Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p

The fusion of intracellular transport vesicles with their target membranes requires the assembly of SNARE proteins anchored in the apposed membranes. Here we use recombinant cytoplasmic domains of the yeast SNAREs involved in Golgi to plasma membrane trafficking to examine this assembly process in vitro. Binary complexes form between the target membrane SNAREs Sso1p and Sec9p; these binary complexes can subsequently bind to the vesicle SNARE Snc2p to form ternary complexes. Binary and ternary complex assembly are accompanied by large increases in alpha-helical structure, indicating that folding and complex formation are linked. Surprisingly, we find that binary complex formation is extremely slow, with a second-order rate constant of approximately 3 M(-1) s(-1). An N-terminal regulatory domain of Sso1p accounts for slow assembly, since in its absence complexes assemble 2,000-fold more rapidly. Once binary complexes form, ternary complex formation is rapid and is not affected by the presence of the regulatory domain. Our results imply that proteins that accelerate SNARE assembly in vivo act by relieving inhibition by this regulatory domain.     

Can the urea breath test for H.pylori replace endoscopy for the assessment of dyspepsia in primary care?

AIMS: The urea breath test may have value in the initial assessment of dyspepsia in primary care. This pilot study tracks patient and general practitioner behaviour which cannot be predicted with modelling studies. METHODS: The urea breath test was made available over a period of 18 months. The test was requested when general practitioners would normally have used a trial of medication or referred for endoscopy. Patients with a positive urea breath test had early endoscopy before treatment. Patients with a negative urea breath test were treated according to symptom response. A follow-up questionnaire was given 6-24 months after the urea breath test. RESULTS: Urea breath tests were requested on 249 patients; clinical notes and follow-up interview data were available for 207 patients (83%). The urea breath test was positive for 89 patients (43%); 70 were referred for endoscopy and peptic ulcer disease was found in 33 (47%). The urea breath test was negative for 118 patients; 14 were follow-up tests after previous H.pylori treatment. For the 104 patients with dyspepsia, a negative test and no previous treatment, 42% had 1 or more previous investigations for dyspepsia and 66% had dyspepsia symptoms for more than one year. During follow-up, 21 patients had endoscopy. Dyspepsia symptom scores were significantly lower at follow-up (p < 0.01). Using a global assessment, 66% had fewer symptoms, 22% same and 12% had more symptoms. The symptom improvement was greater if the duration of symptoms was less than one year (p < 0.05). Medication use did not change significantly. Twelve patients were dissatisfied with management; most of these would have preferred endoscopy. CONCLUSIONS: A negative urea breath test appears to have some reassurance value. The use of the urea breath test as initial assessment for dyspespia may prevent the need for some endoscopy. Further controlled studies of breath testing compared with early endoscopy are required.     

A real-time neural system for color constancy

A neural network approach to the problem of color constancy is presented. Various algorithms based on Land's retinex theory are discussed with respect to neurobiological parallels, computational efficiency, and suitability for VLSI implementation. The efficiency of one algorithm is improved by the application of resistive grids and is tested in computer simulations; the simulations make clear the strengths and weaknesses of the algorithm. A novel extension to the algorithm is developed to address its weaknesses. An electronic system that is based on the original algorithm and that operates at video rates was built using subthreshold analog CMOS VLSI resistive grids. The system displays color constancy abilities and qualitatively mimics aspects of human color perception.     

Variable Resolution Discretization in Optimal Control

The problem of state abstraction is of central importance in optimal control, reinforcement learning and Markov decision processes. This paper studies the case of variable resolution state abstraction for continuous time and space, deterministic dynamic control problems in which near-optimal policies are required. We begin by defining a class of variable resolution policy and value function representations based on Kuhn triangulations embedded in a kd-trie. We then consider top-down approaches to choosing which cells to split in order to generate improved policies. The core of this paper is the introduction and evaluation of a wide variety of possible splitting criteria. We begin with local approaches based on value function and policy properties that use only features of individual cells in making split choices. Later, by introducing two new non-local measures, influence and variance, we derive splitting criteria that allow one cell to efficiently take into account its impact on other cells when deciding whether to split. Influence is an efficiently-calculable measure of the extent to which changes in some state effect the value function of some other states. Variance is an efficiently-calculable measure of how risky is some state in a Markov chain: a low variance state is one in which we would be very surprised if, during any one execution, the long-term reward attained from that state differed substantially from its expected value, given by the value function.The paper proceeds by graphically demonstrating the various approaches to splitting on the familiar, non-linear, non-minimum phase, and two dimensional problem of the Car on the hill. It then evaluates the performance of a variety of splitting criteria on many benchmark problems, paying careful attention to their number-of-cells versus closeness-to-optimality tradeoff curves.     

