The origins and the future of microfluidics

The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.     

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.     

Biographical Notes

Biography

Biographical Notes     

Human genes that limit AIDS

Discernable genetic variation among people and populations has an important role in infectious disease epidemics, including that of acquired immune deficiency syndrome (AIDS). Genetic association analysis of several large AIDS cohorts implicate 14 AIDS restriction genes, polymorphic variants in loci that regulate HIV-1 cell entry, acquired and innate immunity, and cytokine defenses to HIV-1. The influence and translational impact of these genes on individual and population sensitivity to AIDS is considerable.     

Beating the superparamagnetic limit with exchange bias

Interest in magnetic nanoparticles has increased in the past few years by virtue of their potential for applications in fields such as ultrahigh-density recording and medicine. Most applications rely on the magnetic order of the nanoparticles being stable with time. However, with decreasing particle size the magnetic anisotropy energy per particle responsible for holding the magnetic moment along certain directions becomes comparable to the thermal energy. When this happens, the thermal fluctuations induce random flipping of the magnetic moment with time, and the nanoparticles lose their stable magnetic order and become superparamagnetic. Thus, the demand for further miniaturization comes into conflict with the superparamagnetism caused by the reduction of the anisotropy energy per particle: this constitutes the so-called 'superparamagnetic limit' in recording media. Here we show that magnetic exchange coupling induced at the interface between ferromagnetic and antiferromagnetic systems can provide an extra source of anisotropy, leading to magnetization stability. We demonstrate this principle for ferromagnetic cobalt nanoparticles of about 4 nm in diameter that are embedded in either a paramagnetic or an antiferromagnetic matrix. Whereas the cobalt cores lose their magnetic moment at 10 K in the first system, they remain ferromagnetic up to about 290 K in the second. This behaviour is ascribed to the specific way ferromagnetic nanoparticles couple to an antiferromagnetic matrix.     

cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes

Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis. Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis.     

Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy

The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1, OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter. We show that this contraction causes marked hypomethylation of the contracted D4Z4 allele in individuals with FSHD1. Individuals with phenotypic FSHD1, who are clinically identical to FSHD1 but have an unaltered D4Z4, also have hypomethylation of D4Z4. These results strongly suggest that hypomethylation of D4Z4 is a key event in the cascade of epigenetic events causing FSHD1.     

考虑定价、生产能力和原料采购的VMI系统Pareto最优及其实现

首先讨论在考虑定价、生产能力和原料采购的VMI系统非合作博弈的基础上实现VMI系统Pareto最优的一般条件,其次给出了在Stackelberg博弈下的可行Pareto最优集问题,然后提出了实现生产商和定货商Pareto最优的Nash讨价还价模型,最后给出了算例加以说明合作给企业带来了较大的利润增加.