Quantum Holographic Encoding in a Two-dimensional Electron Gas

The advent of bottom-up atomic manipulation heralded a new horizon for attainable information density, as it allowed a bit of information to be represented by a single atom. The discrete spacing between atoms in condensed matter has thus set a rigid limit on the maximum possible information density. While modern technologies are still far from this scale, all theoretical downscaling of devices terminates at this spatial limit. Here, however, we break this barrier with electronic quantum encoding scaled to subatomic densities. We use atomic manipulation to first construct open nanostructures--"molecular holograms"--which in turn concentrate information into a medium free of lattice constraints: the quantum states of a two-dimensional degenerate Fermi gas of electrons. The information embedded in the holograms is transcoded at even smaller length scales into an atomically uniform area of a copper surface, where it is densely projected into both two spatial degrees of freedom and a third holographic dimension mapped to energy. In analogy to optical volume holography, this requires precise amplitude and phase engineering of electron wavefunctions to assemble pages of information volumetrically. This data is read out by mapping the energy-resolved electron density of states with a scanning tunnelling microscope. As the projection and readout are both extremely near-field, and because we use native quantum states rather than an external beam, we are not limited by lensing or collimation and can create electronically projected objects with features as small as ~0.3 nm. These techniques reach unprecedented densities exceeding 20 bits/nm2 and place tens of bits into a single fermionic state.Comment: Published online 25 January 2009 in Nature Nanotechnology; 12 page manuscript (including 4 figures) + 2 page supplement (including 1 figure); supplementary movie available at http://mota.stanford.ed

RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Photopyroelectric Spectroscopy (P2ES) of a-Si:H Thin Semiconducting Films on Quartz

Photopyroelectric Spectroscopy has proven to be a sensitive qualitative [1] and quantitative [2] technique for thin film spectroscopic applications. An important feature of this back-surface detection technique, not shared with the more conventional front-surface photothermal detection methods (Photothermal Deflection Spectroscopy, PDS; and Photoacoustic Spectroscopy, PAS) is its ability to measure directly and separately two independent spectrally-varying parameters: the optical absorption coefficient [3] and the nonradiative quantum efficiency. PDS of thin semiconducting films of amorphous hydrogenated Si [4] readily yields information about the product of the optical absorption coefficient, α(λ), and the nonradiative quantum efficiency, η(λ). The standard assumption is, however, that η(λ) is not a sensitive function of the exciting photon energy. This assumption is generally wrong, and nonradiative quantum efficiencies have been found photoacoustically to vary by one order of magnitude [5] across the optical gap in Ge doped As 2 Se 3 chalcogenide glasses. PAS yields amorphous thin film spectra similar to PDS [6]. The working assumption has been that PA spectra are essentially accurate above the optical gap, as η(λ) is expected to be independent of photon energy. Kitamura et al. [5] were able to derive extended η(λ) spectra of (As 2 Se 3 )100-x Ge xglasses upon combining PA spectra with optical absorption coefficient information obtained in an independent spectrophotometric experiment using ordinary polished bulk samples. These authors, however, were not able to guarantee that the glasses and the bulk samples had the same (or even nearly similar) α(λ) spectra.</p