7,707 research outputs found

    Biodiversity's big wet secret: the global distribution of marine biological records reveals chronic under-exploration of the deep pelagic ocean

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    Background: Understanding the distribution of marine biodiversity is a crucial first step towards the effective and sustainable management of marine ecosystems. Recent efforts to collate location records from marine surveys enable us to assemble a global picture of recorded marine biodiversity. They also effectively highlight gaps in our knowledge of particular marine regions. In particular, the deep pelagic ocean - the largest biome on Earth - is chronically under-represented in global databases of marine biodiversity. Methodology/Principal Findings: We use data from the Ocean Biogeographic Information System to plot the position in the water column of ca 7 million records of marine species occurrences. Records from relatively shallow waters dominate this global picture of recorded marine biodiversity. In addition, standardising the number of records from regions of the ocean differing in depth reveals that regardless of ocean depth, most records come either from surface waters or the sea bed. Midwater biodiversity is drastically under-represented. Conclusions/Significance: The deep pelagic ocean is the largest habitat by volume on Earth, yet it remains biodiversity's big wet secret, as it is hugely under-represented in global databases of marine biological records. Given both its value in the provision of a range of ecosystem services, and its vulnerability to threats including overfishing and climate change, there is a pressing need to increase our knowledge of Earth's largest ecosystem

    Coherent control of nanomagnet dynamics via ultrafast spin torque pulses

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    The magnetization orientation of a nanoscale ferromagnet can be manipulated using an electric current via the spin transfer effect. Time domain measurements of nanopillar devices at low temperatures have directly shown that magnetization dynamics and reversal occur coherently over a timescale of nanoseconds. By adjusting the shape of a spin torque waveform over a timescale comparable to the free precession period (100-400 ps), control of the magnetization dynamics in nanopillar devices should be possible. Here we report coherent control of the free layer magnetization in nanopillar devices using a pair of current pulses as narrow as 30 ps with adjustable amplitudes and delay. We show that the switching probability can be tuned over a broad range by timing the current pulses with the underlying free-precession orbits, and that the magnetization evolution remains coherent for more than 1 ns even at room temperature. Furthermore, we can selectively induce transitions along free-precession orbits and thereby manipulate the free magnetic moment motion. We expect this technique will be adopted for further elucidating the dynamics and dissipation processes in nanomagnets, and will provide an alternative for spin torque driven spintronic devices, such as resonantly pumping microwave oscillators, and ultimately, for efficient reversal of memory bits in magnetic random access memory (MRAM).Comment: 4 pages, 3 figures, submitted to Nature Physic

    ALDH2*2 and peer drinking in East Asian college students

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    Background: The ALDH2*2 allele (A-allele) at rs671 is more commonly carried by Asians and is associated with alcohol-related flushing, a strong adverse reaction to alcohol that is protective against drinking. Social factors, such as having friends who binge drink, also contribute to drinking in Asian youth. Objectives: This study examined the interplay between ALDH2*2, peer drinking, and alcohol consumption in college students. We hypothesized that the relationship between ALDH2*2 and standard grams of ethanol per month would vary based on the level of peer drinking. Methods: Subjects (N = 318, 63.25% female) were East Asian college students in the United States who reported drinking alcohol. Data were from the freshman year of a university survey that included a saliva DNA sample. ALDH2*2 status was coded ALDH2*2(+) (A/G and A/A genotypes) and ALDH2*2(āˆ’) (G/G genotype). Peer drinking was studentsā€™ perception of how many of their friends ā€œgot drunkā€. Results: Main effects of ALDH2*2(āˆ’) and having more friends who got drunk were associated with greater alcohol consumption. The ALDH2*2 Ɨ peer drunkenness interaction showed a stronger positive association with alcohol consumption for ALDH2*2(āˆ’) versus ALDH2*2(+) at increasing levels of peer drunkenness. Follow-up comparisons within each peer drunkenness level identified significantly higher alcohol consumption for ALDH2*2(āˆ’) compared to ALDH2*2(+) at the all friends got drunk level. Conclusion: There was evidence of a stronger effect for ALDH2*2(āˆ’) compared to ALDH2*2(+) with greater alcohol use when students were more exposed to peer drinking. Findings contribute to a growing literature on the interrelationships between genetic influences and more permissive environments for alcohol consumption

    The tumour suppressor protein LIMD1 is a novel regulator of HIF1 and the hypoxic response

