Are R&D collaborators bound to compete? Experience from Cooperative Research Centres in Australia

Increasingly, research of potential socio-economic value is being conducted within cross-sector (government, university, business) inter-organizational networks. Such networks encourage innovation and learning by breaking down rigidities in existing institutions and by providing for ‘knowledge creation in the context of application’. In the process, new organizational forms for research and development (R&D) are emerging. The Cooperative Research Centre (CRC) is the dominant organizational model for cross-sector collaborative R&D in Australia. Joining a cross-sector collaborative R&D centre poses a significant challenge for public sector research managers. Success depends on cooperation with businesses and other organizations whose interests, objectives, expectations and strategies at various times converge or conflict. The game is a risky one, with the possibility of unforeseen and unwelcome consequences such as partner opportunism and competition for resources. Yet little empirical evidence exists on how researchers perceive and manage the risks and rewards of participation in cross-sector R&D centres. Our study gives voice to the researchers within these inter-organizational networks. We draw evidence from a written survey of 370 respondents from public sector organizations involved in the management and conduct of CRC-based research. The survey questions permit an assessment of the main benefits and problems in CRC participation; the management strategies adopted; and the effect of CRC participation on careers. Responses to open-ended questions in the survey convey the ‘CRC experience’ in the participants own words. We find the concepts of risk common in the management and organizational studies literature inadequate to explain the dynamics of interaction in cross-sector R&D. We therefore extend these through notions of the domains of ‘academic’, ‘scientific’ and ‘organizational’ risk. There are two broad implications of our findings: (1) participants in the CRC need to look beyond the traditionally acknowledged risks of contractual arrangements and consider risks that relate to the nature of scientific knowledge structures and the actual concerns and careers of research scientists; and (2) once these ‘academic’ and ‘scientific’ considerations are properly assessed, government research agencies and universities may need to adopt different management responses to their participation in inter-organizational R&D. We speculate that the way these potentially competing domains are dealt with has implications for (1) the survival of individual CRCs and (2) whether cross-sector collaborative R&D organizations remain ephemeral ‘staging posts’ or become entrenched in the national research system. We argue that cross-sector collaborative R&D organizations are an important component of a dynamic ‘science system’, but that they are inherently unstable organizations. They require organizational management that recognises their differences from business IORs that involve firms alone

Links Between Optical and X-ray Light in Scorpius X-1

We observed the low-mass X-ray binary Sco X-1 for 12 nights simultaneously using the Rossi X-Ray Timing Explorer and the Otto Struve Telescope at McDonald Observatory at 1 second time resolution. This is among the most comprehensive simultaneous X-Ray/optical data sets of Sco X-1. Evidence of reprocessing was observed in the form of nine positive, near-zero lag peaks in the cross correlation function, eight of which were relatively small and took the shape of piecewise exponential functions. These peaks were initially identified by eye, after which a computational identification scheme was developed to confirm their significance. Based on their short lags (less than 4 seconds), as well as their occurrence on the flaring branch and soft apex, the small cross correlation features are likely to be caused by reprocessing off the outer disc, although the companion could still make a contribution to their tails. The Z track was parameterized using a rank number scheme so that the system's location on the track could be numerically defined. Plotting the results against the optical reveals an increasing step function when moving from the horizontal to the normal to the flaring branch, with differential optical levels at ~0.47, ~0.57, and ~1.1 respectively. An additional correlation between Z track location and the optical was found on the upper flaring branch. An optical intensity histogram reveals a transition region between the normal and flaring branches with only intermediate fluxes.Comment: Accepted for publication in the Monthly Notices of the Royal Astronomical Societ

A critical analysis of the combined usage of protein localization prediction methods: Increasing the number of independent data sets can reduce the accuracy of predicted mitochondrial localization

In the absence of a comprehensive experimentally derived mitochondrial proteome, several bioinformatic approaches have been developed to aid the identification of novel mitochondrial disease genes within mapped nuclear genetic loci. Often, many classifiers are combined to increase the sensitivity and specificity of the predictions.Here we show that the greatest sensitivity and specificity are obtained by using a combination of seven carefully selected classifiers. We also show that increasing the number of independent prediction methods can paradoxically decrease the accuracy of predicting mitochondrial localization. This approach will help to accelerate the identification of new mitochondrial disease genes by providing a principled way for the selection for combination of appropriate prediction methods of mitochondrial localization of proteins

Evidence for Pleistocene gene flow through the ice-free corridor from extinct horses and camels from Natural Trap Cave, Wyoming

