Interceptor

Successively issued by: Air Force. Air Defense Command; Aerospace Defense Command

Advanced precursors in marine biosynthetic study. Part 3: The biosynthesis of dichloroimines in the tropical marine sponge Stylotella aurantium

The biosynthetic origins of the dichloroimine group in the stylotellanes A and B 1,2 have been investigated by incorporation of [C-14]-labeled farnesyl isocyanide 7 and farnesyl isothiocyanate 3 into the sponge Stylotella aurantium. (C) 2002 Elsevier Science Ltd. All rights reserled.

Antitumor activity of 3-ingenyl angelate: Plasma membrane and mitochondrial disruption and necrotic cell death

Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodes-sication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rates and extended treatment schedules. Here, we describe the preclinical activity of a novel topical chemotherapeutic agent for the treatment of skin cancer, 3-ingenyl angelate (PEP005), a hydrophobic diterpene ester isolated from the plant Euphorbia peplus. Three daily topical applications of 42 nmol (18 mug) of PEP005 cured a series of s.c. mouse tumors (B16 melanoma, LK2 UV-induced squamous cell carcinoma, and Lewis lung carcinoma; it = >14 tumors/group) and human tumors (DO4 melanoma, HeLa cervical carcinoma, and PC3 and DU145 prostate carcinoma; it = >4 tumors/group) previously established (5-10 mm(3)) on C57BL/6 or Fox1(nu) mice. The treatment produced a mild, short-term erythema and eschar formation but, ultimately, resulted in excellent skin cosmesis. The LD90 for PEP005 for a panel of tumor cell lines was 180-220 muM. Electron microscopy showed that treatment with PEP005 both ill vitro (230 tot) and ill vivo (42 nmol) rapidly caused swelling of mitochondria and cell death by primary necrosis. Cr-51 release, uptake of propidium iodide, and staining with the mitochondria dye JC1, revealed that PEP005 (230 muM) treatment of tumor cells ill vitro resulted in a rapid plasma membrane perturbation and loss of mitochondrial membrane potential. PEP005 thus emerges as a new topical anti-skin cancer agent that has a novel mode of action involving plasma membrane and mitochondrial disruption and primary necrosis, ultimately resulting in an excellent cosmetic outcome.

Biosynthetic pathways to isocyanides and isothiocyanates; precursor incorporation studies on terpene metabolites in the tropical marine sponges Amphimedon terpenensis and Axinyssa n.sp.

The biosynthetic origins of the isocyanide and isothiocyanate functional groups in the marine sponge metabolites diisocyanoadociane (1), 9-isocyanopupukeanane (10) and 9- isothiocyanatopupukeanane (11) are probed by the use of [C-14]-labelled precursor experiments. Incubation of the sponge Amphimedon terpenensis with [C-14]-labelled thiocyanate resulted in radioactive diisocyanoadociane ( 1) in which the radiolabel is specifically associated with the isocyanide carbons. As expected, cyanide and thiocyanate were confirmed as precursors to the pupukeananes 10 and 11 in the sponge Axinyssa n. sp.; additionally these precursors labelled 2-thiocyanatoneopupukeanane ( 12) in this sponge. To probe whether isocyanide-isothiocyanate interconversions take place at the secondary metabolite level, the advanced precursor bisisothiocyanate 17 was supplied to A. terpenensis, but did not result in significant labelling in the natural product isocyanide 1. In contrast, in the sponge Axinyssa n. sp., feeding of [C-14]-9-isocyanopupukeanane (10) resulted in isolation of radiolabelled 9- isothiocyanatopupukeanane 11, while the feeding of [C-14]-11 resulted in labelled isocyanide 10. These results show conclusively that isocyanides and isothiocyanates are interconverted in the sponge Axinyssa n. sp., and confirm the central role that thiocyanate occupies in the terpene metabolism of this sponge.