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    There are three prolyl hydroxylases (PHD1, 2 and 3) that regulate the hypoxia-inducible factors (HIFs), the master transcriptional regulators that respond to changes in intracellular O2 tension. In high O2 tension (normoxia) the PHDs hydroxylate HIFĪ± subunits on 2 conserved proline residues inducing binding of the von-Hippel-Lindau (VHL) tumour suppressor, the recognition component of a multi-protein ubiquitin-ligase complex, initiating HIFĪ± ubiquitylation and degradation by the 26S proteasome. However, it is not known whether PHDs and VHL act separately to exert their enzymatic activities on HIFĪ± or as a multi-protein complex. In this thesis, data are presented that shows that the tumour suppressor protein LIMD1 acts as a molecular scaffold simultaneously binding the PHDs and pVHL into a normoxic protein complex (normoxiplex), increasing their physical proximity in order to enable efficient and rapid sequential modifications and thus degradation of HIF1Ī±. Data are presented which indicates that increased LIMD1 expression down regulates HIF transcriptional activity, by promoting HIF1Ī± degradation via the oxygen dependent degradation domain in a manner dependent on hydroxylase and 26S proteasome activities. However, degradation of this domain is not wholly dependent on the well characterised proline residues subject to hydroxylation, suggesting that LIMD1 may alter proline hydroxylation specificity or modulate HIF via a different mechanism. Furthermore, endogenous depletion of LIMD1 results in the converse, leading to HIF1Ī± stabilisation and accumulation, enhancing HIF transcriptional activity. Moreover, Limd1-/- MEFs show increased HIF transcriptional activity. One mechanism by which this is achieved involves the binding of PHD2 within the N-terminal portion of LIMD1 while allowing concurrent binding of VHL to the C-terminal zinc-finger LIM domains. However, the LIMD1 mediated mechanism regulating HIF1Ī± independently of proline residues 402 and 564 is still unclear. Finally, data are presented that show that the LIMD1 family member proteins Ajuba and WTIP all bind specifically to VHL but differentially to PHDs 1, 2 and 3 and thus these three LIM domain containing proteins represent a new group of hypoxic regulators

    Enhancing Cation Diffusion and Suppressing Anion Diffusion via Lewis-Acidic Polymer Electrolytes

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    Solid polymer electrolytes (SPEs) have the potential to increase both the energy density and stability of lithium-based batteries, but low Li^+ conductivity remains a barrier to technological viability. SPEs are designed to maximize Li^+ diffusivity relative to the anion while maintaining sufficient salt solubility. It is thus remarkable that poly(ethylene oxide) (PEO), the most widely used SPE, exhibits Li^+ diffusivity that is an order of magnitude smaller than that of typical counterions at moderate salt concentrations. We show that Lewis-basic polymers like PEO favor slow cation and rapid anion diffusion, while this relationship can be reversed in Lewis-acidic polymers. Using molecular dynamics, polyboranes are identified that achieve up to 10-fold increases in Li^+ diffusivities and significant decreases in anion diffusivities, relative to PEO in the dilute-ion regime. These results illustrate a general principle for increasing Li^+ diffusivity and transference number with chemistries that exhibit weaker cation and stronger anion coordination

    A Dynamic Programming Approach to Adaptive Fractionation

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    We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

    Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: a nested case-control study

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    HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (pā€‰<ā€‰0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting

    Big bang nucleosynthesis as a probe of fundamental "constants"

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    Big Bang nucleosynthesis (BBN) is the earliest sensitive probe of the values of many fundamental particle physics parameters. We have found the leading linear dependences of primordial abundances on all relevant parameters of the standard BBN code, including binding energies and nuclear reaction rates. This enables us to set limits on possible variations of fundamental parameters. We find that 7Li is expected to be significantly more sensitive than other species to many fundamental parameters, a result which also holds for variations of coupling strengths in grand unified (GUT) models. Our work also indicates which areas of nuclear theory need further development if the values of ``constants'' are to be more accurately probed.Comment: Refereed article to be published in Nuclear Physics in Astrophysics III Proceedings, J. Phys. G. Special Issue. Based on work in collaboration with C. Wetterich (Heidelberg). 6 page

    The tumour suppressor protein LIMD1 is a novel regulator of HIF1 and the hypoxic response

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    There are three prolyl hydroxylases (PHD1, 2 and 3) that regulate the hypoxia-inducible factors (HIFs), the master transcriptional regulators that respond to changes in intracellular O2 tension. In high O2 tension (normoxia) the PHDs hydroxylate HIFĪ± subunits on 2 conserved proline residues inducing binding of the von-Hippel-Lindau (VHL) tumour suppressor, the recognition component of a multi-protein ubiquitin-ligase complex, initiating HIFĪ± ubiquitylation and degradation by the 26S proteasome. However, it is not known whether PHDs and VHL act separately to exert their enzymatic activities on HIFĪ± or as a multi-protein complex. In this thesis, data are presented that shows that the tumour suppressor protein LIMD1 acts as a molecular scaffold simultaneously binding the PHDs and pVHL into a normoxic protein complex (normoxiplex), increasing their physical proximity in order to enable efficient and rapid sequential modifications and thus degradation of HIF1Ī±. Data are presented which indicates that increased LIMD1 expression down regulates HIF transcriptional activity, by promoting HIF1Ī± degradation via the oxygen dependent degradation domain in a manner dependent on hydroxylase and 26S proteasome activities. However, degradation of this domain is not wholly dependent on the well characterised proline residues subject to hydroxylation, suggesting that LIMD1 may alter proline hydroxylation specificity or modulate HIF via a different mechanism. Furthermore, endogenous depletion of LIMD1 results in the converse, leading to HIF1Ī± stabilisation and accumulation, enhancing HIF transcriptional activity. Moreover, Limd1-/- MEFs show increased HIF transcriptional activity. One mechanism by which this is achieved involves the binding of PHD2 within the N-terminal portion of LIMD1 while allowing concurrent binding of VHL to the C-terminal zinc-finger LIM domains. However, the LIMD1 mediated mechanism regulating HIF1Ī± independently of proline residues 402 and 564 is still unclear. Finally, data are presented that show that the LIMD1 family member proteins Ajuba and WTIP all bind specifically to VHL but differentially to PHDs 1, 2 and 3 and thus these three LIM domain containing proteins represent a new group of hypoxic regulators
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