University of California

About: University of California is a education organization based out in Oakland, California, United States. It is known for research contribution in the topics: Population & Layer (electronics). The organization has 55175 authors who have published 52933 publications receiving 1491169 citations. The organization is also known as: UC & University of California System.

Efflux-Mediated Drug Resistance in Bacteria

Abstract: Drug efflux pumps play a key role in drug resistance and also serve other functions in bacteria. There has been a growing list of multidrug and drug-specific efflux pumps characterized from bacteria of human, animal, plant and environmental origins. These pumps are mostly encoded on the chromosome, although they can also be plasmid-encoded. A previous article in this journal provided a comprehensive review regarding efflux-mediated drug resistance in bacteria. In the past 5 years, significant progress has been achieved in further understanding of drug resistance-related efflux transporters and this review focuses on the latest studies in this field since 2003. This has been demonstrated in multiple aspects that include but are not limited to: further molecular and biochemical characterization of the known drug efflux pumps and identification of novel drug efflux pumps; structural elucidation of the transport mechanisms of drug transporters; regulatory mechanisms of drug efflux pumps; determining the role of the drug efflux pumps in other functions such as stress responses, virulence and cell communication; and development of efflux pump inhibitors. Overall, the multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.

Generative Visual Manipulation on the Natural Image Manifold

Abstract: Realistic image manipulation is challenging because it requires modifying the image appearance in a user-controlled way, while preserving the realism of the result. Unless the user has considerable artistic skill, it is easy to “fall off” the manifold of natural images while editing. In this paper, we propose to learn the natural image manifold directly from data using a generative adversarial neural network. We then define a class of image editing operations, and constrain their output to lie on that learned manifold at all times. The model automatically adjusts the output keeping all edits as realistic as possible. All our manipulations are expressed in terms of constrained optimization and are applied in near-real time. We evaluate our algorithm on the task of realistic photo manipulation of shape and color. The presented method can further be used for changing one image to look like the other, as well as generating novel imagery from scratch based on user’s scribbles.

Nicotine Chemistry, Metabolism, Kinetics and Biomarkers

Abstract: Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDPglucuronosyltransfease (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml−1. This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking.

Stem cell fate dictated solely by altered nanotube dimension

Abstract: Two important goals in stem cell research are to control the cell proliferation without differentiation and to direct the differentiation into a specific cell lineage when desired. Here, we demonstrate such paths by controlling only the nanotopography of culture substrates. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion or a specific differentiation of hMSCs into osteoblasts by using only the geometric cues, absent of osteogenic inducing media. hMSC behavior in response to defined nanotube sizes revealed a very dramatic change in hMSC behavior in a relatively narrow range of nanotube dimensions. Small (≈30-nm diameter) nanotubes promoted adhesion without noticeable differentiation, whereas larger (≈70- to 100-nm diameter) nanotubes elicited a dramatic stem cell elongation (≈10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for uniqueorthopedics-related hMSC treatments.

Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models.

Abstract: It is a major goal of clinical pharmacology to understand the dose-effect relationship in therapeutics. Much progress towards this goal has been made in the last 2 decades through the development of pharmacokinetics as a discipline. The study of pharmacokinetics seeks to explain the time course of drug concentration in the body. Recognition of the crucial concepts of clearance and volume of distribution has provided an important link to the physiological determinants of drug disposition. Mathematical models of absorption, distribution, metabolism and elimination have been extensively applied, and generally their predictions agree remarkably well with actual observations. However, the time course of drug concentration cannot in itself predict the time course or magnitude of drug effect. When drug concentrations at the effect site have reached equilibrium and the response is constant, the concentration-effect relationship is known as pharmacodynamics. Mathematical models of pharmacodynamics have been used widely by pharmacologists to describe drug effects on isolated tissues. The crucial concepts of pharmacodynamics are potency — reflecting the sensitivity of the organ or tissue to a drug, and efficacy — describing the maximum response. These concepts have been embodied in a simple mathematical expression, the Emax model, which provides a practical tool for predicting drug response analogous to the compartmental model in pharmacokinetics for predicting drug concentration.