Plant canopy shape and the influences on UV exposures to the canopy

The solar spectra at selected sites over hemispherical, conical and pinnacle plant canopy models has been evaluated with a dosimetric technique. The irradiance at the sites varies by up to a factor of 0.31 compared to the irradiance on a horizontal plane. The biologically effective (UVBE) exposures evaluated with the dosimetric technique at sites over the plant canopy are up to 19% of that on a horizontal plane. Compared to a spectroradiometer, the technique provides a more practicable method of measuring the UVBE exposures at multiple sites over a plant canopy. Usage of a dosimeter at one site to provide the exposures at that site for different sun angles introduces an error of more than 50%. Knowledge of the spectra allowed the UV and UVBE exposures to be calculated at each site along with the exposures to the entire canopies. These were dependent on the sun angle and the canopy shape. For plant damage, the UVBE was a maximum of about 1.4 mJ cm-2/min. Compared to the hemispherical canopy, the UVBE exposure for generalised plant damage was 45% less for the pinnacle canopy and 23% less for the conical canopy. The canopy exposures could not be determined from measurements of the ambient exposure

Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice

Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(−/−) or A1(+/−) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2−/−, but not A1+/−, mice. Additionally, A2−/− HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction

Dihydropyrimidine-thiones and clioquinol synergize to target beta-amyloid cellular pathologies through a metal-dependent mechanism

The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer’s disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.D.F.T was funded by NRSA Fellowship NIH 5F32NS061419. D.F.T. and S.L. were supported by WIBR funds in support of research on Regenerative Disease, the Picower/JPB Foundation, and the Edward N. and Della L. Thome Foundation. G.A.C. and S.L. were funded by a Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award. L.E.B., R.T., and S.E.S. were funded by NIH GM086180, NIH GM067041, and NIH GM111625. (5F32NS061419 - NRSA Fellowship NIH; WIBR funds in support of research on Regenerative Disease; Picower/JPB Foundation; Edward N. and Della L. Thome Foundation; Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award; GM086180 - NIH; NIH GM067041 - NIH; NIH GM111625 - NIH)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705239/Accepted manuscrip

A Black Hole of > 6 Solar Masses in the X-ray Nova XTE J1118+480

Observations of the quiescent X-ray nova XTE J1118+480 with the new 6.5-m MMT have revealed that the velocity amplitude of the dwarf secondary is 698 +/- 14 km/s and the orbital period of the system is 0.17013 +/- 0.00010 d. The implied value of the mass function, f(M) = 6.00 +/- 0.36 solar masses, provides a hard lower limit on the mass of the compact primary that greatly exceeds the maximum allowed mass of a neutron star. Thus we conclude that the compact primary is a black hole. Among the eleven dynamically established black-hole X-ray novae, the large mass function of XTE J1118+480 is rivaled only by that of V404 Cyg. We estimate that the secondary supplies 34% +/- 8% of the total light at 5900A and that its spectral type is in the range K5V to M1V. A double-humped I-band light curve is probably due to ellipsoidal modulation, although this interpretation is not entirely secure because of an unusual 12-minute offset between the spectroscopic and photometric ephemerides. Assuming that the light curve is ellipsoidal, we present a provisional analysis which indicates that the inclination of the system is high and the mass of the black hole is correspondingly modest. The broad Balmer emission lines (FWHM = 2300-2900 km/s) also suggest a high inclination. For the range of spectral types given above, we estimate a distance of 1.8 +/- 0.6 kpc.Comment: 4 pages, 2 figures, to appear in ApJ Letters; Minor changes to Fig 1

Stringent constraint on the scalar-neutrino coupling constant from quintessential cosmology

An extremely light ($m_{\phi} \ll 10^{-33} {\rm eV}$), slowly-varying scalar field $\phi$ (quintessence) with a potential energy density as large as 60% of the critical density has been proposed as the origin of the accelerated expansion of the Universe at present. The interaction of this smoothly distributed component with another predominately smooth component, the cosmic neutrino background, is studied. The slow-roll approximation for generic $\phi$ potentials may then be used to obtain a limit on the scalar-neutrino coupling constant, found to be many orders of magnitude more stringent than the limits set by observations of neutrinos from SN 1987A. In addition, if quintessential theory allows for a violation of the equivalence principle in the sector of neutrinos, the current solar neutrino data can probe such a violation at the 10^{-10} level.Comment: 7 pages, MPLA in press, some parts disregarded and a footnote adde

