Protein-mediated DNA Loop Formation and Breakdown in a Fluctuating Environment

Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, which is a common means of regulating transcription, is very much a stochastic process; the loops arise from the thermal motion of the DNA and other fluctuations of the cellular environment. We present single-molecule measurements of DNA loop formation and breakdown when an artificial fluctuating force, applied to mimic a fluctuating cellular environment, is imposed on the DNA. We show that loop formation is greatly enhanced in the presence of noise of only a fraction of $k_B T$, yet find that hypothetical regulatory schemes that employ mechanical tension in the DNA--as a sensitive switch to control transcription--can be surprisingly robust due to a fortuitous cancellation of noise effects

Sensitivity to the KARMEN Timing Anomaly at MiniBooNE

We present sensitivities for the MiniBooNE experiment to a rare exotic pion decay producing a massive particle, Q^0. This type of decay represents one possible explanation for the timing anomaly reported by the KARMEN collaboration. MiniBooNE will be able to explore an area of the KARMEN signal that has not yet been investigated

Description of non-specific DNA-protein interaction and facilitated diffusion with a dynamical model

We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the model successfully reproduces some of the observed properties of real systems and predictions of kinetic models. For example, sampling of the DNA sequence by the protein proceeds via a succession of 3d motion in the solvent, 1d sliding along the sequence, short hops between neighboring sites, and intersegmental transfers. Moreover, facilitated diffusion takes place in a certain range of values of the protein effective charge, that is, the combination of 1d sliding and 3d motion leads to faster DNA sampling than pure 3d motion. At last, the number of base pairs visited during a sliding event is comparable to the values deduced from single-molecule experiments. We also point out and discuss some discrepancies between the predictions of this model and some recent experimental results as well as some hypotheses and predictions of kinetic models

Regional Mapping and Spectral Analysis of Mounds in Acidalia Planitia, Mars

Acidalia Planitia is a approx.3000 km diameter planum located in the northern plains of Mars. It is believed to be a sedimentary basin containing an accumulation of sediments brought by Hesperian outflow channels that drained the Highlands. A large number of high-albedo mounds have been identified across this basin [1-2] and understanding the process that formed them should help us understand the history of this region. Farrand et al. [2] showed that the mounds are dark in THEMIS (Thermal Emission Imaging System) nighttime IR (infrared) image data. This implies that the mounds have a lower thermal inertia than the surrounding plains (Fig. 1), suggesting that the material of the mounds is fine-grained or unconsolidated. Farrand et al. [2] also reviewed potential analogs for the mounds and concluded that a combination of mud volcanoes with evaporites around geysers or springs is most consistent with all the data. We have built on this work by creating regional maps of the features and analyzing CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) data to see if there are mineralogical differences between the mounds and surrounding plains

'Nano' Morphology and Element Signatures of Early Life on Earth: A New Tool for Assessing Biogenicity

The relatively young technology of NanoSIMS is unlocking an exciting new level of information from organic matter in ancient sediments. We are using this technique to characterize Proterozoic organic material that is clearly biogenic as a guide for interpreting controversial organic structures in either terrestrial or extraterrestrial samples. NanoSIMS is secondary ion mass spectrometry for trace element and isotope analysis at sub-micron resolution. In 2005, Robert et al. [1] combined NanoSIMS element maps with optical microscopic imagery in an effort to develop a new method for assessing biogenicity of Precambrian structures. The ability of NanoSIMS to map simultaneously the distribution of organic elements with a 50 nm spatial resolution provides new biologic markers that could help define the timing of life s development on Earth. The current study corroborates the work of Robert et al. and builds on their study by using NanoSIMS to map C, N (as CN), S, Si and O of both excellently preserved microfossils and less well preserved, non-descript organics in Proterozoic chert from the ca. 0.8 Ga Bitter Springs Formation of Australia

Self-referencable frequency comb from a 170-fs, 1.5-μm solid-state laser oscillator

We report measurement of the first carrier-envelope offset (CEO) frequency signal from a spectrally broadened ultrafast solid-state laser oscillator operating in the 1.5μm spectral region. The f-to-2f CEO frequency beat signal is 49 dB above the noise floor (100-kHz resolution bandwidth) and the free-running linewidth of 3.6 kHz is significantly better than typically obtained by ultrafast fiber laser systems. We used a SESAM mode-locked Er:Yb:glass laser generating 170-fs pulses at a 75MHz pulse repetition rate with 110-mW average power. It is pumped by one standard telecom-grade 980-nm diode consuming less than 1.5W of electrical power. Without any further pulse compression and amplification, a coherent octave-spanning frequency comb is generated in a polarization-maintaining highly-nonlinear fiber (PM-HNLF). The fiber length was optimized to yield a strong CEO frequency beat signal between the outer Raman soliton and the spectral peak of the dispersive wave within the supercontinuum. The polarization-maintaining property of the supercontinuum fiber was crucial; comparable octave-spanning supercontinua from two non-PM fibers showed higher intensity noise and poor coherence. Astable CEO-beat was observed even with pulse durations above 200fs. Achieving a strong CEO frequency signal from relatively long pulses with moderate power levels substantially relaxes the demands on the driving laser, which is particularly important for novel gigahertz diode-pumped solid-state and semiconductor laser

