利用神经网络构建超声多普勒栓子信号自动检测系统

对血液中栓子的早期检测有着重要的临床诊断意义。超声多普勒技术使栓子的无损检测成为可能,但是目前的检测尚依赖于医生的手动操作和临床经验,仍缺乏可靠的自动检测系统。本文基于小波包变换和主元分析提取对栓子敏感的特征参数,并利用神经网络构建超声多普勒栓子信号的自动检测系统。仿真研究和临床实验表明:该系统有效提高了栓子检测的准确性,有望应用于临床诊断。     

利用LabVIEW构建血管生物反应器数据采集系统

对组织工程血管的参数监测在血管的培养过程中有着重要的意义。传统的仪表硬件系统能对反应器部分参数进行测量,但仍存在一些不足之处,本文通过分析确定血管生物反应器的监控参数,并利用虚拟仪器技术及LabVIEW软件开发平台构建了血管组织工程参数监测系统,该系统在实际应用中表明:系统简捷、运行稳定,能够监测血管的体外培养并达到了预定的精度要求。Labview的     

A Fully Automated High-Throughput Training System for Rodents

Addressing the neural mechanisms underlying complex learned behaviors requires training animals in well-controlled tasks, an often time-consuming and labor-intensive process that can severely limit the feasibility of such studies. To overcome this constraint, we developed a fully computer-controlled general purpose system for high-throughput training of rodents. By standardizing and automating the implementation of predefined training protocols within the animal’s home-cage our system dramatically reduces the efforts involved in animal training while also removing human errors and biases from the process. We deployed this system to train rats in a variety of sensorimotor tasks, achieving learning rates comparable to existing, but more laborious, methods. By incrementally and systematically increasing the difficulty of the task over weeks of training, rats were able to master motor tasks that, in complexity and structure, resemble ones used in primate studies of motor sequence learning. By enabling fully automated training of rodents in a home-cage setting this low-cost and modular system increases the utility of rodents for studying the neural underpinnings of a variety of complex behaviors.     

Inhibition of microRNA-34a Suppresses Epileptiform Discharges Through Regulating Notch Signaling and Apoptosis in Cultured Hippocampal Neurons

Neurochemical Research - Epilepsy is characterized by recurrent unprovoked seizures and some seizures can cause neuronal apoptosis, which is possible to make contributions to the epilepsy...     

Automated Technique for the Detection of Hemagglutinins to Sheep Erythrocytes

The Technicon autoanalyzer system used for the detection of homologous human hemagglutinins has been modified for the detection of hemagglutinins to sheep red blood cells. Antibody quantitation was obtained by plotting the optical density (OD) readings of peak heights of a serially diluted reference serum versus the serum dilutions. When the OD of the peak height of an unknown sample fell within the linear portion of the plot, a direct determination of the antibody titer was made. If the OD of the sample fell outside the linear portion, dilutions of the sample were carried out until a direct reading could be made. Assay by this method of at least 140 samples was possible within a day. Titers obtained with the autoanalyzer agreed very closely with those obtained by manual titration.     

Automated Detection of Haemophilus influenzae

Addition of heme (X factor) and pyridine nucleotide (V factor) to the medium permits rapid growth of Haemophilus influenzae, with evolution of easily detectable amounts of (14)CO(2). Radiometric media containing X and V factor should be used when evaluating clinical specimens which might contain Haemophilus species.     

A Loop Material Flow System Design for Automated Guided Vehicles

We develop an exact integer programming formulation to design a loop material flow system for unit-load automated guided vehicles. The model simultaneously determines both the design of the unidirectional loop flow pattern and the location of the pickup and delivery stations. The objective is to minimize the total loaded-vehicle trip distances. To solve the problem, we concentrate on developing a better formulation for the LP subproblem, preprocessing the problem, identifying the appropriate set of LP/IP routines, analyzing the mathematical properties of the problem, and developing an intelligent branch and bound solution procedure.     

A System for Automated Bacterial (genome) Integrated Annotation--SABIA

A web-based software suite, SABIA (System for Automated Bacterial Integrated Annotation), is described that provides a comprehensive computational support for the assembly and annotation of whole bacterial genomes from the data derived from sequencing projects. AVAILABILITY: Both SABIA and supplementary materials are available at http://www.sabia.lncc.br     

The Downregulation of Truncated TrkB Receptors Modulated by MicroRNA-185 Activates Full-Length TrkB Signaling and Suppresses the Epileptiform Discharges in Cultured Hippocampal Neurons

Neurochemical Research - Epilepsy is a common neurological disorder characterised by occurrence of spontaneous recurrent epileptiform discharges (SREDs) in neurons. The cellular mechanisms that...     

