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Following the growing popularity of Airbnb, much research has been conducted, while limited attention has been devoted to the spatial patterns of Airbnb, which can provide insights into the geographic logistics of Airbnb supply. To fill this gap, this study investigates the spatial patterns of Airbnb supply in the city of Los Angeles during the years 2014 to 2019. This study integrates exploratory spatial data analysis (ESDA) and explores the determinants of spatial patterns of Airbnb supply in 2019 with spatial regression models. The results of the spatial autocorrelation analysis show that the spatial distribution of Airbnb supply in Los Angeles is positively clustered and shows a geographical logistical trend over time. The distribution of Airbnb supply has a clear center–periphery pattern. The high–high (HH) clusters are concentrated in the central areas of Los Angeles, while low–low (LL) clusters predominate in the peripheral areas. In addition, with spatial regression analysis, several determinants affecting the spatial distribution of Airbnb supply are identified such as resident population, housing units, income, rent, point of interest (POI), and the distance to Hollywood. Further implications of the findings are discussed below.

This study used a consumer survey to identify resources and services that are important to farmers’ market (FM) shoppers. The questionnaire was distributed onsite in six FMs in Tennessee, and a total of 506 FM shoppers responded. The most important resources and services in terms of a shopper’s decision to visit a FM are identified as supporting local food, quality, friendly, and diverse vendors, and food origin. Multivariate analysis of variance (MANOVA) reveals that convenience and close to home are more important to women, price is more important to younger and lower-income shoppers, while quality, convenience, interaction with farmers/producers, and food origin are more important to older shoppers. Content analysis indicated that FM shoppers were impressed with FM atmosphere and liked the quality, variety, and convenience provided by FMs, but disliked not having clear information such as product labels and websites.

Current research investigating the accommodation experience in the sharing economy in China is limited, especially from a cross-cultural perspective. To fill this gap, this study examined the accommodation experience of Airbnb guests using text-mining techniques and compared the accommodation experience perception between two culturally different groups: domestic Chinese and foreign English-speaking Airbnb guests. The results showed that the two groups shared eight common dimensions, including &ldquo, Convenience/Location&rdquo, &ldquo, Amenities&rdquo, Feel at home&rdquo, Check-in/out&rdquo, Experience&rdquo, Availability/Transportation&rdquo, Host&rdquo, and &ldquo, Style/Decoration&rdquo, However, there are differences in the relative importance of each dimension of accommodation experience between the domestic and foreign Airbnb guests. For example, the foreign guests more often mentioned homeliness, location/convenience, and availability/transportation, while the domestic guests showed greater interest in check-in procedures and style/decoration. Additionally, the two groups have several unique dimensions. The dimensions unique to foreign guests are &ldquo, Recommendation&rdquo, Booking flexibility&rdquo, while the dimensions unique to domestic guests are &ldquo, Revisit&rdquo, Cleanliness&rdquo, This study provides both theoretical and practical implications for peer-to-peer accommodation hosts and platforms. For example, Airbnb hosts can improve the satisfaction of Airbnb guests by improving several common extracted topics (e.g., amenities quality and host response) and the fact that foreign guests care more about homeliness, while domestic guests pay more attention to the check-in process and house design and decoration.

Given the importance of booth attractiveness at trade expositions, this study sets out to develop a scale measuring booth attractiveness (Study 1) and to examine its effectiveness in motivating attendees’ purchasing behavior (Study 2). Study 1 includes three steps: (1) item generation through a thorough review of the literature, focus group, and comments from experts, (2) item purification with exploratory factor analysis using 122 samples, and (3) reevaluating items with confirmatory factor analysis using 129 samples. A six-dimensional scale of booth attractiveness was developed in Study 1. Based on the theory of mental budgeting, Study 2 was conducted to examine the effects of booth attractiveness on the mechanism of attendees’ purchasing behavior using 323 samples. Results of Study 2 suggest that booth attractiveness could directly motivate impulse buying or indirectly through mental budgeting. Impulse buying, then, results in post-purchase guilt and anticipated satisfaction. Meanwhile, postpurchase guilt reduces anticipated satisfaction.

