332 research outputs found

    Box Drawings for Learning with Imbalanced Data

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    The vast majority of real world classification problems are imbalanced, meaning there are far fewer data from the class of interest (the positive class) than from other classes. We propose two machine learning algorithms to handle highly imbalanced classification problems. The classifiers constructed by both methods are created as unions of parallel axis rectangles around the positive examples, and thus have the benefit of being interpretable. The first algorithm uses mixed integer programming to optimize a weighted balance between positive and negative class accuracies. Regularization is introduced to improve generalization performance. The second method uses an approximation in order to assist with scalability. Specifically, it follows a \textit{characterize then discriminate} approach, where the positive class is characterized first by boxes, and then each box boundary becomes a separate discriminative classifier. This method has the computational advantages that it can be easily parallelized, and considers only the relevant regions of feature space

    Field-Effect Flow Control in Microfluidics

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    Lab-on-chip (LOC) devices have miniaturized routine laboratory processes for automated, high-throughput chemical analysis. Separations of biomolecules, including protein and DNA, have been performed with high efficiencies in LOC devices, but the need for improved fluid flow control, i.e. pumping and valves, remains a significant challenge for next-generation systems. This dissertation explores the development of novel flow-control technology in polymer microfluidic networks for the realization of inexpensive, next-generation LOC devices. In the microchannels, electroosmotic flow (EOF) is used to electro-kinetically move the fluid with a longitudinal electric field. To modulate the EOF velocity, the technique of field-effect flow control (FEFC) is employed. In FEFC, a second electric field is applied through the microchannel wall to influence the surface charge at the fluid-microchannel interface for independent control of the EOF. Presented in this work is the first demonstration of FEFC in a polymer network. The microchannel walls were composed of Parylene C (1 - 2 um thick), which is an inexpensive, chemical vapor deposited polymer. In this work, FEFC modulated the EOF velocity from 240% to 60% of its original value in a microchannel that was 40 um in height, 100 um in width, and 2 cm long. The next research phase integrated FEFC technology into microfluidic networks with microchannels in the second and third dimensions. At the T-intersection of three microchannels, FEFC established different EOF pumping rates in the two main microchannels. The different flow rates induced pressure pumping in the third, field-free microchannel with ultra-low flow rate control (-2.0 nL/min to 2.0 nL/min). Moreover, adjusting the secondary electric fields enabled bi-directional flow control for the induced pumping in the 2D and 3D field-free microchannels. To improve the microfluidic networks, an electro-fluid flow model was developed to describe the induced pressure and FEFC phenomenon. The model closely predicted the experimentally obtained flow rates in the field-free microchannel. Additionally, the study of multiple gate electrodes along the same microchannel showed that FEFC has only a local effect over the EOF, but revealed that position and size of the electrodes influence the EOF control in the microfluidic network

    Nanotechnology for Cell–Substrate Interactions

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    In the pursuit to understand the interaction between cells and their underlying substrates, the life sciences are beginning to incorporate micro- and nanotechnology-based tools to probe and measure cells. The development of these tools portends endless possibilities for new insights into the fundamental relationships between cells and their surrounding microenvironment that underlie the physiology of human tissue. Here, we review techniques and tools that have been used to study how a cell responds to the physical factors in its environment. We also discuss unanswered questions that could be addressed by these approaches to better elucidate the molecular processes and mechanical forces that dominate the interactions between cells and their physical scaffolds

    The consequence of substrates of large- scale rigidity on actin network tension in adherent cells

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    International audienceThere is compelling evidence that substrate stiffness affects cell adhesion as well as cytoskeleton organization and contractile activity. This work was designed to study the cytoskeletal contractile activity of cells plated on microposts of different stiffness using a numerical model simulating the intracellular tension of individual cells. We allowed cells to adhere onto micropost substrates of various rigidities and used experimental traction force data to infer cell contractility using a numerical model. The model discriminates between the influence of substrate stiffness on cell tension and shows that higher substrate stiffness leads to an increase in intracellular tension. The strength of this model is its ability to calculate the mechanical state of each cell in accordance to its individual cytoskeletal structure. This is achieved by regenerating a numerical cytoskeleton base

    Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone

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    Hong Liu-Seifert1, Bruce J Kinon1, Christopher J Tennant2, Jennifer Sniadecki1, Jan Volavka31Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA; 2CJT Biomedical Consulting, South Lake Tahoe, CA, USA; 3New York University, New York, NY, USAObjective: To better understand sexual dysfunction in patients with schizophrenia and its associations with prolactin and reproductive hormones.Methods: This was a secondary analysis of an open-label, one-day study (N = 402). The primary objective of the study was to assess the prevalence of hyperprolactinemia in patients with schizophrenia who had been treated with conventional antipsychotics or risperidone. Other atypical antipsychotics available at the time of the study were not included due to a more favorable prolactin profile.Results: The majority of patients (59% of females and 60% of males) reported impairment of sexual function. In postmenopausal females, risk of impaired sexual interest was increased by 31% for every 10 ng/ml increase in prolactin (p = 0.035). In males, lower testosterone was associated with higher prolactin (p < 0.001) and with orgasmic (p = 0.004) and ejaculatory dysfunction (p = 0.028).Conclusion: These findings suggest that hyperprolactinemia may be associated with sexual dysfunction. They also provide more information on the relationships between prolactin, reproductive hormones, and sexual dysfunction. Sexual dysfunction is an understudied yet important consideration in the treatment of schizophrenia. More attention is warranted in this area as it may provide opportunities for improved quality of life and adherence to treatment for patients.Keywords: sexual dysfunction, schizophrenia, hyperprolactinemia, antipsychotics, risperidon
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