Jie Chen

The ordinary Bayes information criterion is too liberal for model selection when the model space is large. In this article, we re-examine the Bayesian paradigm for model selection and propose an extended family of Bayes information criteria. The new criteria take into account both the number of unknown parameters and the com-plexity of the model space. Their consistency is established, in particular allowing the number of covariates to increase to infinity with the sample size. Their performance in various situations is evaluated by simulation studies. It is demonstrated that the extended Bayes information criteria incur a small loss in the positive selection rate but tightly control the false discovery rate, a desirable property in many applications. The extended Bayes information criteria are extremely useful for variable selection in problems with a moderate sample size but a huge number of covariates, especially in genome-wide association studies, which are now an active area in genetics research.

This revised and expanded second edition is an in-depth study of the change point problem from a general point of view, as well as a further examination of change point analysis of the most commonly u

The segmental pattern of the spine is established early in development, when the vertebral precursors, the somites, are rhythmically produced from the presomitic mesoderm. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the oscillator associated with this process, the segmentation clock, drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the notch-fibroblast growth factor and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator.

OBJECTIVES: Burma produces approximately 60% of the world's heroin, Laos is the third leading producer. Recent outbreaks of injecting drug use and HIV-1 in Burma, India, China, and Vietnam have been associated with Burmese and Laotian overland heroin trafficking routes. We analyzed findings from narcotics investigations, molecular epidemiology studies of HIV-1, and epidemiologic and behavioral studies of injecting drug use, to evaluate the roles that the heroin export routes play in the spread of drug use and HIV-1 in south and south-east Asia. METHODS: We reviewed the medical and narcotics literature, the molecular epidemiology of HIV, and did key informant interviews in India, China, and Burma with injecting drug users, drug traffickers, public health staff, and narcotics control personnel. RESULTS: Four recent outbreaks of HIV-1 among injecting drug users appear linked to trafficking routes. Route 1: From Burma's eastern border to China's Yunnan Province, with initial spread of HIV-1 subtype B, and later C. Route 2: Eastern Burma to Yunnan, going north and west, to Xinjiang Province, with B, C, and a B/C recombinant subtype. Route 3: Burma and Laos, through northern Vietnam, to China's Guangxi Province, subtype E. Route 4: Western Burma, across the Burma-India border to Manipur, predominant subtype C, and B and E. CONCLUSIONS: Overland heroin export routes have been associated with dual epidemics of injecting drug use and HIV infection in three Asian countries and along four routes. Molecular epidemiology is useful for mapping heroin routes. Single country narcotics and HIV programs are unlikely to succeed unless the regional narcotic-based economy is addressed.

Hematopoietic stem cells (HSCs) maintain hematopoiesis by giving rise to all types of blood cells. Recent reports suggest that HSCs also possess the potential to generate nonhematopoietic tissues. To evaluate the underlying mechanisms in the commitment of HSCs into multitissue and multihematopoietic lineages, we performed oligonucleotide array analyses targeting for prospectively purified HSCs, multipotent progenitors (MPPs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs). Here we show that HSCs coexpress multiple nonhematopoietic genes as well as hematopoietic genes; MPPs coexpress myeloid and lymphoid genes; CMPs coexpress myeloerythroid, but not lymphoid genes, whereas CLPs coexpress T-, B-, and natural killer-lymphoid, but not myeloid, genes. Thus, the stepwise decrease in transcriptional accessibility for multilineage-affiliated genes may represent progressive restriction of developmental potentials in early hematopoiesis. These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation.