IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0-50,000 Years Cal BP

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis

Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age-related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow-derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age-related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell-derived IL-10 was increased in resting and LPS-activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue-resident peritoneal macrophages, but not by bone marrow-derived macrophages/monocytes, and suggest that age-related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.

Transatlantic distribution of the Alaskan White River Ash

Volcanic ash layers preserved within the geologic record represent precise time markers that correlate disparate depositional environments and enable the investigation of synchronous and/or asynchronous behaviors in Earth system and archaeological sciences. However, it is generally assumed that only exceptionally powerful events, such as supereruptions (≥450 km3 of ejecta as dense-rock equivalent; recurrence interval of ∼105 yr), distribute ash broadly enough to have an impact on human society, or allow us to address geologic, climatic, and cultural questions on an intercontinental scale. Here we use geochemical, age, and morphological evidence to show that the Alaskan White River Ash (eastern lobe; A.D. 833–850) correlates to the “AD860B” ash (A.D. 846–848) found in Greenland and northern Europe. These occurrences represent the distribution of an ash over 7000 km, linking marine, terrestrial, and ice-core records. Our results indicate that tephra from more moderate-size eruptions, with recurrence intervals of ∼100 yr, can have substantially greater distributions than previously thought, with direct implications for volcanic dispersal studies, correlation of widely distributed proxy records, and volcanic hazard assessment.

Ageing and the immune system: focus on macrophages

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

A Numerical and Experimental Assessment of the Use of a Turbine Utilizing Splitter Blades for an Automotive Variable Geometry Turbocharger

Automotive manufacturers require improved part load engine performance to further improve fuel economy. For a swing vane VGS (Variable Geometry Stator) turbine this means a more closed stator vane, to deal with the low MFRs (Mass Flow Rates), high PRs (Pressure Ratios) and low rotor rotational speeds. During these conditions the turbine is operating at low velocity ratios. As more energy is available at high pressure ratios and during lower turbocharger rotational speeds, a turbine which is efficient at these conditions is desirable. Another key aspect for automotive manufacturers is engine responsiveness. High inertia designs result in “turbo lag” which means an increased time before the target boost pressure is reached. Therefore, designs with improved performance at low velocity ratios, reduced inertia or an increased swallowing capacity are the current targets for turbocharger manufacturers.

To try to meet these design targets a CFD (Computational Fluid Dynamics) study was performed on a turbine wheel using splitter blades. A number of parameters were investigated. These included splitter blade merdional length, blade number and blade angle distribution.

The numerical study was performed on a scaled automotive VGS. Three different stator vane positions have been analysed. A single passage CFD model was developed and used to provide information on the flow features affecting performance in both the stator vanes and turbine.

Following the CFD investigation the design with the best compromise in terms of performance, inertia and increased MFP (Mass Flow Parameter) was selected for manufacture and testing. Tests were performed on a scaled, low temperature turbine test rig. The aerodynamic flow path of the gas stand was the same as that investigated during the CFD. The test results revealed a design which had similar performance at the closed stator vane positions when compared to the baseline wheel. At the maximum MFR stator vane condition a drop of −0.6% pts in efficiency was seen. However, 5.5% increase in MFP was obtained with the additional benefit of a drop in rotor inertia of 3.7%, compared to the baseline wheel.

Few-cycle driven relativistically oscillating plasma mirrors:A source of intense isolated attosecond pulses

The conditions required for the production of isolated attosecond pulses from relativistically oscillating mirrors (ROM) are investigated numerically and experimentally. In simulations, carrier-envelope-phase-stabilized three-cycle pulses are found to be sufficient to produce isolated attosecond pulses, while two-cycle pulses will predominantly lead to isolated attosecond pulses even in the absence of carrier-envelope stabilization. Using a state-of-the-art laser system delivering three-cycle pulses at multiple-terawatt level, we have generated higher harmonics up to 70 eV photon energy via the ROM mechanism. The observed spectra are in agreement with theoretical expectations and highlight the potential of few-cycle-driven ROM harmonics for intense isolated attosecond pulse generation for performing extreme ultraviolet-pump extreme ultraviolet-probe experiments. © 2012 American Physical Society.

Core outcome sets and trial registries

Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

Genome wide interactions of wild-type and activator bypass forms of σ54

Enhancer-dependent transcription involving the promoter specificity factor σ54 is widely distributed amongst bacteria and commonly associated with cell envelope function. For transcription initiation, σ54-RNA polymerase yields open promoter complexes through its remodelling by cognate AAA+ ATPase activators. Since activators can be bypassed in vitro, bypass transcription in vivo could be a source of emergent gene expression along evolutionary pathways yielding new control networks and transcription patterns. At a single test promoter in vivo bypass transcription was not observed. We now use genome-wide transcription profiling, genome-wide mutagenesis and gene over-expression strategies in Escherichia coli, to (i) scope the range of bypass transcription in vivo and (ii) identify genes which might alter bypass transcription in vivo. We find little evidence for pervasive bypass transcription in vivo with only a small subset of σ54 promoters functioning without activators. Results also suggest no one gene limits bypass transcription in vivo, arguing bypass transcription is strongly kept in check. Promoter sequences subject to repression by σ54 were evident, indicating loss of rpoN (encoding σ54) rather than creating rpoN bypass alleles would be one evolutionary route for new gene expression patterns. Finally, cold-shock promoters showed unusual σ54-dependence in vivo not readily correlated with conventional σ54 binding-sites.