Towards quantum gravity measurement by cold atoms

Peer reviewedPreprin

Gravitational wave bursts from cusps and kinks on cosmic strings

The strong beams of high-frequency gravitational waves (GW) emitted by cusps and kinks of cosmic strings are studied in detail. As a consequence of these beams, the stochastic ensemble of GW's generated by a cosmological network of oscillating loops is strongly non Gaussian, and includes occasional sharp bursts that stand above the ``confusion'' GW noise made of many smaller overlapping bursts. Even if only 10% of all string loops have cusps these bursts might be detectable by the planned GW detectors LIGO/VIRGO and LISA for string tensions as small as $G \mu \sim 10^{-13}$. In the implausible case where the average cusp number per loop oscillation is extremely small, the smaller bursts emitted by the ubiquitous kinks will be detectable by LISA for string tensions as small as $G \mu \sim 10^{-12}$. We show that the strongly non Gaussian nature of the stochastic GW's generated by strings modifies the usual derivation of constraints on $G \mu$ from pulsar timing experiments. In particular the usually considered ``rms GW background'' is, when G \mu \gaq 10^{-7}, an overestimate of the more relevant confusion GW noise because it includes rare, intense bursts. The consideration of the confusion GW noise suggests that a Grand Unified Theory (GUT) value $G \mu \sim 10^{-6}$ is compatible with existing pulsar data, and that a modest improvement in pulsar timing accuracy could detect the confusion noise coming from a network of cuspy string loops down to $G \mu \sim 10^{-11}$. The GW bursts discussed here might be accompanied by Gamma Ray Bursts.Comment: 24 pages, 3 figures, Revtex, submitted to Phys. Rev.

Developing a Model to Simulate the Effect of Hypothermia on Cerebral Blood Flow and Metabolism

Hypoxic ischemic encephalopathy (HIE) is a significant cause of death and neurological disability in newborns. Therapeutic hypothermia at 33.5 °C is one of the most common treatments in HIE and generally improves outcome; however 45-55% of injuries still result in death or severe neurodevelopmental disability. We have developed a systems biology model of cerebral oxygen transport and metabolism to model the impact of hypothermia on the piglet brain (the neonatal preclinical animal model) tissue physiology. This computational model is an extension of the BrainSignals model of the adult brain. The model predicts that during hypothermia there is a 5.1% decrease in cerebral metabolism, 1.1% decrease in blood flow and 2.3% increase in cerebral tissue oxygenation saturation. The model can be used to simulate effects of hypothermia on the brain and to help interpret bedside recordings

BrainSignals Revisited: Simplifying a Computational Model of Cerebral Physiology

Multimodal monitoring of brain state is important both for the investigation of healthy cerebral physiology and to inform clinical decision making in conditions of injury and disease. Near-infrared spectroscopy is an instrument modality that allows non-invasive measurement of several physiological variables of clinical interest, notably haemoglobin oxygenation and the redox state of the metabolic enzyme cytochrome c oxidase. Interpreting such measurements requires the integration of multiple signals from different sources to try to understand the physiological states giving rise to them. We have previously published several computational models to assist with such interpretation. Like many models in the realm of Systems Biology, these are complex and dependent on many parameters that can be difficult or impossible to measure precisely. Taking one such model, BrainSignals, as a starting point, we have developed several variant models in which specific regions of complexity are substituted with much simpler linear approximations. We demonstrate that model behaviour can be maintained whilst achieving a significant reduction in complexity, provided that the linearity assumptions hold. The simplified models have been tested for applicability with simulated data and experimental data from healthy adults undergoing a hypercapnia challenge, but relevance to different physiological and pathophysiological conditions will require specific testing. In conditions where the simplified models are applicable, their greater efficiency has potential to allow their use at the bedside to help interpret clinical data in near real-time

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, postmortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multipurpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A twoparameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head xacceleration peak response correlated with the human response at 8 and 10G 100 ms but not 10G 70 ms. The phase lagged the human response. Head zacceleration was not correlated. Chest xacceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head xdisplacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder xdisplacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head xacceleration was not well correlated. Head and chest zacceleration was in phase but had a higher peak response. Chest zacceleration was highly correlated with heavier subjects at lower G pulses (Cora = 0.86 for 125 kg at 8 G). The human response was variable in shoulder zdisplacement but the THOR was in phase and was comparable to the mean peak response. Head xand zdisplacement was in phase but had higher peaks. Seat pan forces were well correlated, were in phase, but had a larger peak response than most subjects. The THOR does not respond to frontal and spinal impacts exactly the same way that a human does. Some responses are well matched and others are not. Understanding the strengths and weaknesses of this ATD is an important first step in determining its usefulness in occupant protection at NAS