Structural visualization of key steps in human transcription initiation.

Eukaryotic transcription initiation requires the assembly of general transcription factors into a pre-initiation complex that ensures the accurate loading of RNA polymerase II (Pol II) at the transcription start site. The molecular mechanism and function of this assembly have remained elusive due to lack of structural information. Here we have used an in vitro reconstituted system to study the stepwise assembly of human TBP, TFIIA, TFIIB, Pol II, TFIIF, TFIIE and TFIIH onto promoter DNA using cryo-electron microscopy. Our structural analyses provide pseudo-atomic models at various stages of transcription initiation that illuminate critical molecular interactions, including how TFIIF engages Pol II and promoter DNA to stabilize both the closed pre-initiation complex and the open-promoter complex, and to regulate start--initiation complexes, combined with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB and explain its essential role in promoter opening

Key Steps to Reduce Suicide

a call that was dispatched as a suicide attempt. He found a young woman, her husband, their baby, and an empty bottle of Tylenol. The distraught husband said his wife had taken a large amount of the pills to try to kill herself. Jim asked the weary-looking woman, Maria, what had happened. She said she was depressed, had a bad headache, and had taken some Tylenol. Jim asked Maria directly, but compassionately, if she had been trying to kill herself. Maria would not give a clear answer, so Jim asked if she had ever attempted suicide. Then Maria started to cry and said she had attempted when she was a teenager and had vowed to never do it again. But now life was too difficult with the new baby and her husband unemployed, and she just couldn’t take it anymore. Jim suggested that Maria and her husband go to the hospital to talk with a doctor to get some help for Maria, and Maria hesitantly agreed. At the hospital, Jim told the emergency department physician that Maria had taken a large amount of Tylenol, had attempted suicide in the past, and now “just couldn’t take it anymore. ” The physician thanked Jim for the information and said it was helpful

Key Steps to Reduce Suicide

enforcement officers, were dispatched on a general disturbance call. A neighbor had called 911 saying she heard a loud argument in the house next door, and it sounded like someone might get hurt. Arriving at the scene, the officers found a husband and wife arguing, but no one was physically hurt. Stephen, the husband, was intoxicated. His wife, Linda, said that he had been out of work for six months, and they were having financial problems. Recently he’d also been depressed and lethargic, and kept saying things like “I’m tired of all this and just want to end it all. ” Joe asked Stephen if he was thinking of killing himself. Stephen admitted that he had considered taking his life. Joe said that Stephen needed to go to the hospital so that he could be evaluated and get help to deal with his problems. After some hesitation and reluctance, Stephen finally agreed to go. At the hospital, Joe told the emergency department physician that Stephen had become depressed after being unemployed for six months and he had been drinking and had admitted that he considered taking his life. The physician thanked Joe for the information and said it was helpful. (Based on the experiences of a law enforcement officer

A Concise Total Synthesis of (--)-Maoecrystal Z

The first total synthesis of (--)-maoecrystal Z is described. The key steps of the synthesis include a diastereoselective Ti^(III)-mediated reductive epoxide coupling reaction and a diastereoselective Sm^(II)-mediated reductive cascade cyclization reaction. These transformations enabled the preparation of (--)-maoecrystal Z in only 12 steps from (--)-γ-cyclogeraniol

Final report on the force key comparison CCM.F-K3

In the Force Key Comparison CCM.F-K3 the measurand force was compared at the two force steps 500 kN and 1 MN. 12 laboratories participated in this comparison which was organised by PTB as the pilot laboratory in two laboratory groups (group A and B). In group A, the comparison was carried out with two 1 MN compression force transducers at the two force steps 500 kN and 1 MN (CCM.F-K3a) and with 6 participating laboratories. In group B, the comparison was carried out with two 500 kN compression force transducers at one force step of 500 kN (CCM.F-K3b) and with 9 participating laboratories. The key comparison reference values were determined as the weighted mean of all results for the two force steps and set to 500 kN and 1 MN, respectively, with the associated uncertainties. The degrees of equivalence were determined for all 12 laboratories for 500 kN compression force and for 6 laboratories for 1 MN compression force

The Right Track: Building a 21st Century High-Speed Rail System for America

Provides an overview of U.S. investment in high-speed intercity passenger rail, its economic and environmental benefits, analyses by region, and key steps for building an efficient network, including balancing private investment with public safeguards