An Evolutionary Firefly Algorithm for the Estimation of Nonlinear Biological Model Parameters

The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.     

人降钙素类似物的合成及活性研究

通过对鲑鱼降钙素和人降钙素结构的比较,设计并合成了人降钙素类似物ｍｈＣＴ－２。利用空气氧化获得分子内二硫键,经分离纯化,产物达ＨＰＬＣ及毛细管电泳均一,蛋白质序列分析和质谱分析符合理论值。在大鼠降血钙生物活性测定中,利用量反应平行线法进行ｍｈＣＴ－２的生物效价判定达２０００ＩＵ／ｍｇ,比ｈＣＴ的效价高一个数量级。     

Influence of Age on the Rhythm in Basal and Forskolin-Stimulated Adenylate Cyclase Activity of the Rat Heart

-In male rats of three different ages (Group 1:7 weeks, Group II: 4 months, Group III: ≥ 10 months) basal and forskolin-stimulated adenylate cyclase (AC) activity were investigated in rat heart ventricles of animals sacrificed at 8 time points within 24 hours of a day. Maximum (Emax) and half-maximum (EC50) stimulation by a water-soluble forskolin (FOR; 0.1-100 μmol/l) were determined from dose-response curves. In young rats (Group I) significant rhythmicity was found in basal and FOR-stimulated AC activity, which was successively reduced or abolished with age by a reduction in amplitude. Mean basal AC activity increased about 2-fold from Group I to Group II/III. Mean maximum in for stimulation was about 12-fold in Group I and about 7-fold in Group II and ID. EC50-values displayed neither a significant rhythmicity in either group nor an age-dependency. It is concluded that the stimulatory potency of the catalytic subunit of the AC is reduced with age.     

Equivariant Estimation for the Parameters of an Exponential Model Based on Censored Sampling

Lehmann (1983) provides a detailed discussion on equivariant estimation of the parameters of location, scale and location-scale models. Edwin Prabakaran and Chandrasekar (1994) developed simultaneous equivariant estimation approach and illustrated the method with examples. In this paper, we consider exponential models and obtain minimum risk equivariant estimators of the parameters based on Type II censored samples. The equivariant method of estimation is illustrated with biological and reliability applications.     

Cyclic AMP-Dependent Protein Kinase Activity in Human Brain Across Age

Abstract: Cyclic AMP-dependent protein kinase activity was measured in the cerebral cortex of humans 2 days to 83 years of age and in the cortex of F344 rats 3, 22, or 30 months of age. Protein kinase activity was detected in the human brain, but no age-related differences in activity were observed in the presence or absence of cyclic AMP. Age differences were also not seen in protein kinase in the rat cerebral cortex. Enzyme activities in rat and human brain were similar.     

Influence of Biological Age on Professional Efficiency: Communication I. Biological Age and Mental Efficiency

Biological age (BA) and mental efficiency (ME) were studied in truck drivers. The study demonstrated the features of the systemic organization of the functions that determine ME depending on the age and length of service. Premature age-related changes in psychophysiological indices were just risk indicators in truck drivers. However, long-term service was found to be an actual risk factor which accelerated the aging process. This work demonstrates the adequacy and high informative value of the approaches suggested to evaluate the aging rate by ME indices and the necessity of prophylactic measures aimed at preventing the premature aging of employees.     

Seasonal Rhythms of Neuronal Activity in the Human Biological Clock: A Mathematical Model

The mammalian suprachiasmatic nucleus (SCN) is implicated in the temporal organization of circadian and seasonal processes. Photic information may have a synchronizing effect on the endogenous clock of the SCN by inducing periodic changes in the functional activity of specific groups of neurons. The present study was performed to analyze the annual profiles of the arginine vasopressin (AVP)- and vasoactive intestinal polypeptide (VIP)-producing neurons in the human SCN. The populations of AVP- and VIP-expressing neurons in the SCN showed marked annual rhythms with an asymmetrical, bimodal waveform. Time series analysis indicated that these annual cycles in peptidergic activity could be described by a statistical model consisting of multiple-harmonic regression and ARMA components. The annual AVP cycle was adequately described by a two-harmonic model and a third-order autoregressive noise component, whereas the properties of the VIP cycle were best characterized by a two-harmonic model and a first-order autoregressive noise component. The models of both annual cycles reached a maximum in September-October and a minimum in May-June, and their estimated amplitudes, relative to the annual mean, were similar in size. These findings indicate that the biosynthesis of vasopressin and VIP in the human SCN exhibits an annual rhythmicity, and that the temporal organization of these processes is mainly controlled by environmental lighting conditions.     

