A fully automated calibration method for an optical see-through head-mounted operating microscope with variable zoom and focus

Ever since the development of the first applications in image-guided therapy (IGT), the use of head-mounted displays (HMDs) was considered an important extension of existing IGT technologies. Several approaches to utilizing HMDs and modified medical devices for augmented reality (AR) visualization were implemented. These approaches include video-see through systems, semitransparent mirrors, modified endoscopes, and modified operating microscopes. Common to all these devices is the fact that a precise calibration between the display and three-dimensional coordinates in the patient's frame of reference is compulsory. In optical see-through devices based on complex optical systems such as operating microscopes or operating binoculars-as in the case of the system presented in this paper-this procedure can become increasingly difficult since precise camera calibration for every focus and zoom position is required. We present a method for fully automatic calibration of the operating binocular Varioscope M5 AR for the full range of zoom and focus settings available. Our method uses a special calibration pattern, a linear guide driven by a stepping motor, and special calibration software. The overlay error in the calibration plane was found to be 0.14-0.91 mm, which is less than 1% of the field of view. Using the motorized calibration rig as presented in the paper, we were also able to assess the dynamic latency when viewing augmentation graphics on a mobile target; spatial displacement due to latency was found to be in the range of 1.1-2.8 mm maximum, the disparity between the true object and its computed overlay represented latency of 0.1 s. We conclude that the automatic calibration method presented in this paper is sufficient in terms of accuracy and time requirements for standard uses of optical see-through systems in a clinical environment.     

Structure-based design of a lysozyme with altered catalytic activity

Here we show that the substitution Thr 26-->His in the active site of T4 lysozyme causes the product to change from the alpha- to the beta-anomer. This implies an alteration in the catalytic mechanism of the enzyme. From the change in product, together with inspection of relevant crystal structures, it is inferred that wild-type T4 lysozyme is an anomer-inverting enzyme with a single displacement mechanism in which water attacks from the alpha-side of the substrate. In contrast, the mutant T26H is an anomer-retaining enzyme with an apparently double displacement mechanism in which a water molecule attacks from the opposite side of the substrate. The results also show that the mechanism of wild-type T4 lysozyme differs from that of hen egg-white lysozyme even though both enzymes are presumed to have evolved from a common precursor.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Synthese und charakterisierung von butadien-divinylbenzol-copolymeren

The copolymerization of butadiene with a technical divinylbenzene fraction was investigated to study the modification of cis-1,4 polybutadiene. Beside the Ziegler-Natta-catalyst nickeloctanoate/bortrifluoride/aluminiumtriethyl, another catalytic system consisting of nickeloctanoate/titaniumtetrachloride/aluminiumtriethyl was used, which allows to polymerize more divinylbenzene because of its higher activity toward vinylaromates. With the help of spectroscopical, pyrolysis-gaschromatographical and thermoanalytical methods one can obtain relations between glass-, crystallization- and melting temperature and the microstructure of the polymer. It can be shown that not only the divinylbenzene but also the trans-1,4- and the 1,2-vinyl units are statistically distributed in the polymer. By this, beside the pyrolysis-gaschromatography, particularly the differential scanning calorimetry is a useful tool to characterize the structure of partially crosslinked polymers obtained from polymerization of technical fractions.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

Magnetic anisotropy in (Ga,Mn)As on GaAs(1 1 3)As studied by magnetotransport and ferromagnetic resonance

The magnetic anisotropy of a 40-nm-thick (Ga,Mn)As film with 5% Mn grown on GaAs(1 1 3)A is studied by means of magnetotransport and ferromagnetic resonance (FMR) spectroscopy. In addition to the cubic and a weak uniaxial in-plane anisotropy, two uniaxial out-of-plane contributions along [1 1 3] and [0 0 1] are found. Using the anisotropy parameters determined from FMR, the longitudinal and transverse resistivities measured as a function of magnetic field orientation and strength are well modelled within the framework of a single ferromagnetic domain. In particular, the low-field data which are strongly affected by sudden jumps of the magnetization are well reproduced.     

Polycyclic aromatic hydrocarbon-degrading capabilities of Phanerochaete laevis HHB-1625 and its extracellular ligninolytic enzymes

The ability of Phanerochaete laevis HHB-1625 to transform polycyclic aromatic hydrocarbons (PAHs) in liquid culture was studied in relation to its complement of extracellular ligninolytic enzymes. In nitrogen-limited liquid medium, P. laevis produced high levels of manganese peroxidase (MnP). MnP activity was strongly regulated by the amount of Mn2+ in the culture medium, as has been previously shown for several other white rot species. Low levels of laccase were also detected. No lignin peroxidase (LiP) was found in the culture medium, either by spectrophotometric assay or by Western blotting (immunoblotting). Despite the apparent reliance of the strain primarily on MnP, liquid cultures of P. laevis were capable of extensive transformation of anthracene, phenanthrene, benz[a]anthracene, and benzo[a]pyrene. Crude extracellular peroxidases from P. laevis transformed all of the above PAHs, either in MnP-Mn2+ reactions or in MnP-based lipid peroxidation systems. In contrast to previously published studies with Phanerochaete chrysosporium, metabolism of each of the four PAHs yielded predominantly polar products, with no significant accumulation of quinones. Further studies with benz[a]anthracene and its 7,12-dione indicated that only small amounts of quinone products were ever present in P. laevis cultures and that quinone intermediates of PAH metabolism were degraded faster and more extensively by P. laevis than by P. chrysosporium.     

Syntenic assignment of dopamine tautomerase (DCT) to bovine chromosome 12

Heterologous primers were used to amplify an exon and intron-containing segment of the bovine homologue of the human dopachrome tautomerase gene. After confirmation of homology by sequence analysis (exon sequence similarity greater than 90%), bovine-specific primers were developed for synteny mapping purposes. The dopachrome tautomerase gene was assigned to bovine chromosome 12 (BTA12) with 97% concordance to the coagulation factor 10 locus. Together with previous synteny mapping of bovine chromosome 12 genes, fms-related tyrosine kinase, esterase D and 5-hydroxytryptamine receptor 2, this assignment further indicates conservation between human chromosome 13q and bovine chromosome 12.