A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Facial myokymia and spastic paretic facial contracture as the result of anaplastic pontocerebellar glioma

The case of a 36-year-old man who sought treatment of right facial myokymia and spastic paretic facial contracture is reported. Computed tomography and magnetic resonance imaging revealed a tumor located in the right cerebellar peduncle and the right dorsal pons bulging into the fourth ventricle. After microsurgical partial resection of the mass, which was verified histologically as an anaplastic glioma, facial myokymia initially ceased. The vermicular rippling movements were less intense upon recurrence and could be controlled by low-dose dexamethasone in the further course, when magnetic resonance imaging showed an interstitial pontine edema after percutaneous radiation therapy. It is assumed that facial myokymia and spastic paretic facial contracture were generated by ectopic activity due to alterations in the microenvironment at the intrapontine portion of the axons of the seventh nerve caused by the compressive effect of the tumor and later by edema.     

HLA-A26 subtype A pockets accommodate acidic N-termini of ligands

BACKGROUND: Fiberoptic flexible sigmoidoscopy (FFS) is routinely requested preoperatively as part of evaluation of pelvic masses to exclude colonic involvement by the tumor or concurrent colonic neoplasm. The aim of our study was to evaluate the utility of preoperative FFS in patients with suspected gynecologic malignancy. METHODS: FFS, performed using a 60 cm sigmoidoscope, evaluated (1) presence of bowel involvement by the tumor, (2) extrinsic compression by the tumor, and (3) presence of colonic neoplasms. FFS findings were correlated with surgical findings. RESULTS: A total of 107 women underwent preoperative FFS and subsequent surgery. Eleven patients (11%) had lower gastrointestinal symptoms. At surgery, 63% of pelvic tumors were malignant and 37% were benign. The most common abnormality at FFS was colonic polyps in 23 patients (21%). Colonic adenomas were found in 11 patients (10%). Extrinsic compression by the tumor without mucosal abnormalities was seen in 15 patients (14%). The most common intraoperative finding was tumor adhering to the bowel in 18 patients requiring dissection, but only 1 patient required bowel resection. Eight of these 18 patients had preoperative lower gastrointestinal symptoms. All 15 patients with extrinsic compression at FFS had tumor adhering to the bowel. CONCLUSIONS: Pelvic masses cause extrinsic compression at FFS in 14% of patients. This is suggestive of tumor adherent to the bowel at surgery. However, bowel resection is rarely required because of tumor involvement. Most patients with bowel adherence by tumor have lower gastrointestinal symptoms. Colonic adenomas are found in one tenth of patients, mostly in patients older than 50 years of age. Preoperative FFS does not change the surgical management of pelvic tumors. Screening FFS is indicated in all patients with pelvic tumors over age 50, as in persons with average risk, but is otherwise unnecessary in evaluation of pelvic masses.     

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.     

Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

A Cost-Based Approach to Adaptive Resource Management in Data Stream Systems

Data stream management systems need to adaptively control their resources, since stream characteristics and query workload may vary over time. In this paper, we investigate an approach to adaptive resource management for continuous sliding-window queries that adjusts window sizes and time granularities to keep resource usage within bounds. These two novel techniques differ from standard load shedding approaches based on sampling, as they ensure exact query answers for given user-defined quality of service specifications, even under query reoptimization. In order to quantify the effects of both techniques on the various operations in a query plan, we develop an appropriate cost model for estimating operator resource allocation in terms of memory usage and processing costs. A thorough experimental study not only validates the accuracy of our cost model but also demonstrates the efficacy and scalability of the proposed techniques.     

Fabrication of nanoscale tungsten tip arrays for scanning probemicroscopy-based devices

A new fabrication process for nanoscale tungsten tip arrays was developed for scanning probe microscopy-based devices. It is suitable to make a huge array on a device chip and is potentially compatible with CMOS technology. In this study, tungsten was selected as a tip material because of its hardness and conductivity. The newly developed fabrication process mainly consists of several important techniques: a combination of optical lithography and electron beam (EB) lithography to reduce the total exposure time with high resolution and chromium/tungsten/chromium (Cr/W/Cr) sandwich deposition and etching in which the first chromium layer is used as a mask and a second one is used as an etch stop. A periodic array of dots in an EB resist with a spot diameter of less than 50 nm was obtained by a combination of optical lithography and EB lithography with a positive resist (polymethylmethacrylate) in which all processing conditions were optimized carefully. A thin and uniform chromium film, deposited by ion-beam sputtering, allowed the use of thin polymethylmethacrylate (PMMA) film which led to the high resolution. The conditions of dc magnetron sputtering were also optimized in order to deposit a densely packed and low-resistivity film. The resulting tungsten tip arrays had a cylindrical shape with diameters of less than 60 nm and heights of 300 nm     

Ermüdungsrißwachstum in Kerben

Fatigue Crack Growth in Notches Nowadays it is wellknown that an important part of the fatigue life time, usually differenciated in crack initiation and crack growth, is often controlled by fatigue crack growth of cracks in notches. An elastic-plastic on the J-integral based crack growth model considering the crack opening and closure phenomenon will be described to determine crack growth of cracks in notches between crack initiation and failure. Experimental results and finite element analysis were used to verify the developed model.