Interference and zero-bias anomaly in tunneling between Luttinger-liquid wires

We present theoretical calculations and experimental measurements which reveal the Luttinger-liquid (LL) nature of elementary excitations in a system consisting of two quantum wires connected by a long narrow tunnel junction at the edge of a GaAs/AlGaAs bilayer heterostructure. The boundaries of the wires are important and lead to a characteristic interference pattern in measurements on short junctions. We show that the experimentally observed modulation of the conductance oscillation amplitude as a function of the voltage bias can be accounted for by spin-charge separation of the elementary excitations in the interacting wires. Furthermore, boundaries affect the LL exponents of the voltage and temperature dependence of the tunneling conductance at low energies. We show that the measured temperature dependence of the conductance zero-bias dip as well as the voltage modulation of the conductance oscillation pattern can be used to extract the electron interaction parameters in the wires.Comment: 17 pages, 12 figure

Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells

The simplicity of programming the CRISPR (clustered regularly interspaced short palindromic repeats)–associated nuclease Cas9 to modify specific genomic loci suggests a new way to interrogate gene function on a genome-wide scale. We show that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells. First, we used the GeCKO library to identify genes essential for cell viability in cancer and pluripotent stem cells. Next, in a melanoma model, we screened for genes whose loss is involved in resistance to vemurafenib, a therapeutic RAF inhibitor. Our highest-ranking candidates include previously validated genes NF1 and MED12, as well as novel hits NF2, CUL3, TADA2B, and TADA1. We observe a high level of consistency between independent guide RNAs targeting the same gene and a high rate of hit confirmation, demonstrating the promise of genome-scale screening with Cas9.National Institutes of Health (U.S.) (Award 1DP1-MH100706)National Institutes of Health (U.S.) (1R01-DK097768

Bridging the Mid-Infrared-to-Telecom Gap with Silicon Nanophotonic Spectral Translation

Expanding far beyond traditional applications in optical interconnects at telecommunications wavelengths, the silicon nanophotonic integrated circuit platform has recently proven its merits for working with mid-infrared (mid-IR) optical signals in the 2-8 {\mu}m range. Mid-IR integrated optical systems are capable of addressing applications including industrial process and environmental monitoring, threat detection, medical diagnostics, and free-space communication. Rapid progress has led to the demonstration of various silicon components designed for the on-chip processing of mid-IR signals, including waveguides, vertical grating couplers, microcavities, and electrooptic modulators. Even so, a notable obstacle to the continued advancement of chip-scale systems is imposed by the narrow-bandgap semiconductors, such as InSb and HgCdTe, traditionally used to convert mid-IR photons to electrical currents. The cryogenic or multi-stage thermo-electric cooling required to suppress dark current noise, exponentially dependent upon the ratio Eg/kT, can limit the development of small, low-power, and low-cost integrated optical systems for the mid-IR. However, if the mid-IR optical signal could be spectrally translated to shorter wavelengths, for example within the near-infrared telecom band, photodetectors using wider bandgap semiconductors such as InGaAs or Ge could be used to eliminate prohibitive cooling requirements. Moreover, telecom band detectors typically perform with higher detectivity and faster response times when compared with their mid-IR counterparts. Here we address these challenges with a silicon-integrated approach to spectral translation, by employing efficient four-wave mixing (FWM) and large optical parametric gain in silicon nanophotonic wires

Continuously Growing Rodent Molars Result from a Predictable Quantitative Evolutionary Change over 50 Million Years

The fossil record is widely informative about evolution, but fossils are not systematically used to study the evolution of stem-cell-driven renewal. Here, we examined evolution of the continuous growth (hypselodonty) of rodent molar teeth, which is fuelled by the presence of dental stem cells. We studied occurrences of 3,500 North American rodent fossils, ranging from 50 million years ago (mya) to 2 mya. We examined changes in molar height to determine whether evolution of hypselodonty shows distinct patterns in the fossil record, and we found that hypselodont taxa emerged through intermediate forms of increasing crown height. Next, we designed a Markov simulation model, which replicated molar height increases throughout the Cenozoic and, moreover, evolution of hypselodonty. Thus, by extension, the retention of the adult stem cell niche appears to be a predictable quantitative rather than a stochastic qualitative process. Our analyses predict that hypselodonty will eventually become the dominant phenotype.Peer reviewe

Cellular shape reinforces niche to stem cell signaling in the small intestine

Peer reviewe

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. METHODS: The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. RESULTS: NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. CONCLUSIONS: NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed