Influence of DNA repair by ada and ogt alkyltransferases on the mutational specificity of alkylating agents

We investigated the influence of the alkyltransferases (ATases) encoded by the ada and ogt genes of Escherichia coli on the mutational specificity of alkylating agents. A new mutational assay for selection of supF- mutations in shuttle-vector plasmids was used. Treating plasmid-bearing bacteria with N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), and ethyl methanesulfonate (EMS) dramatically increased the mutation frequency (from 33-fold to 789-fold). The vast majority of mutations (89-100%) were G:C-->A:T transitions. This type of mutation increased in ada- (MNU) or ogt- (ENU) bacteria, suggesting that repair of O6-methylguanine by ada ATase and repair of O6-ethylguanine by ogt ATase contribute mainly to the decrease in G:C-->A:T transitions. The analysis of neighboring base sequences revealed an overabundance of G:C-->A:T transitions at 5'-GG sequences. The 5'-PuG bias increased in ATase-defective cells, suggesting that these sequences were not refractory to repair. G:C-->A:T transitions occurred preferentially in the untranscribed strand after in vivo exposure. That this strand specificity was detected even in bacteria devoid of ATase activity (ada- ogt-) and not after in vitro mutagenesis suggests a bias for damage induction rather than for DNA repair. Highly significant differences were found between the in vivo and in vitro incidences of G:C-->A:T substitutions at the two major hotspots, positions 123 (5'-GGG-3'; antisense strand) and 168 (5'-GGA-3'; sense strand). These results are explained by differences in the probability of formation of stem-loop structures in vivo and in vitro.     

Retinoblastoma: clinical and molecular diagnostic aspects

Retinoblastoma, a tumor of the immature retina concerns babies and young infants in particular. They make up for 14% of malignomas in the first years of life. There are two types of retinoblastoma: In the first two alleles of the gene Rb1 must be inactivated sequentially in the same retinoblast cell until this may escape control. In this case the retinoblastoma is always unilateral and unifocal. This is explained by the lower frequency of two mutations in one retinoblast. The other type, however, is inherited: One allele Rb1 is inactivated in all cells of the organism by mutation. The probability that a second mutation arrives in different retinoblasts is thus high. In this case bilateral multifocal tumors develop. Characterization of the Rb1 gene has permitted identification or at least determination of a haplotype in persons at risk. This knowledge is decisive for early recognition of babies at risk and for genetic counselling.     

THE RECURSIVE FITTING OF SUBSET VARX MODELS

Abstract. A vector time series model of the form A(L)y(t) + B(L)x(t) =ε(t) is known as a vector autoregressive model with exogenous variables (VARX model) and involves a regressand vector y(t) and a regressor vector x(t). This paper provides a method for the recursive fitting of subset VARX models. It suggests the use of ascending recursions in conjunction with an order selection criterion to choose an 'optimum' subset VARX model.     

Selecting the forgetting factor in subset autoregressive modelling

Abstract. Conventional methods to determine the forgetting factors in autoregressive (AR) models are mostly based on arbitrary or personal choices. In this paper, we present two procedures which can be used to select the forgetting factor in subset AR modelling. The first procedure uses the bootstrap to determine the value of a fixed forgetting factor. The second procedure starts from this base and applies the time-recursive maximum likelihood estimation to a variable forgetting factor. In one illustration using real exchange rates, we demonstrate the effect of the forgetting factor in subset AR modelling on ex ante forecasting of non-stationary time series. In a second illustration, these two procedures are applied to time-update forecasts for a stock market index. Subset AR models not including a forgetting factor act as a set of benchmarks for assessing ex ante forecasting performance, and consistently improved forecasting performance is demonstrated for these proposed procedures.     

PROJECTION MODULUS: A NEW DIRECTION FOR SELECTING SUBSET AUTOREGRESSIVE MODELS

Selecting a parsimonious subset autoregressive time series model is a valuable objective particularly where there is or may be evidence that a time series may have some form of periodic or quasi-periodic behaviour. An efficient model selection procedure is essential because of the large number of possible alternative models involved. The explanation of an increase in residual variance due to excluding a lag is examined in Hilbert space. As a result, a new statistic, the projection modulus , and its derivatives are developed to assess the significance of any lag in a model. The impact of deleting a lag, as measured by these statistics, helps to produce a selection procedure where true lags have less chance of being removed. We then assess an efficient subset autoregressive model selection procedure employing these statistics. The success of the proposed procedure is illustrated by its efficiency in identifying the true model for simulated and real data.     