Natural Trap Cave (Bighorn Mountains, Wyoming) preserves an abundance of fossil remains from extinct Late Pleistocene fauna and is situated near a past migration route that likely connected populations in Eastern Beringia and the contiguous US—the ice-free corridor between the Cordilleran and Laurentide icesheets. Some palaeontological evidence supports a correspondingly high affinity between fauna recorded in Natural Trap Cave and Eastern Beringia versus elsewhere in the contiguous US, but this hypothesis has not yet been extensively tested using genetic data. In the present study, we analysed 16 horse specimens and one camel specimen from Natural Trap Cave. Of the horse specimens we analysed, we obtained 10 unique and previously unreported mitochondrial haplotypes belonging to two distinct (extinct) genetic clades—two haplotypes corresponded to a caballine horse (Equus sp.) and eight corresponded to the stilt-legged horse (Haringtonhippus francisci). With only one exception, it appears these newly sequenced individuals all shared a common ancestor more recently with Eastern Beringian individuals than with others from the contiguous US. In addition, mitochondrial data from a specimen assigned to Camelops sp. revealed that it shares a closer affinity with specimens from the Yukon Territory than those from Idaho or Nevada, though all appear to belong to a single species (“yesterday''s camel”; Camelops cf. hesternus). Together, these results are consistent with a high level of genetic connectivity between horse and camel populations in the Bighorn Mountains and Eastern Beringia during the Pleistocene. © 2021 Elsevier Ltd and INQU

Glucagon-Like Peptide 1 Receptor Activation Augments Cardiac Output and Improves Cardiac Efficiency in Obese Swine After Myocardial Infarction

This study tested the hypothesis that glucagon-like peptide 1 (GLP-1) therapies improve cardiac contractile function at rest and in response to adrenergic stimulation in obese swine after myocardial infarction. Obese Ossabaw swine were subjected to gradually developing regional coronary occlusion using an ameroid occluder placed around the left anterior descending coronary artery. Animals received subcutaneous injections of saline or liraglutide (0.005-0.015 mg/kg/day) for 30 days after ameroid placement. Cardiac performance was assessed at rest and in response to sympathomimetic challenge (dobutamine 0.3-10 μg/kg/min) using a left ventricular pressure/volume catheter. Liraglutide increased diastolic relaxation (dP/dt; Tau 1/2; Tau 1/e) during dobutamine stimulation (P < 0.01) despite having no influence on the magnitude of myocardial infarction. The slope of the end-systolic pressure volume relationship (i.e., contractility) increased with dobutamine after liraglutide (P < 0.001) but not saline administration (P = 0.63). Liraglutide enhanced the slope of the relationship between cardiac power and pressure volume area (i.e., cardiac efficiency) with dobutamine (P = 0.017). Hearts from animals treated with liraglutide demonstrated decreased β1-adrenoreceptor expression. These data support that GLP-1 agonism augments cardiac efficiency via attenuation of maladaptive sympathetic signaling in the setting of obesity and myocardial infarction

Sustained low-dose treatment with the histone deacetylase inhibitor LBH589 induces terminal differentation of osteosarcoma cells

Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity

Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?

Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. Objective: To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction. Methods: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 y ears (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI. Results: Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol /L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL ( s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL ( s.d. 87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased. Interpretation: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important

Inhibition of sodium–glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization

The goal of the present study was to evaluate the effects of SGLT2i on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in normal, metabolically healthy swine. Lean swine received placebo or canagliflozin (300 mg PO) 24 h prior to and the morning of an invasive physiologic study protocol. Hemodynamic and cardiac function measurements were obtained at baseline, during a 30-min complete occlusion of the circumflex coronary artery, and during a 2-h reperfusion period. Blood pressure, heart rate, coronary flow, and myocardial oxygen consumption were unaffected by canagliflozin treatment. Ventricular volumes remained unchanged in controls throughout the protocol. At the onset of ischemia, canagliflozin produced acute large increases in left ventricular end-diastolic and systolic volumes which returned to baseline with reperfusion. Canagliflozin-mediated increases in end-diastolic volume were directly associated with increases in stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial uptake of glucose, lactate, free fatty acids or ketones, were noted between treatment groups at any time. In separate experiments using a longer 60 min coronary occlusion followed by 2 h of reperfusion, canagliflozin increased end-diastolic volume and stroke volume and significantly diminished myocardial infarct size relative to control swine. These data demonstrate that SGLT2i with canagliflozin preserves cardiac contractile function and efficiency during regional myocardial ischemia and provides ischemia protection independent of alterations in myocardial substrate utilization