Flood is the worst weather-related hazard in Taiwan because of steep terrain and storm. The tropical storm often results in disastrous flash flood. To provide reliable forecast of water stages in rivers is indispensable for proper actions in the emergency response during flood. The river hydraulic model based on dynamic wave theory using an implicit finite-difference method is developed with river roughness updating for flash flood forecast. The artificial neural network (ANN) is employed to update the roughness of rivers in accordance with the observed river stages at each time-step of the flood routing process. Several typhoon events at Tamsui River are utilized to evaluate the accuracy of flood forecasting. The results present the adaptive n-values of roughness for river hydraulic model that can provide a better flow state for subsequent forecasting at significant locations and longitudinal profiles along rivers.

A computer-aided diagnostic system for colonoscopic imaging has been developed to classify colorectal polyps by type. The modules of the proposed system include image enhancement, feature extraction, feature selection and polyp classification. Three hundred sixty-five images (214 with hyperplastic polyps and 151 with adenomatous polyps) were collected from a branch of a medical center in central Taiwan. The raw images were enhanced by the principal component transform (PCT). The features of texture analysis, spatial domain and spectral domain were extracted from the first component of the PCT. Sequential forward selection (SFS) and sequential floating forward selection (SFFS) were used to select the input feature vectors for classification. Support vector machines (SVMs) were employed to classify the colorectal polyps by type. The classification performance was measured by the Az values of the Receiver Operating Characteristic curve. For all 180 features used as input vectors, the test data set yielded Az values of 88.7%. The Az value was increased by 2.6% (from 88.7% to 91.3%) and 4.4% (from 88.7% to 93.1%) for the features selected by the SFS and the SFFS, respectively. The SFS and the SFFS reduced the dimension of the input vector by 57.2% and 73.8%, respectively. The SFFS outperformed the SFS in both the reduction of the dimension of the feature vector and the classification performance. When the colonoscopic images were visually inspected by experienced physicians, the accuracy of detecting polyps by types was around 85%. The accuracy of the SFFS with the SVM classifier reached 96%. The classification performance of the proposed system outperformed the conventional visual inspection approach. Therefore, the proposed computer-aided system could be used to improve the quality of colorectal polyp diagnosis.

We propose an automatic hybrid image segmentation model that integrates the statistical expectation maximization (EM) model and the spatial pulse coupled neural network (PCNN) for brain magnetic resonance imaging (MRI) segmentation. In addition, an adaptive mechanism is developed to fine tune the PCNN parameters. The EM model serves two functions: evaluation of the PCNN image segmentation and adaptive adjustment of the PCNN parameters for optimal segmentation. To evaluate the performance of the adaptive EM-PCNN, we use it to segment MR brain image into gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The performance of the adaptive EM-PCNN is compared with that of the non-adaptive EM-PCNN, EM, and Bias Corrected Fuzzy C-Means (BCFCM) algorithms. The result is four sets of boundaries for the GM and the brain parenchyma (GM+WM), the two regions of most interest in medical research and clinical applications. Each set of boundaries is compared with the golden standard to evaluate the segmentation performance. The adaptive EM-PCNN significantly outperforms the non-adaptive EM-PCNN, EM, and BCFCM algorithms in gray mater segmentation. In brain parenchyma segmentation, the adaptive EM-PCNN significantly outperforms the BCFCM only. However, the adaptive EM-PCNN is better than the non-adaptive EM-PCNN and EM on average. We conclude that of the three approaches, the adaptive EM-PCNN yields the best results for gray matter and brain parenchyma segmentation.

The kinetics of the isochronal austenite γ to ferrite α transformation of Fe–0·055 wt-%N alloy was investigated for cooling rates in the range of 5–15 K min− by high resolution dilatometry. In accordance with thermodynamic characteristics of γ→α transformation investigated in this study and previous kinetic theory, a Johnson–Mehl–Avrami–Kologoromov (JMAK)-like approach for the kinetics of isochronal phase transformations was developed that incorporates three overlapping processes: site saturation nucleation, alternate growth modes (transition from interface- to diffusion-controlled growth) as well as impingement for random distribution nuclei. The JMAK-like approach has been employed to fit the experimental results, and the fitting results show that the γ→α transformation of Fe–0·055 wt-%N alloy does have two stages: a first, short interface-controlled growth stage and a second, long diffusion-controlled growth stage. In addition, soft impingement effect has been recognised to become serious in th...