Principles for developing benchmark criteria for staff training in responsible gambling

One approach to minimizing the negative consequences of excessive gambling is staff training to reduce the rate of the development of new cases of harm or disorder within their customers. The primary goal of the present study was to assess suitable benchmark criteria for the training of gambling employees at casinos and lottery retailers. The study utilised the Delphi Method, a survey with one qualitative and two quantitative phases. A total of 21 invited international experts in the responsible gambling field participated in all three phases. A total of 75 performance indicators were outlined and assigned to six categories: (1) criteria of content, (2) modelling, (3) qualification of trainer, (4) framework conditions, (5) sustainability and (6) statistical indicators. Nine of the 75 indicators were rated as very important by 90 % or more of the experts. Unanimous support for importance was given to indicators such as (1) comprehensibility and (2) concrete action-guidance for handling with problem gamblers, Additionally, the study examined the implementation of benchmarking, when it should be conducted, and who should be responsible. Results indicated that benchmarking should be conducted every 1–2 years regularly and that one institution should be clearly defined and primarily responsible for benchmarking. The results of the present study provide the basis for developing a benchmarking for staff training in responsible gambling

Picosecond diode-pumped 1.5 μm Er,Yb:glass lasers operating at10-100 GHz repetition rate

Stable ultrafast laser sources at multi-GHz repetition rates are important for various application areas, such as optical sampling, frequency comb metrology, or advanced high-speed return-to-zero telecom systems. We review SESAM-mode-locked Er,Yb:glass lasers operating in the 1.5μm spectral region at multi-GHz repetition rates, discussing the key improvements that have enabled increasing the repetition rate up to 100GHz. We also present further improved results with shorter pulse durations from a 100GHz Er,Yb:glass laser. With an improved SESAM design we achieved 1.1ps pulses with up to 30mW average output power. Moreover, we discuss for the first time the importance of beam quality deteriorations arising from frequency-degenerate higher order spatial modes in such laser

The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin - SCL/TAL1-CD44 axis.

The endosteal bone marrow niche and vascular endothelial cells provide sanctuaries for leukemic cells. In murine chronic myeloid leukemia (CML) CD44 on leukemia cells and E-selectin on bone marrow endothelium are essential mediators for the engraftment of leukemic stem cells. We hypothesized that non-adhesion of CML-initiating cells to E-selectin on the bone marrow endothelium may lead to superior eradication of leukemic stem cells in CML after treatment with imatinib than imatinib alone. Indeed, here we show that treatment with the E-selectin inhibitor GMI-1271 in combination with imatinib prolongs survival of mice with CML via decreased contact time of leukemia cells with bone marrow endothelium. Non-adhesion of BCR-ABL1(+) cells leads to an increase of cell cycle progression and an increase of expression of the hematopoietic transcription factor and proto-oncogene Scl/Tal1 in leukemia-initiating cells. We implicate SCL/TAL1 as an indirect phosphorylation target of BCR-ABL1 and as a negative transcriptional regulator of CD44 expression. We show that increased SCL/TAL1 expression is associated with improved outcome in human CML. These data demonstrate the BCR-ABL1-specific, cell-intrinsic pathways leading to altered interactions with the vascular niche via the modulation of adhesion molecules - which could be exploited therapeutically in the future

Virtual Electrode Design for Lithium-Ion Battery Cathodes

Microstructural characteristics of lithium‐ion battery cathodes determine their performance. Thus, modern simulation tools are increasingly important for the custom design of multiphase cathodes. This work presents a new method for generating virtual, yet realistic cathode microstructures. A precondition is a 3D template of a commercial cathode, reconstructed via focused ion beam/scanning electron microscopy (FIB/SEM) tomography and appropriate algorithms. The characteristically shaped micrometer‐sized active material (AM) particles and agglomerates of nano‐sized carbon‐binder (CB) particles are individually extracted from the voxel‐based templates. Thereby, a library of roughly 1100 AM particles and 20 CB agglomerates is created. Next, a virtual cathode microstructure is predefined, and representative sets of AM particles and CB agglomerates are built. The following re‐assembly of AM particles within a predefined volume box works using dropping and rolling algorithms. Thereby, one can generate cathodes with specified characteristics, such as the volume fraction of AM, CB and pore space, particle‐size distributions, and gradients thereof. Naturally, such a virtual twin is a promising starting point for physics‐based electrochemical performance models. The workflow from the commercial cathode microstructure through to a full virtual twin will be explained and assessed for a blend cathode made of the two AMs, LiNiCoAlO$_{2}$ (NCA) and LiCoO$_{2}$ (LCO)