面料设计指导

软结构Soft construct 有一点是毋庸质疑的：10／11秋冬将强调形体。我们需要值得信赖的、稳定的框架结构。然而当设计灵感受到圆润而具亲和力的自然形状的影响时,怎样保证外观的与众不同呢？我们在城市花园和林地等有限的环境中所目击的自然景观,由于特有的环境特点（在城市中）而具备了建筑般的结构感。     

Determination of the complete set of shaking force and shaking moment balanced planar four-bar linkages

A mechanism is said to be force balanced if, for any arbitrary motion, it does not apply reaction forces on the base. Moreover, if it does not apply torques on the base, the mechanism is said to be moment balanced or dynamically balanced. In this paper, a new method to determine the complete set of force and moment balanced planar four-bar linkages is presented. Using complex variables to model the kinematics of the linkage, the force and moment balancing constraints are written as algebraic equations over complex variables and joint angular velocities. Using polynomial division, necessary and sufficient conditions for the balancing of planar four-bar linkages are derived.     

In situ optical variability and relationships in the Santa Barbara Channel: implications for remote sensing

Relationships and variability of bio-optical properties in coastal waters are investigated. Optical proxies indicate that these coastal waters are optically complex and highly variable and are categorized as follows: (1) relatively clear and dominated by high index of refraction, biogenic particles, (2) more turbid, consisting of mostly inorganic particles and little phytoplankton, (3) extremely turbid with high concentrations of inorganic particles, and (4) more turbid and dominated by biogenic particles. We present a method, alternative to traditional remote-sensing algorithms, of classifying coastal waters [the Spectral Angle Mapper (SAM)] and utilize the SAM to successfully isolate plume conditions in time series of downwelling irradiance and total absorption coefficient. We conclude with a discussion of the use of the SAM for coastal management operations.     

Detection of deoxynivalenol in foods and indoor air using an array biosensor

Deoxynivalenol (DON), a mycotoxin produced by several Fusaruim species, is a worldwide contaminant of foods and feeds. Because of the potential dangers due to accidental or intentional contamination of foods with DON, there is a need to develop a rapid and highly sensitive method for easy identification and quantification of DON. In this study, we have developed and utilized a competitive immunoassay technique to detect DON in various food matrixes and indoor air samples using an array biosensor. A DON-biotin conjugate, immobilized on a NeutrAvidin-coated optical waveguide, competed with the DON in the sample for binding to fluorescently labeled DON monoclonal antibodies. To demonstrate a simple procedure amenable for on-site use, DON-spiked cornmeal, cornflakes, wheat, barley, and oats were extracted with methanol-water (3:1) and assayed without cleanup or preconcentration. The limits of detection ranged from 0.2 ng/mL in buffer to 50 ng/g in oats. The detection limit of DON spiked into an aqueous effluent from an air sampler was 4 ng/mL.     

Major advances associated with reproduction in dairy cattle

The purpose of this overview is to review some of the major advances in reproductive technologies, and how they may be applied to meet the challenge of enhancing reproductive efficiency in the high-producing dairy cow of the 21st century. The current population of high-producing dairy cows is considered to be subfertile, as characterized by low pregnancy rates and high rates of embryonic mortality. Coordinated systems of reproductive management have been developed based upon a thorough understanding of the endocrine, cellular, and molecular factors controlling ovarian and uterine function. These systems will partially restore herd reproductive performance. Advances in other reproductive technologies offer possibilities for wider use of superior germplasm. Technologies such as sexed semen, cloning, transgenesis, and preimplantation genetic diagnosis offer the potential to enhance the influence of superior animals on production of food for human consumption. However, at this time, additional research is needed to counteract the higher rates of embryonic and fetal mortality associated with some of these technologies. Furthermore, use of genomics, proteomics, and bioinformatics in the study of reproduction will undoubtedly provide investigators with a greater understanding of the limitations to efficient reproductive processes in the subfertile lactating dairy cow.