Simulated annealing (SA) is known to be one of the most efficient heuristic algorithms for complex nonlinear optimization problems. However, it suffers from the large amount of computing time required to obtain a near-optimal solution. To overcome this problem, a parallel version of the algorithm is worthy of evaluation. This report presents a Parallel Adaptive Simulated Annealing (PASA) algorithm for computer-aided measurement in locating the activation area of functional magnetic resonance images (fMRI). The parallel paradigm is based on a coarse-grained (or island) model performed on a cluster of PCs by using a message-passing interface (MPI) for the information interchange. Performance of this approach is evaluated by computing the receiver operating characteristic (ROC) area and Jaccard similarity. Experimental results show that the coarse-grained PASA outperforms other approaches and can also efficiently and consistently extract activities with different contrast-to-noise ratios and activation-area sizes.

This study was nvestigate the effect of different display media of mammographic images (visual display terminals [VDT] and a view-box) on the display-media diagnostic performance and subjective prefereness of radiologists according to differing professional experience. This study included 30 patients and 120 images (four images per patient) who underwent digital mammography at Changhua Christian Hospital in central Taiwan, using the General Electric digital mammography system. Biopsies indicated that 15 patients had microcalcifications, while the other 15 patients were normal. In this experiment, the interpreting physicians included of five males and one female. The physicians were divided into three groups (attending physicians, radiology residents and interns) according to varying levels of experience and expertise in digital mammography. Three different display media were used, including a medical monitor (BARCO V9601100), a general monitor (SAMSUNG 191T), and an unmasked view-box. A signal-blind test based on these three different display media was used to evaluate the six radiologists' microcalcifications-diagnosis performance and to obtain the area-under-curve (AUC) values from the receiver-operating-characteristic (ROC) curves, sensitivity, and specificity. A five-point Likert-type rating scale was used to evaluate the radiologists' subjective preference. The results of the analyses of variances showed that different professional experience settings had a significant effect on all AUC, sensitivity, and specificity. Attending and resident physicians performed significantly better on AUC, sensitivity, and specificity than interns. Different display-type settings had a significant effect on AUC and sensitivity; however, they had no significant effect on specificity. The physicians performed significantly better on AUC when the display types were a BARCO medical LCD and a SAMSUNG general LCD rather than a conventional unmasked view-box. The physicians performed significantly better on sensitivity when the display type was a BARCO medical LCD rather than a SAMSUNG general LCD or a conventional unmasked view-box. Different professional experience provided significantly different preference evaluating (F(2, 16)=6.50, p

Dynamic programming (DP) is a mathematical technique for making optimal decisions on the sequencing of interrelated problems. It has been used widely to detect borders in magnetic resonance images (MRI). MRI is noninvasive and generates clear images; however, it is impractical for manual measurement of the huge number of images generated by dynamic organs such as those of the cardiovascular system. A fast and effective algorithm is essential for on-line implementation of MRI-based computer aided measurement and diagnosis. In this paper, a branch-and-bound dynamic programming technique is applied to detect the endocardial borders of the left ventricular. The proposed branch-and-bound method drastically reduces the computational time required in conventional exhaustive search methods. Statistical tests are conducted to verify the CPU time performance of the branch-and-bound technique in comparison to the conventional exhaustive search method.

Clinical databases are continually growing and accruing more patient information. One of the challenges for managing this wealth of data is efficient retrieval and analysis of a broad range of image and non-image patient data from diverse data sources. This article describes the design and implementation of a new class of research data warehouse, neuroinformatics database system (NIDS), which will alleviate these problems for clinicians and researchers studying and treating patients with intractable temporal lobe epilepsy. The NIDS is a secured, multi-tier system that enables the user to gather, proofread, analyze, and store data from multiple underlying sources. In addition to data management, the NIDS provides several key functions including image analysis and processing, free text search of patient reports, construction of general queries, and on-line statistical analysis. The establishment of this integrated research database will serve as a foundation for future hypothesis-driven experiments, which could uncover previously unsuspected correlations and perhaps help to identify new and accurate predictors for image diagnosis.

