A 160-kilobit molecular electronic memory patterned at 10(11) bits per square centimetre

The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140 nm pitch wires and a memory cell size of 0.0408 mum(2). Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have 'no known solution'. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10(11) bits cm(-2) (pitch 33 nm; memory cell size 0.0011 microm2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.     

Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13)

We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p. We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein. In both families, deafness is non-progressive and predominantly affects middle frequencies. Mice with a targeted disruption of Col11a2 also were shown to have hearing loss. Electron microscopy of the tectorial membrane of these mice revealed loss of organization of the collagen fibrils. Our findings revealed a unique ultrastructural malformation of inner-ear architecture associated with non-syndromic hearing loss, and suggest that tectorial membrane abnormalities may be one aetiology of sensorineural hearing loss primarily affecting the mid-frequencies.     

Seismic evidence of negligible water carried below 400-km depth in subducting lithosphere

Strong evidence exists that water is carried from the surface into the upper mantle by hydrous minerals in the uppermost 10-12?km of subducting lithosphere, and more water may be added as the lithosphere bends and goes downwards. Significant amounts of that water are released as the lithosphere heats up, triggering earthquakes and fluxing arc volcanism. In addition, there is experimental evidence for high solubility of water in olivine, the most abundant mineral in the upper mantle, for even higher solubility in olivine's high-pressure polymorphs, wadsleyite and ringwoodite, and for the existence of dense hydrous magnesium silicates that potentially could carry water well into the lower mantle (deeper than 1,000?km). Here we compare experimental and seismic evidence to test whether patterns of seismicity and the stabilities of these potentially relevant hydrous phases are consistent with a wet lithosphere. We show that there is nearly a one-to-one correlation between dehydration of minerals and seismicity at depths less than about 250?km, and conclude that the dehydration of minerals is the trigger of instability that leads to seismicity. At greater depths, however, we find no correlation between occurrences of earthquakes and depths where breakdown of hydrous phases is expected. Lastly, we note that there is compelling evidence for the existence of metastable olivine (which, if present, can explain the distribution of deep-focus earthquakes) west of and within the subducting Tonga slab and also in three other subduction zones, despite metastable olivine being incompatible with even extremely small amounts of water (of the order of 100?p.p.m. by weight). We conclude that subducting slabs are essentially dry at depths below 400?km and thus do not provide a pathway for significant amounts of water to enter the mantle transition zone or the lower mantle.     

Structure and dynamics of the M3 muscarinic acetylcholine receptor

Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.     

Extinction risk from climate change

Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.