外源性锌离子对大鼠海马切片癫痫样放电的起源、传播与频率特性的调节作用

本研究采用多电极记录技术,在离体条件下研究外源性锌离子(Zn2+)对无镁人工脑脊液诱导的Sprague-Dawley大鼠海马切片癫痫样放电的起源、传播与频率特性的调节作用。结果表明:1μmol/L和100μmol/L的Zn2+作用于海马切片,不改变海马切片上癫痫样放电的起始位置,但能够降低癫痫样放电顺行和逆行两个方向的传播速度,并改变癫痫样放电不同频率范围成分所占的比例。以上结果提示,1μmol/L和100μmol/L的Zn2+可以对海马切片上的癫痫样放电起到调节作用,减慢癫痫样放电在网络中的传播速度,同时,可能对神经元放电活动起到去同步化的作用。     

An Automated Blur Detection Method for Histological Whole Slide Imaging

Whole slide scanners are novel devices that enable high-resolution imaging of an entire histological slide. Furthermore, the imaging is achieved in only a few minutes, which enables image rendering of large-scale studies involving multiple immunohistochemistry biomarkers. Although whole slide imaging has improved considerably, locally poor focusing causes blurred regions of the image. These artifacts may strongly affect the quality of subsequent analyses, making a slide review process mandatory. This tedious and time-consuming task requires the scanner operator to carefully assess the virtual slide and to manually select new focus points. We propose a statistical learning method that provides early image quality feedback and automatically identifies regions of the image that require additional focus points.     

phenoSeeder - A Robot System for Automated Handling and Phenotyping of Individual Seeds

