The ability to synthesize colloidal semiconductor nanocrystals in a well-controlled manner (i.e., with fine control over size, shape, size dispersion, and composition) has been mastered over the past ...15 years. Much of this success stems from careful studies of precursor conversion and nanocrystal growth with respect to phosphine chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals. Despite the high level of success that has been achieved with phosphine chalcogenides, there has been a longstanding interest in exploring alternate chalcogenide precursors because of issues associated with phosphine chalcogenide cost, purity, toxicity, etc. This has resulted in a large body of literature on the use of sulfur and selenium dissolved in octadecene or amines, thio- and selenoureas, and silyl chalcogenides as alternate chalcogenide precursors for metal chalcogenide nanocrystal synthesis. In this Account, emerging work on the use of diorganyl dichalcogenides (R–E–E–R, where E = S, Se, or Te and R = alkyl, allyl, benzyl, or aryl) as alternate chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals is summarized. Among the benefits of these dichalcogenide synthons are the following: (i) they represent the first and only common precursor type that can function as chalcogen transfer reagents for each of the group VI elements (i.e., to make metal oxide, metal sulfide, metal selenide, and metal telluride nanocrystals); (ii) they possess relatively weak E–E bonds that can be readily cleaved under mild thermolytic or photolytic conditions; and (iii) the organic substituents can be tuned to affect the reactivity. These combined attributes have allowed dichalcogenide precursors to be employed for a wide range of metal chalcogenide nanocrystal syntheses, including those for In2S3, Sn x Ge1–x Se, SnTe, Cu2–x S y Se1–y , ZnSe, CdS, CdSe, MoSe2, WSe2, BiSe, and CuFeS2. Interestingly, a number of metastable phases of compositionally complex semiconductors can be kinetically accessed through syntheses utilizing dichalcogenide precursors, likely as a result of their ability to convert at relatively low temperatures. These include the hexagonal wurtzite phases of CuInS2, CuInSe2, Cu2ZnSn(S1–x Se x )4, and Cu2SnSe3 nanocrystals. The discovery of crystal phases on the nanoscale that do not exist in their bulk analogues is a developing area of nanocrystal chemistry, and dichalcogenides are proving to be a useful synthetic tool in this regard. The most recent application of dichalcogenide synthons for semiconductor nanocrystals is their use as precursors for surface ligands. While there is a rich history of using thiol ligands for semiconductor nanocrystals, the analogous selenol and tellurol ligands have not been studied, likely because of their oxidative instability. Dichalcogenides have proven useful in this regard, as they can be reduced in situ with diphenylphosphine to give the corresponding selenol or tellurol ligand that binds to the nanocrystal surface. This chemistry has been applied to the in situ synthesis and ligand binding of selenols to PbSe nanocrystals and both selenols and tellurols to CdSe nanocrystals. These initial studies have allowed the photophysics of these nanocrystal–ligand constructs to be investigated; in both cases, it appears that the selenol and tellurol ligands act as hole traps that quench the photoluminescence of the semiconductor nanocrystals.
The classical view of an information system is that it represents and reflects physical reality. We suggest this classical view is increasingly obsolete: digital technologies are now creating and ...shaping physical reality. We call this phenomenon the ontological reversal. The ontological reversal is where the digital version is created first, and the physical version second (if needed). This ontological reversal challenges us to think about the role of humans and technology in society. It also challenges us to think about our role as IS scholars in this digital world and what it means for our research agendas.
Traumatic fear memories can be inhibited by behavioral therapy for humans, or by extinction training in rodent models, but are prone to recur. Under some conditions, however, these treatments ...generate a permanent effect on behavior, which suggests that emotional memory erasure has occurred. The neural basis for such disparate outcomes is unknown. We found that a central component of extinction-induced erasure is the synaptic removal of calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in the lateral amygdala. A transient up-regulation of this form of plasticity, which involves phosphorylation of the glutamate receptor 1 subunit of the AMPA receptor, defines a temporal window in which fear memory can be degraded by behavioral experience. These results reveal a molecular mechanism for fear erasure and the relative instability of recent memory.
Huntington disease (HD) is a devastating, late-onset, inherited neurodegenerative disorder that manifests with personality changes, movement disorders, and cognitive decline. It is caused by a CAG ...repeat expansion in exon 1 of the HTT gene that translates to a polyglutamine tract in the huntingtin protein (HTT). The formation of HTT fragments has been implicated as an essential step in the molecular pathogenesis of HD and several proteases that cleave HTT have been identified. However, the importance of smaller N-terminal fragments has been highlighted by their presence in HD postmortem brains and by the fact that nuclear inclusions are only detected by antibodies to the N terminus of HTT. Despite an intense research effort, the precise length of these fragments and the mechanism by which they are generated remains unknown. Here we show that CAG repeat length–dependent aberrant splicing of exon 1 HTT results in a short polyadenylated mRNA that is translated into an exon 1 HTT protein. Given that mutant exon 1 HTT proteins have consistently been shown to be highly pathogenic in HD mouse models, the aberrant splicing of HTT mRNA provides a mechanistic basis for the molecular pathogenesis of HD. RNA-targeted therapeutic strategies designed to lower the levels of HTT are under development. Many of these approaches would not prevent the production of exon 1 HTT and should be reviewed in light of our findings.
The global regulatory nucleotide ppGpp (“magic spot”) regulates transcription from a large subset of Escherichia coli promoters, illustrating how small molecules can control gene expression ...promoter—specifically by interacting with RNA polymerase (RNAP) without binding to DNA. However, ppGpp’s target site on RNAP, and therefore its mechanism of action, has remained unclear. We report here a binding site for ppGpp on E. coli RNAP, identified by crosslinking, protease mapping, and analysis of mutant RNAPs that fail to respond to ppGpp. A strain with a mutant ppGpp binding site displays properties characteristic of cells defective for ppGpp synthesis. The binding site is at an interface of two RNAP subunits, ω and β′, and its position suggests an allosteric mechanism of action involving restriction of motion between two mobile RNAP modules. Identification of the binding site allows prediction of bacterial species in which ppGpp exerts its effects by targeting RNAP.
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► We report an RNAP binding site responsible for ppGpp function ► The binding site is at an interface of two RNAP subunits, ω and β′ ► The location of the binding site suggests an allosteric mechanism of action ► The site predicts species in which ppGpp functions by regulating RNAP
Rapid growth in demand for lignocellulosic bioenergy will require major changes in supply chain infrastructure. Even with densification and preprocessing, transport volumes by mid-century are likely ...to exceed the combined capacity of current agricultural and energy supply chains, including grain, petroleum, and coal. Efficient supply chains can be achieved through decentralized conversion processes that facilitate local sourcing, satellite preprocessing and densification for long-distance transport, and business models that reward biomass growers both nearby and afar. Integrated systems that are cost-effective and energy-efficient will require new ways of thinking about agriculture, energy infrastructure, and rural economic development. Implementing these integrated systems will require innovation and investment in novel technologies, efficient value chains, and socioeconomic and policy frameworks; all are needed to support an expanded biofuels infrastructure that can meet the challenges of scale.
To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up.
The Multicenter AIDS ...Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification.
The frequency of HAND for the 364 HIV+ individuals seen in 2007-2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007-2008, 2009-2010, and 2011-2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009-2010 to 2011-2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition.
HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.
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