such as Pu may lead to cation deficiency. Based on GAXRD and TEM analysis, two regions of resistance/susceptibility to amorphisation have been confirmed with reference to CaTiO3. Increased resistance to amorphisation has been observed for 0.1 ≤ x ≤ 0.4, with an increased susceptibility to amorphisation for x ≥ 0.5. It is proposed that these processes are induced by enhanced recovery from radiation damage for 0.1 ≤ x ≤ 0.4, and reduced tolerance for disorder/the increasingly covalent nature of the A-O bond for x ≥ 0.5. Lattice parameter analysis of the x = 0 and 0.5 samples showed a saturation in radiation damage induced volume swelling at 4.7 ± 0.1% and 1.8 ± 0.1%, respectively, while the saturation limit for the b parameter was lower than the respective a and c orthorhombic parameters. In the x = 0.2 and 0.4 samples, amorphisation was not observed, however the b parameter was found to swell to a lesser extent than the a and c parameters. Swelling was not observed for the ion irradiated x ≥ 0.6 samples

Cancer: evolutionary, genetic and epigenetic aspects

There exist two paradigms about the nature of cancer. According to the generally accepted one, cancer is a by-product of design limitations of a multi-cellular organism (Greaves, Nat Rev Cancer 7:213–221, 2007). The essence of the second resides in the question “Does cancer kill the individual and save the species?” (Sommer, Hum Mutat 3:166–169, 1994). Recent data on genetic and epigenetic mechanisms of cell transformation summarized in this review support the latter point of view, namely that carcinogenesis is an evolutionary conserved phenomenon—a programmed death of an organism. It is assumed that cancer possesses an important function of altruistic nature: as a mediator of negative selection, it serves to preserve integrity of species gene pool and to mediate its evolutionary adjustment. Cancer fulfills its task due apparently to specific killer function, understanding mechanism of which may suggest new therapeutic strategy