Heterogeneity and restricted state selection in FRET with fluorescent proteins

Most fluorescent proteins exhibit multi-exponential fluorescence decays, indicating the presence of a heterogeneous excited state population. In the analysis of FRET to and between fluorescent proteins, it is often convenient to assume that a single interaction pathway is involved. However, in recent work we have shown that this assumption does not hold. Moreover, certain pathways can be highly constrained, leading to the potential misinterpretation of experimental data concerning protein-protein interactions. FRET and single-photon absorption both obey the same global electric dipole selection rules but differ greatly in the mechanism of the acceptor photoselection. In an isotropic medium, single-photon excitation accesses all acceptor transition dipole moment orientations with an equal probability. However, the FRET rate depends on the relative orientation of the donor and acceptor through the κ2 orientation parameter. We show how time- and spectrally- resolved fluorescence intensity and anisotropy decay measurements following direct acceptor excitation, combined with those of the interacting FRET pair, can be used to identify restricted FRET state selection and thus provide accurate measurements of protein-protein interaction dynamics

Uncharted Waters: Treating Trauma Symptoms in the Context of Early Psychosis.

Psychosis is conceptualized in a neurodevelopmental vulnerability-stress framework, and childhood trauma is one environmental factor that can lead to psychotic symptoms and the development of psychotic disorders. Higher rates of trauma are associated with higher psychosis risk and greater symptom frequency and severity, resulting in increased hospitalization rates and demand on outpatient primary care and mental health services. Despite an estimated 70% of individuals in the early stages of psychosis reporting a history of experiencing traumatic events, trauma effects (post-traumatic anxiety or depressive symptoms) are often overlooked in psychosis treatment and current interventions typically do not target commonly comorbid post-traumatic stress symptoms. We presented a protocol for Trauma-Integrated Cognitive Behavioral Therapy for Psychosis (TI-CBTp), an approach to treating post-traumatic stress symptoms in the context of early psychosis care. We provided a brief summary of TI-CBTp as implemented in the context of Coordinated Specialty Care and presented preliminary data supporting the use of TI-CBTp in early psychosis care. The preliminary results suggest that individuals with comorbid psychosis and post-traumatic stress symptoms can be appropriately and safely treated using TI-CBTp within Coordinated Specialty Care

Effects of load mass carried in a backpack upon respiratory muscle fatigue.

The purpose of this study was to investigate whether loads carried in a backpack, with a load mass ranging from 0 to 20 kg, causes respiratory muscle fatigue. Methods: Eight males performed four randomised load carriage (LC) trials comprising 60 min walking at 6.5 km h−1 wearing a backpack of either 0 (LC0), 10 (LC10), 15 (LC15) or 20 kg (LC20). Inspiratory (PImax) and expiratory (PEmax) mouth pressures were assessed prior to and immediately following each trial. Pulmonary gas exchange, heart rate (HR), blood lactate and glucose concentration and perceptual responses were recorded during the first and final 60 s of each trial. Results: Group mean PImax and PEmax were unchanged following 60-min load carriage in all conditions (p > .05). There was an increase over time in pulmonary gas exchange, HR and perceptions of effort relative to baseline measures during each trial (p  .05). Conclusions: These findings indicate that sub-maximal walking with no load or carrying 10, 15 or 20 kg in a backpack for up to 60 min does not cause respiratory muscle fatigue despite causing an increase in physiological, metabolic and perceptual parameters.N/

GJ 9404 b:A Confirmed Eccentric Planet, and not a Candidate

Eccentric orbits can be decomposed into a series of sine curves which affects how the false alarm probability is computed when using traditional periodograms on radial-velocity data. Here we show that a candidate exoplanet orbiting the M dwarf GJ 9404, identified by the HADES survey using data from the HARPS-N spectrograph, is in fact a bona-fide planet on a highly eccentric orbit. Far from a candidate, GJ 9404 b is detected with a high confidence. We reach our conclusion using two methods that assume Keplerian functions rather than sines to compute a detection probability, a Bayes Factor, and the FIP periodogram. We compute these using nested sampling with {\tt kima}.Comment: 3 pages, 1 figur

Properties of permutation-based gene tests and controlling type 1 error using a summary statistic based gene test

