Actuation of Micro-Optomechanical Systems Via Cavity-Enhanced Optical Dipole Forces

We demonstrate a new type of optomechanical system employing a movable, micron-scale waveguide evanescently-coupled to a high-Q optical microresonator. Micron-scale displacements of the waveguide are observed for milliwatt(mW)-level optical input powers. Measurement of the spatial variation of the force on the waveguide indicates that it arises from a cavity-enhanced optical dipole force due to the stored optical field of the resonator. This force is used to realize an all-optical tunable filter operating with sub-mW control power. A theoretical model of the system shows the maximum achievable force to be independent of the intrinsic Q of the optical resonator and to scale inversely with the cavity mode volume, suggesting that such forces may become even more effective as devices approach the nanoscale.Comment: 4 pages, 5 figures. High resolution version available at (http://copilot.caltech.edu/publications/CEODF_hires.pdf). For associated movie, see (http://copilot.caltech.edu/research/optical_forces/index.htm

Regionally Distinct N -Methyl-D-Aspartate Receptors Distinguished by Quantitative Autoradiography of [ 3 H]MK-801 Binding in Rat Brain

Quantitative autoradiography of [ 3 H]MK-801 binding was used to characterize regional differences in N -methyl-d-aspartate (NMDA) receptor pharmacology in rat CNS. Regionally distinct populations of NMDA receptors were distinguished on the basis of regulation of [ 3 H]MK-801 binding by the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). CPP inhibited [ 3 H]MK-801 binding in outer cortex (OC) and medial cortex (MC) with apparent K i values of 0.32-0.48 Μ M , whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent K i values were 1.1-1.6 Μ M . In medial thalamus (MT) and lateral thalamus (LT) the apparent K i values were 0.78 Μ M . In the presence of added glutamate (3 Μ M ), the relative differences in apparent K i values between regions maintained a similar relationship with the exception of the OC. Inhibition of [ 3 H]MK-801 binding by the glycine site antagonist 7-chlorokynurenic acid (7-ClKyn) distinguished at least two populations of NMDA receptors that differed from populations defined by CPP displacement. 7-ClKyn inhibited [ 3 H]MK-801 binding in OC, MC, MS, and LS with apparent K i values of 6.3-8.6 Μ M , whereas in CA1, DG, LT, and MT, K i values were 11.4-13.6 Μ M . In the presence of added glycine (1 Μ M ), the relative differences in apparent K i values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [ 3 H]MK-801 binding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65616/1/j.1471-4159.1993.tb03295.x.pd

Stimulated optomechanical excitation of surface acoustic waves in a microdevice

Stimulated Brillouin interaction between sound and light, known to be the strongest optical nonlinearity common to all amorphous and crystalline dielectrics, has been widely studied in fibers and bulk materials but rarely in optical microresonators. The possibility of experimentally extending this principle to excite mechanical resonances in photonic microsystems, for sensing and frequency reference applications, has remained largely unexplored. The challenge lies in the fact that microresonators inherently have large free spectral range, while the phase matching considerations for the Brillouin process require optical modes of nearby frequencies but with different wavevectors. We rely on high-order transverse optical modes to relax this limitation. Here we report on the experimental excitation of mechanical resonances ranging from 49 to 1400 MHz by using forward Brillouin scattering. These natural mechanical resonances are excited in ~100 um silica microspheres, and are of a surface-acoustic whispering-gallery type

Mouse TRIP13/PCH2 Is Required for Recombination and Normal Higher-Order Chromosome Structure during Meiosis

Accurate chromosome segregation during meiosis requires that homologous chromosomes pair and become physically connected so that they can orient properly on the meiosis I spindle. These connections are formed by homologous recombination closely integrated with the development of meiosis-specific, higher-order chromosome structures. The yeast Pch2 protein has emerged as an important factor with roles in both recombination and chromosome structure formation, but recent analysis suggested that TRIP13, the mouse Pch2 ortholog, is not required for the same processes. Using distinct Trip13 alleles with moderate and severe impairment of TRIP13 function, we report here that TRIP13 is required for proper synaptonemal complex formation, such that autosomal bivalents in Trip13-deficient meiocytes frequently displayed pericentric synaptic forks and other defects. In males, TRIP13 is required for efficient synapsis of the sex chromosomes and for sex body formation. Furthermore, the numbers of crossovers and chiasmata are reduced in the absence of TRIP13, and their distribution along the chromosomes is altered, suggesting a role for TRIP13 in aspects of crossover formation and/or control. Recombination defects are evident very early in meiotic prophase, soon after DSB formation. These findings provide evidence for evolutionarily conserved functions for TRIP13/Pch2 in both recombination and formation of higher order chromosome structures, and they support the hypothesis that TRIP13/Pch2 participates in coordinating these key aspects of meiotic chromosome behavior

The Flagellar Regulator fliT Represses Salmonella Pathogenicity Island 1 through flhDC and fliZ

