Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Very Cold Gas and Dark Matter

We have recently proposed a new candidate for baryonic dark matter: very cold molecular gas, in near-isothermal equilibrium with the cosmic background radiation at 2.73 K. The cold gas, of quasi-primordial abundances, is condensed in a fractal structure, resembling the hierarchical structure of the detected interstellar medium. We present some perspectives of detecting this very cold gas, either directly or indirectly. The H$_2$ molecule has an "ultrafine" structure, due to the interaction between the rotation-induced magnetic moment and the nuclear spins. But the lines fall in the km domain, and are very weak. The best opportunity might be the UV absorption of H$_2$ in front of quasars. The unexpected cold dust component, revealed by the COBE/FIRAS submillimetric results, could also be due to this very cold H$_2$ gas, through collision-induced radiation, or solid H$_2$ grains or snowflakes. The $\gamma$-ray distribution, much more radially extended than the supernovae at the origin of cosmic rays acceleration, also points towards and extended gas distribution.Comment: 16 pages, Latex pages, crckapb macro, 3 postscript figures, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Therapeutic suggestion helps to cut back on drug intake for mechanically ventilated patients in intensive care unit

Research was conducted on ventilated patients treated in an intensive care unit (ICU) under identical circumstances; patients were divided into two groups (subsequently proved statistically identical as to age and Simplified Acute Physiology Score II [SAPS II]). One group was treated with positive suggestions for 15-20 min a day based on a predetermined scheme, but tailored to the individual patient, while the control group received no auxiliary psychological treatment. Our goal was to test the effects of positive communication in this special clinical situation. In this section of the research, the subsequent data collection was aimed to reveal whether any change in drug need could be demonstrated upon the influence of suggestions as compared to the control group. Owing to the strict recruitment criteria, a relatively small sample (suggestion group n = 15, control group n = 10) was available during the approximately nine-month period of research. As an outcome of suggestions, there was a significant drop in benzodiazepine (p < 0.005), opioid (p < 0.001), and the α2-agonist (p < 0.05) intake. All this justifies the presence of therapeutic suggestions among the therapies used in ICUs. However, repeating the trial on a larger sample of patients would be recommended. © 2013 Akadémiai Kiadó, Budapest

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3&gt;2.1×10-12¿¿s/eV at 90% C.L

Outcomes of synchronous and metachronous bilateral small renal masses (&lt; 4 cm):a population‑based cohort study

Objectives: To report longitudinal outcomes of a population based cohort of patients diagnosed with bilateral small renal masses from a period of over 11 years.Patients and Methods: Consecutive patients diagnosed with bilateral small renal masses (synchronous or metachronous) of a defined geographical area were recorded in a large database (TUCAN database) between January 2005 and December 2016. Patients had a unique identifier number and followed during this period using an agreed upon protocol. Clinicopathological characteristics and outcomes of bilateral small renal masses on active surveillance were analysed and compared to propensity score matched sporadic unilateral small renal masses. Data were analysed for renal mass growth rate, rate of intervention and development of metastatic disease and patient survival.Results: A total of 1060 patients were diagnosed with renal cancer, of which bilateral small renal masses accounted for 70 (6.6%) cases. Synchronous SRMs were observed in 63 patients, whereas metachronous lesions were found in seven patients during the study period. Metachronous lesion mean time to appearance was 62 ± 41 months (range, 9 to 149 months). While most cases were sporadic, four were found to be hereditary. Growth rate of bilateral small renal masses did not differ from that of unilateral sporadic small renal masses. Similarly, there were no differences between the groups for rate of interventions and survival.Conclusion: Progression, rate of metastases and survival for patients diagnosed with bilateral small renal masses is similar to those diagnosed with unilateral disease

Deep-level defects in n-type GaAsBi alloys grown by molecular beam epitaxy at low temperature and their influence on optical properties

Deep-level defects in n-type GaAs1-x Bi x having 0 ≤ x ≤ 0.023 grown on GaAs by molecular beam epitaxy at substrate temperature of 378 °C have been injvestigated by deep level transient spectroscopy. The optical properties of the layers have been studied by contactless electroreflectance and photoluminescence. We find that incorporating Bi suppresses the formation of GaAs-like electron traps, thus reducing the total trap concentration in dilute GaAsBi layers by over two orders of magnitude compared to GaAs grown under the same conditions. In order to distinguish between Bi- and host-related traps and to identify their possible origin, we used the GaAsBi band gap diagram to correlate their activation energies in samples with different Bi contents. This approach was recently successfully applied for the identification of electron traps in n-type GaAs1-x N x and assumes that the activation energy of electron traps decreases with the Bi (or N)-related downward shift of the conduction band. On the basis of this diagram and under the support of recent theoretical calculations, at least two Bi-related traps were revealed and associated with Bi pair defects, i.e. (VGa+BiGa)(-/2-) and (AsGa+BiGa)(0/1-). In the present work it is shown that these defects also influence the photoluminescence properties of GaAsBi alloys

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Late Cenozoic deepening of Yosemite Valley, USA

Although Yosemite Valley, USA, catalyzed the modern environmental movement and fueled foundational debates in geomorphology, a century of investigation has failed to definitively determine when it formed. The non-depositional nature of the landscape and homogeneous bedrock have prevented direct geological assessments. Indirect assumptions about the age of downcutting have ranged from pre-Eocene to Pleistocene. Clarity on this issue would not only satisfy public interest but also provide a new constraint for contentious debates about the Cenozoic tectonic and geomorphologic history of the Sierra Nevada in California. Here we use thermochronometric analysis of radiogenic helium in apatite crystals, coupled with numerical models of crustal temperatures beneath evolving topography, to demonstrate significant late Cenozoic deepening of Tenaya Canyon, Yosemite’s northeastern branch. Approximately 40%–90% of the current relief has developed since 10 Ma and most likely since 5 Ma. This coincides with renewed regional tectonism, which is a long-hypothesized but much debated driver of Sierran canyon development. Pleistocene glaciation caused spatially variable incision and valley widening in Yosemite Valley, whereas little contemporaneous erosion occurred in the adjacent upper Tuolumne watershed. Such variations probably arise from glacial erosion’s dependence on topographic focusing of ice discharge into zones of rapid flow, and on the abundance of pre-existing fractures in the substrate. All available data, including those from our study, are consistent with a moderately high and slowly eroding mid-Cenozoic Sierra Nevada followed by significant late Cenozoic incision of some, but not all, west-side canyon