The enormous diversity of seed traits is an intriguing feature and critical for the overwhelming success of higher plants. In particular, seed mass is generally regarded to be key for seedling development but is mostly approximated by using scanning methods delivering only two-dimensional data, often termed seed size. However, three-dimensional traits, such as the volume or mass of single seeds, are very rarely determined in routine measurements. Here, we introduce a device named phenoSeeder, which enables the handling and phenotyping of individual seeds of very different sizes. The system consists of a pick-and-place robot and a modular setup of sensors that can be versatilely extended. Basic biometric traits detected for individual seeds are two-dimensional data from projections, three-dimensional data from volumetric measures, and mass, from which seed density is also calculated. Each seed is tracked by an identifier and, after phenotyping, can be planted, sorted, or individually stored for further evaluation or processing (e.g. in routine seed-to-plant tracking pipelines). By investigating seeds of Arabidopsis (Arabidopsis thaliana), rapeseed (Brassica napus), and barley (Hordeum vulgare), we observed that, even for apparently round-shaped seeds of rapeseed, correlations between the projected area and the mass of seeds were much weaker than between volume and mass. This indicates that simple projections may not deliver good proxies for seed mass. Although throughput is limited, we expect that automated seed phenotyping on a single-seed basis can contribute valuable information for applications in a wide range of wild or crop species, including seed classification, seed sorting, and assessment of seed quality.Seeds play a major role in keeping continuity between successive generations (Esau, 1977) and are key for the distribution and evolution (Moles et al., 2005) of higher plants. Fertile seeds carry an embryo and may contain nutrient storage tissues in cotyledons, endosperm, and/or perisperm, supporting germination and seedling development at early developmental stages. Although this is true for all seed plants, various traits of seeds, such as size, shape, weight, and chemical composition, can be very different between plant species or accessions. For example, the Arabidopsis (Arabidopsis thaliana) accession Cape Verde Islands was reported to yield on average 40% fewer seeds than Landsberg erecta, but they are almost twice as heavy (Alonso-Blanco et al., 1999). Considering today’s plant species, single-seed mass may vary over a range of 11.5 orders of magnitude (Moles et al., 2005). Seed mass is under strong genetic control, whereas the total number of seeds of a plant is largely affected by the environment (Paul-Victor and Turnbull, 2009). It has been demonstrated that the size, mass, and shape of Arabidopsis seeds may be regulated by brassinosteroid (Jiang et al., 2013), and it was shown recently that seed size in rice (Oryza sativa) can be influenced by the epiallele Epi-rav6 (Zhang et al., 2015). The ability of plants to switch between small and larger seeds may be understood as an adaptation to novel environments (Igea et al., 2016). However, it is still not fully understood whether, or to what extent, the variability of seed traits within plant species or genotypes has an impact on the development and further performance of a plant.When comparing biometric seed data of different dimensions such as length (one-dimensional), projected area (two-dimensional [2D]), or volume and mass (both three-dimensional [3D]), one can argue that mass is the most relevant parameter as a proxy for the amount of reserves a seed provides for the offspring. This might be true even when considering that the type of reserves, such as proteins, carbohydrates, or lipids (Rolletschek et al., 2015), and also different seed tissues, such as seed coat, embryo, or endosperm, may contribute differently to seed mass (Alonso-Blanco et al., 1999). While seed mass and time to germination (radicle protrusion) do not necessarily correlate (Norden et al., 2009), in particular under greenhouse conditions, higher seed mass may be advantageous for seedling establishment under adverse environmental conditions (Moles et al., 2005). For example, shade-tolerant species showed largely higher seed masses than cogeneric species growing in open habitats, indicating that seedlings under low-light conditions need more reserves than under good light (Salisbury, 1974). Seedlings of wild radish (Raphanus raphanistrum) emerged more likely from heavier seeds than from small seeds under field conditions but not in the greenhouse (Stanton, 1984), and for Arabidopsis, seed mass was reported to be higher in populations growing naturally at higher altitudes taken as a proxy for harsher conditions (Montesinos-Navarro et al., 2011).Seed mass can be measured individually (Stanton, 1984), but it is generally collected as an average value of batches of 50 to 1,000 seeds (Jako et al., 2001; Jofuku et al., 2005; Montesinos-Navarro et al., 2011; Tanabata et al., 2012). Alternatively, 2D scans are analyzed to determine parameters such as seed length, width, area, and perimeter length as a measure for seed size (Tanabata et al., 2012). This approach can be implemented in high-throughput facilities to obtain projected areas of seed grains combined with genome-wide association studies (Yang et al., 2014). Although projected seed area can easily be measured with a common office scanner (Herridge et al., 2011; Tanabata et al., 2012; Moore et al., 2013), it is not necessarily a precise or reliable measure of the true seed size because it may depend on the shape (Alonso-Blanco et al., 1999) and the orientation of a seed at scan (see “Results”). These issues also apply when using 2D projections to calculate length-to-width ratios as a simple shape factor (Tanabata et al., 2012). Projected seed area also has been used to calculate seed mass, assuming a fixed relationship between these parameters (de Jong et al., 2011; Herridge et al., 2011). This may hold with sufficient accuracy when averaging a large number of seeds but might be misleading when considering individual seeds.From a physical point of view, volume should be a much better proxy for mass than 2D traits. Although it has been stated that for 65 species analyzed seed masses can be compared easily with seed volumes (Moles et al., 2005), it is not clear how these seed volumes were determined. Volumes can be assessed using advanced methods such as x-ray computed tomography (CT) on fruits (Stuppy et al., 2003) or synchrotron radiation x-ray tomographic microscopy applied in paleobiological studies (e.g. on fruits and seed; Friis et al., 2014). Nuclear magnetic resonance (NMR) methods are used to measure water uptake in kidney beans (Phaseolus vulgaris) and adzuki beans (Vigna angularis; Kikuchi et al., 2006) or to estimate seed weight and content (Borisjuk et al., 2011; Rolletschek et al., 2015) rather than volumes. To our best knowledge, affordable methods to measure seed volumes directly are not achievable so far. For that reason, we have set up a volume-carving method for 3D seed shape reconstruction that is described briefly here and in more detail in a recent publication (Roussel et al., 2016).While traits derived from scanning procedures can easily be assigned to individual seeds (Herridge et al., 2011), further handling and processing of phenotyped single seeds is not as simple, in particular for tiny ones like those of Arabidopsis. The aim of this work was to develop an automated seed-handling system that can analyze single seeds of very different sizes or shapes, from Arabidopsis seeds up to barley (Hordeum vulgare) seeds or even bigger. The phenoSeeder system is designed to pick and place seeds, to achieve basic morphometric traits (one-dimensional and 2D data from projections, 3D reconstruction data, and mass) of each individual seed, and to store all analyzed seed traits in a database. Another goal is to use phenoSeeder for seed-to-plant tracking approaches and to analyze whether, or which, particular seed traits have an impact on plant development and performance under various environmental conditions. We describe the main features of the phenoSeeder technology and present results obtained with seeds of three accessions of Arabidopsis, rapeseed (Brassica napus), and barley, respectively. When analyzing the data, we focused particularly on correlations between projected seed area, seed volume, and seed mass, with the hypothesis that the respective seed volume may better correlate with mass than the projected area.     

