Proteomic expression profiling of thyroid neoplasms

Thyroid cancer is the most common endocrine neoplasm with multiple histologic subtypes, each associated with different treatments and outcomes. Differentiating benign neoplasms such as follicular adenomas from malignant entities such as follicular carcinomas and papillary carcinoma can be challenging. To define the proteomic profile of different thyroid tumors, we screened an antibody array of 330 features against five thyroid neoplasms: follicular adenoma, follicular carcinoma, papillary carcinoma, anaplastic carcinoma, and medullary carcinoma as well as normal thyroid epithelium. Eight candidate biomarkers; c-erbB-2, Stat5a, Annexin IV, IL-11, RARα, FGF7, Caspase 9, and phospho-c-myc were identified as differentially expressed on the antibody array, and validated with immunohistochemistry on tissue microarrays, with a total of 144 samples of the same variety of thyroid neoplasms. Analysis revealed c-erbB-2, Annexin IV, and Stat5a have potential clinical utility to differentiate follicular adenoma, follicular carcinoma, and papillary carcinoma from each other. By using an antibody array as a discovery platform and a tissue microarray as a first step in validation on a large number of specimens, we have identified new markers that have potential utility in the diagnosis of thyroid neoplasms.     

Immobilization of dendrimers on Si-C linked carboxylic acid-terminated monolayers on silicon(111)

Poly(amidoamine) dendrimers were attached to activated undecanoic acid monolayers, covalently linked to smooth silicon surfaces via Si-C bonds. The resulting ultra-thin dendrimer films were characterized by X-ray photoelectron spectroscopy (XPS), X-ray reflectometry (XR) and atomic force microscopy (AFM). XPS results suggested amide bond formation between the dendrimer and the surface carboxylic acid groups. XR yielded thicknesses of 10 Å for the alkyl region of the undecanoic acid monolayer and 12 Å for the dendrimer layer, considerably smaller than the diameter of these spherical macromolecules in solution. This was consistent with AFM images showing collapsed dendrimers on the surface. It was concluded that the deformation arose from a large number of amine groups on the surface of each dendrimer reacting efficiently with the activated surface, whereby the dendrimers can deform to fill voids while spreading over the activated surface to form a homogeneous macromolecular layer.     

Design of an Ultrafast G Protein Switch Based on a Mouse Melanopsin Variant

The primary goal of optogenetics is the light-controlled noninvasive and specific manipulation of various cellular processes. Herein, we present a hybrid strategy for targeted protein engineering combining computational techniques with electrophysiological and UV/visible spectroscopic experiments. We validated our concept for channelrhodopsin-2 and applied it to modify the less-well-studied vertebrate opsin melanopsin. Melanopsin is a promising optogenetic tool that functions as a selective molecular light switch for G protein-coupled receptor pathways. Thus, we constructed a model of the melanopsin G_q protein complex and predicted an absorption maximum shift of the Y211F variant. This variant displays a narrow blue-shifted action spectrum and twofold faster deactivation kinetics compared to wild-type melanopsin on G protein-coupled inward rectifying K⁺ (GIRK) channels in HEK293 cells. Furthermore, we verified the in vivo activity and optogenetic potential for the variant in mice. Thus, we propose that our developed concept will be generally applicable to designing optogenetic tools.     

Investigations of ductile damage during the process chains of toothed functional components manufactured by sheet-bulk metal forming

Sheet-bulk metal forming processes combine conventional sheet forming processes with bulk forming of sheet semi-finished parts. In these processes the sheets undergo complex forming histories. Due to in- and out-of-plane material flow and large accumulated plastic strains, the conventional failure prediction methods for sheet metal forming such as forming limit curve fall short. As a remedy, damage models can be applied to model damage evolution during those processes. In this study, damage evolution during the production of two different toothed components from DC04 steel is investigated. In both setups, a deep drawn cup is upset to form a circumferential gearing. However, the two final products have different dimensions and forming histories. Due to combined deep drawing and upsetting processes, the material flow on the cup walls is three-dimensional and non-proportional. In this study, the numerical and experimental investigations for those parts are presented and compared. Damage evolution in the process chains is simulated with a Lemaitre damage criterion. Microstructural analysis by scanning electron microscopy is performed in the regions with high mechanical loading. It is observed that the evolution of voids in terms of void volume fraction is strongly dependent on the deformation path. The comparison of simulation results with microstructural data shows that the void volume fraction decreases in the upsetting stage after an initial increase in the drawing stage. Moreover, the concurrent numerical and microstructural analysis provides evidence that the void volume fraction decreases during compression in sheet-bulk metal forming.     

