Novel method for high throughput DNA methylation marker evaluation using PNA-probe library hybridization and MALDI-TOF detection

The methylation of CpG dinucleotides has become a topic of great interest in cancer research, and the methylation of promoter regions of several tumor suppressor genes has been identified as a marker of tumorigenesis. Evaluation of DNA methylation markers in tumor tissue requires hundreds of samples, which must be analyzed quantitatively due to the heterogeneous composition of biological material. Therefore novel, fast and inexpensive methods for high throughput analysis are needed. Here we introduce a new assay based on peptide nucleic acid (PNA)-library hybridization and subsequent MALDI-TOF analysis. This method is multiplexable, allows the use of standard 384 well automated pipetting, and is more specific and flexible than established methods, such as microarrays and MS-SNuPE. The approach was used to evaluate three candidate colon cancer methylation markers previously identified in a microarray study. The methylation of the genes Ade-nomatous polyposis coli (APC), glycogen synthase kinase-β-3 (GSK3β) and eyes absent 4 (EYA4) was analyzed in 12 colon cancer and 12 normal tissues. APC and EYA4 were confirmed as being differentially methylated in colon cancer patients whereas GSK3β did not show differential methylation

An algorithmic approach to the existence of ideal objects in commutative algebra

The existence of ideal objects, such as maximal ideals in nonzero rings, plays a crucial role in commutative algebra. These are typically justified using Zorn's lemma, and thus pose a challenge from a computational point of view. Giving a constructive meaning to ideal objects is a problem which dates back to Hilbert's program, and today is still a central theme in the area of dynamical algebra, which focuses on the elimination of ideal objects via syntactic methods. In this paper, we take an alternative approach based on Kreisel's no counterexample interpretation and sequential algorithms. We first give a computational interpretation to an abstract maximality principle in the countable setting via an intuitive, state based algorithm. We then carry out a concrete case study, in which we give an algorithmic account of the result that in any commutative ring, the intersection of all prime ideals is contained in its nilradical

Exceptional Multi Stage Mineralization of Secondary Minerals in Cavities of Flood Basalts from the Deccan Volcanic Province, India

Flood basalts of the Deccan Volcanic Province erupted between about 67.5 to 60.5 Ma ago and reached a thickness of up to 3500 m. The main part consists of compound and simple lava flows with a tholeiitic composition erupted within 500,000 years at about 65 Ma. Within the compound lava flows, vesicles and cavities are frequent. They are filled by secondary minerals partly of well development and large size. This study presents data on the secondary mineralization including detailed field descriptions, optical, cathodoluminescence and SEM microscopy, X-ray di�ractometry, fluid inclusions, C and O isotope analyses, and Rb-Sr and K-Ar geochronology. The investigations indicate a multistage precipitation sequence with three main stages. During stage I clay minerals and subsurface filamentous fabrics (SFFs), of probably biogenic origin, formed after the lava flows cooled down near to the Earth’s surface. In stage II, first an assemblage of calcite (I) and zeolite (I) (including mordenite, heulandite, and stilbite) as well as plagioclase was overgrown by chalcedony, and finally a second calcite (II) and zeolite (II) generation developed by burial metamorphism by subsequent lava flows. Stage III is characterized by precipitation of a third calcite (III) generation together with powellite and apophyllite from late hydrothermal fluids. Rb-Sr and K-Ar ages of apophyllite indicate a large time span for stage III. Apophyllite formed within di�erent time intervals from the Paleogene to the early Miocene even within individual lava flows at certain localities. From the Savda/Jalgaon quarry complex, ages cluster at 44–48 Ma and 25–28 Ma, whereas those from the Nashik area are 55–58 Ma and 21–23 Ma, respectively

Infrared skin damage thresholds from 1319-nm continous-wave laser exposures

A series of experiments were conducted in vivo using Yucatan miniature pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1319-nm continuous-wave Nd:YAG laser irradiation. Experiments employed exposure durations of 0.25, 1.0, 2.5, and 10 s and beam diameters of ∼0.6 and 1 cm. Thermal imagery data provided a time-dependent surface temperature response from the laser. A damage endpoint of fifty percent probability of a minimally visible effect was used to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of opticalthermal interaction. Resultant trends with respect to exposure duration and beam diameter are compared with current standardized exposure limits for laser safety. Mathematical modeling agreed well with experimental data, predicting that though laser safety standards are sufficient for exposuress, they may become less safe for very long exposures. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. [DOI: 10.1117/1.JBO.18.12.125002