Seasonal Rhythms of Neuronal Activity in the Human Biological Clock: A Mathematical Model

The mammalian suprachiasmatic nucleus (SCN) is implicated in the temporal organization of circadian and seasonal processes. Photic information may have a synchronizing effect on the endogenous clock of the SCN by inducing periodic changes in the functional activity of specific groups of neurons. The present study was performed to analyze the annual profiles of the arginine vasopressin (AVP)- and vasoactive intestinal polypeptide (VIP)-producing neurons in the human SCN. The populations of AVP- and VIP-expressing neurons in the SCN showed marked annual rhythms with an asymmetrical, bimodal waveform. Time series analysis indicated that these annual cycles in peptidergic activity could be described by a statistical model consisting of multiple-harmonic regression and ARMA components. The annual AVP cycle was adequately described by a two-harmonic model and a third-order autoregressive noise component, whereas the properties of the VIP cycle were best characterized by a two-harmonic model and a first-order autoregressive noise component. The models of both annual cycles reached a maximum in September–October and a minimum in May–June, and their estimated amplitudes, relative to the annual mean, were similar in size. These findings indicate that the biosynthesis of vasopressin and VIP in the human SCN exhibits an annual rhythmicity, and that the temporal organization of these processes is mainly controlled by environmental lighting conditions.     

重组人半乳凝集素-1的原核表达、纯化及生物活性检测

目的:在大肠杆菌中表达半乳凝集素-1(galectin-1),并进行纯化及生物活性检测。方法:将人半乳凝集素-1基因克隆至带有His融合标签的原核表达载体pQE-30上,转化大肠杆菌M15,经IPTG诱导表达,表达产物经亲和层析纯化后,进行Western印迹鉴定,并用红细胞凝集试验检测其生物学活性。结果:双酶切鉴定和核苷酸序列测定表明重组表达质粒pQE-30-Galectin-1构建正确;重组蛋白的表达量约占菌体总蛋白的50%,主要以可溶形式表达,纯化后蛋白纯度达95%以上,且具有良好的红细胞凝集活性。结论:在大肠杆菌中表达了重组人半乳凝集素-1,且具有良好的生物活性。     

重组人KGF制备工艺和活性检测方法的建立

目的:在毕赤酵母中实现了KGF的高效表达,并初步建立了生物学活性检测方法.方法:合成5'端缺失69个核苷酸的KGF基因序列,克隆入pPIC9并转化毕赤酵母菌株GS115中,经诱导表达.发酵液上清采用脱盐层析和阳离子交换层析进行分离纯化.利用貂肺上皮细胞(Mv-1-Lu)检测其生物学活性.结果:表达水平达到了110mg/L发酵液;表达产物经一步离子交换层析就能得到有效分离,总收率在50mg/L发酵液以上;纯化的rhKGF生物学活性与KepivanceTM相当.结论:rhKGF制备工艺和检测方法的建立将为该因子的规模化生产和进一步的临床应用提供良好基础.     

AMPD1 C34T Mutation Selectively Affects AMP-Deaminase Activity in the Human Heart

Possession of the nonsense mutation in AMPD1 C34T gene has been linked to improved survival in patients with heart failure, possibly by promoting the formation of adenosine. This mutation is known to decrease the activity of AMP-deaminase in skeletal muscle. We have found that the AMPD1 mutation decreases the activity of AMP-deaminase in the heart without changing the activity of any other enzymes of adenine nucleotide metabolism. Protective mechanism of this mutation may be thus induced by local cardiac metabolic changes.     