Degradation of Lake Ziway,Ethiopia: A study of the environmental perceptions of school students

Lake Ziway in Ethiopia is a freshwater lake supporting multitude uses, including irrigation, fishing, water supply and recreation. However, the lake is being degraded primarily because of various land‐ and water‐use activities in its watershed. Recognizing these human impacts on the lake's water quality and quantity, the perceptions of school students were surveyed under the belief that the future of the lake is largely dependent on this younger generation. The goal of this study was to better understand how students actually recognize the extent to which various human activities impact the water quantity and quality of Lake Ziway. As major stakeholders in their communities, the perceptions of school students from four high schools regarding the changes to the lake over time were investigated. Students were contacted by purposive sampling, based on criteria of student academic performances, and their proximity to the lake. Their perceptions were studied on the basis of an interview survey. The majority of students indicated that high levels of human activities, especially water abstractions and water pollution, were the main lake impacts. Students believe there is a lack of sustainable utilization and protection of the lake. They suggested coordinated activities among all lake stakeholders in the participation and decision‐making process to properly manage the lake. Provision of awareness to both local administrations and local communities, concern for establishing an appropriate regulatory body and allocating a sufficient budget, and strict controls on flower farm practices in the lakeshore, also was considered to be of high priority as a means of conserving the sustainability of the lake. The result derived from this survey has important implications for facilitating improved school curricula, and for federal, regional and district level water resource management authorities, in setting priorities and developing policies for the sustainability of Lake Ziway.     

(R)-acetoin-female sex pheromone of the summer chafer Amphimallon solstitiale (L.)

Extracts of Amphimallon solstitiale (L.), a well known, widely distributed and rather common European scarab beetle, were analyzed by GC-MS and GC-EAD. Acetoin -(R):(S) < 9:1 - as well as 2,3-butanediol -(2R,3R):(2S,3S) :meso = 1:1:9 - were present in extracts of both males and females. Although (2S,3S)-butanediol did not show any EAD activity, the other compounds elicited strong responses exclusively with male antennae. In contrast, several EAD active green leaf volatiles were detected equally well by male and female antennae. During preliminary field bioassays, (R)-acetoin was highly attractive to swarming males, whereas neither rac-acetoin nor the 2,3-butanediols showed activity. Therefore, (R)-acetoin is the female sex pheromone of A. solstitiale.     

Snow metamorphism as revealed by scanning electron microscopy

Current theories of snow metamorphism indicate that sublimating snow crystals have rounded shapes, while growing crystals have shapes that depend on growth rates. At slow growth rates, crystals are rounded. At moderate rates, they have flat faces with rounded edges. At fast growth rates, crystals have flat faces with sharp edges, and they have hollow faces at very fast growth rates. The main growth/sublimation mechanism is thought to be by the homogeneous nucleation of new layers at or near crystal edges. It was also suggested that the equilibrium shape of snow crystals would be temperature dependent: rounded above -10.5 degrees C, and faceted below. To test these paradigms, we have performed SEM investigations of snow samples having undergone metamorphism under natural conditions, and of snow samples subjected to isothermal metamorphism at -4 degrees and -15 degrees C in the laboratory. In general, current theories predicting crystal shapes as a function of growth rates, and of whether crystals are growing or sublimating, are verified. However, the transition in equilibrium shapes from rounded to faceted at -10.5 degrees C is not observed in our isothermal experiments that reveal a predominance of rounded shapes after more than a month of metamorphism at -4 and -15 degrees C. Some small crystals with flat faces that also have sharp angles at -15 degrees C, are observed in our isothermal experiments. These faces are newly formed, and contradict current theory. Several hypotheses are proposed to explain their occurrence. One is that they are due to sublimation at emerging dislocations.     

Variability, covariation, and invariance with respect to coordinate systems in motor control: Reply to Smeets and Louw (2007).

In their comment on the tolerance-noise covariation (TNC) method for decomposing variability by H. Müller and D. Sternad (2003, 2004b), J. B. J. Smeets and S. Louw (see record 2007-01135-017) show that covariation (C), as defined within the TNC method, is not invariant with respect to coordinate transformations and contend that it is, therefore, meaningless. Although the observation is correct, their interpretation is misleading in the following ways: (a) They equate covariation C with the known statistical quantity covariance and noise (N) with standard deviations. The two quantities C and N are conceptually different statistical measures. (b) Dependency on the reference frame is not only a feature of C but of all 3 components. However, such dependency is ubiquitous in motor control. (c) As the frame of reference in biological systems is poorly understood, the TNC method may afford evaluation of different coordinates for control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

One pediatric neurosurgeon's story

The development of pediatric neurosurgery in the United Kingdom, as experienced by one recently trained neurosurgeon in the late 1940s and the 1950s, is described.