There is an increasing need to efficiently share diverse clinical and image data among different clinics, labs, and departments of a medical center enterprise to facilitate better quality care and more effective clinical research. In this paper, we describe a web-based, federated information model as a viable technical solution with applications in medical refractory epilepsy and other neurological disorders. We describe four such online applications developed in a federated system prototype: surgical planning, image analysis, statistical data analysis, and dynamic extraction, transforming, and loading (ETL) of data from a heterogeneous collection of data sources into an epilepsy multimedia data warehouse (EMDW). The federated information system adopts a three-tiered architecture, consisting of a user-interface layer, an application logic layer, and a data service layer. We implemented two complementary federated information technologies, i.e., XML (eXtensible Markup Language) and CORBA (Common Object Request Broker Architecture), in the prototype to enable multimedia data exchange and brain images transmission. The preliminary results show that the federated prototype system provides a uniform interface, heterogeneous information integration and efficient data sharing for users in our institution who are concerned with the care of patients with epilepsy and who pursure research in this area.

In short axis left ventricular MR images, endocardial borders are the major parameters in evaluation of cardiovascular functions such as end diastolic volume, end systolic volume, and ejection fraction. Functional analysis captures the dynamic behavior of the cardiovascular system as revealed by the movement of the endocardial borders over time. Because of the huge number of MR images, an effective computerized tool is required for real time applications. One of the widely used automatic border detection algorithm-dynamic programming-generates zigzag borderlines, which lead to measurement errors. This paper surveys the performance of the wavelet adaptive filter, the snake, and the medial filter in smoothing over the zigzag borders generated by dynamic programming. Statistical analysis of two hundred and sixty four images from sixteen subjects show that all three algorithms can reduce the border line errors in terms of Hausdorff distance and border area error; however, only the wavelet adaptive filter is effective in providing the physiological measurements such as ejection fraction, end systolic volume and end diastolic volume.

Wavelet-based pattern classification methods, which have been used extensively in imaging applications, have barely been explored in machining monitoring and diagnostic systems. Although the engineering literature recognizes wavelet methodologies as a practical alternative to the FFT for signals containing nonstationary information, most of it concerns only the Wavelet Transform. The WT can detect time-localized pre-failure machining signals, but it leaves two practical questions unanswered. The first is how to post-process the wavelet coefficients (the WT output) to extract the needed information. The second is what method to use for 'scanning' the signal with overlapping windows, since the WT covers only a short segment of the input signal. The Matching Pursuit (MP) approach handles both of these problems in a straightforward manner. As a pattern recognition method, it is adaptable to specific machining diagnostic tasks and eliminates the post-processing requirement. The scanning technique is likewise b...

During cylindrical grinding processes, two types of regenerative chatter— workpiece and grinding wheel—may degrade the accuracy of the surface finish. To maintain productivity and quality, a closed-loop vibration control system should be provided for the grinding system. An algorithm for automated classification of chatter by type is essential in developing such a system. In this paper, an entropy technique is introduced to classify regenerative chatter by type based on the vibration spectrum, the performance of this scheme is compared with that of a neural network approach. Experimental results show that the entropy system yields the same performance as the neural network. Because the entropy technique has several practical advantages, it may be judged preferable for monitoring of cylindrical grinding chatter. This paper also describes the theoretical background of the entropy technique in classifying regenerative chatter.

Since microcalcifications in X-ray mammograms are the primary indicator of breast cancer, detection of microcalcifications is central to the development of an effective diagnostic system. This paper proposes a two-stage detection procedure. In the first stage, a data driven, closed form mathematical model is used to calculate the location and shape of suspected microcalcifications. When tested on the Nijmegen University Hospital (Netherlands) database, data analysis shows that the proposed model can effectively detect the occurrence of microcalcifications. The proposed mathematical model not only eliminates the need for system training, but also provides information on the borders of suspected microcalcifications for further feature extraction. In the second stage, 61 features are extracted for each suspected microcalcification, representing texture, the spatial domain and the spectral domain. From these features, a sequential forward search (SFS) algorithm selects the classification input vector, which consists of features sensitive only to microcalcifications. Two types of classifiers-a general regression neural network (GRNN) and a support vector machine (SVM)--are applied, and their classification performance is compared using the Az value of the Receiver Operating Characteristic curve. For all 61 features used as input vectors, the test data set yielded Az values of 97.01% for the SVM and 96.00% for the GRNN. With input features selected by SFS, the corresponding Az values were 98.00% for the SVM and 97.80% for the GRNN. The SVM outperformed the GRNN, whether or not the input vectors first underwent SFS feature selection. In both cases, feature selection dramatically reduced the dimension of the input vectors (82% for the SVM and 59% for the GRNN). Moreover, SFS feature selection improved the classification performance, increasing the Az value from 97.01 to 98.00% for the SVM and from 96.00 to 97.80% for the GRNN.