Studies on the Phenylphenol Derivatives with Biological Activity

A number of compounds structurally related to phenylphenols were systematically synthesized as herbicides. Some of nitro-substituted derivatives show strong activity in pre-emergence test. The herbicidai activity of this series appears to relate with the pK-value of the compound.

Herbicidai activities of chloro-substituted phenylphenols were investigated. The derivatives of o-phenylpbenol and p-phenylphenol exhibited different selective toxicity between radish and rice, the latter appeared to have a specific inhibitory activity against the root growth of rice. As an attempt to analyze the correlation of herbicidai activity and chemical structure, the dissociation constant and the substituent constant π were applied in this investigation. The herbicidai activity correlated linearly with pK-value.     

Studies on the Phenylphenol Derivatives with Biological Activity

More than ninety phenylphenol derivatives were tested for fungistatic activity toward ten species of agriculturally important fungi. One of N-methylcarbamates and some nitro- or chloro-substituted derivatives were highly toxic against Piricularia oryzae. From the relationship between the chemical structure and the activity, it is supposed that the reactivity, the permeability, the steric effect and the metabolic activation of the compound are the responsible factors for the fungistatic activity.     

nHAP对大鼠肝线粒体的生物活性作用

为了探讨羟基磷灰石纳米粒子(nHAP)对大鼠肝线粒体生物活性的影响,将nHAP直接作用于线粒体,在不同浓度和时间下测定线粒体标志酶琥珀酸脱氢酶(SDH)比活性,并与对照组进行比较。结果显示,当nHAP中水含量在10%以下时,线粒体生物活性未发现改变;当nHAP浓度递增时,在等时间段内,对线粒体SDH比活性呈逐步抑制作用;在不等时间段内,nHAP对线粒体SDH比活性的抑制作用与对照组相比较差异有显著性(p<0.05)。因此,nHAP对线粒体SDH比活性的抑制有浓度和时间的依赖性。     

Twenty-four-Hour Rhythmic Variations of Histamine in Human Female Blood

We have previously observed that blood histamine levels undergo rhythmic 24 hour variations in male normal subjects. In the present study we examined whether similar 24 hour modifications were also present in female subjects. To this purpose, 60 healthy cycling women were enrolled for a chronobiological transverse study. To achieve experimental conditions as homogeneous as possible, the study was carried out on the first day of the menstrual flow. Histamine was determined in whole venous blood by a spectrophotofluorimetric method. The blood histamine levels showed significant rhythmic changes depending on the time of blood sampling, with 1 maximum and 1 minimum within a period of 24 h, with percentage rhythm 15.1, MESOR 0.15 μg/ml, amplitude 0.02 μg/ml and acrophase at 01:20 h. These results reveal the presence of 24 h cyclic variations of histamine levels in the female, as it occurred in male. However, the differences observed in the chronobiological rhythms of histamine between the two sexes may represent a peculiar feature of the first day of the menstrual cycle.     

Biological Activity of Purpurogallin

Purpurogallin showed antibacterial activity toward gram-positive bacteria. Strong activity against methicillin-resistant Staphylococcus aureus [minimal inhibitory concentration (MIC) against methicillin of 1600 μg/ml] was found, with MIC of 11.0/μg/ml. Purpurogallin inhibited the growth of all tested plants and decreased the chlorophyll content in the cotyledons of Brassica campestris subsp. rapa. It showed potent inhibitory activity against prolyl endopeptidase (the 50% inhibitory concentration was 1.6 × 10^?5m), unlike its analogues, hinokitiol and tropolone.     

Biological Activity of O-beta-d-Glucopyranosylzeatin

Concentrations of 10(-8) to 10(-5)m O-beta-d-glucopyranosylzeatin are less active than zeatin and zeatin riboside in the soybean (Glycine max L.) callus bioassay. At a concentration of 10(-4)m the glucoside was, however, more active or alternatively less toxic than similar concentrations of zeatin and zeatin riboside. Applied zeatin-O-glucoside is readily metabolized by soybean callus and both zeatin and zeatin riboside could be extracted from callus grown on basal medium containing the O-glucoside.