Non-linear filtering with discontinuous observations and applications to life sciences

In various applications one faces the problem of estimating a signal from discontinuous observations. For example, in biomedical applications the signal may be the ‘state’ of a given organ and one observes through an external counter the amount of radioactivity sequestered by the organ after injection of a radioactive tracer. Here the problem is studied in the context of nonlinear filtering when the signal can be modelled as either a random variable or a diffusion process, and the observations have a continuous and a purely discontinuous component; both components may be affected by the signal. When the signal is a random variable an explicitly computable solution is obtained; for the diffusion case the solution is given as a sequence of approximating filters that can be computed recursively.     

Synthesis and properties of a new cleavable nucleic acid-protein crosslinking reagent

A new compound, dithiobis[9-(2-ethylenecarbamoylethylamino)-2,3-dimethoxy-6-azido-acridine], was synthesized and used in some preliminary experiments to form cleavable complexes between nucleic acids and proteins. In a first step the azidoacridine moiety of the reagent intercalates between the bases of nucleic acids and is then bound by reaction of the azido group. The disulfide group of the reagent is simultaneously converted under reducing conditions into a thiol which, in a second step, can be bound by oxidation to -SH groups of a vicinal protein (additional -SH groups can be inserted in the protein using 2-iminothiolane). The nucleic acid-protein complexes thus formed can be redissociated by reduction. The potential applications of this new cleavable crosslinking reagent could be extended to topographical investigations of any biological structure composed of nucleic acids and proteins.     

Electrospray ionisation-cleavable tandem nucleic acid mass tag-peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS

The synthesis and characterization of isotopomer tandem nucleic acid mass tag-peptide nucleic acid (TNT-PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach. These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS. In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source. The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence. The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens.     

Melatonin: perspectives in the life sciences

The pineal gland hormone melatonin is now considered an important neuroendocrine component of animal physiology. Although the functional status of melatonin has been well described for subhuman species, there is a paucity of data concerning the physiological role of this hormone in man. This paucity of data has much to do with the limitations of experimental design imposed by the practical and ethical difficulties associated with the study of a nocturnally secreted hormone. The recent advent of salivary melatonin assay has provided a very practical means of monitoring melatonin secretion in long-term longitudinal type community based studies of pineal gland function in human health and disease. The efforts to describe key chronobiological changes in melatonin secretion of possible functional significance have been accompanied by a seemingly less enthusiastic search to describe the nature of the melatonin receptor, another highly important component of the 'melatonin message'. The functional relevance of specific chronobiological changes in melatonin secretion cannot be completely understood without an increased knowledge of melatonin action at the receptor level. The present work describes the recent methodological advance in the investigation of human pineal gland physiology represented by salivary melatonin assay, and discusses the present status of our knowledge of the melatonin receptor.     

Novel ebselen-porphyrin conjugates: synthesis and nucleic acid interaction study

Novel porphyrins bearing ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) moiety were synthesized and characterized. Their interactions with herring sperm DNA were studied by means of UV-visible, fluorescence, circular dichroism spectroscopy, and gel electrophoresis.     

Data clustering in life sciences

Clustering has a wide range of applications in life sciences and over the years has been used in many areas ranging from the analysis of clinical information, phylogeny, genomics, and proteomics. The primary goal of this article is to provide an overview of the various issues involved in clustering large biological datasets, describe the merits and underlying assumptions of some of the commonly used clustering approaches, and provide insights on how to cluster datasets arising in various areas within life sciences. We also provide a brief introduction to Cluto, a general purpose toolkit for clustering various datasets, with an emphasis on its applications to problems and analysis requirements within life sciences.     

Genomics in space life sciences

Since the early days of manned spaceflight, hazardous effects of the space environment on living organisms have been disputed. With the continuous manning of the International Space Station, the planned Chinese space station, and renewed interest in returning to the Moon and sending manned flights to Mars, identifying and addressing the potential outcomes of long-term space exposures is critically important.     

Synchrotron radiation in life sciences

Synchrotron Radiation (SR) presents itself as a "play-ground" with a large range of methods and techniques suitable to unveil the mysteries of life. Here we attempt to present a few of these methods that complement those employed in the home laboratory. SR diffraction, spectroscopy and imaging methods relevant to the atomic structure determination and characterization of the properties and function of chemical compounds and macromolecules of biological relevance, are introduced.     

基因组研究与生命科学工业的崛起

人类基因组的全序列测定预计可提前两年于２００３年完成，特别是基因组内的蛋白质编码序列将更早测定。私人财团斥巨资进入这个领域，并望抢得先手，这意味着基因组研究可创造巨大财富。在过去几年里，国际上一批知名的大型制药集团和化学工业公司已在基因组研究领域内投入大量资金，并形成了一个新的产业部门，即生命科学工业。制药工业是生命科学工业的主要支柱之一，与基因组研究的关系特别密切。药物基因组学研究表明，药物的疗效与患者的基因型相关，因此，今后的药物生产要考虑到药物投放地区人群中有关的等位基因的频率，医疗处方也将因人而异而趋向个人化。比较基因组学研究则有助于从模式生物的资料指出与疾病可能相关的基因，可以此作为靶标来设计药物。     

Electrospray ionisation-cleavable tandem nucleic acid mass tag–peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS

The synthesis and characterization of isotopomer tandem nucleic acid mass tag–peptide nucleic acid (TNT–PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach. These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS. In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source. The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence. The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens.     

Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis,preliminary SAR and comparison with acridine endoperoxide conjugates

A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts.     

Photo acoustic in life sciences

Photoacoustic (PA) measurements provide, by the very nature of the PA effect, the possibility to obtain information on the optical and thermal properties of samples. In addition they can yield information on the enthalpy changes and characteristic times involved in photo-induced processes as the acoustic signal in proportional to the heat produced following the absorption of the modulated excitation. In the study of optical properties the relative insensitivity to scattered light of the PA signal makes such measurement an attractive way to measure biological samples in vivo, or, at least, withpout the need to isolated the absorbing compounds. The dependence of the PA signal on the thermal properties of the sample is particularly useful when heterogeneous samples are studied. As a photocalorimetric method the technique shows considerable promise in the study of photo-biogenergetics, especially photosynthesis. Only in special cases can analytical applications of the method compete with fluorescence measurements (for detection), and with increasingly sophisticated optical transmission and reflectance techniques (for identification). However, the PA method may find important uses in fundamental research and in applied areas such as biomedicine and agricultural biochemistry.