The Aerodynamic Performance of an Over-the-Rotor Liner With Circumferential Grooves on a High Bypass Ratio Turbofan Rotor

While liners have been utilized throughout turbofan ducts to attenuate fan noise, additional attenuation is obtainable by placing an acoustic liner over-the-rotor. Previous experiments have shown significant fan performance losses when acoustic liners are installed over-the-rotor. The fan blades induce an oscillating flow in the acoustic liners which results in a performance loss near the blade tip. An over-the-rotor liner was designed with circumferential grooves between the fan blade tips and the acoustic liner to reduce the oscillating flow in the acoustic liner. An experiment was conducted in the W-8 Single-Stage Axial Compressor Facility at NASA Glenn Research Center on a 1.5 pressure ratio fan to evaluate the impact of this over-the-rotor treatment design on fan aerodynamic performance. The addition of a circumferentially grooved over-the-rotor design between the fan blades and the acoustic liner reduced the performance loss, in terms of fan adiabatic efficiency, to less than 1 percent which is within the repeatability of this experiment

Global adaptation in networks of selfish components: emergent associative memory at the system scale

In some circumstances complex adaptive systems composed of numerous self-interested agents can self-organise into structures that enhance global adaptation, efficiency or function. However, the general conditions for such an outcome are poorly understood and present a fundamental open question for domains as varied as ecology, sociology, economics, organismic biology and technological infrastructure design. In contrast, sufficient conditions for artificial neural networks to form structures that perform collective computational processes such as associative memory/recall, classification, generalisation and optimisation, are well-understood. Such global functions within a single agent or organism are not wholly surprising since the mechanisms (e.g. Hebbian learning) that create these neural organisations may be selected for this purpose, but agents in a multi-agent system have no obvious reason to adhere to such a structuring protocol or produce such global behaviours when acting from individual self-interest. However, Hebbian learning is actually a very simple and fully-distributed habituation or positive feedback principle. Here we show that when self-interested agents can modify how they are affected by other agents (e.g. when they can influence which other agents they interact with) then, in adapting these inter-agent relationships to maximise their own utility, they will necessarily alter them in a manner homologous with Hebbian learning. Multi-agent systems with adaptable relationships will thereby exhibit the same system-level behaviours as neural networks under Hebbian learning. For example, improved global efficiency in multi-agent systems can be explained by the inherent ability of associative memory to generalise by idealising stored patterns and/or creating new combinations of sub-patterns. Thus distributed multi-agent systems can spontaneously exhibit adaptive global behaviours in the same sense, and by the same mechanism, as the organisational principles familiar in connectionist models of organismic learning

Functional reorganisation and recovery following cortical lesions: A preliminary study in macaque monkeys.

Damage following traumatic brain injury or stroke can often extend beyond the boundaries of the initial insult and can lead to maladaptive cortical reorganisation. On the other hand, beneficial cortical reorganisation leading to recovery of function can also occur. We used resting state FMRI to investigate how cortical networks in the macaque brain change across time in response to lesions to the prefrontal cortex, and how this reorganisation correlated with changes in behavioural performance in cognitive tasks. After prelesion testing and scanning, two monkeys received a lesion to regions surrounding the left principal sulcus followed by periodic testing and scanning. Later, the animals received another lesion to the opposite hemisphere and additional testing and scanning. Following the first lesion, we observed both a behavioural impairment and decrease in functional connectivity, predominantly in frontal-frontal networks. Approximately 8 weeks later, performance and connectivity patterns both improved. Following the second lesion, we observed a further behavioural deficit and decrease in connectivity that showed little recovery. We discuss how different mechanisms including alternate behavioural strategies and reorganisation of specific prefrontal networks may have led to improvements in behaviour. Further work will be needed to confirm these mechanisms.This work was supported by the MRC intramural program MC-A060-5PQ10 (MA, DM, JD, AB), an MRC Career Development Award G0800329 (AM)

Life cycles of agriculturally relevant ENSO teleconnections in North and South America

The characteristic evolution of El Niño Southern Oscillation (ENSO) on timescales of months to years means that risks to agriculture have structure between seasons and years. The potential for consecutive ENSO-induced yield anomalies is of particular interest in major food producing areas, where modest changes in yield have significant effects on global markets. In this study, we analyse how multi-year El Niño and La Niña life cycles relate to climate sensitive portions of major crop-growing seasons in North and South America. We analyse the dynamics underlying these life cycles to illustrate which aspects of the system are most important for agriculture. In North America, the same-season teleconnections affecting soybean and maize have been well studied, but we demonstrate the importance of lagged soil moisture teleconnections for wheat in the southern Great Plains. In South America, peak ENSO sea surface temperature (SST) teleconnections are concurrent with, and therefore critical for, wheat and maize growing seasons while soil moisture memory in Argentina plays an important role during the soybean growing season. Finally, we show that ENSO teleconnection life cycles are consistent with historical yield anomalies. Both El Niño and La Niña life cycles tend to force consecutive seasons of either above or below expected yields. While the magnitude of the yield anomalies forced by ENSO is often modest, they occur in major crop-producing regions

Crop production variability in North and South America forced by life-cycles of the El Niño Southern Oscillation

In this analysis we show how globally coherent teleconnections from life-cycles of the El Niño Southern Oscillation (ENSO) lead to correlated crop production anomalies in North and South America. We estimate the magnitude of ENSO-induced Pan-American production anomalies and discuss how increasing crop harvesting frequency may affect Pan-American production variability. We find that ENSO accounts for ∼72%, 30% and 57% of Pan-American maize, soybean and wheat production variability, respectively. ENSO-induced production anomalies are greatest for maize, with median anomalies of ∼5% of Pan-American production. ENSO-induced yield anomalies for maize and soybeans tend to be of the same sign in North America and southeast South America but of an opposite sign in northeast Brazil. Teleconnections for wheat are more complicated because ENSO affects wheat yields via lagged soil moisture teleconnections in the US and an increased probability of disease in South America, but anomalies tend to be of the same sign in North America and southeast South America. After broadly characterizing ENSO-induced production anomalies, we demonstrate that they are not static in time. Increasing crop harvesting frequency has affected the correlated risks posed by ENSO. We use a soil water balance to show that in Brazil changing to a safrinha cropping cycle increases both the mean water stress and the ENSO-induced soil water content anomalies during flowering in both the maize and soybean seasons, which is a result of increasing evaporative demand during times of lower precipitation and moving the flowering seasons into months with strong ENSO teleconnections. Increasing crop harvesting frequency in Brazil has therefore increased ENSO-induced production variability of soybeans and maize

Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer

Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. Methods: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided. Results: We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher’s exact test P < .001) and that DDRD cells expressed the chemokines CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response–proficient cells (P < .01). Conditioned medium from DDRD cells statistically significantly attracted PBMCs when compared with medium from DNA damage response–proficient cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells demonstrated increased cytosolic DNA and constitutive activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle–specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner. Conclusions: We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint–based therapies

The effect of food availability, age or size on the RNA/DNA ratio of individually measured herring larvae: laboratory calibration

RNA/DNA ratios in individual herring (Clupea harengus) larvae (collected from Kiel Bay, Baltic Sea, in 1989) were measured and proved suitable for determining nutritional status. Significant differences between fed and starving larvae appeared after 3 to 4 d of food deprivation in larvae older than 10 d after hatching. The RNA/DNA ratio showed an increase with age or length of the larvae and was less pronounced in starving larvae compared to fed larvae. The individual variability of RNA/DNA ratios in relation to larval length of fed larvae and of larvae deprived of food for intervals of 6 to 9 d is presented. Based on the length dependency and the individual variability found within the RNA/DNA ratios, a laboratory calibration is given to determine whether a larva caught in the field has been starving or not. An example for a field application is shown

Hyperbaric oxygen treatment in autism spectrum disorders

Traditionally, hyperbaric oxygen treatment (HBOT) is indicated in several clinical disorders include decompression sickness, healing of problem wounds and arterial gas embolism. However, some investigators have used HBOT to treat individuals with autism spectrum disorders (ASD). A number of individuals with ASD possess certain physiological abnormalities that HBOT might ameliorate, including cerebral hypoperfusion, inflammation, mitochondrial dysfunction and oxidative stress. Studies of children with ASD have found positive changes in physiology and/or behavior from HBOT. For example, several studies have reported that HBOT improved cerebral perfusion, decreased markers of inflammation and did not worsen oxidative stress markers in children with ASD. Most studies of HBOT in children with ASD examined changes in behaviors and reported improvements in several behavioral domains although many of these studies were not controlled. Although the two trials employing a control group reported conflicting results, a recent systematic review noted several important distinctions between these trials. In the reviewed studies, HBOT had minimal adverse effects and was well tolerated. Studies which used a higher frequency of HBOT sessions (e.g., 10 sessions per week as opposed to 5 sessions per week) generally reported more significant improvements. Many of the studies had limitations which may have contributed to inconsistent findings across studies, including the use of many different standardized and non-standardized instruments, making it difficult to directly compare the results of studies or to know if there are specific areas of behavior in which HBOT is most effective. The variability in results between studies could also have been due to certain subgroups of children with ASD responding differently to HBOT. Most of the reviewed studies relied on changes in behavioral measurements, which may lag behind physiological changes. Additional studies enrolling children with ASD who have certain physiological abnormalities (such as inflammation, cerebral hypoperfusion, and mitochondrial dysfunction) and which measure changes in these physiological parameters would be helpful in further defining the effects of HBOT in ASD

The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis

Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium) of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement.: University of Otago Research Grant (http://www.otago.ac.nz/research/otago004140.html); A grant-in-aid by the School of Medical Sciences, University of Otago (http://osms.otago.ac.nz/); The Mason Foundation (http://research-hub.griffith.edu.au/display/fosc_MASONG); Royal Society of New Zealand Marsden Fund (http://www.royalsociety.org.nz/programmes/funds/marsden/) grant number UOO0711. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A Novel Role for Cathepsin S as a Potential Biomarker in Triple Negative Breast Cancer

Cathepsin S (CTSS) has previously been implicated in a number of cancer types, where it is associated with poor clinical features and outcome. To date, patient outcome in breast cancer has not been examined with respect to this protease. Here, we carried out immunohistochemical (IHC) staining of CTSS using a breast cancer tissue microarray in patients who received adjuvant therapy. We scored CTSS expression in the epithelial and stromal compartments and evaluated the association of CTSS expression with matched clinical outcome data. We observed differences in outcome based on CTSS expression, with stromal-derived CTSS expression correlating with a poor outcome and epithelial CTSS expression associated with an improved outcome. Further subtype characterisation revealed high epithelial CTSS expression in TNBC patients with improved outcome, which remained consistent across two independent TMA cohorts. Further in silico gene expression analysis, using both in-house and publicly available datasets, confirmed these observations and suggested high CTSS expression may also be beneficial to outcome in ER-/HER2+ cancer. Furthermore, high CTSS expression was associated with the BL1 Lehmann subgroup, which is characterised by defects in DNA damage repair pathways and correlates with improved outcome. Finally, analysis of matching IHC analysis reveals an increased M1 (tumour destructive) polarisation in macrophage in patients exhibiting high epithelial CTSS expression. In conclusion, our observations suggest epithelial CTSS expression may be prognostic of improved outcome in TNBC. Improved outcome observed with HER2+ at the gene expression level furthermore suggests CTSS may be prognostic of improved outcome in ER- cancers as a whole. Lastly, from the context of these patients receiving adjuvant therapy and as a result of its association with BL1 subgroup CTSS may be elevated in patients with defects in DNA damage repair pathways, indicating it may be predictive of tumour sensitivity to DNA damaging agents