Analog simulation of mass transfer in droplets with turbulent internal circulation

The object of this thesis is to simulate the Handlos and Baron Model for mass transfer into droplets by using an iterative analog computer in order to obtain eigenvalue and other parameters in a series solution. The eigenvalues λn calculated in this work are compared with the results obtained by Wellek-Skelland using a variational technique and by Patel using numerical approaches on the digital computer. From the analytical series solution, one can calculate the fraction of solute extracted in the droplets as a function of droplet contact time. PACTOLUS, a digital-analog simulator, provides a check on the validity of analog simulation. The PACTOLUS simulation confirmed the results obtained from the analog simulation --Abstract, page i

Semiparametric and Additive Model Selection Using an Improved Akaike Information Criterion

An improved AIC-based criterion is derived for model selection in general smoothing-based modeling, including semiparametric models and additive models. Examples are provided of applications to goodness-of-fit, smoothing parameter and variable selection in an additive model and semiparametric models, and variable selection in a model with a nonlinear function of linear terms.Statistics Working Papers Serie

Score Tests for the Single Index Model

The single index model is a generalization of the linear regression model with E(y|x) = g, where g is an unknown function. The model provides a flexible alternative to the linear regression model while providing more structure than a fully nonparametric approach. Although the fitting of single index models does not require distributional assumptions on the error term, the properties of the estimates depend on such assumptions, as does practical application of the model. In this article score tests are derived for three potential misspecifications of the single index model: heteroscedasticity in the errors, autocorrelation in the errors, and the omission of an important variable in the linear index. These tests have a similar structure to corresponding tests for nonlinear regression models. Monte Carlo simulations demonstrate that the first two tests hold their nominal size well and have good power properties in identifying model violations, often outperforming other tests. Testing for the need for additional covariates can be effective, but is more difficult. The score tests are applied to three real datasets, demonstrating that the tests can identify important model violations that affect inference, and that approaches that do not take model misspecifications into account can lead to very different results.Statistics Working Papers Serie

Tobit Model Estimation and Sliced Inverse Regression

It is not unusual for the response variable in a regression model to be subject to censoring or truncation. Tobit regression models are a specific example of such a situation, where for some observations the observed response is not the actual response, but rather the censoring value (often zero), and an indicator that censoring (from below) has occurred. It is well-known that the maximum likelihood estimator for such a linear model (assuming Gaussian errors) is not consistent if the error term is not homoscedastic and normally distributed. In this paper we consider estimation in the Tobit regression context when those conditions do not hold, as well as when the true response is an unspecified nonlinear function of linear terms, using sliced inverse regression (SIR). The properties of SIR estimation for Tobit models are explored both theoretically and based on Monte Carlo simulations. It is shown that the SIR estimator has good properties when the usual linear model assumptions hold, and can be much more effective than other estimators when they do not. An example related to household charitable donations demonstrates the usefulness of the estimator.Statistics Working Papers Serie

An Automatically Tuning Intrusion Detection System

An intrusion detection system (IDS) is a security layer used to detect ongoing intrusive activities in information systems. Traditionally, intrusion detection relies on extensive knowledge of security experts, in particular, on their familiarity with the computer system to be protected. To reduce this dependence, various data-mining and machine learning techniques have been deployed for intrusion detection. An IDS is usually working in a dynamically changing environment, which forces continuous tuning of the intrusion detection model, in order to maintain sufficient performance. The manual tuning process required by current systems depends on the system operators in working out the tuning solution and in integrating it into the detection model. In this paper, an automatically tuning IDS (ATIDS) is presented. The proposed system will automatically tune the detection model on-the-fly according to the feedback provided by the system operator when false predictions are encountered. The system is evaluated using the KDDCup\u2799 intrusion detection dataset. Experimental results show that the system achieves up to 35% improvement in terms of misclassification cost when compared with a system lacking the tuning feature. If only 10% false predictions are used to tune the model, the system still achieves about 30% improvement. Moreover, when tuning is not delayed too long, the system can achieve about 20% improvement, with only 1.3% of the false predictions used to tune the model. The results of the experiments show that a practical system can be built based on ATIDS: system operators can focus on verification of predictions with low confidence, as only those predictions determined to be false will be used to tune the detection model

FRET-Based Localization of Fluorescent Protein Insertions Within the Ryanodine Receptor Type 1

Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET) measurements were used to localize green fluorescent protein (GFP) insertions within the ryanodine receptor type 1 (RyR1), a large intracellular Ca2+ release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length His-tagged GFP-RyR1 fusion constructs were created, expressed in human embryonic kidney (HEK)-293T cells and then complexed with Cy3NTA, a His-tag specific FRET acceptor. FRET efficiency values measured from each GFP donor to Cy3NTA bound to each His tag acceptor site were converted into intermolecular distances and the positions of each inserted GFP were then triangulated relative to a previously published X-ray crystal structure of a 559 amino acid RyR1 fragment. We observed that the chromophoric centers of fluorescent proteins inserted into RyR1 can be located as far as 45 Å from their insertion sites and that the fused proteins can also be located in internal cavities within RyR1. These findings should prove useful in interpreting structural results obtained in cryo EM maps using fusions of small fluorescent proteins. More accurate point-to-point distance information may be obtained using complementary orthogonal labeling systems that rely on fluorescent probes that bind directly to amino acid side chains

The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998–2008: a nation-wide cancer registry-based study

BACKGROUND: To investigate the incidence of gastrointestinal stromal tumors (GISTs) in Taiwan and the impact of imatinib on the overall survival (OS) of GIST patients. METHODS: GISTs were identified from the Taiwan Cancer Registry (TCR) from 1998 to 2008. The age-adjusted incidence rates and the observed OS rates were calculated. Cox proportional hazards models were applied to examine the mortality risk in three time periods (1998–2001, 2002–2004, 2005–2008) according to the application and availability of imatinib. RESULTS: From 1998 to 2008, 2,986 GISTs were diagnosed in Taiwan. The incidence increased from 1.13 per 100,000 in 1998 to 1.97 per 100,000 in 2008. The most common sites were stomach (47-59%), small intestine (31-38%), and colon/rectum (6-9%). The 5-year observed OS was 66.5% (60.3% for men, 74.2% for women, P < .0001). GISTs in the stomach had a better 5-year observed OS (69.4%) than those in the small intestine (65.1%) (P < .0001). The outcome of GIST improved significantly after the more widespread use of imatinib; the 5-year observed OS increased from 58.9% during 1998–2001 to 70.2% during 2005–2008 (P < .0001). Younger age, female sex, stomach location, and later diagnostic years were independent predictors of a better survival. CONCLUSIONS: The incidence of GIST has been increasing in Taiwan, partially due to the advancement of diagnostic technology/method and the increased awareness by physicians. The outcome of GIST has improved significantly with the availability and the wider use of imatinib

The Pharmacological Effects and Pharmacokinetics of Active Compounds of Artemisia capillaris.

Artemisia capillaris Thunb. (A.capillaris, Yin-Chen in Chinese) is a traditional medicinal herb with a wide spectrum of pharmacological properties ranging from effects against liver dysfunction to treatments of severe cirrhosis and cancer. We used relevant keywords to search electronic databases, including PubMed, Medline, and Google Scholar, for scientific contributions related to this medicinal herb and the pharmacokinetics of its components. The pharmaceutical effects of A.capillaris contribute to the treatment not only of viral hepatitis, cirrhosis, and hepatocellular hepatoma, but also metabolic syndrome, psoriasis, and enterovirus in the clinic. The bioactive compounds, including scoparone, capillarisin, scopoletin, and chlorogenic acid, exhibit antioxidant, anti-inflammatory, antisteatotic, antiviral, and antitumor properties, reflecting the pharmacological effects of A.capillaris. The pharmacokinetics of the main bioactive compounds in A. capillaris can achieve a maximum concentration within 1 hour, but only chlorogenic acid has a relatively long half-life. Regarding the use of the A. capillaris herb by health professionals to treat various diseases, the dosing schedule of this herb should be carefully considered to maximize therapeutic outcomes while lessening possible side effects

Selection of chromosomal DNA libraries using a multiplex CRISPR system.

The directed evolution of biomolecules to improve or change their activity is central to many engineering and synthetic biology efforts. However, selecting improved variants from gene libraries in living cells requires plasmid expression systems that suffer from variable copy number effects, or the use of complex marker-dependent chromosomal integration strategies. We developed quantitative gene assembly and DNA library insertion into the Saccharomyces cerevisiae genome by optimizing an efficient single-step and marker-free genome editing system using CRISPR-Cas9. With this Multiplex CRISPR (CRISPRm) system, we selected an improved cellobiose utilization pathway in diploid yeast in a single round of mutagenesis and selection, which increased cellobiose fermentation rates by over 10-fold. Mutations recovered in the best cellodextrin transporters reveal synergy between substrate binding and transporter dynamics, and demonstrate the power of CRISPRm to accelerate selection experiments and discoveries of the molecular determinants that enhance biomolecule function