Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells

Nonproteinogenic amino acids that either occur naturally or are synthesized chemically are becoming important tools in modern drug discovery. In this context, fluorinated amino acids have great potential in the development of novel pharmaceuticals and drugs. To assess whether different fluorinated aromatic amino acid analogues of phenylalanine, tyrosine, and tryptophan are potentially interesting as therapeutic drugs, we examined their cytostatic and cytotoxic effects on the growth of the human breast cancer cell line MCF-7. Of all the tested analogues L-4-fluorotryptophan, L-6-fluorotryptophan and L-p-fluorophenylalanine effectively and irreversibly inhibited cell growth with IC(50) values in the low micromolar range (3-15 microM). Additionally, using L-4-[14C]fluorotryptophan, and L-6-[14C]fluorotryptophan, we discovered that the cellular uptake of these fluorinated amino acids occurs through active transport with a 70-fold excess of intracellular over extracellular concentrations. We identified system L as the responsible amino acid transporter. Our findings fully support the idea that fluorinated aromatic amino acid analogues are promising chemotherapeutics with the potential for use in combination with classical cancer therapy, and as new cytotoxic drugs for certain tumor types such as melanoma.     

Decrease in tensile strength and in mass of burning wood

Changes in ultimate tensile strength and mass (weight) of burning redwood were measured, and a correlation between the ultimate tensile strength and mass loss was developed. A simple model was employed for calculating the mass loss. The accuracy of this model was assessed by comparing calculated mass loss values to the data.     

Automatic model-based segmentation of the heart in CT images

Automatic image processing methods are a prerequisite to efficiently analyze the large amount of image data produced by computed tomography (CT) scanners during cardiac exams. This paper introduces a model-based approach for the fully automatic segmentation of the whole heart (four chambers, myocardium, and great vessels) from 3-D CT images. Model adaptation is done by progressively increasing the degrees-of-freedom of the allowed deformations. This improves convergence as well as segmentation accuracy. The heart is first localized in the image using a 3-D implementation of the generalized Hough transform. Pose misalignment is corrected by matching the model to the image making use of a global similarity transformation. The complex initialization of the multicompartment mesh is then addressed by assigning an affine transformation to each anatomical region of the model. Finally, a deformable adaptation is performed to accurately match the boundaries of the patient's anatomy. A mean surface-to-surface error of 0.82 mm was measured in a leave-one-out quantitative validation carried out on 28 images. Moreover, the piecewise affine transformation introduced for mesh initialization and adaptation shows better interphase and interpatient shape variability characterization than commonly used principal component analysis.      

Impact of bioavailability restrictions on microbially induced stable isotope fractionation. 1. Theoretical calculation

The microbial degradation of organic substrates often exhibits a fractionation of stable isotopes which leads to an enrichment of the heavier isotope in the remaining substrate. The use of this effect to quantify the amount of biodegraded substrate in contaminated aquifers requires that the isotope fractionation factor is constant in time and space. In many natural and engineered systems the bioavailable concentration at the location of the enzymes differs from the average bulk concentration of the substrate. When enzymatically driven substrate degradation is coupled to a preceding transport step controlling the bioavailability of the substrate, the observed isotope fractionation becomes a function of the bulk substrate concentration. The sensitivity of the observed isotope fractionation factor toward such substrate concentration changes depends on the ratio of bulk substrate concentration and Michaelis-Menten constant and on the ratio between the specific affinity of the microorganisms toward the substrate and the first order rate constant of the bioavailability limiting transport process. Highest sensitivities toward substrate concentration were found for combinations of high substrate concentration with low substrate bioavailability (i.e., high ratios of substrate concentration and Michaelis-Menten constant, and high ratios of specific affinity and transport rate constant). As a consequence, changes in concentration and isotopic composition of a bioavailability limited substrate in batch experiments should not exhibit a linear relation in a Rayleigh plot, and the slope of the Rayleigh plot should show a decreasing trend with concentration decrease. When using isotope fractionation to quantify biodegradation along groundwater flow paths, changes in observed isotope fractionation might occur while contaminant concentration decreases along a flow path.     