Infrared skin damage thresholds from 1940-nm continuous-wave laser exposures

A series of experiments are conducted in vivo using Yucatan mini-pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1940-nm continuous-wave thulium fiber laser irradiation. Experiments employ exposure durations from 10 ms to 10 s and beam diameters of approximately 4.8 to 18 mm. Thermal imagery data provide a time-dependent surface temperature response from the laser. A damage endpoint of minimally visible effect is employed to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Results are compared with current exposure limits for laser safety. It is concluded that exposure limits should be based on data representative of large-beam exposures, where effects of radial diffusion are minimized for longer-duration damage threshold

High-Resolution In Vivo

Purpose. To investigate fundamental mechanisms of regimes of laser induced damage to the retina and the morphological changes associated with the damage response. Methods. Varying grades of photothermal, photochemical, and photomechanical retinal laser damage were produced in eyes of eight cynomolgus monkeys. An adaptive optics confocal scanning laser ophthalmoscope and spectral domain optical coherence tomographer were combined to simultaneously collect complementary in vivo images of retinal laser damage during and following exposure. Baseline color fundus photography was performed to complement high-resolution imaging. Monkeys were perfused with 10% buffered formalin and eyes were enucleated for histological analysis. Results. Laser energies for visible retinal damage in this study were consistent with previously reported damage thresholds. Lesions were identified in OCT images that were not visible in direct ophthalmoscopic examination or fundus photos. Unique diagnostic characteristics, specific to each damage regime, were identified and associated with shape and localization of lesions to specific retinal layers. Previously undocumented retinal healing response to blue continuous wave laser exposure was recorded through a novel experimental methodology. Conclusion. This study revealed increased sensitivity of lesion detection and improved specificity to the laser of origin utilizing high-resolution imaging when compared to traditional ophthalmic imaging techniques in the retina

Minimally invasive computer-navigated total hip arthroplasty, following the concept of femur first and combined anteversion: design of a blinded randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Impingement can be a serious complication after total hip arthroplasty (THA), and is one of the major causes of postoperative pain, dislocation, aseptic loosening, and implant breakage. Minimally invasive THA and computer-navigated surgery were introduced several years ago. We have developed a novel, computer-assisted operation method for THA following the concept of "femur first"/"combined anteversion", which incorporates various aspects of performing a functional optimization of the cup position, and comprehensively addresses range of motion (ROM) as well as cup containment and alignment parameters. Hence, the purpose of this study is to assess whether the artificial joint's ROM can be improved by this computer-assisted operation method. Second, the clinical and radiological outcome will be evaluated.</p> <p>Methods/Design</p> <p>A registered patient- and observer-blinded randomized controlled trial will be conducted. Patients between the ages of 50 and 75 admitted for primary unilateral THA will be included. Patients will be randomly allocated to either receive minimally invasive computer-navigated "femur first" THA or the conventional minimally invasive THA procedure. Self-reported functional status and health-related quality of life (questionnaires) will be assessed both preoperatively and postoperatively. Perioperative complications will be registered. Radiographic evaluation will take place up to 6 weeks postoperatively with a computed tomography (CT) scan. Component position will be evaluated by an independent external institute on a 3D reconstruction of the femur/pelvis using image-processing software. Postoperative ROM will be calculated by an algorithm which automatically determines bony and prosthetic impingements.</p> <p>Discussion</p> <p>In the past, computer navigation has improved the accuracy of component positioning. So far, there are only few objective data quantifying the risks and benefits of computer navigated THA. Therefore, this study has been designed to compare minimally invasive computer-navigated "femur first" THA with a conventional technique for minimally invasive THA. The results of this trial will be presented as soon as they become available.</p> <p>Trial registration number</p> <p>DRKS00000739</p