Salmonella pathogenicity island 1 (SPI1), comprising a type III section system that translocates effector proteins into host cells, is essential for the enteric pathogen Salmonella to penetrate the intestinal epithelium and subsequently to cause disease. Using random transposon mutagenesis, we found that a Tn10 disruption in the flagellar fliDST operon induced SPI1 expression when the strain was grown under conditions designed to repress SPI1, by mimicking the environment of the large intestine through the use of the intestinal fatty acid butyrate. Our genetic studies showed that only fliT within this operon was required for this effect, and that exogenous over-expression of fliT alone significantly reduced the expression of SPI1 genes, including the invasion regulator hilA and the sipBCDA operon, encoding type III section system effector proteins, and Salmonella invasion of cultured epithelial cells. fliT has been known to inhibit the flagellar machinery through repression of the flagellar master regulator flhDC. We found that the repressive effect of fliT on invasion genes was completely abolished in the absence of flhDC or fliZ, the latter previously shown to induce SPI1, indicating that this regulatory pathway is required for invasion control by fliT. Although this flhDC-fliZ pathway was necessary for fliT to negatively control invasion genes, fliZ was not essential for the repressive effect of fliT on motility, placing fliT high in the regulatory cascade for both invasion and motility

Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination. Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.Peer reviewe

Back-action Evading Measurements of Nanomechanical Motion

When performing continuous measurements of position with sensitivity approaching quantum mechanical limits, one must confront the fundamental effects of detector back-action. Back-action forces are responsible for the ultimate limit on continuous position detection, can also be harnessed to cool the observed structure, and are expected to generate quantum entanglement. Back-action can also be evaded, allowing measurements with sensitivities that exceed the standard quantum limit, and potentially allowing for the generation of quantum squeezed states. We realize a device based on the parametric coupling between an ultra-low dissipation nanomechanical resonator and a microwave resonator. Here we demonstrate back-action evading (BAE) detection of a single quadrature of motion with sensitivity 4 times the quantum zero-point motion, back-action cooling of the mechanical resonator to n = 12 quanta, and a parametric mechanical pre-amplification effect which is harnessed to achieve position resolution a factor 1.3 times quantum zero-point motion.Comment: 19 pages (double-spaced) including 4 figures and reference

Temperature Dependence of Backbone Dynamics in Human Ileal Bile Acid-Binding Protein: Implications for the Mechanism of Ligand Binding

Human ileal bile acid-binding protein (I-BABP), a member of the family of intracellular lipid binding proteins plays a key role in the cellular trafficking and metabolic regulation of bile salts. The protein has two internal and, according to a recent study, an additional superficial binding site and binds di- and trihydroxy bile salts with positive cooperativity and a high degree of site-selectivity. Previously, in the apo form, we have identified an extensive network of conformational fluctuations on the millisecond time scale, which cease upon ligation. Additionally, ligand binding at room temperature was found to be accompanied by a slight rigidification of picosecond-nanosecond (ps-ns) backbone flexibility. In the current study, temperature-dependent N-15 NMR spin relaxation measurements were used to gain more insight into the role of dynamics in human I-BABP-bile salt recognition. According to our analysis, residues sensing a conformational exchange in the apo state can be grouped into two clusters with slightly different exchange rates. The entropy-enthalpy compensation observed for both clusters suggests a disorder-order transition between a ground and a sparsely populated higher energy state in the absence of ligands. Analysis of the faster, ps-ns motion of N-15-H-1 bond vectors indicates an unusual nonlinear temperature-dependence for both ligation states. Intriguingly, while bile salt binding results in a more uniform response to temperature change throughout the protein, the temperature derivative of the generalized order parameter shows different responses to temperature increase for the two forms of the protein in the investigated temperature range. Analysis of both slow and fast motions in human I-BABP indicates largely different energy landscapes for the apo and halo states suggesting that optimization of binding interactions might be achieved by altering the dynamic behavior of specific segments in the protein

A Novel Mouse Synaptonemal Complex Protein Is Essential for Loading of Central Element Proteins, Recombination, and Fertility

The synaptonemal complex (SC) is a proteinaceous, meiosis-specific structure that is highly conserved in evolution. During meiosis, the SC mediates synapsis of homologous chromosomes. It is essential for proper recombination and segregation of homologous chromosomes, and therefore for genome haploidization. Mutations in human SC genes can cause infertility. In order to gain a better understanding of the process of SC assembly in a model system that would be relevant for humans, we are investigating meiosis in mice. Here, we report on a newly identified component of the murine SC, which we named SYCE3. SYCE3 is strongly conserved among mammals and localizes to the central element (CE) of the SC. By generating a Syce3 knockout mouse, we found that SYCE3 is required for fertility in both sexes. Loss of SYCE3 blocks synapsis initiation and results in meiotic arrest. In the absence of SYCE3, initiation of meiotic recombination appears to be normal, but its progression is severely impaired resulting in complete absence of MLH1 foci, which are presumed markers of crossovers in wild-type meiocytes. In the process of SC assembly, SYCE3 is required downstream of transverse filament protein SYCP1, but upstream of the other previously described CE–specific proteins. We conclude that SYCE3 enables chromosome loading of the other CE–specific proteins, which in turn would promote synapsis between homologous chromosomes