Background: The advent of genome-wide association studies has led to many novel disease-SNP associations, opening the door to focused study on their biological underpinnings. Because of the importance of analyzing these associations, numerous statistical methods have been devoted to them. However, fewer methods have attempted to associate entire genes or genomic regions with outcomes, which is potentially more useful knowledge from a biological perspective and those methods currently implemented are often permutation-based. Results: One property of some permutation-based tests is that their power varies as a function of whether significant markers are in regions of linkage disequilibrium (LD) or not, which we show from a theoretical perspective. We therefore develop two methods for quantifying the degree of association between a genomic region and outcome, both of whose power does not vary as a function of LD structure. One method uses dimension reduction to “filter” redundant information when significant LD exists in the region, while the other, called the summary-statistic test, controls for LD by scaling marker Z-statistics using knowledge of the correlation matrix of markers. An advantage of this latter test is that it does not require the original data, but only their Z-statistics from univariate regressions and an estimate of the correlation structure of markers, and we show how to modify the test to protect the type 1 error rate when the correlation structure of markers is misspecified. We apply these methods to sequence data of oral cleft and compare our results to previously proposed gene tests, in particular permutation-based ones. We evaluate the versatility of the modification of the summary-statistic test since the specification of correlation structure between markers can be inaccurate. Conclusion: We find a significant association in the sequence data between the 8q24 region and oral cleft using our dimension reduction approach and a borderline significant association using the summary-statistic based approach. We also implement the summary-statistic test using Z-statistics from an already-published GWAS of Chronic Obstructive Pulmonary Disorder (COPD) and correlation structure obtained from HapMap. We experiment with the modification of this test because the correlation structure is assumed imperfectly known

Infiltrated carbon foam composites

An infiltrated carbon foam composite and method for making the composite is described. The infiltrated carbon foam composite may include a carbonized carbon aerogel in cells of a carbon foam body and a resin is infiltrated into the carbon foam body filling the cells of the carbon foam body and spaces around the carbonized carbon aerogel. The infiltrated carbon foam composites may be useful for mid-density ablative thermal protection systems

A practical experiment to teach students continuous flow and physico-chemical methods: acetylation of ethylene diamine in liquid bi-phase

Despite growing applications being reported both in academia and industry, continuous flow chemistry remains a relatively untaught field across most chemistry undergraduate courses. This is particularly true in laboratory practical classes, where it is often deemed simpler to carry out synthetic reactions in traditional batch mode using round-bottomed flasks. Herein, we report the development of an undergraduate project that utilises cheap and readily available materials to construct continuous flow reactors. The students compare the performance of different types of reactors and conditions in a biphasic selective acetylation of a symmetrical diamine. Throughout the investigation, the students can vary multiple parameters as they optimise the reaction, thus actively learning and readjusting them based on their improved understanding. The experiments give the students an appreciation of continuous flow techniques in comparison to batch

Effect of New Zealand Blackcurrant Extract on Substrate Oxidation and Cycling Performance in Normobaric Hypoxia

Blackcurrant is high in anthocyanin content. We have shown enhanced whole-body fat oxidation and increased time trial performance during cycling, in addition to increased femoral artery diameter during a sustained submaximal isometric contraction of the m.quadriceps with intake of New Zealand blackcurrant (NZBC) extract in normobaric normoxia (Cook et al., 2015, 2017). The effect of blackcurrant on metabolic and physiological responses and performance during cycling in normobaric hypoxia are not known. PURPOSE: To examine the effect of NZBC extract on intensity-dependent physiological and metabolic responses and 16.1-km cycling time trial in trained cyclists in normobaric hypoxia. METHODS: The study used a double-blind randomized cross-over design. Eleven healthy men from cycling and triathlon clubs with at least 3 yrs experience and cycling 8-10 hr·wk−1 (age: 38±11 yrs, height: 179±4 cm, body mass: 76±8 kg, V̇O2max: 47±5 mL·kg−1·min−1, maximum power: 398±38 W, mean±SD) ingested NZBC extract (600 mg·day−1 containing 220 mg anthocyanins) or placebo (PL) for 7 days (washout 14 days). Participants performed bouts of 10 min at 45, 55 and 65% V̇O2max, using indirect calorimetry and blood sampling, followed by a 16.1 km timetrial on a SRM ergometer (SRM International, Germany). Participants were familiarized for the time-trial. All testing took place in a temperature controlled (15°C) normobaric hypoxic chamber set at an altitude of ~2500 m (15% FiO2) (TIS Services, Medstead, UK) in morning sessions. Data was analysed using paired t-tests. RESULTS: At each intensity, NZBC extract had no effect on metabolic and physiological responses (e.g. at 65% V̇O2max, heart rate - PL: 133±12, NZBC; 132±12 beats·min-1); fat oxidation - PL: 0.24±0.12, NZBC: 0.20±0.16 g·min-1; carbohydrate oxidation - PL: 2.34±0.42, NZBC: 2.48±0.35 g·min-1; lactate - PL: 1.37±0.45, NZBC: 1.56±0.57 mmol·L-1). No improvements in 16.1 km time-trial performance were observed (PL: 1685±92, NZBC: 1685±99 sec). CONCLUSION: Seven day intake of New Zealand blackcurrant extract does not change whole-body fat oxidation and 16.1 km time-trial performance during cycling in normobaric hypoxia