MRI is noninvasive and generates clear images, giving it great potential as a diagnostic instrument. However, current methods of image analysis are too time-consuming for dynamic systems such as the cardiovascular system. Since dynamic imagery generate a huge number of images, a computer aided machine vision diagnostic tool is essential for implementing MRI-based measurement. In this paper, a wavelet-based image technique is applied to enhance left ventricular endocardial and epicardial profiles as the preprocessor for a dynamic programming-based automatic border detection algorithm. Statistical tests are conducted to verify the performance of the enhancement technique by comparing borders manually drawn with 1. borders generated from the enhanced images, and 2. borders generated for the original images.

The gray levels of gastric sonogram images are usually concentrated at the zero end of the spectrum, making the image too low in contrast and too dark for the naked eye. Though histogram equalization can enhance the contrast by redistributing the gray levels, it has the drawback that it reduces the information in the processed image. In this paper, a wavelet-based enhancement algorithm post-processor is used to further enhance the image and compensate for the information loss during histogram equalization. Experimental results show that the wavelet-based enhancement algorithm can enhance the contrast and significantly increase the informational entropy of the image. Because the combination of the histogram equalization and wavelet approach can dramatically increase the contrast and maintain information rate in gastric sonograms, it has the potential to improve clinical diagnosis and research.

Mammalian tissues contain protein carboxyl methyltransferases that catalyze the transfer of methyl groups from S-adenosylmethionine to the free carboxyl groups of D-aspartyl or L-isoaspartyl residues (EC 2.1.1.77). These enzymes have been postulated to play a role in the repair and/or degradation of spontaneously damaged proteins. We have now characterized a similar activity from Escherichia coli that recognizes L-isoaspartyl-containing peptides as well as protein substrates such as ovalbumin. The enzyme was purified by DEAE-cellulose, hydroxylapatite, Sephadex G-100, polyaspartate, and reversed-phase chromatography and was shown to consist of a single 24-kDa polypeptide chain. The sequence determined for the N-terminal 39 residues was used to design an oligonucleotide probe that allowed the precise localization of its structural gene (pcm) on the physical map of the E. coli chromosome at 59 min. Transformation of E. coli cells with a plasmid containing DNA from this region results in a 3-4-fold overproduction of enzyme activity. The nucleotide sequence determined for the pcm gene and its flanking regions was used to deduce a mature amino acid sequence of 207 residues with a calculated molecular weight of 23,128. This sequence shows 30.8% sequence identity with the human L-isoaspartyl/D-aspartyl methyltransferase and suggests that this enzyme catalyzes a fundamental reaction in both procaryotic and eucaryotic cells.

The derivation and experimental verification of a unified mathematical model for the estimation of drug release rate from drug-polymer composite tablets are presented. Cylindrical coordinates are utilized in the solution of the diffusion equation for a three-dimensional system. The model is applicable to tablets that range from the shape of a flat disk (radius greater than thickness) to that of a cylindrical rod (radius less than thickness). The general solution for the fraction of drug released at a time t is (see article). This approach to a three-dimensional system, utilizing cylindrical coordinates, presents a comprehensive method for the estimation of drug release rates from sustained release tablets with drug distributed homogeneously throughout a polymer matrix. The calculated and experimental drug diffusion rate of pyrimethamine from pyrimethamine-silicone rubber composite tablets that range in shape from that of a disk to a cylinder, and of hydrocortisone from EVA, polycaprolactone, and PVA terpolymer, are compared.

The lifespan of BDF mice with ascitic L1210 leukemia is more than doubled when they are treated with a single subcutaneously or intraperitoneally implanted sustained release cytosine arabinoside capsule. These capsules are drug-polymer composites, with dimensions of 1.0 cm in diameter and 0.15 cm in thickness, and a drug content of 17 +/- 3 mg each. Blank silicone rubber discs implanted intraperitoneally or subcutaneously in the leukemic mice produced no beneficial effects. Control healthy mice receiving the ARA-C releasing capsules continued to live with no obvious signs of drug toxicity. In vitro release of ARA-C from the discs was measured. Drug release was maintained above 20 micrograms per day for more than 35 days. ARA-C extracted from discs recovered from implant studies showed that less than 16% of the total drug content was released in vivo.