Biosynthetic pathways to dichloroimines; precursor incorporation studies on terpene metabolites in the tropical marine sponge Stylotella aurantium

The biosynthetic origin of the dichloroimine functional group in the marine sponge terpene metabolites stylotellanes A ( 3) and B ( 4) was probed by the use of [C-14]-labelled precursor experiments. Incubation of the sponge Stylotella aurantium with [C-14]-labelled cyanide or thiocyanate resulted in radioactive terpenes in which the radiolabel was shown by hydrolytic chemical degradation to be associated specifically with the dichloroimine carbons. Additionally, label from both precursors was incorporated into farnesyl isothiocyanate ( 2). A time course experiment with [ 14C]cyanide revealed that the specific activity for farnesyl isothiocyanate decreases over time, but increases for stylotellane B ( 4), consistent with the rapid formation of farnesyl isothiocyanate ( 2) from inorganic precursors followed by a slower conversion to stylotellane B ( 4). The advanced precursors farnesyl isothiocyanate ( 2) and farnesyl isocyanide ( 5) were supplied to S. aurantium, and shown to be incorporated efficiently into stylotellane A ( 3) and B ( 4). Feeding of [C-14]-farnesyl isothiocyanate ( 2) resulted in a higher incorporation of label than with [C-14]-farnesyl isocyanide ( 5). Farnesyl isocyanide was incorporated into farnesyl isothiocyanate in agreement with labelling studies in other marine sponges. Both farnesyl isocyanide and isothiocyanate were further incorporated into axinyssamide A ( 11) as well as the cyclized dichloroimines (12)-(14), ( 16) that represent more advanced biosynthetic products of this pathway. These results identify the likely biosynthetic pathway leading to the major metabolites of S. aurantium.

Structural and stereochemical revision of isocyanide and isothiocyanate amphilectenes from the Caribbean marine sponge Cribochalina sp.

The absolute stereochemistry of amphilectene metabolites from Cribochalina sp. has been revised by a detailed NMR spectroscopic study of the Mosher ester derivatives of a related alcohol. The relative stereochemistry of the previously described amphilectenes has been reinvestigated and reassigned on the basis of the X-ray structural analysis carried out on one of them. The structure of a new amphilectene metabolite, which is an isothiocyanato analogue is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

Nitrogen is a requirement for the photochemical induced 3-azabicyclo[3.3.1]nonane skeletal rearrangement!

Specific 3-azabicyclo[3.3.1]nonane derivatives undergo skeletal cleavage when subjected to light or Lewis acidic conditions affording novel heteratricycles, which is in stark contrast to 3-oxabicyclo[3.3.1]nonanes. (c) 2005 Elsevier Ltd. All rights reserved.

Realtime telemedicine for paediatric otolaryngology pre-admission screening

We conducted a feasibility study to examine whether a paediatric patient at a regional hospital could be assessed by an ear, nose and throat (ENT) specialist via videoconference, therefore saving at least one journey to the tertiary hospital for a pre-admission appointment. A video-otoscope was used with standard videoconference equipment, and realtime images were transmitted at a bandwidth of 384 kbit/s. In all, 13 telepaediatric ENT clinics were conducted between November 2003 and April 2005, and 98 consultations were facilitated for 64 patients. The main reasons for referral were recurrent tonsillitis (25%) and obstructive sleep apnoea (23%). Of the 64 patients examined by telemedicine, 42 (66%) were recommended for surgery and placed on the surgical waiting list. About 12 patients (19%) required travel to the tertiary centre for further investigations and tests not available locally, while four patients (6%) were reviewed via videoconference during a scheduled clinic. Six patients (9%) required no further follow-up after their initial telepaedliatric consultation. Videoconferencing is an effective method of assessing ENT conditions of paediatric patients and for pre-screening potential surgical admissions to a tertiary hospital. Careful consideration of a number of economic and logistical factors needs to be made before large investments are made to expand the service.

