Click to learn more about author Steve Miller. It?s Fall championship time for NCAA D1 college sports. On Sunday 12/3, college football announced its final four to commence New Year?s day, and other championship tournaments such as men?s and women?s soccer and women?s volleyball are currently in progress. A major challenge before the start of [?]
Let?s see if this scenario sounds familiar. One of the business units has a new application. Management is really excited because it?s been developed to run ?in the cloud,? and you?ve been tasked with finding out how IT is going to take over administration, which is going to be required for security, volume purchasing, and demand-management reasons. The business is also going to want to integrate it with several other corporate apps down the road, and your team will end up being responsible for a lot of that work. When you look into the background you find out that no real evaluation was done before an IaaS provider was selected. The development team simply chose the service they ?thought would be best,? which really means the one that they were most interested in using.
The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. Here we modify BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click-chemistry and can be used as molecular probes in vitro and in vivo. Using click-proteomics and click-sequencing we explore the gene regulatory function of bromodomain containing 4 protein (BRD4) and the transcriptional changes induced by BET inhibitors. Studying mouse models of acute leukemia, we use high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the pre-clinical assessment of a wide range of drugs.
The design of organic compounds with nearly no gap between the first excited singlet (S1) and triplet (T1) states has been demonstrated to result in an efficient spin-flip transition from the T1 to S1 state, that is, reverse intersystem crossing (RISC), and facilitate light emission as thermally activated delayed fluorescence (TADF). However, many TADF molecules have shown that a relatively appreciable energy difference between the S1 and T1 states (~0.2 eV) could also result in a high RISC rate. We revealed from a comprehensive study of optical properties of TADF molecules that the formation of delocalized states is the key to efficient RISC and identified a chemical template for these materials. In addition, simple structural confinement further enhances RISC by suppressing structural relaxation in the triplet states. Our findings aid in designing advanced organic molecules with a high rate of RISC and, thus, achieving the maximum theoretical electroluminescence efficiency in organic light-emitting diodes.
Universalism?the evaluation of scientists' achievements based on merit alone rather than on functionally irrelevant factors ( 1 ? 3 )?has long been an unquestioned norm in science. Its existence is best illustrated by the reactions of outrage whenever a violation of universalism in science is exposed. For example, a study by Moss-Racusin et al. received a lot of attention in the scientific community because it found that when assessing application materials, science faculty rated students with male names as more competent than students who were otherwise identical but had been given female names ( 4 ). In a recent study, Fisman et al. ( 5 ) find evidence for favoritism in Chinese science: The election of membership to the two most prestigious scientific organizations, the Chinese Academy of Sciences (CAS) and the Chinese Academy of Engineering (CAE), appears to be influenced by ?guanxi,? or social network, as measured by hometown ties between candidates and selection committee members.
Bill de Blasio ran for mayor of New York City in 2013 on the promise of providing free preschool to every 4-year-old in the city. After he won, his administration went looking for a high-quality prekindergarten math curriculum, one vetted by researchers, that has improved the math skills of young children in other cities. In short, the mayor wanted something that "worked." In the end, school officials settled on Building Blocks, a program developed by mathematics education professors Douglas Clements and Julie Sarama, which had boosted student achievement in several other cities. But Building Blocks has a dismaying feature that is common to other preschool interventions: Children using it chalk up glowing initial results, only to see the gains fade over the next few years. The fade-out phenomenon has raised questions about how researchers and policymakers should evaluate interventions like Building Blocks, and whether they are asking the right questions.
Tensions between a graduate student and a prominent biomedical researcher at Harvard University have produced a series of extraordinary events, including an involuntary psychiatric evaluation of the student and a court order against the scientist ordering him to stay 30.5 meters away from the student and have no contact. The student says the forced evaluation occurred because he had filed a scientific misconduct complaint against the researcher, and that it constituted retaliation. A state judge agreed. But the researcher says he acted only out of concern for the student's welfare, and is seeking to have the order overturned. All sides say the order has created tense and difficult working conditions. And the dispute has left bystanders wondering how a conflict between a mentor and his student spiraled so dramatically out of control, jeopardizing the reputation of a prominent scientist and an elite research university, along with the future of a promising young scientist.