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Meeting report: a hard look at the state of enamel research.
The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field
Pollution-Affected Fish Hepatic Transcriptome and Its Expression Patterns on Exposure to Cadmium
Individuals of the fish Lithognathus mormyrus were exposed to a series of pollutants including: benzo[a]pyrene, pp-DDE, Aroclor 1254, perfluorooctanoic acid, tributyl-tin chloride, lindane, estradiol, 4-nonylphenol, methyl mercury chloride, and cadmium chloride. Five mixtures of the pollutants were injected. Each mixture included one to three compounds. A microarray was constructed using 4608 L. mormyrus hepatic cDNAs cloned from the pollutant-exposed fish. Most clones (4456) were sequenced and assembled into 1494 annotated unique clones. The constructed microarray was used to identify changes in hepatic gene expression profile on exposure to cadmium administered to the fish by feeding or injections. Thirty-one unique clones showed altered expression levels on exposure to cadmium. Prominently differentially expressed genes included elastase 4, carboxypeptidase B, trypsinogen, perforin, complement C31, cytochrome P450 2K5, ceruloplasmin, carboxyl ester lipase, and metallothionein. Twelve sequences have no available annotation. Most genes (23) were downregulated and hypothesized to be affected by general toxicity due to the intensive cadmium exposure regime. The concept of an operational multigene cDNA microarray, aimed at routine and fast biomonitoring of multiple environmental threats, is outlined and the cadmium exposure experiment has been used to demonstrate functional and methodological aspects of the biomonitoring tool. The components of the outlined system include: (1) spotted array, composed of both pollution-affected and constitutively expressed genes, the latter are used for normalization; (2) standard, repeatable labeling procedure of a reference transcript population; and (3) biomarker indices derived from the profile of expression ratio across the pollution-affected genes, between the field-sampled transcript populations and the reference
On the relationships between kinetic schemes and two-state single molecule trajectories
Trajectories of a signal that fluctuates between two states which originate
from single molecule activities have become ubiquitous. Common examples are
trajectories of ionic flux through individual membrane-channels, and of photon
counts collected from diffusion, activity, and conformational changes of
biopolymers. By analyzing the trajectory, one wishes to deduce the underlying
mechanism, which is usually described by a multi-substate kinetic scheme. In
previous works, we divided kinetic schemes that generate two-state trajectories
into two types: reducible schemes and irreducible schemes. We showed that all
the information in trajectories generated from reducible schemes is contained
in the waiting time probability density functions (PDFs) of the two states. It
follows that reducible schemes with the same waiting time PDFs are not
distinguishable. In this work, we further characterize the topologies of
kinetic schemes, now of irreducible schemes, and further study two-state
trajectories from the two types of scheme. We suggest various methods for
extracting information about the underlying kinetic scheme from the trajectory
(e. g., calculate the binned successive waiting times PDF and analyze the
ordered waiting times trajectory), and point out the advantages and
disadvantages of each. We show that the binned successive waiting times PDF is
not only more robust than other functions when analyzing finite trajectories,
but contains, in most cases, more information about the underlying kinetic
scheme than other functions in the limit of infinitely long trajectories. For
some cases however, analyzing the ordered waiting times trajectory may supply
unique information about the underlying kinetic scheme
Spin Echo Decay in a Stochastic Field Environment
We derive a general formalism with which it is possible to obtain the time
dependence of the echo size for a spin in a stochastic field environment. Our
model is based on ``strong collisions''. We examine in detail three cases
where: (I) the local field is Ising-like, (II) the field distribution is
continuous and has a finite second moment, and (III) the distribution is
Lorentzian. The first two cases show a T2 minimum effect and are exponential in
time cubed for short times. The last case can be approximated by a
phenomenological stretched exponential.Comment: 11 pages + 3 postscript figure
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
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
The Quantum-Classical Crossover in the Adiabatic Response of Chaotic Systems
The autocorrelation function of the force acting on a slow classical system,
resulting from interaction with a fast quantum system is calculated following
Berry-Robbins and Jarzynski within the leading order correction to the
adiabatic approximation. The time integral of the autocorrelation function is
proportional to the rate of dissipation. The fast quantum system is assumed to
be chaotic in the classical limit for each configuration of the slow system. An
analytic formula is obtained for the finite time integral of the correlation
function, in the framework of random matrix theory (RMT), for a specific
dependence on the adiabatically varying parameter. Extension to a wider class
of RMT models is discussed. For the Gaussian unitary and symplectic ensembles
for long times the time integral of the correlation function vanishes or falls
off as a Gaussian with a characteristic time that is proportional to the
Heisenberg time, depending on the details of the model. The fall off is
inversely proportional to time for the Gaussian orthogonal ensemble. The
correlation function is found to be dominated by the nearest neighbor level
spacings. It was calculated for a variety of nearest neighbor level spacing
distributions, including ones that do not originate from RMT ensembles. The
various approximate formulas obtained are tested numerically in RMT. The
results shed light on the quantum to classical crossover for chaotic systems.
The implications on the possibility to experimentally observe deterministic
friction are discussed.Comment: 26 pages, including 6 figure
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