A Physiology-Based Seizure Detection System for Multichannel EEG

Background

Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. Electroencephalogram (EEG) signals play a critical role in the diagnosis of epilepsy. Multichannel EEGs contain more information than do single-channel EEGs. Automatic detection algorithms for spikes or seizures have traditionally been implemented on single-channel EEG, and algorithms for multichannel EEG are unavailable.

Methodology

This study proposes a physiology-based detection system for epileptic seizures that uses multichannel EEG signals. The proposed technique was tested on two EEG data sets acquired from 18 patients. Both unipolar and bipolar EEG signals were analyzed. We employed sample entropy (SampEn), statistical values, and concepts used in clinical neurophysiology (e.g., phase reversals and potential fields of a bipolar EEG) to extract the features. We further tested the performance of a genetic algorithm cascaded with a support vector machine and post-classification spike matching.

Principal Findings

We obtained 86.69% spike detection and 99.77% seizure detection for Data Set I. The detection system was further validated using the model trained by Data Set I on Data Set II. The system again showed high performance, with 91.18% detection of spikes and 99.22% seizure detection.

Conclusion

We report a de novo EEG classification system for seizure and spike detection on multichannel EEG that includes physiology-based knowledge to enhance the performance of this type of system.     

Automated Detection of Actinic Keratoses in Clinical Photographs

Background

Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions.

Objective

The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible.

Methods

Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group.

Results

The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group.

Conclusions

The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face.     

Automated Detection of Infectious Disease Outbreaks in Hospitals: A Retrospective Cohort Study

Background

Detection of outbreaks of hospital-acquired infections is often based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. These rules typically focus on only a few pathogens, and they do not account for the pathogens'' underlying prevalence, the normal random variation in rates, and clusters that may occur beyond a single ward, such as those associated with specialty services. Ideally, outbreak detection programs should evaluate many pathogens, using a wide array of data sources.

Methods and Findings

We applied a space-time permutation scan statistic to microbiology data from patients admitted to a 750-bed academic medical center in 2002–2006, using WHONET-SaTScan laboratory information software from the World Health Organization (WHO) Collaborating Centre for Surveillance of Antimicrobial Resistance. We evaluated patients'' first isolates for each potential pathogenic species. In order to evaluate hospital-associated infections, only pathogens first isolated >2 d after admission were included. Clusters were sought daily across the entire hospital, as well as in hospital wards, specialty services, and using similar antimicrobial susceptibility profiles. We assessed clusters that had a likelihood of occurring by chance less than once per year. For methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), WHONET-SaTScan–generated clusters were compared to those previously identified by the Infection Control program, which were based on a rule-based criterion of three occurrences in two weeks in the same ward. Two hospital epidemiologists independently classified each cluster''s importance. From 2002 to 2006, WHONET-SaTScan found 59 clusters involving 2–27 patients (median 4). Clusters were identified by antimicrobial resistance profile (41%), wards (29%), service (13%), and hospital-wide assessments (17%). WHONET-SaTScan rapidly detected the two previously known gram-negative pathogen clusters. Compared to rule-based thresholds, WHONET-SaTScan considered only one of 73 previously designated MRSA clusters and 0 of 87 VRE clusters as episodes statistically unlikely to have occurred by chance. WHONET-SaTScan identified six MRSA and four VRE clusters that were previously unknown. Epidemiologists considered more than 95% of the 59 detected clusters to merit consideration, with 27% warranting active investigation or intervention.