Fourier Transform Infrared Microspectroscopy Combined with Principal Component Analysis and Artificial Neural Networks for the Study of the Effect of β-Hydroxy-β-Methylbutyrate (HMB) Supplementation on Articular Cartilage

The potential of Fourier Transform infrared microspectroscopy (FTIR microspectroscopy) and multivariate analyses were applied for the classification of the frequency ranges responsible for the distribution changes of the main components of articular cartilage (AC) that occur during dietary β-hydroxy-β-methyl butyrate (HMB) supplementation. The FTIR imaging analysis of histological AC sections originating from 35-day old male piglets showed the change in the collagen and proteoglycan contents of the HMB-supplemented group compared to the control. The relative amount of collagen content in the superficial zone increased by more than 23% and in the middle zone by about 17%, while no changes in the deep zone were observed compared to the control group. Considering proteoglycans content, a significant increase was registered in the middle and deep zones, respectively; 62% and 52% compared to the control. AFM nanoindentation measurements collected from animals administered with HMB displayed an increase in AC tissue stiffness by detecting a higher value of Young’s modulus in all investigated AC zones. We demonstrated that principal component analysis and artificial neural networks could be trained with spectral information to distinguish AC histological sections and the group under study accurately. This work may support the use and effectiveness of FTIR imaging combined with multivariate analyses as a quantitative alternative to traditional collagenous tissue-related histology.     

An enzyme-based extraction process for the purification and enrichment of vegetable proteins to be applied in bakery products

In the current study an efficient aqueous extraction procedure using glucoamylase was developed to produce food grade protein extracts from lentils and white beans. The extracts contained 50.3 ± 0.6 and 49.2 ± 0.05 g protein per 100 g dry extract, respectively. The nutritional value of lentil and white bean protein extracts proved to be satisfying according to the amino acid composition, where methionine was the limiting amino acid. The produced extracts were tested for their technological properties. Both lentil and white bean protein extracts showed similar or even better technological properties regarding foaming and emulsifying capacities, heat stability and gelling properties compared to soy and pea protein extracts. Food application tests in white bread, pound cake and sponge cake proved lentil and white bean protein extracts to be potential alternatives to soy protein in replacing proteins from animal origin.     

Combinatorial Alloy Design by Laser Additive Manufacturing

The authors uses laser additive manufacturing (LAM) as a combinatorial method for synthesizing microstructurally and compositionally piecewise graded bulk alloys. Authors fabricate blocks consisting of a sequence of ≈500 μm thick tool steel layers, each with different chemical composition, by laser metal deposition where alloy powders are deposited layer‐wise on a substrate. The reference materials are a Cr–Mo–V hot working tool steel and a Ni‐based maraging steel. The layers between them consist of corresponding blends of the two materials with varying composition from layer to layer (alloy volume fractions 80:20, 60:40, 40:60, and 20:80). The bulk alloy is hot rolled and heat treated. Subsequently each layer is characterized for microstructure, chemical composition and mechanical properties using electron back scatter diffraction, tensile testing, and indentation. The approach is an efficient high‐throughput method enabling rapid probing of novel compositional alloy blends. It can be applied for finding new alloys both, by LAM and for LAM. For the tool steel blends synthesized here, authors observe that the Cr–Mo–V tool steel, when mixed with the Ni‐base maraging steel, can be continuously tuned for a strength‐ductility profile in the range of 800–1650 MPa strength and 15–25% tensile elongation.     

Traglastberechnung unterspannter Träger

Ultimate limit loads of externally reinforced beams. For practical purpose the 3‐dimensional stability problem of an externally reinforced beam is often reduced to a plane model. This paper however is based on a geometrically nonlinear analysis by second order theory using the 3‐dimensional model. The results of both methods are compared. Furthermore the sensibility of those systems to a variation of the essential influences on the ultimate limit loads are studied based on exemplary parameter variation.