Chp8, a diguanylate cyclase from Pseudomonas syringae pv tomato DC3000 suppresses the PAMP flagellin, increases EPS and promotes plant immune evasion.

The bacterial plant pathogen Pseudomonas syringae causes disease in a wide range of plants. The associated decrease in crop yields results in economic losses and threatens global food security. Competition exists between the plant immune system and the pathogen, the basic principles of which can be applied to animal infection pathways. P. syringae uses a type III secretion system (T3SS) to deliver virulence factors into the plant that promote survival of the bacterium. The P. syringae T3SS is a product of the hypersensitive response and pathogenicity (hrp) and hypersensitive response and conserved (hrc) gene cluster, which is strictly controlled by the codependent enhancer-binding proteins HrpR and HrpS. Through a combination of bacterial gene regulation and phenotypic studies, plant infection assays, and plant hormone quantifications, we now report that Chp8 (i) is embedded in the Hrp regulon and expressed in response to plant signals and HrpRS, (ii) is a functional diguanylate cyclase, (iii) decreases the expression of the major pathogen-associated molecular pattern (PAMP) flagellin and increases extracellular polysaccharides (EPS), and (iv) impacts the salicylic acid/jasmonic acid hormonal immune response and disease progression. We propose that Chp8 expression dampens PAMP-triggered immunity during early plant infection.

In vitro and in vivo methodologies for studying the Sigma 54-dependent transcription.

Here we describe approaches and methods to assaying in vitro the major variant bacterial sigma factor, Sigma 54 (σ54), in a purified system. We include the complete transcription system, binding interactions between σ54 and its activators, as well as the self-assembly and the critical ATPase activity of the cognate activators which serve to remodel the closed promoter complexes. We also present in vivo methodologies that are used to study the impact of physiological processes, metabolic states, global signalling networks, and cellular architecture on the control of σ54-dependent gene expression.

Research Methods in Psychology For Dummies

Your hands-on introduction to research methods in psychology.  
Looking for an easily accessible overview of research methods in psychology? This is the book for you! Whether you need to get ahead in class, you're pressed for time, or you just want a take on a topic that's not covered in your textbook, Research Methods in Psychology For Dummies has you covered. 
Written in plain English and packed with easy-to-follow instruction, this friendly guide takes the intimidation out of the subject and tackles the fundamentals of psychology research in a way that makes it approachable and comprehensible, no matter your background. Inside, you'll find expert coverage of qualitative and quantitative research methods, including surveys, case studies, laboratory observations, tests and experiments—and much more. 
- Serves as an excellent supplement to course textbooks - Provides a clear introduction to the scientific method - Presents the methodologies and techniques used in psychology research- Written by the authors of Psychology Statistics For Dummies 
If you're a first or second year psychology student and want to supplement your doorstop-sized psychology textbook—and boost your chances of scoring higher at exam time—this hands-on guide breaks down the subject into easily digestible bits and propels you towards success.

Incentives and rewards: what do adult populations truly want? Insights from the physical activity loyalty (PAL) scheme

Background
Trials depend on good recruitment and retention, but efforts to improve these have had varying success. This may be due to inadequate understanding of what participants would value in return for taking part. An opportunity arose in one trial to investigate the incentives that might help recruit and retain participants to another.

Aim
To determine what adults value as an incentive for involvement in a trial.

Methods
In the PAL Scheme, employees used a ‘loyalty card’ to monitor their physical activity over 12 weeks. The incentive group (n=199) collected points and received rewards for physical activity (1 minute = 1 point, max: 30 pts/day). A comparator group (n=207) self-monitored their physical activity only. Points could be redeemed as retail vouchers. 17 different incentives were available, from 75 pts (£2.50, a sandwich) to 1800 pts (£60, 1 month gym membership).

Results
148 of the 199 intervention participants used their card at least once, earning a mean of 374 pts. 121 earned sufficient to collect a reward and 76 redeemed points for vouchers but only 48 exchanged the vouchers for rewards. The most popular reward was not that of highest monetary value: two cinema tickets (300 pts, £10).

Conclusions
The value that participants place on a reward might be more important than its monetary value. Some might appreciate receiving the voucher, without spending it. In choosing incentives to boost trial participation, it may help to allow people to choose from a variety of rewards, rather than reimbursing in money.