ANÁLISE CEFALOMÉTRICA COMPARATIVA ENTRE CRIANÇAS RESPIRADORAS BUCAIS E NASAIS

Existem muitas controvérsias sobre a real interferência da respiração no crescimento craniofacial. Este estudo avaliou a possível relação da influência do padrão respiratório com as variáveis cefalométricas: 1) variáveis esqueléticas sagitais: convexidade do ponto A, profundidade facial, profundidade da maxila e comprimento do corpo mandibular; 2) variáveis esqueléticas verticais: altura facial inferior, eixo facial, cone facial, plano palatal, plano mandibular, altura facial posterior e arco mandibular; 3) variáveis dentárias: protrusão do incisivo inferior e protrusão do incisivo superior. A amostra constituiu-se de 120 crianças do sexo masculino e do sexo feminino com más-oclusões dentárias de Classe I e II-1, respiradores bucais e nasais na fase da dentadura mista e permanente, com indicação para tratamento ortodôntico. Após as avaliações ortodôntica, otorrinolaringológica e fonoaudiológica a amostra foi dividida em 2 grupos: 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras bucais e 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras nasais, sendo cada grupo divididos em 3 subgrupos nas faixas etárias: 7 a 8 anos, 9 a 10 anos e 11 a 12 anos. Após a obtenção dos resultados e a interpretação da análise estatística, foi possível concluir que: 1) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas sagitais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Convexidade pto. A: aumentada no grupo de respiração bucal, idade de 7 a 8 anos com má-oclusão Classe I. Profundidade facial : aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1. Profundidade maxila: aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1; 2) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas verticais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Cone facial: diminuída no grupo de respiração bucal, idade 9 a 10 anos com má-oclusão Classe I. Arco mandibular : diminuída no grupo de respiração bucal, idade 7 a 8 anos com má-oclusão Classe II-1.; 3) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis dentárias: constatou-se que não houve diferença estatisticamente significante para nenhuma das variáveis dentárias analisadas: protrusão do incisivo inferior e superior , não se relacionando com os padrões respiratórios (bucal e nasal).

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual im pairm ent. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessm ent of quality-of-life in the visually im paired and should support studies which evaluate the effectiveness of low vision rehabilitation services. © Copyright International Journal of Ophthalmology Press.

Analysis of the Distributions of Color Characteristics in Art Painting Images

In this paper we study some of the characteristics of the art painting image color semantics. We analyze the color features of differ- ent artists and art movements. The analysis includes exploration of hue, saturation and luminance. We also use quartile’s analysis to obtain the dis- tribution of the dispersion of defined groups of paintings and measure the degree of purity for these groups. A special software system “Art Paint- ing Image Color Semantics” (APICSS) for image analysis and retrieval was created. The obtained result can be used for automatic classification of art paintings in image retrieval systems, where the indexing is based on color characteristics.

Prevalência e fatores associados à morbidade materna: inquérito populacional em Natal/RN

INTRODUCTION: Severe maternal morbidity , also known as maternal near miss , has been used as an alternative to the study of maternal mortality , since being more frequent shares the same determinants and enables the implementati on of epidem iological surveillance of cases . Since then, hospital audits ha ve been carried out to determine the rates of maternal near miss, its mai n causes and associated factors . More recently, population surveys based on self - reported morbidity have als o been presented as vi able in identifying these cases . OBJECTIVE: The aim of this study was to determine the prevalence and associated factors of maternal near miss and complications during pregnancy and puerperal period in Natal/RN. METHODS: A cross - secti onal population - based study was conducted in Natal /RN , Brazil, which has as its target population women aged 15 to 49 years who were pregnant in the last five years. It was carried out a probabilistic sam pling design based on a multi - stage complex sample , in which 60 census tracts were selected from three strata (north , south - east and west). Afterwards, domiciles were visited in order to obtain a sample of the 908 eligible women in whom a questionnaire was applied. The descriptive analyzes and bivariate ass ociations were performed using the Chi - square test and the estimate of the prevalence ratio (PR ) with 95% confidence interval (CI) and considering the weights and design effects . The Poisson regression analysis , also with 5% significance and 95% CI, was us ed for analyzes of associated factors. RESULTS: 848 women were identified and interviewed after visits in 8.227 households corresponding to a response rate of 93 . 4 %. The prevalence of maternal near miss was 41 . 1 /1 000NV, being the Intensive Care Unity stay i ng (19 . 1 /1 000 LB ) and eclampsia (13 . 5/1000LB) the most important marker s . The prevalence of complications in the puerperal peri od was 21 . 2 %, and hemorrhage (10 . 7%) and urinary tract infection (10 . 7%) the most frequently reported clinical conditions and rema in ing in the hospital for over a week after delivery the mo st frequent intervention (5.4%) . Regarding associated factors , the bivariate analysis showed an association between the increased number of complications in women of black/brown race ( PR= 1 . 23; CI95 % : 1 . 04 - 1 . 46) and lower socioeconomic status ( PR= 1 . 33; CI95%: 1 . 12 - 1 . 58) in women who had pre natal care in public service ( PR= 1 . 42; CI95%: 1 . 16 to 1 . 72 ) and that were not advised during prenatal about where they should do the d elivery (PR= 1 . 24; CI95%: 1 . 05 - 1 . 46), made the del ivery in the public service (PR= 1 . 63; CI95%: 1 . 30 - 2 . 03), had to search for more than one hospital for delivery (PR=1 . 22; CI95%: 1 . 03 - 1 . 45) and had no companion during childbirth ( PR =1 . 19; CI95%: 1 . 01 - 1 . 41) or at all times of childbirth c are - before, during and after childbirth - ( PR= 1 . 25, CI95%: 1 . 05 - 1 . 48) . Moreover, the number of days postpartum hospitalization was higher in women who had more complications (P R= 1 . 59 ; CI95%: 1 . 36 - 1 . 86). In the final regression model for both birth place (P R= 1 . 21 ; CI 95% : 1 . 02 to 1 . 44 ) and socioeconomic status (PR = 1.54 ; CI95%: 1 . 25 - 1 . 90 ) the association remained. CONCLUSION : Conducting population surveys using the pragmatic definition of near miss is feasible and may add importa nt information about this ev ent . It was possible to find the expression of health inequalities related to maternal health in the analysis of both socioeconomic conditions and on the utilization of health services.

Estimativa do fluxo de calor e da difusividade térmica do solo, baseado na solução da derivada temporal fracionária de meia ordem em ferramenta de software

The soil heat flux and soil thermal diffusivity are important components of the surface energy balance, especially in ar id and semi-arid regions. The obj ective of this work was to carry out to estimate the soil heat flux from th e soil temperature measured at a single depth, based on the half-order time derivative met hod proposed by Wang and Bras (1999), and to establish a method capable of es timating the thermal diffusivity of the soil, based on the half order derivative, from the temporal series of soil temperature at two depths. The results obtained in the estimates of soil heat flux were compared with the values of soil heat flux measured through flux plates, and the thermal di ffusivity estimated was compared with the measurements carried out in situ. The results obtained showed excellent concordance between the estimated and measured soil heat flux, with correlation (r), coeffici ent of determination (R 2 ) and standard error (W/m 2 ) of: r = 0.99093, R 2 = 0.98194 and error = 2.56 (W/m 2 ) for estimated period of 10 days; r = 0,99069, R 2 = 0,98147 and error = 2.59 (W/m 2 ) for estimated period of 30 days; and r = 0,98974, R 2 = 0,97958 and error = 2.77 (W/m 2 ) for estimated period of 120 days. The values of thermal di ffusivity estimated by the proposed method showed to be coherent and consis tent with in situ measured va lues, and with the values found in the literature usi ng conventional methods.

Construção de um classificador automático de severidade de bugs para sistemas open source

Software bug analysis is one of the most important activities in Software Quality. The rapid and correct implementation of the necessary repair influence both developers, who must leave the fully functioning software, and users, who need to perform their daily tasks. In this context, if there is an incorrect classification of bugs, there may be unwanted situations. One of the main factors to be assigned bugs in the act of its initial report is severity, which lives up to the urgency of correcting that problem. In this scenario, we identified in datasets with data extracted from five open source systems (Apache, Eclipse, Kernel, Mozilla and Open Office), that there is an irregular distribution of bugs with respect to existing severities, which is an early sign of misclassification. In the dataset analyzed, exists a rate of about 85% bugs being ranked with normal severity. Therefore, this classification rate can have a negative influence on software development context, where the misclassified bug can be allocated to a developer with little experience to solve it and thus the correction of the same may take longer, or even generate a incorrect implementation. Several studies in the literature have disregarded the normal bugs, working only with the portion of bugs considered severe or not severe initially. This work aimed to investigate this portion of the data, with the purpose of identifying whether the normal severity reflects the real impact and urgency, to investigate if there are bugs (initially classified as normal) that could be classified with other severity, and to assess if there are impacts for developers in this context. For this, an automatic classifier was developed, which was based on three algorithms (Näive Bayes, Max Ent and Winnow) to assess if normal severity is correct for the bugs categorized initially with this severity. The algorithms presented accuracy of about 80%, and showed that between 21% and 36% of the bugs should have been classified differently (depending on the algorithm), which represents somewhere between 70,000 and 130,000 bugs of the dataset.

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed