Artificial Cilia: Generation of Magnetic Actuators in Microfluidic Systems

Magnetic artificial cilia are fabricated from photoreactive copolymer precursors filled with magnetic nanoparticles by a new photolithographic process. Two different crosslinkers and UV‐radiation of two different wavelengths are used to generate arrays of planar magnetically actuatable rubber flaps. The cilia are integrated into a microfluidic channel and operated in water using a rotating permanent magnet.     

Establishment and Characterization of Novel Human Intestinal In Vitro Models for Absorption and First-Pass Metabolism Studies

Commonly used intestinal in vitro models are limited in their potential to predict oral drug absorption. They either lack the capability to form a tight cellular monolayer mimicking the intestinal epithelial barrier or the expression of cytochrome P450 3A4 (CYP3A4). The aim of this study was to establish a platform of colorectal cancer patient-derived cell lines for evaluation of human intestinal drug absorption and metabolism. We characterized ten 2D cell lines out of our collection with confluent outgrowth and long-lasting barrier forming potential as well as suitability for high throughput applications with special emphasis on expression and inducibility of CYP3A4. By assessment of the transepithelial electrical resistance (TEER) the cells barrier function capacity can be quantified. Very high TEER levels were detected for HROC60. A high basal CYP3A4 expression and function was found for HROC32. Eight cell lines showed higher CYP3A4 induction by stimulation via the vitamin D receptor compared to Caco-2 cells (5.1- to 16.8-fold change). Stimulation of the pregnane X receptor led to higher CYP3A4 induction in two cell lines. In sum, we identified the two cell lines HROC183 T0 M2 and HROC217 T1 M2 as useful tools for in vitro drug absorption studies. Due to their high TEER values and inducibility by drug receptor ligands, they may be superior to Caco-2 cells to analyze oral drug absorption and intestinal drug–drug interactions. Significance statement: Selecting appropriate candidates is important in preclinical drug development. Therefore, cell models to predict absorption from the human intestine are of the utmost importance. This study revealed that the human cell lines HROC183 T0 M2 and HROC217 T1 M2 may be better suited models and possess higher predictive power of pregnane X receptor- and vitamin D-mediated drug metabolism than Caco-2 cells. Consequently, they represent useful tools for predicting intestinal absorption and simultaneously enable assessment of membrane permeability and first-pass metabolism.     

Static extensivity analysis for λ-definable functions over lattices

We employ a static analysis to examine the extensivity (∀x:x≤f(x)) of functions defined over lattices in a λ-calculus augmented with lattice operations. The need for such a verification procedure has arisen in our work on a generator system (called Zoo) of static program-analyzers. The input to Zoo is a static analysis specification that consists of lattice definitions and function definitions over the lattices. Once the extensivity of the functions is ascertained, the generated analyzer is guaranteed to terminate when the lattices have finite-heights. The extensivity analysis consists of a sound syntax-driven deductive rules whose satisfiability check is done by a constraint solving procedure. Hyunjun Eo: He is a Ph.D. candidate of Computer Science Dept. at KAIST (Korea Advanced Institute of Science and Technology). He received his B.S. and M.S. in Computer Science from KAIST in 1996 and 1998, respectively. For 1998–2003, he was a research assistant of the National Creative Research Initiative Center for Research On Program Analysis System. His research interest has been on static program analysis, program logics, and higher-order and typed languages. He is currently working on developing a tool for automatic generation of program analyzers. Kwangkeun Yi, Ph.D.: His research interest has been on semantic-based program analysis and systems application of language technologies. After his Ph.D. from University of Illinois at Urbana-Champaign he joined the Software Principles Research Department at Bell Laboratories, where he worked on various static analysis approaches for higher-order and typed programming languages. For 1995–2003, he was a faculty member in the Department of Computer Science, Korea Advanced Institute of Science and Technology. Since Fall 2003, he has been a faculty member in the School of Computer Science and Engineering, Seoul National University. Kwang-Moo Choe, Ph.D.: He is a professor of Computer Science at Korea Advanced Institute of Science and Technology. He received his B.S. from Seoul National University in 1976, and his M.S. and Ph.D. from Korea Advanced Institute of Science and Technology in 1978 and 1984, respectively. For 1985–1986, he was a technical staff of AT&T Bell Labs at Murray Hill. His research interest is formal language theory, parallel evaluation of logic programs, and optimizing compilers.     

Impact of Elaboration on Socially Desirable Responding and the Validity of Biodata Measures.

