Spatiotemporal Characterization of Supercontinuum Extending from the Visible to the Mid-Infrared in Multimode Graded-Index Optical Fiber

We experimentally demonstrate that pumping a graded-index multimode fiber with sub-ns pulses from a microchip Nd:YAG laser leads to spectrally flat supercontinuum generation with a uniform bell-shaped spatial beam profile extending from the visible to the mid-infrared at 2500\,nm. We study the development of the supercontinuum along the multimode fiber by the cut-back method, which permits us to analyze the competition between the Kerr-induced geometric parametric instability and stimulated Raman scattering. We also performed a spectrally resolved temporal analysis of the supercontinuum emission.Comment: 5 pages 7 figure

The Effect of the Environment on alpha-Al_2O_3 (0001) Surface Structures

We report that calculating the Gibbs free energy of the alpha-Al_2O_3 (0001) surfaces in equilibrium with a realistic environment containing both oxygen and hydrogen species is essential for obtaining theoretical predictions consistent with experimental observations. Using density-functional theory we find that even under conditions of high oxygen partial pressure, the metal terminated surface is surprisingly stable. An oxygen terminated alpha-Al_2O_3 (0001) surface becomes stable only if hydrogen is present on the surface. In addition, including hydrogen on the surface resolves discrepancies between previous theoretical work and experimental results with respect to the magnitude and direction of surface relaxations.Comment: 4 pages including 2 figures. Submitted to Phys. Rev. Lett. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

On-line monitoring and controlling of cell apoptosis in mammalian cell culture processes using dielectric spectroscopy

We investigate a method to control critical quality attributes and apply Process Analytical Technology (PAT) via online dielectric spectroscopy (DS) feedback. This system has been intensively explored and successfully implemented in GMP manufacturing processes at Biogen. The present bioreactor application however, is basic and only allows the prediction of biomass. To further enhance the cell culture process robustness, we investigated the feasibility of using the full-spectrum dielectric spectroscopy scanning function to detect dielectric property changes in the cells associated with shifts in cell health and/or metabolism. In this proof of concept study, we used several CHO cell processes to demonstrate that DS probes can be used to not only measure the biomass but also reflect the cell’s physiological state changes (e.g. cell apoptosis). The results showed that one or more of the key parameters of delta capacitance (De), critical frequency (fc), and Cole-Cole Alpha (a) from the multi-frequency scanning data could reflect the cell’s early apoptosis induced by chemical treatment, nutrient depletion, or shear stress, which were seen earlier than that obtained from off-line methods (e.g. trypan blue exclusion). In some cases, by responding to the earlier detection, the cell apoptosis was reversed in time and the batch was saved. This enables a potential application, transferrable across programs, of full-spectrum dielectric spectroscopy for earlier detection of physiological changes, allowing for timelier bioreactor process adjustments. In addition, the feasibility of the application of multifrequency scanning in cGMP process for monitoring and control was also explored in this study

The blood transfer conductance for nitric oxide: infinite vs. finite θNO

Whether the specific blood transfer conductance for nitric oxide (NO) with hemoglobin (θNO) is finite or infinite is controversial but important in the calculation of alveolar capillary membrane conductance (DmCO) and pulmonary capillary blood volume (VC) from values of lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). In this review, we discuss the background associated with θNO, explore the resulting values of DmCO and VC when applying either assumption, and investigate the mathematical underpinnings of DmCO and VC calculations. In general, both assumptions yield reasonable rest and exercise DmCO and VC values. However, the finite θNO assumption demonstrates increasing VC, but not DmCO, with submaximal exercise. At relatively high, but physiologic, DLNO/DLCO ratios both assumptions can result in asymptotic behavior for VC values, and under the finite θNO assumption, DmCO values. In conclusion, we feel that the assumptions associated with a finite θNO require further in vivo validation against an established method before widespread research and clinical use

Genomic Signature of Shifts in Selection in a Subalpine Ant and Its Physiological Adaptations

Understanding how organisms adapt to extreme environments is fundamental and can provide insightful case studies for both evolutionary biology and climate-change biology. Here, we take advantage of the vast diversity of lifestyles in ants to identify genomic signatures of adaptation to extreme habitats such as high altitude. We hypothesized two parallel patterns would occur in a genome adapting to an extreme habitat: 1) strong positive selection on genes related to adaptation and 2) a relaxation of previous purifying selection. We tested this hypothesis by sequencing the high-elevation specialist Tetramorium alpestre and four other phylogenetically related species. In support of our hypothesis, we recorded a strong shift of selective forces in T. alpestre, in particular a stronger magnitude of diversifying and relaxed selection when compared with all other ants. We further disentangled candidate molecular adaptations in both gene expression and protein-coding sequence that were identified by our genome-wide analyses. In particular, we demonstrate that T. alpestre has 1) a higher level of expression for stv and other heat-shock proteins in chill-shock tests and 2) enzymatic enhancement of Hex-T1, a rate-limiting regulatory enzyme that controls the entry of glucose into the glycolytic pathway. Together, our analyses highlight the adaptive molecular changes that support colonization of high-altitude environments.Research was supported by the Austrian Science Fund (FWF, P23409 and P30861)

A Natural Love of Natural Products

Recent research on the chemistry of natural products from the author’s group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery. My first real exposure to natural products chemistry came in my third and final year as an undergraduate at Cambridge University, when I attended a course of lectures on the chemistry of natural products by the Nobel Prize-winning chemist Sir Alexander Todd (later to become Lord Todd). The lectures included many references to his own work in the field, with stories of his early work on the structure of cholesterol, th

Timeless standards for species delimitation

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Exploration of new multivariate spectral calibration algorithms.

A variety of multivariate calibration algorithms for quantitative spectral analyses were investigated and compared, and new algorithms were developed in the course of this Laboratory Directed Research and Development project. We were able to demonstrate the ability of the hybrid classical least squares/partial least squares (CLSIPLS) calibration algorithms to maintain calibrations in the presence of spectrometer drift and to transfer calibrations between spectrometers from the same or different manufacturers. These methods were found to be as good or better in prediction ability as the commonly used partial least squares (PLS) method. We also present the theory for an entirely new class of algorithms labeled augmented classical least squares (ACLS) methods. New factor selection methods are developed and described for the ACLS algorithms. These factor selection methods are demonstrated using near-infrared spectra collected from a system of dilute aqueous solutions. The ACLS algorithm is also shown to provide improved ease of use and better prediction ability than PLS when transferring calibrations between near-infrared calibrations from the same manufacturer. Finally, simulations incorporating either ideal or realistic errors in the spectra were used to compare the prediction abilities of the new ACLS algorithm with that of PLS. We found that in the presence of realistic errors with non-uniform spectral error variance across spectral channels or with spectral errors correlated between frequency channels, ACLS methods generally out-performed the more commonly used PLS method. These results demonstrate the need for realistic error structure in simulations when the prediction abilities of various algorithms are compared. The combination of equal or superior prediction ability and the ease of use of the ACLS algorithms make the new ACLS methods the preferred algorithms to use for multivariate spectral calibrations