An asymptotic expansion is obtained for an incomplete beta-type integral, which arises in the study of probabilities of large deviations. The expansion obtained yields large deviation results for binomial, quantile, and related probabilities. Our approach is based on a generalized version of Laplace’s method.

In the literature of point estimation, the Cauchy distribution with location parameter is often cited as an example for the failure of maximum-likelihood method and hence the failure of the likelihood principle in general. Contrary to the above notion, we prove that even in this case the likelihood equation has multiple roots and that the maximum-likelihood estimator (the global maximum) remains as an asymptotically optimal estimator in the Bahadur sense. Dans la litterature de l'estimation ponctuelle, on cite souvent le cas du parametre de position d'une loi de Cauchy lorsqu'on veut donner l'exemple d'un cas ou la methode du maximum de vraisemblance ne donne pas satisfaction et, partant de la, on conclut a la nonuniversalite du principe de vraisemblance. Contrairement a cette opinion, nous montrons que dans ce cas l'equation de vraisemblance possede des racines multiples et que l'estimateur fourni par la methode du maximum de vraisemblance (le maximum global) demeure malgre tout un estimateur asymptotiquement optimal au sens de Bahadur.

Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo.

Complete regression of Walker 256 solid rat tumor was brought about by the subcutaneous implantation of a single sustained-release cyclophosphamide capsule adjacent to the tumor mass. Untreated control animals died within 3 weeks after receiving the tumor with large necrotic masses. Rats with sustained-release capsules experienced complete tumor regression within 28 days. Upon examination, the tissues around the previous tumor mass has regenerated, and no viable tumor cells could be found in the area where the previous tumor mass was. Around the implanted sustained-release cyclophosphamide capsule a fibrous sheath has developed over the 3 weeks it was in situ. This study suggests an alternate means of cytoxic drug administration in the treatment of solid tumors in experimental animals.

In the literature of point estimation, Cauchy distribution with location parameters was often cited as an example for the failure of maximum likelihood method and hence the failure of likelihood principle in general. Contrary to the above notion, we proved, even in this case that the likelihood equation has multiple roots, that the maximum likelihood estimator (the global maximum) remains as an asymptotically optimal estimator in the Bahadur sense. (Author)

Randomly bred Sprague-Dawley rats with the intramuscular form of Walker 256 tumor growing in the right thigh region were treated with sustained-release cyclophosphamide capsules as well as with cytosine arabinoside capsules. A disk-shaped caps-le was implanted subcutaneously adjacent to the tumor mass. Tumor regression, weight gain, and prolongation of lifespan were observed in animals treated with cyclophosphamide capsules of 10 mg or 20 mg total drug content each. However, the walker 256 intramuscular tumor did not respond to ARA-C capsules implanted, and the animals died at the same rate as the controls, with large ulcerated tumor masses and some metastasis. The in vitro diffusion data of ARA-C capsules is shown. Gross and histological changes associated with cyclophosphamide administered in this manner are reported.

Aneurysmal aortic tissue and the mitral valve of a patient with Marfan's syndrome were examined. Biochemical analysis of the tissue showed a qualitative and quantitative defect in alpha 2 chain production of Type I collagen. On polyacrylamide gel electrophoresis of the aortic extract, two separate bands in the alpha 2 region and an increase of the alpha 1 to alpha 2 ratio were found. Examination by electron microscopy revealed elastic fibre degeneration, helical collagen fibres, and metabolically active modified smooth muscle cells. The formation of helical collagen fibres is attributed to a defect in the development of chains and cross-links of collagen precursors produced by the hypertrophic smooth muscle cells. Elastic fibre disintegration is believed to be due to a lack of support by Type I collagen fibres, which have decreased tensile strength. A scheme for the pathogenesis of aortic aneurysm and other connective tissue abnormalities in Marfan's syndrome is proposed as follows. Type I collagen fibres have decreased tensile strength because of a defect in the alpha 2 chain biosynthesis and decreased cross-linking. Over many years the wall of the ascending aorta is subjected to cyclic stresses and it dilates. Elastic fibres disintegrate. The attempt at repair by metabolically activated modified smooth muscle cells is abortive, and rupture is likely to occur.

The daily in vitro release of hydrocortisone from composite polymer capsules is reported here for over 120 days. Increase in vinyl acetate comonomer content of the ethylene-vinyl acetate copolymer matrix brought about an increase in the diffusion rate. Variation in the initial drug content of the capsules from 40 mg to 20 mg affects the daily drug release less significantly than the variation in copolymer ratio. The correlation between vinyl acetate comonomer content and the percent crystallinity of the copolymer matrix is suggested as one of the possible major factors in controlling diffusion rate from this drug-polymer system. The diffusion constant (D) calculated was 0.212 X 10(10) cm2/sec when the copolymer carrier has 30% vinyl acetate content and 0.430 X 10(11) cm2/sec when the copolymer carrier has 20% vinyl acetate content for capsules with 20 mg initial drug content, and 0.118 X 10(-11) cm2/sec and 0.226 X 10(-11) cm2/sec, respectively, for capsules with 40 mg initial drug content.

Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo.

The rate of diffusion of pyrimethamine, a pyrimidine-based antimalarial drug, from silicone rubber is compared to the diffusion of this drug from a flexible epoxy. Specific amounts of drug were mixed into the epoxy resin prior to the addition of an aliphatic diamine curing agent in the reparation of the epoxy-drug capsules and into the silicone rubber prior to vulcanization with stannous octoate in the preparation of silicone drug capsules. These capsules, in the form of discs, were separately immersed in water which was replenished at regular time intervals. The amount of drug released was determined spectrophotometrically (λ max = 275 mμ). Silicone rubber discs with 20 mg of drug incorporated/disc showed a much higher initial release rate than epoxy discs with an equivalent amount of drug incorporated. The rate of drug release is shown to be a nonlinear function of the amount of drug initially incorporated. The amine functional groups on pyrimethamine, and the possibility of its participation in the curing of the epoxy is noted. In silicone rubber, such interaction is not expected. The addition of a silica filler to the epoxy drug mixture is associated with greater uniformity in the observed drug release rates of capsules made from the same batch of polymer drug mixture. The Shore A durometer hardness of these drug capsules are 30 and 70 for silicone rubber and epoxy, respectively.

Quantitative investigation of the rate of diffusion (in vitro) of chloroquine diphosphate, an antimalarial drug, from silicone rubber (Silastic) discs is reported here. The viscosity of the polymer is reduced to facilitate the formation of a more homogeneous drug-polymer mixture from which the discs are made. The average quantity of drug released daily from these vulcanized silicone rubber discs is measured as a function of the amount of drug initially incorporated in the polymeric mass. Discs with 9 and 36 mg of chloroquine diphosphate incorporated continue to release drug in microgram quantities for a period of over four months. The presence of low viscosity silicone fluid (20 centistokes) in the discs was found to cause no significant alteration in the drug release rate. The effect of agitation of the fluid in which the discs are immersed is also investigated. Results from samples prepared from different batches of polymer showed comparable results, indicating the rather homogeneous nature of the polymer-drug system. All samples showed high release rates during the first few days followed by much lower and more or less constant drug release on subsequent days over a period of months. Concentrations of the drug in the eluant is determined spectrophotometrically by utilizing the 220- and 343-mμ peaks of chloroquine diphosphate as well as spectrofluorometrically by measuring the percent fluorescence at 405 mμ (360-mμ excitation).

1-(p-Acetyl benzenesulfonyl)-3-cyclohexyl urea, commonly known as acetohexamide, is incorporated into prevulcanized silicone rubber. Capsules in the form of discs 1.5 cm in diameter and 0.22 cm thick, made from the drug-polymer mixtures, are shown to release the drug into water in microgram quantities for a period of over 6 months. The rate of drug release is affected by the total drug content of the capsule as well as the rate of drug removal from the surrounding medium. Capsules with 19 mg of acetohexamide incorporated per disc release 14.2% (2.69 mg) of drug in 200 days while capsules with 38 mg of drug incorporated per disc release 10.9% (4.14 mg) of drug into water during the same period. UV spectra of acetohexamide is scanned to ensure that gross structural changes have not occurred during the course of the experiment. Optical density reading at the 247-nm peak is utilized for the quantitative determination of drug released.