The current study investigated the impact of requiring respondents to elaborate on their answers to a biodata measure on mean scores, the validity of the biodata item composites, subgroup mean differences, and correlations with social desirability. Results of this study indicate that elaborated responses result in scores that are much lower than nonelaborated responses to the same items by an independent sample. Despite the lower mean score on elaborated items, it does not appear that elaboration affects the size of the correlation between social desirability and responses to biodata items or that it affects criterion-related validity or subgroup mean differences in a practically significant way. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain metastases as the only manifestation of an undetected primary tumor

BACKGROUND: The prognosis of patients with brain metastasis as the only manifestation of an undetected primary tumor generally is considered to be poor. Therefore, most treatment is palliative. The authors reviewed the clinical outcomes and treatment results of patients presenting with brain metastasis from an undetected primary tumor at The University of Texas M. D. Anderson Cancer Center. METHODS: Between 1977-1996, 220 patients were referred to the study department for the treatment of brain metastasis from an undetected primary tumor. The patients' records were reviewed to identify those for whom brain metastasis was the only manifestation of the primary tumor. The majority of patients were excluded from the current analysis because extracranial metastasis also were present. Thirty-nine patients qualified for this retrospective review. The level of neurosurgical excision varied, but all patients received radiotherapy. Tumor control in the brain and survival were analyzed by various tumor-related and treatment-related factors. RESULTS: In 31 patients, the brain metastasis were adenocarcinomas, whereas the remaining patients had tumors of various other histologies. In 12 patients, the primary tumor eventually was found, most commonly in the lung. The median survival time for all patients was 13.4 months. Overall survival rates (OS) at 1, 3, and 5 years were 56%, 19%, and 15%, respectively. Intracranial disease control was 72% at 5 years. Patients who received gross total resection (GTR) and radiotherapy had significantly better OS than patients who received radiotherapy alone. The OS of patients whose primary tumor was identified was similar to that of patients in whom the primary tumor remained occult. CONCLUSIONS: Brain metastasis as the only manifestation of an unknown primary tumor is a distinct clinical entity. The prognosis for patients with this presentation is better than that of patients with brain metastasis in general. Although the majority of patients die of extracranial disease, a few will achieve long term survival. Treatment to the brain is effective in controlling local disease; aggressive treatment with GTR and radiotherapy is recommended.     

Beta-thalassemia in Iran: a high incidence of the nonsense codon 39 mutation on the island of Queshm

Optic disc blood flow velocity was measured in healthy patients, those with primary open angle glaucoma (POAG), and patients with normal pressure glaucoma (NPG). The velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head (ONH) has been measured with a laser Doppler velocimeter (LDV), and blood viscosity has been evaluated notably by determining the aggregability of the RBCs with an erythroaggregameter. Our results in POAG patients and NPG patients showed that their optic nerve blood flow velocity was reduced and that the aggregability of the RBCs was increased. The hyperaggregability of the erythrocytes is responsible for the increase of the local viscosity in the papillary capillary network. These haemodynamic modifications observed in patients with glaucoma support the hypothesis of a vasogenic mechanism that could impair the optic nerve in glaucoma patients.     

Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular calcification and stone formation

Calcium phosphate is deposited in many diseases, but formation mechanisms remain speculative. Nanobacteria are the smallest cell-walled bacteria, only recently discovered in human and cow blood and commercial cell culture serum. In this study, we identified with energy-dispersive x-ray microanalysis and chemical analysis that all growth phases of nanobacteria produce biogenic apatite on their cell envelope. Fourier transform IR spectroscopy revealed the mineral as carbonate apatite. The biomineralization in cell culture media resulted in biofilms and mineral aggregates closely resembling those found in tissue calcification and kidney stones. In nanobacteria-infected fibroblasts, electron microscopy revealed intra- and extracellular acicular crystal deposits, stainable with von Kossa staining and resembling calcospherules found in pathological calcification. Previous models for stone formation have led to an hypothesis that elevated pH due to urease and/or alkaline phosphatase activity is a lithogenic factor. Our results indicate that carbonate apatite can be formed without these factors at pH 7.4, at physiological phosphate and calcium concentrations. Nanobacteria can produce apatite in media mimicking tissue fluids and glomerular filtrate and provide a unique model for in vitro studies on calcification.     

IgE, IgA, and IgG responses to common yeasts in atopic patients

To assess the incidence of HIV infection and risk factors associated with HIV seroconversion among patients attending clinics for sexually transmitted diseases (STD), medical record reviews were conducted in 12 clinics in 7 U.S. cities. The records of all patients who initially tested negative for HIV from 1991 through 1996 and who received at least one additional HIV test during the study period were reviewed. In each of 7 cities, 5 to 112 patients seroconverted. Of the 286 seroconverters identified in total, 53% (152 of 286) were heterosexual men and 28% (81 of 286) were women. HIV incidence rates among men who have sex with men (MSM) ranged by city from 0.81 to 7.0 new infections/100 person-years. Rates among heterosexual men and women ranged from 0.018 to 1.2 infections/100 person-years. Multivariate analyses showed that drug use was associated with HIV seroconversion only among heterosexuals. Most new HIV infections in these clinics are being transmitted heterosexually and are associated with drug use. Nevertheless, MSM, particularly young MSM, are at greatest risk for HIV in this population: 1 of 47 seroconvert/year. The effective use of targeted prevention efforts depends upon the continued ability to monitor the incidence of HIV infection.     

Molecular and cell biological aspects of neuroendocrine tumors of the gastroenteropancreatic system

Neurons and neuroendocrine cells share a variety of common characteristics. Cell and molecular biological studies in recent years have improved our understanding of physiological and pathophysiological processes such as cellular growth, adhesion, and secretion of neuroendocrine cells. Here we review current findings from the area of basic research and from current clinical research relevant to improving the diagnosis and therapy of neuroendocrine tumors of the gastroenteropancreatic system.