Log-linear allometry of fetal craniofacial growth in Down's syndrome

Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes during either the first or second meiotic division. One of the more important consequences of these genetic alterations is the predictable, although variable disturbance in the architecture of the craniofacial region [1]. Postnatal craniofacial morphology has been extensively studied in Down's syndrome (DS). However, little information is available on human prenatal development of the head and face in such patients. The time at which changes in craniofacial phenotype first emerge in Down's syndrome fetuses and at which physical growth begins to diverge from normal is unknown. To explore these questions, we compared prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555 fetuses judged to be "typical for body weight and age" using the method of log-linear allometry [2].     

The primary aortoenteric fistula in The Netherlands--the unpublished cases

OBJECTIVE: Primary aortoenteric fistula is a rare disorder of which only four patients have been reported in the Dutch literature so far. The objective of our study was to obtain more realistic figures on the incidence of this condition, with data on the clinical presentation, diagnostic procedures, treatment and results in a group of patients not previously reported as "case histories". METHODS: A questionnaire was sent to all surgical clinics in The Netherlands. Out of 180 questionnaires, 102 have been returned reporting 27 patients to which data of eight others treated in our own institution were added. RESULTS: In all but one of these 29 patients the fistula was caused by an atherosclerotic aneurysm, the one exception being caused by an ingested cocktail pin. Gastrointestinal haemorrhage was the predominant symptom, being present in 28 of the patients, while the complete triad of haemorrhage, pain and a pulsating mass was found in only eight patients. Twenty-seven patients were treated with an in situ graft of which 14 are doing well at long term follow-up. CONCLUSIONS: Primary aortoenteric fistula is far more common than one would expect from the number of patients reported in literature. A high index of suspicion based on a complete physical examination remains the key to a correct diagnosis. Direct closure of the intestine and in situ grafting of the aorta is the treatment of first choice.     

Occurrence of gastric ulcer after Nissen fundoplication

Of 160 patients who underwent Nissen fundoplication for treatment of symptomatic peptic reflux esophagitis, five patients (3.1%) developed gastric ulcers. Four of these five patients experienced the "gas-bloat" syndrome. All ulcers were located on the lesser curvature of the stomach. Analyses of our experience with use of various types of hiatal hernia repair suggests that creation of the valvuloplastic mechanism unique to the Nissen procedure may be of etiologic significance in the development of gastric ulcers following this procedure.     

一种适用于无线多媒体传感器网络的JPEG图像编码算法

在资源受限的无线多媒体传感器网络中进行图像编码和传输,需要综合考虑能量消耗、压缩率和图像质量三者之间平衡的图像编码方案.研究无线多媒体传感器网络中视频监控图像序列的压缩,提出一种基于变化检测和改进JPEG算法的低复杂度图像编码方案.通过变化检测算法定位监控图像中的运动目标即感兴趣区域,仅传输兴趣区域以显著减少数据传输量...     

Effects of morphine and halothane anesthesia on coronary blood flow

This study was undertaken to determine the relative effects of morphine and halothane anesthesia on coronary blood flow. Right heart bypass was instituted in 20 dogs by draining the vena cava blood into a cardiotomy reservoir and returning it to the main pulmonary artery. Coronary sinus drainage was measured by a right ventricular cannula. Group I (10 dogs) was sequentially given 0.5, 1, 1.5, 2.0, and 2.5% halothane. Group II (10 dogs) was given 1, 2, 3, 4, and 5 mg per kilogram of morphine intravenously. Arterial pressure, coronary sinus blood flow, cardiac output, arterial pH, PCO2, and PO2 were determined and repeated at each dose level of anesthesia and compared to the control values. Morphine significantly increased coronary flow at 3, 4, and 5 mg/kg without pressure adjustment and at 2 mg/kg after pressure adjustment. Coronary flow with halothane was unchanged from control values except for a decrease at 2.5%. Coronary flow was significantly greater with 3, 4, and 5 mg/kg of morphine than with 1.0 and 1.5% halothane.