Trophoblast organoids as a model for maternal-fetal interactions during human placentation.

The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries2. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria3. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G+ extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.Centre for Trophoblast Reearch Royal Society Dorothy Hodgkin Fellowship Marie Curie Intra-European Fellowshi

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Measurement and Analysis of Spyware in a University Environment

Abstract Over the past few years, a relatively new computingphenomenon has gained momentum: the spread of "spyware. " Though most people are aware of spyware, theresearch community has spent little effort to understand its nature, how widespread it is, and the risks it presents.This paper is a first attempt to do so. We first discuss background material on spyware, in-cluding the various types of spyware programs, their methods of transmission, and their run-time behavior.By examining four widespread programs (Gator, Cydoor, SaveNow, and eZula), we present a detailed analysis oftheir behavior, from which we derive signatures that can be used to detect their presence on remote computersthrough passive network monitoring. Using these signatures, we quantify the spread of these programs amonghosts within the University of Washington by analyzing a week-long trace of network activity. This trace was gath-ered from August 26th to September 1st, 2003. From this trace, we show that: (1) these four pro-grams affect approximately 5.1 % of active hosts on campus, (2) many computers that contain spyware have morethan one spyware program running on them concurrently, and (3) 69 % of organizations within the universitycontain at least one host running spyware. We conclude by discussing security implications of spyware and spe-cific vulnerabilities we found within versions of two of these spyware programs.

Denali: Lightweight Virtual Machines for Distributed and Networked Applications

The goal of Denali is to safely execute many independent, untrusted server applications on a single physical machine. This would enable any developer to inject a new service into third-party Internet infrastructure; for example, dynamic content generation code could be introduced into content delivery networks or caching systems. We believe that virtual machine monitors (VMMs) are ideally suited to this application domain. A VMM provide strong isolation by default, since one machine cannot directly name a resource in another machine. In addition, VMMs defer the implementation of high-level abstractions to guest OSs, which greatly simplifies the kernel and nullifies “layer-below ” attacks. The main challenge in using a VMM for this application domain is in scaling the number of concurrent VMs that can simultaneously execute on it. The distinction between Denali and existing VMMs is that we make aggressive use of para-virtualization techniques. Para-virtualization entails selectively modifying the virtual architecture to enhance scalability, performance, and simplicity. By using para-virtualization, we believe Denali will be able to scale to an order-ofmagnitude more virtual machines than existing VMMs. We have implemented a virtual machine monitor that runs in kernel mode on bare x86 hardware. In addition, we have built a simple guest OS tailored to writing Internet services