A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Combining molybdenum carbide with ceria overlayers to boost Mo/CeO2 catalyzed ammonia synthesis

The design of an efficient non-noble metal catalyst is of burgeoning interest for ammonia synthesis. Herein, we report a Mo₂C/CeO₂ catalyst that is superior in ammonia synthesis activity. In this catalyst, molybdenum carbide coexisted with the ceria overlayers which is from the ceria support as the strong metal–support interaction. There is a high proportion of low-valent Mo species, as well as high concentration of Ce³⁺ and surface oxygen species. The presence of Mo₂C and CeO₂ overlayers not only leads to enhancement of hydrogen and nitrogen adsorption, but also facilitates the desorption and exchange of adsorbed species with the gaseous reagents. Compared with the Mo/CeO₂ catalyst prepared without carbonization, the Mo₂C/CeO₂ catalyst is more than sevenfold higher in ammonia synthesis rate. This work not only presents an explicit example of designing Mo-based catalyst that is highly efficient for ammonia synthesis by tuning the adsorption and desorption properties of the reactant gases, but opens a perspective for other elements in ammonia synthesis.     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach contents of poisoned birds

Ten natural bloom samples of cyanobacteria from the Danish lakes Knud s? (5), Ravn s? (4), and Salten Langs? (1) collected during 1993-1995 were assayed for toxicity by mouse bioassay, for acetylcholinesterase inhibiting activity by a colorimetric method, and for microcystins by enzyme-linked immunosorbent assay. In the mouse bioassay, seven samples were neurotoxic, two were non-toxic and one gave a protracted toxic response. One of the non-toxic and the single protracted toxic sample both contained anticholinesterase activity equivalent to 4 micrograms anatoxin-a(s) g-1. The neurotoxic samples contained equivalents to 20-3300 micrograms anatoxin-a(s) g-1. The highest anticholinesterase activities (equivalent to 2300 and 3300 micrograms anatoxin-a(s) g-1, respectively) were found in samples collected from Lake Knud s? in connection with bird-kills in 1993 and 1994. Small amounts of microcystins (0.1-0.9 microgram g-1) were detected in all samples but one. All Lake Knud s? and Lake Ravn s? samples were dominated by Anabaena lemmermannii, and the Lake Salten Langs? sample by several species of Anabaena. Gel filtration profiles indicated similarity between the toxic component from the Lake Knud s? 1994 bloom with registered bird-kills and anatoxin-a(s) isolated from Anabaena flos-aquae NRC-525-17. Anticholinesterase-producing cultures of A. lemmermannii were isolated from the Lake Knud s? 1993 bloom. These laboratory cultures produced anatoxin-a(s) equivalents of 29-743 micrograms g-1. Other cultures of A. lemmermannii isolated from Lake Knud s? and Lake Ravn s? were hepatotoxic or non-toxic. Dead birds collected from Lake Knud s? during the neurotoxic 1993 Anabaena bloom possibly died from cyanobacterial toxicosis. The stomach contents contained colonies and single trichomes of Anabaena, and anticholinesterase activities equivalent to 2.1-89.7 micrograms anatoxin-a(s) kg-1 body weight and microcystins (53-95 ng kg-1) were also detected.     

Finite-difference time-domain simulation of scattering from objectsin continuous random media

A three-dimensional (3D) finite-difference time-domain (FDTD) scheme is introduced to model the scattering from objects in continuous random media. FDTD techniques have been previously applied to scattering from random rough surfaces and randomly placed objects in a homogeneous background, but little has been done to simulate continuous random media with embedded objects where volumetric scattering effects are important. In this work, Monte Carlo analysis is used in conjunction with FDTD to study the scattering from perfectly electrically conducting (PEC) objects embedded in continuous random media. The random medium models under consideration are chosen to be inhomogeneous soils with a spatially fluctuating random permittivities and prescribed correlation functions. The ability of frequency averaging techniques to discriminate objects in this scenarion is also briefly investigated. The simulation scheme described in this work can be adapted and used to help in interpreting the scattered field data from targets in random environments such as geophysical media, biological media, or atmospheric turbulence     

Reliability Analysis of Single-Degree-of-Freedom Elastoplastic Systems. II: Suboptimal Excitations

A method for constructing an approximation of the critical excitation that drives an elastoplastic system from rest to a target threshold at a specified time instant, referred to as the “suboptimal excitation,” is presented in this paper. It is based on the observations gained from study of the critical excitations in the companion paper. Essentially, for the usual case of interest where the failure time is not small compared to the natural period, the duration of the positive and negative pulses of the critical excitation are roughly equal to half of the natural period. This consideration allows for a simple intuitive approximation of the critical excitation. The amplitudes of the positive and negative pulses are obtained in closed forms using energy balance. Numerical investigations show that the critical excitations are well approximated by the suboptimal excitations.     

Ascorbic acid is a stimulatory cofactor for mitochondrial glycerol-3-phosphate dehydrogenase

We describe in this report a sensitive and direct method for the analysis of tamoxifen (TAM) in microsamples of plasma. The drug and internal standard (quinine bisulfate, I.S.) were separated on a 10-microm particle, 10 cm X 8 mm CN cartridge in conjunction with a radial compression system. The mobile phase was a mixture of 0.1 M sodium acetate in 0.001 M tetrabutylammonium phosphate solution (pH 6) and methanol (30:70, v/v) at a flow-rate of 4 ml/min. After addition of I.S. and o-phosphoric acid in acetonitrile (0.6 M) to the plasma (30 microl), the mixture was placed in an ultraviolet shortwave transluminator for 2 min prior to injection into the chromatograph. The compounds were detected in the effluent fluorometrically at excitation and emission wavelengths of 258 and 378 nm, respectively. Under these conditions, no interference in the assay from any endogenous substance or other concurrently used drugs was observed and the retention times of I.S. and TAM were 4.4 and 10.15 min, respectively. The concentration of TAM in plasma was linearly (r>0.9983) related to the peak height ratio (TAM/I.S.) in the range 0.01-2.0 microg ml(-1) and C.V. at 0.075, 0.4 and 1.2 microg ml(-1) was < or = 4.96%. We are currently using this assay for monitoring TAM in plasma and investigating its pharmacokinetics in cancer patients receiving cytotoxic drugs in addition to TAM as a multi-drug resistance modifier.     

Diurnal thermal cycling effects on microwave signatures of thin seaice

To investigate effects of diurnal thermal cycles on C-band polarimetric backscatter and millimeter-wave emission from sea ice, the authors carried out a winter experiment at the outdoor geophysical research facility (GRF) in the cold regions research and engineering laboratory (CRREL), the ice sheet grew from open sea water to a thickness of 10 cm in 2.5 days, during which they took polarimetric backscatter data with a C-band scatterometer, interlaced with brightness temperature measurements at 90 GHz in conjunction with meteorological and sea ice characterizations. The initial ice growth in the late morning was slow due to high insolation. As the air temperature dropped during the night, the growth rate increased significantly. Air temperature changed drastically from about -12 to -36°C between day and night, the diurnal thermal cycle repeated itself the next day and the growth rate varied in the same manner. Ice temperature profiles clearly show the diurnal response in the ice sheet with a lag of 2.5 h behind the time of the maximum short-wave incident solar radiation. The diurnal cycles are also evident in the millimeter-wave brightness temperature data, measured sea ice backscatter revealed substantial diurnal variations up to 6 dB with repeatable cycles in synchronization with the temperature cycles and the brightness temperature modulations, the diurnal cycles in backscatter indicate that the dominant scattering mechanism related to thermodynamic processes in sea ice is reversible, a diurnal backscatter model based on sea ice electrodynamics and thermodynamics explains the observed diurnal signature. This work shows that diurnal effects are important for inversion algorithms to retrieve sea ice geophysical parameters from remote sensing data acquired with a satellite synthetic aperture radar (SAR) or scatterometer on Sun-synchronous orbits     

Rotationplasty

Today rotationplasty is well established as an acceptable procedure for limb salvage in patients who have a malignant tumor in the femur or tibia. The main indication is that it is the alternative to amputation. Rotationplasty should further be used in the very young child because of growth-dependent complications that can be expected after tumor resection and any kind of reconstruction. This article covers the classification of the different types of rotationplasties, the operative procedure, prosthetic care, and the functional results.