Progression and Dissemination of Pulmonary Mycobacterium Avium Infection in a Susceptible Immunocompetent Mouse Model

Pulmonary infections caused by the group of nontuberculosis mycobacteria (NTM), Mycobacterium avium complex (MAC), are a growing public health concern with incidence and mortality steadily increasing globally. Granulomatous inflammation is the hallmark of MAC lung infection, yet reliable correlates of disease progression, susceptibility, and resolution are poorly defined. Unlike widely used inbred mouse strains, mice that carry the mutant allele at the genetic locus sst1 develop human-like pulmonary tuberculosis featuring well-organized caseating granulomas. We characterized pulmonary temporospatial outcomes of intranasal and left intrabronchial M. avium spp. hominissuis (M.av) induced pneumonia in B6.Sst1S mice, which carries the sst1 mutant allele. We utilized traditional semi-quantitative histomorphological evaluation, in combination with fluorescent multiplex immunohistochemistry (fmIHC), whole slide imaging, and quantitative digital image analysis. Followingintrabronchiolar infection with the laboratory M.av strain 101, the B6.Sst1S pulmonary lesions progressed 12–16 weeks post infection (wpi), with plateauing and/or resolving disease by 21 wpi. Caseating granulomas were not observed during the study. Disease progression from 12–16 wpi was associated with increased acid-fast bacilli, area of secondary granulomatous pneumonia lesions, and Arg1+ and double positive iNOS+/Arg1+ macrophages. Compared to B6 WT, at 16 wpi, B6.Sst1S lungs exhibited an increased area of acid-fast bacilli, larger secondary lesions with greater Arg1+ and double positive iNOS+/Arg1+ macrophages, and reduced T cell density. This morphomolecular analysis of histologic correlates of disease progression in B6.Sst1S could serve as a platform for assessment of medical countermeasures against NTM infection.     

APPLICATION OF A PERTURBATION THEORY FOR EVALUATION ALGORITHMS FOR IDENTIFICATION OF A CONTINUOUS PLANT FROM DISCRETE DATA

Abstract

A perturbation theory for evaluation algorithms of arithmetic expressions is applied to the generalized least-squares identification of the continuous parameters by using nonperiodic discrete data. The sampling instants are distributed in such a way that a sequence of the elemental arithmetic expressions of the identification algorithm are suboptimized according to bang-bang rules on the extrema of appropriate variation intervals. The weighting scalars in the generalized least-squares method are updated with the same purpose.     

Phase equilibria in the Al–Si–V system: The vanadium rich part

The V-rich part of the Al–Si–V phase diagram was determined by a combination of optical microscopy, powder X-ray diffraction (XRD), differential thermal analysis (DTA) and electron probe microanalysis (EPMA). Phase equilibria were investigated at two isothermal sections at 850 and 1300 °C. High temperature DTA was performed to identify the ternary invariant reactions yielding a ternary reaction scheme and the vertical section at 50 at.% V. As cast samples were investigated in order to gain additional information about primary crystallization fields. A liquidus surface projection was constructed for the entire ternary system by combining our experimental data with those from literature.     

Genetic Variation of Maize Hybrids in Grain Yield Response to Potassium and Inhibiting Nitrification

Nine maize hybrids were grown under five N levels with or without a nitrification inhibitor (nitrapyrin or an experimental inhibitor, XDE474) to evaluate the effect of inhibiting nitrification on grain yield performance and cannibalisation of nutrients from vegetative tissues during kernel maturation. Grain yield response of these hybrids also was evaluated under a paired combination of four N levels and two K levels. Hybrids responded differently to N, the form of N, and K treatments, and there appeared to be a genetic basis for preference of the form of N (ammonium versus nitrate nitrition). Crosses that involved the Mo17 family responded positively to inhibiting nitrification which provided a larger portion of the N in the ammonium form, but incorporation of early maturing genes reduced the positive response to ammonium nutrition. Like ammonium nutrition, maize hybrids showed a differential response to K treatments, and the availability of a large amount of K early in the growing season produced a negative effect on grain yield. The experimental nitrification inhibitor, XDE474, was more effective than nitrapyrin in increasing grain yield and minimising cannibalisation of nutrients in the leaf tissue.     

Imaging dynamics of charge-auto-organisation in glass capillaries

Multiply charged ion beam transmission through insulating capillaries is today a very active field of research. Thanks to the work of several groups during the last five years, several features of this unexpected process have been evidenced. The open challenge is to understand and control the self-organized charging-up of the capillary walls, which leads finally to the ion transmission. Up to now, the specific charge distribution on the inner surface, as well as the dynamics of the build-up, are still to be understood. While capillaries usually studied are microscopic pore networks etched in different materials, our concern is in macroscopic single capillaries made of glass. With a length of several centimeters and a diameter of a few micrometers at the exit, these capillaries have nevertheless the same aspect ratio as the etched pores (length/diameter ≈ 100). One of the leading goals of this research on single capillaries is to produce multi-charged ion beams with diameters smaller than a micrometer (nano-beams). These glass capillaries offer the opportunity to be used as an ion funnel due to their amazing properties of guiding and focusing highly charged ion beams without altering neither their initial charge state nor the beam emittance (<10⁻³ π mm mrad). However, the understanding of the underlying process is not complete and relies on models assuming charge patches distributed along the capillary and which still need to be tested. We present the first observation imaging the dynamics of the charging-up process in single glass capillaries. During the build-up of the self-organized charge deposition on the capillary walls, the 230 keV Xe²³⁺ transmitted beam is deflected back and forth several times as the outgoing current increases. This is in agreement with the picture of charge patches created sequentially along the capillary and thus deflecting the beam until a stationary state is reached.     

Experimentelle und simulative Untersuchungen zum Einfluss der Lageabweichungen im Nocken-Rollen-Kontakt auf die Ventiltriebskräfte

As part of a cooperation project, Daimler AG and the Institute of Machine Elements, Gears, and Transmissions (MEGT) at the Technische Universität Kaiserslautern are carrying out detailed investigations on a valve train with roller lever. The aim of the project is to develop a detailed simulation method that allows the secondary movement of the valve train to be modeled and thus represents an extension of the classic valve train dynamics simulation. This opens up the opportunity to evaluate the processes within the valve train in detail in the early stages of the product development process. This report introduces the validation of the methodology based on experimental results. First, the focus is placed on the cam-roller contact, which induces the secondary movement of the valve train. This movement takes place in the axial direction of the camshaft so that the validation takes place on the basis of the measured force in this direction. The force is dependent on the load, i.?e. the combination of speed and normal force, as well as the angular misalignments between cam and roller. Following the validation of the detailed modeling of the cam-roller contact, the gained knowledge is transferred into the extended valve train simulations. Finally the valve train simulation is validated.     

Near-Surface Wind-Induced Mixing in a Mine Lake

Wind sheltering can have a strong effect in small, sheltered water bodies; wind-induced mixing in the surface layer of a small mine lake has been investigated using field measurements. Wind speed was recorded at three locations and data suggested sheltering by topography and surface roughness changes with both fetch and the land–water transition. Wind sheltering effects in the near-surface waters were assessed using turbulent microstructure profiler measurements, providing an estimate of the sheltering distance consistent with the literature on “backward-facing” steps. A numerical simulation of the annual density stratification cycle was then performed, using the model DYRESM. Simulations indicated that inclusion of a sheltering algorithm based on the results of the field campaign significantly improved the model’s performance in capturing the surface mixed layer deepening associated with strong wind events.     

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.