Conclusions

Automated statistical software identified hospital clusters that had escaped routine detection. It also classified many previously identified clusters as events likely to occur because of normal random fluctuations. This automated method has the potential to provide valuable real-time guidance both by identifying otherwise unrecognized outbreaks and by preventing the unnecessary implementation of resource-intensive infection control measures that interfere with regular patient care. Please see later in the article for the Editors'' Summary     

A Permanent Automated Real-Time Passive Acoustic Monitoring System for Bottlenose Dolphin Conservation in the Mediterranean Sea

Within the framework of the EU Life+ project named LIFE09 NAT/IT/000190 ARION, a permanent automated real-time passive acoustic monitoring system for the improvement of the conservation status of the transient and resident population of bottlenose dolphin (Tursiops truncatus) has been implemented and installed in the Portofino Marine Protected Area (MPA), Ligurian Sea. The system is able to detect the simultaneous presence of dolphins and boats in the area and to give their position in real time. This information is used to prevent collisions by diffusing warning messages to all the categories involved (tourists, professional fishermen and so on). The system consists of two gps-synchronized acoustic units, based on a particular type of marine buoy (elastic beacon), deployed about 1 km off the Portofino headland. Each one is equipped with a four-hydrophone array and an onboard acquisition system which can record the typical social communication whistles emitted by the dolphins and the sound emitted by boat engines. Signals are pre-filtered, digitized and then broadcast to the ground station via wi-fi. The raw data are elaborated to get the direction of the acoustic target to each unit, and hence the position of dolphins and boats in real time by triangulation.     

A Partially Automated Radioligand Binding Assay System for use in Clinical and Pharmaceutical Research

Abstract

Using a Tecan robotic sample processor and IBM compatible PCs we have developed a flexible, partially automated radioligand binding assay system. It handles pipetting parameters of up to 16 saturation or competition experiments at a time with up to 24 radioligand- or competitor-concentrations in a range over 4 orders of magnitude per experiment. The system provides enough flexibility so that all pipetting parameters including different tube-, rack-sizes, sample volumina and pipetting sequences may be easily adapted to the large variety of experimental requirements in binding assays. It rationalizes and increases assay throughput (up to 70% spare of working time), improves reliance and reproducibility of results. Radioactive exposure is minimized to the time preparing the radioligand working solution and transferring the sample tubes to and from the sample processor. The system has proven effective in various investigations on binding interactions, as well as in clinical studies on receptor expression under physiologic, pathological and therapeutic conditions.     

Automated Radiometric Detection of Bacteria in 2,967 Blood Cultures

A new radiometric method for the automatic detection of bacterial growth in blood cultures has been compared with conventional methods. A total of 2,967 cultures from 1,280 patients suspected of having bacteremia were studied. A 2-ml amount of blood was inoculated into culture media in which the glucose was labeled with carbon-14. The release of (14)CO(2) by bacterial metabolism was checked hourly for 18 to 24 hr, daily for the next 2 days, and, on the 12th day, with an automated instrument. A 10-ml amount of blood was studied by conventional bacteriological techniques. In 125 cultures from 50 patients, there was bacterial growth in at least one of the routine media. Of these, the radiometric method detected 102 cultures from 40 patients. In 111 cultures from 48 patients, there was radiometric detection of bacterial growth. In all of these cultures, there was detection of bacterial growth in subcultures from the radioactive medium. Of these, the routine laboratory detected 98 cultures from 40 patients. Neither method detected all patients with bacteremia. Among the 57 patients positive by one or both methods, routine techniques detected bacteria in 87% and the radiometric method detected bacteria in 85%. Seventy per cent of the cultures were detected first by the radiometric method, 65% on the day of inoculation. Our results suggest that the radiometric method is faster than conventional techniques and comparable in accuracy. Its great advantage is that it is simple, automatic, and can be extended to automatic detection of bacterial sensitivity to antibiotics.     

Automated System for Single Molecule Fluorescence Measurements of Surface-immobilized Biomolecules

Fluorescence Resonance Energy Transfer (FRET) microscopy has been widely used to study the structure and dynamics of molecules of biological interest, such as nucleic acids and proteins. Single molecule FRET (sm-FRET) measurements on immobilized molecules permit long observations of the system -effectively until both dyes photobleach- resulting in time-traces that report on biomolecular dynamics with a broad range of timescales from milliseconds to minutes. To facilitate the acquisition of large number of traces for statistical analyses, the process must be automated and the sample environment should be tightly controlled over the entire measurement time (~12 hours). This is accomplished using an automated scanning confocal microscope that allows the interrogation of thousands of single molecules overnight, and a microfluidic cell that permits the controlled exchange of buffer, with restricted oxygen content and maintains a constant temperature throughout the entire measuring period. Here we show how to assemble the microfluidic device and how to activate its surface for DNA immobilization. Then we explain how to prepare a buffer to maximize the photostability and lifetime of the fluorophores. Finally, we show the steps involved in preparing the setup for the automated acquisition of time-resolved single molecule FRET traces of DNA molecules.